TOC

Housestaff Manual
July 2020 - June 2021
Department of Medicine
Massachusetts General Hospital
Harvard Medical School
Boston, MA

Editors
Jacqueline Henson, MD
Alexandra Wick, MD
TOC

MGH Housestaff Manual Preface

It is an honor to present the 26th edition of the MGH Department of Medicine Housestaff Manual. “The White Book” is a trusted
resource for medical residents and other clinicians at MGH and a great tradition of the Department of Medicine Residency Program.
It exemplifies the rigor, autonomy, and pride with which MGH medical residents approach their work and their training.

The White Book is comprised of a collective of clinical experiences on the medical services as well as an annual review of the
literature. This book is a product of diligent work of many resident contributors (listed on the bottom of each page) as well as past
generations of authors and editors.

We extend our sincere gratitude to those junior and senior residents who contributed significant time and energy in editing entire
sections of this manual:
Cardiology: Shawn Li, Avanthi Raghavan Endocrinology: Max Petersen, Seth Tobolsky
Pulmonology & Critical Care: Robert Arao, Anna O’Kelly Allergy & Immunology: Jessica Plager
Gastroenterology: Ryan Flanagan, Sally Knooihuizen Neurology: Jeffrey Gluckstein
Nephrology: Daniel Gromer, Elizabeth Kurtz Psychiatry: Alexandra Wick
Infectious Disease: Rebecca Abelman, Hawra Al-Lawati Primary Care: Nate Alhalel
Hematology: Nora Abo-Sido Consultants: Jacqueline Henson, Alexandra Wick
Oncology: Leon Pappas, Vinayak Venkataraman Radiology: Sam Cartmell
Geriatrics & Palliative Care: Paige McLean Procedures: Sean Mendez, Chitra Mosarla
Rheumatology: Leslie Chang

We would like to thank the many faculty and fellows who assisted with this book, particularly Jonathan Dau for his work on the
Rheumatology section. In addition, we are grateful for the contributions from residents in the neurology and radiology programs.

Multiple sections have had significant updates and there are some new articles including: Infectious Disease – COVID-19;
Hematology – Anticoagulation Management; Allergy & Immunology – Mast Cell Disorders; Primary Care – Eye & Ear Complaints;
Consultants – OB/GYN; Logistics – Peri-Procedural Anticoagulation.

Our work would not be possible without the countless hours of work by the previous editors of the MGH Department of Medicine
Housestaff Manual. We hope we have lived up to their example:
1994 Albert Shaw & Ravi Thadhani 2009 David Dudzinski & Elizabeth Guancial
1995 Barry Kitch 2010 Roby Bhattacharya & Paul Cremer
1996 Sam Hahn 2011 Kerry Massman & Vilas Patwardhan
1998 Marc Sabatine 2012 Michelle Long & Mihir Parikh
2000 Sherri-Ann Burnett & Bill Lester 2013 Molly Paras & David Sallman
2001 Jose Florez 2014 Zaven Sargsyan & George Anesi
2003 Andrew Yee 2015 Ang Li & Jehan Alladina
2004 Ishir Bhan 2016 Nino Mihatov & Tessa Steel
2005 Aaron Baggish & Yi-Bin Chen 2017 Michael Abers & C. Charles Jain
2006 Bobby Yeh & Eugene Rhee 2018 Kelsey Lau-Min & Jonathan Salik
2007 Rajeev Malhotra 2019 Melissa Lumish & Shilpa Sharma
2008 Maha Farhat & W. Steve Sigler

And of course, none of this would be possible without the guidance and support of so many amazing people that make up the
Department of Medicine. In particular, we extend special thanks to Gabby Mills, Libby Cunningham, and Paula Prout for supporting
this project. In addition, we would like to thank our Chief Residents – Pierre Ankomah, Alyssa Castillo, Kelsey Hills-Evans, and
Aisha James – as well as Jay Vyas and Katrina Armstrong for their undying support and endless devotion to the housestaff and our
education. We will always be grateful for their unwavering leadership during the COVID-19 pandemic.

It has been an incredible honor to edit The White Book. We look forward to the contributions of future generations of authors and
editors in the years to come.

Jacqueline Henson, MD & Alexandra Wick, MD

Department of Medicine, Massachusetts General Hospital
June 2020

As with any other medical reference, this manual is NOT intended to provide specific clinical care decisions in an individual case,
and should NOT substitute for clinical judgment. Every clinical care decision must be made by the exercise of professional
judgment by the individual responsible for the care of a patient based on the facts of that individual case, which may differ from the
facts upon which entries in this manual are based. You should consult other references and your fellow residents, fellows, and
attendings whenever possible. We have carefully inspected every page, but errors may exist. If you find any errors, we would
appreciate it if you would inform next year’s editors (via this link: bit.ly/mghwhitebook) to make sure these errors are corrected.
MGH Housestaff Manual Table of Contents
CARDIOLOGY Sodium Disorders 94 Calcium Disorders 175
ACLS: Cardiac Arrest & Cooling 1 Potassium Disorders 95 Osteoporosis 176
ACLS: Bradycardia 3 Magnesium & Phosphorus Disorders 96 Thyroid Disorders 177
ACLS: Tachycardia 4 IV Fluids & Electrolyte Repletion 97 ALLERGY & IMMUNOLOGY
ACLS: Defibrillation, Cardioversion, Pacing 5 Urinalysis 98 Drug & Contrast Allergy 179
EKG Interpretation 6 The Nephron 99 Angioedema & Anaphylaxis 181
Narrow & Wide Complex Tachycardia 8 INFECTIOUS DISEASE Mast Cell Disorders 182
Atrial Fibrillation & Flutter 10 Empiric Antibiotics 100 Primary Immunodeficiency 183
QTc Prolongation 12 Gram Stain Interpretation 101 NEUROLOGY
Chest Pain 13 Multidrug Resistant Organisms 102 Altered Mental Status 184
Acute Coronary Syndrome 14 Community Acquired Pneumonia 103 Delirium 185
MI Complications 17 HAP/VAP & Aspiration Pneumonia 104 Dementia 186
Cardiac Catheterization 19 Viral Respiratory / Head & Neck Infections 105 Headache & Vertigo 187
Non-Invasive Cardiac Testing 20 COVID-19 106 Stroke & TIA 188
Echocardiography 22 Urinary Tract Infections 108 CNS Emergencies 190
Inpatient Heart Failure 23 Skin & Soft Tissue Infections 109 Seizures 191
Right Ventricular Failure 26 Osteomyelitis 110 Weakness & Neuromuscular Disorders 192
Pulmonary Artery Catheterization 27 Bacteremia & Endocarditis 111 Neuroprognostication 193
Mechanical Support & Transplant 28 Meningitis & Encephalitis 112 PSYCHIATRY
Cardiac Devices: PPM & ICD 29 C. Difficile Infection 113 Psychosis & Agitation 194
Valvular Heart Disease 30 Invasive Fungal Infections 114 Consent & Capacity 195
Pericardial Disease 32 Tuberculosis 115 Catatonia, NMS & Serotonin Syndrome 196
Aortic Disease 33 HIV/AIDS & Opportunistic Infections 116 Depression & Anxiety 197
Syncope 35 Transplant ID 117 Alcohol Use Disorder & Withdrawal 198
Hypertensive Urgency & Emergency 36 STIs & Travel Medicine 118 Opioid Use Disorder & Withdrawal 200
Peripheral Artery Disease / Cardio-Onc 37 Tick-Borne Diseases 119 Other Substance Use 201
Outpatient CV Health 38 Fever of Unknown Origin 120 PRIMARY CARE
Anti-Arrhythmic Medications 40 Rare Diseases 121 Health Screening & Maintenance 202
PULMONOLOGY & CRITICAL CARE Infectious Precautions 122 Women’s Health 204
Respiratory Distress 41 Vancomycin & Renal Antibiotic Dosing 123 LGBTQ Health 206
Hypoxemia & Hypercarbia 42 MGH Antibiogram 124 Immigrant & Refugee Health 207
Noninvasive Oxygenation/Ventilation 43 HEMATOLOGY Musculoskeletal Pain 208
Asthma 44 Anemia & Pancytopenia 125 Respiratory Complaints 210
COPD 45 Thrombocytopenia 127 Eye & Ear Complaints 211
Bronchiectasis & Hemoptysis 46 Eosinophilia 128 Nodules 212
Interstitial Lung Disease 47 Coagulation Disorders 129 CONSULTANTS
VTE 48 Anticoagulation Agents 130 Calling Consults 213
Pulmonary Hypertension 50 Anticoagulation Management 131 Perioperative Medicine 214
Mechanical Ventilation 51 Transfusion Medicine 132 Dermatology 216
ARDS 53 Transfusion Reactions 134 Surgery 219
ECMO 55 ONCOLOGY Urology 220
Sedation 56 Acute Leukemia 135 ENT 221
Shock 57 Lymphoma 137 Ophthalmology 222
Sepsis 58 Plasma Cell Disorders 138 OB/GYN 223
Vasopressors 60 MDS & MPN 139 RADIOLOGY
Toxicology 61 Stem Cell Transplantation 140 Contact Information 224
GASTROENTEROLOGY CAR T-Cell Therapy 143 Radiology Basics 225
Upper GI Bleeding 63 Solid Organ Malignancies 144 Contrast 226
Lower GI Bleeding 64 Chemotherapy & Toxicities 146 Protocols 227
GERD & Peptic Ulcer Disease 65 Immune Checkpoint Inhibitors 148 Interpretation of Common Studies 229
Nausea & Vomiting 66 Oncologic Emergencies 150 PROCEDURES
Diarrhea 67 Febrile Neutropenia 151 Ultrasound Basics 231
Constipation & Colonic Disorders 69 GERIATRICS & PALLIATIVE CARE Ultrasound-Guided Peripheral IV 233
Motility Disorders 70 Frailty & Polypharmacy 152 Central Line 234
Inflammatory Bowel Disease 71 Pain Management 153 Arterial Line 236
Intestinal Ischemia 72 Non-Pain Symptom Management 155 Intraosseous Line 237
Nutrition & Feeding 73 Adv Care Planning & Code Status 156 Paracentesis 238
Pancreatitis 74 End of Life & Pronouncement 158 Arthrocentesis 239
Liver Chemistry Tests 75 Organ Donation 159 Lumbar Puncture 240
Biliary Disease 76 RHEUMATOLOGY Thoracentesis 241
Acute Liver Injury & Failure 77 Approach to Rheumatologic Disease 160 Pericardial Drain 242
Viral Hepatitis 78 Arthritis 161 Fluid Analysis 243
Alcohol-Related Liver Disease 79 Connective Tissue Diseases 163 Tube Management 244
End Stage Liver Disease 80 Vasculitis 164 Exposures & Needle Sticks 247
Hepatorenal Syndrome 84 Miscellaneous Rheumatologic Diseases 166 LOGISTICS
Liver Transplant 85 Autoantibodies 167 Monitoring & Prophylaxis 248
NEPHROLOGY Rheumatologic Medications 168 Peri-Procedural Anticoagulation 249
Acute Kidney Injury 86 ENDOCRINOLOGY Senior On Encounters 250
Glomerular Disease 88 Outpatient Type 2 Diabetes 169 Post-Acute Care 251
Chronic Kidney Disease 89 Inpatient Diabetes Management 171 Formulas 252
Dialysis & Transplant 90 DKA/HHS 172 MGH Directory 254
Advanced Diuresis 91 Adrenal Insufficiency 173 NWH Directory 256
Acid-Base Disorders 92 Pituitary Disorders 174
TOC

Cardiology ACLS: Cardiac Arrest & Cooling

Code Tasks: Assess for responsiveness, pulse, and spontaneous respirations (C-A-B) High Quality CPR
 Access (IO), Airway No definite pulse within 10 seconds = start chest compressions (CPR)  Minimize interruptions
 Backboard  Fast: 100-120/min
 Code status  Compress 2-2.4 in deep
1. Call Code Blue (x6-3333, blue button on the wall)
 Defibrillator, Drips  Allow complete recoil
2. Call for defibrillator pads, backboard & Ambu bag for mask ventilation
 ECMO pager <10 mins  Change compressors
3. Establish monitoring: tele, defibrillator, O2 sat probe, place BP cuff
 Family (call) every 2 mins
4. In both witnessed AND unwitnessed arrest, rhythm check ± defib
 Run tele + meds  30:2 CPR:vent (mask)
as soon as pads are on (Class IIa recommendation)
 PETCO2 >10, DBP>20
2015 AHA Guidelines Update, 2018 AHA Focused Update

DEFIBRILLATOR YES NO Reversible Causes (H&Ts)

Biphasic (MGH) 120J-200J Pulse/rhythm check  Hypovolemia,
Monophasic 360J SHOCKABLE hemorrhage
 Hypoxia
- If unknown, use max setting VF or VT PEA or Asystole  H+ ion (acidosis)
- Repeat shocks at same or  Hypo/hyperkalemia
higher dose  Hypothermia
If return of spontaneous  Thrombosis, coronary
SHOCK!
circulation (ROSC), (ACS) & pulmonary (PE)
AIRWAY go to post-arrest  Tension pneumothorax
Obtain advanced airway care/cooling evaluation  Tamponade (cardiac)
Avoid excessive ventilation
 Toxins (drugs, accidents)
(10 breaths/min with
continuous CPR)
TREAT REVERSIBLE
ACCESS HIGH QUALITY CPR 2 MINUTES CAUSES (H&Ts)
Establish IV/IO access; Hyperkalemia Treatment:
consider femoral central Ca gluc 1-2g IV (or CaCl2),
Epinephrine 1mg IV/IO q3-5 mins
line if volume resuscitation Bicarb 1-2 amp IV, D50W 1-
needed 2 amp (give first) + insulin
10 units IV
LABS TO ORDER VT/VF Additional IV/IO Medications
Stat ABG with K & Hgb, PROGNOSTICATION
CBC, BMP, LFTs, lactate, In intubated pts, failure to
Amiodarone (Dose 1 = 300mg, Dose 2 = 150mg) OR achieve ETCO2 >10
T&S, coags, fibrinogen,
Lidocaine (Dose 1 = 1-1.5mg/kg, Dose 2 = 0.5-0.75mg/kg) mmHg by waveform
cardiac enzymes
capnography after 20 min
If torsades, can bolus 1-2g Magnesium CPR90% sensitive for
Medication Notes inability to get ROSC
- Epinephrine: If no IV/IO access, epinephrine can be given via endotracheal tube at 2.5x the IV dose
diluted in 10cc water or saline. **For non-shockable rhythms, epinephrine can be administered as ROSC CRITERIA
soon as available rather than waiting 3-5 minutes (Class IIb recommendation)** 1. Pulse + blood pressure
- VSE protocol: Can consider vasopressin 20U with first 5 doses of epi + hydrocortisone 200mg x1; 2. Sustained increase
class IIb evidence for in hospital cardiac arrest; not currently used at MGH ETCO2 >40
- Lidocaine: 1-1.5mg/kg IV/IO (often 100mg); may follow with 0.5-0.75mg/kg (usually 50mg) every 5- 3. Spontaneous arterial
10min x3, maximum dose of 3 mg/kg; consider infusion at 1-4mg/min pressure waves on monitor
Thrombolysis for Known or Suspected PE During Code
• Alteplase (tPA) MGH Code Roles:
- Pulseless: 50mg IV/IO bolus over 2 min, may repeat 50mg IV/IO in 15 min - Sr On: code leader
- Pulse present: 100mg infusion over 2 hours - Code Whisperer
• Reteplase: 10 units IV, may repeat 10 units in 30 min (consult SAR during
• Contraindications (absolute): prior ICH at any time, ischemic CVA or head trauma within 3mos, day, units NT at night):
known intracranial neoplasm or AVM, suspected aortic dissection or active bleeding facilitates other aspects
• Will need anticoagulation after lysis for compensatory up-regulation of pro-coagulant factors. ASA of code
325mg + UFH or LMWH. If already on heparin gtt, discontinue infusion and restart without bolus after - CCU JAR: brings I/O;
lysis (if PTT<100). If not on heparin, start with bolus. can help w/ tasks (e.g.
• Must continue cardiac arrest protocol for at least 15 min after tPA infusion to give time to work run tele, recent labs –
ECMO in Cardiac Arrest check in w/ whisperer)
• Consider if possible reversible cause to arrest and ECMO a bridge to definitive treatment (Class IIb - SDU JAR: hand on
recommendation). At MGH, recommended to contact ECMO team <10 minutes from code pulse
initiation. STAT page “ECMO Consult MGH” or use “MGH Heart” app to call ECMO consult and for - Interns: compressions
MGH ECMO guidelines (Circ 2015;132:S444; Intensive Care Med 2016;42:1922).
Brad Petek

1
TOC

Cardiology ACLS: Cardiac Arrest & Cooling

Return of Spontaneous Circulation (ROSC) / Post-Arrest Care
Pulse and blood pressure measurable or spontaneous arterial pressure waves on A-line tracing
1. Ventilation and Oxygenation: maintain SpO2 > 94%. Do not hyperventilate (can induce cerebral vasoconstriction). Start at
10-12 breaths/minute. Consider advanced airway waveform capnography. Target ETCO2 of 35-40 mm Hg.
2. Hypotension: cycle blood pressure and continuously monitor pulses. Goal MAP > 65mmHg.
− IV/IO fluid boluses as needed (LR may be > than NS at larger volumes for treatment of shock)
− Start vasopressor infusion (bolus code meds will wear off)
 Epinephrine IV infusion 0.1-0.5 mcg/kg/minute
 Norepinephrine IV infusion 0.1-0.5 mcg/kg/min
 Dopamine IV infusion 2-10 mcg/kg/min
3. Revascularization: obtain 12-lead EKGconsider emergent coronary angiography
− Hypothermia does not contraindicate PCI and is not associated with worse outcomes (Resuscitation 2010;81:398)
4. Targeted temperature management: consider if patient not able to follow commands
− If patient does not follow commands, call neurology stroke fellow for full evaluation prior to starting cooling protocol

Targeted Temperature Management after Cardiac Arrest (Circ 2015;132:2448)

Rationale: TTM decreases cerebral oxygen demand and ischemia-related inflammation
• Class I recommendation for comatose cardiac arrest patients following ROSC for in- and out-of-hospital arrest (Circ 2015;132:S465)
• Improves neurologic outcomes (NNT 6) and survival to discharge (OR 5.25) following out-of-hospital cardiac arrest from VF,
pulseless VT, or PEA/asystole of presumed cardiac cause, although the benefit may be from avoidance of hyperthermia rather
than from hypothermia (NEJM 2002;346:549; NEJM 2002;346:557; NEJM 2013;369:2197; Circ 2015;132;2146; NEJM 2019;381:2327)

Cooling Criteria
• Comatose (GCS<8, not following commands, no purposeful movements to noxious stimuli) within 6 hours of cardiac arrest
• Able to maintain a blood pressure +/- vasopressors +/- IABP following ROSC

Relative Exclusion Criteria

• Major head trauma: rule out intracranial hemorrhage with non-contrast head CT
• Recent major surgery within 14 days: hypothermia increases risk of infection and bleeding
• Bleeding diathesis/active bleeding: hypothermia can lead to coagulopathy (check PT/PTT, fibrinogen, D-dimer), though patient may
still receive thrombolytics, antiplatelets, or anticoagulants if indicated for primary cardiac condition
• Systemic infection/sepsis: hypothermia inhibits immune function
• Coma from drug intoxication or pre-existing coma prior to arrest

Abbreviated Therapeutic Hypothermia Protocol (MGH 2019 protocol)

• Preparation:
o Consult neurology Stroke/ICU consult (p20202) prior to initiation of hypothermia
o Non-contrast head CT, baseline labs including electrolytes, PT/PTT/INR, fibrinogen, D-dimer
o Access: A-line, central line +/- PA catheter, temperature probe (esophageal/bladder/rectal); access is challenging once patient is
hypothermic
• Temperature targets: reach hypothermia target of 32-34ºC ASAP  maintain at hypothermia target for 24h (starting at the time
from initiation of therapy)  rewarm at 24h @ 0.5ºC/hr to goal temp 37ºC  upon rewarming, maintain at normothermia target
(37ºC) for 24h
• Monitoring: maintain normal Na, K, pCO2 (35-45 mmHg), MAP (>70), glucose (140-180)
o If water temp <70ºF, pursue fever workup and consider starting antibiotics
o Maintain sedation and paralysis to prevent pain and shivering

• Neuro-prognostication (Lancet Neurol 2016;15:597) (also see Neurology: Neuroprognostication)

o AHA 2015 Guidelines: Recommended Markers of Poor Neurologic Outcomes (Circ 2015;132:S465)
 Exam: absence of pupillary light reflexes (>72 hrs post arrest), status myoclonus (72-120 hrs post arrest)
 Blood markers (should not be used alone, no cutoff established): high neuron specific enolase (NSE, 48-72 hrs)
 Imaging: brain MRI (extensive restriction/diffusion, 2-6 days post arrest), head CT (reduced gray-white ratio, <2 hrs post
arrest if no TTM)
 Neuro testing: bilateral N20 SSEP absence (24-72 hrs post arrest), EEG with absence of reactivity, persistent burst
suppression, or intractable status epilepticus (72 hrs post arrest)
o In-hospital mortality at 72h post-rewarming (100% if ≥2 criteria present) (Ann Neurol 2010;67:301)
1. unreactive EEG (most helpful)
2. bilaterally absent SSEP
3. early myoclonus
4. incomplete recovery of brainstem reflexes

Brad Petek
2
TOC

Cardiology ACLS: Bradycardia

Circ 2010;122:S729

Bradycardia with Pulse

DDx of Sinus Bradycardia: HR<60 bpm and symptomatic
- Med toxicity, especially in
liver/renal failure (BB, CCB,
digoxin, amiodarone) Assess patient, treat underlying causes
- Nocturnal
• Maintain airway, give supplemental O2 to
- Athletic heart
maintain SpO2 >94%
- Elderly
• IV access
- SSS
- Infiltrative diseases (sarcoid) • Monitor BP frequently
- Ischemia/ACS • 12-lead ECG and telemetry
- Vasovagal • Prepare pacing pads if needed
- ICP • Review recent medications, hospital events
- Hypothermia • Obtain labs: BMP, Mg, lactate & troponin if
- Hypoxemia concern for ischemia/ACS
- Hypothyroid
- Carotid disease, recent stent
Unstable or inadequate perfusion?
- Hypo/HyperK
• Hypotension / shock
- Endocarditis
- Chagas, Lyme • Altered mental status
• Ischemic chest discomfort
• Acute heart failure / pulmonary edema

NO If pulseless arrest develops, go to YES

PEA/Asystole ACLS algorithm

Type II second-degree AV block Place pacing pads

or
Third-degree AV block
Atropine 0.5 mg bolus, repeat q3-5min up to
NO YES max of 3g (6 doses)
- Caution if 2nd degree AVB Mobitz II (will
accelerate sinus rate, leading to worsening of
- Call Cardiology for block)
- Observe
possible temp wire - May not be effective in heart transplant (lack of
- Avoid nodal blockers
placement vagal stimulation) or complete heart block
- Use transcutaneous
pacemaker or beta- If atropine
adrenergic agents as ineffective
bridge to transvenous
pacemaker (see right side
of algorithm) Dopamine IV infusion 2-20 mcg/kg/min
OR
Epinephrine IV infusion 2-10 mcg/min
OR
Isoproterenol 2-10 mcg/min
Specific antidotes by cause: OR
- Beta blocker: glucagon 5mg IV q10 min (up to 3 doses), insulin 1U/kg Transcutaneous/transvenous pacing
bolus (FYI glucagon causes severe nausea) If transcutaneous, consider sedation with
- Calcium channel blocker: calcium gluconate 3g, insulin 1U/kg bolus versed/fentanyl or ativan/morphine
- Digoxin: Dig immune FAB 10-20 vials
AND/OR
- Opioids: naloxone 0.4-0.8 mg IV, consider gtt
- Organophosphate: atropine 2mg IV (double dose q5-30 mins), Antidotes by cause
pralidoxime 1-2g IV over 15-30 mins

Alexandra Wick
3
TOC

Cardiology ACLS: Tachycardia

Assess patient, treat underlying causes
Tachycardia with Pulse • Maintain airway, give supplemental O2 to maintain SpO2 >94%
HR>100 bpm and symptomatic • IV access
• Monitor BP frequently
Circulation 2010;122:S729 • 12-lead ECG and telemetry
• Prepare defibrillation pads if needed
If pulseless arrest develops, go to • Review recent medications, hospital events
cardiac arrest ACLS algorithm • Obtain labs: BMP, Mg, lactate & troponin if concern for
ischemia/ACS

Unstable or inadequate perfusion?

NO YES
• Hypotension / shock
• Altered mental status
• Ischemic chest discomfort Place defibrillation pads
Wide QRS? • Acute heart failure / pulmonary edema
≥120ms

NO YES

If regular narrow Cardioversion

- Vagal Ventricular tachycardia? complex, can Rhythm Dose* Mode
maneuvers give adenosine Narrow
50-100 J Sync
- Adenosine (if (see below for regular
regular) dosing). Narrow
Monomorphic Polymorphic 120-200 J Sync
- Beta blocker or irregular
calcium channel Wide
PMVT is inherently 100 J Sync
blocker regular
- Amiodarone unstable and requires Wide
immediate treatment 120-200 J Defib
irregular
because it is likely to *Biphasic (MGH)
Preserved LVEF (>40%) deteriorate to pulseless
• First line: arrest. Prepare for
o Amiodarone defibrillation.
o Procainamide
o Lidocaine Normal baseline QTc
o Adenosine (to • Treat myocardial ischemia
differentiate SVT w/ • Lidocaine
aberrancy from WCT • Amiodarone
Circ 2015;132:S444) • Procainamide
• Other:
Prolonged baseline QTc)
o Metoprolol
(Torsades de Pointes)
o Sotalol (not first line,
expert consultation • IV Magnesium
advised) • HR: dopamine, isoproterenol,
overdrive pacing
Impaired LVEF (<40%) • QTc: lidocaine
• Amiodarone • Avoid bradycardia: hold nodal
• Lidocaine agents and amiodarone

Drug Dosing
• Amiodarone: 150 mg IV over 10 min (may repeat x1); then infusion at 1 mg/min x6hrs followed by 0.5 mg/min x18h
(max 2.2 g/24 hours). May complete 10g load with up to 400mg PO TID.
• Lidocaine: 1-1.5 mg/kg IV bolus—usually 100 mg (may repeat 0.5-0.75 mg/kg q5-10min, max 3mg/kg); then
maintenance infusion at 1-4 mg/min; agent of choice when prolonged QT
• Procainamide: 20 mg/min until either VT ceases or hypotension or QRS duration prolongs by 50% from baseline or
total 17 mg/kg given (~1.2 g for 70kg person); then maintenance infusion at 1-4 mg/min (adjusted for CrCl); avoid in
prolonged QT
• Sotalol: 1-1.5 mg/kg IV over 5 min; then maintenance infusion at 10 mg/min; avoid in prolonged QT
• Adenosine: 6mg rapid IV push (followed by NS flush) 12 mg for second dose if required

Alexandra Wick
4
TOC

Cardiology ACLS: Defibrillation/Cardioversion/Pacing

External Defibrillation/Cardioversion/Transcutaneous Pacing:
• About the device: the Zoll R Series is on all code carts and ICUs at MGH. This device allows for external defibrillation, cardioversion,
and pacing with additional benefits (e.g. display ET-CO2, CPR quality feedback, and upload rhythm strips into Epic).
• Additional supplies/resources: Ambu bag, intubation equipment, RICU staff, backboard, suction
• Medications: use procedural sedation (typically 50 mcg fentanyl then 2mg midazolam) when possible and call Cardiac
Anesthesia/pharmacy early. Morphine 4mg IV then lorazepam 2mg IV are reasonable alternatives in an acute situation as they are
often readily available
Display/Operation of Zoll R Series:
• Remove all clothing covering the
patient’s chest. Dry chest if necessary.
If the patient has excessive chest hair,
shave it to ensure proper adhesion of
the electrodes
• Attach hands-free therapy electrodes in
anteroapical position (pictured) or
anteroposterior position

Pearls:
- CPR ok to perform while pacing, take R-sided pulses (L not reliable)
- Failure to capture? Increase output, ensure pads are in correct location,
Manual consider ddx (barrel chest, COPD, tamponade/pericardial effusion, acidosis,
hyperK, obesity, MI, cardiac drug tox [dig, anti-arrhythmic])
- Failure to sense? Only happens with synchronous pacing – can switch to
asynchronous pacing, reposition pads

Defibrillation Synchronized Cardioversion Transcutaneous Pacing

Indications: pulseless VT or VF Indications: Unstable SVT or VT Indications: Unstable bradycardia
FIRST turn the Selector Switch to ON. Then press Manual (bottom left soft key) to change to ALS.
1. The default energy selection is 1. Select the desired energy using the up and 1. PACER will appear as an option on the
120 J. Use Energy Select (UP) and down arrow keys on the front panel. Selector Switch. Turn to PACER.
(DOWN) arrow keys to increase the • Narrow, regular: 50-100 J (atrial flutter
2. Set the PACER RATE to a value 10-20
energy. often converts with 50 J)
bpm higher than the patient’s intrinsic heart
2. If there is a shockable rhythm on • Narrow, irregular: 120-200 J (atrial rate. If unknown or absent intrinsic rate,
the pulse/rhythm check, press fibrillation typically requires 150 J) use 100 bpm.
Charge. Continue CPR while • Wide, regular: 100 J • Observe the pacing stimulus
charging. • Wide, irregular: 150-200 J (defib dose) marker on the display and verify
2. Press the Sync On/Off button that it is well-positioned in diastole
3. Once charged, the red shock
button illuminates. Shout “Clear!” • Confirm that a Sync marker ( ) appears 3. Increase PACER OUTPUT until the
then press and hold the illuminated on the monitor above each detected R- paced beats demonstrate capture
Shock button at the top right of the wave to indicate where discharge will (“threshold”); the output mA value is
console. occur displayed on the screen.
• If necessary, use the LEAD and SIZE • Capture = widened QRS complex +
4. Resume CPR for 2 minutes buttons to establish settings that yield the
before the next pulse/rhythm check. loss of underlying intrinsic rhythm
best display
4. Set the PACER OUPUT to the lowest
3. Press the CHARGE button on the front setting that maintains consistent capture
panel. Ensure patient is “clear”. • Usually ~10% above threshold
4. Press and hold the illuminated SHOCK (typical threshold: ~40-80 mA)
button on the front panel. The defibrillator • Pressing and holding the 4:1 button
will discharge with the next detected R temporarily withholds pacing
wave. stimuli, thereby allowing you to
observe pt’s underlying EKG
5. If additional shocks are necessary, increase rhythm & morphology
the energy level as needed.
• Treat underlying cause and/or
• Confirm that a Sync marker ( ) appears pursue transvenous/permanent
above each R-wave; you may need to pacing
press Sync between shocks

Andrew Abboud

5
TOC

Cardiology EKG Interpretation

Approach all EKGs systematically. Note: rate, rhythm, QRS axis, intervals, complexes, chambers, ischemia/infarction. Compare with prior EKG.
Rate (atrial, ventricular)
• If the rhythm is regular, use the counting method (300 / #large boxes)
• If the rhythm is irregular, count R waves in rhythm strip and multiply by 6 (EKG
printout records 10 sec)
• Normal 60-100bpm; <60 = bradycardia, >100 = tachycardia
Rhythm (regular or irregular; sinus vs. non-sinus)
• Sinus rhythm = P before every QRS and QRS following every P, regular w/ rate 60-100, P wave upright in I, II, aVF, V5-V6
• P waves/morphology: determine 1) if P wave is present (best leads to visualize P wave are II and V1), 2) atrial rate (100-180: sinus tachycardia;
140-220: atrial tachycardia, AVNRT, AVRT; 260-320: atrial flutter), and 3) axis (e.g. P wave upright in II, biphasic V1)
• QRS morphology: narrow (<120 ms) = supraventricular rhythm; wide (>120 ms) = aberrant supraventricular conduction or ventricular origin
• P wave/QRS complex association: if not 1:1, determine if number of P>QRS (AV block) or P<QRS (accelerated junctional or ventricular rhythm). If P
precedes QRS, evaluate PR interval. If P after QRS, evaluate RP interval. Determine if PR or RP interval is fixed or variable.
o AVB: first degree (PR >200ms); second degree Mobitz I/Wenckebach (PR progressively longer until dropped QRS); second degree Mobitz
type II (sudden dropped QRS without PR lengthening); third degree (dissociation of P and QRS)
QRS Axis (use direction of QRS complex)
Axis Deviation Lead I Lead II Lead aVF Differential Diagnosis
Normal (-30 to +90º) ⊕ ⊕ ⊕/-
Normal variant, mechanical shifts, LVH, LBBB, LAFB,
Leftward
⊕ - - congenital heart disease, emphysema, hyperK,
(-30 to -90º)
ventricular ectopic rhythms, WPW, inferior MI
Normal variant, mechanical shifts, RVH, LPFB,
Rightward
- ⊕ ⊕ dextrocardia, ventricular ectopic rhythms, WPW,
(+90 to +180º)
lateral MI (RBBB rarely causes RAD)
Extreme/Northwest Lead transposition, ventricular ectopic rhythms,
- - -
(180 to -90º) hyperK, artificial pacing, severe RVH
• Clockwise/counterclockwise rotation (“R wave progression”): R wave amplitude typically increases from V1 to V5, with transition of R>S in amplitude
at V3 or V4. CCW: transition occurs prior to V3 due to RVH, WPW, LAFB, posterior MI. CW: transition occurs after V4 due to cardiomyopathy, LVH,
LBBB, anterior MI. Both rotations are nonspecific and can be normal. (Am Heart J 2004;148:80)
• Low voltage: average QRS amplitude <5 mm in I, II, III and <10 mm in precordial leads
o DDx: obesity, pericardial effusion, pneumothorax, COPD, restrictive or infiltrative CM (particularly amyloidosis),
severe hypothyroidism, or anasarca
Complexes and Intervals (Circ 2009;119:e241)
• P wave: right and left atrial depolarization. Normal duration <120ms
• PR interval: atrial depolarization, AV node and His-Purkinje conduction. Normally 140-200ms, changes with rate
(shortened at faster rates, longer at lower rates d/t autonomic effects on AV nodal conduction
• QRS: ventricular depolarization. Normal duration 60-110ms, not influenced by HR. QRS 100-120ms = incomplete
BBB or intraventricular conduction delay (IVCD). QRS >120ms = BBB, ventricular activation (PVC, VT, fusion beats,
WPW, paced beats), hyperK, Na channel poisoning, aberrancy, hypothermia

LAFB: left axis deviation, QRS <120, qR in I, aVL and rS in II, RBBB: QRS >120, rSR’ in V1, wide LBBB: QRS >120, wide negative QS
III, aVF. Common, nonspecific. qRS in V6, shallow broad S in I in V1, wide tall R in V6
LPFB: right axis deviation, QRS <120, rS in I, aVL and qR in
II, III, aVF. No alternate reason (RVH, emphysema, lateral MI,
PE). Rare to see in isolation, usually occurs with RBBB.
Bifascicular block: RBBB with either LAFB or LPFB

• ST segment: represents a time of electrical silence. See below.

• T wave: ventricular repolarization, with a slow upstroke and a rapid return to the isoelectric line after peaking. Usually asymmetric and in the same
direction as the QRS. Should have smooth contours (bumps in T are usually buried P waves)
• U wave: occurs in the same direction as the T wave, rate-dependent (shorter at faster rates); DDx: bradycardia, hypoK/Mg/Ca, hypothermia
• QT interval: ventricular depolarization and repolarization. Excludes U wave unless fused with T wave. Rate-dependent (shortened at faster rates).
Normal <450ms (M) and <470ms (F). Reassuring if QT is less than half R-R interval with normal HR.
Chamber Enlargement (Circ 2009;119:e251) All have low Sn and Sp
• LVH: Sokolow-Lyon criteria: S in V1 + R in V5 or V6 ≥35mm OR R in aVL ≥11mm. Cornell criteria: S in V3 + R in aVL >28mm (M) or >20mm (F).
Suggestive if R in aVL >11mm.
• RVH: R>S or R ≥7mm in V1, S ≥7mm in V5 or V6
• LAE: negative P wave in V1 >1mm wide and deep, total P wave duration >110ms
• RAE: P wave >2.5mm in II
Ischemia/Infarction (JACC 2009;53:1003)
• Analyze abnormalities along the vectors of ventricular depolarization and repolarization (QRS-ST-T)
• T wave abnormalities: hyperacute, symmetric T waves can be found within minutes, followed by T wave inversions (≥1mm in 2 contiguous leads).
TWI not abnormal if only in aVR, V1 or III.

Paula Rambarat
6
TOC

Cardiology EKG Interpretation

o TWI DDx: myocardial ischemia (symmetric), prior MI, acute PE, intracranial pathology (“cerebral T waves”, asymmetric), myocarditis,
pericarditis, BBB pattern, ventricular-paced, LVH with “strain”, normal variant, digoxin effect
o deWinter’s T waves: 2% of STEMis present with tall, symmetric T waves + >1mm STD at J point in precordial leads + 0.5-1mm STE in aVR c/w
acute LAD occlusion (NEJM 2008;359:2071)
• ST depression: suggests subendocardial injury, ≥0.5mm below the baseline (PR segment), measured at the J point in 2 contiguous leads
o Downsloping or horizontal = more ominous. STD do not localize to territories. (Circ Res 1998;82;957)
o Always look for STE to rule out reciprocal STD. STD in V1-V3 can be posterior MI (check posterior leads).
• ST elevation: suggests transmural ischemia, ≥0.1mV, except for leads V2-V3 (≥2mm in M ≥40y and ≥1.5mm in F), use PR segment (isoelectric
interval), measured at the J point.
o Differential Diagnosis (NEJM 2003;349:2128, Annals 2004;141:858, NEJM 2004;351:2195)
Diagnosis Characteristic ECG Findings
Acute STEMI STE in ≥2 continguous leads in coronary distribution (see table), reciprocal STD
LVH Concave STE in V1-V3 with STD and TWI in I, aVL, V5-V6, voltage criteria as above
LBBB Concave STE in V1-V3, discordant with negative QRS
Acute pericarditis Diffuse STE (usually <5mm), PR depression, amplitude of STE:T wave (in mm) >0.26 is specific
Printzmetal’s angina/vasospasm Transient STE in coronary distribution as in STEMI but are transient
Acute PE STE in inferior and anteroseptal leads, mimics acute MI, complete or incomplete RBBB
Stress-induced cardiomyopathy (Takotsubo’s) Diffuse STE in precordial leads w/o reciprocal inferior STD, STE followed by deep TWI
Ventricular aneurysm Persistent STE after MI, often with abnormal Q waves
Early repolarization J point elevation ≥1mm in 2 contiguous leads (esp V4), slurred/notched, reciprocal STD in aVR
Brugada syndrome rSR’ and downsloping STE in V1-V2 (see below)
Male pattern 1-3mm concave STE, often highest in V2
Normal variant STE in V3-V5, TWI, short QT, high QRS voltage
Hyperkalemia STE in V1-V2, wide QRS, tall/peaked T waves
Cardioversion Marked (often >10mm) and transient following DCCV
o Coronary Distribution
EKG Lead Territory Coronary Vessel Sgarbossa Criteria:
V1-V2 Anteroseptal Proximal-mid LAD Used to diagnose acute MI in the
V5-V6 Apical Distal LAD, Distal LCx, RCA presence of LBBB (does not apply to
I, aVL Lateral LCx (proximal) pacers). Score >3 is 90% Sp
II, III, aVF Inferior RCA (85%), LCx • Concordant STE >1mm in any
V7-V9 Posterior LCx > RCA lead = 5 points
V4R RV RCA, LCx • Discordant STE >5mm in any
aVR L main or 3vD lead = 2 points
• STD >1mm in V1-V3 = 3 points
• Q wave: usually a marker of scar, pathologic Q waves must be deep (>1mm), 25% height of QRS, and 40ms long. More likely 2/2 prior MI if inverted
T wave in same lead. Small “septal” Q physiologic in V5, V6, I, aVL.
• Wellen’s Syndrome: sign of critical proximal LM or LAD lesion, 75% MI in <2wks. Often pain free with h/o angina.
Normal/slightly elevated troponin. Symmetric, deeply inverted T waves or biphasic T waves in V2 and V3. Isoelectric or
minimally elevated (<1mm) ST segment. No precordial Q waves (Am J Emerg Med 2002;20:7).

Other
• J-Point Elevation Syndromes: J point is when QRS transitions to ST segment
o Early repolarization pattern: benign STE in absence of chest pain, terminal QRS slur, or terminal QRS notch
Suspicious features: FH of sudden cardiac arrest or early unexplained death, eval and workup suggestive of
channelopathy, h/o unheralded sycnope suggestive of arrhythmogenic pathogenesis (Circ 2016;133:1520) Wellens Type B
o Brugada Syndrome: autosomal dominant SCN5A loss of function mutation in 10-30%, M>F, more common to have
nocturnal cardiac arrest, p/w VT/VF or sudden cardiac death (Circ Arrhythm Electrophys 2012;5:606).
o Osborn wave: hypothermia T<93ºF, elevation of J point height ~ proportional to degree of hypothermia
o Epsilon wave: found in ARVC, most specific in V1 (30% with ARVC), low frequency, positive terminal deflection in
V1-V3

Brugada Syndrome: Type 1 Epsilon wave

• Electrolyte Abnormalities
Electrolyte Derangement Characteristic ECG Findings
Hypokalemia Prolonged QT, ST depression, flattened T wave, prominent U wave
Hyperkalemia Peaked, symmetric T wave, prolonged PR, flattened P and widened QRS (severe)
Hypocalcemia Prolonged QT, unchanged T wave
Hypercalcemia Shortened QT

Paula Rambarat
7
TOC

Cardiology Narrow & Wide Complex Tachycardia

Narrow Complex Tachycardia (QRS < 120 ms)
(NEJM 2012;367:1438, Mayo Clin Proc 1995;70:371)
Diagnostic approach & general principles:
1. Determine if regular or irregular rhythm
2. Assess P-wave characteristics
3. Compare to baseline ECG
4. Treatment (See ACLS: Tachycardia and Atrial Fibrillation/Flutter)
• If unstable  synchronized cardioversion
• If stable  vagal maneuvers/carotid massage/adenosine can resolve
diagnostic dilemmas and treat AVNRT and AVRT
• Acute treatment for all others is BB, CCB or amiodarone (consider risk
of pharmacologic cardioversion if pt is not anticoagulated)

Long RP Tachycardias
Short RP Tachycardias
Sinus Tachycardia
Junctional Tachycardia
• Gradual in onset
• Arises from increased automaticity in the AV junction
• Most important to determine underlying cause: hypovolemia,
• Usually short RP, can be no RP
hemorrhage, withdrawal (EtOH, BZD, opiate, BB), intoxication,
• If P waves present, must be negative in aVF
fever/infection, pain, hypoxemia, PE, anemia, tamponade,
dissection, hormonal (hyperthyroidism, adrenal insufficiency, Atrioventricular Re-entrant Tachycardia (AVRT)
pheo) • Arises from true re-entry via bypass tract
Atrial Tachycardia (AT) • Usually short RP, uncommonly long RP
• Single P morphology, non-sinus P wave axis • Ventricular activation via AV node (orthodromic, narrow
QRS) more common than accessory tract (antidromic,
• Arises from increased automaticity at single atrial focus
wide QRS)
• Classic digoxin toxicity is AT w/ variable AVB
• Rates usually 150-250
Multifocal Atrial Tachycardia (MAT)
Atrioventricular Nodal Re-entrant Tachycardia (AVNRT)
• ≥3 P wave morphologies
• Arises from functional re-entry within AV node
• Irregular d/t varying PP, PR, and RR intervals
• Short RP (when conducting fast-slow), however more
• Seen in COPD, pHTN, CAD, electrolyte disarray, theophylline
commonly no RP (when conducting slow-fast)
Atrial Flutter (AFL) • Trigger PAC (slow-fast) > PVC (fast-slow)
• Arises from true (isthmus-dependent, typical) or functional • Young adults, F>M
(isthmus-independent, atypical) re-entry in R atrium
• PP interval constant but RR may vary (variable AV block) No RP Interval
• Counterclockwise: negative flutter waves in II, III, aVF
Atrial Fibrillation (AF)
• Clockwise: positive flutter waves in II, III, aVF
• No coordinated atrial activity (P wave absent), irregular
• Signature: no isoelectric baseline, atrial rate ~300, always
• Arises from numerous re-entrant tracts in atria or
>250, usually with 1:2 conduction
pulmonary veins

AVNRT vs AVRT
• Both are regular, paroxysmal, re-entrant NCTs w/ variable RPs that
terminate w/ adenosine/vagal/AV block
• Use baseline ECG, trigger, terminal activity to help distinguish
 AVNRT: look for terminal pseudo-r’ in V1-2 (below) during
tachycardia that is absent on baseline ECG
 AVRT: look for pre-excitation on baseline ECG (short PR or delta
wave/WPW), followed by a PAC which triggers NCT (QRS often
more narrow than baseline)

AVNRT: terminal pseudo-r’ AVRT: pre-excitation (circle), PAC (arrow)

Andrew Abboud 8
TOC

Cardiology Narrow & Wide Complex Tachycardia

Wide Complex Tachycardia (QRS ≥ 120 ms)
Etiology
• Ddx: VT (90%), SVT with aberrant conduction, pacemaker-induced tachycardia
ECG Factors that Favor VT ECG Factors that Favor SVT
- Very broad QRS (>160 ms) with Aberrancy
- Superior axis (II, III, aVF neg) or northwest - Pre-existing BBB 
axis (I, aVF neg) Other important considerations:
functional/rate-dependent BBB
- AV dissociation (often V rate > A rate)  - Hyperkalemia, antiarrhythmic drugs
d/t encroachment on bundle
diagnostic of VT (digoxin, class IA or IC, amiodarone), TCA
refractory period; RBBB > LBBB
- Concordance: all QRS across precordium overdose
- QRS with sharp initial
completely positive or completely negative deflection followed by broad
- Partial (fusion beat) or complete (capture - Pacemaker/endless loop tachycardia:
terminal deflection
beat) depolarization of ventricle by underlying retrograde VA conduction of V-paced beat
- Pre-excitation on baseline
supraventricular rhythm misidentified as native A-beat  V-pacing
ECG  antidromic AVRT
- Brugada criteria (Circ 1991;83:1649) – only
applicable if rhythm is regular

Management of VT (also see ACLS: Tachycardia)

• Often no way to confidently distinguish VT or SVT with aberrancy. If there is any doubt, treat like VT.
• Underlying processes: active ischemia, CAD with scar, electrolyte derangement (low K, low Mg), indwelling lines
• Check and replete lytes (K>4, Mg>2), think about ischemia
Monomorphic VT Polymorphic VT
DDx: ischemia (acute, CAD, ICM) vs. prolonged QTc
Torsades de Pointes
DDx: ischemia, structural heart disease, idiopathic

Polymorphic VT that
1. Non-sustained VT (>3 complexes, <30 secs) 1. Evaluate for ischemia & need for
occurs with underlying
 nodal blockade (e.g. BB/CCB) revascularization
prolonged QTc (congenital
2. Stable and sustained (>30 seconds)  2. Stable  magnesium 2-4g, HR
or acquired). Can be
antiarrhythmic agent (e.g. amiodarone) (dopa, epi, iso, overdrive pacing), QTc
prompted by PVC falling
3. Unstable  synchronized cardioversion (100J) (lido), avoid bradycardia (amio, CCB/BB)
on T wave of previous beat
if pulse; defibrillation if pulseless 3. Unstable  defibrillation
(R on T phenomenon)

VT Storm: multiple sustained episodes of unstable VT within 24 hours

• Reduction of autonomic tone: intubation and sedation
• Treatment of underlying ischemia: revascularization, IABP to improve coronary perfusion, reduce cardiac afterload
• Anti-tachycardia pacing (ATP): over-drive pacing at a faster rate than VT
• Amiodarone 150 mg IV + gtt, co-administer propranolol 60mg q6h (superior to metoprolol JACC 2018;71:1897)
• VANISH trial: in patients with ischemic CM and ICD w/ persistent VT, ablation superior to escalation of antiarrhythmic drugs (lower
rate of death, VT storm and ICD shocks)

Andrew Abboud 9
TOC

Cardiology Atrial Fibrillation & Flutter

Epidemiology (Heart Rhythm 2012;9:632) Classification of Atrial Fibrillation
• RF: age, obesity, HTN, smoking, EtOH, DM, previous MI, HF, OSA Self-termination within 7 days
Paroxysmal
• Reoccurs in majority of cases due to secondary precipitant (surgery, (includes if cardioverted within 7 days)
infection, MI, thyrotoxicosis, acute alcohol, PE) Persistent Continuous afib lasting >7 days
• Often co-exists with atrial flutter (Circ Arrythmia EP 2009;2:393) Long-standing
Continuous afib lasting >12 mos
persistent
Clinical Evaluation of New-Onset AF
Term used when decision is made to
• H&P: presence and timing of sx, HTN, DM, valvular disease, CHF, Permanent stop further attempts to restore and/or
angina, congenital heart disease, OSA, FH of AF, acute precipitants maintain sinus rhythm
(e.g. EtOH, thyrotoxicosis, sympathomimetic drugs, surgery, myocardial
ischemia, myocarditis, PE, acute pulmonary disease, infection)
• ECG: absence of discernible p waves, irregularly irregular R-R intervals (if regularized, may represent escape rhythm and CHB)
• TTE: LV function, LA/RA size, valve function, pulmonary HTN, LA thrombus (better visualized with TEE
• CXR: evaluate for pulmonary parenchymal processes, pulmonary vasculature/edema
• Labs: TFTs, LFTs, BUN/Cr, CBC, NT-proBNP
• May also need longer term rhythm monitoring (Holter, Zio patch)
Acute Management of AF with Rapid Ventricular Response
Hemodynamically stable?

Stable (SBP >90) Peri-stable (SBP 80-90) Unstable (SBP<80)

1. Address underlying etiology of RVR (sepsis, If borderline BP, carefully attempt Usually with HR >150, signs of
hypovolemia, hypervolemia, etc.) low dose BB or CCB (can try shock (AMS, cool extremities),
2. Rate control agents (IV if HR >130 or sx, follow concomitant IVF if pulm edema refractory pulmonary edema or
with PO agent once rates controlled) not a concern) angina
- Beta blocker: metoprolol preferred in most cases Consider BP-sparing agents: Synchronized cardioversion:
- IV: bolus 2.5-5 mg over 2min, repeat as (weigh risk of pharmacologic typically start with 150J
required q5min for max 15 mg total cardioversion if not on AC)
If pressors are required,
- PO: fractionated, up to 400 mg total daily dose - Amiodarone: 150mg IV over 10
phenylephrine is first-line given
- Caution if severe bronchospasm and w/ rapid min, can repeat x1 if needed and
reflex bradycardia
escalation in pts w/ ADHF start gtt at 1mg/min
- Calcium channel blocker: diltiazem - Digoxin: 0.5mg IV followed by Higher HRs (>140) are more
- IV: bolus 0.25 mg/kg (average adult dose 10-25 0.25mg IV q6h x2, total load 1mg. likely to cause HoTN alone; lower
mg) over 2min, repeat as needed q10-15min Can lead to toxicity with renal HRs may cause HoTN if
- PO: fractionated, up to 360 mg total daily dose impairment, contraindicated if systolic/diastolic dysfunction or
- Reduce dose with hepatic or renal impairment accessory pathways. decreased preload (“loss of atrial
- Avoid in pts with LVEF<40% and in ADHF kick”)

Correct underlying causes or precipitants whenever possible once stable

Cardioversion (ALWAYS consider high risk of embolic stroke if any breaks in AC for one month prior)
• Indications: Urgent: ischemia, end-organ hypoperfusion, symptomatic hypotension, severe pulmonary edema; Elective: new-onset AF or
unacceptable symptoms from persistent AF
• Synchronized Electrical Cardioversion (DCCV): start with 150J (biphasic), increase energy in stepwise fashion if sinus rhythm not
achieved
o Use procedural sedation if possible (consult cardiac anesthesia). If elective, should be performed in ICU or EP lab.
o Consider anti-arrhythmic drugs as adjunct (e.g. amiodarone)
• Chemical Cardioversion: success rate significantly higher for acute (<7d) compared with longer duration AF
o Pill-in-pocket (flecainide, propafenone), dofetilide, ibulitide
o Amiodarone (IV infusion weakly effective for cardioversion, PO load over 3-4wk 27% rate of cardioversion)
• Anticoagulation (applies to BOTH chemical and electrical)
o Pre-procedure: if definitive new onset <48 hrs: may proceed without anticoagulation. If onset >48 hrs: must anticoagulate for 3 wks
prior to DCCV or obtain TEE immediately prior to DCCV (NEJM 2001;344:1411)
o Post-procedure: anticoagulate for at least 4 weeks after DCCV (due to myocardial stunning)
Long-Term Rate vs. Rhythm Control
• Overall, rate control is noninferior to rhythm control for AF symptoms, CV mortality, and stroke risk. (AFFIRM, RACE, PIAF, STAF, HOT
CAFÉ, AF-CHF).
o Consider rhythm control if persistent AF sx impairing quality of life, age <65, or comorbid HF (esp if systolic dysfxn). Restoration of
NSR may lead to increased quality of life and exercise performance (NEJM 2005;352:1861, JACC 2004;43:241).

Krishan Sharma

10
TOC

Cardiology Atrial Fibrillation & Flutter

• Rate Control
o BB more successful than CCB in achieving rate control (70% vs. 54%), either alone or in combination with digoxin
o Digoxin alone is moderately effective in controlling V-rate at rest, ineffective during exertion or high adrenergic tone
 Long-term digoxin a/w increased mortality in AF patients (JACC 2018;71:1063)
o Rate Targets: lenient rate control (resting HR <110) non-inferior to strict rate control (HR <80) with similar outcomes in CV death,
stroke, bleeding, arrhythmia and hospitalization for HF (RACE II). Stricter HR (or rhythm control) may be beneficial in younger pts or
pts w/ HF.
o Contraindications/Warnings: evidence of pre-excitation on ECG (in these patients, IV procainamide is 1st line), cautious use in high-
degree AVB. CCB should not be used in pts with LVEF <40% given negative inotropy.
• Rhythm Control (Circ 2012;125:381)
o Choice of Agents:
 No structural heart disease: “pill-in-pocket” (flecainde/propafenone), dofetilide, dronedarone, sotalol, amiodarone
 Structural heart disease: CAD: dofetilide, dronedarone, sotalol, amiodarone; HF or LVH: amio, dofetilide
o “Pill-in-Pocket”: for pts with recent pAF and infrequent and well-tolerated episodes, ppx may have risk>benefit. PRN flecainide or
propafenone at sx onset is safe and effective (NEJM 2004;351:2384).
o Catheter ablation (pulmonary vein isolation [PVI]):  long-term AF recurrence rate vs. antiarrhythmic agents in both pAF (MANTRA-
PAF, RAAFT-2) and persistent AF (EHJ 2014;35:501). Ablation in pts with HF  morbidity/mortality CASTLE-AF
o AV nodal ablation with PPM: indicated when pharm rate/rhythm control not achievable (JACC 2014;64:2246)
Antithrombotic Therapy (Stroke 2010;41:2731)
• Treatment recommended for all pts except those with CHA2DS2-VASc 0, lone AF episode, or contraindications to therapy (AHA/ACC/HRS
Guidelines: Circ 2019;140:e125)
• LA appendage is the source of at least 90% of thrombi in pts with CVA and AF.
• Subclinical AF still associated with increased stroke/systemic embolism (ASSERT)
• Patients at relatively low risk for thromboembolism may be maintained on ASA alone (see below), but no reliable data exist to guide
decision between 81mg vs 325mg dose
Risk Assessment
• CHA2DS2-VASc: 1pt for CHF, HTN, Age 65-74, DM, female Sex, Vascular disease; 2pt for Age≥75, Stroke/TIA. CHA2DS2-VASc >
CHADS2 in “truly low risk” subjects (Thromb Haemostasis 2012;107:1172).
o Score 0 = no AC or ASA; Score 1 = no AC vs. ASA vs. oral AC based on clinical judgment  how high is risk from specified risk
factor? (e.g. HTN, DM, age bring greater risk compared to female sex, vascular dz); Score ≥2 = oral AC
CHA2DS2-VASc Score 0 1 2 3 4 5 6 7 8 9
Adjusted stroke rate (%/yr) 0 1.3 2.2 3.2 4 6.7 9.8 9.6 6.7 15.2
• HAS-BLED: risk stratification of bleeding risk w/ oral AC. HTN (SBP>160); abnml renal function (CrCl<50); liver disease (cirrhosis or Bili 2x
ULN or AST/ALT/AlkPhos 3x ULN); stroke; bleeding history; labile INR (<60% in Rx range); elderly (>65y); antiplatelet meds (ASA,
NSAID); alcohol (>8 drinks/wk) or other drug use. Score ≥3 suggests caution and regular follow-up.
• http://www.sparctool.com/ can aid in risk assessment and choice of anticoagulation
Choice of Antithrombotic Agent (AHA/ACC/HRS Guidelines: Circ 2019;140:e125)
• DOACs vs warfarin: DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) are recommended over warfarin in all pts (except with mod-
severe mitral stenosis or mechanical heart valve). DOACs have  risk of stroke, mortality, and ICH but higher risk of GI bleeding compared
to warfarin (Lancet 2014;383:955).
• Dosing: see section in Hematology for dosing. Dose-reduce apixaban to 2.5mg BID if Cr ≥1.5 AND age ≥ 80 OR weight ≤60kg
• Renal impairment: for pts w/ CrCl<15 or on dialysis, can use either warfarin or apixaban
• Bridging AC: see Hematology: Anticoagulation Management.
• LAA closure (Watchman device): In non-valvular AF, device placementcomparable stroke prevention to warfarin with bleeding risk
and improved mortality (JACC 2017;70:2964)
Atrial Flutter (less prevalent but often coexists or precedes AF)
• ECG: “Sawtooth” P waves (F waves), atrial rate typically 300bpm w/ 2:1 conduction (~VR 150), though can
be variable block, 3:1, or 4:1. 1:1 conduction can briefly precede VT/VF.
o Type 1 (typical): reentrant loop in RA via cavo-tricuspid isthmus
 Counterclockwise: more common, inverted flutter waves in II, III, aVF + upright flutter waves in V1
 Clockwise (less common, upright flutter waves in II, III, aVF + inverted flutter waves in V1)
o Type 2 (atypical): does not meet criteria for Type 1; is typically faster and often refractory to ablation
• Anticoagulation: risk of thromboembolism lower than AF (J Stroke Cerebrovasc 2018;27:839) but
management is similar to AF (Chest 2012;141:e531S)
• Rate control: similar strategies (BB,CCB) to AF, but more difficult to successfully rate-control
• Rhythm control: cavo-tricuspid isthmus (CTI) ablation for typical flutter > 90% effective at 1yr (Circ Arrhythmia EP 2009;2:393)

Krishan Sharma

11
TOC

Cardiology QTc Prolongation

Definition
• QT interval correlates with repolarization time of ventricles
• Prolonged QTc >450ms (M) or >470ms (F)
• Measure from beginning of QRS to end of T wave in a lead with T wave >
2mm (best in II, V5), define end point using tangent from peak of steepest
slope to isoelectric line
• QTc is QT corrected for HR
o Bazett = QT/√RR; overcorrects at high HR and undercorrects at low HR
o Fridericia = QT/3√RR; more accurate at high or low HR (Am J Cardiol
1993 26;72:17B)
o Hodges = QT + 0.00175 * (60/RR – 60)

Assessment of QT with Underlying BBB (Heart Rhythm 2014;11:2273)

• Bundle branch blocks lengthen QT interval. Can obtain rough estimate using QT – (QRS-120)
o JT Interval = JT(HR + 100)/518, with a JTI ≥ 112 identifying repolarization prolongation in all ventricular conduction defects
o Modified QT = QTb – (0.485 x QRSb), where QTb = measured QT and QRSb = measured QRS

Congenital Long-QT Syndromes

• Majority of pts are asymptomatic and syndrome often discovered d/t findings on ECG
• Sx include presyncope/syncope, hemodynamic compromise, sudden cardiac death. Triggered by exercise, stress
• Tx: beta blockers, ICD if previous cardiac arrest and expected survival >1yr (Circ 2006;114:e385)

Drug-Induced Prolonged QT Interval (Heart 2003;89:1363)

• Drugs inhibit IKr causing prolonged ventricular repolarization and exaggerate heterogeneity in repolarization times in different layers of
myocardium leading to reentry and tachyarrhythmia
Danger of prolonged QT = increased risk of Torsades de Pointes which can degenerate into VF
Longer QT increases risk for “R on T” phenomenon and development of torsades (higher risk if PVCs)

Risk factors for TdP in Hospitalized Patients QT-Prolonging Drugs

Class of Drug
(Circ 2010;121:1047) (NEJM 2004;350:1013, Br J Clin Pharm 2010;70:16)
Elderly, female, congenital - Class IA: quinidine, disopyramide, procainamide
Demographics
LQTS - Class III: sotalol, dofetilide, ibutilide, amiodarone
Antiarrhythmics
Renal failure, hepatic (rarely a/w TdP due to uniform delay in repolarization
dysfunction (or drug-drug across myocardium)
Comorbidities
interactions impairing liver - Macrolides (clarithromycin, erythromycin, azithro)
metabolism), HF, MI - Fluoroquinolones (moxifloxacin > levo, cipro)
Antimicrobials
QTc > 500ms, bradycardia - Anti-fungals (fluconazole, voriconazole)
Rhythm-related (sinus, AV block, ectopy - Anti-malarials (quinine, chloroquine)
causing pauses), PVCs - Haloperidol, thioridazine, chlorpromazine,
Hypomagnesemia, ziprasidone, quetiapine, risperidone increase QTc 15-
Electrolytes Antipsychotics 30 ms at usual doses and have risk of TdP
hypokalemia, hypocalcemia
QT-prolonging drugs (esp. - Olanzapine, aripiprazole carry less risk of QTc
Medication- IV infusions, use of >1 prolongation and TdP
related concurrently), diuretic use, Antidepressants TCAs > SSRIs (citalopram, escitalopram, fluoxetine)
beta blocker use
Anti-emetics Droperidol, ondansetron, metoclopramide (lower risk)
Others Methadone, propofol, hydroxyzine, donepezil
Monitoring for QT/QTc Prolongation
• Check QTc before and 12 hours after initiation/increased dose of QT-prolonging drug. Continue monitoring if prolongation is seen.
• Class I indications for QTc monitoring with ECG (Circ 2004;110:2721)
o Initiation of QT-prolonging medication and dose changes Q8-12H
o Overdose of proarrhythmic drug
o New bradyarrhythmia
o Severe hypokalemia or hypomagnesemia

Management of Acquired LQTS

• Stop offending drug if QTc >500ms or increase in QTc of >60ms
• ECG should be checked for bradyarrhythmias and signs of impending TdP (R on T). Stop drugs causing bradycardia.
• Check electrolytes checked and replete (K >4, Mg >2.4). Supratherapeutic repletion of K to 4.5-5.0 can be used in pts on QT-
prolonging drugs who have had TdP

Mubeen Shakir
12
TOC

Cardiology Chest Pain

HISTORY PHYSICAL EXAM
CVD risk: Use Framingham or ASCVD Risk Likelihood Ratios for ACS
Estimator. Women, elderly, and diabetics may (JAMA 2015;314:1955) • New S4, MR (ischemia)
have atypical presentations. Age, h/o CAD, Low Risk • CHF (rales, +S3, JVP, pedal
and male sex most predictive of ACS (NEJM Pleuritic (0.3) Syncope (0.5) edema)
2000;342:1187). Intermediate Risk • Carotid, subclavian, and abdominal
Radiation to left Diaphoresis bruit (indicates vascular disease)
Angina (NEJM 1979:300:1350): arm, neck, or (1.4); exertional
Stable • Bilateral femoral and radial pulses
(1) substernal chest pain jaw (1.3-1.5) (1.5)
Angina/ACS (document pre-cath)
(2) brought on by stress/exertion Pressure / Pattern change
(3) relieved by rest or TNG typical (1.9) /24h (2.0)
• Frank’s sign: bilateral diagonal
3/3 = typical, 2/3 = atypical, 1/3 = noncardiac High Risk earlobe crease (slight  in likelihood
Similar to prior Pain radiating to of CAD)
Antianginals: nitrates - 1st SL, then IV; ischemia (2.2) both arms (2.6) • Less likely ACS: pleuritic, positional,
avoid if preload sens. (HoTN, AS); BB (avoid Abnormal prior reproducible by palpation (LR 0.28)
in ADHF, long PR, 2˚/3˚ AV block); CCB. PAD (2.7)
stress test (3.1)
Abrupt onset of tearing/sharp thoracic or abdominal pain BP variation >20 mmHg between arms,
Acute Aortic
RF: known aneurysm, Marfan syndrome, HTN, M:F 2:1, 60-80yrs, cocaine use, high- pulse deficits, new diastolic murmur, focal
Syndromes
intensity exertion (weightlifting) neurologic changes
Acute Pleuritic, sharp, improves upon leaning forward. Friction rub (breath hold to distinguish
Pericarditis May have URI prodrome, though consider bacterial pericarditis if high fevers from pleural rub); tamponade (pulsus >10)
Sudden onset, dyspnea/hypoxemia, pleuritic Tachycardia, tachypnea, hypoxemia,
PE
RF: hx of cancer/recent surgery/immobility, hemoptysis, calf/thigh pain/swelling calf/thigh erythema, swelling, tenderness
Sudden onset dyspnea; RF: 20-40yrs (more likely if tall), FH or personal history, Ipsilateral absence of breath sounds,
Pneumothorax
smoker, known emphysema, M > F, recent chest procedures/lines contralateral deviation of trachea
Pneumonia/ Sharp, pleuritic CP associated with fever/leukocytosis, productive cough, recent
Bronchial breath sounds, rales, dullness
Pneumonitis radiation, autoimmune (SLE, RA, drug-induced lupus, collagen vascular diseases)
Cardiac: HOCM, AS, vasospasm (Prinzmetal’s angina, drug/toxin), Takotsubo CM; MSK: costochondritis, Zoster; GI: GERD,
Other
esophageal spasm (may be relieved by TNG), Boerhaave’s, PUD, biliary colic, pancreatitis; Psych: panic attack
Basic Chest Pain Algorithm

ECG: Compare w/ prior ECGs & check q10-15m if Non-diagnostic

suspicious, but <50% sens for dx of acute MI. Check CXR
posterior (if STD in V1-3 or R>S in V1-2) or R-sided
leads (if STE in II/III/AVF) to better evaluate LCx/RCA

PTX PNA
Pericarditis NSTEMI STEMI Signs of PE
Diffuse upsloping 0.5mm STD or New ≥1mm STE in RAD, new RBBB,
STE and PR TWI (consider any 2 consecutive TWI V1-4, Widened
depression, PR leads compared to S1Q3T3 Normal
posterior infarct) mediastinum
elevation in AVR prior ECG or new suggestive of RV
LBBB strain (Sp, not Sn)

+/- hs-troponins
Consider PE, Consider non- Consider
valvulopathy, or cardiopulmonary Aortic
ACS Pathway myopathy etiology Dissection

Non-Invasive Tests Angiography Echo CT

(For patients w/ resolved chest pain)
- Emergently for STEMI - Useful for assessing valvular CT-PE if c/f PE
Stress test: used to r/o ACS if pt - Early for high risk disease, RV strain (in PE), and - NPV 60%/89%/96% for
low-intermediate risk NSTEMI EF high/intermediate/low risk PE
Coronary CTA: 100% NPV in pt - All pts with confirmed - TEE first test if evaluating (PIOPED II)
w/o CAD. No Δ in LOS or ED d/c ACS should undergo prosthetic MV, suspected
rate vs hs-Tn (JACC 2016;67:16) CTA chest if c/f aortic dissection
angiography. Use GRACE, proximal aortic dissection (can
- Sn 97-100%, Sp 83-100% for
TIMI, HEART and Mayo eval aortic root and valvular
aortic dissection (NEJM
Clinic CPC score for risk function)
1993;328:35)
stratification.

Daniel Amponsah
13
TOC

Cardiology Acute Coronary Syndrome

Myocardial infarction: myocardial necrosis (trop >99th percentile + ∆) w/ ischemia (4th universal def. of MI: JACC 2018;72:2231)
• Type 1 MI: spontaneous plaque rupture, ulceration, fissure, erosion, dissectionintraluminal thrombus
• Type 2 MI: supply-demand mismatch – supply may be compromised by dynamic obstruction (e.g. vasospasm), microvascular
ischemia (e.g. Takotsubo), non-plaque thromboembolism (e.g. infectious, via PFO), coronary dissection, vasculitis, vascular steal
o Must have a clear precipitating factor. If not, treat as a type 1 MI until further evaluation
o 50-70% have obstructive CAD – reasonable to initiate ASA, BB, and high-intensity statin
Myocardial injury: defined as any patient with an increased troponin without evidence of myocardial ischemia (sx of ischemia, new
ischemic ECG changes, new wall-motion abnormalities, and/or acute coronary thrombus on angio). NOT the same as T2MI.

Evaluation of CP with hsTnT

Emergency Department – CP onset ≥ 3h PTA Inpatient or Emergency – CP onset < 3h
Check hsTNT immediately and at 1h Check hsTNT immediately and at 3h
Rule in: hsTnT ≥ 52 OR ∆ ≥ 5 from baseline Rule in: hsTnT ≥ 10 (F) or ≥ 15 (M) AND ∆ ≥ 7 from baseline AND sx
 consider ACS or ECG changes or concerning imaging (CCTA, cath)
Rule out: hsTNT <10(F) or < 12(M) AND ∆ <3 from baseline  unlikely ACS  consider ACS
Intermediate: calculate HEART score, repeat hsTnT in 3h and apply inpatient Rule out: no significant ∆ in 3h
criteria (right)  unlikely ACS
STEMI NSTEMI Unstable Angina
1mm STE in two contiguous leads (if V2-V3: >2.5mm in M<40, ⊕ ECG or hx, ⊕ ECG or hx,
2mm in M>40, 1.5mm in F) OR New LBBB AND (+) biomarkers ⊕ biomarkers ⊝ biomarkers

Clinical Evaluation & Risk Stratification:

• Consider pt’s baseline CAD risk. Review prior stress test and
cath data. Increased risk of MI w/ resp infxn (esp flu) (NEJM
2018;378:345)
• Treat secondary causes of myocardial demand
ECG: (NEJM 2003;348:993)
• Obtain serial tracings (q15-30min) if initial ECG non-diagnostic
in pts with compelling hx & sx
• Non-STE ischemic EKG changes: ≥0.5mm STD (horizontal,
downsloping), new TWI ≥1mm or normalization
(“pseudonormalization”) of prior TWI in s/o sx
Cardiac Biomarkers:
• hsTnT 99th percentile among normal subjects: M 15ng/L, F
10ng/L
• 75% of healthy individuals will have measurable hsTnT

Risk Stratification for PCI Timing in NSTEMI/UA:

• Multiple risk models: GRACE, TIMI, PURSUIT, AMIS. Grace score is based on predictors of 6mo mortality (age, HR, SBP, Cr, cardiac
arrest at admission, ST deviation, elevated trop) (BMJ 2006;333:1091)
• Four subgroups for urgency to revascularization (JACC 2014;64:e139)
1. Very high risk (“immediate invasive,” within 2 hrs): refractory/recurrent angina, hemodynamic or electrical instability
2. High risk (“early invasive,” within 24 hrs): temporal change in troponin, EKG changes (STD, TWI), high risk pt (GRACE>140)
a. Conflicting results between TIMAC (NEJM 2009;360:2165) and VERDICT (Circ 2018;138:2741) trials about outcome benefit
of early cath. However both show improved outcomes with early cath in patients with GRACE >140.
3. Intermediate risk (“delayed invasive,” within 72 hrs): none of above but risk factors at baseline (e.g. EF <40%, GFR <60)
4. Low risk (“ischemia guided,” no cath): no risk factors, GRACE <109, TIMI 0-1
Revascularization:
• PCI Indications: recommended over fibrinolysis at a PCI-capable center (1A)
o STEMI: PCI if <12h sx onset, goal to PCI ideally <60min at PCI centers. PCI regardless of time from onset for cardiogenic shock,
malignant arrhythmia, persistent STE and/or CP. Late PCI (>48h post-event) generally not indicated in stable pts (NEJM
2006;355:2395)
o NSTEMI/UA: see Risk Stratification above
• PCI Strategies:
o In pts with STEMI and no cardiogenic shock, complete revascularization strategy (culprit + non-culprit) has a  risk of CV death
and MI at 3yrs (COMPLETE NEJM 2019;381:1411)
o In pts with cardiogenic shock, culprit-lesion only PCI has a  risk of death/RRT (CULPRIT-SHOCK NEJM 2018;379:1699)
o Access: radial > fem | Stent: DES > BMS (NEJM 2016;375:1242)

Daniel Amponsah and Shauna Newton

14
TOC

Cardiology Acute Coronary Syndrome

• CABG: preferred for 3VD (SYNTAX NEJM 2009;360:961, NEJM 2008;358:331), left main disease (Lancet 2016;388:2743, NEJM
2016;375:2223), 2VD with prox LAD stenosis or EF <50%, large area of viable myocardium or high risk. Consider if DM + 2VD
(FREEDOM NEJM 2012;367:2375)
Adjuncts to Revascularization
1. ASA: established mortality benefit, give to all pts in an immediate load/maintenance strategy (325mg/81mg) (Lancet 1988;2:8607)
2. P2Y12 Inhibitors: (pre-cath load not done at MGH, controversial if beneficial and may delay CABG by 5-7 days)
o Ticagrelor:  mortality compared to clopidogrel w/o increasing major bleeding. Reversible with platelet transfusion. Side effect:
mild dyspnea on initiation. Avoid in liver disease, prior CVA, oral AC (PLATO NEJM 2009;361:1045)
o Prasugrel:  death, MI, CVA compared to ticag (NEJM 2019;381:1524). Contraindicated if prior TIA/CVA, wt <60kg, or >75yr
o Clopidogrel:  death, repeat MI when load/maintenance with PCI (Lancet 2001;358:527I). Prodrug, metabolized by CYP219, less
effective in those with LOF allele (NEJM 2009;360:354)
o Cangrelor: IV reversible inhibitor with immediate onset and return of platelet function in 1h. Used in pts with recent PCI who are
unable to take PO or are periprocedure.
3. Nitrates: TNG SL x3, transition to gtt if refractory CP. Nitropaste and gtt have shorter half-life than SL if c/f HoTN. No mortality benefit.
Caution in inferior MI/RVMI, SBP<100, or PDEi use in last 48h. If CP despite  dose of TNG, indication for earlier cath.
4. Anticoagulation:
o UFH: usually stopped after 48h if ECG changes improving and concern for ongoing ischemia resolved (BMJ 1996;313:652). Start
gtt w/ bolus and use low intensity PTT goal (63-83). No bolus if giving lytics or if on warfarin and INR<2.
o LMWH: possible reduction in death w/ minimal evidence for  major bleeding, trials vs UFH largely null (BMJ 2012;344:e553)
o Fondaparinux: preferred to UFH/LMWH if medically managed. Contraindicated in PCI 2/2  catheter thrombosis/complications
(JAMA 2006;295:1519)
o IIb/IIa Inhibitors: eptifibatide (Integrilin) used at MGH. Initiated in cath lab if PCI high-risk (extensive thrombus).
o Bivalirudin: direct thrombin inhibitor, preferred for patients w/ HIT, otherwise cost does not outweigh benefit
5. Beta Blockers: start within 24h (1b), mortality benefit. Consider early initiation if ischemic arrhythmias present.
o Caution in decompensated HF,  risk for cardiogenic shock (>70yr, SBP<120, HR>110 or <60)
o Contraindications: cocaine-induced MI, PR>240ms, 2nd or 3rd degree AVB, severe bronchospasm (Lancet 2005;366:1622)
6. ACEi or ARB: start within 24h if BP/renal function normal
o Mortality benefit maximal if EF<40%, pulm edema, or anterior MI (Lancet 1995;345:669)
7. Statin: atorvastatin 80mg daily regardless of baseline LDL (NEJM 2004;350:1495)
o Early high-dose statin within 24-96h may reduce death/adverse cardiac events if given pre-PCI (JACC 2009;54:2157, JAMA
2018;319:1331). Early inflammatory effect may stabilize plaque (JAMA 2001;285:1711, JAMA 2004;291:1071).
8. Morphine: consider only if unacceptable level of pain refractory to TNG, careful if suspicious for inferior MI/RVMI
9. Discontinue NSAIDs:  risk of mortality, re-infarction, CHF, and myocardial rupture after ACS
Secondary Prevention:
1. Aspirin: 81mg w/o enteric coating indefinitely (NEJM 2010;363:930)
2. Dual antiplatelet therapy (DAPT): recommend 6-12mo DAPT after DES (Circ 2016;134:e123). New evidence trending towards
shorter DAPT duration (JAMA 2019;321:2428, JAMA 2019;321:2414). Based on individual pt risks. Use DAPT score to help risk
stratify.
3. Beta blockers: start in all pts (1b) w/o contraindication indefinitely
4. ACEi or ARB: start in all pts (2b) but stronger recommendation (1a) in anterior STEMI, EF<40%, stable CKD, HTN, or DM
5. Statin: high intensity statin (atorvastatin 40-80mg or rosuvastatin 20-40mg QD) indefinitely for pts ≤75y, moderate intensity in >75y.
o If very high risk clinical ASCVD w/ LDL>70 mg/dL, add ezetimibe and consider PCSK9i (JACC 2019;73:3168)
6. Triple therapy: P2Y12 inhibitor + DOAC > triple therapy in pts with AF + PCI.  bleeding and non-inferior for ischemic events
(AUGUSTUS NEJM 2019;380;1509, RE-DUAL PCI NEJM 2017;377:1513, NEJM 2016; 375:2423). See Hematology: Anticoagulation
Management for more details.
7. Lifestyle: smoking cessation, BP <130/80 (start treatment if >140/90), cardiac rehab (1c), depression screening (1b)

Daniel Amponsah and Shauna Newton

15
TOC

Cardiology Acute Coronary Syndrome

MGH P2Y12 Switching Guidelines (does not apply to triple therapy patients)
Acute Setting – within 30 days of index event

Agent switching TO/STARTING

Clopidogrel1 Ticagrelor Prasugrel Cangrelor2,3
180 mg when decision is 60 mg when decision is
Start 0.75 mcg/kg/min
made to switch (no delay made to switch (no delay
Clopidogrel 48 hours after
Agent switching FROM/STOPPING

time needed), then 90 time needed), then 10 mg

discontinuation
mg BID daily

600 mg 24 hours after 60 mg 24 hours after last Start 0.75 mcg/kg/min

Ticagrelor last dose of ticagrelor, dose of ticagrelor, then 10 48 hours after
then 75 mg daily mg daily discontinuation

600 mg 24 hours after 180 mg 24 hours after Start 0.75 mcg/kg/min

Prasugrel last dose of prasugrel, last dose of prasugrel, 96 hours after
then 75 mg daily then 90 mg BID discontinuation
180 mg dose 0 to 120 60 mg dose 0 to 30
600 mg at time of drip
minutes before drip minutes before drip
Cangrelor discontinuation, then 75
discontinuation, then 90 discontinuation, then 10
mg daily
mg BID mg daily
1If a patient has active bleeding or is very high-risk for bleeding, consider clopidogrel half load (300 mg) or maintenance dose (75 mg), in lieu of full

600mg loading dose.

2If there is concern for lack of absorption of initial LOADING DOSE of oral P2Y12i at time of cangrelor initiation and patient is not at high bleeding

risk, could bolus with 30 mcg/kg before starting infusion

3Dose of cangrelor recommended here is for bridging. This is different than the dose used in the catheterization lab.

Chronic/Maintenance Setting – >30 days after index event

Agent switching TO/STARTING

Clopidogrel Ticagrelor Prasugrel Cangrelor
Start 0.75 mcg/kg/min
90 mg BID 24 hours after 10 mg daily 24 hours after
Clopidogrel 48 hours after
Agent switching FROM/STOPPING

last dose of clopidogrel last dose of clopidogrel

discontinuation

600 mg 24 hours after 60 mg 24 hours after last Start 0.75 mcg/kg/min

Ticagrelor last dose of ticagrelor4, dose of ticagrelor, then 10 48 hours after
then 75 mg daily mg daily discontinuation

75 mg daily 24 hours Start 0.75 mcg/kg/min

90 mg BID 24 hours after
Prasugrel after last dose of 96 hours after
last dose of ticagrelor
prasugrel4 discontinuation

600 mg at time of drip 180 mg at the time of 60 mg at time of drip

Cangrelor discontinuation, then 75 drip discontinuation, then discontinuation, then 10
mg daily 90 mg BID mg daily
4If switch is for high risk of bleeding/active bleeding, could consider starting clopidogrel 75 mg 24 hours after last dose of ticagrelor or prasugrel.

*Consider concomitant PPI therapy if patient on triple therapy or high-risk for GI bleeding
5Initiate at a dose of 0.75 mcg/kg/min (NO
Peri-operative P2Y12 Bridging
bolus) for a minimum of 48 hours and a
maximum of 7 days
6 600 mg loading dose of clopidogrel as soon

as oral administration is possible and when

surgical bleeding risk is acceptable; use of
prasugrel or ticagrelor is discouraged. If a
patient is at very high-risk for bleeding,
consider clopidogrel half load (300 mg) or
maintenance dose (75 mg), in lieu of the full
600mg loading dose.
7ONLY resume cangrelor if oral administration

is NOT possible (patient NPO or not

absorbing oral medications)

Daniel Amponsah and Shauna Newton

16
TOC

Cardiology MI Complications
Mechanical Complications (JACC 2013;61:e78)

Complication Prevalence / Risk Factors Timing / Clinical Signs Evaluation Treatment

Early Complications (Hours – Days)
 STEMI ~6%  STEMI: 50% develop shock w/in
 Inotropes/pressors
 NSTEMI ~3% 6h of MI, 75% w/in 24 h
 Emergent PCI, CABG
Cardiogenic  Anterior MI, LBBB, prior MI,  NSTEMI: 72-96 h after MI  TTE
(<75y + STEMI + shock
Shock 3VD, age, HTN, DM,  New onset CP, cold/wet  PA catheter
w/in 36h of MI). (NEJM
(see Inpatient HF) mechanical complications physiology, HoTN, tachycardia,
1999;341:625)
 Accounts for 50% post-MI dyspnea, JVD, rales (66%), new
 IABP and other MCS
death murmur
 0.5% in modern era  40% w/in 24h, 85% w/in 1 week
Myocardial Free
 Transmural MI, 1-vessel MI,  Tamponade in 85%
Wall Rupture
1st MI (poor collaterals),  Olivia’s triad: pericarditis,
(Pseudoaneurysm:
anterior and lateral MI, HTN, repetitive emesis,  TTE
LV defect contained
late thrombolysis (>14 h), restlessness/agitation (PPV 95%  STAT cardiac  Emergent surgery
by only pericardium/
fibrinolysis>>PCI, NSAIDs, w/ 2/3). (JACC 1993;22:720) surgery consult
scar, more prone to
female, >70 y  Electromechanical dissociation,
rupture than
 Accounts for 10% post-MI aberrant T wave evolution, abrupt
aneurysm)
death episodes of HR/BP
 0.2-3%
 Emergency surgery
 1st MI, 1-vessel MI (esp. LAD),  Bimodal: 24 h and 3-5 days (can  TTE w/ doppler
 IABP
Interventricular anterior infarct w/ inferior STE occur up to 2 weeks out)  RHC: O2 sat
 Vasodilators (use
Septal Rupture 2/2 wrap-around LAD, older  New, harsh holosystolic murmur step-up between
cautiously) to decrease L
VSD age, female (50% w/ thrill), S3, loud P2, RA and PA >5
to R shunt (nitroprusside
 Accounts for 5% post-MI hypotension, BiV failure (R>L) suggestive
preferred)
death
 No reperfusion: 2-7 d
 TTE
 1%  With reperfusion: median 13 h
 CXR: edema
 Posteromedial (supplied by  Abrupt dyspnea, pulmonary
(can be  Aggressive afterload
Papillary Muscle PDA, a/w inf. or post. MI) >> edema, hypotension
asymmetric to reduction (nitroprusside)
Rupture anterolateral (dual blood  Hyperdynamic LV, holosystolic
RUL if MR jet  IABP
Acute MR supply by LAD and LCx) murmur at apex (radiates to LSB
directed at right  Emergent surgery
 Accounts for 5% post-MI w/ posterior pap muscle rupture)
pulm. veins)
death possible thrill; NB: murmur may
 Large v wave
be absent in severe HF
Late Complications (Weeks – Months)
 Acute: management of
 Days to weeks
CHF, ACEi, avoid
 Acute: diffuse, displaced PMI, S3
LV Aneurysm  No reperfusion: 10-30%  ECG w/ NSAIDs/steroids, heparin
and/or S4, MR murmur, CHF
(can be acute or  Apical transmural > posterior- persistent STE (if EF<35%)
 Chronic: HF, VT/VF, systemic
chronic) basal MIs, steroids, NSAIDs  TTE  Chronic: ACEi, digoxin,
embolization, may be
diuretics, warfarin (if
asymptomatic
EF<35%)
 Occurs in 15% of AMI pts post-  Can occur within 24h
 Warfarin (INR 2-3)
PCI  90% of thrombi are formed at a
 When to stop anticoag
 Usually in LV apex maximum of 2 weeks  TTE with
LV Thrombus unclear, check for
 Large infarct size, severe  Embolization risk persists for contrast
resolution of thrombus on
apical akinesis or dyskinesis, chronic LV thrombus for 6 mo,
TTE at 3-6 mos.
LV aneurysm, anterior MI occurs in 3%, but most at <4 mo.
 5% of pts in the ED w/ CP and  ECG
no MI, male predominance  10% at 2-4d post-transmural MI  TTE  ASA + colchicine
 85-90% idiopathic (viral/post  May be focal or diffuse  CMR and/or  Avoid NSAIDs and
Pericarditis
viral), infectious, post-MI,  Dressler’s syndrome: late cardiac CT (If steroids for fear of
uremic, autoimmune, autoimmune carditis, rare needed to mechanical complications
malignancy, XRT, meds confirm dx
 ECG  PCI
 Highest risk is absence of
Coronary Artery  Most cases occur within 30 days  Biomarkers  Long term anti-platelet
P2Y12 inhibitor
In-Stent of PCI irrespective of stent type (troponin/ therapy (adherence to
 1% at 1 year. Yearly rate
Thrombosis  ACS symptomatology CKMB) therapy)
following one year is ~0.2/ yr

Urgent Assessment of Post-MI Complication (page cardiology)

• Assess VS for hemodynamic instability and perform a focused physical exam (eval for new murmur, pericardial friction rub, elevated JVP)
• Stat labs (troponin, PT/INR, PTT, T&S, BMP, lactate) and ensure adequate vascular access (≥2 PIVs)
• Run telemetry, repeat EKG, urgent echocardiography, consider STAT CTA if concern for RP bleed/aortic dissection

Daniel Amponsah and Shauna Newton

17
TOC

Cardiology MI Complications
Electrical Complications
• Overview
o Bradyarrhythmia/conduction block: may be due to coronary artery occlusion (see below) or Bezold-Jarisch reflex (Anes 2003;98:1250)
o Tachyarrhythmia: related to creation of re-entrant circuit from scar formation and/or  automaticity from adrenergic surge

Arrhythmia Location/Mechanism Incidence/Timing Treatment/Outcome

Sinus  Anterior or inferior MI  Up to 40% of acute MI  Atropine, atrial pacing if sx/unstable,
bradycardia  Protective by  O2 demand  Occurs early in STEMI dopamine if also hypotensive
 Inferior:  vagal tone or AV node
 If 2/2 inferior MI, transient (vagal)
First degree AV ischemia (RCA)  narrow QRS
 More common in inferior MI  Usually continue CCB or BB unless PR
block  Anterior: septal necrosis below AV
interval is longer than 240ms.
node  RBBB, wide QRS
Bradyarrhythmia

Second degree
 Usually inferoposterior MI ( vagal  Usually transient; observe
AV block:  Usually within first 24h of MI
tone  narrow QRS)  Atropine if symptoms or HR < 45
Mobitz Type I
Second degree  Usually anterior MI with infranodal  Consider temporary pacing
AV block: conduction injury, wide QRS, HR  Usually within first 24h of MI  In infranodal block, atropine may
Mobitz Type II often < 30, 33% progress to CHB paradoxically worsen AV block
 3-7% acute MI
 If inferior MI: intra-nodal lesion;  Recovery 3-7 days; temp pacing required
 Inferior: gradual, stable, more
Third degree AV narrower QRS escape  Inferior: more benign, resolves on own
common
block  If anterior MI: infra-nodal lesion;  Anterior: carries high mortality rate (80%)
 Anterior: sudden, 12-24h
wide, unstable escape rhythm b/c indicates extensive necrosis
after MI
 50% already present on 1st ECG,  Pts w/ BBB are more likely to have
Intraventricular may represent antecedent disease comorbid conditions, less likely to have
 2-5% of MI
Conduction Blocks of conduction syndrome received therapies, have larger area
 Suggests more extensive infarct infarcts, and have high mortality
 Undesirable b/c decreases coronary
 Persistent sinus tach. may be
Sinus perfusion time, increases O2 demand,
Supraventricular

compensatory for LV dysfunction,  25% of acute MI

tachycardia and may worsen ischemia
Arrhythmias

common in anterior MI
 Treat underlying cause
Atrial premature
 May reflect  LA pressure
beats
 Early: due to atrial ischemia  6-8%, may be >30% of acute  Associated with mortality, particularly if
Atrial fibrillation
 Late: due to atrial stretch/HF MI late (>30d) AF (Circ 2011;123:2094)
Premature  Correct electrolyte deficits. Do NOT treat
 Due to electrical instability and
Ventricular  Variable with class I anti-arrhythmic  a/w 
increased sympathetic tone
Contractions mortality (NEJM 1991;324:781)
Accelerated  50-110bpm, higher V- vs. A-rate; in  Up to 20% of STEMI  Do not treat unless symptomatic or
Ventricular Tachyarrhythmias

Idioventricular 40%, considered a reperfusion  Usually within 12-48 h, hemodynamically unstable, usually short
Rhythm (AIVR) rhythm occurs after reperfusion duration and does not affect prognosis
 NSVT 1-7%, sustained VT
 Monomorphic VT<170bpm is  Antiarrhythmic agents
(2-3% of STEMI, <1%
unusual early after STEMI;  Cardioversion/defibrillation as ppx
Ventricular NSTEMI)
suggests pre-existing against VF and restore hemodynamic
Tachycardia  Usually 48h post STEMI, late
arrhythmogenic scar (mono VT) vs instability
VT (>48h) has very poor
recurrent ischemia (poly VT)  Correct underlying abnormalities (pH, K)
prognosis
 Risk factors:  age, prior MI (scar),
 ACLS/defibrillation
anterior MI, cardiogenic shock, 
Ventricular  5% of STEMI  Anti-arrhythmic infusion (24-48h
LVEF, CKD
Fibrillation  1% of NSTEMI amiodarone post-defibrillation)
 VF >48h post-MI may indicate LV
 Maintain K>4, Mg>2
dysfunction

Circuit Coronary Vessel Supply

Sinus Node RCA in 60% of pts, LCx in 40% of pts
AV Node Distal RCA in 90% of pts, distal LCx in 10% of pts
Bundle of His AV nodal artery (RCA), LAD septal perforators
RBB LAD septal perforators, collaterals from RCA/LCx
LAD
LBB
LAD septal perforators, 50% w/ AV nodal collaterals
LAFB
Prox AV nodal arteries, distally dual supply from
LPFB
LAD/PDA septal perforators

Daniel Amponsah and Shauna Newton

18
TOC

Cardiology Cardiac Catherization

Anatomy
• LCA and RCA w/ their branches create two rings around the heart: RCA + LCX in AV plane; LAD + PDA in IV plane (see above)
• 80% of PDA arises from RCA (right dominant), thus inferior MI more likely due to RCA lesion
Preparation for Catheterization
• NPOpMN; INR<2; monitor Cr closely, no ppx abx. Continue ASA, statin, BB, heparin gtt (hold when on call) or lovenox (hold 24h prior
to cath; see Logistics: Peri-Procedural AC). Hold metformin (usually 1d pre-, 2d post-proc.). May need to hold/delay starting ACEi.
• Document bilateral radial, femoral, popliteal, DP pulses, and Allen’s test prior to cath. Check for bruit. Note hx of HIT, PVD, Ao
aneurysm/dissection.
• Contrast allergy: pre-treatment with steroids and benadryl if patient has documented allergy. See Radiology section for MGH 13h
protocol. Consult allergy service for expedited protocol if the cath is required emergently.
• Respiratory distress: patient will need to lie flat; consider intubation if prohibitive hypoxemia/pulmonary edema
• Pre-hydration w/ crystalloids and NAC/bicarb have not been shown to prevent CIN in most patients with moderate CKD (Lancet
2017;389:1312; NEJM 2018;378:603); CIN risk calculator; diagnostic cath = 25cc contrast (CT-PE = 80-100cc)
Percutaneous Coronary Intervention Considerations
• Access: fewer bleeding/vascular complications if radial (vs. femoral), possible death in ACS (JACC 2018;71:1167)
• BMS vs DES:  in-stent thrombosis with DES  subsequent  revascularization; however,  risk of late stent re-stenosis 
requires longer duration of DAPT
• Contraindications to stents: predicted DAPT non-adherence, anticipated major surgery within treatment time, elevated bleeding risk
• Antiplatelet Tx: 81 mg ASA indefinitely (Circ 2016;134:e123). P2Y12 inhibitor added after cath.
o No high bleeding risk: for ACS, 12 mos of DAPT (DES or BMS); for stable ischemic heart disease, at least 6 mos of DAPT (DES)
or 1 mo (BMS)
o High bleeding risk: for ACS, 6 mos of DAPT (DES or BMS); for stable ischemic heart disease, at least 3 mos of DAPT (DES) or 1
mo (BMS)
o Triple therapy: See ACS section
Post-Procedure Care
• Groin access: 4-6 hrs bedrest after procedure. Closure devices decrease time needed for bedrest.
o Groin checks immediately post- and 6h, 8h post-procedure: check bilateral pulses, palpate for pulsatile masses, auscultate
for bruits
o Sheaths: during pass-off, ask interventional fellow about timing of arterial removal; only cardiology fellows remove sheaths
 Radial access: TR band x 4-6h
Post-Catherization Complications
• Access site complications: always inform the interventional fellow who performed the procedure, diagnose by exam and U/S
o Hematoma: mass w/out bruit. Apply compression. If unable to control, may require Fem-Stop device to apply external pressure.
o Pseudoaneurysm: presents as pulsatile mass with bruit at access site. Treat with compression; if <2 cm, may require thrombin
injection or surgery if >2 cm. Urgent U/S and vascular surgery consult.
o AV fistula: presents as continuous bruit with no mass. Evaluate w/ U/S. Surgical repair is usually necessary.
o Limb ischemia: from thrombus, dissection, or malpositioned closure device. Evaluate pulses, limb warmth, and PVRs.
o Retroperitoneal bleed: presents within hours post-cath, often with hemodynamic instability +/- flank pain +/- ecchymoses.
STAT CT A/P if stable. Transfuse, IV fluids, discussion with attending re: stopping/reversing anticoagulation.
• Other complications:
o Infection: more common in setting of vascular closure devices
o Atheroembolism: eosinophilia; livedo reticularis; blue toes; mesenteric ischemia; acute, subacute, or chronic renal dysfunction
o CIN: peak  Cr 2-5d post contrast load, risk correlated with contrast load and initial GFR
o Tamponade: post-cath hypotension from coronary or cardiac perforation. Check pulsus paradoxus (Δ >10mmHg), STAT TTE,
alert cath fellow. Give IVF.
o MI/CVA: due to in-stent thrombosis (MI) or distal embolization post-cath (CVA). Discuss all CP/neuro changes with cath fellow
o Radiation injury: more common in CTO cases. Occurs days to weeks after PCI. Ranges from erythema to skin ulceration.

Daniel Amponsah and Shauna Newton

19
TOC

Cardiology Non-Invasive Cardiac Testing

STRESS TESTING
• Indications:
o Diagnose CAD: sx of stable angina in pts with intermediate-high risk of CAD. Not indicated for low risk or asymptomatic pts
o Evaluate new or changing sx concerning ischemia in pts with known CAD
o Post-revascularization: evaluate pts with angina or asymptomatic pt if incomplete revasc or >2yrs post-PCI/5yrs post-CABG
o Pre-op risk assessment: not routinely indicated (see Perioperative Medicine)
o Newly diagnosed HF or cardiomyopathy likely due to ischemia, functional capacity (for exercise prescription), viability testing,
valvular disorders
• Contraindications: untreated ACS, MI within 2d, high risk or LM CAD, uncontrolled arrhythmia, acute CHF, severe AS or HOCM,
recent DVT/PE, acute myo-/peri-/endocarditis, aortic dissection, uncontrolled HTN
• Preparation: NPO 3h prior, longer if imaging or adenosine. Must reverse DNR/DNI for test.
o If the question is “Does the patient have CAD?”  hold BB and Stress Modality Imaging Modality
nitrates Exercise (treadmill) EKG, TTE, SPECT
o If the question is “How well are meds working in known CAD?”  Vasodilator (adenosine,
continue BB and nitrates regadenoson) TTE, SPECT, PET, MRI
o Hold caffeine >12h for adenosine. Hold BB >24h for dobutamine. Inotropy (dobutamine)
• Caveats:
o Majority of vulnerable plaques are angiographically insignificant (<70% stenosis)  stress testing unable to identify the presence
of these plaques (CTA more sensitive)
o Angiographically significant (>70% stenosis) 3VD may produce false-negative vasodilator stress test  ”balanced ischemia”
• Positive test results: optimize medical tx. Decision re: angiography/revascularization varies by pt (degree of sx, known stenosis,
current meds). In recent ISCHEMIA trial, revascularization did not decrease ischemic CV events for pts with stable CAD (NEJM
2020;382:1395)
Schematic Approach to Noninvasive Cardiac Testing (adapted from UpToDate)

Shauna Newton

20
TOC

Cardiology Non-Invasive Cardiac Testing

Exercise Tolerance Test (ETT)  ECG or imaging (TTE, SPECT)
• ETT preferred over pharmacologic testing if pt is able to reach goal exertion
• Assesses exercise duration, METs, BP/HR response, HR recovery, double product (HR x SBP), Duke Treadmill Score
• Duke Treadmill Score = estimates risk of CAD in pts w/ chest pain undergoing exercise stress testing (Circ 1998;98:1622)
o Exercise time (min. based on Bruce protocol) – (5x max ST deviation in mm) – (4x exercise angina [0 = none, 1 = non-limiting, 2 =
exercise-limiting]). Low risk: score ≥ +5; Moderate risk: score from -10 to +4; High risk: score ≤ -11
• Protocols: Bruce (large changes in workload between stages), modified Bruce (for less fit pts  adds stages of lower workload)
• Diagnostic if >85% max-predict HR (220-age), peak double product (HRxBP) >20k, HR recovery (HRpeak – HR1min post-exercise) >12
• Increased probability of ischemia:  # of leads with STD,  degree of max STD,  METs when EKG changes occur, ventricular
ectopy during recovery, increased time to recovery of EKG, failure of SBP to rise with exercise
Pharmacologic Stress Test  imaging only (TTE, SPECT, PET, MRI)
1. Choosing an agent:
o Adenosine/Regadenoson: detects ischemia by coronary steal (vasodilation via cAMP). Stenosed coronary arteries are unable
to further dilate to adenosine  limited flow reserve to distal areas and relative perfusion deficit
 Side effects: wheezing, bradycardia, HoTN. Caution if ACTIVE bronchospasm, high grade AVB, SSS, severe AS
 Regadenoson: decreased respiratory/conduction side effects, more cost-effective in obese pts. Caution if seizure hx
(reversal agent aminophylline  seizure risk)
 False negative can occur in 3VD because no relative perfusion deficit exists when all 3 vessels affected equally (“balanced
ischemia”)
o Dobutamine: workload induced by positive inotropy and chronotrophy via β-1 receptor agonism
 Extremly high dose of dobutamine is given, dose titrated up to 40 mcg/kg/min
 Side effects: tachyarrhythmias. Caution if MI<48h, hx of malignant arrhythmia, severe AS, HOCM, severe HTN, severe
PAH, aortic dissection
2. Choosing an imaging modality:
o TTE: preferred if primary objective is to exclude CAD (76% Sn / 88% Sp). Can give info regarding hemodynamics/valve
disorders.
 Do not use in pts with LBBB, V-pacing or extensive wall motion abnormalities at rest.
o Nuclear imaging: utilizes a radioactive tracer to detect areas of  perfusion between rest and stress states. More expensive
than TTE and high amount of radiation (SPECT > PET).
 PET is more sensitive and specific than SPECT with faster image acquisition. Less widely available and most expensive.

VIABILITY TESTING
• Indication: determine viability of ischemic myocardial tissue (“hibernating myocardium”)
• Imaging modalities: SPECT (thallium or sestamibi), PET, TTE, MRI
o SPECT is performed using exercise or pharmacologic stress. PET/TTE/MI performed using pharmacologic stress only.

REST IMAGING
Coronary CTA: used to evaluate for presence and extent of CAD (JACC 2010;55:2663)
• Requires cardiac gating (goal HR 60-70, may need to give BB) and respiratory gating (breath hold for 5+ sec)
• Indications:
o Should NOT be used to screen asymptomatic pts
o Low risk pts: has high NPV (99%) for CAD rule-out (JACC 2008;52:1724)
o Moderate risk pts: reasonable for further risk stratification in pts at intermediate risk of CAD or pts with equivocal stress test
results
• Findings: 2 yr ACS risk significantly elevated if high-risk plaque (16%) and/or stenotic disease (6%) (JACC 2015;28:337)
o Higher sensitivity and specificity for coronary stenosis compared to cMRI (Annals 2010;152:167)
• Less useful in pts with extensive calcifications or stented vessels due to “blooming” artifact (can’t evaluate patency)
Cardiac MRI:
• Modality of choice for assessment of funtional and tissue properties of the heart than cannot be adequately assessed with
echocardiography or CCTA (inflammation, infiltration, cardiac tumors, pericardial disease)
• Preferred for post-CABG vessel imaging, evaluation of suspected or known congenital or acquired coronary abnormalities

Shauna Newton

21
TOC

Cardiology Echocardiography
View/Description Position View
Patient: lying on left side, with left arm under head.
PARASTERNAL LONG AXIS Probe: 2-3 inches left of sternum at 3rd-4th intercostal
• LV size, function, wall thickness space, probe indicator at 10 o’clock (facing R shoulder).
(septum/posterior wall)
• MV/AoV function/flow (w/
Doppler)
• LVOT diameter, aortic root size

Patient: same as above.

Probe: from long axis view, turn probe clockwise until
indicator at 2 o’clock (facing L shoulder).
PARASTERNAL SHORT AXIS
• Cross-sectional views of the
heart from base to apex, at level
of AoV, MV and mid-
ventricle/papillary muscles

Patient: lying flat on back.

APICAL 4 CHAMBER
Probe: at PMI w/ probe indicator at 3 o’clock (to the pt’s
• RV/LV size, function, thrombus L side). For 5-chamber view, tilt head of probe upward.
• TV/MV function/flow (w/
Doppler)
• Septal size/motion
• Pericardial effusion
• In 5-chamber view, can see
AoV and proximal ascending
aorta
Patient: lying flat on back, consider slightly elevating
head or bending legs.
SUBCOSTAL VIEW Probe: below xyphoid process
• IVC diameter and respiratory
variation gives estimate of
volume status and RA pressure
• Pericardial effusion

Reviewing the MGH Report: for questions or clarification of findings, call Echo Lab (x6-8871) or page on-call Echo Fellow
• Valvulopathy: look for stenosis/regurgitation (valve area, gradients, severity), leaflet numbers/motion, vegetations
• Structure/chamber dimensions:
AoSinus = aortic sinus ASC AO = ascending aorta
LVIDd = LV internal diameter in diastole (range 37-52 mm) LVIDs = LV internal diameter at end-systole (range 22-35 mm)
PWT = posterior wall thickness ( thickness seen in LVH, IVS = intraventricular septum (if  along with  PWT, consider diastolic
diastolic dysfxn) dysfunction; if isolated  consider HOCM)
• EF: “preserved” EF ≥50%, “borderline” EF 40-50%, “reduced” EF <40%
• WMA: territory correlates w/ coronary vessels (anterior + septal = LAD, inferior = RCA, lateral = LCx). If global WMA, r/o diffuse ischemia vs non-
ischemic insult (sepsis, stress)
• RVSP: RVSP=4v2 + RAP. RAP assumed to be 10 mmHg (often not clinically accurate) and v = TR jet velocity.
o Clinically, often used as surrogate marker for pHTN (present if >35; not gold standard for dx and requires euvolemia)
Clinical Questions and Associated TTE Findings:
• Right heart strain in acute PE: RV WMA or hypokinesis, RV dilation (RV:LV ratio >1), interventricular septal bowing, IVC collapse
o McConnell’s sign: RV free wall akinesia w/ normal RV apex motion (77% Sn / 94% Sp for acute PE)
o D sign: septal flattening due to overloaded RV bowing into LV (ventricular interdependence)
• Tamponade: large effusion, swinging heart, R-sided chamber collapse, interventricular septal bowing, dilated IVC (no  w/ inspiration)
• ACS/mechanical complications of ACS: regional WMA, septal/free wall rupture, acute MR, LV thrombus
• Stress (Takotsubo) cardiomyopathy: LV apical ballooning and akinesis/hypokinesis
• Heart failure: depressed EF, RV/LV hypertrophy and/or dilation, regional WMA
• Constrictive pericarditis: thickened or hyperechoic pericardium, abnormal septal motion, respiratory variation in ventricular size, dilated IVC
Indications for STAT Echocardiography:
• Evaluation of hemodynamic instability of suspected cardiac etiology (assess for biventricular dysfunction, acute valvular dysfunction, tamponade)
• Evaluation of early MI complication (myocardial free wall, septal, or papillary muscle rupture)
• Evaluation of acute chest pain with suspected MI in patients with non-diagnostic lab markers and ECG
• Identify the cause of cardiac arrest (i.e. PE with RV dysfunction, ACS with WMAs or EF decrement, tamponade)

Shauna Newton
22
TOC

Cardiology Inpatient Heart Failure

Definitions: HFrEF: EF<40% ; HFmrEF (“mid-range” EF 41-49%); HFpEF (EF>50%)
Etiologies
• Dilated: ischemic (most common cause, 50-75%), HTN/LVH, valvular
(e.g. MR), myocarditis, stress-induced (Takotsubo), tachyarrhythmia,
infiltrative (as below) CTD, ARVC, LVNC, HIV,
cocaine/methamphetamines, EtOH, chemotherapy, nutritional
deficiency, cirrhosis, sepsis, peripartum, idiopathic/genetic
• Restrictive: infiltrative (amyloid, hemochromotosis, sarcoid), Löffler’s,
radiation, metabolic storage disease, carcinoid
• High-output HF: anemia, thyroid dysfxn, liver failure, Paget’s, systemic
infection, AV shunts
Initial Workup: New Heart Failure Diagnosis
• Echo: TTE for all new presentations; obtain thereafter only if concern for
clinical/functional change. TEE can provide better visualization of MV
and AV
• Dx: Ischemic: EKG, TnT, stress test, coronary angiogram vs CCTA; Non-ischemic: CBC, BMP, LFTs, lipid panel, TSH, A1c, urine
hCG, iron studies, HIV, SPEP w/ UFLC
1. Consider: ANA, T. cruzi serologies, viral panel, antimyosin Ab, tox screen, thiamine, genetic testing, cardiac MRI,
endomyocardial bx (if serologic testing neg, new onset <6 mo unexplained HF, major arrhythmias) to r/o myocarditis, ARVC,
sarcoid, cardiac masses
Specific Causes of Cardiomyopathy
• Hypertrophic Cardiomyopathy (HCM) (Circ 2011;124:2761)
o LV and/or RV hypertrophy of various morphologies ± LVOT dynamic obstruction (HOCM), diastolic dysfxn, ischemia, MR
o Exam: SEM at LLSB/apex that augments with Valsalva or on standing (due to  preload); S2 paradox split, S4
o Dx: EKG (prominent voltages w/ depolarization abnormalities, large abnormal Q waves in inferior/lateral leads, LAD, giant
negative T waves in V2-V4 (apical HCM variant“Yamaguchi’s syndrome”), TTE (unexplained LVH >15mm, SAM of MV,
outflow tract gradient), cMR (late gadolinium enhancement [LGE] = fibrosis)
o Tx: avoid volume depletion or high dose vasodilators (may worsen obstruction). Phenylephrine is pressor of choice if no
response to IVF bolus for HoTN ( afterload, stents open LVOT). Activity restriction, meds (BB > verapamil), septal ablation or
surgical myectomy for medically refractory sx, ICD (for high SCD risk)
o Clinical genetic testing (mutation in ~70%) helpful for family screening; not useful for dx or risk stratification
o Risk factors for SCD/VT: prior VT/SCD/unexplained syncope; FHx of SCD in 1° relative; massive LVH (>30mm); NSVT on
Holter; abnormal BP response to exercise; burden of LGE on cMR
• Stress-induced (Takotsubo) (JACC 2018;72:1955)
o Potential mechanisms: catecholamine surge from physical/emotional stress, coronary artery spasm, microvascular ACS
o May present like ACS with CP (most common), SOB, shock, syncope. If in shock, urgent TTE to assess for LVOT obstruction.
o Diagnostic criteria (ALL needed): (1) transient dysfunction (hypo-/dys-/akinesis) of LV mid-segments. Regional WMA extend
beyond a single coronary distribution; (2) rule out ACS/obstructive coronary disease (via cath); (3) new EKG ∆ (STE or TWI)
OR  troponin; (4) absence of pheo or myocarditis
o Tx: Remove stressor. ACEi (may improve survival), BB, diuretic.
o Prognosis: most recover LV function in 1-4 wks
• Alcohol-induced
o Associated with >80g/day of EtOH over >5 years (toxic to myocytes via O2 free radicals + defects in protein synthesis)
o Tx: abstinence + HF therapy
o Prognosis: better/equivalent to idiopathic CM if able to abstain/consume <20g/day, worse w/ continued EtOH abuse
• Restrictive Cardiomyopathy (JACC 2010;55:1769) – conditions below may also manifest as DCM
o Tx: Treat underlying disease and HF as below. For amyloidosis: tafamidis ( TTR deposition) (NEJM 2018;379:1007)
Condition Presentation EKG Echo cMRI
- Decreased voltage, - Symmetric LV/RV  wall
Amyloidosis - HF with other findings of amyloid
pseudoinfarct pattern in thickness, speckled - LGE in subendocardium
(AL, TTR) (renal, neurologic, hepatic disease)
inferolateral leads myocardium
- If hereditary: M>30 yo; F> 40 yo
- SVT (ventricular
- If 2°: any age - Dilated LV with global - Iron overload with T2
Hemochomotosis conduction abnormalities
- Abnl LFTs, arthralgias, DM, systolic dysfunction protocol
are rare)
hyperpigmented skin
- Variable wall thickness,
- Young adult w/ HF - Infrahisian block, atypical - Patchy enhancement of
Sarcoidosis focal/global hypokinesis,
(more commonly presents as DCM) infarction pattern basal and LV walls
LV aneurysm

Evan Whitehead

23
TOC

Cardiology Inpatient Heart Failure

Inpatient Acute Decompensated Heart Failure (ADHF)
• Admission orders: tele, Na (2g) restricted diet, daily weights, strict I/Os, DVT ppx
• Avoid: CCB (esp. non-dihydropyridines), NSAIDs, flecainide
• Check NT-proBNP (and weight) on admission and at discharge.
o ADHF unlikely if NT-proBNP < 300 (NPV 98%), likely if >450 (>900 if age >50) (Am J Cardiol 2005;95:948)
o Difficult to interpret in CKD/dialysis. May be falsely low in obesity, HFpEF.
• Screen for and treat iron deficiency in all HF pts independent of Hgb (JACC HF 2019;7:36)
1. Dx: ferritin <100 or ferritin <300 + TSat <20% (JACC 2017;70:776); though some evidence that TSat ≤ 19.8% or serum iron ≤
13µmol/L most predictive & ferritin may be less useful (Circ Heart Fail 2018;11:e004519)
2. Tx: replete with IV iron (JACC 2018;71:782) to sx, functional capacity, QOL (FAIR-HF NEJM 2009;361:2436); PO ineffective in HF
(JAMA 2017;317:1958)
ADHF Management – Floor/SDU
1. Identify hemodynamic profile, & triage accord. (JACC 2019;74:1966)
• Warm vs. Cold: adequate vs. inadequate tissue perfusion
(AMS, lactate, cool extremities, narrow PP)
• Dry vs. Wet: presence vs. absence of congestion (JVD, rales,
pleural effusions, ascites, LE edema, interstitial/alveolar
edema on CXR)
• Evaluate for signs of pulmonary congestion on exam. Pulm
edema may be absent on CXR in chronic HF due to lymphatic compensation (Chest 2004;125:669)
• ~80% of decomp HFrEF and nearly all decomp HFpEF pts will be warm and wet
2. Identify precipitants: dietary/med non-compliance (~40%), new ischemia/infarction, uncontrolled HTN, arrhythmia, inadequate
diuretic dose, meds (NSAIDs, steroids, CCB, TZDs, anthracyclines), acute infection (URI, PNA, UTI), AKI, PE, toxins (EtOH,
cocaine), new/worsening valve disease, myocarditis
3. Early/Acute Management:
• Diuresis: CVP, PCWP to optimize Starling curve mechanics & relieve sx (NEJM 2017;377:1964; JACC 2020;75:1178)
o Initial tx: IV loop diuretics (furosemide, bumetanide, torsemide), start with 2x home dose (IV/PO). No difference between
continuous gtt vs bolus dosing (DOSE NEJM 2011;364:797). See Advanced Diuresis for conversions.
o Refractory diuresis: metolazone 2.5-5mg (or chlorothiazide 500mg IV) administered 30min before loop diuretic. May need
RHC to clarify hemodynamics or inotropes to augment diuresis. May need RRT in the setting of cardiorenal syndrome
(NEJM 2012;367:2296).
o Worsening renal function: occurs in ~23% of pts treated for ADHF. Mild-mod “Cr bumps” are likely benign hemodynamic
changes, should not necessarily preclude further diuresis of pt still congested (Circ 2018;137:2016).
o Endpoints: target resolution of symptoms (SOB) and signs of congestion (JVD). Daily weights and hemoconcentration are
useful adjuncts.
• If acute pulmonary edema, NIPPV may improve mortality and need for intubation (Annals 2010;152:590).
• Vasodilators: arterial/venous dilation can relieve symptoms by  afterload,  PCWP and  SV. Can acclerate early sx relief.
Consider esp. in severe HTN, acute MR, acute AR.
o Floor: isosorbide dinitrate, hydralazine, nitropaste, captopril; SDU/CCU: TNG, nitroprusside
• Guideline-Directed Medical Therapy (GDMT): if not in cardiogenic shock, continue ACEi/ARB and βB during ADHF (but do
not newly initiate βB) (B-Convinced EHJ 2009;30:2186)
4. Pre-Discharge Optimization: document d/c weight and NT-proBNP, appt in HF Transitions Clinic if pt has MGH cardiologist
• HFrEF (EF<40%) GDMT
o Beta blockers (1A): initiate, uptitrate evidence-based βB (carvedilol, metoprolol succ., bisoprolol) (COPERNICUS, MERIT-
HF). Caution if recently weaned from inotropes.
o RAAS inhibitors (1A): if renal fxn stable, initiate/titrate ACEi/ARB (CONSENSUS, CHARM) or ARNI (sacubitril/valsartan)
(PARADIGM-HF, PIONEER-HF). Switch to ARNI from ACEi/ARB if tolerating and NYHA II-III, needs 36hr washout period.
♦ Guidance for GDMT in advanced CKD: JACC HF 2019;7:371
o Mineralocorticoid receptor antagonist (1A): initiate spironolactone or eplerenone if CrCl>30 (EMPHASIS-HF, RALES).
Watch for rebound hyperK after de-escalation of diuretics (check K, Cr within 72h of discharge)
o Hydralazine/isosorbide dinitrate: consider if contraindication to ACEi/ARB (unstable renal fxn) or in African Americans w/
persistent NYHA III-IV sx despite BB and ACE/ARB (A-HeFT)
o SGLT2i (dapaglifozin): if DM2 and NYHA II-IV already on standard GDMT (DAPA-HF)
• Diuretic plan: determine maintenance diuretic dose and provide specific instructions for taking additional rescue doses.
Observe on maintenance dose and decide if needs K replacement
• HFmrEF (EF 40-49%): treat with diuretics and consider adding GDMT agents for HFrEF (Curr Heart Fail Rep 2020;17:1)
• HFpEF (EF >50%): prevent volume overload, treat with diuretics, treat comorbidities (DM, HTN, AF)
o Consider spironolactone if normal renal fxn/K, improv. in CV death/admits in N/S Am. sites in TOPCAT (Circ 2015;131:34)
o No proven benefit to BB (EHJ 2018;39:26), ACEi (PEP-CHF), ARNi (PARAGON-HF), ARB (CHARM-Preserved, I-PRESERVE)
• ICD indicated if: ischemic CMP w/ EF ≤30 or ≤35% w/ NYHA II-III; CRT if: EF ≤35% & prolonged QRS ± LBBB & some w/ EF
≤50% (see Cardiac Devices: PPM/ICD and guidelines for specifics: JACC 2013;61:e6; EHJ 2016;37:2129)
Evan Whitehead

24
TOC

Cardiology Inpatient Heart Failure

2019 SCAI Classification Pyramid (Cath Cardio Interv 2019;94:29)
Cardiogenic Shock – CCU:
• Definition: HoTN (SBP<90 for 30 mins or pressor req) +
hypoperfusion (cold extremities, oliguria, lactate) +
hemodynamics (CI <2.2, PCWP >15, EHJ 2019;40:2671)
• Etiology: acute MI ± mechanical complications, end-stage heart
failure, acute myocarditis, acute MR/AR, myocardial contusion
• Evaluation: EKG, troponin to r/o acute MI. TTE to exclude
tamponade/mechanical lesions/contraindications to MCS
• Monitoring: A-line, consider PA catheter for inotropes/pressors
and MvO2 monitoring
Immediate Management:
• If c/f acute MI, activate cath lab for immediate revascularization
(only intervention proven to definitely improve outcomes in cardiogenic shock) (NEJM 1999;341:625)
• Consider early SHOCK consult (p11511). Escalating inotropes/pressors exacerbate myocardial supply/demand imbalance and are
associated with poor outcomes. Emerging evidence supports early initiation of MCS (Cath Cardio Interv 2019;93:1173)
• Stabilize MAP with norepinephrine PRN prior to obtaining PA catheter to guide tailored therapy

Tailored Therapy: uses invasive hemodynamic monitoring (i.e. PAC) to guide medical therapy
• Goals: tissue perfusion ( CO, MAP), decongestion ( CVP, PCWP), ventricular unloading (minimize myocardial O2 demand)
1. Preload: LVEDV ∝ LVEDP ≈ PCWP; goal PCWP 14-18, PAD 16-20, CVP 8-12
o Diuresis, UF with RRT, or TNG
2. Afterload: wall stress ∝ MAP (Laplace’s law); SVR = (MAP - CVP)/CO; goal MAP >60, SVR <800-1200
o Vasodilators: captopril, hydralazine, nitroprusside, TNG, IABP
o Vasopressors:  afterload but sometimes necessary to stabilize MAP in mixed shock or to counteract vasodilatory effect
of inodilators
3. Contractility: ∝ CO for given preload/afterload; goal CO>4, CI >2.0-2.2, MvO2 >65
o Dobutamine (inodilator): β1>β2 agonist ( production of cAMP)
• Watch for tachycardia, increased ventricular response to AF, arrhythmias, ischemia, HoTN, tachyphylaxis in
infusions >24-48 hrs
o Milrinone (inodilator): PDE-3 inhibitor ( breakdown of cAMP)
• Watch for tachycardia, arrhythmias, ischemia, HoTN. Compared to dobutamine, milrinone has longer half-life,
greater pulmonary vasodilatation, slightly less chronotropy, fewer arrhythmic events.
• Preferred in patients on βB and w/ RV failure. Is renally cleared. Often choice for home inotrope for palliative therapy
o Epinephrine, norepinephrine, dopamine (inopressors): use if severe HoTN, unable to tolerate inodilators
• Watch for tachycardia, arrhythmias, end-organ hypoperfusion
4. Advanced: consideration of need for mechanical circulatory support or transplant
o Goal of mechanical circulatory support: improve systemic perfusion while reducing myocardial oxygen demand (in
contrast to inotropes which  CO at the expense of increased oxygen demand)
o Types of MCS at MGH: IABP, Impella, VAD, VA-ECMO (see MCS & Transplant) – if considering, obtain SHOCK c/s
(p11511)
• Limitations:
o CO measured via thermodilution or calculated using Fick equation: CO = VO2/(13.4 x Hgb x [SpO2-MvO2]); CI = CO/BSA; VO2
estimate = 125 x BSA
 Thermodilution: uses temp gradient between two points on PAC. Less reliable if shunt/valvular insufficiency (e.g. TR)
 Fick equation: assumes a VO2 (oxygen consumption) that in reality varies depending on physiologic state (e.g. infxn)

Evan Whitehead

25
TOC

Cardiology Right Ventricular Failure

Right Ventricle Physiology

• RV has thinner myocardium compared to LV compliance compared to LV, so it does not adapt well to acute increases in pressure
• RV and LV are interdependentfailure of RV leads to failure of LV through several mechanisms: (1) decreased LV preload because
RV output = LV preload and (2) septal bowing into LV, causing diastolic impairment (“Bernheim effect”)
Acute Changes in RV Hemodynamics RV “death spiral”
•  RV afterload (e.g. PE),  RV preload (e.g. LR shunt or TV disease), or 
RV contractility (e.g. MI) all lead to increased RV wall stress and resultant
ischemia
• RV CO subsequently  and RV dilates, precipitating RV “death spiral”
•  RV CO leads to  MAP (and  RVP), resulting in  coronary perfusion
pressure (CPPRV = MAP – RVP)
•  CPPRV leads to more RV ischemia, propagating “death spiral” further
Clinical Features and Workup
• Exam: elevated JVP, peripheral edema, RV heave, pulsatile liver. Less
common: split S2, new tricuspid regurgitation (loudest: RLSB)
• Imaging: CXRhard to evaluate RV 2/2 position, lateral film can help; CT
RV/LV ratio >0.9 suggests RV strain
• Echo: measure RV size/function to elucidate underlying etiology. RVEF based
on displacement of base towards apex; TAPSE = tricuspid annular plane systolic Eur Heart J 2020;41:543
excursion
o RVSP: correlates w/ RHC but can vary up to 10mmHg (esp w/ chronic lung disease, positive pressure ventilation)
• RHC: gold standard for measurement of ventricular filling pressures, CO, PA pressures
o RV function: CVP / PCWP ratio: normal = 0.5;  is sign of RV failure; PAPi: (PAs – PAd)/CVP <0.9 = RV failure; RV stroke work
index: (mPAP – CVP) x (CI/HR) x 0.0136 (normal 8-12 g/m/beat/m2)
• Labs:  NT-proBNP, troponin, also Cr and LFTs 2/2 venous congestion
Management (AHA Guidelines: Circ 2018;137:e578)
• Treat reversible causes (RVMI, PE, hypoxemia, infections)
• Preload: clinical assessment of optimal preload is challenging. Both hypo- and hypervolemia may  CO.
o Acute: judicious IVF use in pts with acute RVMI or PE in absence of marked CVP elevation (goal CVP 10-14 in RVMI)
o Subacute/chronic: diuresis to  RV filling pressures,  functional TR and and improve LV CO by relieving ventricular
interdependence
• Afterload:
o Systemic: if pt hypotensive, start pressors – do not tolerate hypoTN as propagates RV death spiral (CPP); no clinical data
regarding pressor of choice, but often choose vasopressin or norepinephrine (vaso affects PVR less than norepi)
o Pulmonary: remove factors that  pulm vasc tone (e.g. hypoxemia, acidemia). Consider pulm vasodilators (inhaled>oral to
deliver vasodilators to ventilated vascular beds).
 Types: iNO, prostacyclin agonists (epoprostenol, inhaled or IV), endothelin antagonists (e.g. bosentan, ambrisentan), nitric
oxide enhancers (e.g. PDE-5 inhibitors: sildenafil, tadalafil)
• Contractility: dobutamine or milrinone (milrinone causes  reduction in RV afterload but higher risk of hypotension)
• Devices: if refractory RVF, consider RV MCS (Impella RP, VA-ECMO)
Intubation and Mechanical Ventilation (Curr Heart Fail Rep 2012;9:228)
• Intubation/NIPPV in RV failure precipitate risk for hemodynamic collapse and cardiac arrest
o Drugs commonly used in intubation (BZDs, propofol, muscle relaxants)  tendency towards vasodilation and negative
inotropy  decreased venous return  decreased LV preload  systemic hypoTN  propagates death spiral
o Consider RSI (etomidate >> propofol for induction) and push dose epinephrine (10-20mcg)/vasopressin (1-2U) if emergent
intubation anticipating hypotension
• Positive pressure ventilation  increased pulmonary pressures and RV afterload  increased RV dilation  “death spiral”
• Vent management: prevent hypoxemia and hypercarbia ( PVR), consider moderate TV (~8cc/kg), low PEEP (<12 cm H2O), and
moderate plateau pressure goal (<30 mmHg)
Right Ventricular Myocardial Infarction (ACC/AHA Guidelines: Circ 2012;127:e362)
• EKG: check R-sided EKG leads in pts with inferior STEMI (10-15% of pts with inf. STEMI have RV involvement)
o 1mm STE in V4R  88% Sn, 78% Sp in inferior STEMI; STE III>II suggests RCA > LCx and ∴RVMI
o High-grade AV block seen in ~50% of pts with RVMI
• Management: pts with RVMI may initially benefit from fluid bolus; caution w/ TNG ( preload) and BB
o If CVP >15mmHg and BP not improving w/ IVF, additional fluids may worsen RV failure/overload (Eur Heart J Acute Cardiovasc
Care 2013;2:226)

Evan Whitehead
26
TOC

Cardiology Pulmonary Artery Catheterization

Overview:
• Indications: (1) diagnose etiology of shock (e.g. cardiogenic vs. distributive); (2) diagnose cardiogenic vs. non-cardiogenic pulm edema; (3)
tailored therapy; (4) diagnose PH; (5) diagnose L R shunting; (6) diagnose valve disease (7) diagnose pericardial disease
• Efficacy: controversial - ESCAPE trial (JAMA 2005;294:1625) showed no mortality benefit to PAC use in pts w/ ADHF, but pts on inotropes
were excluded. PACs are still standard of care and guideline-recommended in cardiogenic/mixed shock or in pts w/ MCS (JACC
2013;62:e147)
• Line course: central vein (IJ/subclavian/femoral)  SVC/IVC  RA  RV  PA  distal pulmonary arteriole
Venous Waveforms (CVP/PCWP):
• a wave: atrial contraction; coincides with QRS complex (on CVP tracing)
• c wave: bowing of TV/MV into atrium during ventricular contraction; more visible in 1st degree
AV block. Often absent on PCWP.
• x descent: atrial relaxation (early x descent), downward mvmt. of TV/MV (late x descent)
• v wave: passive atrial filling (venous return) when TV/MV closed; coincides with T wave
o Prominent v waves seen in MR and TR
• y descent: rapid atrial emptying following opening of the TV/MV (ventricular diastole)
o Prominent y descent + x descent seen in pericardial constriction
o Blunted y descent seen in tamponade
Obtaining PA Line Numbers on AM Rounds:
1) Position patient supine with head-of-bed 0-60° elevation
2) Check level of transducer with phlebostatic axis (4th intercostal
space and mid-axillary line)
3) Zero transducer to air and assess waveform for dampness
4) Record PA systolic, PA diastolic, PA mean, CVP, and line position
5) Open the PA catheter balloon port and remove 1.5cc air
6) Inject 1.5cc air slowly until PCWP waveform observed (use minimum air required to reduce risk of PA infarction/rupture) and record PCWP
(limit balloon inflation to no more than 8-10 seconds)
7) Release safety syringe and allow balloon to deflate passively. Verify balloon deflated by confirmation of PA waveform.
8) Troubleshooting: CXR to evaluate position
a. Arrhythmia: catheter may be in RVOT. Talk to fellow/attending and consider repositioning catheter
b. Dampened waveform: kinked tubing, air/thrombus, or catheter tip against vessel wall. Flush and/or withdraw catheter.
c. No PCWP tracing: catheter tip is not far enough, balloon has ruptured, or catheter coiled in RV
Calculating Hemodynamic Parameters:
• Normal: “rule of 5s”  RA 5, RV 25/5, PA 25/10, PCWP 10, LV 125/10
• Cardiac output:
o Fick = VO2 / (13.4 * Hgb * [SpO2 – MvO2]) [nml: 4-7 L/min]
 VO2 ≈ 250 ml/min OR 3*wt(kg) OR 125*BSA
o Thermodilution: temperature change (measured by thermistor in
PA) is proportional to LV CO (inaccurate w/ TR, intracardiac shunt)
• Cardiac index = CO/BSA [normal: 2.6-4.2 L/min/m2]
• SVR = (MAP-CVP) / CO x 80 [normal: 700-1200 dynes*s*cm5]
• PVR = (mPAP-PCWP) / CO [normal: <2 Woods units]
Hemodynamic Considerations:
• All quantitative pressure measurements (especially PCWP) should be
made at end-expiration (when intrathoracic pressure is zero)
o Spontaneous respiration: RA and PCWP  with expiration  measure from the higher a waves (“patient = peak”)
o Positive pressure ventilation: RA and PCWP  with expiration  measure from the the lower a waves (“vent = valley”)
• Measure RA and PCWP at end-diastole (i.e. just before the c wave)
• Correlate PCWP with PA diastolic pressure; if well correlated, can trend PAd as proxy for PCWP
Clinical Considerations:
• Placement: usually through RIJ Cordis. Advance ONLY with balloon inflated. Deflate balloon when withdrawing and at ALL other times.
Must have cardiology or pulmonary fellow present to place/advance at MGH.
o Cath lab insertion if: severe PH (PAP>70mmHg), large RV, LBBB, PPM/ICD, temp wire, severe TR, prosthetic TV/PV
• Contraindications: RA/RV mass/thrombosis, mechanical TV/PV, endocarditis (TV/PV)
• Markings on PA catheter: each thin line=10cm; each thick line=50cm.
• Position: on CXR: should be in middle 1/3 of the chest bilaterally. Ability to wedge more important than CXR position.
• Complications: infection, bleeding, PTX, VT, RBBB, CHB, PA rupture (place patient on side with the catheter “bleeding side down”, order
STAT CXR, CBC, coags, CT surgery consult), pulm infarct, PE
• Duration: no data defining maximum length of time; at MGH, standard is 7d; others suggest 4-5d

Evan Whitehead
27
TOC

Cardiology Mechanical Circulatory Support & Transplant

Mechanical Circulatory Support (MCS) – if inotrope-refractory cardiogenic shock, call SHOCK team (p11511)
Selected MCS Modalities
Device Indications Support Provided Considerations Management Complications
Minimal hemodynamic - Bedside insertion
support (0.5 L/min), - Does not require AC - Limb ischemia
greater in ADHF than (when at 1:1) - ✓CXR daily (tip 1-4cm - Vascular injury
IABP - Refractory heart acute MI shock (Am J - No  mortality in below Ao notch) - Thromboemoblism
(intra- failure (bridge to
aortic
Card 2019;124:1947) cardiogenic shock - ✓ Waveform daily - Bleeding
durable MCS) -  LV afterload (IABP-SHOCK II, - Infection
balloon - Wean by  ratio (then
- Cardiogenic -  Coronary NEJM 2012;367:1287) return to 1:1, stop AC, - Balloon leak/rupture
bump)
shock/massive perfusion - Prevents mobility (if pull) (STAT vascular surg
PE - Requires native femoral placement) c/s)
contractility to work - Least costly
- Refractory
malignant Partial LV support - P1 (lowest) to P9 (highest
- Ventricular unloading - Infection
arrhythmias - Cath lab placement: support)
- Requires AC (purge - Bleeding
Impella 2.5 (2.5 - ✓ Urine color
- Support during +/- systemic) - Limb ischemia
L/min), Impella CP (hemolysis), LDH
high-risk - Allows pt mobilization - Thromboembolism
(3.5 L/min)
Impella procedures: (if axillary placement) - ✓ Suction events ( - Thrombocytopenia
- OR placement:
o Complex PCI - Longer-term support preload, RV failure, - Vascular injury
Impella 5.0 (5 L/min)
o Ablation of (days to weeks) position) - Position alarm
or 5.5 (6.5 L/min)
ventricular Partial RV support
-  complications - ✓ Ventricular arrhythmias (reposition under
arrhythmias compared to IABP (device migration) fluoro/echo)
- Impella RP (4 L/min)
o Percutaneous - Bedside and urgent
valve repair Full bi-ventricular HD insertion possible
- Acute allograft support (4-10 L/min) + - Short-term support
VA-
failure oxygenation & CO2 (days/weeks) See ECMO chapter
ECMO
clearance - Often requires
additional device for
LV venting, i.e. Impella
- Bridge to
transplant - BP via manual cuff w/ - Acquired vWF defic.
- Destination doppler (goal MAP 70- - Hemolysis (possible
Full LV support (10
therapy (DT) 80) pump thrombosis)
L/min)
- “Bridge to - Mobility - If hypotensive, place A- - Ventricular
Durable - HeartMate II
decision” (on - Long-term support line arrhythmias
VAD - HeartMate 3
transplant or DT) (years) - If unconscious, w/o hum, - Thromboembolism
- HeartWare HVAD
- Bridge to and MAP<50: chest - RV failure
recovery (LV compressions - AR
unloading can be - TTE if any concern - Driveline infections
therapeutic)

Heart Transplant
2018 UNOS Adult Heart Allocation Criteria:
Status 1: VA-ECMO, MCS with life-threatening vent. arrhythmia; Status 2: non-dischargeable LVAD, MCS + device malfunction, IABP;
Status 3: ≥2 inotropes or single high-dose + continuous hemodynamic monitoring, dischargeable LVAD for discretionary 30 days, VA-
ECMO after 7d, IABP after 14d; Status 4: re-transplant, inotropes without hemodynamic monitoring, dischargeable LVAD without
discretionary 30 days; Status 5: awaiting dual organ Tx; Status 6: all others; Status 7: inactive listing
Transplant evaluation at MGH: (orders are typically placed by transplant coordinators)
• Labs: blood typing (2 samples on separate days), second sample for PRA (check with tissue typing x63722), BMP, LFTs, amylase,
CBC+diff, INR/PTT, TFTs, lipids, PTH, 25-OH-D, 1,25-Vit-D, HIV, CMV, Toxo Igs, EBV, VZV serology, MMR, RPR, hepatitis
serologies, IGRA, UA, 24h urine CrCl (and 24h urine protein if diabetic)
• Vaccines: HBV, PPSV23, Tdap
• Consults: Psychiatry (Dr. John Purcell), SW (Kathryn Tsagronis), Tx coordinators (Sally Keck, Coral Haggan, Kerry Gaj, Karen
Turvey – they can all consent patient for Tx), Dental (Panorex, inpatient consult), Nutrition, Endocrine, Palliative Care
• Diagnostics: RHC (eval for presence & reversibility of pHTN with vasodilator challenge; if unsuccessful vasodilator challenge, note
that PVR often declines after 24-48h of treatment [e.g. diuretics, inotropes, vasoactive agents]), +/- LHC, level 1 CPET (x4-7825),
abdominal U/S, carotid U/S, TTE, ECG, CXR, DXA, ABIs +/- angiography, cancer screening up-to-date
Post-transplant immunosuppression: steroids (typically tapered off over 6 months, 1st line for acute rejection), calcineurin inhibitors
(cyclosporine/tacrolimus), anti-proliferatives (azathioprine/mycophenolate), mTOR inhibitors (sirolimus/everolimus – most effective for
coronary allograft vasculopathy; avoid in immediate post-tx phase as inhibit wound healing)
Monitoring: protocolized schedule of RV biopsies to r/o cellular/humoral rejection, RHC/LHC and TTE to assess graft function and for
coronary artery vasculopathy

Evan Whitehead

28
TOC

Cardiology Cardiac Devices: PPM & ICD

Permanent Pacemakers (PPM), Implantable Cardioverter-Defibrillators (ICD), & Cardiac Resynchronization Therapy (CRT):
• Types: single chamber (RA or RV lead), dual chamber (RA + RV leads), biventricular (+/- RA + RV + coronary sinus leads)
• PPM: sense/pace the RA and RV to treat bradyarrhythmias (see tables for nomenclature and common modes)
• ICD: device with an RV lead capable of terminating re-entrant ventricular tachyarrhythmias via pacing, cardioversion, or defibrillation
• CRT: provides simultaneous RV+LV pacing in HFrEF pts w/ wide QRS to  desynchrony  LV reverse remodeling and  LVEF
o CRT-P = BiV +/- RA pacing; CRT-D = CRT-P w/ ICD functions
NASPE/BPEG Codes for Pacing Operating Modes

Hardware Overview: system consists of pulse generator + leads. Usually Position I Position II Position III Position IV
implanted SQ in upper chest (L>R) >> abdominal. Chamber(s) Chamber(s) Response to Rate
• Types: traditional (SQ pulse generator + IV leads in ventricle), leadless Paced Sensed Sensing Modulation
(pulse generator directly implanted into RV; no pocket complications; when O = None O = None O = None O = None
battery dies, device retrieval is rare), SQ ICD (no IV hardware; low risk for A = Atrium A = Atrium T =Triggered
R = Rate
infection but NO pacing capabilities) Modulation
• Placement: RA lead  RA appendage; RV lead  RV apex; LV lead V = Ventricle V = Ventricle I = Inhibited
 coronary sinus  branches of great cardiac vein D = Dual D = Dual D = Dual
(A+V) (A+V) (A+V)
• Interrogation: page EP Technician (PPM, p16939) during normal business
hours; EP fellow on call if after-hours/weekend.
• MRI compatibility: not all devices are MRI Code Action Use
compatible, however even non-MRI compatible Single Chamber Modes
devices may be safe to scan after re-programming Atrial Demand; atrium paced, atrium Isolated SN dysfxn,
AAI
(NEJM 2017;376:755). Determined on case-by-case sensed, atrial activity inhibits PM intact AV node
basis by radiology. Need to know device model. High-grade AV blocks,
Ventricular Demand; ventricle paced,
bradycardia; does not
VVI ventricle sensed, ventricular activity
track atrial activity (i.e.
PPM Indications (Class I): (JACC 2013;61:e6) inhibits PM
chronic AF)
Sinus Node Dysfunction: Asynchronous; atrium or ventricle Obsolete (AOO), Temp
• Symptomatic sinus bradycardia (± sinus pauses) AOO / VOO
paced, no sensing wire pacing (VOO)
or chronotropic incompetence Dual Chamber Modes
• Symptomatic medication-induced bradycardia if Tracking Modes
medication (e.g. βB) is required for underlying Allows coordination of
Synchronous; paces and senses in
medical condition A and V pacing; most
DDD atrium and ventricle; atrial activity is
AV Block (AVB)/Conduction Disease: closely mimics intrinsic
tracked/triggers ventricular activity
conduction system
• Symptomatic 2° AVB or 3°AVB
Atrial Synchrony Possible; ventricle
• Asymptomatic 2° AVB Mobitz II or 3° AVB with: Rarely used; high-
VDD paced, atrium and ventricular activity is
asystole ≥3 sec (≥5 seconds if in AF), escape grade AV block
sensed
rate ≤ 40 BPM (or >40 BPM if cardiomegaly also Non-Tracking Modes
present), or wide-complex escape rhythm AV Sequential; paces and senses in
SSS or sinus brady
• Permanent 2° AVB Mobitz II or intermittent 3° AVB DDI
atrium and ventricle; atrial activity not
with intermittent atrial
(regardless of symptoms) tracked; atrial tachyarrhythmia does not
tachycardias
• Alternating bundle branch block trigger RVR
Neurocardiogenic: Avoid sensing
Asynchronous Fixed Rate; paces electrocautery or
• Recurrent syncope AND inducible asystole ≥ 3 sec DOO
atrium and ventricle, no sensing electromagnetic
with carotid massage interference

ICD Indications (Class I):

• Primary prevention indications only apply to pts on optimized medical therapy (OMT) and have a reasonable expectation of 1-year
survival. (JACC 2013;61:e6)
Primary Prevention Secondary Prevention
Ischemic CM: - Prior episode of cardiac arrest (VF/pulseless
NYHA Class I: EF ≤ 30% at least 40d s/p MI VT) or sustained unstable VT if no reversible cause
NYHA Class II/III: EF ≤ 35% at least 40d s/p MI found
Other: EF ≤ 40% at least 40d s/p MI + NSVT + inducible VT/VF on EP study - Structural heart disease with spontaneous
*Non-ischemic CM: EF ≤ 35% + NYHA Class II/III sustained VT (stable or unstable)
Other: Unexplained syncope w/ hemodynamically significant inducible VT/VF on EP study
*DANISH demonstrated that in pts with non-ischemic CM, ICD implantation reduces risk of sudden cardiac death, but does not provide a mortality benefit
CRT Indications:  mortality compared to OMT (ACA/AHA/HRS 2012 Guidelines, JACC 2013;61:e6)
NYHA I NYHA II NYHA III / NYHA IV
LVEF ≤ 35%, QRS ≥ 150ms, LBBB, &
Class I None LVEF ≤ 35%, QRS ≥ 150ms, LBBB, & sinus rhythm
sinus rhythm
LVEF ≤ 35%, QRS 120-149ms, LBBB, LVEF ≤ 35%, QRS 120-149ms, LBBB, & sinus rhythm
Class IIa None
and sinus rhythm LVEF ≤ 35%, QRS ≥ 150ms, & non-LBBB
LVEF ≤ 30%, QRS LVEF ≤ 35%, QRS ≥ 150ms, non- LVEF ≤ 35%, QRS 120-149ms, non-LBBB pattern, & sinus
Class IIb
≥150ms, LBBB, & iCM LBBB pattern, & sinus rhythm rhythm

Andrew Abboud
29
TOC

Cardiology Valvular Heart Disease

Aortic Stenosis
• Etiology: senile calcific (most common cause >70yo; a/w metabolic syndrome, CAD, CKD), bicuspid valve (most common cause
<70yo), rheumatic heart disease (leaflets fuse, often with concurrent MV disease)
• Clinical Manifestations: most important determinant of prognosis  50% mortality at 5y for angina, 3y for syncope, 2y for HF
o Angina:  afterload/outflow obstruction LV pressures LVH O2 demand and compression of coronary arteries
o Syncope: exercise-induced vasodilation  inability to augment CO due to obstruction  hypotension
o Heart failure (dyspnea): LVH  diastolic dysfunction (systolic dysfunction is a late finding)
o Acquired vWF def: 20% of severe AS, can expose bleeding from GI AVMs (Heyde’s syndrome) (NEJM 2012;367:1954)
• Diagnosis:
o Physical exam: harsh, mid-systolic crescendo-decrescendo murmur at RUSB radiating to carotids. If more severe: murmur late-
peaking, delayed carotid upstroke (pulsus parvus et tardus), soft S2 (Am Heart J 1999;137:298)
o TTE: measure mean (not peak) gradient, valve area, and jet velocity; also important to assess EF (gradient can be
underestimated with reduced EF  low flow, low gradient AS)
 Severe AS: peak aortic valve velocity >4m/s, mean aortic valve pressure gradient >40 mmHg, aortic valve area <1cm2
(AHA/ACC Guidelines: JACC 2014;63:2438)
o EKG: LVH, LAE, LAFB, LBBB
o Exercise stress testing: recommended in asymptomatic severe AS to assess for symptoms; do not perform in pts w/ sx
• Natural History: variable, but on average, AVA  ~ 0.1 cm2/yr and mean gradient 8 mmHg/yr (JACC 1989;13:545)
• Aortic Valve Replacement (AVR) (AUC Severe Aortic Stenosis 2017): determining indication for valve replacement is based on
evaluating: (1) presence of symptoms, (2) severity by TTE criteria, (3) LV function (EF)
o Symptomatic, severe AS: AVR indicated
o Asymptomatic, severe: AVR appropriate if LVEF<50% or undergoing other cardiac surgery
o If suspect low-flow (LVEF<50%) and low-gradient (<40mmHg) w/ AVA <1cm2: dobutamine stress TTE to distinguish between
low-flow, low-gradient AS versus “pseudosevere AS” (Circ 2011;124:e739)
 Low-flow, low-gradient severe AS: if dobutamine stress echo results in Vmax >4 m/s or pressure gradient >40mmHg while
AVA remains <1cm2, then AVR is indicated
 Pseudosevere AS: if dobutamine stress echo results in AVA >1cm2, then AVR not indicated
o SAVR vs TAVR: depends on surgical risk (STS-PROM score) and/or concomitant heart/vascular disease that is amenable to
surgery. TAVR is recommended for those at extreme surgical risk (compared to medical therapy, PARTNER). TAVR is
noninferior to SAVR in those at high (NEJM 2011;364:2187), intermediate (PARTNER 2), and low surgical risk (PARTNER 3).
Valve-in-valve TAVR may additionally be beneficial in pts with surgical bioprosthetic AV failure (JACC 2017;69:2283).
o TAVR Evaluation: consult structural cardiology, cardiac surgery. Obtain TTE, TAVR-protocol CT, dental clearance (Panorex).
o TAVR Complications: valve embolization, valvular regurgitation, paravalvular leak/regurgitation, cardiogenic shock, coronary
occlusion, annular rupture, ventricular perforation, CHB requiring PPM, stroke (ischemic/hemorrhagic), bleeding/hemorrhage,
access site complication
• Medical Management: AS is a surgical disease and medical management is only utilized for sx management
o Treat HTN: reduce the “double load” on the ventricle. However, no optimal regimen exists because many anti-hypertensives can
lead to hemodynamic issues (diuretics reduce preload which lead to decreased CO, vasodilators can reduce coronary artery
perfusion, BB can reduce needed contractility). Bottom line: start low and go slow.
o Control volume status: these patients operate within a narrow preload range, prone to both underfilling (“preload-dependent”)
and overfilling (volume overload)
• Anticoagulation after Valve Replacement:
o DOACs are not approved for valve replacement and may cause harm (RE-ALIGN)
o Bridging UFH or LMWH if AC interrupted only in mechanical MV or mechanical AV with RFs (Class I)
o Risk factors: AF, LV dysfxn, previous VTE, hypercoagulable state, older generation mech AVR (Star-Edwards valve or disc valve
other than Medtronic Hall) (Circ 2014:129:2440)
o Bleeding risk: mechanical > bioprosthetic (likely AC related). Reoperation risk: bioprosthetic > mechanical

Prosthesis Location Timing and Risk Factors INR Class

Mitral Indefinitely 2.5-3.5 (+ ASA 81) I
Mechanical Indefinitely, (+) risk factors 2.5-3.5 (+ ASA 81) I
Aortic
Indefinitely, (-) risk factors 2.0-3.0 (+ ASA 81) I
First 3 months after placement, regardless of RFs 2.0-3.0 (+ ASA 81) IIa
Mitral
>3 months after placement ASA 81 IIa
Bioprosthetic
First 3 months after placement, regardless of RFs 2.0-3.0 (+ ASA 81) IIb
Aortic
>3 months after placement ASA 81 IIa
No high-level trial data. DAPT does not provide mortality benefit with available data though active
research ongoing. Expert consensus recommends lifelong ASA + 3-6mo. clopidogrel for patients
TAVR Aortic
in sinus rhythm. AC considered for AF or other indication for long term AC. Avoid DAPT in these
patients (ACC 2017 Guidelines).

Other Valvular Disease

Daniel Amponsah and Mubeen Shakir
30
TOC

Cardiology Valvular Heart Disease

Aortic Regurgitation Mitral Stenosis Mitral Regurgitation Tricuspid Regurgitation
Acute: aortic dissection, valve - 80% due to RHD (only 50- - Dilated annulus (“functional - Dilated annulus,
perforation (usually due to MI or 70% report h/o rheumatic MR”), MVP, ischemic papillary pulmonary hypertension
endocarditis), traumatic valve fever), endocarditis, annular muscle dysfunction, ruptured (“functional TR”), direct
leaflet rupture calcification (rarely significant), chordae, endocarditis, RHD, valve injury, endocarditis,
Etiology Chronic: leaflet abnormalities congenital, autoimmune CTD RHD, carcinoid, ischemic
(bicuspid valve, endocarditis, valvulitis (SLE), carcinoid, papillary muscle
RHD) or root dilation (HTN, CTD, endomyocardial fibroelastosis, dysfunction, CTD, drug-
dissection, syphilis) XRT (10-20 yrs after Hodgkin’s induced
treatment)
Acute: diastolic regurgitant flow - Elevated LAP  pulmonary - LA/LV volume overload  LV - Similar to MR
 sudden LVEDP (w/o HTN, AF (47%) dysfunction, progressive
remodeling time)  CO  - Demand for  CO enlargement of LV  dilated
pulm edema precipitates symptoms mitral annulus  worsening MR
Pathophys. Chronic: diastolic regurgitant flow - Valve narrows 0.1cm2/yr
 LVEDV  initial
maintenance of SV/CO 
progressive dilatation, eventual
failure
- Cardiogenic shock (acute), - Dyspnea (most common Acute: flash pulmonary edema, - Right-sided HF:
angina, left-sided HF symptom), pulmonary edema, HTN, shock hepatosplenomegaly,
Clinical - 31 eponyms for signs in chronic hemoptysis, thromboembolism Chronic: DOE, orthopnea, PND, ascites, edema
AI, most due to large initial SV even w/o AF (Annals edema, AF
(Int J Car 2006;107:421) 1998;128:885), RV failure
-  pulse pressure (bounding - Loud S1, high-pitched - Holosystolic murmur at apex - Holosystolic murmur at
pulses, bouncing head/uvula, nail opening snap (earlier more radiating to axilla, S3, displaced left mid or lower sternal
bed capillary pulse). severe, indicating higher LAP) PMI border that increases with
- High-pitched, blowing diastolic - Low-pitched diastolic rumble - Early diastolic rumble and S3 inspiration, S3.
decrescendo murmur along LSB heard best at apex at end- may be the only signs in acute
Exam
- Longer = more severe/chronic. expiration MR
- May also hear low-pitched
diastolic murmur at apex due to
regurgitant jet displacing anterior
leaflet
Acute: usually needs urgent Medical: warfarin if LA Acute:  afterload (e.g. Medical: diuresis,
surgery. Nitroprusside to  thrombus, AF, prior embolism nitroprusside), inotropes management of underlying
afterload; ino- and chronotropes (Class I) or LA > 55mm (Class (dobutamine), diuresis cause
to  diastole time. IIb) - If hemodynamically unstable
- Do not use vasoconstrictors or - β-blocker if tachycardic or (esp. post-MI or endocarditis), Intervention: TVR if:
IABP (worsens regurg) or beta- dyspneic consider IABP and/or urgent undergoing left-sided
blockers (blocks compensation,  - diuresis if pulm vasc surgical repair (NEJM valve surgery AND severe
diastolic regurgitant time) congestion 2012;366:2466). TR, tricuspid annular
- If ischemic, consider dilatation, or evidence of
Chronic: ACE-I, nifedipine, or Intervention: need to have revascularization. right heart failure (Circ
hydralazine/nitrates (to reduce LV severe MS + symptoms to be 2017;135:e1159).
considered for surgery (unless Chronic: MVR if: primary - Isolated TV surgery a/w
afterload)
noted below) symptomatic severe MR and high mortality, although
- Proceed to AVR if: symptomatic,
- Tx is percutaneous balloon EF >30% OR asymptomatic but may be recommended for
LV systolic dysfunction (EF
mitral commissurotomy EF 30-60% or significant LV severe TR refractory to
<50%), LV end-systolic
Treatment (PBMC) if pt has favorable dilatation (LVEDD >40mm) medical therapy
dimension >50mm, need for
valve morphology (Wilkins (NEJM 2005;352:928, Circ - Numerous transcatheter
CABG or other valve surgery
Score based on TTE). 2013;127:1870). therapies are potential
- Proceed to MVR if not PBMC - If excessive surgical risk, options but still lack long-
candidate, PBMC fails, or percutaneous MV clip/repair or term clinical
undergoing another cardiac CRT are also options outcome/performance
surgery (even if asymptomatic) (EVEREST II). data (JACC 2018;71:2935)
- If severe functional MR, repair
equivalent to chord-sparing
replacement (NEJM
2014;370:23).
- Benefit of percutaneous clip if
HF and secondary
symptomatic failing GDMT
including CRT (COAPT)

Daniel Amponsah and Mubeen Shakir

31
TOC

Cardiology Pericardial Disease

CARDIAC TAMPONADE
• Definition: hemodynamic insufficiency caused by impaired cardiac filling due to  pericardial pressure due to effusion, leading to 
intracardiac chamber pressures & eventually equalization of diastolic pressure in all 4 heart chambers.
• Etiologies of pericardial effusion: idiopathic (20%), iatrogenic (16%), malignant (13%), uremic, HF, autoimmune (Am J Med
2000;109:95). Tamponade more likely in malignant, post-viral, uremic, iatrogenic (i.e. post-cath) etiologies. Also seen with prox. aortic
dissection & myocardial wall rupture.
Clinical Manifestation and Diagnosis: 5 Clinical Features Associated with
• Beck’s Triad: BP, JVP, muffled heart sounds Tamponade (JAMA 2007;297:1810)
• Pulsus paradoxus (PP): exaggeration of normal decrease in SBP during inspiration. Sign/Sx Sensitivity 95% CI
(If >10mmHg, ⊕LR=3.3. If ≤10 mmHg, ⊕LR=0.03). Dyspnea 87-88% n/a
o How to measure PP Tachycardia 77% 69-85%
Pulsus paradoxus 82% 72-92%
1. Slowly deflate cuffnote pressure when systolic Korotkoff sounds only
Elevated JVP 76% 62-90%
heard w/ during expiration (will sound irregular) (a)  continue slowly
Cardiomegaly on
deflating cuff until heard throughout (b). PP = a – b CXR
89% 73-100%
2. Via A-line tracing (PP = height exp. – height insp. systolic waveform)
o False-negative PP conditions: pre-existing disease w/ LVEDP (e.g. chronic HTN), regional tamponade, pericardial adhesion,
acute MI, arrhythmia, ASD/VSD, severe AI, hypotension/shock, RVH
o PP DDx: severe COPD/asthma, massive PE, hypovolemic shock, RVMI, constrictive CVP tracing in tamponade
physiology, tense ascites
• ECG: sinus tach, low QRS voltage (50%; limb ≤ 5mm, precordial ≤ 10mm), electrical
alternans (20%; precordial leads).
• TTE: inspiratory leftward septal shift, diastolic collapse of cardiac chambers (R > L-sided),
respirophasic changes in transvalvular velocities, IVC plethora. SIZE of effusion does NOT
predict tamponade – RATE of accumulation is more important.
Treatment:
• Fluid resuscitation: administer volume urgently to increase intracardiac pressures (monitor closely as overfilling can worsen
tamponade), starting w/ 250-500cc bolus
• Inotropes: administer if IVF insufficient. Unclear benefit b/c endogenous catecholamines already at max level. Avoid BB.
• PPV: avoid if possible as  positive intrathoracic pressure will further impede ventricular filling
• Pericardial effusion removal: catheter pericardiocentesis, surgical pericardiectomy (if aortic/myocardial rupture), or HD (if uremic)
o Analysis of pericardial fluid: cell count, total protein, LDH, gram stain/cx, viral markers/cx (Coxsackie, HSV, CMV, EBV, HIV),
AFB smear/cx, ADA/IFN-gamma/lysozyme (if concerned for TB pericarditis), cytology/tumor markers
o Removal of drain: when output <50 cc/day, otherwise may need pericardial window (pleural>abdominal)
PERICARDITIS
• Classification: acute (<6 wks), subacute (6 wks to 6 mo), chronic (>6 mo)
ECG Evolution in Pericarditis
• Epidemiology: 5% of pts in ED w/ CP and no MI, male predominance
• Etiology: 85-90% idiopathic (usually viral/post-viral), bacterial, fungal, post-
MI, uremic, mycobacterial (TB), autoimmune (CTD, vasculitis), malignancy
(e.g. lung, breast), XRT, drugs (procainamide, hydral, INH)
Clinical Manifestations and Diagnosis:
• Symptoms: sudden onset, pleuritic, retrosternal CP relieved w/ sitting up & leaning forward (may radiate to trapezius muscles), +/-
viral prodrome if infectious etiology. Uremic or CTD pericarditis: CP may be absent.
• Exam: pericardial friction rub (~30% cases), best heard at LLSB w/ diaphragm of stethoscope at end-expiration w/ pt leaning forward
• ECG: 4 stages: (1) diffuse ST & PR (PR & ST in aVR/V1); (2) ST & PR normalize; (3) diffuse TWI; (4) TW normalize. May see
continual low-voltage or electrical alternans if effusion present. Uremic pericarditis: ECG can be normal b/c epicardium not inflamed.
• Diagnosis: ≥ 2 of the following: (1) characteristic CP, (2) friction rub, (3) suggestive ECG changes, (4) pericardial effusion
o Workup: infectious w/u, BUN/Cr, ANA/RF/CCP, HIV, IGRA, ESR/CRP, troponin (elevated in ~30%, indicative of myopericarditis)
o TTE: assess for presence/size/location of co-existent effusion and/or tamponade physiology
o Pericardiocentesis/Surgical Drainage: if (1) suspect malignancy or bacterial etiology (2) large effusion (>2cm) (3) tamponade
Treatment: self-limited (days-weeks) in 70-90% of cases
• Hospitalize if: fever,  WBC, large effusion (> 2cm), immunocompromised, anticoagulated, trauma,  troponin, unstable/signs of
tamponade, failure to respond to NSAIDs after 7d. Also consider hospitalization if subacute presentation.
• 1st-line treatment: NSAIDs (e.g. ibuprofen 600-800mg TID; ASA 650-1000mg TID) ± colchicine 0.6mg BID (QD if pt <70kg)
o Colchicine  sx at 72hrs, improves 1-wk remission, and 18-mo recurrence in acute idiopathic pericarditis (Circ 2005;112:2012,
NEJM 2013;369:1522). No benefit w/ malignant or uremic cases.
o ASA: preferred over NSAIDs if: post-MI, CAD, concomitant anti-platelet/anticoagulant therapy
• Glucocorticoids (prednisone 0.2-0.5mg/kg/d): preferred over NSAIDs if: sx refractory to 7d of NSAID treatment, recurrent (>2
episodes), uremic pericarditis, CTD pericarditis, or contraindication to NSAIDs
• Duration: NSAIDs: until sx resolve (1-2wks), then taper (total 3-4wks). Colchicine: 3mo. Glucocorticoids: 2wks, then taper (3mo total).

Erika J. Parisi
32
TOC

Cardiology Aortic Disease

Aortic Aneurysms (JACC 2016;68:1054)
AAA TAA
• 4-6:1 M:F ratio • 1.7:1 M:F ratio
Epidemiology • 4-8% if age >65 • Mostly 50s-70s
• Most infrarenal • 50% ascending Ao, 40% descending Ao, 10% arch
• Usually due to atherosclerotic disease • Atherosclerotic: majority of cases. Mostly in
• Risk factors: smoking, male sex, age, pre- descending Ao. Risk factors: smoking, HLD, HTN
existing atherosclerosis, obesity, HLD, • Structural/genetic: mostly in root and ascending aorta.
HTN, FHx Causes: CTD disease (Marfan, Ehlers-Danlos, Loeys-
Dietz), Turner, bicuspid AoV, trauma
Etiology
• Infectious: 3° syphilis, mycotic aneurysm (most
common org: Staph spp., Salmonella spp.)
• Inflammatory: GCA (~10% have TAA), Takayasu, RA,
psoriasis, Behcet’s, Wegener’s, IgG4

• ACC/AHA: one-time abdominal U/S in all men • General population: not recommended
>60 w/ FHx of AAA (IIC) and all men >65 that • Indications: at time of dx of Marfan (IC), Turner (IC),
have ever smoked (IA) Loeys-Dietz, Takayasu or GCA. 1° relatives of pt w/
• USPSTF: one-time abdominal U/S for men TAA, dissection, bicuspid valve (IB/IC)
age 65-75 who have ever smoked (Grade B) • Surveillance: if aneurysm only, then same as AAA. If
Screening/ and selective screening for male never also with dissection, image at 1, 3, 6, & 12 months then
Surveillance smokers 65-75 (Grade C). Screening women annually. Image entire aorta (CT/MRI) if multiple
not recommended. aneurysms (~25% TAA will have AAA; ~25% AAA will
• Surveillance: have TAA).
o 3-3.4 cm: U/S q3y
o 3.5-4.4 cm: U/S or CT q12mo
o 4.5-5.4 cm: U/S or CT q6mo
• Abdominal U/S: screening and surveillance of infrarenal AAAs. High Sn/Sp (>90%), operator-dependent
• CT w/ contrast: high Sn/Sp, better than U/S for suprarenal AAAs
Imaging
• MRI/MRA: good Sn/Sp, preferred for aortic root imaging and for imaging tortuous aortas
Modalities
• CXR: “enlarged aorta” nonspecific (tortuous aorta vs. aneurysm)
• TTE: useful for root and proximal thoracic aorta; TEE: will visualize entire thoracic aorta but rarely used.
Medical Medical
• Smoking cessation (slows AAA growth by up • Reduce BP (<140/90 or <130/80 if DM or CKD; little
to 25%) actual evidence, IB)
• Reduce BP in accordance with ACC/AHA • Meds: BBs (decrease TAA growth in Marfan pts), ARBs
standards (slow aortic root aneurysm in expansion in Marfan pts,
• Meds: statins (reduce all-cause mortality in likely via TGF-β inhibition), statins (goal LDL<70)
pts s/p surgery); BBs (may slow expansion; IA • Smoking cessation
for perioperative use); ACEi (controversial; • Avoid straining
Treatment may prevent rupture but may speed growth); • Stress test used to guide BP management (follow SBP
low dose ASA (may slow growth) response to stress)

Surgical Surgical
• Men: >5.5cm OR growing >0.5cm/yr OR sx • Root/ascending TAAs: usually concomitant aortic valve
Women: >4.5-5cm (controversial) replacement
• Open repair (~4-6% 30 day mortality) vs. • Arch/descending TAAs: mostly open graft (EVAR).
EVAR (only ~50% suitable, c/b endoleaks) Ischemic brain/spine injury most worrisome
complication.
• Rupture: devastating mortality. AAA annual rupture rates are 4%, 7%, 20% at 5, 6, and 7cm, respectively.
Risk factors: size, rate of expansion, female gender.
Complications Sx: triad of abd/back pain + pulsatile abd mass + HoTN  immediate OR (don’t image)
• Dissection: pain (chest/abdomen/back), occlusion of aortic vessels, thromboembolism
• Post-repair: EVAR: endoleak, graft failure, thrombosis. Open: MI, embolization, AKI, ischemic colitis

Alexandra Wick
33
TOC

Cardiology Aortic Disease

Acute Aortic Syndromes (AAS) (Nat Rev Cardiol 2015;12:103)
Definitions: three distinct processes within the aortic wall, all which have
inherent risk of aortic rupture
• Aortic dissection (AD): intimal tear resulting in development of false
lumen
• Intramural hematoma (IMH): rupture of vasa vasorum causing
hemorrhage within aortic wall resulting in hematoma w/o tear
• Penetrating aortic ulcer (PAU): ulceration of atherosclerotic plaque
that penetrates into intima of aortic wall
Classification:
• DeBakey: type I (ascending + descending aorta); type II (ascending aorta only); type III (descending aorta only)
• Stanford: type A (ascending ± descending); type B (descending only)
Epidemiology:
• Prevalence: among AAS, aortic dissection most common (62-88%), followed by IMH (10-30%) and PAU (2-8%)
• Risk factors: male, HTN, age 60-70 (If <40yo, think Marfan syndrome or other CTD), atherosclerosis, prior cardiac
surgery, aortic aneurysm, FHx of AAS, aortitis, trauma, pregnancy
• Aortic dissection prognosis:
o Type A: Medical: 50% 2-week mortality, 90% 1-year mortality. Surgical: 10-35% mortality.
o Type B: Medical: 9% in-hospital mortality, 16% 1-year mortality, 20% 5-year mortality.
• IMH will progress to complete dissection in 28-47% of pts. PAU will progress to aortic rupture in 42% of pts.
Diagnosis:
• Clinical features: AD, IMH, and PAU cannot be distinguished by presentation alone
o Signs: AI murmur, pulse deficit, upper extremity BP differential (>20mmHg), CHF
o Sx: chest or back pain most commonly reported (radiates to neck/jaw if ascending; back/abdomen if descending;
may be migratory pain)
• Complications: syncope, shock, tamponade, branch artery occlusion (MI, CVA, paraplegia, cold extremity, renal failure)
• Labs: D-dimer <500ng/mL (96% NPV for absence of aortic dissection), troponin (high Sn and Sp for diagnosis of ACS,
but AAS may still be present if ⊕ [extension into coronaries])
• Imaging:
CXR - 50% of patients with AAS have normal CXR; only 1/3 will have widened mediastinum
- Sn 95% / Sp 87-100%; first-line imaging modality in patients with high clinical
probability of AAS.
CT
- Combined I+/I- (assess for IMH, mediastinum hemorrhage, or hemopericardium)
- Sn 73-100% Sp 71-91%, least accurate of diagnostic imaging modalities
TTE
- Useful for identifying AV dysfunction, prox dissections extending to Ao root/pericardium
- Sn: 99% / Sp: 90-100% for AAS. Often used intra-op to confirm dx prior to surgery.
TEE
- Invasive nature limits use; cannot detect pathology below the diaphragm
- Sn: 95-100% / Sp: 94-98% for AAS
MRI
- Rarely used in the initial evaluation of AAS due to long acquisition time in the MRI suite
Management:
• Goal: “impulse control”  minimize aortic wall stress by decreasing LV ejection force (dP/dT): HR <60, SBP <100-
120mmHg
• Agents: first-line is IV beta blockade (esmolol, labetalol). If additional BP control required, consider IV nitroprusside,
TNG, nicardipine
o NEVER use vasodilators without concomitant beta blockade  will increase wall stress, thereby increasing dP/dT
• Aortic Dissection:
o Type A: immediate open surgical repair 26% mortality vs. >50% with medical management (JAMA 2000;283:897)
o Type B: Uncomplicated: medical therapy (80% survival at 5 years); Complicated (compromise of renal/mesenteric
vessels): TEVAR preferred to open surgery (which has 25-50% in hospital mortality)
• IMH and PAU:
o Type A: urgent (i.e. within days) open surgical repair
o Type B: medical management or TEVAR (endovascular repair generally reserved for those with higher risk features
such as persistent pain, growth over time, aortic expansion or rupture, compromise of renal/mesenteric vessels)

Alexandra Wick
34
TOC

Cardiology Syncope
Overview:
• Definition: transient (self-limited) loss of consciousness due to cerebral hypoperfusion that is associated with loss of postural tone,
followed by complete spontaneous recovery; excludes metabolic causes (e.g. hypoglycemia, hypoxia, intoxication)
• Risk assessment and need for hospitalization:
o High-risk symptoms: preceding palpitations, exertional syncope, bleeding, syncope while supine, lack of prodrome, trauma
o High-risk features: angina, CHF, mod-severe valvular or structural heart disease, ECG features of ischemia/arrhythmia, FHx of
SCD, preexcitation syndromes, high-risk occupation (e.g. airline pilot)
o Risk calculators (e.g. SFSR, SRS) have high NPV (>95%) but do NOT replace clinical judgment
 San Francisco Syncope Rule (SFSR): admit pt if >1 of: EKG changes or non-sinus rhythm, dyspnea, Hct<30, SBP<90, HF
• Ddx: seizure, metabolic causes (hypoglycemia, hypoxia), intoxication, vertebrobasilar TIA, fall, psychiatric
Etiology and Diagnosis: 2017 AHA/ACC/HRS Syncope Guidelines
Etiology Historical Features Diagnosis Treatment
Reflex (60%) Vasovagal: prodrome of dizziness, • Vasovagal: can dx w/ tilt table test • Avoid provocative stimuli
• Vasovagal nausea, warmth, diaphoresis, (Class IIa) (Sn 32-85%, Sp 90%) • Isometric counterpressure
• Situational pallor; a/w intense emotion, pain, (JACC 1996;28:263) maneuvers of the limbs
• Carotid sinus or stress. • Carotid sinus syncope: diagnose via carotid (e.g. leg crossing, hand
syncope Situational: cough, sneeze, laugh, sinus massage (if no underlying bruits or grip, Valsalva, squatting)
micturition, defecation CVA history) • Meds used in select cases
CSS: neck only (i.e. midodrine,
turning/surgery/irradiation fludrocortisone, βB).
(NEJM 2005;352:1004)
Orthostasis (15%) Prodrome of dizziness, nausea, • Orthostatic vital signs (systolic  20mmHg • Primary: fludrocortisone
• Autonomic failure warmth, diaphoresis, pallor. or diastolic  10mmHg within 3 min of (0.1-0.2mg QD),
(1° or 2°) Risk factors for autonomic failure: standing) midodrine (5-20mg TID),
• Drug-induced - 1°: PD, Lewy body, Shy-Drager -  HR is NOT part of definition pyridostigmine, droxidopa
• Volume - 2°: DM, amyloid, spinal cord • Consider: Hct, A1C, SPEP if c/f amyloid, (for PD-associated
depletion injury, chronic EtOH, Lyme, RPR, B12 orthostasis)
syphilis, B12 deficiency, meds • Secondary: treat
(vasodilators, diuretics, BB, TCAs, underlying etiology, replete
PD meds, opiates, α-blockers) volume, d/c culprit meds
Cardiac (15%) No prodrome, syncope while in • Causes of cardiac syncope in young people • Based on etiology, follow
• Arrhythmia sitting or supine position, (+ ECG signs): guideline-directed
• Structural (AS, palpitations, FHx or personal 1. WPW (delta wave) management and therapy
LVOT obs.) history of heart disease 2. HOCM (LVH, apical TWI)
• Obstruction 3. Brugada (pseudo-RBBB with
(e.g.,PE, coved/saddleback pattern in V1-V2)
tamponade) 4. Long QTc syndrome (QTc >500ms)
• Dissection 5. ARVC (Epsilon wave)
• Consider cardiac monitoring on basis of
frequency and nature of syncope events
(inpatient telemetry, Holter, Zio patch,
implantable cardiac monitor).
• ONLY consider TTE if hx suggestive of
cardiac cause (<1% yield if no underlying
heart disease and normal ECG)
• Consider PE if no other apparent cause
identified in 17.3% of pts hospitalized with
1st syncope episode (and 25.4% of pts with
no other apparent cause for syncope)
(NEJM 2016;375:1524)

Neurologic (<10%) Seizure: tongue biting, • Seizure: EEG • Based on etiology,

• Seizure urinary/fecal incontinence, aura, • Stroke: CT, MRI/MRA consider neurology consult
• Stroke/TIA postictal confusion • Steal: UENI w/ Dopplers (specify for and follow guideline-
• Subclavian Focal deficits: stroke, TIA subclavian steal) directed management and
steal Steal: syncope after arm exercise • Carotid dopplers are of low clinical utility therapy
(changes management in <2% of patients)
(JAHA 2014;3:e001063)

Avanthi Rhagavan
35
TOC

Cardiology Hypertensive Urgency & Emergency

Definitions, Triage, and Management: See Outpatient CV Health for workup. (Chest 2007;131;194, NEJM 2019;381:1843, HTN 2018;71:1269)
• Hypertensive urgency: BP ≥180/120 without evidence of end-organ damage (may have mild headache)
o Assess adherence to prior Rx before aggressively uptitrating regimen to avoid overcorrection of BPs and hypotension.
• Hypertensive emergency: BP ≥180/120 with evidence of end-organ damage (rate of BP rise may be more impt. than actual BP)
o End-organ damage: Neuro: HTN encephalopathy (severe HA, seizure, AMS), PRES, TIA, CVA (SAH, ICH); Retinopathy:
papilledema, hemorrhage; Resp/CV: pulm edema, MI, +TnT, angina, Ao dissection; Heme: MAHA; Renal: AKI, hematuria
Hypertensive Urgency Hypertensive Emergency
Floor vs. outpatient mgmt (with close Floor vs. ICU (ICU if needs arterial line, antihypertensive gtt, or if
Triage location
follow up) (JAMA IM 2016;176:981) severe end-organ damage)
Reduce BP to <160/100 over several Reduce no more than 25% within the first hour, and to no lower
Correction time course
hrs; then to normal (<130/90) over 1-3d than 160/100 within 2-5 hrs; reduce to normal range over 1-3 days.
Route of medication Initial PO short-acting medications; Start with short-acting, titratable IV agents; transition to PO agents for
administration convert to long-acting prior to discharge floor/discharge
PO: captopril, labetalol >> hydralazine IV: labetalol >> hydralazine
Suggested meds
(unpredict., reflex tachy), isosorbide Topical: nitro paste (may be used on the floor)
(see below for dosing)
dinitrate Drips: see below
Disease Process-Specific Recommendations for Hypertensive Emergency
BP Goal Suggested Medications
TNG, esmolol > labetalol, nicardipine. BBs contraind. if LV failure w/ pulm
ACS SBP <140 within 1 hr; keep DBP >60 edema, HR <60, SBP <100, poor peripheral perfusion, or 2˚/3˚ heart block;
TNG contraind. in RV MI
Acute pulm edema SBP <140 within 1 hr TNG, nitroprusside, clevidipine; BBs contraindicated
Aortic dissection SBP <120 and HR <60 within 20 min IV BB first (esmolol, labetalol), followed by vasodilator (nitroprusside)
<185/110 if tPA; <220/120 if no tPA or
Ischemic stroke Nicardipine, labetalol, clevidipine > nitroprusside
end-organ damage
Antihypertensive Dosing – ICU
Agent Dosing Onset Duration Indications
500 µg/kg load + 25-50 µg/kg/min; then adjust by 25
Esmolol (IV) <1 min 10-20 min Ao dissection, CAD
µg/kg/min q10-20min up to 300 µg/kg/min
Labetalol (IV) 0.5-2mg/min, adjust to goal; max 10mg/min <5 min 3-6 hr Ao dissection
0.25-2 µg/kg/min (dose limit to avoid cyanide toxicity), AS/LVSD and HF; CI in
Nitroprusside (IV) <1 min <2 min
temporarily (<10min) can use up to max 10µg/kg/min. CAD (coronary steal)
Start 5 µg/min, titrate by 5µg/min q5-10min; max 400 µg/min
Nitroglycerin (IV) 2-5 min 5-10 min ACS, flash pulm edema
(if no response by 200 µg/min = non-responder)
Nicardipine (IV) Start at 5mg/h;  by 2.5mg/h q5-15 min; max 15mg/h <10 min 30 min SAH, Ao diss. (w/ BB)
Clevidipine (IV) Start at 1 mg/hr; max 21mg/h 2-4 min 5-15 min HTN post-CT surg
Antihypertensive Dosing – Floor
Agent Dosing Onset Duration Specific Indications
IV 10-80mg q10min until effect seen, then use PO 5-10 min 3-6 hrs Ao dissection, CVA;
Labetalol
PO Start 100mg q8-q12h (max: 2400mg/day) 20 min 8-12 hrs avoid in ADHF
IV 5-20mg q15-30min until see effect, then use PO 10-20 min 1-4 hrs
Hydralazine Eclampsia
PO Start 10 mg Q6H, inc by 10-25mg/dose q2-5d 20-30 min ~8 hrs
Captopril (PO) 12.5-25mg q8h (NOT TID) 30-90 min 6-8 hrs
Initial 2.5-5 mg QD. Inc 10 mg q2 weeks to max of 40 mg
Lisinopril (PO) 1 hr 24 hrs
QD. (Can use ARB if ACEi intolerance).
Initial 5 mg QD. Inc 2.5 mg q7 days to max 10 mg QD.
Amlodipine (PO) 24-48 hrs 24 hrs
Requires few days to take effect.
10-30mg TID. Use with caution (may cause pronounced
Nifedipine (PO) 20 min 6-8 hrs
vasodilation, orthostasis)
Hydrochlorothiazide Initial 12.5 mg QD (max: 50 QD, doses >25 mg
2 hrs 6-12 hrs
(PO) associated with  electrolyte derangements)
Isosorbide dinitrate Initial 5-20mg 2-3 times/day (dose TID not q8h for nitrate
1 hr ~8 hrs Anti-anginal, CHF
(PO) holiday). Mononitrate = long-acting
0.5-1.5 inches. Apply to chest. Need 10-12hr nitrate If lacking IV/PO
Nitropaste (topical) 15-30 mins ~12 hrs
holiday to avoid tachyphylaxis. access
David Olshan
36
TOC

Cardiology Peripheral Artery Disease / Cardio-Oncology

PERIPHERAL ARTERY DISEASE
Overview:
• Definition: arterial stenosis or occlusion causing an imbalance of blood flow relative to muscular metabolism
• Epidemiology: smoking, DM, HTN, HLD,  age (20% prevalence >70yrs) (Lancet 2013;382:1329)
Clinical Presentation and Diagnosis:
• Sx: classic claudication - reproducible exertional pain distal to occlusion; atypical leg pain (most common); asymptomatic (Circ
2006;113:e463). Critical Limb Ischemia: rest pain (improved w/ hanging feet off bed or walking), ulcers at pressure points, dry
gangrene, >2wks duration
• Exam: arterial bruit,  peripheral pulses (palpation, doppler),  cap refill, pallor on elevation, ulcers, atrophic changes,  hair growth
• ABI: doppler U/S. Ratio of DP/PT (higher of the two) SBP to brachial SBP. Abnormal: ≤0.9. ABI ≥1.30 suggests compressibility
usually due to  calcifications (e.g. elderly, DM, ESRD).
o If ABI abnormal: obtain segmental ABI w/ pulse volume recordings (PVR) to localize disease.
• Exercise testing: if high suspicion for PAD and normal resting ABIs
• CTA (w/ distal run off), MRA, or angiography: if considering revascularization
Treatment:
• Optimize cardiac risk factors (e.g. HTN, DM, HLD, weight loss), formal exercise program, high-intensity statin, smoking cessation.
• Ischemic ulcers: wound care, may also need revascularization for appropriate healing depending on ABI.
• Anti-platelets: if symptomatic, ASA 81-325mg QD or clopidogrel 75mg QD:  MI, CVA, vascular death (NEJM 2017;376:32). If
asymptomatic, can give ASA 81mg. Avoid DAPT (NEJM 2006;354:1706) unless clinically indicated, usually post-revascularization.
• Anticoagulation: rivaroxaban 2.5mg BID +ASA:  major adverse cardiac and limb events vs ASA alone (Lancet 2018;391:219). Caution
as  major bleeding, but no  fatal bleeding in pts w/ stable PAD in study
• Cilostazol: 100mg BID. Adjunct agent,  exercise capacity (Am J Cardiol 2002;90:1314). Contraindicated in HF.
• Endovascular repair (angioplasty vs stent) if: critical limb ischemia and/or severe symptoms refractory to medical management
Acute Limb Ischemia
• Sudden decrease in limb perfusion threatening viability (BMJ 2000;320:764). Surgical emergency - consult vascular surgery STAT.
o Viable: no immediate threat of tissue loss; audible arterial doppler signal, intact motor/sensory
o Threatened: salvage requires prompt intervention; no audible arterial doppler signal, motor or sensory
• Etiologies: embolic (e.g. AF, endocarditis) > acute thrombosis (e.g. atherosclerosis, APS, HITT), trauma
Precipitating factors: dehydration, HoTN, abnormal posture (i.e. kneeling), malignancy, hyperviscosity, hypercoagulability
• Presentation: (6Ps) Pain, Poikilothermia, Pallor, Pulselessness, Paresthesia (unable to sense light touch), Paralysis
• Diagnosis: pulse (w/ doppler) + neuro checks; angiography (CTA w/ run-off or arteriography)
• Treatment: urgent vasc surgery consult; anti-coagulation ± IA lytic; endovascular repair.
o After treatment, monitor for reperfusion acidosis, hyper-K, myoglobinemia (ATN) and compartment syndrome (BMJ 2000;320:764)

C A R D I O - O N C O L O G Y (JACC 2017;70:2536; JACC 2017;70:2552)

Overview: toxicities include HF, ischemia, HTN, myocarditis, pericardial Common Cardiotoxicities (Circ Res 2016;118:1008)
disease, thromboembolism, QTc prolongation, arrhythmia
Chemo-induced CM = EF drop ≥10% to <55% w/o sx or decline ≥5% to <55% Anthracyclines (doxorubicin): HF, LV dysfunction (5-
w sx (Eur Cardiol. 2018;13:64) 23% pts), based on cumulative dosage
Risk factors: heart disease, DM, HLD, young or old, female, high-dose chemo HER2 agents (trastuzumab): 2.1% risk in reducing LV
Dx: TTE (compare to baseline), EKG, TnT (correlates to adverse cardiac function, resolves once stopped, TTE q3mo
events post-chemo), MRI/PET/bx if suspect ICI myocarditis (Lancet Onc TKI (esp. sunitinib): HF, cardiac dysfunction
2018;19:e447) Angiogenesis inhibitors (bevacizumab,
Prevention: lenalidomide): HTN, 3-fold  in arterial TE events
• Consider BB/ACE-I if EF <50%, EF drop >10% or abnml TnT (Am J Clin Platinum-based (cisplatin): HTN, HL, CAD,
Onc 2018;41:909), ARB > BB protection against LVEF decline in early thromboembolic, in advanced testicular disease
breast Ca with adjuvant tx (EHJ 2016;37:1671)
Microtubule inhibitors (paclitaxel): arrhythmias
• Consider pre-emptive vasodilators/serial EKGs in 5-FU + capecitabine
Monitoring: Anti-metabolites (5-FU, cytarabine): MI, angina, CP,
• TTE surveillance schedule depends on therapy and baseline cardiac risk; EKG changes, 1-8% pts, early onset
ranges from Q3-Q6 months with long-term risk >10yrs Immune checkpoint inhibitor (ICI): fulminant
• Monitor weekly BP in first cycle, then Q2-3wks on therapy, initiate therapy lymphocytic myocarditis, HF, cardiac arrest; onset
when DBP >20mmHg variable, risk factor = combo therapy
Treatment: cessation of chemotherapy is a last resort Radiation: CAD (up to 85%), pericardial dz (6-30%),
• Appropriate risk factor modification, standard HF therapy, ischemia w/u CM (up to 10%), valvular abnormalities, PVD,
and tx (stress/cath, ASA if PLT >10k, DAPT if PLT >30K) arrhythmias, autonomic dysfunction, can occur 10-15
• HTN management as above yrs later, many RF incl dosage, metabolic RF
• Stress testing w/in 5-10 yrs after chest radiation
• ICI myocarditis: stop therapy, glucocorticoids/other immunosuppressives; re-challenging will depend on type of cardiotoxicity

Charlotte Lee and Erika Parisi

37
TOC

Cardiology Outpatient CV Health

EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE
Overview: leading cause of death in developed countries; CVD includes: CAD, CVA, PAD, aortic disease
Risk Factors:
● Non-modifiable: M 3x > F, age (each decade older confers 2x risk), FHx (1st degree relative <55M or <65F with CVD)
● Modifiable: HTN, HLD, DM, obesity, smoking, alcohol, exercise, diet, psychosocial stress, chronic inflammation, radiation, HIV, CKD
ASPIRIN FOR CVD PREVENTION
● 2019 ACC/AHA primary prevention guidelines recommend considering low-dose ASA for 1˚ prevention in select pts aged 40 to 70
yrs at higher ASCVD risk but not at increased bleeding risk. Avoid aspirin for 1˚ prevention in pts age >70 (Circ 2019;140:e596)
● ASCEND (pts >40 with diabetes), ARRIVE (moderate CVD risk pts), and ASPREE (elderly pts >70) showed variable CV benefit for low-
dose aspirin, at expense of increased bleeding events
OUTPATIENT BLOOD PRESSURE SCREENING AND MANAGEMENT
2017 ACC/AHA guidelines: HTN = SBP >130 or DBP >80 independent of kidney function or age; US prevalence 46% (HTN 2018;71:1261)
● Method: 2 checks > 1wk apart, sitting 5min with arm at heart level, cuff bladder 80% length & 40% width of arm circumference
● 24h ambulatory SBPs show greater association w/ all-cause mortality than clinic BPs. Masked HTN (normal BP in clinic,  outside)
more strongly associated than sustained HTN ( in both) or white coat HTN ( in clinic, normal outside) (NEJM 2018; 378:1509)
● Definition: Normal: <120/(and)<80; Elevated: 120-129/(and)<80; Stage 1 HTN; 130-139/(or)80-89; Stage 2 HTN: >140/(or)>90
Initial Workup: BMP, UA (with protein/Cr ratio), CBC, fasting glucose, TSH, lipids, baseline ECG (consider TTE to assess for LVH)
2˚ HTN: indications for workup include:
● Severe HTN (control w/ 4+ agents) or resistant HTN (not controlled on 3+ agents, one of which is a diuretic)
● Acute rise in blood pressure in a previously well-controlled patient, esp. diastolic BP
● Age < 30 years without risk factors (e.g. obesity, FHx)
Secondary Causes of HTN
Cause Clinical Clues Work-up
Medications/Drugs NSAIDS, OTC decongestants, OCPs, sudden
Thorough history
(use or withdrawal) d/c of anti-HTN meds (i.e. clonidine)
OSA Obesity, snoring, smoking Sleep study
Renal disease Elevated Cr, protein/blood on UA See AKI and CKD sections
Plasma aldo:renin activity; ratio >30. MUST measure in
Hypokalemia, hypernatremia, adrenal
Primary aldosteronism the morning (~8AM), after being upright/ambulatory for
incidentaloma, FHx
>3 hrs, with both drawn at the same time
>50% rise in Cr after ACEi initiation If intervention likely to be pursued, begin with Duplex
Renal artery stenosis Lateralizing abdominal bruit Doppler US (Sn 85%, Sp 92%)  if stenosis
Atrophic or asymmetric kidneys (ARAS>50%) or ambiguous results, then angiography.
Rare: pheochromocytoma (screen w/ 24h urine fractionated metanephrines/catecholamines [Sn 98%, Sp 98%], plasma fractionated
metanephrines if high suspicion), Cushing’s disease, hyper/hypothyroidism, hyperparathyroidism, aortic coarctation, ADPKD
Lifestyle Counseling (JACC 2014;63:2960)
Exercise 40 min per day, 3-4x/week, moderate to vigorous intensity  5mmHg for aerobic exercise, unclear for resistance
Diet Dash diet (salt intake <2g per day);  sweets & red meat  8-14 mmHg (DASH); dec by 2-8 mmHg (low Na)
Caffeine Limit to <2 cup per day  5/2.5 mmHg
Alcohol Limit consumption (<2-3 standard drinks per day)  2-4 mmHg
Medical Management – 2017 ACC/AHA Guidelines
When to Treat Stage II HTN or Stage I if: clinical CVD, DM2, CKD, or ASCVD ≥10%
Target BP <130/80
First-line: thiazides (recent data suggests that chlorthalidone may not be > HCTZ,  side effects JAMA Int
Choice of Agent Med 2020;180:542), ACEi/ARB, CCB
Other: βB, hydralazine, isosorbide, clonidine, α-blockers (e.g. doxazosin), minoxidil (rare)
African-Amer: CCB, thiazide HF: βB, ACEi/ARB, diuretic, spiro DM2: ACEi/ARB (if proteinuria)
Compelling Indications
CAD: βB Pregnancy: labetalol, CCB CKD: ACEi/ARB
BP check 2-4 weeks after change in medication (home readings vs. office),
Monitoring
Labs: yearly BMP/Mg if on ACEi/ARB or diuretic
SPRINT: high risk for CVD: SBP goal <120 vs 135-139  CVD events and all-cause mortality but  non-
Important Trials orthostatic hypotension, syncope, electrolyte abnormalities, and AKI.
ACCORD BP: showed no benefit for CV mortality in pts w/ DM for SBP goal of <120 vs <140.
OUTPATIENT CHOLESTEROL SCREENING AND MANAGEMENT
2018 ACC/AHA guidelines refine ASCVD risk categories w/ focus on “risk-enhancing” factors to further est. CV risk (Circ 2019;139:e1082)
● Screen adults ≥ 20 years
● Fasting not routinely needed unless evaluating for hyperTG; if non-fasting TG >440, then obtain 12- to 14-hr fasting panel
● AHA criteria for FH: LDL-C >190 and either: 1° relative similar or premature CAD or genetic testing for LDLR, APOB, PCSK9
● Assess lipids 4-12 wks after initiation of med or dose change, repeat 3-12 mo. as needed
Mitu Bhattatiry
38
TOC

Cardiology Outpatient CV Health

Lifestyle modification: weight loss, exercise, smoking cessation, diet low in sat. fat a/w 15-20 mg/dL  in LDL-C, ~50%  risk of CAD
Can also refer to ESC Guidelines, overall stricter with absolute goal of LDL <55 in “very high risk” patients (EHJ 2020;41:111)
Indications for Lipid-Lowering Therapy
ASCVD Risk Score
Clinical ASCVD Maximally-tolerated statin to reduce LDL-C by ≥50%
LDL-C ≥190 High-intensity statin; if LDL-C remains ≥100, sequentially consider adding ezetimibe and PCSK9 inhibitor
Diabetes (age 40-75) Moderate-intensity statin; consider high-intensity statin for ASCVD risk >7.5% to reduce LDL-C by ≥50%
Age 40-75 w/o above For low risk <5%, lifestyle changes; borderline risk 5-7.5%, consider mod-intensity statin based on risk-
enhancers*; intermediate risk 7.5-19.5%, statin to  LDL-C ≥30%; high risk >20%, statin to  LDL-C ≥50%
ASCVD risk enhancers: FHx premature ASCVD, LDL-C ≥160, CKD, metabolic syndrome, inflammatory dz (RA, HIV, psoriasis), ethnicity
(South Asian), TG ≥175, hs-CRP ≥2, Lp(a) ≥50, apoB ≥30, ABI <0.9.
Coronary artery calcium (CAC) score 1-99 favors statin therapy; CAC 100+, initiate statin.
Common Medications
Medication Mechanism Indication %  in LDL-C Effect on CV outcomes Adverse effects
For 1° & 2°prevention, Myopathy,  LFTs,
HMG-CoA reductase 1st-line therapy for 1° & 20-60% LDL-C
Statins* CV events (ARR 1.1%, memory loss and
inhibitor 2°prevention reduction
NNT 91, HOPE-3) confusion
- Statin-intolerant
Ezetimibe + Ezetimibe + statin CV
Ezetimibe intestinal cholesterol - LDL-C >70 w/ CVD or Mild  LFTs
statin therapy  events (ARR 2%, NNT
(10mg QD) absorption <50% LDL-C w/o CVD (usually w/ statin)
LDL-C by ~23% 50, IMPROVE-IT)
on max-tolerated statin
Evolocumab + statin
PCSK9 High risk pts w/ CVD 38-72% CV events (ARR 1.5%, Uncommon; mainly
Promotes degradation
inhibitors and LDL-C >70 on reduction; ~60% NNT 67 at 48 wks, injection site
of LDL-R on
(alirocumab, statin+ezetimibe; in pts on statin FOURIER); Alirocumab + reactions.
hepatocyte surface
evolocumab) approved for use in FH therapy statin CV events (ARR Cost: 150k/QALY
1.6%, ODYSSEY)
O3FAs (e.g. TG ≥30% with EPA + statin CV Med interaction
Incorporates into Severe hyperTG, CVD
Vascepa no change in events (ARR 4.8%, NNT (e.g. warfarin), GI
phospholipids prevention
[EPA]) LDL 21, REDUCE-IT) sx
Note: if patient has concomitant severe hypertriglyceridemia (TG > 886 mg/dL), then also start fenofibrate (many formulations)
Statin Potency *Statin Properties:
High-intensity atorvastatin 40-80mg, rosuvastatin 20- Biggest change in LDL: rosuvastatin > atorvastatin > simvastatin
(≥50% LDL-C) 40mg Safest in CKD: atorvastatin, fluvastatin (no renal dose adj. required)
atorvastatin 10-20mg, rosuvastatin 5- Safest in cirrhosis: pravastatin
Moderate-intensity Lowest rate of myopathy: pravastatin, fluvastatin
10mg, simvastatin 20-40mg,
(30-49% LDL-C) Least DDI: pravastatin, rosuvastatin, fluvastatin (no CYP450 metabol.)
pravastatin 40-80mg, lovastatin 40mg
Low-intensity simvastatin 10mg, pravastatin 10- Lower overall side effects: pravastatin, rosuvastatin (hydrophilic)
(<30% LDL-C) 20mg, lovastatin 20mg ACC Statin Intolerance Tool: to assess for muscle side effects

OUTPATIENT OBESITY SCREENING AND MANAGEMENT

Definition: Overweight: BMI 25.0-29.9 kg/m2; Obesity: BMI ≥ 30 kg/m2; Severe Obesity: BMI ≥ 40 kg/m2
Management:
Set goals: target initial weight loss of 5-7% body weight To lose 1-2 pounds per week:
Diet: diet compliance ( # calories) more important than macronutrient • Total daily caloric intake should = daily caloric requirement
composition. No data to guide specific diet choice (JAMA 2014;312:923) – 500
● Mediterranean: high in monounsaturated fats, fruits, vegetables, • Daily caloric requirement = basal metabolic rate (BMR) +
legumes, grains; moderate dairy & EtOH; low meat ( overall daily activity level + thermic effect of food [theoretically]
mortality, CV mortality; may  DM incidence independent of
weight loss) (NEJM 2018;21:378) Benefits of Weight Loss on Comorbidities
● DASH: high in fruits/vegetables, moderate dairy, <25% DM or at 2.5-5kg wt loss over ≥2 yrs: risk T2DM 30-60%
caloric intake from fat (SBP/DBP) (Br J Nutr 2015;14:113) risk 2-5% wt loss: HbA1c by 0.2-0.3% in 1-4 years
Exercise: HLD 5-8kg weight loss:  LDL 5 mg/dL,  HDL 2-3 mg/dL
● >30 min, 5-7 days/wk; combine aerobic + resistance training HTN 5% weight loss: SBP 3 mmHg & DBP 2 mmHg
for optimal health gains (Arch Intern Med 2009;169:122) CVD MI: HR 1.26 for overweight and HR 1.88 for obese
● Not sufficient for wt loss; improves glycemic control, BP, and (Curr Obes Rep 2017;6:187)
functioning; CVD risk, predicts long-term weight mgmt
Medications:
● Consider pharmacotherapy if BMI ≥30 or BMI ≥27 with ≥1 comorbidity
● Options: Orlistat, phentermine/topiramate, naltrexone/bupropion, lorcaserin, liraglutide, metformin (if pre-diabetic)
● All have significant short-term weight loss (~5-15 lbs), but weight is typically gained back when medication d/c’ed
Bariatric surgery: recommended for: BMI ≥40 OR BMI ≥35 with comorbid conditions; BMI <35 with insufficient evidence

Mitu Bhattatiry
39
TOC

Cardiology Anti-Arrhythmic Medications

Anti-Arrhythmics
Class Generic Mechanism Usage Dosing Side effects
Na+ channel blockade; Load 20mg/min until total 17 mg/kg reached
VT; AF, especially in HoTN, PVCs, VT,
Procainamide slows conduction; (e.g. ~1h, BP q5 min); then 1-4 mg/min
accessory bypass QT, drug-induced
(IV) lengthens action (in urgent situations, up to 50 mg/min may be
tracts (WPW) lupus, agranulocytosis
potential given for a total max dose 17 mg/kg)
IA VT: If <50kg load 200mg x1, then 100mg
Used in HOCM (efficacy Anticholinergic side
Na+ channel blockade; q6h; if >50kg load 200mg x1, then 150mg
Disopyramide relates to negative effects, negative
also has anticholinergic q6h
(PO) inotropic effect), VT, AF, inotropy, hypotension, 
effects AF conversion: 200mg q4-6h
A-flutter QTc
AF prevention: 400-750mg daily divided q6h
Bradycardia, junctional
Na+ channel blockade; Load: bolus 1.0-1.5 mg/kg. May give additional arrhythmia, HoTN,
Lidocaine no effect on conduction; 0.5-0.75 mg/kg IV push PRN q5-10 min; max angina, AMS, tremor,
VT, pulseless VT/VF
(IV) may shorten action total: 3 mg/kg seizure, dysarthria,
IB potential Maintenance: 1-4 mg/min (30-50 mcg/kg/min) paresthesias, nausea,
dizziness
Mexiletine PO analogue of Load: 400mg x1
VT Tremor, nausea
(PO) lidocaine Maintenance: 200mg q8hrs
pAF (“pill in the pocket”), Pill in the pocket: 200mg (<70kg) or 300mg Ventricular arrhythmia
Flecainide
Na+ channel blockade rarely ventricular (>70kg). Max: once/24hrs (high risk if any structural
(PO)
arrhythmia Maintenance of sinus rhythm: 50-150mg BID heart disease)
IC Pill in the pocket: 450mg(<70kg) or 600mg
Propafenone Na+ channel blockade; GI sx, dizziness, pro-
Same as above (>70kg). Max: once/24hrs
(PO) Some β1 blockade arrhythmia
Maintenance of sinus rhythm: 225-425 BID
Load: 20-30 mg IV (500 mcg/kg) x1 min
Esmolol β1 antagonist. Acute HR/BP control in
Maintenance: 2-21 mg/min IV (25-300
(IV) t 1/2 = 9 min Ao dissection, SVT
mcg/kg/min) Same as other β-blockers
β1 antagonist; atenolol SVT, ACS, post-MI, CAD, Atenolol is renally cleared
Atenolol
2x more potent than 25-50mg QD (max: 100mg QD)
(PO) HTN, chronic HF
metoprolol
II
Thyroid storm, Ao
IV: 0.5-1mg load, followed by 1-3mg every Crosses BBB and may
Propranolol dissection, tremor,
several hours cause AMS. Less HoTN
(IV, PO) variceal bleed ppx, pheo,
Non-selective β-blocker PO: 120-320 mg/day (based on indication) than β1 antagonists.
anxiety
Nadolol Variceal hemorrhage Changes in mental
20-80mg QD (max: 240mg)
(PO) prophylaxis status. Less HoTN
HoTN (IV),
Pulseless VT/VF: 300 mg IV push, may repeat
bradycardia,QT. Long
Blocks K channels,
+ 150 mg IV push every 3-5 min as needed
t1/2 (58d). Multiple
slowing repolarizaqtion. WCT:
systemic side effects with
Multiple effects - IV: load with 150 mg IV x1 (may repeat q10
Amiodarone SVT, VT, pulseless long-term use (lung,
including class Ia, II, min as needed), then 1 mg/min IV x 6h (360
(IV/PO) VT/VF hepatotoxic, thyrotoxic;
and IV properties. Class mg), then 0.5 mg/min IV x 18h (540 mg)
check baseline PFTs,
II property (i.e. BB) is - PO: total 8-10 grams over days (200-400mg,
LFTs, TFTs). Do NOT
fastest effect. BID-TID)
use for torsades, pre-
- Maintenance: 100-200 mg PO QD-BID
excitation.
III IV: start 75mg IV q12h, may increase dose by
Nonselective 37.5mg/dose q3d (max: 600mg/day)
Sotalol QT prolongation, typical
β1/β2 antagonist, K+ AF, VT PO: start 80mg PO q12h, may increase dose
(IV, PO) effects of β-blockade
channel blockade by 40mg/dose q3d (max: 640mg/day)
- Adjust dosing interval in renal impairment
>60kg: 1mg over 10min; can repeat x1 in
Ibutilide QT prolongation, 1.7%
AF, AFlutter 10min; <60kg: 0.01mg/kg over 10min; can
(IV) Blocks K+, prolongs TdP, HA
repeat x1 in 10min
action potential
Dofetilide Intial dose 500 mcg BID max QT prolongation, renally
AF, AFlutter, SVT
(PO) Decrease dose if CrCl<60 cleared (CI if CrCl<20)
IV: 0.25 mg/kg (max 25 mg, usual 15-20 mg) IV
Diltiazem over 2 min; may repeat q15min as needed; gtt
(IV, PO) Contraindicated in SSS,
CCBslows AV node @ 5-15 mg/hr
bradycardia, 2°AVB,
conduction and phase II AF, AFlutter, SVT, MAT, PO: 120-320mg QD (max: 480/day)
IV of the cardiac angina IV infusion: 5-10mg IV bolus over 2 min, repeat
3°AVB, VT,
Verapamil AF + WPW, hypotension,
action potential q15-30min PRN (max: 20-30mg); start gtt at
(IV, PO) pulmonary edema, HFrEF
0.3mg/kg/hr if needed
PO : 80-120mg TID (max : 480/day)

Jacqueline Henson
40
TOC

Pulmonary & Critical Care Respiratory Distress

Respiratory distress is a constellation of symptoms that portends impending Dyspnea DDx:
respiratory collapse. It is different from dyspnea, which is the subjective - CV: MI, HF, valv. disease, arrhythmia,
sensation of shortness of breath. Key symptoms of respiratory distress are: tamponade, PE, PHT
• Tachypnea (go look at the patient and measure yourself. RR ≥20) - AIRWAYS: asthma, COPD, mucus plugging,
• Cyanosis (typically SpO2 <80%) angioedema, anaphylaxis, foreign body
•  WOB (nose flaring, retractions, grunting, tripod-ing, diaphoresis) - ALVEOLI: edema, PNA, hemorrhage
• Obstruction (wheezing, stridor) - PLEURAL: large effusion, PTX
- CNS: CVA, intox (CO, ASA), met. acidosis
APPROACH: 2/2 sepsis, DKA, etc, psych/anxiety
- OTHER: anemia, abd girth, ALS/GBS/MG,
1) Confirm code status
spinal cord, deconditioning
2) Low threshold to call Rapid Response for assistance
3) Assess respiratory status
o Place on supplemental O2: NRB to start, can always wean later
o Red flags (CALL RICU STAT for intubation, x6-3333): GCS <8 (hard criteria for intubation), pooling airway
secretions, hemoptysis, life-threatening hypoxemia despite supplemental O2 (SpO2 <80%, PaO2 <55 mmHg), severe
hypercarbia despite BiPAP, tiring out (increased work of breathing, progressive hypercarbia), RR >35
– Temporize: suctioning, jaw-thrust or chin lift to open airway, AMBU bag ventilation
4) Initial workup (think about PNA, CHF, COPD, sepsis, ARDS) (J Hosp Med 2013;8:76)
o EKG: ST depressions/elevations (ischemic changes), sinus tach / e/o RV strain (PE), arrhythmia (AF+RVR, SVT, VT)
o CXR (order STAT and must call x6-3050): look for new infiltrate (aspiration, PNA), pulmonary edema, lobar collapse
(consider mucus plug), PTX. Call x4-1533 for read. If normal, think about ischemia, PE, acidosis, etc.
o ABG: worrisome if PaCO2 >45 mmHg (poor ventilation), PaO2 <60 mmHg (poor oxygenation), pH <7.25
o Labs: VBG (and ABG if possible, helpful to correlate to VBG), hs-Trop, NT-proBNP, lactate, BMP, CBC
o Additional studies based on clinical suspicion: CT-PE (if stable to travel), TTE (acute valvular disease, RH strain)
5) Subsequent workup: see specific pages for further guidance

TREATMENT:
• Supplemental oxygen therapy (see Oxygen Delivery Therapies section for more detail):
o NC: for every liter increase in O2,  FiO2 0.03/L (max: 6L = 0.40 FiO2)
o Venturi masks: pre-set FiO2 (0.24, 0.28, 0.31, 0.35, 0.40) (flow rate decreases with increasing FiO2)
o NRB: can give FiO2 ~0.90, but in tachypneic patient, FiO2 ~0.60 (due to entrainment of room air)
o HFNC: FiO2 0.6 to 1.0 at 10-60 L/min (humidified air); 90-day mortality vs. NIPPV for pts with hypoxemic respiratory
failure not due to pulmonary edema or obstructive lung disease (NEJM 2015;372:2185)
• NIPPV (BIPAP for COPD; CPAP for CHF): RR >25-30, accessory muscle use, pH <7.35, PaCO2 >45mmHg
• Intubation: See red flags above

DISEASE SPECIFIC TREATMENT:

• CHF: CPAP, IV diuresis, nitrates (paste or drip, if BP room), low dose morphine (1-2mg)
• COPD: BiPAP, nebulizers (stacked DuoNebs x3), steroids (PO pred 40mg = IV methylpred 32mg); if severe exacerbation,
consider methylpred 60-125mg q6h; abx if 2/3: sputum volume, purulence, or dyspnea
• PE: if high suspicion and no contraindication, start empiric anticoagulation (Lovenox therapeutic faster than heparin gtt)
• PTX: if unstable, needle thoracostomy (14G angiocath, 5th ICS at mid-axillary line or 2nd ICS at mid-clavicular line); STAT
page Thoracic Surgery/IP for chest tube
• Pleural effusion: thoracentesis (see Procedures; must be performed by IP or supervised by pulm attending)
• Opioid overdose: Narcan 0.4-2mg IV/IM Q2 minutes, observe response; given short half-life, consider gtt if response
• Anaphylaxis: Epi (1:1000) 0.3 mL = 0.3 mg IM, methylprednisolone 125mg IV, diphenhydramine, ranitidine
• Cardiac ischemia: ACS treatment (see Cardiology section) – ASA 325, atorva 80, TNG (SLgtt), heparin gtt, BB

Rapid Response x6-3333 (Senior On, nursing supervisor, RT, pharmacy) | STAT page RICU x6-3333
• RICU communication guide: have information ready for RICU prior to intubation; greet RICU in patients’ room
Code status Urgency/acuity of decline
Hemodynamics – LV, RV, valves, volume status, access Difficult airway (look for prior intubation notes)
Aspiration risk – NPO status, last meal, risk factors Allergies
• Have ready: sedation (propofol/fentanyl/versed), pressor (Neo >> Levo), IV fluids w/ push line; RICU brings paralytic
• MICU/CCU: Resource RN will call for RICU; make sure attending/OI, fellow, RT and RN are aware of plan
• INTUBATION IS NOT AN ACT OF WEAKNESS: do not delay intubation in patients with impending respiratory failure

Matthew Emmett and Sirus Jesudasen

41
TOC

Pulmonary & Critical Care Hypoxemia & Hypercarbia

Respiratory Failure: inability to oxygenate (deliver O2) or ventilate (blow off CO2). Can be hypoxemic (PaO2 <60 mmHg),
hypercarbic (PaCO2 >45 mmHg), or both. A quick algorithm can be used to determine the etiology based upon ABG results:
Hgb Dissociation Curve

O2 sat (%)
PaO2 (mmHg)

P:F Ratio
Quick surrogate for A-a gradient
Can’t use if significant pCO2
P=PaO2 / F=FiO2
P:F<300 = mild ARDS
P:F<200 = moderate ARDS
P:F<100 = severe ARDS

HYPOXEMIC RESPIRATORY FAILURE

• Hypoventilation; low FiO2: decreased O2 delivery to lungs Pulmonary Physiology
• V/Q mismatch: imbalance in delivery of oxygenated air & blood flow
Normal
1. FOCAL alveolar infiltrates: PNA, edema, hemorrhage Deadspace Shunt
2. Airway: asthma, COPD, bronchiectasis
VA/Q > 1→ ↑CO2 VA/Q < 1→ ↓O2
3. Vascular: pHTN, PE
4. Iatrogenic: too much PEEP
• Shunt: flow of blood through lung without encountering oxygenated
air, “perfusion without ventilation” (severe V/Q mismatch)
1. DIFFUSE alveolar infiltrates: above + ARDS
2. Alveolar collapse: PTX, atelectasis, mucus plug
↑ventilation ↑perfusion
3. Intra-cardiac/intra-pulmonary shunt: PFO, AVM (e.g.
↓perfusion ↓ventilation
hepatopulmonary)
NOTE— continuum between
• Impaired diffusion ( DLCO): hypoxemia worse w/ exertion these extremes - can still have
o ILD (correlates with severity on CT), pHTN, advanced COPD V/Q mismatch

HYPERCARBIC RESPIRATORY FAILURE

• “Won’t breathe” (RR): sedatives, obesity hypoventilation, central
sleep apnea, brainstem stroke/tumor/infection (pons & medulla), Acid-Base Interpretation:
hypothyroidism (myxedema coma), compensation for metabolic alkalosis HypercarbiaRespiratory acidosis ( pCO2)
(chemoreceptors) • Acute: HCO3  by 1 (per pCO2  10)
• “Can’t breathe” (VT): nerves/muscles/chest wall/airways • Chronic: HCO3  by 3-4 (per pCO2  10)
1.  Alveolar dead space (airspace which does not participate in gas HypocarbiaRespiratory alkalosis ( pCO2)
exchange; “ventilation without perfusion”) • Acute: HCO3  by 2 (per pCO2  10)
 Dead space = anatomic (~150cc upper airway air without • Chronic: HCO3  by 5 (per pCO2  10)
perfusion) + alveolar (~0 normally; in disease, capillaries get destroyed or compressed  VD)
 Parenchyma: emphysema, ILD/fibrosis, CHF, PNA, ARDS
 Airway: asthma, COPD, CF, bronchiectasis, OSA, tumor, foreign body, high PEEP
 Vascular: severe PE (wasted ventilation due to blocked circulation; more often see pCO2 2/2 hyperventilation)
2. Chest wall/pleural constraints  lung volume: effusion/fibrosis, obesity, kyphosis/scoliosis, abd distension, PTX
3. Neuromuscular (Neurol Clin 2012;30:161): neuropathy (C-spine/phrenic nerve, GBS, ALS, polio), NMJ disorder
(MG, botulism), myopathy (polymyositis/dermatomyositis, hypophosphatemia), critical illness. Consider EMG.
•  CO2 production (VCO2):  WOB, fever, seizure, sepsis, steroids, overfeeding, thyrotoxicosis

Michael Kelly and Krystle Leung

42
TOC

Pulmonary & Critical Care Non-Invasive Oxygenation/Ventilation

OXYGEN DELIVERY DEVICES
Low Flow Devices
● Nasal cannula: FiO2 24-40%. Variable flow/FiO2 relationship (3-4%/L). Max flow 6L. Humidify if >4L
● Simple facemask: FiO2 35-50%. Keep flow >5L to avoid rebreathing trapped CO2 in mask. Max flow 10L.
● Shovel mask: FiO2 24-50%. Difficult to control FiO2 – consider in patients with stable need for O2 who do not tolerate NC
or require more humidity for comfort.
Reservoir Systems
● Oxymizer: FiO2 24-45%. Small (20cc) reservoir stores O2 and delivers a “push” of high FiO2 oxygen with inspiration. Can
deliver slightly higher FiO2 than NC. Can decrease flow needs (esp. for outpatients) by increasing available O2.
● Non-rebreather: easily accessible – consider starting with this for the acutely hypoxemic patient
o Theoretically delivers 100% FiO2, but true delivery 60-90% FiO2 due to entrainment of room air
o Air entrainment is increased (true FiO2 lower) when patient is tachypneic or drawing large tidal volumes
o Flow should be set >10L to adequately fill the reservoir – want bag collapse <1/3 on inspiration. Max flow 15L.
High Flow Devices
● Venturi mask: FiO2 24-50%. Colored valve designed to permit constant flow of room air mixed with O2 source to deliver a
fixed FiO2 independent of patient’s RR and tidal volume. Total gas flow rate decreases with increasing FiO2.
o Color coded by FiO2: Blue 24%, White 28%, Yellow 35%, Red 40%, Green 60%
o Consider for patients who need careful titration of oxygen, such as a COPD patient with set SpO2 goals.
NOT for use in acute respiratory distress.
• High-flow nasal cannula (HFNC): delivers up to 100% FiO2 (when mouth is closed) at flow rates 10-60 L/min and
provides small amount of PEEP (approximately 0.7 cm H2O/L) when patient’s mouth is closed
o Consider use in pure hypoxemic respiratory failure
o No Δ in intubation rates vs. NIPPV, but may  90-day mortality for pts with hypoxemic respiratory failure not due to
pulmonary edema or obstructive lung disease (NEJM 2015;372:2185)
o Mixed data in immunocomp. pts on whether  intubation (Intensive Care Med 2017;43:1808, JAMA 2018;320:2099)
o Extubation to HFNC similar to extubation to NIPPV in terms of reintubation rate (JAMA 2016;316:1565)
Caution: liberal supplemental of oxygen to improve SpO2 above 94-96% in acutely ill adults is associated with mortality
(Lancet 2018;391:1693)
NONINVASIVE POSITIVE PRESSURE VENTILATION (NIPPV)
• CPAP (continuous positive airway pressure): provides PEEP, which prevents upper airway collapse (e.g. OSA) and lower
airway collapse (e.g. atelectasis) while raising intrathoracic pressure and decreasing venous return (e.g. helpful in CHF)
o In CHF,  intubation,  mortality (NEJM 2008;359:142, Cochrane Rev 2013)
• BiPAP (bi-level positive airway pressure): provides both inspiratory positive airway pressure (IPAP) and expiratory
positive airway pressure (EPAP = PEEP)
o Can be helpful for hypercarbic respiratory failure caused by hypoventilation as IPAP decreases respiratory
fatigue/WOB, especially in obstructive lung disease and neuromuscular disease.
o In COPD,  mortality, intubation, and LOS (Cochrane Rev 2017)
Strong Indications for NIPPV (ERS/ATS: ERJ 2017;50) Weak Indications for NIPPV
• Cardiogenic pulmonary edema (CPAP/BiPAP) • Hypoxemic resp. failure (other than CHF/COPD)
• COPD exac. w/ acute resp. acidosis (BiPAP) • Patient is DNI w/ indication for intubation
• Ppx against extubation failure in high risk pts • Palliation for increased WOB, dyspnea
• Respiratory failure in immunocomp. pts • Asthma exacerbation w/ acute resp. acidosis
Contraindications to NIPPV
• Risk of delay: emergent indication for intubation, acute life-threatening non-respiratory organ failure
• Risk of aspiration: cannot clear secretions, AMS if pt cannot remove mask (exception: AMS due to hypercarbia)
• Risk of injury: pneumothorax (can induce tension physiology), recent esophageal anastomosis or tear, patient cannot
tolerate decreased preload ( venous return), facial trauma or recent facial surgery
• Will not work: patient cannot initiate breath, anatomic deformity or facial hair interrupting seal

BiPAP/HFNC on the floor: huddle with nursing and RT (also notify Senior On). Trial BiPAP or HFNC no more than 2-3
hours and assess response; consider ABG/VBG to assess change in oxygenation or ventilation. If no improvement,
discuss escalation of care to ICU.
REMEMBER: BiPAP/HFNC should NOT be used to delay intubation!

Matthew Emmett and Krystle Leung

43
TOC

Pulmonary & Critical Care Asthma

PULMONARY FUNCTION TESTING

ASTHMA – DIAGNOSIS & OUTPATIENT CARE

DEFINITION: chronic, variable airway narrowing with intermittent dyspnea, wheeze, and/or cough (JAMA 2017;318:279)
DIAGNOSIS:
Spirometry Obstructive, reverses w/ bronchodilator, worsens w/ methacholine (can be nml before provocation)
Peak expiratory flow (PEF) Estimates degree of control. <80% personal best c/w poor control. ♀: 300-500, ♂: 450-750 L/min
Allergy testing If allergic component suspected (sx w/ exposure/persistent sx):  IgE, CBC+diff (Eos), refer to Allergy.
New-onset adult cases unusual  should consider systemic disease (ABPA, EGPA, systemic mastocytosis), occupational
asthma (10-25%; NEJM 2014;370:640), aspirin-exacerbated resp. disease (esp. if nasal polyps; J Allergy Clin Immunol 2015;135:676)
MANAGEMENT: (GINA guidelines: ERJ 2019;53:1901046)
• Controller + reliever: stepwise based on severity (see below); step up if not controlled; step down if well controlled 3mo.
o Note: changes in recent guidelines to recommend that all receive ICS-containing controller; no longer rec. SABA only tx as
a/w  allergic responses & airway inflammation,  response when SABA needed, & overuse a/w  severe exacerbations
o In mild asthma, PRN budesonide-formoterol (Symbicort) > PRN SABA (Novel START NEJM 2019;238:2020; SYGMA1 NEJM
2018;378:1865) & non-inferior to maintenance ICS for preventing exacerbations (though  sx; SYGMA2 NEJM 2018;378:1877)
o In mild/mod., maintenance ICS-LABA + PRN ICS-LABA also > + PRN SABA (AJRCCM 2005;171:129; Chest 2006;129:246).
PRN ICS w/ SABA > PRN SABA alone (TREXA Lancet 2011;377:650).
o May be some phenotypes however w/ low eos. inflamm. (<2% in sputum) in whom ICS  effective (NEJM 2019;380:2009)
• Trigger avoidance: e.g.: exercise, cold air, irritants (smoke, perfume), allergens, infxn, drugs (ASA, NSAIDs, β-blockers)
• Exacerbations: short course pred. 40-50mg x5-7d on top of controller/reliever regimen. Severe
o Consider 4x controller ICS for mild exacerbations (NEJM 2018;378:902) Severe Step 5
Moderate Step 4
High-dose
Mild Step 3
ICS-LABA
Mild Step 2
Medium-dose + referral to
Step 1 Daily low-dose ICS or Low-dose
ICS-LABA specialist
PRN low dose PRN low-dose ICS- ICS-LABA
Preferred Controller (consider biologics)
ICS-formoterol formoterol
Low-dose ICS taken High-dose ICS, add-
Low-dose ICS taken Med-dose ICS or Low-dose oral
Other Options w/ SABA (if combo on tiotropium or add-
w/ SABA; or LTRA low-dose ICS + LTRA corticosteroids
not available) on LTRA
PRN low-dose ICS-formoterol
Preferred Reliever PRN low-dose ICS-formoterol
NOTE: Pt must also be ICS on maintenance
Other Options PRN SABA
ICS: inhaled corticosteroids | LABA: long-acting β-agonists (e.g. formoterol) | SABA: short-acting β-agonist | LTRA: leukotriene receptor antagonist
Biologics: anti-IL4: dupilumab; anti-IgE: omalizumab (Annals 2011;154:573); anti-IL5: mepo-, res-, benra- lizumab, tezepelumab (AJRCCM 2019;199:433)
Contraindicated to use LABA without ICS (CHEST 2006;129:15; NEJM 2010;362:1169)
ASTHMA - INPATIENT CARE
•  PEF (via RT; severe <50%), CXR ± RVP; ABG if severe. Expect resp. alkalosis; norm./ pH may = impending resp. failure.
Floor Patient ICU Patient (Thorax 2003;58:81)
- Bronchodilators: albuterol +/- ipratropium - Bronchodilators: albuterol + ipratropium
o DuoNebs in ED a/w  admit (Cochrane Rev 2017) but evidence - Methylpred 125mg IV q6h (Archives 1983;143:1324)
in children that no benefit after hospitalized - BiPAP: limited data, generally avoided in adults
o Can Δ to SABA alone after admit unless severe/worsening - Rescue therapies: continuous albuterol nebs (CAB), Heliox
- Steroids: pred 40-60mg or IV methylpred 40-60mg q12-24 (if (lower density gas, data controversial)
 PO / impending arrest); total x5-7d (Cochrane Rev 2016) - Mechanical ventilation: large ET tube, high insp flow rate
- O2 >92% (93-95% in severe; >95 pCO2; Thorax 2011;66:937) (80-100 L/min), low VT (6-8 cc/kg), low RR (10-14), paralysis;
- If impending respiratory failure: stacked DuoNebs (x3/hr), Goal: maximize expiratory phase, permissive hypercapnia
methylpred IV 60-125mg, Mg IV 2g / 20 min, transfer to ICU
A S T H M A / C O P D O V E R L A P ( A C O ) (GINA Guidelines; ATS/NHLBI: AJRCCM 2017;196:375; NEJM 2015;373:1241)
• Some patients have persistent airflow limitation together w/ clinical features c/w both asthma and COPD
• ICS-containing treatment is essential; LAMA or LABA should not be given without ICS. Can escalate to triple therapy, biologics.

Michael Kelly
44
TOC

Pulmonary & Critical Care COPD

DEFINITION: persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities
Diagnosis of COPD (GOLD Guidelines: AJRCCM 2017;195:557)
1. Diagnosis: spirometry w/ FEV1/FVC <0.7 (actual, not predicted; no sig. Δ w/ bronchodilator)
2. Determine severity of airflow limitation: GOLD grade based on FEV1 
3. Evaluate sx/risk of exacerb.: mMRC, CAT score, exacerbation hx  GOLD ABCD group
mMRC
0 = SOB w/ strenuous exercise
1 = SOB when hurrying or walking up slight hill
2 = walks slower d/t SOB or has to stop
3 = stops for breath after 100yds or few min.
4 = too SOB to leave house, SOB w/ dressing

Management of Stable COPD (GOLD 2020 Guidelines; NEJM 2019;381:1257)

Pharmacologic interventions: based on level of sx and risk of exacerbations
GOLD A GOLD B GOLD C GOLD D
(Less sx, low risk) (More sx, low risk) (Less sx, high risk) (More sx, high risk)
LAMA (+ PRN SABA)
PRN SABA, SAMA or LAMA (or LABA)
Starting tx: LAMA (+ PRN SABA) If severe sx (e.g. CAT >20), start with
SABA+SAMA + PRN SABA (or SAMA)
LAMA+LABA or LABA+ICS (if Eos >300)
LAMA+LABA+ICS (unless Eos <100)
LAMA+LABA LAMA+LABA
Escalate to: LAMA If persistent sx: PDE4i, azithro, theophylline
or LABA+ICS or LABA+ICS
If refractory: lung vol. reduction, transplant
- SABA+SAMA > - LAMA > LABA (in ≥C) (Cochrane Rev 2012, NEJM 2011;364:1093) - LAMA+LABA+ICS > LAMA+LABA (Lancet
either alone (Chest - LAMA+LABA > monotx (Chest 2014;145:981, Cochrane Rev 2015) 2018;391:1076; NEJM 2018;378:1671)
1994;105:1411) - LAMA+LABA > LABA+ICS (NEJM 2016;374:2222) but - Consider d/c ICS if persist. exacerb, PNA
- LAMA may   LABA+ICS may be pref. if asthma/allergies/rhinitis, hx of (NB if Eos >300 high risk exacerb. w/ d/c)
Notes decline in FEV1 in exacerbations, Eos >300, or combination - PDE4i   exacerb (Lancet 2015;385:857)
early-stage COPD; - LABA+ICS may have  mortality vs. LABA but no Δ in - Azithro   exacerb. but hearing loss,
(NEJM 2017;377:923) exacerbations and  in PNA (AJRCCM 2008;177:19) risk of abx resistance (NEJM 2011;365:689;
- Little benefit to ICS if Eos <100 (Lancet Resp Med 2018;6:117) Lancet RM 2014;2:361, Cochrane Rev 2018)
• Vitamin D supplementation   exacerbations if baseline level <25 (Thorax 2019;74:337)
Non-Rx interventions:  smoking ( mortality; Annals 2005;142:233), pulm. rehab (Cochrane Rev 2015), vaccines (flu, PCV13, PPSV23)
• Lung CA screening: annual low-dose CT (age 55-80 w/ 30 pack-year hx & active/quit <15yr) (NEJM 2011;365:395, USPSTF 2014)
• Home O2: if PaO2 ≤55 or SpO2 ≤88% or if pulmonary HTN or polycythemia (Hct >55%) with PaO2 ≤59 or SaO2 ≤89%
• Nocturnal NiPPV: if daytime pCO2 ≥52 & nocturnal SpO2 ≤88% (despite 2L O2) or if recent exacerb. & persistent pCO2 >53 (
risk of readmit & mortality: JAMA 2017;317:2177)
COPD Exacerbation (AECOPD) (ERS/ATS Guidelines: ERJ 2017;49, GOLD 2020 Guidelines)
• Hx: dyspnea, /Δ sputum, and/or cough; ask re: URI sx, CHF sx, DVT/PE risk fx, tob. hx, prior exacerbations/steroids/intubations
• Work-up: CXR, CBC w/diff, BMP, ABG/VBG (for pH/pCO2) ± EKG, trop, NT-proBNP. Consider flu/RVP, PE eval (PE in 25% w/
severe exacerbations w/o clear trigger: Annals 2006;144:390)
Management: • Antibiotics: controversial;  mortality but challenging to
• SpO2 88-92%: hyperoxia   vent. via Haldane effect & hypoxic identify who will benefit (Chest 2008;133:756, Coch Rev 2012)
vasoconst., V/Q mismatch; mortality (BMJ 2010;341:c5462) o Indicated if:  all 3 cardinal sx, 2/3 w/  sputum
• Bronchodilators: albuterol, ipratropium, DouNebs (combo) purulence, or require NPPV/mechanical ventilation
o “Stacked” DuoNebs (x3 in 1 hr) initially  space to standing  CRP may be useful in outpt (NEJM 2019;381:111)
DuoNebs q4 w/ albuterol PRN q2  space further as able  PCT may be useful but mortality when utilized in
o Ok to hold home inh. while on scheduled short-acting agents ICU setting (Eur Resp Rev 2017;26; ICM 208;44:428)
• Steroids: pred 40mg x5d. PO ~ IV (Chest 2007;132:1741) & 5d ~ o Abx choice: based on PsA risk, prior SCx, resistance
14d (REDUCE JAMA 2013;309:2223, Cochrane Rev 2018); though  ⊝ PsA RFs: FLQ, CTX; outpt: amox/clav, azithro
some may need higher dose/longer course if severe  ⊕ PsA RFs: FLQ, cefepime, pip/tazo
o If severe: IV methylpred 60-125mg q6-q12 x72hrs  Duration: 5-7d inpt; 3-5 outpt (varies by drug)
• NPPV: if resp acidosis, severe dyspnea w/ resp. muscle fatigue  Concurrent CAP: treat by CAP guidelines
or  WOB (access. muscles, thoracoabdominal paradox, etc), or • Antivirals: oseltamivir if influenza⊕, even if ≥48-72hrs.
persistent hypoxemia. mortality, intub., LOS (Cochrane Rev 2004)
Inhaled Therapies for Asthma & COPD
Class Example Meds
Short-acting β-agonist (SABA) Albuterol, levalbuterol (SE: HR; levalbuterol more selective so less HR effect but $$)
Short-acting muscarinic antagonist (SAMA) Ipratropium (Atrovent) (SE: may  urinary retention)
Long-acting β-agonist (LABA) Salmeterol, formoterol (N.B. in asthma, do not use without ICS)
Long-acting muscarinic antagonist (LAMA) Tiotropium (Spiriva), umeclidinium (Incruse Ellipta)
Fluticasone-salmeterol (Advair), budesonide-formoterol (Symbicort), mometasone-formoterol
Inhaled corticosteroid (ICS) + LABA
(Dulera), fluticasone-vilanterol (Breo Ellipta)
LAMA + LABA Umeclidinium-vilanterol (Anoro Ellipta)
LAMA + LABA + ICS Fluticasone-umeclidinium-vilanterol (Trelegy Ellipta)
Mitu Bhattatiry and Cody Cichowitz
45
TOC

Pulmonary & Critical Care Bronchiectasis & Hemoptysis

BRONCHIECTASIS (CYSTIC FIBROSIS AND NON-CF )
DEFINITION: permanent airway dilatation from recurrent infection/inflammation (AJRCCM 2013;188:647, NEJM 2002;346:1383)
Symptoms Chronic productive cough, recurrent bronchitis/pneumonia, wheezing, dyspnea, hemoptysis
Recurrent insult: infection (PNA, MAC, TB, childhood infection, ABPA), inhalation, GERD/aspiration
Impaired immunity:  mucus clearance (CF, primary ciliary dyskinesia), immunodeficiency (e.g. IgG)
Etiology Obstruction: foreign body, tumor, COPD, tracheomalacia, CTD (Marfan’s), radiation
Systemic disease: RA, Sjogren’s, SLE, IBD, A1AT
Idiopathic = ~50%
Initial: HRCT, PFTs, CBC w/ diff, Ig levels, sputum Cx As indicated: exclude CF w/ gene/sweat Cl- testing,
(bacterial, mycobacterial, fungal) Aspergillus Ab, ANA, RF/CCP, SSA/SSB, A1AT;
Workup
- CT: bronchial diameter > 1.5x adj artery; bronchi fail to consider nasal NO (PCD), pneumococcal vaccine titers
taper, thickened bronchi (Thorax 2010;65;1) (often low), bronch., GI eval
Natural Hx Exacerbations (avg 1.5/yr), progressive  in FEV1, PsA colonization  worsening disease
Chronic Management Acute Exacerbation
CF: AJRCCM 2013;187:680, AJRCCM 2009;180:802; non-CF: AJRCCM 2013;188:647, ERS Guidelines: Eur Resp J 2017;50
Principles originally arose in CF population then applied to non-CF • Sx:  cough/sputum/dyspnea; usually  fever
• Airway clearance: nebs (albuterol, hypertonic saline) + chest PT • Obtain resp cx prior to abx
(acapella, vest) • Micro: PsA + S.aureus > H. flu, Moraxella,
o CF: add DNase to neb bundle; not effective in non-CF Burkholderia; treat Stenotrophomonas and
• Antimicrobials/anti-inflammatories: Achromobacter as pathogenic; Aspergillus in
o Non-CF: CF not treated
 Azithro has some benefits w/  exacerb. also but c/f  abx • Abx: use previous Cx data; tx 14d
resistance (Lancet 2012;380:9842, JAMA 2013;309:1251, Coch o No prior Cx data: empiric FLQ (for PsA)
Rev 2018, Lancet RM 2019;7:845). Ensure no NTM first. o If prior R-PsA: IV abx; 2 agents – β-lactam
 Trial inhaled abx if PsA colonization & ≥3 exacerb./yr & either FLQ or IV tobra (dosed QD)
 Consider eradication of new PsA isolate  No great evidence for double coverage
o CF: azithro + inhaled tobramycin (for PsA; alt: aztreonam, colistin) of PsA though is standard of care in CF
• Disease specific treatment: o If β-lactamase⊕ H flu or Moraxella:
o Non-CF: treat underlying cause if found; consider PPI/H2 blocker amox/clav, doxy, macrolide, or FQ
o CF: CFTR mut defective Cl-/HCO3- transport on airway surface) o Home abx: continue azithro ± inh tobra
 Potentiators open CFTR channel (ivacaftor); correctors bring (practice varies)
CFTR to surface (lumacaftor, tezacaftor, elexacaftor) • Steroids not used unless concomitant asthma
 Dual/triple txlong-term FEV1 benefits (NEJM 2015;373;220, or ABPA
NEJM 2017;377:2013, NEJM 2018;379:1599, NEJM 2019;381:1809) • Continue chronic treatment (airway clearance)
 Pancreatic enzyme supplementation, vitamins ADEK
HEMOPTYSIS
DEFINITION: expectoration of blood from lower respiratory tract
• Airway: bronchitis, bronchiectasis (incl. CF), CA (usually primary lung CA), trauma (incl. foreign body)
• Pulmonary parenchyma: infection (PNA, abscess, TB, aspergilloma), ANCA-vasculitis (GPA), anti-GBM
Etiology: (Goodpasture syndrome), immune-complex vasculitis (SLE, cryo, HSP), drug-induced vasculitis (cocaine,
PTU, TNFi, hydral), coagulopathy, endometriosis, inhalation injury, sarcoid, pulmonary hemosiderosis
• Pulmonary vascular: PE, CHF (esp if on AC), mitral valve dz, bronchovascular fistula, aneurysm, AVM
1) Consider other sources (GI or nasopharyngeal)
Work-up: 2) CXR (most important), CBC, coags, U/A (for vasculitis, anti-GBM), sputum Cx, CT chest (if stable)
3) Consider NT-proBNP, D-dimer, ESR/CRP, C3/C4, ANA, ANCA, anti-GBM, APLAS, IGRA/AFB
Management if • If minimal & likely infectious: observe.
non-massive: • If active & without clear etiology or recurrent: chest CT  bronch.
MASSIVE HEMOPTYSIS (>500mL/day or >100mL/hr) is a life-threatening emergency with mortality rate 50-80%. Asphyxiation
NOT exsanguination is mechanism of death. (CCM 2000;28:1684)
• LIE PATIENT ON SIDE OF SUSPECTED BLEED (preserve gas exchange in unaffected lung)
• Control airway: if very dyspneic, poor gas exchange, or rapid bleed, STAT RICU consult (x6-3333), largest ET-tube possible
(8mm+). Note: ensure suction (+/- IP) available upon intubation as blood can rapidly fill ET tube
• Ensure hemodynamic stability, correct coagulopathy. Inhaled TXA may be beneficial (Chest 2018;154:1379).
• Call IP  bronch to localize; temporize w/ balloon tamponade, bronchial blockade, electrocautery, topical vasoconstriction
Call IR  if stable, can CTA to localize; otherwise bronchial angiography to embolize site
If refractory, thoracic surgery evaluation.
• Can consider pulse dose methylprednisolone if vasculitis suspected

Michael Kelly and Krystle Leung

46
TOC

Pulmonary & Critical Care Interstitial Lung Disease

Overview: diverse group of disorders that cause scarring/fibrosis in the lungs, often leading to structural changes in the parenchyma
(alveoli, interstitium, alveolar-capillary interface)  loss of lung volume/compliance
Presentation: progressive dyspnea, non-productive cough, hypoxemia (esp. w/ exercise); some (e.g. AIP, HSP, COP) often w/ systemic sx
History: tempo, hx CTD/IBD/malig., rheum ROS, meds, exposures (chemicals, dusts, barns, pets, AC, humidifier, hot tub), smoking, FH
Physical exam: “velcro-like” crackles, clubbing, e/o CTD (heliotrope rash, Gottron’s papules, mechanic’s hands, joint disease, muscle
weakness, skin fibrosis, sicca), extrapulmonary manifestations of other systemic diseases
Etiologies: known and idiopathic causes broken down by subcategories (ATS/ERS classification: AJRCCM 2013;188:733)
Idiopathic Interstitial PNAs (IIPs) Known Causes
Chronic Acute/subacute Smoking-rel. Systemic Connective Exposures
Idiopathic Acute interstitial Diseases Tissue Disease Inhalation Drugs
pulmonary pneumonia Resp. Organic Amiodarone,
Scleroderma, Inorganic
fibrosis (IPF; (AIP; DAD bronchiolitis- Sarcoid, Grains, molds, nitrofurantoin,
Poly/dermato- Silica, asbtesos,
UIP pattern), pattern), ILD (RB-ILD), amyloid, AC/humidifier, methotrexate,
myositis, coal, metals, etc.
idiopathic non- cryptogenic desquamative ANCA- birds, etc. nivolumab,
RA, SLE,
specific organizing interstitial vasculitis, pembrolizumab,
Sjogren’s, Hypersensitivity
interstitial PNA pneumonia PNA (DIP) IBD, CA Pneumoconiosis ipilimumab, talc,
MCTD pneumonitis
(NSIP) (COP) radiation, etc.
Others: Lymphangioleiomyomatosis (LAM): seen in young ♀ with reticular opacities on CXR & thin walled cysts on CT chest. Pulmonary Langerhans cell
histiocytosis (PLCH): young adults w/ upper-zone-predom. cysts (can be bizarrely shaped) & nodules. Eosinophilic PNA: acute form (AEP) w/ <1mo of
sx, BAL with >25% eos; chronic (CEP) with >1 mo. of sx, periph. eos (>6%), BL periph. consol. that are “photo. negative” of pulm edema; Tx w/ steroids.
Idiopathic PNA w/ autoimmune features (IPAF): idiopathic PNA pattern (NSIP, UIP) w/ features of autoimmune dz that do not meet criteria for CTD dx.
Diagnostic Evaluation:
• Labs: CBC+diff, CMP, U/A, ESR/CRP, CPK/aldolase, C3/C4, auto-antibodies (ANA, RF/anti-CCP, anti-RNP, anti-Ro/La, Scl-70, ANCA,
hypersensitivity panel, myositis panel 3, anti-Jo1 [part of myositis panel but comes back faster])
• Radiology: HRCT ILD-protocol; upper- (HSP, smoking-rel., dusts) vs. lower-predom. (IPF, NSIP), LAD (CA, sarcoid), pleural dz?
• PFTs: restrictive defect (TLC, FRC, RV; FEV1/FVC normal to ); DLCO can be early sign
• BAL: if acute onset or hemoptysis (eval for AEP, alveolar hemorrhage, CA, infection); if more chronic, can perform if suspect HSP,
sarcoidosis, infection, or pulm. Langerhans histiocytosis. Not useful if suspect IPF except to exclude chronic HSP.
• Lung biopsy: if diagnosis unclear and will change management

Above: Usual Interstitial Pneumonia (UIP) is the

radiographic corollary of IPF
Features: basilar-predominant, honeycombing,
Treatment: traction bronchiectasis
• IPF (NEJM 2018;378:19)
o Acute exacerbations: ddx infxn, VTE, CHF; no data, but steroids (~1mg/kg/d
pred) & broad-spectrum abx (x7d) generally given (AJRCCM 2011;183:788). Can
re-pulse & slow taper if tx failure during taper.
o Chronic therapy: consideration for pirfenidone (antifibrotic; SE: nausea,
fatigue), nintedanib (TK inhibitor; SE: diarrhea) (FVC decline but no Δ in
survival) (NEJM 2014;370:2083). Azathioprine/pred/NAC w/  mortality (NEJM
2012;366:1968) & no clear benefit to NAC monotx (though minimal side effects;
NEJM 2014;370:2093). GERD tx & aspiration precautions may be beneficial
(Lancet RM 2013;1:369). Steroids NOT indicated. Lung txp evaluation.
• NSIP: remove inciting exposures, tx underlying condition (if non-idiopathic); can be
steroid-responsive (pred 0.5-1mg/kg/d or pulse solumedrol if severe & requiring
hospitaliz.); 2nd agent (AZA, MMF, ritux, CYC) pending response. Nintedanib may Above: many non-IPF pathologies (e.g. idiopathic,
benefit non-IPF progressive fibrotic disease (NEJM 2019;381:1718, Lancet RM 2020) CTD, meds, some HSP) may have a NSIP pattern
• COP: monitor; if sx persist/progress  pred ~0.75-1mg/kg/d (pulse if fulminant) Features: subpleural sparing, increased reticular
markings, ground glass, mosaic attenutation due
• AIP: many cases of idiopathic ARDS; tx is supportive; usually not steroid-
to air trapping (requires inspiratory/expiratory
responsive, but often give high dose steroids, empiric abx as in-hospital mortality HRCT), HSP will be upper lobe predominant
>50%
Cody Cichowitz and Mubeen Shakir
47
TOC

Pulmonary & Critical Care VTE Diagnostics

CLINICAL MANIFESTATIONS
Signs/Symptoms
DVT
• S/Sx: pain, warmth, erythema or cyanosis, edema (esp. asymmetric), palpable cord, venous distention, Homan’s sign (sudden
dorsiflexion of ankle w/ knee flexed to 30˚ pain in upper calf ); though none Sn/Sp for DVT (JAMA 1998;279:1094) & can be asx
• Types: proximal = iliac, femoral, popliteal veins; distal = calf veins below knee (ant./post. tibial, peroneal, soleal, gastrocnemius)
o Massive iliofemoral DVT: phlegmasia alba dolens (edema, pain)  phlegmasia cerulean dolens (cyanosis, venous gangrene)
o May Thurner syndrome: compression of L common iliac vein  DVT  LLE edema, pain, venous claudication
• Ddx: superficial thrombophlebitis, cellulitis, arthritis, arterial occlusion, varicose veins, lymphedema, ruptured Baker cyst, chronic
venous insufficiency (Arch IM 1998;158:2315)
PE (Chest 1991;100:598; Am J Med 2007;120:871)
• Sx: dyspnea (73-79%), pleuritic CP (47-66%), cough (37-43%), orthopnea (36%), leg swelling/pain (26-42%), syncope (10%),
hemoptysis (13%), diaphoresis (4-11%), palpitations (10%), angina (4%); many may be asymptomatic
o Syncope: among pts hospitalized for syncope, PE in 2-17% (NEJM 2016;375:1524, JACC 2019;76:744)
• Signs: tachypnea (57-70%), tachycardia (26-30%), rales (21-51%), S4 (24%), P2 (15-24%),  breath sounds (21%), JVD (13%),
fever (2-7%), wheezing (3-5%), RV heave (4-5%), pleural friction rub (1-3%), S3 (3%)
• EKG Δs: sinus tach., atrial arrhythmias (AF, AFL), RBBB, inf. Q, anterior STΔs/TWIs, S1Q3T3 (McGinn-White sign) (ERJ 2005;25:843)
Risk Factors: Virchow’s triad of venous stasis, vascular injury, hypercoagulability (Circulation 2003;107:I9; JAMA 2003;290:2849)
Strong (OR >10) Moderate (OR 2-9) Weak (OR <2)
- Fracture (hip/leg) - Arthroscopic knee surgery - CHF (JACC 2020;75:148) - Bed rest >3 days - Pregnancy (antepartum)
- Hip or knee - Central venous lines - Resp. failure - Immobility due to sitting - CKD (J Thromb. Haemost
replacement (PICC: Lancet 2013;382:311) - Asthma (ERJ 2014;43:801) (e.g. airplane, car) 2014;12:1449)
- Major general - Hormone replacement tx/OCPs - Malignancy/chemotherapy - Increasing age - Smoking (mixed;
surgery - Pregnancy (postpartum) - Paralytic stroke - Laparoscopic surgery Am J Hem 2008;83:97)
- Major trauma - Hospitalized/SNF (w/o surgery) - IBD (e.g. CCY) - Cirrhosis (Thromb Haemost
- Spinal cord injury - Previous VTE - Nephrotic syndrome - Obesity (Circ 2008;117:93) 2017;117:139)
- Thrombophilia - Sepsis (Chest 2015;148:1224)
D I A G N O S I S / R I S K S T R A T I F I C A T I O N (ASH: Blood Adv 2018;2:3226; AHA: Circ 2011;123:1788; ESC: EHJ 2019;41:543; JAMA 2018;320:1583)
• Pre-test prob: Wells' for LE DVT (NEJM 2003;349:1227), Constans’ for UE (Thromb Haemost 2008;99:202), Wells’ for PE (Annals 2001;135:98)
o If low (or mod. DVT), can r/o w/ D-dimer (see below) or PERC; if D-dimer ⊕, further eval. If high (or mod. PE)  imaging.
Wells’ Criteria for PE PERC Rule
Clinical s/sx of DVT 3 points 0-1 = low risk Age ≥50 Hemoptysis If meets none of
PE #1 dx OR equally likely 3 points 2-6 = mod. risk HR ≥100 Surgery/trauma ≤4wks criteria to left, no
HR >100 1.5 points >6 = high risk SpO2 <95% Prior DVT/PE further testing
Immobilization x3d or surgery ≤4wks 1.5 points Unilateral leg swelling Hormone use needed.
Hemoptysis 1 point ≤4 = unlikely
Malignancy w/ tx last 6mo. or palliative 1 points ≥5 = likely Interpreting D-Dimer (Nml <500)
- DVT: if nml + low pretest prob, excludes DVT
• DVT diagnosis: venous doppler U/S (“LENIs” = Lower Extremity Non-Invasives; (NEJM 2003;349:1227, JAMA 2006;295:199)
“UENI” = Upper Extremity Non-Invasives) - PE: if nml + low pretest prob, excludes PE
• PE diagnosis: (Thromb Haemost 2009; 101:886).
o PE-CT: study of choice; may also detect alt dx (PIOPED II NEJM 2006;354:2317) - Adjusted D-dimer:   imaging w/o  in PE
o V/Q scan: validated in PIOPED (JAMA 1990;263:2753). Performed if c/i to  Age-adjusted: if >50, use age x10 as cut off
CT/contrast. Need nml CXR (minimize other causes of V/Q mismatch) (JAMA 2014;311:1117)
o LENIs: if suspect PE & unable to CT or V/Q & ⊕, can treat; if ⊖, however,  Prob.-adjusted: use of <1000 cutoff w/ low prob.
does not exclude PE (clot may have migrated or be from other source) (NEJM 2019;381:2125)
- Ddx for  D-dimer: arterial thrombus (MI, stroke,
o Echo: most useful for risk stratification (not dx), though demonstration of clot
AF/intracardiac, acute limb ischemia), DIC, CA,
or new RV strain can provide presumptive diagnosis if needed rapidly inflammation/infection, ESLD, CHF, renal disease,
o ABG: hypoxemia ( A-a gradient, normal in ~20%), respiratory alkalosis  age, aortic dissection, trauma, surgery
• PE risk stratification:
High Risk (Massive) Intermediate Risk (Submassive) Low Risk (Nonmassive)
Hemodynamically Right heart strain w/o hypotension No right heart strain or
unstable • Biomarkers: hypotension
• SBP <90 or o NT-proBNP >500; though >600 cut-off Sp. (ERJ 2014;43:1669) • Normal biomarkers
requiring o hs-TnT; age-adjusted cut-off of ≥14 in age <75 & ≥45 in age >75 • Low risk per PESI &
vasopressors & not may  NPV (ERJ 2015;45:1323) sPESI
due to hypovolemia, • Echo: RV overload/dysfunction – enlarged RV, flattened IVS,
arrhythmia, etc. mod/severe TR, McConnell’s sign (RV free wall akinesis sparing apex),
• Cardiac arrest  TAPSE
• CT: RV/LV diameter ratio >0.9 (EHJ 2011;32:1657)
• PE severity index (PESI): class III-V; short PESI (sPESI) ≥1
ESC further classifies into intermediate-high (both TnT & RV dysfunction
on TTE or CT) & int.-low (⊕ biomarkers or TTE or neither w/ PESI III-V)
Jose Castellanos
48
TOC

Pulmonary & Critical Care VTE Management

M A N A G E M E N T O F V T E (CHEST Guidelines for VTE: Chest 2016;149:315; ESC for PE: EHJ 2020;41:543)
Proximal DVT (popliteal, femoral, iliac vv.) Distal DVT (calf: ant./post. tibial, peroneal vv.)
Anticoagulate (unless contraindications), regardless of symptoms Serial imaging vs. anticoagulation
Agent: DOAC > VKA > LMWH; if malig.: DOAC or LMWH > VKA Serial imaging: if asx, low risk for extension, or high risk
(*For dosing & more info on choosing agent see Hematology section) for bleeding
Duration: at least 3 months for all. Extend >3mo. if: • Repeat U/S at 1-2wks (1/3 will extend;  risk in
• 1 or 2 unprovoked prox. DVT & low/mod. bleeding risk. If
st nd muscular veins: soleal, gastrocnemius)
high bleeding risk (see below), stop at 3mo. Unprovoked have  Anticoagulate if: (see  for choice/duration)
recurrence rate (10% <1yr off AC, 5% each subsequent yr). • Severe symptoms
o If stop AC after 1st VTE, D-dimer at 1mo. may be useful in • Risk factors for extension: (1) ⊕ D-dimer, (2)
deciding to resume, esp. in ♀ (NEJM 2006;355:1780, Blood extensive (>5cm, mult. veins, >7mm in diam.), (3)
2014;124:196, Annals 2015;162:27) close to prox. veins, (4) no reversible provoking
o If stop AC, low-dose ASA rec’d if no contraind. (may  factor, (5) active CA, (6) h/o VTE, (7) inpatient
recurrence: NEJM 2012;367:1979 & 366:1959, Circ 2014;130:1062) • On serial imaging, extends into proximal veins. AC
• Cancer-associated also suggested if extends but remains in distal vein.
If contraindications to AC (active bleeding, recent/planned high
bleeding-risk procedure, major trauma, acute ICH)  IVC filter
UE DVT (NEJM 2011;364:861): brachial, axillary, subclav. vv.;  complications vs. LE DVT. Tx same as LE DVT. If PICC/CVC, no
need for catheter removal if needed/functional/infected. AC continued while catheter in place (esp. if CA), though no data.
Bleeding risk: low = 0 RFs (1.6%/3mo; 0.8%/yr after 3mo.); mod. = 1 (3.2%/3mo; 1.6%/yr); high = ≥2 (12.8%/3mo; ≥6.5%/yr)
RFs: age >65-75, previous bleeding, CA, renal failure, liver failure, thrombocytopenia, previous CVA, DM, anemia, anti-platelet tx,
poor AC control,  functional capacity, recent surgery, frequent falls, EtOH use disorder, NSAID use
Testing in unprovoked VTE: age-appropriate cancer screening (found in 1/20 within 1yr; Annals 2017;167:410) & sx-directed
studies only. Do not perform thrombophilia testing at time of VTE event or while on AC (affects testing results & $$$). Can test
after treatment for acute event if will Δ mgmt. (which it rarely does). See Hematology: Coagulation Disorders.

High Risk PE (Massive) Intermediate Risk PE (Submassive) Low Risk PE

PERT consult (x47378)
Resuscitation: Anticoagulation: LMWH preferred > UFH (faster time to Anticoagulation:
• Limit IVF: can try 500cc if CVP low, but therapeutic range) unless impending hemodynamic collapse See above (DVT)
RV distention  CO / thrombolysis (or CrCl <30 or severe obesity) and Hematology
• Vasopressors: NE generally preferred section
Thrombolytic therapy in select pts: (AHA: Circ
• O2: HFNC pref. for severe hypoxemia. 2011;123:1788) Disposition: if
Mech vent. very high risk: hypoTN from • No strict guidelines, but may include: developing no other reasons
induction & pos. pressure  venous circulatory failure (episode of hypoTN, persistent HR > for hospitaliz., &
return  RV CO & RV failure SBP) or respiratory failure, mod/severe RV adequate
• Circulatory collapse/arrest: VA ECMO dysfunction/injury on TTE (RV hypokinesis, RVSP >40) support, can d/c
w/ major  in hs-TnT/NT-proBNP (>900) home
Anticoagulation: UFH (w/ bolus)
Thrombolysis: systemic unless contraind. • May be observed x24hrs on AC first pending trajectory
Embolectomy: if thrombolysis contraind./fails; • Routine tPA in int. risk PE   hemodynamic decomp.
can be catheter-directed; surgery if all options but no clear long-term Δ in mortality or CTEPH; 
contraind./fail or if clot in transit in RA/RV, PFO major bleeding & hemorrhagic CVA (PEITHO NEJM
2014;370:1402, JACC 2017;69:1536)
Thrombolysis:   mortality (Am J Card 2019;123:684, JAMA 2014;311:2414)
Systemic: alteplase 100mg/2hr (bolus 50mg/2min if cardiac arrest). Hold AC during infusion (but do not delay if got LMWH). No
convincing evidence to support routine use of lower dose tPA (MOPETT Am J Card 2013;111:273)
• Absolute contraindications: intracranial neoplasm, recent CNS surgery/trauma (<2-3mo.), h/o ICH, active bleeding, non-
hemorrhagic stroke <3mo.
Catheter-directed: may be preferred if high-risk for bleeding, failed systemic thrombolysis, or otherwise selected patients; can
couple w/ U/S-assisted thrombolysis (EKOS) or suction thrombectomy. Studies show in RVSP, RV/LV ratio but no data for
mortality benefit (ULTIMA Circ 2014;129:479, SEATTLE II JACC Card Interv 2015;8:1382, Am J Med 2019;132:240, Am J Card 2019;124:1470)
Anticoagulation: if started on LMWH/UFH, transition to DOAC after has stabilized for 2-3d (unless other agent indicated).

PERT (x47378): call if large PE w/ abnormal VS (tachycardia, hypotension), evidence of RH strain (TTE, EKG, biomarkers),
central/saddle PE. Order (if not already obtained): CBC w/ diff, BMP, LFTs, lactate, D-dimer, ABG, PT/INR, PTT, T&S, NT-
proBNP, hs-troponin, EKG, CT-PE protocol, LENIs, TTE.

Jose Castellanos
49
TOC

Pulmonary & Critical Care Pulmonary Hypertension

Pulmonary Hypertension = mean PA pressure (mPAP) ≥20 Clinical Manifestations
mPAP = (PVR x CO) + PCWP ; PVR = (mPAP - PCWP) / CO Sx: nonspecific; 2yr delay to dx in 20% (Chest 2011;140:19)
∴  in PVR or PCWP can  pulmonary hypertension (PH) - Early: DOE, lethargy, fatigue (2/2 inadequate CO w/ activity)
 Pre-capillary PH:  PVR ≥3, nml PCWP ≤15,  DPG & TPG - Late: exertional CP, syncope, edema, anorexia, abdominal
 Post-capillary PH: nml PVR <3,  PCWP >15, nml DPG &TDPG distention (2/2 progressive RV failure)
 Mixed PH:  PVR ≥3,  PCWP >15,  DPG & TPG - Rare: cough, hemoptysis, hoarseness (Ortner’s syndrome)
Transpulmonary gradient (TPG) = mPAP – PCWP; nml <12 Exam: loud P2;  JVP, edema, ascites, TR murmur, R-sided
Diastolic pulm. gradient (DPG) = PA diastolic (PAd) – PCWP; nml <7 gallop, parasternal heave (LSB), PA tap (L 2nd ICS), edema,
hepatomegaly, ascites
Diagnosis (ERJ 2019;53:1801904) Imaging: CXR w/ enlarged PA, RA, RV (retrosternal space on
• RHC: gold-standard for diagnosis (though may not be needed in all lat.), pruning of peripheral vessels; CT w/ PA/Ao diameter ≥1
circumstances). Can also do iNO vasoreactivity testing (guides EKG: normal vs. signs of RV hypertrophy/strain: RAD, R/S >1
treatment in idiopathic PAH). in V1, RBBB, p pulmonale in II (RAE)
• Evaluation for etiology: TTE:  tricuspid regurg. jet velocity (≥2.9 = int. prob for PH),
o TTE: eval for left HF (& whether severity explains PH) RVSP (ePASP) >36; IVS flattening, RVH  RV dilation, RV
o PFTs, HR-CT, 6MWT +/- PSG, CPET: chronic lung dz, OSA hypokinesis, RA dilation, TR, PR, PA size, IVC w/  collapse
o V/Q scan: eval for CTEPH
o Labs: NT-proBNP, BMP, LFTs, eval for systemic disorders in groups 1 & 5 (if not already known) – HIV, connective tissue
diseases (ANA, RF/CCP, ANCA, Scl-70, Ro/La), schistosomiasis (if clinically appropriate)
WHO Classification (6th World Symposium on PH: ERJ 2019;53:1801913; JACC 2013;62:D34)
Pre-Capillary Post-Capillary
Group 1: pulmonary arterial Group 3: lung disease Group 4: pulmonary artery Group 2: left heart
hypertension (PAH) and/or hypoxemia obstructions disease
- Idiopathic (♀>♂) Obstructive: COPD Chronic thromboembolic HFpEF
- Heritable (e.g. BMPR2) Restrictive: ILD disease (ERJ 2019;53:1801915) HFrEF
- Drug/toxin-induced: cocaine, Mixed obstructive/restrictive NB: only ~33-75% had known Valvular disease
anorexigens, dasatanib, amphetamines Chronic hypoxia w/o lung prior VTE. Occurs after ~4% Congenital/acquired
- Associated with: CTD, HIV, portal HTN, disease: OSA of PEs (NEJM 2004;350:2257) conditions
congenital heart disease, schisto. Developmental lung disorders Other PA obstructions: (ERJ 2019;53:1801897)
- PAH long-term responders to CCBs (ERJ 2019;53:1801914) malignancy, arteritis without
- PVOD and/or pulmonary capillary CTD, parasites, congenital PA
hemangiomatosis stenosis
- Persistent PH of newborn
Group 5: Misc.: chronic hemolytic anemia (e.g. sickle cell), myeloproliferative d/o, sarcoid, metabolic d/o, complex congenital HD

WHO Functional Classes: similar to NYHA for CHF & guides intensity of therapy. Class I = asx w/ ordinary activity, class II = sx w/
ordinary activity, class III = sx w/ minimal activity, class IV = sx at rest.
Management: Treat underlying etiology: CTD, CHF, hypoxemia (O2), VTE, etc. Advanced therapies (see below): guided by WHO
functional class (reserved for II-IV). Most evidence in Group 1. Surgery: pulmonary thromboendarterectomy (CTEPH), atrial septostomy
(R L shunt), lung txp in select pts. General: exercise/pulm rehab, O2, diuresis (for RHF), contraception in ♀
Mechanism Medication Route Indication Side effects
Endothelin Bosentan, Group 1: sx,  6MWT (NEJM 2002;346:896, Circ Anemia, PNA, edema, hepatotox.
receptor ambrisentan, PO 2008;117:3010) Macitentan: also flu, HA, UTI,
antagonists macitentan Macitentan: morbid/mortality (NEJM 2013;369:809) bronchitis
Group 1: sx,  6MWT (NEJM 2005;353:2148, Erythema, flushing, indigestion,
PDE5 inhibitors:
PO NEJM 2009;361:1864) HA, insomnia, epistaxis, rhinitis,
sildenafil, tadalafil
(NO)-cGMP retinal hemorrhage
enhancers Group 1 & Group 4: sx, 6MWT (NEJM BP, n/v/d/constipation, GERD,
sGC stimulator:
PO 2013;369:330) anemia, dizziness, HA,
riociguat
hemorrhage
Analogues: IV or inh.; Group 1: 6MWT, QOL; reserved for sickest CP, BP, HR, flushing, abd pain,
Prostacylin epoprostenol, treprostinil patients (NEJM 1996;334:296) anorexia, n/v/d, jaw pain, MSK
pathway treprostinil, iloprost also SC Group 5: some etiologies pain, dizziness, HA, hemorrhage
agonists Receptor agonist: Group 1:  hospitalization; no Δ mortality (NEJM Diarrhea, nausea, jaw pain, HA,
PO
selexipag 2015;373:2522) anemia
Positive vasoreactivity test (mPAP by ≥10 BP, LE edema
CCB Nifedipine, diltiazem PO
mmHg & to ≤ 40 mmHg w/o CO).  RV failure.
• Per CHEST guidelines: If WHO FC II or FC III w/o rapid progression, start w/ ambrisentan/tadalafil combo (pref. over monotx w/ ERA,
PDE5i, or riociguat; NEJM 2015;373:834). If FC III w/ rapid progression or FC IV, start w/ IV prostanoid. If unacceptable clinical status,
add 2nd/3rd class (Chest 2019;156:187).

Jose Castellanos and Louisa Mounsey

50
TOC

Pulmonary & Critical Care Mechanical Ventilation

Indications for Intubation: Call RICU for intubation: x6-3333
• Failure of NIPPV: no clinical improvement RICU will ask: AMPLE
• Cannot ventilate: PaCO2 >60 with severe acidemia (COPD or other A = allergies
obstruction, sedation, neuromuscular disease, resp. muscle fatigue, trauma) M = medications (current)
• Cannot oxygenate: worsening P:F ratio (PNA, pulmonary edema, ARDS, PE) P = past medical hx (incl. h/o LVEF and RV function,
• Airway protection/instability: unconsciousness, AMS (GCS <8), shock, prior intubations or difficult airway)
L = last meal, last K (Succinylcholine can cause
facial/head trauma, nausea/vomiting/UGIB, severe secretions, severe
hyperK)
bronchospasm/anaphylaxis E = events (prompting intubation)
• Persistent increased work of breathing: severe bronchospasm, airway During intubation, have at bedside:
obstruction, inability to compensate for severe acidemia (1) Good access (2) IVF (3) sedative agent (e.g.
• Hemodynamic instability: unstable arrhythmia, severe shock propofol) (4) pressors (neo >> levo)

General Principles (NEJM 2001;344:1986; Respir Care 2017;62:629)

Five main variables: (1) RR, (2) tidal volume (VT), (3) FiO2, (4) positive end-expiratory pressure, (PEEP) (5) mode of ventilation
• Ventilation (determines CO2):  PaCO2 by increasing RR and/or VT ( minute ventilation where MV = RR x VT)
1) RR: often adjust this first; avoid >RR 30-35 due to risk of inadequate expiratory time  air trapping/auto-PEEP
2) VT (often set at ≤ 6cc/kg IBW): when , ensure Pplat ≤30 and driving pressure (ΔP = Pplat – PEEP) ≤15 to minimize lung injury
• Oxygenation:  PaO2 by increasing PEEP and/or FiO2
3) FiO2: avoid FiO2 >0.6 for prolonged periods due to oxygen toxicity
4) PEEP:  alveolar recruitment, improves V/Q matching; if PEEP  PaO2/FiO2 (P/F) & Pplat stable, suggests recruitable lung; if
PEEP  no Δ/ P/F or PaCO2, suggests not recruitable & instead causing shunt or dead space (should PEEP)
Ventilator Modes (Respir Care 2007;52:301)
SET MEASURED
MODE PROS/CONS HOW TO READ
Indep. variables Dep. variables
AC/VC VT :  control over ventilation (fixed VT prevents “Pt is on Volume Control w/ VT of
barotrauma or atelectrauma) 400 (4cc/kg), set at a rate of 16
Assist Control/Volume PEEP PIP & Pplat : fixed inspiratory flow regardless of effort,  pt- breaths/min, PEEP of 8, and FiO2
Control: delivers a RR
breath until set tidal FiO2
I:E or flow vent dyssynchrony
0.6; they are breathing at the set
rate of 16 (or over) with VT ~400
volume is reached I:E or flow
for MV of 6.4L”
AC/PC Pinsp : variable flow (& variable VT) during inspiration “Pt is on Pressure Control of 18
PEEP to satisfy pt demand,  dyssynchrony (Pinsp) over 5 (PEEP), set at a rate
Assist Control/Pressure Flow : can cause volutrauma as compliance or pt of 16 breaths/min, and FiO2 0.3;
Control: delivers a RR
VT effort changes they are breathing VT ~400, at the
breath until set FiO2 set rate of 16 (or over) for a MV of
pressure is reached I:E 6.4L.”
PSV : better tolerated, less sedation required, used “Pt is on Pressure Support of 10
Pressure Support Pinsp I:E as trial setting prior to extubation (i.e. SBT on 0/0 (Pinsp) over 5 (PEEP) with an FiO2
Ventilation: delivers a PEEP Flow or 5/5) 0.3; they are breathing VT of ~500
set pressure triggered FiO2 VT : less control over respiratory parameters, at 20 breaths/min. for a MV of 10L.
by patient’s RR (backup) RR volutrauma possible, no fixed RR (only backup)
spontaneous breathing

Ventilator Complications:
• Dynamic hyperinflation (auto-PEEP): due to incomplete alveolar emptying during expiration; measured during expiratory hold
o Diagnosis: end-expiratory flow >0 (residual pressure); see graphic Auto-PEEP (Adapted from Medscape)
o Risk factors: vent strategy causing hyperinflation (high RR,  I:E ratio)
or obstructive disease (asthma, COPD, CF)
o Consequences: adverse hemodynamic effects (hypotension due to 
venous return), alveolar over-distention (volu-/barotrauma);  effort
for pt to trigger ventilator-assisted breath
o Treatment: allow longer exhalation ( I:E ratio, RR), set exogenous
PEEP to 2/3 auto-PEEP, bronchodilators for obstruction
o If severe hemodynamic or resp. compromise, transiently disconnect pt
from ventilator and manually bag ventilate to allow deflation
• Ventilator-induced lung injury (VILI): alveolar injury alveolar permeability, interstitial & alveolar edema, alveolar hemorrhage,
hyaline membranes, & alveolar collapse (similar to ARDS) (NEJM 2013;369:2126). Avoid w/ lung protective ventilation (see ARDS).
o Volutrauma: over-distension of alveoli due to high VT; or, if there is heterogenous consolidation or atelectasis, a disproportionate
volume from each breath is delivered to open alveoli
o Atelectrauma: shear forces from cyclic alveolar recruitment and de-recruitment injure adjacent alveoli/airways
o Biotrauma: cytokine release from lung epithelium  multi-organ dysfunction
o Oxytrauma: elevated FiO2  free radical production and lung injury
o Barotrauma: injury from high Pplat (highest risk >35)  PTX, subcutaneous emphysema, pneumomediastinum
• Other complications: ventilator-associated pneumonia, laryngeal edema, tracheal stenosis

Louisa Mounsey and Mubeen Shakir

51
TOC

Pulmonary & Critical Care Mechanical Ventilation

•  Peak inspiratory pressure (PIP) = airway resistance + Pplat,; normal PIP <35cm H2O; can be elevated due to increased airway
resistance OR decreased airway compliance (higher Pplat). See flowchart for differential.
o Management: consider steroids, nebulizers, or bronchoscopy to clear secretions/mucus plugs
decreased PIP normal

Air leak PE
increased (eg, >40)
↓airway resistance extrathoracic process

Pplat
normal increased (eg, >30)
↑airway resistance = PIP – Pplat (nl <10) ↓ lung compliance =
VT
(nl >60)
Pplat −PEEP
- Bronchospasm
- Asynchronous breathing
- Secretions
- Auto-PEEP - Pulmonary edema
- Aspiration
- Pneumothorax - PE
- Ventilator tubing problem
- Pneumonia - ILD

Monitoring Mechanics
• Target values: VT ≤6cc/kg IBW, Pplat ≤30; driving pressure (ΔP = Pplat-PEEP) ≤15; compliance >50; resistance <10
o Non-ARDS: VT 10cc/kg vs 4cc/kg  no difference in mortality or vent-free days (PReVENT JAMA 2018;320:1872)
• Ventilator maneuvers for monitoring mechanics:
o Expiratory hold: end expiratory pause; measures auto-PEEP
o Inspiratory hold: end inspiratory pause; measures Pplat and compliance
 At end-inspiration, resistive pressure is 0 and PIP = Pplat

Algorithm for Respiratory Plan on MICU Rounds (REMIX)

R Reason for intubation ARDS, PNA, COPD, pulmonary edema, aspiration, hypoventilation, altered mental status, etc.
E Exchange (gas exchange) Recent ABG; how to improve PaO2 (i.e. diuresis, pulmonary vasodilators) and/or PCO2 (i.e. RR)
M Mechanics Resistance (PIP) and compliance (Pplat, ΔP); chest wall/respiratory muscle strength, cuff leak
I ID/infection (abx) Sputum Cx data, abx day #, source control, need for bronchoscopy; assess for VAP/tracheobronchitis
X eXtubation barriers Daily SAT/SBT, secretion clearance, mental status, planned procedures
(S) Sedation Current sedation, whether changes needed (e.g. start Precedex as bridge peri-extubation)

Liberation & Extubation (ATS/CHEST: AJRCCM 2017;195:115 & Chest 2001;120:375S; NEJM 2012;367:2233; ERJ 2007;29:1033)
• Requirements for extubation: (1) adequately treated underlying disease process, (2) adequate oxygenation and ventilation:
PaO2/FiO2 ≥150-200, PEEP ≤5-8, FiO2 ≤0.4-0.5, pH >7.25, (2) ability to cough, (3) able to manage secretions, (4) hemodynamic
stability. Ideally sufficient mental status (alert, following commands), but as long as protecting airway, AMS does not preclude
extubation.
o Rapid Shallow Breathing Index (RSBI) = RR/VT; RSBI >105 predicts extubation failure (Sn>Sp) (NEJM 1991;324:1445)
• Liberation protocol:
o Daily Spontaneous Awakening Trial (SAT) + Spontaneous Breathing Trial (SBT)
 SAT:  ventilator time, ICU LOS, and mortality if paired with SBT (NEJM 2000;342:1471, Lancet 2008;371:126)
 SBT: ~30min (up to 2hrs) daily trials with little/no support (PEEP ≤5 on PSV; generally 0) =  vent time (NEJM 1996;335:1864;
NEJM 1995;332:345)
- Ways to fail SBT: hypoxemia (SaO2 <90%, PaO2<60), hypercarbia (PaCO2  by >10), inadequate VT, respiratory
distress (HR, RR, HTN, accessory muscle use, diaphoresis), arrhythmia, hemodynamic instability, anxiety/agitation,
somnolence
- Causes of SBT failure: underlying etiology not corrected, volume overload, cardiac dysfunction, neuromuscular
weakness, delirium, anxiety, metabolic abnormalities
• Extubation strategies:
o Extubation to NIPPV or HFNC in patients with hypercarbia / risk factors for reintubation   post-extubation respiratory failure
(Lancet 2009;374:1082, JAMA 2016;316:1565). HFNC w/ intermittent NIV post-extubation   reintubation compared to HFNC
alone (JAMA 2019;322:1465).
o Check for absence of cuff leak before extubation (concerning for laryngeal edema)  consider methylpred 20mg IV q4h
12hrs prior to extubation or IV methylpred 40mg x1 4hrs prior or IV dexamethasone 5mg q6h (Eur J Anaesthesiol 2010;27:534)
o If agitation is limiting ability to extubate, consider dexmedetomidine  may improve odds of extubation (JAMA 2009;301:489)
• Post-extubation respiratory failure: usually due to poor secretion clearance, CHF, aspiration, bronchospasm, laryngeal edema.
o NB: no benefit to NIPPV as rescue therapy during post-extubation respiratory failure and may be associated w/ worse
outcomes (NEJM 2004;350:2454). Not recommended per ERS/ATS guidelines (ERJ 2017;50).
• Tracheostomy: usually performed if still intubated for 14 days
o Early tracheostomy (7 days) if expect intubation >14 days  comfort, allows  sedation,  risk of tracheal stenosis,  vent-
free and  ICU days, though no change in VAP rate (JAMA 2010;303:1483, Crit Care 2015;19:424, Br J Anaesth 2015;114:396)
Louisa Mounsey and Mubeen Shakir
52
TOC

Pulmonary & Critical Care ARDS

Berlin Definition for ARDS & Management Summary
(JAMA 2012;307:2526)
1) Onset within 1 week of insult (usually 72 hours)
2) Not primarily due to hydrostatic/cardiogenic pulmonary edema
3) Imaging showing bilateral opacities on CXR

Mild ARDS Moderate ARDS Severe ARDS

- PaO2/FiO2 (P:F) 200-300 on - P:F 100-200 on PEEP ≥5 cm H2O - P:F ≤100 on PEEP ≥5 cm H2O
PEEP ≥5 cm H2O - Mortality: 32% - Mortality: 45%
- Mortality: 27%

Mechanical Ventilation
Is the patient stable, tolerating NO
noninvasive ventilation, P:F > - VT 4-6cc/kg predicted body weight (PBW), Pplat ≤30, ΔP ≤15
200mmHg? - Optimal PEEP titration
- Keep PaO2 55-80 mmHg or SpO2 88-95% with pH ≥7.25
YES

Continue noninvasive ventilation Is P:F ≤150?

NIPPV = HFNC
YES
(Chest 2017;151:764)
1) Prone Consider VV
2) Paralysis if dyssynchrony Is P:F ECMO
3) Consider iNO ≤100-150

Management Principles in ARDS

(ATS/ESICM/SCCM Guidelines: AJRCCM 2017;195:1253)
Treat underlying etiology: Direct lung injury: pneumonia, aspiration, inhalational injury, near drowning, pulmonary contusion;
Indirect lung injury: sepsis, trauma, pancreatitis, drugs, burns, cardiopulm bypass/pump, transfusion-related acute lung injury (TRALI)
⇒ Common pathway: diffuse, immune-mediated lung injury causing pulmonary capillary and alveolar epithelial damage leading to
increased vascular permeability, impaired gas exchange, and decreased lung compliance (NEJM 2017;377:562)
Strategy (in order of decreasing level of evidence) Effects
• Maintain oxygenation while preventing ventilator-induced lung injury (VILI)
 Mortality (31% vs
Low Tidal Volume • VT 4-6 cc/kg PBW w/ goal Pplat ≤30, driving pressure ≤15 (ΔP=Pplat-PEEP) 39.8%) and  vent-free
o May allow Pplat if ascites, obesity, etc. as may not accurately reflect
Ventilation (LTVV) days vs. “traditional” VT
transpulmonary pressure (see “esophageal balloon catheter” on next page) (12 cc/kg, Pplat <50)
(NEJM 2007;357:1113)
• Permissive hypercapnia: pH goal ≥7.25 allows for lower VT to minimize VILI (NEJM 2000;342:1301)
o Contraind: ICP, RV fail./PH (pulm. vasoconst.), TCA/ASA o/d, pregnant
• V/Q mismatch by compressive atelectasis from heart & diaphragm  more  Mortality (28d &
homogenous vent.  alveolar recruit.   regional volutrauma & compliance 90d) in mod/severe
Prone Positioning
• Contraind.: hemodynamic instability, ICP, inability to turn neck (fixed/unstable ARDS (PROSEVA
C-spine), 2/3rd tri. pregnancy, recent sternotomy NEJM 2013;368:2159)
• Minimize pulmonary edema: “dry lungs are happy lungs” FACTT: ICU LOS &
Conservative Fluid
• Avoid ⊕ fluid balance after reversal of shock vent-free days, no Δ in
Management
• FACTT Trial: CVP<4 (conservative) vs. CVP ≤10-14 (liberal) (NEJM 2006;354:2564) 60d mortality or AKI
• Maximize recruitment, minimize trauma from cyclic atelectasis
Positive End-
• Higher PEEP distributes VT over more alveoli  less over-distention  No clear mortality
Expiratory
improves oxygenation (via V/Q mismatch and  shunt fraction) & compliance benefit. ? benefit for
Pressure (PEEP)
• CV effects of PEEP: preload, RV afterload, LV afterload, CO but variable PEEP if P:F ≤200
(NEJM 2004;351:327;
• Harms of PEEP: barotrauma,  dead space, hemodynamic effects (JAMA 2010;303: 865)
AJRCCM 2010;181:578)
• See next page for more on PEEP optimization
• Maximize oxygenation by vent dyssynchrony and chest wall compliance
ROSE: no Δ in 90d
• Routine early paralysis (cisatracurium) for moderate-severe ARDS (P:F <150) w/o
Neuromuscular mortality,  CV
survival benefit (ROSE NEJM 2019;380:1997); previous trial had shown
Blockade adverse events vs.
possible mortality benefit (ACURASYS NEJM 2010;363:1107)
non-paralyzed
• Can use as bolus/infusion to maintain vent synchrony in mod./severe ARDS

Krishan Sharma
53
TOC

Pulmonary & Critical Care ARDS

Summary of Rescue Therapies for Hypoxemia (6 P’s of refractory hypoxemia):
• Pee: consider diuresis to reduce pulmonary edema (see “conservative fluid management” above)
• PEEP: optimize PEEP (see “PEEP” below)
• Prone positioning: should be implemented early (12-24hrs) if P:F <150 (or 200) despite optimal PEEP titration
o Maintain prone ≥16 hours. If supinate and P:F remains >150 (or 200) and ΔP ≤15 after 2hours, can remain supine.
• Pulmonary vasodilators: start with iNO trial (40ppm; up to 80ppm) and if effective, use inhaled Epoprostenol.
o Should see at least 20%  in PaO2, otherwise do not continue therapy due to cost and risks, including hypotension
o  V/Q mismatch by selectively dilating vessels that perfuse well-ventilated lung; also  PVR and  RV afterload
o No mortality benefit and  risk of renal failure, but may improve oxygenation in first 24hrs and total lung capacity at 6
months (Cochrane Rev 2016, Crit Care 2012;16:R36). NB: risk of methemoglobinemia w/ iNO.
• Paralysis: can be used to maintain vent synchrony (see “neuromuscular blockade” above). Start w/ intermittent boluses &
transition to infusion if persistent dyssynchrony >3 boluses/2hrs (cisatracurium/Nimbex 0.1-0.2 mg/kg q30min PRN 
0-5mg/kg/min; rocuronium 0.6-1.2mg/kg q30-60min PRN  0-20mcg/kg/min, start at 8-12mcg/kg/min)
• Perfusion (ECMO): consider for severe, refractory hypoxemia; for details see ECMO section.
o Mortality benefit, but unclear if due to ECMO vs. transfer to specialized center (CESAR Lancet 2009;374:135, JAMA 2011;306:1659)
o Unclear if mortality benefit to upfront ECMO vs. as rescue therapy (EOLIA NEJM 2018;378:1965)
o Call for evaluation by the ECMO Team (typically the HCICU/Blake 8 attending) - p24252, 857-310-0335

Lung Protective Ventilation: ARDSNet Ventilation

• Initial ventilator set-up: VT = 6 cc/kg PBW, RR to approximate baseline MV (RR <35), moderate PEEP (8-10)
• Adjustments: adjust VT & RR to achieve Pplat ≤30 cm H2O, driving pressure ≤15 (ΔP=Pplat-PEEP), and pH 7.25-7.45
o Oxygenation: goal PaO2 55-80 mmHg or SaO2 88-94%
 SpO2 target <94% a/w  mortality (JAMA 2016;316:1583); hyperoxia  mortality (Crit Care 2014;18:711)
 If persistent hypoxemia requiring high FiO2 (~0.6), should optimize PEEP (see below)
o Mechanics: goal plateau pressure (Pplat) ≤30 (obtain with inspiratory pause); goal ΔP ≤15
 If Pplat >30 and/or ΔP>15:  VT by 1 cc/kg PBW (minimum VT 4 cc/kg PBW); limit on ability to  is MVpCO2/pH
 If Pplat <25 and VT <6cc/kg PBW: can  VT by 1 cc/kg until Pplat >25 or VT 6 cc/kg PBW
o pH: 7.25-7.45 (“permissive hypercapnea” unless contraindicated – see previous page)
 pH >7.45:  RR
 pH <7.25:  RR (up to 35/min) until pH ≥7.25 or PaCO2 <25; watch for auto-PEEP development at high RR
 pH <7.15: set RR = 35/min;  VT by 1 cc/kg until pH >7.15 (may exceed Pplat goal)

Optimal PEEP for ARDS

• ARDSNet FiO2/PEEP scale: http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf
o If P:F <150 on PEEP 5 cm H2O, assess ability to recruit lung by increasing PEEP from 5 to 15 cm H2O
o If improvement, use ARDSNet high PEEP/low FiO2 scale; if no improvement, use low PEEP/high FiO2 scale
• Best PEEP trial: goal is to select the PEEP corresponding to best global recruitment with lowest risk for over-distention based
upon respiratory system compliance (CRS = VT / [Pplat - PEEP])
o Keep VT constant and use decremental titration of PEEP; choose best PEEP based on balance of highest compliance,
lowest driving pressure, acceptable oxygenation, and stable hemodynamics
o Consider performing if persistent hypoxemia (FiO2 ≥0.6) w/ P/F <150
• Driving pressure: ΔP = Pplat - PEEP (goal: ≤15)
o Represents the relationship between tidal volume and lung compliance (ΔP = VT/CRS)
o Lower ΔP associated with  survival independent of other variables (VT, PEEP, Pplat) (NEJM 2015;372:747)
• Recruitment maneuvers:
o Used to open collapsed alveoli to  tidal opening and closing (atelectrauma) and  participation in gas exchange
o Begin with high PEEP to open up alveoli, then decremental PEEP titration to optimize mechanics (JAMA 2008;299:637)
o Outcomes are mixed w/ both  (JAMA 2017;318:1335) and  mortality (Cochrane Rev 2016); avoid massive PIPs (>50)
• Esophageal balloon catheter: estimates intrapleural pressure; used to calculate transpulmonary pressure (Ptp = alveolar
pressure [Pplat] - intrapleural pressure). PEEP then titrated to maintain optimal Ptp (<25 at end-inspiration to prevent VILI, 1-2 at
end-expiration to prevent atelectrauma) (NEJM 2008;359:2095)
o No effect on mortality, ventilator free days, or ICU days, despite improved oxygen and lung compliance, but  risk of
needing advanced rescue therapy (JAMA 2019;321:846)
o Consider in cases of high intra-abdominal pressure (e.g., obesity, ascites, abdominal compartment syndrome)
Controversial Management Strategies
• Steroids: conflicting data; generally not used. Possible benefit in early mod/severe ARDS but  mortality if persistent ARDS
≥14d (CHEST 2007; 131:954; NEJM 2006;354:1671). Avoided in viral pneumonia (influenza, COVID-19).
• High frequency oscillatory ventilation: no vs.  mortality w/ HFOV in ARDS (OSCILLATE NEJM 2013;368:795; OSCAR NEJM
2013;368:806)

Krishan Sharma
54
TOC

Pulmonary & Critical Care ECMO

Types of ECMO: (JACC 2014;63:2769) ECMO: MGH ECMO App;
1. Venoarterial (VA, replaces heart and lungs): treats cardiogenic shock and hypoxemic resp. failure p24252, # 857-310-0335
o Venous blood is removed, oxygenated, CO2 extracted, and returned to arterial system
o Venous cannula is placed in common femoral vein (drainage from IVC or RA); arterial cannula is placed in R femoral artery
2. Venovenous (VV, replaces lungs): treats hypoxemic respiratory failure; relies on native hemodynamic (cardiac) support
o Venous blood is removed, oxygenated, CO2 extracted, and returned to venous system
o Either two venous cannulae (common fem. vein and SVC) or a single bicaval device via R IJ (Avalon) that allows for early mobility
Indications: (criteria suggested by ELSO, MGH Heart App) Contraindications
• Acute resp failure (VV): PaO2/FIO2 <100-150 despite optimization, • Absolute (VA or VV): non-recoverable multi-organ
unable to achieve safe inflation pressures (Pplat <30), uncomp. failure/neurological disease; unwitnessed arrest or CPR > 30
CO2 retention (>80) with inability to mechanically ventilate minutes w/o ROSC; active severe bleeding; contraindication to
• Cardiogenic shock (VA): refractory low cardiac output AC, recent NSGY procedure/active intracranial bleed (<10d)
(CI<2L⁄min⁄m2) and hypotension (SBP<90mmHg) despite adequate • Absolute VA: BMI>40; Ao dissection; severe AI; ESLD/ESRD
volume, inotropes, and intra-aortic balloon pump • Absolute VV: severe right or left HF
• Reversible etiology (ARDS, massive PE, cardiac arrest) • Relative: age>70; multi-organ failure; severe pHTN; unknwn neuro
• Bridge to definitive therapy (transplantation, VAD, recovery) status; GVHD; active malignancy; significant immunosuppression;
• Less invasive strategies have failed: ventilated >7d (ECMO most effective if started within 7d); DIC;
o VV: FiO2 1.0, paralysis, iNO/Veletri, proning, PEEP, diuresis survival <30% based on RESP and SAVE Scores (respscore.com
o VA: volume, pressors, inotropes, IABP, mechanical support / save-score.com)
ECMO Variables
• Sweep: increasing sweep lowers PaCO2 in blood returning to pt;
titration of sweep affects CO2 elimination >> oxygenation
• FiO2: (circuit oxygen) usually set at 1.0
o Note: VV circuit oxygenates fraction of native CO; if native CO
increases, more blood naturally flows via lungs  may allow
FiO2 settings to be decreased if the lungs are functioning
• RPM: RPM is predominant determinant of blood flow (2-5 L/min;
also affected by cannula size and native CO)
• Hgb goal: >7.5g/dL
• Clotting: PTT 60-80 (q2h, check with team on goal); Plt >75K; Fibrinogen >150 (may Diagram of VV ECMO
change if bleeding). Use UFH for anticoagulation and check AT-III and anti-Xa. (NEJM 2011;365:1905)
Complications: (Heart Lung Circ 2014;23:10)
• Clots (oxygenator, pump, tubing, hemofilter), 0.13-22% pts; bleeding (cannulation site, GI, intracranial, hemolysis, DIC), 5.3-79% pts;
neurologic & MSK (intracranial bleed, stroke, seizure, encephalopathy), 10–33% pts; limb ischemia,13–25% pts; infection, 17-49%
pts; AKI, 30-58% pts; multi-organ failure, 10% pts; cannulation problems, 0.8-8% pts; hyperbilirubinemia, 27% pts
Troubleshooting the Circuit:
• Chatter: “shaking” sound caused by high (-) pressure in the tubing; usually due to hypovolemia, treat w/ volume (5% albumin)
• Poor oxygenation (as measured on patient ABG):
a) Recirculation: blood recirculates from the outflow (return) catheter back into the inflow (drainage) catheter, bypassing body; usually
due to catheter malposition  discordant circuit O2 and patient O2 content (treatment: reposition cannula,  RPM)
b) Machine malfunction: hypoxemia on post-membrane ABG (treatment: replace membrane)
c) Shunt: occurs if native CO > ECMO CO (large fraction of blood travels through diseased lungs rather than ECMO circuit and is
poorly oxygenated)  hypoxemia on patient ABG only (treatment:  RPM, reduce fever, reduce inotropes, +/- beta blockade)
• Harlequin syndrome (VA only): hypoxia of upper extremities, heart, brain – can occur only when femoral artery is cannulated.
Cardiac recovery, but poor lung fx  native cardiac output (de-oxygenated) pushes against oxygenated ECMO blood in aortic arch
leading to hypoxia of UE, brain, heart; treated by relocation of arterial cannula to R subclav or aorta (Heart Lung Ves 2015;7:320).
Outcomes:
• Acute respiratory failure: 2 major studies show  mortality, though unclear if benefit from referral to ECMO center or ECMO itself
o 75 matched pairs ARDS d/t H1N1; transfer to ECMO center mort. (23% vs. 52%); 85% tx w/ ECMO (JAMA 2011;306:1659)
o CESAR: RCT of 180 pts w/ severe ARDS randomized to referral to single ECMO center vs. conventional management. ECMO-
referred group  survival without disability at 6 months (63% vs. 47%) (Lancet 2009;374:135)
o EOLIA: RCT of 249 with severe ARDS (P:F <80) to ECMO w/in 7d vs. conventional therapy; early ECMO showed more days free
of renal failure (46 vs 21 days), fewer ischemic strokes (0% vs 5%), and no significant difference in 60d mortality (35% vs 46%)
(NEJM 2018;378:1965) though stopped early d/t prelim results in favor of ECMO (NEJM 2018;378:2031)
• Refractory cardiogenic shock: 40-41% survive to discharge (all comers); ECMO implantation while under CPR was strongest
predictor of death (CCM 2008;36:1404, ASAIO 2017;63:60)
• ECPR: ECMO as extension of CPR in pts with cardiac arrest – in-hospital cardiac arrest: improved survival (OR: 0.17) compared to
conventional CPR (CCM 2011;39:1); out-of-hospital arrest: 22% with meaningful neurologic recovery (Resuscitation 2016;101:12);
overall: 29% survive to discharge (ASAIO 2017;63:60). Consider calling ECMO team if 10 minutes w/o ROSC to discuss ECMO.
MGH ECMO App (download here): “Call MGH ECMO Consult”, consult/transport info, ECMO guidelines

Ryan Dodge and Sean Mendez

55
TOC

Pulmonary & Critical Care Sedation

GOAL OF ICU SEDATION: addressing ICU triad of pain, agitation, & delirium (NEJM 2014;370:444) Agitation
1. Pain: common,  energy expenditure; analgesia alone adequate in some (Lancet 2010;375:475)
2. Agitation: target light sedation in intubated pts; no benefit to non-sedation approach (NEJM 2020;382:1103)
3. Delirium: 16-89% ICU pts; a/w  mortality,  QOL, poor cognitive outcomes (JAMA 2004;291:1753,
CCM 2010;38:1513; CCM 2010;38:2311);  risk w/ deeper sedation (Intensive Care Med 2007;33:66) Pain Delirium
ABCDE bundle: a/w  vent-free days (21 vs. 24d over 28d study period),  delirium (CCM 2014;42:1024)
A – Spontaneous awakening trial (SAT): daily interruptions RASS (Richmond Agitation Sedation Scale) (AJRCCM 2002;166:1338)
of sedation   ICU LOS, vent days (NEJM 2000;342:1471), +4 Combative Overtly combative, violent, immediate danger to staff
PTSD sx (AJRCCM 2003;168:1457) +3 Very agitated Pulls or removes tube/catheters; aggressive
B – Spontaneous breathing trial (SBT): for pts who pass +2 Agitated Frequent, non-purposeful mvmt; fights ventilator
SAT, assess for suitability of extubation (Lancet 2008;371:126) +1 Restless Anxious, but mvmt not aggressive or vigorous
C – Choice of sedation: see below 0 Alert and calm
D – Delirium: assess CAM-ICU daily -1 Drowsy Sustained awakening to voice (≥10sec)
E – Early mobility:  pressure sores,  functional status,  -2 Light sedation Briefly awakens w/ eye contact to voice
-3 Mod. sedation Mvmt or eye opening to voice but no eye contact
vent days,  delirium (Lancet 2009;373:1874; NEJM
No response to voice but movement or eye opening
2014;370:1626) -4 Deep sedation
to physical stimulation
SEDATION AGENTS: (SCCM guidelines: CCM 2018;46:e825) -5 Cannot be aroused No response to voice or physical stimulation
Opioids: primarily analgesia. Side effects (SEs): resp. depression, tolerance, constipation (Rx w/ bowel reg), ileus,  delirium w/  use
Agent Notes Clearance
Hydromorphone May accumulate in hepatic/renal failure
 potency (compared to morphine)
bolus 0.25-1mg q1hr, gtt 0.5-5mg/hr but least affected by end-organ dysfunction.
Fentanyl t1/2 30-60m w/ bolus; t1/2 with gtt (9-16h) Accumulates in adipose
bolus 25-50mcg q30m, gtt 50-200 mcg/hr can cause chest wall rigidity No renally excreted metabolites
Morphine Inexpensive, generally well-tolerated but
Accumulates in renal failure
bolus 2-4mg q1hr, gtt 2-30mg/hr can cause pruritus, bradycardia, HoTN
Non-benzodiazepine sedatives: primarily anesthesia, amnesia; do NOT provide analgesia
Agent Notes Clearance
1st line sedative. Immediate onset/rapid awakening.  ICP & seizures so also used
Metabolism
Propofol in status epilepticus & EtOH w/d. Earlier extubation &  mortality vs benzos (AJRCCM
unaltered by
5-50mcg/kg/min 2014;189:1383)
renal/liver failure
(max of 83) SEs: HoTN, bradycardia, hypertriglyceridemia  pancreatitis (follow TGs), green
Accumulates in
Mechanism unclear urine, propofol infusion syndrome (PRIS) (>48 hrs): acidosis, bradycardia,
adipose
renal/liver failure, rhabdo, HLD, HSM
Sympatholytic w/ anxiolysis w/o resp. depression or amnesia. No sig. analgesia
A/w  delirium & earlier extubation (JAMA 2016;315:1460);  vent days vs. midazolam
Dexmedetomidine
(JAMA 2012;307:1151, JAMA 2009;301:489),  delirium vs. lorazepam (JAMA
(Precedex) Dose-reduce in
2007;298:2644) and propofol (Eur J Anaesthesiol 202;37:121); nightly admin. may prevent
0.2-1.5mcg/kg/hr renal, liver failure
delirium (AJRCCM 2018;197:1147). No Δ in mortality (NEJM 2019;380:2506)
Central α2 agonist
SEs: bradycardia, HoTN, withdrawal syndrome (agitation, tachycardia); can cross-
titrate to clonidine (Pharmacotherapy 2015;35:251)
Ketamine “Dissociated amnesia” & analgesia w/o resp depression; some bronchodilator effects Metabolites
5-30mcg/kg/min SEs: sympathetic stimulation (hypertension, bronchodilation, hypersalivation), accumulate in renal,
NMDA antagonist hallucinations, delirium upon withdrawal, falsely  BIS activity liver failure
Benzodiazepines: primarily amnesia, anxiolysis. SEs: resp depression, agitation, withdrawal/tolerance
*For sedation, propofol (& dexmedetomidine) preferred > BZDs due to  mortality,  time to light sedation & extubation,  delirium
Agent Notes Clearance
Midazolam CYP3A4 metab  med interactions (fluconazole, azithro, flagyl, amio) Accumulates in adipose
bolus 0.5-4mg q2h, gtt Shorter t1/2 vs. lorazepam (~2-6h vs 14h), both w/ fast onset (2-5min) Metabolites accumulate in
2-8mg/hr Only IV BZD not in propylene glycol hepatic/renal failure
Propylene glycol (solvent) toxicity w/  dose (lactic acid, HoTN, Preferred in renal, liver failure
Lorazepam
arrhythmia). Risk of oversedation due to delayed over midazolam but caution in
bolus 1-2mg
response/accumulation. severe liver disease
Anti-Psychotics: useful in treating delirium + helping to liberate agitated pts from ventilator; SEs:  QTc, EPS, anti-cholinergic, NMS
Agent Notes Clearance
Quetiapine
May  time to resolution of delirium w/ haldol (CCM 2010;38:419); No dosing adjustment in renal or
50mg q12  max
 NMS, EPS; also treats insomnia hepatic failure
400mg/d
Haloperidol Does not  mortality, delirium incidence, duration of ICU stay or No dosing adjustment in renal or
2.5-5mg q6 PRN hospitalization, vent time (JAMA 2018;319:680; NEJM 2018;379:2506) hepatic failure

Krishan Sharma

56
TOC

Pulmonary & Critical Care Shock

Overview: (NEJM 2013;369:1726)
• Definition: state of tissue hypoxia due to decreased or dysregulated oxygen delivery or extraction, resulting in end-organ damage
o Initially reversible, but rapidly progresses: cell death  end-organ damage  multiorgan failure  death
• Clinical manifestations: hypotension (SBP <90mmHg or SBP >40mmHg from baseline); end organ dysfunction: oliguria (UOP
<0.5cc/kg/hr), altered mental status, metabolic acidosis (+/- anion gap, lactate); cool & clammy vs. warm & flushed extremities.
(N.B. any of these can be normal—including BP—in a patient who is in shock, so a high index of suspicion is needed.)
• Initial workup: focused H&P, ensure access, review meds, order EKG/CXR, labs (ABG/VBG, CBC+diff, CMP, TnT, lactate, CVO2)
MAP: determined by CO (cardiac output) and SVR (systemic vascular resistance) Lactic Acidosis
(NEJM 2014;371:2309)
MAP = RAP + CO x SVR SVR determined by vessel
Type A: due to tissue Type B: NOT marked tissue
diameter/length and blood viscosity hypoperfusion, typically hypoperfusion. Metformin,
seen in shock; can be malignancy (e.g. Warburg),
profound in the setting EtOH, thiamine deficiency,
(2/3) DBP + (1/3) SBP HR x SV SV determined by preload,
of bowel ischemia and albuterol, D-lactate, mito.
afterload, & contractility necrosis dysfunction, liver disease
Etiologies of Shock:

Signs of CO: Signs of CO:

- Widened pulse pressure
SHOCK
- Narrow pulse pressure
- Low diastolic BP - Cold extremities
- Warm extremities CO CO - Slow cap refill
- Normal cap refill (early)

Distributive (66%) Hypovolemic (16%) Cardiogenic (16%) Obstructive (2%)

 systemic vascular resistance &
Pathophys.  cardiac output  inadequate oxygen delivery
altered oxygen extraction
Sepsis, SIRS, anaphylaxis, adrenal Hemorrhagic (GI, RP, MI, HF, myocarditis, Extra-cardiac causes:
insufficiency, liver failure, abdomen, thigh), GI losses, severe valve disease, PE, tension PTX,
Examples
toxins/meds, neurogenic (NEJM 3rd spacing (pancreatitis) arrhythmias tamponade
2013;369:840; NEJM 2001;345:588) (NEJM 2018;378:370)
Extremities Warm and dry Cold and dry Cold and wet Cold and dry
CVP/PCWP  / normal    (tamponade) / normal
CO or CVO2  / normal   
SVR    
Tamponade: pericardial
Normal chamber size, normal/ Small chambers, Large chambers, poor
TTE Findings effusion
contractility normal/contractility contractility
PE/PTX: dilated RV
All causes: fluids, pressors Ensure adequate access! HF: diuresis, Tamponade: acutely,
Sepsis: source control, abx Most cases: fluids inotropes, +/- PA line fluids; pericardiocentesis
Basic
Adrenal insuff: steroids (hydrocort) Hemorrhage: pRBCs, Arrhythmias: PE: AC/lysis
Management
Anaphylaxis: epi 0.3mg IM, H1RA. hemostasis via electricity, anti- PTX: chest tube vs.
H2RA, solumedrol, albuterol surgery/IR/GI arrhythmics needle decompression
If the etiology of shock is unclear, the most useful ways to quickly distinguish include:
• First step: vitals: wide vs. narrow (<25% of SBP) pulse pressure; exam: warm vs. cold, dry vs. wet, rashes or mottling
• Quick data points: CVO2 (normal CvO2 = 70%), CVP, TTE (consider POCUS and/or STAT TTE)
• Consider: PA catheterization for shock differentiation. See PA Catheterization for full discussion, but no benefit in terms of mortality,
LOS, or cost in unselected ICU or CHF pts (Cochrane Rev 2013, ESCAPE JAMA 2005;294:1625, PAC-Man Lancet 2005;366:472)
Management Considerations
• Ventilatory support: intubate if necessary (concomitant respiratory failure, unable to compensate for metabolic acidosis, marked
hemodynamic instability), but have pressors available as intubation often worsens hypotension; be aware that SpO2 is often
unreliable due to peripheral vasoconstriction (even on earlobe), & may require frequent ABG plus (includes SaO2)
• Antibiotics: if septic shock is on the differential, get early cultures and start broad spectrum antibiotics without delay
• Fluid resuscitation: crystalloid bolus (not infusion). Can predict fluid responsiveness by pulse pressure variation, passive leg raise,
IVC diameter (see Sepsis). Good approximation = improvement in BP/UOP/lactate with fluid challenge. Appropriate fluid challenge
should raise CVP by 2. Be more cautious with fluids if possible cardiogenic shock. (NEJM 2013;369:1243)
• Vasoactive agents (see Vasopressors): typically titrate to MAP >65 mmHg (if cardiogenic, MAP >60 mmHg)
• Steroids: if known adrenal insufficiency or chronic steroid use, consider stress-dose steroids such as hydrocortisone 50mg q6h or
100mg q8h x5-7 days pending clinical stability; unclear role & highly debated for septic shock (see Sepsis).
• Bicarbonate: if pH <7.1 or <7.2 w/ severe AKI, can temporize while fixing underlying etiology. HCO3  CO2 that pt must ventilate off,
so cautious if CO2 or otherwise tenuous resp. status. No mortality benefit except in AKI (BICAR-ICU Lancet 2018;392:31)
• Specialized teams: STEMI (x6-8282), PERT (x4-7378), SHOCK (p11511 – IABP, Impella), ECMO (p24252 / 857-310-0335)
Sirus Jesudasen
57
TOC

Pulmonary & Critical Care Sepsis

OVERVIEW
• Definitions: recently updated in 2016 by Sepsis Definitions Task Force (Sepsis-3) (JAMA 2016;315:801) qSOFA
o Sepsis: life-threatening organ dysfunction ( SOFA ≥2) caused by dysregulated host response to infection 1. RR>22
o Septic shock: sepsis + (1) pressors to sustain MAP >65 AND (2) lactate >2 w/o hypovolemia 2. AMS
• Diagnosis: SIRS + infectious source failed to identify 1/8 w/ sepsis & organ failure (NEJM 2015;372:1629) 3. SBP≤100
o Sequential Organ Failure Assessment (SOFA) score: includes PaO2/FiO2, plts, bili, BP, GCS, & Cr
o Quick SOFA (qSOFA) ≥2 can help identify pts w/ suspected infection w/ early sepsis outside of ICU (ICU LOS, mortality)
P A T H O P H Y S I O L O G Y / C L I N I C A L M A N I F E S T A T I O N S (NEJM 2013;369:840, BMJ 2016;353:i1585)
• Microbial components bind immune cells   inflammatory mediators, PMN migration; if exceeds boundaries of local environment 
sepsis (generalized inflammatory response)  tissue ischemia (thrombosis in microcirculation 2/2 altered coag., RBC deformability
 O2 extraction), cytopathic injury (mitochondrial dysfunction), impaired endothelial barrier ( edema)  organ dysfunction
Cardiovascular Vasodilation  hypotension; ventricular function may be either hyperdynamic or depressed
Pulmonary Pulmonary edema, ARDS/ALI
GI  Intestinal permeability   bacterial translocation  worsening systemic inflammation
Hepatic Cholestasis (“sepsis-induced cholestasis”), impaired reticuloendothelial function
Renal AKI of multifactorial etiology, including microvascular dysfunction, oxidative stress, global hypoperfusion
Hematologic Early inflammation, late immunosuppression; procoagulant and anticoagulant disequilibrium: DIC,  plt
Endocrine Altered glycemic control, adrenal dysfunction, euthyroid sick syndrome
Neurologic Encephalopathy
I N I T I A L M A N A G E M E N T (2016 Surviving Sepsis Guidelines: Intensive Care Med 2017;43:304)
Sepsis & septic shock are medical emergencies, so early recognition is critical. Components of initial management include:
1) Antibiotics: empiric broad spectrum IV antibiotics should be administered within one hour of recognition. Order STAT.
• Delay   mortality by 7.6%/hr (CCM 2006;34:1589; CCM 2010;38:1045). More rapid abx   mortality (NEJM 2017;376:2235)
• Abx selection: guided by site of infection, prior pathogens, exposures (SNF, lines, recent abx, etc), immunocompromise, etc.
o Consider double coverage of PsA if known/suspected PsA infection w/: severe sepsis/septic shock, bacteremia in neutropenic pt,
burn pt, or otherwise high incidence of resistance to chosen class (10-15%). Usually β-lactam + (FLQ or aminoglycoside).
o If there is suspicion of toxic shock syndrome, add clindamycin for anti-toxin effects and staph/strep coverage
o If risk factors for invasive Candida infection (neutropenia, chemotherapy, transplant, indwelling catheters, TPN, recent major
surgery [esp. abdominal], prolonged admission/abx) can consider empiric antifungals (typically micafungin)
 In nonneutropenic pts w/ Candida colonization, empiric antifungals not a/w  fungal infection-free survival but did 
invasive fungal infections (JAMA 2016;316:1555)
• De-escalation: once causative organism identified, Δ to narrowest effective agent, w/ duration individualized to pt/etiology/trajectory
o Procalcitonin may be useful in guiding cessation (Lancet 2010;375:463; Lancet ID 2016;16:819; CCM 2018;46:684)
2) Resuscitation: initial fluid resuscitation with 30 mL/kg of crystalloid completed within 3 hours
• Balanced crystalloids (e.g., LR) with  mortality and  renal impairment in critically ill adults compared to NS (NEJM 2018;378:829);
no mortality benefit to colloids > or in addition to crystalloids (NEJM 2004;350:2247, JAMA 2013;310:1809; NEJM 2014;370:1412)
• After the initial resuscitation effort, further fluid administration should be guided by dynamic measures of fluid responsiveness:
Assessing Fluid Responsiveness (JAMA 2016;316:1298)
Method Fluid responsive if:
Pulse pressure variation: must be
mechanically ventilated w/ Vt ≥8 mL/kg,
not spontaneously triggering ventilator, & in
NSR (Crit Care 2014;18:650) PPV ≥12%
PPV = (PPmax- PPmin)/ PPmean

Passive leg raise: raise legs to 45° w/ torso horizontal x1 min. in mech.
ventilated patient to provide “autotransfusion” of ~250-350cc; assess Δ in Pulse pressure  ≥10%
hemodynamics (surrogate for SV if invasive
measures of CO not available)

Δ in IVC diam: measure 1cm prox. to hepatic vein junction in M-mode; if mech. vent, calc. distensibility: dIVC ≥15%
dIVC = (Dmax-Dmin)/Dmin; if spont. breathing, calc. collapsibility: cIVC= Dmax-Dmin/Dmax cIVC ≥40%
Fluid challenge: bolus 250-500cc fluids; measure CVP before and immediately after and if  by ≥2 Improvement in
then was appropriate volume challenge. If chosen parameter(s) improve, then fluid responsive. If do BP/vasopressors, UOP, lactate;
not, then not fluid responsive.  in pulse pressure ≥10%
• Resp. variation w/ vent: pos. pressure during expiration  venous return & RV preload  LV preload. If on ascending portion of
Starling curve, sensitive to Δs in preload. Volume responsive pts will show larger variations in PP or SV during respiratory cycle.
• Lack of volume responsiveness suggests patient is on the flat part of the Frank-Starling curve; use/increase vasopressors instead.
• Targets of resusc.: lactate clearance (normalization or >20%/2hrs) (JAMA 2010;303:739); cap. refill (<30s) (JAMA 2019;321:654)

Sirus Jesudasen
58
TOC

Pulmonary & Critical Care Sepsis

3) Vasopressors: target a mean arterial pressure (MAP) of >65 mm Hg (NEJM 2014;370:1583) (see Vasopressors page for full details)
• Norepinephrine (NE, Levophed): first choice vasopressor
• Vasopressin: can be added to NE to reduce dose or MAP; ?vaso deficiency in septic shock (Circulation 1997;95:1122)
• Epinephrine: recommended when 2nd or 3rd agent is needed; can be used instead of vaso
• Phenylephrine (Neo): recommended primarily when: (a) NE is associated with serious arrhythmias, (b) CO is high and BP persistently
low, (c) as salvage therapy when NE + vaso have failed to achieve MAP target (d) hypotension a/w AFRVR
• Dopamine: reserved for highly selective patient population with bradycardia and low risk of tachyarrhythmia; a/w  risk of
arrhythmias/mortality in all-comers (CCM 2012;40:725; NEJM 2010;362:779)
• Methylene blue: uncommonly used, pressor of last resort when NO-mediated vasoplegia is suspected
• Angiotensin II: not currently available at MGH; anticipate eventual availability given ATHOS-3 trial (NEJM 2019;377:419)
4) Source Identification and Control
• Cultures: obtain cultures prior to antimicrobials (unless will significantly
Where to draw blood cultures?
delay administration) as  sensitivity (Annals 2019). Get at least 2 sets of BCx
Drawing cultures from vascular access devices
with at least one drawn percutaneously.
can lead to high rates of false positives. Obtain
o Routine blood cultures will grow Candida, Trichosporon, Fusarium and
cultures from vascular access devices only
Cryptococcus. Consider 1,3 beta-D-glucan assay, galactomannan,
if concerned for CRBSI (rigors with infusion,
and/or cryptococcal Ag if concerned for fungemia.
erythema/induration around line site); otherwise
• Identify conditions that require source control: necrotizing soft tissue infection, obtain only peripheral blood cultures.
abscess, cholangitis, cholecystitis, GI perforation/ischemia, pyelo a/w
obstructive renal stone or abscess, empyema, septic arthritis, devices
• Failure to improve on broad spectrum antibiotics should prompt evaluation for an occult source with imaging
OTHER ASPECTS OF MANAGEMENT
Renal Dysfunction
• Timing: no mortality benefit to early (<12h) vs. delayed (>48h) initiation of RRT in patients with septic shock and severe AKI
without urgent indication (NEJM 2018;379:1431; NEJM 2016;375:122)
• Modality: CVVH and HD are largely equivalent for treating AKI, but CVVH minimizes fluid shifts in hemodynamically unstable patients
Metabolic Acidosis / Lactic Acidosis
• Ultimately, need to correct underlying etiology. Can temporize with bicarbonate if:
o Severe acidemia w/ pH <7.1: used as cutoff as evidence in animal/tissue studies of myocardial depression, catecholamine
efficacy, arrhythmias, though generally not replicated in human studies & pts w/ DKA can have pH <7 w/o these effects
o Less severe acidemia (pH <7.2) w/ AKI: BICAR-ICU showed that bicarb infusion to keep pH >7.3 (max 1L/24hrs) a/w  mortality
(Lancet 2018;392:31)
• Bicarbonate administration: 1 amp = 50mEq / 50mL (or 8.4%); or infusion of solution of 150 mEq (3 amps) in 1L of D5W
o Caution: HCO3  pCO2 that must be ventilated off, so must have sufficient resp. drive / be intubated. Also   iCa.
Transfusions
• Transfusion goal of Hgb 7g/dL similar to 9g/dL unless cardiac ischemia or active hemorrhage (TRISS NEJM 2014;371:1381)
CONTROVERSIAL MANAGEMENT STRATEGIES
Corticosteroids
• Rationale: critical illness affects HPA axis, may cause relative adrenal insufficiency (i.e. inadequate cortisol for total body demands) /
“critical illness-related corticosteroid insufficiency” (CIRCI)
• Diagnosis: cortisol levels/stim. have not reliably predicted pts who will benefit from steroids, but random AM cortisol ≤10 or Δ in
baseline cortisol of ≤9 after 250mg cosyntropin stim. are indicators of likely adrenal insufficiency (NB: etomidate can interfere w/ stim.)
• Controversy: initial study (“Annane / French trial”) w/ mortality benefit w/ IV hydrocort 50mg q6 + fludricort 50mcg/d x7d in pts w/
septic shock w/ abnormal cort stim (Δ ≤9) (JAMA 2002;288:862). Similar results by same group in more recent study (APROCCHSS
NEJM 2018), but mortality benefit not seen in other trials (CORTICUS NEJM 2008, HYPRESS JAMA 2016, & ADRENAL NEJM 2018).
• Conclusion: if refractory septic shock (esp. if e/o CIRCI), consider IV hydrocort 50mg q6 or 100mg q8 (max 400mg/d) ± fludricort
(hydrocort likely has sufficient mineralcorticoid effect) for 5-7d w/ taper guided by response (Intensive Care Med 2017;43:1751)
Vitamin C
• Rationale: Vitamin C is an antioxidant; may also act synergistically with hydrocortisone to  inflammation
• Controversy: single study by Marik et al. (Chest 2017;151:1229) showed  mortality w/ combination of high-dose Vit C (1.5g q6 x4d),
hydrocort (50mg q6 x7d), & IV thiamine (200mg q12 x7d) but was small, single-center cohort (not RTC) and has not been validated.
No benefit to vitamin C alone in meta-analysis (CCM 2019;47:774) or in sepsis w/ ARDS (JAMA 2019;322:1261). Also no benefit to Vit
C/thiamine in addition to hydrocort (VITAMINS JAMA 2020).
• Conclusion: no proven benefit to Vitamin C, either alone or in combination w/ thiamine & hydrocortisone.
Esmolol
• Rationale: β-blockade may attenuate harmful effects of sympathetic adrenergic response in septic shock
• Controversy: single RCT w/ significantly  mortality in pts w/ septic shock treated w/ esmolol to keep HR 80-94 (JAMA 2013;310:1683),
but control group had a significantly  mortality rate (80.5%) than expected. Not confirmed in subsequent studies.
• Conclusion: need further validation of findings; esmolol not routinely used in septic shock

Sirus Jesudasen
59
TOC

Pulmonary & Critical Care Vasopressors

Category Name α β1 β2 D PVR SVR CO α1: vasoconstriction,  duration of heart contraction
Norepinephrine 4+ 2+ (+) 0 1+   α2: sedation/analgesia, vasoconstriction (if
Dopamine (low) 0 1+ 0 2+ ± -/  peripheral) vs. vasodilation (if central, e.g.,
Inoconstrictors Dopamine (med) 1+ 2+ 0 2+ ±   clonidine)
Dopamine (high) 2+ 2+ 0 2+ ±   β1:  inotropy, chronotropy
Epinephrine 4+ 3+ 2+ 0 1- -/  β2:  vasodilation
Dobutamine (+) 3+ 2+ 0 1-   D: renal/splanchnic/coronary/cerebral vasodilation
Inodilators V1: vasoconstriction (especially splanchnic)
Milrinone PDE inhibitor 2-  
Phenylephrine 5+ 0 0 0 2+   *If vasopressor extravasates into surrounding
Vasoconstrictors tissue, give phentolamine 5-10mg in 10cc NS
Vasopressin V1 ±  -/
Chronotrope Isoproterenol 0 3+ 3+ 0 0  
\
directly into area of extravasation
VASOPRESSORS & INOTROPES (Circulation 2008;118:1047)
Name Mechanism Uses Side effects Dosing
α1 > β1 agonist: Initial: 5-12 mcg/min
 SVR ,  CO (0.1-0.15 mcg/kg/min)
Norepinephrine Septic shock (1st ) Arrhythmia
Levophed Reflex brady from Cardiogenic shock (1st) Digital ischemia
vasodilation can Max: 35-100 mcg/min
“Levo” Hypovolemic shock (1st)  FSBG
negate HR from (0.75 mcg/kg/min)
chronotropy
Initial: 100-180 mcg/min
Septic shock if  HR from NE
Phenylephrine Reflex bradycardia (0.5-2 mcg/kg/min)
Pure vasopressor or CO w/  BP or 3rd agent
Neosynephrine  CO,  PAP,  SVR Max: 360-1000 mcg/min
α1 agonist:  SVR needed
“Neo” Digital ischemia (6 mcg/kg/min)
AFRVR, HOCM, AS, RV failure
PIV: <250 mcg/min
Septic shock (2nd) ( mortality w/
Usual: 0.04 U/min
V1 agonist:  SVR NE vs. NE alone) (VASST NEJM
Vasopressin Coronary ischemia
Pitressin 2008;358:877) Mesenteric ischemia
V2 agonist:  renal Anaphylaxis (2nd) Max: 0.08 U/min
“Vaso” H2O reabsorption  Na
Pulmonary HTN/RV failure (only as salvage therapy)
VASOPRESSORS

Hepatorenal syndrome
Low: β1 >β2 >α1: ACLS (1st)  HR, arrhythmias
Low: 1-4 mcg/min
Epinephrine  CO, neutral SVR Anaphylaxis (1st) Myocardial ischemia
Adrenalin Symptomatic bradycardia (2nd)  lactate
“Epi” High: α1 > β1>β2: Septic shock  splanchnic SVR High: 5-35 mcg/min
 CO,  SVR Bronchospasm  FSBG
Low: D1 >β1: Symptomatic bradycardia
 CO,  UOP Tachyarrythmia Low: 1-2 mcg/kg/min
Septic shock w/ bradycardia
Dopamine Myocardial ischemia
Med: β1>D1:  mortality vs. levophed in
Intropin  BP (low dose) Med: 5-10 mcg/kg/min
 CO,  SVR septic (CCM 2017;45:486) &
“Dopa”  PCWP, pulm shunt
High: α1>β1>D1: cardiogenic shock (SOAP-II NEJM  FSBG High: 10-50 mcg/kg/min
 SVR 2010;362:779)
Refractory vasoplegia due to Falsely  SpO2
sepsis/anaphylaxis Arrhythmias Initial: 1-2 mg/kg
 NO and cGMP 
Methylene Post-cardiopulm bypass  PVR
 Sm musc tone:
blue Amlodipine overdose Rash, hemolysis,
 SVR Max: 5 mg/kg
Metformin overdose serotonin syndrome
Methemoglobinemia Contraindicated in G6PD
Refractory septic shock
Angiotensin II ANG-II agon.:  SVR Peripheral ischemia 10-20ng/kg/min; max 40
(NB: not avail at MGH)
 BP,  HR Initial: 0.5-1 mcg/kg/min
Dobutamine
β1, β2>α1 agonist: Cardiogenic shock Arrhythmias (2.5 if more severe)
Dobutrex
 CO,  SVR Sepsis + LV EF (added to NE) Myocardial ischemia
“Dobuta” Max: 20-40 mcg/kg/min
Tachyphylaxis
PDE inhibitor
Initial: 0.125 mcg/kg/min
INOTROPES

(cAMP)  Hypotension
Milrinone Cardiogenic shock
 inotropy, Arrhythmias
Primacor RV failure (PVR, LVEDV)
vasodilation: Myocardial ischemia Max: 0.75 mcg/kg/min
 CO,  PVR/SVR
 BP,  HR 2-10 mcg
Isoproterenol β1 = β2 agonist: Symptomatic bradycardia Arrhythmias (can bolus 2-6mcg first)
Isuprel  HR,  SVR Mg-refractory Torsades Myocardial ischemia
30 mcg/min
Flushing, anxiety
Sirus Jesudasen
60
TOC

Pulmonary & Critical Care Toxicology

Toxicology resident pager 21827 • Toxicology/Poison Control Center 1-800-222-1222 • http://mghlabtest.partners.org
MGH Laboratory Toxicology Screen Guru: Dr. Jim Flood ([email protected]; great resource for questions re: tox screens)
Drug/Toxin Presenting Symptoms Diagnostic Workup Management
Acetaminophen See Acute Liver Injury & Failure
Avoid intubation (if required,
Tinnitus, fever, vertigo, N/V/D, ABG (mixed respiratory alkalosis /
hyperventilate to avoid acidemia),
tachypnea, pulmonary edema, AMS metabolic acidosis), BMP, CXR,
IVF, charcoal (1 g/kg), glucose (100
Salicylates (can have neuroglycopenia w/ normal salicylate level (>30-50 mg/dL toxic,
mL D50), bicarb, alkalinize urine to
serum glucose), respiratory alkalosis though a clinical dx).Repeat levels
pH 7.5-8, avoid acetazolamide.
(early), metabolic acidosis (late) and ABG Q2H until improving.
Consider HD.
IV or intranasal naloxone (0.4-2 mg).
Repeat PRN. Naloxone ½-life shorter
RR and tidal volume, CNS
Opioids EKG, core temp, glucose, CPK than most opioids  repeated dosing
depression, bowel sounds, miosis
or gtt, esp if long-acting opioids (2/3
effective bolus dose per hr).
Depressed MS, ataxia, slurred speech, Hx, urine tox can give qualitative Supportive; avoid flumazenil as it
Benzodiazepines
hyporeflexia, RR, coma result precipitates withdrawal + seizures.
Supportive, cooling for hyperthermia;
Anticholinergics Mydriasis, hyperthermia, decreased
charcoal (1 g/kg) if <1hr, benzos for
Atropine, Benztropine, sweating, flushing agitated delirium,
Hx, EKG, CPK agitation & seizure, physostigmine if
Scopolamine, urinary retention, ileus, tachycardia,
severe (ICU, atropine at bedside; not
Diphenhydramine HTN
for TCA ODs).
Cal c i u m (2-3 g), pressors,
Hx, EKG (brady, long PR), blood
N/V, HoTN, CHF, brady, AV block, glucagon, HIGH DOSE-insulin (1 U/kg
levels slow & correlate poorly.
CCBs stupor, c a r d i a c a r r e s t , bolus, then 0.5-1U/kg/hr gtt, adjust to
Extended release preps dangerous.
hyperglycemia cardiac response), IVF; consider
High glucose = poor prognosis.
pacing, atropine, ECMO.
HoTN, bradycardia, AV block, long Pressors, calcium, glucagon (0.05-
Hx, EKG, blood levels slow and
QTc (sotalol), CHF, bronchospasm, 0.15mg/kg bolus q3-5min or gtt), high-
B-Blockers correlate poorly; propranolol highest
hypoglycemia, stupor, hyperkalemia, dose insulin (see above), IVF; atropine,
mortality.
seizure (propranolol), miosis pacing, ECMO.
EKG, digoxin level (nl 0.9-2.0 ng/mL;
Bradycardia, AV block, N/V/abd pain, may not be accurate if drawn within Digoxin-specific Fab fragments (if
hyperkalemia, AMS, xanthopsia 6h of last dose, also tests for bound K>5.5, severe end-organ dysfxn, or life-
Digoxin
(yellow-green halo), bidirectional VT, Fab fragments, may need send out threatening arrhythmia), magnesium,
“regularization of AF” “free” dig level after treatment), lytes, AVOID hypokalemia.
BUN/Cr, UOP.
Tox screen, EKG (↑ QRS duration,
IV bicarbonate (for the Na not the
Prolonged QRS, arrhythmia, terminal R wave >3mm in aVR,
alkalization) if QRS >100ms or
TCAs hypotension, anticholinergic toxicity, QRS >100ms correlates w/ 26%
hypotensive. Benzos for seizure.
myoclonus, hyperthermia, AMS, coma, seizure risk; >160ms correlates w/
Salvage Rx: hypertonic (3%) saline,
seizure 50% risk. Monitor for ventricular
lipid emulsion
arrhythmia, CPK.
N/V/D, tremor, hyperreflexia, clonus,
BUN/Cr, serial Li levels (nl 0.5-1.5
ataxia, AMS, seizure, Frequent neuro checks; IVF (NS
mmol/L), EKG
Lithium hyper/hypothyroidism, AV block, sinus preferred), maintain UOP, HD if
Toxicity common with AKI from
brady, long QT, nephrogenic diabetes encephalopathy, renal dysfunction.
NSAIDs, ACEi, diuretics
insipidus if chronic
Benzos for agitation (avoid
Serotonin Syndrome AMS, hyperreflexia (LE predominant), antipsychotics); supportive care for
Search for causative agent. CBC,
Antidepressants, hyperthermia, mydriasis,  HR, HTN, altered VS (esmolol, nitroprusside for
CPK, BMP, coags, LFTs, UA, CXR.
Linezolid, Tramadol diarrhea, diaphoresis, clonus, rigidity HR and HTN, cooling). If all else fails,
consider cyproheptadine.
Search for causative agent. CPK D/c causative agent (restart dopamine
AMS, “lead pipe” rigidity, sialorrhea,
(often very high), CBC if d/c-ed), IVF, cooling blanket,
Neuroleptic hyperthermia, dysautonomia,
(leukocytosis), LDH, LFTs, BMP, nitroprusside for HTN, BZD for
Malignant Syndrome diaphoresis.
serum iron (often low); consider agitation. Dantrolene, bromocriptine,
(NMS) Typically no N/V/D or hyperreflexia
brain imaging, LP, EEG. amantadine.
Disinhibition, stupor, nystagmus, Thiamine (before glucose), folate,
EtOH level, methanol and ethylene
EtOH memory loss, discoordination, RR, MVI, IVF w/ dextrose. Calculate
glycol if + osmol gap. BMP, LFTs.
coma discriminant fxn if EtOH hepatitis.
AG metabolic acidosis (severe), Fomepizole (15 mg/kg bolus over
Inebriation, AMS; flank pain,
Ethylene glycol osmol gap, oxalate crystalluria, renal 30min then 10mg/kg Q12H), bicarb if
hematuria, reversible kidney injury,
Antifreeze failure, hypocalcemia, lactate pH<7.3, leucovorin 50mg IV, consider
calcium oxalate crystals in urine
elevation HD
Methanol
Inebriation, retinal injury (visual AG metabolic acidosis (severe), As above, fomepizole (or ethanol),
Windshield fluid,
blurring, papilledema, blindness) osmol gap, visual acuity testing bicarb, or HD.
“moonshine”

Nathan Kunzler
61
TOC

Pulmonary & Critical Care Toxicology

Agitation, psychosis, seizure, HTN,
Serum, urine tox (metabolites Hyperthermia treatment (cooling,
HR, vasospasm/MI, arrhythmia,
Cocaine detectable for 2-5d), ECG, cardiac benzos), treat chest pain with ASA,
stroke, vasculitis, lung injury,
biomarkers if chest pain, CPK, UA. CCB, nitrates, labetalol (no pure BB).
rhabdomyolysis
Sympathomimetics Agitation, mydriasis, hallucinations,
EKG, chem 7, lactate, CPK, LFTs, IV benzos, atypical antipsych. if
Amphetamines, paranoia, tachycardia, HTN,
coag. refractory agitation, avoid
MDMA, cathinones diaphoresis, hyperthermia,
succinylcholine and ketamine.
“bath salts” piloerection, seizure
History (house fires, winter w/ indoor
Minor sx: headache, N/V space heaters), carboxyhemoglobin 100% O2 (t½ 6h60 min); Hyperbaric
Carbon Monoxide Major sx: confusion, LOC, seizure, level, cyanide level, CO-oximetry b/c O2 (t½ 6h20 min); watch for delayed
coma, cardiac ischemia, arrhythmias pulse ox (SpO2) invalid, AG acidosis, neuropsychiatric sequelae.
EKG, troponin.
Cholinergics “DUMBBELLS”: Diaphoresis/Diarrhea, 100% O2, atropine (2-5 mg IV, redose
Organophosphates, Urination, Miosis/Muscle spasm, ABG, ECG, Chem 7, CPK, lactate. to effect q3-5 min, no effect on
carbamate Bronchoconstriction/Bronchorrhea, Can monitor RBC AChE inhibitor if muscular symptoms); Pralidoxime
insecticides, Bradycardia, Emesis, Lacrimation, available. (30mg/kg over 30 min8-20mg/kg/hr.
nicotine Lethargy, Salivation/Seizure Only for organophosphate toxicity).
HA, nausea, AMS, seizure, coma, Cyanide level, lactate, anion gap Hydroxocobalamin (5g over 15 min)
Cyanide
shock. Suspect in structural fires, metabolic acidosis, and sodium thiosulfate (use amyl nitrate
prolonged nitroprusside infusion. carboxyhemoglobin level. if hydroxo unavailable).
Not detected on routine toxicology
Gamma-hydroxy- Agitation, coma (sudden Supportive; benzodiazepines for
screen, need 100mL urine and 10-30
butarate (GHB) onset/resolution), bradycardia, ↓RR, withdrawal. Note: OD at low dose if on
mL blood for send-out. EKG, r/o other
low BP, co-intoxicants common protease inhibitors.
causes, B-hCG.
Synthetic Anxiety, paranoia, sedation, memory Not detected on routine toxicology Supportive care. Benzos for agitation
Cannabinoids impairment, hallucinations, psychosis, screen, can send blood and urine and seizure. Antipsychotics for
Spice, K2 seizure, tachycardia, HTN, N/V, AKI sample for send-out. agitation.
(Pharmacotherapy 2015;35:189; Chest 2011;140:795; Crit Care Clin 2012;28:479)
Anion and Osmol Gaps:
Anion Gap Osmolal Gap
Methanol With normal AG:
Uremia (CKD) EtOH, isopropyl-OH Anion Gap = (Na+) – (Cl- + HCO3-)
Ketoacidosis Ether *Normal 8-16 (avg: 12)
INH glycine/sorbitol/mannitol
Osmolal Gap = Osmplasma - Osmcalc
Iron hyperproteinemia
*Normal ≤10, but wide variability, so interpret
Lactic Acidosis hyperlipidemia with caution
Ethylene/propylene glycol With elevated AG:
Salicylates Ethylene/propylene glycol Osmcalc = 2×[Na+] + [BUN]/2.8 + [gluc]/ 18 +
CO Methanol [EtOH (mg/dL)]/4.6
Cyanide Ketoacidosis
Sympathomimetics Lactic Acidosis
Decontamination Therapies:
• Activated Charcoal
o Most effective if given when substance is still in stomach (usually considered to be within 1hr of ingestion, but data is lacking)
o Not useful for: Cyanide, Lithium, Ethanol/methanol, Glycols, Mineral acids (e.g., sulfuric acid, nitric acid), Alkali metals
(potassium, magnesium, sodium, including sodium hydroxide [Drano]); Iron; Ammonia
o Other therapies not routinely used: whole bowel irrigation (with polyethylene glycol), gastric lavage, Ipecac

• Dialyzable Toxins and Acid/Alkaline Diuresis:

Dialyzable Toxins
EtOH, methanol, isopropyl
alcohol Acid Diuresis Alkaline Diuresis
Glycols (give Vitamin C) (give NaHCO3)
Acetone Quinine Phenobarbital
Lithium PCP Salicylates
Salicylates Methotrexate
Barbiturates TCAs
INH
Atenolol, sotalol

Nathan Kunzler
62
TOC

Gastroenterology Upper GI Bleeding

MGH GI Taskforce Protocol for Acute Upper GI Bleed Management
• Criteria: BP < 90 and HR > 100 x2 30min apart; Hct <20 regardless of vital signs, and evidence of active significant bleed in 12hrs;
requirement of > 2L IVF or 2U pRBCs to prevent instability/keep Hct > 25; ATLS hemorrhagic shock class III; clinical judgment
• Consults: page/call GI fellow; call Med Sr for MICU bed; consult Trauma team and/or Interventional Radiology when needed
• Resuscitation: crystalloid IVF via 2 18G or larger PIVs; pRBC to keep Hb >7 or higher if co-morbidities (i.e. CAD); IV PPI (+
octreotide if portal HTN), fix coagulopathy if needed.
• Urgent EGD in the ICU: performed after effective resuscitation and securing safe airway; ideally w/in 8 hr. If no ICU bed, should
be performed in ED Acute (sedation and intubation if needed); IV erythromycin/azithromycin is recommended 30 mins prior to EGD

Urgent Assessment & Management of GI Bleeding Etiologies of Upper GIB (Dig Dis Sci 2018;63:1286)
• Assess & reassess V/S for hemodynamic stability  Ulcers (~50%): PUD: H. pylori, NSAID, ZE, EtOH
• Attempt to quantify amount & rate of blood loss  Varices (~5%): EVB (esophageal) > gastric
• ≥ 2 PIV (18G or larger) – rarely done by IV nurse; look at their arms  Esophagitis or gastritis (~30%): GERD, pill, ASA,
(green = 18; pink = 20; blue = 22) NSAIDs, clopidogrel, EtOH, infectious
• Type & screen (type & cross if plan to transfuse), IVF (and blood if  Vascular lesions (~5-10%): Dieulafoy’s, AVM, GAVE,
indicated): liberal transfusion if active bleed or unstable VS. Hct drop HHT, XRT, aortoenteric fistulae
lags 24-72h from onset of bleeding.  Traumatic (~5%): Mallory-Weiss, foreign body,
• Correct coagulopathy: IV vit K, FFP, Plt, PCC. If severe/life- Boerhaave’s
threatening, consider reversal agent. If uremic, consider ddAVP (0.3  Neoplastic (~5%): primary > metastatic
mcg/kg); if ESLD, consider amicar, avoid FFP (volume).  Post-procedural (varies): polypectomy, sphincterotomy
• Transfusion goals: Hb >7 (avoid overtransfusion if EVs), Plt >50k, INR <2 (unless ESLD), PTT <50, Fibrinogen >100
o See Transfusion Medicine for Massive Transfusion; generally, give FFP/plts after 4U
• GI consult for EGD and/or colonoscopy High Risk Features in UGIB
• Surgery or IR consult if hemodynamic instability or difficult endoscopic correction  Hypotension
• Intubation: if high volume hematemesis, AMS, variceal bleeding requiring balloon tamponade  Tachycardia
 Coagulopathy (INR > 1.5)
Acute Upper GI Bleeding (International Guidelines: Annals 2019;171:805; NEJM 2016;374:2367)  AMS
• Definition: bleeding proximal to ligament of Treitz  Syncope
• S/Sx: hematemesis, melena (+LR 25); brisk UGIB can p/w hematochezia, orthostasis; BUN/Cr  Age > 65
>30 (⊕ LR 7.5; JAMA 2012;307:1072), especially >35 (100% Sp; J Clin Gastro 1990;12:500).  Liver Dx
 CHF
• Risk stratification (30d mortality): Glasgow-Blatchford Score recommended over AIMS65
(Annals 2019;171:805, BMJ 2017;356:6432); Machine Learning Scoring System with > specificity (100%) than both (Gastro 2020;158:160)
• Management: EGD generally within 24hrs (debated), but no Δ in outcomes if between 0-6hrs vs. 6-24hrs (NEJM 2020;382:1299)
Pre-EGD Post-EGD
- Transfusion: Hb >7 (NEJM 2013;368:11). Consider higher - If high risk PUD, intensive PPI x72 hr  re-bleeds & need
threshold if CVD (Annals 2019;171:805). Avoid overtransfusion in for repeat EGD: pantoprazole 40mg IV BID (intermittent dosing
variceal bleed – can  portal pressures and worsen bleeding. non-inferior to bolus+gtt; JAMA Intern Med. 2014;174:1755). Oral
- IV PPI:  high-risk lesions requiring endoscopic therapy, but PPI may replace IV PPI if good PO intake.
unclear clinical impact pre-EGD (Cochrane Rev. 2010) - Treat H. pylori if positive
- IV erythromycin or azithromycin: 250mg 30m prior to EGD  - If variceal bleed: continue octreotide x 3-5d, consider TIPS or
gut motility & visualization (AJG 2006;101:1211) BRTO if refractory to EGD
- If cirrhosis: IV octreotide: 50 mcg x1  50 mcg/hr + IV CTX 1g - If angiodysplasia: consider long-term octreotide (AJG
q24hr x7 days for ppx against bacterial infections (Gastro 2007;102:254), bevacizumab or thalidone w/ GI help
2006;131:1049; APT 2011;34:509); stop β-blockers - If re-bleed: repeat EGD, consider angiography, surgical/IR
- If continues to bleed, consider amicar (5 g bolus followed by 1 consult. If variceal, consider balloon tamponade, TIPS, BRTO
g/hr, max ~24g in 24h), ddAVP (if uremia)
Management of anticoagulation/antiplatelet agents (ASGE Guidelines: Gastrointest Endosc 2016;83:3)
Warfarin: hold during bleed; resume after hemostasis (w/ UFH bridge at ~48hrs if indicated; see Hematology section);  risk of
thrombosis, death in AF if resumed w/in 7d (Am J Cardiol 2014;113:662)
DOAC: hold during bleed; no data to guide, but generally resume 48-72hr after hemostasis
ASA: hold during bleed (unless recent PCI/ACS – see below); resume in pts w/ CAD (2° prev.) after hemostasis, best if w/in 1-7d;
risk of 30d mortality if not resumed (Annals 2010;152:1); if PUD, add PPI to  risk of bleeding
DAPT for PCI/ACS: d/w cardiologist though generally if very recent (<30d PCI, <90d ACS) continue both unless life-threatening; if more
distant, continue ASA but less risk in holding P2Y2i. Resume w/in 1-7d if able, esp if low rebleed risk.
In general, restarting AC/AP sooner   risk of vasc. events, though  risk of bleeding (APT 2019;50:8)

• Prognosis:
o PUD rebleeding w/o med management: 90% if active bleed, 50% if visible vessel, 30% if clot, 20% if oozing, else < 10%
o Esoph variceal bleed: 50% resolve spontaneously; 30% mortality  70% if continued bleeding; 60% risk re-bleeding overall

Gregory Fricker
63
TOC

Gastroenterology Lower GI Bleeding

History Etiologies (NEJM 2017;376:1054)
Acute Lower GI Bleed (NEJM 2017;376:1054) Painless Divertic. (30-65%), angioectasias (5-10%), hemorrhoid (5-20%)
• Definition: hematochezia from colon or Abd. pain IBD (3-5%), ischemic colitis (5-20%), perforation
rectum; classic def.: distal to lig. of Treitz Weight loss Malignancy (2-15% neoplasm or polyp), IBD (3-5%)
• Sx: hematochezia (maroon stools, bright Fever/diarrhea IBD (3-5%), acute mesenteric ischemia, infectious colitis (2-5%)
red blood, or blood clots); less commonly AS/ESRD/LVAD Angioectasias (5-10%)
melena (dark, sticky; requires that blood Recent colo. Post-polypectomy (2-7%)
spend 14hr in GI tract) Constipation Stercoral ulceration (0-5%)
o Stool appearance is a poor indicator Abd/pelvic XRT Radiation proctopathy/colitis (0-2%)
of bleeding source; hematochezia NSAIDs NSAID-induced colopathy (0-2%)
can also be seen with brisk UGIB Liver disease Colorectal varices (0-3%)
(suspect if pt is hemodyn. unstable) AF Acute mesenteric ischemia
o Anorectal/L colon: bright red blood Prior GI surgery Anastamotic ulcers
o R colon: maroon-colored stools, AAA repair Aortoenteric fistula
melena possible if slow transit Brisk bleed UGIB (13%)
• Diagnosis:
o Exonerate UGIB first with EGD if brisk bleed/hemodynamic instability (10-15% of patients with severe hematochezia)
o Consider NGT placement if there is moderate suspicion for UGIB (not done often at MGH)
 Coffee-ground material, bright red blood  EGD
 No blood or bile seen: indicates indeterminate source  consider EGD before colonoscopy
 Bilious fluid: no active UGIB source  colonoscopy
o Colonoscopy is mainstay of diagnostic therapy; imaging can also be used to help localize active bleed
 CT angiography: (bleeding rate 0.3-0.5mL/min); available, fast, minimally invasive; first line (ACR Approp. Criteria)
 IR angiography: (>0.5 mL/min); allows for intervention (e.g. embolization) but risk of bowel ischemia, vascular injury
 Tagged RBC scan: (>0.1 mL/min); most sensitive, but time-consuming, poor localization
• Risk stratification:
o Several risk-factor models have been developed. Overall limited ability to predict which patients will have poor outcomes.
 NOBLADS score: NSAID use, no diarrhea, no abdominal tenderness, SBP <100 mmHg, antiplatelet agent, albumin
<3.0 g/dL, ≥2 comorbidities, syncope (CGH 2016;14:1562)
 HR >100 bpm, SBP <115 mmHg, syncope, non-tender abodomen, bleeding in <4 hr of eval, ASA use, >2
comorbidities (AJG 2005;100:1821)
 Patients with coexisting cardiopulmonary, renal or hepatic conditions have worse outcomes (Colorectal Dis 2011;14:8)
• Management: (ACG Guidelines: AJG 2016;111:459)
o Transfusion goals: Hgb >7 (consider >9 in active CAD), Plt >50k, INR <1.5 (INR 1.5-2.5 ok to perform endoscopic
hemostasis before reversing; INR >2.5 consider using reversal agent)
o Initial labs: CBC, CMP, coags, T&S; trend Hgb Q2-8 hrs depending on severity of bleed
o IF HEMODYNAMICALLY STABLE: prep for colonoscopy (after discussion with GI); need 8 hrs w/o solid food prior
 If ongoing bleeding or high-risk, perform colonoscopy within 24hr; use order set for colonoscopy prep
 OK to place NG tube for high-risk patients with ongoing bleeding who are intolerant of prep (if no known h/o varices)
 Some evidence that performing colonoscopy at 24-36 hours is a safe approach in most stable patients (Gastro
2020:158:1); however, remains controversial, as may reduce identification of stigmata of recent hemorrhage, LOS
 For refractory angioectasias, can treat with thalidomide and bevacuzimab
o IF HEMODYNAMICALLY UNSTABLE: EGD to r/o UGIB causing brisk hematochezia followed by urgent colonoscopy, IR
(embolization), surgical consult (subtotal colectomy if cannot locate colonic bleed), massive transfusion
o Diverticular hemorrhage, angioectasia, post-polyp. bleed, hemorrhoids, rectal varices amenable to endoscopic treatment
o Anticoagulation/antiplatelet management: generally extrapolated from UGIB data
 ASA for 1° prev. should be stopped & generally not resumed. ASA for 2° prev. should not be held; if it is, should be
resumed soon after bleed resolves (Gastro 2016;151:271). If on DAPT for recent PCI/ACS (<30d PCI, <90d ACS),
should continue unless life-threatening bleed. If less recent, can likely hold P2Y12i for 1-7d though d/w cardiologist.
Unidentified Source after EGD/Colonoscopy: ~75% small bowel, 25% missed UGIB/LGIB (ACG Guidelines: AJG 2015;110:1265)
• Small bowel causes: IBD (esp. <40), Dieulafoy’s, neoplasm, Meckel’s (esp. <40), polyposis synd. (esp. <40), NSAID ulcers
o Rare: small bowel varices, portal hypertensive enteropathy, amyloid, HHT, Kaposi, inherited connective tissue disorders &
congenital vascular abnormalities; rare non-small bowel: aortoenteric fistula, hemobilia, hemosucccus pancreaticus
• Diagnosis/management:
o 2nd look EGD +/- push enteroscopy (prox 60cm jejunum) if recurrent UGI sx; 2nd look colo. if recurrent hematochezia
o Video capsule (VCE): 1st line; dx in 38-83%, may miss duodenal/prox. jejunal lesions; contraind. if strictures (retention)
o CT/MR enterography: CTE if ⊖VCE or if risk of strictures (IBD, XRT, prior SB surgery, suspected stenosis); CTE>MRE
o Deep enteroscopy: if strong suspicion of SB lesion and therapy required; can use to intervene after ⊕VCE
o If brisk bleed: CTA or tagged RBC if stable, angio. if unstable; can intervene w/ embolization, enteroscopy, or surgery
o If no source identified: iron repletion, consider octreotide, antiangiogenic tx; replace AV if Heyde’s & ongoing bleeding

Zoe Memel
64
TOC

Gastroenterology GERD & Peptic Ulcer Disease

G A S T R O E S O P H A G E A L R E F L U X D I S E A S E ( G E R D ) (ACG Guidelines: AJG 2013;108:308, AGA: Gastro 2008:135:4)
Signs & Sx: “heartburn” w/ food (i.e. spicy foods, coffee, soda, chocolate, EtOH) or position (reclining), regurgitation, sour taste
after awakening, sore throat, dysphagia, globus, chronic cough/throat clearing, hoarseness, asthma exacerbation, chest pain
• Alarm symptoms: dysphagia/odynophagia, wt loss, GIB, Fe def. anemia, persistent vomiting, anorexia, new onset age ≥60
Ddx: infectious esophagitis, pill esophagitis, eosinophilic esophagitis (EoE), motility disorder, reflux hypersens./functional dyspepsia
Evaluation: if sx’s suggestive of GERD, PPI trial is dx test of choice (though has limitations: Sn 78% / Sp 54%; Annals 2004;140:518)
• If alarm symptoms  EGD w/ biopsy: look for tissue damage and/or complications, alternative DDx (i.e. EoE, malignancy)
• Ambulatory pH monitoring/impedence testing: if endoscopy ⊝ but persistent symptoms
• Esophageal manometry: if GERD sx w/ CP and/or dysphagia and normal EGD  assess for motility disorder
Management: (Gastro 2018;154:302)
• Lifestyle Δs: weight loss, HOB elevation, tobacco cessation, reduce food triggers, no meals 2-3hrs before bed
• PPIs: > than antacids/H2RAs for sx relief in empiric tx and optimal for erosive esophagitis (Cochrane Rev 2013)
o Start low-dose PPI (e.g. 20mg omeprazole) 30min before AM meal. Reassess 4-8wk, uptitrate to high-dose (e.g. 40mg
omeprazole) then BID if no relief. Assess at 8w if able to d/c.
o Maintenance PPI: if continue to have sx after PPI discontinued or if severe complications (erosive esophagitis, Barrett’s)
o Discontinuing PPI: if on PPI >6mo., taper by 50% per wk to prevent rebound hypersecretion.
o PPI risks (controversial): probable association: Mg wasting (QTc), AIN; possible association:  risk of osteoporosis,
dementia, CKD, C. diff/other enteric infxn (Gastro 2017;152:706)
• H2RAs (ranitidine, famotidine): can be given for nighttime sx PRN w/ PPI, tachyphylaxis common after wks
• Others: PRN antacids, sodium alginate (APT 2013;38:1059; APT 2014;39:595), baclofen (as adjunct)
Severe/Refractory Symptoms:
• If no sx relief after 8w on high-dose BID PPI, refer for EGD & consider alternative dx such as functional dyspepsia (need
symptoms >6mo; NEJM 2015; 373:1853), EoE, or rumination syndrome (effortless regurgitation)
o EoE: dysphagia, GERD sx, food impaction; a/w allergic conditions. Eos on bx. PPI, topical steroids (Gastro 2020;158:1776)
• Gastric fundoplication may be superior to medical treatment for refractory heartburn (NEJM 2019;381:1513)
Complications:
• Barrett’s Esophagus (BE): squamous epithelium  columnar intestinal epithelium. AdenoCA risk 0.1-2%/yr. Screen w/ EGD
in: men w/ chronic (>5yrs) or freq. (>weekly) GERD sx + ≥2 RFs (>50, Caucasian, central obesity, tobacco hx, FH of BE or
adenoCA) (ACG: AJG 2016;111:30). Mgmt: indefinite PPI; some evidence for NSAIDs/ASA  risk of CA (Lancet 2018;392:400)
• Esophageal stricture: p/w progressive solid food dysphagia. Endoscopy w/ biopsy can differentiate stricture from cancer.

P E P T I C U L C E R D I S E A S E ( P U D ) (BMJ 2019;367:I5495)
Signs & Sx: intermittent gnawing, dull, aching, or “hunger-like” epigastric pain relieved w/ antacids though 70% are asx; duodenal
ulcers p/w pain 2-5hrs after meal & at night night (persistent acid w/o buffer). Associated sx: early satiety, bloating, n/v.
Etiology: 90% caused by H. pylori or NSAIDs. Others: meds (bisphosphonates, steroids, clopidogrel, sirolimus), ZES, mastocytosis,
HSV, CMV, EBV, fungal infxn, post-surgical, XRT, ischemia (crack cocaine), Crohn’s, sarcoid, critical illness
Ddx: other causes of dyspepsia: biliary disease, gastric CA, celiac, chronic pancreatitis, drug-induced, functional dyspepsia
Evaluation: H. pylori testing in all w/ dyspepsia; if >60  EGD to exclude CA. (ACG Guidelines for Dyspepsia: AJG 2017;112:988)
• H. pylori testing: Stool Ag or urea breath test (not avail. at MGH) preferred to assess for active infection though affected by
PPI & abx ( false ⊝). Serology (IgG) not affected by PPI/abx/bismuth but cannot accurately distinguish active vs. past
infection; a ⊝ serology is helpful in excluding infection if low pre-test probability. Bx w/ urease, histolology, Cx.
• EGD: biopsy malignant-appearing & select benign-appearing ulcers; obtain samples for H. pylori testing.
Management: PPI (duration depends on etiology), add sulcralfate if duodenal ulcer 2/2  acid, H. pylori tx, d/c offending agents; if
need to continue ASA, continue w/ PPI (NEJM 2005;352:238, Gastro 2010;138:82). F/u EGD after 8-12w if refractory sx (see below) or
gastric ulcer w/o clear etiology (ASGE Guidelines: Gastrointest Endosc 2010;71:663)
H. pylori treatment: (ACG Guidelines: Gastro 2017:112:2)
• First line = quadruple therapy (assuming resistance of clarithromycin >15%): PPI BID, bismuth 300mg QID, tetracyline 500mg
QID (alternative: doxy 100mg BID), metronidazole 500 QID x 14d. Combo pill (Pylera) available; add PPI BID for quad tx.
• Triple therapy: clarithromycin 500mg BID + amoxicillin 1g BID (or flagyl 500mg TID if PCN-allergic) + PPI BID x14d. Addition of
bismuth may  eradication (CGH 2020;18:89).
• Confirmation of eradication: stool Ag, urea breath test (not avail. at MGH) or EGD >4 wks after completion of abx and PPI.
Refractory PUD: ulcer that does not heal after 8-12wks adequate tx; 5-10% of ulcers are refractory to PPI tx.
• Ensure H. pylori eradicated, NSAIDs & other contributing meds discontinued. Test for ZES w/ fasting serum gastrin ( if on PPI,
recheck 1 week s/p cessation); secretin stimulation test if non-diagnostic.
• Continue PPI x additional 12w and then reassess w/ EGD. If still refractory, surgical tx: resection, vagotomy, partial gastrectomy
Complications and Management: ulcer consider complicated if any of the following are present:
Bleeding: IVF/pRBC, IV PPI, EGD. Perforation: IVF, IV PPI, abx ± surgery. Penetration. Gastric outlet obstruction: pyloric channel/
duodenal ulceration  spasm, edema, inflammation, dysmotility  fibrosis/scarring; Tx: IVF, correct electrolytes, NGT; may need
endoscopic dilatation or surgical tx if persists w/ medical mgmt.

Zoe Memel
65
TOC

Gastroenterology Nausea & Vomiting

General approach to patient with nausea/vomiting (Gastro 2001;120:1)
(1) Seek out etiology. Make sure to consider chronicity & comorbidities
(2) Treat underlying cause if possible; symptom management based on underlying etiology
(3) Anticipate and address complications of N&V (aspiration, volume depletion, hyperchloremic metabolic alkalosis, hypokalemia, MW tear)
Evaluation Etiologies (VOMITING mnemonic) Receptor Targeted treatment
History Acute/gait instability; Labyrinthitis, Scopolamine, dimenhydrinate,
Vestibular & ACh
- Acute <1mo. or chronic BPPV, vestibular neuritis, diphenhydramine, meclizine, Dix-
Vertigo H1
(AJG 2018;113:5) Meniere’s disease Hallpike  Epley maneuver
- Relation to time of day Prochlorperazine, ondansetron,
- Triggers: relation to POs, Adhesions, hernia, volvulus,
bowel rest, NGT, IVFs, surgery
recent foods/meds, sick Obstruction constipation, gastric outlet Multiple
consult, serial exams/KUBs, NO
contacts, headache, head obstruction
metoclopramide (risks perf)
trauma, last BM Post-op nausea/vomiting (PONV; Serotonin antagonist, aprepitant,
- Hematemesis, melena risk factors: female, nonsmoker, dexamethasone (use 2 in combo as
- Abd pain, heartburn Operative Multiple
post-op opioids, hx of PONV, ppx if 3+ risk factors present),
- Prior abd surgery type of surgery) 1/3rd cases gabapentin
- CP, SOB, diaphoresis Low fat & insoluble fiber diet,
- Vertigo, uncontrolled DM Gastroparesis (common in
metoclopramide, erythromycin
Labs to consider uncontrolled DM), autonomic
(tachyphylaxis after 4 wks; motilin
- Chem 10, LFTs, Motility dysfunction, cyclic vomiting D2 (periph)
agonist),diphenhydramin, cannabis
amylase/lipase syndrome, chronic idiopathic
abstinence, TCAs, gabapentin,
- hCG, UTox, VPAIN nausea (See Motility Disorders)
olanzapine, benzos, SSRI/SNRI
- UA, ABG, lactate Meds Antibiotics, anti-epileptics, Stop offending medication if
- Cort stim (drugs & chemo, opioids, illicits (cannabis D2 (central) possible, prochlorperazine,
- Troponin withdrawal) hyperemesis), anti-arrhythmics haloperidol
Studies to consider
Chemo, XRT, bowel ischemia, Ondansetron, prochlorperazine,
- KUB/upright Inflammation/
gastroenteritis, PUD, 5-HT3 dexamethasone, olanzapine &
- EKG Infection/
hepatitis, pancreatitis, NK1 aprepitant (chemo), treat underlying
- CT abdomen (I+/O+) Ischemia
cholecystitis, pyelonephritis disorder (antibiotics, surgery, etc)
- Barium swallow or EGD
- Gastric emptying study Uremia, ketoacidosis,
Prochlorperazine, haloperidol, treat
- CT head Toxins hypercalcemia, food poisoning, D2 (central)
underlying disorder
Can’t-miss diagnoses hypo/hyperglycemia
- SBO, mesenteric ischemia Elevated ICP, migraine, ACh
Dexamethasone (if ICP),
- Cardiac ischemia Intracranial meningeal irritation, H1
treat underlying disorder
- Pancreatitis, pyelo, acute glaucoma 5-HT3
cholecystitis Anxiety, depression, Lorazepam (anticipatory N/V),
Nerves Multiple
- Pregnancy anticipatory nausea, pain dexamethasone, pain control
- AI, DKA
-  ICP Gums/mouth Mucositis thrush, oral HSV Multiple Treat cause; magic mouthwash

Management Receptor Med Dose Side effects

Address underlying cause Ondansetron (Zofran) 4-8 mg PO/IV q8h QTc, constipation, HA
5HT3
while treating symptoms Palonosetron (Aloxi) 0.075-0.25mg IV x1 No in QTc, more potent
with targeted agents EPS (black box), dystonia
Metoclopramide (Reglan) 10-20 mg PO/IV q6-8h
• Non-pharm options: (peripheral), promotility agent
Acupuncture/acupressure D2 Prochlorperazine
5-10 mg PO/IV/PR q6h QTc, EPS, sedation
to anterior wrist (P6), (Compazine)
meditation, ginger root Haloperidol (Haldol) 0.5-4 mg PO/IV q6h QTc, EPS, sedation
• Chemo PPX: dex ± Dexamethasone (Decadron) 4-8mg PO q4-6h Psychosis, CHF, appetite
lorazepam ± Cortical
Lorazepam (Ativan) 0.5-2 mg PO/IV q6h Delirium, sedation
ondansetron ± aprepitant NK1 Aprepitant (Emend) 125mg day 1, 80mg days 2-3 CYP3A4 inhib, GI upset
± olanzapine (NEJM
CB1 Dronabinol (Marinol) 2.5-10 mg q4-6h Dysphoria, asthenia, appetite
2016;375:134)
• Adhesive SBO (prior GI Metabolic (wt gain, lipids),
surg): conserv. mgmt x 5HT 2A,D2 Olanzapine (Zyprexa) 5-10mg PO QD QTc;  mortality in dementia
48h (NGT, NPO)  (blackbox)
undiluted therapeutic H 1,ACh,D2 Promethazine (Phenergan) 12.5-25 mg PO/IV/PR q4-6h EPS, sedation
gastrografin (100cc) per Scopolamine 0.3-0.6 mg q24h Delirium, sedation, dry
NGT  surgery by 74% ACh,H1 Hyoscyamine 0.125-0.25 mg SL/PO/IV q4h mouth, urinary retention, ileus,
(BJS 2010;97:470) Diphenhydramine (Benadryl) 25-50 mg PO/IV q6h blurry vision

Sally Knooihuizen and Zoe Memel

66
TOC

Gastroenterology Diarrhea
Acute Diarrhea: ≥3 loose stools/d for <14 days (ACG: AJG 2016;111:602; IDSA: CID 2017;65:e45; NEJM 2014;370:1532)
• Evaluation: character of sx (small bowel=watery, large vol., +cramping/bloating; large bowel=freq., small vol., painful, +/- fever, blood,
mucus), exposure hx (travel, abx/hospitalization, food, sick contacts, daycare), immunocompromised, s/sx volume depletion
• Workup: BMP if vol. depletion; BCx if fever/ill, immunocompromised; stool Cx if severe (>6BMs/d, severe pain), inflammatory, high-
risk host (age >70, immunocompromised, IBD), or persistent >2w; O&P if persistent, immunocompromised, MSM; C. diff if RFs
• Common pathogens: Viral (most cases): norovirus (outbreaks during winter; n/v prominent), rotavirus (often daycare-assoc.),
adenovirus. Bacterial (most severe cases): E. coli (toxigenic = traveler’s diarrhea; hemorrhagic, O157:H7 = undercooked meats, a/w
Shiga toxin, HUS), Campylobacter (undercooked/unpasteurized foods, can be a/w reactive arthritis or GBS), Salmonella (eggs,
poultry, milk, often bacteremic), Shigella (low inoculum, often hematochezia), Vibrio spp. (shellfish/salt water; *cirrhosis), Yersinia
(undercooked pork, “pseudoappendicitis”), C. diff (see Clostridium difficle). Parasitic: Giardia (outdoor streams; watery stool
progressing to malabsorptive/greasy), Cryptosporidia (water-related outbreaks), Cyclospora (contaminated produce); E. histolytica
(contam food/water outside US, a/w liver abscesses). Immunocompromised: CMV, C. diff, Cryptosporidia, Isospora, Microsporidium,
MAC, TB, Histoplasma, Cryptococcus.
• Treatment: Volume & lyte repletion critical (PO if able). Empiric abx: controversial; if febrile, septic, inflammatory diarrhea: FQ or
azithro. Consider in age ≥70, hospitalized, serious comorbidities. Avoid abx if suspect EHEC as can  risk of HUS. Caution w/
loperamide (OK if no fever or bloody stool). Probiotics controversial: not recommended by ACG except for post-abx diarrhea.

Chronic Diarrhea: ≥3 loose stools/d for >4wk. 5 types: secretory, osmotic, Disease Process Physical Exam Findings
functional, malabsorptive, and inflammatory. See table below. Dehydration, neuropathy Orthostasis, hoTN
Evaluation: (Gastro 2017;152:515, CGH 2017;15:182, Gut 2018;67:1380) Hyperthyroidism Tremor, lid lag
• Hx: freq., stool vol., tenesmus, abd pain, fever, bloating, wt loss, Addison’s disease Hyperpigmentation
nocturnal sx, postprandial sx, steatorrhea, surg hx (CCY, resection,
Carcinoid Flushing, murmur, wheezing
bariatric, vagotomy), travel, immunocompromised, meds, radiation
Amyloidosis Hepatomegaly, macroglossia
• Labs: CBC, BMP, ESR/CRP, LFTs; TSH; stool lytes (Na, K, pH), fecal
HIV, lymphoma, CA Lympadenopathy
WBC/calprotectin, fecal fat (24-48h coll.), FOBT
Glucagonoma Migratory nec. erythema
• Stool osmotic gap for watery diarrhea: 290 – 2*(stool [Na] + [K]);
Celiac disease Dermatitis herpetiformis
Normal 50-100 mOsm/kg
Watery Fatty
Inflammatory
Secretory Osmotic Functional Malabsorptive/Maldigestive
Addison’s, neuroendocrine
Malabsorption: mesenteric IBD, invasive
tumors, hyperthyroidism, Lactose
IBS, ischemia, mucosal disease bacterial/parasitic
medullary CA of thyroid, intolerance,
functional (CD, Whipple’s), short gut infxn (C. diff, E.
mastocytosis, microscopic mannitol,
diarrhea syndrome, SIBO histolytica, Yersinia,
Etiologies colitis (lymphocytic or sorbitol,
Maldigestion: bile acid TB), ulcerating viral
collagenous), DM autonomic magnesium,
(see Motility malabsorption (ileal disease) infxn (CMV, HSV),
neuropathy, laxative
Disorders) or ↓ synthesis, pancreatic colon CA, lymphoma,
amyloidosis, bile salt (4-5%), use/abuse
exocrine insufficiency radiation colitis
lymphoma, villous adenoma
Structural problem, mucosal Inflammation
Secretagogue, rapid transit, Osmotic Multi-
Mechanism disease, panc. or bile acid interferes w/ nml
 surface area substance factorial
insufficiency function/absorption
Osmotic gap <50 >125 50-100
Response to
No change Improves Variable Improves No change
fasting
Exclude infxn. +/- colo with bx Sudan stain, 24hr fecal fat
Stool pH (<6), Exclude infxn.
(esp. if immunosupp). As (>20g likely panc dysfxn, 14-
Further H2 breath ESR/CRP,
appropriate: chromogranin, None 20g likely small bowel
Testing test, laxative calprotectin, colo w/
gastrin, somatostatin, calcitonin, cause), stool elastase or
screen biopsies
5-HIAA, TSH, ACTH stim, SPEP chymotrypsin, see celiac
Bile salt: cholestyr. 4g QD-QID Fiber
Microscopic colitis: budesonide (Citrucel >
Pancreatic enzyme
VIP: somatostatin (octreotide 50- D/c offending Metamucil),
replacement therapy Abx vs.
Treatment 250 ug TID SQ) agent; dietary Viberzi
(pancrealipase 500-2500 immunosuppression
Other: opiates via mu receptor review (+pain),
units/kg/meal),
(eg loperamide 2-4mg QID, Rifaxamin
diphenoxylate 2.5-5mg QID) (+bloating)
Celiac Disease (NEJM 2012;367:2419): abnormal immune response to gluten  diarrhea, wt loss, abd pain, Fe def anemia, vit D def
Diagnosis:  tTG-IgA (Sn >95%, Sp >95%) + total IgA. If IgA def,  DGP- & TTG-IgG. If any ⊕, EGD w/ biopsies. If gluten-free &
⊝ serologies, HLA-DQ2/DQ8. If ⊝, dx excluded. If ⊕, should challenge w/ gluten x2-8w and then  serologies and EGD w/ bx.
Bx:  intraepithelial lymphs, elongation of crypts, villous atrophy. If Bx & serologies discordant, HLA. (ACG: AJG 2013;108:656)
• Treatment: strict adherence to gluten-free diet; IgA anti-tTG titer should decrease and return to normal over time. Ensure no
deficiency in vitamins (A, D, E, B12), Cu, Zn, carotene, folic acid, Fe +/- thiamine, vit B6, Mg, and selenium.

Rebecca Liu
67
TOC

Gastroenterology Constipation & Colonic Disorders

CONSTIPATION
Definition: dissatisfaction with defecation; Rome IV criteria: at least 2 of: straining during defecation, lumpy/hard stool, sensation of
incomplete defecation, manual facilitation of BM, <3 BMs per week
Etiologies (AGA guidelines: Gastro 2013;144:211 Gastro 2013;144:218, JAMA 2016;315:185)
• 1º constipation:
o Slow-transit constipation (STC): sitz-marker study shows delay in colonic transit; associated with bloating & pain
o Normal-transit constipation (NTC): normal testing, doesn’t meet criteria for IBS-C, but has constipation sx
o Defecatory disorders: impaired rectal evacuation w/ normal or delayed colonic transit; inadequate rectal propulsive forces or
increased resistance to evacuation (e.g. failure to relax or inappropriate contraction)
o IBS-C: see Motility Disorders; recurrent abd. pain or discomfort a/w hard or infrequent stools or relieved by defecation
• 2º constipation:
o Lifestyle: low fiber, sedentary o Metabolic: hyperCa, hypothyroid, hypoMg, hypoK, uremia,
o Medications: analgesics, opioids, anticholinergics heavy metal poisoning, pregnancy
(antihistamines, antidepressants, antipsychotics), iron, o Neuro: autonomic neuropathy, DM, Hirschsprung’s, multiple
aluminum (antacids, sucralfate), diuretics, clonidine, sclerosis, spinal cord injury, Parkinson’s, stroke
amiodarone, CCB, ondansetron o Obstruction: anal stenosis, colon cancer, stricture, rectocele,
o CTD: amyloidosis, sarcoidosis compression
Diagnosis/Treatment (AGA guidelines: Gastro 2013;144:211, Gastro 2013;144:218, JAMA 2016;315:185)
• History: duration of sx, frequency & consistency of stools, straining, incomplete
evacuation, use of manual maneuvers, alarm sx (sudden change in BMs in
>50 y/o, blood, weight loss, strong FH of CRC), medications
• Initial workup: DRE (fissures, hemorrhoids, tone), CBC (for anemia);
colonoscopy if +FOBT or alarm sx or fevers (or if concern for IBD); TSH, Ca,
glucose, & other labs not needed unless otherwise clinically warranted
• Initial management and further workup: see algorithm from AGA guidelines 
o Anorectal manometry (ARM), balloon expulsion test: identifies
defecation disorder
o Barium, MR defecography: useful when ARM inconsistent with clinical
impression, can identify anatomic abnormalities
o Colonic transit study: via radio-opaque makers (Sitz markers) or
wireless motility capsule study (less commonly used)
• Management: see medications on next page
o Secondary constipation: treat underlying cause
o STC/NTC: fiber, laxatives (PEG, stimulant); add secretory agents if persists; consider UGI eval if still no improvement
o Defecatory disorder: biofeedback/pelvic floor PT; if persists, eval. for STC/NTC; surgery if structural abnormality
Hospital Constipation Prophylaxis and Bowel Regimens
• Risk factors: >60 yo, prolonged immobility, decreased fluid intake, preexisting constipation, meds (see above)
• Colace lacks evidence in hospitalized pts (J Pain Symp 2000;2:130) & increases cost & pill burden (JAMA Int Med 2016;178:1216);
senna 2 tabs QHS > senna + colace (J Pall Med 2008;11:575)
• General ppx for at-risk patients: senna 2 tabs QHS or BID standing + Miralax 17 gm daily prn
• High-risk ppx for patients on opioids: senna 2 tabs BID standing + Miralax 17 gm daily standing
• Step-wise approach: senna  miralax  lactulose  mag citrate/MOM  bisacodyl PR  enemas  disimpaction
(NB: disimpaction can cause vasovagal syncope; all rectal procedures are contraindicated in neutropenic pts)
• Avoid Mg and Phos containing products in renal insufficiency (MOM, Mg citrate, Fleets enema)  can cause nephrocalcinosis
Colonoscopy Prep: adequate preparation is essential for successful colonoscopy. General instructions: place pt on clears at noon
the day prior to colonoscopy; the prep should start no later than 6PM the day prior to colonoscopy. Sample prep:
• 4L Nulytely (can be split day before and morning of) + 10mg Dulcolax (preferred prep at MGH)
• Alternatively, could Rx 238g Miralax mixed in 2 quarts Gatorade + 10mg Dulcolax
• Tricks to make more tolerable: chill in the fridge; drink through straw; also Rx gas tabs (e.g. simethicone, Mylanta)
Contact GI team if not clear (completely see-through) in the AM, as the procedure will need to be rescheduled. Rx additional Nulytely
(ex. 2L) or magnesium citrate to continue with prep in this case (avoid mag citrate in cases of IBD, dehydration)
DIVERTICULOSIS
• Definition: herniation of colonic mucosa into muscularis propria, where vasa recta penetrate
• Risk factors: low fiber diet ± chronic constipation, obesity,  age (present in 50% of patients >60yo; common incidental finding
on imaging), smoking, NSAIDs, red meat consumption, ♀ = ♂. No data for avoidance of seeds or popcorn.
• Location: 90% L-sided (primarily sigmoid) in “Western” populations; 75-85% R-sided in Asia.
• Bleeding: painless bleeding of vasa recta within the diverticuli. 75% are self-limited & resolve with bowel rest. Recurrence is
common. Tx if bleeding does not stop: 1) endoscopic, 2) angio (IR embolization), 3) surgery. See Lower GI Bleed.
• Diverticulitis: develops in 4% of pts with diverticulosis; see next page

Rebecca Liu
68
TOC

Gastroenterology Constipation & Colonic Disorders

DIVERTICULITIS
• Diverticulitis: infection of diverticuli: micro-perforation 2/2 erosion of the diverticular wall by increased intraluminal pressure
• Uncomplicated (75%): abdominal pain (LLQ), fever, leukocytosis, anorexia, Δ in BMs (diarrhea or constipation)
• Complicated (25%): bowel obstruction, abscess, fistula (potentially with bladder, vagina, skin or peritoneum), or perforation
• Diagnosis: characteristic s/sx + imaging findings (diverticula, bowel wall >4mm, inflammation w/in pericolic fat +/- abscess/fistula)
• Management: (AGA Guidelines: Gastro 2015;149:1944, Gastro 2015;149:1950)
o Uncomplicated (medical): PO abx x7d (Cipro/Flagyl, Bactrim/Flagyl, or Augmentin), bowel rest. Per AGA, use of abx
should be selective (immunosupp., pregnant, significant comorbid disease, chronic steroid use, SIRS/sepsis) & if mild
disease, may not benefit from abx (Gastro 2015;149:1650) – based off RTCs in Europe (Br J Surg 2012;99:532; Br J Surg
2017;104:52). Others, however, still recommend routine abx for uncomplicated diverticulitis.
o Complicated (surgical): IV abx (GNR + anaerobe coverage), bowel rest, and surgical evaluation (peritonitis typically
present; evaluation for abscess drainage or colonic resection).
• Follow-up: colonoscopy 6w after acute diverticulitis to evaluate for malignancy (if no colonoscopy within prior year)
S E G M E N T A L C O L I T I S A S S O C I A T E D W I T H D I V E R T I C U L O S I S ( S C A D ) (WJG 2016;22:8067, CGH 2007;5:27)
• Sx: chronic diarrhea, cramping abd pain (LLQ), or intermittent hematochezia. Ddx: diverticulitis, IBD, infxn, med-assoc., XRT.
• Dx: WBC usually nml; fecal calprotectin may be  if severe; endoscopy shows inflammation of the interdiverticular mucosa
(diverticular orifices uninvolved), spares rectum.
• Tx: no direct evidence; can consider Cipro/Flagyl; if no response to abx, add mesalamine; if fail abx + mesalamine, consider
prednisone 40mg x1wk  slow taper.
S Y M P T O M A T I C U N C O M P L I C A T E D D I V E R T I C U L A R D I S E A S E ( S U D D ) (Dig Dis Sci 2016;61:673)
• Definition: persistent abdominal sx (pain, discomfort, bloating, constipation, diarrhea) attributed to diverticulae in the absence of
macroscopically overt colitis or diverticulitis.
M E D I C A T I O N S F O R C O N S T I P A T I O N (Gastro 2013;144:218, JAMA 2016;315:185, ACG: AJG 2014;109:S2)
Type Agent Dose Notes
Psyllium (Metamucil), 1tsp up to TID (for In some (esp. STC), can increase bloating & distention in
Bulk agents
Methylcellulose (Citrucel) psyllium: up to 30g/d) large amounts. Should start low & .
Less effective than other laxatives; may be inferior to
Surfactants Docusate (Colace) 50-360mg QD
psyllium. See data in hospitalized patients above.
 colonic secretions and stimulates motility. Can cause
Senna 1-4 tabs QD or BID
cramping.
Stimulants
 colonic motility. Can cause cramping. Can be given PO
Bisacodyl (Dulcolax) 5-15 mg up to 3x/w
(best QHS) or PR (AM).
Polyethylene glycol
Modestly more effective and better tolerated (less
Miralax (PEG alone)
17 g QD; max 34g/d bloating) than lactulose (Cochrane Rev 2010). Dose PEG
GoLytely, NuLytely (PEG
daily.
+ salts)
Non-absorbed
Lactulose, sorbitol 15-30 ml QD or BID  flatulence/bloating. Less effective than PEG.
substances
Benefit of simultaneous neutralization of gastric acidity
(osmotic) Milk of magnesia (MOM) 15-30 mL QD or BID
and water retention in stool. Avoid if renal failure (Mg).
Exact mechanism unknown. Can be used as a lower-
Magnesium citrate 150-300 mL QD volume alternative to PEG bowel prep (2+ bottles +
Dulcolax PR). Avoid if renal failure (Mg).
Tap water, soapsuds All work via lubrication. Soapsuds also stimulates
Enemas mineral oil, fleets (sodium Varies peristalsis. Fleets is hypertonic and also has osmotic
phos.), milk & molasses effect. Avoid Fleets in elderly or renal failure (phos).

24μg BID for STC/NTC; Binds Cl- channel & increases secretion,  small bowel &
Lubiprostone (Amitiza)
8μg BID for IBS-C colon transit. Most common side-effect is nausea.
Secretory drugs Linaclotide: 145μg QD for
Linaclotide (Linzess),
STC/NTC; 290μg QD for Agonists of guanylate cyclase-C;  Cl, HCO3 secretion &
plecanitide
IBS-C colonic transit.
(Trulance)
Plecanatide: 3g daily
Methylnaltrexone: At MGH, methylnaltrexone approved only if on stable
1 dose SQ QOD PRN dose of opioids ≥ 2 weeks x3d w/o BM AND failed
Peripheral Methylnaltrexone,
- 38-62kg: 8mg multiple other laxatives. Contraindicated in obstruction,
opioid receptor naloxegol (pegylated
- 62-114kg: 12 mg small risk of perforation. See AGA Guidelines for opioid-
antagonists naloxone), alvimopan
- <38, >114kg: 0.15mg/kg induced constipation: Gastro 2019;156:218 & Gastro
- CrCl <30: 1/2 dose 2019;156:229.
Rebecca Liu
69
TOC

Gastroenterology Motility Disorders

Oropharyngeal Dysphagia Esophageal Dysphagia
Symptoms Difficulty initiating swallowing; drooling, coughing, aspir. Difficulty seconds after initiation, food stuck in esophagus
Central: tumor, stroke, PD, ALS, MS, polio 1°: achalasia, esophageal motility disorders (e.g. distal
Neuro- Peripheral: neuropathy, myasthenia gravis esophageal spasm, hypercontractile “Jackhammer” esoph.)
muscular Muscular: polymyositis, muscular dystrophy
2°: diabetes, scleroderma, amyloid, Chagas
Etiologies

(solids + liq.)
(Chicago classification: Neurogastro Motil 2015;27:160)
Intrinsic: tumor, XRT, trauma/surgical resection, Zenker’s Intrinsic: tumor, stricture, infxn, EoE, rings, webs (e.g.
Structural Extrinsic: anterior mediastinal mass, goiter, cervical Plummer-Vinson), pills (NSAIDs, doxy, tetracyc., bisphosph)
(solids >
liquids) spondylosis Extrinsic: vascular rings (e.g. dysphagia lusoria), Ao. enlarge.,
LA compression, mediastinal, substernal thyroid, LAD
History: sx onset & duration, solid/liq & localization of dysphagia, +/- odynophagia, underlying conditions (e.g. CNS,
malignancy, thyroid, DM, scleroderma), use of offending meds (pill esophagitis), immunocompromise (Cand., CMV,
Work-up HSV infectious esophagitis or lymphoma in HIV), radiation, etc. Dysphagia in older adults, is not normal aging. PE: gen
appearance (?systemic disease or CNS issue), HEENT exam (?evidence of LAD, tumor, asymmetry), FOBT Labs
(consider): CBC, TFTs, ANA, α-Scl-70, α -centromere, α -RNP, α -Jo, HgbA1C, iron studies, HIV, AChR-Ab
1) Modified barium swallow, ENT and neuro evals, +/- 1) EGD is the most useful test +/- barium swallow (mucosal
EGD to identify obstructive structural problem pathology or structural abnormality)
Diagnostics
2) Consider chest/neck CT to dx extrinsic compression 2) if normal  esoph. manometry to diagnose motility d/o
3) Consider chest/neck CT to dx extrinsic compression
Zenker’s diverticulum: p/w halitosis, regurgitation of food/aspiration, cough. Tx w/ endoscopic surgery (rigid vs. flexible).
Strictures & rings: if lumen <13mm, dysphagia common. Tx PPI, dilation, intralesion steroid inj, stent
Distal esophageal spasm: uncoordinated peristalsis a/w intermittent chest pain & regurgitation; barium swallow:
corkscrew (vs. nml). Hypercontractile esophagus: similar sx; nml barium swall. Tx (both): PPI, nitrates/CCB/PDEi,TCA.
Selected Infectious esophagitis: odynophagia; often immunosuppressed – Candida, HSV, CMV
Conditions Eosinophilic esophagitis (EoE): dysphagia, refractory GERD sx. EGD w/ stacked rings, strict. Bx >15 eos/hpf. Tx PPI,
diet Δs (dairy, wheat > soy, eggs, nuts, fish), topical steroids (MDI/neb/liq.); consider dilation. (AGA: Gastro 2020;158:1776)
Achalasia: progressive dysphagia solids/liquids, + regurgitation; barium swallow with bird’s beak appearance of distal
esophagus; manometry: absent distal peristalsis, incomplete LES relaxation; EGD to r/o pseudo-achalasia (2/2 CA); tx w/
pneumatic dilation, Heller myotomy, POEM, botox, CCBs. (AGA Guidelines: AJG 2013;108:1238; JAMA 2015;313:18)
Gastroparesis Ileus
Definition: decreased gastric motility w/o obstruction Definition: slow motility of the gut w/o obstruction, often post-op
Sx: n/v, early satiety, postprandial fullness, bloating +/- abd pain Sx: nausea/vomiting, BMs and flatus, abd distention
Etiologies: diabetes (vagus nerve damage 2/2 hyperglycemia), Studies: KUB/CT w/ colonic dilatation w/o mechan. obstruction
post-surgical (e.g. vagus nerve injury post-bariatric surgery), Paralytic ileus: s/p intra-abdominal surgery or a/w peritonitis,
post-viral, systemic disease (thyroid, critical illness, Parkinson’s, ischemia, meds (opioids, anti-cholinergics); worsened by hypoK
connective tissue d/o), meds (opiates, CCB, anti-cholinergics) Tx: bowel rest, decompression via NGT if mod/severe/ongoing
Exam: +/- TTP in epig, succussion splash (sloshing on abd ausc) sx, avoid opiates, replete lytes. Methylnaltrexone PRN if opioids.
Dx: exclude mech obstruction w/ EGD, CTE/MRE/SBFT  Acute colonic pseudo-obstruction (Ogilvie’s): typically in elderly,
gastric emptying nuc. study (hold motility meds 48 hrs prior) hospitalized, ill pts. A/w severe illness (e.g. sepsis, pancreatitis,
Labs: TSH, ANA, A1c, tot protein, alb, CBC w/ diff. peritonitis), systemic disease (thyroid dis., DM, renal or liver
Treatment: small meals w/ low fat & non-digestible fiber, failure), neuro (spinal cord compression or trauma, Parkinson’s,
prokinetic agents before meals (metoclopramide or erythromycin; MS), meds (opiates, CCB, anticholinergics).
give drug holidays due to tachyphylaxis / to assess benefit), Tx: conservative (NPO, IVF, NGT/rectal tube), neostigmine if
antiemetics; venting G-tube if refractory sx, J-tube for nutrition if cecal diam. >12 or if fail conserv tx. Colonic decomp. if fails.
wt loss. (ACG Guidelines: AJG 2013;108:18) (ASGE Guidelines: Gastro Endosc 2020;91:228)
FUNCTIONAL GI DISORDERS: GI disorders caused by aberrant neuronal signaling (dysfunction of the gut-brain axis) rather than
structural or known molecular abnormality. Classification of >20 disorders per the Rome IV Criteria. (Gastro 2016;150:1393)
Functional dysphagia Sense of dysphagia w/o structural d/o, abnl motility, GERD or EoE. Sx ≥ 1x/wk. Tx: CCB, TCA
Functional dyspepsia Early satiety, epigastric pain. Must r/o structural/organic cause. Tx: PPI/H2RA, TCA, metoclopramide
Globus sensation Sensation of obstruction in the throat when there is none, Tx: PPI, antidepressants, CBT
Episodic, stereotyped. Kids>adults. Often trigger and prodrome. May be better w/ hot shower. Tx:
Cyclical vomiting syndrome
anti-emetics (Zofran), benzos to sedate, triptans may abort, TCAs may ppx; overall limited evidence
Cannabis hyperemesis syndrome Frequent cannabis, n/v (temp. relieved by MJ), relieved by hot shower. Tx: topical capsaicin;  MJ
Sphincter of Oddi dysfunction Biliary pain, +/- pancreatitis 2/2 inability to relax, often post-CCY. Tx: trial CCB/nitrate; ERCP
Irritable Bowel Syndrome (IBS):
Definition (per Rome IV Criteria): recurrent abd discomfort ≥ 1x/wk on average for 3 months a/w 2+ of the following: (1) related to
defecation, (2) change in stool frequency, (3) change in stool form. No nocturnal pain, weight loss, bleeding, or calprotect/lactoferrin.
Types: IBS-C (constipation-predominant), IBS-D (diarrhea-predominant), IBS-M (mixed), IBS-U (unclassified), by Bristol Stool Score
Epidemiology:  risk w/ younger age, ♀ > ♂, psychosocial stressors, low QoL, hypochondriasis; gastroenteritis may be trigger.
Treatment: all: exercise, diet Δ (low FODMAP), fiber (psyllium), rifaximin (esp. non IBS-C), anti-spasmodics (dicyclomine), peppermint oil,
TCAs, CBT. IBS-C: laxatives (linaclotide, plecanatide, lubiprostone); IBS-D: eluxadoline, loperamide, alosetron (♀) (ACG: AJG 2018;113:1)
Rebecca Liu
70
TOC

Gastroenterology Inflammatory Bowel Disease

Epidemiology: onset 15-40y, bimodal in CD w/ 2nd peak 50-80y. Genetic predisposition (up to 25% variance per GWAS studies;
incidence in Jews, Caucasians) + environment ( risk w/ Western diet, abx exposure, NSAID use; smoking  risk for CD &  risk for UC)
Ulcerative Colitis (Lancet 2017;389:1756) Crohn’s Disease (Lancet 2017;389:1741)
Bloody diarrhea, lower abd pain, cramps, tenesmus Abd pain, grossly nonbloody diarrhea, n/v, wt loss, perianal dz
S/Sx Extra-GI: rheum (seroneg. arthritis, sacroilitis), cutaneous (erythema nodosum, pyoderma gangrenosum, apthous ulcers),
ophthalmic (uveitis, iritis, episcleritis), heme (DVT, AIHA), GI (PSC), GU (Ca-Ox / UA stones), pulm (bronchiectasis, ILD)
Continuous colonic mucosal inflammation spreading Skip lesions (including TI & upper GI), strictures, fistulae,
Dx
proximally from rectum, crypt abscesses, pseudopolyps transmural inflamm., noncaseating granulomas, cobblestoning
Toxic megacolon, anorectal strictures/dysfxn Obstruction (2/2 strictures), abscesses, fistulae, malabsorption
Complic.
 risk CRC: colo after 8yrs of active disease, q1-3yrs w/ random 4-quadrant bx q10cm of colon; 2° amyloid
Classif. Montreal Criteria: UC: proctitis/L-sided/extens.; CD: age at dx, dz location, behavior (stricturing, penetrating) (Gut 2006;55:749)
Inpatient Work-up and Management:
H&P: baseline pain, BRBPR, #BM/consistency, #BM at night, surgical hx, date of onset, presenting sx, dz extent (fistulizing, stricturing, for
CD), new meds (OTCs, NSAIDs, abx), smoking, nutrition/TPN, travel, extra-intest. sxs, current/past IBD meds & compliance/efficacy
Labs: CBC, Chem 10, LFTs (ALP?PSC), ESR/CRP, Mg, pre-albumin (for malnutrition), fecal calprotectin, Stool Cx, O&P, C. diff,
Fe/TIBC/B12 (if anemic). Prior to medication initiation: Hep serologies and TSpot (immunomodulators), TPMT enzyme (azathioprine)
Imaging: if concern for peritonitis/obstruction/mass (abscess)  KUB, CT A/P. Consider MRE to eval small intestine.
Severity UC (True-Love Witts) CD (CD Activity Index)
Mild <4 stools (bloody or not), afebrile, nml ESR Ambulatory, tolerates PO/no dehydration, no pain/toxicity
Moderate 4-6 BM, bloody BM, low fever, pain, mild anemia Failed 1st line tx, low fever, N/V, wt loss, pain, anemia
Severe >6 BMs, Hb <10.5, fever, HR>90, wt loss, ESR >30 Failed advanced tx, toxic, abscess, obstruction, peritonitis, cachexia
IBD Flare Therapy
† Methylpred 20mg q8h IV
Mild/Moderate (outpatient) Severe (inpatient)
‡ risk of DVT/PE in IBD pts
ΔIn pts w/ fistula, abscess,

peritonitis, pouchitis,
Aminosalicylates (UC>>CD) IV steroids† +/- rectal steroids, IV Fluids/lytes perforation, high fever,
Budesonide oral/topical (UC/CD) High-risk DVT ppx‡, +/- Cipro/FlagylΔ leukocytosis, bandemia
PO prednisone (UC/CD)  Tspot, Hep serologies, TPMT enzyme ϒ
risk of tox meg in UC
Antibiotics (CD) No NSAIDs/opiods/antidiarrhealsϒ * Bridge to maintenance tx
Thiopurines (UC/CD) NPO for endoscopy (c/s IBD team, inform outpt GI), ADAT σAnti-TNF, anti-integrin, etc.

Refractory disease/toxic Resolution* Refractory after 3-5 days: Advance therapyσ, surgical consult
Indications for surgery: CD: undilatable stricture, fistulae, abscess failing medical tx. UC: refractory disease, perforation, toxic megacolon
Management guidelines: CD: ACG: AJG 2018;113:481, AGA: Gastro 2017;152:271; UC: ACG: AJG 2019;114:384, AGA: Gastro 2019;156:748 & 2020;158:1450
Class Drug* Use Notes & Adverse Effects (AE)
PO budesonide 1st-line in mild CD, 2nd-line to ASA for mild UC, but can
Budesonide (PO/PR), Pred
Steroids Induction be 1st-line for mod
(PO), Methylpred (IV)
AE: osteoporosis, infection, AVN, AI, weight gain, mood lability, delirium
Sulfasalazine Induction + Sulfasalazine: pro-drug with more AEs, also systemic effects
Amino-
Mesalamine (PO: Pentasa, Maintenance for Mesalamine forms differ in gut penetration: Pentasa (ileum, R>L colon),
salicylates
Ascol, Lialda, Apriso. mild-moderate Ascol (R>L colon), Lialda & Apriso (pancolon), Canasa & Rowasa (distal).
(UC>>CD)
PR: Canasa, Rowasa) disease AE: HA, fever, rash, diarrhea, pancreatitis, sperm count, kidney injury
Typically as combination therapy for induction; can be monotherapy for
Azathioprine (pro-drug) Induction +
Thiopurines maintenance
6-MP Maintenance
AE: n/v, hepatitis, BM suppression, pancreatitis, NHL, skin cancer
Contraindicated if toxic megacolon, pyogenic infections.
Infliximab (Remicade) Induction +
If flare during maintenance: measure trough (24hrs prior to dose) and
Adalimumab (Humira) Maintenance for
Anti-TNF antidrug Ab levels, determine if dose escalation or new drug is required.
Certolizumab (Cimzia)-CD mod-severe
If pt non-responsive despite adequate levels, switch to another class
Golimumab (Simponi)- UC
AE: site rxn, infxn, TB/HBV reactiv., demyelinating dz, HF, malignancy
Induction + VARSITY3- In mod-severe UC, achieved  clinical remission at 52wks vs.
Anti-integrin Vedolizumab1,2 (Entyvio) Maintenance for adalimumab, but w/ greater steroid use
mod-severe AE: infusion reactions, nasopharyngitis
IL-12, -23 Induction + AE: infection, HA, nasopharyngitis, nausea, abdominal pain, arthralgias
Uztekinumab4,5 (Stelara)
inhibitor Maintenance
JAK Induction + Consider if previously failed anti-TNFs
Tofacitinib6 (Xeljanz)
inhibitor Maintenance AE: infection, herpes zoster, HA, nasopharyngitis, arthralgias
Calcineurin Induction only C/i in s/o toxic megacolon. Labs: troughs (q2-3d) Cr, Mg, lipids, LFTs
Cyclosporine
inhib (IV) for severe UC AE: renal injury,K, infxn, neurotox/seizures (esp. if Mg or cholesterol)
*For UC and CD unless otherwise noted
1. NEJM 2013;369:699, 2. NEJM 2013;369:711, 3. NEJM 2019 381:13, 4. NEJM 2016;375:1946, 5. NEJM 2019;381:13, 6. NEJM 2017;376:1723
Xing Li and Amanda PeBenito
71
TOC

Gastroenterology Intestinal Ischemia

Overview
• Acute or chronic insufficiency of blood flow to GI tract; due to systemic hypoperfusion, arterial/venous occlusion, or arterial vasospasm
• Can present in a variety of ways (see below); often in elderly pts or young pts with cardiovascular disease, vasoconstrictive meds
(digoxin, α-adrenergic agonists – e.g. phenylephrine, cocaine), or vasculitis
• Must consider intestinal ischemia in patient with abdominal pain + lactic acidosis (or unexplained elevated lactate)
• Risk factors: CAD, AF, Valvular disease, CHF, PAD/PVD, vasculitis (SLE/PAN), CKD, HD, hypercoagulable states, prior
embolism/DVT, intraabdominal pathology (adhesions, hernias, intussusception, volvulus), intraabdominal infxn/sepsis, aortic surgery
Ischemic Colitis Acute Mesenteric Ischemia Chronic Mesenteric Ischemia
Reference ACG Guidelines: AJG 2015;110:18 NEJM 2016;374:959 NEJM 2016;374:959
- Cramping pain (mostly LLQ)  - Arterial: sudden severe abd pain out of - Recurrent, post-prandial pain
mild/mod hematochezia proportion to exam; hx ASCVD (CHF, MI, AFib) (“intestinal angina”); dull,
Signs/ - Often not critically ill, but can - Venous: often insidious onset, waxing/waning abd crampy, starts 10-30m after PO &
Symptoms present w/ gangrenous bowel or distention, N/V, diarrhea +/- occult blood lasts 1-3 hr
fulminant colitis - n/v, early satiety, BM Δs
- Wt loss, fear of eating
Blood - SMA & IMA - SMA (prox. duodenum by GDA) - SMA (prox. duodenum by GDA),
Supply IMA, celiac artery
Non-occlusive: (95%) SMA occlusion: (~75%) - Due to progressive
- Watershed areas (splenic - Embolic (40-50%): SMA has narrow take-off atherosclerotic narrowing at
flexure, rectosigmoid) most angle; AF / endocarditis / aortic plaque  risk of origins of visceral vessels
susceptible; 25% R-sided total occlusion - Assoc. w/ ASCVD risk factors:
- Predisposing factors: general - Thrombotic (20-35%): acute-on-chronic in s/o tobacco, HTN, DM, HLD
risk factors above as well as underlying ASCVD -  risk > 60 yo, female
cardiopulmonary bypass surgery - Dissection / inflammation (<5%) - Less common risk factors:
(low flow state), and extreme Non-occlusive: (5-15%) dissection, vasculitis,
Pathophys. exercise (shunting of blood flow fibromuscular dysplasia, radiation
- Splanchnic arterial hypoperfusion/vasospasm,
away from splanchnic circulation + typically after CV event/surgery, cocaine, - If pain becomes constant,
dehydration) vasopressin, vasculitis (SLE, PAN) consider acute thrombosis (see
Acute Mesenteric Ischemia to left)
Mesenteric vein thrombosis: (5-15%)
- Hypercoag due to thrombophilia (JAK2, PNH),
trauma, local inflammatory Δs (pancreatitis,
diverticulitis, biliary infxn/inflammation, surgery);
stasis due to cirrhosis/portal HTN; malignancy
Labs: lactate, WBC, LDH, CK, Labs: nonspecific, most abnormalities arise after Imaging:
& amylase if advanced ischemia progressed to necrosis: pH, lactate, - CTA (preferred; alt. = MRA): ⊕ if
- Stool guaiac ⊕ in ~50% AGMA (in 50%), WBC >15K (75%), stool guaiac ⊕ stenosis of ≥ 2/3 major vessels
-  Stool Cx, O+P, C. diff in ~50%; normal D-dimer may help exclude (celiac, SMA, IMA). 91% with 2
Imaging: Imaging: vessels, 55% with all 3 vessels
- Abd CT (I+/O+): wall thickening, - KUB: Ileus, colonic dilatation, pneumatosis - Doppler U/S to measure
Diagnosis edema, thumbprinting, intestinalis; free air  immediate surgery mesenteric blood flow (and r/o
pneumatosis (late), no vessel - Abd CT (ideally CTA; no oral contrast): wall median arcuate ligament
occlusion thickening, pericolonic fat stranding, pneumatosis, syndrome)
- Colonoscopy (to confirm/assess ± arterial occlusion, portomesenteric venous gas - Gastric tonometry exercise
extent): petechial blood, pale - Angiography: consider if CTA non-diagnostic but testing
mucosa, segmental suspicion remains high, or in cases of vasculitis - Angiography (see left)
edema/ulceration, rectal sparing affecting small-medium size vessels; can stent/tPA
- Bowel rest For occlusive disease: - Elective revascularization (if sx):
- IVF resuscitation - NGT/NPO, IVF/blood product resuscitation open (aortomesenteric grafting)
- D/C vasoconstrictive meds - broad-spectrum abx vs. endovascular (angio ±
- GNR/anaerobic abx if - Anti-coagulation if not bleeding (heparin +/- tPA) stenting)
mod./severe disease (no data) - If infarction/peritonitis/perforation  surgical - Nutrition/TPN support
Treatment
- If suspicion for bowel necrosis, emergency - AC if acute-on-chronic
gangrene, or perforation, call - If SMA occlusion: thrombectomy/embolectomy vs. mesenteric ischemia
surgery intra-arterial vasodilators vs. thrombolysis - In absence of sx, no role of
Non-occlusive: treat underlying cause prophylactic intervention
Mesenteric vein thrombosis: anticoag x3-6 mo
- Favorable prognosis: 85% - Mortality 50%, but can be 70-90% if delay in - Periop mortality 0-16%
spontaneous resolution in 2 wk diagnosis leading to intestinal gangrene - Restenosis is common (7% for
Prognosis
(rarely life-threatening) open revasc; 34% for
- 5% have recurrence endovascular)

Natasha Merali
72
TOC

Gastroenterology Nutrition & Feeding

GENERAL APPROACH
1) Assess nutritional status (Clin Nutr ESPEN 2018;26:13-20)
o History/Exam: dietary intake/tolerance, n/v/d, muscle and fat wasting, weight loss (% over time), myalgias, dermatitis, loose
skin/clothes, edema, functional capacity (grip strength, ADLs)
o Weight loss as indicator of malnutrition: >2% in 1 wk, >5% in 1 month, >7.5% in 3 months, >10% in 6 months, >20% in 1 yr
o Labs: albumin, pre-albumin, transferrin, retinol binding protein (RBP) to assess synthetic function. Note that all are negative acute
phase reactants and will decrease during inflammation. INR prolongation may be indicator of malnutrition. Consider checking
vitamin levels if history/exam is suggestive (i.e. if dermatitis Vitamin C level, if encephalopathy  thiamine, etc.)
o 24-hr calorie count; nutrition consult if c/f malnutrition (screen with NRS-2002 or the NUTRIC Score in hospitalized pts)
2) Determine dietary route (oral > enteral [EN] > parenteral [PN]):
o Oral: aspiration risk, dysphagia, odynophagia? Consider SLP c/s for dietary modifications (e.g. pureed, thick liquids etc.)
o Enteral: if pt unable to tolerate oral diet safely, or unable to meet caloric needs through oral diet alone may need NGT. Place tube
post-pyloric if gastroparesis, obstruction, intractable nausea/vomiting, or high risk for aspiration
o Parenteral: TPN (central access) or PPN (peripheral). Used when GI tract non-functional.
3) Determine nutritional needs: healthy: ~25 kcal/kg/d; increased needs: (e.g. lung disease, IBD, burn): increase by 1.2-2x
4) Initiate diet: nutrition/TPN consult for specifics, may need to test pre-albumin, CRP at 2-3 d. Watch for refeeding (see below)
For reference, see ACG 2016 Nutrition Guidelines for hospitalized patients: AJG 2016;111:315
ARTIFICAL NUTRITION
Supplements: Ensure Plus (standard), Ensure Clear (low fat), Mighty Shake (standard, has lactose), Magic Cup (pudding for dysphagia),
Glucerna Shake (DM), Nepro (CKD), Beneprotein (protein powder), Prosource Protein (liquid)
Tube Feed Formulas:
ISOTONIC FORMULAS HYPERTONIC FORMULAS
Respiratory failure/ARDS
Osmolite 1.0 Normal absorptive capacity Osmolite 1.5
Volume overload (high protein)
Long-term TF Renal or liver failure (low
Jevity 1.5 Nepro
Prevent constipation (high fiber) Na/K/phos)
Wound healing (high protein) Beneprotein/ProSource Liq Protein
Promote Wound healing
ICU patients (on propofol) (modular protein)
Vital IBD, pancreatitis TwoCal HN
Max fluid restriction
(semi-elemental) Post-abdominal surgery (normal protein, no fiber)
TPN (page “TPN (Nutritional Support Team)” in paging directory): consider if NPO ≥7d. Need central access w/ new/clean dedicated
TPN lumen. Order by 1 PM to start same day.
• Monitor for complications of TPN (if applicable):
o Metabolic effects: hyperglycemia (2x >enteral), serum electrolyte alterations, refeeding syndrome (see below), Wernicke’s
encephalopathy, hepatic dysfunction, biliary sludge/gallstones. Monitor BMP, Mg, Phos, LFTs, and TGs.
o Bloodstream infection: increased risk of infection (fungal and bacterial)
• If no central access, Clinimix (amino acid solution in dextrose) can be given as PPN
• To stop TPN, coordinate careful transition to EN w/ nutrition; stop when EN provides >60% energy needs (AJG 2016;111:315)
REFEEDING SYNDROME
Electrolyte/fluid shifts caused by initiation of nutrition in severely malnourished patient, can be fatal; most likely to occur within 72h of
starting nutritional therapy (Nutrition 2018;47:13)
• Risk factors: minimal/no intake for 5 (minor) to 10 (major) days, significant wt loss, age, excessive alcohol use, malnutrition 2/2
chronic dz/malabsorptive conditions, anorexia nervosa, persistent n/v/d, low initial lytes (J Clin Med 2019;8:2202)
• Characteristics: early: hypo-Phos, hypo-K, hypo-Mg2+, vitamin deficiency (thiamine); late: cardiac damage (CHF), respiratory failure
(volume overload); other S/sx: AMS, n/v, diarrhea, tremors, paresthesias
• Prevention and management: close monitoring of labs w/ aggressive repletion of electrolytes (Phos, K, Mg2+, Ca2+, IV preferred) for
first 3 days & administer thiamine before refeeding regardless of level, slow/hypocaloric initial feeding, consider fluid/sodium
restriction, cardiac monitoring in high risk patients. Stop feeding if electrolyte abnormalities persist
SPECIAL CONSIDERATIONS
• IBD flares, pancreatitis: early enteral feeding (ideally within 24-72 hrs of admission)
• Critical care: enteral feeding should start within 48 hrs of ICU stay (superior to TPN if GI tract functional); contraindications include
significant GI pathology (e.g. GI bleed or obstruction) for which patient should be NPO (Clin Nutr ESPEN 2019;38:48)
• Bariatric surgery (e.g. RYGB, Gastric Sleeve): high risk of micronutrient deficiency from poor intake + malabsorption
o Post-op micronutrient screening: generally q3-6mo during first year (labs and ROS), then annually; includes Vit A, D, iron, folate,
B12, Ca, Cu, Zn, lipids; Vit E+K, thiamine (in select pts); see Table 2 in AMBS guidelines: Surg Obes Relat Dis. 2017;13:727
o Management: ensure patient taking chewable/liquid MVI with minerals/iron (2 pills if RYGB), Ca2+/Vit D, B12
o Dumping syndrome: nutrients rapidly enter duodenum leading to pain, diarrhea, flushing, tachycardia, syncope (<30min after
meal), hypoglycemia (1-3hr later). Tx w/ low carb, high protein/fat diet and frequent small meals
• Dementia: avoid dietary restrictions, use nutritional supplements as needed; lack of evidence to support tube feeding; guidelines
recommend against TFs in advanced dementia (a/w higher mortality) (Nutr Clin Pract. 2014;29:829, Clin Nutr 2015;34:1052)

Nicole Curatola
73
TOC

Gastroenterology Pancreatitis
E T I O L O G Y (CGH 2007;5:648)
- Gallstones/sludge (40-75%): #1 in women - Drugs (<5%): Class Ia: ACEi, dapsone, lasix, flagyl, pentamidine,
- Alcohol (30%): #1 in men statins, sulfa, tetracycline, valproate, mesalamine; Class Ib:
- Hypertriglyceridemia (10%): #3; suspect if TG>1000 amiodarone, azathioprine/6-MP, dexamethasone; Class II:
- Anatomic: ampullary diverticula/stenosis, duodenal didanosine, estrogen, propofol, tamoxifen, hydrochlorothiazide
stricture, tumor, divisum, parasites, foreign body - Toxins: organophosphates, scorpion venom, methanol, smoking
- Post-ERCP (3-5%): in high-risk pts, rectal NSAIDs  rate - Infections: viral (Coxsackie, EBV, CMV, HIV, Mumps, VZV, HAV,
of pancreatitis (NEJM 2012;366:1414) HBV, HSV), bacterial (Mycoplasma, Legionella, Salmonella), fungal
- Autoimmune:  IgG4, +ANA (rare) (Aspergillus), parasitic (Toxoplasma, Crypto, Ascaris)
- Hypercalcemia: Ca activates pancreatic enzymes - Ischemia: vasculitis (SLE, PAN), hypoTN/shock, cholesterol emboli
- Genetic - Tropical: pt from low SES in SE Asia, first bout as child
- Trauma: blunt, especially s/p MVA - Idiopathic (10-25%)
D I A G N O S I S / S E V E R I T Y / P R O G N O S I S (Revised Atlanta Classification: Gut 2013; 62:102, Pancreatology 2014; 14:324)
• Presentation: abd pain (90%) (band-like pain to back is specific but only 50%), n/v (90%), ileus, jaundice, flank/umbilical ecchymoses
• Diagnosis – need 2/3: 1) consistent clinical presentation, 2) lipase >3x ULN, 3) characteristic imaging
• Severity: mild: absence of organ failure and local or systemic complications; moderate: organ failure that resolved within 48 hours or
local/systemic complication; severe: organ failure >48 hours (22% mortality)
• Prognosis: many scoring systems; BISAP is quick. SIRS  mortality. Ranson, APACHE II, & other organ failure scores less practical.
WORKUP
• History: prior episodes, EtOH/smoking, prior GI procedures (e.g. CCY, ERCP), meds, infx sx, autoimmune hx, FH
• Labs:  lipase (Sn vs. amylase; no need to trend; false + in CKD, DKA, others), CBC (often Hct), BMP w/ Ca, LFTs ( ALT
>3.5ULN w/ 95% PPV for gallstone pancreatitis: AJG 1994; 89:1863), lipids (TGs)
• Imaging: CT if need to establish dx or to eval. for complications; RUQUS to r/o gallstones. MRI/MRCP can detect necrosis, stones.
M A N A G E M E N T (AGA Guidelines: Gastro 2018;154:1096)
• IV fluids: aggressive in first 24hrs: boluses + infusion 150-250/hr. LR>NS (SIRS, CRP; but avoid if Ca: CGH 2011;9:710). Goal-
directed: HR, Hct, BUN (Δ BUN a/w mortality: Gastro 2009;137:129), UOP 0.5-1cc/kg/hr. Generally  aggressive resuscitation
after 24-48hr. Overresuscitation   risk for abdominal compartment syndrome, need for intubation.
• Pain control: IV opioids | Abx: no role for prophylactic abx
• Nutrition: start PO (low fat) immediately once no n/v or abd pain. At 5-7d, if PO not tolerated start TFs (NG or NJ). Enteral > TPN:
maintains intestinal barrier, prevents gut flora translocation. TPN a/w  risk of infections, organ failure/death (Cochrane Rev 2010)
• Reverse precipitants: treat Ca or TG (see below), stop culprit meds. For gallstone pancreatitis, urgent ERCP (24hrs) if cholangitis
or CBD obstruction. CCY ideally prior to discharge as  biliary complications if CCY is delayed (AJG 2004;99:2417)
o HyperTG: insulin gtt (0.1-0.3U/kg/hr) + D5, q1h FSBG (initially), q12h TG. Goal TG <500 (may take several days). No good
evidence for apheresis so typically not done at MGH. Once can take PO, fibrates are first line. DC: lifestyle Δs, lipid clinic referral.
COMPLICATIONS (AGA Guidelines: Gastro 2020;158:67; NEJM 2016;375:1972)
Local Vascular Systemic
< 4 weeks > 4 weeks Thromboses: splenic, Abd. compartment
Acute peripancreatic fluid Pancreatic pseudocyst: fluid portal, SMV; AC if  portal syndrome: intra-abd
Interstitial collection: w/o features of collection w/ well-defined wall. If vein or bowel ischemia pressure >20 w/ new organ
edematous pseudocyst; resolve dx unclear, EUS w/ FNA Pseudoanuerysm: erosion failure.  bladder pressure
pancreatitis spontaneously w/o drainage (amylase). Drain if sx, rapidly , of GDA/splenic artery  if in ICU.
infxn. (endo vs. perc/surg) bleeding into pseudocyst. ARDS: via phospholipase
Acute necrotic fluid Walled off necrosis: Suspect if Hgb, expansion degradation of surfactant
collection: intra- or encapsulated collection of of fluid collection,
extrapancreatic collection of necrosis. Drainage if sx or infected unexplained GIB. Metabolic: Ca, Glc, TG
Necrotizing fluid & necrosis (endo vs. perc) Dx: arterial phase CT. GIB: via pseudoaneurysm
pancreatitis Infected necrosis: initially sterile but 1/3 become infected, Tx: IR embo. prior to AKI
usually later in course; abx: (cefepime or cipro) + flagyl vs. drainage of fluid collection.
pip/tazo vs. carbapenem in critically ill. Necrosectomy – can DIC
delay 4wks if stable.
• Chronic pancreatitis (ACG Guidelines: AJG 2020;115:322): repeat acute attacks (esp EtOH & smoking; AJG 2019; 114:656)  fibrosis &
loss of glandular tissue  chronic abd pain, exocrine insufficiency ( steatorrhea, weight loss), endocrine insufficiency ( brittle
DM). Lipase/amylase may be  early but nml/low as more tissue lost. ⊕ Fecal fat,  stool elastase. CT/MRI pref. for dx: calcifications,
ductal dilation. Tx: pancreatic enzyme replacement (Creon), ensure vit ADEK replete, pain control.  risk of pancreatic CA.
PANCREATIC MASSES (Curr Gastro Rep 2013;15:347)
• Solid: adenoCA (85-90%), autoimmune panc, neuroendocrine (1-5%), 1o lymphoma (<1%), mets (melanoma, RCC, etc)
• Cystic: inflammatory (pseudocyst, paraduodenal wall cyst), IPMN (mucinous cystic or serous adenoma or adeno Ca) (Guidelines
for dx & mgmt. of pancreatic cysts: AJG 2018;113:464; Gastro 2015;148:819)
• Imaging: CT abd pancreatic mass protocol; EUS with FNA allows biopsy (87% Se & 96% Sp); MRI useful in <2 cm lesions or
when vascular involvement needs to be delineated better); consider PET-CT, MRCP for malignancy in IPMN (70% Se, 92% Sp)
• Labs: CA 19-9 (⊕ in 80% of panc CA, 86% Sn / 87% Sp), CEA (mucinous lesions), ANA, IgG4 (if autoimmune panc suspected)
Thomas Wang
74
TOC

Gastroenterology Liver Chemistry Tests

Upper Limit of Normal (ULN): ALT (IU/L): 33 (males), 25 (females); ALK-P: 115 (males), 100 (females)
1. Causes of hepatocellular injury (↑AST/ALT;
Patterns ofR Liver
ratio >5):
Chemistry Test Elevation:
Always consider relevant history (meds, OTCs, herbals) and clinical picture
Hepatocellular: ALT and AST  Calculate the De Ritis “R ratio”:
Cholestatic: ALK-P + direct hyperbilirubinemia R ratio = (ALT/ULN) ÷ (Alk Phos/ULN)
Infiltrative: ALK-P  w/o significant bilirubin or AST/ALT elevation Hepatocellular: R ratio > 5
Non-hepatic: e.g. indirect hyperbili, non-hepatic alk phos , non-hepatic AST  Cholestatic: R ratio < 2
Mixed: R ratio between 2-5
Causes of hepatocellular injury: AST/ALT; R ratio >5. Always consider relevant history (meds, OTCs, herbals) and clinical picture
Any degree of AST/ALT elevation: Extreme AST/ALT elevation >1000: acute processes
• Meds/toxins: see list below • Ischemia: shock, cardiac arrest, Budd-Chiari
• Alcohol-related (acute alc hep: typically 2:1 AST:ALT ratio, <400) o Natural history:  in ALT/AST (often >50xULN) then
• Viral infections (Hep A-E, CMV, EBV, VZV, HSV)  bilis (lag behind) and peak 1wk later
• Sepsis/ischemia o ALT:LDH ratio <1.5 favors dx of ischemia > viral
• Biliary obstruction (mixed picture) hepatitis (Sn 94%/Sp 84%) (JCG 1994;19:118)
• NAFLD (often AST & ALT <4x ULN) • Meds/toxins: esp. APAP
• Cirrhosis (usually normal or only mildly elevated) • Acute viral infection: hepatitis A-E, HSV, VZV, EBV, CMV,
• Congestive hepatopathy (usually w/ indirect hyperbili) consider HBV reactivation if immunosuppressed
• Autoimmune hepatitis (AIH) • Autoimmune hepatitis (acute)
• Wilson’s disease (AST>ALT often >2; nml/ALP & ALP/Tbili <4) • Acute biliary obstruction
• Other systemic diseases: celiac, thyroid, hemochromatosis, A1AT • Acute Wilson’s (very rare if >40)
(even in absence of lung disease) • Malignant infiltration
Workup and Management
• Stop potentially offending medications/toxins •  INR, assess for HE (acute liver injury vs. failure)
• Viral hepatitis serologies • Stop offending meds/toxins, send tox screen
• RUQUS: steatosis (NAFLD vs. EtOH), cirrhosis  Fibroscan • Viral hepatitis serologies, including HSV, EBV, CMV
• AIH: ANA, ASMA, LKM-1, IgG • RUQUS with doppler
• Wilson’s: ceruloplasmin (), urinary Cu () • See Acute Liver Injury & Failure for further
• Hemochromatosis: iron studies: ♂: Fe/TIBC ≥45% & ferritin >200; diagnostic/treatment reccomendations
♀ Fe/TIBC ≥40% & ferritin >150  HFE testing
• See ESLD for further reccomendations

Commonly used drugs that can cause hepatocellular injury: acetaminophen, allopurinol, amoxicillin-clavulanate (Augmentin),
amiodarone, aspirin, carbamazepine, clindamycin, fluconazole/ketoconazole, fluoxetine, glyburide, heparin, hydral, INH, labetalol, lisinopril,
losartan, methotrexate, niacin, nitrofurantoin, NSAIDs (some), phenytoin, protease inhibitors, statins, sulfa drugs, trazodone, valproic acid
Illicit drugs: anabolic steroids, cocaine, ecstacy, PCP. See livertox.nih.gov for full list. (APT 2007;25:1135, NEJM 2019;381:264)

Workup and Management

Causes of cholestatic injury pattern:  ALK-P and bili; R ratio<2
• Biliary obstruction: choledocholithiasis, malignancy (cholangio, pancreatic, • Stop offending meds/toxins
ampullary), primary sclerosing cholangitis (PSC), chronic pancreatitis with strictures • RUQUS for biliary obstruction
• Intrahepatic cholestasis: meds (anabolic steroids, Augmentin, PCN / • May need MRCP or ERCP
cephalosporins, captopril, macrolides, estrogens, Bactrim; see livertox.nih.gov) •  AMA if persists
TPN, sepsis, primary biliary cholangitis (PBC) • If chronic, consider liver bx
• Biliary epithelial damage: hepatitis, cirrhosis

Causes of infiltrative pattern: primarily ALK-P elevation

•  GGT and/or fractionated
• Sarcoidosis or other granulomatous disease (e.g. TB, certain fungal infxns) ALK-P to confirm liver origin
• Malignancy: lymphoma, metastasis to liver, HCC • Imaging: RUQUS or CT;
• Amyloidosis MRCP if negative
• Abscess • Consider SPEP + IgG4
• Hepatic extramedullary hematopoiesis • If chronic, consider liver bx
• PSC can also have ALK-P with normal bilirubin

Non-hepatic causes of abnormal LFTs:

• Indirect hyperbilirubinemia: Gilbert’s syndrome (5% of population), hemolysis,
• If indirect bili: hemolyis labs
resorption of large hematoma
• If ALK-P: GGT, fractionated
• Alk phos elevation: also expressed in bone (e.g.  in Paget’s, bony mets),
alk phos (bone, gut, hepatic)
intestines (e.g.,  in SBO), and placenta (third trimester pregnancy)
• If AST/ALT: CK
• AST elevation: AST is most abundant in liver tissue but also present in muscle
(e.g.,  rhabdomyolysis, heat stroke, acute MI), kidney, brain, and RBCs
(AGA guidelines: Gastro 2002;123:1367; ACG Guidelines: AJG 2017:112:18)
Gregory Fricker
75
TOC

Gastroenterology Biliary Disease

G A L L S T O N E D I S E A S E S (J Hep 2016;65:146)
Cholelithiasis: presence of stones in GB (6% of ♂, 9% of ♀) Choledocholithiasis: stones in common bile duct
- Sx: asx vs. biliary colic (dull RUQ/epigastric pain, 30m-6 hrs, caused by - Sx: RUQ pain, n/v, jaundice; may be asx
GB contracting around sludge/stone, often postprandial & w/ n/v) - Labs: ALP, Bilis +/- AST/ALT
- Labs: normal - Dx: RUQUS to look for CBD dilation >7mm (poor Sn for
- Dx: RUQUS (Sn 84%, Sp 99%) > CT (Sn 55-80%); EUS if ⊝ visualizing stones themselves); MRCP or EUS if equivocal
- Stone types: cholesterol (most common)  5 Fs: fat, female, forty, fertile - Tx: ERCP w/ stone removal; interval CCY
(multiparous), fair (Caucasian); pigment: Crohn’s/ileal disease, extravasc. - Complications: ascending cholangitis, acute pancreatitis
hemolysis, TPN NB: can occur in pts s/p CCY if de novo formation in CBD
- Tx: asymptomatic: observe; CCY only if at  risk for GB CA (stone >3cm,
porcelain GB, GB adenoma); symptomatic: elective CCY
- Complications: cholecystitis, choledocholithiasis, pancreatitis, GB CA,
gallstone ileus, Mirizzi syndrome (compression of CBD/CHD)
Cholecystitis: stone in cystic duct  inflammation of GB ± infxn Cholangitis: ascending biliary infxn 2/2 obstruction in CBD
- Sx: RUQ pain (w/ radiation to back/shoulder), Murphy’s sign, n/v, fever - Etiologies: stone, stricture (malig., PSC, AIDS), liver fluke
- Labs: WBC; may have mild ALP, Bili; but if , c/f CBD obstruction - Sx: Charcot’s triad: RUQ pain, fever, jaundice; Reynold’s
- Acalculous cholecystitis: GB stasis/ischemia w/o obstruction. Unexplained pentad: + shock and AMS
fever, WBC, in ICU pt. Risk factors: trauma, burns, TPN, severe illness, - Labs: WBC, ALP, Bili, +/- AST/ALT (can be )
fasting, sepsis, immunosuppression (CGH 2010;8:15) - Dx: RUQUS (ductal dilation), MRCP/ERCP. Tokyo
- Dx: RUQUS (GB wall thickening, pericholecystic fluid, sonographic Guidelines for dx & severity (J Hep Panc Sci 2018;25:17)
Murphy’s)  HIDA scan if ⊝; pre-tx w/ 2mg IV morphine Sn (given by - Tx: broad spectrum abx (Zosyn or CTX/flagyl; carbapenem
nuclear rads at MGH) (AJR 2016; 207:865). Tokyo Guidelines for dx & if life-threatening) x7d; urgent ERCP w/ decompression
severity (based on deg. of organ dysfunction) (J Hep Panc Sci 2018;25:41) (<24-48hrs) if severe (associated organ dysfunction/shock)
- Tx: abx (Zosyn or CTX/Flagyl). Early (<7d) CCY during hospitalization or if fails to improve on abx x24hrs. Perc drainage if ERCP
 morbidity (Br J Surg 2015;102:1302). If critically ill or high surgical risk & not feasible. Interval CCY if due to gallstones.
fails to improve after 1-3d abx, perc. cholecystostomy. Stop abx 24hrs
post-CCY unless septic/perc chole: 4-7d. (JAMA Surg 2019;154:873)
- Complications: gangrenous cholecystitis, emphysematous cholecystitis
(gas-forming org.), perforation, enteric fistula, gallstone ileus
AUTOIMMUNE BILIARY DISEASES
Primary Biliary Cholangitis (PBC) (AASLD: Hepatology 2019;69:394) Primary Sclerosing Cholangitis (PSC) (NEJM 2016;375:1161)
Autoimmune destruction of intrahepatic bile ducts Affects intra- + extrahepatic bile ducts
- Clinical manifestations: ♀>♂; asx, (50-60%), pruritus, fatigue, - Clinical manifestations: ♂>♀; asx (50%), pruritus and fatigue
sicca symptoms, cirrhosis (late) (most common), cirrhosis (late); can be c/b episodes of cholangitis
- Dx: ≥2 of the following: ALP ≥1.5x upper limit of normal; AMA due to strictures
>1:40 titer (95% pts); biopsy findings - Dx:  ALP ± bili; may have +auto-Abs but of unclear significance;
- Associated with: hypothyroidism (20% pts), anemia, metabolic MRCP (segmental strictures), ± biopsy;  AMA/IgG4 to exclude
bone disease, Sjogren’s, autoimmune hepatitis (overlap) alternative dx
- Tx: ursodiol: first line, progression & survival (NEJM - Associated with: IBD (60-80%; UC>Crohn’s), cholangioCA (10-
1994;330:1342); obeticholic acid: adjunctive/replacement for 15% pts), metabolic bone disease, AIH (overlap)
ursodiol, fibrates: off label altern.; cholestyramine for pruritus; - Tx: none; liver transplant (MELD exceptions for recurrent
?modafinil for fatigue; liver transplant: 22% recurrence in 5yrs cholangitis, intractable pruritus): 20% recurrence 5 years post-LT
MALIGNANT DISEASE OF THE BILIARY TRACT
Gallbladder carcinoma: risk factors: gallstone disease (34x more likely to develop CA), porcelain GB, GB polyps, PSC, chronic infxn
• Clinical manifestations: usually asymptomatic; sx may include n/v, weight loss, biliary colic, jaundice (if obstruction)
• Diagnosis: LFTs usually normal, CA19-9/CEA; RUQUS best screening test, then CT/MRI/MRCP
Cholangiocarcinoma: may be extrahepatic (90%) or intrahepatic (10%); risk factors: PSC, liver flukes, intrahepatic gallstones
• Clinical manifestations: cholestasis (jaundice, pruritus, acholic stool, dark urine), RUQ pain, n/v, weight loss, fever
• Diagnosis: ALP, Bili, CA19-9/CEA +/- AST/ALT depending on deg. of obstruction; RUQUS best screening test, then
ERCP/MRCP/EUS (depending on location)
R A D I O G R A P H I C A S S E S S M E N T O F S U S P E C T E D B I L I A R Y P A T H O L O G Y (Am J Roentgenol 2011;197:551)

Thomas Wang
76
TOC

Gastroenterology Acute Liver Injury & Failure

Acute Liver Failure (ALF): encephalopathy & coagulopathy (INR >1.5) of <26wks in pts without cirrhosis or known liver dz
Acute Liver Injury (ALI): acute liver injury <26wks with coagulopathy but NOT encephalopathy
Presentation: non-specific fatigue, lethargy, anorexia, n/v, RUQ pain, pruritis, +/- jaundice  confusion in ALF (and may  coma).
Initial diagnostics: CBC, CMP, PT/INR, T&S, lactate, ABG, arterial NH3, FSBG, hCG, HIV, APAP, tox screen, viral serologies (see
below), HIV-1 & -2 Ab, autoimmune serologies (see below), amylase/lipase, RUQUS w/ doppler
Type Etiologies Diagnostics
Acetaminophen: most common cause of ALF in US, dose-depend. (>4g)
History: ask re: all APAP-cont. meds, herbal supp.,
Herbal supplements: including Amanita phalloides mushroom
Drugs new meds/OTCs, EtOH use
Idiosyncratic DILI: see LiverTox; abx (*Augmentin), AEDs, anti-TB, etc.
Labs: APAP level, EtOH, tox screen
(Alcohol-related hepatitis: considered acute-on-chronic and not ALF)
History: travel, IVDU, occupational exposures,
HAV, HBV, HCV (rare w/o HBV co-infection), HDV (risk co-infection > sexual exposures, vesicular rash, blood transfusion,
superinfection > HBV alone), HEV (pregnant or in endemic areas) immunocompromised state
Viral
Others: HSV (may be anicteric, WBC ), adenovirus, EBV, CMV, VZV (if Labs: HAV IgM, HBsAg & core IgM, HCV Ab &
immunocompromised) PCR, HSV Ab;  HDV if +HBV, HEV if preg. VZV if
immunocompromised
History: hypoTN, hypercoag. state, drugs/meds
Systemic hypoTN (sepsis, cardiac dysfunction), vasoconstricting drugs
Ischemic/ Imaging: U/S w/ doppler; CT or MRI/MRV are
(cocaine, meth.), Budd-Chiari (hepatic vein thrombosis), veno-occlusive
vascular alternatives; consider TTE if suspect ischemia but
disease (post-HSCT); ALT/LDH <1.5 suggestive of ischemic
no known cause
Autoimm. AIH: F>M; can present as ALF but uncommon Labs: IgG(), ANA, ASMA, anti-LKM-1
History/exam: FH, slit-lamp exam for Kayser-
Wilson’s: <40, F>M; AST>ALT often >2; nml/ALP & ALP/Tbili <4; a/w
Genetic Fleischer rings (if suspect)
DAT-neg. hemolytic anemia, uric acid, rapidly progressive renal failure
Labs: ceruloplasmin (though may be nml/ in ALF)
HELLP, acute fatty liver of pregnancy, malignant infiltration (breast CA, Labs: U/A if pregnant
Others
SCLC, lymphoma, myeloma), HLH, heat stroke, hepatectomy Liver bx if dx remains elusive after thorough eval.
G E N E R A L M A N A G E M E N T O F A C U T E L I V E R F A I L U R E (AASLD: Hep 2012;55:965; AGA: Gastro 2017;152:644; NEJM 2013;369:2525)
• Consult Hepatology for OLT workup. Urgency based on HE severity (grade 3-4 ASAP). Hepatic Encephalopathy
• Disposition/monitoring: ICU if HE grade ≥2;  freq. INR, CBC, ABG, Glc, Na, K, Cr, Mg, Phos; Grade Mental Status Asterixis
freq. exams to assess for signs of worsening HE or ICP (esp. grade 3-4), e.g. Cushing’s triad I Attention deficit +/-
• Hemodynamics: IVF (NS) and/or pressors (norepi ± vaso); goal MAP ≥75 for cerebral perfusion. Lethargy
II +
• N-Acetylcysteine (NAC): tx of APAP toxicity, but may benefit non-APAP ALF w/ grade 1-2 HE Moderate confusion
(Gastro 2009;137:856); given initially in all/most cases: 150mg/kg over 15min  100mg/kg over 16hr III
Somnolence
+
• Encephalopathy: intubation for HE gr. ≥3; cerebral edema in HE gr. 3 (25-35%) & 4 (65-75%). Marked confusion
o Lactulose in ALF controversial: no Δ outcomes,  bowel distent. Rifaximin’s role uncertain. IV Coma +
o If high risk for cerebral edema (grade 3-4, NH3 >150, ARF, pressors), prevent w/ 3%
saline for Na 145-155 (Hep 2004;39:464), HOB 30,  stimulation, avoid overhydration & Complications of Acute Liver Failure
high PEEP. HE, cerebral edema (esp. if
Neuro
NH3 >200, grade 3-4 HE)
o Treat cerebral edema w/ IV mannitol (0.5-1g/kg bolus x1-3); if impending herniation,
CV Shock, high-output state
hyperventilate to PaCO2 ~25-30 (temporary; concern that may worsen edema by  Pulm. Pulm. edema, ARDS
ischemia). Pentobarbital/thiopental coma if other measures fail (though may cause hoTN GI GIB, pancreatitis (esp. APAP)
which   CPP) Endo. Glc, adrenal insuff.
• Seizures: treat w/ phenytoin; benzos if refractory. Consider routine EEGs for subclinical SZ. Renal dysfxn in >50%; met.
• Infection: high risk for bacterial (Staph, Strep, GNRs) & fungal.  serial BCx, UCx, SCx, CXR. Renal acid. (lactate), Na, K, P
May not fever,  WBC, or have localizing s/sx, though worsening HE or AKI may be sign. Low Heme Coagulopathy, Plt, DIC
threshold for empiric abx +/- antifungal (esp. if prolonged hosp., abx, steroids, CVVH) Infection In ~90%; bacterial + fungal
• Coagulopathy/bleeding: can trial vit K but routine FFP not recommended. In ICU, ppx w/ PPI.
ETIOLOGY-SPECIFIC MANAGEMENT
• APAP  NAC w/in 8hrs. Rumack-Matthew Algorithm • HSV/VZV  acyclovir (5-10mg/kg q8h); may need OLT.
• HBV  OLT. Possible role for antivirals. • AIH  glucocorticoids; OLT if needed.
• HCV  OLT. • Wilson’s  OLT. Chelation ineffective.
• HAV/HEV  supportive care, possible OLT. • Budd-Chiari  TIPS, surgical decompression, lysis, OLT.
• AFLP/HELLP  delivery. Follow up for need for OLT. • Alcoholic Hepatitis  see Alcohol-Related Liver Disease

Prognosis: MELD score >30.5 = poor prognosis; King’s College Criteria – list for OLT if:
Acetaminophen-induced ALF:
consider liver transplant. King’s College Criteria also
Arterial pH <7.3 OR all 3 of: INR >6.5, Cr >3.4, grade 3-4 HE
used for prognosis – more specific but less sensitive All other causes of ALF:
vs. MELD. Poor prognosis for ALF due to HBV, INR >6.5 OR 3/5 of: age<10 or >40, Tbili ≥17, INR >3.5, time from jaundice to
Wilson’s, Budd-Chiari, autoimmune, drug injury. encephalopathy >7d, unfavorable etiology (seronegative hepatitis, DILI, Wilson’s)

Amanda PeBenito
77
TOC

Gastroenterology Viral Hepatitis

HEPATITIS A (J Hep 2018;68:167)
Fecal-oral transmission from person-person contact or contam. food/water, international travel. Sx: abrupt-onset n/v, anorexia, malaise,
fever, jaundice, RUQ/abd pain, ALT>AST (often >1000),  bilirubin, ALP. 70% of adults w/ sx, last 2-8 weeks, jaundice peaks after 2
weeks. Dx: ⊕ anti-HAV IgM (persists 3-6 months after infxn). Anti-HAV IgG forms at 2-3 weeks; persists for life and confers immunity. Tx:
supportive unless ALF (rare)  transplant. Vaccinate if: MSM, IVDU, chronic liver disease, travel, etc.
H E P A T I T I S B (AASLD Guidelines: Hepatology 2018; 67:1560)
Risk Factors Vertical transmission (SE Asia), sexual contact, IVDU, needlestick, unvaccinated (US before 1994), immunosuppress.
Acute: 70% subclinical / w/o jaundice, 30% w/ jaundice, <1% ALF. S/Sx: anorexia, nausea, fatigue, RUQ discomfort.
Clinical Pres.
ALT>AST in 1000s, +/- Bili. Chronic: ⊕sAg >6mo. (often w/ persistent ALT), occurs <5% adults. 40%cirrhosis.
Extrahepatic PAN, membranous nephropathy/MPGN, aplastic anemia, arthritis
Diagnosis Screening: HBsAg, anti-HBs, anti-HBc total (identifies all infected). Interpretation below.
Treatment First line: tenofovir or entecavir (Hepatology 2016;63:284). Goal: suppress HBV DNA, lose HBsAg & HBeAg
HCC Screen. Indications: all HBsAg+ w/ cirrhosis, HBsAg+ & high-risk (Asian/Black ♂ >40; Asian ♀ >50; +HDV; +FH HCC)
sAg sAb cAb Interpretation Next Steps
⊕ - ⊕ Hepatitis B infected (acute or chronic)  IgM anti-HBc (acute vs. chronic), HBV DNA, HBeAg
- ⊕ ⊕ Past infection (resolved) None;  risk of reactivation w/ chemo / immunosuppression
(1) Recovery from remote acute infxn (w/ sAb Differentiate possibilities w/ IgM anti-HBc (acute infxn vs. others),
titers that have waned), (2) chronic infxn (& low anti-HBe, HBV DNA, repeat anti-HBc (later). NB: “occult HBV” =
- - ⊕
level sAg), (3) acute HBV in window period, (4) DNA⊕ w/ sAg⊝ +/- cAb⊕. Low risk reactivation but  if
false ⊕ anti-HBc or false ⊝ sAg chemo/immunosuppression.
- ⊕ - HBV-immune from prior vaccination None
- - - Uninfected, non-immune Vaccinate
HBV reactivation: indicated by: (1)  in HBV DNA vs. baseline or (2) reverse seroconversion from sAg-/anti-HBc+ to sAg+
• High risk therapies: rituximab, anti-TNF, high dose steroids (>20mg pred/d x4w), HSCT, chemotherapy, anti-rejection therapy
• Greatest risk if sAg+: should receive ppx before immunosuppressive/cytotoxic tx. Lower risk if sAg-/anti-HBc+ but still at risk (even if
sAb+) – in some situations, can be monitored for reactivation; in others (HSCT, rituximab, other B-cell agents) should receive ppx.
Management: Acute: unless severe, supportive; see if becomes chronic. Chronic: tx if decompensated cirrhosis or if compensated w/ DNA
>2k (& consider if <2k) regardless of ALT to reduce risk of decompensation. If no cirrhosis, depends on eAg/ALT/DNA – see below.
HBeAg ⊕ HBeAg ⊝
ALT ≤ULN‡ ALT 1-2x ULN ALT ≥2x ULN ALT ≤ULN ALT 1-2x ULN ≥2x ULN
ALT q3-6mo DNA >20K: DNA >20K: tx DNA >2K: - Exclude other DNA >2K: tx
HBeAg q6-12mo. - Exclude other causes ALT DNA <20K: - ALT & DNA causes ALT DNA <2K:
- If ≥ F2 fibrosis*, tx. - monitor q1-3mo.; q3mo x1yr, then - If ≥ F2 fibrosis*, tx. - Exclude other causes
- If ALT persists, tx. if >2k for 6mo, tx. q6mo. - If DNA >2k & ALT ALT
DNA <20K: DNA <2K†: persists, tx. - If ≥ F2 fibrosis*, tx
- monitor q1-3mo.; if >2k for - ALT & DNA q3- - If DNA becomes >2k &
6mo, tx. 6mo., HBsAg q1yr ALT persists, tx.
NB: ALT ULN > 35 for ♂ and >25 for ♀ (not local reference values). *Fibrosis stage determined with Fibroscan & FIB-4. If indeterminate  liver Bx.
‡HBeAg+ w/ DNA ≥10k but nml ALT = “immune-tolerant” – consider liver bx if age >40. †HBeAg-, anti-HBe+ w/ DNA <2k, nml ALT = “inactive”; monitor for

spont. sAg clearance  “functional cure” (NB: still HCC risk).

HEPATITIS C (AASLD/IDSA Guidelines: Hepatology 2020;71:686; Lancet 2019;394:1451)
Screening HCV Ab: all ≥18 x1 (CDC: MMWR Rec Rep 2020;69:1; USPSTF: JAMA 2020;323:970). Annual if IVDU or MSM w/ HIV.
Blood products before 1992 or from infected individual, MSM, HIV, IVDU, chronic HD, incarceration, immigration
Risk Factors
from high prevalence area, birth to HCV infected mother, sex with HCV partner.
Diagnosis If ⊕Ab, RNA. If ⊕RNA, HCV genotype and tx. If RNA-, spontaneously cleared (NB: can still get reinfected).
Acute HCV: 75% subclinical. If sx, develop 2-26w after exposure, last 2-12w. Fulminant rare (<1%).
Natural History Chronic HCV: 80%  chronic; if younger, ♀, genotype-1, IL28B, jaundice, ALT more likely to clear spontaneously.
20%  cirrhosis ( risk if ♂, EtOH, obesity, HIV, immunosupp.). HCC risk 1-13%/yr.
Extrahepatic Mixed cryo., porphyria cutanea tarda, lichen planus, LCV, thyroiditis, Sjogrens, renal dz (e.g. MPGN), NHL
Varies based on fibrosis/cirrhosis (stage w/ FIB-4, Fibroscan, FibroTest), genotype (1-6), comorbidities (cirrhosis,
CKD, HIV), prior tx regimens. DAAs x8-12 weeks. HCV RNA 12 weeks after therapy to assess SVR. See
Treatment
hcvguidelines.org. If acute HCV, can tx w/o waiting to see if clears, esp. if risk of loss to f/u, behaviors that could
result in transmission. NB: if cirrhosis, still  risk HCC s/p HCV tx & need ongoing surveillance.
HEPATITIS D (Gastro 2019;156:461)
Coinfection or superinfection with HBV. Coinfection similar to HBV but more severe,  risk ALF; often biphasic ALT course w/ 2 peaks.
Superinfection most severe, highest risk ALF & chronic infxn (90%)  cirrhosis in 80% in 5-10y. 3x  risk HCC vs. HBV mono-infection.
HEPATITIS E (APT 2017;46:126, Gastro 2012;142:1388)
Most common cause of viral hepatitis in endemic areas. Transmission: fecal-oral, vertical, zoonotic (swine organ meats). Most are asx &
resolve spontaneously. Extra-hepatic: neuro (e.g. GBS), renal, arthritis, anemia, pancreatitis.  Risk of acute hepatic failure/mortality in
pregnant women (Annals 2007;147:28). Rarely chronic HEV in transplant recipients. Rx with supportive care in immunocompetent pts.
Thomas Wang
78
TOC

Gastroenterology Alcohol-Related Liver Disease

Alcohol-Related Liver Disease (ALD): (AASLD Guidelines: Hepatology 2020;71:308; ACG Guidelines: AJG 2018;113:175)
Risk factors: sex (F>M), pattern ( daily, ± binge), obesity, genetics (e.g. PNPLA3), smoking, comorbid HCV/NAFLD/etc.; coffee  risk
Pathophysiology: EtOH  fat accumulation; EtOH   gut permeability   innate immune response, liver cell inflammation, injury,
necrosis, fibrosis; may be important role for gut microbiota (Nature 2019; 575:505)
Disease spectrum:
• Steatosis: usually asx; may have mild  AST>ALT, GGT; develops in 90% w/ >60g/d EtOH after 2wks; reversible w/ 4-6 wks
abstinence
o 20-40% develop fibrosis  8-20% to cirrhosis  20-40% decomp./acute-on-chronic liver failure. HCC in 3-10% w/ cirrhosis.
• Steatohepatitis: histopathologic correlate of AH; can develop at any stage of ALD; often  to fibrosis (40-50%) & cirrhosis (>75%)
• Alcohol-related hepatitis (AH): an acute inflammatory syndrome that can occur at any stage of ALD

Alcohol-Related Hepatitis:
Presentation: varies from few sx to liver failure; jaundice, anorexia, fever, abd pain (tender hepatomegaly), malaise, weakness, nausea
• Can lead to portal HTN & its sequelae (EVs, ascites, HE) in the absence of cirrhosis due to hepatic swelling & portal venous obstruct.
Diagnosis: onset of jaundice w/in prior 8wks, ongoing heavy EtOH (F >40 g/d, M >60 g/d) for >6mo. with <60d abstinence before onset of
jaundice, AST moderate  (50-400) w/ AST/ALT >1.5, Tbili >3 (Consensus Dx: Gastro 2016;150:785). Often WBC (<20k,  PMNs),  INR.
• Ddx: other etiologies of acute hepatitis/jaundice (viral, meds/herbs, ischemia, AIH, Budd-Chiari, biliary obstruct.), decompensated
cirrhosis (can be difficult to distinguish). HAV/HBV/HCV, U/S w/ doppler, ± others. Assess for signs of cirrhosis.
• Transjugular Bx: consider if atypical presentation and/or labs (e.g. AST or ALT >400), uncertain alcohol intake hx, confounding factors
such as use of hepatotoxic meds w/in last 30 days, possible ischemic insult (e.g. hypoTN, cocaine use) or other etiology
Exclude infection:  BCx, U/A, UCx, diag. para if ascites, CXR ± sputum Cx if indicated. Some will have SIRS/fever due to inflamm., but
important to screen for infxn as at high risk (esp. if severe AH: 12-26% at admission), can be difficult to dx, and has tx implications.
Prognostic tools:
Tool Use Components Stratification
Maddrey Discriminant Initiation of steroids, PT, PT control (14.5 at ≥32 = severe  1mo. mortality 30-50%;
Function (MDF) prognosis MGH), Tbili start steroids (Gastro 1978:75:193)
Prognosis, consider >20 = 3mo. mortality 20%;
MELD Tbili, INR, Cr, Na
initiation of steroids consider steroids (Hepatology 2005;41:353)
≥0.45: Nonresponse  stop steroids
Day 7 continuation or Day 0: Age, Albumin, PT, Cr
Lille <0.45: Response  continue steroids
cessation of steroids Day 0 & Day 7: Tbili
(Hepatology 2007;45:1348)

Treatment of Alcohol-Related Hepatitis

Corticosteroids: see algorithm. NAC may benefit, no harm (though is large vol. load)
• No MDF ceiling but if very severe (e.g. MDF >90, MELD >30), need to closely
assess for occult infxn or other contraindications. Single study w/ MDF >54 a/w
mortality has not been replicated (Alc Clin Exp Res 1995;19:635)
• Prednisolone used as no hepatic metabolism (methylpred 32mg is IV alternative):
40mg x 28d w/ 2-4w taper (e.g.  10mg q4d until 10mg then 5mg q3d)
• STOPAH trial:  28d mortality but not 90d, &  infxn (NEJM 2015;372:1619); recent
meta-analysis also w/  28d mortality (Gastro 2018;155:458)
Supportive therapy: monitor for infxn, HRS; hold βB if MDF ≥32 as  incidence of AKI
Nutrition: ensure adequate kcal, protein; supplement w/ MVI w/ thiamine, folate, B6, &
consider Zn. Low kcal in severe AH a/w  infxn &  6mo. mortality (Gastro 2016;150:903)
Abstinence: can result in rapid improvement in outcomes w/in 3 mo.
• Acamprosate 666mg TID, naltrexone 50mg QD ( dose in cirrhosis), baclofen 5-
10mg TID (Lancet 2007;370:1915), gabapentin 600mg TID (JAMA 2014;174:70),
topiramate 75-400mg/d

Liver Transplantation: definitive therapy for ALD. Traditionally required 6mo.

abstinence but recent European and US studies showing that early LT in appropriately
selected pts   6mo. survival with low risk of alcohol relapse and low impact on donor
pool (NEJM 2011;365:1790, Am J Transplant 2016;16:841) Other therapies with potential efficacy:
• MGH pilot program offers early LT eval. prior to abstinence for pts with 1) 1st • NAC: w/ steroids x5d, a/w mortality at
alcohol-related decompensating event (i.e. no prior knowledge of alcohol-related 1mo, but not 3 or 6mo. (NEJM 2011;365:1781,
liver disease or alcohol-related legal issues), 2) MDF ≥32, 3) not responsive to Gastro 2015;149:958)
steroids, 4) not grade 3-4 HE (to allow for psych eval), 5) strong social support, 6) • Pentoxifylline: consider if steroids contraind.
absence of severe psychiatric co-morbidities, and 7) no other substance use No convincing data on mortality benefit
disorder. Consult hepatology for candidacy. though AKI/HRS (Gastro 2000;119:1637,
APT 2013;37:845)
Alcohol Liver Evaluation Team p26299: will evaluate inpts with known ALD or AUD • G-CSF: currently only in clinical trials
without known ALD. If hepatology team following, they will coordinate w/ them. (Hepatology 2019;70:802, AJG 2014;109:1417)

Vlad Fomin and Blair Robinson

79
TOC

Gastroenterology End Stage Liver Disease

Definitions
• Cirrhosis: advanced state of fibrosis and regenerative nodules that distorts hepatic architecture and vasculature
• Decompensated cirrhosis: development of ascites, hepatic encephalopathy, jaundice, or variceal hemorrhage in patient w/ cirrhosis
• End-stage liver disease (ESLD): accompanying pathophysiologic state of impaired liver function

Clinical Manifestations and Diagnosis (JAMA 2012;307:832)

• Symptoms: fatigue/weakness, jaundice, pruritus, nausea, anorexia, abdominal distention, GIB, confusion, muscle cramps
• Exam: BP, splenomegaly, caput medusae, ascites, jaundice, spider angiomata (>3), gynecomastia, testicular atrophy, palmar
erythema, asterixis, nail Δs, Dupuytren’s contracture
• Labs: TBili, INR, Alb, Na, platelets, +/- Hgb/Hct, WBC; AST, ALT, alk phos, and GGT may be elevated or normal
• Diagnostics: viral hepatitis panel, iron studies, ANA, ASMA, AMA, α1AT, ceruloplasmin, SPEP
• Imaging: RUQUS (with doppler) to assess echogenicity/morphology of liver, ascites, vascular patency, biliary tree, HCC
• Non-invasive fibrosis assessment: goal: stratify as low, indeterminate, or high risk for adv. fibrosis; ideally combine multiple tests
o Radiographic: transient elastography best in HBV/HCV, is affected by obesity; MRE better in NAFLD (Gastro 2017;152:1536)
o Serum tests: APRI best studied in HCV & ALD (Hepatology 2011;53:726); FIB-4 index in HCV & NAFLD (Liver Int 2010;30:546);
NAFLD fibrosis score in NAFLD (Hepatology 2007;45:846); FibroSure (6 biomarkers) in HCV & HBV
• Biopsy: gold standard but now performed less often. Main indications are dx uncertainty or indeterminate fibrosis severity (NEJM
2017;377:756). Perc. (cannot do through ascites, massive obesity) or transjugular (allows HVPG measurement; pref. if coagulopathy).
Etiologies
• Most common: alcohol, viral (HCV, HBV), non-alcoholic fatty liver disease (NAFLD), hemochromatosis
• Genetic disorders: hemochromatosis, Wilson’s, α1AT deficiency (NEJM 2020;382:1443), CF, inherited disorders of glucose metabolism
• Immune-related: autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosis cholangitis (PSC), celiac disease
• Vascular: post-hepatic portal HTN (right heart failure, Budd-Chiari syndrome, veno-occlusive disease)
• Other: infection (i.e. schistosomiasis), meds (e.g. MTX, isoniazid, amiodarone; see livertox.nlm.nih.gov), cryptogenic/idiopathic
Complications of Cirrhosis
• Portal hypertension: esophageal varices, portal hypertensive gastropathy, hypersplenism (cytopenias), ascites, SBP, hepatorenal
syndrome, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary hypertension, cirrhotic cardiomyopathy
• Hepatic encephalopathy: mucosal & luminal NH3, clearance of NH3 & endogenous BDZ-like compounds (NEJM 2016;375:17)
• Immune dysfunction: increased risk of infection; bacterial and fungal infections are major causes of morbidity & mortality
• Endocrinopathies: hypoglycemia, thyroid dysfunction, hypogonadism, hyperestrinism (palmar erythema, spider angiomata)
• Coagulopathy:  in both pro- (II,V, VII, IX, X, XI) AND anti-coagulant factors (protein C/S, ATIII, plasminogen). Coags do not reflect
risk of bleeding or thrombosis & patients are not auto-anticoagulated (NEJM 2011;365:147).
• Portal vein thrombosis:  risk due unbalanced hemostasis & slowing of portal flow. Start AC for acute PVT w/ LMWH (unless high
bleeding risk); transition to VKA/DOAC once stable & continue 6mo. (AASLD: Hepatology 2009; 49:1729; AGA: Gastro 2019;157:33)
• Hepatocellular carcinoma: 1-8% risk per year. May be asymptomatic, lead to decompensation, and/or have sx related to mass effect
(pain, early satiety, palpable mass). Screen with US/MRI +/- AFP q6 months (AASLD guidelines: Hepatology 2018;68:723).
VIBES: a systematic approach to the management of cirrhosis
For all patients: etiology of cirrhosis, complications, compensated or decompensated & etiology of decompensation (infection
[including new/reactivation of HBV/HCV], SBP, GIB, EtOH, HCC, PVT, LVP, dehydration, meds, surgery, etc.), current MELD score
Volume (ascites, edema, hepatic hydrothorax, hepatorenal syndrome)
• Current diuretics (spironolactone/lasix 5:2 ratio) & response; dietary Na+ restriction (<2 g/d), fluid restriction 1.5L (only if Na<125)
• Prior history of LVPs, thoras for hepatic hydrothorax, consideration of TIPS if refractory
Infection (SBP)
• Prior history of SBP, whether has indication for 1° or 2° ppx
• Current treatment (if diagnostic paracentesis reveals PMNs >250 or +Cx) or ppx (CTX if active GIB; otherwise cipro or Bactrim)
Bleeding (esophageal/gastric varices, portal hypertensive gastropathy, coagulopathy)
• Prior history/source of bleeding, therapies (e.g. banding, sclerotherapy, TIPS), current prophylaxis (e.g. βB)
• Current bleed: severity, IV access, H/H trends, medical therapy (PPI/octreotide), results/plan for EGD, SBP ppx as above
Encephalopathy (portosystemic encephalopathy)
• Prior history, precipitant, and treatment
• Current severity, trend, precipitant, goal #BM on lactulose/rifaximin (e.g. goal 4 BM/d, 500cc stool, or mental status improvement)
Screening/Surgery (transplant)
• Vaccinations: HAV, HBV, Influenza, Pneumovax, Prevnar (and up-to-date on all other vaccines), should see Transplant ID
• Maintenance: alcohol abstinence, avoid NSAIDs
• Malignancy: HCC screening with q6 mo. RUQUS/MRI + AFP
• Transplant status: listed or not listed, MELD score, Milan criteria if HCC, classically requires 6 months sobriety

Krishan Sharma
80
TOC

Gastroenterology End Stage Liver Disease

COMPLICATIONS OF CIRRHOSIS
A S C I T E S (AASLD Guidelines: Hepatology 2013;57:1651)
• Most common complication of cirrhosis (50% in 10 years); development of ascites  15% 1-yr mortality, 44% 5-yr mortality
• Pathophysiology: portal hypertension  NO, prostaglandins  splanchnic vasodilation  EABV  RAAS, ADH  Na & water
retention. Severity of hypoNa (from ADH secretion) correlates with worsening survival.
• Diagnosis: dx para indicated for all new-onset or worsening ascites & pts w/ ascites w/ acutely decomp. cirrhosis or hospitalized
o Studies: cell count w/ diff, albumin, total protein, GS/Cx +/- glucose, LDH, amylase, cytology (malignancy), AFB Cx/ADA (TB)
o DDx: portal HTN vs. non-portal HTN. SAAG differentiates 97% of time (Annals 1992;117:215).
 Can confirm portal HTN with measurement of hepatic venous pressure gradient (HVPG): gradient b/w portal vein
(estimated by wedged hepatic venous pressure) and IVC (measured free hepatic venous pressure)
 Normal HVPG <5mmHg; Portal HTN ≥6; Clinically-significant portal HTN: ≥10; Risk of EV bleed: ≥12
 Limitation: may be normal in pre-sinusoidal portal HTN (e.g. PVT) as will generally not increase pressure in sinusoids
SAAG ≥1.1 g/dL SAAG <1.1 g/dL
Etiology related to portal hypertension Etiology not related to portal hypertension
• Cirrhosis (ascites fluid total protein [AFTP] <2.5) • Secondary bacterial peritonitis
• CHF, constrictive pericarditis (AFTP >2.5) • TB peritonitis
• Acute hepatitis (including EtOH) • Peritoneal carcinomatosis (+cytology)
• Massive liver metastases • Chylous ascites (triglycerides >200)
• Hepatocellular carcinoma • Hypoalbuminemia (nephrotic synd., protein-losing enter.; AFTP <2.5)
• Budd-Chiari syndrome (AFTP >2.5) • Serositis (e.g. SLE)
• Portal vein thrombosis • Pancreaticobiliary
• Management of ascites:
o 1st line: <2g Na, EtOH, NSAIDs, diuretics (see below), avoid ACEi/ARB; fluid restrict 1.5L if Na <120
 Initiating therapy: 100mg/d spironolactone + 40mg/d furosemide is usual starting dose (5:2 ratio). Combo maintains
normokalemia & mobilizes fluid faster. May start lower if older. Consider spironolactone alone for mild first ascites if outpt.
 Ongoing therapy: dose q3-5 days if inadequate diuresis (5:2 ratio, though can adjust PRN if abnormal K). Max doses:
400mg spironolactone and 160mg furosemide. Δ to amiloride 10-40mg qd if painful gynecomastia w/ spironolactone.
 If unsuccessful: Check UNa/UK ratio if pt gaining weight/requiring LVPs on diuretics. Value >1 suggests >2g Na dietary intake
(i.e. >2g UNa excretion). Value <1 suggests ineffective diuretic dose or resistance.
o Weight loss goals: 0.5 kg/d (TBB -500) if no peripheral edema (AKI risk if too fast); if edema, 1kg/d or -1L ok. Avoid IV
diuretics. Ascites mobilizes fluid slower than other compartments (Gastro 1986;90:1827)
o Therapeutic LVP: indicated for tense or refractory ascites (see below) or inability to use diuretics; if >5L, transfuse 6-8g
albumin for every L ascites removed (~30-40g or 2-3 bottles of 25% albumin)
o Albumin: long term administration may offer survival benefit for cirrhotic patients with ascites (Lancet 2018;391:2417).
• Refractory ascites:
o Defined as: (1) unresponsive to Na-restricted diet and high-dose diuretics or (2) rapid reaccumulation after LVP
o Management: consider d/c βBs (mortality in refractory ascites; Hepatology 2010;52:1017), avoid ACEi/ARB as above (renal
perfusion), midodrine TID (J Hepatol 2012;348), serial LVPs (usually ~q2w), TIPS as bridge to OLT
S P O N T A N E O U S B A C T E R I A L P E R I T O N I T I S ( S B P ) (AASLD Guidelines: Hepatology 2013;57:1651)
• Must r/o SBP in all inpatients w/ cirrhosis & ascites w/ dx para; 10-30% hospitalized pts w/ cirrhosis have SBP
• Diagnosis: >250 PMN/L w/ positive GS/Cx (SBP) or negative GS/Cx (CNNA = similar mortality to those w/ +Cx; treated similarly)
⊕ Ascites culture ⊝ Ascites culture
Spontaneous bacterial peritonitis (SBP)
PMN ≥250/μL Culture negative neutrocytic ascites (CNNA)
(secondary peritonitis  polymicrobial)
PMN <250/μL Non-neutrocytic bacterascites (NNBA) Normal
Hemorrhagic ascites: RBC >50,000/mm3, often due to traumatic tap  correct PMN count by subtracting 1 PMN for every 250 RBCs
o Usually monomicrobial; GNR 70% (E. coli, Klebsiella), GPC 25% (S. pneumoniae), anaerobes 5%
o If polymicrobial, consider secondary bacterial peritonitis 2/2 perforation vs. loculated abscesses
o Bowel perf. suggested if ≥2 of the following: TP >1, LDH >ULN, or Glc <50; also CEA >5 & ALP >240 (Runyon’s criteria)
• Treatment:
o CTX 2g q24h x5d AND 25% Albumin (1.5 g/kg on day 1 and then 1.0 g/kg on day 3, max 100 g; indicated if Cr >1, BUN >30, or
TBili >4); IV cipro (400mg q12) is alternative if unable to take cephalosporin (unless taking cipro for ppx)
o Discontinue βBs indefinitely given increased risk of AKI & HRS once SBP is diagnosed (Gastro 2014;146:1680)
o Repeat para if no improvement in 48hr to rule out 2° peritonitis  add anaerobic coverage, CT A/P +/- surgery c/s
• Prophylaxis:
o IV CTX 2g q24 x7 days if GIB; can switch to tx dose PO cipro (500mg q12) or PO Bactrim (DS BID) if not bleeding & stable
o All patients w/ prior SBP should receive 2° PPX (after full tx above) w/ PO cipro 500 qd (at MGH) or PO Bactrim DS qd
o Consider 1° prophylaxis if ascitic TP<1 or TP <1.5 AND 1 of following: BUN ≥25, Cr ≥1.2, Na ≤130, or Child-Pugh ≥9 w/ TB ≥3

H E P A T O R E N A L S Y N D R O M E ( H R S ) : See Hepatorenal Syndrome page.

Krishan Sharma
81
TOC

Gastroenterology End Stage Liver Disease

E S O P H A G E A L V A R I C E S (AASLD Guidelines: Hepatology 2017;65:310)
• Screening: baseline EGD at diagnosis unless liver stiffness <20kPa (by transient elastography) & platelets >150 (very low probability)
o Repeat EGD q2yrs (if ongoing injury/condition), q3yrs (if injury quiescent), or if decompensation event & previously no/small EVs
EVs identified ppx if high risk of bleeding:
- Medium/large: non-sel. βB (see below), carvedilol (6.25mg QD for 3 days   to
1° (1) medium/large size (>5mm)
6.25mg BID), OR serial endoscopic variceal ligation (EVL) q2-8wk until eradication
PPX (2) small (<5mm) w/ red wale signs
- Small: non-selective βB
(3) decompensated cirrhosis w/ small varices
- Non-selective βB: nadolol 20-40mg QD or propranolol 20-40mg BID; adjust to
Episode of variceal bleeding ppx to
2° goal HR 55-60, SBP>90; max dose in patients with/without ascites: propranolol
prevent recurrence w/ combination of non-
PPX 160mg/320mg QD or nadolol 80mg/160mg QD
selective βB + EVL
- Serial EVL: q1-4 wks until obliteration; repeat EGD 3-6mo. after & then q6-12mo.
• Acute bleeding: IV access, IVF, pRBC, PPI, octreotide, CTX, EGD. May need intubation, Blakemore as a bridge (GI), TIPS (IR),
surgery, Amicar (if fibrinogen). Conservative transfusion: goal Hgb 7-9 (NEJM 2013;368:11). See Upper GI Bleeding.
• Indications for TIPS: early “preemptive” TIPS (<72hrs) in pts with high risk of treatment failure or rebleeding (NEJM 2010;362:2370;
Hepatology 2019;69:282); “rescue” TIPS if uncontrolled bleeding or if recurs despite max medical & endoscopic therapy
• Gastric varices: generally managed similar to EVs w/ βBs for ppx, similar mgmt. of acute bleed; BRTO is an option for fundal GVs
• Stop βB if: SBP, refractory ascites, HRS, low BP, sepsis; “window hypothesis” (J Hepatol 2014;60:643; Gastro 2014;146:1597)
H E P A T I C E N C E P H A L O P A T H Y ( H E ) (NEJM 2016;375:1660; AASLD Guidelines: Hepatology 2014;60:715)
• Pathophysiology: NH3  neurotoxic effects, abnl neurotransmission, GABA- & BDZ-like neurotransmitters & altered glutaminergic
inputs  excitatory transmission. In ALF, acute NH3  cerebral edema.
Grades of Hepatic Encephalopathy
• Diagnosis: clinical. Serum NH3 should not be used to screen for HE. NH3 does (West Haven Criteria)
not add diagnostic, staging, or prognostic value in chronic liver disease. Only
helpful in ALF (predicts mortality). Trend by regularly assessing for asterixis and/or Inattention, euphoria/
concentration. Covert Grade 1 anxiety, altered sleep
• Asterixis: “flapping tremor” is negative myoclonus w/ loss of postural tone; pattern,  attention span
alternative is hand grip: oscillates b/w tight and loose (APT 2010;31:537) Lethargy, behavior Δs, time
• Precipitants: infection, dehydration/overdiuresis, GIB, hypoK or alkalosis (renal disorientation, asterixis,
NH3), constipation, sedatives/BZD, new HCC, new clot, TIPS Grade 2
personality Δs, hypoactive
• Treatment:  GI NH3 absorption, avoid/correct precipitating factors DTRs
o Lactulose: Δs gut microbiome, has laxative effect; 30mL q2h until BM 
titrate to 3-4 soft BM/day (PO, PR or NG) Somnolence to semi-
Overt
o Lactulose + rifaximin 550 mg BID > lactulose alone for HE reversal (NNT stupor, responsive to
= 3) & all-cause mortality (NNT = 4) (AJG 2013;108:1458); prevents recurrence Grade 3 stimuli, time & place
of HE (NEJM 2010;362:1071). Add rifaximin if refractory HE or after second disorientation, asterixis,
episode of overt HE. hyperactive DTRs
o If refractory, consider non-standard therapies: oral branched-chain AAs
(Cochrane Reviews 2017;5), IV L-ornithine L-aspartate (Hepatology 2018;67:700), Grade 4 Coma
neomycin, Flagyl, metabolic NH3 scavengers, probiotics (Cochrane Rev 2017),
zinc, PEG (JAMA Int Med 2014;174:1727)
o FMT may have role (Hepatology 2017;66:1727; Gastro 2019;156:1921)
H E P A T O C E L L U L A R C A R C I N O M A ( H C C ) (AASLD Guidelines: Hepatology 2018;68:723 and Hepatology 2018;67:358)
• Screening indicated in:
o Cirrhosis due to any etiology: HCV (including after cure w/ DAA treatment), HBV, NAFLD, EtOH, others
o HBV carriers without cirrhosis if: Asian M >40, Asian F >50, African/African-American, or FHx HCC
o Screening not recommended in patients with Child’s class C cirrhosis unless on the transplant list
• Screen with: RUQUS +/- AFP q6 months (MGH practice to include AFP); if U/S inadequate, can use multiphase CT or MRI.
o If nodule <1cm, repeat US in 3-6 months
o If nodule ≥1cm or AFP ≥20, obtain multiphase CT or MRI & proceed according to LI-RADS class
• Staging: Barcelona stage; incorporates size, # of nodules, LN & portal vein involvement, mets, Child-Pugh score, performance status
• Management: surgical resection (1st line if CPS A & T1-T2 nodule), OLT (non-resectable but within Milan criteria), ablation (RFA),
TACE (chemoembolization), TARE (radioembolization), SBRT, systemic chemotherapy (sorafenib)
o Within Milan criteria  local-regional tx (LRT) as bridge to OLT. Outside Milan  LRT to downstage to w/in Milan  OLT.
o Not OLT candidate (and non-resectable)  LRT and/or systemic chemotherapy (if advanced).
H E P A T I C H Y D R O T H O R A X (AASLD Guidelines: Hepatology 2013;57:1651)
• Transudative effusion due to shift of ascites into pleural space (due to neg. intrathoracic pressure) via small diaphragmatic defects.
Can be seen without significant ascites. Usually unilateral: R- (~75%) > L-sided (~15%) > bilateral (~10%) (Medicine 2014;93:135).
• Diagnosis: exclude other causes of transudative effusion; can visualize w/ radioisotope injection into ascites if dx unclear
• Treatment: same as for ascites (diuretics, <2g Na). Therapeutic thora for dyspnea. TIPS if refractory. Chest tube not recommended.
• Spontaneous bacterial empyema: can become infected (~15%) due to translocation of bacteria from abd. cavity, even in the
absence of SBP (~40%) (Hepatology 1996;23:719). Dx: >250 PMNs w/ +Cx or >500 PMNs w/o +Cx. Tx: same as for SBP.

Krishan Sharma
82
TOC

Gastroenterology End Stage Liver Disease

H E P A T O P U L M O N A R Y S Y N D R O M E ( H P S ) (NEJM 2008;358:2378; EASL: J Hepatol 2018;69:406; ILTS: Transplantation 2016;100:1440)
• Syndrome of intrapulm. shunting through intrapulm. vascular dilatations; mechanism unclear, possibly due to circulating NO
• Presentation: shunting tends to occur at bases  platypnea (dyspnea when upright, relieved when supine) & orthodeoxia (upright
hypoxemia, PaO2  by 4 mmHg or ≥5%), clubbing, cyanosis, diffuse telangiectasias, hypoxemia (PaO2 <70-80).
• Diagnosis: TTE with late bubbles (3-6 cardiac cycles after RA), A-a gradient ≥15 (or ≥20 if age >64)
o 99mTc MAA scan is alternative to TTE but more invasive, less sensitive. May be useful in quantifying shunting if severe
hypoxemia and coexistent intrinsic lung disease
o Pulmonary angiography performed if severe hypoxemia poorly responsive to 100% O2 & areas amenable to embolization
o PFTs can be performed to evaluate for intrinsic lung disease; DLCO in HPS
• Risk stratification: mild: PaO2 ≥80, moderate: PaO2 60-79, severe: PaO2 50-59, very severe: PaO2 <50
• Management: O2; no effective medical therapies; OLT can significantly improve (and reverse) HPS – MELD exception points if severe

P O R T O P U L M O N A R Y H Y P E R T E N S I O N (EASL Guidelines: J Hepatol 2018;69:406; ILTS Guidelines: Transplantation 2016;100:1440)

• Rare cause of group 1 pulmonary hypertension in setting of portal HTN
• Pathogenesis: unknown; possibly 2/2 humoral substances (ex. serotonin, interleukin-1, endothelin-1, normally cleared by liver) that
reach pulmonary circulation through portosystemic collaterals
• Presentation: DOE, chest pain, fatigue, palpitations, syncope, hemoptysis, orthopnea; often w/ TR murmur, EKG w/ RVH, RAB, RBBB
• Diagnosis: RHC w/ PAH (mPAP >20 mmHg, PCWP <15 mmHg, PVR ≥3) in pt with established portal hypertension in absence of
other etiology of PAH or venous hypertension.
• Risk stratification: mild: mPAP <35, moderate: mPAP 35-44, severe: mPAP ≥45
• Management: may benefit from advanced therapies (epoprostenol, bosentan, sildenafil, iloprost); OLT can improve/normalize the
PAH (MELD exception points given if moderate); βB and TIPS may be harmful and should be avoided.
• Transplant: increased risk of morbidity/mortality with mPAP ≥35; mPAP ≥45 is a contraindication

C I R R H O T I C C A R D I O M Y O P A T H Y (Hepatology 2020;71:334; EASL Guidelines: J Hepatol 2018;69:406)

• Definition: chronic cardiac dysfunction in cirrhotic patients with no known cardiac disease; characterized by 1) impaired cardiac
contractility in response to stress, 2) altered diastolic relaxation, 3) electrophysiological abnormalities such as prolonged QTc
• Prevalence: up to 50% of patients undergoing liver transplantation have signs of cardiac dysfunction
• Diagnosis: echocardiography with dynamic stress testing w/ pharmacologics or exercise
• Pathophysiology: myocardial dysfunction 2/2 systemic inflammation; shear stress from portal hypertension  mechanical force on
myocardial fibers; other possible mechanisms involve collagen configuration, sodium retention and activation of RAAS
• Treatment: same as HF management in non-cirrhotic patients
• Prognosis: largely subclinical and asymptomatic; however poses risk in the presence of stress such as infection, TIPS, or OLT; thus
detailed cardiac assessment required prior to interventions

H E M A T O L O G I C A B N O R M A L I T I E S (AGA: Gastro 2019;157:33; NEJM 2011;365:147, CGH 2013;11:1064, Thromb Haemost 2018;118:1491)
• Cytopenias: multifactorial; thrombocytopenia (splenomegaly, TPO), leukopenia (splenomegaly), anemia (bleeding, spur cell
anemia); also may have BM suppression by EtOH/infection, nutritional deficiencies (e.g. folate), direct effect of HCV/HBV
• Coagulation abnormalities:  coagulation factors (except for FVIII),  anticoagulant proteins (C, S, ATIII), dysfibrinogenemia,
accelerated fibrinolysis (tPA)   risk of both clotting and bleeding & patients not auto-anticoagulated; balance tends to favor
thrombosis in early stages vs bleeding in late stages of cirrhosis
o Labs: PT/INR, PTT, /nml fibrinogen (though does not function normally;  if fulminant), /nml D-dimer (vs.  in DIC),
factor VIII (vs.  in DIC); note PT and PT/INR do NOT correlate with risk of bleeding or clotting
• Anticoagulation: (J Hepatol 2017;66:1313, JACC 2018;71:2162, Gastro 2019;157:33)
o VTE ppx: should not be withheld unless high risk of bleeding or plts<50
o Systemic AC: ok unless decompensated CPS C or high risk of bleeding. EGD for EVs prior to starting. VKA, LMWH, or DOAC all
options. VKA dosing can be c/b baseline PT/INR; LMWH can be c/b ATIII levels; DOACs relatively safe in stable pts though
all have some degree of hepatic metabolism – can use all except rivaroxaban w/ caution in CPS B, avoid all in CPS C
• Bleeding: consider role of coagulation factor deficiency, dysfibrinogenemia, hyperfibrinolysis, thrombocytopenia
o If suspect vitamin K deficiency, give vitamin K 10mg x3 days to correct nutritional component
o Transfuse pRBCs Hgb <7, platelets <50k, cryo for fibrinogen <100-120 (or if c/f dysfibrinogenemia)
o Persistent bleeding despite cryo or requiring many pRBCs  can give FFP (though large volume   portal pressures)
o Delayed bleeding or oozing from mucocutaneous sites  c/f hyperfibrinolysis  topical and/or systemic Amicar (3g PO QID or
4-5g IV over 1hr 1g/hr) or TXA (1g IV q6hr)
• Procedures:
o Platelets: >50k for surgery, TIPS, liver biopsy, or other procedure w/ high bleeding risk; TPO agonists can reduce need for peri-
procedural plt transfusions but take ~10d to plts (NEJM 2012;367:716; Gastro 2018;155:705).
o PT/INR: NO benefit to giving FFP pre-procedure to “correct” INR.  volume can  bleeding risk by  portal pressures.

Krishan Sharma
83
TOC

Gastroenterology Hepatorenal Syndrome

Hepatorenal Syndrome (HRS) (NEJM 2009;361:1279; Clin Gastro Hep 2018;16:162)
• Pathophysiology: portal HTN  NO, prostaglandins  splanchnic vasodil.  EABV  RAAS, ADH, SNS  renal vasoconstr.
• Diagnosis: dx of exclusion; need: (1) chronic or acute hepatic disease w/ portal HTN, (2) Cr >0.3/48hrs or >50%/7d, (3) absence of
shock, (4) no parenchymal disease, (5) no current/recent nephrotoxins, (6) no improvement after 2d cessation of diuretics + albumin
challenge (1g/kg albumin x2d, max 100g/d; use 25% albumin; goal is  oncotic pressure, not volume expansion) (Gut 2015;64:531)
• Type I: Cr 2x baseline and >2.5 mg/dL in <2wk + multiorgan dysfunction; Type II: slower decline, often have refractory ascites
• Precipitants: infection (SBP > other), GI bleed, fluid shifts after LVP, alcohol-related hepatitis
• Management: see below. Use albumin + octreotide + midodrine or levophed to increase MAP & albumin levels. No diuretics, βB, & or
other vasodilators or nephrotoxins. RRT if management ineffective and a candidate for OLT. OLT is definitive treatment.

MGH Algorithm for the Diagnosis and Treatment of Hepatorenal Syndrome

(Int. Club of Ascites guidelines: Gut 2015;64:531; Dig Dis Sci 2014;59:471; Dig Dis Sci 2015;60:1474; Nephron 2015;131:191)
sCr = serum creatinine
AKI and Cirrhosis Diagnostics and Early Treatment MAP = mean arterial pressure
AKI =  sCr ≥ 0.3 1. Check urine Na, sediment, renal U/S HRS = hepatorenal syndrome
mg/dL within 48h OR 2. Remove risk factors (nephrotoxic drugs,
sCR ≥ 1.5x baseline NSAIDs, diuretics, vasodilators/ Meets criteria for HRS?
within 7d antihypertensives, treat infections/GIB) Cirrhosis and ascites
3. Volume expansion with albumin (1g/kg albumin No shock
x2d, max 100g/d) No recent nephrotoxic drugs
Inpatient: closely No signs of structural kidney injury
monitor Cr (<500 mg/day proteinuria, <50
Outpatient: early f/u
Has sCr returned to within RBCs/HPF, normal renal US,
with renal and Yes No
hepatology 0.3 mg/dL of baseline after inactive sediment)
48h of initial treatment?
Yes No
Baseline MAP:
MAP-Directed Calculate average MAP for Hepatology Consult Workup
Treatment of HRS the 24h prior to
midodrine/octreotide
(consider transplant &
evaluation) treatment
∆MAP = Current Average MAP – Baseline

If… Midodrine TID Octreotide SC TID

Initiation of therapy 5mg 100ug Administer Albumin PRN
 ∆MAP = 10-20 mmHg No Δ No Δ (25-50g/d unless more is
 ∆MAP <10 mmHg, 1st 24h  10mg 200ug clinically indicated).
 ∆MAP <10 mmHg, 2nd 24h  15mg No Δ Consider CVP goals or
 ∆MAP> 20 mmHg  by 50% of current dose No Δ serum albumin goal > 3

Once ∆MAP > 10 mmHg is achieved,

continue to treat until sCr falls to within After 24h of max midodrine and
0.3 mg/dL of baseline sCr (representing Yes octreotide, does MAP increase
resolution) > 10 mmHg from baseline?
Initiate and titrate norepinephrine or
vasopressin to achieve  in MAP above pre-
No
Resolution
treatment baseline by 10-15 mmHg
Discuss ICU transfer for
vasopressors with patient,
1. Continue treatment for ≥ No resolution after 7 Med Senior, attending, and
24hr after resolution days despite desired No ∆MAP > 10 mmHg consultants
2. Discuss possible TIPS with
hepatology consult team
∆MAP
Consider RRT or escalation
of care
Multidisciplinary discussion of options: only if candidate for liver
If recurrence, resume 1. Continue MAP-directed HRS treatment transplant
2. Renal replacement therapy
MAP directed HRS 3. Palliative care
treatment

Gregory Fricker
84
TOC

Gastroenterology Liver Transplant

INDICATIONS FOR LIVER TRANSPLANT (AASLD Guidelines: Hepatology 2014;59:1144)
• Acute liver failure: onset of severe acute liver injury w/ HE and coagulopathy w/in Milan Criteria:
26wks in pt w/o known cirrhosis or liver disease (see Acute Liver Injury & Failure) One lesion ≤5cm or up to 3
• Cirrhosis with MELD ≥15 or complication (e.g. ascites, HE, EV bleed, HRS). Survival lesions all ≤3cm
benefit of OLT > risk at MELD ≥15 (AJT 2005;5:307). No extra-hepatic involvement
• HCC: if within Milan Criteria (NEJM 1996:334:693); can be “down-staged” to within Milan No major vessel involvement
with treatment (see End-Stage Liver Disease)
• Liver-based metabolic disorders w/ systemic manifestations: A1AT deficiency, familial amyloidosis, Wilson’s,
hemochromatosis, glycogen storage disease, primary oxaluria
• Condition qualifying for exception (see below under “Prioritization”)

TRANSPLANT EVALUATION PROCESS (AASLD guidelines: Hepatology 2014;59:1144)

• Laboratory testing: order set in EPIC; BMP, Ca, Mg, Phos, LFTs, GGT, CBC w/ diff, PT/PTT, T&S, Fe/TIBC, ferritin,
ceruloplasmin, A1AT level, autoimmune (ANA, ASMA, AMA, SPEP), viral hepatitis (HAV IgG, HBsAg, HBsAb, HBcAb
[total], HBeAb, HBV DNA, HCV Ab & PCR, HDV Ab), HIV-1/2, EBV, CMV, VZV, HSV, RPR, toxo, measles/mumps/rubella
titers, TB spot, AFP, PSA, amylase, uric acid, total cholesterol, U/A, UCx
• Additional tests: ABG (on RA), EKG, CXR, U/S w/ doppler, abdominal CT or MRI (I+) (eval. for HCC), age-appropriate
cancer screening (colonoscopy, mammogram, pap smear), bone density (outpt), cardiopulmonary eval. as below
• Immunizations: HAV, HBV, Prevnar13, influenza, Tdap
• Consults: transplant surgery, psychiatry, social work (address psychosocial issues, adequacy of support, financial
screening, insurance counseling), nutrition
• Cardiopulmonary eval.: TTE w/ bubble ± PFTs. Dobutamine stress echo may be indicated (typically if >40 or CAD RFs).
Optimal CV risk assessment strategy debated – AASLD: stress testing in all candidates (Hepatology 2014;59:1144);
AHA/ACC: if multiple CAD risk factors (JACC 2012;60:434).
• ID eval.: eval. for latent TB as above and tx pre-LT if able. Coccidiomycosis, strongyloides testing if from endemic area.
Dental extractions pre-LT. HIV not a contraindication if immune function adequate. HBV tx pre-LT. HCV can be tx pre- or
post-LT (timing depends on if LT imminent, access to HCV+ donor, comorbidities). Transplant ID consult if needed.
• Combined kidney transplant: eligible if CKD w/ GFR ≤30 / ESRD on HD; sustained AKI w/ dialysis ≥6wk or GFR ≤25 for
≥6wk; or metabolic disease (e.g. hyperoxaluria) (UNOS/OPTN policy: AJT 2016;16:758)
• Living Donor Transplant (LDLT): recipients should fulfill same minimal listing criteria as for deceased donor

PRIORITIZATION FOR LIVER TRANSPLANT (AASLD guidelines: Hepatology 2014;59:1144)

• Prioritized based on MELD Score & stratified by blood type. Updated regularly & more frequently if more severe disease.
• Certain conditions result in impaired survival but are not directly accounted for in the MELD score  some specific
disease-related criteria for MELD exceptions that upgrade MELD score w/ subsequent automatic upgrade q3mo.
• Standard MELD exceptions: HCC (w/in Milan criteria & AFP <1000), hepatopulmonary syndrome (RA PaO2 <60mmHg),
portopulmonary HTN (only if mPAP <35), familial amyloid polyneuropathy (TTR gene mutation), primary hyperoxaluria,
cystic fibrosis (FEV1 <40%), hilar cholangiocarcinoma, hepatic artery thrombosis (w/in 14d of LT but not meeting status
1A criteria)
• Can also petition review board for non-standard exceptions (e.g. recurrent cholangitis in PSC, intractable pruritus in PBC,
refractory complications)

CONTRAINDICATIONS TO LIVER TRANSPLANT (AASLD guidelines: Hepatology 2014;59:1144)

• Absolute: severe cardiac or pulmonary disease, AIDS, HCC w/ metastatic spread, ongoing EtOH/illicit substance use
(though this is changing for EtOH in select cases; see Alcohol-Related Liver Disease), uncontrolled sepsis, anatomic
abnormality that precludes LT, intrahepatic cholangiocarcinoma, extrahepatic malignancy (not meeting criteria for cure),
fulminant hepatic failure with sustained ICP >50mmHg or CPP<40 mmHg, hemangiosarcoma, persistent nonadherence
to medical care, lack of adequate social support system
• Relative: BMI ≥40, advanced age, HIV (all center-specific)

Blair Robinson
85
TOC

Nephrology Acute Kidney Injury

DEFINING AKI (KDIGO 2012 Guidelines)
AKIN
Serum Creatinine Urine Output Work-up and management
Stage
 ≥ 0.3 mg/dl within 48h or < 0.5 ml/kg/hr for ≥ 6 (1) H&P, (2) monitor Cr & UOP, (3) UA and sediment (4)
1
 1.5-1.9x baseline hours urine electrolytes, (5) renal U/S and other tests (below)
< 0.5 ml/kg/hr for ≥ 12 Above +
2  2-3x baseline
hours (1) renally dose meds, (2) eval need for RRT,
 3x baseline, Cr ≥ 4, < 0.3 ml/kg/h for ≥ 24 h, (3) consider ICU admission for CVVH, pressors for renal
3
 eGFR to < 35 (<18 yo), or RRT or anuria ≥ 12 h perfusion, (4) avoid subclavian catheters and PICC
Diagnostic Tips
• Serum Cr approximates GFR at steady state only (unable to estimate GFR w/ ∆Cr): must assume GFR< 10 if ∆Cr >1/day
• Drugs can impair Cr excretion without ∆GFR (BUN remains stable): trimethoprim, H2 blockers (cimetidine), dronaderone.
•  BUN out of proportion to Cr: pre/post-renal, UGIB, steroid
•  Cr out of proportion to BUN: rhabdo, AIN, Bactrim, Vanc toxicity,  nutrition

STEPWISE WORKUP
1) History/exam: vitals (hyper/hypoTN), volume status, exposures (contrast, meds, see below), recent infection (IgA nephropathy 1-2d,
post-strep GN in 10-14d), active infection (sepsis can induce ATN independent of BP or RBF (JASN 2011;22:999), trauma/myalgias
(rhabdomyolysis), rashes (AIN, vasculitis)
2) Urinalysis (UA): See Urinalysis page
3) Urine chemistries:
o FENa: FENa< 1% c/w pre-renal AKI, >2% c/w ATN. Note this is ONLY verified in oliguric AKI; overall limited use except to rule
out HRS with elevated FeNa (J Hosp Med 2016;11:77)
o FEUrea: if on diuretics, FENa unreliable. Calculate FEUrea as above, <35% consistent with pre-renal (Kid Int 2002;62:2223)
o Urine Osm: >500 is consistent with a pre-renal etiology. Patients with ATN are only rarely able to concentrate to this degree.
o Urine protein: if proteinuria on UA, send serum albumin, urine total protein, urine microalbumin and urine Cr. Urine
albumin/protein ratio(APR) > 0.4 suggests glomerular > tubulointerstitial process (Sn 88% / Sp 99%) (Nephro Dial Trans
2012;27:1534)
4) Urine sediment: see Urinalysis page. Important if clinical history/above studies are not strongly suggestive or if AKI fails to respond to
initial management.
5) Eosinophilia/eosinophiluria: poor test for AIN. Urine eos >1% has Sn 31%, Sp 68% (J Hosp Med 2017;12:343)
6) Renal U/S: exclude hydronephrosis. In absence of a suggestive history, <1% of renal U/S for AKI showed post-renal etiology; can
provide evidence of chronic processes if no known hx (BMC Nephrol 2013;14:188).
7) Monitor Cr: what is the response to empiric treatment of presumed cause?
8) Next: if sediment or history suggests glomerular disease, broaden workup with C3/4, ANCA, anti-GBM, ANA, anti-dsDNA,
HBV/HCV/HIV, cryo, SPEP w/ IMFX/SFLC as per below. Consider biopsy if expected to change treatment.

DIFFERENTIAL DIAGNOSIS (Kid Int 1996;50:811)

PRE-RENAL (21%) INTRINSIC POST-RENAL (10%)
Absolute  volume GLOMERULAR (<4%) TUBULO-INTERSTITIAL VASCULAR Urinary retention
- Bleeding Anti-GBM ATN (45%) Microvascular - BPH, meds,
- GI or skin loss ANCA + - Ischemia, sepsis, toxic (<4%) neurogenic
- Diuretics - Microscopic polyangitis - Contrast, rhabdo, - TTP/HUS - Foley dysfunction
- Osmotic diuresis - Granulomatosis with aminoglycosides - APLAS Urinary obstruction
- Cerebral salt wasting polyangiitis (GPA) AIN (2%) - HELLP/Eclampsia (bilateral)
Effective  volume - Eosinophilic GPA 1) Meds (see below) - Scleroderma - Stones (single
- CHF / cardiorenal - Drug-induced ANCA 2) Infectious: CMV, lepto, - Meds (calcineurin kidney/transplant)
- Cirrhosis/hepatorenal Immune complex legionella inhib/CIN, - Malignancy
- Nephrotic syndrome Low complement: 3) Autoimmune / infiltrative: gemcitabine) - Retroperitoneal
- Sepsis / third-spacing - PSGN, SLE, cryo, MPGN, TINU, IgG4 disease, sarcoid Macrovascular (1%) fibrosis
Δ renal dynamics MGRS Crystals - RAS (athero, FMD)
- NSAIDs / COX-2s Normal complement: - TLS, acyclovir, ethylene - Dissection
- ACEi / ARBs - IgA nephropathy/HSP glycol - Renal artery/vein
- Abd compart. syndr. - Fibrillary/immunotactoid Proteins thrombosis
Relative hypotension - MM, amyloid, Ig deposition

Common medications related to AKI (not comprehensive):

AIN: β-lactams, NSAIDs, PPIs (delayed effect), rifampin, cimetidine, mesalamine, ciprofloxacin, allopurinol, sulfa drugs
Direct tubular injury: NSAIDs, calcineurin Inhibitors, ACEi/ARB, methotrexate, acyclovir (IV>>PO), protease inhibitors, amphotericin,
tenofovir (prox tub), vancomycin (esp in combo w/ Zosyn) (CID 2017;64:116)

Audrey Carr
86
TOC

Nephrology Acute Kidney Injury

MANAGEMENT
“A Euvolemic Kidney is a Happy Kidney; Fluids are NOT always the answer”
1. Optimize hemodynamics, avoid nephrotoxins: Correct volume status - IVF if hypovolemic, diuretics if overload. Stop
NSAIDs/ACEi/ARBs, spironolactone, diuretics (if prerenal). Avoid  glucose and contrast. No evidence of benefit for empiric diuretics
in oliguria (JAMA 2002;288:2547).
2. Renally dose meds: Abx, narcotics, LMWH  UFH, Keppra. Pre-hydrate if GFR<30 for contrast (MGH protocol).
3. Manage complications:
o HyperK: calcium gluconate, insulin/dextrose  patiromer, bowel reg, furosemide
o Hyperphos: sevelamer vs. phoslo depending on calcium
o Metabolic acidosis: sodium bicarb PO/IV
o Bleeding with concern for uremic platelets: DDAVP 0.3 mcg/kg IV, onset 1hr, lasts 4-8hr
4. Indications for HD (AEIOU): Acidosis (esp. pH<7.0), Electrolytes (refractory hyperK+), Intoxication (lithium, ethylene glycol,
metformin, salicylates, theophylline), refractory Volume Overload, Uremia (encephalopathy, neuropathy, pericarditis)

RENAL EMERGENCIES (when to page the renal fellow overnight)

• Acidosis: severe metabolic acidosis, unstable patient, usually in the ICU with pH < 7.0. Temporize with NaHCO3 pushes and isotonic
bicarb gtt, intubation and hyperventilation if unable to compensate by breathing off CO2. May need RRT. CVVH does not remove
lactic acid and is similar in correction rate to bicarbonate infusion.
• Hyperkalemia: marked hyperkalemia leading to ECG changes or arrhythmia (K>6.5). Temporize with Ca gluconate, Lasix,
Insulin/D50, etc. Note HD much faster at clearing K than CVVH.
• Hyponatremia: call if severely symptomatic (AMS with low GCS, seizures, etc) requiring bolus hypertonic saline.
• Ingestions: ethylene glycol, methanol (elevated osmolar gap) with end organ damage (i.e. renal failure, vision loss).
• RPGN: when clinically suspected, urgent Nephrology consultation to consider pulse dose steroids +/- plasmapheresis. See
Glomerular Disease.

SPECIFIC MANAGEMENT BY CAUSE

• Acute interstitial nephritis (AIN): stop offending agent, consider prednisone 40-60mg QD for 1-2wk if biopsy-confirmed or high pre-
test prob though not great evidence (CJASN 2018;13:1851)
• Cardiorenal syndrome (type 1): (Nat Rev Neph 2013;9:99, Circ 2019;139:e840)
o Definition: 5 phenotypes which impact the heart and kidneys with various causal relationships. Type 1 is HF resulting in AKI.
o Pathophysiology: decreased renal perfusion from  venous congestion +/-  CO lead to a low trans-renal perfusion pressure.
More of a problem with “underdraining” (congestion) than with “underfilling” (perfusion).
o Treatment: relief of renal venous congestion. Trend Cr against TBB to test hypothesis but expect a lag effect.
 Loop diuretics are first line for type 1 +/- addition of thiazide (metolazone/diuril).
 No benefit of low dose dopamine or nesiritide to improve forward flow - ROSE trial
 In CARESS-HF trial, ultrafiltration showed similar outcomes in regard to weight loss and decompensated CHF symptoms, but
worsened renal function compared to pharmacologic therapy with loop/thiazide diuretics.
• Contrast-Induced nephropathy (CIN): (Circ 2012;122:2451)
o Definition: Cr ≥ 0.5 or 25% within 48-72h of contrast without other causes.
o Clinical syndrome: starts 24-48hr, peaks 3-5d, resolves 10d; Usually non-oliguric.
o Controversy: pathogenesis unknown - vasospasm vs acute tubular injury due to osmotic injury. Recent studies: unclear risk of
AKI following contrast, likely lower than previously estimated (Ann Em Med 2017;69:577). Exclude other causes.
o Risk factors include higher contrast load, hyperosmolar contrast, intra-arterial injection, DM, proteinuria, concomitant AKI.
o Prophylaxis: See Contrast in Radiology section for MGH protocol. Only prehydrate if GFR<30. For high risk pts receiving arterial
or IV contrast, consider IV NS at 100mL/h for 6-12h pre, 4-12h post. If treating volume overload, hold diuretics day of contrast
with no additional IVF. No added benefit for IV bicarb or NAC (NEJM 2018;378:603), or pre/post/intra HD (Am J Med 2012;125:66).
• Crystalline nephropathy: discontinue drug; fomepizole/HD if ethylene glycol toxicity; rasburicase if TLS
• HRS: See Hepatorenal Syndrome in GI section.
• Myeloma kidney (Cast Nephropathy):
o Dx: TP/Cr, SPEP/UPEP, SFLC, kidney bx if dx unclear.
o Tx: IV hydration to target UOP >3L/day to minimize precipitation (volume overload can be treated with diuretics), initiation of
bortezomib based chemotherapy to decrease production of SFLC per oncology. Unclear benefit of plasmapheresis given
rebound of light chain production.
• Post-renal: foley, α-antagonists; 5α-reductase inhibitor (effect not immediate); urology/IR if perc nephrostomy tube needed
• Rhabdomyolysis: AKI unlikely unless CK >2k-5k; aggressive IVF for UOP >250cc/hr with NS. Consider isotonic sodium bicarb if
marked acidosis (NEJM 2009;361:62), but no convincing evidence that HCO3 is superior to NS. Monitor for electrolyte abnormalities:
hyperK, hypoCa. Continue aggressive IVF until CK < 5000; continue IVF and add diuresis if volume overload.
• Scleroderma renal crisis: ACEi (captopril) at maximum tolerated dose. Avoid steroids.

Audrey Carr
87
TOC

Nephrology Glomerular Disease

NEPHROTIC SYNDROME (NS)
Etiology:  podocyte integrity (foot process effacement)
 Triad: proteinuria > 3.5g/day (albuminuria), Alb < 3.0g/dL, edema (periorbital, peripheral)
Associated sequelae: HLD + premature atherosclerosis, foamy urine, hypercoagulability (10-40% VTE risk 2/2 loss of antithrombin &
plasminogen), Vit D deficiency (loss of binding protein), infectious risk (IgG/opsonins, esp. strep pneumo), protein malnutrition
Workup: Basic: UA/sed, spot urine P/C (if abnl, send 24h urine protein). First send HbA1c (most proteinuria 2/2 DM) to r/o DM.
Advanced: ANA, anti-dsDNA, anti-PLA2R, SPEP, SFLC, HBV, HCV, HIV, C3/C4, nephrology c/s for possible renal biopsy.
Labs: 3+ protein (dip detects albumin) or spot urine P/C > 3000 mg/g, fatty casts or oval fat bodies = epithelial cells w/ engulfed lipid
(Maltese crosses when polarized), Cr normal or , may have mild nephritic features (hematuria, HTN more common in primary dz)
Disease Associations Biopsy Findings
Diabetes T1DM > 5-10y, T2DM, retinopathy. Most common cause of NS. Nodular glomerulosclerosis
1°:  in black patients (APOL1)
Mesangial collapse & sclerosis.
2°: viral (HIV, parvo, EBV, CMV), drugs (NSAIDS, pamidronate, INF,
FSGS Collapsing variant rapidly progresses
rapamycin, heroin), adaptive (2/2 nephrectomy, CKD, obesity, reflux,
to ESRD
HTN), chronic hypoxia (OSA, sickle cell).
1°: Abs to podocyte PLA2R (75%) (NEJM 2009;361:11) or THSD7A. Thick BM w/ electron-dense
Membranous
2°: SLE, HBV, syphilis, drugs (NSAIDs, penicillamine, gold), solid tumors subepithelial deposits
Minimal
Idiopathic, a/w NSAIDs, lymphoma (HL #1), children > adults Foot process effacement (EM)
change
Mixed nephritic/nephrotic. Immune complex-mediated: chronic infxn
Thick BM, mesangial proliferation,
MPGN (HBV, HCV+cryos), SLE, lymphoma, MM. Complement-mediated:
subendothelial ± subepithelial deposits
alternative complement pathway activity. C3
Diffuse amorphous hyaline glomerular
Amyloidosis AL (myeloma) and AA (systemic inflammation, e.g. RA)
deposits; +Congo red. IF κ/λ, LC if AL
Treatment: edema: diuretics + low Na diet; HLD: statin; VTE risk: ppx AC; consider ACE/ARB (glom pressure). Steroids may have role.
GLOMERULONEPHRITIS (GN)
Etiology: immune-mediated inflammation of the glomerulus leading to endothelial and podocyte injury  hematuria w/ active sediment
(dysmorphic RBC; specific but less sensitive), RBC casts (rare but very specific), subnephrotic proteinuria (<3.5g/d, but 10-30% >3g/d).
Clinical presentation: AKI, HTN, edema, proteinuria, and hematuria. If systemic vasculitis, often fatigue, fever, weight loss, small-vessel
involvement of other organ systems (palpable purpura, DAH, mononeuritis multiplex).
1) Asymptomatic urinary abnormalities: subnephrotic proteinuira, +/- microscopic hematuria; no renal impairment, edema, or HTN.
2) Rapidly progressive GN (RPGN):  GFR > 50% in ~3 mo, glomerular crescents on bx, 0.5-2.5 g/d proteinuria, dysmorphic RBC.
Consult Renal ASAP, consider methylpred (0.5-1g IV QD x3d). Per etiology/biopsy: CP or MPA ± rituximab ± plasma exchange.
3) Chronic GN: persistent proteinuria, +/- hematuria, slow progression
Workup: UA/sed, C3/C4, ESR/CRP, HBV/HCV/HIV, SPEP/SFLC, ANA (dsDNA, Sm), ANCA, anti-GBM, RF/cryos, anti-DNAse, ASO
Disease Associations Labs
Renal-Limited Immune Complex Deposition
Post-strep GN ~1-2wk post-pharyngitis, 3-6wk post-cellulitis ⊕ASO, C3
Fibrillary GN Idiopathic; cancer; autoimm (Crohn's, SLE, Graves', ITP) Normal C3, C4. (bx IF +DNAJB9)
IgA nephropathy 1°: ~1-2 d post-viral URI or GI infx. 2°: liver dx, Celiac, HIV +/- IgA, normal C3
Systemic Immune Complex Deposition
Photosensitivity, malar rash, sicca, pleuritis, cytopenias, ⊕ANA, ⊕anti-dsDNA, ⊕anti-Sm, C3,
SLE (Classes 3, 4)
arthralgias C4
Cryoglobulinemia (Type 2) HCV > HBV, ESLD, MM ⊕Cryos (⊕RF), ⊕HCV, C3, C4
Endocarditis Fever, valve dx, emboli ⊕BCx, C3
Post-URI, (malignancy), IgA nephropathy, purpura, arthritis, +/- IgA, normal C3 (IgA does not fix
HSP
GIB complement)
ANCA Vasculitis
Multi-system, granulomatous sinusitis/otitis, other ENT sx, c-ANCA/anti-PR3 (80%), p-ANCA/anti-
Granulomatosis with
pulmonary sx (DAH, granuloma), arthritis, palpable purpura, MPO (10%)
polyangiitis (GPA)
RPGN
Eosinophilic
Multi-system, new-onset asthma, allergic rhinitis/sinusitis,
granulomatosis w/ p-ANCA/anti-MPO (50%), eos ≥ 1500
mononeuritis multiplex
polyangiitis (EGPA)
Microscopic polyangiitis
Multi-system, non-granulomatous Anti-MPO (60-70%)
(MPA)
High-titer p-ANCA (95% drug-induced;
Hydralazine, PTU, allopurinol, adulterated cocaine
Drug-induced vasculitis MPO/HNE); c-ANCA (50%; anti-
(levamisole  ear necrosis)
histone)
ANCA Vasc: Tx: Induction: Steroids + RTX or CYC (NEJM 2010;363:221). Maintenance: RTX > AZA (NEJM 2014;371:1771). Induction w/o
plasma exchange and w/ lower-dose steroids appears non-inferior and lowers infx risk in PEXIVAS trial
Anti-GBM: RPGN, DAH (=Goodpasture), linear IgG along BM. Alport’s: mutant COL4A (renal, hearing, eye dx). EM w/ split GBM.
Zandra Walton
88
TOC

Nephrology Chronic Kidney Disease

OVERVIEW
Percentage of US Population by
• CKD definition: GFR <60 ml/min OR presence of eGFR and Albuminuria Category:
kidney damage (typically albuminuria ≥ 30mg/d) for KDIGO 2012 and NHANES 1999-
2006. Colors represent risk for
≥ 3 months (JAMA 2015;313:837) progression, morbidity, and
o Estimating GFR: CKD-EPI preferred (Cr- mortality: green (low), yellow
Cystatin C); Cockcroft-Gault overestimates, (moderate), orange (high), red
(very high). Lancet 2012;379:165
MDRD underestimates.
o Albuminuria is an independent predictor of all-
cause mortality, CV mortality, and progression
of CKD at all stages. Note: UA detects
albumin but not other proteins; if UA with +
protein  check TP:Cr to quantify
• Etiologies: DM (47%), HTN/nephrosclerosis (29%),
GN (7%), cystic kidney (3%), unknown (14%)
(USRDS 2017)
• Epidemiology: 15% US adults: White (60%), Black
(30%), Hispanic (17%), Asian (5%) (Natl Kidney Fndn
2016)
• Staging/Action: G1-G3a: risk factor reduction, dx and tx, slow progression. G3a-G3b: evaluate and treat complications. G4: nephrology
referral, preparation for RRT +/- transplant. G5: RRT if uremia or other indication, consider transplant
MANAGEMENT
• BP control: reduce to goal <130/80 if proteinuria (Alb/Cr>30) (NEJM 2015;373:2103)
o If proteinuria: ACEi, then non-dihydropyridine CCB; if edema: loop diuretic if eGFR <30, thiazide for eGFR > 30
• Proteinuria: reduce to goal <300mg/d with RAAS blockade (ACEi or ARB, but not both simultaneously) (NEJM 2013;369:1892)
• Glycemic control: use oral agents or insulin to achieve HgbA1c < 7%. Decreased rate of CKD progression with SGLT2i (NEJM
2019;380:2295) and GLP-1 agonist (NEJM 2017;377:839).
• HCV: Tx to slow progression (Kidney Int 2020;97:193)
• CVD risk reduction: risk 2-4x general population. ASA 1° prev if high ASCVD risk (ACC/AHA 2019), statin, exercise,  smoking
• Avoid nephrotoxins: NSAIDs, herbals w/ aristocholic acid, aminoglycosides, acyclovir, contrast (iodinated, gadolinium), baclofen
(stage G4/5)
• Renally dose meds: esp. abx/antivirals, atenolol, colchicine, fluconazole, gabapentin, glyburide, levetiracetam, metoclopramide,
opioids
• Nutrition: nephrocaps (B-complex + C), Na <2 g/d, K/phos/fluid restriction as needed. Protein 0.6-0.8 gm/kg/d only if GFR <60 and
nephrotic syndrome is not present. Very low protein diet not clearly shown to be beneficial (AJKD 2009;53:208).
• Monitoring: q1-3mo Cr & electrolytes, annual UAlb/Cr & UProt/Cr ratios, PTH, 25-vitD, CBC, Fe studies. Renal U/S at time of dx.
• Nephrology referral: GFR approaching 30, sudden decline in GFR, severe proteinuria, active urinary sediment with decrease in GFR,
resistant HTN
• Prognosis: based on 1) cause of CKD, 2) GFR category, 3) albuminuria category, 4) other risk factor/comorbidity; use Tangri risk
score to assess 2 and 5 year risk of requiring HD (JAMA 2016;315:164)
COMPLICATIONS
GFR threshold: hyperPTH (50), anemia (44), acidosis (40), hyperK (39), hyperPhos (37) JASN 2009;20:164.
• Hyperparathyroidism:
Type Ca PO4 PTH VitD Pathophysiology
1º HyperPTH    nl Excess PTH production by parathyroid gland
2º HyperPTH (2/2  Vit D)     Decreased Ca absorption stimulates PTH secretion
2º HyperPTH (2/2 CKD) nl /  nl/  nl /   PO4 excretion increases PTH secretion
3º HyperPTH    nl /  Longstanding 2º hyperPTH leads to PTH gland hyperplasia
• Mineral and bone disorder: check Ca, PO4, ALP, 25-OH vit D (1,25-OH vit D level will fluctuate) (KDIGO Guideline Update 2017)
o PTH rising/persistently above goal (non-HD <3.5, HD 3.5-5.5): restrict dietary phos, non-Ca phos binders (sevalemer preferred,
w/ meals), goal phos <5.5 mg/dl, calcium/Vit D supplements if low 25-OH Vitamin D.
o Severe/refractory PTH > 1000: calcitriol vs calcium mimetic vs parathyroidectomy if non-responsive to medical therapy
• Anemia: q3-6m for goal Hb 10-11.5 (NEJM 2006;355:2071). Hb >13 with ESA increases risk of CVA
o Iron repletion (PO or IV) when Tsat <30% and ferritin <500 ng/mL, hold if ferritin >500-800
o Erythropoiesis stimulating agents (ESA)  transfusions, risk of Fe overload, Ab formation; contraindicated in cancer, SBP>160,
HF, stroke (NEJM 2009;361:2019)
• Metabolic acidosis: NaHCO3 650-1300mg up to TID for goal HCO3 >22; decreases progression of CKD and improves bone health
(CJASN 2019;14:1011)
• Uremic bleeding: no need to treat unless pre-preprocedure with DDAVP
• Preparation for HD access: avoid BP measurements and venipuncture in non-dominant arm, avoid subclavian/PICC lines due to risk
of central stenosis (precludes future AVF placement), prefer small bore tunneled IJ placed by IR

Mitu Bhattatiry
89
TOC

Nephrology Dialysis & Transplant

OVERVIEW (NEJM 2012;367:2505)
• Diffusion: concentration gradient drives small molecules (e.g. urea, creatinine) across Emergent Indications for RRT (AEIOU)
semi-permeable membrane • Acidosis: pH <7.2
• Convection: hydrostatic pressure forces medium-weight molecules across membrane • Electrolytes: refractory K+ > 6.0 mEq/L
• Ultrafiltration (UF): removal of plasma water by hydrostatic pressure or rapidly rising K+
• Hemodiafiltration: uses all three of the above • Ingestions: dialyzable toxins (eg: Li,
Important Considerations ASA, methanol, ethylene glycol,
• Timing: controversial - ELAIN RCT: early RRT (within 8h)  renal recovery,  RRT metformin, phenobarbital, dabigatran)
duration,  mechanical ventilation duration,  LOS,  90d mortality; IDEAL-ICU: multi- • Overload: diuretic-refractory volume
center RCT showed no significant difference for early RRT in patients w/ septic shock overload
and severe AKI • Uremia: encephalopathy, pericarditis,
• Access: dialysis lines can only be accessed by dialysis/ICU RNs (except in codes); coagulopathy with uremic bleeding
contact dialysis unit (6-3700) to request new access
• PICCs: HD pts or future HD candidates cannot receive PICCs unless first cleared by Renal (to preserve options for vascular access)
• Abx: be sure to dose abx based on IHD vs. CRRT vs. PD and w/ pharmacy; communicate directly w/ dialysis fellow to give during HD
INTERMITTENT HEMODIALYSIS (IHD) (NEJM 2010;363:1833; consider in critically ill pts Lancet 2006;368:379)
• Mechanism: Cr, Urea, K+ move from blood to dialysate; Ca2+ and HCO3- move from dialysate to blood (down concentration gradients)
• Volume removal: occurs via UF; HD can rapidly remove solute and volume; usually three 4h sessions weekly (MWF or TTSa)
• Access: double-lumen central catheter (tunneled or temporary,  infection); AV graft ( maturation time but  thrombosis & long-term
complications); AV fistula ( infection,  overall mortality vs. catheters/AVG, but 6+ week maturation time + 50% primary failure rates)
• Intradialytic medications: erythropoietin, iron, vitamin D analogues, antibiotics
• Complications: HoTN, cramps, dialyzer rxn (SOB, urticaria, diffuse pain), HIT, hemolysis, EtOH withdrawal (rapid clearance of EtOH)
PERITONEAL DIALYSIS (PD) - call PD RN (617-720-1317) on call 24/7 for any inpatient on PD
• Mechanism: peritoneum acts as membrane; infusion of fluid rich in osmotic agent (e.g. dextrose)  solute removal via diffusion and
osmotic gradients  similar survival to pts on IHD (Arch Int Med 2011;171:110).
• Benefits: preserves residual GFR better than IHD, better medium weight molecule clearance, no access complications, independence
• Modalities: continuous ambulatory PD (CAPD): manual exchanges occurring both day and night. All inpatients receive CAPD.
Automated PD (APD): multiple automated exchanges overnight
• Complications: peritonitis, encapsulating peritoneal sclerosis, hernia, pleural effusion, hyperglycemia, HLD, hyperNa, catheter leaks
CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT)
• Principles: depends on high UF rate to achieve clearance  replacement fluid must be added back to restore volume, acid base
balance + electrolytes. Solute clearance + volume removal are slow and not effective in toxin removal or significant volume overload
- CVVH: continuous veno-venous HF, removes solute via convection; AVVH: intermediate CVVH circuit setting w  flow rates / 12h
- CVVHD: continuous veno-venous HD, removes solute by diffusion; CVVHDF: combines convection and diffusion to remove solute
- SCUF: slow continuous ultrafiltration, removes plasma water via hydrostatic pressure applied across hemofilter (NO dialysate)
• Indications: hemodynamic instability; continuous large volume IV fluid in pt who cannot undergo intermittent HD; increased ICP. Not
ideal for hyperK or toxins. Not ideal for acidosis given slow rate of correction with bicarbonate replacement fluid.
• Volume management: run negative (up to -250cc/hr), even, or slightly positive. Replacement fluid w/ bicarb, lactate acetate or citrate
• Anticoagulation: used to risk of circuit clotting, use heparin + bicarbonate OR citrate, citrate achieves regional AC by Ca chelation 
follow iCa levels (will see  total Ca but  iCa), metabolized in liver  AG = possible citrate toxicity (avoid in liver failure)
• Complications: HoTN, arrhythmias, hypothermia,  iCa/ K/PO4, bleeding, thrombocytopenia (mechanical destruction in circuit), HIT
• Drug dosing: drugs can bind to circuit resulting in  VD  work with pharmacy to re-dose all meds based on flow rate

RENAL TRANSPLANT
• Listing: refer EARLY, pts can be listed when GFR <20; pt and graft survival are improved if transplant occurs PRIOR to starting HD
• Contraindications: short life expectancy, active malignancy, SUD, nonadherence; age/HIV/psych comorbidities NOT contraindications
• Allograft dysfunction: delayed graft function: <1wk (prerenal, ATN, thrombus, obstruction), early: 1-12 wks (prerenal, CNI tox, infxn
[BK virus, CMV], acute rejection), late acute: > 3mo (prerenal, CNI tox, noncompliance), late chronic: yrs (HTN, CNI toxicity, BK
virus, recurrence of original renal pathology, chronic allograft nephropathy
IMMUNOSUPPRESSION
Class Examples Mechanism of Action Adverse Events
Calcineurin Cyclosporine Inhibits calcineurin-mediated activation of Nephrotoxicity (long-term fibrosis), HTN,
inhibitor Tacrolimus (FK506) NFAT  blocks T-cell cytokine production tremor, insomnia, hirsutism (CsA only)
Pulmonary edema,  wound healing,
mTOR inhibitor Sirolimus (Rapamycin) Inhibits mTOR  blocks IL-2 production
hyperTG
Mycophenolate
Inhibits de-novo purine synthesis N/V/D
Antimetabolite (Cellcept, Myfortic)
Azathioprine Purine analogue BM suppression, N/V/D, hepatitis

Helen D’Couto
90
TOC

Nephrology Advanced Diuresis

GENERAL PRINCIPLES
• Obtain daily standing weights, Na+ restriction 2g/day, consider fluid restriction

Fractional Excretion
• Loop diuretics have a sigmoidal dose-response curve so double dose until adequate

of Sodium (%)
response is achieved
• Transient increases in serum Cr are common in diuresis. No association between
worsening renal function during diuresis and biomarkers of kidney tubule injury;
increased survival in HF (Circ 2018;137:2016)
Urinary Diuretic Concentration or
Excretion Rate (log value)

Loop Diuretics Thiazide Diuretics

Chlorthalidone, HCTZ, metolazone, chlorothiazide
Furosemide Torsemide Bumetanide
(IV/PO)
Inhibit Na-K-2Cl transporter in ascending limb of
Inhibit NaCl channel in DCT to  Na reabsorption and
Mechanism of loop of Henle to  Na reabsorption and “break”
prevent urinary dilution (avoid if SIADH); no effect on
Action medullary concentrating gradient (unable to
medullary concentrating gradient
concentrate urine)
PO
20-50% 80-90% 80% Variable
Bioavailability
Duration ~6 hours 6-8 hours 4-6 hours Variable
Dosing 1 Bumetanide IV/PO = 20 Torsemide PO = Administer 30 min before loop diuretic to “disable” DCT
considerations 40 Furosemide IV = 80 Furosemide PO (PO metolazone, IV chlorothiazide)
 K+,  Mg2+,  Ca2+,  urate,  HCO3-,  Na+,  K+,  Mg2+,  Ca2+,
Side effects
ototoxicity, allergy  urate, HLD, pancreatitis
Consider dosing BID-QID to avoid anti-natriuresis Try metolazone 2.5-10mg PO before chlorothiazide 500-
Other
seen in QD dosing 1000mg IV ($$$)
Other Diuretics
• Carbonic anhydrase inhibitors: acetazolamide 250-1000mg PO QD, can do TID x1d vs QD x3d for metabolic alkalosis (pH > 7.6)
• Aldosterone antagonists: spironolactone 25-200mg QD-BID, eplerenone 25-50mg QD-BID
o  K, gynecomastia (10%, only spironolactone); eplerenone has  aldosterone receptor selectivity but more expensive
DISEASE-SPECIFIC CONSIDERATIONS
Condition Mechanism Treatment
-  GFR so  delivery of diuretic to nephron so higher - High-dose loop ± thiazide augmentation
Renal Insufficiency doses needed in patients with CKD
- Organic acids accumulate and compete w/ diuretics
Chronic Diuretic - Compensatory DCT hypertrophy - Add metolazone or chlorothiazide
Use
- GI edema leads to  absorption of PO furosemide - DOSE trial: in ADHF, no difference in sx or renal
-  GFR in ADHF is driven by renal venous HTN function for pts receiving low vs high dose diuretics
CHF ( CVP,  PCWP) more so than low perfusion (CI) and continuous gtt vs bolus dosing of diuretics
- High sympathetic tone   RAAS, Na+ reabsorption - No benefit of RRT over stepwise diuresis
- Consider sequential nephron blockade
- Loop diuretic (binds to albumin) leaks out of - Consider bumetanide (lower albumin-binding)
Hypoalbuminemia
vasculature ( VD) resulting in  delivery to nephron - No evidence for benefit of albumin + loop diuretic
- Decreased delivery to nephron in setting of - Avoid IV diuretics unless respiratory distress
hypoalbuminemia - Spironolactone alone if hypokalemia
- Splanchnic vasodilation   EABV   renal - Can do spironolactone:furosemide 5:2 (optimal K
Cirrhosis hypoperfusion (pre-renal azotemia) balance), uptitrate q3-5d up to 400mg:160mg
- SNS and RAAS   Na reabsorption - If gaining weight, measure urine Na and K; if K >
Na (ineffective diuresis), uptitrate meds; if Na > K
(effective diuresis) enforce Na restriction
Nephrotic - Decreased delivery to nephron due to low albumin - Use 2-3x normal dose of diuretic
Syndrome - Urinary albumin binds drug  loss of diuretic in urine
Stepwise Approach in Heart Failure (NEJM 2017;377:1964)
1. IV loop diuretic. Starting dose: 2.5x home dose as IV furosemide (CHF) (e.g. if home 80mg PO, give ~80-100mg IV) vs Cr×30 as IV
furosemide (e.g. if Cr=4, use lasix 120mg IV); if unknown, start with furosemide 20-40mg IV
2. Reassess in 1-2 hrs and double dose Q1H until response achieved. An adequate dose should cause brisk diuresis.
3. Consider loop diuretic bolus + gtt (should bolus when initiating gtt and re-bolus every time gtt increased)
4. If refractory edema, consider adding a thiazide (metolazone PO or chlorothiazide IV) to achieve sequential nephron blockade
o This counteracts natural  in DCT Na reabsorption from loop diuretics; monitor closely K+, Mg2+, bicarb
5. Nephrology consult for consideration of short term UF/RRT as a bridge to advanced therapies (e.g. MCS, OHT)

Andrew Abboud and Evan Whitehead

91
TOC

Nephrology Acid-Base Disorders

OVERVIEW
• ABG vs VBG: pH VBG~0.04 lower), HCO3 (VBG~2mEq lower; calculated on blood gas so BMP more accurate), CO2 (VBG~8
± 17 mmHg higher). VBG can screen for hypercarbia w/ pCO2 cutoff ≥ 45 mmHg (100% Sn) but does NOT accurately assess
degree of hypercarbia. When in doubt  check ABG (AJEM 2012;30:896)
• Severe acidemia (pH < 7.2)  vasodilation,  inotropy / SVR / MAP, response catechols, arrhythmia, K, insulin resistance,
AMS
• Severe alkalemia (pH >7.6)  vasoconstriction, cor/cerebral perfusion, SVT/VT, K/Ca/Mg/P, AMS, seizure,
hypoventilation
STEP-WISE APPROACH (NEJM 1998;338:26, NEJM 2014;371:1434) EXPECTED COMPENSATION (JASN 2010;21:920)
1. Is there acidemia (pH < 7.36) or alkalemia (pH > 7.44)? Metabolic acidosis: 2-24 hr
2. Is primary disorder metabolic (parallels pH ∆) or respiratory (opposite Winter’s formula: pCO2 = 1.5 x HCO3 + 8 ± 2
pH ∆)? Metabolic alkalosis: start 30 min, complete 24 hrs
3. Is pt compensating? (respiratory takes min-hrs, renal 3-5 days) PaCO2 = 0.7 x (HCO3 -24) + 40 ± 2 = HCO3 + 15
4. Is there an anion gap? Regardless of pH or HCO3 ∆ HCO3  1  expect ∆ pCO2  0.7
AG = Na – (Cl + HCO3) = unmeasured anions – unmeasured cations Respiratory acidosis:
Correct AG for albumin: AGc = AG + 2.5(4 – albumin) Acute: ∆ pCO2  10  ∆ HCO3  1 or  pH 0.08
Negative AG: Na, lipids (interfere w/ chloride), bromide intox Chronic: ∆ pCO2  10  ∆ HCO3  4 or  pH 0.03
5. If there is  AG, calculate “delta-ratio” Respiratory alkalosis:
∆/∆ = ∆ AG /∆ HCO3 = AG – (albumin x 2.5) / (24 – HCO3) Acute: ∆ pCO2 10  ∆ HCO3  2 or pH 0.08
6. Consider Osm gap = 2x (Na + K) + Urea/2.8 + glucose/18 – serum Chronic: ∆ pCO2 10  ∆ HCO3  4 or pH 0.03
Osm
ALGORITHMIC APPROACH

AG OG Ingestions Toxin Manifestations

∆MS, blurry vision, pupil dilation,
Methanol Formic acid
papilledema
Ethylene glycol Oxalic acid ∆MS, Ca, Ca oxalate crystals → AKI
 
Propylene glycol Lactic acid AKI, liver injury
AKI, n/v, pancreatitis, neuropathy,
Diethylene glycol Diglycolic acid
 lactate
Isopropyl alcohol Acetone ∆MS, fruity breath, pancreatitis,  lactate
nl/ 
Ethanol Acetaldehyde Keto/lactic acidosis ± met. alk 2/2 emesis

(via 5-oxoproline)

Krishan Sharma
92
TOC

Nephrology Acid-Base Disorders

MANAGEMENT OF ACID-BASE DISORDERS: treat the underlying cause
• Metabolic acidosis:
o Acute:
 In the BICAR-ICU trial pts with metabolic acidosis (pH < 7.2) treated with IV HCO3 for goal pH > 7.3 had no change in overall
mortality but  RRT initiation. A subset of pts with AKIN stages 2-3 had improved mortality at 28d.
 If pH < 7.1 or HCO3- < 6: if HDS, can start isotonic HCO3 gtt. Monitor VBG/ABG+ q1h. Bolus admin is controversial due to
possible intracellular acidification in s/o CO2 accumulation and a pH-dependent  in levels of iCa  hypercarbia,
hypernatremia, hypocalcemia, hypertonicity, hypervolemia, overshoot alkalosis.
 For bicarb to have full effect on serum pH, pt must be able to increase minute ventilation to ventilate off CO2
o Special considerations:
 Toxic alcohols: Tx with HCO3, fomepizole, or HD (If vision Δ, AKI, methanol >50 mg/dL, ethylene glycol >300 mg/dL).
 Salicylate poisoning: sodium HCO3 to urine pH >6.5 or HD (if level >80 mg/dL, coma, AKI, hypervolemia)
o Chronic: in CKD, replete with PO sodium HCO3 for goal HCO3 >22. See CKD.
• Metabolic alkalosis: replete volume, K, and Cl
o Treat both (1) underlying cause of metabolic alkalosis and (2) cause of renal retention of HCO3
o If saline responsive: NS w/ KCl until urine pH >7. For pts with CHF/cirrhosis and alkalosis 2/2 diuresis, consider K+-sparing
diuretic
o If saline resistant: for mineralocorticoid excess  use K+-sparing diuretic (amiloride) and consider surgical removal of adenoma
o If pH >7.6 and persistently volume overloaded, give acetazolamide vs KCl + loop diuretic with close K+ monitoring
• Respiratory acidosis: NaHCO3 unlikely to be helpful, theoretically harmful if unable to blow off CO2 produced by conservation of
mass (CO2 + H2O  H2CO3  HCO3 + H+). For every 100mEq HCO3 administered, 2.2 L CO2 must be exhaled (~10 min of nml
body production)
• Respiratory alkalosis: address underlying cause (correct hypoxemia, treat pain/anxiety/fever); adjust vent settings if intubated

RENAL TUBULAR ACIDOSIS (RTA) (Int J Clin Pract 2011;65:350)

Consider in any patient with non-AG or hyperchloremic metabolic acidosis or hyperK (Type IV). R/o GI losses & excessive Cl use first!
Pathophysiology: inappropriate net retention of acid or inadequate excretion of bicarb
o In acidemia, kidney should  NH4+Cl- excretion; urine pH should be < 5.3; this process is defective in RTAs
o Caveat: CKD of any etiology is associated with  NH4+ production and acidosis
Etiologies:
- Proximal RTA (Type II): new  setpoint for proximal tubule HCO3- reabsorption so more HCO3 spills into urine
o Primary (rare): Na-HCO3 cotransporter defect
o Acquired: amyloidosis, MM, post-renal transplant, heavy metals (Pb, Cd, Hg, Cu),  Vit D, Wilson’s disease, PNH
o Meds: acetazolamide, cisplatin, tenofovir, aminoglycosides, topiramate
o Often a/w Fanconi Syndrome: glycosuria (w/ serum gluc <180), hypouricemia, aminoaciduria
- Distal RTA (Type I): inability to secrete H+ in distal tubule
o Primary: genetic loss of H+ or HCO3 transporters in intercalated cells
o Acquired: autoimmune disease (RA, SLE, SS); hypercalciuria (any cause); obstructive nephropathy; SCD, MM, amyloid,
cryoglobulinemia, tubulointerstitial injury, renal transplant rejection, cirrhosis, glue sniffing (toluene)
o Meds: amphotericin B, Li+, ifosfamide
- Type IV: effective hypoaldosteronism:  aldo secretion OR tubular resistance   K   NH3 synthesis   NH4+ excretion
o Acidosis due to inhibition of ammonia-genesis by hyperkalemia of any cause
o Hyporeninemic hypoaldosteronism (most common): diabetic nephropathy, CIN, NSAIDs, calcineurin inhibitor, HIV
o  Aldo production: ACEi/ARB > heparin >, adrenal insufficiency, severe illness
o Aldosterone resistance: (ENaC inhibition) K-sparing diuretic, trimethoprim, pentamidine
Workup: clinical history (PMH – autoimmune or malignancy, med review, stones), response to HCO3 supplementation
o ABG/VBG, BMP (AG, HCO3, K), UA (pH). Consider urine Ca/Cr to differentiate proximal vs distal RTA
o Estimate of Urine NH4+: UAG = Na + K - Cl (less useful when urine anions or UNa < 25)
PROXIMAL RTA (TYPE II) DISTAL RTA (TYPE I) TYPE IV RTA
Defect Proximal HCO3- resorption Distal H+ secretion Hyperkalemia
Serum HCO3- 12 – 20 < 10 > 17
Serum K  or normal  or normal 
Urine pH during acidemia Varies, but > 5.5 after HCO3- > 5.5 < 5.5, but can’t buffer w/ NH4+
Urine AG = Na + K – CL ⊝ ⊕ ⊕
Additional dx testing Urine Ca/Cr nml Urine Ca/Cr elevated Renin, aldosterone, cortisol
Complications Rickets, osteomalacia CaPO4 urinary stones Hyperkalemia
Challenging. NaHCO3 (10-20
Tx Treat hyperK: loop, low K diet
mEq/kg) or KCitrate. K NaHCO3 (1-4 mEq/kg)
(Goal HCO3 22-24) If hypoaldo then can give fludricort
supplement

Krishan Sharma
93
TOC

Nephrology Sodium Disorders

H Y P O N A T R E M I A : free water excess relative to serum sodium (NEJM 2015;372:55)
Symptoms: often asymptomatic; AMS, HA, vertigo, N/V, weakness, falls, seizures
Step-wise approach:
1. History and exam, volume status
2. Check SOsm to confirm hypotonic hyponatremia
3. Determine if ADH is present (UOsm >100). Can approx UOsm from UA: last 2 digits of SG x30 (e.g. SG 1.010 ≈ UOsm 300)
4. If ADH is present, check UNa to determine if  ADH is appropriate. UNa unreliable if on diuretics.
o UNa < 30 suggests  EABV state; UNa > 30 suggests the kidney is not retaining Na
o Fractional excretion of uric acid can distinguish  EABV (FEUA < 12%) from SIADH/renal cause (> 12%), 100% PPV (J Clin
Endo Metab 2008;93:2991). Serum uric acid <4 is almost always SIADH (Clin Nephro 1994;42:102).
o Consider TSH, AM cortisol, urine K

HYPOtonic hyponatremia (SOsm < 300) ISOtonic hyponatremia (SOsm ≈ 300) HYPERtonic hyponatremia (SOsm > 300)
AKA “pseudohyponatremia” Hyperglycemia
Hyperproteinemia, Hyperlipidemia (True Na= SNa +[(Sgluc-100)/100])
✓ Uosm Osmolal gap (mannitol, sorbitol, IVIG)

Uosm < 100 Uosm > 100 ✓ UNa

ETIOLOGY

ADH Absent ADH Present RAAS active?

ADH Absent States UNa < 30: RAAS active, Na avid UNa > 30: RAAS inactive, Na wasting
Overwhelming kidney’s ability to dilute  effective art blood volume (EABV)
1° Polydipsia True hypovolemia ( TBW and  EABV) Common: diuretics, Na-wasting nephritis, SIADH
 Solute intake: Tea & Toast TBW but  EABV cerebral Na wasting / pain / nausea , SSRIs
Beer Potomania 3rd spacing (pancreatitis, musc injury)  Mineralocorticoid /  glucocorticoid
CHF, cirrhosis, nephrotic syndrome Hypothyroidism (severe)

1° Polydipsia: restrict fluids, psych Hypovolemia: replete volume Correct underlying cause:
TREATMENT

eval,  risk for overcorrection, avoid Pancreatitis: replete volume Hold diuretics, fix endocrinopathy
DDAVP CHF, Cirrhosis, Nephrosis: diuresis SIADH: restrict free H2O. Consider NaCl tabs (1g
Tea & Toast or Potomania: SLOW TID Na delivery thus H2O excretion). If UOsm >
introduction of solute, will correct Figure adapted from 2x SOsm or if UNa + UK > SNa  consider Lasix
RAPIDLY, at VERY  risk for Am J Med 2010;123:652. (10-20mg BID;  cortico-medullary gradient).
overcorrection Consider vaptans (NEJM 2006;355:2099). Treat
pain.
Treatment: depends on acuity, severity, and etiology (JASN 2017;28:1340)
• Safest to assume hypoNa is chronic unless accurately known from labs/hx. Strict I/O, fluid restriction and monitor BMP frequently. In
general, do not give isotonic saline. Consult renal if starting hypertonic saline.
• Severe symptomatic hypoNa (seizures, AMS): 3% NaCl bolus (100mL up to 3x over 10min until sx resolve or Na  4-6 mEq/L)
• Severe asymptomatic hypoNa (Na<120): Goal Na  6 mEq/L in first 24h. 3% NaCl with rate based on Sodium Correction Rate,
usually 15-30mL/hr. Stop 3% NaCl when Na>125 or if correcting too fast. Consider DDAVP clamp (below).
• Mild/mod hypoNa (Na≥120): if not hypovolemic in etiology, fluid restriction <1.5L, +/- salt tablets 1g TID
• Overcorrection: ADH  once euvolemic  free water diuresis and  rate of correction. Increased risk of osmotic demyelination
syndrome if Na ≤ 105, hypovolemic hypoNa, tea/toast, beer potomania, low K, EtOH, ESLD, malnourished
o Definition: Na  > 8 mq/L in 24h or ≥ 18 mEq/L in 48h. If overcorrecting or UOP rises > 300cc/hr x 2h, consider DDAVP
“clamp”: 2mcg IV or SC q8h for 24-48h or until Na > 125; plus 3% NaCl based on Sodium Correction Rate. Augment with D5W
and 3% NaCl PRN to achieve above goal. (Am J Kidney Dis 2013;61:571)
• Concurrent hypokalemia: K and Na freely exchanged, giving 1 mEq of K = giving 1 mEq of Na; be aware of overcorrection
H Y P E R N A T R E M I A : free water loss in excess of NaCl loss (Crit Care 2013;17:206, NEJM 2015;372:55)
Etiologies: impaired access to free water or impaired thirst,  urinary concentrating ability or DI ( production or efficacy of ADH)
• Renal losses: Uosm <700–800; either ADH not released or kidney unable to respond: post ATN diuresis, osmotic diuresis, DI, rarely
loop diuretic; elderly ( max concentrating ability)
• Extrarenal losses: Uosm >700–800; GI loss from NGT, vomiting, diarrhea, insensible losses, hypodipsia
Acute HyperNa (<48h, rare  salt poisoning, acute DI crisis). BMP q2-4h.
• Goal: correct to normal Na within 24H with D5W IV at 3-6ml/kg/hr until Na 145, then reduce D5W to 1ml/kg/hr until Na 140.
Chronic HyperNa (>48h, most common). BMP q12-24h. Strict I/O, UOP.
• Goal: correct at rate of 10-12mEq/L/day to prevent cerebral edema, though risk is low (CJASN 2019;14:656).
1. Calculate free water deficit. Shortcut FWD = (Current Na – Goal Na)/3. Target Na should be 24h goal based on correction rate
(i.e. <10-12mEq/L/day). Obese patients will have decreased %TBW.
2. Account for ongoing losses: insensible losses (600-800cc/day), UOP, stool output, burn patients to avoid undercorrection
3. Calculate hourly rate of free water replacement, adding ongoing losses and provide as PO free water, enteric tube free water
boluses (e.g. 200-400mL Q6-8h) or IV D5W. If DI, may need DDAVP (See Pituitary Disorders in Endocrine section).

Audrey Carr
94
TOC

Nephrology Potassium Disorders

N O R M A L P O T A S S I U M H A N D L I N G / H O M E O S T A S I S (NEJM 2015;373:60)
• Ingested K+ absorbed in intestines  taken up primarily by liver/muscle cells via insulin & β2 receptors  Na-K ATPase activity
• 98% of K+ is intracellular; remaining extracellular levels trigger aldosterone secretion  principal cell K+ secretion excretion in urine
HYPERKALEMIA
• Signs and symptoms: muscle cramps, paralysis, conduction delays (e.g. CHB, BBB, sinus arrest) and arrhythmia (VT/VF, asystole,
idioventricular rhythms) (CCM 2008;36:3246)
• Dx: confirm true  K+ and not d/t hemolyzed sample, Plt >
500K, WBC > 120, or infusion of K+-containing IVF; consider
ABG/VBG+
• Low utility in checking transtubular potassium gradient
• EKG: peaked T waves  flat P   PR interval ± AVB  wide QRS ± BBB  sine wave pattern  PEA / asystole / VF
o ECG does not correlate w/ K+ level (Clin J Am Soc Nephrol 2008;3:324)
• Etiologies: Acidosis, aldosterone; B-blocker, blood; Cell lysis / turnover; Drugs, DM, decreased GFR
o Redistribution: cell lysis (hemolysis, rhabdo, TLS, RBCs, crush injury), acidosis,  insulin (DM, octreotide), hyperosm, meds
(digoxin, β-blockers, succ, calcineurin inhib [CNI], minoxidil), hyperK periodic paralysis, post-hypothermia
 Usually transient unless impaired K+ excretion
o  Renal K excretion: required for persistent hyperK+
  Aldo production / action: ACEIs/ARBs, NSAIDs, K+-sparing diuretics, CNI, pentamidine, TMP, type IV RTA
 Impaired Na delivery to distal nephron: CHF, cirrhosis
 AKI/CKD (esp. if oliguric): usually GFR <15
 Other: ureterojejunostomy – urine K+ reabsorbed
• Management: acute changes are most dangerous  STAT ECG. Treat if EKG changes, K+ > 6.5, rapid rise, or symptomatic
o Key is elimination, other measures are temporizing. Address reversible factors (optimize volume status, low K+ diet, meds)
HYPERKALEMIA TREATMENT
Strategy Treatment Onset Duration Notes
Calcium: calcium gluconate or CaCl2 (central line) 1-2 g 1st line if any ECG Δs. Stabilizes
Stabilize 1-3m 30-60m
IV, can repeat after 5 min PRN cardiac membrane. Avoid if on dig
Bicarb (sodium bicarbonate 1-2 amps IV vs gtt) 5-10m 1-2h Drives K+ into cells. Only if  pH
Redistribute Insulin (10U IV; 5U if ESRD) + D50 25g (if BS<250) 10-30m 4-6h Drives K+ into cells.  K+ 0.5-1.5
Albuterol (10-20mg neb preferred over IV) 15-30m 15-90m mEq/L
Furosemide ≥40mg IV; can approx. as 30x Cr if K >6. 30m Variable Urinary K+ excretion
Patiromer (8.4 g/d PO) favored over Kayexalate* (15- Swaps K+ for Ca++ or Na+ in gut
Eliminate 7h 24h
30g PO/PR)
Hemodialysis lowers K immediately (faster than CVVH) N/A 3h Removes K+, may rebound d/t shifts
*GI ischemia/necrosis reported w/ Kayexalate, contraindicated post-op, ileus, bowel obstruction, colitis (JAMA Intern Med 2019; 179:1023)

HYPOKALEMIA
 Signs and symptoms: usually with K+ < 2.5  cramps, ileus,
weakness (LEs > trunk/UEs > respiratory muscle paralysis),
rhabdo (Annals 2009;150:619)
• ECG: flat T waves, ST dep, U waves,  QT, atrial or ventricular
ectopy  VT, VF (esp if K+ <3, susceptible pts, or on digoxin)
• Etiologies:
o Lab artifact (pseudo-hypokalemia): WBC >100  WBC absorb K if sample sits out (check K on ABG+)
o Inadequate intake unlikely to be 1° cause, usually combined with another etiology
o Redistribution:  pH,  insulin, hypoK/thyrotox periodic paralysis,  blood cell prod (e.g. s/p G-CSF), hypothermia,  β-
adrenergic activity (e.g. albuterol, epi), refeeding syndrome, toxins (cesium, barium, chloroquine)
o Extrarenal losses: diarrhea (esp. if chronic, VIPoma, villous adenoma, laxatives), insensible losses, vomiting/NGT
o Renal losses (w/o HTN): urine flow (psych polydipsia, excess IVF),  Mg++, meds (ampho B, ifosphamide, cisplatin, gent)
 Acidemia: DKA, RTA (proximal and some distal)
 Alkalemia: diuretics, UGI losses (2° hyperaldo), Bartter’s (~loop diuretic), Gitelman’s (~thiazide)
 Other:  urine excretion of anions (β-OH-butyrate in DKA, bicarb [e.g. UGI losses], toluene + PCN metabolites)
o Renal losses (with HTN):
 1° hyperaldo:  aldo.  renin (e.g. adrenal adenoma); 2°:  a, r (e.g. renin-secreting tumor, renal art. stenosis)
 Other:  glucocorticoid or  ENaC activity (e.g. Cushing’s, Liddle’s syndrome, black licorice)
• Management: 10mEq raises K+ by 0.1 mmol/L; caution if Cr or if due to transcellular shifts
o Oral KCl (ER = pill, IR = powder) preferred for tx as SAFER, quick acting,  retention of K+, and many pts are Cl depleted
o IV formulation KCl if unable to take PO or if severe / symptomatic  max 10mEq/hr (floor), 20mEq/hr (ICU)
o Always replete Mg++, otherwise K+ repletion ineffective (JASN 2007;18:2649)
o Avoid dextrose-containing solutions  can acutely worsen hypoK (dextrose  insulin secretion  K+ shifts into cell)

Zandra Walton
95
TOC

Nephrology Magnesium & Phosphorus Disorders

H Y P O M A G N E S E M I A (Med Sci (Basel) 2019;7:E56)
• Signs/symptoms: other electrolyte disturbances ( K,  Ca), weakness, anorexia, confusion, hyperreflexia, tetany,
 PR,  QRS,  QTc, peaked/inverted T waves, U waves, VT/torsades de pointes, accentuation of digitalis toxicity
• Etiologies:
o  GI absorption:  intake (EtOH, malnutrition),  loss (diarrhea, pancreatitis, malabsorption,
small bowel resection, PPIs)
o  renal loss: diuretics (thiazide, loop), Gitelman’s, amphoB, aminoglycosides, foscarnet, cyclosporine A, cisplatin,
pentamidine
o Distinguish GI vs renal with FeMg (>3% suggests renal wasting)
• Treatment: oral (slow) vs. IV (fast, typically used inpatient) (Am J Health Syst Pharm 2012;69;1212)
o IV: MgSO4 1-2g over 15 min, max 1-2g/h; can give 4-8g over 12-24h; ½ dose if eGFR <30
o PO: MgCl2 6-8 tabs/day causes less diarrhea than Mg oxide 800-1600mg/day, always use in divided doses
o If hypoMg due to thiazide or loop diuretic, add K-sparing diuretic to decrease Mg excretion
H Y P E R M A G N E S E M I A (rarely pathologic)
• Signs/symptoms: (typically only if Mg >6): neuromuscular (hyporeflexia [first sign], areflexia, lethargy, weakness/paralysis,
resp failure), CV (hypotension, bradycardia, conduction defects [PR, QRS, QTc, CHB, cardiac arrest]), hypocalcemia
(hyperMg can suppress PTH)
• Etiologies: Mg intake/repletion > renal clearance (only method of excretion)
o Medication overdose (Epsom salts, laxatives, Maalox, Mg enemas)  avoid these agents in ESRD
o Increased Mg absorption with gastritis/PUD/colitis
o Mild hyperMg may be seen in DKA, hypercatabolic states (TLS), lithium, adrenal insufficiency
• Treatment: (symptomatic only): Ca gluconate 1g IV over 10 min vs gtt to counteract resp depression/hypotension.
IVF, loop diuretics to enhance renal excretion. If oliguric/anuric ESRD, requires HD for removal.
HYPOPHOSPHATEMIA
• Signs/symptoms: (typically only if phos <1.0 mg/dL, esp. if acute),  intracellular ATP  AMS/encephalopathy, seizures,
CHF, hemolysis, respiratory depression, proximal myopathy, rhabdomyolysis, dysphagia/ileus, mineral ∆ (bone pain,
hypercalciuria, rickets/osteomalacia) (JASN 2007;18:1999)
• Etiologies:
o Redistribution (into cells):  insulin (DKA, HHNK, refeeding), acute respiratory alkalosis (pH glycolysis),
hungry bone syndrome (deposition of Ca and phos in bone immediately following parathyroidectomy)
o  GI absorption: poor PO, chronic diarrhea, antacid use (aluminum, Mg),  vit D (steatorrhea, chronic diarrhea),
overuse of phos binders
o  renal excretion:  PTH (1° or 2° hyperPTH), Fanconi syndrome (multiple myeloma, meds),  FGF-23
(genetic/paraneoplastic), meds (acetazolamide, tenofovir, metolazone, IV iron) (QJM 2010;103:449), osmotic diuresis
(glucosuria), proximally acting diuretics (acetazolamide, metolazone), CVVH (esp at high bicarb dose)
o Distinguish GI/redistribution vs renal with FePhos (>5% suggests renal wasting)
• Treatment:
o Severe (<1 mg/dL) or symptomatic:
 Na or K phos 30mmol q4-6h with frequent levels (can give 15, 30, or 45mmol doses at MGH). Change to PO
once >1.5mg/dL. Give ½ dose in CKD/ESRD
 Aggressive IV tx can cause Ca precipitation, hypotension (often due to hypocalcemia), AKI, arrhythmia
o Asymptomatic (<2 mg/dL): Na or K phos 1mmol/kg/d PO in 3-4 divided doses (total 40-80mmol)
 NeutraPhos: 1 packet = 250mg phos (8mmol), 7.1mEq K, 6.9mEq Na; preferred if also need K or if want lower
Na
 K-Phos Neutral: 1 tablet = 250mg phos (8mmol), 1.1mEq K, 13 mEq Na; preferred if do not need K
 If poorly tolerated (causes diarrhea), can give scheduled skim milk (8oz = 8mmol phos)
A C U T E H Y P E R P H O S P H A T E M I A (for chronic hyperphosphatemia, see CKD)
• Signs/symptoms: result from effects of hypocalcemia (muscle cramps, tetany, tingling, perioral numbness)
• Etiologies:
o Acute phos load (TLS, rhabdo, exogenous/phosphate-containing laxatives)
o Acute extracellular shift (DKA, lactic acidosis, severe hyperglycemia)
o Acute kidney injury due to decreased clearance (including acute phosphate nephropathy)
o Increased tubular reabsorption (vit D toxicity)
o Pseudohyperphosphatemia (hyperglobulinemia, hyperlipidemia, hyperbilirubinemia, hemolysis)
• Treatment: normal saline (though can worsen hypocalcemia), dialysis

Daniel Gromer and Elizabeth Kurtz

96
TOC

Nephrology IV Fluids & Electrolyte Repletion

IV FLUIDS
• Types: crystalloid (e.g. NS or LR), free water (e.g. D5W), and colloid (e.g. albumin, blood products)
o Crystalloid can be isotonic (NS, LR), hypotonic (1/2 NS, 1/4 NS), or hypertonic (3% saline)
• Bolus fluids = volume expansion in shock, sepsis (30 ml/kg up to fluid responsiveness though debated: J Anes
2016;116:339), hemorrhage (initial resuscitation), GI losses, burns
o Rate: ~500cc-1L over 30 min-2 hr. If concerned about volume overload, start w/ smaller volume (250-500cc)
o NS in large volumes can cause hyperchloremic non-AG metabolic acidosis and  need for RRT
o LR or PlasmaLyte associated with better renal outcomes compared with NS though still debated
(NEJM 2018;378:829, NEJM 2018;378:718)
o Colloid is not superior to crystalloid for volume resuscitation in shock (JAMA 2013;310:1809)
• Maintenance fluids = replace daily losses (~1.6L per day in adults w/ normal renal function and perspiration). Also used
at higher rates in conditions such as pancreatitis and rhabdomyolysis (NEJM 2015;373:1350)
o If patient is taking PO, there is no need for maintenance IV fluids. Always order with time limit.
o D5-1/2 NS is typical maintenance fluid for NPO patients. Insufficient calories to replace a diet (~170 kcal/L).
o Maintenance rate: 60 ml/hr + 1 ml/kg/hr for every kg above 20 kg  ex. 60 kg adult = 100 ml/hr

Fluid pH Osm [Na+] [Cl-] [K+] [Ca2+] Dextrose Other

275-295 135-145 94-111 3.5-5.0 2.2-2.6 60-100
Human plasma 7.35-7.45 1-2 mEq/L lactate
mOsm/L mEq/L mEq/L mEq/L mg/dL mg/dL
Normal Saline 4.5-7 308 154 154
Lactated Ringers 6-7.5 280 130 109 4 1.35 29 mEq/L lactate
1/2 NS 5 154 77 77
D5-1/2 NS 3.5-6.5 406 77 77 5 g/dL
Used in hyperNa
D5W 3.5-6.5 252 5 g/dL (see Sodium
Disorders)

MGH Albumin Policy (Ellucid): put in place to prevent non-evidence-based overuse (ASA Choosing Wisely)
Albumin 25% = 12.5g albumin in 50ml solution; Albumin 5% = 12.5g albumin in 250ml solution
Use to replace serum oncotic pressure. If you need volume, give crystalloid.
• SBP: improves renal outcomes. Dosing: albumin 25% at 1.5g/kg IV within 6hrs arrival, decrease to 1g/kg on Day 3.
• Large volume paracentesis in cirrhosis: only if >5L removed. Dosing: Albumin 25% at 6-8g/L ascites removed.
• Augmenting diuresis in ARDS: already on high dose loop diuretic AND Albumin <2.5 or Total Prot <6
Dosing: Albumin 25% at 25g IV q8h for 3 doses (requires attending approval; sop once alb >2.5. MAX 3 days).
• Hepatorenal syndrome: diagnosis and/or treatment by protocol. See Hepatorenal Syndrome in GI section.
• Other: chatter in ECMO/VADs, burns, nephrotic syndrome

ELECTROLYTE REPLETION – see Potassium Disorders, Magnesium & Phosphorus Disorders, and Calcium Disorders
(Endocrinology) for more specific guidelines
Potassium Magnesium Phosphorus Calcium
- CAD/arrhythmia: ≥4
- Replete if sx, long QTc,
- Everyone else: ≥3.5 - CAD/arrhythmia: ≥2 - Replete if sx or phos <1
Goal Ca <7.5, iCal
- Do not replete if on HD - Everyone else ≥1.7 - At risk for refeeding: >2
<1.15mmol/L
unless <3.0
IV if severe,
PO or IV? PO > IV IV > PO PO > IV
PO if mild
- KCl IR (powder): q4-6 hr
- Mg oxide 400mg (240 mg - K-Phos: 1 packet QID - Ca carbonate 1250 mg
PO repletion - KCl ER (pills): giant pills
elemental Mg) TID x1 day - Neutra-Phos: 1 packet QID PO BID
- If K <3.5, ≥20 mEq KCl IR
- Peripheral: 10 mEq/hr - Give 15-45 mmol Phos at a time - Ca gluconate 1-2gm IV;
IV repletion - Central: 20 mEq/hr w/ - Mg sulfate 2g IV - K-Phos (1.5 mEq K/mmol Phos) - CaCl2 used in codes,
telemetry monitoring - Na-Phos (1.3 mEq Na/mmol Phos) 0.5-1g q2-5 min
- Correct for low Alb and
- 10 mEq K  serum K by 0.1 - 2g will  serum Mg by 0.5
- IV Phosphate can precipitate Ca hyperphos first
Comments - Max 80 mEq  re-check K - Mg can cause K and
 causing hypocalcemia - 1g Ca gluconate 
- Correct hypoMg Ca
serum Ca by 0.5

Helen D’Couto
97
TOC

Nephrology Urinalysis
URINE DIPSTICK – urine should be analyzed within 2-4 hr
Can help approximate urine osm: decimal of SG x 30 (e.g. SG 1.020  20 x 30  ~ 600mosms)
Specific SG < 1.010: post-ATN (concentrating defect), diuretics, DI, polydipsia, hypovolemic hypoNa after resuscitation
Gravity SG 1.010 – 1.025: normal
SG >1.025: prerenal, contrast (esp >1.030), EABV, glycosuria (DM), proteinuria, SIADH
Normal 4.5 - 8, but strongly depends on serum pH and dietary intake
pH If normal urine pH + metabolic acidosis, suspect distal RTA (kidney not secreting NH4+)
If pH ≥7, suspect urease-producing organisms (Proteus, PsA), strict vegetarians (low protein diet), type I RTA
LE Released from lysed PMNs; FP:  pH or  SG (lyses WBCs); FN: proteinuria, glucosuria. For UTI, Sn 80% / Sp low
Nitrite Indicates nitrate-reducing GNR (E. coli, Klebsiella, Proteus, PsA – NOT Enterococcus). For UTI, Sn 60% / Sp>90%
UTI; if sterile pyuria, consider AIN, GN, Chlamydia, Ureaplasma, urethritis, TB, foreign body, exercise, steroid use,
WBC
cyclophosphamide
Detects heme (glomerular, renal, or urologic); FP: hemoglobinuria (hemolysis), myoglobinuria (rhabdo), semen,
Blood
drugs (rifampin, chloroquine, iodine), peroxidase producing bacteria
Detects albumin when excretion >300mg/d: glomerular, tubular, and overflow causes; does NOT detect light chains
Protein Semiquantitative categories (trace, 1+, 2+, and 3+) are not reliable, vary with SG
Falsely elevated by high SG, heavy hematuria (heme protein), and iodinated contrast (w/in 24h)
Ketones Detects only acetoacetate, NOT β-hydroxybutyrate; yield decreases as collected urine sits
Reflects glomerular overflow (serum glucose >180mg/dl or SGLT-inhibitor/mutation) OR
Glucose
PCT failure (glucosuria w/ normal serum glucose  consider Fanconi’s syndrome 2/2 MM, heavy metal, drugs, etc.)

URINE SEDIMENT (MICROSCOPY)

• Urine microscopy room: to the left of Harris room, outside White 10. Ask a Nephrology fellow or attending from the offices/HD unit
nearby (day) or Security (night) to let you in.
1. Obtain 10cc of fresh urine
2. Dipstick Findings Description
3. Centrifuge using a balance @ 3000 RPM x 3-5 min Glomerular (dysmorphic RBCs “mickey
4. Invert/drain supernatant and resuspend sediment in the few mouse ears”) vs non-glomerular: trauma,
drops of urine that remain in the tube. Place one drop of sample RBCs
exercise, infection, tumors, stones, sickle
on slide and place coverslip. cell disease
5. Standard or bright field microscopy: keep light source subdued, UTI/cystitis, pyelonephritis, AIN,
lower condenser to maximize contrast, start at low power (10x) WBCs atheroembolic, glomerular injury,
to obtain a general impression. Pay attention to coverslip edge renal/bladder TB, nephrolithiasis
where casts tend to migrate, increase power as needed to Tubular (ATN), transitional (proximal
examine formed elements. Epithelial
urethra to renal pelvis), squamous
6. Phase contrast microscopy: maximizes contrast and definition Cells
(contamination by genital secretions)
and allows better visualization of casts and cells. Raise Viewed best w phase contrast: Hyaline,
condenser up high and turn light source to maximum brightness. Casts RBC, WBC, Muddy brown, Granular,
Rotate the condenser annulus to 40 and the objective to 40 Waxy, Fatty
(objective and condenser annulus should always match). Viewed best w phase contrast: Acyclovir
Analyze for dysmorphic RBCs or casts by focusing up and Crystals (“needles”), Tenofovir, Struvite
down, through the casts. (NH4⸱Mg⸱PO4), ethylene glycol (oxalate)
7. Please use the urine sediment guide adjacent to microscope to
guide analysis. Keep in mind: there is no
polarized filter on our microscope

CONDITION UA CELLS CASTS / CRYSTALS COMMENTS

Pre-renal azotemia SG > 1.010 Hyaline, granular  FENa,  FEUrea
CIN SG >1.010; +Pro Tubular cells Granular, muddy brown  UNa,  FENa, FP: proteinuria
Nephrotic syndrome 3+ Pro Oval fat bodies, hyaline
Glomerulonephritis 3+ heme Dysmorphic RBCs RBC casts, WBC, granular
ATN SG ~ 1.010 Tubular cells Granular, muddy brown
Acellular hyaline casts
Rhabdomyolysis, 3+ heme w/o
NO cells with red or brown  FENa, red/brown urine
hemolysis RBCs
pigmentation
AIN WBCs; +/- eos WBC casts, granular Urine eos NOT Sens or Spec
Renal infarct Sterile pyuria; +Pro +Eos, RBCs, WBCs  urine LDH ( serum LDH)
Cholesterol emboli Sterile pyuria +Eos Cholesterol
Myeloma kidney Bland Bland Proteinuria NOT detected by UA
Ethylene glycol Ca oxalate
CKD Waxy +/- impaired ability to concentrate

Daniel Gromer and Elizabeth Kurtz

98
TOC

Nephrology The Nephron

For an additional schematic, see the nephron

schematic at this Columbia Nephrology link.

Daniel Gromer and Elizabeth Kurtz

99
TOC

Infectious Disease Empiric Antibiotics

Principles of Antibiotic Selection (Empiric Therapy from MGH, IDSA Guidelines, Sanford Guide, Johns Hopkins Abx Guide)
• HOST: presence of foreign bodies (eg. drains), structural organ disease (eg. CF, bronchiectasis, IBD), prior surgeries; when immune clearance is
poor (i.e. neutropenia, endocarditis, meningitis, etc.), cidal antibiotics are preferred to static antibiotics
• PATHOGENS: prior micro data; risk factors for MDRO, especially IV antibiotic use within 90d
• ANTIBIOGRAM: identify local susceptibility and resistance patterns for likely pathogens
• SOURCE CONTROL: remove infected lines/hardware, evaluate for and drain abscesses/effusions
**CULTURES BEFORE ANTIBIOTICS** **TIME TO ABX CORRELLATES WITH MORTALITY IN SEPSIS**
***More nuanced discussions on antibiotic choices can be found on topic-specific pages***
***See the Antibiotic Stewardship Program Page: http://intranet.massgeneral.org/id/asp/ for further information if needed***
Suspected Process Microbiology Empiric Antimicrobial Therapy Additional Info
-Vanc AND CTX 2g Q12
-Viral, HSV, S. pneumo > N. meningitis -Dex 10 mg PO/IV q6h x 4 days w/
Meningitis -If concern for Listeria: add Amp or
-If >50yo, immunocompromised, EtOH use: initial abx dose if S. pneumo
(IDSA: CID 2004;39:1267; TMP/SMX (if severe PCN allergy)
Listeria -If healthcare-assoc / hardware / VP
CID 2017;64:e34) -If concern for HSV: add Acyclovir
-If hardware or nosocomial: Staph, PsA; P. shunt / IVDU: Cefepime or Ceftaz or
-CNS abx penetration: Clin Micro Rev
acnes if VP shunt Meropenem in place of CTX
2010; 23:858
-Healthy outpt: Amox or doxy
+Comorbid: (amox/clav or cephalo) AND
Community Acquired -Consider flu testing + Oseltamivir
macrolide OR levofloxacin
Pneumonia (CAP) -Viral (most common), S. pneumo, H. flu, -If post-flu/cavitation/empyema:
-Inpt w/o MRSA/PsA RFs (below): β-lact.
(IDSA/ATS: AJRCCM Moraxella, S. aureus, Legionella, add Vanc for MRSA
AND azithro OR levofloxacin
Mycoplasma, Chlamydia, Klebsiella, (EtOH) -If structural lung dz: Levo>Azithro
2019;200:e45) -Prior respiratory isolation of MRSA/PsA
-If Legionella: Levo>Azithro
OR [recent hosp AND IV abx in past 90d]:
vanc + cefepime + azithro
Hospital-Acquired and
-Vanc + Cefepime (NB: double GNR
Ventilator-Associated -CAP organisms + S. aureus + GNRs -See HAP / VAP for more nuanced
coverage usually not necessary, but
Pneumonia (HAP/VAP) including PsA discussion; consider local MDRO
consider if ICU + shock)
(IDSA/ATS: CID and MRSA prevalence
2016;63:e61)
-ID c/s improves mortality!
Endocarditis -Native: S. aureus, Strep, Enterococcus, -Native: Vanc + CTX
(IDSA/AHA: Circulation few GNRs, HACEK <5% -Prosthetic: Vanc + Gent (or Vanc + CTX -MSSA: β-lactam >> Vanc
2015;132:1435) -Prosthetic: S. aureus, S.epi if prosthetic valve >1 year) -Check Rx list for rif interactions
-Consider GNRs if subacute
Cholecystitis/Ascend. -E. coli, Klebs; less likely Enterococcus,
-[CTX +/- MNZ] or Pip/Tazo -Source control with ERCP vs. perc
Cholangitis (IDSA: CID anaerobes. Often polymicrobial; broad abx
-If nosocomial: consider cefepime cholecystostomy
2010;50:133) for 48h even if BCx growing 1 org
-Abscess: GNRs, anaerobes, Enterococ, -Need CT/US-guided drainage
-[CTX or Cipro] AND MNZ
Other Intra-abdominal Candida; S. aureus, Strep rare -Severe: Pip/Tazo or Mero or Imi
-If nosocomial/severe: cover PsA, add
(IDSA: CID 2010;50:133) -Diverticultis: Polymicrobial, enteric GNR, -Surgical indication: peritonitis, perf,
Vanc if recent instrumentation
anerobes, role of Enterococcus unclear fistula, recurrent diverticulitis
Spontaneous Bacterial
-Enteric GNR, includ Enterobacter, Strep, -Cipro reserved for patients w/ β-
Peritonitis (AASLD: Hep -CTX
Enterococcus; rarely anaerobes lactam allergies and for ppx
2013;57:1651)
Uncomplicated: E.coli, Klebsiella,
UTI (requiring -Comp: If afeb x48h, transition to
S.saprophyticus, Proteus Uncomp: NFT or Fosfomycin or Bactrim
hospitalization, non- PO FQ; can consider Bactrim or
Complicated (i.e. w/ s/sx of systemic infxn; Comp: CTX or Cefepime (if c/f PsA),
pregnant) cefpodoxime but need longer
includes Pyelonephritis): above + penem if ESBL, add Vanc if c/f GPC
(IDSA: CID 2011;52:e103) course
Enterococcus, PsA, Serratia, Providencia
Catheter-Associated UTI -Tx only if sx; repeat UA/UCx 48
-GNR’s, Enterococcus -CTX AND Vanc; consider PsA if risk
(CAUTI) (IDSA: CID hrs after removal or replacement
-Prior cx data useful MDRO, hosp. acquired
2010;50:625) (pyuria ≠ Infection)
-Hematogenous source: S aureus
-No abx until after bone bx+cx unless -Dx: MRI, ESR/CRP, bone bx
Osteomyelitis -Direct inoculation/vascular (e.g. DM ulcer):
HD unstable/ severe neuro symp -Debride (ortho/vasc surg/plastics)
(IDSA: CID 2012;54:e132; S aureus > Strep, PsA (diabetic), GNR,
-Vanc; ADD CTX or Cefepime if w/ bone bx+cx
CID 2015;61:e26) Enterococ, Eikenella (human bites),
DM/PVD/Ulcer or direct innoculation -Bite: Amp/Sulbact 1.5-3g IV q6h
Pasteurella (animal bites)
Septic Arthritis -Staph, Strep, N. gonorrhea (sex. active), E. -Blood + joint aspirate cx prior to abx -GC: CTX AND Azithro
(Curr Opin Rheumatol coli; Salmonella (sickle cell); PsA (IVDU); -Vanc AND CTX (consider Cefepime if -PCN allergy: Vanc + FQ
2008;20:457) Lyme, viruses (poly-articular) IVDU, other risk factor for PsA) -Consult ortho for joint washout
-Impetigo: S. aureus > Strep -Purulent: Vanc; Non-purulent: cefazolin -DM/PV ulcer: Vanc AND [CTX or
Skin/Soft Tissue (SSTI)
-Cellulitis/Erysipelas: Strep > Staph -Nec Fasc: Vanc AND [Pip/Tazo or Mero] Cefepime]
(IDSA: CID 2014;59:e10)
-Nec Fasc: Strep, C. perfringens, MRSA AND Clinda -If abscess: I&D is 1º therapy
-If TSS: add Clinda 900 IV q8h
Septic shock, no source -Vanc AND [CTX or Cefepime or Ceftaz -MDRO: Meropenem/Imipenem
-GNRs, S. aureus, Strep, PsA, anerobes.
(Intensive Care Med or Pip/Tazo] ± MNZ (if c/f anaerobes and -Critical illness/immuno-
Consider toxic shock syndrome (TSS)
2017;43:304) not on Pip/Tazo) compromised: consider adding
Aminoglycoside

Daniel Amponsah
100
TOC

Infectious Disease Gram Stain Interpretation

Coagulase ⊕ Staphylococcus aureus
Clusters or tetrads (never Novobiocin
Staphylococcus lugdunensis, S. epidermidis
chains > 4) sensitive
Coagulase ⊝
Novobiocin
Staphylococcus saprophyticus
resistant
Long chains > 6 (never in α-hemolytic Viridans group (optochin resistant)
tetrads) β-hemolytic Streptococcus pyogenes (GAS)
Cocci Streptococcus pneumoniae (optochin sensitive)
α-hemolytic (partial, green Enterococci (GDS) (also γ-hemolytic)
hemolysis) Gemella (facultative anaerobe, variable
Pairs and hemolysis)
short chains < 6
Gram β-hemolytic (complete
Streptococcus agalactiae (GBS)
Positive hemolysis)
γ-hemolytic (no hemolysis) Streptococcus bovis (GDS, variable hemolysis)
Anaerobic γ-hemolytic Peptostreptococcus
Aerobic Bacillus
Large (and spore forming)
Anaerobic Clostridium
Aerobe Gardnerella
Short Facultative anaerobe Listeria, Erisypelothrix
Rods Anaerobe Lactobacillus
Aerobe (“club” shaped) Corynebacterium
Irregular/Pleomorphic
Anaerobe Propionibacterium
Aerobe Nocardia, Tropheryma
Filamentous
Anaerobe Actinomyces
CSF or genital Facultative intracellular Neisseria
Cocci
Lower respiratory Aerobe Moraxella
Acinetobacter
Bordetella
Respiratory and Oropharyngeal Haemophilus (H. parainfluenzae = HACEK)
Aerobic
Coccobacilli Cardiobacterium hominis (HACEK)
and Kingella kingae (HACEK)
Pleomorphic Zoonoses Brucella, Francisella, Bartonella
Aggregatibacter actinomycetemcomitans
Facultative Anaerobe Respiratory and Oropharyngeal
(HACEK)
Anaerobic Eikenella corrodens (HACEK)
Campylobacter
Gram Microaerophilic
Negative Curved Rods Helicobacter
Halophilic Vibrio
Oxidase ⊝ Stenotrophomonas
Obligate Aerobes (all
Oxidase Variable Burkholderia
lactose non-fermenters)
Oxidase ⊕ Pseudomonas, Alcaligenes
Respiratory Legionella
Enteric Gram Negative Rods: Escherichia, Enterobacter, Klebsiella
Straight Rods Lactose Fermenting (Coliforms) Citrobacter, Serratia (slow fermenters)
Aerobes Proteus
Enteric Gram Negative Rods:
Salmonella
Non-Lactose Fermenting
Shigella
Zoonoses Pasteurella, Yersinia
Anaerobes Bacteroides, Fusobacterium, Prevotella
Acid Fast Mycobacteria
Spirochetes Borrelia, Leptospira, Treponema
Tick borne Anaplasma, Ehrlichia, Rickettsia
Obligate Cell wall present
Respiratory Chlamydophila, Coxiella
Intracellular
No cell wall Mycoplasma, Ureaplasma
Budding, pseudohyphae Candida
Yeast (unicellular) Encapsulated, ⊕ India Ink, budding Cryptococcus
Trophozoite, sporozoite, cyst forms Pneumocystis
Fungi Lives part of life cycle as yeast and part of cycle as a Blastomyces, Histoplasma, Coccidioides,
Dimorphic
mold Sporothrix
Branching, septated hyphae Aspergillus
Mold (multicellular)
Irregular aseptate hyphae, sporangia Mucor, Rhizopus (zygomycetes)

Jacqueline Henson
101
TOC

Infectious Disease Multidrug Resistant Organisms

EXTENDED-SPECTRUM BETA LACTAMASES (ESBL)
• Definition: plasmid-mediated enzymes exclusively seen in GN organisms
conferring resistance to PCNs, most cephalosporins, and aztreonam
o MGH Lab definition of potential ESBL: GNR resistant to Ceftriaxone
o Two specific subtypes include AmpC producers, CRE (see below)
• Pathogens: Klebsiella (#1), E. coli (#2), Proteus mirabilis (#3), other GNs
• Risk factors: abx within past 6mo, long inpt hosp., nursing home, >65yo,
lines/cath/tubes/vent, TPN, HD, travel to Asia
• Treatment: AVOID penicillins, cephalosporins (cefepime ok under specific
conditions), & pip/tazo even if listed as susceptible (JAMA 2018;320:984).
o See algorithm to right. For non-AmpC GNR, if CTX-R w/ cefepime MIC ≤2
and pip/tazo MIC ≤4, ok to tx with cefepime 2g q8 (CID 2014; 58:1554).
o If critically ill and prior ESBL ⊕BCx, can tx empirically with meropenem
(1g q8) while awaiting sensitivities.
o If not critically ill, can use non-β-lactam alternatives if susceptible (e.g.
FQ, fosfomycin, TMP/SMX, doxy, nitrofurantoin) (CID 2017;64:972). If
isolated UTI, pip/tazo may be ok.
AmpC Beta-Lactamases (Cephalosporinases)
• Neutralize 3rd gen ceph., pip/tazo. AmpC expression can be constitutive or inducible (can appear S to CTX in vitro)
• Inducible AmpC producers include MISPACE (aka SPICE, SPACE-M) organisms: Morganella, Indole-positive Proteus
(non-mirabilis species), Serratia, Providencia, Acinetobacter, Citrobacter, Enterobacter
• Treatment: do not treat these organisms with 3rd gen. cephalosporin (i.e. CTX) or pip/tazo, regardless of susceptibilities.
o If critically ill, tx with meropenem (1g q8) or cefepime if MIC ≤2.
o If not critically ill, can use non-β-lactam alternatives (e.g. FQ, TMP/SMX, doxy, or nitrofurantoin) if susceptible.
Carbapenem Resistant Enterobacteriaceae
• Mechanisms: 1) Carbapenemase or 2) AmpC/ESBL (some hydrolyze penems) + Porin loss (limits penem entry)
• Risk factors: cephalosporin/carbapenem use in past 3mo. (*penem exposure not req*), medical care in India/Pakistan
• Laboratory detection: suspicious when MIC >2 for imi-, mero-, or ertapenem
• Treatment: limited options; may include aminoglycosides, ceftaz-avibactim, colistin/polymixin B, Tigecycline, etc. C/s ID.
METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)
• Community-associated MRSA: no healthcare exposure
o Skin & soft tissue infections in young & healthy
o Risk factors: HIV, IVDU, prior abx use; outbreaks: incarceration, military, sports, sharing needles/razors
• Healthcare-associated MRSA: occurs >48hrs following hospitalization or w/in 12mo. of healthcare exposure
o Risk factors: recent hospitalization/surgery, HD, LTC facility residence
o Nasal swab: high NPV for pneumonia (up to 96.5%), not as well studied for other MRSA infections. Therefore more
useful if ⊝ swab  consider discontinuing MRSA coverage in pneumonia (CID 2018;18:67)
• Treatment: check the Vanc MIC!
o Vancomycin-intermediate and resistant (VISA/VRSA): MIC ≤2 mcg/mL = vanc-susceptible (though  tx failure and
mortality when MIC=2). Intermediate (VISA) when 4 ≤ MIC ≤ 8. Resistant (VRSA) if MIC ≥16.
o Serious infections (i.e. bacteremia): vanc (w/ full loading dose) and ID c/s. If persistent bacteremia or MIC ≥2,
consider dapto (NOT in PNA [inactivated by surfactant] or meningitis [doesn’t cross BBB]) OR add ceftaroline
o Mild infections (e.g., PNA, SSTI): Bactrim, doxycycline >> clindamycin (less sensitive); linezolid
VANCOMYCIN RESISTANT ENTEROCOCCI (VRE)
• Low virulence, colonizer. E. faecium: often resistant & generally less virulent. E. FaecaLIS is facile: i.e. less resistance.
• Risks: multiple prior abx, urinary catheters & indwelling lines; proximity to other VRE infected/colonized patients; long
hospitalization or nursing home residence; transplant / HIV / DM / ESRD or HD.
• Clinical sites of infection: UTI (NB: more commonly asymptomatic bacteriuria and rarely causes UTI in normal host; if pt
not critically ill, pull catheter first if possible and retest urine); bacteremia (2nd most common CLABSI); intra-abdominal and
pelvic infections; endocarditis (esp. if prosthetic valve); meningitis (rare unless immunocompromised or VP shunt)
• Treatment:
o Invasive infection (e.g. bacteremia, endocarditis): dapto 8-12mg/kg q24 (+ amp or CTX or ceftaroline) OR linezolid
600mg q12
o Uncomplicated UTI: fosfomycin 300mg x1 (consider repeat dose on days 4 and 7) OR nitrofurantoin 100mg q6

Theodore Pak
102
TOC

Infectious Disease Community Acquired Pneumonia

COMMUNITY ACQUIRED PNEUMONIA (CAP)
● Definition: PNA acquired in the community, including patients from nursing homes, dialysis, or with outpatient clinic exposure
● Diagnosis: new CXR consolidation (required) AND signs/sx (e.g. fever, cough, leukocytosis, purulent sputum, hypoxemia)
o Elderly at  risk of blunted s/sx but also  prevalence of atelectasis/aspiration
o Radiographic consolidation NOT specific for bacterial vs viral PNA; lobar consolidation can be viral
o If CXR ⊝ but clinical suspicion is high  treat and repeat CXR in 24hrs (PNA may “blossom” after fluid resuscitation and/or
time); if still negative  consider chest CT or other dx
● Triage: CURB-65 (Confusion, BUN>20, RR>30, BP<90/60, age>65)  outpatient if Score 0-1, inpatient if 2, consider ICU if 3-5.
Pneumonia Severity Index (PSI) more comprehensive  outpatient if <70, inpatient if >90.
● Severe CAP: 1 Major (pressors or mech vent) OR 3 Minor (RR>30, P:F<250, multilobar infiltrates, confusion, BUN>20, WBC<4K
[*not due to chemo], Plt<100K, T<36C, HoTN requiring aggressive fluid resuscitation) (CID 2007;44:S27)
● Micro: S. pneumoniae (most common in inpts, ICU), H. influenzae, GNRs, S. aureus, Legionella. Most common pathogens identified
are viruses – rhinovirus, influenza, others (NEJM 2015;358:415)
● Work-up (inpatient):
o Sputum culture and gram stain (ET aspirate if intubated): adequate sample if >25 PMN/lpf and <10 SEC/lpf. NOTE: “abundant
squamous cells” or more squamous cells than polys suggests the sample is saliva.
▪ Not recommended routinely. Obtain if: severe CAP, empirically tx for w/ MRSA/PsA, prev. MRSA/PsA, hosp. w/ IV abx ≤90d
o Blood cultures: controversial benefit, positive <20% of inpt PNA, 2/3rd of positive Cx are S. pneumoniae.
▪ Not recommended routinely. Obtain if: severe CAP, empirically tx for w/ MRSA/PsA, prev. MRSA/PsA, hosp. w/ IV abx ≤90d
o Procalcitonin (PCT): should NOT replace clinical judgment for dx of CAP / use of abx (also has slow turnaround at MGH).
▪  in acute resp. infxns from bacterial causes but unclear cut-off to distinguish from viral. Not validated in immunocomp. pts.
o S. pneumo urine Ag (Sn 70% / Sp 96%); only ⊕ in 44% of S. pneumo PNA.  if severe CAP.
o Legionella urine Ag (Sn 70% / Sp 99%); detects only serogroup 1 (80-90% in US).  if severe CAP or recent exposure/travel.
Clinical predictors include HypoNa, fever, diarrhea, and recent travel (CID 2019;68:2026)
o MRSA nasal swab: high NPV (~98%). Neg test can be used to de-escalate MRSA coverage (CID 2018;67:1)
o Influenza: test seasonally. Tx: oseltamivir regardless of duration of illness (though best if initiated <48h).
● IDSA/ATS CAP Empiric Treatment (NOTE: additional considerations for travelers, immunocompromised) (AJRCCM 2019;200:e45)
Outpatient Preferred Alternative/Other info
No Comorbidities or Amox 1g TID OR Doxy 100mg BID OR Macrolide NOTE: U.S. has high rates of macrolide- and doxy-
MRSA/PsA RFs (Azithro OR Clarithro) (if resist. <25%) resistant S. pneumo
[Amox/Clav 2g BID AND Azithro] OR Cefpodox or cefurox. can replace Amox/Clav, Doxy can
Comorbidities°
Levofloxacin 750mg QD monotherapy replace Azithro, Moxiflox./Gemiflox. can replace Levoflox.
Inpatient Preferred Alternative/Other info
(β-lactam (CTX) AND Macrolide [Azithro]) OR Amp/sulb can replace CTX, Clarithro can replace Azithro,
Non-Severe
Levofloxacin monotherapy** Moxifloxacin can replace Levofloxacin
β-lactam (CTX 1-2g QD) AND In ICU, azithro >> levofloxacin (anti-inflamm. effect);
Severe/ICU
(Azithro OR Levofloxacin) consider addt’l agents for drug-resistance (see below)
MRSA/PsA RFs# Vancomycin AND Cefepime Obtain Cx and nasal MRSA swab to inform de-escalation.
° Chronic heart, lung, liver, or renal disease; DM; AUD; malignancy; or asplenia. **CAP START showed β-lactam monotherapy
noninferior to combo β-lactam/macrolide or fluoroquinolone alone, however trial was conducted in areas with lower rates of atypical
organisms (NEJM 2015;372:1312). # Prior respiratory isolation of MRSA/PsA or recent hospitalization w/ IV abx (≤90d)
● Risk factors for drug-resistant pathogens in CAP:
o General: hospitalization & IV abx in past 90d; prior respiratory isolation of MRSA, PsA or other resistant organisms
o PsA: GNR on gram stain, h/o PsA, bronchiectasis, COPD w/ freq exacerbations req abx/steroids. Tx: (for normal renal function)
Cefepime 2g q8h, Ceftazidime 2g q8h, Pip/tazo 4.5 q6h, Mero/Imipenem; double coverage usually not necessary
o MRSA: GPC clusters on gram stain, recent flu-like illness, necrotizing/cavitation/empyema, ⊕ nasal swab, risk factors for
colonization (ESRD, IVDU, prior abx [esp. fluoroquinolones]). Tx: Vancomycin or Linezolid.
● Anaerobic coverage: only if suspicion for empyema or lung abscess Tx: ampicillin-sulbactam (or amox/clav if not severely ill);
alternative: (CTX + flagyl) OR clindamycin (AJRCCM 2019;200:e45)
● Steroids: some data for benefit in severe CAP but routine use not rec. by IDSA/ATS unless o/w indicated for refractory septic shock
or COPD/other comorbidity (Cochrane Rev 2017). AVOID in INFLUENZA as might  mortality (Cochrane Rev 2016).
● Duration: 5d assuming clinical stability (afebrile x48h + ≤1 sign of CAP instability: HR >100, RR >24, O2>90%, AMS, no PO intake);
if have not achieved clinical stability, extend course & eval. for resist. pathogen, complication (empyema, abscess), alt. source of infxn
o Convert IV  PO when clinically improving; no need to observe x24h on PO
o Can utilize procalcitonin to help guide discontinuation of therapy: repeat PCT every other day and stop abx when PCT<0.25 or
decreases by >80% from peak if initial PCT>5 ng/mL, though this does not supersede clinical judgment (JAMA 2009;302:1059)
o Excessive abx duration (>5d) is associated with increased adverse effects w/o clinical benefit (Annals 2019;171:153)
● Response to therapy: tachycardia resolves by 2-3d; fever resolves by 2-4d; hypoxemia resolves by 3-6d
o CXR clears by 1mo in 50% (delayed up to 12wks in older pts, pts with lung disease); do not repeat CXR for f/u if clinical
improvement (CID 2007; 45:983)
o If no response to therapy after 72h: consider chest CT (+/- BAL) to evaluate for empyema, abscess, fungal infxn

Rahul Nayak
103
TOC

Infectious Disease HAP/VAP & Aspiration Pneumonia

HOSPITAL-ACQUIRED AND VENTILATOR-ASSOCIATED PNEUMONIA (IDSA/ATS Guidelines: CID 2016;63:e61)
• Definitions:
Hospital-acquired pneumonia (HAP) Pneumonia that develops ≥48 hrs after admission
Ventilator-associated pneumonia (VAP) Pneumonia that develops ≥48 hrs after endotracheal intubation
Dx criteria: new/progressive infiltrates on CXR + 2/3 of fever, leukocytosis, purulent tracheal secretions
• Common microbiology: enteric GNRs (Klebsiella, E. coli), MRSA/MSSA, PsA, Acinetobacter
• Workup: CXR, SCx, BCx, MRSA swab; consider induced sputum, bronch with BAL
• Antibiotic choices and empiric treatment:
o MDRO risk factors: IV abx use within 90 days preceding onset (most important); high local prevalence (>10%) of
MDR GNRs & MRSA; structural lung disease (CF, bronchiectasis)
 MDR VAP risk factors: septic shock/ICU, ARDS, onset ≥5 days in hospital, or RRT preceding onset
o HAP/VAP with MDRO risk: 1 anti-PsA (β-lactam pref.) AND 1 anti-MRSA agent (typically Vancomycin)
 Consider empiric double PsA coverage if: septic shock, rapid progression of PNA/requires mech. ventilation, hx
of MDR PsA
Antipseudomonal β-lactams Antipseudomonal non-β-lactams Anti-MRSA agents
- Cefepime 2g IV q8H - Levofloxacin 750mg IV qday - Vancomycin IV (trough 15-
- Ceftazidime 2g IV q8H (*PsA susceptibility only 70% at 20)
- Pip/Tazo 4.5g IV q6H MGH) - Linezolid 600mg IV q12H
- Meropenem 1g IV q8H - Ciprofloxacin 400mg IV Q8H
- Aztreonam 2g IV q8H (only if severe PCN - Tobramycin 5-7mg/kg IV x1, then
allergy: https://id.partners.org/allergy/) dose by level
*Adjust dosing above as needed for renal function - Polymyxin B (call ID)
• Tailoring therapy:
o If improvement after 48h or pathogen identification  narrow abx and discontinue MRSA + PsA coverage if possible.
Neg MRSA swab w/ 96% NPV for MRSA infection (CID 2018;18:67; CID 2019). In VAP, if neg. tracheal aspirate,
consider d/c abx after 72 hours (NPV 94% for VAP).
o If no improvement after 48h  broaden to cover MDROs (if not currently covering), consider other sites of
infection/abscess, non-infectious causes of clinical syndrome
• Duration: 7d for both HAP/VAP. Can consider serial procalcitonin levels (though long turnaround at MGH)  discontinue
abx when <0.25ng/mL (ERJ 2009;34:1364)
ASPIRATION PNEUMONIA
• Definition: pneumonia caused by the excessive entry of secretions, particulate matter, or fluid into airways. Micro-
aspirations are common and the definition of aspiration pneumonia as a distinct clinical entity remains unclear.
• Predisposing factors:  consciousness (seizure/overdose), esophageal dysmotility, post-bronchial obstruction, gum
disease / poor dentition
• Microbiology: most common organisms are GNRs and standard CAP/HAP organisms (AJRCCM 2003;167:1650). Role
of anaerobes is likely overstated in conventional wisdom with large studies demonstrating minimal recovery of anaerobic
pathogens from bronchial samples (Chest 1999;115:178).
• Characteristics: indolent, putrid sputum, pulmonary necrosis w/ cavitation/abscess/empyema
• Workup: CXR, SCx (anaerobic respiratory culture not performed at MGH due to low utility)
• Empiric treatment: same as CAP/HAP empiric treatment
o Anaerobic coverage: per 2019 IDSA guidelines, anaerobic coverage only routinely recommended in pts w/
suspected lung abscess or empyema (AJRCCM 2019;200:e45)
o First line: ampicillin-sulbactam (or amox/clavulanate if not severely ill); alternative: (CTX + flagyl) OR clindamycin
• Duration: 7d unless complicated by cavitation/abscess/empyema
ASPIRATION PNEUMONITIS
• Definition: aspiration of chemical substances into the airways without bacterial infection
• Clinical manifestations: abrupt onset (2hr), low-grade fever,  WBC, hypoxemia, CXR consolidation (RML/RLL upright,
RUL supine)  often indistinguishable from pneumonia in the acute setting!
• Treatment: if concern for aspiration pneumonia (i.e., bacterial infection), cover with abx for 48hrs  d/c if no
consolidation develops on CXR OR if signs/sx/consolidation resolve rapidly (less likely to be PNA)

Emily Moin
104
TOC

Infectious Disease Viral Respiratory/Head & Neck Infections

VIRAL RESPIRATORY INFECTIONS (for bacterial pharyngitis see Respiratory Complaints)
● Epidemiology
o URI: rhinovirus (30-50%), coronavirus (10-15%), influenza (5-15%), parainfluenza (5%), RSV (5%)
o LRTI (bronchitis, bronchiolitis, PNA): influenza, RSV, parainfluenza, adenovirus (Lancet 2011;377:1264)
o In immunocompromised hosts consider reactivating latent viruses (HSV, CMV, adenovirus)
● Presentation
o Risk factors: extremes of age, chronic illness, immunosuppression, malnutrition, tobacco use
o Transmission: hand contact, droplet, peak viral shedding at 2-3 days, lasts 2 weeks
o Symptoms: nasal congestion, dry throat, cough, wheeze, fever, malaise, headache, ear and face pain (for significant
systemic illness consider influenza, measles, SARS, Hantavirus)
o Complications: viral PNA; secondary bacterial PNA (initial improvement followed by worsening after ~7days  micro:
S. pneumo [1st], S. aureus [2nd]), asthma / COPD exacerbation, acute otitis media, ARDS
● Diagnosis
o Resp. viral panel: nasopharyngeal swab PCR for adenovirus, parainfluenza, metapneumovirus; can rapidly detect
viral agent and help avoid unnecessary antibiotics; should be collected within 5 days of symptom onset, though
approx. 15% healthy persons harbor respiratory tract viruses (Pediatr Infect Dis J 2008;27:1103)
o Influenza testing: (IDSA guidelines: CID 2019;68:47)
▪ RT PCR is most sensitive and specific; can differentiate A,B and subtypes (1-8 hours)
▪ Rapid molecular assays is 92% sensitive, 96% specific, can differentiate A, B (15-30 min)
▪ Rapid antigen testing is 62% sensitive, 98% specific (<15 min); during season negative test does not exclude
influenza and is not sufficient to stop treatment (when in season)
● Influenza Post-Exposure Prophylaxis
o Indication: severely immunocompromised persons who are unvaccinated and their unvaccinated household contacts,
residents of LTCF during outbreak
o Dosing: oseltamivir 75mg daily x7 days after last day of exposure, ideally no later than 48 hours after exposure (if
symptoms arise, test for influenza, then transition to treatment dose) (CID 2019;68:47)
● Influenza Treatment
o When indicated, treatment should not be withheld while awaiting results of diagnostic testing
o Indications: severe disease (hospitalized or LRTI) or high risk population (>65, LTCF, pregnant / 2 wks post-partum,
immunosuppressed, cirrhosis, DM, CHF/CAD, CKD, COPD, SCD, asthma, BMI>40, neuro disease)
o Treatment: oseltamivir 75mg BID x5d; dose reduce for CKD; no data to support double dose if severe/ICU (BMJ
2013;346:3039); ideally initiate within 48h of sx but >48h OK if severe disease or hospitalized pt
HEAD AND NECK INFECTIONS (Principles of Crit Care. Chow AW. 4th edition. McGraw-Hill, NY 2015)
• Epidemiology: typically from odontogenic, otogenic or sinogenic infection with contiguous spread
• Organisms: streptococci, H flu, oral anaerobes. PSA in otogenic source. MRSA in sinogenic source and IVDU.
• Diagnostics: blood cultures, Panorex, CT Neck, MRI (evaluate for osteo), IR or ENT for tissue or abscess culture
• Treatment: β-lactam + anaerobic agent or β-lact. inhibitor. Early involvement of ENT for drainage and airway monitoring
• Clinical subtypes:
o Submandibular space (Ludwig’s angina): arising from a periodontal infection presenting with mouth pain, tongue
swelling, neck stiffness, can progress to airway compromise, most commonly due to strep viridans
o Internal jugular septic thrombophlebitis (Lemierre’s syndrome): presents with pharyngitis and septic embolic
phenomenon. Most commonly due to fusobacterium. Treat with abx and anticoagulation.
o Deep neck space: involving retropharyngeal, danger and paravertebral spaces. Presents with neck pain and
systemic toxicity. Can progress to carotid sheath abscess, mediastinitis, vertebral osteo, paravertebral abscess.
ORBITAL AND PRESEPTAL CELLULITIS (Surv Opthalmol 2018;63:505)
Preseptal Orbital
• Epidemiology: local trauma • Epidemiology: bacterial sinusitis
• Organisms: staph, strep • Organism: staph, strep; mucor and aspergillus in immunocompromised
• Symptoms: eyelid pain and edema • Symptoms: pain with eye movement, proptosis, vision changes, pupil
• Diagnosis: clinical though CT orbit and and extraocular muscle deficits
sinus can distinguish preseptal from • Diagnosis: blood cultures, CT of orbit and sinus
orbital cellulitis • Treatment: Vanc and CTX (add anaerobic coverage if concern for CNS
• Treatment: PO TMP-SMX or involvement); ophthalmology consult for daily vision checks and
clindamycin and amoxacillin possible surgical debridement
• Complications: subperiosteal abscess, orbital abscess, CNS spread,
cavernous sinus thrombophlebitis
Jessica O’Neil
105
TOC

Infectious Disease COVID-19

Virology/Epidemiology Transmission
Clinical Illness: Coronavirus Disease 2019, COVID-19 Main Route:
Virus: SARS-CoV-2, 2019 Novel Coronavirus, 2019-nCoV ● Person to person via (large) respiratory droplets + direct
● 4 genera of coronavirus exist, some cause common cold contact; aerosolization thought to only occur with specific
(or viral PNA in pts w/comorbidities). Genus procedures
Betacoronavirus includes SARS-CoV, MERS-CoV, and ● Median duration of viral shedding 20 days. Resp. viral
SARS-CoV-2 shedding highest early in course; evidence for pre-
● Source: zoonotic, reservoir unknown (Nature Med symptomatic transmission (JAMA 2020;323:1406); may
2020;26:450), original association with live animal market persist after sx resolution depending on illness severity.
in Wuhan, China No good evidence for late transmission. Peak
● Host entry: Viral S spike binds ACE2 receptor (Cell infectiousness around 1 day before symptoms
2020;181:271) on type 2 alveolar cells & intestinal epithelia Extra-pulmonary transmission:
(same as SARS). ACE2 also in olfactory epithelium, liver, ● Fomites: droplet  lives hours to days on surfaces (NEJM
kidney, endothelium, & myocardium (Cardiovasc Res 2020;382:1564)
2020;116:1097) ● Viral RNA also detected in stool in pts with GI sxs (NEJM
● Epidemiology: 2020;382:929; no known fecal-oral transmission, but could
o R0 estimate 2-4; decrease to 1 with control measures have direct contact transmission since ACE2 receptors in
(Lancet ID 2020;20:553) oropharynx), conjunctiva (Acta Ophth 2020), serum (Emerg
o Symptomatic CFR 1-2%, though varies with age and Microbes ID 2020;9:469; more common in critically ill pts),
comorbidities; Incubation 4-24d (median 5.1d, 1/100 and very rarely urine.
develop sxs after 14d; Annals 2020;172:577) ● Vertical transmission: recent evidence of IgM in newborns
o True # cases may be much higher than reported is suggestive (JAMA 2020;323:1848 & 1846), no viral
(Science 2020;368:489) shedding in breast milk. Placental infxn may cause
miscarriage (JAMA 2020)
Symptoms (NEJM 2020;382:1708)
Prevention:
● No universal symptom; can vary widely
● Social distancing; CDC Patient Guidance
● Constitutional: fatigue (23-70%), myalgia (15-35%),
● Hand washing soap > alcohol; don’t touch face; wipe
anorexia (40-78%). Fever: 80%-96% throughout the
surfaces w/alcohol, bleach, EPA-approved disinfectant
course, but not always present on admission. May be low
grade (i.e. 99.5F/37.5C)
● Respiratory: dry cough: (41-79%), sputum production (10-
45%), dyspnea (11-80%), rhinorrhea (5-15%), sore throat,
anosmia and ageusia
● GI: (e.g. n/v/d): 10-50% (Gastro 2020)
● Skin: localized or widespread urticaria, petechial rash
Laboratory Findings: for frequency and indications for testing, refer to MGH guidelines
Labs Findings/Notes
Leukopenia & lymphopenia (60-80%), AKI in ~3-9% (more common later
Basic labs: CBC w/ diff, BMP, LFTs
in course), AST/ALT/Tbili (Lancet RM 2020;8:475)
Inflammatory markers and acute phase reactants:
All may be elevated
CK, ferritin, CRP, ESR, LDH
Coagulation studies: PT/PTT, fibrinogen, D-dimer D-dimer (associated with mortality), fibrinogen can be  or 
Viral serologies: HBsAg, HBsAb, HBcAb, HCV Ab, 20% of COVID-19 cases have abnormal LFTs, want to r/o other causes,
HIV) may influence treatment choice (esp. remdesivir and lopinavir/ritonavir)
Only if c/f bacterial infection (note: rate of co-infection with bacterial PNA
Bacterial infection studies: BCx, procalcitonin, Strep
thought to be low. Procal initially low in COVID-19 but may rise after ~10
pneumo + legionella urinary Ag
days of infxn, even w/o superimposed bacterial infxn)
Extended infectious studies: Tspot, sputum Please refer to MGH guidelines for testing indications. DO NOT obtain
AFB/fungal Cx, pneumocystis DFA, 1,3-BDG, IgG induced sputum due to risk of aerosolization
Troponin  troponin in some cases (see Complications below)
β-hCG Women of childbearing age
UA + spot urine protein:Cr If AKI
IL-6 If category 2 or 3 risk factors
Risk Factors (for severe COVID-19)
● Category 1 – epidemiological: age>65, BMI >30, underlying pulmonary disease, CKD, DM with A1c>7.6, HTN, CVD,
immunosuppression (s/p transplant or on biologics), HIV with CD4 count <200 or unknown CD4 count.
● Category 2 – vital signs: RR >24, HR>125, SpO2 ≤93% on RA, P:F<300
● Category 3 – labs: D-dimer>1000, CPK> 2x ULN, CRP >100, LDH >245, elevated troponin, admission absolute lymphocyte
count <0.8, ferritin >500
COVID Council-CME Committee 05/10/2020
106
TOC

Infectious Disease COVID-19

Imaging
● EKG (COVID-19 can cause cardiomyopathy, some tx meds prolong QTc)
● CXR on admission; may be unremarkable early. NO clear diagnostic pattern, but
often hazy bilateral, peripheral opacities (JAMA 2020). Avoid daily CXR, only
obtain when indicated.
● Higher threshold to obtain CT given limited dx utility & infxn risk. May show
peripheral GGOs, crazy paving, consol.; rarely unilateral (AJR 2020). CT abn. can
precede or lag behind +viral PCR (Rad 2020, J ID 2020;11:1770)
● POCUS: many B-lines, pleural line thickening, consolidations w/ air bronchograms

Testing/Diagnosis/Treatment and Precautions: refer to MGH guidelines

Complications and Critical Care Management (see MGH Critical Care Guidelines; NEJM 2020)
● Suspect 5-15% of hospitalized COVID-19 patients will develop critical illness; low threshold to call Sr On if concerned
o Sr On will work with ICU Triage intensivist to decide whether needs ICU transfer
o Note: RICU needs ~10min to don PPE for intubation. Can call RICU attending (via x63333 – STAT vs. non-STAT) to
discuss concerning pts (generally >4LNC or rapidly  O2 requirement ≥1L NC/hr). Confirm Code Status before calling.
● ARDS may develop ~8-9 days after initial sx.
o Warning signs for deterioration:
worsening hypoxemia (P:F < 300,
room air O2 saturation <93%),
progressive lymphopenia,
increasing lactate and CRP,
worsening CXR
o Consider proning (MGH protocol)
as a rescue therapy for floor pts
requiring supplemental O2 (esp.
escalating levels)
o Note: early intubation is for lung
protection from barotrauma (due
to large spontaneous tidal
volumes/transpleural pressures;
avoiding HFNC/NIPPV is NOT
just about aerosol generation)
● Septic shock less common. If shock
worsens, consider myocarditis or
cardiomyopathy  cardiogenic shock
(JAMA 2020;323:1612)
● Cardiac injury: elevated troponin
associated with increased risk of
death (HR 4.26; JAMA 2020)
● Coagulopathy: MGH Heme Guidelines
o Clotting: venous: PE/DVT seen in
7-27% of pts; arterial: reports of
large vessel strokes (NEJM 2020);
microvascular: lung, kidney, and
liver (rates of clotting are higher
in critically ill patients)
o Bleeding: 2-5%
o As many as 21% of pts with severe COVID may meet criteria for DIC (JTH 2020;18:1094)
● Causes of death: 53% respiratory, 33% combined respiratory/cardiac, 7% cardiac, 7% unattributed (ICM 2020;46:846)

Disclaimer: this page is updated in real time as more data emerge – for the most recent version, please refer to the White Book App
(https://mghwhitebook.app/). The management guidelines are also actively evolving, so these are linked within this page.

COVID Council-CME Committee 05/10/2020

107
TOC

Infectious Disease Urinary Tract Infections

ASYMPTOMATIC BACTERIURIA
Definition: bacteriuria (≥ 105 CFU/mL) without symptoms, irrespective of pyruria (>20% of ♀ age >80; 6-15% of ♂ age >75)
• Treatment: Bacteriuria or pyuria should NOT be treated in the absence of sx (exceptions: pregnant woman, s/p renal transplant
in past 1mo., prophylaxis for invasive urologic procedures) (IDSA Guidelines: CID 2019; 68:1611)
CYSTITIS (UTI)

Clinical features: frequency, urgency, dysuria (premenopausal); malaise, incontinence, nocturia, suprapubic
tenderness (Infect Dis Clin NA 2014;28:1)

Fever, other s/sx of systemic illness e.g., chills/rigors, flank pain, CVA tenderness, pelvic or perineal pain (men)?
No Yes
Uncomplicated UTI (JAMA 2014; 312:1677) Complicated UTI
• Diagnosis: clinical; U/A can be used to confirm; pyuria (>10 • 30% w/ UTI and fever are bacteremic (usually older, flank /
WBC) has NPV>PPV, sensitivity (nearly 100%) >> specificity suprapubic pain,  CRP, BP) (JAMA 2018;378:48)
o Women: if dysuria and  frequency without vaginal • Pyelonephritis is a complicated UTI, & may itself be
discharge/irritation, >90% likelihood of UTI. In outpatient, complicated by perinephric or renal abscess
U/A unnecessary unless immunocompromised or w/ risk o WBC casts on U/A are suggestive of pyelo
factors for complicated UTI • Microbiology: same as UTI plus Serratia, Morganella,
o In outpatient, get UCx only if male, atypical sx, persist Providencia, Pseudomonas, Citrobacter. Gram-positives still
48-72 hr after abx initiated, or recur w/in 3 mo. of tx rare. If S. aureus, think bacteremia. Increasingly resistant
o Nitrites: only positive with Enterobacteriaceae (convert organisms (especially to FQ, TMP/SMX)
urinary nitrate to nitrite) • Dx: UCx in all; imaging if ill, suspect. obstruction, persistent sx
o Only test for pyuria if dipstick shows +LE • Treatment: Outpt: CPO 500mg BID OR LVO 750mg x 5-7d
• Differential diagnosis: vaginitis, urethritis, structural OR T/S DS BID x 7-10d. Can give 1x IV CTX prior to oral tx.
abnormality, PID, nephrolithiasis Inpt: CTX OR CEFE OR P/T; CBPN if c/f ESBL. Narrow to
• Microbiology: E. coli, Klebs, Proteus, S. Saprophyticus. oral agent if improving. Add Vanc / Linezolid if GPC on urine
Enterococcus rarely causes true infection. G/stain. Duration for inpt: depends on clinical course & oral
• Treatment: NFT 100mg BID x5d OR T/S DS BID x 3d OR agent chosen (5-7d for FQ; 7-10d for T/S; 10-14d for β-
fosfomycin 3g x1; alternatives: oral β-lactam (e.g. Augmentin lactam).
500mg BID, Cefpodoxime 100mg BID) x7d o Avoid NFT & fosfomycin (poor soft tissue penetration)
o Avoid NFT if CrCl < 30 o Remove/replace coated urologic devices
o Avoid empiric T/S if resistance >20% (E. Coli resistance o Prostatitis: FQN preferred for better penetration; tx
28% at MGH) duration up to 6 weeks

CATHETER-ASSOCIATED UTI ( C A U T I ) (IDSA Guidelines: CID 2010; 50:625)

• Definition: leading healthcare-assoc. infection; requires: (1) s/sx with no other identified source of infection; AND (2) UCx with
one uropathogenic species >103 CFU/ml from single catheterized urine specimen (catheter in place >2d) OR midstream voided
specimen from patient whose catheter was removed w/in previous 48hrs
o In pts w/ neurogenic bladder and  sensation, other signs of UTI include new onset incontinence, autonomic hyperreflexia,
malaise, lethargy, bladder pain (Urology 2015;6:321)
• Prevention: restrict catheters to pts w/ appropriate indications; remove catheters ASAP; consider short-term straight cath
• Dx: don’t screen asx patients; pyuria, turbidity, odor cannot differentiate asymptomatic bacteriuria from CAUTI. Ideally remove
catheter & collect midstream; if not possible, obtain from port in drainage system. Do not use Cx from bag to guide tx.
o Purple urine bag syndrome: occurs due to byproducts from bacterial enzymes in urine; benign and ≠ UTI
• Micro: same as complicated UTI, with addition of Candida (see below); can be polymicrobial
• Treatment: same abx as uncomp./complicated UTI as approp., taking into account RFs for resistant infection. If recent
catheterization/instrumentation, h/o MRSA in urine, add Vanc. Use Cx to narrow. Duration: 7d if improving; 10-14d otherwise.
o Remove catheter ASAP, obtain repeat UA/UCx from new catheter PRIOR to abx
FUNGURIA (IDSA Guidelines for Candidiasis: CID 2016;62:e1)
• Asymptomatic colonization common; only treat if symptoms present OR neutropenic OR before urologic procedure
• Tx: Fluc 200-400mg (pyelo) PO QD 14d OR for resistant C.glabrata or krusei, AmB 0.3-0.6 mg/kg QD x1-7d
RECURRENT UTI
• Abx ppx (usually dosed T/S or NFT) may be used in some ♀ w/ recurrent simple cystitis (≥2 UTI/yr) if behavior Δs ineffective.
Either post-coital or continuous (Cochrane Rev 2004: 6-12mo continuous abx ppx  rate of UTI in non-pregnant women).
• In pts w/ recurrent admission for complicated UTI, review prior micro data & consider resistant orgs. Consider involvement of ID
+/- urology. Abx ppx not indicated in these pts.
KEY: NFT–nitrofurantoin; T/S–TMP/SMX; CTX–ceftriaxone; FQ–fluoroquinolone; P/T–piperacillin/tazobactam; CEFE–cefepime; CBPN–carbapenem;
AMG–aminoglycoside; CPO–ciprofloxacin; LVO–levofloxacin; FLUC–fluconazole; AmB–amphotericin B; R–resistance

Grace Gillis
108
TOC

Infectious Disease Skin & Soft Tissue Infections

CELLULITIS (IDSA Guidelines: CID 2014;59:147; JAMA 2016;316:325)
• Clinical features: erythema, warmth, tenderness, edema, induration +/- purulence; smooth, poorly demarcated (vs. erysipelas
which is well demarcated). May have lymphangitis, LAD, vesicles/bullae, fever (20-77%), leukocytosis (34-50%).
• Risk fx: edema (esp. lymphedema), venous stasis, PVD, DM, obesity, IVDU, tinea pedis, ulcer, trauma/bite, eczema, XRT
• Differential diagnosis: (NB: if “bilateral cellulitis,” strongly consider alternative diagnosis)
o Non-infectious: inflammatory (contact dermatitis, drug rxn, angioedema, Sweet syndrome, gout, bursitis, erythema
nodosum, pyoderma gangrenosum, eosinophilic cellulitis, sarcoidosis, GVHD); vascular (stasis dermatitis, lymphedema,
DVT, superifical thrombophlebitis, calciphylaxis), neoplastic (leukemia, lymphoma, breast CA, extramammary Paget’s)
o Infectious: abscess (may coexist), necrotizing fasciitis/gas gangrene, septic joint, osteo, zoster, HSV, erythema migrans
• Diagnosis:
o CLINICAL. Can use ALT-70 score (shown to reduce abx use) (J Am Acad Derm 2017;76:618; JAMA Derm 2018;154:529).
Consider ultrasound to assess for presence of abscess.
o BCx & wound Cx are NOT recommended for typical cellulitis. Obtain if: systemic toxicity, extensive skin involvement,
immunosuppression, special exposures (bites, water), recurrent/persistent cellulitis.
• Treatment: based on 1) purulence and 2) severity. Duration: 5 days; up to 14 days if delayed signs of improvement.
Severity Purulent (abscess or fluctuance) Non-purulent †
MRSA (67%) > MSSA (17%) > Strep (5%) Strep >> S. aureus > aerobic GNRs
Mild I&D only PO: cephalex., diclox., pen VK, amox/clav
Moderate: systemic signs of infxn‡ OR I&D + culture + TMP-SMX OR doxycycline IV: cefazolin, ceftriaxone, pen G
abcess >2cm
Severe: systemic signs of infxn‡ AND I&D + culture + IV Vanc OR Dapto OR Vanc + Pip-tazo OR Vanc +
HoTN, immunocomp., rapid evolution, Linezolid. In TSS add clinda for toxin imi/meropenem. In TSS add clinda for
deeper infection, or failed PO tx inhibition. toxin inhibition.
† If non-purulent w/ MRSA risk factors (prev. MRSA infx/colonization, hosp./surgery/abx in prev 8wks, IVDU, penetrating trauma,

hemodialysis, HIV, athletes, prisoners, military, LTC facility residents): add empiric PO/IV MRSA coverage (T/S or doxy)
‡ Systemic signs of infection include: T >38C or <36C, tachycardia (HR >90), tachypnea (RR >24), WBC >12 or <4

NB: erythema may worsen initially; should improve w/ 72h of abx. Take pictures and draw margin lines to track progress.
o Additional coverage: anaerobes (if necrosis, putrid smell, crepitus, certain diabetic infections [see below], animal bite); GNRs
(cirrhosis w/ severe infection, immunocomp, certain diabetic infections [as below]); PsA (neutropenic, trauma, post-op)
o Specific associations: gas gangrene (myonecrosis)  C. perfringens; dog/cat bite  Capnocytophaga, Pasteurella; human
bite/IVDU  Eikenella; water exposure  Aeromonas (freshwater); saltwater  Vibrio vulnificus (esp. in cirrhosis)
o IVDU: discuss safe injection practices with patient. Links to printable patient resources: (CDC 1, CDC 2, HRC)
o Emerging data on long-acting injectables: oritavancin, dalbavancin, & telavancin (OFID 2018;5;S118; DIC 2018;7;1)
NECROTIZING FASCIITIS (NEJM 2017;377:2253)
• Microbiology: Type I: polymicrobial (mixed aerobes/anaerobes), risk factors include DM, immunosuppression, PVD; Type II:
monomicrobial (usually GAS, less often other Strep or Staph, Vibrio, Aeromonas), associated with TSS; myonecrosis (i.e., gas
gangrene); caused by C. perfringens, presents with gas in tissues, severe pain, toxin-mediated shock
• Risk factors: immunosupp., DM (esp. Fournier’s), cirrhosis, neutropenia, EtOH, trauma (even minor), skin/mucosal breach
• Clinical manifestations: pain out of proportion to exam, bullae, induration (risk of compartment syndrome), tissue anesthesia,
rapid skin changes (purple-red  blue-grey), crepitus (suggestive of myonecrosis); systemic toxicity, CK, lactate, Cr, WBC
• Diagnosis: early suspicion and involvement of a surgeon for surgical exploration and ID is critical
o LRINEC score ≥ 6 raises high suspicion for nec fasc; 90% Sn / 95% Sp (CCM 2004;32:1535)
• Treatment: urgent surgical debridement + Abx: (vanc or linezolid) + (pip/tazo or penem) + clinda for toxin inhibition
DIABETIC FOOT INFECTIONS ( D F I ) (IDSA Guidelines: CID 2016;63:944)
• Severity: mild (superficial ulcer, no involvement of deeper structures, erythema <2 cm); moderate (ulcer with involvement of
deeper structures or erythema >2 cm); severe (moderate + systemic signs of infxn)
• Initial evaluation: cleanse, debride, probe, culture. Check pulses/sensation, ABIs (40% will have PAD), consider XR/MRI
• Diagnosis: wound culture. Most polymicrobial w/ GPCs>GNRs, anaerobes. For mod-severe infxn: add blood Cx + ESR/CRP
o Osteomyelitis:  risk if: visible bone/probe to bone (Sn 87%/Sp 83%), ulcer >2 cm2, ulcer >1-2 weeks, ESR >70mm/h
(JAMA 2008;299:806, CID 2008;47:519)
o If suspicious for osteo, obtain plain films ± MRI ± surgical consult for bone/tissue biopsy ± ID consult
• Treatment: definitive tx based on deep cx obtained PRIOR to the initiation of abx. Appropriate wound care is critical.
o Mild: oral  target GPCs (cephalexin, amox/clav, diclox, levoflox); TMP-SMX or doxy for MRSA; 1-2 weeks tx
o Moderate/severe: IV  target GPCs, GNRs, ± anaerobes: (CTX or FQ) + flagyl; or amp/sulb. MRSA coverage w/ vanc,
linezolid, or dapto if: severe infxn, prior MRSA infxn/colonization, other RFs (see above). PsA coverage w/ cefepime or
pip/tazo if: severe infxn, immunocomp, neutropenic, water exposure, burn/puncture, nosocomial.
o If improved, may de-escalate IV to highly bioavailable PO regimen to complete course

Darshali Vyas
109
TOC

Infectious Disease Osteomyelitis

Clinical Manifestations:
• Acute: days to weeks; dull pain, local tenderness/warmth/erythema/swelling, can have systemic sx (fevers, rigors)
• Chronic: months to years; pain (absent if neuropathy), erythema, swelling; poorly healing ulcers; draining sinus tract is
pathognomonic, sequestra (pieces of necrotic bone) often present. Unusual to have fevers.
• Etiologies: hematogenous seeding (usually monomicrobial) from bacteremia ( risk if endocarditis or indwelling device)
or contiguous spread (polymicrobial) via direct inoculation after surgery/trauma.
o Hip, vertebra, pelvis: often have fewer symptoms, can present as septic arthritis
o Vertebral: pt tenderness, unremitting, >50yo (except IVDU), +/- fever (NEJM 2010;362:1022, IDSA: CID 2015;61:e26)
o Pelvic: a/w bacteremia, sacral pressure ulcers, trauma (esp. athletes), urogyn/pelvic surgery, femoral access site;
many present subacutely, may have localized pain or poorly localized, may not have fever
o Sternoclavicular: ant. chest wall swelling, pain, tenderness; may be mistaken for abscess or atypical cellulitis; can
occur via hematog. spread or post-CT surgery +/- mediastinitis (33% mortality: J Thor. Card Surg 2006;132:537).
o Mandibular: usually contiguous spread of oral flora/odontogenic infxn; often w/ anaerobes

Diagnostic Approach: (JAMA 2008;299:806) Risk Factors Likelihood Ratio

• Physical exam: probing to bone sufficient for dx in patients w/ DM (83% Ulcer area > 2 cm 7.2 (1.1-49)
Sp, 90% PPV) w/o need for further imaging (CID 2016; 63:944)
• Blood Cx: often ⊕ with hematogenous infxn involving vertebra, clavicle, Probe-to-bone 6.4 (3.6-11)
pelvis (always obtain BCxs before starting antibiotics) ESR >70 mm/h 11 (1.6-79)
• Labs: ESR/CRP (if high can use for monitoring response), leukocytosis Abnormal plain X-ray 2.3 (1.6-3.3)
• Imaging: MRI c/w osteo 3.8 (2.5-5.8)
o If >2 weeks of sx, obtain plain XR 1st. If <2 weeks of sx, suspected
vertebral osteo, or pt w/ DM, start w/ advanced imaging (MRI). If XR Normal MRI 0.14 (0.08-0.26)
non-diagnostic and story concerning, obtain advanced imaging (MRI)
o MRI: Sn 90%, Sp 82% w/ high NPV (Arch Intern Med 2007;167:125); best in DM or if c/f vertebral osteo (CID 2015;61:e26)
o CT: if MRI not available; can demonstrate periosteal reaction and cortical and medullary destruction
 CT & MRI very sens. but non-spec; false⊕ if contiguous focus with periosteal reaction, Charcot changes
o Radionuclide bone scan: very sens, but non-spec (false⊕ if soft-tissue inflamm.); option if hardware prevents MRI
• Bone biopsy: gold standard diagnostic test
o C/s Ortho vs. IR; Ortho > IR if concern for overlying cellulitis to mitigate risk of seeding. Open Bx preferred to
percutaneous. (CID 2009;48:888). If perc. Bx ⊝ and suspicion high, repeat vs. open biopsy.
o Bone Cx may be ⊕ even on abx; need 2 specimens: GS/Cx (aerobic, anaerobic, mycobacterial, fungal) + histopath
o If evidence of osteo on imaging or positive probe to bone, bone biopsy positive up to 86% of cases (CID 2006;42:57).
Biopsy not required if ⊕ blood Cx and clinical/radiographic findings of osteomyelitis.

Treatment: Empiric Tx
• Antibiotics (tx based on culture data, see table) Vancomycin + GNR coverage (typically ceftriaxone 2g
o Delay empiric tx until Bx if pt HD stable, no q24). Include PsA coverage (cefepime) for IVDU
neurologic compromise or epidural abscess
Organism-Specific Tx
o Common organisms: MSSA/MRSA, coag-neg staph,
Nafcillin 2g IV q4h; cefazolin 2g IV q8h
strep, enterococci, aerobic GNRs. Other: Brucella, MSSA
(not if a/w CNS infxn).
Mycobacteria, Fungal.
o Can consider adding rifampin if Staph + hardware MRSA or CoNS Vancomycin; daptomycin
(for biofilm) (Arch Intern Med 2008;168:805) Pen G 4 mill U IV q4h; Ampicillin 2g q4;
PCN-S Strep
o Duration: usually ≥4-6 wks, PO may be adequate CTX 2g q24; Vanc.
but discuss w/ ID (OVIVA trial). If using PO, FQ + Pen G 4 mill U IV q4h; Ampicillin 2g q4
Enterococci
rifampin most commonly used (NEJM 2019;380:425) +/- CTX 2g q24; Vanc; Dapto.
o If no residual infected bone (i.e. amputation), short CTX 2g q24h; Cipro 750 PO BID;
course abx 2-5d  up to 10-14 if associated soft GNR Levoflox. 750mg PO/IV q24; Cefepime
tissue infection. 2g IV q12h, q8h if PsA
o Consider rechecking ESR/CRP; if elevated at end of abx course, consider further w/u (NB: routine repeat MRI NOT
done b/c MRI findings take weeks to months to resolve)
• Surgical debridement: indicated if failure to respond to medical therapies, chronic osteomyelitis, complications of
pyogenic vertebral osteo (e.g., early signs of cord compression, spinal instability, epidural abscess), or infected prosthesis

Katie Miller
110
TOC

Infectious Disease Bacteremia & Endocarditis

BACTEREMIA
Evaluation (JAMA 2012;308;502)
• Signs: fevers/chills, poor food intake (J Hosp Med 2017;12:510), SIRS (high Sn, low Sp); severity of “chills” correlates w/ risk of
bacteremia: ⊕ LR of 4.7 for rigors (“shaking chills”) (Amer J Med 2005;118:1417.e1; Diagn Microbiol Infect Dis 2012;73;168)
• Sources: lines, procedures, endocarditis, PNA, UTI, osteomyelitis/septic arthritis, soft tissue infection, abscesses, meningitis
• Blood Cx: obtain prior to initiation of abx; 2 sets minimum, ideally 3 diff. periph. venipunctures over 1hr (NOT from port or IV cath. at
time of insertion); draw from central line only if c/f catheter-related infxn (criteria: catheter CFUs 3x peripheral blood OR cath. growth
2h before peripheral) (IDSA: CID 2009;49:1). Daily surveillance BCx until 48h neg Cx. Not necessary for GNRs (CID 2017;65:1776).
• TTE/TEE for Staph aureus and Staph lugdunensis. Consider TTE for high grade Strep spp. No need for routine echo for GNRs.
Empiric Management
• GPCs: Vancomycin. Staph: ID consult. Adding β-lactam (cefazolin/nafcillin) before final Cx known may improve outcomes (CID
2013;57;1760). MSSA: vanc inferior to β-lactam for long-term tx (CID 2015;61;361). See MGH PCN allergy pathway if allergic.
• GPRs: diverse resistance patterns; Call ID on call. Empiric regimen will depend on Gram stain and rod forms.
o More likely true infection in immunocomp. hosts, multiple bottles, indwelling catheters or assoc. with other GPR infections (e.g.,
Erysipelothrix [SSTI], Actinomyces [H+N infxn], neutropenia/GVHD [Clostridia spp.])
• GNRs: CTX (community-acquired) or cefepime (HCA, comorbidities); consider mero if prior MDRO/ESBL
• Other considerations: anaerobes (intra-abdominal, empyema, obstruction, cavitation)  add metronidazole or substitute pip/tazo;
Candida  micafungin + ID c/s; catheter-assoc.  generally remove line except in long-term lines; c/s ID (IDSA: CID 2009;49:1).
E N D O C A R D I T I S (AHA/IDSA Guidelines: Circ 2015;132:1435)
• Etiology: point of entry = cutaneous (40%), oral (29%), GI (23%) Modified Duke Criteria for Infective Endocarditis
• Clinical manifestations: bacteremia (f/c, anorexia, wt loss, fatigue), valv. MAJOR CRITERIA
complic. (HF, conduction abnorm.), septic emboli (CVA/CNS, pulm/PE, MI, ⊕ BCx (likely organism in 2 cultures 12 hrs apart or 3 Cx
kidneys, spleen, joints), immune-complex (arthritis, GN) 1 hr apart) or C. burnetii IgG titer 1:800
• Diagnosis: Duke criteria  2 major OR 1 major + 3 minor OR 5 minor Endocardial involvement: vegetation, abscess, dehiscence,
o TTE in all; TEE if: ⊝ TTE w/ high susp.; prosth. valve; intracardiac or new regurgitation
device; suspected complications (AHA/ACC: JACC 2014;63:e57) MINOR CRITERIA
• Monitoring: repeat BCx q24h until sterile x48hrs; serial ECGs for signs of Risk factors: valve disease, IVDU, prior infxn, indwelling
perivalvular ext. (i.e. new AVB: PPV 88% for abscess but only 45% Sn) line, prosthetic material
Temperature > 38C or 100.4F
• Microbiology: Native Valve: Strep, Staph, CoNS/Enterococcus (esp.
Vascular phenomena: septic arterial or pulm emboli,
>60yo)/Cx neg; Prosthetic Valve (<12mo.): CoNS, Staph, Enterococc./ mycotic aneurysm, ICH, conjunctival hemorrhages, Janeway
GNR/Fungal; Prosthetic Valve (>12mo.): similar to NVE (w/ more CoNS) lesions
• Indications for surgical consideration: valve dysfunction w/ HF (emergent Immunologic phenomena: GN, Osler, Roth spots, ⊕RF
indication), L-sided S. aureus/fungal/MDRO, HB/annular or aortic ⊕ BCx not meeting major criteria
abscess/destructive penetrating lesion, persistent infection 5-7d after
approp abx, PVE w/ relapsing infxn, large vegetations (>10mm on L, >20mm on R) and embolic phenomena despite abx (AATS
Guidelines: JTCS 2017;153:1241; differ slightly from AHA)
• Anticoag./antiplatelet: controversial; generally ok to continue but no indication to initiate; if CVA/ICH, hold x2 weeks.
Endocarditis Antibiotic Regimens (IDSA/AHA: Circulation 2015;132:1435; ESC: EHJ 2015;36:3075)
Empiric: NVE or PVE >12 mo. post-op: Vanc AND CTX 2g q24h; PVE w/in 12 mo. post-op: Vanc AND CTX 2g q24h AND Gent if normal GFR
PO option: POET RCT showed partial PO non-inferior to IV in L-sided IE. However no MRSA cases, only 1% IVDU included (NEJM 2019;380;415)
Organism Native Valve (NVE) Prosthetic Valve (PVE) Notes
Streptococcus such as VGS PCN MIC ≤0.12: PCN OR CTX x4w PCN MIC≤0.12: PCN OR CTX Dosing: PCN 12-18MU/d (div. q4) for
(e.g., mitis, mutans, -Option for 2w combo regimen w/ gent. OR AMP x6w +/- Gent x2w NVE & MIC <0.12; otherwise 24MU/d;
anginosus, etc.); S. bovis PCN MIC 0.12-0.5: PCN OR CTX x4w PCN MIC 0.12-0.5: PCN OR CTX 2g q24; Amp 2g q4; Vanc trough
(a/w colon cancer); Gemella AND Gent x2w CTX x6w AND Gent x6w 10-15; Gent 1mg/kg q8, target peak 3-4,
spp.; Abiotrophia (treat as  PCN MIC ≥0.5: PCN OR Amp OR CTX PCN MIC ≥0.5: PCN OR Amp trough <1
MIC) x4w AND Gent x4w AND Gent x6w Vanc monotherapy is alt. regimen but
inferior to β-lactams –attempt desens.
Staphylococcus (S. aureus, MSSA: Nafcillin OR Cefazolin x6wks Early surgical consult Dosing: Naf 2g q4; Cefazolin 2g q8;
CoNS – often methicillin- MRSA: Vanc OR Dapto x6w MSSA: Naf OR Cefazolin AND Vanc trough 15-20; Dapto 8-12mg/kg
resistant); S. lugdunensis is Note: If R-sided (85% of IVDU), can do Rifampin x6w + Gent x2w q24; Gent 1mg/kg q8, target peak 3-4,
virulent and should be Naf x2w, Dapto x2w, or Vanc x4w MRSA: Vanc AND Rifampin trough <1
treated like S. aureus x6w AND Gent x2w -Do not use cefazolin for CNS
involvement due to  penetration
Enterococcus (E. faecalis, PCN OR Amp OR Vanc (if PCN-R or Early surgical consult Dosing: as above; higher dose PCN,
E. faecium) allergic) AND Gent OR Streptomyin (if -Same as for NVE; 6w tx Vanc trough 15-20
Gent-R) x4-6w -4w Amp+Gent sufficient if NVE and <3
Alternative: Amp AND CTX x6w mo. sx; 6w if >3 mo. or PVE
VRE: Dapto + Amp. OR Linezolid
Gram-neg (HACEKs mostly, HACEK: CTX OR Amp OR Cipro x4w Early surgical consult -Rare etiology, minimal data to firmly
PsA, other GNRs possible) GNRs: β-lactam + (Aminogly or FQ) x6w -Same as for NVE; 6w tx direct treatment modalities
Fungi (Candida, Aspergillus) Candida: Ampho B 3-5 mg/kg/d (± Early surgical consult -Risk factors: TPN, lines, PPM / ICD,
flucytosine) OR Micafungin 150mg q24 -Same as for NVE; lifelong prosthesis, IVDU
Aspergillus: Voriconazole or Ampho B suppressive tx if no removal -Ophtho c/s for candidemia
• IVDU assoc IE: refer to MGH Drug Use Endocarditis Team (DUET) includes CT surgery, ID & ACT (refer: epic phrase: .MGHDUET)
Darshali Vyas
111
TOC

Infectious Disease Meningitis & Encephalitis

BACTERIAL MENINGITIS
Clinical Features
● History: 95% have ≥2 of: fever, nuchal rigidity, AMS, and HA (NEJM 2004;351:1849). Lethargy, hypothermia may be common in
elderly. Abdominal pain, peritonitis can be seen in those with VP shunts (CID 2017;64:701)
● Exam: most findings more specific than sensitive, e.g., nuchal rigidity (30% Sn / 68% Sp); Kernig’s sign (5% Sn / 95% Sp);
Brudzinski’s sign (5% Sn, 95% Sp) (CID 2002;35:46); jolt sign (worsening headache with horizontal rotation of the head) (64% Sn /
43% Sp) (Am J Emerg Med 2013; 31:1601). Meningococcemia associated with petechial rash, palpable purpura.
Diagnosis (CID 2004;39:1267)
● Blood cultures STAT; draw blood cultures BEFORE antibiotics, but DO NOT delay antibiotics for LP or imaging
● Lumbar puncture ASAP
o Head CT prior to LP only indicated if: immunocompromised, known CNS disease (mass lesion, CVA, focal infection), new
seizure, papilledema,  level of consciousness, focal neurological deficit
o Obtain opening pressure with simple column manometer (nml 200mm H2O; mean 350mm H2O in bacterial meningitis)
o For a list of what studies to send and CSF analysis/interpretation, see Procedures: Lumbar Puncture
o Repeat LP if no clinical improvement after 48 hours of appropriate antibiotics
Microbiology (NEJM 2011;364:2016; NEJM 2010; 362:146)
Community Nosocomial (intracranial procedure,
Adults 18-34 Adults 35-49 Adults >50 >48hrs in hospital, head trauma)
S. pneumoniae (50%) S. pneumoniae (75%) S. pneumoniae (76%) Gram neg bacilli (40%)
N. meningitidis (35%) N. meningitidis (10%) GBS (8%), Listeria (7%), S. aureus (10%)
H. influenzae (7%) GBS (7%) H. influenzae (6%) Coag neg Staph (10%)
GBS (6%) H. influenzae (5%) N. meningitidis (5%) P. acnes (takes 10 days to grow!)
Listeria (2%) Listeria (3%) Aerobic gram neg bacilli
Empiric Treatment (Lancet 2012;380:1693)
Adults < 50 Adults > 50 Immunocompromised Nosocomial SEVERE β-lactam allergy
Vanc (trough 15- Vanc (trough 15-20) Vanc (trough 15-20) + Vanc (trough 15-20) + Vanc (trough 15-20) +
20) + CTX 2g + CTX 2g q12h + [Cefepime 2g q8h OR [Cefepime 2g q8h OR Meropenem 2g q8h OR
q12h (consider Ampicillin 2g q4h Meropenem 2g q8h] + Ceftazidime 2g q8h OR Moxifloxacin 400mg QD
acyclovir) (consider acyclovir) Ampicillin 2g q4h (not Meropenem 2g q8h] [If >50 or immunocomp., for
needed if on Mero) Listeria: Bactrim 5mg/kg IV
(consider fungal & viral) QD div q6-12h] if not on Mero.
● Note: vancomycin is added empirically to cover PCN-resistant S. pneumo, not MRSA.
● Duration: N. meningitidis/H. flu (7d); S. pneumo (14d); Listeria (2-4 wks if immunocompetent; 4-8 wks if immunocompromised)
● Dexamethasone: greatest benefit in suspected or confirmed pneumococcal meningitis w/ GCS 8-11 ( mortality, hearing loss, and
short-term neuro sequelae in high-income countries). 0.15 mg/kg q6h x 4d; start prior to or w/ 1st dose of abx, but do not delay abx.
● CSF shunts: consult Neurosurgery for assistance with mgmt and/or shunt removal (CID 2017;64:701)
A S E P T I C M E N I N G I T I S : meningeal inflammation with negative bacterial cultures
● Clinical presentation: similar to bacterial, usually less toxic. LP: lymphocytic pleocytosis
● Etiology: Infectious: partially treated endocarditis (most common cause), enteroviruses, HACEK orgs (NB: usually NOT culture
negative!), HSV, VZV, partially tx’d bacterial meningitis (usually days-wks of tx), any stage of syphilis, Lyme, leptospirosis, mumps,
Nocardia, TB, HIV (primary infection), LCMV, fungal (e.g. Cryptococcus, Coccidioides – see below), brain abscess; Non-infectious:
autoimmune (Behcets, sarcoid, SLE, SJS), neoplastic (leukemia, lymphoma), drugs (NSAIDs, antimicrobials, IVIG)
● Treatment: if concern for encephalitis (HSV, VZV)  acyclovir 10 mg/kg IV q8h; otherwise tx is supportive. If suspect TB, call ID for
consideration of quadruple therapy with INH, RIF, PZA and 4th agent (FQ or Aminoglycoside) + steroids (Tuberculosis 2010;90:279)
Fungal Meningitis
● Causes: Primary (immunocompetent pts): Cryptococcus, Blastomyces, Histoplasma, Coccidioides, and other dimorphic fungi;
Secondary (immunocompromised pts): Candida, Aspergillus, other molds
● Diagnosis: submit CSF for acid-fast stain, India ink preparation, & cryptococcal antigen. Obtain large volumes (40-50 mL) for Cx.
● Cryptococcal meningitis treatment: ampho B IV 3-4 mg/kg qd + flucytosine PO 25mg/kg q6h (CID 2010;50:291)
ENCEPHALITIS (IDSA Guidelines: CID 2008;47:303)
● Presentation: AMS w/ focal neuro deficits or seizures. Abnormal brain function (vs. normal cerebral function in meningitis).
● Etiology: Infectious: HSV, VZV, arbo (West Nile, WEE/EEE, St Louis, Japanese), enteroviruses, HIV, CMV (extremely rare), JC,
echo, adeno, influenza, Powassan virus; Non-infectious: post-infectious demyelination (ADEM), autoimmune, paraneoplastic (anti-
Hu [(SCLC)], anti-Ma2 [testicular], anti-CRMP5 [SCLC/thymoma], anti-NMDA receptor [ovarian teratoma, idiopathic])
● Diagnosis: send CSF for HSV and VZV PCR; other viruses less common, only send if clinical suspicion high (West Nile IgM, JC,
CMV/EBV [extremely rare]); consider MRI (HSV=temporal lobe enhancement, W. Nile=basal ganglia/thalamic foci); EEG
● If Sx recur s/p Tx, consider viral relapse vs. autoimmune enceph. – high rates of autoimm. dz wks later (Lancet Neurol 2018:17:760)
● Treatment: HSV, VZV → acyclovir 10 mg/kg IV q8h; otherwise supportive care

Grace Gillis
112
TOC

Infectious Disease C. Difficile Infection

Overview (IDSA Guidelines: CID 2018;66:987; ACG Guidelines: AJG 2013;108:478)
• Risk factors: abx w/in last 3 months (all abx, including 3rd/4th gen ceph. FQ, carbapenems, clinda), age, hosp. days,
IBD, chemo/immunocomp., GI sugery, tube feeding ± PPI/H2RA. Receipt of abx by prev. pt in bed also weakly assoc.
• Pathogenesis: fecal-oral, colonized host; most often infection requires both acquisition of C. diff plus loss of gut microbial
abundance/diversity (i.e., due to abx). Symptoms are toxin-mediated: toxin A (enterotoxic) & toxin B (cytotoxic).
• Community-acquired CDI: ~1/3 new cases; p/w diarrhea w/o traditional RFs. Sources: contam. food, H2O, pets, asx
colonization in family, babies, outpt visits.  mortality vs. nosocomial (AJG 2012;107:89; JAMA Int Med 2013;173:1359).

Clinical Manifestations
• Features: watery diarrhea (≥3 loose stools in 24/hrs) +/- mucus/occult blood; fever, abd pain, isolated WBC (CID
2002;34:1585); ileus in severe infection
• Ddx: non-C. diff abx-associated diarrhea, infectious diarrhea, postinfectious IBS, IBD, microscopic colitis, celiac disease
• Severity: see table below; severe colitis may be c/b hypovolemia, AKI, marked leukocytosis, lactic acidosis, protein-losing
enteropathy; fulminant colitis characterized by hypotension/shock, ileus, or toxic megacolon & has high mortality

Diagnosis
• MGH protocol: see algorithm to right. NB: indeterminant results can be
2/2 asymptomatic (non-toxin-producing) colonization.
o GDH: enzyme produced by all C. diff strains; assay sensitive but
cannot distinguish toxigenic & non-toxigenic strains
o Toxin A/B: assay detects toxin production; high Sp. but poor Sn.
o NAAT/PCR toxin gene: high Sn. but can be ⊕ even in the absence of
active infection (strain may have toxin gene but not produce it)
• DO NOT retest within 7d w/o significant clinical change & DO NOT test for
“cure” (stool assays may remain ⊕ for up to 6w in pt w/ resolution of sx).
• CT A/P: if severe illness or fulminant colitis to assess for complications
warranting surgical intervention (e.g. toxic megacolon, bowel perf)
• Flex sig: in rare cases when alt dx suspected and need visualization/bx

Treatment (MGH ID Recs, IDSA Guidelines: CID 2018;66:987)

Category Criteria Treatment
-Vanc 125 mg PO q6h or Fidaxomicin* 200 BID
Non-severe WBC <15 AND Cr <1.5 -Alternative: Metronidazole 500mg q8 (no longer first-line due to resistance)
-D/c antiperistaltics & all non-essential abx. D/c cholestyramine (binds vanc).
Severe WBC >15 OR Cr >1.5 -Vanc 125 mg PO q6h or Fidaxomicin* 200 BID
-Vanc 500 mg PO q6h AND metronidazole 500 mg IV q8h
Hypotension/shock,
Fulminant -If ileus: can add Vanc PR 500mg in 100cc NS as retention enema Q6H
ileus, megacolon
-Surgery consultation
Duration: 10d for non-fulminant; if concurrent abx, continue through abx course and 7-14d after (no clear data on this)
*Fidaxomicin: bactericidal,  recurrence vs. Vanc, some data for rates of cure but $$$ (NEJM 2011;364:422, CID 2011;53:440,
Lancet ID 2012;12:281, Cochrane Rev 2017)

Recurrence: up to 25% within 30d; often due to relapse as opposed to reinfection

• 1st recurrence: pulse-tapered PO Vanc x6-8wks OR fidaxomicin 200mg BID x10d (unless was used for initial episode)
• 2nd recurrence: pulse-tapered PO vanc x6-8wks OR 125mg PO Vanc q6 x10d followed by rifaximin 400mg TID x20d OR
fidaxomicin 200mg BID x10d (unless used for prior episode)
• 3rd recurrence: evaluate for fecal microbiota transplant (FMT); more effective than vancomycin or fidaxocomycin alone
(NEJM 2013;368:407, APT 2015;41:835, Gastro 2019;156:1324). At MGH, consult ID (Dr. Libby Hohmann) for evaluation.

Other Considerations
• Prophylaxis: mixed data but secondary ppx w/ PO vanc (standard or reduced dose 125-250mg BID) may  recurrence in
pts w/ prior CDI receiving systemic abx (AJG 2016;111:1834, CID 2016;63:651, ICHE 2019;40:662). May also be effective as
primary ppx in high-risk patients (older, recent systemic abx) w/ 125mg daily dosing (CID 2019).
• Probiotics: insufficient evidence & therefore not in guidelines; some evidence however does support use w/ abx to
reduce abx-associated diarrhea (JAMA 2012;307:1959) and potentially prevent CDI (Gastro 2017;152:1889)

Grace Gillis
113
TOC

Infectious Disease Invasive Fungal Infections

Risk Factors: heme malignancy, HSCT >> solid organ
transplant >> patients on biologic Tx

Diagnostic Testing
Fungal markers:
• 1,3-β-D Glucan (BDG) (CID 2011;52:750): cell wall
polysaccharide, detects Candida, Aspergillus,
Pneumocystis (PCP/PJP), Fusarium, Trichosporon,
Histo, Coccidio; CANNOT detect Mucor, Rhizopus,
Blasto, Crypto; Sn 77%, Sp 86% w/ cut-off of 80
o False ⊕ w/ IVIG, albumin, HD, meds (cefepime)
• Galactomannan (GM) (Cochrane Rev 2015): detects
Aspergillus cell wall component; Sn 65-80% for serum
test (BAL 90-95%), Sp 88%. Can be used to monitor tx.
o False ⊕ w/ some TPN formulations
• Histo urine/serum Ag: UAg Sn 90% if disseminated (vs.
serum Ag 80%); Sp limited by cross-reactivity
• Crypto Ag: serum Ag Sn & Sp > 90% if disseminated,
less so for pulm. disease only
• Blastomycoses: urine > serum Ag; high Sn, but modest
Sp due to cross-reactivity
Culture: Candida grows in blood/urine Cx but Sn if deep
tissue infxn; if high concern for Coccidio, alert lab (biohazard) Notes: [1] Variable utility, e.g., sens for Histo but not Blasto. [2] 91% of MGH C.
Antibody detection: clinically most useful if testing for Coccidio glabrata is fluc-S. [3] Only approved for invasive aspergillosis/mucor. [4] In aspergillosis
vori + mica not superior to vori alone. [5] Covers all invasive fungi w/ rare exceptions,
e.g., C. lusitaniae. Always order AmphoB w/ pre & post hydration AND BMP, Mg BID.
Pathogen-Specific Information Adapted from JA Freed and AJ Hale, IDModules.com
Invasive Opportunistic Fungi
Risk factors: neutropenia, immunocompromised, TPN, IVDU, CVC, prior abdominal surgery
Spectrum of illness: sepsis (25% mortality), macronodular skin lesions (10%), endophthalmitis, endocarditis, osteo
Diagnostics: blood cultures (Candidemia never a contaminant in blood); obtain ophtho exam & ID consult
Candida Treatment: micafungin 1st line/empiric, transition to fluc if albicans, high dose fluc/vori if glabrata/krusei (or AmphoB for resistant
strains); Duration: 2 weeks after 1st neg Cx and no dissemination in candidemia, longer for deep-seated infxn
Source: non-neutropenic: lines most likely source (remove early); neutropenic: GI most likely source
Prophylaxis: fluconazole, posaconazole or micafungin (for SOT, SCT, neutropenic)
Risk factors: immunocompromised, liver disease, HIV, but can occur in immunocompetent (IDSA guidelines: CID 2010;50:291)
YEAST

Spectrum of illness: meningitis, pulmonary, cutaneous nodules, liver abscesses

Cryptococcus Diagnostics: serum/CSF CrAg, LP/CSF: OP >20, glucose, TP, lymphs, +India ink
Treatment: amphoB + flucytosine (x2 wks), followed by fluconazole (≥8 wks), serial LPs if OP>25 or symptoms of ICP
Prophylaxis: typically not recommended
Risk factors: HIV with CD4 <200, steroids equiv. to pred 20mg x4 wks
Spectrum of illness: pulm symptom onset over days/weeks, PTX, hypoxemia out of proportion to CXR (BL diffuse GGO)
Pneumocystis Diagnostics: LDH >500 (Sn not Sp), BAL > induced sputum for silver stain, 1,3-BDG (Eur J Clin Microbiol Infect Dis 2014;33:1173)
Treatment: TMP/SMX w/ steroids (if A-a >35, PaO2 <70); Alternatives: atovaquone or pentamidine; Duration: 21 days
Prophylaxis: TMP/SMX (1 SS qD or 1 DS MWF), atovaquone or dapsone; Indications: pred 20mg ≥4wk, SCT, and others
Risk factors: immunocompromised esp. neutropenia/steroids/transplant, COPD with prolonged ICU stay
Spectrum of illness: invasive pulm w/ hemoptysis, PTX, aspergilloma, sinusitis, CNS, endophthalmitis
Aspergillus Diagnostics: CT with halo sign, BAL/sputum culture, 1,3-BDG (not Sp), GM (Sp; can trend in tx, BAL > sputum)
Treatment: vori (requires monitoring of drug levels and drug-drug int) or isavuconazole; Duration: 6-12 weeks min. for pulm disease
MOLD

Prophylaxis: consider posaconazole in grade III-IV GVHD (NEJM 2007;356:348), vori in lung transplant w/ h/o aspergillus.
Risk factors: DKA, iron overload, heme malig, prolonged neutropenia, immunocomp. (Semin Respir Crit Care Med 2015;36:692)
Spectrum of illness: rhino/orbital/cerebral invasion, pulmonary, GI, renal; black eschars over ulcers, rapidly progressive
Mucor Diagnostics: culture, wet prep (non-septating hyphae with wide-angle branches), CT with reverse halo sign
Treatment: DEBRIDEMENT, AmphoB, consider posaconazole or isavuconazole (for salvage therapy or if renal disease)
Endemic Fungi
Endemic areas: Houston, OH/MS river valleys, Central America, Asia, Africa (CID 2007;45:807)
Spectrum of illness: PNA, meningitis, mediastinal disease, disseminated disease
Histoplasmosis Diagnostics: Ag from urine/serum/BAL, Cx; NB: chest imaging may appear similar to sarcoid
Treatment: itraconazole (mild-mod) or ampho B (severe), followed by itraconazole; Duration: 6-12 weeks
Prophylaxis: for both Histo and Blasto (below), consider itraconazole ppx for HIV+ with CD4 <150 in hyperendemic areas
Endemic areas: OH/MS river valleys)
Spectrum of illness: fever, PNA, ARDS in severe, ulcerated skin lesions, prostatitis, CNS
Blastomycosis Diagnostics: wet prep (broad-based, budding yeast), culture, urine > serum Ag, never a colonizer
Treatment: itraconazole (mild-mod) or ampho B (severe), followed by itraconazole; Duration: 6-12 mos
Endemic areas: SW and S US
Spectrum of illness: fever, cough, rash, HA, eosinophilia, meningitis, osteo.
Coccidiomycosis Diagnostics: serologies, cx, spherules on bx/aspirate
Treatment: fluconazole or itraconazole, consider amphoB if severe; Duration: 3-12 mos
Prophylaxis: fluconazole for 1° ppx ONLY for transplant recipients in endemic areas, not in HIV; use fluconazole for 2° ppx

Theodore Pak
114
TOC

Infectious Disease Tuberculosis

Epidemiology: world: 1 in 4 infected; US: incidence 2.8/100,000, with 5.6% HIV coinfection and 1% MDR (CDC MMWR TB US 2017)
Risk Factors: acquisition: travel hx to/from high-prevalence area, homelessness or incarceration, PWID, health care work,
racial/ethnic minority; reactivation: risk is 5% in first 2 years and 5%-10% over lifetime, but higher if pt has ≥1 of the following: HIV+,
immunosupp, CKD (esp. HD), DM, CA, txp, TNFα inhib., silicosis, malabsorption malnutrition, tobacco, EtOH (NEJM 2011;364:1441)
Screening for Latent TB: test based on likelihood of exposure + progression to active disease. IGRA preferred (Quant-GOLD test
of choice at MGH); TST acceptable (NB: only 60% spec in pts who received BCG vaccine). Both IGRA and TST are 80-90% sens
and >95% spec in immunocompetent,  sens in immunocomprom. TST Size at 48-72 Hrs Patient Population
Neither test rules in/out active TB and they can be discordant ~30% HIV, prior TB hx, CXR c/w prior TB,
≥5 mm
of the time. If ⊕ test but no risk factors, repeat either IGRA or TST silicosis, immunosuppression
prior to treatment. If ⊕ test in high risk pt, proceed to treatment. ≥10 mm Diabetes, CKD, IVDU
(ATS/CDC/IDSA Guidelines: Clin Infect Dis 2017;64:111 [Figures 1+2 ≥15 mm No risk factors
especially!]; CDC Risk Assessment Tool; TST/IGRA Interpreter) NB: size reflects skin induration, NOT erythema
Clinical Manifestations:
• Primary TB: fever, chest pain, cough, arthralgias. CXR often normal or ⊕ hilar LAD
• Reactivation TB: fever, cough, hemoptysis, night sweats, weight loss; CXR often involves posterior/apical upper lobe or
superior aspect of lower lobe, or cavitation (seen in 1/3 of pts, a/w  org. burden   infectious, AFB⊕); more common than
primary TB!
Diagnostics for Active Pulmonary and Extrapulmonary TB (J Clin Microbiol 2007:45:4064; Lancet 2007;369:9578)
Site of Infection Diagnostic Tests
Expectorated or induced, AFB smear and culture x3 ≥8hrs apart, add NAAT/PCR to one of the specimens;
Sputum
smear may be ⊝ if burden is low (~20% if HIV-, ~60% if HIV+)
Lungs

Send brushings, washings, BAL, sputum for AFB smear, NAAT/PCR (Xpert) and culture; +/- transbronchial
Bronch
biopsy. Obtain post-bronch induced sputum to increase yield.
Ascites or pleural Adenosine deaminase (ADA): if >39 units/L  high Sn/Sp; free IFN-gamma (if elevated, high Sn/Sp); AFB
fluid smear, NAAT/PCR (Xpert), & culture (poor sensitivity, helpful if positive)
At least 3 large vol (10-15cc) serial LPs if possible ( dx yield). Cell counts w/  glucose,  protein,
CSF
lymphocyte predominance;  ADA useful adjunct. Send smear, Cx, and NAAT/PCR (Xpert)
Wound/Tissue AFB-positive staining and caseating granulomas; if cytopenic, consider bone marrow biopsy
Urine UA shows “sterile” pyuria; send first AM void (large vol -50cc) for culture x3 days
Blood Can send mycobacterial cultures (isolators) for AFB
Patient Isolation: clinical decision based on likelihood of active TB
• When: cough, dyspnea, or hemoptysis + ≥1 risk factor (HIV+, foreign born, substance use disorder, homeless, recent
incarceration, prior TB or exposure). First obtain CXR; if CXR normal (and HIV- or CD4>200), TB less likely. If CXR
abnormal/equivocal (or HIV+ and CD4<200), maintain isolation and obtain 3 sputum samples for AFB smear and mycobacterial
culture as above. Consider ID c/s.
• Discontinue: if alt dx OR AFB smear neg x3 w/ very low suspicion OR on TB tx x2wks + AFB smear neg x3 + clinical improv.
Approach to Treatment (ATS/CDC/IDSA Guidelines: Clin Infect Dis 2016;63:e147; NEJM 2015;373:2149)
• Prior to starting treatment:
o General: check baseline LFTs/Cr, visual acuity/color discrimination, screen for HIV, Hep A/B/C, DM, EtOH use, pregnancy
o Before treating latent TB: need to rule out active TB (obtain relevant history, CXR)
o Before treating active TB: obtain ID consult, send TB for drug sensitivity testing
• Treatment regimens:
o Active TB: isoniazid (INH) + rifampin (RIF) + pyrazinamide (PZA) + ethambutol (EMB) x2mo., followed by INH+RIF x4mo.
o Latent TB: INH+rifapentine (RPT) qweek x12 (DOT no longer required) OR RIF x4mo. OR INH+B6 x6-9mo (less preferred)
(CDC Tx Table; CDC Tx Specifics; NEJM 2011;365;11; NEJM 2011;365;2155)
o Quinolones: 1st line w/ MDR-TB, avoid in bacterial PNA if suspicious for active TB ( dx yield & risk of resistance)
• Drug-resistant TB: suspect if previously treated, treatment failure, from prevalent area (India, China, Russia, S. Africa), or
known exposure. Treatment regimen depends on drug susceptibility profile; usually for 12-24 month tx course. 80% mortality
• HIV co-infection: if CD4<50 or CD4>50 with severe clinical disease but not meningitis, start ART within 2 weeks after starting
TB therapy. Discuss with ID.
• Extrapulmonary TB: highly variable presentation/therapy, duration depends on site of infection & response. For meningitis,
glucocorticoids confer 25% short term RR reduction in mortality (Cochrane Rev 2016)
• Medication side effects: hepatotoxicity (INH, RIF, PZA), optic neuritis (EMB), peripheral neuropathy (INH  add pyridoxine [B6]
with initiation of treatment), orange bodily fluids (RIF), numerous drug-drug interactions (especially RIF)

Daniel Gromer
115
TOC

Infectious Disease HIV/AIDS & Opportunistic Infections

Definition and Clinical Manifestations:
• Acute HIV: mono-like syndrome  rash, LAD, fever, oral ulcers, pharyngitis, myalgias, diarrhea; presents 3-6 wks after infection
• AIDS: HIV+ with: CD4 count<200 or CD4 T-cell <14% of total lymphs or AIDS-defining illness
HIV Screening and Diagnostics:
• Screen all 13-64yrs once, every pregnancy, if another STI, IVDU (annually), commercial sex workers (CSW), MSM >1 partner since last
test, partners of all high-risk pts. In MA: opt out verbal consent (“We’ll be conducting a number of tests, including for HIV”)
• 4th gen combined HIV 1/2 Ab/p24 Ag assay: mean detection limit @ 18d (5d sooner than 3rd gen.) (STD 2017;44:739)
• HIV RNA PCR/viral load (VL): mean 12d, high Sn/Sp but slow, expensive; used for: 1) concern for acute HIV (Ab/Ag testing are negative
early in disease course); 2) confirmation of HIV diagnosis; 3) viral load
Prophylaxis
• PrEP (Pre-Exp): pts w/ high risk of HIV (sero-discordant couples, STI in last 6mos, inconsistent condom use in MSM, IVDU, high risk sex,
CSW, transgender pts). If partner of pt is HIV+ but has undetectable VL, risk of HIV transmission is near 0! (JAMA 2016;316:171)
o Regimen: TDF/FTC (Truvada) QD  risk (40-75%, >95% w/excellent adherence), d/c when risk is no longer present.
o Event-driven PrEP (“2-1-1”) is also option: double dose 2-24h before sex, then 1 dose each day after. Prior to initiation HBV/HCV; STI,
Cr, pregnancy q3mos. TAF/FTC (Descovy) FDA-approved, but not for women w/ receptive vaginal intercourse.
• nPEP (Non-Occupational Post-Exp): persons presenting at ≤72hrs after non-occupational high-risk exposure from HIV+ source; case-
by-case decision if HIV status of source unknown; test w/ HIV Ab/Ag at baseline & test for STIs, HBV, HCV.
o Regimen: TDF/FTC (Truvada) + [raltegravir or dolutegravir] x28d; if ≥1 course nPEP in last year, consider PrEP
Basic Evaluation for Newly Diagnosed HIV/AIDS Patients:
• CD4 count, VL, genotype/resistance testing, CBC w/diff, BMP, U/A, LFTs, lipase, lipids, Hep A/B/C, hCG, cervical and/or anal pap, RPR,
GC/CT, PPD or IGRA; CMV, VZV, toxo, mycobacterial BCx if CD4 < 100, dilated eye exam if CD4<50
• Initiate ART early through referral (p36222) at all CD4 levels to decrease mortality (NEJM 2015;373:795). In many cases, ART can be
initiated on site, even prior to genotype return, even in high-risk patients (AIDS 2018;32:17) Make sure ID is involved in this decision.
• Treatment as Prevention (TasP): ART initiation has public health benefit to prevent HIV transmission (NEJM 2016;375:830)
Treatment for ARV-Naïve Patients: many options, choose based on indiv. pt factors, drug-drug interactions, resistance testing
• 1st line: 2 NRTI “backbone” (typically TAF/FTC or TDF/FTC [Truvada]) + 1 from diff. class, typically integrase inhibitor
Hospital Management of HIV/AIDS Patients:
• If patient is on ART: determine regimen & adherence; typically continue ARVs (interruptions can  disease progression)
o If must hold ARVs because of significant non-adherence or recent severe adverse reaction, hold all ARVs and consult ID
o Beware of drug-drug interactions, particularly with boosted PIs (e.g. PPIs, check https://www.hiv-druginteractions.org/)
• If patient not yet on ART: prioritize OI tx, ppx, consult ID for help on early inpt vs outpt initiation of ART
• IRIS: worsening sx of underlying infxn (TB, MAC, CMV, others) 1-3 mos post-ART initiation, high risk if low CD4 count
o Early ARV initiation safe after OI dx, except in crypto meningitis (PLoS ONE 2009;4:e5575)
1. Opportunistic Infections Prophylaxis Summary Recommendations for HIV in the US (JAMA 2018;320:379)
CD4 Opportunistic Infection Prophylaxis Criteria for D/C
Influenza, HAV, HBV, HPV, VZV, S. Vax: Flu; HAV, HBV, HPV, PCV 13, PPSV23 after 8 wks;
All None
pneumo, TB no live vax w/ CD4<200; latent TB: INH/B6 x 9mo
TMP-SMX DS QD (preferred) or 1 SS QD or dapsone
<200 Pneumocystis jirovecii (or hx of thrush) CD4 >200 x 3mo
100mg QD or atovaquone 1500mg QD
<150 Histo (only if endemic; not in MA) Itraconazole 200 mg PO QD CD4 >150 x 6 mo
TMP-SMX DS QD or dapsone 50mg QD +
<100 Toxoplasma CD4 >200 x 3mo
pyrimethamine 50mg qWk + leucovorin 25 qWk
<50 Mycobacterium avium complex (MAC) Ppx no longer recommended if ARVs started CD4>100 x3mo
Treatment of OIs in Adults with HIV/AIDS (also see Invasive Fungal Infections)
Pathogen Diagnosis 1st Line Treatment
(Azithro 600mg qday or clarithro 500mg
MAC Cx (blood/sputum/bronch/marrow/tissue), AFB stain
BID) + ethambutol 15mg/kg QD
Typically induced sputum (Sn 50-90%) or BAL wash TMP-SMX (15-20 mg/kg/day of TMP IV) x
Pneumocystis jirovecii
(Sn >90%) for dx; Cx not reliable 21d, +/- steroids if PaO2 < 70 or A-a >35
CT/MRI: ring-enhancing; most pts have IgG+ but not Pyrimeth 200mg x1; then by weight +
Toxoplasma gondii
IgM+, brain Bx if Rx fails (r/o CNS lymphoma) sulfadiazine + leucovorin x6wks
Oral/genital: DFA, PCR, viral cx Acycl. 400 PO q8h or valacycl. 1g PO q12h
Herpes Simplex Virus (HSV) x5-10d; CNS: acycl. 10mg/kg IV q8h x3wk
CNS: LP + CSF PCR
Retinitis: exam; Colitis/esophagitis: bx; PNA: bronch; In general: ganciclovir or foscarnet IV,
Cytomegalovirus (CMV) switch to PO w/improvement
Neuro: LP with PCR, brain Bx, Blood: PCR
PML MRI: non-enhancing lesions; LP with JCV PCR Only disease-modifying tx is ARVs
Cryptococcus (rare in US Serum and CSF CrAg, serum and/or CSF culture, Ambisome + flucytosine x 2wk then high-
pts)  CSF opening pressure dose fluc x 8wk then low-dose x1yr
Mucocutaneous candidiasis Clinical dx. White plaque removed w/tongue depressor, Oral: fluc 100mg PO x7-14d vs nystatin
(esophageal/oral) +KOH; EGD + Bx S&S; Eso: fluc 100-400mg PO/IV x14-21d)

Rahul Nayak
116
TOC

Infectious Disease Transplant ID

General Principles (Am J Transplant 2017;17:856)
• Early infections: donor-derived, nosocomial/reactivation early, followed by OIs as immune suppression peaks
• Late infections: community-acquired infections, fungal infections
• Pre-transplant evaluation:  mumps IgG, measles IgG, rubella IgG, VZV IgG, HAV IgG, HBV (sAb, sAg, cAb), HCV, HIV, syphilis,
CMV IgG, EBV IgG. Consider: T. Spot, redemic fungi, T. cruzi, Strongy Ab. Goal is to immunize or treat prior to solid organ transplant.
Infections After Hematopoietic Stem Cell Transplant Infections After Solid Organ Transplant
<4wk. 1-12mo. >12mo.
Adeno, BK
EBV, HCV, HBV
Donor- HSV

Virus
derived HHV 6,7 HPV, JC/PML, PTLD
VZV
CMV, community-acquired
Aspergillus Aspergillus

Fungus
Candida Endemic fungi Crypto
Mucor PCP Mucor

Surg.- Listeria, Nocardia

Bact.
related TB, non-TB mycobacteria
Toxo, leishmaniasis

Para.
HSCT Prophylaxis (J NCCN 2016;14:882) Strongy, T. cruzi
Adapted from Am J Transplant 2017;17:856
- Candida: fluconazole 400mg PO (d0-365 at MGH)
- HSV/VZV: famciclovir 250mg PO BID or acyclovir (d0-365)
- PJP: TMP/SMX SS QD or DS TIW; also covers Toxo, Nocardia, Listeria; alternative: atovaquone, dapsone (d0-180 or 365)
- High-risk HBV reactivation: entecavir, tenofovir, or lamivudine (duration varies)
- CMV: pre-emptive monitoring of VL in high-risk pts & initiate tx (valganciclovir or ganciclovir) when  vs. ppx in high-risk pts. Letermovir
(CMV-specific; no activity against HSV) can be considered for ppx in select cases (NEJM 2017;377:2433)
Select Transplant-Associated Infections
Pathogen Clinical Syndrome Diagnosis/Treatment Additional comments
Dx: serum PCR +/- bx involved organ (GI
Most common infxn s/p solid tx.
bx, BAL, CSF). Serum PCR may be ⊝ in
P/w fever, leukopenia, +/- Highest risk: D+/R- in SOT and D-/R+ in
colitis (15%).
hepatitis, colitis/esophagitis, HSCT. May  rejection and
CMV Tx: c/s ID. PO valganciclovir vs. IV
pancreatitis, retinitis, susceptibility to OIs. Repeat VL testing
ganciclovir. Consider resistance testing if
meningoencephalitis should be at least 7d apart (t1/2 of CMV).
not improving (UL97, UL57).
VL not comparable between labs.
Alt Tx: foscarnet or cidofovir
Dx: BAL PJP stain/PCR +/- TBBx, LDH, 1-
In contrast to HIV, there is limited data
Subacute dyspnea, hypoxemia, 3-β-D-Glucan
PJP to support the routine use of
fevers. Tx: TMP-SMX (15-20 mg/kg/day of TMP IV
glucocorticoids
in divided doses q6h)
Nephritis w/ AKI, ureteral Dx: BK PCR +/- biopsy
BK Virus Mainly in renal tx and HSCT pts
stenosis, hemorrhagic cystitis. Tx:  immunosuppression
Hyperinfection syndrome:
fever, n/v/d, cough / wheeze /
Ivermectin 200 ug/kg/day until stool ⊝ x2 Identify at-risk individuals and treat pre-
Strongyloides hemoptysis, no eos with
weeks transplant
hyperinfection; 2° polymicrobial
bacteremia (e.g., GNRs)
Symptom-Driven Diagnostics
CXR, CT chest w/ contrast, induced sputum (GS/Cx, consider AFB stain, MB Cx, PJP stain), legionella urine Ag (Sn 70-
SOB 90% / Sp 100%), viral resp panel. If cavitating or nodular lesions: β-D-glucan/galactomannan, crypto Ag, urine/serum
histo Ag, early bronch w/ BAL. NB: engraftment syndrome, cryptogenic organizing PNA also on DDx
Stool Cx, O+P (consider micro add-on for: Cryptosporidium, Isopora, Cyclospora, Microsporidia), C. diff, CMV PCR. If high
Diarrhea
suspicion for viral colitis (e.g., CMV, adeno), c/s GI re: colo w/ Bx. In HSCT, consider typhlitis and GVHD.
CT head, LP (OP, GS/Cx, glucose, TP, HSV PCR, crypto Ag, save extra for additional tests). NB: fludarabine, cytarabine
AMS/HA
and calcineurin inhibitors (via PRES) can also lead to encephalopathy
Rash GVHD, medication allergy, HSV, cellulitis, fungal infection
Leukopenia CMV PCR, EBV PCR, consider tick-borne illnesses during the correct season or if frequent blood transfusions
If post-HSCT, consider viral (HAV, HBV, HCV, EBV, CMV, adenovirus + more rarely enterovirus and HHV6), Candida, and
Hepatitis
non-infectious (GVHD, iron tox., meds, hepatic sinusoidal occlusion syndrome)
AKI UA/UCx, renal U/S, BK PCR if renal transplant. Consider med toxicity and check levels (tacro, cyclosporine)
Rahul Nayak
117
TOC

Infectious Disease STIs & Travel Medicine

SEXUALLY-TRANSMITTED INFECTIONS
Routine STI testing in asymptomatic adults: HIV, syphilis, GC, chlamydia
Lesions Symptoms Diagnosis Treatment
1°: painless, firm, round ulcer 1st step: treponemal testing (Sn 96% / 1°/2°/early latent: PCN G
2°: fever, condyloma lata of skin/mucus Sp 98%); detect IgG specific to T benzathine 2.4 million units IM x1
membranes, LAD, uveitis pallidum; ⊕ for life. 3°/late latent: PCN G benzathine 2.4
Syphilis 3°: aortitis/aneurysm, disseminated 2nd step: confirm w VDRL/RPR titers million units IM qweek x3
(T pallidum) gummas, CN palsies, tabes dorsalis (Sn 86% / Sp ~90%) to track response Neuro: IV PCN G 3-4 million units
(impaired gait, sensation, reflexes) to tx; detect anti-cardiolipin Ab; q4 hours/continuous infusion x10-
Latent = asymptomatic nonspecific. CSF titres if concern for 14d. (CID 2011;53:S110)
Painless

- Early latent <1yr; Late >1yr/unknown neurosyphilis (IJSTD AIDS. 2006;17)

1°: transient, painless anogenital lesion Positive IgG/complement fixation + Doxy 100mg bid x21d + aspiration
LGV 2°: 2-6w later, painful inguinal LAD clinical diagnosis; NAAT in pipeline of buboes
(C trachomatis) 3°: “Genitoanorectal syndrome” pelvic &
abd LAD +inflamm diarrhea/abscess
GI Painless progressive beefy red Presence of Donovan bodies in Azithro 1g qwk/ 500mg qd x3
(K granulomatis) ulcerative genital lesions in tropics phagocytes on bx specimen weeks, until healed (MMWR 2015;64)
Prodrome  painful vesicles  ulcers Confirm clinical dx with PCR or viral Cx Acyclovir/Valacyclovir. Episodic tx
Genital herpes 1° infection: possible systemic sxs +/- vs. chronic suppressive tx (if 6
(HSV2>1) LAD outbreaks/yr)
Painful

Painful genitals/perianal ulcer 5-7d Usually clinical with negative Azithro 1g or CTX 250mg IV; PCN
Chancroid post-exposure w/ inguinal LAD +/- syphilis/HSV; also gram stain, Cx, PCR often also given empirically for
(H ducreyi) drainage in tropics in some labs syphilis; evaluate partners as well
Discharge Symptoms Diagnosis Treatment
♀: mucopurulent cervicitis, urethritis, ♀: vaginal swab NAAT (Sn >65%) > Ceftriaxone 250mg IM +
Gonorrhea PID (abd pain, adnexal/cervical urine NAAT (Sn >57%) azithromycin 1g PO
(N gonorrhoeae), tenderness, +/- fever), frequently asx
♂: dirty catch urine NAAT NB: consider Cx to test for
♂: dysuria + purulent discharge, All: consider pharyngeal/anal swab resistance- Asia (EID 2018; 24:381);
Chlamydia
epididymitis based on hx (pts can self-swab) Doxy not alternative to azithro but
(C trachomatis)
All: pharyngitis (BMJ Open 2019;9) used in PID to treat C trachomatis
Suspect in pts who fail tx for GC/CT Testing unavailable in USA, but: If failed tx for GC/CT & trich:
Mycoplasma ♀: cervicitis, PID, often asymptomatic ♀: vaginal swab NAAT moxifloxacin 400mg x7d (CID
genitalium ♂: dysuria + purulent discharge, ♂: urine NAAT 2015;60)
proctitis
♀: purulent malodorous discharge, Wet mount  vaginal swab NAAT Metronidazole 2g PO or tinidazole
Trichomoniasis pruritus, dysuria, frequency, 2g PO +/- GC/CT tx; treat partner
(T vaginalis) dyspareunia
♂: usually asymptomatic

TRAVEL MEDICINE
Pre-Travel Evaluation
• Patient: medical conditions (immunosuppressed?), allergies (esp. vaccines), pregnant/planning to get pregnant, immunization hx,
prior travel history (experience with malaria prophylaxis/prior travel related illlnesses), med list
• Trip: place, duration, season, purpose of a trip, itinerary (urban vs. rural, cruise ship, exposure to animals, cave / water exposure)
• Counsel re: safety: sunscreen (SPF 50+), seatbelt/helmet, sexual practices etc. Provide patient with CDC Travel Tips.
Immunizations
• Ensure routine vaccinations are up to date then use MGH developed “Pre Travel PREP” or CDC site to get country-specific recs
• Common travel vaccines: Yellow Fever, HAV, Typhoid, Japanese Encephalitis, pre-exposure rabies, Cholera
Malaria Prophylaxis (typically South/Southeast Asia, Africa, Central/South America)
• Vector avoidance: DEET, permethrin, mosquito nets, cover exposed skin
• Rx per CDC tool based on resistance pattern. Start ~1 week before travel and up to 4 weeks after. Daily Rx: atovaquone-proguanil
(Malarone), doxy, primaquine. Weekly meds: mefloquine, chloroquine
Traveler’s Diarrhea
• Common pathogens: ETEC > C. Jejuni, Shigella & Salmonella spp, Giardia, E. histolytica, Strongyloides
• Tx: mild / moderate: loperamide/bismuth; severe (fever, interference w/ activity, dysentery): azithro 1g x1 > FQ (CDC Yellow Book)
Infections in a Returning Traveler
• Assess if life threatening illness or if transmissable via respiratory droplets, contact, etc (isolate pts)
• Broad ddx, consider geography, exposure risk, pt vulnerability, incubation periods. Common culprits: Malaria, dengue, TB, STIs, tick-
borne, typhoid fever, regular infections (CAP/UTI etc.) (NEJM 2017;376:548)
Ryan Dodge and Brady Page
118
TOC

Infectious Disease Tick-Borne Diseases

L Y M E D I S E A S E (IDSA Guidelines: CID 2006;43:1089; Lancet 2012;379:461; NEJM 2014;370:1724)
• Etiology: Borrelia burgdorferi, transmitted by Ixodes scapularis (deer tick). Endemic regions: NE/Midwest US & Europe in summer.
• Western blot interpretation: IgM considered positive if 3 particular bands present; IgG positive if any 5 of 10 total bands present
• NB: always consider possible co-infection w/ other tick-borne illnesses (see below)
Disease Stage Presentation Diagnosis Treatment
- Erythema migrans (spreading Clinical dx only (serologic If EM: doxycycline 100mg PO BID x 14d
Early localized red patch +/- central clearing) conversion >1wk after EM (amoxicillin 500mg TID x 14d if pregnant)
(within 1 month) - Fever, fatigue, myalg./arthralgia appears) If no EM: consider serology in 2 weeks
- Multiple EM lesions 2-Tier Testing: Abx: CTX 2g IV QD OR doxycycline
Early - Neuro (CN palsies, meningitis, 1. Screening ELISA IgM/IgG 100mg PO BID
disseminated mononeuritis, radiculopathy) 2. Western blot if serology
(days to months) - Cardiac (heart block, positive or equivocal Duration: 14-28 days depending on
myopericarditis) indication and severity (IV abx for
IgG becomes positive after 6- encephalitis or severe cardiac
- Arthritis (mono- or polyarthritis
Late 8wks; if only IgM positive on involvement)
of large joints, esp. knee)
disseminated ELISA/Western blot after 6-
- Neuro (mild encephalopathy,
(months to yrs) 8wks = false positive
peripheral neuropathy)
• Recurrent symptoms after completion of treatment course are likely re-infection, NOT relapse (NEJM 2012;367:1883)
• Chronic Lyme disease: not a scientific entity; while post-infectious syndromes (fatigue, depression) are reported in up to 20% of pts
after treatment for Lyme disease, these are NOT due to persistent Lyme infection  abx NOT indicated (NEJM 2007;357:1422)
• Prophylaxis: doxy 200mg PO x1 IF Ixodes tick attached & engorged ≥36h in endemic area AND pt presents <72h after tick removed
O T H E R T I C K - B O R N E I L L N E S S E S (CDC Guide: includes maps)
Disease Vector / Geography Presentation Diagnosis Treatment
Common: fever, myalgias, HA - PCR
Anaplasmosis I. scapularis tick
- Morulae seen in 20-80%
(HGA) NE, MW, Atlantic Uncommon: rash rare in HGA, 36% in
of neutrophils on smear
HME Doxy 100mg BID x 10d
A. americanum - PCR
Ehrlichiosis Labs: leukopenia, thrombocytopenia, - Morulae seen in 0-20% of
(Lone-star tick)
(HME) ALT/AST, CK
South, MW, Atlantic monocytes on smear
Mild-to-moderate: viral-like sx (fever, Pref: atovaquone +
fatigue, chills, sweats), less commonly - Blood smear: ring forms azithromycin (dose
I. scapularis tick arthralgias, myalgias, HA, n/v, cough within RBC: Maltese cross
Endemic to the rare; malaria appears varies with severity)
Babesiosis Severe: immunosupp/HIV+, similar. NB: parasitemia
regions surrounding Alt: clinda + quinine
(NEJM (functionally) asplenic, rituximab, >50 determined by % infected
Cape Cod, Southern Exchange transfusion if
2012;366:2397) y/o; can p/w severe hemolysis, DIC, RBCs on smear
NE, NY, north central severe hemolysis,
ARDS, multiorgan failure
MW - PCR: Sn & Sp but $$; not parasitemia ≥10%, or
Labs: DAT-negative hemolytic routine at MGH
anemia, thrombocytopenia, ALT/AST end-organ failure
Borrelia miyamotoi I. scapularis tick Fever, HA, chills; leukopenia, - PCR > serology
(NEJM Same regions as thrombocytopenia, ALT/AST (mimics NB: EIA cross-reacts w/ B. Doxy 100mg BID x 14d
2013;368:2910) Lyme disease anaplasmosis); rash usually absent burgdorferi
Fever, encephalopathy
I. scapularis tick MRI: T2/FLAIR hyperintensities (esp. - Serum/CSF serology
Powassan virus Supportive; consider
Summer in NE, MN, basal ganglia enhancement) (send-out test to state lab)
(CID 2016;62:707) steroids, IVIG
WI, NY CSF: lymphocytic pleocytosis (can also - Consider WNV
be neutrophilic)
Early (3d): non-specific (fever, myalgia,
HA, conjunctivitis, N/V/abd pain) - Clinical dx initially; start
empiric tx Doxy 100 mg BID x 5-7d
Dermacentor tick Late (2 wks): fever/HA/rash triad in
Canada, Mexico, ~60%; rash (90%) progresses from - Serology: undetectable and at least 3 days after
Rocky Mountain Central/South wrist/ankle (palms/soles)  trunk; rash until 7-10d after sx onset; afebrile (still give doxy to
Spotted Fever America, OK, TN, macular (3d)  petechial (6d) need to repeat at kids & pregnant women)
(Rickettsia rickettsii) AR, MD, VA, NC, Severe: shock, DIC, organ failure; 20% convalescence (14-21d
after sxs onset) to confirm Chloramphenicol is the
SC; peaks spring & mortality if untreated; 5% if treated. only alternative, if
summer dx
Labs: leukocytosis or leukopenia, - Skin biopsy: 70-90% Sn / available
thrombocytopenia, hypoNa, AKI, 100% Sp
LFTs

Brady Page
119
TOC

Infectious Disease Fever of Unknown Origin

Definition (CCM 2008;36:1330, Medicine 1961;60:1)
• Clasically defined as: temp >38.3C, assessed on multiple occasions, for ≥3 weeks without an obvious cause or etiology
• FUO is far more often caused by an atypical presentation of a more common disease than by a very rare disease.

Workup Etiologies of FUO

• Ddx: most commonly ID vs. cancer vs. rheumatologic vs. meds (see box) Abscess (abdomen/pelvis, perianal, brain,
o In 25-50% of cases, no source is identified (Medicine 2007;86:26) dental), HIV, EBV, CMV, HHV6-8, HBV/ HCV,
• History: verify fever trend/pattern, past medical history including dental endocarditis (fastidious/HACEK, nutrionally
history and history of immunocompromise, travel, animal/tick/mosquito/ variant Strep), nosocomial infection, vascular
environmental/food exposures, h/o blood product transfusions, sick contacts, graft infection, osteomyelitis, septic arthritis,
sexual history, illicits, occupation, TB history, meds, vaccines, family history,

Infectious
sinusitis, prostatitis, TB (miliary), tick-borne
valve disorders, recent procedure/hospitalization, changes in weight/anorexia infections, endemic fungi (e.g.
• Exam: assess for dental caries/thrush, sinus and temporal artery tenderness, cocci/histo/paracocci), malaria, cat-scratch
thyromegaly, CV murmur, abd tenderness, HSM; inspect eyes, fundi; perform disease, toxoplasmosis, Q fever (Coxiella),
complete lymph node, skin/nails, rectal, and joint exam brucellosis, Bartonella, salmonella, typhus,
mellioidosis, schistosomiasis, visceral
Diagnostic Testing leishmaniasis, Whipple’s disease,
• Initial: CBC w/ diff, BMP, LFTs, ESR/CRP, UA/UCx, BCx x3 (diff. sites), CXR lymphogranuloma venereum
(AJM 2015:128;1138e1) Lymphoma, leukemia, MM, myeloproliferative

Malig.
• Inflammatory markers: disorders, RCC, HCC, pancreatic, cervical,
o ESR: measure of chronic inflammation. Falsely elevated in ESRD (can mets, myxoma
be very high), paraproteinemia, anemia, obesity, and advanced age. Cryo, PMR/GCA/TA, RA, Adult Still’s
Correct for age  (age / 2) for males and (age / 2) + 10 for females.

Rheum.
(JRA)/MAS, SLE, dermato/polymyositis,
o CRP: rises more acutely than ESR; may be falsely low in cirrhosis sarcoid, HSP, PAN, Kikuchi’s, Takayasu’s,
• Other labs to consider: IGRA, HIV Ab/Ag/PCR, RPR, LDH, TFTs, Behcet’s, GPA/MPA/EGPA
SPEP/SFL, ANA, ANCA, RF/CCP, cryo, CK/aldolase, EBV serologies, CMV Drug fever, serotonin syndrome, NMS,
PCR, ferritin, blood smear, HBV/HCV DVT/PE/hematoma, hypothalamic dysfunction,
• Imaging (Arch Intern Med 2003;163:545): CT C/A/P (19% Sn / 71% Sp), LENIs, pheo, thyroiditis, alcoholic hepatitis, cirrhosis,
Other

TTE, FDG-PET/CT (Sn 50-100% / Sp 46-90%), tagged WBC scan (Sn 60- IBD, factitious, HLH, familial periodic fever
75% / Sp 82-92%), maxillofacial CT syndromes (FMF, Hyper-IgD Syndrome,
• Tissue diagnosis: biopsies of LN, liver biopsy (14-17% yield), BM (low yield Schnitzler’s, TRAPS)
at 0-2%), temporal artery biopsy (GCA), kidney (RPGN), consider LP in *bold = common causes (AJM 2015;128:1138e1)
patients with CNS findings

Treatment
• Try to avoid empiric antibiotics and observe (unless hemodynamic instability or immunocompromised)
• Discontinue possible offending medications
• If high suspicion for GCA/vasculitis, strongly consider empiric steroids (prior to biopsy) to prevent vision loss / end-organ damage
• If extensive workup is negative, prognosis is usually good and most cases defervesce (AJM 2015:128;1138e1)

Etiologies by Patient Population

Patient Population Etiologies
General Infection 16-35%, rheumatic 13-36%, malignancy 3-10%; undiagnosed 16-51%
(Am J Med Sci 2012;344:307)
Elderly patients Infection 35% (abscess 12%), rheum 28% (most common GCA/PMR), malignancy 19% (heme 10%,
(Am Geriatr Soc 1993;41:1187) solid 9%)
Uncontrolled HIV* Infection 88% (dMAC 21%, PJP 13%, CMV 11%, histo 7%, other viral 7%), malignancy 8%
(CID 1999;28:341) (lymphoma 7%)
Neutropenic (refractory to abx) Fungal infections 45%, bacterial infections 10% (resistant, biofilms), GVHD 10%, Viral 5%, Misc 25%
(NEJM 2002;346:222)
*Mean CD4 count 53/mm3
Select Causes of FUO
• Drug fever: diagnosis of exclusion that broadly refers to any febrile response to medication. Can occur at anytime while taking drug,
with resolution ~2-3 days post-cessation (can take up to 1 week)
o Fevers can be in excess of >102F. Rarely, have accompanying signs (e.g., morbilliform rash, LFT elevations, eosinophilia)
o Mechanisms of drug fever include: hypersensitivity reaction (including SJS/TEN), dysfunctional thermoregulation, aseptic
meningtitis, Jarisch-Herxheimer reaction, NMS/serotonin Syndrome, G6PD deficiency
o Medications commonly assoc. with drug fever: antimicrobials (β-lactams, sulfa, macrolides), AEDs, dexmedetomidine, chemo
• VTE: DVT, PE, and thromboplebitis may cause fever. Likely low grade (6% w/ fever >101F and 1.4% >102F) (Chest 2000;117:39)
• Central fever: most commonly associated with SAH, intraventricular bleed, brain tumors (JAMA Neurol 2013;70:1499)

Nicole Curatola
120
TOC

Infectious Disease Rare Diseases

Organism/Syndrome Epi & Transmission Symptoms Labs Diagnostic Tests Treatment
Africa, Latin Am, Asia, MidEast, 12-35d incub. (up to yrs
Anemia, plt, AKI, BinaxNOW (RDT) +
Malaria Eastern Europe if P. vivax); fever, HSM,
LFTs, glucose, thick/thin blood smear Variable, d/w ID
(Plasmodium spp) AMS, jaundice,
Anopheles spp. (nocturnal) acidemia w/ Giemsa
petechiae
Mosquito-borne viruses: Dengue, Chikungunya, and Zika are often indistinguishable clinically/epidemiologically; consider testing for all 3 if concerned
Dengue fever (DENV India, Asia/Pac, Africa, Lat Am Fever, retro-orbital HA, Lymphopenia, Serum RNA early  Rest, fluid; avoid
serotypes 1-4; A. aegypti and A. albopictus arthralgia “break bone thrombocytopenia, IgG/IgM (cross-rxn w/ NSAIDs due to 
Flavivirus) (diurnal feeders) fever”, petechiae, shock Hct Zika); tourniquet test hemorrhagic sx
Chik: PCR if <7d sxs;
Chikungunya fever Africa, Asia/Pac, Caribbean, Lat 1-14d incubation; fever Chik: lymphopenia,
Am, S USA serology if ≥7d.
(Alphavirus) (>102 in chik), HA, thrombocytopenia, Rest, fluid; avoid
Zika: serum/urine PCR
A aegypti and A albopictus (diurnal polyarthrlagia, rash, LFTs, AKI
if <14d sxs 
NSAIDs unless
Zika virus feeders); sexually-transmitted conjunctivitis, GBS + definitely not dengue
serology/plaque reduct.;
(Flavivirus) (Zika) fetal microcephaly (Zika) Zika: labs freq. nml
serology if ≥14d of sxs
West Nile virus Africa/MEast, Europe, Americas Asx; fever, HA, myalg., CSF pleocytosis Serum + CSF Abs >
Rest, fluid
(Flavivirus) Culex spp. (nocturnal feeders) 1% meningitis (lymphs) PCR
Leishmaniasis, C/S America, S Europe, Mid East, CL: painless ulcer(s), Varable, call ID; abx
VL: cytopenias, Clinical dx, tissue
cutaneous/visceral E Africa, S Asia regional lymphaden. if superinfected
LFTs smear/cx; rarely Ab
(Leishmania spp) Lutzomyia/Phlebotomus sandfly VL: fever, HSM, wt lesions
Bacterial Zoonoses: Coxiella, Bartonella quintana, and Brucella are important causes of culture-negative endocarditis
Cat scratch disease Worldwide Fever, LAD 1-3 wks, PCR 1-3d; Ab 1-2wks;
ESR/CRP,LFT Regimens vary
(Bartonella henslae) Cat bite/scratch, fleas neuro, ocular histology
Worldwide; tropics > temperate Fever, HA, myalgia, Outpt: doxy 100 bid
Leptospirosis AKI, ALF, rhabdo,
Water contaminated by animal jaundice, conjuc. Serology if 3-5d sxs x7d; inpt: PCN G,
(Leptospira spp.) anemia, hypoNa,
urine/sewage, esp. after floods suffusion doxy, or CTX
Q fever Worldwide (not New Zealand) Fever, HA, myalgia, AST/ALT, Bili, PCR if <7d sxs,
Doxy 100 bid x14d
(Coxiella burnetii) Aerosolized ungulate fluid PNA, endocarditis Plt, CK serology if ≥7d
Worldwide
Brucellosis Fever, arthritis AST/ALT, WBC Doxy 100 bid x6 wks
Dairy products, ungulate contact, Serology if 7-1d sxs
(Brucella spp) (SI/spine), endocarditis with relative lymph + gent/rifampin
lab exposure
N America, Europe > Asia Nonspecific;
Regional LAD; Serology if sxs ≥2wks; Streptomycin 7-10d;
Tularemia ESR/CRP; nl
6 syndromes: PNA, Cx cysteine+ media; cipro or doxy 10-21d
(Francisella tularensis) Arthropod bite, animal contact WBC, LFTs, Cr;
(rabbit), food/water, airborne glandular, etc. gram stain if mild dz
Plt
Rickettsia: in general, rickettsial diseases with eschars are scrub typhus, African tick-bite fever, RMSF, Mediterranean spotted fever, and rickettsialpox
Murine typhus SE Asia, N Africa, N America Fever, centrifugal rash, Serology performed
Plt, AST/ALT Doxy 100 bid x7d
(Rickettsia typhi) Feces of infected rat fleas HA, myalgia 2wks apart
Scrub typhus India  E Asia; Pacific, Chile Eschar, fever, Plt, AST/ALT, Serology performed Doxy 100 bid x7d;
(Orientia Bites from infected mite larvae lymphadenopathy, Bili, AKI, WBC 2wks apart; consider azithromycin if
tsutsugamushi) (AKA chiggers) centrifugal rash, HA usually wnl eschar bx tetracycline-resist.
Helminths: if concerned about intestinal worms, albendazole is an effective and safe medication to give empirically while awaiting lab results
Africa, Brazil, MidEast, Asia Acute (3-8wks): fever, Acute: pred 20-40
Eos (30-60%) in Serology at 6-12wks;
Schistosomiasis urticaria, HA x5d + praziquantel
acute, Plt; LFTs stool/urine microscopy
(Schistosoma spp) Fresh water with free cercariae Chronic: HSM, portal Chronic: 40-60 x1 of
from infected snails usually nml for speciation
HTN, hematuria praziquantel
Worldwide, esp. Europe Abd pain, n/v, diarrhea Albendazole 400 bid
Trichinellosis Eos, WBC, CK, Serology 2-8d; muscle
 myalgia, weakness, + pred 30-60 qd x8-
(Trichinella spp) Undercooked meat, esp. pork LDH biopsy
+/- fever 14d
Rural tropics/subtropics; Eos, WBC; in Serology more Sn stool
Skin rxn, epigastric pain, Ivermectin 200
Strongyloidiasis Appalachia, SE USA immunosupp. pts  but less Sp.  BCx,
diarrhea, resp. sxs; mcg/kg/day x2d;
(Strongyloides Skin contact with soil hyperinfection & may have GN
fever, n/v, sepsis or treat for x5-7d if
stercoralis) contaminated w/ human feces, disseminated dz bacteremia (gut
shock if hyperinfection disseminated dz
fecal-oral, autoinfection (normal eos) translocation)
Other Infections
Fever, lethargy, abd HR, LFTs, Stool/blood Cx. BMBx
Typhoid fever India, SE Asia, Africa Azithro/ciprofloxacin
pain, ‘rose spots’, WBC (WBC sign 90% Sn. Serology
(Salmonella enterica Severe: CTX (mero-
diarrhea (>50%), of intest. perf.), effective in non-
serotype Typhi) Fecal oral; asymptomatic carriers constip. (30%), HSM penem if Pakistan)
anemia, abnl coags endemic regions
Melioidosis India  SE Asia; N Australia Fever, PNA, skin WBC; other Abscess I&D + IV
Blood Cx on Ashdown’s
(Burkholderia Soil; aspiration, inhalation, abscess, community- nonspecific values mero/ceftaz x2wks
agar, gram stain
pseudomallei) percutaneous inoculation acquired sepsis, GU c/w organ failure  TMP-SMX x3mo
Hantavirus SW USA, Lat Am, Europe, Asia Hemorrhagic fever, renal PTT, Plt, AKI, Serology via state
Supportive care
(Sin nombre, Andes) Aerosolized rodent excreta failure, ARDS proteinuria department of health
Toxoplasmosis Worldwide Atypical lymphs, Serology 1-7d; CSF 2- Tx if CNS, preg, or
Mono-like symptoms
(Toxoplasma gondii) Cats; contaminated meat/water AST/ALT 5d chorioretinitis
Multiple: NEJM 2017;376:548, NEJM 2018;379:557, NEJM 2007;357:1018, NEJM 2015;372:954, JAMA 2002;287:2391; Malaria: JAMA 2010;304:2048; Dengue: NEJM 2012;366:1423;
Zika: NEJM 2016;374:1552; Chikungunya: NEJM 2015;372:1231; West Nile: JAMA 2013;310:308; Brucellosis: NEJM 2005;352:2325; Schistosomiasis: NEJM 2002;346:1212; Typhoid:
NEJM 2002;347:1770; Melioidosis: NEJM 2012;367:1035

Brady Page
121
TOC

Infectious Disease Infectious Precautions

Resources: visit Ellucid (EPIC -> Resources -> Handbook -> Manuals-> MGH Infection Control Manual & Policies) for the most up to date
MGH policies and list of disease/ conditions requiring isolation. For additional support work with unit specific nursing supervisors and
contact Infection Control (x62036).
Standard Precautions: apply to all patients
• **Hand hygiene**: disinfect with an alcohol-based hand rub before AND after gloving, contact in room or with patient. If hands are
visibly soiled, wash hands with soap and water, dry hands, and apply an alcohol-based hand rub.
o Gloves/gowns for contact w/blood, bodily fluids (e.g., wound), secretions, excretions, mucous membranes, broken skin
o Mask + eye protection for procedures that can splash blood, bodily fluids, or secretions (e.g., ABGs, paracenteses)
o Dispose of materials heavily soiled with blood or bodily fluids into biohazardous waste (red bag)
o Disinfect reusable equipment (e.g., personal stethoscope, U/S) using correct wipes after patient use
• Cough etiquette: cover mouth/nose, mask coughing person, prompt disposal of used tissues, hand hygiene, spatial separation (>3ft)
• Safe injection practices: use sterile, single-use, disposable needle/syringe and single-dose vials whenever possible
Transmission-Based Precautions (in addition to standard precautions above):
Pt Population &
Isolation Description Examples
Transmission
- Hand hygiene + nonsterile gloves + isolation gowns
MRSA†
- Do not touch phones, beepers, notes while in room
Transmitted by direct or - Remove gown and gloves together with only touching VRE†
indirect contact with MDROs†
inside of PPE with bare hands, dispose of in the room
Contact CRE
patient or his/her - Dedicate the use of equipment (stethoscope, BP cuff) to
Lice / Scabies
environment avoid sharing with other patients. All equipment residing
Uncontained drainage
within the Contact Isolation room is presumed contaminated.
(abscesses)
- Disinfect using correct wipes for pathogen of concern
Patients with
- Contact instructions as above C. diff
known/suspected spore
- After doffing; wash hands with soap and water for 15-20 Norovirus
Contact forming or alcohol-
seconds, dry, then use CalStat; Bleach wipes for equipment C. auris
PLUS resistant organisms
- Isolate patient empirically while awaiting results of Cutaneous anthrax
transmitted by
tests for C. diff and Noro
indirect/direct contact
N. meningitidis (1st 24 hrs
Patients with organisms - Disposable surgical mask must be worn when entering the
of effective antimicrobial
transmitted by large room. Discard upon exit.
therapy)
Droplet respiratory droplets - Patient travel: surgical mask
Influenza (*N95 for
(coughing, sneezing, - Isolate patient empirically while awaiting results for
aerosol-generating proc.)
talking) bacterial meningitis, influenza, pertussis
Pertussis
Enhanced - Contact + Eye Protection + N95
Respiratory COVID-19 - Isolation; no need for ⊕ press. unless aerosolizing proced. COVID-19
Isolation - Patient travel: surgical mask
- Isolation in negative pressure room with door closed
Pulmonary TB
Transmitted by droplet - N95 respirator (fit-tested) to enter the room; retest if weight
Measles
nuclei that can remain +/- 20lbs; PAPR for facial hair or if not fit-tested
Airborne Varicella
suspended in the air - Patient travel: surgical mask
Disseminated herpes
and disperse widely - Visitors are asked to wear N95 respirator, no fit testing
zoster
required, but should be shown how to wear it correctly
Enhanced Required for patients
- Contact + private room limitations on use of shared spaces
Isolation with Cystic Fibrosis
Strict Patients w/ highly Airborne + Contact + Eye Protection SARS / MERS
Isolation pathogenic organisms If suspected, isolate and contact Biothreats Pager (26876) Avian Influenza
† Pts will be identified in the Infection Status banner in EPIC, removal of precautions discussed below
Immunocompromised Hosts: BMT, lung transplant and neutropenic patients.
• Generally standard precautions + positive pressure room + N95 maks for patient during travel + dietary precautions
• BMT: gloves and surgical mask for healthcare workers
• Lung transplant: gown, glove and surgical mask for healthcare workers
• See Immunocompromised Host Policy on Ellucid for details
When to Remove Precautions:
For questions regarding screening for resolution of infection status for patients with histories of MRSA, VRE, and MDROs call the Infection
Control Unit (x6-2036). Discontinuation of isolation should be discussed with Infection Control directly.
• TB: 3 negative sputum specimens (via cough or induction at least 8h apart or 24h if known) is not sufficient for rule out; TB must be
excluded entirely from the differential. Please consult Infection Control to discuss discontinuation of isolation.
• Influenza: 7d after onset or until 24h after resolution of fever and non-cough symptoms (whichever is longer); although in some
patients shedding may be prolonged; discuss with Infection Control
Jessica O’Neil
122
TOC

Infectious Disease Vancomycin & Renal Antibiotic Dosing

Drug (By Class) Usual Dosing CrCl 50-25 CrCl 25-10 CrCl<10 HD
PENICILLINS
Ampicillin IV (bacteremia) 2g q6h CrCl 50-10: 2g q8-12h CrCl <10: 2g q12h 2g q8-12h*
Ampicillin IV (endocarditis,
2g q4h CrCl 50-10: 2g q6-8h CrCl <10: 2g q12h 2g q8-12h*
meningitis)
Ampicillin-sulbactam IV
3g q6-8h CrCl 30-15: 3g q8-12h CrCl<15: 3g q12h 3g q12h*
(blood, intra-abd, PID)
Piperacillin-tazobactam IV
3.375g q6h CrCl 20-40: 2.25g q6h CrCl <20: 2.25g q8h 2.25g q8h
(non-Pseudomonas)
Piperacillin-tazobactam IV
4.5g q6h CrCl 40-20: 3.375g q6h CrCl<20: 2.25g q6h 2.25g q8h
(Pseudomonas)
CEPHALOSPORINS
1gm daily q24 OR
Cefazolin IV 2g q8h CrCl 50-10: 2g q12h CrCl <10: 2g q24h
2g post-HD
Ceftriaxone IV 1–2 g q24h No change with renal function; meningitis dosing is 2g q12h to max 4g/day; on HD days, give post-HD
Ceftazidime IV (most CrCl 15-5: 1g q24h; 2g x1  1g daily* OR
2g q8h CrCl 50-31: 2g q12h CrCl 30-16: 2g q24h
except UTI, meningitis) CrCl<5: 1g q48h 2g post-HD
Cefepime IV (febrile 1g q24h* OR
2g q8h CrCl 59-30: 2g q12h CrCl 29-10: 2g q24h CrCl<10: 1g q24h
neutropenia, PNA) 2g post-HD
1g q24h* OR
Cefepime IV (others) 1-2g q8-12h CrCl 59-30: 1g q12h CrCl 29-10: 1g q24h CrCl<10: 1g q24h
2g post-HD
FLUOROQUINOLONES
Ciprofloxacin IV (if
critically ill or PNA, q8 400 mg q8-12h CrCl<30: 400mg q24h 400 mg q24h*
dosing)
Levofloxacin IV/PO (CAP,
750mg q24h CrCl 49-20: 750mg q48h CrCl<20: 750mg x1  500mg q48h 750mg x1  500mg q48h
complicated infx)
CARBAPENEMS
Meropenem IV (most
CrCl 25-10: 500mg
except meningitis, CF, in 1g q8h CrCl 50-26: 1g q12h CrCl<10: 500mg q24h 1g q24h*
q12h
which case double dose)
OTHER ANTI-INFECTIVES
Acyclovir IV (most; higher CrCl 25-10: CrCl <10: 2.5-5mg/kg
5-10mg/kg q8h CrCl 49-26: 5-10mg/kg q12h 2.5-5mg/kg q24h*
dose for CNS/systemic) 5-10mg/kg q24h q24h
Clindamycin IV 600-900mg q8h Usual dose since Clindamycin not renally eliminated; max 2,700mg/day
12mg/kg x1  6mg/kg x1  3mg/kg
6mg/kg q24h OR CrCl <50: 6mg/kg x1  3mg/kg q24h OR q24h* OR
Fluconazole IV/PO
800mg x1  400mg x1  200mg q24 400-800mg x1  200mg
400mg q24h q24 (or 400 post-HD)
Metronidazole IV/PO 500mg q8h Usual dose. Can use q6h dosing interval for CNS dosing
*Dialysis dosing: if drug dosed multiple times/day, administer 1 of the doses after HD. If drug dosed QD, administer after HD on HD days
Adapted from MGH/Partners antibiotic dosing guidelines: http://handbook.partners.org/content/pdf/AntimicrobialRenalDosingGuidelines.pdf. For more information on renal
dosing for other antimicrobials (including CVVH dosing): see http://handbook.partners.org/pages/3805
VANCOMYCIN DOSING (https://hospitalpolicies.ellucid.com/documents/view/1719l; HD/CVVH dosing: https://hospitalpolicies.ellucid.com/documents/view/13031)
• Typical dosing regimen: 20mg/kg LOAD (max 2g)  15mg/kg q8 maintenance; adjustments for renal function per table below:
Loading Dose Maintenance Dose (actual OR adjusted body weight (if ≥120% of IBW), age, & CrCl)
Weight (per ACTUAL CrCl <20, AKI
Age ≤65 y/o AND CrCl 40-79 OR CRRT OR
(kg) BODY WEIGHT, CrCl 30-39 CrCl 20-29 OR Labile Renal
CrCl ≥80 Age >65 y/o iHD4
max 2,000mg) Function
40-45 1000mg 500-750mg q8h 750mg q12h 750mg q24h 750 mg q24-48h
46-50 1000mg 750mg q8h 750mg q12h 750mg q24h 750 mg q24-48h
51-55 1000-1250mg 750mg q8h 750-1000mg q12h 750-1000mg q24h 750-1000 mg q24-48h
56-60 1250mg 750-1000mg q8h 1000mg q12h 1000mg q24h 1000 mg q24-48h
61-65 1250mg 1000mg q8h 1000mg q12h 1000mg q24h 1000 mg q24-48h
Load followed
66-70 1250-1500mg 1000mg q8h 1000mg q12h 1000mg q24h 1000 mg q24-48h
Load followed by by Renal
71-75 1500mg 1000-1250mg q8h 1250mg q12h 1250mg q24h 1250 mg q24-48h
dose by level Replacement
76-80 1500-1750mg 1250mg q8h 1250mg q12h 1250mg q24h 1250 mg q24-48h
Protocol
81-85 1500-1750mg 1250mg q8h 1250mg q12h 1250mg q24h 1250 mg q24-48h
86-90 1750mg 1250-1500mg q8h 1250-1500mg q12h 1250-1500mg q24h 1250-1500 mg q24-48h
91-100 1750-2000mg 1250-1500mg q8h 1500mg q12h 1500mg q24h 1250-1500 mg q24-48h
101-110 2000mg 1500mg q8h 1500-1750mg q12h 500-1750mg q24h 1500-1750 mg q24-48h
>110 2000mg 1500mg q8h 1750-2000mg q12h 1750-2000mg q24h 1750-2000 mg q24-48h
• Dose monitoring: check trough 1hr prior to 4th dose (goal typically 15-20; 10-15 for simple skin/soft tissue infection); if fluctuating renal function,
check 24hr level (or random level, depending on the circumstances) and discuss dosing with pharmacy
• Subtherapeutic level: if first trough ≤10% from target (e.g. 13.5, w/ goal 15-20), continue same dose; if first trough <5mcg lower than target (e.g. 12
w/ goal 15-20),  each dose by 250mg (e.g. 1000mg  1250mg); if if first trough >5mcg lower than target, shorten dosing interval (e.g. q12  q8).
• Supratherapeutic level: if 21-25, hold next dose and reinitiate at 250mg less (e.g. 1000mg from 1250mg) when expected to be within target range; if
26-30, hold next dose and adjust dosing to next longer interval (e.g. q12 from q8); if >30, hold until random level falls w/in target range
Jacqueline Henson
123
TOC

Infectious Disease MGH Antibiogram

YEAST No. of strains Fluconazole (% susceptible)

Candida albicans 341 94
Candida glabrata 155 89
Candida parapsilosis 64 94
Candida tropicalis 32 88
Candida krusei: intrinsically resistant to fluconazole

Jacqueline Henson
124
TOC

Hematology Anemia & Pancytopenia

ANEMIA
GENERAL APPROACH (Williams Hematology 2018)
• S/Sx: O2 delivery (fatigue, lightheadedness, DOE, pallor, angina, claudication, retinal hemorrhage), nonspecific sx (cramps, abd
pain, n/v), compensatory mechanisms (RR, HR, palpitations, orthostasis, pulsation, flow murmur, bruit)
• Other findings: jaundice (hemolysis), glossitis (folate / B12 / Fe def.), motor / sensory deficits (B12 def), PICA / koilonychias / angular
cheilitis (Fe def), splenomegaly (cirrhosis, infxn, thalassemia, malig., chronic hemolysis), constipation / bone pain (myeloma), melena
(GIB, CRC), Mediterranean / Asian / Black (thal/SS), unusual thromboses (PNH), petechiae / purpura (coagulopathy, pancytopenia)
• Initial labs (draw/add on labs prior to transfusion!): CBC w/ diff (Δs in other cell lines, MCV, RDW), retic count, special slide, T&S
• Calculate reticulocyte index (RI) to determine if adequate BM response: hypo- (RI <2%) vs hyper-proliferative (RI >2%)
o Very low RI (<0.1%) indicative of aplastic anemia or red cell aplasia
• Additional labs depend on retic index and clinical history:
o RI <2% -“Anemia labs”: Fe/TIBC/ferritin, folate / B12 (in last 6 mo.), BMP, LFTs, TSH, CRP
 If unrevealing / otherwise indicated by history: +/- SPEP/SFLC, Hb electrophoresis, AM testosterone, Epo, BMBx
o RI >2% - “Hemolysis labs”: LDH, bilirubin, haptoglobin, DAT (Coombs), Coags, UA
CLASSIFICATION OF ANEMIA (NEJM 2014;371:1324, Lancet 2018;391:155, Williams Hematology 2018)
UNDERPRODUCTION (RI <2%)
Microcytic (MCV < 80 µm3) Normocytic (MCV 80-99 µm3) Macrocytic (MCV ≥ 100 µm3)
Inflammation & variant: Megaloblastic: smear shows hyper-seg
Iron deficiency anemia (IDA)
• Early anemia of inflammation PMNs and macro-ovalocytes; MCV >110
•  Fe,  TIBC,  ferritin (<30 high Sp.;
• Early IDA •  Folate:  homocysteine, nl MMA
<15=Fe in BM), Fe/TIBC <16%,  RDW
• Mixed IDA &  folate/B12 (dimorphic: •  B12:  homocysteine,  MMA
Anemia of chronic inflammation
nml MCV w/ RDW) ( anti-IF Ab,  gastrin if pernicious
•  Fe, /nl TIBC,  ferritin (<100 if ACI+IDA
Organ-specific: anemia; falsely nml B12 possible)
or <200 in ESRD), Fe/TIBC /nl (>18%)
• Renal (CKD/ESRD): Epo (should • Early myeloproliferative d/o
Thalassemias
10x per 10% Hct drop) Non-megaloblastic: MCV usually <110
• Fe studies nml, MCV  (often <70),
• Endocrine (thyroid, pituitary, adrenal, • Cirrhosis, EtOH
MCV/RBC <13 (Mentzer index; high Sp.);
parathyroid, testosterone; metab. • Reticulocytosis: lysis or bleed
 Hb electrophoresis
rateO2 demand): Epo • Hypothyroidism
Sideroblastic anemia
• Marrow (red cell aplasia, AA, MDS, • MDS (refractory anemia) & MM
•  ferritin, Fe/TIBC nml, basophilic stippling
myelofibrosis, myelophthisis, PNH, Meds: HAART, 5FU, AraC, Hydrea
(Pb), ringed sideroblasts (BM)
MM):  SPEP, serum FLC, BMBx
 DESTRUCTION / LOSS (RI >2%)
Extrinsic (transfused RBC has shortened life span) Intrinsic (transfused RBC has normal life span)
MAHA (-DAT, +schisto): see Thrombocytopenia Hereditary:
• Smear (≥2 schisto/HPF), PLT ~25K,  LDH,  indir bili,  hapto • Hb disease (SS, HbC, thal): Hb electrophoresis
Immune (+DAT, +spherocytosis): Ab- and/or complement-mediated • Enzyme deficiency (G6PD, PK): G6PD levels often
• Warm autoimmune (CLL, HIV, lymphoma, SLE): +DAT anti-IgG/C3 nml in attack; check 4wk later & repeat in 3mo if neg.
• Cold autoimmune (EBV, lymphoid malig., Mycoplasma): +DAT anti-C3 • Membrane defect: spherocytosis, elliptocytosis
• Drugs (PCN, cephalosporins), alloimmune (hemolytic transfusion rxn) Acquired (new onset):
Non-immune (-DAT, +/- RBC inclusion): • PNH (paroxysmal nocturnal hemoglobinuria): flow
• Infection: babesia, malaria, bartonella, C. perfringens, H. flu (type B) cytometry +/- FLAER for GPI anchor, smear nml, UA
• Toxin: lead, copper, insect / spider / snake bites, hypotonic infusion (hgb/hemosiderin), thrombosis (intra-abd/cerebral)
• Hypersplenism: many; massive SM usually 2/2 heme malignancy Acute blood loss: GI blood loss, hematoma
Intravascular: LDH, hapto, hemoglobinemia & -uria; Extravascular: indir bili ± LDH ± hapto (if free Hb escapes spleen), SM
IRON DEFICIENCY ANEMIA (NEJM 2015;372:1832; Blood 2019;133:30)
• Etiology: loss due to chronic bleeding (PUD/UGIB [BUN w/o Cr], LGIB/CRC, menses, parasites, intravascular hemolysis),
demand (Epo, pregnancy, blood donation), intake (malnutrition) or absorption (Crohn’s, pH [e.g. PPI], post-gastrectomy, celiac)
• Evaluation: GI bleed eval, H. pylori; consider celiac (esp. if not responsive to PO iron).
• Treatment: PO 325 mg FeSO4 x1-3 QD or QOD ( absorp. w/ QOD: Lancet Haematology 2017;4:e524).~6wk to correct anemia, ~3-6mo
to replete stores. Absorp.  on empty stomach, w/ VitC,  w/ Ca foods, antacids. GI SE: constipation, epigastric pain, N/V.
o IV iron if excessive SEs, CKD, malabsorption, IBD, intolerant to PO, or CHF (FAIR-HF NEJM 2009;361:2436-48). Typical dose: iron
sucrose 200mg QOD x5 or 300mg QOD x3. SE: n/v, pruritus, flushing, myalgia/arthralgia, CP;  by 48h. Anaphylaxis rare.
ANEMIA OF CHRONIC INFLAMMATION (NEJM 2019;381:1148-57, Blood 2019;133:40)
• Etiology: autoimmune, infection, malignancy, chronic disease (HF, CKD); inflammatory cytokines (IL-1, IL-6 & TNFα)  hepcidin
  ferroportin degradation/internalization   intestinal Fe absorption,  Fe recycling by macrophage & hepatic Fe mobilization
• Time course: usually 1-2mo. to develop, but can Hgb 2-3g/dL in 1-2d in acute illness
• Treatment: Tx underlying disease. Fe if concomitant Fe deficiency: Tsat <15-20%, ferritin <100 (<200 in ESRD+IDA), or no response
to EPO; can soluble transferrin receptor/ferritin index to distinguish pure ACI vs. ACI+IDA but typically hx & Fe studies sufficient.
o Erythropoiesis stimulating agents (ESA): FDA-approved for anemia a/w CKD & HIV on HAART. Controversial in cancer pts,
but there are specific indications for it (ASCO/ASH Guidelines: JCO 2019;37:1336). Evidence against use in CHF (RED-HF NEJM
2013;368:1210). Maintain Tsat ≥20%, ferritin ≥100 for EPO therapy.
Cody Cichowitz
125
TOC

Hematology Anemia & Pancytopenia

MEGALOBLASTIC ANEMIA: RBC size due to abnml cell division in BM; macrocytosis = RBC MCV >100 & can be non-megaloblastic
•  Folate: foliage, 3mo. stores; intake (EtOH, elderly), absorption (celiac, jejunal processes), Check B12
demand (pregnancy, hemolysis, malig.), meds (MTX, TMP, AEDs); severe form a/w hemolytic
anemia, pancytopenia; homocysteine, MMA nml; Tx: 1-5 mg PO QD (NB must  B12 before tx) >350 200-350 <200
•  B12: beef, 3yr. stores; intake (EtOH, vegan), pernicious anemia (Ab to IF, gastric parietal
cells), absorption (gastrectomy, celiac, Crohn’s, PPI, chronic pancreatitis), competition B12 def. NL MMA &  B12 def.
(bacterial overgrowth, tapeworm); severe form a/w pancytopenia & subacute combined unlikely HCY likely
degeneration (dorsal columns, corticospinal tract) w/ dementia, ataxia, paresthesia,
homocysteine, MMA. Tx: 1-2 mg PO B12 QD (as effective as IM if not 2/2 malabsorption) (Blood 1998;92:1191). Treat &
For pernicious anemia, typically given IM. Post-tx, neuro sx start to improve 3mo-1yr (NEJM 2013;368:149). anti-IF Ab
AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA) (NEJM 2019;381:647-654)
• Mechanism: antibody-mediated (warm) or complement-mediated (cold) hemolysis. DAT detects IgG / C3 bound to RBCs.
• Warm AIHA (idiopathic, CLL/lymphoma, SLE/autoimmune disease, HIV, Babesia, meds): +DAT anti-IgG +/- C3, extravascular
hemolysis in spleen; Tx: transfuse if Hb <6 & treat w/ steroids: prednisone 1-2 mg/kg/d for up to 3 weeks with slow taper when Hb
>10 (effective 50–90% of cases), 2nd line: rituximab, immunosuppressants, IVIG, splenectomy. Notify Blood Bank if rapid hemolysis.
• Cold AIHA: most often cold agglutinin disease (lymphoid malignancies, EBV, Mycoplasma), rarely cold IgG; +DAT anti-C3 at room
temp. (can  thermal amplitude, consider titer), intravascular hemolysis; Tx: avoid cold; if sx/transfusion-dependent,
plasmapheresis/IVIG as temporizing, rituximab; NO steroids or splenectomy
• Drugs: both Ab & non-Ab-mediated; abx (PCN, cephalosporins, sulfa); NSAIDs; CV (methyldopa, procainamide); rasburicase (G6PD)
o If +DAT but no hemolysis, think Drugs,  IgG (IVIG/RhIg/myeloma), CTD (e.g. controlled SLE)
SICKLE CELL ANEMIA (NEJM 2017; 376:1561, JAMA 2014;312:1033)
• Manifestations: HbS  sickling when O2  hemolysis (chronic anemia: Hb ~8-10, normocytic unless +thalassemia or IDA,
reticulocytosis ~3-15%, LDH, hapto) + microvascular occlusion (acute chest, CVA, pain crises, splenic sequest., hand-foot synd.,
renal pap. necrosis, priapism);  risk of encapsulated infxn ( spleen), osteomyelitis (infarct. bone), aplastic anemia w/ parvo B19
• Inpatient: CXR (r/o acute chest), CBCd, retic, LDH, CMP, T&S; Mgmt in all: VTE ppx, adequate hydration, incent. spirometry
• Pain crises: pain ctrl: opioids +/- NSAIDs; check for Acute Care Plan. If unknown prior dose: IV morphine 0.1-0.15mg/kg (max
10mg) or Dilaudid 0.02-0.05mg/kg (max 1.5mg)  PCA; O2 if <92%, IVF if hypovol.; incent. spir. (acute chest: NEJM 1995;333:699)
• Acute chest syndrome: fever, WBC, pulm. infiltrate; r/o PE, ACS, PNA; Tx: O2 if <92%, transfusions (goal Hb >10; simple vs.
exchange if severe), pain ctrl (see above), abx (CTX/azithro or FQ), bronchodilators. NB: 50% preceded by/assoc. w/ pain crisis.
• Hyperhemolytic crisis: rare complication (1%); presentation: pain, fever, worsening anemia w/in 7-15 days of transfusion, dropping
reticulocyte count, DAT may be negative. Tx: notify blood bank, hydration +/- steroids, IVIG, rituximab, eculizumab.
• Transfusions: indicated in acute stroke, multiorgan failure, acute chest syndrome, sequestration, and peri-op. Goal Hb >10.
Exchange > simple due to risk of hyperviscosity. Transfusions should be judicious; ASH guidelines: Blood Adv 2020;4:327.
• Outpatient treatment: hydroxyurea ( HbF; continue as inpt), folate & MVI, vaccines for encapsulated bacteria (Mening, HiB,
Pneumo), HepB & Flu. Consider L-glutamine (NEJM 2018;379:226), voxelotor (NEJM 2019;381:509), crizanlizumab (NEJM 2017;376:429).
PANCYTOPENIA
Etiologies
BM cellular (aplastic, myelofibrosis, chemo, PNH, mets), nml cellular (MDS, PNH), cellular (leukemia, lymphoma, MM)
Systemic spleen (cirrhosis), toxin (EtOH, cocaine), nutrition (B12/folate, Cu), CTD (SLE, RA), sepsis, HLH/MAS
Meds NSAIDs, PPIs, sulfas, antihistamine, chemo, anticonvulsants, antiprotozoals, heavy metals, many others
Infxn viral (HIV, HBV/HCV, CMV/EBV, parvo), bacterial (Brucella, TB), fungal (Histo), parasitic (leish, malaria, schisto)
Work-up
Initial/Mild  meds, CBC w/ diff, retics, smear, LFTs, TSH, B12, folate, PT/PTT, fibrinogen, HIV, HBV, HCV
Severe  HcY/MMA, Cu, Zn, LDH, DAT, ANA, RF/CCP, ESR/CRP, SPEP, CMV, EBV, Parvo, Tox, Abd US+Doppler
Heme  BMBx (strongly consider if pancytopenic w/o obvious systemic causes), flow cytometry (if c/f PNH)
• HLH: infxn/malig./rheum dz (MAS)/CART/checkpoint inhib.hyperinflamm. in some, cytokine storm. Dx: 5/8 of fever, spleen, 2/3
cytopenias, TG /fibrinog., ferritin ≥500 (NB usually >7-10k), sIL-2R, hemophagocytosis in BM, low/no NK activity. Usually
LFTs, hepatomegaly, LDH, D-dimer. H-score for probability. Tx: depends on etiology (ASH guidelines: Blood 2019; 133:2465)
A P P R O A C H T O T H E P E R I P H E R A L B L O O D S M E A R (NEJM 2005;353:498)
• Low power (200x): scan slide for WBC distribution. Identify the “thick” edge and the “feathered” or thin edge.
• Med power (400x): examine feathered edge for rouleaux, parasites, abnormal WBC, platelet aggregation / microsatellites.
• Oil Immersion (1000x): assess the size, shape, and morphology of major cell lineages:
o RBC: examine where RBCs are close but not touching, compare to lymphocyte nucleus size for scale
o WBC: concentrate on edges and thin end of film, normal WBC include PMN, eos, basos, lymphocytes, monocytes
Hypochromia / microcytes (Fe, thal); spherocytes (AIHA, HS); schistocytes (valve, MAHA); target cells (thal, Hb dz, liver
RBCs disease, asplenia); tear drops / nRBCs (myelofibrosis, myelophthisis, thal.); bite cells / Heinz bodies (G6PD); basophilic
stippling (thal, Pb, sideroblastic); acanthocytes / echinocytes (liver/renal disease); Howell-Jolly bodies (sickle cell, asplenia)
HypOsegmented PMNs (MDS); hypERsegmented PMNs (folate/B12); toxic granulation (sepsis); myeloid vs. lymphoid
WBCs
precursors (left shift, myelocytes, blasts, Auer rods), basophils (MPD)
Platelets Clumping (pseudothrombocytopenia); large platelets ( production, ITP, or congenital disease)

Cody Cichowitz
126
TOC

Hematology Thrombocytopenia
THROMBOCYTOPENIA (Hematology 2012;2012:191) Anti-infectives:
Definition: platelet count < 150k. Risks: <50k w/ surgery, <20k spont. bleed (less so in ITP), <10k severe bleed TMP/SMX
SEQUESTRATION / Vancomycin
 PRODUCTION  DESTRUCTION
POOLING / DILUTIONAL Penicillin
- Infxn: late HIV/HCV, parvo, sepsis - Infxn: early HIV/HCV, H. pylori > - Splenomegaly (e.g. Ampicillin
- Nutrition: B12/folate/Cu, EtOH HSV/VZV/CMV/EBV, tick-borne illness cirrhosis & portal HTN): may Piperacillin
- Drugs: see list in margin - Immune: ITP (+AIHA=Evan’s), SLE/APS, sequester 90% of circulating
Ceftriaxone
- Malignancy: leukemia, MDS, PMF, RA, CLL, CVID, post-transfusion platelets
aplastic anemia, infiltrate - Drugs: immune (see list; NEJM 2007;357:580) - Massive transfusion  10U Rifampin
- Congenital: Bernard Soulier, vWD - MAHA: DIC, TTP/HUS, mHTN, HELLP pRBC  plt by 50% Ethambutol
(specific types), other rare causes - Shearing/aggregation: CVVH, CPB, IABP; - Hypothermia Quinine
vasculitis, hemangioma (Kasabach-Merritt) - Gestational (in tonic water,
Workup: initial labs: CBC w/ diff (Δ other cell lines), review special slide (schistos, other), HIV, HCV (if not  recently) bitter lemon)
• If c/f hemolytic anemia (Hgb & Plts)  also  LDH / hapto / bili, DAT (AIHA), retic count Quinidine
• If schistocytes on slide  also  coags, D-dimer, fibrinogen (eval for DIC vs. TTP/HUS), consider heme consult
• Consider ANA (SLE), ACL/LA (APLS) if appropriate based on other clinical signs/symptoms Anti-epileptics:
• If >60 yo, splenomegaly, or systemic sx  consider BMBx to r/o MDS, AA, leukemia, infiltrate Cabamazepine
• Rule out pseudo-thrombocytopenia  platelet clumping 2/2 EDTA (can order Platelet Count, Citrated) Phenytoin
Valproic acid
PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) (ASH: Hem 2018;2018:568, Blood 2017;129:2829, NEJM 2019;381:945)
Pathophys: thrombocytopenia d/t auto Ab-mediated megakaryocyte destruction and  plt production Anti-platelets:
Presentation/Dx: p/w mucocutaneous bleeding (or asx); defined by isolated plt <100k, dx of exclusion; 10% have ITP Abciximab
+ AIHA = Evans Syndrome. BMBx only done if atypical; anti-plt Ab not useful. Screen for H. pylori (tx may plts in ITP)
Eptifibatide
Management: treat if <30k, but 20-30k w/ no/mild bleeding (i.e. skin only) can be observed; response = >30k & 2x
• Severe bleeding: plts, IVIG, methylpred 1g/d IV x3d (or dexamethasone 40mg/d x4d), consider romiplostim. Tirofiban
o If no response in plts, consider Amicar (0.1g/kg/30min0.5-1g/hr) / tranexamic acid / activated FVII
Others:
• 1st line: dexamethasone 40 mg/d x4d (or prednisone 1 mg/kg/d PO x2-3wk  taper) +/- IVIG 1 g/kg/d IV x 2d
Heparin (HIT)
• No response/recurrence: romiplostim (Nplate) / eltrombopag / avatrombopag, rituximab, splenectomy (after 6mo-
1y) Ranitidine
Simvastatin
HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) (Blood Adv 2018;2:3360, Blood 2017;129:2864, NEJM 2015;373:252) Haloperidol
Pathophys: anti-PF4-heparin complex Ab binds & activates plts,  thrombin  hypercoag. state,  plts Amiodarone
Presentation: 5-10d after exposure, plt >50%, nadir 40-80K, thrombosis in 30-50% (skin necrosis, DVT/PE, arterial) Oxaliplatin
•  risk w/ UFH; major surgery restarts the clock; consider rapid-onset HIT if <24hrs with prior exposure <1-3mo.;
Irinotecan
delayed-onset can present up to 3wks after heparin is discontinued
Acetaminophen
Diagnosis: calculate 4Ts Score. If ≥4, D/C heparin and anti-PF4. If high prob 4T w/ any degree of ⊕PF4 or int. prob
4T w/ mod/strong ⊕PF4,  serotonin release assay. Otherwise, if neg PF4 or int. prob 4T w/ only weakly ⊕PRA, HIT Naproxen
unlikely, ok to resume heparin. 4T of ≤3 has high NPV (99%). Ibuprofen
Management: D/C all heparin products & add to allergy list. C/s heme, start alternative AC (NEJM 2013;368:737). Do Furosemide
NOT transfuse platelets unless severe hemorrhage. Needs AC until plt >150k if ⊝ thrombosis, ≥3mo. if ⊕. OTC/herbal
• Fondaparinux (synthetic, IV or subQ): for stable non-surgical patients, contraindicated if GFR <30, irreversible
• Argatroban (DTI, IV): monitor w/ chromogenic Xa (goal 20-40%), preferred in renal failure & surgical pts Direct  BM:
• Bivalirudin (DTI, IV): only approved for HIT undergoing PCI, preferred in liver failure Linezolid
• DOACS for non-urgent AC: apixaban, edoxaban, rivaroxaban, dabigatran Thiazide
• VKA: not until plt >150K for 2 consecutive days Chemo/XRT
EtOH
THROMBOTIC MICROANGIOPATHIES (TMAs) (NEJM 2014;371:654)
Pathophys: small-vessel irregularities  microthrombi  MAHA (Hb, LDH, haptoglobin, +schistos, -DAT), plt
(aggregation, consumption), ischemic end-organ injury (vascular occlusion)
Diagnosis: special slide, CBC w/ diff, coags, D-dimer, fibrinogen, LDH, haptoglobin, retics, Cr, LFTs
Secondary etiologies: DIC, infxn, malignancy, SLE, APLAS, HELLP syndrome, scleroderma, severe HTN, post-HSCT
Primary etiologies: in addition to below, also metabolism-mediated (B12 metab. d/o) & coag.-mediated; rare & typically present in infants
• TTP (plt <30K): inherited/acquired ADAMTS13 def.  vWF multimers. S/Sx: fatigue, purpura, GI sx, neuro sx in 60%; fever
uncommon, AKI rare, pentad rare. Dx: PLASMIC score  if mod/high prob., ADAMTS13 (<10% = TTP). Tx: plasma exchange,
steroids, ritux. Caplacizumab may be option (NEJM 2019;380:335). No plts unless bleeding. (Blood 2017;129:2836, NEJM 2019;381:1662)
• HUS (plt >30K): Shiga-toxin-mediated bloody diarrhea w/ abd pain (O157:H7 E. coli, Shigella). S/Sx: severe AKI; severe neuro sx
(SZ, coma, hemiparesis) rare. Dx: stool⊕ for organism or toxin; Tx: supportive, often w/ HD, unclear role for Abx (Blood 2017;129:2847)
• Complement-mediated (“atypical HUS”): S/sx: severe AKI + 20% w/ extra-renal sx (CNS, cardiac, pulm hemorrhage, panc.); Dx:
complement genotyping, anti-complement Ab. Tx: plasma exchange; eculizumab (NEJM 2013;368:2169; Blood 2017;129:2847)
• Drug-induced: 1) Immune-mediated (gemcitabine, oxaliplatin, quetiapine, quinine)  acute f/c, abd pain, n/v/d, AKI
2) Dose-dependent (gemcitabine + other chemo; tacrolimus, CSA + other IS; cocaine)  subacute fatigue, HTN

Eftitan Akam
127
TOC

Hematology Eosinophilia
OVERVIEW (Am J Hematol 2017;92:1243, Hematology 2015;2015:92)
• Eosinophilia: AEC >500. Hypereosinophilia: AEC >1500. Hypereosinophilic syndromes (HES): AEC >1500 + organ dysfunction.
o Eosinophils are quickly eliminated by steroids  eosinophilia may be unmasked as pts taper off chronic glucocorticoids.
• Either primary and due to clonal expansion (HES/leukemia) or secondary (reactive) due to infection, atopy, meds, rheum dz, etc.
Helminth: Strongyloides, toxocariasis, shistosomiasis, ascaris, filariasis, trichinellosis. Fungal: Aspergillus (ABPA),
Infections
coccidiomycosis, histoplasmosis. Protozoal: isospora. Viral: HIV, HTLV1/2.
Malignancy Primary HES (PDGFRA-assoc.), eosinophilic leukemia, CML, NHL, HL, mastocytosis; less common with solid tumors
Autoimmune EGPA (see Vasculitis), PAN, eosinophilic fasciitis, RA, IBD, IgG4, sarcoidosis, GVHD, blistering disease
Allergic Drugs, DRESS Syndrome, asthma/atopy, ABPA, hyper IgE syndrome, AIN, episodic angioedema (Gleich syndrome)
Misc Adrenal insufficiency, cholesterol emboli syndrome, acute arterial thrombosis.
WORKUP (Br J Haematol 2017;176:553, J Allergy Clin Immunol Pract 2018;6:1446, Hematology 2015;2015:92)
• Hx: meds/supplements (<6 wks), diet, travel, occupational exposures, atopy, infxn, malignancy, rheumatic dz, full ROS
• Exam: assess for rashes, cardiac/pulmonary abnormalities, nasal/sinus involvement, LAD, hepatosplenomegaly, neuropathy
• Initial diagnostics: CBC w/ diff (repeat), special slide, BMP, LFTs, LDH, ESR/CRP
o If AEC 500-1500: check troponin, B12/tryptase, CXR if clinically indicated
o If AEC >1500, assess for HES: check U/A, CK, troponin, EKG, CXR, PFTs, CT C/A/P (for adenopathy, organomegaly, masses,
organ infiltration), tissue biopsy of affected organs; also obtain B12, tryptase, serum Ig levels
• Additional diagnostics (as clinically indicated): Strongyloides serology & stool O&P, other serologies if potential exposure; ANCA if
?EGPA; ANA, RF, CCP if ?rheum dz; IgE levels + allergy testing if ?allergic; imaging/bronch, serologies (e.g. aspergillus IgE) if
?pulm. dz; imaging/endoscopy if ?GI dz; TTE/CMR if ?cardiac dz; periph. flow +/- BMBx if ?MPD or >1500 & no obvious 2° cause
TREATMENT (Hematology 2015;2015:92)
• Urgent Tx: if cardiac, neuro, or thromboembolic complications, AEC >100,000/rapidly rising, or s/sx of leukostasis  1mg/kg to 1g
solumedrol (+empiric ivermectin 200mcg/kg if potential Strongyloides exposure); obtain HES diagnostics above prior to initiating
• Non-urgent Tx: symptomatic or evidence of end-organ damage but does not need urgent Tx; see below for Tx by condition
• No Tx: if asymptomatic, no organ involvement, & no identified cause to treat, can monitor for resolution & organ damage
DRUGS: can be isolated Eos or accompanied by systemic illness (DRESS, hepatitis, AIN, etc). In hospital, PCNs/cephalosporins
common culprits. Suspect DRESS if new drug 2-6w prior, fever, rash, facial edema, LAD, abnml LFTS, ± organ involvement, atyp. lymphs.
ORGAN-SPECIFIC PATHOLOGY
Cardiac: (JACC 2017;70:2363, Immunol Allergy Clin North Am 2007;27:457)
• Eosinophilic endomyocarditis: necrosis  thrombus formation ( embolic events)  fibrosis  restrictive CM, valve involvement
o May be due to hypersensitivity myocarditis, parasitic infections, malignancy, idiopathic HES
o Dx: TTE (LV/RV apical dysfunction, signs of restriction, intracardiac thrombi) and cardiac MRI (+subendocardial LGE)
o Tx: high dose steroids (≥1mg/kg pred) & remove culprit med (if hypersensivity), treat underlying disorder (parasite, HES)
• Eosinophilic coronary arteritis: rare complication of EGPA; may mimic ACS
Pulmonary: (Clin Microbiol Rev 2012;25:649, Chest 2014;145:883, J Allergy Clin Practice 2014;2:703)
• Acute eosinophilic PNA: <7d fever, cough, SOB; a/w smoking; periph. Eos often absent at presentation; Dx: BAL Eos ≥25%
• Chronic eosinophilic PNA: subacute fever, cough, SOB, wt loss; a/w asthma; Dx: BL periph/pleural infil, UL-predom; BAL Eos≥25%
• Allergic bronchopulmonary aspergillosis (ABPA): asthma/CF c/b recurrent exacerbations w/ fever, malaise, brown mucus plugs; Dx:
Eos, total IgE, Aspergillus IgE & IgG, imaging w/ central bronchiectasis, UL/ML consolidations; Tx: steroids + itraconazole
Loeffler syndrome: transient/migratory pulm. opacities, Eos 2/2 helminth larvae; Dx: larvae in resp secretion (stool usually ⊝)
GI: (AGA EoE: Gastro 2020;158:1776; NEJM 2015;373:1640; Clin Rev Allergy Immunol 2016;50:175)
• Eosinophilic esophagitis (EoE): dysphagia, food impaction, GERD-like sx/refractory GERD, assoc w/ allergic conditions; Dx: EGD w/
bx, exclude other causes (GERD, motility d/o, Crohn’s, infxn, CTD, etc.); Tx: dietary Δs, PPI, topical steroids (MDI/neb, PO liquid)
• Eosinophilic gastroenteritis (EGE): stomach/duod. +/- esoph., colon; Sx: n/v/d, abd. pain, ascites; Tx: dietary Δs, PO steroids
Others: neuro (peripheral neuropathy, encephalopathy, CVA/TIA from thromboemboli), thrombotic complications, skin Δs
PRIMARY HYPEREOSINOPHILIC SYNDROMES (HES) (Am J Hematol 2017;92:1243, Hematology 2015;2015:92)
• Myeloproliferative HES (~20% of HES in US): acute/chronic eosinophilic leukemia, PDGFRA-associated MPN  clonal expansion
of Eos; 80% pts have FIP1L1-PDGFRA fusion gene; remainder have PDGFRA, FGFR1, JAK2 rearrangements
o Dx: anemia, thrombocytopenia,  tryptase,  B12, special slide (dysplastic eosinophils), flow cytometry (PDGFRA, BCR-ABL1,
JAK2, FGFR1, KIT), BM Bx (fibrosis, hypercellularity)
o Tx: if PDGDR+, imatinib; if JAK2+, JAK2 inhibitor; if FGFR1+, chemo; 2nd line or no rearrangment: hydroxyurea, IFN-α, other
TKI/empiric imatinib
• Lymphocytic HES: clonal T-cell expansion IL-5  Eos. Often p/w skin/soft tissue involv., polyclonal hyper-IgG, IgE. Episodic
angioedema (Gleich syndrome) is very rare subset of L-HES. Up to 25% risk of progression to lymphoma.
o Dx: flow cytometry for CD3, CD4 (clonal IL-5-secreting CD3- CD4+ T-cells)
o Tx: steroids; 2nd line: IFN-α, hydroxyurea, mepolizumab (anti-IL-5; NEJM 2008;358:1215), alemtuzumab
• Idiopathic HES: eosinophilia without identified cause and evidence of end-organ damage  consider ANCA-neg EGPA (50% cases)
o Tx: steroids; 2nd line: hydroxyurea, IFN-α, imatinib, mepolizumab, alemtuzumab

Rahul Nayak
128
TOC

Hematology Coagulation Disorders

H Y P E R C O A G U L A B L E S T A T E S (NEJM 2017;377:1177)
WORKUP OF FIRST VTE
Provoked by strong trigger: Unprovoked / provoked by weak trigger &: Unusual site:
- Major surgery/trauma - Recurrent thrombosis - Arterial thrombosis
- Immobility ≥3d - Young (<45 y/o) - Portal, hepatic, splenic, renal,
Presentation
- CA, pregnancy/OCP, SLE, IBD, - Strong FH mesenteric, or cerebral venous
nephrotic sx, HIT thrombosis
- Paget-Schroetter, May-Thurner
- No role for hypercoag. testing - May benefit from testing from inherited - Arterial: test for APLAS
- Consider age-appropriate cancer conditions if will alter mgmt (e.g. OCP use, AC - Cerebral veins: inherited + APLAS
Workup
screen duration, s/p pregnancy loss) - Splanchnic veins: inherited
- APLAS if young or recurrent events conditions + APLAS + JAK2 + PNH
Hypercoag testing: no evidence that improves outcomes, rarely changes mgmt (inherited thrombophilic abnormality does not sig.  risk of
recurrent VTE [JAMA 2005;293,2352]), $$$. Do NOT perform at time of event (affected by VTE & AC); wait until 2 wks after AC d/c’ed.
• Panel includes: APC resistance (reflexes to FVL), protein C/S (reflexes to FVIII/fibrinogen), ATIII, LA, prothrombin G20210A (PTG),
anti-cardiolipin. Does NOT include anti-β2 glycoprotein. Only FVL, PTG, aPL Ab are reliable in acute VTE or on AC.
See VTE Management & Anticoagulation Management pages for guidance on AC agents / duration of treatment.
CONDITION CLINICAL PEARLS TESTING
Inherited Conditions
Factor V Leiden/
- Most common inherited cause of hypercoagulability - APC resistance assay  reflex FVL genetic test
APC resistance
Prothrombin - 2nd most common cause of hypercoagulability
- PCR for PTG G20210A mutation (most common)
gene mutation -  prothrombin (FII)
- Free protein C/S functional assays
- Activated protein C/S inactivate FVa and FVIIIa;  level
Protein C/S -  by acute thrombosis, Vit K antagonists, liver dz,
(more common) or function leads to hypercoagulability
deficiency nephrotic syndrome, DIC, pregnancy (S only), chemo
- A/w warfarin-induced skin necrosis (screen if hx)
-  by DOACs
-  level or function - ATIII functional assay assessing FXa inhibition
Antithrombin III
- NB: heparin works via ATIII to inactivate FIIa and FXa; if -  by acute thrombosis, UFH/LMWH
deficiency
ATIII defic., will be heparin-resistant & require  doses -  by VitK antagonists, DOACs
Others -  FVIII, dysfibrinogenemia, hyperhomocysteinemia - FVIII & fibrinogen  by inflamm. (acute phase rxn)
Acquired Conditions
- Lab criteria: ⊕ LA, anti-cardiolipin, or anti-β2
- Sapporo criteria = 1 clinical + 1 lab criterion
glycoprotein >2x ULN, 12 weeks apart
- Clinical criteria: venous/arterial thrombosis, pregnancy
- LA unreliable on AC; anti-CL and β2GP not affected
complications
APLAS - NB: ⊕ aPL Ab can be seen in infxn, rheum dz,
- Catastrophic APS: ⊕aPL w/ ≥3 organ thromboses in
malig, meds w/o clinical APLAS; unclear significance
<1 wk, mortality ~50% (Autoimm. Rev 2010;10:74)
- False ⊕VDRL
Tx: LMWH acutely  warfarin +/- ASA (if arterial)
(NEJM 2018;378:2010)
Other - Hyperhomocysteinemia (also inherited), HIT; NB: Hyperhcy/HIT/APLAS are the d/o freq. a/w arterial thrombosis
C O A G U L O P A T H Y (NEJM 2014;370:847)
Disorders of 1° hemostasis ( platelet # or function, VWD  mucocutaneous bleeding, petechiae, menorrhagia) or 2° hemostasis
(factor deficiency/ activity  deep tissue bleeding, joint, organ, brain; prolonged PT / PTT)
• Rule out artifact, anticoagulant use, or systemic disease (cirrhosis, DIC, abx, malnutrition, renal disease, cancer)
• If prolonged PT / PTT and etiology is not clinically apparent, order mixing study w/ normal plasma (JAMA 2016;316:2146)
o If PT / PTT corrects: supports clotting factor deficiency (confirm w/ factor specific assays)
o If no (or partial) correction: supports presence of inhibitor (confirm w/ inhibitor specific assays)
 Types: drugs (e.g. heparin), acquired factor inhibitor (VIII, V>>IX, XI; autoimmune d/o, malig.), nonspecific inhib. (e.g. LA)
o If work-up is unrevealing, think VWD, platelets, can check FXIII (most commonly presents w/ delayed surgical bleeding)
• Tx: replace missing factor, eliminate inhibitor (immunosuppressants), treat underlying condition
Coagulation Defect Normal aPTT Prolonged aPTT
Platelet dysfunction (VWD, other platelet disorders) Intrinsic pathway:
Normal PT  Factor XIII  Factor VIII, IX (hemophilias), or XI (Ashkenazi)
VWD ( factor VIII in severe cases)
Extrinsic pathway: Common pathway:
Prolonged PT  Factor VII inhibitor or early systemic defect (liver, Liver disease, DIC, Vit K deficiency, warfarin
DIC, Vit K deficiency, warfarin); FVII has shortest t1/2 Rarely common pathway deficiency/inhibitor

DIC: massive activation of coag cascade  consumption of coag. factors (bleeding), microvascular thrombosis (MAHA, organ
ischemia). 2/2 various inflamm. etiologies (sepsis, CA, trauma, pancreatitis). Dx: PT/PTT, D-dimer, fibrinogen, plts, +schistos,
LDH, hapto. NB: often normal coags in chronic DIC. Can differentiate DIC from liver dz w/ FVIII (in endothelium, not liver). DIC score.
Tx: underlying cause, transfuse plts if <10k (or serious bleeding <50k), cryo if fibrinogen <100, FFP if INR >2. Amicar generally contraind.
John Schell
129
TOC

Hematology Anticoagulation Agents

O R A L A G E N T S (ASH Guidelines: Blood Adv 2018;2:3257; CHEST Guidelines: Chest 2012;141:e152S, Chest 2012;141:e44S)
Agent Dosing Bridging/Switching/Reversal
- Initiation: 5mg QD x2d; if frail, HF, kidney/liver dz: Bridging:
consider 2.5mg; If BMI >40: consider 7.5mg - To parenteral A/C: start IV w/o bolus when INR <2
Warfarin (Coumadin) - Adjust by INR, which lags 48h behind dose Δ - From parenteral A/C: see below
- Vitamin K antagonist: Monitoring: (UW Dosing Nomogram) Reversal: IV vitamin K faster > PO at 6h, ~ at 24h
inhibits vitamin K- - INR <2:  up to 10-20%/wk - Active bleeding:
dependent gamma- - INR 2–3: no change • IV vit K 10mg + FFP (10mL/kg; 1U = 200-250mL)
carboxylation of F II, VII, - INR 3–4:  10%/wk • Kcentra (4-factor PCC) 50U/kg if life-threatening
IX, X, Protein C, S (Circ 2013;128:1234; Transfusion 2016;56:799)
- t1/2 40h (variable)
- INR >4: hold until INR 2-3, restart  5-15%/wk
- If overlap w/ direct thrombin inhibitor, check - No active bleeding
chromogenic FXa: goal 20-40% • INR >10  PO vitamin K 2.5-5 mg OR IV 1-2.5 mg
• INR <10  hold warfarin, no need for reversal
Dabigatran (Pradaxa) - Non-valvular AF: 150mg PO BID if GFR >30, 75 mg Bridging/switching:
- Direct thrombin (IIa) PO BID if GFR 15-30 (RE-LY NEJM 2009;361:1139); some - To parenteral A/C: start 12h after last dose
inhibitor use 100mg PO BID dose if high bleeding risk - From parenteral A/C: start <2h before next dose/gtt 
- t1/2 12-17 h - VTE: 150mg PO BID after 5d UFH/ LMWH (RE-COVER - To warfarin: start 3d before dabigatran  if CrCl ≥50;
- 80% renal clearance NEJM 2009;361:2342) 2d if CrCl 31-50, 1d if GFR 15-30; bridge PRN
- P-gp substrate
- Other:  dyspepsia, ?
- PPX: 110mg x1 then 220mg PO QD (RE-NOVATE II - From warfarin: hold warfarin, start when INR <2
coronary events vs. Thromb Haemost 2011;106:721) Reversal if life threat.: (NB can be dialyzed, lipophilic)
VKA? - Idarucizumab 5g (REVERSE NEJM 2017;377:431)
- NV AF: 20mg PO QD if GFR >50, 15mg if GFR 15-50 Bridging/switching: (J Thromb Thrombolysis 2016;41:206)
Rivaroxaban (Xarelto) (ROCKET-AF NEJM 2011;365:883) - To parenteral A/C: start when next DOAC dose due
- Direct Xa inhibitor - VTE: 15mg PO BID x21d, then 20mg QD. After 6mo.  - From LMWH/fonda: start w/in 0-2h of next sched. dose
- t1/2 5-9h; 11-13 in elderly
to 10mg QD if no absolute indication for indef. tx - From UFH: start immediately after  gtt (for
- 66% renal clear.
- interacts w/ CYP-3A4 & (EINSTEIN-DVT, PE, & CHOICE: NEJM 2010;363:2499, edoxaban, start 4h after stopping UFH)
P-gp inhib. 2012;366:1287, & 2017;376:1211) - From warfarin:
- PPX: 10mg PO QD (MAGELLAN NEJM 2013;368:513) • Start rivaroxaban when INR <3
Apixaban (Eliquis) - NV AF: 5mg PO BID, 2.5 mg BID if 2/3: Cr ≥1.5, Wt • Start apixaban when INR <2
- Direct Xa inhibitor ≤60kg, age ≥80; some use 2.5mg BID if CrCl 15-29 • Start edoxaban when INR ≤2.5
- t1/2 12h (ARISTOTLE NEJM 2011;365:981) - To warfarin: (NB all  INR;  just before dose if able)
- ~25% renal clear. - VTE: 10mg BID x7d, then 5mg BID x6mo; after 6mo.  • Rivaroxaban/apixaban: coadminister until INR ≥2
(Can use in ESRD) to 2.5mg BID if no absolute indication for indef. tx • Edoxaban: cut edoxaban dose by ½ and begin
- interacts w/ CYP-3A4 & (AMPLIFY & AMPLIFY-EXT: NEJM 2013;369:799 & 368:699)
warfarin,  edoxaban once INR ≥2
P-gp inhib. - PPX: 2.5 mg BID (NEJM 2009;361:594) - DOAC to DOAC: start when next dose due
Edoxaban (Savaysa) - NV AF: 60mg PO QD; 30mg if CrCl 15-50 or wt ≤60kg; Reversal if life-threat.: (NB not dialyzed off, protein-bound)
- Direct Xa inhibitor do not use if CrCl>95 (ENGAGE-AF NEJM 2013;369:2093)
- t1/2 10-14 h - VTE: 60mg QD after 5d UFH/ LMWH, 30mg QD if CrCl - Andexanet alfa (recombinant FXa): low or high-dose
- 50% renal clearance 15-50, ≤60kg, or taking P-gp inhib. (NEJM 2013;369:1406) bolus depending on dose/timing  2h gtt (ANNEXA-R & -
- P-gp substrate - PPX: not FDA-approved (15-30mg PO QD) 4: NEJM 2015;373:2413 & 2019;380:1326)

PARENTERAL AGENTS
Agent Dosing/Monitoring Bridging/Switching Reversal Other
Heparin (UFH) - ACS: 60U/kg  12U/kg/hr; PTT 63-83 - To LMWH: give LMWH & - Protamine: 1 mg per - Preferred in renal
- Binds & activates - VTE: 80U/kg  18U/kg/hr; PTT 70-100  UFH at same time 100U heparin or 1mg failure (CrCl <30),
ATIII inactivates - PPX: 5,000U SC q8-12h - To warfarin:  UFH LMWH (max 50mg). peri-procedure, poor
Xa & IIa - Monitoring: PTT; anti-Xa (goal 0.3-0.7) if once therapeutic ≥2d 60% reversal for absorption, pregnancy
- t1/2 60-90min baseline  PTT or high doses; ACT if ) LMWH, most effective
Enoxaparin - ACS/VTE: 1mg/kg BID; QD if GFR <30 - To UFH:  LMWH & if last dose within 8 hr - Acute VTE: LMWH >
(LMWH, Lovenox) - PPX: 40mg SC QD; 30mg BID if risk; start UFH w/o bolus 1-2h - Do NOT give FFP UFH (Cochrane Rev
- Binds & activates 30% if BMI ≥40; 30mg QD if GFR <30 before LMWH dose due (has ATIII, which 2017)
ATIIIinact. Xa>>IIa - Monitoring: not routine; can anti-Xa 4h - To warfarin:  LMWH potentiates A/C effect) - Prolonged t1/2 in renal
- t1/2 4.5-7hrs after 4th dose, goal 0.5-1.0 once therapeutic INR ≥2d failure
Fondaparinux - VTE: <50kg  5mg QD | 50-100kg  - To warfarin:  fonda. - No reversal agent -  aPTT at
(Arixtra) 7.5mg QD | >100kg  10mg QD once therapeutic INR ≥2d therapeutic doses
- Binds & activates - PPX: 2.5mg SC QD - To UFH: start UFH (no - If CrCl 30-50,
ATIIIinact. Xa only - CrCl <30: contraindicated bolus) 1-2hrs before due consider Δ to different
- t1/2 17-21 hrs - Monitoring: not routine; can 4hr anti-Xa - From UFH: start 1hr after agent
UFH 
Argatroban - HIT: 1-2mcg/kg/min - To warfarin:  once - No reversal agent - Only dabigatran (PO)
- Direct IIa (thrombin) - Monitoring: PTT, goal 1.5-3x baseline PTT chromogenic factor Xa is has antidote
inhibitor - Caution in critically ill, cardiac dysfunction, 20-40% (argatroban (idarucizumab)
- t1/2 45min liver disease INR)
Mubeen Shakir
130
TOC

Hematology Anticoagulation Management

CHOOSING AN ANTICOAGULATION AGENT
Guidelines: CHEST for VTE: Chest 2016;149:315, ASH for VTE: Blood Adv 2018;2:3257, ASCO for VTE in CA: JCO 2020:38;496; ACC/AHA/HRS for AF:
JACC 2019;74:104, CHEST for AF: Chest 2018;154:1121; AHA/ACC for Valvular HD: JACC 2017;70:252
All Others DOACs > warfarin > LMWH
Apixaban (CARAVAGGIO NEJM 2020;382:1599), edoxaban (NEJM 2018;378:615), rivaroxaban (JCO 2018;36:2017), LMWH >
Active warfarin (CLOT NEJM 2003;349:146). Both edoxaban & rivaroxaban w/  bleeding risk vs. LMWH, so avoided in GI/GU CA
VTE Malignancy w/ intralum. lesions. Effect not seen w/ apixaban. NB: use of apixaban in CA population not yet in published guidelines.
DOAC ppx a/w  VTE in high-risk outpts: consider if Khorana ≥2 (AVERT NEJM 2019;380:711; CASSINI NEJM 2019;380:720).
Obesity Avoid DOACs if BMI ≥40 or wt ≥120kg, though rivarox. may be ok. If use, peak/trough level (ISTH: JTH 2016;14:1308)
Recurrent If on non-LMWH: switch to LMWH. If on LMWH: increase LMWH dose.
Non-valvular DOACs > warfarin for stroke risk, mortality, and bleeding risk.
Valvular Warfarin if mod./severe MS (regardless of CHADS2VASC).
Dual (P2Y12i + OAC) vs. triple therapy (+ ASA): dual w/  bleeding, likely no  events (Annals 2020; EHJ 2019;40:3757)
Dual therapy: DOAC + clopidogrel x12mo. Rivaroxaban 15mg QD (some use 20mg) (PIONEER AF NEJM 2016;375:2423)
AF & dabigatran 150mg BID (RE-DUAL PCI NEJM 2017;377:1513) in guidelines, but now also data for apixaban (5mg BID
+ PCI unless 2.5mg indicated) (AUGUSTUS NEJM 2019;380:1509) & edoxaban 60mg QD (*though edox. w/o  bleeding vs. VKA)
(ENTRUST-AF PCI Lancet 2019;394:1335). Warfarin + clopi or ticag also option (WOEST Lancet 2013;381:1107). Ticag may be
used in-hospital or if very high thrombotic risk. After 12mo., can likely Δ to OAC alone (AFIRE NEJM 2019;381:1103).
If triple therapy chosen due to high thrombotic/low bleed risk, typically d/c ASA & transition to dual therapy at 4-6 weeks.
Mechanical Warfarin + ASA. Warf. > dabigatran (RE-ALIGN NEJM 2013;369:1206). INR for AVR 2.5 (3 if +AF, VTE, etc.); MV & TV = 3.
Valve
Bioprosthetic Surg: Warfarin (INR 2.5) + ASA 3-6moASA. TAVR: ASA/clopi 3-6moASA. If AF/VTE, OAC+clopiOAC. (Evolving)
APLS Warfarin. Warfarin > rivaroxaban in high-risk APLS (TRAPS Blood 2018;132:1365)
ACS ( PCI) Very low dose rivaroxaban (2.5mg BID) added to ASA/clopidogrelCV mortality but major bleeding (NEJM 2012;366:9)
CAD Very lose dose rivaroxaban (2.5mg BID) + ASA   MACE vs. ASA alone;  major bleeding but no Δ in ICH or fatal
2° prevention
bleeding (COMPASS NEJM 2017;377:1319). Can consider if high risk for events & low bleeding risk.
ANTICOAGULATION BRIDGING
Guidelines: ACC: JACC 2017;69:871; ASH: Blood Adv 2018;2:3257; CHEST: Chest 2012;141:e419s
Indication AF VTE Mechanical Valve
Thrombotic
Risk Factors Bridge? Risk Factors Bridge? Risk Factors Bridge?
Risk
- CHA2DS2-VASc ≥7 Bridge unless - VTE <3 mo. Bridge - Any mechanical MV Yes
(or CHADS2 5-6) major bleed/ICH - Severe thrombophilia: - Caged ball/tilt disc AVR
High - CVA/TIA, or systemic <3mo. protein C/S or ATIII def, - Any mechanical valve w/
embolism <3mo. APLAS, multiple CVA/TIA <6mo.
- Rheumatic valv. HD abnormalities
- CHA2DS2-VASc 5-6 (or Likely bridge if - VTE 3-12mo. No bridge - Bileaflet AVR w/ ≥1 CVA Consider
CHADS2 3-4) prior CVA/TIA - Recurrent VTE risk factor: age >75, AF, based on
- CVA/TIA or systemic and if not  risk - Active malignancy prior CVA/TIA, HTN, DM2, risk of
Moderate
embolism >3mo. of bleeding - Non-severe thrombophilia: CHF bleeding in
heterozygous factor V patient/from
Leiden, PTG mutation procedure
- CHA2DS2-VASc ≤4 (or No bridge - VTE >1yr & no other risk No - Bileaflet AVR w/o AF or No
CHADS2 0-2) factors CVA
Low
- No prior CVA/TIA or
systemic embolism
• BRIDGE trial (NEJM 2015;373:823) demonstrated  risk of bleeding w/ bridging in pts with AF undergoing invasive procedure requiring
interruption of VKA (NB: excluded pts w/ mech. valves, stroke/TIA <12wk, major bleeding <6wk, CrCl <30, Plt <100k)
• Bridging VKA w/ UFH or LMWH:
o Stop VKA 5d prior to procedure if therapeutic INR. Start UFH or LMWH when INR <2.
o Stop UFH 4-6h prior to surgery and LMWH 12 or 24hrs prior to surgery (depending on dosing interval).
o Restart UFH/LMWH at 24hrs postop. if low postprocedural bleeding risk or 48-72hrs if high risk.  when INR >2.
o Resume VKA w/in 24hrs postop if no bleeding complications (will not  early bleeding risk because effect takes 24-72hrs).
• DOACs: no bridging required; most can be stopped 24-72h prior to surgery, depending on procedural bleeding risk & renal function:
High Bleed Risk Low Bleed Risk
CrCl >50 CrCl <50 CrCl >50 CrCl <50
Dabigatran ≥48hrs (4 doses) ≥96hrs (8 doses) ≥24hrs (2 doses) ≥48hrs (4 doses)
Rivaroxaban ≥48hrs (2 doses) ≥48hrs (2 doses) ≥24hrs (1 dose) ≥24hrs (1 dose)
Apixaban ≥48hrs (4 doses) ≥48hrs (4 doses) ≥24hrs (2 doses) ≥24hrs (2 doses)
Edoxaban ≥48hrs (2 doses) ≥48hrs (2 doses) ≥24hrs (1 dose) ≥24hrs (1 dose)
o If low bleeding risk, can resume 24hrs after procedure. If high bleeding risk, wait 48-72hrs. If unable to take PO for prolonged
period or second procedure is anticipated, start UFH/LMWH at the above time points instead.
See Peri-Procedural Anticoagulation for MGH-specific peri-procedural guidance for cardiac cath. lab & IR procedures.
Mubeen Shakir
131
TOC

Hematology Transfusion Medicine

TRANSFUSION MEDICINE TERMINOLOGY (http://handbook.partners.org  Clinical Topics  Transfusion Medicine)
• ABO typing: front type: A/B antigens (pt's RBC + reagent anti-A or B); back: anti-A or B in plasma (pt’s plasma + reagent RBCs)
• Rh(D) typing: tests for D antigen on RBC (pt’s RBC + reagent anti-D) – NB: anti-D is not a naturally occurring antibody
• Screening (T&S): tests for unexpected antibodies in pt’s plasma (pt’s plasma + screening RBC + Coomb’s reagent), “active” x3d
• Crossmatching (T&C): final confirmation test by mixing pt’s plasma & donor RBC; performed just prior to transfusion
• Direct antiglobulin test (DAT/Coomb’s Test): tests for Ab or complement on RBCs (RBCs + Coomb’s reagents [anti-IgG, anti-C3])
BLOOD PRODUCTS
Product Description Indications Notes
1U = 330cc = $895
- Hgb <7 (NEJM 2014;371:1381, NEJM 2013;368:11)
Processing
Red Blood - Hgb <8 if CAD/ACS, ortho/cardiac surgery - Response: 1U Hgb ~1
1. Leukocyte reduction
Cells - AIHA and MDS (no specific Hgb threshold) - Hct ~55%
2. Irradiation
- Sickle cell disease (see Anemia: Sickle Cell Disease)
3. Washing (rarely)
1U = 6pk = 300cc = $3400 Low platelets or functionally abnormal platelets
- Response at 30-60m:
Types - <10k: PPX spont bleeding. Consider antifibrinolytics in
1U  PLT ~ 30K.
1. Apheresis platelets refractory thrombocytopenia in CA (NEJM 1997;337:1870)
- No evidence that
derived from 1 donor - <50k: major bleed, intra- or post-op surgical bleed, ppx
apheresis > pooled plts.
Platelets 2. Pooled platelets from prior to invasive operative procedures (no data)
- No evidence that
multiple donors - <100k: post-bypass bleed, ICH/ophthalmic (no data)
platelets reverse anti-
Processing - ITP: only if life-threatening CNS/GI/GU bleed (often
platelet agents (PATCH
1. Leukocyte reduction preceded by wet purpura, mucus membrane bleeding)
Lancet 2016;387:2605)
2. Irradiation - HIT/TTP: avoid PLTs unless bleeding
1U = 250cc = $460 - Active bleed d/t deficiency in multi coag. factors or - Response: 1U  coag
1 Dose ~ 10-20 cc/kg isolated coag factors for which concentrate is not available activity ~ 10%
- Cirrhosis: consider anti-fibrinolytics instead. Treating - Max correction INR 1.7
Fresh Frozen Non-cellular portion of INR w/ FFP can  bleeding due to  portal pressures. - Effect < 6H due to short
Plasma blood containing all coag - ALF: consider for  Plt or  INR only if bleed or pre-op t1/2 of FVII
factors; separated and - VKA reversal: IV Vitamin K first. PCC if life-threatening. - Potentiates effect of
frozen after collection. - Trauma, DIC in presence of bleeding, congenital TTP heparin by providing ATIII
- Fibrinogen <100: 50-100mg/dL, give 10U; <50, give 20U - Fibrinogen replacement:
10U = 150cc = $2850 - Massive transfusion w/  fibrinogen or abnl ROTEM/TEG 0.2 bag/kg  100 mg/dL
- Complex cardiac surgery (JAMA 2017;217:738) fibrinogen w/ t1/2 3-5d
Cryoprecipitate Contains factor VIII, factor - Postpartum hemorrhage (Br J Anaesth 2015; 114:623) - FVIII or vWF
XIII, VWF, and fibrinogen - FVIII deficiency, VWD replacement: cryo is last
- Cirrhosis: also consider antifibrinolytics resort therapy
1-factor: VIII, IX, rF VIIa
(NovoSeven), ATIII
- Blood Transfusion
3-factor (II, IX, X; Profilnine) - Coagulation factor deficiency / inhibitor
Coagulation Service approval required
4-factor PCC (II, VII, IX, X; - Von Willebrand’s disease (Humate-P, NovoSeven)
Factors - S/E: allergic rxn,
Kcentra) - Life-threatening bleed due to VKA (PCC > FFP)
thrombosis
FEIBA (anti-inhib. complx)
vWF/FVIII (Humate-P)
Contain Lysine derivatives - Trauma (CRASH-2 Health Tech 2013;17:1) - Amicar: load 4-5g over
that bind to plasminogen - Postpartum hemorrhage (WOMAN Lancet 2017;389:2105) 1hr  1g/h for 8h or until
to  fibrinolysis and  - Cardiac surgery (NEJM 2017;376:136; ATACAS J Thor C bleeding controlled
hemostasis Surg 2019;157:644), ECMO - TXA: load 1g over
Antifibrinolytics
Types (topical, PO, IV) - Cirrhosis: see End Stage Liver Disease 10min  1g over 8h
1. Aminocaproic acid - Major orthopedic surgery, platelet refractoriness due to cont. infusion
(Amicar) HLA alloimmunization, fibrinolysis of serosal surface and - S/E: risk of seizures w/
2. Tranexamic acid (TXA) closed space bleeding, coagulation factor inhibitor patients high dose TXA
Types ~$40/bottle 5% if hypovol/intravasc depl., 25% if fluid/Na restricted - C/I: traumatic brain
1. 5% (iso-oncotic) - Cirrhosis: HRS, SBP, LVP (see End Stage Liver Disease) injury (SAFE trial
2. 25% (hyper-oncotic) - Shock: 4% albumin similar to 0.9% NS for IVF subgroup)
Albumin
Both contain 12.5g resuscitation (when alb. >2) (SAFE NEJM 2004;350:2247)
albumin & 154 mEq Na - ARDS: 25% albumin (25g) q8h x3d + lasix gtt x3d  (Also see IV Fluids and
(isotonic) O2, neg. TBB (when alb. <2) (Crit Care 2005;33:1681) Electrolyte Repletion)
- Immunodeficiency: hypogammaglobulinemia IgG <400: - SE: hemolysis (in A-
Types ($280/g)
0.3-0.5 g/kg q mo. type), aseptic meningitis,
Polyclonal IgG and trace
IVIG - Immunosuppression in autoimmune disease (e.g. ITP, hyperosm renal tubular
plasma contaminants
AIHA, Kawasaki disease, acquired VWS) injury, allergic reaction,
Dose adjust for obesity
- Certain infections thrombosis

Annabelle Anandappa
132
TOC

Hematology Transfusion Medicine

TRANSFUSION MODIFICATIONS
• Leukoreduction (LR): filters leukocytes to (1)  HLA sensitization in chronically transfused pts / heme malignancies, bone marrow /
kidney / heart / lung transplant candidates (not liver transplant) (2)  CMV risk & (3)  febrile non-hemolytic transfusion reaction
• Irradiation: prevents proliferation of donor lymphocytes from attacking the recipient (transfusion-associated-GVHD in 1st degree
directed donors); indications: heme malignancy & BMT to prevent GVHD; not indications: solid tumor, solid organ transplant, HIV+
• Saline-washing: removes anti-IgA Ab & plasma proteins; indications: severe anaphylaxis to blood products (w/ or w/out IgA def.)
ADMINISTERING BLOOD PRODUCTS
• Consent: required for administration of all blood products, discuss type of product, indication, benefits/risks, possible alternatives
• Ordering: “Prepare RBC” (or platelets/FFP/cryo)  select number of units to prepare, indication, applicable modifications (see below)
and “Transfuse RBC”  select number of units to administer, and rate of admin (usually over 2-4h)
• Monitoring response: order post-transfusion CBC to be drawn 15-30 mins after transfusion if clinically indicated
MASSIVE TRANSFUSION: call Blood Bank (x63623) and physically run down pick-up slip to Gray/Bigelow 2 to pick up cooler
• Activate when anticipate transfusing 50% TBV (~5U pRBC) in 2h OR 100% TBV (~10U pRBC or 5L plasma) in 24h
• Emergency release un-crossmatched pRBCs (O- for pre-menopausal females, O+ ok for males and older females)
• No universally accepted ratio; for 2-4U pRBCs, transfuse 1U FFP, 1U PLT, & 10U cryo (can modify to goals below as stabilizes)
o Goals: Hb >7-10, INR <2.5, PLT >50k, fibrinogen >100
o No evidence for 1:1:1 transfusion protocol; combat trauma studies confounded by survival bias (JAMA 2015;313:471)
o Excessive FFP a/w higher ARDS in pts not requiring massive transfusion
• Correct coagulopathy  IV vit K, FFP 15cc/kg; platelet dysfunction (ASA, plavix, uremia)  PLTs, DDAVP 0.3 mcg/kg
• Consider IV amicar @ 5g bolus over 1h, then 1g/hr gtt x 8h or IV TXA @ 1g bolus over 10min, then 1g over 8h
• Complications: dilutional coagulopathy, hypothermia, hypocalcemia (citrate), metabolic alkalosis (citrate metabolized to bicarb)
PLATELET REFRACTORINESS: failure to achieve acceptable  platelet count following transfusion. Normal t1/2 of 3 days.
• Causes:
o Alloimmune: Ab to class-I HLA antigens (e.g. +PRA) or PLT-specific antigens. Risk factors: multiple pregnancies, prior
transfusions with non-leukoreduced blood products, and organ transplants (NEJM 1997;337:1861)
o Non-alloimmune: non-HLA Ab-mediated; 2/3 of cases; Ddx: sepsis/DIC, HIT, TTP, CVVH/CPB/IABP, splenomegaly, HSCT,
viral infection (HIV/HCV) & meds (sulfa, vanc, linezolid, piperacillin, rifampin, amphotericin, heparin, thiazide, anti-GpIIb/IIIa)
• Evaluation: check plt post-transfusion on 2 occasions and assess plt recovery (15min-1hr later) & plt survival (18-24hr later)
o Inadequate plt recovery: corrected count increment <5k on 2 occasions; also usually indicated by plt  <10k x2  alloimmune
refractoriness (JCO 2001;19:1519)
o Normal plt recovery but  survival  non-alloimmune refractoriness
• Alloimmune refractoriness workup:
o Consult Blood Transfusion Service p21829. Studies will not be processed without discussing w/ them first.
o Send Panel Reactive Antibody: test for alloreactivity against HLA antigens. Normal is 0%, range 0-100%.
To order: HLA Lab, MGH (choose: Blood > Platelet Refractory > Platelet Refractory Workup, HLA class I Ab screen). Test is
only run on Tuesdays and Fridays.
o If platelets required urgently (i.e. actively bleeding), notify Blood Bank and ask for send out to Red Cross
• Management: with each platelet transfusion, must check a post-transfusion CBC within 15-60 minutes of completion
o Compatible platelets (specific HLA-antigen negative) or crossmatch compatible
o ABO/HLA-matched apheresis single-donor plts from Red Cross. Takes days to process. Each unit costs approximately $3000
and has a shelf life ~3 days.
o Consider Amicar if bleeding (contraindicated in thrombotic DIC); correct coagulopathy with DDAVP if e/o uremia
MANAGEMENT OF ANEMIA IN JEHOVAH’S WITNESSES (Am J Hematol 2017; 92:1370)
• Discuss management with patients on a case-by-case basis
• Acceptable products: hematinics (iron, folate, B12, recombinant human EPO), non-blood volume expanders (NS, LR, hydroxyethyl
starches), hemostatic agents (amicar, tranexamic acid, DDAVP, albumin-free clotting factors)
• Acceptable to some: autotransfusion, HD/apheresis/CBP/ECMO, hemostatic products w/ blood fractions (coag. factors, PCC),
plasma-derived products (albumin, cryo, Ig), products potentially containing albumin (rhEPO, vaccines), BM/organ transplantation
• Unacceptable products: whole blood, pRBCs, platelets, FFP, cryo, autologous blood transfusion
• Bleeding, preop: consider IV iron + rhEPO to speed up erythropoiesis  rhEPO onset 2-6 days if Fe/folate/B12 replete
• Critically ill: no expert consensus, consider rhEPO 200-300U/kg IV q24h or 250-500U/kg SQ q48h for goal periop Hb >10-12  can
be extrapolated to hemodynamically unstable/bleeding pts
THERAPEUTIC APHERESIS
• Plasmapheresis (plasma exchange): removes plasma, replaces with saline, albumin or plasma (depending on pt. condition)
Indications: TTP (replace ADAMTS13, NEJM 1991;325:393), hyperviscosity, cryo, Guillain-Barre, CIDP, MG, ANCA, anti-GBM
• Cytapheresis: removes abnormal or excessive # blood cells
Indications: leukapheresis for hyperleukocytosis (goal WBC < 100); erythrocytopheresis for sickle cell crisis, severe babesiosis (high
grade parasitemia >10, severe hemolysis, or pulm/liver/renal dz); platelet removal for thrombocytosis rarely done (goal plts <1000)

Annabelle Anandappa
133
TOC

Hematology Transfusion Reactions

INITIAL EVALUATION: Blood Bank (x63623, p21829) Acute Delayed
• Sx: fever / chills, hives / flushing / jaundice, infusion site pain, shock / oliguria, AHTR
wheezing / rales, DIC FNHTR DHTR
Immune-
1. STOP transfusion, ABCs, VS q15min, clerical check Urticaria/hives TA-GVHD
mediated
2. If only urticarial sx  treat symptomatically, resume transfusion once Sx resolve Anaphylactic Post-tx purpura
3. If suspected rxns  Purple Top (10cc EDTA tube for hemoglobinemia, DAT, TRALI
repeat ABO/Rh), UA (for hemoglobinuria) Cold toxicity
Non-
o High suspicion for hemolysis: bilis, LDH, hapto, crossmatch, smear Citrate toxicity Iron overload
immune
o High suspicion for sepsis: GS/BCx of both pt & blood product Sepsis Viral infection
mediated
o High suspicion for TRALI/TACO: JVP, BNP, ABG, portable CXR TACO

Reaction / Incidence Presentation / Diagnosis Pathophysiology Treatment / Prevention

ACUTE TRANSFUSION REACTIONS (<24 HRS)
Sx: first 15 min; fever / chills, back - ABO / Kidd incompatibility (preformed Tx: NS (+/- lasix) for goal UOP >
Acute Hemolytic / flank pain, bleeding / DIC Abs)  intravascular hemolysis (IgM), 100 cc/hr x 24h
(AHTR) Dx: +Hb (blood / urine), +DAT, cytokine / complement activation - Monitoring: HoTN, AKI, DIC,
76,000-137,000 +DBili / IBili / LDH, +smear - Rh / Kell / Duffy incompatibility  mortality ∝ volume transfused
(spherocytes) less severe extravascular hemolysis PPX: vigilance
- Donor WBCs produce TNFα, IL1, IL6
Febrile Non-Hemolytic
Sx: 1-6h; low-grade fever, chills, - RBC: donor WBCs activated by Tx: APAP +/- meperidine
(FNHTR)
HA, flushing recipient anti-HLA Abs PPX: leukoreduction, little
200-2,500 (RBC)
Dx: hemolysis workup negative - PLT: donor WBCs make cytokines evidence for pre-medication
50-1,600 (PLTs)
before transfusion
Sepsis (Bacterial Sx: 15-60 min; high fever, rigors, - Bacteria >> Viruses in donor blood Tx: antibiotics, quarantine all
Contamination) abd sx, HoTN / shock - RBC: Yersinia, PsA (endotox-GNRs) other similar products
75,000 (PLTs) Dx: GS / BCx of both pt & bag - PLTs: Staph epi (GPCs) PPX: routine screening
Sx: anytime during / after Tx: pause  diphenhydramine
Urticaria / Hives transfusion; localized or diffuse - IgE-mediated hypersensitivity to  resume if urticaria resolves
33-100 hives & redness donor plasma proteins PPX: washed products, no
Dx: no work-up necessary evidence for pre-medication
- IgE-mediated hypersensitivity in Tx: ABCs, O2, IVF +/- pressors,
Sx: within min; acute HoTN,
Anaphylactic recipient lacking IgA or haptoglobin epi IM Q15min,
angioedema, urticaria, wheezing,
Anaphylactoid - Bradykinin-mediated flushing/HoTN in methylprednisolone 125 mg,
abd pain
20,000-50,000 pt taking ACEi or neg charged filters diphenhydramine 25-50 mg
Dx: clinical; consider IgA deficiency
(e.g. TPE w/ albumin) PPX: washed products
Transfusion-Related Sx: 1-6h; hypoxemia 2/2 Tx: ABCs, O2, intubation
- Pre-transfusion stress activates lung
Acute Lung Injury noncardiogenic edema (ARDS); +/- PPX: male donor plasma (fewer
endothelial cells & primes PMNs
(TRALI) fever anti-HLA, anti-PMN Abs); defer
- Donor anti-HLA Abs/bioactive factors
5,000 (FFP > PLT > Dx: BNP nml, bilateral CXR donors w/ prior assoc. TRALI
attack primed PMNs of recipient
RBC) infiltrates w/o CHF cases
Transfusion-Assoc.
Sx: 1-6h cardiogenic pulm. edema Tx: O2, IV diuretics, ± nitrates,
Circulatory Overload - Highest risk in elderly, HF, CKD,
2/2 vol. overload NiPPV
(TACO) chronic anemias
Dx: elevated BNP, CXR PPX: slower rate (1cc/kg/hr)
350-5,000
- Inflammatory rxn: fever, chills, - Inflammatory rxn: Ab/Ag interaction
IVIG Transfusion
flushing, myalgias i/s/o concurrent infxn Tx: IVF, sx mgmt
Reactions
- Anaphylactoid rxn: urticaria, - Anaphylactoid rxn: unknown, PPX: slow, space out infusions
5-15% of infusions
flushing, chest pain, N/V, HTN potentially kinin-mediated, rare
DELAYED TRANSFUSION REACTIONS (>24 HRS, <28 DAYS)
Sx: ~3d; fever, anemia, jaundice, Tx: none
Delayed Hemolytic - Anamnestic IgG against previously
flu-like illness NB: delayed serologic transfusion
(DHTR) exposed antigen (Kidd / Duffy / Kell)
Dx: +DAT, +DBili / LDH, +smear w/ reaction is the same except w/o
2,000  extravascular hemolysis
spherocytes hemolysis
- Donor T cells attack non-HLA
TA-GVHD
Sx: 2-30d; fever, rash, mucositis, matched recipient organs in s/o
Rare (typically PPX: irradiation
diarrhea, hepatitis, pancytopenia immunosuppression or 1st degree
immunosuppressed)
relative donor
Post-Transfusion Sx: 3-14d; purpura, - HPA-1A neg women develop anti-
Tx: 1st line: IVIG | 2nd: PLEX
Purpura (PTP) mucocutaneous bleed HPA-1A Abs, which is common in
PPX: HPA-1A negative PLTs
Rare (women>>>men) Dx: plt < 10,000, anti-HPA-1A donor PLTs

Vinayak Venkataraman
134
TOC

Oncology Acute Leukemia

General Admission Approach
• History: note sibling status (for donor search), and if pre/peri menopausal, obtain date of last LMP, full ROS
• Laboratory workup:
o Peripheral smear: anemia, thrombocytopenia, variable WBC, circulating blasts, Auer rods (indicates myeloid origin)
o Peripheral flow cytometry: do not delay ordering, even overnight. Collect and send in yellow top tube, then hand-carry
specimen to the Warren 506 flow lab and inform them this is RUSH for New Leukemia. On Epic: Orders  Flow cytometry (not
bone marrow flow); must fill in flow cytometry clinical history and check “Flow Cytometry CBC and differential, Special Slide Box,
Leukemia Panel;” Inpatient Leukemia Attending manages results, but CC outpt Oncologist; Rush samples.
o Screening labs: CBC w/ diff, BMP, LFTs, coags, UA, bHCG, HBV/HCV, CMV IgG, T&S
o DIC labs: CBC, PT/PTT/INR, fibrinogen, D-dimer (esp if concern for APL)
o TLS labs: BMP, LDH, uric acid, Ca, Mg, Phos; diagnosis requires 2 lab (uric acid, K, PO4, Ca) + 1 clinical (AKI,
arrhythmia, seizure) criteria
• BM Bx: >20% blasts, flow cytometry, cytogenetics (karyotype, FISH), molecular testing (FLT3 ITD/TKD, NPM1, IDH1/2)
• Studies: EKG, CXR, TTE (needed prior to induction due to cardiotoxic chemotherapies), +/- CT head (if CNS sx)
• Access: double-lumen Hickman vs. triple-lumen PICC in anticipation of chemotherapy. Coordinate central access with attending.
• LP +/- intrathecal chemo: indications for LP include all ALL; AML w/ CNS or ocular symptoms; APL with systemic relapse
o CT or MRI before LP: AMS, focal neurologic signs, papilledema, seizure within the last week
• HLA-typing, HSCT work-up (if ≤80 yo): collect in 2 yellow top tubes, send to American Red Cross; siblings>parent/children as donor
o On Epic: Orders  HLA Lab  Specimen Type: Blood  Pt: Recipient  Type: Bone Marrow/HSC  Test: Allotransplant, if
HLA, to AmRedCross  if Panel-Reactive Antibody (PRA), Class I/II Ab screen
• Utiilize the Leukemia Admission Order Set: includes Neutropenic precautions, BMT diet, PRNs, among others.
o TLS ppx: allopurinol 300mg QD
o GI ppx: omeprazole 20mg QD
o VZV reactivation ppx: Famvir 500 mg QD
o Hibiclens daily and Peridex mouthwash BID
o No VTE ppx (thrombocytopenia)
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
• Epi: bimodal. Peak incidence in 3-5 y/o, another peak in >45 yo (68% 5-year survival),
Most common cancer in children.
• S/sx: pancytopenia sx, bone pain (if acute disease), masses (LAD, HSM, anterior
mediastinal mass in T-ALL), CNS sx (CN palsy, n/v, HA), TLS, DIC
• Smear: lymphoblasts with scant cytoplasm, large nuclei containing nucleoli
• Subtypes: precursor B-cell ALL, mature B-cell ALL, mature T-cell ALL
• Risk stratification:
o Precursor B-cell ALL (cytogenetics >> WBC/age effect on risk)
 Favorable: WBC < 30k, age < 35 years; hyperdiploidy (trisomy 4, 10, or 17
most favorable), t(12;21)(p13;q22): ETV6-RUNX1; rapid response to treatment (<0.01% minimal residual dz on Day 29 BM)
 Unfavorable: WBC ≥ 30k, age ≥ 35 years, hypodiploidy, KMT2A rearrangement, t(9;22)(q34;q11.2): BCR-ABL1, BCR-
ABL1-like (Ph-like) ALL, iAMP21, t(v;14q32)/IgH, complex karyotype (≥5 chromosomal abnormalities), CNS or testicular
involvement; slow response to treatment (>0.01% minimal residual dz on Day 29 BM)
o Mature T-cell ALL: poorer prognosis than precursor B cell, associated with t(8;14)
o Mature B-cell ALL: poor prognosis, generally in elderly and with elevated WBC
• Treatment (NEJM 2006;354:166, JCO 2011;29:532)
o General: no single superior regimen, many regimens. Involves 1) induction, 2) consolidation (can be multiple rounds), 3)
intensification (if needed), 4) CNS therapy (if needed), 5) maintenance, 6) allo-HSCT (high risk disease)
 AYA versus adult: if pt is AYA (age 15-39), pediatric-inspired regimen are often used
o CNS ppx: intrathecal MTX/cytarabine vs. systemic high-dose MTX w/ leucovorin rescue
o Maintenance: weekly MTX/6-MP + monthly Vinc/Pred x2-3 yrs;  prognosis if young, WBC < 30K, T-cell type, early CR
o For refractory/relapsed ALL, blinatumombab (Blincyto) (B-ALL) and anti-CD19 CAR-T cell therapy

ACUTE PROMYELOCYTIC LEUKEMIA (APML)

• Subtype of AML with distinct biology and excellent prognosis (NEJM 2013;369:111)
• S/sx: pancytopenia sx (fatigue, anemia, ecchymoses, infections). Especially high risk for DIC and bleeding
• Smear: atypical promyelocytes (large, “dirty” granular, bilobed nuclei, +Auer rods)
• Cytogenetics: t(15;17)  PML-RARα (>97%), rarely t(11;17), t(5;17)
• Treatment: EARLY Tx w/ ATRA CRITICAL given high early mortality 2/2 to
coagulopathy; should start ATRA if there is even mild suspicion for APL as there is low
drug toxicity and high mortality with delayed treatment
o Induction
 Low-risk (WBC≤10K): ATRA (all-trans retinoic acid) + ATO (arsenic trioxide)
(JCO 2017;35:583)
 High-risk (WBC>10K): ATRA + idarubicin or daunarubicin/cytarabine
David J. Lee
135
TOC

Oncology Acute Leukemia

o Consolidation
 ATRA + (daunorubicin vs. ATO), may depend on induction therapy
 After completion, check for remission; goal molecular complete remission (absence of PML-RARα on RT-PCR)
• Complications of ATRA therapy:
o Differentiation syndrome: SIRS, hypoxemia, edema, pulmonary infiltrates, AKI  high-dose steroids (dexamethasone 10mg
q12h), consider temporary cessation of ATRA
o Hyperleukocytosis: see Oncologic Emergencies
o Idiopathic intracranial hypertension: headache, vision loss, papilledema  hold ATRA, pain control +/-
steroids/acetazolamide
ACUTE MYELOID LEUKEMIA (AML)
• Epi: most common leukemia in adults (80%). Risk Category Genetic Abnormality (NCCN 2019 AML Guidelines)
Median age of dx: 68yo. t(8;21)(q22;q22.1); RUNX1-RUNX1T1
• S/sx: pancytopenia (fatigue, petechiae, inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
ecchymoses, infections), myeloid sarcoma (i.e. Favorable
Biallelic mutated CEBPA
chloroma), leukemia cutis (non-tender Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow
red/brown papules/nodules), neutrophilic Mutated NPM1 and FLT3-ITDhigh
dermatosis (i.e. Sweet syndrome: tender Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow
red/violet papules/plaques), gingival Intermediate (without adverse-risk genetic lesions)
hypertrophy (due to leuk. infiltration), joint t(9;11)(p21.3;q23.3); MLLT3-KMT2A
swelling (leuk. infiltration, gout), leukostasis Cytogen. abnormalities not classified as favorable or adverse
(WBC >50K; SOB, HA, blurry vision, stroke) t(6;9)(p23;q34.1); DEK-NUP214
• Subtypes: t-AML (therapy-related from chemo, t(v;11q23.3); KMT2A rearranged
radiation), s-AML (secondary from preceding t(9;22)(q34.1;q11.2); BCR-ABL1
heme disorder, e.g. MDS, MPN, PNH) inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);
• Risk stratification: based on cytogenetics, Poor/Adverse
GATA2,MECOM(EVI1) -5 or del(5q); -7; -17/abn(17p)
mutations, performance status Complex karyotype, monosomal karyotype
(Karnofsky/ECOG). Worse if t-AML or s-AML. Wild-type NPM1 and FLT3-ITDhigh
• Treatment: (NEJM 2009;361:1249) Mutated RUNX1; Mutated ASXL1; Mutated TP53
1) Day 1 Induction Chemotherapy: standard regimen for “medically fit” pts: “7+3”, cytarabine continuous infusion x 7d +
ida/daunorubicin (bolus/short infusion) days 1-3. Older pts (≥60 yrs) receive lower-intensity therapy. Regimen will kill leukemia &
healthy BM cells but will not ablate the marrow. The goal is for healthy BM cells to recover more quickly and restore normal
marrow function. Additional/alternative targeted agents for pts with certain cytogenetic abnormalities:
• Midostaurin (tyrosine kinase inhibitor) added to 7+3 in AML with FLT3 mutations (NEJM 2017;377:454)
• Liposomal cytarabine/daunorubicin (Vyxeos): improved survival in therapy- and MDS-related AML compared w/ standard
7+3 (JCO 2018;36:2684)
• Gemtuzumab ozogamicin added to 7+3 in CD33-positive AML (Blood 2017;130:2373)

3a) Residual Leukemia: if 3b) No Residual Leukemia: if BM is

2) Day 14 Bone Marrow: residual leukemia cells, re- ablated (i.e. sufficiently acellular without
check for residual leukemia induction chemo (e.g. 7+3, 5+2, evidence of residual leukemia), check for
Vyxeos) may be given. complete remission (CR) at day 28.

5) Day 28 BM Biopsy: 4) Day 21-25 Count Recovery:

check for CR (<5% blasts, nl CBC) expect count recovery (may be delayed
70-80% if < 60 yo; 40-50% if >60 w/ addition of experimental therapies).

6) Consolidation Therapy: initiated soon after remission is achieved. Goal to eradicate

residual disease & sustain lasting remission. Options include chemo or allogeneic stem cell
transplant (allo-SCT), depending on pt- and disease-specific factors. In general, allo-SCT is
preferred in higher-risk disease and if pt medically able to tolerate it. Chemo in lower-risk 7) Surveillance:
disease & in pts who are not allo-SCT candidates. Risk stratification (Blood 2017;129:424): CBC every 1-3 months for
• Favorable risk: HiDAC (high dose AraC) x 3-4 cycles vs. standard dose AraC 2 years, then every 3-6
• Intermediate risk: chemo vs. allo-HSCT months up to 5 years.
• Unfavorable risk: allo-HSCT vs. clinical trial
• Older pts with high-risk dz can be treated with intermed-dose cytarabine or hydroxyurea

• Complications: (1) DIC (if presentstrong suspicion for APL, see below); (2) febrile neutropenia; (3) TLS  allopurinol, fluids,
consider rasburicase if uric acid >10; (4) leukostasis  hydroxyurea, fluids, consider leukapheresis
David J. Lee
136
TOC

Oncology Lymphoma
Lymphadenopathy (LAD) Evaluation (Am Fam Phys 2016;94:896)
• Generalized LAD DDx: HIV, EBV, mycobacteria (TB), SLE, medications (e.g. phenytoin), sarcoid, lymphoma/malignancy
• Localized LAD DDx: cervical (EBV, CMV, toxo, TB, lymphoma), supraclav (malignancy), axillary (infxn, breast CA), inguinal (STDs)
• Hx: exposures, travel, meds, B Sx (fevers/drenching night sweats, >10% unintentional wt loss in 6 mo), other s/sxs of infxn or malig
• Exam: localization (think about area of nodal drainage), size (abnormal >1 cm), consistency, fixation, tenderness (inflammation)
• Labs: CBC, HIV (RNA if acute), LDH, HBV/HCV, PPD/TSpot, RPR, ANA, heterophile Ab; consider HTLV and EBV serologies
• Imaging: CT C/A/P (I+), PET (can define node size and distribution, more helpful for monitoring of disease treatment/progression)
• Biopsy: consider if large node (>2cm), persistence 4-6 wks, or increase in size, with immunophenotyping and cytogenetics
o Excisional (open) biopsy: reveals abnormal cells and nodal architecture (THIS IS THE PREFERED METHOD)
o Core needle biopsy: tissue for molecular studies, alternative to open if node inaccessible; ask IR to use large-bore needle
o FNA: can be used as initial screening test for LAD, not diagnosis; no info on tissue architecture, high false neg rate
General Lymphoma Staging: for Hodgkin lymphoma (HL), add “B” if presence of B symptoms
Stage I: ≥ 1 LN in a single LN group, or single extralymphatic organ Stage III: LN groups above and below diaphragm
Stage II: ≥ 2 LN groups on same side of diaphragm Stage IV: disseminated ≥ 1 extralymphatic organs
BM biopsy, PET (except in HL stage IA/IIA w/ favorable features, CLL by flow cytometry), labs above, HBV serologies if Rituximab needed
Hodgkin Lymphoma: Reed-Sternberg cells (CD15+ CD30+ CD20-) in inflammatory background; bimodal age distribution (Lancet
2012;380:836)
• WHO classification (classical HL, separate from NLPHL): Hodgkin Lymphoma
o Nodular Sclerosis (70%): mediastinal mass, good prognosis International Prognostic Score (IPS)
o Mixed Cellularity (25%): periph LAD, HIV/EBV, poor resource areas 1 point per factor (JCO 2012;30:3383)
o Lymphocyte Rich (5%): periph LAD, good prognosis Age >45 Points 5y PFS
o Lymphocyte Depleted (<1%): worst prognosis (late stage @ pres) Male 0 88%
• Treatment: note risk of late effects – cardiotox, 2° malignancy, pulm tox Stage IV 1 84%
o Stage I-II: ABVD + XRT (curative intent) Albumin <4 2 80%
o Stage III-IV: ABVD x 6 cycles vs. escalated BEACOPP ± XRT Hb <10.5 3 74%
o Refractory/relapsed: salvage chemo + auto-SCT, followed by WBC ≥15,000 4 67%
maintenance Brentuximab; PD1/PD-L1 blockade (JCO 2018; 36:1428) Lymphocytes <600 or <8% ≥5 62%
Non-Hodgkin Lymphoma (NHL): a/w immunosupp (e.g. HIV, txp), autoimmune disease (e.g. Sjogren), infection (e.g. H. pylori, HCV,
HTLV1, EBV) (Lancet 2012;380:848)
• Indolent: incurable but better prognosis, follicular lymphoma international prognostic index (FLIPI) (Blood 2004;104:1258)
• Aggressive: higher chance of cure but worse prognosis, aggressive NHL revised international prognostic index (IPI) (Blood
2007;109:1857)

Diagnosis Age Prevalence Clinical Features Treatment

Aggressive, rapidly growing, nodal / - Stage I-II: R-CHOP + RT
extranodal site; BCL-2, BCL-6 or MYC - Stage III-IV: R-CHOP +/- targeted tx (lenalidomide, ibrutinib,
translocations common bortezomib-based on subtype, CD47 Ab (NEJM 2018;379:1711);
DLBCL 70 25-35%
*Double-hit lymphoma (DHL): more CAR-T in relapsed/refractory disease
aggressive subtype w/ both MYC and BCL-2 *DHL treated with aggressive tx similar to Burkitt (ie R-EPOCH, R-
or 6 translocations hyperCVAD, R-CODOX-M/IVAC)
- Stage I/contiguous II: RT preferred
Indolent, painless LAD
Follicular 60 20-25% - Stage II-IV: anti-CD20 +/- bendamustine, lenalidomide, CHOP, or
t(14:18) BCL2+
CVP (in III-IV observe to progression first)
- SLL Lugano Stage I: RT preferred
Indolent, painless LAD
SLL/CLL 65 <5% - CLL or SLL Lugano Stage II-IV: Ibrutinib, acalaburtinib +
IgM paraprotein
obinutuzumab (anti-CD20) or venetoclax + obinutuzumab
- Stage I/non-bulk II: BR, VR-CAP, R-CHOP, or LR + R maint
Aggressive, splenogemaly
Mantle Cell 60-70s <5% - Stage II-IV: RDHA and platinum, R-CHOP/R-DHAP, NORDIC
t(11;14) cyclin D1+
regimen, or HyperCVAD + auto-HSCT + R maint
Good prognosis, mucosal sites (GI) - Gastric: triple therapy if H. Pylori+
MALT 65 <5%
associated with H. pylori - Non-gastric: similar to follicular
Splenic Indolent, splenomegaly - HCV treatment can lead to regression
70s <5%
MZL associated with HCV - If HCV negative, tx with R (preferred) or splenectomy
Aggressive, rapidly growing, extranodal sites
Adult - R-CODOX-M, R-EPOCH or R-HyperCVAD
45 <1% (jaw-African, abdomen-American)
Burkitt - Diff doses for Low (single site, <10cm, nl LDH) vs. High Risk
t(8:14), cMYC+, a/w EBV & HIV
ABVD = Doxorubicin, Bleomycin, Vinblastine, Dacarbazine EPOCH = Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin
BEACOPP = Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, HyperCVAD = Hyper-fractionated Cyclophosphamide, Vincristine, Doxorubicin,
Procarbazine, Prednisone Dexamethasone
CHOP = Cyclophosphamide, Doxorubicin, Vincristine, Prednisone VR-CAP = Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone
CODOX-M/IVAC = Cyclophosphamide, Vincristine, Doxorubicin, HD-Methotrexate, RDHA and platinum = Rituximab, Dexamethasone, Cytarabine and Carboplatin, Cisplatin,
Ifosfamide, Etoposide, HD-Cytarabine or Oxaliplatin
BR = Bendamustine, Rituximab, LR = Lenalidomide, Rituximab NORDIC regimen = dose-intensified Rituximab, Cyclophosphamide, Doxorubicin,
CVP = Cyclophosphamide, Vincristine, Prednisolone Vincristine, Prednisone (maxi-CHOP) alternating with Rituximab + high dose Cytarabine

Howard J. Lee
137
TOC

Oncology Plasma Cell Disorders

E V A L U A T I O N O F P L A S M A C E L L D I S O R D E R S (Am Fam Phys 2005;71:105, Leukemia 2009;23:215)
Evaluation Utility When to Send
If suspect a 1° (e.g. B cell deficiency) or 2° humoral
Quantify immunoglobulins (Ig): IgG, IgM, IgA, IgD, IgE. Will not
Ig Levels immunodeficiency (e.g. immunosupp, marrow
discern clonal vs. polyclonal
crowding). IgG/A/M included in SPEP order set.
Detect/quantify M-protein (monoclonal protein, paraprotein;
SPEP typically, immunoglobulin from an abnormally expanded
If suspect a monoclonal B cell or plasma cell
B/plasma cell = monoclonal gammopathy). Appears as “M-spike”
process, send SPEP/SFLC. SFLC adds sensitivity.
Identify the type of M-protein (intact Ig [G, M, A, D, E], light
Serum IF (“SPEP panel” order in Epic contains quantitative
chain only [LC: κ or λ], or heavy chain only [HC])
IgG, IgA, and IgM, total protein, SPEP, and reflexive
More sensitive than IF for identifying abnormal LC abundance
IF (if M-spike detected). SFLC assay needs separate
SFLC (i.e. outside normal κ/λ ratio of 0.26-1.65). Normal ratio w/:  LC
order.)
Assay = immunosupp/def., LC = infxn/inflammation (i.e. polyclonal
activation; includes some autoimm dz) or LC renal clearance**.
Detect/quantify Bence Jones Protein (BJP) (= urine monoclonal Generally after serum M-protein confirmed, to assess
UPEP
protein, typically κ or λ LC). Dipstick will miss BJP. for nephrotoxic FLC/BJP. Use 24h urine to quantify.
Urine IF Identify the type of BJP (κ or λ) If UPEP positive for BJP.
Ig = immunoglobulin = antibody ≈ gammaglobulin (i.e in the gamma region on an electrophoresis gel; thus, “gammopathy”). SPEP = serum protein
electrophoresis. SFLC = serum free light chain. UPEP = urine protein electrophoresis. IF = immunofixation.
**ESRD can  serum LCs and skew ratio up to 3. Get UPEP + urine IF to rule out urine Bence Jones Protein.
Note, some therapeutic antibodies may show up in above assays as false positives (e.g. daratumumab).
C L A S S I F Y I N G P L A S M A C E L L D I S O R D E R S (Lancet Oncol 2014;15:e358)
CRAB symptoms: Ca++ (>11 mg/dL) or Renal dz (Cr >2) or Anemia (Hgb <10) or Bone lesions (≥1 focal lesion on survey, CT, or PET).
All those with M-protein ≥1.5 g/dL, IgA M-protein of any size, abnormal SFLC assay, or CRAB sx need BM biopsy.
MGUS Smoldering MM Multiple Myeloma (MM) Waldenstrom’s (WM) AL Amyloidosis
BM Involvement (%) < 10 10-60 ≥ 10 (or plasmacytoma) ≥ 10 < 10
Serum M-protein (g/dL) <3 ≥ 3 [IgG or IgA] Present Present (IgM) <3
Clinical Signs Absent Absent CRAB LAD/HSM or hyperviscosity Present
• Monoclonal Gammopathy of Undetermined Significance (MGUS): premalignant clonal plasma or lymphoplasmacytic cells.
incidence w/ age (50+: 3%, 85+: 7.5%). Classified as non-IgM, IgM, or LC. IgG>M>A>D. κ>λ. BJP in 20%. Risk of progression to
MM (or AL amyloid, LC deposition disease [LCDD], other lymphoproliferative dx). Risk of WM if IgM. MM risk if IgD. Abnl SFLC ratio
predicts prog to MM (~1%/yr). Generally, can omit BM biopsy if IgG M-protein <1.5 g/dL, normal SFLC ratio, and no CRAB symptoms.
• Smoldering Multiple Myeloma (MM): M-protein ≥3 g/dL or 10-60% BM clonal cells and no CRAB.
• MM: ≥10% BM clonal cells & CRAB. If ≥60% BM, SFLC ratio ≥100, or ≥1 focal bone lesion, meets criteria even w/o CRAB.
• Smoldering Waldenstrom’s Macroglobulinemia (WM): IgM MGUS ≥3 or ≥10% BM involved but no below symptoms.
• WM: lymphoplasmacytic lymphoma in BM, IgM MGUS in blood, and symptoms: LAD/HSM, hyperviscosity (IgM = large pentameter;
HA, vertigo, vision Δ), anemia, constitutional. Measure viscosity.
• AL amyloidosis: monoclonal LC-derived fibrils form β-pleated sheets (amyloid) and deposit in tissues. Bind Congo red (apple-green
birefringent) and thioflavine T (yellow-green). Sx: cardiomyopathy, purpura, nephrotic syndr, neuropathy, orthostasis, HSM,
macroglossia.
• Light chain deposition disease: like AL amyloid but deposition of globular monoclonal LC often in kidney.
• POEMS syndrome: (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes), a/w VEGF, sclerotic bone lesions,
and Castleman’s disease. Polyneuropathy and MGUS required for dx. Almost always λ MGUS.
M U L T I P L E M Y E L O M A W O R K U P A N D M A N A G E M E N T (Nat Rev Dis Primers 2017;3:17046; NCCN 2020 MM Guidelines)
• Lab findings/workup: AG, globulin, ESR, peripheral smear (rouleaux RBCs), LDH, β2M, SPEP/IF/SFLC, whole body low-
dose CT +/- PET (more sensitive than skeletal survey), BM biopsy (IHC, flow, cytogenetics, FISH)
• Prognosis: depends on age, performance status, comorbidities, R-ISS staging (incorporates cytogenetics, LDH, β2M, albumin)
• Treatment agents: most common induction regimens combine a proteasome inhibitor, immunomodulator and steroids:
o Proteasome inhibitors: bortezomib (Velcade – V, Bor), carfilzomib (Cz), ixazomib (Ix)
o Immunomodulatory agents (IMiDs): lenalidomide (Revlimid - R), pomalidomide (Pom), thalidomide (T),
o Steroids, chemo: dexamethasone (D), prednisone (P), melphalan (M), cyclophosphamide (Cy), doxorubicin (dox)
o Monoclonal Abs: daratumumab (anti-CD38, Dara; NEJM 2018;378:518); elotuzumab (anti-SLAMF7, Elo)
• Induction & consolidation: NOT curative
o Induction: triplet therapy with VRd most common, other combos also seen; CyBorD used if renal failure at presentation.
o If candidate for autologous SCT  consolidation w/ auto-SCT; consider early SCT if > standard risk
 Well-established PFS benefit with auto-SCT; improved OS also seen in most RCTs (NEJM 2017;376:1311)
 Early (SCT directly after SC collection) vs. delayed SCT (at time of relapse): better PFS, but no clear OS benefit
o Maintenance therapy (e.g. single agent R or V) following SCT or if not SCT candidate
o Relapsed/refractory: combinations of above agents or repeat auto-SCT; CAR-T under investigation (NEJM 2019;380:1726)
• Other Tx: aimed at reducing skeletal lesions/fractures (bisphosphonates, denosumab, XRT), hyperCa++, renal damage, hyperviscosity,
infection (PCP, HSV, fungal, VZV; depending on therapy), VTE (immunomodulator-induced higher risk), anemia (EPO).

Zandra Walton
138
TOC

Oncology MDS & MPN

MYELODYSPLASTIC SYNDROME ( M D S ) : clonal stem cell mutation  ineffective/dysmorphic hematopoiesis  risk of AML
• Presentation: age > 50, cytopenia sxs (fatigue, bleed, infxns), most are asymptomatic with unexplained cytopenias (~90% anemia)
• Risk factors: male, exposure (benzene, tobacco), tx-related (alkylating agents, XRT), genetic (Down, Li-Fraumeni, Diamond-Blackfan)
• Diagnosis: smear: hypogranulated PMNs, pseudo-Pelger-Huet (hypolobated PMNs), ovalomacrocytosis, blasts (<20%). BM Bx:
usually hypercellular w/ single- or multi- lineage dysplasia, +/- blasts <20%, +/- ring sideroblasts, +/- fibrosis
o Exclude other reasons for cytopenias: ANA, HIV/HCV, EBV/CMV/Parvo, EtOH, B12/folate/copper, Zinc, TSH, Fe/TIBC/ferritin,
DAT, SPEP/SFLC, CD55/59 flow (PNH), erythropoietin, review meds (e.g. MTX, mycophenolate mofetil, cyclophosphamide)
• Prognosis: based on IPSS-R; median survival ranges from 0.7 yr in “very high” risk, to 8.8 yrs in “very low” risk
o IPSS-R is based on blast %, cytogenetics, cytopenias. Correlates w/ survival & progression to AML
• Treatment: based on IPSS-R, performance status & age; see NCCN 2020 MDS Guidelines
o Low risk: observation and supportive care. Anemia: Epo (if serum epo < 500), pRBC (watch for Fe overload). Neutropenia: abx
ppx +/- G-CSF (if infxn). Thrombocytopenia: if suspect ITP, TPO agonist +/- steroids
o Intermediate/high risk: hypomethylating agent (decitabine, azacitidine) to prolong time to transplant or if poor SCT candidate
 If good PS: allogeneic HSCT (only curative tx, though with high up-front toxicity)
o Special variants: del(5q) = lenalidomide; hypoplastic MDS with PNH+ cells, HLA-DR15 or age <60 = ATG + cyclosporine
M Y E L O P R O L I F E R A T I V E N E O P L A S M S ( M P N ) : clonal expansion of one or more myeloid lineages
Most common: CML, polycythemia vera (PV), essential thrombocythemia (ET), & primary myelofibrosis (PMF). Sequelae vary depending
on lineage; PV & ET can progress to 2° MF; all can transform to AML. Goals of Tx: improve sx, prevent thrombosis, prevent transformation
to AML; only potentially curative therapy for any MPN is allogeneic HCT. (NCCN 3.2019 MPN Guidelines, NCCN 3.2020 CML Guideline)
PV ET Primary MF CML
(Hgb WBC Plt) (Plt) (Hgb WBC Plt) (Hgb WBC Plt)
Hyperviscosity (HA, dizziness, Up to 50% asx at dx. Fatigue, night sweats, weight Often asymptomatic; fatigue,
Δ vision, abdominal pain, Similar to PV loss, abd pain, satiety, night sweats, bleeding, abd
Sx ruddy complexion), (erythromelalgia), hepatosplenomegaly, anemia, pain, weight loss,
thrombosis (VTE, stroke, bleeding (2/2 acquired thrombotic/hemorrhagic splenomegaly (most common
Budd-Chiari), aquagenic vWF disorder, consider events physical exam finding)
pruritus, erythromelalgia if plt > 1 million)
Major WHO criteria: Major WHO criteria: Major WHO criteria: Mutation: BCR-ABL
- Hgb >16.5 (♂), Hgb >16 (♀) - PLT >450k - BM Bx w/ “dry” tap showing (by FISH, RT-PCR)
- BMBx showing trilineage - BM Bx shows reticulin or collagen fibrosis CBC with  granulocytes of all
proliferation enlarged - Mutations: JAK2 50%, CALR maturities (myelo, metamyelo,
- Mutations: JAK2 V617F or megakaryocytes with 40%, MPL 5% bands), basophilia, eosinophilia
Dx
JAK2 exon 12 mutation hyperlobulated nuclei Minor WHO criteria:
Minor WHO criteria: - Mutations: JAK2 50%, - Leukoerythroblastic smear Can be chronic, accelerated, or
- Low Epo (below reference) CALR 30%, MPL 5% (left-shift, nucleated and blast phase. In blast phase,
Minor WHO criteria: teardrop RBCs), LDH, can convert to AML (80%) /
- Other clonal markers anemia, splenomegaly ALL (20%)
All: phlebotomy (goal HCT < All: ASA 81 (unless Allo-HSCT (only cure), BCR-ABL inhibitors: imatinib,
45), ASA 81 (*if no bleeding), vWF disorder) transfusion, hydroxyurea, nilotinib, dasatinib. Allo-HSCT if
allopurinol, antihistamine If age>60 or risk ruxolitinib (JAK2 inhibitor, resistant or in accelerated/blast
Tx If >60, risk thrombosis: thrombosis: primary benefit is symptom phase.
hydroxyurea (but risk AML hydroxyurea > reduction) (NEJM 2012;366:787)
transformation) > interferon-α interferon-α >
2nd line: ruxolitinib (NEJM anagrelide (NEJM
2015;372:426) 2005;353:33)
Epo: hypoxia-induced Infection, inflammation, Other MPNs (especially ET); Leukemoid rxn (LAP), drugs
(heart/lung dz, carboxy-Hb, iron deficiency, MDS; hairy cell leukemia; (steroids, GCSF, ATRA),
DDx smoking) vs. Epo-producing splenectomy, neoplasm other marrow-infiltrating infection (C. diff, mono), severe
tumor. Epo: activating epo malignancies hemorrhage, splenectomy,
receptor mutation (rare) DKA, organ necrosis.
OTHER MDS/MPN TYPES:
• Chronic myelomonocytic leukemia (CMML): MDS/MPN overlap syndrome w/ monocytosis >1000 & splenomegaly
• Systemic mastocytosis: rare, mast cells and precursors (CD34+); Dx: skin bx (cutaneous), BMBx (systemic),  tryptase, KIT D816V
mutation, urinary histamine; Sx: flushing, pruritus, anaphylaxis, Eos; Darier Sign: erythema/urticaria when rubbing skin. Tx: no
cure, treat sx; hydroxyurea, interferon-α; c-kit inhibitor Masitinib. Epi available for anaphylaxis. H1- and H2-block for systemic sx.
• Hypereosinophilic syndrome: eosinophilia (>1500) w/o other etiology; Tx: steroids, imatinib if FIP1L1–PDGFRA fusion gene,
mepolizumab, HSCT. See Hematology: Eosinophilia.
• Hemophagocytic lymphohistiocytosis (HLH): “cytokine storm” syndrome, 1° or 2° (infectious, inflammatory, neoplastic – esp.
lymphoma); Dx: pathologic mutation or 5+: fever, cytopenia, splenomegaly, TG, ferritin, NK cells, CD25, hemophagocytosis in
BM/Spleen/LNs. H-score for prob. Sx: fever, HSM, rash, sepsis; Tx: depends on etiology. HLH-94 protocol (dexamethasone/etoposide
then Cyclosporine A +/- IT MTX if CNS involvement), survival ~2 mo w/o therapy. Also see: Anemia & Pancytopenia.
John Schell
139
TOC

Oncology Stem Cell Transplantation

TERMINOLOGY
• One-liners include: underlying malignancy; day since transplant (transplant day = day 0, day before = day -1, day after = day +1);
conditioning regimen (myeloablative vs reduced-intensity/non-myeloablative); autologous vs. allogeneic transplant; donor type
(matched related/unrelated, haploidentical) and source (bone marrow, peripheral blood stem cells, cord blood); GVHD prophylaxis
regimen, and include day 0
• Example one-liner: “35M w/ AML (FLT3-mutated) who is now day +4 from his myeloablative (flu/mel) matched related donor (MRD)
peripheral blood stem-cell transplant (PBSCT) with tacrolimus/methotrexate GVHD prophylaxis (day 0 = 1/1/19).”

Allogeneic Transplant Autologous Transplant

Definition Transplant of non-self (donor) stem cells Transplant of self (patient) stem cells
Reconstitute hematopoiesis after high-dose Reconstitute hematopoesis after high-dose
chemo and graft-versus-tumor (GVT) effect to kill chemo to kill all cells in BM (tumor/normal).
Goals
high-risk disease or treat profound marrow failure. Intent is mostly curative except for myeloma
Always curative intent (goal deep remission)
High-risk AML (40-60% 5YS), ALL (40-50% 5YS), 1st relapsed lymphomas (40-50% 5YS),
MDS (45% 5YS), high-risk myelofibrosis, TKI- myeloma (35% 5YS); relapsed Waldenström,
Indications resistant CML, indolent relapsed lymphomas, AL amyloidosis, select solid tumors (germ cell,
aplastic anemia, thalassemia, sickle cell dz, primary neuroblastoma, Ewing sarcoma, breast),
immunodeficiency (SCID), inborn errors of metab. autoimmune dz (MS, SS, Crohn, SLE)
Traditionally BM, now more commonly PBSC. Usually peripheral blood stem cells (PBSC) –
Source of cells
Umbilical cord blood also used (delays engraftment) less invasive, more rapid engraftment than BM
Donor HLA matching  mobilize and harvest donor Mobilize and harvest cells from self 
Timeline overview cells  conditioning with chemo ± RT to eradicate conditioning with chemo ± RT to eradicate
(see below for disease  transplant  engraftment (count disease  transplant  engraftment (count
details) recovery)  monitor for infectious, transplant, and recovery)  monitor for infectious & transplant-
graft-versus-host (GVHD) complications related complications
Time to engraftment 14-28 days (time for CB > BM > PBSC) 7-10 days
Yes, skin, liver, GI most commonly affected. No
Graft-versus-host
Acute (w/in 6 mo, peri-transplant mortality)
disease (GVHD)
Chronic (>3 mo, morbidity/mortality mo/yrs later)
Graft-versus-tumor Yes (therapeutic mechanism – goal for donor T cells No
(GVT) effect to engraft and attack host tumor cells)
Immunosupression Yes (sometimes for 1-2 years) No

T I M E L I N E (NEJM 2006;354:1813)
(1) Mobilization and harvest of stem cells: few weeks prior to transplant admission
o Stem cells mobilized using G-CSF ± chemotherapy ± plerixafor (CXCR4 inhibitor)
(2) Conditioning: day -8 to -3; varies based on conditioning regimen and donor type (Blood 2014;124:344)
o Goal: (i) eradicate/debulk tumor (ii) produce adequate immunosuppression to allow donor cell engraftment
o Types: myeloablative, reduced-intensity/nonmyelablative regimens of chemotherapy / radiation
(3) Transplantation: day 0, infusion of stem cells
(4) Engraftment (count recovery): day +7 to +28 varies based on stem cell source
o Defined as persistent ANC > 500 & Plt > 100k after nadir (nadir occurs 3-6d after conditioning)
o G-CSF (neupogen/filgrastim) accelerates neutrophil engraftment by a few days: 10 mcg/kg/d (Day +1 until ANC > 500)
o Transfusions (irradiated & leukoreduced), Hct>25, Plt>10K (>50K if bleeding), attending-dependent
 Check post-transfusion CBC in 15-60 min

ALLOGENEIC STEM CELL TRANSPLANT: SPECIAL CONSIDERATIONS

• Donor types: matched to pt by HLA typing to minimize GVHD; matching at alleles A, B, C, DR, DQ
o Matched-related donor (MRD): preferred, compatible siblings, matched at 10/10 HLA alleles
o Matched-unrelated donor (MUD): common, NMDP database, matched at 8-9/10 HLA alleles
o Haploidentical: any parent/sibling/child, match at 5/10 HLA alleles,  GVHD (Blood Rev 2015;29:63)

Stem Cell Source Harvest Engraft GVHD Risk Notes

Aspirated from iliac No longer favored despite lower GvHD risk,
Bone marrow (BM) 18-21d Reference
crest due to higher graft failure rate than PBSC
Peripheral blood stem Mobilization and Preferred source due to faster engraftment
12-15d Higher risk
cells (PBSC) peripheral aphersis and improved graft versus tumor effect
Immature SC from  txp-mortality compared to MUD (similar
Cord blood (CB) 28d (most
umbilical cord at Lower risk DFS/OS)
(Blood 2013;122:491) variable)
delivery Allows for more HLA disparity
Annabelle Anandappa
140
TOC

Oncology Stem Cell Transplantation

• Conditioning (preparative) regimens: determined by underlying condition, disease status, performance status/comorbidity
o Agents: chemo (ex. alkylating agents - busulfan, cyclophosphamide, melphalan) ± total body irradiation ± mAb
o Myeloablative conditioning: complete disease eradication & ablation of host BM/immune cells
 Used for young healthy patients, with MRD or no CR;  toxicity,  immunosuppr,  txp-mortality,  relapse
o Reduced intensity conditioning (RIC): tumor debulking & immunosuppress enough to allow engraftment
 Permits transplant in elderly w/ co-morbidities;  toxicity,  txp-mortality,  relapse,  GVHD
 Result is mixed chimerism: host and donor hematopoiesis coexists – rely on Graft vs. Tumor effect for cure
• GVHD PPX: day -3 to indefinite (tapered after months to years), goal is to prevent graft rejection & acute/chronic GVHD
o Immunosuppression regimens: combined Tacrolimus/Methotrexate or Tacrolimus/Sirolimus most common
o T-cell depletion regimens: (ATG, decreased T-cell dose) no longer favored;  chronic GVHD but no effect on OS
Immunosuppressant Mechanism Dosing Toxicities
Tacrolimus (FK506) Calcineurin inhibitor Trough goal: 5-10 ug/L AKI, K, Mg, LFTs, N/V, TMA, tremor, DM risk
Sirolimus AKI, Sinusoidal obstruction syndrome (SOS),
mTOR inhibitor Trough goal: 3-12 ug/L
(Rapamycin) leukopenia, TMA, HLD, cytopenias
Methorexate Anti-metabolite Given on day +1,3,6,11 w
Mucositis, myelosuppression, hepatotoxicity, AKI
(MTX) (inhibits thymidine) cyclosporine or tacrolimus
Mycophenolate Anti-metabolite
N/A Myelosuppression, N/V/D
(MMF/Cellcept) (inhibits purines)
Post-transplant Given days +3 and +4,
Kills early
cyclophosphamide particularly for
alloreactive T-cells
(PTCy) haploidentical

I N F E C T I O U S C O M P L I C A T I O N S : 2/2 chemo-related pancytopenia & immunosuppression (ASBMT/IDSA Recommendations)

• Infectious PPX: items with asterisks have well-established benefit and are employed at all institutions
o Bacterial: cipro 500 BID or levofloxacin 500 QD (Day -1 to ANC > 500)
o Viral (HSV/VZV)*: acyclovir 400 TID/800 BID or famciclovir 500 BID (Day -1 to +365 [auto]; 2 yrs min & until off IS [allo])
o Fungal*: fluconazole 400 QD or vori 200 BID or posaconazole 200 TID (Day -1 to ANC>500 [auto], until 3-6 mo [allo])
o PCP/Toxo*: Bactrim DS QD (start after engraftment as outpatient for 6 months [auto], >1 year or off IS [allo])
o CMV*: no ppx, if CMV+ pre-emptive treatment with IV ganciclovir or PO valganciclovir (Day -1 to +100)
 Letermovir is a novel anti-CMV drug approved for use in high-risk allo-HCT patients
• Timeline:
Day 0-30 Day 30-90 Day 90+
Pre-Engraftment Early Post-Engraftment Late Post-Engraftment
Neutropenic, mucositis, lines Poor cellular immunity Poor cellular and humoral immunity
Immune Defect
Acute GvHD Acute GvHD Chronic GvHD
GPCs & GNRs (F&N) GPCs & GNRs Encapsulated bacteria (SHiN)
Bacterial
Neutropenic enterocolitis (typhlitis) Nocardia
Resp/enteral (adeno, flu, RSV, para) Resp/enteral (adeno, flu, RSV, para) Resp/enteral (adeno, flu, RSV, para),
Viral HSV EBV (risk of PTLD), CMV EBV (PTLD), VZV, BK (hemorrhagic
HHV6 (screen for in cord blood tx) cystitis), JC (PML)
Fungal Aspergillus, candida Aspergillus, candida, PCP Aspergillus, PCP
Parasitic - Toxo Toxo (can mimic PCP PNA)
• Neutropenic enterocolitis (typhlitis): polymicrobial infxn leading to necrotizing enterocolitis, most often involving cecum
o Sx: fever, ANC < 500, abdominal pain (often RLQ), n/v, watery/bloody diarrhea
o Micro: polymicrobial (GPC/GNR/anaerobes/fungal), clostridium septicum a/w fulminant course & high mortality rate
o Dx: CT (I+/O+) w/ bowel wall thickening, mesenteric stranding, bowel dilatation, mucosal enhancement, pneumatosis
o Tx: pip/tazo vs. -penem vs. cefepime/flagyl + surgery c/s + add fungal coverage if persistently febrile > 72h

N O N - I N F E C T I O U S C O M P L I C A T I O N S : immune-mediated organ damage, toxic effects of chemo, or immunosuppression

• Non-infectious PPX:
o Tumor lysis syndrome: allopurinol 300 QD (admit to Day -1, but much lower risk in SCT than with induction chemo)
o Hepatic sinusoidal obstruction syndrome (SOS): ursodiol 300 TID (admit to Day +30)
• Day 0-30: common to have mucositis, nausea/vomiting, alopecia, rash, diarrhea
o Nausea/vomiting: optimal management varies based on timing relative to chemo initiation
 Immediate (day 0-1): 5-HT3 blockade (Zofran, Aloxi), neurokinin-1 antagonists (Emend), steroid (decadron)
 Delayed (day 2-5 post chemo): dopamine (D2) blockade (Compazine, Reglan, Haldol)
 Late (5+ days post chemo): Ativan, steroids, Marinol (more helpful in younger pts, marijuana users)
o Mucositis: most HSCT patients get some degree of mucositis; duration and severity are worse in allogeneic HSCT.
Treatment is focused on pain and caloric intake.
Annabelle Anandappa
141
TOC

Oncology Stem Cell Transplantation

 Pain: topical/IV opiates; low threshold for PCA
 Nutrition: TPN initiated if PO intake impaired by mucositis, and expected to continue for ≥1 week
 Palifermin (recombinant keratinocyte growth factor): can reduce duration, severity of mucositis
o Liver – sinusoidal obstruction syndrome (SOS) (previously veno-occlusive disease):
 Cause: direct cytotoxic injury to hepatic venules leading to hypercoaguable state and microthrombi
 Sx: RUQ pain, jaundice, ascites/edema; ALT/AST/TBili, INR/Cr (if acute liver failure or HRS)
 Dx: doppler U/S c/w reversal of portal vein flow, liver bx; Dx criteria: Tbili >2mg/dL, hepatomegaly/RUQ pain, sudden
weight gain (fluid) >2-5% baseline body weight
 PPX: ursodiol 300 TID
 Tx: defibrotide
o Pulm – idiopathic interstitial pneumonitis/diffuse alveolar hemorrhage (DAH):
 Cause: direct cytotoxic injury to alveoli
 Sx: fever, hypoxemia, diffuse lung infiltrates (ARDS)
 Dx: bronchoscopy w/ serial lavage (r/o infection, blood) – progressively bloodier on serial lavage c/w DAH
 Tx: high-dose steroids; + for DAH: FFP to correct coagulopathy, maintain plt >50k; limited data for recombinant FVIIa
o Heme – graft failure:
 Primary: persistent neutropenia without engraftment
 Secondary: delayed pancytopenia after initial engraftment (immune or infectious)
o Engraftment syndrome: sudden PMN recovery causing cytokine storm and vascular leak
 Sx: fever, rash, weight gain, bone pain; if severe – pulmonary edema,  LFTs, AKI, seizures
 DDx: infection, drug reaction, acute GVHD (dx of exclusion)
 Tx: high-dose IV steroids (*discuss with attending prior to initiation of steroids!)
• Day 30+
o Acute GVHD: ~40% in MRD, ~60% in MUD (cellular immune response, TH1 cell-mediated) (NEJM 2017;377:2167)
 Risk factors:  HLA mismatch,  age, female donor/male recipient, TBI-myeloablation, PBSC > BM > CB
 Cause: donor T-cell recognizes and attacks recipient native cells (usually day 0 to +100, but can be later)
 S/Sx: skin (rash, graded by biopsy findings, % body surface, desquamation), liver (cholestatic injury, graded by
bilirubin), GI (diarrhea, graded by volume of diarrhea/day)
 DDx: skin (viral, drug, engraftment), liver (viral, drug, SOS, TPN), GI (C. diff, CMV, adeno, GNR, typhlitis, drug)
 Tx: Grade I (topical), II-IV (IV methylpred 1-2 mg/kg x 5d; if severe or steroid-refractory: MMF, etanercept, ruxolitinib
(Jakafi; NEJM 2020;382:1800), antithymocyte globulin (ATG); many other agents proposed. Consider trial enrollment.
o Chronic GVHD: 30-70% of patients s/p allo-HSCT (humoral immune response, TH2 cell-mediated) (NEJM 2017;377:2565)
 Cause: both donor T-cell & B-cell mediated attacks on recipient after day +100
 Risk factors: prior acute GVHD, HLA mismatch,  age, PBSC > BM
 Sx: resembles scleroderma (sicca, dysphagia, arthritis, skin tightening, malar rash), lung (obliterative bronchiolitis),
liver (cholestasis), cytopenias/immunodeficiency; any organ system can be affected
 Tx: steroid +/- broad immunosuppression, photopheresis (ECP) for skin; novel agents including ruxolitinib (Jakafi),
ibrutinib, rituximab have been shown to be effective in steroid-resistant disease
o PTLD (post-transplant lymphoproliferative disease): ~1% in allo-SCT; median day +70-90 (NEJM 2018;378:549)
 Cause: IS leads to EBV reactivation (dormant in B cells) & clonal B cell proliferation (usually donor-derived)
 Risk factors: T-cell depleted donor graft, treatment with ATG, HLA-mismatch, cord blood transplant
 Dx: plasma EBV DNA monitoring can raise suspicion for PTLD (thousands of copies/microL compared with
hundreds); biopsy with immunophenotyping for true dx
 Tx: reduce IS, anti-viral, rituximab-based chemo (if systemic) vs. surgery/RT (if localized)
QUICK REFERENCE
(Day -8 conditioning to Day +30 engraftment)
DDx abdominal
Monitor S/Sx: DDx fever: DDx dyspnea/hypoxia:
pain/ascites:
• Chemo toxicity: • Infection (bacterial, • Neutropenic • Existing dz: CHF, COPD, asthma
mucositis, N/V/D, viral, fungal, parasitic) enterocolitis • PNA: bacterial, fungal, aspiration
S/Sx of infection • Drug rxn • Colitis: C. Diff, CMV • Volume (often on mIVF with chemo)
• GVHD: rash, jaundice, • Engraftment (d7-9 for • SOS • Drug: chemo-induced lung injury or
diarrhea (24h volume) auto, d14-21 for allo) • GVHD cardiotoxicity
• SOS: RUQ pain, • Tumor (initial lysis & • Obstruction/ileus/ • Engraftment (pulmonary edema
jaundice, ascites, cytokine release) constipation from capillary leak)
edema • Immobility (Atelectasis, • Pneumonitis
• Engraftment aspiration, DVT/PE) • Alveolar hemorrhage
syndrome: fever, • GVHD • PE, TRALI, GVHD
dyspnea, edema

Annabelle Anandappa
142
TOC

Oncology CAR T-Cell Therapy

MECHANISM OF ACTION (NEJM 2018;379:64)
• Chimeric antigen receptor T cells (CAR-T cells): type of autologous therapy; T lymphocytes
collected from the patient, genetically modified with a gene encoding a chimeric antigen receptor
(CAR) that directs the T-cells against a selected antigen on the patient’s tumor
• CAR: transmembrane engineered protein consisting of extracellular immunoglobulin (antibody)-
derived domains (ScFv), which target and bind a tumor antigen (i.e. CD19), fused to an intracellular
T-cell receptor domain (CD3z) and a costimulatory domain that signal for T-cell activation (see figure)

FDA-APPROVED THERAPIES: anti-CD19 cell-based therapies

• Yescarta (axicabtagene ciloleucel; aka axi-cel)
o Aggressive, refractory adult B-cell lymphoma: ZUMA-1, Phase II trial, 54% complete response (NEJM 2017;377:2531)
• Kymriah (tisagenleucel)
o Relapsed/refractory B-ALL age <25y: ELIANA, Phase II: NEJM 2018;378:439. Adult phase I long-term f/u: NEJM 2018;378:449
o Adults with relapsed/refractory DLBCL: JULIET- Phase II, 52% OR (40% CR), 65% w/o relapse at 1y (NEJM 2019;380:45)
• Other CAR-Ts for hematologic malignancies (CD19, CD123, etc.) and other antigen/solid malignancies under investigation:
BCMA/multiple myeloma (NEJM 2019;380:1726), IL13Rα2/GBM (NEJM 2016;375:2561), others (Front Immunol 2019;10:128)
• Also under investigation: combination of immune checkpoint blockade (anti-PD, anti-PD-L1) with CAR-T (Cancer Cell 2019;36:471)

TOXICITIES (NCCN 1.2020 Guidelines; Nat Rev Clin Oncol 2018;15:47) CRS Grade Therapy
• Cytokine-release syndrome (CRS) If >3 days, consider tx
o Most common toxicity. Typically 2-3d post-infusion, lasts 7-8d. 1 Fever
as in grade 2.
Fulminant cytokine release (IL‐2, sIL2R, IFNγ, IL‐6, GM‐CSF) Tocilizumab q8h PRN
triggered by CAR-T engagement of antigen and T cell Fever w/: hypotension
up to x4. Add steroids
proliferation. risk in bulky disease and specific constructs. 2 not requiring pressors
per below if still BP
o Signs/Sx: fever, BP, HR, pO2, malaise, anorexia, myalgia. or hypoxemia on NC
after 1-2 doses. Fluids.
Can affect any organ (CV, lung, GI/liver, renal, CNS) w/ Fever w/: BP
arrhythmia, ARF, capillary leak, HLH/MAS. requiring pressors or Tocilizumab as above.
o Diagnosis: monitor for 14 days post infusion (inpt or possibly 3 pO2 requiring HFNC / Dexamethasone 10 mg
close outpt); vitals, basic labs, ferritin, coags, CRP, TLS labs. face mask / Venturi / IV q6h (or equiv.).
When suspect: admit, tele, r/o infection. NRB
o Therapy: if plan to treat CRS with steroids or anti-IL6, first get Fever w/: BP Tocilizumab + dex as
clear approval by the treating attending requiring multiple above. If refractory,
 Broad-spectrum abx if fever or neutropenic until r/o infxn 4
pressors or pO2 consider methylpred
 MGH: tocilizumab (anti-IL6R) 8 mg/kg IV over 1h (max 800 requiring NIPPV / MV 1g/d IV x 3d w/ taper
mg); siltuximab (anti‐IL6) also exists; 2nd line: steroids
• CAR-T-cell-related encephalopathy syndrome (CRES) Immune Effector Cell-Associated Encephalopathy
o Etiology is unclear; passive cytokine diffusion into brain (IL-6, IL- (ICE) Assessment Tool
15 a/w neurotoxicity) vs. CAR-T trafficking into CNS AAOx3 (4 pts), naming x3 (3 pts), follows
Max score:
o Timing: typical onset 4-10d post-infusion, duration 14-17d, commands (1 pt), writes sentence (1 pt),
10
variable. Can be concurrent w/ CRS or after (more severe) serial 10s from 100 (1 pt)
o S/Sx: toxic encephalopathy. See ICE tool and ICANS ASBMT Immune Effector Cell-Associated Treatment
grade. Neurotoxicity (if CRS, add
o Diagnosis: neuro consult, ICANS (or CARTOX‐10) Syndrome (ICANS) Grade tocilizumab)
score. If ≥ grade 3: MRI brain w/wo contrast + EEG ± Grade 1 ICE = 7-9 Supportive
LP. Funduscopic exam. ICE= 3-6, or does not awaken Dex 10 mg IV x1. If
o Therapy: Ppx: if CAR-T known to cause neurotoxicity, Grade 2 spontaneously worsens, advance.
start seizure ppx on day of infusion (levetiracetam ICE = 0-2, or awakens only to Dex 10 mg IV q6h
500-750 mg q12h for 30d). Tx per chart. Grade 3 tactile stimulus, or focal edema on PRN or methylpred
o Prognosis: generally reversible, rare fatal cases neuroimaging 1 mg/kg IV q12h.
• CAR-T-cell-related hemophagocytic ICE = 0, difficult to arouse,
lymphohistiocytosis (HLH) / macrophage activation prolonged seizure >5m or w/o Methylprednisolone
syndrome (MAS) Grade 4 return to b/l, or deep focal motor IV 1g/d x 3d or
o Profound systemic inflammatory state characterized weakness (e.g. paresis), or equivalent w/ taper.
by cytotoxic T cell hyperactivation (IFNγ)  diffuse cerebral edema or ICP
macrophage activation (IL-6), lymphohistiocytic tissue infiltration, and multiorgan failure; develops in ~1% of patients treated with
CAR‐T. S/Sx: fever, cytopenias, multiorgan dysfunction
o Criteria for considering: rapidly rising ferritin >5K with cytopenias in context of CRS, especially if any: oliguria or Cr >4 or 3x
b/l, or pulmonary edema, or AST or ALT 5x ULN, or Tbili 1.5x ULN; hemophagocytosis in bone marrow or other organs.
o Dx: labs resemble HLH. CBC w/ diff, ferritin, sIL2R, LDH, fibrinogen, TGs, LFTs, Cr. BMBx rarely critical (low Sn/Sp).
o Tx: high mortality, do not delay diagnosis, escalate therapy aggressively. Manage as per CRS with addition of steroids. If no
improvement in 48h, consider etoposide or intrathecal cytarabine for neurotoxicity.
See Anemia & Pancytopenia for further details on HLH.

Zandra Walton
143
TOC

Oncology Solid Organ Malignancies

Organ Risk factors/screening Staging/diagnostics Treatment
Prostate Risk factors: Staging: Low risk (T1c/T1-T2a + Gleason score ≤6 + PSA
 Adenocarcinoma  Age, AA race, genetic  AJCC Stages I- IV: ≤10) (JCO 2015;33:3379, NEJM 2016;375:1415):
(95%) factors (BRCA1/2 and TNM, PSA and active surveillance (PSA, DRE +/- Bx) vs. external
 Transitional, basal family history), smoking Grade Group beam radiation therapy (EBRT) +/- brachytherapy
cell, intraductal  Grade Group: (BT) vs. radical prostatectomy (RP) +/- EBRT +/- ADT
carcinomas; Screening with PSA Gleason Score (GS) Intermediate risk (≥1 risk factor: T2b-T2c, PSA 10-
neuroendocrine, (JAMA 2018;319:1901): and Pattern 20, GS 7) (JNCCN 2019;17:479):
carcinosarcoma,  55-69: individualized risk-  NCCN risk: PSA,  Favorable (1 RF, <50% Bx cores positive): above +
lymphoma, stromal benefit discussion grade, TNM, Biopsy. RP +/- pelvic LND +/- EBRT +/- ADT
sarcoma (~5%)  70 and above: no testing Use with life  Unfavorable (≥1 RF or >50% cores +): EBRT &
Androgen deprivation expectancy to guide ADT or EBRT & BT +/- ADT, RP +/- pelvic lymph
therapy (ADT): treatment. node dissection (PLND) +/- EBRT +/- ADT
 Orchiectomy High risk (T3a/T3b-T4b or GS 8-10 or PSA >20):
After diagnosis:
 LHRH agonist: EBRT & ADT, ERBT & brachy & ADT, or RP with
 TRUS, MRI,
goserelin, histrelin, extended PLND +/- EBRT +/- ADT
leuprolide, triptorelin biomarkers, evaluate
Metastatic/recurrent (Lancet 2016;387:1163, NEJM
 LHRH antagonist: for metastases (CT,
2015;373:737, NEJM 2010;363:411):
degarelix radio-nucleotide
 Castration-sensitive: ADT +/- abiraterone/ pred vs
 Androgen R blocker bone scan)
docetaxel vs apalutamide v. enzalut. v. EBRT
(+ LHRH agonist):
Germline testing:  Castration-resistant: ADT (goal testo <50ng/dL) and
enzalutamide,
darolutamide,
 High/very high doxcetaxel (chemo naïve) or cabazitaxel (dox
flutamide NCCN risk exposed) v. mitoxantrone + pred v. abiraterone/pred
 Androgen synthesis  Any risk level if v. enzalut. vs sipuleucel-T. Bone mets: radium-223
inhib: abiraterone (+ positive FHx or or denosumab/zoledronic acid. MSI-H/dMMR:
prednisone) intraductal histology pembrolizumab. (NCCN Guidelines v. 4.2019)
Breast Risk factors: Staging: Early stage (I, IIA, IIB through T2N1):
 Infiltr. ductal (76%)  Age, genetics (BRCA1/2),  AJCC Stage I-IV:  Breast Conserving Surgery + RT vs mastectomy +/-
 Invas. lobular (8%) FHx, obesity after pathologic stage RT & HR tx & HER2 tx (≥1cm) & chemo if high risk
 Ductal/lobular (7%) menopause, menopause (TNM) + clinical Locally advanced (Stage IIB T3N0, IIA-IIIC):
 Mucinous (2%) >55, chest RT, 1st birth stage: ER/PR, Her2;  Surg + RT w/ neoadj +/- adj chemo & HR/HER2 Tx
 Tubular (1.5%) >30, nulliparity, HRT, Recurrence score (Neo)adjuvant therapy:
 Medullary (1%) menarche <13y, ETOH, (RS): OncotypeDx  ER/PR+, HER2- (NEJM 2015;372:436, Lancet
 Papillary (1%) benign breast disease, gene panel for 2013:301;805): tamoxifen or AI (no AI in
tobacco Her2(-), HR+, LN-, premenopausal) +/- ovarian suppression (OS) if
>0.5cm high risk x2-5 yrs f/b 5 yrs endo rx. Chemo: AC-T or
 TCH(P): docetaxel, Screening: TC (give for most LN+ & LN- if RS>16, <50yo)
carboplatin,  USPTF: q2y mam 50-74 Diagnostics:  HER2+: TCH(P) or ACTH(P) + ER/PR rx if HR+
trastuzumab +/-  NCCN: q1y mam > 40 or  Dx mam (Bi-RADS),  Triple Neg (NEJM 2017:372;2147): adjuvant cape
pertuzumab 10y before earliest FHx US, FNA or core Bx Metastatic/recurrent (Stage IV):
 AC-TH(P): if > 30 or 10y after RT if > (> excisional), breast
doxorubicin/
 ER+: As above +/- fulvestrant (ER antagonist) +/-
30 MRI if young or to CDK4/6 inhib or everolimus (mTOR inhib)
cyclophosphamide 
weekly paclitaxel +
 ACOG: q1-2y mam; offer assess extent (good  HER2+: THP (1st line). Or: T-DM1 (trastuzumab-
trastuz +/- pertuz 40-50, recommend 50-75 Sn, but Sp 72%) drug conjugate), trastuzumab+lapatinib
 Aromatase inh (AI):  BRCA mutation (NEJM 2017;377:523, NEJM
anastrozole, 2018;379:753): olaparib or talazoparib, platinum-
letrozole,exemestane based chemo
 Triple neg (NEJM 2018;379:2108): atezolizumab +
nab-paclitaxel. (NCCN Guidelines v.3.2020)
Pancreas Risk factors: Staging:  Resectable: surgery +/- neoadj (FOLFIRINOX vs.
 Exocr./adeno  Tobacco, EtOH, obesity,  AJC Stage I-IV: gem/abraxane) + adj (FOLFIRINOX vs. gem/cape)
(94%) DM, chronic pancreatitis, TNM system +/- chemoRT. Resect depending on vasc. involv.
 Endocrine (6%) age, male, FHx, HNPCC, Diagnostics:  Borderline: surg + neoadj +/- adj +/- chemoRT
BRCA1/2  CT C/A/P pancreas,  Locally advanced: FOLFIRINOX v. gem/abraxane
 FOLFIRINOX: EUS+Bx, MRCP +/- v. chemoRT v. stereotactic body radiation (SBRT)
leucovorin, 5-FU, ERCP, CA19-9,  Metastatic (NEJM 2011;364:1817): 1st line:
irinotecan, oxaliplatin germline testing FOLFIRINOX v. gemcitabine/abraxane. 2nd line:
 ChemoRT: +tumor gene profile FOLFIRI v. FOLFOX v. Gem v. Cape +/- pall RT
capecitabine or CI 5-  Bx b/f neoadj tx &  BRCA: FOLFIRINOX or gemcitabine/cisplatin (only
FU + RT
locally adv dz. Bx for BRCA) +/- chemoRT. Consider olaparib.
met site in  NTRK fusions: larotrectinib, entrectinib
metastatic dx.  MSI-H/dMMR (NEJM 2015;372:2509): consider
pembrolizumab (NCCN Guidelines v.1.2020)
Leon Pappas
144
TOC

Oncology Solid Organ Malignancies

Colon and rectum Risk factors (JAMA Oncol Staging: Colon:
 Adenoca (98%) 2018;4:e173695):  AJCC stage I-IV: I: surgery + observation
 Neuroendocrine  Obesity, inactivity, TNM system II: surgery +/- adj 5-FU/leucovorin v capecitabine. Add
 Lymphoma tobacco, red/processed oxali if T4 or high-risk. Neoadj for T4b. No adj for
meat, ETOH, adenom. Diagnostics: MSI-H/dMMR (Ann Surg Onc 2011;22:630)
 FOLFOX: oxaliplatin, polyps, IBD, FHx, genetic  Colonoscopy, CT III: surg + FOLFOX/CAPEOX. Neoadj if bulky nodal
leucovorin, 5-FU (FAP, HNPCC), age, AA C/A/P, CEA IV: liver/lung met resection* (+/- neoadj) + FOLFOX v
 CAPEOX:  Increased death w/ R-  Pelvic MRI or CAPEOX v FOLFIRI v FOLFOXIRI +/- bevacizumab
capecitabine, sided (BRAF/KRAS mut) endorectal US for  KRAS/NRAS/BRAF Wt + left-sided tumors (IV):
oxaliplatin Protective factors: rectal CA FOLFOX/FOLFIRI + EGFR inhibitor
 FOLFIRI: irinotecan,  ASA for 50-59 yo and  Genetic testing:  BRAF V600E: encorafenib + EGFR inhibitor
leucovorin, 5-FU MSI/MMR status in
≥10% CVD risk (Annals  MSI-H/dMMR (NEJM 2015;372:2509):
 FOLFOXIRI:
2016;164:814) all, K/N-RAS, BRAF immunotherapy (pembrolizumab, nivolumab or
irinotecan, oxaliplatin,
leucovorin,
 VitD data inconclusive status in metastatic nivolumab + ipilimumab)
fluorouracil Screening: Rectal: (I): low anterior (LAR) v abdominoperineal
 EGFR inhibitor:  Colo, flex sig, CT colo, resection (APR) +/- neo v adj chemoRT. Chemo as in
cetuximab, FIT, FOEBT for 50-75yo. colon cancer. (II-III): resect + neo +/- adj chemoRT
panitumumab Per ACS: 45-75yo. (NCCN Guidelines v.2.2020) * limited mets only
Lung Risk factors (Nat Rev Ca Staging: NSCLC: (NCCN Guidelines 1.2020)
 NSCLC (84%): 2007;10:778):  NSCLC stage I-IV:  IA: surgery vs. definitive RT
adeno, large>SCC  Tobacco, asbestos, TNM system  IB-IIIA: surgery if able +/- adjuv chemoRT.
 SCLC (13%) occup. exposures, lung  SCLC staged with  IIB/IIIA unresectable, IIIB: definitive chemoRT +
fibrosis, age, male, AA, TNM system as adjuvant Durvalumab (NEJM 2018;379:2342)
 ChemoRT: cisplatin/ SE status limited (St I-III) vs.  IV: targeted, immunotx, and systemic tx
etoposide, cisplatin/
 25% lung cancer extensive (St IV and  Targeted inhibitors: EGFR (EGFR sensitizing
vinblastine,
carboplatin/ worldwide not due to T3-T4 with extensive mut); ALK/ROS1 (ALK v ROS1 rearrangement),
pemetrexed, smoking (50% of women nodules). Limited BRAF/MEK (BRAF V600E), TRK (NTRK fusion)
cisplatin/pemetrexed, with NSCLC are never can be tx with RT.  Immunotherapy (if no driver mutation) (Lancet
paclitaxel/carboplatin smokers, 60-80% in Diagnostics: 2016;387:1540, NEJM 2018;378:2078): pembrolizumab
 EGFR inhibitors: Asian populations are  CT chest/upper abd, (≥50% PD-L1). Pembro + chemo (1st line
osimertinib (1st line), women) more likely PET/CT, brain MRI regardless of tumor PD-L1 level). Alternative:
erlotinib, afatinib, single mutation (ALK, ipi/nivo, atezolizumab+platinum+taxane
gefitinib, dacomitinib  Evaluate pathologic
EGFR, ROS1) LNs with biopsy  Initial: non SCC: pembro/platinum agent/
*T790M∆ assoc w/ pemetrexed. SCC: pembro/carbo/paclitaxel. If
TKI resistance. (EUS, EBUS,
Screening (Annals mediastinotomy, immunothx c/i: cisplatin v carboplatin + docetaxel v
 ALK/ROS1 inhibitors:
2014;160:330): mediastinoscopy, pemetrexed v gemcitabine v etoposide
alectinib (1st line),
crizotinib, ceritinib,  Annual low dose CT thoracoscopy) SCLC: (NCCN Guidelines v.3.2020)
brigatinib, lorlatinib chest for pts 55-80yo with  Molecular testing for  Limited: surgery + chemo +/- mediastinal RT
 BRAF/MEK inhibitors: ≥30 pack-yr hx and NSCLC (EGFR,  Extensive (NEJM 2018;379;2220): chemo &
dabrafenib/trametinib smoking within last 15 yrs ALK, ROS1, PD-L1) atezolizumab vs durvalumab +/- RT for lobar
 NTRK inhibitors: before starting obstruction, SVC synd, bone/brain mets
larotrectinib, systemic therapy  Chemo: platinum agents, etoposide, irinotecan
entrectinib
Melanoma Risk factors: Staging: Surgical excision:
 Superficial  Sun exposure (UVB >  AJCC Stage I-IV:  Margins (0.5-2cm) based on tumor thickness +/-
spreading (75%) UVA), atypical nevi, high TNM system sentinel LN bx vs. complete regional LN dissection
 Nodular (15-30%) nevi count, family or  For classification of Adjuvant treatment or for metastatic disease:
 Lentigo maligna personal hx, immuno- primary tumor (T)  Immunotherapy (NEJM 2015;373:23, NEJM
(10-15%) suppression AJCC 8th ed. uses 2015;372:2521): anti-PD-1 (pembrolizumab or
 Acral lentiginous  Genes mutated in familial Breslow thickness nivolumab); ipilimumab if prior anti-PD1; nivolumab
(<5%) melanoma: CDKN2A, and ulceration but + ipilimumab (NEJM 2019;381:1535)
 Amelanotic (2- CKD4, POT1. no longer mitotic  Targeted tx (NEJM 2014;371:1867): BRAF/MEK
10%) rate. M stages inhibitor combination (BRAF V600 activating
 Ocular (5%) Most common somatic subdivided by mutations), binimetinib for NRAS mutated after prior
mutations are: BRAF 40- met site and ICI, KIT inhibitor imatinib (KIT-mutant tumors)
BRAF/MEK inhibs: 50%, NRAS 15-20%, cKit presence/absence of  Radiation: considered with symptomatic localized
dabrafenib & trametinib, 10-15% (acral). Genetic LDH elevation. disease (e.g. brain mets)
vemurafenib & testing recommended for St  Serum LDH is an  Regional tx: isolated lib perfusion with melphalan
cobimetinib, III-IV disease. important prognostic  Talimogene laherparepvec (T-VEC) (JCO
encorafenib & factor used in active 2015;33:2780): intralesional injection of HSV tumor
binimetinib (approved
6/2018)
surveillance and cell lysis & GM-CSF expression
treatment (NCCN Guidelines v.1.2020)

Leon Pappas
145
TOC

Oncology Chemotherapy & Toxicities

Common Chemotherapy Toxicities
• Severe n/v: any AC combinations (doxo/epi/ida/daunorubicin+ifos/cyclophosphamide), carmustine, dacarbazine, cisplatin, mechlorethamine,
streptozocin; HiDAC (AraC), aldesleukin/IFNα, amifostine > 300, ATO, azacitidine, bendamustine, busulfan, clofarabine, dactinomycin, irinotecan,
melphalan, methotrexate > 250, temozolomide; refer to NCCN Guidelines for management (NCCN Guidelines v.1.2020)
• Severe BM: busulfan, carmustine, cyclophosphamide, dacarbazine, ifosfamide, 5-FU, methotrexate, doxorubicin (daunorobicin), taxotere, taxol,
carboplatin, melphalan, fludarabine
Drug Indications Toxicities
Anti-Metabolites
Breast, colorectal, pancreatic, gastric, Coronary vasospasm, acute cerebellar ataxia, hand-foot syndrome, stomatitis,
5-Fluorouracil
esophageal, H&N hemorrhage, GI ulcers/bleeding, hiccups, diarrhea, BM
Monitor INR (if on warfarin), hand-foot syndrome, SJS-TEN, n/v/d, cytopenias
Capecitabine Breast, colorectal
(worse with stage IV breast CA), hepatotoxicity
Cytarabine Acute cerebellar ataxia, PRES, BM, chemical conjunctivitis (Rx dexamethasone
AML, ALL, CLL, meningeal leukemia
(HiDAC) eye drops), LFTs, cutaneous tox, hand-foot syndrome
Gemcitabine Breast, ovarian, NSCLC, pancreas, bladder Capillary leak syndrome, PRES, TMA/HUS, ARDS, LFTs, n/v, hematuria
Biliary cholestasis & hepatocellular necrosis, BM (consider TPMT SNP testing if
Mercaptopurine ALL (w MTX), CML
severe BM), n/v/d
BM, IS, autoimmune hemolytic anemia, neurotoxicity, fatal pulm toxicity (when
Fludarabine CLL, NHL, AML
used w/ pentostatin for CLL)
Hydroxyurea CML, cervical, sickle cell, H&N BM, cutaneous tox, n/v/d, LFTs, Cr, BUN
Anti-Folates
ALL, breast, H&N, CTCL, SCLC, NSCLC, BM, aplastic anemia, AKI, LFTs, hepatic fibrosis/cirrhosis, cutaneous tox, IS
Methotrexate
NHL, osteosarcoma (PCP), pneumonitis/PF, teratogenic, ulcerative stomatitis/diarrhea, IF
Pemetrexed Mesothelioma, NSCLC BM, desquamating rash, pneumonitis, renal tox
Alkylating Agents (all cause BM, infertility & increased risk of MDS/AML)
Busulfan HSCT conditioning, CML BM, sinusoidal obstruction/VOD, tamponade, ILD, seizures, renal tox
Ifosfamide Testicular, breast, lung, HL, NHL, bone Hemorrhagic cystitis, encephalopathy, renal/pulmonary/cardiac tox
Melphalan MM, ovarian BM, hypersensitivity, amnesia, pulmonary fibrosis, mucositis, rash, IF
Carmustine CNS tumors, HL, NHL, MM BM, pulm tox (dose-related), LFTs, renal tox, ocular sx
Cyclophos- Leukemia, MM, breast, NHL, ovarian, Hemorrhagic cystitis, renal/cardio tox, pulm fibrosis, IF, sinusoidal
phamide retinoblastoma obstruction/VOD, IS, hypoNa
Dacarbazine HL, melanoma Hepatic necrosis, teratogenic, hepatic vein thrombosis, n/v, BM
Cisplatin Bladder, ovarian, testicular, H&N N/v, renal tox, ototoxicity, neurotoxicity, BM, uric acid
Carboplatin Ovarian, lung, H&N, CNS tumors N/v, ototoxicity, neurotoxicity, BM (less nephrotoxic than cisplatin)
Oxaliplatin Colorectal, pancreatic N/v, renal/pulm/liver tox, neurotoxicity, BM, rhabdo, QT, PRES
Antibiotics
Bleomycin HL/NHL, testicular, ovarian, H/N Late pulm fibrosis, dermatographia, hyperpigmentation, Raynaud’s
Mitomycin Gastric, esoph, anal, bladder, pancreas BM, renal/cardiac tox, HUS, interstitial pneumonitis/ARDS, bladder fibrosis
Hormonal Therapy
Tamoxifen Menopausal sx (hot flashes, vaginal atrophy/pruritus /bleeding), VTE (DVT/PE),
ER+ breast
Raloxifene endometrial cancer (tamoxifen only)
Anas-/Letrozole
ER+ breast (post-menopausal) Sexual dysfunction, bone/joint pain, osteoporosis, premature menopause
Exemestane
Fulvestrant ER+ breast (post-menopausal) Sexual dysfunction, bone/joint pain, osteoporosis, injection site reactions
Megestrol Breast, endometrial Teratogenic, weight, hypogonad, VTE, hot flashes, adrenal suppression
Leuprolide Hypogonadism, edema, depression, bone pain, osteoporosis, transient worsening
Prostate, breast (goserelin)
Goserelin of prostate CA sx 2/2 brief testost. surge (ppx w/ AR inhibitors), seizure, CVD risk
Flutamide Hot flashes, gynecomastia, libido, n/v/d, muscle atrophy/pain, hepatotoxicity (> w/
Prostate
Nilutamide F), interstitial pneumonitis, visual changes (N), osteoporosis
Bicaludamide Prostate Hypogonadism, sexual disfunction, depression, fatigue, hepatotoxicity, ILD
Topoisomerase Inhibitors
Anthracyclines
Cardiotoxicity (DCM, myopericarditis); BM, IS, 2nd malignancies, local tissue
(Dauno/Epi/ Breast, ALL, AML, MM, lung, bladder
necrosis in setting of extravasation, liver/renal tox, typhlitis, “chemo brain”
Doxorubicin)
Mitoxantrone Breast, ALL, AML, breast Cardiotoxicity (DCM, myopericarditis); BM, IS, n/v
Irinotecan (I) Colorectal (I), SCLC (I,T), cervical (T),
BM, diarrhea, late ILD, thrombosis, typhlitis
Topotecan(T) ovarian (T)
Etoposide SCLC, testicular, KS, glioblastoma BM, acute infusion reaction (HoTN), metallic food taste, SJS/TEN
Mitotic Inhibitors
Paclitaxel Breast, ovarian, NSCLC, KS, H&N BM, hypersensitivity, acute infusion reactions, peripheral neuropathy
Docetaxel Breast, NSCLC, prostate, gastric, H&N Hepatotoxicity, BM, hypersensitivity, fluid retention
Lymphoma, mycosis fungoides, testicular,
Vinblastine Extravasation, BM, neuropathy, bronchospasm, stomatitis
KS, Histiocytosis X
Neurotoxic (deaf, blind, ataxia, peripheral neuropathy, areflexia, ileus), MI, SIADH,
Vincristine ALL, CNS, HL, NHL
extravasation, bronchospasm
Monoclonal Antibodies
Trastuzumab Cardiotoxicity (EF), hypersensitivity, pulm tox, headaches, diarrhea, URI sxs,
Anti-HER2: HER2+ breast cancer
Pertuzumab extremity pain, teratogenic
Sara Khosrowjerdi
146
TOC

Oncology Chemotherapy & Toxicities

Rituximab Anti-CD20: NHL, CLL Hypersensitivity, cytokine release syndrome, HBV reactivation, PML, renal toxicity
Anti-VEGF: cervical, colorectal, GBM, Perforations (septal, GI), wound dehiscence, nec. fasc., hemorrhage, HTN, eye
Bevacizumab
ovarian, RCC, NSCLC infection 2/2 endophthalmitis
Cetuximab Anti-EGFR: colorectal (KRAS wt), H&N Cardiopulmonary arrest, hypersensitivity, angioedema, ILD
Panitumumab Anti-EGFR: colorectal (KRAS wt) Rash, photosensitivity, n/v/d, hypoMg, ocular sxs, ILD/pulm fibrosis
Immunomodulators
Capillary leak syndrome, sepsis (PMN chemotaxis), cardiopulmonary disease,
Aldesleukin Aldesleukin: melanoma, RCC; Denileukin:
CNS toxicity, hypersensitivity, renal insufficiency, autoimmune diseases, vision loss
Denileukin CTCL
(denileukin)
Lena/poma/ Teratogenicity, neutropenia/thrombocytopenia, DVT/PE, MI, stroke, rash, SJS
MM, MDS (lena)
thalidomide (lena), hepatotoxicity, peripheral neuropathy, ?2° malignancy
IFN-alpha Hairy cell leukemia, KS, CML Flu-like sx, LFTs, fatigue, depression, HLD, anorexia, cytopenias
ATRA APL Differentiation syndrome, hemorrhage, ICP, xerosis, DIC, teratogenicity
Arsenic APL Differentiation Syndrome, QTc, confusion, n/v/d, respiratory sx
Azacytidine MDS BM, constipation, n/v, renal/liver tox
Decitabine AML, CML, MDS BM, constipation, n/v/d, hyperglycemia, MSK pain, respiratory sx
Tyrosine Kinase Inhibitors (TKIs)
Imatinib (I), BCR-ABL: Ph+ CML/ALL (I,D), GIST (I,D) , Renal toxicity (I) hepatotoxicity, CHF, edema, DRESS/SJS (I), n/v/d, BM,
Dasatinib (D) MDS (I), HES/CEL (I) hemorrhage, pleural/pericardial effusion, PAH (D), QTc (D)
Nilotinib (N)
QTc, hepatotoxicity, edema, n/v/d, BM, hemorrhage, MI (N), arterial occlusions
Bosutinib BCR-ABL: Ph+ CML/ALL
and VTE (P), CHF/arrhythmias (P)
Ponatinib (P)
Gilteritinib FLT3: FLT3+ AML Myalgia/arthralgia, LFTs, n/v/d, rash, stomatitis, differentiation syndrome, FN
FLT3: FLT3+ AML (combination tx), syst N/v/d, edema, BM, mucositis, LFTs, renal insufficiency, QTc, pyrexia, fatigue,
Midostaurin
mastocytosis, mast-cell leukemia URI, hyperglycemia, hyperuricemia
BTK: CLL, B cell lymphomas (marginal, Afib, edema, diarrhea, URIs, bruising/ bleeding including SDH/ICH (may want to
Ibrutinib
mantle), Waldenstrom’s, cGVHD avoid if on DAPT), fatigue, HTN
Osimertinib
Acneiform rash (predictive of response), late ILD, LFTs, pneumonitis, ocular tox
Dacomitinib
EGFR: met EGFR+ NSCLC, pancreas (E) from keratitis/conjunctivitis to corneal perf/ulceration (E), n/v/d, risk of MI (E), GI perf
Gefitinib
(E), liver failure and HRS (E)
Erlotinib (E)
Lapatinib EGFR: breast (EGFR & HER2) ILD/pneumonitis, hepatotoxicity, n/v/d, rash
Crizotinib
QTc, bradycardia, pneumonitis, n/v/d, edema, LFTs, visual disturb (blurred
Brigatinib ALK: NSCLC (ALK+)
vision, diplopia, acuity), neuropathy, K, phos, BM, hyperglycemia (Ce)
Ceritinib (Ce)
Lorlatinib ALK, ROS1: NSCLC HLD, edema, hyperglycemia, neuropathy, BM, LFTs, alb, n/v/d, myalgia
N/v/d, central serous retinopathy, skin SCC (vemurafenib monotherapy),
Vemurafenib +
BRAF/MEK: melanoma (BRAFV600E) keratoacanthomas, photosensitivity, arthralgia, rash, hand-foot syndrome, QT,
Cobimetinib
EF, hepatotoxicity, pyrexia
Dabrafenib +
HA, pyrexia (often tx-limiting, less w/ E+B), n/v/d, rash, hyperkeratosis, skin SCC,
Trametinib, BRAF/MEK: melanoma (BRAFV600E/K),
hand-foot syndrome, photosensitivity, central serous retinopathy, HTN, CHF, edema,
Encorafenib + NSCLC (D+T)
arthralgia
Binimetinib (E+B)
Vandetanib VEGF: medullary thyroid N/v/d, rash, QTc, dry mouth, cerebrovascular ischemia
Neratinib Pan-HER: breast N/v/d, stomatitis, rash, hepatotoxicity, muscle spasm
Sorafenib (So) Hemorrhage, HTN, renal tox, hand-foot skin reaction (So, Su, R?), palmar-plantar
VEGF: RCC (So, Su, L), HCC (So, R, L),
Sunitinib (Su) erythrodysesthesia (L), CHF/MI (So), neuropathy, K, phos, Ca, LFTs, liver
GIST (Su, R), thyroid (So), pNET (Su), CRC
Regorafenib (R), failure (Su,R), GI perf, QT, EF (Su), mucositis (Su), thyroid impairment (So), ONJ
(R), Endometrial (L), thyroid (L)
Lenvatinib (L) (Su), TLS, arthralgia/myalgia (L), fistula/GI perf (L), arterial thrombosis (L)
VEGF: medullary thyroid, RCC, HCC, Fistula, GI perf, hemorrhage, osteonecrosis, LFTs, cytopenias, hand-foot
Cabozantinib
NSCLC (ROS1) syndrome, HTN, triglycerides, abnormal electrolytes, PRES
Axitinib (A) Hepatotoxicity (P), QT (P), EF (P), n/v/d, HTN, hemorrhage, hypothyroidism,
VEGF: RCC (A, P), soft-tissue sarcoma (P)
Pazopanib (P) dysphonia (A), BM (P), perf/fistula (P), arterial thrombosis (A)
Bortezomib Proteasome: MM, mantle lymphoma Neuropathy, PRES, PML, ARDS, BM, AIN, n/v/d, HoTN, shingles, EF
Larotrectinib NTRK fusion inhibitor (tissue agnostic) N/v/d, LFTs , fevers, BM, neurotox (dizziness, dysarthria, delirium, enceph.)
N/v/d, edema, mouth sores, anemia, increased thirst/hunger, pneumonitis,
Temsirolimus mTOR: RCC
metabolic effects (HLD, hyperglycemia), proteinuria, renal failure, fever
PARP Inhibitors
Olaparib BRCA-mutant ovarian (3rd line), breast N/v, fatigue, somnolence, pneumonitis, BM
Rucaparib BRCA-mutant ovarian (2nd line) N/v/d, constipation, fatigue/asthenia, BM
Niraparib Ovarian, peritoneal BM (usually mild), n/v, constipation, HTN
Cyclin-Dependent Kinase (CDK) 4,6 inhibitors
Palbo/ribociclib, HR+ metastatic breast Leukopenia, anemia, thrombocytopenia, fatigue
Abemaciclib HR+ metastatic breast Diarrhea, leukopenia, thrombocytopenia
*Key: BM= myelosuppression, IS=immunosuppression, IF=infertility, DHFR=dihydrofolate reductase, HES (hypereosinophilic syndrome), ONJ=
osteonecrosis of the jaw. **Table does not include all off-label clinical indications. ***See “Immune Checkpoint Inhibitors” for immunotherapy toxicities.

Sara Khosrowjerdi
147
TOC

Oncology Immune Checkpoint Inhibitors

IMMUNE CHECKPOINT INHIBITORS (ICIs)
• Mechanism of action: ICIs increase
antitumor immune response by blocking
down-regulators of T cell activation. These
down-regulators include cytotoxic T-
lymphocyte antigen 4 (CTLA-4),
programmed cell death 1 (PD-1), or its
ligand, programmed cell death ligand 1
(PD-L1) (Nat Rev Clin Oncol 2016;13:473,
NEJM 2018; 378:158, NEJM 2016;375:1767).
ICIs with alternative modes of action
(CD137, LAG-3, TIM-3) are in development.
• Indications: melanoma, NSCLC, RCC,
urothelial, gastric, colorectal, HCC, H&N,
HL, cutaneous SCC (cemiplimuab), triple negative breast, cervical, numerous other indications are under investigation. PD-1 inhibitors
are FDA-approved for any microsatellite instability-high (MSI-H) or mismatch-repair deficient cancers (dMMR) (NEJM 2017;377:1345,
NEJM 2018;378:1277)
o Pre-existing autoimmune disease is NOT an absolute contraindication to the use of ICIs. Can be associated with flare but rarely
treatment-limiting (JCO 2018;36:1905, Ann Oncol 2017;28:368)

IMMUNE-RELATED ADVERSE EVENTS (irAEs) (NEJM 2018;378:158, Ann Oncol 2017;28:iv119, J Immunother Cancer 2017;5:95)
• Definition: systemic autoimmune or inflammatory events due to immune system activation by ICIs
• Risk factors:
o Combination immunotherapy (anti-CTLA-4 + anti-PD-1): associated w/ earlier, higher incidence, and  severity; significantly less
with anti-PD1 compared with anti-CTLA-4
o No predictors of who will develop irAEs. Patients with pre-existing autoimmune disease can flare (see above).
• Timing: highly variable based on organ system involved, drug target, Timing of irAE after ipilimumab
monotherapy vs combination. Can present over weeks to years. (adapted from Ann Oncol 2017;28:iv119)
• Clinical presentation: dermatologic toxicity (rash, vitiligo), hepatitis, Rash, pruritus
thyroiditis, colitis, myocarditis, pneumonitis, DM1, neurotoxicity (aseptic Liver toxicity
Diarrhea, colitis
meningitis, encephalitis, transverse myelitis, neuropathy/mononeuritis, Hypophysitis
Toxicity grade

GBS, myasthenia), arthralgias>arthritis, Sicca syndrome. See below for

organ-specific details.
• Tx: absence of prospective data, treatment recommendations based on
expert consensus, see ASCO guidelines (J Oncol Pract 2018;14:247). First
line immunosuppressant is prednisone. Treatment-refractory cases:
infliximab [except hepatitis], MMF, tacrolimus, MTX, ATG,
IVIG/plasmapheresis in autoAb-mediated/neurologic irAEs Time (weeks)

IRAE Grading (ASCO Guidelines: JCO 2018;36:1714; NCCN Guidelines v.1.2020)

Additional reading: hepatitis Oncologist 2018;23:991; pneumonitis: Chest 2017;152:271, JCO 2017;35:709

Sara Khosrowjerdi
148
TOC

Oncology Immune Checkpoint Inhibitors

Adapted from Curr Oncol 2018; 5:342

Skin toxicity: typically manifests as rash, pruritis, rarely SJS/TEN. Common, up to 30-40% of patients (higher with CTLA-4 than PD-1/L1
blockade). Vitiligo seen only in melanoma, associated w/ response to tx (JAMA Dermatol 2016;152:45)
• Timing: early, within the first few weeks of treatment initiation
• S/Sx: four types of skin reactions
1) Inflammatory: psoriasiform or lichenoid reactions
2) Immunobullous: dermatitis herpetiformis or bullous pemphigoid
3) Keratinocyte alteration: acantholytic dyskeratosis
4) Immune reaction mediated by alteration of melanocytes (regression of nevi, tumoral melanosis, vitiligo)
• Dx: exam; r/o other etiologies (i.e. infection, DRESS, TEN/SJS); grade based on BSA (<10% Gr 1, 10-30% Gr 2, >30% Gr 3)
• Tx: topical steroids, oral antihistamines for inflammatory/pururitic reaction. If severe, consider systemic steroids and derm consult.
Often does not require treatment interruption.
Hypophysitis (JAMA Oncol 2018;4:173): primarily w/ anti-CTLA-4, est. prev. 3.2%. Rarely w/ anti-PD-1/PD-L1 (0.5%). Mechanistically
distinct from other irAEs; ?mediated by direct binding of ipi. to CTLA-4 on normal cells of ant. pituitary (Sci Transl Med 2014;6:230)
• Timing: median onset is 8 weeks
• S/Sx: HA most common (can be severe); fatigue, n/v, dizziness, weight loss, hot flashes, cold intolerance, hyponatremia (anterior
hypopituitarism); no central diabetes insipidus (posterior pituitary spared)
• Dx: MRI brain/pituitary shows transient diffuse pituitary enlargement (generally resolved by 2 months); test hormonal axes: 8AM
serum cortisol + ACTH and/or cort stim; TSH w/ fT4/T4/T3; PRL; LH/FSH, serum testosterone/SHBG (in men); IGF-1.
• Tx: symptoms resolve with appropriate hormone substitution; hormone deficiencies tend to persist
o Hypocortisolism: physiologic glucocorticoid replacement (prednisone 3-5mg daily equivalent; increase x2-3 with
infection/illness), high-dose glucocorticoids do not improve outcomes (may be associated with reduced survival); counsel about
adrenal crisis; obtain medical bracelet (Cancer 2018;124:3706, Oncologist 2016;21:804)
o Central hypothyroidism: hormone replacement with levothyroxine (hyperthyroidism can also occur, but rare)
o Hypogonadism: consider testosterone replacement if persists
o GH deficiency: GH theoretically contraindicated due to active malignancy, although no evidence
Myocarditis (JACC 2018;71:1755): rare, but serious AE of ICI a/w high mortality (46% in severe myocarditis); risk higher with combo tx
• Timing: generally within 3 months (Oncologist 2018;23:874, Lancet 2018;391:933)
• S/Sx: sx of heart failure (SOB, LE edema), chest pain, palpitations, arrhythmia
• Dx: EKG/tele; troponin, CK-MB, NT-proBNP, ESR/CRP; TTE; consider myocardial bx; CPK/aldolase; EMG/muscle bx
• Tx: pulse-dose steroids (1g IV x3d, then PO pred 1mg/kg); 2nd-line consider ATG/IVIG (if unstable), or infliximab/MMF/tacro (if stable)
(Oncologist 2018;23:879); βB, ACEi/ARB (if EF low)
Pneumonitis: more common w/ anti-PD-1, but serious toxicity rare. Combination therapy confers significantly higher risk. (Chest
2017;152:271, JCO 2017;35:709); risk also increased in combination with targeted therapy for lung CA
• Timing: highly variable onset, later than other irAEs
• S/Sx: dyspnea (53%), cough (35%); AIP/ARDS; 1/3 asymptomatic (JCO 2017;35:709, Clin Cancer Res 2016;22:6051)
• Dx: VBG, influenza/RSV/RVP, BCx, SCx/smear, PCP if at-risk, consider BAL; NT-proBNP, troponin, TTE, CT-PE/LENIs. CT/HRCT
(CXR often unhelpful). Findings non-specific: GGOs, NSIP-like, COP-like, HP-like.
• Tx: oxygen, glucocorticoids (pred 1-2 mg/kg/d or methylpred 1mg/kg) prolonged taper, consider empiric abx, diuresis
Colitis: more commonly seen with anti-CTLA-4; grade 3/4 colitis is higher with ipilimumab (<10%) than with anti-PD-1 agents (1-2%)
• Timing: 6-8 weeks (median) after initiation of therapy
• Dx: CBC, BMP, CRP, ANCA, consider lactoferrin/calprotectin; rule out alternative etiologies: C diff., bacterial or viral pathogens (stool
Cx, O&P, CMV PCR, cryptosporidia); CT A/P can show mild diffuse bowel thickening or segmental colitis associated with
diverticulosis; GI c/s for EGD/flex sig/colo (can affect upper/lower) for grade 2 sxs (4-6 BM/d >baseline); path: active acute colitis
• Tx: antidiarrheal agents after exclusion of infection; Grade 1/2 (<3/4-6 BM >baseline): antidiarrheal; budesonide 9 mg PO or
prednisone PO if fails to improve (G1>14d; G2>3d); Grade 3/4 (>6 BM over baseline): systemic steroids (prednisone 1-2 mg/kg or
methylprednisolone 1-2 mg/kg IV) with taper; infliximab in refractory cases
Sara Khosrowjerdi
149
TOC

Oncology Oncologic Emergencies

T U M O R L Y S I S S Y N D R O M E (NEJM 2011;364:1844, JCO 2008;26:2767)
• Pathophys: tumor lysis (in s/o cytotoxic tx initiation; rarely spontaneous in NHL and acute leukemia)  release of intracellular
components (nucleic acids  uric acid, K+, PO4+); clinical effects (can be deadly): renal failure (uric acid precipitates in renal
tubules); seizure/Ca-phos crystal deposition (phos  Ca); arrhythmias (K); timing: 1-2d after tx (can occur w/in hrs)
• Presentation: n/v/d, constipation, UOP, weakness/cramps, seizure, arrhythmia
• Risk factors: high risk: ALL/AML (WBC ≥100k), CLL (on venetoclax & uric acid), stage 3/4 Burkitt’s/lymphoblastic NHL, bulky
DLBCL; intermediate risk: ALL (WBC <100k), AML (WBC 25-100k or <25k & LDH), Burkitt’s, DLBCL, CLL (chemo-specific &
WBC), rare chemo-sens bulky solid tumor; low risk: HL, indolent NHL, CML, CLL (on alkylating tx & WBC <50k), MM
o High risk substrate: WBC >50k, LDH >2x ULN, bulky tumor (>10 cm), hypovolemia, uric acid >7.5, renal failure
• Labs/workup: BMP (electrolytes, Cr), ionized Ca, Mg, phos (calculate Ca-phos product), uric acid, CBC w/ diff, ECG
• Diagnosis (Cairo-Bishop criteria):
o Laboratory diagnosis: ≥2 criteria within 3d before or 7d after cytoxic therapy: uric acid ≥8 mg/dL, K ≥6 mEq/L, phos ≥4.5mg/dL,
or Ca ≤7mg/dL. Criteria also satisfied if 25% change from baseline.
o Clinical diagnosis: laboratory dx & ≥1 clinical criteria: Cr 1.5x ULN, arrhythmia, seizure, death (not attributable to chemo agent)
• Prophylaxis and treatment: while treating, labs should be checked Q2-Q4H & pt should be on telemetry given electrolyte abn
o Hydration: 2-3 L/m2 per day. Maintain UOP ≥100 cc/hr for optimal excretion of uric acid and phos; can use diuretics PRN
 Use bicarb only with marked acidosis, as urine pH will uric acid crystals but Ca-phos crystals
o Electrolyte abnormalities: K (hyperK tx), phos (binders), Ca (avoid correction until Phos nml or sx of Ca)
o Allopurinol: 100mg/m2 PO q8h or 200-400mg/m2 IV, administer 24-48 hr before chemo, continue until hyperuricemia resolved
 Renally dose; note reduced clearance of other meds (e.g. cyclophosphamide, MTX, 6-MP, azathioprine, ampicillin)
o Rasburicase (discuss with attending): 0.2 mg/kg IV, administer if high risk or baseline uric acid ≥8 mg/dL
 Risk of anaphylaxis, hemolysis, methemoglobinemia. Contraindicated in G6PD deficiency (risk of hemolysis)
o Renal replacement therapy: indicated if Ca-phos product ≥70 mg2/dL2
H Y P E R V I S C O S I T Y S Y N D R O M E / L E U K O S T A S I S (Blood 2012;119:2205, Blood 2018;132:1379)
• Etiology: 1) hyperproteinemia from monoclonal gammopathies (mostly commonly Waldenström’s macroglobulinemia [IgM],
uncommonly myeloma) 2) hyperleukocytosis/leukostasis seen in AML with blasts >50k (uncommon in ALL/CLL unless very high
counts); 3) other diseases such as rheumatoid disease, polycythemia, sickle cell, spherocytosis
• Symptoms: most common: pulmonary (SOB) and CNS (blurry vision 2/2 retinal venous engorgement, headache, dizziness, ataxia,
confusion, coma), fever  if concerned, page hematology fellow on call and clinical pathology resident for EMERGENCY
VISCOSITY STUDY, p21828, (notify attending ASAP as pheresis will involve attending-level decision)
• Diagnosis:  Ostwald tube serum viscosity, light chains, SPEP, WBC (often >100k, but can be lower in blast crisis)
o Lab artifacts from hyperleukocytosis: spurious K (use ABG K), falsely low arterial pO2 (use oximeter)
• Treatment: always start with plasma volume expansion with IV NS
o Hyperproteinemia: plasmapheresis (aiming for resolution of symptoms); reduces viscosity by 20-30% per session
o Leukostasis: leukapheresis; cytoreduce (hydroxyurea); induction chemo; avoid RBC & plt transfusion (viscosity)
M E T A S T A T I C E P I D U R A L S P I N A L C O R D C O M P R E S S I O N (Seminars in Neurology 2010;30:245, Lancet Neurology 2008;7:459)
• Primary CA: lung > prostate & breast > non-Hodgkin's lymphoma, renal cell, multiple myeloma, lymphoma
• Location: T (60%) > L (25%) > C (15%); multiple sites in 20-35%; ESCC score for spinal level (JNCCN 2016;14:70)
• Symptoms: back pain (usually 1st sx; radicular, localized, worse at night/recumbent/valsalva)  weakness, gait instability  sensory
deficits (saddle anesthesia in cauda equina lesions), bowel/bladder dysfunction
• Exam: pain precedes other sx by ~7 wks, weakness/ataxia, paresthesia,  reflexes, ⊕ Babinski,  anal sphincter tone
• Diagnosis: STAT vs. urgent FULL spine MRI with cord compression/metastasis protocol, alternative is CT myelography
• Treatment: call Spine Surgery & Radiation Oncology ASAP  more effective than chemo (except for heme, germ cell malignancies)
o Severe deficits: dexamethasone 96mg x1, then 24mg IV q6hr x3d, then taper x10d
o Minimal deficits: dexamethasone 10mg IV x1, then 4mg IV q6hr
B R A I N M E T A S T A S E S W I T H I N C R E A S E D I N T R A C R A N I A L P R E S S U R E (Ann Palliat Med 2015;4:225, JCO 2015;33:3475)
• Intracranial tumors present in ~10-30% of patients with metastatic disease; call Neurosurgery & Radiation Oncology
• Primary CA: lung (48%), breast (18%), melanoma, RCC, osteosarcoma, head and neck, thyroid, colorectal
• Symptoms: headaches (40-50%; “tension”, worse w/ Valsalva, n/v), focal neuro deficits (20-40%, hemiparesis most common),
cognitive dysfunction (30-35%), new onset seizures (10-20%), stroke (5-10%)
• Diagnosis: contrast MRI w/  sensitivity > non-enhanced MRI or CT with contrast
• Treatment: control vasogenic edema (dexamethasone 10mg IV x1, then 8mg BID), consider AED (usually not recommended for 1°
ppx); avoid AC if concern for active hemorrhage; definitive treatment will  local recurrence: stereotactic radiosurgery > whole-brain
XRT ( neurocognitive impairment; hippocampal sparing helpful) > surgery
SUPERIOR VENA CAVA SYNDROME ( S V C S Y N D R O M E ) (NEJM 2007;356:1862, Mayo CP 2017;92:609)
• Etiology: external compression of SVC from a mediastinal mass (commonly lung CA or NHL) causing  upper body venous pressure
• Symptoms: cerebral edema (HA, confusion, herniation), narrowing of larynx/pharynx (dyspnea, stridor, cough, dysphagia,
hoarsness), head/neck swelling (visually striking, often not clinically significant), hemodynamic instability ( venous return)
• Diagnosis: venography, CT chest w/ contrast, obtain/ensure tissue diagnosis to guide tx (extremely important!)
• Treatment: secure airway, RT/chemo, intravascular stent (emergent/refractory), steroids (stridor/resp distress only, clear with onc)
John Schell
150
TOC

Oncology Febrile Neutropenia

D E F I N I T I O N S A N D E T I O L O G Y (J Oncol Pract 2019;15:19, NCCN Prevention and Treatment Guidelines)
• Fever: single temperature ≥101°F (38.3°C) orally or ≥100.4°F (38°C) >1h
• Neutropenia: defined as ANC <500 or <1000 and predicted nadir ≤500 within 48h
o Functional neutropenia: defective PMNs, common in leukemia ( neutrophil function despite ANC>500)
• Microbiology:
o Only 40-50% have infectious source identified; others attributed to translocation of intestinal bacteria
o 25% organism identified: 40% GNRs (E. coli, Klebs > PsA); 60% GPCs (CoNS > MSSA/MRSA, strep, enterococcus/VRE) esp w/
indwelling lines or mucositis; fungal (Candida, Aspergillus) more likely w/ prolonged  ANC, broad-spectrum abx use, or TPN
EVALUATION
• H&P: prior micro data, time since last chemo, recent antibiotic therapy/ppx, major comorbid illness, use of devices
• Exam: mouth (mucositis), emphasis on skin, perineum/rectal (visual inspection, avoid DRE), indwelling lines (erythema)
• Studies: BCx x2 sites (≥1 periph, 1 per CVC lumen), UA/UCx, CBC, BMP, LFTs, CXR, sputum Cx/GS, viral panel, CMV PCR (SCT)
• Further site-specific studies to consider:
o Diarrhea: stool culture, O&P, C. diff; abdominal pain: CT A/P (may not have abdominal pain, consider imaging)
o Pulmonary symptoms: influenza/RSV PCR, CXR/CT chest, +/- bronch/BAL (especially if prolonged F&N)
o HA/sinus pain: CT face/sinus
o Fungal markers: LDH, β-D-glucan; galactomannan if high risk for Aspergillus (SCT, GVHD, neutropenia >10-14d)
• Risk stratification: (J Oncol Pract 2019;15:19, NCCN Prevention and Treatment Guidelines)
o MASCC Risk Index score (JCO 2000;18:3038): identifies cancer patients with febrile neutropenia at low risk of complication
o High risk: anticipated ANC ≤100 for ≥7d, inpt status, MASCC<21, co-morbidities/infections (renal/hepatic impairment, PNA,
central line infxn), allogeneic HSCT, mucositis grade 3-4, alemtuzumab use within past 2 months  inpatient management
o Low risk (JCO 2018;36:1443): anticipated ANC ≤100 for <7d, no co-morbidities, good performance status (ECOG 0-1), strong
home social support, MASCC ≥21,  treated with PO antibiotics after brief inpatient stay versus strictly outpatient
T R E A T M E N T / P R O P H Y L A X I S (NCCN Prevention and Treatment Guidelines)
• Empiric abx: within 1hr; up to 70% mortality if delayed abx (Antimicrob Agents Chemother 2014;58:3799)
o Gram-negatives (PsA dosing): broad gram negative coverage (including PsA) within 60 min of presentation
 Cefepime 2g q8h (or ceftazidime 2g q8h), pip/tazo 4.5g q6h, or meropenem 1g q8h
 PCN allergy: confirm allergy; use Penicillin Hypersensitivity Pathway and test-dose cefepime or meropenem; consider
allergy consult. If true allergy, use aztreonam (avoid in ceftazidime allergy) + levofloxacin
 High-risk ESBL: meropenem 1g q8h (2g q8h if meningitis)
 Low risk: PO regimen; cipro/levofloxacin + amox-clav vs. clinda (if PCN allergy); avoid if prior FQ ppx
o Gram-positives:
 First line: Vanc; VISA/VRSA or VRE: daptomycin (unless pulmonary process, poor lung penetration) or linezolid
 Indications: hypoTN/severe sepsis, GPC bacteremia, catheter-related infxn (rigors with infusion), SSTI, PNA on imaging,
MRSA colonization (esp in HSCT), severe mucositis + prior FQ ppx + GNR coverage with ceftaz
 Vancomycin NOT part of FN empiric regimen (JAC 2005;55:436); indwelling lines, mucositis alone, FQ ppx, & persistent fever
despite GN coverage are NOT indications
o Anaerobes:
 Indications: intra-abd source, C. diff, oral ulcer/periodontal infxn, post-obstructive PNA, necrotizing ulceration
o Fungal (invasive molds):
 Indications: F&N >4-7d despite abx, ⊕ fungal biomarkers, ⊕ CT chest (circumscribed, air crescent, cavity), ⊕ BAL Cx
 Micafungin 100mg q24h or Amphotericin 3mg/kg (admin after 500cc NS)
• Modification/duration: refer to NCCN guidelines for additional modifications
o Resolution of fever:
 Documented infxn: narrow abx and tx for recommended course, then switch to FQ ppx until ANC >500
 Culture negative: continue empiric treatment until afebrile & ANC >500 vs. narrow to FQ ppx if afebrile x4-5d
o Fever continues >4-7d:
 Clinically stable: do not broaden abx or add vanc, consider other causes (e.g. engraftment, differentiation, GVHD, TLS, drug
fever, thrombophlebitis, hematoma, hepatosplenic candidiasis)
 Clinically worsening: broaden abx +/- fungal coverage, consider CT chest +/- bronch to evaluate for fungal infxn
o Catheter-associated infection:
 Coag-negative staph, non-VRE Enterococcus: can keep line if IV abx + abx lock x2 wks
 Staph aureus, PsA, fungi: must remove line. For gram negative, d/w attending; line removal vs. lock therapy.
 Complicated infxn (endocarditis, septic thrombosis, bacteremia/fungemia >72 h): remove line, abx x4-6 wks
• Prophylaxis
o Anti-microbial ppx: refer to NCCN guidelines for more specific indications
 Antibacterial (FLQs): high-risk pts (heme malignancy) and attending discretion for intermediate-risk pts
 Antifungal (azole vs echinocandin): heme malignancies during neutropenia and 75 days post-allo HSCT
 PCP (TMP-SMX): if ≥20 mg prednisone daily for ≥1 month, purine analog (Azathioprine) use, and allo/auto HSCT
 HSV/VZV (acyclovir vs. famciclovir): sero+ undergoing tx while neutropenic, or 1 yr post-auto and 2 yrs post-allo HSCT
o G-CSF: recommended if risk of F&N >20%  shortens duration of F&N, but does NOT decrease mortality (JCO 2006;24:3187)

Rahul Nayak
151
TOC

Geriatrics & Palliative Care Frailty & Polypharmacy

FRAILTY
Screening: consider for all admissions >70 years old, or admissions for “failure to thrive”
• Reframe “failure to thrive” as frailty, which has evidence-based assessment criteria and diagnostic approach
• Definition: “medical syndrome with multiple causes and contributors characterized by diminished strength, endurance,
and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency
and/or death” (JAMDA 2013;14:392). Older age is a risk factor but is not necessary or sufficient for the diagnosis
• Most cited tool is Phenotype of Frailty (J Geront 2001;56:M146; BMC Geriatr 2013,13:64) but can use quick screen below
• FRAIL screen: frail = 3 or more positive answers; pre-frail = 1-2 positive answers (J Nutr Health Aging 2012;16:601)
o Fatigue: “In the past four weeks, do you feel tired all or most of the time?”
o Resistance: “By yourself, do you have any difficulty walking up 10 steps without resting?”
o Ambulation: “By yourself, do you have any difficulty walking a city block?”
o Illnesses: Does patient have more than 4 comorbidities?
o Loss of weight: Greater than 5% weight loss over past year?
Inpatient frailty assessment: find the root cause!
• Thorough H&P and workup to evaluate for new/progressive illness and reversible causes
• Ddx: anemia, cancer, CHF, COPD, cirrhosis, CKD, DM, PMR, thyroid dz, nutritional deficiencies (incl vit D), depression
• Physical functioning: goal is to identify ADL/IADL deficits for targeted intervention
o Katz ADL Scale (“Does anyone help you with: walking, feeding, dressing, bathing, grooming, toileting?”)
o Instrumental ADLs (“Does anyone help you with: cooking, cleaning, shopping, driving, medications, finances?”)
• Cognition and mental health:
o Evaluate for delirium with Confusion Assessment Method (see Psychiatry: Mental Status Exam)
o If negative, proceed to Mini-Cog evaluation to screen for dementia; if any deficits, refer for outpatient evaluation
o Always screen for depression with PHQ-2 (see Primary Care: Health Screening & Maintenance)
• Social functioning: how much social support does the patient require? Address advanced directives/HCP/Code Status
Interventions for frailty (Age Ageing 2017;46:383)
• Establish patient- and family-centered goals to guide treatment plan
• Exercise: inpatient and outpatient PT; exercise programs can reduce fall risk (JAMA 2018;319:1705)
• Nutrition: nutrition consult particularly for patients with weight loss
• Cognition training (outpatient OT consult): improve short-term memory, information processing, problem-solving
• Home environment assessment and modifications: consider social work consult, OT consult, iCMP referral
• Referral to OP geriatrics / palliative care for regular review of medications and reduction in polypharmacy
POLYPHARMACY AND INAPPROPRIATE MEDICATIONS
Polypharmacy
• No consensus definition; “you know it when you see it.” High prevalence: >50% inpts >75yo (BMC Geriatr 2017;17:230)
• Should communicate with PCP about simplifying med list
Inappropriate medications for elderly patients
• Classes to (usually) AVOID in geriatric patients:
o Anticholinergics: delirium, falls, blurred vision, urinary retention, tachycardia. Avoid antihistamines, TCAs, MAOIs,
antimuscarinics (oxybutynin), muscle relaxants (cyclobenzaprine), prochlorperazine
o Benzodiazepines: delirium, falls, cognitive impairment, etc. (also risk w/ non-BZD hypnotics)
o Antipsychotics: increased mortality with antipsychotics in the elderly (JAMA Psych 2015;72:438)
o Peripheral alpha blockers and central alpha-agonists: -zosins and clonidine confer risk of orthostasis and falls
o Long-acting sulfonylureas and rapid/short acting insulin: hypoglycemia
o PPIs: C. diff, bone loss/fracture (switch to H2 blockers unless clear indication for PPI)
o NSAIDs: GI bleed and AKI (especially in elderly patients with decreased CrCl)
o Aspirin for primary cardiac or CRC prevention: bleeding (use with caution and reevaluate at age >70)
• See American Geriatric Society Beer’s List and STOPP-START for further details on potentially inappropriate meds
• Parkinson’s disease: ondansetron is anti-emetic of choice. Avoid metoclopramide, prochlorperazine, antipsychotics
• Dosage adjustments: ensure appropriate renal and weight-based dose adjustment for anticoagulants (enoxaparin,
apixaban, rivaroxaban, and dabigatran), antibiotics, etc.
• Ask about OTC medications and herbal/dietary supplements which can be easily missed culprits of drug-drug interactions
Preadmission Medication List (PAML) on admission: especially important for patients with frailty!
• Boston-area 24/7 pharmacies: CVS: 781-894-1600 (dial 2, 2); Walgreens: 617-389-2188 (dial #,0)
• Coordinate discharge Rx planning and education with patient, pharmacy, and PCP  lower risk of readmission with
intensive pharmacist intervention (med rec and education) and coordination with PCP (JAMA IM 2018:178:375)

Jessica O’Neil and Miranda Ravicz

152
TOC

Geriatrics & Palliative Care Pain Management

General Approach to Pain Management (NEJM 2015;373:2549, Lancet 2011;377:2236)
• Pain history and etiology can help guide therapy. Goal is to maximize level of functioning and quality of life.
o Time course, location, radiation, quality, severity, exacerbating/relieving factors, associated symptoms, side effects from prior
analgesics, functionality (e.g., ADLs, ambulation)
o Use adjuvant medications and non-pharmacologics: PT/exercise/activity, heat or ice, CBT, treating comorbid psych dx,
addressing existential issues, massage, acupuncture or other integrative therapies
• Step-wise approach to pain management: (WHO Guidelines, CDC guidelines, DFCI Pink Book)
o Mild to moderate pain: non-opioids and adjuvants
 Acetaminophen: max dose 3g daily, 2-3g safe in liver disease (Br J Clin Pharmacol. 2016;81:210)
 NSAIDs: celecoxib if GI risk , naproxen if CV risk , ketorolac if severe pain
o Moderate to severe pain: ensure non-opioid options ordered as scheduled, then consider short-acting opioids
o Severe pain requiring around the clock opioids: consider adding extended release (ER) medications
 Avoid ER opioids if pain source expected to resolve (e.g., bone fracture, hematoma)

Pain Archetypes and Useful Adjuvant Analgesics

• Somatic/musculoskeletal: easily localized, sharp, aching, gnawing *Caution using steroids in
o Bony pain: high dose NSAIDs or steroids*. Consider palliative XRT (if cancer-related) or surgery. cancer patients, may
o Muscle spasm: topical lidocaine, capsaicin, methy salicylate-menthol ointment (Bengay); muscle interfere with treatment (e.g
relaxants such as cyclobenzaprine, baclofen, tizanidine (watch for sedation & delirium) immunotherapy)
• Visceral: deep tisues and internal organs, vague, referred or difficult to localize
o Visceral distension (e.g., hepatic capsular stretch from liver mets, malignant bowel obstruction): depends on etiology but
steroids* can be helpful
• Inflammatory: associated with other signs of inflammation (swelling, erythema, warmth)
o NSAIDs, steroids*
• Neuropathic: burning, stinging, allodynia (perceiving innocuous stimuli as painful), hyperalgesia
o Topical camphor/menthol, lidocaine, diclofenac gel (NB: short-term benefit, often not covered by insurance as outpatient)
o Pregabalin, gabapentin, clonidine, SNRIs (duloxetine, venlafaxine), TCAs (amitriptyline, nortriptyline, desipramine)

Opioids
• Opioid-tolerant defined as total daily dose (TDD) x7 days: morphine 60 mg/oxycodone 30 mg/hydromorphone 8 mg/fentanyl 25 mcg/h
• Patients on suboxone or methadone for OUD  consult ACT for assistance with pain management
• No max dose. Goal is to find minimum dose needed to
control sx w/ minimal SE __________________Converting Opioids____________________
Ex: Pt takes morphine ER 60 mg PO q12h and uses two morphine IR
• Avoid using combo pills (limits titration flexibility)
15 mg PO breakthrough doses per day
• Treat constipation prophylactically
• Rotate opioids if side effects, dose reduce by 25-50% Step 1) Calculate total daily opioid requirement
TDD = (60 mg x 2 doses) + (15 mg x 2 doses) = 150 mg
morphine per day
Opioid Equianalgesic Doses Step 2) Convert TDD to equivalent dose of new opioid
Drug PO (mg) IV (mg) 30 mg morphine 150 mg morphine
Morphine 30 10 = x = 100 mg oxycodone
20 mg oxycodone x
OxyCODONE 20 n/a
HYDROcodone 20 n/a Reduce dose by 25-50% to account for incomplete cross-tolerance
HYDROmorphone 7.5 1.5  ~60 mg oxycodone total daily dose
FentaNYL* n/a 0.1 (100 mcg) Step 3) Divide TDD by number of doses per day
Fentanyl patch (mcg/hr) Morphine PO (mg/day) - If initiating or converting to long-acting opioid, divide TDD into ER
25 50 doses and add breakthrough dose (10-20% of TDD of ER opioid)
*Use caution converting to Fentanyl (short duration of action) Final dose: oxyocodone ER 30 mg q12h with 10 mg oxycodone q4h
prn breakthrough

Route Onset (min) Peak Effect (min) Duration of Effect (hr) Clearance/Metabolites
IV 5-10 10-30 3-5
Morphine AVOID in renal disease
PO 15-60 90-120 4
IV 5-20 15-30 3-4
HYDROmorphone Safer in renal disease
PO 15-30 90-120 4-6
OxyCODONE PO 15-30 30-60 4-6 2nd line for renal disease
HYDROcodone PO 30 90 3-4 AVOID in renal disease
FentaNYL IV <1 5-7 45 min to 2+ hr Safest in renal and liver disease
IV 10-20 60-120 4-6
Methadone Safest in renal disease
PO 30-60 90-120 4-12

Howard J. Lee and Jessica O’Neil

153
TOC

Geriatrics & Palliative Care Pain Management

Methadone and Fentanyl: initiate with assistance of Palliative Care or Pain consult!
• Methadone: both a mu agonist and NMDA antagonist • Fentanyl:
o Beneficial in neuropathic pain o Safer in both liver and renal dysfunction
o Cannot be converted linearly from other opioids o Safety concerns: must remove patch if febrile (cutaneous
o Safety concerns: bimodal short and long half-life (up to vasodilation  faster transdermal absorption)
150 hours), QTc prolongation o Requires 18-24h for therapeutic level (patch)
o TID dosing for pain vs daily for OUD

Pain Crisis Management: severe worsening of pain; while treating, pursue reasonable diagnostic workup for etiology (e.g., bowel
perforation/peritonitis, procedural complication, bleeding). Goal is reduction in pain score by >50%.
1) Opioid-naïve: give morphine IV 2-5 mg or hydromorphone IV 0.2-0.4 mg bolus dose
Opioid-tolerant: convert usual breakthrough PO dose or 10-20% of total daily ER dose to IV and administer
2) Assess for response after 15 min:
o No pain relief and no side effects  increase dose by 50-100%
o Minimal relief and no side effects (<50% reduction in pain score)  repeat the same dose
o Pain reduced >50% and no side effects  reassess in 2-3 hours, use this dose as new breakthrough dose
o Side effects with no pain relief  rotate to different IV opioid (no dose reduction if uncontrolled pain)

Uptitration: if pain only moderately controlled with scheduled doses (not in pain crisis),  total daily dose by 30-50%
• If taking ER opioid and needing >3-4 rescue doses daily,  ER dose by 50-100% of total rescue dose used in past 24 hrs

Patient-Controlled Analgesia (PCA): appropriate for patients who are alert & oriented and able to use equipment. Families may NOT use
PCA by proxy at MGH.
• Quickest relief if episodes sudden and severe (pain onset to drug administration; don’t have to call/wait for RN to pull medication).
• PCA and/or continuous infusion, when implemented safely, reduce burden on nursing for patients who need frequent administration of
pain medications (generally q1-2h is the most frequent a PRN can be ordered on the floor)
• Medicine residents can order “General PCA” (for opioid-naïve patients) or “High Risk PCA” (BMI >40, hx OSA, RAAS -2 to -5, age
>65). If opioid-tolerant, requiring continuous infusion, or pain difficult to control, consult Palliative Care or Pain.

General Opioid-Naïve PCA Dosing

Morphine Hydromorphone
Patient Administered (PCA) Dose 1.5 mg 0.2 mg
Lockout Interval (in minutes) 10 minutes 6 minutes
One-Hour Dose Limit 6 mg 1.4 mg
RN/Clinician Bolus Dose (for breakthrough) 2 mg q30min PRN 0.3 mg q20min PRN
Continuous Infusion Rate 0 mg/hr 0 mg/hr

Adverse Effects of Opioids and Management

• Respiratory depression: hold opioid, consider low doses of naloxone but CAUTION if on high dose ER opioids
o Dilute 0.4 mg naloxone (1 ml) in 9 ml saline, give 1-2 ml q2 min until  RR or mental status improves
o Naloxone half life is shorter than many opioids, watch for recurrence of resp depression
o All patients being discharged on opioids should also be given a naloxone prescription
• Constipation: ALWAYS start standing senna and miralax when initiating opioids; lactulose, bisacodyl and other laxatives if needed;
methylnaltrexone QOD if failed laxative therapy (but can cause severe nausea and cramping; avoid if concern for GI obstruction)
• Myoclonus: reduce dose or rotate opioid, increase hydration / IVF; can give low dose BZD, baclofen or gabapentin
• Nausea/vomiting: prochlorperazine, metoclopramide, haloperidol; avoid ondansetron (constipating)
• Pruritus: pruritus mediated by mu receptor (not histamine - Benadryl ineffective) unless rash/allergic reaction; treat with nalbuphine 5
mg IV q6h or low dose continuous naloxone infusion
• Sedation: consider CNS stimulants (dextroamphetamine, methylphenidate)
• Delirium: reduce dose or rotate opioid; Haldol 0.5-1 bid-qid or Zyprexa 2.5-5 mg PO QD-BID

Opioid Use and Aberrant Use Definitions

• Addiction: neurobiologic disease with environmental and psychosocial factors, manifested by impaired control over drug use,
compulsive use, continued use despite harm, and cravings. See Psychiatry section.
• Misuse: use that is contrary to prescriber directions (e.g., not taking as diected, altering route of delivery)
• Diversion: redirection of a drug from its lawful purpose to illicit use
• Tolerance: physiologic adaptation from exposure to a drug resulting in diminished effect from the drug over time
• Physical dependence: withdrawal syndrome in response to abrupt cessation of a drug, rapid dose reduction, or drug antagonist;
tolerance/ physical dependence are expected with long-term use and shouldn’t be confused with addiction
• Pseudoaddiction: addiction-like behavior that occurs when pain is undertreated; behaviors resolve when pain is adequately treated

Howard J. Lee and Jessica O’Neil

154
TOC

Geriatrics & Palliative Care Non-Pain Symptom Management

Resources: Palliative Care Network of Wisconsin fast facts and concepts for disease specific resources; DFCI “pocket resources”: Pink
Book for pain, Green Book for nausea/vomiting
Palliation in serious illness and end of life can be challenging and often is helped by a Palliative Care consultation
• “Comfort measures only” is NOT a one-size-fits-all set of orders, be thoughtful about standard CMO orders (foley, discontinuation of
scheduled meds such as diuretics, antibiotics) and how they may or may not provide comfort
• For persistent/recurring sx, meds should be made standing, with additional PRNs for breakthrough
• Consider the route of medication to maximize comfort (sublingual, concentrated elixirs); avoid IM
Anxiety: all palliative care patients should be screened for anxiety and depression. See Psychiatry section for further details.
• Exacerbated by meds (steroids, appetite stimulants), withdrawal (opioids, BZDs, nicotine), insomnia, undertreated pain, dyspnea
• Non-pharmacologic strategies: psychotherapy, integrative therapies c/s, SW & spiritual care for coping/support
• For acute anxiolysis: olanzapine 2.5-5mg Q6H PRN, lower doses if elderly. Use BZDs with caution due to delirium risk and
physiologic dependence. Avoid long acting BZDs and use lowest dose possible for symptomatic relief.
• Longer-term, consider SSRIs and SNRIs. Mirtazapine (15mg QHS) for simultaneous anxiety/depression, insomnia and/or anorexia.
Depression: difficult to distinguish MDD, demoralization, adjustment disorder; clincal depression however is not a normal part of the dying
process and should be addressed with nonpharmacological or pharmacological interventions. (Palliative Care Network of Wisconsin.2020)
• Non-pharmacologic strategies: psychotherapy, integrative therapies c/s, SW & spiritual care for coping/support
• If prognosis <4 weeks consider CNS stimulants (methylphenidate, dextroamphetamine) over SSRIs due to faster onset of action
• Longer-term, consider SSRIs: citalopram and escitalopram are preferred agents as they have have mildest side effect profile, fewer
drug interactions and are neither activating nor sedating (Palliat Med. 1999;13:243)
• SNRIs may be helpful for simultaneous anxiety, vasomotor symptoms (hot flashes) or neuropathic pain
• Consider psychiatry consult for pre-existing psychiatric diagnosis, refractory symptoms or polypharmacy
Fatigue: often related to disease progression, medications, other treatments, deconditioning, malnutrition, sleep disturbances, sxs
• Treat uncontrolled sx; for cancer-related fatigue, exercise and psychological interventions >> medications (JAMA Oncol. 2017;3: 961).
Consider steroid trial (JCO 2013;31:3076). Psychostimulants (modafinil, methylphenidate) have limited evidence.
Anorexia/Cachexia: common in AIDS, heart failure, COPD, advanced cancer; often highly concerning for family > patient.
• Rule out reversible causes (depression, medication side effects). In general, allow PO for comfort if near end-of-life. Remove NGTs.
• Meds to consider: dexamethasone, megestrol (VTE risk), dronabinol, mirtazapine
• During the dying process, artificial nutrition and hydration are generally not recommended and do not improve QoL or survival
Nausea/Vomiting, Diarrhea, Constipation: see relevant pages in GI section.
Xerostomia: side effect of chemo/XRT, head/neck surgery, or medications
• Oral hygiene, oral hydration, ice chips, sugarless gum, artificial saliva (Biotene)
Insomnia (inpatient management):
• Use non-FDA approved treatments on a short-term basis: melatonin (3-5mg Q6PM), trazodone (12.5-50mg QHS, QTc prolonging),
mirtazapine (7.5mg QHS)
• Use with caution: quetiapine (12.5-25mg QHS, QTc prolonging); concern for  mortality with antipsychotics in the elderly (JAMA Psych
2015;72:438). Reserve for patients with additional indication (e.g., requiring pharmacologic tx for agitated delirium).
• Avoid BZDs and non-BZD hypnotics (e.g. zolpidem, zaleplon, eszopiclone) for inpatient management due to delirium risk. Avoid H1
blockers (diphenhydramine, hydroxyzine) due to risk of delirium, next-day sedation, anticholinergic side effects.
Delirium: common and often multifactorial. See Neurology: Delirium for further details.
• Prevention: remove unnecessary monitoring (tele and pulse ox)/lines/catheters/restraints; family and friends can be more effective at
reorientation; use signage to minimize staff/room changes; manage other symptoms. Melatonin 5mg Q6PM.
• No FDA-approved delirium med, but if hallucinations or agitation interfering w/ staff or pt safety consider antipsychotics: quetiapine
12.5-25mg if taking PO or Zydis ODT 2.5-5mg Q6H PRN. If IV needed, haloperidol 0.5-1mg IV Q4H PRN.
• For hyperactive delerium in patients with terminal delirium, consider lorazepam PRN
Dyspnea: exacerbated by deconditioning, cachexia, worsens at EOL, exacerbates anxiety. Does not always correlate w/ hypoxemia.
• Treat contributing causes for comfort: diuresis for volume; nebulizers/steroids for reactive airways; saline nebs for mucous pluging
• For refractory dyspnea, opioids are gold standard (often at lower doses than required for pain). BZDs less supported by evidence;
can be used for associated anxiety though must weigh risk of delirium.
Secretions: pooled secretions  “death rattle”. Disturbing to observers, less bothersome to patient.
• Prepare family, position pt to facilitate postural drainage, stop feeds/fluids, don’t deep suction (uncomfortable to pt), continue oral care
• Glycopyrrolate 0.2-0.4mg IV Q4H PRN (less deliriogenic). Alternatives: scopolamine patch, atropine (SL, IV), hyoscyamine (PO, SL)
Catastrophic hemoptysis or hemorrhage: impending catastrophic hemorrhage that will likely result in death (hemoptysis in ENT and
lung cancer, variceal bleed in ESLD, vaginal bleeding in GYN cancers). Often preceded by “sentinel” small bleed.
• Develop palliative treatment plan with goal of rapid anxiolysis and sedation with medications at bedside (BZDs q5-10 min +/- opioids)
• Prepare room with dark linens/basins ( contrast w/ blood), PPE for caregivers, suctioning, warm blankets (hemorrhage  chills)

Howard J. Lee and Jessica O’Neil

155
TOC

Geriatrics & Palliative Care Adv Care Planning & Code Status
Serious Illness Conversations
● When? Preferred early in disease course as outpatient, but in the inpatient setting some scenarios include:
o New or progressive serious medical illness such as advanced cancer, ESRD, ESLD, HF, COPD
o Prognosis trigger: “Would I be surprised if this patient died in the next year?” (J Palliat Med 2010;13:837)
o Indicator of life expectancy <6 months (calculator, J Palliat Med 2012;15:175)
o Age > 80 and hospitalized; see Geriatrics: Frailty
● Why? Ascertain how the patient wants to live, what they value; more than just end of life care preferences
● How? Often best to plan patient or family meeting (NEJM 2014;370:2506)

Preparation
● Identify time and location to accommodate all meeting participants in an appropriate manner
● Include patient and their preferred participants, primary team, RN, SW, and other providers as appropriate
● If complex decisions/psychosocial issues/family conflict, consider a palliative care consult
● Pre-meet with team to decide meeting leader, discussion goals, unified assessment of clinical scenario, treatment
options, and team recommendation

Serious Illness Conversation: suggested outline / prompts (adapted from Ariadne Labs SICG)
Step Suggested Prompts
Open the conversation “I’d like to talk about what is ahead with your illness. Would that be ok?”
“What is your understanding of your illness?”
Assess prognostic awareness “Looking to the future, what are your hopes about your health?”
“What are your worries?”
“Would it be ok if we talked more about what lies ahead?”
“I hear you’re hoping for ____ and I’m concerned the decline we’ve seen will
Share hope and concerns
continue” or “I’m concerned something serious may happen in next (time
window: weeks, months, years)”
Align “I wish we didn’t have to worry about this”
“If your health worsens, what is most important to you?”
Explore what’s important
“How much do your family or friends know about your priorities and wishes?”
“It sounds like ____ is very important to you”
Close the conversation
“Given what’s important to you, I would recommend______”
**Note: some patients may respond better to being asked about their “health” rather than their illness--especially those
who are semi-stable in clinic but have frailty or multimorbidity

Next Steps:
● Debrief with team: How did that feel? What went well? What could have gone better?
● Document Serious Illness Conversation in Epic:
o Patient ID banner (top of chart): click “Code: ___”  “Advance Care Planning Activity”  “Serious Illness
Conversation” in left tab; fill out SIC form  “Close”
o Write ACP note: Within “Advance Care Planning Activity”  “ACP Notes”  “Create ACP Note”  type
.ACPSICDOCUMENTATION; write rest of the note if relevant

Advance Care Planning Forms

● Health Care Proxy (HCP) / medical power of attorney: an advance directive document that designates a healthcare agent
to make future medical decisions if patient loses capacity. Expressly authorized in MA by statute.
o If no HCP: surrogate hierarchy: see Section 3, bullet 6 of MA: An Act Improving Medical Decision Making
● Living Will: an advance directive document in which a competent person specifies future medical treatments in the event
of incapacity, usually at end-of-life or if in a persistent vegetative state. Can be used as evidence of a person’s wishes,
but not considered to have legal authority (no MA statute that expressly authorizes).
● MOLST (MA Medical Orders for Life-Sustaining Treatment; hot-pink forms available on all medical units): medical orders
for patients with advanced serious illness and limited prognosis that documents preferences for CPR, intubation, hospital
transfer, artificial nutrition, and more
o Transferrable to outside facilities; complete MOLST prior to discharge to rehab/SNF if patient DNR/DNI
o Remember that you do not have to discuss everything on the back page (clinical discretion)
● Links to MOLST/HCP forms are found in banner at the top of a pt’s Epic chart or scanned into the Media tab

Krystle Leung
156
TOC

Geriatrics & Palliative Care Adv Care Planning & Code Status
Code Status Discussions
General Considerations
● Ideally code status should be confirmed in Epic at time of admission
● Confirm directly with the patient/HCP, MOLST, and/or prior documentation by outpatient providers
● Readdress if a patient’s clinical status changes, or if code status is deemed inappropriate for the clinical setting, but do
not need to routinely readdress on admission if has been addressed by outpatient providers
● Code status should reflect a patient’s values and preferences and is not equivalent to ACP (it is a specific medical
procedure for which harms/benefits should be weighed given clinical context)
Survival Outcomes (Circulation 2019;139:e56)
● Out-of-hospital cardiac arrest: survival to hospital discharge 10.4%; survival with good neurologic function 9.9%
● In-hospital cardiac arrest: survival to discharge 25.6%; survival with good neurologic function 22%
o Favorable outcomes: ACS, drug overdose, drug reaction (up to 40% survival)
o Unfavorable outcomes: age >80 (<10% survival), multiorgan failure, sepsis, advanced cancer, ESRD, ESLD,
dementia
o Post-arrest complications: hypoxic-ischemic brain injury, rib fractures, pulmonary contusion, prolonged ICU care

Conducting Code Status Discussions (JAMA 2012;307:917)

● Initial tips:
o Suggested framing of CPR for patients: “CPR is a medical procedure that we would do if you were to die, that is, if
your heart were to stop and you were to stop breathing. CPR includes pressing on your chest to pump the heart and
the use of a breathing machine to help you breathe”
o Do not offer DNI alone, as resuscitation almost always requires intubation
● Two main types of code status discussions:
1. Information-gathering code status discussion
 Who? Patients you would expect and would recommend to be full-code OR when you are meeting the patient for
the first time w/ limited rapport (you may need to revisit the conversation later)
Step Suggested Prompt
Introduce “Would it be okay if we did some emergency planning? I want to talk about a procedure called CPR.”
“What do you know about CPR?”
Assess patient
“Do you have any personal or family experience with CPR?”
understanding
“Have you spoken with other doctors about CPR?”
Share information / Describe CPR as above. If not vocalizing clear desire for DNI or DNR, “Right now, if your heart were
confirm goals to stop, you would receive CPR. Is this consistent with your goals?”
“In the future, your doctor may no longer recommend CPR because it would be unlikely to help. At
Forecast the future
that time, your team will talk with you more.”
2. Decision-making code status discussion
 Who? Patients you would recommend being DNI or DNR/DNI as CPR would be unlikely to reverse their
underlying chronic illness/frailty
 Be prepared: know details of your patient’s condition and prognosis.
 Consider if warrants discussion w/ outpatient providers.
 Often may end up conducting a serious illness conversation within discussion of code status
Step Suggested Prompts
Introduce/assess See table above for suggested prompts
“Unfortunately, we are in a different place now.” (Discuss medical situation, share
Share information
concerns using hope/concern statements from serious illness conversation.)
Align “I wish we didn’t have to worry about this.”
Explore goals/what’s important “Given where we are, what is most important to you?”
“If something were to happen and you were to die, I would recommend focusing on
Close the conversation comfort, allowing a natural death, and not doing CPR. Medical procedures such as CPR
cannot reverse your illness and may prolong suffering in the dying process.”

Krystle Leung
157
TOC

Geriatrics & Palliative Care End of Life & Pronouncement

Practical Steps for Making a Patient CMO
• D/c all unnecessary lines and tubes (usually maintain IV access but d/c central line if possible; discuss Foley w/ RN)
• D/c labs, routine VS, and other interventions that do not contribute to comfort
• Run order list and d/c unnecessary medications. Continue medications that contribute to comfort, that will prevent uncomfortable
events (e.g. maintain rate control to avoid AFRVR), or that have a withdrawal syndrome (e.g. SSRIs).
• Generally avoid artificial nutrition and hydration; may cause volume overload without meaningful benefit (JCO 2013;31:111)
• See Pain Management and Non-Pain Symptom Management. Most often require PRN meds for pain and dyspnea (opioids, may
require gtt), delirium (e.g. zydis, haldol), secretions (e.g. glycopyrrolate, scolpolamine patch).
General Inpatient Hospice (GIP)
● Pts with terminal diagnosis and prognosis of < ~2wks, transitioned to CMO, w/ sx management needs requiring inpatient care (e.g.
high flow O2, uncontrolled sx requiring IV medications, high RN needs for wound care/suctioning)
● Discuss w/ floor CM team (for insurance benefit screen and coordinate w/ hospice liaison) and Pall Care
● If admitted to GIP, pt transitions off Housestaff team, Pall Care attending becomes AOR, Pall Care clinician becomes RC
Prior to Death
• Involve family +/- chaplaincy (available 24/7), other care team members (e.g. PCP). Ask about religious/cultural traditions.
• Consider early contact of the New England Organ Bank (NEOB) 800-446-6362. The NEOB determines eligibility for donation. They
are trained in how to discuss donation with the family; DO NOT discuss this with the family. See Organ Donation.
• When passing off a patient who may pass away, prep the “Report of Death” form (at minimum the cause of death section)
Withdrawing Ventilatory Support: palliative extubation or discontinuation of NIPPV
• Prior to extubation: see MGH MICU Policy and ATS Guidelines (AJRCCM 2008;177:912)
o Allow family time with patient (if desired). Discuss with family the extubation process, expected dying process (e.g. agonal
breathing), plans for sx control, and expected timeline (death usually occurs in min to hrs Chest 2010;138:289)
o Have PRN meds ready to address air hunger and pain (IV opioids) and anxiety (IV haldol, IV BZD) aggressively and discuss
w/ RN. May need infusions. Glycopyrrolate for secretions. STOP paralytic agents (cisatracurium).
o Do not withhold appropriate sx management because of concern for hastening death (Principle of Double Effect: your focus
should be on managing sx, including palliative sedation if no other reasonable options). If in doubt, ask for help.
o Discuss vent withdrawal plan with RT (immediate withdrawal vs down-titration of vent support).

DEATH PRONOUNCEMENT
PRONOUNCEMENT. Introduce yourself to the family, explain what you are doing, express condolences
• FEEL for pulse, LISTEN for heart sounds/breath sounds (> 60 sec), SHINE light to determine absence of pupillary light reflex, and
NOTE time at the end of your exam, which becomes the time of death

QUESTIONS FOR NEXT OF KIN (Not HCP, but Next of Kin (NOK): Husband/Wife > Children > Other Family)
• If no NOK in room, call NOK to notify of patient’s death.
• Ask the family if they would like to see a CHAPLAIN or SOCIAL WORK AUTOPSIES are free and do not delay funerals
(can still have open casket). In addition to
• Ask if family would want an AUTOPSY?
helping determine cause of death, they can be
• If family accepts autopsy, ask about DISPOSITION OF ORGANS. Consider
instrumental in advancing research.
recommending the option of MGH retaining organs for further testing,
education, research (if not, value of/info from autopsy lower)
• Are there OTHER FAMILY MEMBERS they would like you to inform?
• Will anyone else be COMING TO VIEW THE BODY prior to morgue?
• What you can tell family: body is kept at MGH until the funeral home calls MGH (path: 617-726-2967) and arranges for pick-up.
Ask family if they plan to contact funeral home or if they have a preferred funeral home they want notified.

ONCE YOU LEAVE THE ROOM:

• Notify ATTENDING and PCP. Email acceptable if death was expected.
• Obtain “Report of Death” form from OA. Fill out in BLACK ink. If any mistakes, you will need to START OVER.
o Log into Epic before calling the numbers listed on the form.
o Call the Medical Examiner if necessary or in doubt (most cases not necessary; NB: alcohol-related deaths, including EtOH-
related liver diease, are reportable). Document the first name of the staff member.
o Call New England Organ Bank: 800-446-6362: will need patient’s demographics, cause of death. May require: history of
cancer, recent infections, recent labs, hx dementia, other PMHx.
o Call the Admitting Office (x6-3393) to inform them of the death. They will ask cause/time of death, Med Examiner, NEOB.
o The “Report of Death” goes to admitting with the chart. Chart/patient cannot leave the floor until the Report of Death is
completed.
• Document a brief “note of patient death”: SmartPhrase “.MGHDOMDEATHNOTE”.
• Complete short discharge summary using “Deceased Patient” portion of the Discharge tab in Epic.

Emily Moin
158
TOC

Geriatrics & Palliative Care Organ Donation

Organ Donation after Brain or Circulatory Death
• ~75% of transplanted organs are from deceased donors, including donation after brain death (DBD) and donation after
circulatory death (DCD). DCD represents ~8% of organs procured nationally, ~20% in the Boston area (NEJM
2007;357:209). Organs from DCD and DBD donors have similar long-term outcomes (NEJM 2002;347:248).
• DBD = death based on neurologic criteria (“brain death,” or irreversible loss of all functions of the brain, including the
brain stem
• DCD = death based on cardiopulmonary criteria (irreversible cessation of circulatory and respiratory function and
mechanical ventilatory support is no longer medically indicated, but criteria for brain death are NOT fulfilled)

Eligibility for Organ Donation

• Medical team determines that discontinuation of medical support is appropriate and discusses this with the HCP or legal
next-of-kin
• DO NOT broach the topic of potential organ donation with family; New England Organ Bank (NEOB) is specifically trained
to do this.
• If family wishes for withdrawal of support, the medical team notifies NEOB (800) 446-6362 who will coordinate the
process for consent and donation. This process can take up to 24 hours.

Care of the Patient Prior to Organ Donation

• Patients with potential for organ donation need to maintain organ viability in response to potentially severe autonomic and
inflammatory responses that occur after severe neurologic insult or brain death.
• Interventions often require a delicate balance to preserve multiple organs: (CCM 2015;43:1291, NEJM 2004;351:2730)
o Continuous temperature monitoring, telemetry, and lab monitoring for renal function, electrolytes, acid-base status
o Hemodynamics – goal MAP 60-110 (JAMA Surg 2014;149:969)
 Hypertensive autonomic storm after brain death. Esmolol to preserve cardiac function. (Am J Transplant
2005;5:684)
 Fluids and vasopressors for hypotension/vasoplegia. Consider vasopressin before catecholamines (helps w/ DI)
 Dobutamine for reduced EF
o Maintenance of normothermia via external warming or cooling
o Urine output monitoring: goal 0.5-1.0 cc/kg/hr. Monitor for DI with brain death.
o Proper ventilatory support and pulmonary toilet; lung-protective LTVV as in ARDSNet. Prevent pneumonia with
head elevation, etc. (JAMA 2010;304:2620)
o Maintenance of eunatremia, euvolemia, and acid-base status
o Consider glucocorticoids for adrenal insufficiency/general inflammation; thyroid hormone for EF <45% or HD
instability (poor evidence)
o Empiric antibiotics if concern for infection
• NEOB and transplant team may request additional testing (e.g. TTE, bronchoscopy)

Death Pronouncement in the Operating Room for DCD patients

• Generally, withdrawal of medical support, including extubation, occurs in the OR after pt is prepped by surgical team
• All members of the organ recovery teams must be outside of the room from the time of withdrawal of support to
declaration of death; otherwise this poses a conflict of interest. Family may be present in the OR if they wish.
• Medical team (MD and RN) are present to coordinate end of life care from time of withdrawal of support to death,
including PRN palliative medications. NEOB staff may not participate in the administration of medications or declaration of
death.
• Death must occur and be declared within 2 hours of extubation, otherwise organs are deemed nonviable.
o “Dead-donor rule” (DDR) = recovery of organs cannot be the cause of death, and organs should be taken only from
persons who are already dead (NEJM 2013;369:1287)
• MD declares death based on the irreversible cessation of circulatory and respiratory function (checks carotid artery for
pulsations and auscultates for breath sounds using a sterile ultrasound cover over stethoscope)
o PEA arrest meets criteria for cessation of circulatory function so long as there is no pulsatile flow on arterial line.
Death can be declared even if cardiac electrical activity persists.
o After death is declared, a a 5-minute observation period begins to ensure no ROSC
• Death paperwork should be signed by declaring MD in the OR (i.e. bring prepped death paperwork with you)

Emily Moin
159
TOC

Rheumatology Approach to Rheumatologic Disease

Overview: rheumatologic diseases may be roughly separated into 4 categories:

Category Connective Tissue

Inflammatory Arthritis Vasculitis Other
Disease

RA, SLE, Sjӧgren’s, Autoinflammatory

Small, medium,
Diseases spondyloarthropathies, scleroderma, MCTD, diseases, sarcoid,
large (GCA, PAN,
PMR, crystalline UCTD, myositis (DM, IgG4-related disease
GPA, EGPA)
arthritis PM)

ANA first
C3/C4, anti-Sm, anti-
Work-up RF, anti-CCP, ANA dsDNA, anti-Scl70, ANCA, Limited role for ACE,
anti-histone, anti- cryoglobulins can send IgG4
U1RNP, anti-Ro/La,
antiphospholipid Abs

Treatment* NSAIDS/Glucocorticoids

Hydroxychloroquine *DMARD = disease-modifying

antirheumatic drug, MTX =
methotrexate, SSZ =
Severity

DMARDS (MTX, SSZ) DMARDS (MTX, AZA, MMF) sulfasalazine, AZA =

azathioprine, MMF =
mycophenolate mofetil, RTX =
Most Biologics RTX, belimumab RTX, TCZ rituximab, TCZ = tocilizumab.
Nuances of treatment not
encapsulated by this figure.
Cyclophosphamide

• Rheumatologic ROS: fevers,

rashes/photosensitivity, alopecia, nail/nailfold
abnormalities, sicca symptoms, conjunctivitis,
uveitis, episcleritis, scleritis, Raynaud's,
oral/genital ulcers, polychondritis, enthesitis,
serositis sx, thromboses, neuropathy, pregnancy
loss.
• Basic labs: CBC w/ diff, BMP, LFTs, UA,
ESR/CRP, TSH
• Ddx: Always consider malignancy and infection
as alternative diagnoses prior to initiation of
immunosuppressants unless at risk of
permanent organ damage (i.e. do not withhold
glucocorticoids when suspecting GCA,
mononeuritis multiplex, RPGN, etc.)

Helen D’Couto
160
TOC

Rheumatology Arthritis
Approach to the Patient with Arthritis

Acute Arthritis Syndromes

Arthritis Joint pattern Presentation Diagnosis Treatment

- Mono>poly - Triggers: diuretics, meat, - Arthrocentesis: - Acute: colchicine (1.2mg x1,
- Podagra (1st seafood, EtOH, HTN, neg birefringent 0.6mg 1h later, 0.6 mg QD until 2-3d
sx in 50% pts), DM2, CKD needle-shaped after resolved), pred 40mg QD until
hindfoot, - Acute flareschronic crystals, WBC 10k- resolved then taper, NSAIDs (approx
Gout fingers, ankle, arthropathy (tophi) 100k 5-7d), intra-articular steroids
knee - Urate nephrolithiasis, - can co-exist with - Chronic: urate lowering tx if ≥2
chronic nephropathy septic arthritis attacks/yr, CKD, tophi (uric acid
goal<6), diet changes, stop diuretics.
Do not stop during acute attack.
- Mono>poly - Can be asymptomatic - Arthrocentesis: - Acute: if ≤2 joints  intra-articular
- Knee>wrist, - Can coexist with gout, small pos steroids (1st line). 2nd line is same as
CPPD shoulder, ankle OA birefringent gout (prefer colchine w/in 24h sx
(pseudogout) rhomboid crystals, onset)
WBC 10k-100k - Chronic: consider HCQ, low-dose
ACUTE

- chondrocalcinosis pred, MTX

- Mono - Hematogenous spread - Arthrocentesis: - Antibiotics for 3-4 weeks
- Knee (50%), (most common), positive GS/Cx, - Joint drainage/washout (ortho c/s)
Septic
>1 joint (20%) endocarditis WBC 50k-150k
arthritis - risk in RA
- Staph>strep>GNRs
- Oligo > mono - 1-4 weeks post-infxn - Presence of - If GU infxn, treat. If GI infxn, may
> poly (small - Enteric: Salmonella, preceding infxn not need to treat.
joints) Shigella, Yersinia, - Arthrocentesis: - Acute: NSAIDs (1st line), intra-
- Asymmetric Campylobacter, C. diff GS/Cx articular steroids (2nd line),
Reactive
- LE > UE - GU: Chlamydia, E. coli, - Stool cx (if prednisone (3rd line)
arthritis Ureaplasma, Mycoplasma diarrhea) - Chronic: if >6 mo, MTX or SSZ
- Conjunctivitis, urethritis, - GC/Chlamydia
cervicitis, oral ulcers,
keratoderma, E nodosum

Jacquelyn Nestor
161
TOC

Rheumatology Arthritis
Chronic Arthritis Syndromes

Arthritis Joint pattern Presentation Diagnosis Treatment

- Poly - Age >45 - Clinical dx - PT, braces
- Knees, hips, 1st - AM stiff <30min, slow - Bony swelling, - Topical NSAIDs, PRN NSAIDs
MTP, CMC, PIP, progression, no warmth, joint deformity, - Duloxetine 60-120mg QD
DIP, C-spine, L- muscular wasting limited ROM - Intra-articular steroids
Osteoarthritis spine - Stage 1: pain limits - If severe, refer to ortho
high-impact activity - Not recommended: glucosamine,
- Stage 2: constant bisphosphonates (ACR Guideline
pain, affects ADLs 2019)
- Stage 3: intense pain
- Mono in early - F>M, age 35-65 - RF, anti-CCP - Acute: prednisone or NSAIDs,
stage, then poly - AM stiff >30min - Joint XR initiate DMARD if not on
- Small peripheral - Joint deformity - Exclude other - Chronic: DMARD (MTX > HCQ >
Rheumatoid
(MCP, PIP, wrists, causes SSZ > lefulomide); if fails monotx,
Arthritis MTP) consider combination or transition to
- Symmetric biologic (infliximab, abatacept,
CHRONIC

tocilizumab)
- 5 patterns (distal - 70% with psoriasis - Clinical dx - NSAIDs (1st line)
DIP, asymm oligo, - Extra-articular: -  ESR/CRP - If mod/severe, MTX > SSZ,
symm poly, arthritis synovitis, enthesitis, (40%) leflunomide
Psoriatic mutilans, dactylitis, nail - HLA-B27 - If severe/erosive, TNFα inhibitor
arthritis spondyloarthritis pits/onycholysis, uveitis - CASPAR criteria infliximab, adalimumab, golimumab
[sacroiliitis]) (91% Sn / 99% (ACR Guideline 2018)
- axial (spine) Sp)
involvement (42%)
- Spine & SI joints - Gradual onset - Sacroiliitis (XR - NSAIDs (1st line)
- AM stiff >30min or MRI) - No steroids
- Pain in low back, - Impaired spine - DMARDs not effective
buttock, ankle, TMJ mobility - TNFα inhibitor (2nd line)
Ankylosing
- Extra-articular: -  ESR/CRP infliximab, etanercept, adalimumab
spondylitis synovitis (mono or - HLA-B27 (90%
oligo), enthesitis, Sn/Sp)
dactylitis, uveitis,
psoriasis, IBD

Synovial Fluid Analysis

NON-
NO RMA L I NFL AM MATOR Y S E P TI C H EMORR HAG IC
INFLAMMATORY
Clarity Transparent Transparent Transparent-opaque Opaque Bloody
Color Clear Yellow Yellow to opalescent Yellow to green Red to brown
Viscosity High High Low Variable Variable
WBC (per mm3) < 200 0 - 2,000 2,000 - 100K 50 - 150K 200 - 2,000
PMNs (%) < 25 < 25 ≥ 50 ≥ 75 50 - 75

Jacquelyn Nestor
162
TOC

Rheumatology Connective Tissue Diseases

Disease Clinical Presentation Work-up Treatment Complications
- F> M, 15-40 y/o ⊕ ANA (>95%) - Lupus nephritis: - High risk
⊕ anti-dsDNA (~ 70% pts, a/w MMF (1st line) VTE/ATE
- Discoid/malar rash (spares active dz and lupus nephritis) - Skin, joint, serositis: - CNS, Renal dz
nasolabial fold), photosensitivity, ⊕ anti-Sm (30% pts, specific, prednisone 20mg and - 40% w/ APLAS
serositis, nephritis, oral/nasal remains + in remission) HCQ - Osteonecrosis
SLE ulcers, psychosis, neuro d/o, ⊕ anti-RNP - Other end organ (both 2/2 SLE
arthritis, cytopenias, constitutional ⊕ anti-SS-A/Ro, +anti-SS-B/La involvement: high and steroids)
sx (fever, weight loss, fatigue) ⊕ antiphospholipid antibodies dose prednisone,
HCQ + other DMARD
-  CK suggests myositis - C3, C4, ESR, CRP, UPCR
(2019 EULAR/ACR Criteria)
- F>M, 40-60 y/o ⊕ANA - Sicca only: sx mgmt - 5-10% lifetime
⊕ anti-SS-A (Ro), ⊕ anti-SS-B - Systemic: risk of NHL,
- Sicca sx (dry mouth/eyes),
(La) HCQ/chloroquine, MALT lymphoma
Sjogrens caries, parotid enlargement,
MTX, AZA, RTX,
vasculitis, interstitial nephritis,
- Schirmer test, parotid gland cyclophosphamide,
neuropathy, cytopenias, RA/SLE
ultrasound, salivary gland biopsy glucocorticoids
a/w 2° SS
- F:M (2:1), 40-50 y/o ⊕ ANA (50%), ⊕ anti-Jo1 (a/w - Initiation: - Occult
ILD, mechanic hands, arthritis, prednisone 1mg/kg malignancy in
- Proximal > distal muscle
20%), ⊕ anti-Mi2 (15-20%, a/w x4-6wk then taper DM (9-32%
weakness
acute onset, shawl sign, good incidence):
- Extramuscular: constitutional sx, - Maintenance:
prognosis) commonly
Myositis AZA/MTX
arthralgias, dysphagia, pulm sx ⊕ anti-MDA5 ovarian, breast,
(polymyositis,
(cough, DOE, ILD), HTN, DM2 - Resistant/severe: colon, lung, NHL,
dermatomyosi
- DM skin findings: heliotrope rash, - CK, aldolase, myositis panel, pulse steroids, AZA, nasopharyngeal
tis, inclusion
LDH, AST/ALT MTX, MMF, IVIG, - ILD in 10%
body poikiloderma (chest: V-sign; back:
RTX, - upper
myositis) shawl sign; thigh: Holster sign), - Muscle biopsy cyclophosphamide (if esophageal dz
scalp rash, Gottron’s papules DM: CD4 cells ILD) - increased risk of
- DM sine myositis = skin features PM/IBM: CD8 cells MI
w/o muscle weakness, a/w severe
ILD
- F:M 4:1, 30-50 y/o ⊕ ANA (95%) - Skin: MMF, MTX - Increased risk of
⊕ anti-centromere* (a/w limited, - GI: PPIs, motility multiple cancers
- Systemic: may be limited
only seen in 5% pts with diffuse) agents
cutaneous (67%, skin thickening
in hands/face only, commonly with ⊕ anti-Scl-70* (a/w diffuse) - Lung: CCBs, - Scleroderma
⊕ RNA-pol-III* (a/w diffuse and endothelin-1 renal crisis
CREST sx, PAH) or diffuse
scleroderma renal crisis) antagonist, PDE (<20%): AKI,
cutaneous (33%, diffuse skin
inhibitors, prostacyclin abrupt HTN; a/w
thickening, multi-organ dz, less
- HRCT, PFT, TTE to eval for ILD agonists anti-RNA-pol III;
commonly with CREST sx)
Systemic and pHTN - MSK: Low dose treat with ACEi
Sclerosis - CREST: Calcific nodules, prednisone, HCQ, (captopril) +
(scleroderma) Raynaud’s, Esophageal *Ab are >99% specific MTX avoid steroids
dysmotility, Sclerodactyly, (Arthritis Rheum 2013;11:2737) - Raynaud’s: CCBs
Telangiectasias
- Other systemic sx: renal crisis,
ILD (>70%), PAH (10-40%)
- Systemic sclerosis sine
scleroderma = pts with
scleroderma but w/o skin findings
- 80% F ⊕ ANA (often speckled) - SLE features: Main cause of
⊕ anti-RNP (100%) by definition glucocorticoids, RTX death is PAH
- Overlap of SLE, systemic
MCTD - Scleroderma
sclerosis, and polymyositis;
features: less
Raynaud’s; non-erosive arthritis
responsive to steroids
- Early Raynaud’s, incomplete - Diagnosis of exclusion; - Managed according - According to
UCTD & lupus does not meet criteria for to symptoms dominant clinical
Overlap diagnosis of specific disease presentation
syndromes

Cody Cichowitz
163
TOC

Rheumatology Vasculitis
D I A G N O S T I C O V E R V I E W (Arthritis Rheum 2013;65:1)
• Classified by size and type of blood vessel involved. Large vessels (aorta and its branches) vs. medium-sized vessels (main visceral
arteries = named) vs. small vessels (vessels without names such arterioles, capillaries, venules)
STEP 1 – SUSPECT VASCULITIS
Overview:
• No “typical” presentation but consider in
constitutionally ill patient with evidence of
multisystem organ involvement and
evidence of inflammation
• LARGE vessel: aorta/branches, e.g.
external carotid, temporal, ophthalmic 
limb claudication, bruits, asymmetric BP,
absent pulses, HA, visual loss
• MEDIUM vessel: renal/hepatic/mesenteric
arteries, etc.  cutaneous nodules,
“punched out” ulcers, livedo racemosa,
digital gangrene, mononeuritis multiplex
(e.g. foot/wrist drop), renovascular HTN
• SMALL vessel: vessels of skin, small
airways, glomeruli  palpable purpura,
glomerulonephritis, alveolar hemorrhage,
mononeuritis multiplex, scleritis
General testing:
• Inflammation?  CBC w/ diff (ACD, thrombocytosis, neutrophilia, eosinophilia), ESR, CRP
• Organ involvement?  BMP, LFTs, stool guaiac, CXR, brain MRI (if neurologic symptoms), CTA (if GI/claudication)
Presentation-specific testing (i.e. small-vessel s/sx): difficult to discern clinically
• Immune complex formation?  complement levels (C3, C4), ANA, RF/Cryoglobulins
o ANA/RF are NOT positive in 1° vasculitis; ⊕RF could suggest cryoglobulinemia or endocarditis (in addition to RA)
o C3/C4  in cryoglobulinemia, SLE, and 25% of PAN; normal complement levels in all other vasculitides (rarely low in HSP)
• ANCA-associated?  send ANCA for IIF; will reflex to MPO (p-ANCA) and PR3 (c-ANCA) antibody ELISA if positive

STEP 2 – RULE OUT MIMICS: based on suspicion/atypical presentation

• Ddx: infections (SBE, HIV, HBV, HCV, EBV, Neisseria, Syphilis), malignancies (leukemia, lymphoma, myeloma, MDS, solid tumors),
IgG4-Related Disease (IgG4-RD; NEJM 2012;366:539), cocaine / levamisole, other drug-induced vasculitides, hypercoagulable states
(APLAS, TTP)
o If skin necrosis of lower extremities  consider cholesterol emboli or calciphylaxis
o If renal artery, internal carotid artery, vertebral artery involvement  consider fibromuscular dysplasia
• Tests: BCx, HBV, HCV, HIV, SPEP/UPEP/SFL/UFL, tox screen, consider IgG4

STEP 3 – CONFIRM DIAGNOSIS

Tissue biopsy: may be required to secure diagnosis
• Skin, sural nerve and muscle (PAN, EGPA, first prove abnormal NCS), temporal artery (GCA), kidney (GPA, MPA), lung (GPA, MPA)
• Less common: testicle (PAN), rectum/gut, liver, heart, brain (1° CNS vasculitis), sinus (GPA)
Conventional angiography: particularly if tissue biopsy is unfeasible
• Celiac/superior mesenteric, renal (PAN), chest (Takayasu, GCA), extremities (Buerger disease), brain (1° CNS vasculitis)

GENERAL TREATMENT APPROACH

• Remove inciting agents (meds, drugs), treat primary conditions (infections)
• Induction: often steroids + cyclophosphamide (CYC) or biologic, i.e. rituximab (RTX) for ANCA-associated (RAVE), nephrology at MGH
tends to use steroids + CYC + RTX (RITUXVAS)
• Maintenance: less well defined, typically azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), RTX
• Monitoring: disease activity and drug toxicity
• Prevention of treatment complications: PPD, HBV serologies, Pneumovax (and other vaccines), glucocorticoid prophylaxis (consider
PPI, TMP-SMX, calcium/vit D)

Helen D’Couto
164
TOC

Rheumatology Vasculitis
L A R G E – V E S S E L V A S C U L I T I S (NEJM 2003;349:160)
GIANT CELL ARTERITIS: inflammation of the aorta & its extracranial branches (i.e. spares ICA), often involves temporal artery (TA), most
common primary systemic vasculitis. Age >50, 2:1 M:F. Rare <50 yo = consider alternative diagnoses, mimics.
• Sx: constitutional (low grade fevers, fatigue, wt loss, anorexia), new/different HA, abrupt visual disturbance (amaurosis fugax, blindness,
diplopia), jaw claudication (most specific sign; fatigue with chewing, NOT PAIN)
• Exam: asymmetric BP/pulse; tender, thickened or pulseless TA; jaw claudication (r/o TMJD)
• Dx: a combination of 2-3+ symptoms and exam findings should prompt doppler U/S and rheum consult. Gold standard = temporal
artery biopsy. ESR (ESR usually high but <50 in 10%), CRP (correlates with disease activity) IL-6
o TA biopsy: start w/ unilateral; if ⊝, consider bilateral ( yield by 5%); up to 30-45% of bx may be false neg due to “skip areas”
o If concern for large-vessel GCA (e.g. aorta, subclavian): pursue imaging (CTA vs. MRA)
• Rx: start prednisone 1mg/kg/d immediately (up to 60mg) if high suspicion; NEVER delay Rx for Bx
o Steroid sparing regimens include tocilizumab, MTX
POLYMYALGIA RHEUMATICA: seen in 50% of GCA pts; 10% develop GCA, peak age 70-80
• Sx: symmetrical AM stiffness/pain (+/- weakness) in neck, shoulders/prox arms, hips/prox thighs
• Rx: prednisone 12.5-20 mg/day with slow taper, consider addition of MTX if refractory (Ann Rheum Dis 2015;74:1799)
TAKAYASU ARTERITIS: “pulseless disease,” inflammation of thoracoabdominal aorta & branches. Age <40, 8:1 M:F, Asians
• Sx: inflammation (fever, arthralgias/myalgias, weight loss, night sweats), vessel inflammation (carotidynia, limb claudication), vascular dz
(TIA/stroke, HF, CAD, mesenteric ischemia)
• Exam: unequal pulses and BPs (lower > upper extremities),  pulses, bruits, formal eye exam
• Dx: MRA or CTA; arteriography will show occlusion, stenosis, aneurysms; consider carotid ultrasound/Doppler studies
• Rx: prednisone 1mg/kg/d; 50% of patients will need 2nd agent for chronic sx (MTX, tocilizumab, TNFi)

MEDIUM–VESSEL VASCULITIS
POLYARTERITIS NODOSA: kidneys, skin, muscles, nerves, GI, joints (almost always spares lung). Age 40-60, associated with HBV
• Sx: mononeuritis multiplex (in up to 70% of pts), GI distress (mesenteric ischemia), myalgias, AKI (GN suggests alternate etiology),
testicular/ovarian pain (>10%), seizures
• Exam: HTN, skin lesions (erythematous nodules, purpura, livedo reticularis, ulcers, bullous eruption, palpable purpura), neuropathy
• Dx: gold standard = biopsy; HBV/HCV serologies, C3/C4, CTA/MRA showing focal stenosis or microaneurysm (renal/mesenteric vessels)
• Rx: prednisone 1mg/kg/d ± CYC 2 mg/kg/d PO or IV pulse (if mod-severe or steroid-refractory); antivirals if HBV-related
THROMBOANGIITIS OBLITERANS (BUERGER’S DISEASE): segmental inflammation of small-med arteries and veins of extremities; occlusive
intravascular thrombi. Age ≤ 45, 70-90% ♂, strongly associated with tobacco use, Raynaud’s in 40% of pts
• Dx: clinical - 1) age 2) tobacco use 3) distal ischemia 4) arteriographic findings 5) exclusion of autoimmune, thrombophilia, DM, embolism
• Rx: smoking cessation! Iloprost (PG analog) for pain, CCB (for Raynaud’s), intermittent pneumatic compression (painful ulcers)

ANCA–ASSOCIATED SMALL–VESSEL VASCULITIS

c-ANCA = cytoplasmic staining (proteinase 3 [PR3]), p-ANCA = perinuclear staining (myeloperoxidase [MPO])
GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S GRANULOMATOSIS): necrotizing vasculitis with granulomatous features by sx
(sinusitis, mass lesions [orbital pseudotumor, subglottic stenosis, large pulm nodules]) or on path, usually involving upper and lower airways (90%)
and kidney (80%), +/- cutaneous leukocytoclastic vasculitis
• Dx: sinus CT (+/- bone erosions), Bx w/ granulomatous inflammation of vessel walls, ⊕PR3-ANCA 90%
• Rx: limited disease: MTX + prednisone; severe disease: IV pulse steroids x3 days (with oral taper) + RTX or CYC
MICROSCOPIC POLYANGIITIS (MPA): necrotizing vasculitis of small vessels without granulomas. All ages (mean 50-60), M>F,  in
Caucasians; most common cause of pulmonary-renal syndrome (NEJM 2012;367:214)
• Dx: ⊕p-ANCA 70%, ⊕c-ANCA rare, BAL, gold standard = skin/renal biopsy; r/o HIV, cryo, hep B/C
• Rx: similar to GPA  methylprednisolone and cyclophosphamide or RTX (NEJM 2010;363:221)
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (CHURG-STRAUSS SYNDROME): necrotizing granulomatous inflammation of
vessels in lungs, skin, nerves; strongly associated with asthma/allergic rhinitis (asthma precedes vasculitis)
• Dx: ≥4 of following: asthma, >10% peripheral eos, neuropathy, pulm opacities, paranasal sinus disease, consistent bx. 50% ⊕ p-ANCA
• Rx: IV pulse steroids x3 days (with oral taper) ± CYC or RTX (if severe disease) or mepolizumab (if not severe)
• Do not delay rx if mononeuritis as can lead to nerve infarction
IMMUNE COMPLEX–ASSOCIATED SMALL–VESSEL VASCULITIS
HENOCH-SCHÖNLEIN PURPURA: 70% in children; ♂>♀; preceding URI, in adults, more severe presentation, med related, a/w malignancy
• Sx: classic tetrad of 1) palpable purpura (100%, on LEs/buttocks = dependent areas), 2) colicky abdominal pain (60%), 3) arthritis (75%), 4)
renal involvement (40-50%, proteinuria, microscopic hematuria, RPGN)
• Rx: children: supportive, usually self-limited; adults may require immunosuppression: steroids, dapsone. NSAIDs if mild GI/ arthralgias
CRYOGLOBULINEMIA: immunoglobulins that precipitate at low temperatures and re-dissolve on rewarming
• Type 1: monoclonal (usually IgM or IgG), associated with Waldenstrom’s, MM
o Sx: peripheral neuropathy, renal impairment, hyperviscosity (Raynaud’s, digital ischemia, livedo)
• Type 2: “mixed” monoclonal IgM against polyclonal IgG (often IgM with RF activity), associated with HCV, HIV, HBV, EBV
• Type 3: “mixed” polyclonal Ig (IgM or IgG) against polyclonal Ig (IgM or IgG), associated with CTDs, lymphoproliferative disorders, HCV
o Sx: palpable purpura, arthralgias, myalgias, mononeuritis multiplex
• Rx: treat underlying cause (e.g. HCV); prednisone ± 2nd immunosuppressive agent (RTX, CYC); consider plasma exchange for Type 1

Helen D’Couto
165
TOC

Rheumatology Miscellaneous Rheumatologic Diseases

Behcet’s Disease: autoinflammatory condition characterized by recurrent aphthae, vasculitis, and skin/GI/neuro/joint sx
• Epi: F>M, age 20-40, Turkey, Middle East, and Asian countries
• Sx: recurrent painful oral ulcers and ≥2 of the following: painful genital ulcers (specific), ocular disease (most commonly
uveitis or retinitis), skin lesions (pustules, folliculitis, papules, erythema nodosum),
o Other manifestations: GI (similar to IBD), neurologic disease (parenchymal, extra-parenchymal), vascular disease
(ATE/VTE, vasculitis, aneurysms [PA]), arthritis (nonerosive, asymmetric). Less common: kidney, heart, lung
disease
• Dx: clinical dx only, no specific laboratory tests exist; may have  ESR/CRP
• Rx: (Ann Rheum Dis. 2018; 77:808)
o Mild (arthritis, ulcers): colchicine 1-2 mg daily, low dose prednisone. Apremilast (PDE-4 inhibitor) for ulcers (NEJM
2019;381:1918)
o Severe: prednisone 1mg/kg/d, may add 2nd line agents: AZA, anti-TNF, IFNα, CYC, CP, MTX
o If organ failure (esp. ophthalmic involvement): IV pulse steroids x 3d

Familial Mediterranean Fever (FMF): autoinflammatory disorder due to mutations in MEFV gene, autosomal recessive
inheritance, characterized by recurrent bouts of fever and serosal inflammation
• Epi: most common in Jews, Armenians, Turks, and Arabs. Onset <10 yo (65% pts), <20 yo (90% pts)
• Sx: recurrent acute attacks (1-3d, resolves spontaneously) of fever associated w/ peritonitis (often mistaken for surgical
abdomen), unilateral pleuritis, arthritis (monoarticular, sterile joint), or skin lesions (erysipelas-like).
o Other manifestations include: exertional myalgia, pericarditis, testicular pain, and aseptic meningitis.
o Long-term complications: secondary (AA) amyloidosis: renal disease (major cause of mortality), SBO, infertility
• Dx: During acute attack:  WBC,  ESR/CRP. Check UA for amyloidosis (proteinuria). Genetic testing for confirmation.
o Diagnostic criteria: requires 1 major or 2 minor criteria (Arthritis Rheum 1997; 40:1879)
• Rx: colchicine 1-3 mg/day (to prevent acute attacks and progression to amyloidosis). 5-10% colchicine resistant, add on
IL-1 inhibitors (Ann Rheum Dis. 2016;4:644)

Adult Onset Still’s Disease (AOSD): systemic inflammatory disorder characterized by fevers, arthritis, and rash. Can present
as single episode (wks-mos), multiple flares, or be persistently active.
• Epi: F=M, bimodal (15-25 yrs old and 36-46 yrs old)
• Sx: fever; arthralgias; evanescent, salmon-colored maculopapular rash that coincides w/ fever, usually on the trunk,
may be precipitated by trauma (Koebner phenomenon); pericarditis; pleural effusions; macrophage activation
syndrome (rheum-associated HLH; see Hematology)
• Dx: Yamaguchi criteria requires ≥5 features, including ≥2 major criteria (J Rheumatol 1992;19:424)
o Major: fever ≥39ºC for ≥1 week, arthralgias/arthritis ≥2 weeks, salmon-colored rash,  WBC (≥10K + ≥80% PMN)
o Minor: sore throat, LAD, HSM, AST/ALT,  LDH, negative ANA/RF
o Other labs (not part of criteria):  ESR/CRP, ferritin >3000 ng/mL (if >10,000, consider MAS spectrum),  plt,  Hgb
• Rx:
o Mild: NSAIDs
o Severe: prednisone 0.5-1mg/kg/d (may not respond). If uncontrolled: MTX, anti-TNF, anti-IL6R, anti-IL1

Fibromyalgia: NOT a rheumatic disease. Chronic widespread musculoskeletal pain, often w/ fatigue, sleep disturbance, and
multiple somatic symptoms.
• Epi: F>M, 20-55 yo. Can coexist with other inflammatory diseases like SLE, RA. Often psychiatric comorbidities.
• Sx: widespread MSK pain, fatigue, cognitive disturbance (decreased attention & ability to perform complex tasks),
psychiatric sx (depression), headache, parasthesias, IBS. Pan-positive ROS not uncommon.
• Dx: clinical diagnosis, > 3 months duration of sxs, multiple tender points. Newer criteria involve widespread pain index
(WPI) and symptom severity (SS) scale (J Pain 2019;6:611)
o Labs: normal ESR, CRP, TSH, CBC, BMP
• Rx:
o Initial therapy: patient education, exercise program
o Pharmacologic therapy: 1st line includes amitriptyline, duloxetine, or milnacipran; also may consider
cyclobenzaprine, gabapentin, and pregabalin (monotherapy > combo therapy). Avoid narcotics.

Leslie Chang
166
TOC

Rheumatology Autoantibodies
Antibody Antigen ANA pattern Disease Comments
Inflammatory polyarthritis
RA (50-75%), - Nonspecific despite name: RA, CTD, cryoglobulinemia, chronic infxn (e.g.
Sjogren’s (30%), HCV, SBE).
RF (IgM) Fc gamma negative Cryoglobulinemia - Positive in 10% of healthy patients
(90%), chronic - RA: “seropositive”, a/w erosive and extraarticular manifestations (nodules,
infection scleritis, ILD, pleuritis, rare rheumatoid vasculitis)
- Most specific test for RA, positive in 50-75% (“seropositive RA”), a/w
Citrullinated
CCP negative RA (50-75%) erosive dz & extraarticular manifestations
proteins
- Used for dx only, NOT marker of dz activity
Connective tissue diseases (SLE, Sjogren’s, SSc, MCTD, UCTD, DM/PM)
- ANA = antinuclear antibodies (specific ANA Abs listed below). Low titer ≤1:160 are often false positive. If ⊕, order specific
autoantibodies guided by clinical presentation
ANA - ⊕ ANA: MCTD (100%), SLE (98%), scleroderma (90%), drug-induced lupus (90%), Sjogren’s (60%), PM/DM (50%)
- Ddx for ⊕ ANA: Autoimmune: autoimmune hepatitis, PBC, IBD, myasthenia gravis, Graves’, Hashimoto’s; ID: malaria, SBE,
syphilis, HIV, HSV, EBV, HCV, parvo-B19; Systemic inflammation: lymphoproliferative disorders, IPF, asbestosis
- Specific for SLE, a/w SLE activity and lupus nephritis, consider TNF
dsDNA ds/mtDNA homogeneous SLE (40-60%)
inhibitor drug-induced lupus
SLE, drug-induced - Sensitive, but not specific for drug-induced lupus (DIL)
Histone histones homogeneous lupus (90%), - Common meds: procainamide, hydralazine, phenytoin, lithium
Felty’s
U1-snRNP MCTD (100%), - MCTD: high-titer anti-U1 RNP
RNP speckled
SLE (30%)
Smith snRNP speckled SLE (30%) - Specific for SLE, not indicative of dz activity
- Can be seen with myositis
Sjogren’s (75%),
SS-A/Ro Ro52, Ro60 speckled - In SLE, a/w skin disease and congenital heart block
SLE (40%),
- 2% SLE pts have ⊝ ANA but ⊕ anti-Ro Abs
Sjogren’s (40%), - In SLE a/w congenital heart block
SS-B/La La speckled
SLE (10-15%)
- A/w limited systemic sclerosis,  risk of PAH,  risk of ILD, esophageal
ACA CENP A-F centromere lcSSc (15-40%)
disease
Scl-70 topo-I speckled dcSSc (10-40%) - A/w diffuse systemic sclerosis;  risk of ILD, scleroderma renal crisis
RNA pol III RNA pol. III nucleolar dcSSc (4-25%) - A/w scleroderma renal crisis, rapidly progressive skin disease, cancer
Fibrillarin U3-RNP nucleolar dcSSc (<5%) - A/w PAH, pulmonary fibrosis, and myositis, esp. in African-Americans
- A/w limited systemic sclerosis,  risk of pulmonary and renal dz,  risk
PM-Scl exosome nucleolar SSc (5-10%)
inflammatory myositis
Myositis
PM/DM (30%), - Antisynthetase syndrome: myositis (DM/PM), ILD (70%), polyarthritis,
Jo-1* tRNA (His) cytoplasmic anti-synthetase mechanic’s hands, Raynaud’s, fever
syndrome (~20%)
homogenous/ - More likely in acute DM, good prognosis
Mi-2* Mi-2 DM (15-20%)
speckled
MDA-5* MDA-5 negative DM - Clinically amyopathic dermatomyositis, rapidly-progressive ILD
TIF1g* TIF1g fine speckled Juvenile DM - A/w malignancy in adult DM
signal recog. - Immune-mediated necrotizing myopathy (degenerating, regenerating, and
SRP* cytoplasmic PM
particle necrotic cells on bx), rapidly progressive disease course
- Immune-mediated necrotizing myopathy, 70% with statin exposure (at any
HMG CoA
HMGCR negative myositis time in past), ≠ statin myopathy (does not respond to discontinuation of
reductase
statin), very high CPK, often steroid-refractory, good response to IVIG
Vasculitis
PR3 - Poor correlation of titer with disease flare/remission
proteinase 3 negative GPA (90%)
(c-ANCA) - Antibody frequency lower in GPA without renal involvement
MPA (70%), - Poor correlation of titer with disease flare/remission
MPO myelo- EGPA (50%), - Drug-induced vasculitis (DIV): high-titer positive for MPO (hydral, PTU,
negative
(p-ANCA) peroxidase Renal-Limited, minocycline)
DIV (95%) - Levamisole vasculitis 2/2 cocaine use: MPO or PR3/MPO
Cryo- Cryoglobulinemic - HCV > HBV, HIV, CTDs, lymphoproliferative disease
Fc gamma negative
globulins vasculitis - A/w low C4, glomerulonephritis, +RF
* ordered as part of myositis panel

Jacquelyn Nestor
167
TOC

Rheumatology Rheumatologic Medications

DRUG/CLASS INDICATIONS COMMON TOXICITIES
GI, bruising, myelosuppression, lymphoproliferative
Azathioprine (AZA; Imuran, Azasan) d/o, hepatotoxicity. Test for TPMT deficiency as low
DM/PM, RA, SLE levels can  toxicity. (TPMT metabolizes 6-MP to
6-MP is downstream metabolite of nephritis, vasculitis inactive metabolites  deficiency increases circulating
AZA 6-MP levels). Do not give with xanthine oxidase
inhibitors (allopurinol, febuxostat)
Myelosuppression, hemorrhagic cystitis (MESNA for
SLE (LN), vasculitis
Cyclophosphamide (CYC; Cytoxan) ppx), lymphoma, infertility (cumulative dose,
(most severe)
leuprolide ppx), <1% pneumonitis, teratogen
N/V, retinopathy (q1y retinal exam), dizziness,
Hydroxychloroquine (HCQ; Plaquenil) RA, SLE, Sjogren’s
alopecia, myelosuppression
N/V, alopecia, rash, diarrhea, HTN, hepatotoxicity,
Leflunomide (LFM; Arava) PsA, RA
URI, dizziness/HA, teratogen
Methotrexate (MTX; Rheumatrex, Myelosuppression, hepatotoxicity (co-administer
RA (first line), PsA
Trexall, Otrexup, Rasuvo, Xatmep) folate), pneumonitis, stomatitis, rash, teratogen
Mycophenolate Mofetil (MMF; AAV, DM/PM, PsA, Cardiac (HTN, edema, CP, tachycardia), HA, insomnia,
CellCept, MyFortic) Scleroderma, SLE diarrhea, rash, pain, fever, stomatitis, teratogen
AS, IBD, JRA, psoriasis, Sore throat, stomatitis, myelosuppression, N/V, rash,
Sulfasalazine (5-ASA; Azulfidine)
RA HA; check G6PD
Apremilast (Otezla); PDE4 inhibitor PsA, severe psoriasis N/D, URI, depression, weight loss
Infection, hepatotoxicity, lymphoma, diarrhea, clotting
Tofacitinib (Xeljanz); JAK inhibitor RA, AS, psoriasis
risk
BIOLOGIC, non-TNF*
Abatacept (Orencia); CTLA4 PsA, RA Infection, HA, nausea, HTN, dizziness, dyspesia
AOSD/MAS, gout, Myelosuppression (neutropenia), rash/injection
Anakinra (Kineret); anti-IL-1R
Schnitzler syndrome reactions, HA, arthralgia, fever
Belimumab (Benlysta); anti-BAFF SLE Depression, HA, infusion reaction, PML, GI
Canakinumab (Ilaris); anti-IL-1b CAPS, CAD (CANTOS) Infection, HA, vertigo, GI, MSK pain, nasopharyngitis
APLAS, GPA/MPA, Infection, HTN, infusion reaction (use premeds),
Rituximab (Rituxan); anti-CD20
IgG4-RD, Scl-ILD, (SLE) TLS, PML, fever, rash/pruritus, LE edema, HACA
Tocilizumab (Actemra); anti-IL-6R GCA, RA Infection, hepatotoxicity, HLD, GI perforation
Secukinumab (Cosentyx); anti-IL17A AS, PsA, psoriasis Infection, IBD flare
Ustekinumab (Stelara); anti-IL-12/23 PsA, psoriasis Infection, RPLS, seizures
APLAS, DM/PM, IBM, Transfusion reactions/anaphylaxis, aseptic
IVIG
IMNM, Kawasaki’s meningitis, thromboembolism, HA
BIOLOGIC, TNF inhibition* (all can cause myocardial toxicity)
AS, IBD, PsA, psoriasis,
Adalimumab (Humira); anti-TNF
RA
AS, IBD, PsA, psoriasis,
Infliximab (Remicade); anti-TNF HA, nausea, rash, infection, drug-induced lupus
RA
Golimumab (Simponi); anti-TNF AS, IBD, PsA, RA
Certolizumab (Cimzia); anti-TNF AS (axial), IBD, RA
Etanercept (Enbrel); sol. TNF-R AS, PsA, psoriasis, RA
*Can cause HBV /TB reactivation (check hepatitis serologies, PPD and/or IGRA prior to starting). If positive, start
antiviral prophylaxis with entecavir (HBV reactivation) and prophylaxis with INH (latent tuberculosis) as per ID/rheum. TNF-
alpha inhibitors are safe in HCV infection may be beneficial (Expert Opin Biol Ther 2012;12:193)

AAV (ANCA-associated vasculitis), AOSD (Adult-onset Still's disease), APLAS (anti-phospholipid antibody syndrome), AS (ankylosing
spondylitis), DM (dermatomyositis), EGPA (eosinophilic granulomatosis with polyangiitis), GCA (giant cell arteritis), GPA (ranulomatosis
with polyangiitis), IBD (inflammatory bowel disease), IMNM (immune-mediated necrotizing myopathy), JRA (juvenile rheumatoid
arthritis), MAS (macrophage activation syndrome), MPA (microscopic polyangiitis), PM (polymyositis), PsA (psoriatic arthritis), RA
(rheumatoid arthritis), SLE (systemic lupus erythematosus), UC (ulcerative colitis)

Jacquelyn Nestor
168
TOC

Endocrinology Outpatient Type 2 Diabetes

Screening: begin at age ≥45 years OR after gestational DM (GDM) OR if BMI ≥25 (≥23 in Asian-Americans) + RF (1st degree relative with
DM, nonwhite, history of CVD, HTN, HDL<35, triglycerides >250, PCOS, sedentary); screen q3y if normal (ADA Guidelines 2019)

Pre-Diabetes (Diab Care 2019:42:S13)

• Diagnosis: A1c 5.7-6.4%; fasting plasma glucose (FPG) 100-125; or 75g OGTT w/ 2hr glucose 140-199
• Monitoring: A1c at least q1y; if A1c 6-6.4%, screen q6mo (25-50% 5-year risk of progression to diabetes if A1c 6-6.5%)
• Treatment: lifestyle interventions most effective; metformin also effective, esp. if BMI ≥35, age <45, or GDM hx (Cochrane Rev 2019)

Diabetes (Diab Care 2019:42:S13)

• Diagnosis: A1c ≥6.5%; FPG ≥126; 75g OGTT with 2hr glucose ≥200; or random BG ≥200 & symptoms. Unless diagnosis is made by
symptoms & random glucose >200, confirm with repeat or additional test. For T1DM, check TSH, celiac screen at diagnosis. Use
FPG if high RBC turnover: sickle cell disease, 2nd/3rd trimester of pregnancy, G6PD, HD, recent blood loss/transfusion, EPO tx.
A1c less reliable post-partum, with certain HIV drugs, and Fe-deficient anemia.
• Treatment: goal A1c <7%; liberalize to <8-8.5% if life expectancy ≤10 years or high risk for hypoglycemia.

Healthcare Maintenance for Diabetic Patients

• Review blood sugar log: goal AM FPG 80-130, postprandial (1-2h) <180; screen for hypoglycemia awareness
• Blood pressure: goal <140/90; ACEi/ARB first line
Every visit • Weight, BMI: weight center referral if BMI ≥40 or ≥35 with poor control; nutrition referral for all patients
• Foot exam (inspect skin, joints, pulses, sensation) esp. if known neuropathy or PVD; ABIs/vascular referral if PVD
• Smoking cessation counseling (Advise, Assist, Arrange)
Q3-6mo • A1c q6 months if controlled; q3-6 months if A1c above target
• Lipids: moderate-intensity statin if age 40-75; high-intensity if CVD, mult. risk factors, LDL ≥190, or 10yr ASCVD
>20%
• Urine mAlb/Cr, BMP; ACEi/ARB if hypertensive w/ proteinuria or GFR <60; refer to renal if GFR <30
Annually
• Neuropathy exam: 10g monofilament (+ if no sensation at 4/10 sites, see PCOI); pinprick, vibration, or reflexes
• Retinopathy screen w/ dilated eye exam or retinal photography; can consider q2-3yr if normal exam(s)
• LFTs: consider elastography and/or hepatology referral if elevated to evaluate for NASH
• Influenza annually
Vaccines • Hepatitis B series if age <60 and not immune
• PPSV23 x1 age <65; re-dose x1 ≥65 with at least 5 years between doses; PCV13 x1 age ≥65

Basal Insulin Management

Criteria • Consider if A1c ≥ 9%, random BG ≥ 300, fasting BG ≥ 250, or symptomatic; suspicion for T1DM; < 65yo on two
for agents with A1c >8% (or ≥ 65yo and A1c > 8.5%) on two occasions >3 months apart; or A1c rising quickly
initiation • Able to perform self-monitoring with glucometer; consider referral to DM educator
• Starting dose: 0.1-0.2U/kg/day or 10U/day (if weight >80kg, may consider starting at 20U/day)
Initial
• Choice of agent: choose long-acting (glargine, detemir QD) or intermediate-acting (NPH BID  cheaper!)
dose
• Route: pen (easier to use, more expensive) vs. needle/syringe
• Increase by 2-4U or 10-15% q3 days until AM fasting BS is 80-130; savvy patients can self-titrate
Titration
• If hypoglycemia occurs or FPG < 80 without clear reason, decrease dose by 10-20% or 4U, whichever is greater

Prandial Insulin Management

Criteria • Consider if A1c still not at goal with basal insulin >0.7-1.0U/kg/day and fasting glucose within target range (80-130)
• Strategy 1: add 1 rapid-acting insulin before largest meal  start w/ 4U or 0.1U/kg or 10% basal dose
Initial
• Strategy 2: change to mixed insulin (e.g. fixed 70/30, NPH + regular) BID (before breakfast and dinner). Divide
dose
current basal dose into 2/3 AM, 1/3 PM or 1/2 AM, 1/2 PM. Counsel to avoid missing meals to avoid hypoglycemia.
• Increase dose by 1-2U or 10-15% q3d until target glucose reached (pre-prandial: 80-130; 1-2h post-prandial <180)
Titration • If A1c still not controlled: add rapid-acting insulin to another meal and titrate as above
• If hypoglycemia occurs or FPG <80 without clear reason, decrease dose by 10-20% or 4U, whichever is greater

Insulin Supplies
• Needles: come as universal pen needles, or attached to syringes, made by many companies. 32G 4mm is less painful (higher gauge
= thinner and shorter needle), but obese patients and high insulin doses often require deeper/wider needle.
• Syringes: boxes of 100. Long-acting insulin only = 1 box/3 mo. Use this barrel size… With this dose range…
Basal/bolus insulin = 4 syringes/day (4 boxes/3 mo). Choose smallest 3/10 mL 30 units or less
syringe that will hold the dose (smaller barrel  clearer scale 1/2 mL 31-50 units
markings). 1 mL 51-100 units
• Alcohol swabs (or patients can wash hands/skin with soap and water)
• Glucometer & test strips: Many choices (insurance dependent), each with own strip brand. Most test strips come in boxes of 50-100.
• ** All durable medical equipment including test strips and glucometers requires an ICD-10 code on the script itself **

Radhika Jain
169
TOC

Endocrinology Outpatient Type 2 Diabetes

Non-Insulin Agents
%
Drug/Dose Range Contraindications Indications/Benefits Side Effects/Considerations Cost
A1c
Metformin: 1st line anti-diabetic medication; many effects, primary mechanism is decreasing hepatic glucose production
GFR cutoffs: - First line therapy - Nausea, bloating, diarrhea $5
Metformin
- <45ml/min don’t initiate - Weight loss - B12 deficiency (IR)
(Glucophage)
1-2 - <30ml/min discontinue - Improvement in lipids - Lactic acidosis in severe $10
500-1000mg BID
- Metabolic acidosis liver/renal disease or (ER)
hypoperfusion state
Metformin pearls: to increase adherence, warn patients about GI side effects but remind that side effects usually go away with time.
Can be minimized by uptitrating SLOWLY (250-500mg/week), taking WITH food, or switching to ER formulation. Benefits and side-
effects are dose-dependent – maintain highest dose tolerated. Can also take a break (e.g. with antibiotics) and re-introduce later.
SGLT-2 Inhibitors: block renal glucose reabsorption, increase glucosuria
Canagliflozin GFR cutoffs: -  CV events, ASCVD - FDA Black Box Warning:
(Invokana) - <45ml/min new data mortality, CHF risk of amputation
100-300mg QD suggests ok to initiate hospitalization, and (canagliflozin); avoid in PAD
Empagliflozin - <30ml/min discontinue CKD progression (NEJM - UTI & GU fungal infections $475
0.8-
(Jardiance) 2019;380:2295) - Small risk of euglycemic DKA -
0.9
10-25mg QD - Weight loss - Risk of dehydration/HoTN $500
Dapagliflozin -  risk of hypoglycemia - Risk of fracture (canagliflozin)
(Farxiga) -  BP 3-5 mmHg - May  LDL cholesterol
5-10mg QD
SGLT2i pearls: counsel patients on diuretic effect and to replace water losses to avoid euglycemic DKA. Uptitrate to effective dose after
1 month at low dose. For potency, empagliflozin > canagliflozin > dapagliflozin. Benefit is probably not a function of A1c lowering.
GLP-1 Receptor Agonists: stimulate glucose-dependent insulin release from beta cells
Liraglutide (Victoza) - FDA Black Box - ASCVD - GI: n/v, diarrhea
0.6-1.8mg QD Warning:  risk thyroid - Weight loss - Injection site reactions
$600
Dulaglutide (Trulicity) 0.5- C-cell tumors. Avoid if - Alternative to basal - Delayed gastric emptying
-
0.75-1.5mg Qwk 1.1 hx thyroid ca/MEN2 insulin -  risk of pancreatitis
$800
Semaglutide (Ozempic) - GFR 30-45: avoid -  risk of hypoglycemia
0.25-1mg Qwk exenatide
GLP-1 RA pearls: for weight loss, semaglutide > dulaglutide > liraglutide > others. Uptitrate to effective dose in 1 month intervals.
DPP-4 Inhibitors: inhibit degradation of DPP4, increasing glucose-dependent insulin secretion and decreasing glucagon secretion
Sitagliptin (Januvia) - No contraindications, - Safe in CKD/ESRD - Saxagliptin, alogliptin 
$400
25mg-100mg QD 0.5- but very weak (dose-reduce sitagliptin) hospitalizations for CHF
-
Linagliptin (Tradjenta) 0.8 -  risk of hypoglycemia - Joint pain
$500
5mg QD - Weight neutral
Insulin Secretagogues: stimulate release of insulin from pancreatic beta cells, thus only effective in pts who still have beta cell function
Sulfonylureas: - T1DM, DKA - Affordable - Weight gain
Glipizide 2.5-20mg QD 1-2 - low cross-reactivity in - Hypoglycemia (esp glyburide) $5 -
pts with sulfa allergy - Possible  CV mortality $10
Glimepiride 1-8mg QD
- Severe liver disease - Use like bolus insulin - Weight gain
Meglinitides: - Concurrent gemfibrozil (short-acting) - Hypoglycemia
0.5- $15 -
Repaglinide (Prandin) therapy - CKD -  serum conc. w/ clopidogrel
0.7 $20
0.5-4mg QAC -  nocturnal - TID dosing
hypoglycemia
Thiazolidinediones: increase insulin sensitivity by acting on adipose, muscle, and liver to  glucose uptake,  ectopic lipid deposition
- Avoid if hx bladder -  risk of hypoglycemia - FDA Black Box Warning:
Pioglitizone (Actos) 1- cancer - Possible benefit in risk of CHF
$10
15-30mg QD 1.6 - NYHA Class III/IV HF NASH - Weight gain
-  risk of fracture
* Monthly costs in Boston area pharmacies (GoodRx)

Algorithm for Oral Anti-Diabetic Therapy (Diab Care 2020;43:487)

1. A1c ≥6.5: lifestyle changes +/- metformin. Counsel for whole foods, carbohydrate restriction, and time-restricted eating.
2. Regardless of A1c:
a. If ASCVD or high risk: add GLP-1RA and/or SGLT2i ( CV events)
b. If HF (esp. HFrEF) or CKD (eGFR >30 or mAlb/Cr >30): add SGLT2i ( CKD progression,  CV events,  HF hospitalizations,
CV death), avoid TZD
3. If A1c targets not met with above therapy:
a. If weight loss/neutrality desired: add GLP1RA and/or SGLT2i > DPP4i, avoid sulfonylurea, TZD
b. If cost is a major concern: add sulfonylurea or TZD

Radhika Jain
170
TOC

Endocrinology Inpatient Diabetes Management

INSULIN NOMENCLATURE
Type Basal insulin: fixed intermediate / long-acting for basic metabolic
Formulation Peak Duration
(Onset) requirements
lispro (Humalog) Prandial insulin: fixed rapid / short-acting to cover meals
Rapid 0.5-2.5
(10 min)
aspart (Novolog)
hr
< 5 hr Correctional insulin: sliding scale rapid / short-acting to correct
glulisine (Apidra) hyperglycemia (not intended to cover meals)
Short regular Pre-Mix (avoid in hospital, but consider for transition to outpatient
2.5-5 hr 4-12 hr
(30 min) (Humulin R, Novolin R) regimen): combine basal and prandial insulin into one injection
Intermediate NPH
4-12 hr 12-18 hr Insulin gtt: use in ICU if BG>180 x 2 and anticipated ICU LOS >3
(1-2 hr) (Humulin N, Novolin N)
days; reference MICU Insulin Protocol in Partners Handbook.
glargine (Lantus) QD,
Long Ensure an active source of dextrose (e.g. D10W @ 30 cc/hr).
detemir (Levemir) BID, none 24 hr
(3-4 hr) Always overlap with SC insulin by 2-3h before stopping insulin gtt.
degludec (Tresiba) QD

I N P A T I E N T M A N A G E M E N T (Diabetes Care 2019;42:S173) 3

• Glycemic targets: Floor: fasting 100-140 mg/dL, random <180 mg/dL. ICU: 140-180 mg/dL (NOT stricter) (NEJM 2009;360:1283)
• Check FSBG AC & QHS (at least for 24-48h) in (1) known diabetics, (2) non-diabetics with BG >140 mg/dL, (3) those receiving
therapies a/w hyperglycemia (corticosteroids, octreotide). Check FSBG q6h if on continuous TF or TPN.
Note: FSBGs inaccurate in hypotension (esp. on pressors) and hypothermia due to altered blood flow to skin. Confirm w/ serum glucose.
Admission Orders (NEJM 2006;355:1903)
1. Hold home oral antihyperglycemic agents (NEVER hold basal insulin for T1DM). Write for consistent carbohydrate diet.
2. Check A1c in all patients with hyperglycemia if not done in last 3 months
3. Continue home insulin regimen with dose reduction (~25-50% reduction) given expected change in diet while hospitalized.
Hypoglycemia is associated with increased mortality in elderly, so reasonable to be cautious.
4. If not on home insulin:
a. Well-controlled: reasonable to start with ISS and soon change to basal-bolus once TDD established
b. Not well-controlled: start with basal (0.2 U/kg) & ISS! Add prandial insulin in 1-2 days.
5. If NPO: 50% dose reduction or 0.1 U/kg/day for basal insulin. Be sure to change correctional ISS and FSBG from TID AC to q6h.
6. Correctional insulin sliding scale: use low-dose if insulin-sensitive/ESRD/ESLD/frail, otherwise moderate-dose for most T2DM
Adjusting Insulin Dosing: In general, increase by no more than 20% of total daily insulin requirement every day
Fasting or AM BG high (w/ other BGs in range)  basal insulin dose* *Avoid titrating basal

insulin more than q2-3d
Fasting BG high + HS BG high (w/ other BGs in range)   pre-dinner prandial insulin dose
(d/t long half life, requires
Pre-lunch or dinner BG high (w/ other BGs in range)   prandial insulin dose of preceding meal time to reach steady
BG rising steadily over course of day   prandial insulin dose at each meal state) to avoid “stacking”
and hypoglycemia
Special Situations:
1. Glucocorticoids: NPH 0.1 U/kg/d for every 10 mg pred, up to 0.4U/kg/d (dosed BID); if dexamethasone, use glargine QD instead
2. Tube feeds: if not on insulin already, start with regular ISS q6h. Convert to NPH BID based on needs. If on insulin, use ½ basal
(NPH BID) + ½ bolus (regular insulin q6h) + ISS. If TF stopped, give D5W at TF rate until next NPH dose, and  NPH dose by 50%
or more based on pre-TF insulin requirements. TPN: regular insulin can be added to TPN (discuss w/ nutrition), does not cover basal!
3. Insulin pumps: continuous SQ infusion of rapid-acting insulin. Set basal rate (e.g. ~0.01 U/kg/h; can adjust throughout day); carb
ratio (units insulin:gram carbs e.g. 1:10); sensitivity factor (units insulin:mg/dl above target - like sliding scale e.g. 1:50); insulin action
time (e.g. 4hrs). Complications: site infection, system failure interrupting infusion. Back-up insulin: give 3-4x hourly rate of rapid-acting
q3-4h, or give TDD as NPH BID or glargine QD
Disposition: if new home insulin  nutrition c/s + floor RN teaching and arrange outpatient f/u. Using discharge order set, send rx for
glucometer, test strips, lancets, syringes/vials or pens/needles to MGH outpatient pharmacy and bring up to floor for RN teaching.
INPATIENT HYPOGLYCEMIA
 Risk: T1DM, malnutrition, emesis,  body weight,  PO intake,  steroid dose, AKI ( insulin clearance), CKD (esp. dialysis)
Beware of hypoglycemia unawareness in T1DM and longstanding T2DM
Manifestations: <70: shakiness, anxiety, diaphoresis, visual ∆, HA, AMS. <55: seizure, coma.
Treatment: PO (15g gel, tabs, juice) > IV (12.5-25g D50) > IM/SQ (1mg glucagon); recheck in 15 min, chase with PO if due to insulin OD
If sulfonylurea OD: 50-75 mcg octreotide SQ. Review and adjust insulin regimen!
Ddx: If ill/medicated: drugs (insulin [secretagogues], EtOH), sepsis, ESLD, ESRD, HF, adrenal insufficiency, nonislet cell tumor
If well-appearing: insulinoma, post-gastric bypass (late dumping), insulin or insulin receptor antibodies, insulin (secretagogues)
Workup: must meet Whipple’s Triad to merit eval: sx c/w BG, reliable BG while sx present, sx relief once BG corrected
1. Mixed-meal with postprandial eval (q30min labs for 5h
Pro- C-
post-meal), or fasting eval with admission for 72-hr fast if Insulin
Insulin Peptide
Ddx
no episodes (labs if sx and FSBG <60)    Insulinoma, oral hypoglycemic, autoimmune
2. Check: serum glucose, insulin level, C-peptide, beta-    Exogenous insulin administration
hydroxybutyrate, proinsulin, sulfonylurea, meglitinide nl nl nl Nonislet cell tumor
screen

Radhika Jain
171
TOC

Endocrinology DKA/HHS
DIABETIC KETOACIDOSIS (DKA)
Pathophysiology: think about each element of Diabetic Keto-Acidosis
• Diabetes:  insulin &  opposing hormones (glucagon, catechols, cortisol)  hyperglycemia  osmotic diuresis hypovolemia
• Ketones:  insulin   lipolysis   free fatty acids   ketones (acetoacetate, β-hydroxybutyrate, acetone [fruity breath])
• Acidosis:  β-hydroxybutyrate and acetoacetate, and contraction alkalosis with total body HCO3 deficit (NEJM 2015;372:546)
Precipitants (the “I’s”): infection (30-40% of cases), initial presentation of DM (20-25% of cases), insulin non-adherence, inflammation
(pancreatitis – but  amylase / lipase in DKA even w/o this), ischemia/infarction (MI, CVA, gut), intoxication (EtOH, cocaine), iatrogenesis
(e.g. SGLT2 inhibitors, steroids, thiazides, dobutamine/terbutaline, atypical anti-psychotics), infant (pregnancy)
Presentation: dehydration, polyuria/polydipsia, n/v/abd pain, weakness, AMS, Kussmaul’s respirations, fruity breath (acetone)
Dx: BG 250-800, pH <7.3, AG >10, urine/serum ketones. Consider euglycemic DKA in pt on SGLT2i, EtOH liver dz, pregnancy.
• Check BMP, CBC w/ diff, UA, Sosm, serum β-hydroxybutyrate, ABG/VBG. Consider hs-trop, EKG, BCx/UCx, CXR, lipase/amylase.
• Na correction  use absolute sodium value when calculating anion gap. Use corrected value to assess for underlying hypotonic
hypoNa  add 1.6 mEq/L to Na for every 100 mg/dL of serum glucose >100 mg/dL (e.g. if glucose 300 mg/dL, add 3.2 mEq/L to Na)
• UA ketone does not test for β-hydroxybutyrate, which is the predominant ketone in DKA (must measure from serum)
Management: prioritize ABCs, volume status, identifying precipitant  THEN electrolytes (especially K+)  THEN glucose
Labs: BMP q2h until AG closes, then q4h until normal K+; VBG, β-hydroxybutyrate q2-4h; FSBG q1h while on insulin gtt
Step 1: volume resuscitation (typically 5-8L deficit)
o Bolus NS 15-20cc/kg/hr for initial resuscitation in first 1-4 hours (unless CHF, ESLD, ESRD, hypoxemia)
o Corrected Na  if low, start NS±K+ at 250-500cc/hr; if normal/high or hyperCl acidosis, start ½NS±K+ at 250-500cc/hr
o Add D5 to IVF once BG<200 (DKA) or <300 (HHS)
Step 2: potassium repletion and management
Potassium Action K+ may be normal/elevated at presentation, but total body K+
K<3.3 Give 20-40 mEq KCl IV per hour + hold insulin! actually low. Multifactorial causes: solute drag of K+ into
3.3≤K≤5.3 Add 20 mEq K to IVF extraceullar space, osmotic diuresis,  insulin not driving K+
into cells. Aggressive K+ repletion is critical: HYPOkalemia
K>5.3 Continue to monitor q2h will limit your ability to administer the necessary insulin
Step 3: insulin therapy (Diab Care 2009;32:1335)
o The #1 goal of insulin therapy in DKA is to stop ketogenesis and close the AG; glucose correction is secondary
o Don’t start insulin until you have control of K+
o Don’t stop the insulin gtt unless true hypoglycemia (<65 mg/dL) or hypokalemia (<3.3 mEq) occurs
o Initial: bolus 0.1 U/kg regular insulin, then start 0.1 U/kg/hr IV regular insulin gtt; OR no bolus and start 0.14 U/kg/hr IV gtt
 Goal is to  BG by 50-75 mg/dL each hour
 For mild DKA, subcutaneous insulin regimens may be used instead of IV (Cochrane Rev 2016)
o Titrating insulin drip: MICU insulin gtt protocol is for general glycemic management, NOT for DKA
 If BG does not  by 50-75 mg/dL in the first hour, re-bolus (DKA) or double the gtt (HHS)
 No evidence for hourly titration of the insulin infusion rate in DKA while BG>200
 Once BG <200 (DKA) or <300 (HHS),  gtt to 0.02- For BG < 150 ∆ Insulin gtt and glucose source
0.05 U/kg/hr and add D5 to fluids
BG 91-149  gtt by 25% +  D5 gtt by 50 cc/hr
 Goal is to maintain BG at 150-200 (DKA) or 250-300
BG 66-90  gtt by 50% + ½ amp D50 + continue D5 gtt
(HHS)
BG ≤ 65 hold insulin + 1 amp D50 + continue D5 gtt
Other electrolytes:
• HCO3: no proven benefit w/ pH > 6.9. If pH <6.9, give 2 amps HCO3 dissolved in 400mL sterile water w/ 20mEq KCl over 2h
• Phos: total body deficit but serum phos may be  / nml; will  w/ insulin; only replete if < 1.0 to prevent cardiac dysfunction
Transitioning to SQ insulin: start if BG < 200 and pt is able to eat and two of the following are met: AG<12, HCO3≥15, pH>7.3. Start
basal regimen w/ either: home glargine dose OR glargine at 0.25-0.4 U/kg/d OR glargine at (# units on IV gtt over past 6h x 4 x 0.7). Start
bolus regimen w/ either: 0.25-0.4 U/kg/d divided (if T1DM or unknown) OR ISS only (if T2DM). Overlap IV gtt/SQ insulin by 2-4h.
Ketosis-prone diabetes: characterized by DKA w/ hx T2DM or atypical substrate for T1DM (older age, overweight). Patients should be
discharged on insulin and see an endocrinologist for antibody (GAD65, IA2) and β-cell function (C-peptide levels) testing to determine
diabetes subtype (antibody +/-, β-cell function +/-). Patients may not require long-term insulin therapy.
HYPEROSMOLAR HYPERGLYCEMIC STATE (HHS)
Pathophysiology: hyperglycemia  osmotic diuresis  volume depletion; ketogenesis suppressed by low (but present) insulin levels
Precipitants: same as DKA (note: pts w/ T2DM and burnt-out pancreas can also present with DKA)
Presentation: AMS (25-50%), obtundation, seizure, focal neuro def, volume depletion, evolves over days-weeks (vs hours-days in DKA)
Dx: glucose >600 mg/dL (frequently >1000), osmolality >320 mOsm/kg, pH >7.3, absent or minimal ketones
Management: as above for DKA w/ modifications: more aggressive IVF (~8-10 L deficit); goal glucose 250-300 mg/dL (in DKA, 150-200);
transition to SQ insulin when BG<300 and mental status improved and patient is able to eat. Mortality >> DKA (Diab Care 2014;37:3124)

Audrey Carr
172
TOC

Endocrinology Adrenal Insufficiency

E T I O L O G Y (Lancet 2014;383:2152, NEJM 2009;360:2328)
Primary AI:  adrenal hormone   ACTH. Lesion localizes to the adrenal gland.
• Causes: autoimmune (80-90% cases in developed countries; anti-21-hydroxylase Ab in 86%, autoimmune polyglandular
syndromes) >> infxn (TB, HIV, CMV, histo, meningococcus), bilateral adrenal hemorrhage (infxn, DIC, APLAS), malignancy
(mets), genetic (CAH, adrenal leukodystrophy), meds (keto/fluconazole, etomidate, phenobarb, phenytoin, rifampin, opioids)
Secondary AI:  ACTH   adrenal hormone. Lesion localizes to pituitary gland.
• Causes: chronic glucocorticoids, opioids, medroxyprogesterone and megestrol. Ask about topical, inhaled and intra-articular
steroids. Other major etiologic consideration is a pituitary lesion (see Pituitary Disorders)
CLINICAL MANIFESTATIONS
Primary AND Secondary:
• Signs/symptoms: weakness, fatigue, anorexia, GI complaints, myalgias, psychiatric sx, wt loss, orthostasis, vasodilatory shock
• Lab abnormalities: hyponatremia, hypoglycemia, hypercalcemia, non-AG acidosis, anemia, eosinophilia, lymphocytosis
Primary only ( serum aldosterone): hyperK, salt craving, hyperpigmentation; if long-term, nausea/vomiting, abdominal pain
Secondary only (RAAS intact): ± hypopituitarism, hypoglycemia more common than in primary
DIAGNOSIS
• Diagnostic test: cosyntropin stimulation test (aka “cort stim”) (JCEM 2016;101:364),  AM cortisol is a late finding in AI.
• 6-8AM cortisol: definite AI if ≤3 µg/dL (<5 µg/dL highly suggestive); definitely not AI if ≥18 µg/dL
• Cort stim protocol: check serum cortisol and ACTH  give cosyntropin (ACTH) 250 μg IV  serum cortisol 30-60 min later
o Normal response: serum cortisol at 30-60 min is ≥18µg/dL (note: this rules out all cases of 1° AI + chronic cases of 2° AI)
 In acute 2° AI, adrenal glands have not had time to atrophy, so cort stim test will be normal!
o Can be performed at any time of day; initial cortisol check will be higher in the morning but stim will always be appropriate
o If abnormal cort stim, consult endocrine
• Falsely low serum cortisol:  albumin (e.g. cirrhotics, nephrotic syndrome, malnutrition, critical illness;  bound and total
cortisol, but free cortisol may be nl); PM testing (cortisol responses are greatest in morning)
• Falsely high serum cortisol: pregnancy, estrogen tx ( cortisol binding globulin,  bound/total cortisol, free cortisol may be )
• Additional labs for primary AI:  ACTH >2x ULN,  aldo, plasma renin, 17-OH-prog, 21-OHase Ab, CT A/P
• Additional labs for secondary AI:  ACTH, normal aldo
ADRENAL CRISIS
• Acute-onset AI with distributive shock in s/o major stressor (infxn, trauma, major surgery, critical illness). Consult endocrine.
• No known AI ± not taking chronic steroids: draw ACTH/cortisol but don’t delay empiric treatment; defer cort-stim until stable
• Known AI or taking chronic steroids: start treatment; diagnosis can be presumed by history; no role for cort stim test
T R E A T M E N T (JCEM 2016;101:364)
• Adrenal crisis  stress dose steroids (hydrocortisone 100 mg IV or dexamethasone 4mg IV x1) and >2-3L NS. Follow
with hydrocortisone 50mg IV q6h or dexamethasone 4mg IV q24hr ± fludrocortisone 0.1mg QD when off saline infusion if 1° AI.
o May taper once patient’s clinical status improves and underlying precipitant is adequately addressed
o Dexamethasone not detected in cortisol assay; steroid of choice if considering early cort stim dx (Clin Chem 2004;50:2345)
o Treat AI BEFORE treating severe hypothyroidism; otherwise can precipitate adrenal crisis
• Chronic AI  glucocorticoid: hydrocortisone 15-25 mg PO QD (2/3 AM, 1/3 early PM) or prednisone 3-5 mg PO QAM;
Mineralocorticoid (only in 1° AI): fludrocortisone 0.05-0.1 mg PO QD
o If minor illness or minor surgery  sick dose: “3x3 rule” = 3x daily dose for 3 days
o If severe illness  stress dose: hydrocortisone or dexamethasone (as above)
o Supply patients with medical alert bracelet if new diagnosis
STEROID PEARLS
• Taper: not necessary if steroid use <3 wks (independent of dose)  low risk of HPA suppression. Patients needing to taper
off long-term corticosteroids should do so with endocrinology guidance. May need cort-stim before stopping.
• Side effects of supra-physiologic doses:  weight, insomnia, skin thinning, AMS, hyperglycemia, edema, osteoporosis, gastritis
• Prophylaxis: PJP: if taking prednisone ≥20mg for ≥4 weeks plus second reason for immunocompromise; PUD: if also taking
aspirin/NSAIDs; osteoporosis: start calcium 1200mg/day + vitamin D 800IU/day if on glucocorticoids (any dose) >3 months
(consider bisphosphonates for pts at intermediate to high risk of fracture); DM2: monitor glucose/A1C, consider NPH dose
(0.1U/kg/day up to 0.4U/kg/day) with glucocorticoid if BG/A1C high.
Equivalent Relative Relative Na Duration
Steroid
Anti-inflammatory Dose (mg) Anti-inflammatory Activity Retention Activity (hrs)
Hydrocortisone 20 1 2 8-12
Predniso(lo)ne 5 4 0.8 12-36
Methylprednisolone 4 5 0.5 12-36
Dexamethasone 0.75 30 0 36-72
Fludrocortisone n/a 10 125 12-36

Audrey Carr
173
TOC

Endocrinology Pituitary Disorders

HYPOPITUITARISM
Definition:  pituitary hormone production/release resulting from diseases of pituitary (1°) or hypothalamus/stalk (2°)
Causes:
• Surgery, radiation, infection (meningitis), infiltration (sarcoid, hemochromatosis), trauma, tumors (1°: pituitary tumors, mets; 2°:
external stalk compression [e.g. craniopharyngioma, meningioma, mets])
• 1° only: Sheehan’s (infarction), apoplexy (hemorrhage), meds (ipilimumab), autoimmune (classically in 3rd trimester/postpartum)
Clinical Manifestations & Diagnosis:
Hormone Deficiency Signs/Symptoms Laboratory Tests
Prolactin Reduced lactation PRL
Fatigue, weight loss, nausea, orthostatic
ACTH (2° adrenal insufficiency) 8 AM cortisol, cort stim test, ACTH
dizziness, muscle/joint pain, hypotension
Fatigue, low energy, central obesity, decreased
GH IGF-1, insulin tolerance test
bone mineral density
Fatigue, weight gain, constipation, bradycardia,
TSH (2° hypothyroidism) TSH, free T4
hair loss, dry skin, hyporreflexia
LH/FSH Amenorrhea, decreased libido, ED, infertility LH, FSH, estradiol, AM testosterone
Treatment: replace deficient hormone (JCEM 2016;101:3888) with endocrine consult. Most sensitive issue is cortisol/thyroid hormone
replacement: if concurrent deficiencies, treat AI before hypothyroidism as can otherwise precipitate adrenal crisis.
HYPERPITUITIARISM
Definition: excess of any of the hormones secreted by the anterior pituitary gland (PRL, ACTH, GH, TSH, LH/FSH)
Causes: (1) hyperfunctioning pituitary adenoma, (2) elevated prolactin due to disruption of pituitary stalk, drugs (antipsychotics,
antidepressants, antiemetics, verapamil, opioids, cocaine)
Clinical Manifestations: if pituitary adenoma  headaches, visual field deficits
Hormone Excess Signs/Symptoms
Prolactin (Prolactinoma) Infertility, amenorrhea, galactorrhea, ED
Weight gain, fatigue, irritability, anxiety, depression, insomnia, easy bruising, poor wound healing,
ACTH (Cushing’s disease)
central obesity, acne, hirsutism, wide violaceous striae, prox muscle weakness, HTN
Arthralgias, fatigue, paresthesias (carpal tunnel syndrome), hyperhidrosis, OSA, CHF, enlarged
GH (Acromegaly)
jaw, hands, feet, coarse facial features, deepening of voice, skin tags, hirsutism, HTN
TSH (2° hyperthyroidism) Fatigue, exertional intolerance, irritability, palpitations, diarrhea, tachycardia, tremor, hyperreflexia
Diagnosis:
• Labs: should be targeted based on symptoms – prolactinoma (PRL), Cushing’s disease (overnight 1 mg dexamethasone
suppression test, late-night salivary cortisol, or 24h urinary free cortisol excretion), acromegaly (IGF-1, confirm with GH level after
glucose tolerance test), 2° hyperthyroidism (TSH, free T4, total T3)
• Imaging: MRI brain w/ and w/o contrast, pituitary protocol
Management:
• Prolactinoma: if >1cm or symptomatic, first-line treatment is a dopamine agonist (cabergoline first choice, bromocriptine preferred
in preconception setting). If <1cm or asymptomatic, can monitor closely with MRI and prolactin levels (JCEM 2011;96:273)
• For all other hypersecreting pituitary adenomas, treatment is transsphenoidal pituitary surgery +/- radiation therapy
• For GH secreting adenomas in patients who are poor surgical candidates, can treat with somatostatin analog (octreotide)
DIABETES INSIPIDUS (DI)
Definition: polyuria (>3L/day) in setting of insufficient amount of ADH (central) or insufficient response to ADH (nephrogenic)
Causes: (1) central – trauma, surgery, hemorrhage, infarction, neoplasm, infiltrative (sarcoidosis, histiocytosis), infection, autoimmune,
drugs (EtOH, phenytoin); (2) nephrogenic – drugs (lithium, cisplatin), hyperCa, infiltrative (sarcoidosis, amyloidosis, MM), sickle cell
Diagnosis:
• Water restriction test: normal physiology: water restriction  SOsm  ADH  UOsm (JCEM 2012;97:3426)
o Check Na, SOsm, UOsm, UVol q2hr
 If UOsm > 800 mEq/kg, stop test due to appropriate vasopressin response (dx: primary polydipsia)
 If (1) SOsm > 295 mEq/kg, (2) Na > 145 mEq/L (adequate ADH stimulus) AND (3) UOsm stable on several checks despite
 SOsm (ADH response plateaued), administer desmopressin 4 mcg IV, then check UOsm, UVol q30min x 2hr
- UOsm < 300 mEq/kg prior to desmopressin suggests complete DI; UOsm 300-800 mEq/kg suggests partial DI
• > 50%  UOsm following desmopressin = central
• < 50%  UOsm following desmopressin = nephrogenic
Treatment: correct hypernatremia (see Sodium Disorders). Allow patient to drink to thirst. PO preferred to avoid rapid ∆ in serum sodium.
• Central: desmopressin (exogenous ADH) given intranasally (5mcg qhs + 5mcg QD-TID), can augment with adjunctive meds
• Nephrogenic: if partial, may try desmopressin; if complete, use adjunctive meds
• Salt/protein restriction: low solute intake reduces thirst, thereby reducing free water intake
• Adjunctive meds: HCTZ (volume depletion  increases proximal Na/water reabsorption, decreasing distal Na delivery where ADH
acts); amiloride (mechanism similar to HCTZ, beneficial in Li-induced nephrogenic DI by blocking entry of Li across ENaC), NSAIDs
(enhance renal response to ADH), chlorpropamide (enhances renal response to ADH)

Alexandra Wick
174
TOC

Endocrinology Calcium Disorders

HYPERCALCEMIA
***MAKE SURE TO CORRECT CALCIUM FOR ALBUMIN: Corrected Ca = Serum Ca + 0.8 x (4-Alb)***
Definition: mild (corrected Ca < 12); moderate (corrected Ca 12-14); severe (corrected Ca >14)
Clinical signs/symptoms: MSK (“bones”)  Osteitis fibrosa cystica (1° hyperPTH), arthralgia, osteoporosis, weakness; renal
(“stones”)  polydipsia, polyuria, nephrolithiasis, Type 1 RTA, AKI/CKD; GI (“groans”)  n/v, anorexia, constipation, ileus, pancreatitis,
peptic ulcers; neuropsych (“overtones”)  fatigue, depression, anxiety, confusion, stupor, coma; CV  bradycardia, short QTc, AV
block, valve/vessel calcification, HTN
Diagnostic approach: Low
High PTH

- Primary HyperPTH (adenoma >

 PTHrP  1,25(OH)D  25(OH)D Normal:
hyperplasia > carcinoma)
- Ectopic production - Lymphoma - Vitamin D - Multiple myeloma
- a/w MEN
(lung SCC, breast, - Granulomatous toxicity - Hyperthyroidism
- FHH (24h urine calcium/Cr ratio <0.01);
RCC) disease (sarcoid, - Adrenal insufficiency
in 1° HyperPTH, UCaCr >0.01 (unless pt
TB) - Immobilization
w/ CKD/vit D deficiency)
- Pheo
- Tertiary hyperPTH
- Vit A intox
- Drugs (thiazides, Li)
- Milk-alkali syndrome
Management: (BMJ 2015;305:h2723, NEJM 2005;352:373)
• In general, asymptomatic mild-moderate hyperCa can be managed conservatively as outpatient; patients with symptomatic or severe
hyperCa (>14) should be admitted for treatment and endocrine consult.
• Conservative measures: avoid contributory meds; oral hydration; oral PO4 repletion to 2.5-3.0 (IV could lead to hypoCa)
• Volume resuscitation: patients are typically very dehydrated; bolus NS then gtt @ 200-300cc/hr with goal UOP 100-150cc/hr
• Loop diuretics: ONLY if concurrent HF, CKD (and only once volume replete), elderly; otherwise avoid as they can worsen dehydration
• Bisphophonates: best studied in malignancy; zoledronate >> pamidronate (except in MM: more ATN). Takes 2-4d for effect.
Side effects: hypoCa (check 25(OH)D & replete prior to admin), flu-like illness. Reduce dose if CKD. Avoid if CrCl <30.
• Denosumab: monoclonal Ab against RANKL  blocks pre-osteoclast maturation; good option in patients with CKD
• Calcitonin: 4-8U/kg SC BID for 48 hours (substantial Ca reduction within 12-24 hours). Tachyphylaxis usually occurs within 48-72h.
• Other: glucocorticoids (effective in calcitriol mediated etiologies, takes 2-5 days for effect), HD (if refractory or life-threatening)
• Special considerations for 1° hyperPTH: surgery is curative. Indicated if (1) symptomatic OR (2) asymptomatic with Ca > 11.5,
osteoporosis/vertebral fracture, CCl <60, nephrolithiasis, or age <50. If poor surgical candidate, consider cinacalcet, bisphosphonate,
tamoxifen (JAMA Surg 2017;152:878, JCEM 2014;99:3607)
HYPOCALCEMIA
Clinical signs/symptoms: neuromuscular (paresthesias, muscle cramps/spasms, tetany, Trousseau sign [carpal spasm w/ BP cuff
inflation 94% Sn, 99% Sp], Chvostek sign [circumoral muscle twitch w/ facial nerve tapping poor Sn / 85% Sp]); seizures;  QTc,
laryngospasm, bronchospasm, AMS, abdominal pain, dysphagia (BMJ 2008;336:1298)
Diagnostic approach:
PTH High
Low

- Hypoparathyroidism (surgical,
autoimmune, infiltrative dz, radiation)  PO4  PO4
- Hypomagnesemia (causes PTH - Vitamin D deficiency - CKD (2° HyperPTH)
suppression/resistance) - Pancreatitis - Tumor lysis
- Drugs (bisphosphonate, - Rhabdo (early)
phenytoin, cinacalcet) - Pseudohypoparathyroidism
- Critical illness
- Transfusions (citrate)
Management:
• Replete magnesium (hypoCa can be hard to correct without first correcting hypoMg  causes PTH resistance and  secretion)
• IV Ca repletion: if severe (corrected Ca < 7.5, iCa < 1), symptomatic, or prolonged QT
o 1-2g IV Ca gluconate or CaCl2 (in codes: via central line, risk of skin necrosis if extravasates) over 10-20 min
o IV therapy  serum levels for only 2-3h (chase w/ gtt or PO); can do sliding scale repletion in ICU
o Telemetry recommended as arrhythmias may occur
• PO Ca repletion: if Ca > 7.5 or asymptomatic: 1-2 g elemental Ca QD in divided doses (Ca citrate better absorbed vs CaCO3 esp. if pt
on PPI)
• Vitamin D repletion: 800-1000 IU Vit D3 daily (if severely deficient trial 50,000 IU Vit D2 or D3 qweek x 6-8wks and measure 25(OH)D
level in 3-4mos). In patients w/ poor conversion of 25(OH)D (e.g. hypoparathyroidism, CKD) use calcitriol (start w/ 0.25mcg PO QD)

Jiby Yohannan
175
TOC

Endocrinology Osteoporosis
Definitions:
• Osteoporosis: history of fragility fracture or T-score ≤ -2.5 on DXA. Osteopenia: T-score -2.4 to -1.
o T-score: SD compared to mean for normal, healthy young adults
o Fragility fracture: fracture from a fall from standing height or less or with no trauma, particularly spine, hip, wrist, rib, and
pelvis
Etiology:
• Primary osteoporosis is the most common. Risk factors: age ≥65, low body weight (<57.6 kg), FH osteoporosis or fractures,
smoking, early menopause, excessive EtOH intake
• Secondary osteoporosis caused by: renal disease, liver disease, hyperthyroidism, hyperPTH, vit D deficiency, hypogonadism,
glucocorticoids (≥5mg prednisone for >3mos), myeloma, malabsorption (celiac, IBD), RA, SLE, COPD, drugs (PPI, AED, long-
term heparin, leuprolide, aromatase inhib, MTX, GnRH agonists)
Diagnosis:
• Screen women with DXA scan at age 65 or younger if RF or high risk as determined by FRAX (USPSTF guidelines)
• Screen men ≥70 or age 50-69 who have RF (low body weight, prior fracture, smoking) (Endocrine Society Guidelines)
• Labs for secondary causes: CBC, BMP, LFTs, 25(OH)D, TSH, PTH, SPEP
Management:
• Inpatient following fragility fracture: assess need for surgical treatment, consult Fracture Liaison Service (p25656), can start
medical management (bisphosphonates); zoledronic acid has been shown to decrease mortality post-hip fracture (HORIZON
trial)
• Lifestyle measures: weight-bearing exercises 3-4x/week, smoking cessation, decrease EtOH intake, RDA 800-1000 IU
vitamin D (goal level >30), calcium 1200 mg ideally from diet
• Pharmacologic therapy:
o Bisphosphonates: must have normal vit D and calcium levels prior to initiating therapy
 Indicated for: all patients with osteoporosis, osteopenia in men and postmenopausal women with FRAX 10-yr
risk >20% for any fracture, >3% for hip; consider when initiating long-term glucocorticoids in pts with med-high risk of
fracture.
 PO alendronate 75mg or PO risendronate 35mg weekly for 5-10 yrs. Avoid if GFR <30. Provide strict instructions to
prevent pill esophagitis: take on empty stomach w/ full glass of water, sit upright and wait 30 min prior to taking other
meds or food.
- If contraindication to PO bisphosphonate (e.g. GI intolerance, roux-en-Y gastric bypass), IV zoledronic acid
 Re-evaluate q3-5yrs and if low-moderate risk consider a “bisphosphonate holiday” (JCEM 2019;104:1592)
o Denosumab (monoclonal antibody with affinity for RANKL): option for patients with renal dysfunction or other
contraindication to bisphosphonates, 60 mg SQ q6mo; treat with teriparatide first if severe osteoporosis. FREEDOM trial
showed denosumab improves fracture risk and bone mineral density compared to placebo
o Anabolic agents (teriparatide: recombinant PTH; abaloparatide: PTHrP analog): VERO trial
 For severe osteoporosis or for patients with contraindications to bisphosphonates, daily SQ injection

Jiby Yohannan
176
TOC

Endocrinology Thyroid Disorders

INPATIENT TFTs
• If thyroidal illness is suspected, TSH alone is inadequate; should also test for FT4 & T3. TSH will reflect changes within 4-6
wks.
• Nonthyroidal illness “euthyroid sick": alterations in thyroid function due to illness rather than 1° endocrine disorder; may be
adaptive (anti-catabolic); no indication to treat; most likely cause of abnormal TFTs among inpatients (Lancet Diab Endo
2015;3:816)
o Typical pattern: (1) acute illness: T3, T4, /nl FT4, /nl TSH. (2) recovery phase:  TSH  recovery of T4, T3.
o Sequential FT4 should  in recovering sick euthyroid but remains low in 1° hypothyroid. rT3 can differentiate central
hypothyroidism () from sick euthyroid (), but rarely needed. FT3 only helpful to dx hyperthyroidism w/ altered TBG.
o Undetectable TSH (<0.01) suggests true hyperthyroidism, and TSH >20 + low T4 suggests true hypothyroidism.
• Biotin supplementation can interfere with TSH and other assays, ensure pt off biotin x 1wk before testing
•  TSH also seen with glucocorticoids, dopamine, dobutamine, octreotide,  β-HCG levels (pregnancy, trophoblastic disease)

HYPOTHYROIDISM
• Definition: elevated TSH with low T4 (primary) or low/normal TSH with low T4 (secondary/central)
• Signs/symptoms: general (fatigue, cold intolerance, constipation, dry skin, myalgias), neuro (depression, cognitive
dysfunction, carpal tunnel), CV (bradycardia [severe dz], diastolic HTN)
o Exam: delayed relaxation phase of DTRs, non-pitting edema, lateral TSH FT4
eyebrow thinning, macroglossia, froggy voice Primary  
• Labs:  LDL,  triglycerides, macrocytic anemia,  Na Secondary /normal 
o Check other pituitary axes if concern for central hypothyroidism Subclinical  Normal
• Workup: TSH with reflex, anti-TPO ab. No role for thyroglobulin or anti-thyroglobulin ab (only useful for monitoring thyroid Ca)
• Causes:
o 1°: Hashimoto’s (most common, +TPO Ab), infiltrative disease (hemochromatosis, sarcoid), transient thyroiditis
(lymphocytic, granulomatous, postpartum), drugs (lithium, amio, TKIs, contrast), iatrogenic (thyroidectomy, radiation),
iodine deficiency
o 2°: see Pituitary Disorders
o  T4 requirement: pregnancy, estrogen ( THBG), weight gain, malabsorptive states (e.g. celiac disease), nephrotic
syndrome ( excretion), rifampin, phenytoin, carbamazepine, phenobarbital
• Treatment: levothyroxine (T4) starting dose ~1.6 mcg/kg/d PO (use 25-50 mcg QD for elderly or comorbidities); IV = 50-75%
PO
o Take on an empty stomach 1h before food/meds; several hrs apart from PPI, aluminum hydroxide, iron, cholestyramine
o Check TSH q6 weeks and adjust by 12-25 mcg until normal TSH

Subclinical hypothyroidism: elevated TSH with normal FT4 (biochemical diagnosis)

o Dx: can check anti-TPO Ab (if ⊕, monitor TFTs regularly because at higher risk for Hashimoto’s)
o Treatment: treat if TSH ≥10. If TSH <5, consider risk factors (e.g. CV disease, CAD, HLD) to guide tx
o Elderly patients often have higher TSH levels and this can be normal

MYXEDEMA COMA
• Manifestation of severe hypothyroidism, STAT endocrine consult
• Mortality >30%, most common cause of death is hypercarbic respiratory failure
• Precipitants: infection, MI, cold exposure, surgery, administration of sedative drugs (esp opioids) in a poorly controlled
hypothyroid pt
• Signs/symptoms: AMS (lethargy/obtundation, not always coma), hypothermia, hypotension, bradycardia, ventricular
arrhythmias, hypercarbic resp failure, seizures
o Exam: puffy hands and face, swollen lips, enlarged tongue
• Labs:  Na (be careful with IVF),  Glu,  T4
• Treatment: do not wait to start tx for lab confirmation
o Test and empirically treat adrenal insufficiency: give hydrocortisone 50-100mg BEFORE T4 (if concomitant AI,
replacing thyroid hormone first will catabolize residual cortisol and cause HoTN/death). Draw serum cortisol before
initiating therapy.
o Levothyroxine (T4) 12.5-50mcg IV QD in elderly or at risk for MI, up to 200mcg if sick and young.
o Liothyronine (T3) (5-10mcg Q8H) only given if pt is critically ill (T4 conversion to T3 takes several days), give only with
endo guidance, can cause rebound hypermetabolism
o Recheck FT4 in 3-7d; if giving T3, monitor peak levels
o Patients are hypometabolic: use lower drug doses at lower frequency, avoid MS-altering meds.

Jiby Yohannan
177
TOC

Endocrinology Thyroid Disorders

HYPERTHYROIDISM
• Definition: low TSH with high T4 (primary) or high/normal TSH with high T4 (secondary/central) (Thyroid 2016;26:1343)
• Signs/symptoms: general ( weight,  appetite, heat intolerance, tremor, weakness), CV (palpitations, AFib, systolic HTN),
hyperdefecation, dyspnea, sweating, anxiety, emotional lability, urinary frequency, abnormal menses, osteoporosis
o Exam: lid lag, exophthalmos and pretibial myxedema (Graves’ only), hyperreflexia, thyroid bruit
o Apathetic thyrotoxicosis: depression, weakness, seen in elderly TSH FT4 Total
• Labs:  HDL,  LDL, normocytic anemia,  Ca,  AlkP,  Glu T3
• Workup: 1) TSI and TBII (Graves’), 2) RAIU (not for amio-induced or if Primary   
recent IV contrast), 3) thyroid US w/ Doppler Secondary /normal  
• Causes: Subclinical  Normal Normal
o 1°: Graves’ disease (most common, T3:T4 ratio >20), toxic
adenoma, toxic multinodular goiter, transient thyroiditis (lymphocytic, granulomatous, postpartum, viral), drugs (amio,
iodine, lithium), iatrogenic (radiation, palpation), exogenous T3 or T4 ingestion (low thyroglobulin), HCG-mediated, struma
ovarii
o 2°: see Pituitary Disorders
• Treatment: β-blocker for adrenergic symptoms (e.g. metoprolol, propranolol)
o Graves’ disease: thionamides (methimazole > PTU due to hepatotoxicity), radioiodine (risk of opthalmopathy),
thyroidectomy (watch for hypoparathyroidism). Monitor total T3 and fT4 q6wks.
o Toxic adenoma or multinodular goiter: radioiodine, surgery, less commonly thionamides

THYROID STORM
• Manifestation of severe thyrotoxicosis, STAT endocrine consult
• Mortality rate 10-30%, most common cause of death is cardiovascular collapse
• Precipitants: surgery (thyroid or other), trauma, infection, iodine load, irregular use or discontinuation of antithyroid drugs
• Signs/symptoms: AMS (agitation, delirium, psychosis, coma), hyperthermia, tachycardia, atrial arrhythmias, CHF
o Exam: goiter, tremor, warm/moist skin, exophthalmos (Graves’)
• Labs: T4/T3, TSH
• Dx: Burch-Wartofsky Point Scale (BWPS) >44 highly suggestive
• Treatment:
o βB: only propranolol decreases T4T3 conversion, may require high doses (2g/day). Titrate to sx and HR (i.e. <80).
o Anti-thyroid meds: only stop formation of new hormone, not release of stored hormone.
 Methimazole (20mg q4h-q6h) is preferred unless pt is critically ill. PTU (200mg q4h-q6h) decreases T4T3 but
higher rates of fulminant hepatic necrosis.
o Iodine (100-250mg q6h-q8h) blocks release of thyroid hormone, must be given at least 1hr after thionamide; can cause
Jod-Basedow in toxic adenoma and Wolff-Chaikoff in Graves.
o Hydrocortisone (300 mg loading dose then 100 mg Q8H) to reduce T4T3
o Patients are hypermetabolic and will clear drugs quickly

AMIODARONE-INDUCED THYROID DISEASE

Check TSH prior to treatment, q4-6 mo while on amio, and for 1 yr after amio discontinued.
• Typical response to amio acutely:  TSH (2-3x nl),  T4 and FT4,  T3,  rT3  levels return to normal in 3-6 months
• May cause hypothyroidism (due to Wolff-Chaikoff or destructive thyroiditis) OR hyperthyroidism
o Type 1 (early)   synthesis due to  iodine
o Type 2 (late)  direct toxicity of drug causing thyroiditis and stored hormone release without increased synthesis

Jiby Yohannan
178
TOC

Allergy & Immunology Drug & Contrast Allergy

CLASSIFICATION:
Adverse Drug Reactions (ADRs): (JACI 2010;125:S126)
• Type A = predictable (~85-90%): dose-dependent reactions related to drug’s known pharmacological action which occur
in otherwise healthy patients if given sufficient dose and exposure (e.g. gastritis d/t NSAIDs)
• Type B = unpredictable (10-15%): dose-independent, unrelated to pharm action, and occur only in susceptible pts
o Drug intolerance: undesirable pharmacologic effect without abnormalities of metabolism/excretion/bioavailability of
drug (e.g. tinnitus after aspirin)
o Drug idiosyncrasy: abnormal effect caused by underlying abnormalities of metabolism/excretion/bioavailability (e.g.
hemolysis after antioxidant drug in G6PD deficiency)
o Pseudoallergic reaction (formerly known as anaphylactoid): drug causes direct release of mediators from mast
cells/basophils (e.g. flushing during vancomycin infusion, exacerbation of asthma/rhinitis w/ aspirin in AERD)
o Drug allergy: immunologically-mediated hypersensitivity reactions (see table)
Hypersensitivity Reactions (Gell and Coombs Classification): (Clin All 1998;18:515)
Type Reaction Mechanism Presentations
Anaphylaxis, allergic rhinitis,
I Immediate Ig-E mediated degranulation of mast cells due to antigen
allergic asthma, urticaria,
(min-hr) binding and cross-linking of IgE
angioedema
Drug-induced cytopenia (incl.
II Antibody IgM/IgG:antigen interactions on target cell surfaces
AIHA)
Immune- Immune complex formation and deposition in tissues Serum sickness, vasculitis, drug
III
complex complement activation  local / systemic inflammation induced lupus
Ag activates T cells  Ag later binds to activated T cells
Contact dermatitis, SJS/TEN,
IV Cell-mediated  cytokine release  macrophage & cytotoxic T cell
DRESS, AGEP
accumulation
EVALUATION
• Key Qs in drug allergy hx: approximate date, drug, dose and route, doses/days into course, co-administered meds,
coincident infections, sx, severity (home/office/ED/hospitalization), how treated, exposures since
• PLEASE document appropriately in EPIC allergy section. Document rxn, date, and other meds tolerated (e.g. “hives to
penicillin 2015, tolerated ceftriaxone 2019”) and distinguish true drug allergies from drug intolerances.
DIAGNOSIS
• Labs (sometimes helpful): CBC w/ diff (eos), tryptase (if anaphylaxis), auto-Abs (e.g. anti-histone in drug induced lupus)
• Skin testing: evaluates for drug-specific IgE antibodies for a limited number of medications
o NPV of penicillin skin testing = 95% (Drug Allergy Practice Parameter 2010)
• Deliberate re-challenge = graded challenge = test dose procedure
o Used when there is a low suspicion for true allergic reaction to a medication. Does NOT assess cross-reactivity of
structurally-related drugs. Contraindication = severe non-IgE mediated HSR (ex: DRESS, SJS, etc.)
o How to order: Antibiotic Test Dose in Epic order sets (can also type “penicillin” “allergy” “test dose”)
 Automatically orders the rescue medications, nursing communication orders, and fills in doses of desired med
(FYI test dose = 1/10 of rx dose for IV meds and ¼ of rx dose for oral meds)
o If negative: patient is not allergic to that agent and can safely receive it
 If agent was a related agent (e.g. CTX administered in PCN-allergic pt): update “comments”
 If agent was same agent as recorded allergy (e.g. PCN administered in PCN-allergic pt): remove allergy
o If positive: Epi 1:1000 IM (0.3 mg), Benadryl 50 mg IV/PO. Page allergy fellow (13042) and file incident report
DRUG DESENSITIZATION JACI 2010;125:S126 (used if true allergy)
• Indications: ⊕skin test, ⊕test dose, or h/o severe type I HSR AND no alt. tx. ONLY for Type I (IgE-mediated) rxns.
• Method: administer drug with increasing doses over hours such that it induces state of TEMPORARY tolerance
• At MGH, consult Allergy for advice on dose, administration, and monitoring. Generally, desensitization needs to be done
in the ICU (exception: chemo on Lunder, ASA on cardiology floors)
• If patient stops medication: procedure must be performed again if pt stops medication for >2-3 half lives

Jessica Plager
179
TOC

Allergy & Immunology Drug & Contrast Allergy

PENICILLIN & CEPHALOSPORIN ALLERGY
• Pathway: Ellucid (or stepwise via Resources  Handbook  EPIC Quick Links  Medication Pathways)
• 10% of pts report a PCN allergy, but 90% of patients with a h/o PCN allergy can tolerate PCN (JACI 2010;125:S126)
• Patients with a PCN allergy have a <1% cross reactivity to carbapenems (CID 2014;59:1113)
• Early studies evaluating the cross-reactivity between PCN and cephalosporins were performed before 1980, when
cephalosporins were contaminated with trace amounts of PCN. More recent studies have found that <2% of patients
with skin test-proven sensitivity to PCN will react to cephalosporins (Annals 2004;141:16)
• PCN allergy is typically mediated by the β-lactam ring, while cephalosporin allergy is due to the R-group side chain. The
risk of cross-reactivity is higher with those β-lactams sharing identical R side chains
Groups of common β-lactam antibiotics that share identical R-group side chains
Amoxicillin Ampicillin Ceftriaxone Cefoxitin Ceftazidime
Cefadroxil Cephalexin Cefotaxime Cephalothin Aztreonam
Cefpodoxime

OTHER COMMON DRUG ALLERGIES

• Taxanes/platinum-based Chemotherapy
o Must differentiate infusion reaction (SIRS response to chemo agent) from true anaphylaxis (type I HSR)
o Rates differ between agents: 19.5% with carboplatin, 30% with taxanes (NEJM 1995;332:1004)
o Increased frequency of infusion reactions occur with subsequent infusions (AAAAI 2009;102:179)
o Refer patient to Chemotherapy Allergy Clinic for skin testing or desensitization
• Allopurinol
o Allopurinol hypersensitivity syndrome (AHS): rash, fever, hepatitis, and/or renal impairment after exposure.
Usually occurs 4-8 wks after initiation (Drug Saf 2013;36:953)
o In patients of E. Asian descent, unless initiating for TLS, consider sending HLA-B5801 genotyping (high risk for AHS)
• Aspirin/NSAIDs (JACI 2010;125:S126)
o Wide spectrum of drug-induced allergic reactions, including exacerbation of underlying respiratory disease, urticaria,
angioedema, anaphylaxis, and rarely pneumonitis and meningitis
o Management: avoid NSAIDs (COX-1 inhibitors). If NSAIDs are necessary, consult Allergy/Immunology
o Aspirin-Exacerbated Respiratory Disease (AERD) (aka Samter’s Triad): triad of asthma, rhinosinusitis w/ nasal
polyps, and ASA/NSAID sensitivity (nasal congestion, bronchospasm). Tx: ASA desensitization
IV RADIOCONTRAST MEDIA (ACR Guidelines 2018)
Type Pathogenesis Epidemiology Presentation Clinical pearls Pre-Treatment
RCM directly 1-3% patients Immediate pruritus, No evidence that Elective (13h protocol)
stimulates mast with ionic RCM & urticaria, iodine levels in 1. Prednisone 50 mg PO at
cells / basophils 0.5% pts w/ non- angioedema, airway seafood or topical 13, 7, & 1h prior AND
*Minority of pts ionic RCM. obstruction, HoTN, solutions are related to 2. Diphenhydramine 50 mg
have + skin tests Severe rxns occur abdominal pain adverse events from PO 1h prior
indicating that in 0.22% for ionic RCM. Seafood allergy Accelerated (4-5h)
minority of pts RCM, 0.04% for is not a 1. Methylprednisolone 40
Pseudoallergic have IgE non-ionic RCM contraindication. mg IV now & q4h until scan
(Anaphylactoid) mediated rxn Risk Factors: Oral contrast is NOT AND
*Use low/iso- female, asthma, contraindicated in a 2. Diphenhydramine 50 mg
osmolar RCM hx of previous rxn patient with IV contrast IV 1h prior
when possible to RCM, BB allergy, though rarely Emergent (1h)
exposure, CV can cause a reaction. 1. Methylprednisolone 40
disease mg IV 1h prior AND
2. Diphenhydramine 50 mg
IV 1h prior
T cell-mediated 2% of patients >1h - 1 wk. Usually Tx: Supportive care
Delayed mild, skin eruption.
Rare: SJS/ TEN

Jessica Plager
180
TOC

Allergy & Immunology Angioedema & Anaphylaxis

Angioedema (Allergy 2018;73:1393)
• Definition: localized non-pitting swelling of the skin or mucosal tissue due to interstitial edema; may affect face,
extremities, genitals, bowels. Often asymmetric. Occurs in min-hrs and resolves within 24-48hrs.
• Common triggers include heat, cold, delayed pressure, solar, vibratory, cholinergic, contact, and aquagenic
• Classification/etiology:
Type Urticaria Triggers
Mast Cell Usually ASA, NSAID, CCB, platinum-based chemo, β-lactams, metoprolol, siro/everolimus, risperidone
Histamine Rarely Idiopathic / spontaneous
ACE/ARB: 0.1-0.7% pts; may occur any time during therapy and last 6 mo after cessation
Bradykinin Never Hereditary angioedema: autosomal dom. C1 esterase deficiency/dysfunction. Screen: C4
• Treatment: in ALL: ABCs, secure airway
o If urticaria: identify & remove exposure  tx with antihistamines, glucocorticoids, +/- epi if breathing affected
o If no urticaria:
 On ACE  stop ACE inhibitor  supportive care (if severe, consider icatibant)
 Known hereditary or acquired angioedema  page allergy for C1-inhibitor, icatibant. FFP is 2nd line.
 Not on ACE; no known disorder  diphenhydramine 50 mg x1 + prednisone 40 mg x1
Anaphylaxis (AAAI 2015;115:341; WAO Guidelines: World Allergy Org J 2011;4:13)
• Definition: acute, life-threatening, multi-system syndrome due to allergy or hypersensitivity
• Causes:
Type Mechanism Triggers
Food (e.g., nuts, shellfish, milk, eggs), insect venom, meds (e.g. NSAIDs,
IgE mediated β-lactams, biologics), latex, occupational allergens, aeroallergens,
Immunologic
radiocontrast media (RCM)
Non-IgE mediated NSAIDs, dextrans (e.g. HMW iron), biologics, RCM
Direct mast cell
Nonimmunologic Physical factors (exercise, heat, cold, sunlight), ethanol, meds (opioids)
activation
Idiopathic No apparent trigger Mastocytosis / clonal mast cell disorder, previously unrecognized allergen
• S/Sx: skin/mucosal swelling, angioedema, rash/urticaria, bronchospasm/stridor, GI sx (n/v/d/pain), HoTN/shock
o Associated with biphasic reaction in 4-23% pts  return of symptoms 8-72 hrs after initial symptom resolution
• Diagnostic criteria: 1 of 3 must be met
1) Skin and/or mucosal involvement AND either respiratory compromise OR reduced BP after exposure to
POTENTIAL allergen
2) Two or more of following after exposure to LIKELY allergen: skin/mucosa swelling, respiratory sx, HoTN, GI sx
3) Low BP (SBP<90 or >30% drop from baseline) after exposure to KNOWN allergen for pt
• Labs: consider histamine (within 10-30 min of symptom onset) and tryptase (within 15 min-3 h of symptom onset and
24h after symptoms resolve to assess baseline). Normal levels do not rule out anaphylaxis!
• Treatment:
o Establish and maintain airway, administer oxygen/IVF, remove trigger if possible
o Epinephrine: only medication that reverses airflow obstruction & prevents cardiovascular collapse
 Dosing: 0.3-0.5mg IM at 1:1000 dilution (1mg/mL) OR 0.1-0.3mg IV at 1:10,000 dilution (0.1mg/mL)
 May repeat q5-15 minutes; if >3 doses required, consider continuous epi gtt (1-10mcg/min)
 If on beta blockers and resistant to epinephrine, administer glucagon (1-5mg bolus followed by gtt @ 5-
15mcg/min)
o Adjunctive agents: albuterol for bronchospasm (stacked nebs x3), diphenhydramine 50 mg IV/IM for hives/pruritis,
methylprednisolone 125 mg IV QD x2 to prevent biphasic reaction
o Make sure to discharge home with EpiPen!
o If history of anaphylaxis to stinging insect, refer for skin testing. If positive, consider SQ venom immunotherapy,
which decreases risk of subsequent anaphylaxis from 50-60% to 2-3% (NNT = 2). False negative skin testing may
occur w/in first few weeks after anaphylaxis (NEJM 2014;370:1432)

Ashli Fitzpatrick
181
TOC

Allergy & Immunology Mast Cell Disorders

Mast Cell (MC) Physiology (NEJM 2015:373;163)
• Activated by antigens (allergens), anaphylatoxins (C3a/C5a), meds, venoms, physical stimuli (pressure/temperature
change), cytokines/neuropeptides. MCs degranulate and secrete vasoactive & pro-inflammatory mediators including
histamine, serotonin, proteases (e.g. tryptase), TNF, cytokines, and chemokines.
• Serum tryptase most useful clinically (relatively specific for MCs)
Signs & Symptoms
• Cutaneous: flushing, pruritis, urticaria, angioedema
• GI: heartburn & nausea (histamine  hypersecretion of acid from parietal cells), diarrhea, abdominal cramps
• Respiratory: rhinorrhea, bronchoconstriction, nasal pruritis, throat swelling
• Cardiovascular: episodic hypotension associated with compensatory tachycardia, recurrent syncope
• Neuro: Headache, fatigue, mood disorder, insomnia, decreased concentration
Classification of Mast Cell Disorders
• Primary: systemic and cutaneous mastocytosis, monoclonal mast cell activation syndrome (MMAS)
• Secondary: allergic conditions, physical urticarias, chronic inflammatory conditions & neoplastic disorders
• Idiopathic: idiopathic anaphylaxis, idiopathic urticaria, idiopathic histaminergic angioedema, idiopathic mast cell activation
PRIMARY MAST CELL DISORDERS: clonal population of mast cells from affected progenitor (Blood 2017;129:1420)
Systemic Mastocytosis Cutaneous Mastocytosis
Mainly adults. Incidence: 1: 10,000 - 20,000 Mainly infants and young children, resolves by
Epidemiology
adolescence. Incidence < 1:20,000.
Multifocal infiltration of mast cells in various Skin only, but mast cell mediators may enter
Organ internal organs (e.g. GI tract, spleen, liver). Bone circulation and cause systemic symptoms.
systems marrow is involved in virtually all patients. Skin
more common w/ indolent mastocytosis.
1. Indolent SM (most common) 1. Urticaria pigmentosa (UP) = maculopapular CM
2. Smoldering SM 2. Localized mastocytoma of the skin
Variants
3. SM a/w non-mast cell hematologic neoplasm 3. Diffuse cutaneous mastocytosis
4. Mast cell leukemia
Elevated baseline serum tryptase (>20ng/mL) in Normal baseline tryptase for most children with UP
Lab findings non-symptomatic state strongly suggestive of SM or mastocytoma; pt with diffuse CM may have
elevated baseline tryptase
Diagnosis requires: major criterion + 1 minor Skin lesions consistent with UP, mastocytomas, or
criterion OR 3 minor criteria diffuse CM, and typical histologic infiltrates of mast
Major criterion: multifocal infiltrates of mast cells in cells in a multifocal or diffuse pattern in an
≥1 visceral organ adequate skin biopsy.
Minor criteria:
Diagnostic 1. ≥25% of MCs in infiltrates in extracutaneous In addition, an absence of features/criteria
Criteria biopsies or BM smear spindle-shaped or atypical sufficient to establish the diagnosis of SM.
2. KIT point mutation in BM or other extracutaneous
organ
3. MCs in BM or blood or another extracutaneous
organ exhibit CD2 and/or CD25
4. Baseline serum tryptase level >20ng/mL
Monoclonal Mast Cell Activation Syndrome (MMAS)
• Adult with recurrent / episodic symptoms of mast cells similar to SM (flushing, abdominal cramping, and hypotension)
but do NOT have UP or characteristic mast cell aggregates in BM
• Baseline serum tryptase normal or mildly increased
• Meets 1-2 minor clonality criteria for SM but does not meet the full diagnosis
SECONDARY MAST CELL DISORDERS
• Allergic diseases: IgE-mediated allergies to food, medications, environmental allergens
• Physical forms of urticaria: physical factors may activate MCs in susceptible hosts (quick change in temperature,
pressure/vibration on skin, exposure to water or UV light, exercise)
• Chronic inflammatory/autoimmune disorders: SLE, RA, psoriasis, atopic dermatitis, pulmonary fibrosis
• Neoplasms: breast cancer, Hodgkin’s, skin and connective tissue tumors

Rebecca Liu
182
TOC

Allergy & Immunology Primary Immunodeficiency

Primary Immunodeficiency Disorders (JACI 2015;136:1186, JCI 2015;35:696)
• Definition: inherited deficits of immune system  increased incidence/severity/frequency of infections
• Prevalence: 1/300 – 1/10,000 pts
• Warning signs in adults: 2 new ear infxn/yr, ≥2
new sinus infxn/yr, recurrent viral infxn (e.g. HSV,
VZV), ≥1 PNA/yr x multiple yrs, chronic diarrhea,
recurrent deep abscesses, persistent fungal
infection, recurrent need for IV abx, infxn w/
benign mycobacteria
• H&P: dev hx, FH, age at onset, frequency & type
of infections, syndromic features
• Need to r/o 2º causes (HIV, immunosuppressants,
cancer, cirrhosis)
• General principles of management: vaccination,
abx ppx, immunoglobulin replacement, HSCT
Disorder Advanced Testing
Presentation Infectious Organisms
(% Total) (JACI 2010;125:S297)
Any age Bacteria: encapsulated esp. Complement levels
Complement - Sinusitis, PNA, meningitis Neisseria CH50 or AH50 (alt pathway)
(5%) - Lupus-like syndrome
INNATE

- Rheumatoid disorders
Infancy/childhood Bacteria: S aureus, PsA, ANC
Phagocytic - Oral, anorectal, SSTI Serratia, Klebsiella, non-TB Oxidative burst via DHR/NBT test
(10%) - Unusually severe infections mycobacteria for CGD
- Granulomas, poor wound healing Fungi: Candida, Aspergillus
T cell subset Infancy Bacteria: Mycobacteria Flow cytometry
defects (5%) - Oral thrush Fungi: Candida Anergy/proliferation tests
>6 mos, can present in adulthood Bacteria: H flu, Strep, Staph, SPEP, flow cytometry
- Recurrent sinusitis, PNA, viral URI Moraxella cat, PsA, Vaccine response
- Chronic GI malabsorption, diarrhea mycoplasma pneumoniae Polysaccharide PPSV23 titers:
- Autoimmune disease (29% in Virus: Enterovirus (esp with IgA ≥70% of serotypes ≥1.3 =
B cell /
CVID) (Blood 2012;119:1650) deficiency) adequate. If not, give PPSV23 &
Antibody (65%)
- Post-vaccination paralytic polio Parasites: Giardia repeat titers in 4-6 wks
ADAPTIVE

with live vaccine Protein: tetanus, diphtheria IgG

- Anaphylaxis to blood products (IgA Conjugated: Hib IgG
deficiency)
Infancy Bacteria: Salmonella, Listeria, As above for B & T cell
- FTT non-TB mycobacteria deficiencies
- Oral thrush, viral infections Viruses: CMV, EBV, VZV
Combined B &
- Diarrhea Fungi: Candida, Aspergillus,
T cell (15%)
cryptococcus, histoplasmosis
Parasites: PCP, toxoplasmosis,
Cryptospordium
Immunoglobulin Replacement (JACI 2017;139:S1)
• Manufactured using donor pools of donated human plasma & contains IgG antibodies, administered as IVIG or SQ Ig
• In addition to antibody replacement, it also has anti-inflammatory and/or immunomodulatory effects at higher doses
• Starting doses: 400-600 mg/kg q3-4 wks for trough level >500-600 mg/dL (higher in pregnancy & bronchiectasis)
• Once on IVIG, cannot check serologies for 3-4 months. Can check PCR instead (e.g. HBV PCR)
• IVIG in infection: depends on host & infection. If CVID w/ infection, can check SPEP for IgG trough. Beneficial in CMV
pneumonitis in solid organ tx recipients, rotaviral enterocolitis & bacterial infections in lymphoproliferative dz (e.g. CLL),
Kawasaki disease, ped HIV.
Therapeutic Use of Vaccines in Patients with PID (JACI 2018;141:474)
• ALL patients with PID can receive INACTIVATED vaccines according to routine schedule. Prioritize yearly influenza
vaccine and HPV vaccine. For LIVE ATTENUATED vaccine safety/benefit, see UpToDate Table.
• Pts on immunoglobulin replacement have adequate titers to measles, mumps, varicella, rubella, pneumococci, Hib, and
variable titers to meningococcus. If exposed to an infection in which a “hyperimmune” Ig is recommended (rabies, HBV,
tetanus), they should still receive the pathogen-specific Ig.

Jessica Plager
183
TOC

Neurology Altered Mental Status

Causes of AMS: major categories include 1) Metabolic, 2) Infectious, 3) Drugs/Toxins/Medications, 4) Primary CNS, 5) Delirium
• Duration: Hyperacute (sec-min): trauma, intracerebral bleed, stroke, seizure, ICP; Acute (min-hr): expanding bleed or
edema, med/toxin, metabolic; Subacute (hr-days): infectious, autoimmune, neoplastic, metabolic; Chronic (wks-months):
neurodegeneration, nutritional, neoplastic, autoimmune, psychiatric
• AEIOU TIPS: Alcohol (intox, HE, withdrawal, DTs, Wernicke’s)/Arrythmia, Electrolyte/Endocrine (gluc, thyroid, adrenal),
Infection, Oxygen (hypoxia, hypercarbia)/Overdose (opiate), Uremia/Urine retention, Trauma/Tumor/TTP/Temp, Iatrogenic
(meds - anticholinergics, BZDs, antidopaminergics, etc), Psych/Poison, Seizure (+post-ictal)/Stroke/Syncope
Approach to Acute AMS
• ABCs & vitals:
o If unresponsive & pulseless call Code Blue; if hypoxemic & GCS < 8 call Rapid Response & RICU for intubation
o Check RR (hypercarbia – opiates, COPD), BP (hypertensive encephalopathy), EKG (hypoperfusion, arrhythmia)
• Bedside exam:
GCS:
o Establish arousal (GCS), command following, attention (days of wk backwards);
Eye Opening:
look for cranial nerve problems or focal weakness - Spontaneously (+4)
o If not arousable, coma exam off sedation: pupils (CN 2/3), Doll’s eyes (CN - To verbal command (+3)
3/4/6/8), corneals (CN 5/7), symmetric grimace (CN 7), cough/gag (CN 9/10); - To pain (+2)
withdrawal to pain in extremities, posturing (JNNP 2001;71:i13) - No eye opening (+1)
o Pupil clues: absent light reflex (brainstem bleed/stroke, sedation, opioid, anoxia, - Not assessable (+1)
eye drops); b/l fixed, dilated (severe anoxia); u/l fixed, dilated (herniation w/ CN Verbal:
III compression); pinpoint (narcotic, ICH) - Oriented (+5)
o Trauma (c-spine), asterixis/myoclonus (toxic, metabolic), volume status, - Confused (+4)
- Inappropriate words (+3)
infectious/meningeal signs, cherry red discoloration (CO), findings c/f
- Incomprehensible sounds (+2)
toxidromes, tongue bite, incontinence (sz), tenderness (hip fx, fat embolus) - No verbal response (+1)
• STAT orders: - Intubated (+1),
o ALWAYS check fingerstick glucose for acute change in mental status +” T” to score (“3T”)
o Consider: ABG; if c/f stroke, head CT +/- CTA head & neck Motor:
• Work-up: - Obeys commands (+6)
o Review meds: hypoglycemic (insulin), BZD, opioid, steroid, anticholinergic - Localizes pain (+5)
(TCA), antihistamine, antihypertensive (methyldopa, reserpine), antiepileptic, - Withdrawal from pain (+4)
OTC’s, anti/dopaminergics, antibiotics (esp w/AKI, incl. cefepime, other CSPs, - Flexion to pain (+3)
- Extension to pain (+2)
PCN’s, FQs (Neurology 2016;86:963) - No motor response (+1)
o Check BMP, LFTs, CBC w/diff (infxn, PV, blast crisis, high/low plts), lactate,
NH3, VBG, UA/UCx/BCx, CXR, bladder scan (retention)
o Consider ESR, CRP, drug levels, serum/urine tox screen, CK (rhabdo/NMS), nutritional deficiency (B1, B12), TSH
o Consider TTP (classic:  plts, anemia, renal failure, fever, AMS). Check LDH & STAT smear for schistocytes
o Consider substance use or withdrawal, serotonin syndrome (T, HR, BP, RR, mydriasis, hyperactive bowels, hypertonia
esp in LE’s; e.g. SSRI + tramadol, MAOi, linezolid [NEJM 2005;352:1112]), neuroleptic malignant syndrome (T, HR, BP,
RR, rigidity; e.g. antipsychotic), toxic drug levels (salicylate, valproate, dig, lithium)
Approach to Subacute AMS: consider neurology consult prior to further extensive work-up
o Consider EEG with LTM: eval for intermittent seizures or non-convulsive status if routine EEG shows seizures
o Consider MRI w/ Gad (check CrCl first): eval for stroke, malignancy, infxn/inflammatory process, Wernicke’s
o Consider LP: image to r/o herniation first; eval for cancer, infxn (if c/f infxn, imaging should not delay abx)
 Standard studies: opening pressure, cell count, protein, glucose, Gram stain/Cx
 Malignancy: cytology, flow cytometry, IgH gene rearrangement (for CNS lymphoma), autoimmune encephalopathy
panel (d/w Neuro before sending)
 Infection: HSV, VZV, HIV (requires consent), cryptococcal Ag, AFB stain/Cx, fungal Cx, whipple PCR
 Other: AI encephalitis panel (d/w neuro first), IgG index and oligoclonal bands (will need SPEP to compare)
o Consider infection (HIV, lyme, syphilis), autoimmune (anti-NMDA, sarcoid), metabolic (thyroid, B1, B3, B12, Wilson’s), med
(MTX), HTN encephalopathy, PRES (tacro/cyclosporine), Addison’s crisis, porphyria (urine PBG)
o Consider neurodegenerative disease if more chronic presentation
Treatment of AMS: treat underlying cause; see disease-specific pages
• Hypovolemia: IVF; Hypoglycemia: D50 1-2 amps; Hypoxemia: O2; Seizure: protect airway, IV lorazepam 4mg if GTC > 2
min, then long-term AED; Trauma: stabilize C-spine; Meningitis: LP, empiric abx; EtOH toxicity: thiamine 500 mg IV TID
before sugar, then 100 PO QD; EtOH w/d: BZD vs. phenobarb; Opiate toxicity: naloxone IV/IM/SC bolus q3min (0.04 dilution
if mild, 0.4-2 bolus if coding); BZD toxicity: consider flumazenil 0.2 mg IV q1min; Hepatic encephalopathy: lactulose 30 ml
q4h titrate to BM + rifaximin 550 mg BID, consider SBP tx (diag para)
• Agitation management: ensure QTc <500. Haloperidol (IV/IM/PO; if dystonic rxn, give benadryl 25-50 IM/IV), olanzapine
(SL/PO/IM), quetiapine (PO) (Psych Clin Neurosci 2013;67:323)

Jef Gluckstein
184
TOC

Neurology Delirium
DELIRIUM or “Acute Brain Failure”: an acute disturbance of attention with fluctuating severity over the course of the day or
week & concomitant disturbance in cognition, neither of which are better explained by pre-existing/evolving neuro-cognitive
disorder or newly developed reduction in arousal. Presentation is a direct consequence of a medical condition, intoxication, or
withdrawal (DSM-5)
• Risk factors: Hx delirium/TIA/CVA/dementia, long hospitalization, EtOH, age >65 (~50% have delirium inpatient), infection,
visual/hearing impairment, comorbidity/severe illness, depression, HIV, h/o TBI
• Associated with mortality (JAMA 2010;304:433), institutionalization (Lancet 2014;383:911), cognition (NEJM 2012; 367:30)
• Both HYPERactive and HYPOactive delirium warrant treatment

AVOID DELIRIUM BY PREVENTING IT IN VULNERABLE PATIENTS

• Minimize deliriogenic meds: anticholinergics, antihistamines, benzodiazepines, opioids (optimize pain w/ non-opioids)
• Precautions: frequent reorientation, mobilize with PT/OT, OOB to chair, glasses/hearing aids, minimize
lines/telemetry/catheters, early volume repletion if c/f dehydration. Avoid room changes or physical restraints.
• Anticipate circadian dysfunction: standing melatonin 3 mg q6PM, lights on during day and off at night, schedule rx for
earlier in evening, avoid late diuresis, reduce noise.

CAM (Confusion Assessment Method)

If CAM⊕
• Do additional mental status exam
• Exam for inattention: reciting months of the
year backwards (Sn 84%); days of the week
backwards (Sp 82%) (JHM 2018;13:551)
• Start delirium precautions (see above)
• Evaluate for precipitating factors

Sn 94-100%, Sp 90-95%, high inter-rater reliability

(Annals 1990;113:941)

Management:
• Behavioral management (see top of page)
• Identify & treat UNDERLYING CAUSE w/ special attention to life-threatening conditions (see Altered Mental Status)
• Daily EKG to monitor QTc (goal <550ms); Daily repletion of K>4 & Mg>2 (in anticipation of pharmacotherapies)

Medical Management (for dangerous behavior ONLY, i.e. if pt is a danger to self or others)
1:1 sitter (re-orients) >> meds >> restraints (deliriogenic)
• For HYPERactive delirium/AGITATION  start PRN, escalate to scheduled (Nat Rev Neur. 2009; 5:210)
o Haloperidol 2-5mg IV q3h PRN vs. 0.5-1mg PO q4h PRN vs. IM q1h PRN (NB: can lead to EPS, acute dystonias in
Parkinsonism)
o Quetiapine 12.5-50 mg PO q6-12h PRN
o Olanzapine 2.5-10 mg SL/PO/IM qd-q4h PRN
• If continued severe agitation  consider Psych/Geri consult:
o Haloperidol PRN: double PRN dose q20 min till effective, ~5-20 mg IV, consider standing or gtt (ICU)
o Quetiapine PRN: standing 25-50 mg TID, extra dose HS
o Olanzapine PRN: standing 2.5-10 mg BID, extra dose HS
• QTc  severity: haloperidol > quetiapine > olanzapine; ∆ tx if QTc  by 25-50%, QTc>500, ⊕U-wave/T-wave flattening
• Discontinue when able, avoid benzos. Prolonged antipsychotic use in elderly can increase mortality.

When to Consider Psychiatry/Geri Consultation: When to Consider Neurology Consultation:

• Escalating/persistent delirium, Hx agitated delirium, • New focal finding suggesting stroke: Stroke p20202
underlying neurodegen. disorder (esp PD), hx TBI • Other concerning findings (convulsions, meningismus,
• Co-morbid EtOH or other substance use disorders e/o elevated ICP, abnl spot EEG/LP): General p20702
• Mult. med co-morbidities (esp CV dz)/critical illness • Know last seen well, baseline deficits, anticoag use
• At risk for disinhibition/impulsivity before calling!

Jef Gluckstein
185
TOC

Neurology Dementia
INITIAL EVALUATION: should almost always be in outpatient setting where can assess over time without acute illness or delirium
• Obtain collateral, determine symptom onset, ADLs/IADLs, assess safety, screen for depression
• Review medications for those with cognitive s/e’s (e.g. analgesics, anticholinergics, psychotropic medications, sedative-hypnotics)
• Assess cognitive impairment (MOCA >> MMSE), track score at subsequent visits
• Labs: CBC, TSH, BMP, B12; consider: tox, RPR, Lyme, HIV, UA, metals, ESR, LFT, folate, B1, B6 (Amer Fam Phys 2005;71:1745)
• Neuroimaging: NCHCT or MRI brain (preferred) to r/o structural lesion (tumor), assess atrophy pattern, eval for vascular dementia
and microhemorrhages (CAA). PET can be considered if dx unclear but often unnecessary.
• Formal neuropsych testing: pattern of deficits can suggest particular dementia syndrome; also helpful to r/o comorbid psych disease
• Inpatient evaluation should be considered for any rapidly progressing dementia syndrome or a new dementia diagnosis in pts <55
(consult Neuro for ?LP, consider RT-QuIC >14-3-3 [CJD], ACE [sarcoid], autoimmune encephalitis [only after d/w Neuro]), new focal
neurologic deficits (?stroke), fall with head trauma or LOC
• Outpatient Neurology referral to Memory/Cognitive clinic
DEMENTIA SYNDROMES (Prog Neurol Psych 2012;16:11, BMJ Neurol, Neurosurg, & Psych 2005;75:v15, Annals of Neurol 2008;64:97)
Syndrome Presentation Exam Imaging Treatment
Gradually Progressive
• Amnesia earliest sx; • Normal neuro exam (excluding Hippocampal (+/- • AChE-inhibitors
Alzheimer also language and MS) global) volume loss; (mild-severe dz)
Dementia visuospatial deficits • Neuropsych: amnesia w/ short ?microhemorrhages • NMDA-inhibitors
• Apraxia in later stages memory span, alexia, agraphia (CAA) (mod-severe dz)
• Fluctuations in • Parkinsonism: resting tremor Global volume loss • AChE-inhibitors
attention/alertness (can be absent), cogwheel (specifically
• Visual hallucinations rigidity, bradykinesia, rivastigmine) for
• REM behavior d/o stooped/shuffling gait – named memory sx
Lewy Body • Falls/syncope Parkinson’s dementia if • Carbidopa/levodopa
Dementia • Neuroleptic intolerance movement sx present for >1 yr trial for motor
• Memory problems late before dementia deficits
• Neuropsych: fluctuations w/ • Sx management of
intrusions and confabulation, autonomic dysfxn
visuospatial impairment
Behavioral variant most • May have frontal release Atrophy predominantly • Management of
common: signs (non-specific) in frontal and temporal behavioral sx (low
• Changes in personality • 15-20% get motor neuron dz lobes threshold c/s psych)
Frontotemporal (disinhibition, apathy) • Neuropsych testing: poor • AChE-inhibitors not
Dementia • Stereotyped behaviors impulse control, difficulty in helpful
• Lack of insight organization • Avoid NMDA-
Primary Progressive inhibitors
Aphasia variant
Stepwise Progressive
• Abrupt focal sx, • Focal deficits (depending on Cortical or subcortical • Secondary stroke
stepwise progression stroke location), can include: punctate lesions, prevention and risk
Vascular
• Depression common weakness, dysarthria, ataxia, white matter disease, factor modification
Dementia
• Hx: CVA, HTN, HLD, AF gait changes and volume-loss • AChE-inhibitor for
• Often look older than age memory deficits
Rapidly Progressive
• Rapidly progressive sx • Myoclonus, exaggerated MRI: cortical • No tx
Prion Diseases in memory, startle response ribboning on DWI, • Death w/in 1 year
(Sporadic, concentration, judgment • EPS: bradykinesia, nystagmus, subcortical (median disease
Variant • Mean onset age ~60 for ataxia hyperintensity on FLAIR duration 6 mo.)
Creutzfeldt- sporadic, 28 for variant • UMN signs (hyperreflexia, EEG: 1-Hz periodic
Jacob Disease) • Younger pts: more sig ⊕Babinksi, spasticity) epileptiform discharges
psychiatric sx • LP: RT-QuIC>>14-3-3
• Sx evolve days-weeks • Prominent psych features MRI: FLAIR • Immunotherapy:
Limbic (more indolent possible) • Dyskinesias, rigidity hyperintensity or steroids, IVIG,
Encephalitis • Short-term memory sx • Autonomic instability contrast enhancement PLEX, rituximab,
(Autoimmune, • Psych sx: agitation, • LP: lymphocytic pleocytosis, (esp in temporal lobe) cyclophosphamide
Paraneoplastic) delusions, hallucinations oligoclonal bands, EEG: extreme delta • Tumor resection
• Focal seizures autoantibodies (CSF + serum) brush very specific
TREATMENT: treat sx but do not slow the progression of disease
• AChE inhibitors: donepezil (first line), rivastigmine (patch), galantamine. Small effect on cognition, ADLs.
Major side effects: GI (n/v/d); less common bradycardia and heart block (increased vagal tone)
• NMDA inhibitors: memantine. Can precipitate agitation and exacerbate neuropsychiatric sx (caution in pts with sig behavioral sx)
Jef Gluckstein
186
TOC

Neurology Headache & Vertigo

HEADACHES: distinguish primary headaches (tension, migraine, etc.) from secondary headaches (tumor, ICP, vessel lesion, etc.)
Tension HA: ~40% population, ♀>♂. Band-like, radiate forehead to Red flags for secondary HA evaluation
occiput, mild-mod severity, 30m to 7d. Rarely seek eval. (Am Fam Physician
Symptoms Imaging
2002;66:797).
New HA >35 yo, abn neuro exam, MRI brain w/
• Abortives: NSAIDs, Tylenol. Can add caffeine/bultalbital, antiemetic acute, severe, positional, worse w/ contrast
(metoclopramide, promethazine). Use abortives no more than 2 days/wk. exertion, immunosuppressed,
• Preventatives: amitriptyline, nortriptyline, SSRI, tx OSA, smoking wakes at night
cessation Vestibular, brainstem, retinal, MRA or CTA head
motor sx & neck
Migraine HA: sx >3/5 criteria POUND (Pounding, Photo/phonophobia, Onset
4-72hrs, Unilat, N/V, Disabling) (JAMA 2006;296:1274)
• Migraine w/ aura: 1 reversible sx: visual (scintillating scotoma, visual field deficit), sensory (tingling, numbness), speech/lang, motor
(wkness, hemiplegic), basilar (dysarthria, vertigo, ataxia, diplopia), vestibular (vertigo), retinal (monocular field deficit). Similar
symptoms spread over minutes with each headache (stroke mimic). Aura without migraine headache possible (acephalgic migraine)
• Menstrual migraine: before/during menstruation  tx w/ NSAIDs or sumatriptan (Neurology 2008;70:1555). Consider preventive tx
perimenstrually w/ slow triptan (frovatriptan) 2.5mg QD/BID (begin 2d premenstrually, for total 6d/month)
• Abortives: Tx early, escalate stepwise. Triptans (max 4x/d, 2x/wk)
o Mild/mod pain: Tylenol, Mg (2g IV), NSAIDs, IVF (Headache 2012;52:467) Nasal: Sumatriptan 5-20mg q2hrs (max 40mg/day),
o Mod/sev pain: IVF, triptan, antiemetics (metoclopramide, prochlorperazine Zolmitriptan 5mg q2hrs (max 10mg/d)
10mg IV q8h), VPA 500mg IV, DHE, steroids (dexameth 10-25mg IV x1) SC: Sumatriptan 4-6mg q1hr (max 12mg/d; 70-80%
(Headache 2012;52:114). pts w/ sx reduction; 35% resolution)
• Preventatives: if >3 d/mo, long aura, or disability (Neurology 2012;78:1337) PO: Sumatriptan 25-100mg q2hr (max 200mg/day),
o BB/CCB: propranolol 20mg BID, incr to 40-160mg/day. Metoprolol 25mg Zolmitriptan 1.25-2.5 q2hrs (max 10mg/d)
BID, inc to 50-200mg/day. Verapamil 80mg TID, increase gradually. C/I: ischemic CVD/CAD (vasoconstriction), PVD,
liver disease, basilar migraine, MAOIs within 2 wks
o Antidepressants: amitryptiline/nortriptyline 10mg qhs, incr to 150mg.
*Caution w/ SSRIs 2/2 risk of serotonin syndrome
Venlafaxine 37.5 mg QD, inc to 75-150 mg. Dihydroergotamine (DHE)
o Anticonvulsants: topiramate 25mg QD, inc gradually 100mg BID. VPA IV: 0.5-1mg IV Q8h x5 days preferred to x1 dose
500-1500 mg qD (avoid both of these in young ♀). (max 3mg/day)
o Supplements: magnesium 400mg QD, riboflavin 400mg QD, feverfew Nasal: 1 spray /nostril q15min (max 6 spray/day,
o Botox: referral to headache clinic 8/week); SC: 1mg SC q1hr (max 3mg/day)
Same C/I as Triptans, do not mix with triptans w/in
VERTIGO: illusion of motion of self or world 2/2 vestib dysfxn; a/w n/v, postural/gait 24hrs
instability. Important to distinguish: central vs peripheral (Am Fam Physician 2017;95:154)
• Hx/Exam: duration of sx, episodic/persistent, triggers (position Δ), prior sx, assoc sx (5D’s for brainstem: dysarthria, diplopia,
dysphagia, dysphonia, dysmetria). Orthostatics. Dix-Hallpike. HINTS.
• HINTS exam: everything must be c/w peripheral to be reassuring. In acute vertigo, Sn 97% / Sp 85% for stroke (better than MRI!)
Head Impulse (pt looks at your nose, passively rotate head. No saccade = ambiguous. Catchup saccade = peripheral).
Nystagmus (unidirectional e.g. always left-beating = peripheral; L-beating in L gaze, R-beating in R gaze, any vertical = central).
Test of Skew (cover one eye then other, any vertical skew/correction = central) (Acad Em Med 2013;20:986)
Symptoms Ddx Imaging
Benign positional paroxysmal vertigo (BPPV), infection
Severe nausea, mild
(labyrinthitis, vestibular neuritis, herpes zoster oticus), If exam reassuring,
Peripheral imbalance, hearing
Meniere’s, vestibular migraine, otosclerosis, trauma none
loss/tinnitus
(perilymphatic fistula)
Cerebral infarction (vertebrobasilar ischemia), TIA,
Mild nausea, severe MRI brain w/wo
hemorrhage, toxic, cerebellopontine mass (vestib
Central imbalance, rare hearing contrast, coronal DWI,
schwannoma, ependymoma, brainstem glioma,
sx MRA head & neck
medulloblastoma, neurofibromatosis, MS, vestibular migraine
• Treatment: metoclopramide, prochlorperazine, meclizine (2 wks max, vestib suppression), lorazepam, diazepam AND vestibular PT

Approach to Acute Dizziness Acute Add sx c/f

Med w/u
dizziness medical etiology

Episodic Ongoing

Position Not Position

HINTS+ exam
triggered triggered

Dix Hallpike + Medical w/u, No catchup saccade OR +catchup saccade AND

Orthostatics
Supine Roll Test consider imaging Direction changing nystagmus OR Unidirectional nystagmus AND
Vertical skew OR No vertical skew AND
Nystagmus? New unilateral hearing deficit No new unilateral hearing deficit

Hallpike (upbeat Other / None: Image to r/o Likely

torsional) OR Image to r/o central lesion peripheral
Supine Roll central lesion
(horizontal)
c/w BPPV

Jef Gluckstein
187
TOC

Neurology Stroke & TIA

**Consider stroke for any sudden-onset focal neurologic symptoms** IV tPA
ACUTE STROKE ACTIVATION Inclusion:
1) If high suspicion and onset of sx within past 24h, page stroke resident 1. Clinical dx w/ measurable deficit, age ≥ 18
p20202. If they agree with stroke diagnosis, activate acute stroke code. 2. Time since last seen well <4.5 hrs
2) BE AT BEDSIDE. Consider this a code-equivalent. Ensure 18g PIV is (may be 9h soon NEJM 2019; 380:1795)
in place and bed is ready for travel with travel monitor in place Exclusion:
3) ABC/Vitals: check VS, EKG, telemetry, glucose, keep NPO & History: stroke/head trauma in last 3 mo.;
HOB >30°. Do not treat HTN unless BP >220/120, ACS, or ICH (see recent head/spine surg; prior ICH; intracranial
below) malignancy, AV malformation, aneurysm;
4) Be ready to provide the following information: incompressible arterial puncture last 7 days
a) Last seen well (LSW) time (last time patient confirmed to be Clinical: SAH sx; BP ≥185/≥110 (treat!); BG
normal) – this is NOT the time that sx were noticed by you or patient <50; active internal bleeding; bleeding diathesis
b) AC or antiplatelets, CrCl, allergies, code status, baseline function Heme: Plt <100K; current AC (warfarin w/
c) Contraindications to tPA - even if present, call an acute stroke INR >1.7; therapeutic heparin use w/in 48 hrs
(patient may be candidate for thrombectomy) w/ PTT; DOAC within 48 hours)
d) Use NIH stroke scale (NIHSS) to quantify severity Head CT: hemorrhage; multilobar infarct >1/3
e) Most predictive physical exam findings: facial paresis, arm involvement of cerebral hemisphere
drift/weakness, and abnormal speech (JAMA 2005;293:239)
5) STAT CTA Head and Neck (only need to order CTA; it includes non-con
Intra-arterial therapy
head CT). If unable to receive contrast and/or LSW ≥6 hrs, stroke team Inclusion:
will consider STAT MRI +/- MRA. 1. Clinical: NIHSS ≥ 6, LSW ≤ 24 hrs, age 18-
6) Labs: check BMP, LFTs, CBC, PT/INR/PTT, Trop, UA/UCx, tox screen, 85, baseline mRS ≤1, life expectancy > 12 mo.
& AED levels (if appropriate) 2. Radiological: ICA or MCA M1/2 occlusion,
basilar or dominant vert occlusion, small infarct
ACUTE STROKE INITIAL MANAGEMENT core volume (CT: ASPECTS ≥ 6 + collaterals;
(Stroke team will provide guidance, but IV tPA may be given by any MD) MRI: 70 cc by DWI)
1. ISCHEMIC STROKE: (MGH In House Stroke Protocol) Exclusion:
• IV (intravenous) thrombolysis (tPA): Clinical: BP ≥185/≥110 (treat!), BG<50 or >400
o LSW 0-3 hr: goal to start IV tPA w/in 60 min of ED arrival (AHA/ASA Heme: Plt <40k, INR >3
Guidelines Stroke 2018)
o LSW 3-4.5 hr: IV tPA recommended but w/ relative exclusion criteria including age >80, AC (regardless of INR), NIHSS score
>25, ischemia >33% of the MCA territory, h/o both stroke & DM2 (ECASS III NEJM 2008;359:1317) (note: guidelines are actively
changing)
o Dosing: 0.9 mg/kg; 10% bolus over 1min, remainder infused over 1hr
• Intra-arterial therapy (thrombectomy, thrombolysis):
o Patients with disabling deficit & large vessel occlusion with LSW <6 hours (MR CLEAN NEJM 2015;372)
o May extend time to LSW 6-24 hr based on imaging criteria (DAWN NEJM 2018;378:11)
• BP control: low SBP (<150) a/w poor outcome (Arch Intern Med 2003;163:211)
o If tPA candidate: goal BP ≤185/110 prior to tPA (treat STAT if higher!); goal BP ≤180/105 after tPA for 24 hours
o If no tPA: goal BP ≤220/120 (allow auto-regulation) for 1d; lower SBP <20 per day subsequently
o If anticoagulated: goal SBP ≤180
o If active cardiovascular disease (ACS) & requires tighter BP control, discuss w/ neuro
o Monitor neuro exam - sx worse at low BP suggests critical stenosis  lay bed flat, give IVF bolus, STAT page neuro
2. HEMORRHAGIC STROKE (see intracerebral hemorrhage section in CNS Emergencies)

INPATIENT POST-STROKE CARE

• Frequent neuro checks q1-2 hr x 24 hrs if unstable/ICU; q4h if stable/floor pt, STAT head CT if change in exam.
• Consult PT, OT, SLP (NPO until bedside swallow eval). Keep euthermic (antipyretics), euglycemic (FSG<180), Mg>2.
• If received tPA: NCHCT 24 hrs post-tPA  if no e/o hemorrhagic transformation, start antiplatelet + DVT ppx.
• If did not receive tPA: ASA 325 mg x1, followed by long-term antiplatelet or AC (may delay AC for large ischemic strokes). Start DVT
ppx if ischemic stroke (unless large hemorrhagic conversion).
• Antiplatelet long-term 2° prevention
o ASA 81mg QD (50-325 mg/d effective; ≤200 mg/d lower risk of major bleed) (Am J Cardiol 2005;95:1218)
o Clopidogrel 75mg QD (may be superior to ASA for atherosclerotic vascular dz) (CAPRIE Lancet 1996;348:1329)
o DAPT (ASA + clopidogrel)
 TIA or minor stroke: consider in patients w/ NIHSS<4 or TIA. ASA+clopidogrel for 3 wks followed by clopidogrel (or ASA)
alone (CHANCE NEJM 2013;369:11). Can consider clopidogrel load (300-600 mg) w/in 24 hrs of symptoms.
 Symptomatic intracranial stenosis: can consider ASA/clopidogrel for 3 mo (SAMMPRIS NEJM 2011;365:993)
 Recurrent stroke on ASA or clopidogrel alone + significant athero: some use DAPT long-term; no clear evidence &
higher bleed risk (CHARISMA NEJM 2006;354:1706 & MATCH Lancet 2004;364:331) – discuss w/ neurology.
• Anticoagulation long-term 2° prevention (embolic infarcts from AFib, paradoxical embolus, LV thrombus or hypercoagulable state)
o Warfarin or DOAC for pts w/ AF (hold off x 2-4 wk if hemorrhagic conversion or large hemispheric stroke)
o No need for both antiplatelet & anticoagulation
Jef Gluckstein
188
TOC

Neurology Stroke & TIA

• Start Atorvastatin 80 mg w/ LDL goal < 70 (NEJM 2020;382:9)
• Work up/secondary prevention: (see below)
o Labs: lipids, A1c, TSH, ESR/CRP; if <60 y/o, send tox screen (cocaine), hypercoagulability w/u (if recommended by neuro)
o Imaging: head and neck CTA or MRA (can do TOF if low GFR); carotid U/S as alternative
o Cardiac workup: EKG, TTE (with bubble if <60), inpatient tele then 30-day MCOT vs. LINQ if tele is negative for AFib

CARDIOEMBOLIC STROKE
SUSPECT WHEN: DX WORKUP:
• ACA/MCA/PCA occlusion w/o sig vascular dz • TTE (w/ bubble if < 60 yo) - if PFO, r/o venous thrombus (LENIs/
• Infarcts in multiple territories or cerebellar stroke MRV pelvis), can consider closure (RESPECT NEJM 2017;377:1022)
• Known risk factors (LA/LV thrombus, AFib, • Inpatient telemetry followed by 30-day MCOT vs. LINQ at discharge
LVEF<25%, aortic disease, intracardiac shunt) (unless known AFib)
• Hypercoagulability/hyperviscosity (solid organ or ACUTE MANAGEMENT CONCERNS:
heme malignancy, HbSS, cryo, clotting d/o) • Avoid immediate AC unless known intracardiac thrombus or
mechanical valve. Transition to long-term AC in 2-4 weeks.
SYMPTOMATIC CAROTID STENOSIS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• Carotid stenosis present on ipsilateral side • If >50% carotid stenosis causing stroke/TIA, consider carotid
• H/o amaurosis fugax revascularization (stent/angioplasty/endarterectomy) – ideally w/in 2
DIAGNOSTIC WORKUP: weeks of sx (NASCET II NEJM 1998;339:1415)
• CTA vs. MRA head & neck usually sufficient • Consider temporary anticoagulation (d/w neurology)
• Alternatives: carotid US - typically need carotid • Consider induced HTN if symptoms fluctuate with BP
U/S prior to carotid endarterectomy (CEA)
INFECTIVE ENDOCARDITIS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• Unexplained fever w/ stroke or pt with valvular dz • Immediate antibiotics; caution with tPA
DIAGNOSTIC WORKUP: • Early cardiac surgery if small non-hemorrhagic stroke; delayed cardiac
• Blood cultures, TTE followed by TEE if neg surgery (2-4 wk) if large or hemorrhagic stroke
• CTA head to identify mycotic aneurysms (↑risk • Avoid anticoagulation or antiplatelet w/o a separate indication
bleeding)
• If CTA negative, may need conventional angio
(CTA not as sensitive for mycotic aneurysms)
CAROTID AND VERTEBRAL DISSECTIONS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• <60 yo or posterior circulation stroke in pt w/o RFs • Goal of tx is to prevent stroke: highest risk in first few days
• Neck pain, HA, or Horner’s syndrome • Anticoagulation vs antiplatelet. Prefer antiplatelet if: sx onset >3d
• Trauma (vertebral fx), chiropractor, coughing spells ago, dissection extends intradurally (no AC due to risk of SAH), large
DIAGNOSTIC WORKUP: infarct (risk of hemorrhage) (CADISS Lancet Neurol 2015;14:361)
• CTA vs. MRA with T1 fat saturation • High rate of recanalization  Tx 3 months then re-image vessel
• Consider comorbid conditions (Marfan’s, FMD)
CEREBRAL VENOUS SINUS THROMBOSIS
SUSPECT WHEN: ACUTE MANAGEMENT CONCERNS:
• Positional HA, vomiting, papilledema, vision Δ • Immediate anticoagulation even in presence of hemorrhage
• P/w seizure (common, may be difficult to control) • AEDs if seizures (not indicated for ppx)
DIAGNOSTIC WORKUP: • IV fluids, avoid dehydration, modify risk factors (smoking, OCPs)
• NCHCT: hyperdensity in torcula (dense delta sign)
• CTV vs. MRV to assess intracranial venous system
• Consider hypercoagulable workup

TRANSIENT ISCHEMIC ATTACK (TIA)

• Definition: transient neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia w/o acute infarction or end-organ
injury as assessed clinically or by imaging
• Causes: atherothrombotic stenosis (ICA, vertebral, basilar, small vessel), embolic (arterial, aortic, cardiac, paradoxical), dissection
(ICA, vertebral) – identification will guide tx (antiplatelet therapy vs. search for underlying arrhythmia +/- anticoagulation)
• Imaging: MRI (w/ DWI/ADC) w/in 24hr of sx onset and vessel imaging of head and neck for large vessel occlusive disease (e.g. MRA
(time of flight if low GFR) vs. CTA vs. carotid ultrasound
• Cardiac w/u: TTE to excl thrombus & PFO (age <60) & tele/MCOT vs. LINQ monitoring to exclude Afib if suspected embolic TIA
• ABCD2 score (Age, BP, Clinical features, Sx Duration, Diabetes): used to identify pts w/ high risk of ischemic stroke w/in 1wk of TIA
• Management: immediate intervention reduces the risk of recurrent stroke (1.5-3.5% risk within 48h), see 2° Prevention above

Jef Gluckstein
189
TOC

Neurology CNS Emergencies

Intracranial Hemorrhage (ICH): epidural (EDH), subdural (SDH), subarachnoid (SAH), intraparenchymal hemorrhages (IPH)
• Causes: trauma (all), ruptured aneurysm/AVM (SAH, IPH), IPH also caused by HTN, cerebral amyloid, tumor (most common w/ met
breast Ca, lung Ca, melanoma, RCC, choroid, thyroid CA’s), cortical vein thrombosis, venous sinus thrombosis
• Presentation: acute focal neuro deficit, +/- progressive consciousness, n/v. SAH: thunderclap HA, N/V, meningismus; EDH/SDH:
s/p trauma, lucid interval with EDH; IPH: focal neuro symptoms (may mimic ischemic stroke clinically); often with HA.
• Tests: STAT imaging (NCHCT for all; +CTA head if SAH/IPH), coags/PLTs; need f/u scan at 6h to assess progression
• STAT management:
− STAT Neurosurg (p21111) if SAH/SDH/EDH; otherwise, Neuro (inpatient: p20202; in ED: p20000).
− Elevate HOB to 30-45° to reduce ICP and prevent aspiration
− BP control: SBP < 140 (studied in SAH or ICH due to ruptured aneurysm/AVM), use IV labetalol or nicardipine drip (avoid
hydralazine if possible), place arterial line (INTERACT Lancet Neurol 2008;7:391, ATACH Crit Care Med 2010;38:637)
− Correct coags: warfarin/INR>1.5: tx (vitamin K 10 mg IV x 1) AND (3-5U FFP or Kcentra); Plt (transfuse, goal >50);
Uremia/antiplt use: consider DDAVP 0.3mcg/kg IV; heparin/LMWH: protamine; s/p tPA (check fibrinogen, give cryo, +/- amicar),
rivaroxaban/apixaban: give Andexanet Alfa; dosing based on size and timing of last dose (call pharmacy)
− Venous sinus thrombosis (VST): anticoagulate w/ LMWH/heparin despite hemorrhage (Lancet 1991;338:597). Manage ICP and
seizures.
− Prognosis depends on age, GCS, pre-ICH cognitive impairment and ICH volume/location (FUNC Score) (Stroke 2008;39:2304)
− Typically acceptable to restart DVT ppx in smaller hemorrhages if stable after 48hrs, but confirm w/ neurology

Elevated Intracranial Pressure (ICP) / Herniation

• Etiologies: mass (tumor, abscess, hemorrhage), cerebral edema (infarction, inflammation, hyperammonemia, DKA), hydrocephalus
(tumor, intraventricular hemorrhage, leptomeningeal disease, meningitis), PRES. High ICP may cause compression/ischemia. Severe
local swelling or CSF drainage with large space-occupying lesions causes herniation (displacement and compression of brain).
• Signs of herniation: fixed/dilated/asymmetric pupil (often 1 first) accompanied by nausea, somnolence/confusion, or limited upgaze;
flexor/extensor posturing; ipsilateral hemiparesis (uncal herniation); Cushing’s triad (bradycardia, sys HTN, & irreg. breathing)
• Tests: STAT head CT
• Management:
− STAT Neurosurg (p21111) (for ICP monitor/EVD placement/decompressive hemicraniectomy)
− Secure ABCs, elevate HOB to 30-45˚, keep head midline (to secure venous drainage), treat pain/agitation
− Neuro-ICU level monitoring (p20202 can help coordinate)
− Hyperventilate to PaCO2 ~ 30-35 mmHg (if suspect herniation, transiently reduces ICP), only for short-term management
− IV mannitol therapy 1g/kg q6h (use with caution in pts on HD) and/or 23% saline 15cc q6h. Check BMP, Sosm q6h. No mannitol
if osm gap >15, Na >160, or serum osm >340. No 23% saline if Na >160
− If related to edema from malignancy or bacterial infection, give 10mg IV dexamethasone x 1, then 8mg BID
− Complications during LP: if sx of herniation/opening pressures > 40 cm H2O with space occupying lesion, consider
STAT head CT. Immediately replace stylet into needle, only drain CSF in the manometer, STAT Neurosurg.

Hypertensive Encephalopathy: PRES (posterior reversible encephalopathy syndrome)

• Typically associated with: severe HTN, but also relative HTN in setting of preeclampsia/eclampsia, cytotoxic/immunosuppressive
drugs (cyclosporine, tacrolimus, cisplatin, bevacizumab), acute/chronic renal failure, uremia, sepsis, vasculitides, TTP due to
impaired cerebral autoregulation and endothelial dysfunction, hypoMg (NEJM 1996;334:494)
• Symptoms: HA, confusion, decreased consciousness, visual disturbances, seizures, can result in ICH and ICP
• Tests: Brain MRI w/con: FLAIR w vasogenic edema w/in white matter in the posterior cerebral hemispheres; DWI/ADC nl (but can
have strokes also); add’ll regions can be incl including brainstem, cerebellum, basal ganglia, frontal lobes
• Management: ICU if severe, strict BP control (reduce 25% daily, if severe use nicardipine or labetalol drip), treat seizures, Mg2+ (esp
in eclampsia), remove inciting factor
• Prognosis: often fully reversible; complications include progressive cerebral edema, ICH, stroke, death

Cord Compression: high level of suspicion in cancer patients with back pain, urinary sx or LE weakness
• Etiologies: subacute (tumor/mets, abscesses) vs acute (disc herniation, trauma, hemorrhage)
• Symptoms: back pain, motor weakness, hyperreflexia below lesion if chronic (*can be hyporeflexic in acute injury or w/cauda equina),
⊕Babinski, loss of sensation (assess level), bowel/bladder incontinence OR retention, loss of rectal tone, saddle anesthesia
• Tests: STAT whole spine MRI w/contrast (cord compression protocol), call ED MRI (x63050) or inpt MRI (x64226)
• STAT page NSGY/Ortho spine +/- Rad Onc (x68652) for possible XRT if tumor related
• Dexamethasone (10mg IV x1 then 8mg IV BID), esp in malignancy. Solumedrol in acute cord injury 2/2 trauma is controversial

Jef Gluckstein
190
TOC

Neurology Seizures
Definitions (Epilepsia 2014;55:475, Epilepsia 2015;56:1515, Continuum 2019;25:306, MGH Status Epilepticus Treatment Protocol)
• Epilepsy: ≥2 unprovoked seizures >24h apart or 1 unprovoked seizure + recurrence risk ≥60% over the next 10 yrs
• Status epilepticus: at least 5 mins of continuous seizure or 2+ seizures w/ incomplete recovery of consciousness in between
• Non-convulsive status epilepticus: non-convulsive electrographic seizure ≥10s or rhythmic EEG responsive to seizure treatment
• Tonic: persistent flexion/extension; Clonic: limb jerking; Atonic: loss of postural tone; Myoclonic: sudden brief muscle contraction
• Psychogenic Non-Epileptic Seizures (PNES): important to distinguish from epileptic events. Common features: waxing and waning
movements or fluctuating course, long duration of events, eye closure, ictal crying, gradual onset, asynchronous movements, pelvic
thrusting, recall during the period of apparent unresponsiveness, and hyperventilation (Ann Neurol 2011;69:997)
• Classification (Epilepsia 2017;58:522)
o Focal: unilateral, occuring in one hemisphere +/- impaired awareness (formerly simple partial, complex partial)
o Generalized: occuring in and rapidly engaging b/l distributed networks
Etiology: provoked vs not? Primary epilepsy, vascular (stroke/ischemia/hemorrhage), withdrawal (EtOH/BZDs), mass lesions (tumor,
abscess), trauma, metabolic ( glc, CO2, O2, Ca), meds, infection (systemic, CNS), HTN or HoTN, high fever, eclampsia, PRES
• Ddx: syncope, TIA, migraine, PNES (~30% also have epilepsy), myoclonus, dystonia, cataplexy, tremor
• H&P: previous sz history, prodrome (palpitation, sweating, N/V, aura), med list (many lower sz threshold), triggers (exertion,
pain/fatigue/emotional stress, cough/urination/defecation), tongue biting, incontinence, lateralizing signs, alcohol. GET COLLATERAL.
• Labs: FSBG, Tox, AED levels, lytes, CBC, LFTs, NH3, VBG, CK, INR, lactate, troponin, blood cx, b-hcg. Prolactin Sn ~50%
• Monitoring: tele ( risk for fatal cardiac arrhythmias during ictal/post-ictal period; ictal arrhythmias  risk of sudden death)
• Neuroimaging: obtain in all w/ unprovoked 1st sz (MRI w/ con more sens) (Neuro 2015;84:1705) or if focal neuro exam, h/o trauma,
malignancy, HIV, or focal seizure (Neuro 2007;69:1772). Imaging changes management in ~10% (Neuro 2007;69:1996).
• LP/BCx: if febrile, HIV/immunocompromised, or if no clear etiology
• EEG: within 24h-48h if not seizing, emergent EEG if seizing: DO NOT wait to manage. If emergent, contact EEG fellow (p16834)
TREATMENT OF STATUS EPILEPTICUS
 ABCs: VS, O2, EKG First 5-10 min (1st line):  Correct reversible  Concurrently: call neuro, RICU,
 Assess pt safety  Ativan 4 mg IV over 2 min  causes: FSBG continuous EEG
 Place 2 PIVs (BZD + repeat 4 mg x1 PRN in 5min (start IV thiamine +  Check AED levels and rebolus if
PHT incompatible)  If no IV, diazepam 20 mg PR or D50), lytes, fever, needed  PHT, VPA, PHB 1 hr
midaz 10 mg IM/nasal/buccal O2 after load, FOS-PHT 2 hrs after
(RAMPART Trial) load (correct for albumin)
Persistent SZ (10-30 min, 2nd line): Refractory SZ (30-60 min, 3rd line):
 Levetiracetam, VPA, fosphenytoin/phenytoin, phenobarb, +/-  Intubate, continuous EEG
lacosamide (pre/post EKG to check PR) Midaz (if HD unstable) +/- propofol gtt
Seizure PPX: no AED in 1st seizure unless previous brain injury (Level A) OR abnormal EEG (Level A) OR significant abnormal imaging
(Level B). Early AED reduces short term recurrence (<2yr), not sustained remission (3+ yrs) (Neuro 2015;84:1705).
• ETOH seizure: Ppx not indicated when intoxication or withdrawal is the cause of seizure (Neuro 2006;67:s45)
• Brain tumor: no ppx (Cochrane 2008;CD004424). If seizures occur, start AEDs: Keppra > Lacosamide (fewer chemo interactions)
• Severe TBI: Keppra 500-750 mg BID x 7 days (Neurosurg Focus 2008;25:E3)
• ICH: AED only if clinical seizure or traumatic etiology, Keppra 500mg BID x 7days (Stroke 2016;47:2666)
• PNES: treatment with outpatient Cognitive Behavioral Therapy (CBT), psychiatry involvement. In acute setting it may be helpful to
educate patients about functional neurologic symptoms (http://www.neurosymptoms.org), and place social work consult.
• In MA, no driving for LOC event until 6 mos event free. Counsel pt and include in discharge summary. (Driving laws database)
AED Loading Dosing Goal Level Side Effects
60mg/kg No goal, level to Psychiatric sx (irritability, anxiety, depression, sedation,
Levetiracetam (Keppra) 1:1 PO:IV
Max 4.5g check adherence psychosis).
Teratogenic. Abnormal LFTs, weight gain, hair loss, N/V,
Valproic acid 20- 50-100 mcg/mL
1:1 PO:IV encephalopathy (NH3), pancreatitis, thrombocytopenia.
(Depakote) 40mg/kg (>1h post load)
Good for mood disorders.
10-20 mcg/mL, Teratogenic. Gingival hypertrophy, hair growth, rash, AMS,
Phenytoin (Dilantin), 20 pheny
1:1 PO:IV correct for alb, diplopia, ataxia, slurred speech, hypotension/arrhythmia (if
Fosphenytoin equiv/kg
(2h post load) run faster than 50mg/min; Fosphenytoin is less cardiotoxic).
Headache, diplopia, dizziness, nausea, hypotension. Obtain
Lacosamide (Vimpat) 200-400mg 1:1 PO:IV 10-20 mcg/mL
EKG prior and after load, and watch for PR prolongation.
Rash, SJS, nausea, somnolence, dizziness, ataxia. Good in
Lamotrigine (Lamictal) No Load Only PO 3-15 mcg/mL
mood disorders.
Weight loss, fatigue, teratogenic. Nephrolithiasis,
Topiramate (Topamax) No Load Only PO N/A
cognitive decline, anxiety, anorexia, tremor
Carbamazepine SIADH, N/V/D, rash, pruritis, fatigue, blurred vision, diplopia,
No Load Only PO 4-12 mcg/mL lethargy. Screening for HLA-B*1502 in Asians.
(Tegretol)

YanCheng Luo
191
TOC

Neurology Weakness & Neuromuscular Disorders

APPROACH TO WEAKNESS
• Ask about functional issues (getting out of chair, tripping over curbs/stairs)
• UMN signs: spasticity, increased tone, hyperreflexia, ⊕Babinski; LMN signs: fasciculations, atrophy, decreased tone, hyporeflexia
• Pattern: UMN (extensors in UEs, flexors in LEs), proximal (many myopathies), bulbar (dysphagia, dysarthria, diplopia)
• Associated sensory sx: reduced sensation, tingling, burning, allodynia, hyperalgesia, decreased temperature sense, imbalance
• Autonomic sx: orthostasis, constipation, urinary retention, erectile dysfunction, changes in sweating, hair loss, post-prandial nausea
• EMG/NCS: can be helpful with localization, determining fiber type involved, determining if disease is axonal vs demyelinating (which
guides tx), and determining injury extent (which guides prognosis). Often higher yield at least 2-3 weeks into illness and as outpt.
Localization Associated Signs/Sx Diagnostics Important/Common Causes
Cortical signs MRI Brain best initial test (+gad if c/f Vascular (hemorrhage or ischemia), tumor,
(language/visual cancer, infxn, demyelinating dz) trauma, demyelinating
Brain
field/neglect), cerebellar
sx, UMN signs
Sensory level, MRI Spine (level based on sx, +gad if Transverse myelitis (MS, NMO, connective
bowel/bladder dysfxn, c/f cancer, infxn, demyelinating dz) tissue dz), infxn (viral myelitis, HTLV),
Spinal Cord
UMN signs. CSF if c/f inflammatory or infxn compression (tumor/disc/abscess), vascular,
trauma, paraneoplastic, toxic, B12/Cu
LMN signs. If motor NCS/EMG ALS, SMA, polio, acute flaccid myelitis
Anterior Horn
neuron dz: both UMN +/- MRI brain and spine; LP (pediatric)
Cell
and LMN signs.
Motor/sensory sx MRI Spine (level based on sx) Nerve root compression (disc herniation,
corresponding to nerve LP if polyradiculopathy spondylosis) by far most common;
Radiculopathy root. ⊕Radiating pain. NCS/EMG: helpful for localization polyradiculopathy: GBS, iatrogenic (post-op,
(sensitivity imperfect  clinical dx) chemo), ischemic, infxn (HIV, Lyme, CMV,
EBV), DM (typically thoracic), sarcoid, malig.
Sensory symptoms; Labs: highest yield = A1c, B12 + Symmetric/length-dependent:
autonomic dysfxn if MMA, SPEP + immunofixation toxic/metabolic/nutritional (DM, chemo, EtOH,
small fibers affected. Add’l labs (in select pts): Lyme, RPR, B12, critical illness), paraprotein-related,
Peripheral Often symmetric and HIV, malnutrition (B1, B6, vit E, B3, hereditary (CMT); polyradiculoneuropathy:
Neuropathy length dependent. GBS Cu), vasculitis (ANCA, ANA, ESR, GBS/CIDP, DM, Lyme; mononeuropathy:
is ascending. CRP, RF, C3/C4), celiac, ACE compression/trauma; mononeuropathy
NCS/EMG: localization & pattern (NB: multiplex: vasculitis, amyloid, sarcoid, HNPP
nl NCS doesn’t exclude small fiber dz)
Weakness is fatigable Ice pack test, tensilon (rarely) Myasthenia gravis, Lambert–Eaton, botulism,
and improves with rest. Labs: myasthenia panel (see below) tick paralysis
NMJ A/w ptosis, diplopia. No NCS/EMG: repetitive stimulation,
sensory sx. single fiber EMG
CT chest I+ if above c/w myasthenia
Proximal weakness Initial labs: CK, aldolase, LDH, LFTs, Critical illness, medication-related (steroids,
most common. Pain TSH/fT4, PTH, ESR/CRP statins, colchicine, cyclosporine, NRTI),
Myopathy uncommon. EMG: e/o muscle irritability, chronicity inflammatory myopathies (inclusion body
May need muscle biopsy myositis, dermatomyositis, polymyositis)
GUILLAIN-BARRÉ SYNDROME (Acute Inflammatory Demyelinating Polyradiculoneuropathy): symmetric, ascending numbness &
weakness, absent reflexes (may be present acutely), facial weakness, autonomic instability, acute resp failure (30% of patients)
• Causes: often recent infection (Campylobacter jejuni, HIV, CMV, EBV, Zika) or vaccination (rare)
• Dx: LP w/ albuminocyt. dissoc. (high protein, norm WBCs). Anti-GQ1B in CMF variant. NCS/EMG: highest yield 2-3wks after sx onset
• Tx: IVIG or plasmapheresis (equiv. outcomes); monitor respiratory function with NIF/VC TID (done by RT) - more frequent if crisis
• Elective intubation w/ 20-30-40 Rule: VC <20mL/kg, NIF weaker than -30cm H2O, MEF <40 cm H2O, OR ≥ 20% decline in ~24 hrs
MYASTHENIA GRAVIS/LAMBERT EATON (MG/LEMS): weakness of voluntary muscles, worse w/ exertion & repetitive movements and
in the evening. Typically involves ocular (ptosis, diplopia), bulbar, respiratory, neck and proximal>distal limb muscles.
• Cause: auto-Abs against postsynaptic ACh-R in skeletal muscle (MG) or voltage-gated calcium channels (LEMS)
• Exam: upgaze fatiguability – hold sustained upgaze for 1 min, look for development of ptosis. After observing ptosis, place ice on eyes
for 1 min, weakness will improve (Tensilon test rare, requires atropine at the bedside. Only improves MG not LEMS).
• Dx: Ach-R Ab (80-90% seropositive, specific); if neg. check anti-MUSK. EMG/NCS: order w/ repetitive stim; will show decremental
response (MG) or potentiation (LEMS). Chest CT I+: r/o thymoma (in 70-80% MG). Find underlying malignancy in LEMS.
• Tx: symptomatic (pyridostigmine); immunotherapy: rapid (IVIG, plasmapheresis), chronic (steroids+/-azathioprine/MMF); thymectomy
MYASTHENIC CRISIS: MG exacerbation requiring intubation or delayed extubation post-surgery
• Triggers: surgery, infection, IV contrast, pregnancy, certain drugs/meds (antibiotics including fluoroquinolones, aminoglycosides;
anticonvulsants; antipsychotics; BBs; CCBs; Mg). AVOID succinylcholine during intubation.
• Respiratory failure: bedside exam  follow number counting in single breath, assess cough/swallowing. Trend mechanics with RT:
NIFs/VC as above (see 20-30-40 Rule). Aggressive pulm toilet. HOLD pyridostigmine if bulbar sx and/or intubated (can  secretions).
Jef Gluckstein
192
TOC

Neurology Neuroprognostication
Neurological prognostication after cardiac arrest is challenging and uncertain (Seminar in Neurology 2017;37:040). The introduction
of therapeutic hypothermia alters the timeframe for neurological recovery and the interpretation of prognostic markers. Studies of
neurological prognostication are hampered by heterogenous patient populations and variable definitions of “coma”. We will discuss
the clinical predictors of recovery and available diagnostics – clinical exam, electrodiagnostic testing, and neuroimaging.

Cerebral performance category (CPC)

• Good Outcome:
o CPC 1. Mild deficits. Able to work. May have have mild neurologic/psychologic deficits.
o CPC 2. Moderate deficits. Capable of independent activities of daily life. Able to work in sheltered environment.
• Poor Outcome:
o CPC 3. Severe deficits. Conscious but dependent on others. Ranges from ambulatory to severe dementia/paralysis.
o CPC 4. Coma (no wakefulness) or vegetative state (wakefulness but unawareness).
o CPC 5. Brain death: apnea, areflexia, EEG silence, etc.

Therapeutic hypothermia: post-cardiac arrest patients are cooled within 6 hours of return of spontaneous circulation (ROSC),
to 32–34°C, where they are maintained for 24 hours via surface or endovascular cooling methods (Nat Rev Neurol 2014;10:190).
Targeted temperature management to 36°C, has equivalent efficacy (NEJM 2013;369:2197). During this period, patients can be
paralyzed with neuromuscular blocking agents to prevent shivering, and are commonly maintained on propofol, midazolam, fentanyl
and other sedatives. After completion of 24 hours of TH, patients are typically rewarmed in a controlled fashion over 8-12 hours, with
discontinuation of paralytics (if used) only once the shivering threshold—estimated at around 36°C—is passed; sedative-hypnotics
are continued while patients are paralyzed.

Timeframe post cardiac arrest diagnostics:

• Day 1-2: therapeutic hypothermia and rewarming
o Electroencephalography (EEG)
 Timing: started during TH and continued for 24 hours post normothermia.
 Positive prognosis: continuous background pattern and reactivity at day 3 or later.
 Poor prognosis: absence of EEG activity, seizures, burst suppression (Neurology 2013;80:339)
o Clinical exam
 Poor prognosis: status myoclonus at <48 hours post cardiac arrest or normothermia. Defined as spontaneous,
repetitive, unrelenting, generalized multifocal myoclonus involving the face, limbs and axial musculature. There may
be no EEG correlate. Absent brainstem reflexes: bilateral pupillary, corneal, and oculocephalic reflexes. Absent
brainstem reflexes, along with apnea and other criteria (depending on local guidelines), may signify brain death.
• Day 3-5:
o Somatosensory evoked potentials (SSEP) – measurement of brain activity in reponse to somatosensory stimulation
 Timing: 48 hours post cardiac arrest or normothermia.
 Poor prognosis: Bilateral absence of N20, which reflects the integrity of thalamocortical projections.
o Neuron specific enolase (NSE) – non-specific marker of neuronal injury (misnomer as it is found in RBC and platelets).
 Timing: 24-72 hours post cardiac arrest or nomothermia. Check serially at 24. 48, and 72hrs post-ROSC.
 Poor prognosis: >33 ug/l and increasing daily NSE levels (Neurology 2011;77:623). NSE is prognostic in the pre-
therapeutic hypothermia era but is not well validated in patients who received therapeutic hypothermia.
o CT head, 48 hours post cardiac arrest or normothermia
 Poor prognosis: widespread hypodensity, loss or reversal of grey-white differentiation.
o Brain MRI, 72 hours post cardiac arrest or normothermia
 Poor prognosis: DWI and ADC changes suggestive of ischemic injury (Ann Neurol 2009;65:394). Quantitative ADC
values may correlate with severity. MRI can be insensitive to lesions if not performed during normothermia.

Combining prognostic indicators (MGH Neuroprognostication Guidelines, 2019):

• Prognostic value of at least 2 of the following findings (measured after completion of re-warming following TH, between 36-72
hours post cardiac arrest)
o Bilaterally absent SSEP
o Unreactive EEG background
o Early myoclonus
o Incomplete recovery of brainstem reflexes
• 79% sensitivity for in-hospital mortality and 62% sensitivity for poor 3-6 mo neurological outcomes (severe
disability/dependency, coma, or death). 100% PPV for both in-hospital mortality and poor neurological outcomes.

Alexandra Wick
193
TOC

Psychiatry Psychosis & Agitation

MENTAL STATUS: document daily if new AMS or worsening psychiatric sx (AFP 2009;80:809)
APPEARANCE/BEHAVIOR: grooming/hygiene, eye contact, attitude/cooperation, abnormal mvmt (fidgeting, tics, TD)
SPEECH/LANGUAGE: mechanics - rate, volume, prosody, articulation, fluency (pt can place 5 words together), paucity
of speech, mutism, echolalia (copying provider’s speech), verbigeration (repeating meaningless phrases)
THOUGHT PROCESS: presence of disorganization (including derailing/tangentiality); also note vague use of references
(common in psychosis); thought blocking (pt appears unable to produce responses to questions)
MOOD/AFFECT: pt’s own description, observed affect, future views, self-attitude (worthlessness, grandiosity)
THOUGHT CONTENT/PERCEPTIONS: SI/HI, delusions, hallucinations, overvalued ideas, obsessions, poverty of content
COGNITION: level of consciousness, orientation, MOCA
INSIGHT/JUDGMENT: use examples - insight (pt recognizes sx as pathological/accepts dx); judgment (pt takes meds)

PSYCHOSIS
• Characteristics: delusions, hallucinations (auditory>visual), thought disorganization
• Ddx: schizophrenia, schizoaffective, MDD w/ psychosis, bipolar w/ psychosis, malingering, substance-induced (cocaine,
amphetamines, MJ, bath salts, hallucinogens, EtOH), less frequently OCD/PTSD/borderline PD, intellectual disability,
dementia, due to another medical condition (delirium, epilepsy, AIP, paraneoplastic limbic encephalitis)
o New onset psychotic disorders in patients >50 is fairly rare. Medical cause of psychotic symptoms in this age group
(delirium, CNS pathology, dementia) is more likely unless known psych diagnosis.
• Labs: CBC, BMP, UA, Utox+VPAIN, serum tox including EtOH, UA, med levels, delirium workup (see neuro page)
• Refer to psych: outpatient = always, inpatient = if decompensated (can be associated with fear, agitation, aggression)
Treatment Basics: confirm home antipsychotics/mood stabilizers early in admission, continue only if patient reliably taking;
otherwise, dose reduce. Ask if patient on long-acting injectable medication/date of last injection, ask which PRN medications
work well for patient. Obtain Depakote, lithium, clozapine levels.
• Antipsychotics:
o Avoid multiple antipsychotics in 1 patient. If med list includes >1 antipsychotic, confirm before ordering as it’s unlikely
they’re taking all in outpatient setting.
o Continue home Cogentin (benztropine) if prescribed to reduce EPS sx (common in 1st gen antipsychotics)
o If on clozapine, consult psychiatry early to continue medication in house
• Mood stabilizers:
o Include lithium, Depakote, lamotrigine, some antipsychotics. Confirm compliance with lamotrigine given risk of SJS.
o Consider lithium toxicity in patients with n/v/d, tremor, ataxia, confusion, agitation  seizures, nonconvulsive
status, encephalopathy if severe. Precipitating factors include dehydration, AKI, new medications (NSAID, ACE/ARB,
diuretics).
AGITATION IN DELIRIUM: (see Delirium in neuro section)
• Safety: #1 priority is patient and staff safety. LISTEN to nursing concerns. Very low threshold to page security.
o Can always page psychiatry (page APS resident after 6PM on weekdays/5PM on weekends)
o Offer oral medications early. Consider lorazepam 1st line if strong suspicion for stimulant intoxication or catatonia
o If patient requires restraints, ensure appropriate sedation as agitated patients are at risk of rhabdo/MSK injury
o 2nd generation antipsychotics carry a black-box warning for increased all-cause mortality in pts with dementia (who
commonly present with superimposed delirium) – goal is lowest effective dose for shortest time possible
• Treat underlying cause:
o Carefully review pts’ medications and assess risk/benefit of continuing anticholinergics & benzodiazepines. If opiates
are required, use PO oxycodone or IV hydromorphone if needed
• Management:
o Use behavioral strategies (including frequent re-orientation & light/physical activity (OOB/PT) cues) as first-line
o If medication is required for adults with QTc <550ms, can trial oral quetiapine (initial doses 12.5-25mg q6 hrs)
o If requires IV, trial IV haloperidol (initial dose 2.5-5mg, 1-2mg in elderly/frail). May be effective and is less associated
with dystonia than IM or PO dosing. Prefer early psych consultation for pts requiring higher/more frequent doses.
o Monitor QTc, replete Mg ≥2 and K ≥4 while using antipsychotics.
o AVOID antipsychotics in patients with Parkinsonian syndromes, catatonia, NMS
• IM medications: use only as a last resort in case of emergencies. Consult psychiatry for pts requiring IMs.
o IM haloperidol (5mg) should be co-administered with either IM diphenhydramine (25-50mg) or IM benztropine (0.5-
1mg) to reduce risk of dystonia although these medications may temporarily worsen delirium.
o IM olanzapine or thorazine may be given alone but should be used cautiously in elderly pts given risk of orthostasis
o IM olanzapine cannot be administered with IM benzos/barbiturates due to risk of cardiorespiratory depression

Alexandra Wick
194
TOC

Psychiatry Consent & Capacity

Three Elements of Valid Informed Consent (Psychosomatics 1997;38:119; NEJM 2007;357:1834)
1. Relevant clinical information: at minimum: diagnosis, proposed intervention, its purpose, its risks/benefits, alternatives, and
risks/benefits of alternatives (including no intervention)
2. Voluntary decision: the decision must be voluntary and without coercion from hospital staff or family/friends
3. Capacity: confirm patient has the ability to make a decision about the specific question being addressed
Exceptions to Informed Consent
1. Emergency: imminent risk of death or serious harm without medical intervention. All attempts should be made to find HCP/other
surrogate decision-maker. Always discuss with team attending. Document emergent situation, lack of capacity, lack of available
surrogate, need for emergent intervention. Consider 2nd opinion/consulting MGH lawyer-on-call.
2. Lack of capacity or competency: turn to the appropriate HCP/surrogate decision-maker
Capacity Assessment
• Capacity: person’s ability to make an informed decision about a specific question. It can change over time.
• Competence: legal designation made by a judge. Determines a person’s ability to make decisions in multiple areas of life.
• Any physician can make a determination of capacity. Psychiatry should be consulted only for complex cases, such as when
neuropsychiatric illness may be impairing decision-making or when the pt, family, and medical team disagree. Inform consultant of pt’s
expressed decision and risks/benefits of each intervention.
• The strictness of the capacity test varies as the risk/benefit ratio of a decision changes: the more favorable the risk/benefit
ratio, the lower the standard for capacity to consent and higher the standard to refuse, and vice versa.
Criteria for Determining Capacity (ALL must be met for patient to have capacity) (NEJM 2007;357:1834 NEJM 1988;319:1635)
Criterion Approach in Physician’s Assessment
Ask patient to indicate a choice. No expression is a presumption of
Communicate a clear and stable choice incapacity. Frequent reversals of choice may indicate lack of capacity.
Ask patient to describe his/her understanding of the information given by the
Understand relevant information physician (diagnosis, proposed intervention, purpose of intervention,
risks/benefits, risks/benefits of alternatives including no intervention).
Ask patient to describe views of diagnosis, interventions, and likely
Appreciate the situation and its consequences
outcomes. Is patient aware of her illness? Its seriousness? Consequences?
Be able to manipulate information provided in a Ask patient to compare treatment options, consequences, and reasons for
rational fashion choice. Does the patient weigh the risks and benefits logically?
Documention: “Based upon my evaluation of the pt, he/she [does/does not] express a consistent preference regarding the proposed
treatment, [does/does not] have a factual understanding of the current situation as evidenced by [example], [does/does not] appreciate the
risks and benefits of treatment and non-treatment, and is [able/unable] to rationally manipulate information to make a decision as
evidenced by [example]. Therefore, in my opinion, this pt [has/lacks] capacity to make this medical decision.” If capacity present: “We
should respect the patient’s right to make this decision to [details].” If lacks capacity: “Surrogate decision-maker needed.”
Surrogate Decision-Makers
• Encourage each pt to sign legal HCP form specifying surrogate. Activated (court procedure) when pt lacks capacity.
• Surrogate’s job is to make the decision pt would have made for herself if able—not what the surrogate wants. If a pt’s wishes cannot
be known, the surrogate should make the decision in the best interest of the patient.
• HCP may be uncomfirmed (most common) or confirmed. Court-confirmed HCP is required when pt’s surrogate is activated & pt
actively objects to surrogate’s decision. If HCP confirmation required, contact Guardianship team.
• Guardianship: legal process by which the MA Probate Court grants a guardian the authority to make decisions on behalf of someone
whom a judge has ruled is not competent. Required when there is no HCP identified & pt is unable to designate a HCP. Note: a
patient may not have capacity to make a certain medical decision and still be able to designate a HCP. For help: contact
‘Guardianship Team’ - Lisa Lovett, LICSW & Mary Lussier-Cushing, RN/PC
• Emergency guardianship is not required to provide lifesaving treatment & should not delay care. Can consult MGH lawyer-on-call.
Temporary Involuntary (Psychiatric) Hospitalization (Section 12 in MA - MGL ch.123 §12): Consult psychiatry for all pts on 12a.
• Section 12a (the front of the “pink paper”): MD uses this form to apply for involuntary psych hospitalization of a pt who, based on
MD’s exam & opinion, requires hospitalization to avoid likelihood of serious harm by reason of mental illness
• Authorizes pt’s transport to psych facility and, if necessary, the use of restraint of the pt to maintain safety.
• Issued when likelihood of serious harm to self and/or others is imminent (general rule of thumb is within 24-72 hrs) AND
1. Is the result of a “serious mental illness”: must be supported in writing with specific evidence. Symptoms caused soley by
alcohol or drug intake, organic brain damage, or intellectual disability do not consistute a serious mental illness.
2. Meets ≥1 of the following 3 criteria: (1) substantial risk of physical self-harm; (2) substantial risk of physical harm to others;
(3) very substantial risk of physical self-impairment or injury as manifested by evidence that the person’s judgment is so
affected (i.e. by serious mental illness) that he/she is unable to protect him/herself in the community.
• Section 12b (reverse side of the “pink paper”, “72 hr hold”): completed by evaluating MD at receiving psychiatric facility
Civil Commitment for Substance Use Disorder Treatment (Section 35 in MA - MGL ch.123 §35)
• Process by which the court may involuntarily commit someone to inpatient substance use disorder treatment when there is likelihood
of serious harm as a result of the disordered substance use; must be pursued via petition filed at courthouse

Celeste Peay
195
TOC

Psychiatry Catatonia, NMS & Serotonin Syndrome

CATATONIA: behavioral syndrome that occurs in the context of underlying psychiatric or medical diagnosis, marked by
inability to move normally despite full physical capacity; pathophysiology incompletely understood
• Subtypes: retarded: immobility, mutism, withdrawal; excited: mania, hyperkinesis, stereotypy, disorientation; malignant:
accompanied by hyperthermia, autonomic instability, rigidity & delirium (Arch of Gen Psych 2009;66:1173)
Etiology: (Schizophr Bull 2010;36:239, Behav Brain Sci 2002;25:555)
• Psychiatric: mood disorders > thought disorders (schizophrenia, autism) > dissociative disorders
• Medical: seizures (including NCSE), PRES, CNS lesion, infection, TBI, PLE, delirium, anti-NMDAR encephalitis, SLE
• Drug: dopamine-blockers, dopamine withdrawal, sedative/hypnotic withdrawal, hallucinogens, synthetic MJ, opiates
Diagnosis: DSM-V or Bush-Francis Catatonia Rating Scale (BFCRS), requires ≥ 2 of 1st 14 (Psych Scand 1996;93:129)
• Most common signs include: (World J Psych 2016;6:391)
o >80%: immobility, mutism, withdrawal & refusal to eat, staring
o >50%: negativism (oppose/no response to instruction), posturing/catalepsy (spontaneous maint of posture), rigidity
o >10%: waxy flexibility (ability to mold limbs with initial resistance), stereotopy (repetitive, purposeless movements),
echophenomena (repetition of examiner’s words or movements), verbigeration
o Other signs: automatic obedience, mitgehen, ambitendency (motorically stuck in indecisive movement), grasp reflex
• Exam: observe for 30s outside pt room. Attempt to engage in conversation. Scratch head or gesture in exaggerated
manner (echopraxia). Examine for cogwheeling in arms, alternate force, attempt to reposture. Test for mitgehen. Extend
hand & say, “Do not shake my hand” (ambitendency, pt will appear stuck). Reach into pocket & say, “Stick out your
tongue. I want to put a pin in it” (automatic obedience). Check for grasp reflex.
• Ddx: delirium, dementia, stroke, PD, stiff person & locked in syndromes, NCSE, akinetic & elective mutism, anti-NMDAR
encephalitis; If malignant: NMS, malignant hyperthermia, SS, DTs, CNS infection/vasculitis, anticholinergic toxicity
Treatment: (Schizophr Bull 2010;36:239)
• Hold D2 blockers (e.g., typical/atypical antipsychotics; prochlorperazine, promethazine, metoclopramide)
• Ativan Challenge: 2mg IV x1 (1mg in frail elderly), repeat BFCRS in 30 min. If response, 2mg IV Ativan q6-8h, uptitrate as
tolerated. DO NOT HOLD FOR SEDATION (signs of catatonia can be mistaken for sedation  write hold for resp
depression). If no response, consider ECT.
• Adjunctive agents: amantadine (100mg QD up to 600 QD), memantine (10-20mg QD), zolpidem, AEDs
NEUROLEPTIC MALIGNANT SYNDROME: (Am J Pysch 2007;164:870)
• Overview: abrupt onset of 1) ∆ in mental status 2) rigidity 3) fever 4) autonomic dysfunction associated with DA blocking
agent or withdrawal of pro-dopamine agent (List of Meds Associated with NMS)
• Risk factors: initiation/increase of above agent (typically occurs within hours/days but can be idiosyncratic), hx of
NMS/catatonia, withdrawal from EtOH/sedatives, basal ganglia disorders, exhaustion, dehydration, agitation
• Labs:  WBC and CK = most common lab abnormalities ( CK only seen in 50% of cases). Low serum iron is 92-100 %
sensitive for NMS but not specific. May also see mild elevations in LDH, alk phos, AST, ALT, electrolyte abnormalities
• Ddx: serotonin syndrome, malignant hyperthermia, malignant catatonia (significant overlap), CNS infection, spinal cord
injury, seizure, heat stroke, acute dystonia, CNS vasculitis, thyrotoxicosis, drug intoxication/toxicity, withdrawal states
Stage Clinical Presentation Intervention
Mild rigidity, confusion, • Stop offending agent & ?contributors (serotonergics, Li, anticholinergics)
Early T<100.4F, HR <100 • Lorazepam 1-2mg IM/IV Q4-6H • Aggressive fluids
Moderate Moderate rigidity, T100.4- • Cooling measures +/- ICU
(may require ECT) 104F, HR 100-120 • Bromocriptine 2.5-5mg PO Q8H or amantadine 100mg PO Q8H
Severe Severe rigidity, +/- coma, • ICU level of care (if intubation required, versed>propofol for sedation)
(may require ECT) T >104F, HR >120 • Dantrolene 1-2.5 mg/kg IV Q6H x 48hr
SEROTONIN SYNDROME (NEJM 2005;352:1112)
• Overview: exposure to serotonergic agent leading to triad of 1) ∆ mental status, 2) neuromuscular hyperreactivity
(tremor, hyperreflexia, clonus), 3) autonomic instability (tachycardia, tachypnea, diaphoresis, mydriasis, hyperthermia,
shivering, sialorrhea, urinary incontinence, diarrhea). Note: n/v/d common in SS prodrome but rarely seen in NMS
• Causative agents: amphetamines, bupropion, buspirone, carbamazepine, carbidopa-levodopa, cocaine,
cyclobenzaprine, diphenhydramine, fentanyl, levodopa, linezolid, lithium, LSD, MAOIs, MDMA, meperidine, methadone,
methylene blue, metoclopramide, ondansetron, SNRIs, SSRIs, TCAs, tramadol, trazodone, triptans, tryptophan, VPA
• Diagnosis: can use Hunter's criteria for diagnosis of serotonin toxicity if unclear (QJM 2003;96:635)
• Treatment: 1) hold offending agent (generally will resolve within 24 hrs), 2) use BZDs if agitation present (lorazepam 2
mg IV, repeat PRN), 3) if unsuccessful, can use cyproheptadine 12 mg x1 then 2mg Q2h until clinical response seen.
Very severe cases with hyperthermia may require ICU level of care with cooling, intubation, sedation, and paralysis.
Celeste Peay

196
TOC

Psychiatry Depression & Anxiety

MAJOR DEPRESSIVE DISORDER (MDD)
Overview:
• Epi: common in general population; estimated U.S. prevalence 9% (CDC Morb Mort Wk Rep 2010;59:1229)
• Screening: USPSTF (2013) recommends universal screening of adult primary care patients (Grade B)
o PHQ-2: In last month, have you 1) felt down/depressed/hopeless? 2) had little interest/pleasure in doing things?
 ≥1 = pos. screen, 97% Sn / 67% Sp for MDD  PHQ-9 to grade severity. (AFP 2012;85:139)
• DSM-5 criteria: must have depressed mood and/or loss of interest/pleasure + ≥4 of following sx: or  weight/appetite,
 or  sleep, psychomotor agitation/slowing, fatigue, worthlessness/guilt, poor concentration, thoughts of death or SI; sx
must be present over same 2 wk period and cause significant impairment/distress
o Ddx: drugs/meds, OSA, hypothyroidism, stroke, TBI, dementia, MS, HIV, bipolar, schizoaffective
• Treatment: drugs + therapy more effective than either alone, but monotherapy of either acceptable (APA 2010). SSRIs
generally 1st line (other common options: bupropion, SNRI). Consider escitalopram & sertraline as 1st line (better
efficacy/acceptability profile vs duloxetine, paroxetine) (Lancet 2009;373:746)
Side Effect Profiles of Commonly Prescribed Antidepressants
Sexual Orthostatic QTc
Drowsiness Insomnia/Agitation GI upset Weight gain
dysfxn HoTN Prolongation
--/ / (fluox, sert) / /    
SSRIs
(sertraline) (paroxetine) (paroxetine)
--/ ---/  ---/ / ---/ ---/
SNRIs
(venlafaxine)
Bupropion∆ --- ↑  ---/ --- --- 
Mirtazapine  --- ---   --- 
Trazodone¶  ---     
∆Bupropion lowers the seizure threshold; contraindicated in pts w/ seizure disorder, anorexia/bulimia nervosa
¶Trazodone is rarely (1/1,000-1/10,000) associated w/ priapism (i.e. urological emergency)
Dosing of Common Antidepressants
Adequate trial is 6-12 wks at full dose; if poor tolerance/response after 4-6 wks, augment or switch classes.
Starting Dose Titration Usual (Max) Dose Discontinuation
Citalopram 20mg QD  20mg Qwk 20-40mg QD (40)
Escitalopram 10mg QD 10mg after ≥1wk 10-20mg QD (20) Taper over 2-4 wks
Sertraline 50mg QD 25-50mg Qwk 50-200mg QD (200)
Fluoxetine 20mg QD 20mg Q3-4wk 20-80mg QD (80) 0-2 wks (long t1/2)
Paroxetine – IR 20mg Qam 10mg Q ≥1wk 20-50mg QD (50) 3-4 wks (short t1/2)
withdrawal effects
Paroxetine – CR 25mg Qam 12.5mg Q≥1wk 25-50mg QD (62.5) more common/severe
Duloxetine (SNRI) 40-60mg QD or divided BID; ≥60mg QD w/o additional benefit 2-4 wks
Venlafaxine (SNRI) 37.5 QD or in 2-3 divided doses; 75mg Q≥4d, 75-375mg daily or divided 37.5-75mg QD x4wks
Refer to psych: concern for bipolar depression, failure of 2 adequate rx trials, severe MDD w/ SI/HI, psychosis, or catatonia
GENERALIZED ANXIETY DISORDER (GAD)
Overview:
• Epi: US lifetime prevalence is ♀7.7% & ♂4.6% (AFP 2015;91:617). 90% will meet criteria for at least 1 co-morbid psych
condition in their lifetime (MDD, dysthymia, AUD, simple phobia, social anxiety) (Arch Gen Psych 1994;51:355)
• Excessive worry associated w/ poor CV health, coronary heart disease, CV mortality (Nat Rev 2012;9:360).
• Screening: GAD-7: score ≥5 indicates mild GAD (97% Sn / 57% Sp, LR 2.2); score ≥10 indicates moderate GAD (89%
Sn / 82% Sp, LR 5.1) (Arch Intern Med 2006;166:1092). Commonly done annually with PHQ2; no USPSTF recs.
• DSM-5 criteria: A) excessive anxiety/worry occurring most days for ≥ 6 months re: multiple life domains, that is B) difficult
to control, and C) associated w/ ≥3 sx: restlessness, fatigue, poor concentration, irritability, muscle tension, sleep
disturbance. Must also cause D) significant distress/impairment; and E/F) not better explained by drugs/meds/other psych
• Treatment: 1st line therapy = SSRIs/SNRIs and/or CBT, based on availability/pt preference; no head-to-head trials (meta-
analyses have found effect sizes ≈ equivalent). No individual SSRI/SNRI shown more effective; select based on side
effects and pt treatment history/preference; titrate & adjust as for MDD above.
o In general, SSRIs have lower risk of insomnia/agitation over SNRIs. Citalopram, escitalopram, paroxetine cause least
agitation; sertraline and fluoxetine cause more agitation
• Refer to psych: failure of 2 adequate next-step trials or severe GAD w/ recurrent panic
Desta Lissanu
197
TOC

Psychiatry Alcohol Use Disorder & Withdrawal

ALCOHOL USE DISORDER (AUD)
Diagnosis and Presentation:
• Screen all patients with the Audit C. Risky drinking is >4 drinks per occasion for men and >3 for women OR >14 drinks a
week for men and >7 drinks per week for women.
• If the patient screens positive, ask about the 5 Cs: Control, Cravings, health and relationship Consequences, Compulsion
to drink, and being unable Cut back.
• AUD is based on the DSM-5 criteria (11 criteria; 2-3 = mild, 4-5 = moderate, ≥ 6 = severe). Criteria include physiologic
dependence, damage to personal life, and compulsion (6). If pt meets criteria can initiate a brief intervention/motivational
interviewing at bedside. Consult ACT if concerned.
• Chronic use: cytopenia (low Hb, WBC, Plt) low K/Mg/Ca/Phos/VitD – EtOH toxic to renal tubules, lowers GI absorp;
ketoacidosis – EtOH metab  less gluconeogenesis  rel hypoglycemia  low insulin state  FFA to ketones. Lactic
acidosis (increase ratio of NADH/NAD) (NEJM 2017;377:1368).
Treatment for Moderate/Severe AUD:
• More successful when combining medications and individual/group therapy. Consider consulting ACT to refer to
CSS/TSS/halfway house for those without housing and/or IOP/WestEnd Clinic.
• 1st line: naltrexone and acamprosate equal in efficacy but data suggest naltrexone>acamprosate (JAMA 2006;295:2003).
o Naltrexone (MOA: reward/cravings) PO 25mg to start50mg daily or IM (Vivitrol) 380mg q4wk (CI: acute
hepatitis/ALF, current opioid use)
o Acamprosate (cravings) 666mg TID (CI: severe renal impairment CrCl<30, pregnancy).
• 2nd line: disulfiram, topiramate, gabapentin (can be used for mild alcohol withdrawal and reduces heavy drinkining days
(Addiction 2019;114:1547), and baclofen (Am J Psych 2018;175:86).
• Success can range from reducing heavy drinking days to abstinence. Remember to utilize principles of harm reduction.
Wernicke-Korsakoff Syndrome:
• Wernicke encephalopathy: acute
o Clinical diagnosis w/ Caine Criteria (85% Sn) requires ≥2: (1) dietary deficiency, (2) oculomotor dysfxn, (3)
cerebellar dysfxn (LE ataxia), (4) either AMS or poor memory. Note: Serum B1 level NOT diagnostic (J Neuro, Nsgy,
and Psych 1997;62:51)
o Tx: thiamine IV 500mg TID x 5d (1st dose before glucose)  IV 250mg QD x 3d  PO 100mg TID x1-2wks  then
PO 100mg QD.
o Ppx: IV 250mg QD x3-5d  100mg TID 1-2wk 100mg QD (Intern Med J 2014;44:911).
• Korsakoff’s (chronic): antero+retrograde memory deficits (confabulation), apathy, intact sensorium

ALCOHOL WITHDRAWAL SYNDROME

Pathophysiology: GABA (inhibitory) and glutamate (excitatory) work in balance

• Chronic EtOH use: high GABA stim  glutamate upregulation. After chronic stim, GABA receptors are less sensitive &
require more EtOH to balance increased glutamate.
• Abrupt Cessation of EtOH: decreased GABA  unbalanced excess Glutamate activity  noradrenergic surge 
increased dopamine release  complicated withdrawal sxs
Clinical Presentation
• Withdrawal symptoms by timecourse after last drink: (Ind Psych 2013;22:100)
o Minor withdrawal: 6-48h; tremors, sweats, HR, BP headache, anxiety, intact orientation
o Alcoholic hallucinosis: 24h-6d; visual/tactile > auditory hallucinations (patient is typically aware of hallucinations),
clear sensorium
o Withdrawal seizure: 6-48h; generalized tonic-clonic, can have multiple in short span
o Delirium Tremens (DTs): 48h-5d, can last 2wks; tremors, sweats,  HR, HTN, fever, inattention, paranoia,
hyperalert, hallucinations, disorientation, agitation. Usually CIWA >20. Death 1-4%.
Vladislav Fomin
198
TOC

Psychiatry Alcohol Use Disorder & Withdrawal

Initial Evaluation
• H&P: last drink time, hx complex withdrawal (sz, ICU/intubation, DTs), hx of leaving AMA, co-ingestions (including BZD),
EtOH use history (drinks per day/week, type of alcohol, binge driking, recent changes in drinking)
• Labs: CMP, CBC, serum osm if HCO2 <15 or AG, CPK if found down, tox screen, serum EtOH (clear ~15-35 mg/dL/hr,
chronic= faster metab, higher tolerance) (J Forensic Sci 1993;38:104)
• Predictors of severe withdrawal: age, comorbidities, hx of DT/withdrawal, BP, hyponatremia/hypokalemia BUN >26
Plt <150 (JAMA 2018;320:825).
Management
• Initial Tx for all EtOH withdrawal:
o IV thiamine (if concerned for Wernicke’s, see above), D5NS (after thiamine) to fix ketoacidosis, replete lytes, folate
1mg QD, MVI, place on CIWA, offer ACT c/s for AUD treatment
• Decide phenobarbital vs. BZD protocol: no difference in outcome/sedation between the two (Psychosom 2019;60:458)
o Consider phenobarbital if: hx DTs, seizures, BZD-resistance, success w/phenobarb, or prior ICU admissions for
w/d; current Sx of DTs; not responding to BZDs; risk of paradoxical response to BZDs (chronic CNS dz)
 Contraindications: >30mg ativan equivalents; high likelihood of leaving AMA; Hx SJS/TEN; Hx AIP; unstable
respiratory status
 Advantages: auto-taper, long half-life, predictable effect, uniform efficacy, level is accurate if needed, wide
therapeutic window, no paradoxical agitation, doesn’t require CIWA evaluation.
o Consider BZD if: mild-mod w/d sx, no hx complicated w/d, phenobarb contraindicated

Phenobarbital Protocol: binds GABA-A and glutamate, t1/2 = 1-4d

• NO MORE BZD after phenobarb started. Total of prior BZD in last 24h must be <30mg Ativan equivalents
• Side effects: apnea, hypoventilation, hypotension, bradycardia, laryngeal spasm
• IM load (80% given initially) + PO taper
o To calculate doses: use excel sheet and http://stagehandbook.partners.org/pages/4281
o Input: 1) height (IBW) 2) high-risk withdrawal?: past DTs +/- sz AND (EtOH use in <2wks OR active w/d sx
OR ⊕BAL with labs predictive of severe w/d: low plts, high MCV, low K) 3) high-risk sedation?: age>65, liver
dz, head injury, recent benzos, concurrent sedatives
o *If cirrhosis: slower excretion/metabolism, max load 8mg/kg, check level and adjust taper, stop taper after 2d
o *If lung disease: consider max load 8-10mg/kg
o Serum level not required. Check 5h after load if considering re-load
• ED IV phenobarb load: must stay 1hr in ED after IV load. NO MORE IM after IV unless re-load (see below). Start
PO 8hrs after IV load, dose per excel sheet.
• Assess frequently! IM loading dose is split to allow monitoring: 40% 0h, 30% 3h, 30% 6h. Peak plasma
concentration 30m-4h post-IM dose and 2-8h post-PO. If uncontrolled sx or developing sedation, call for help
from pharmacy to change doses.
• Consider reload: for breakthrough sx despite IV or IM load. If 5h level <15, OK to reload, Target level 12-15.
Consult psych, ACT, or pharmacy.
o Options: 1) reload IM, e.g. if serum level 6, give equivalent IM load again to target 12 OR 2) increase taper:
jump up to PO doses for higher serum target
• Discharge: phenobarb increases receptor sensitivity to benzos/EtOH; drinking after IV/IM load can be fatal. Will
autotaper over days. If exam/VS stable, ok to d/c patient before all doses complete, no earlier than day 3. No
PO doses on d/c.

Benzodiazepine Protocol:
• Use Epic Alcohol Withdrawal Order Set!
• Route: PO Ativan if able to take POs>IV Ativan>>Valium and Librium (long half-life, delayed toxicity, cleared by
the liver)
• PRN: use CIWA scale (only if patient can communicate), NOT HR, BP alone as poor predictors of DTs (JGIM
1996;11:410). PRN protocol inappropriate if AMS, DTs, or severe w/d. Consider switching to RAAS scoring.
• Standing: if likely to have severe w/d
• Beware paradoxical response, resistance (>6mg ativan/hr), or BZD toxicity (similar to DTs) w/ escalating dose
• Consider switch to phenobarb if CIWA consistently >16 and BZD dose <30mg Ativan equivalents

Vladislav Fomin
199
TOC

Psychiatry Opioid Use Disorder & Withdrawal

OPIOID USE DISORDER (OUD): chronic, relapsing d/o of opioid use due to dysfunction of brain reward circuits (J Addict Med 2015;9:358)
• Screen all patients with: “How many times in the past year have you used an illegal drug or used a prescription medication for
nonmedical reasons?” Confirm diagnosis using DSM-5 Criteria for opioid use disorder. Use ≠ addiction.
• Focus on building a therapeutic alliance and performing risk assessment (Med Clin N Am 2018;102:587)
o Assess risk of withdrawal: current opioids, frequency of use, last use PTA, g/day or $ spent per day, recent withdrawal
o Assess treatment readiness: treatment hx (medications, counseling, mutual-aid organizations), social circumstances (housing,
food security, legal issues). Understand patient’s current goals, including safer use vs. abstinence.
o Assess for high-risk injection practices: history of bacterial/fungal complications (endocarditis, SSTIs, bone/join infections), viral
complications (HIV, HCV, HBV). If currently injecting, use PCOI harm reduction conversation guide to review injection practices.
Consider PrEP for patients with high-risk injection practices (see “HIV/AIDS” page).
o Assess risk of overdose: h/o non-fatal OD,  tolerance from recent incarceration or abstinence-based treatment, access to
naloxone, high-dose Rx’d opioids and/or other sedatives (check PDMP), injection use (Addiction 2015;110:996)
• Labs: serum/urine tox, LFTs, HIV, HBV/HCV, TB, RPR, EKG. NB: urine fentanyl is separate order, takes days to result
• Pain control: pts w/ OUD and/or chronic opioids likely have developed tolerance and require higher doses of opioids to treat pain
o If using non-prescribed opioids: can initiate methadone for withdrawal & add short-acting opioids titrated to pain
o If taking meth_Jadone: give usual dose once confirmed & add short-acting opioids (e.g., oxycodone) titrated to pain
o If taking buprenorphine: there are several strategies:
 For pain of short duration, may continue daily bup & add short-acting opioids (may need high doses, consider PCA)
 Give TDD of bup divided 3-4x daily (e.g. 4-8 mg q6-8h for mod-severe pain)
 D/c bup & use short-acting opioids to tx acute pain. Blocking effects of bup wear off after 24-72 hrs, so pt must be monitored
for OD (b/c initial opioid dose will be higher than ultimately needed). After acute pain resolved, re-start bup. (CMAJ
2016;188:1232; Annals 2006;144:127)

ACUTE OPIOID OVERDOSE (OD): (NEJM 2012; 367:1372)

• Signs: mental status, RR, tidal volume, miosis. Normal pupils do not exclude opioid toxicity  co-ingestions may be
sympathomimetic/anticholinergic. Rare: hypoxic seizure. Acute toxicity is a clinical diagnosis; ⊕tox screen does NOT confirm toxicity
• Acute stabilization: assess airway (mental status). If apnea and/or stupor, bag valve mask (with O2). Administer naloxone.
• Naloxone: goal is to improve mental status, oxygen saturation, and ensure RR>10, NOT to achieve normal level of consciousness
o Dose: 0.04mg IV, if no response increase dose q2 min:0.5mg2mg4mg10mg15mg.
o Administer intranasally or IM if no IV access
o NB: too much naloxone will precipitate opioid withdrawal. Consider diluting 0.4 mg in 10 ml saline and push 1 ml q2-3min.
o If failing to respond, consider endotracheal intubation (STAT RICU consult)
• Post-resuscitation: continuous O2 monitoring (naloxone effect shorter than many opioids), CXR (post-OD pulmonary edema does
NOT respond to diuretics, may evolve to ARDS), APAP level. Examine skin for fentanyl patch. Consider naloxone gtt.

ACUTE OPIOID WITHDRAWAL: agonist treatment with buprenorphine or methadone is first line treatment for opioid withdrawal and OUD.
Should be offered to every patient. Long-term agonist therapy decreases mortality and morbidity (BMJ 2017;357:j1550)
• Sx: dysphoria, restlessness, irritability, yawning, piloerection, mydriasis, rhinorrhea, lacrimation, mylagias/arthralgias, n/v/d, abdominal
cramping. Onset: 6-12h after short-acting opioids, 24-48 hours after last methadone use, variable with fentanyl analogs
• Medications:
o Buprenorphine (Suboxone): high affinity partial agonist with less risk of respiratory depression/OD than methadone
 Wait until Clinical Opioid Withdrawal Scale (COWS) >10, usually 10-12h after last heroin use/short acting opioids. Avoid
precipitated withdrawal—rapid, intense withdrawal due to displacement of full agonist by partial agonist.
 First dose: 4mg/1mg (1/2 of an 8mg/2mg Suboxone tablet)
 Second dose: if continued withdrawal sx, give another 4mg/1mg after 45-60 minutes
 Third dose: if recurrent withdrawal sx, give another 4mg/1mg after 6-12 hours
 Maximum dose for Day #1 is 12mg buprenorphine
 Prescribe total from Day 1 for Day 2, then reassess later in the day. Can give additional 4mg/1mg for withdrawal symptoms,
but max dose for Day #2 is 16mg buprenorphine
o Methadone: long-acting full agonist. Check and trend EKG for QTc, use with caution with other QTc-prolonging meds
 Day 1 Initial dose: 10-20mg x1. COWS q2h: If <6  observe; if 6-12  5mg dose x1; if ≥ 12  10mg dose x1.
REQUIRED to call ACT if ≥40 mg daily dose.
 Day 2 Stabilization: day 1 dose if COWS <6, increase by 20% if COWS 6-12.
 If not planning to transition to methadone maintenance, decrease dose by 20% per day.
o If unable to initiate suboxone/methadone, offer symptomatic medications and short-acting opioids for pain:
 Autonomic dysregulation: clonidine 0.1-0.2mg TID PRN (monitor BPs; avoid w/ 1st Suboxone/methadone dose)
 GI upset: Bentyl 10-20mg Q6H PRN abd cramps; promethazine 25-50mg IM PRN N/V; loperamide 2mg PRN diarrhea
 Anxiety: hydroxyzine 25mg Q8H PRN or trazodone 50-100mg q8h PRN
• Discharge: ensure pts have insurance, PCP, provider who can prescribe suboxone/methadone, list of shelters/needle exchanges
o Last dose letter for patients on methadone maintenance (includes date/amount of last methadone dose)
o Prescribe naloxone and teach OD response. Emphasize that Narcan reverses OD for ~30m. After OD  EMS to the ED.
o Bridge clinic: Call 617-643-8281 Mon-Fri 8am-4pm to schedule appt or present as walk-in

Emily Moin
200
TOC

Psychiatry Other Substance Use

MGH Tox Screens:
• Basic serum toxicology screen: quantitative assays for EtOH, salicylates, acetaminophen; qualitative assay for TCAs
• Drug screen, prescription/OTC (“full tox”): send out to Mayo, will take >3 days to return (www.mayomedicallaboratories.com)
o Common OTCs: caffeine, acetaminophen, salicylates, ibuprofen, naproxen, dextromethorphan, diphenhydramine, guaifenesin
o Neuro/psych drugs: barbiturates, AEDs (incl. carbamazepine, lamotrigine, levetiracetam, topiramate), propofol, TCAs, SSRIs,
SNRIs, bupropion, phenothiazines (incl. chlorpromazine, thioridazine), clozapine, muscle relaxants (cyclobenzaprine,
metaxalone), sleep meds (i.e. zolpidem, zaleplon)
o Others: lidocaine, trazodone, theophylline, some pesticides
o Limited use for illicit drugs: benzos, some opiates (incl. codeine, meperidine, methadone, oxycodone, fentanyl), amphetamines
o Drugs NOT on screen: cocaine, lithium, digoxin, ethylene glycol, iron, lead (order separately and note some are send-outs)
• Urine toxicology screen: amphetamines, barbiturates, benzodiazepines, THC, cocaine, opiates, phencyclidine
• VPAIN (“urine pain panel”): buprenorphine, oxycodone, methadone, 6-monoacetyl morphine (heroin metabolite)
o NB: urine fentanyl is an add-on test—consider sending for suspected opioid OD (esp. with PEA arrest) given prevalence of high
prevalence of synthetic fentanyl analogues in the community
• Oral fluid drug test: differentiates TYPE of benzo (lorazepam vs diazepam), opiate (codeine vs heroin), amphetamine
Urine Test Characteristics: (Mayo Clin Proc 2008;83:66)
Class Detection Time (days) False Positives False Negatives
Ritalin &
1-2d after use (2-4d for chronic Bupropion, labetalol, trazodone, ranitidine,
Amphetamines atomoxetine won’t
exposure) pseudoephedrine, selegiline
test ⊕
Barbiturates 2-20d after use Fioricet (contains butalbital)
Lorazepam,
Benzodiazepines 1-5d (most), 2-30d after diazepam Oxaprozin (NSAID) clonazepam
<1mg/day
1-7d after use, Synthetic
Cannabinoids Hemp products, Marinol
up to 1mo heavy chronic use cannabinoids
Opiates Poppy seeds (unlikely); At MGH, Oxycodone,
(NOT methadone, methadone, naloxone, fluoroquinolones do oxymorphone,
1-3d after use, 6-8d after heavy use
fentanyl, meperidine) NOT interfere Suboxone
Cocaine 2-4d after use, 1-3wks after heavy use NONE
Lamictal, Effexor, Tramadol,
Phencyclidine (PCP) 7-14d after use
dextromethorphan, doxylamine
High doses of opiates/methadone/tramadol;
Buprenorphine 5-10d
quinine, hydroxychloroquine, naltrexone
Methadone 1-5d Quetiapine, diphenhydramine, doxylamine
Substances that change urine color (e.g.,
Oxycodone 2-4d
Flagyl) will cause refusal
Cocaine Intoxication/Withdrawal:
• Intoxication: grandiosity, euphoria, hyperactivity, anorexia, anxiety, psychotic sx (formication, paranoia, AH/VH), fever, mydriasis.
Vasospasm can cause HTN emergency, stroke, MI and seizures. Tx: labetalol, phentolamine (AVOID unopposed alpha stimulation)
• Withdrawal: depression, fatigue, nightmares, cravings, sleep/appetite. Tx: Acute: propranolol, quetiapine for severe sx; Chronic:
consider topiramate and/or baclofen for cravings/dependence (consult ACT) (Psychiatry 2005;2:44)
Benzodiazepine Withdrawal: manage withdrawal per protocol (see “Alcohol Withdrawal” section). Higher risk for delirium with BZD
withdrawal. If possible, initiate taper with same BZD agent (e.g. due to extremely short half-life, alprazolam requires alprazolam taper).
Commonly Used Benzos Comparative Dosages (approx) Half-life (hours) (approx)
Alprazolam (Xanax)* 0.5mg 6-27 (oral peak 1-2) *Most common illicit
Chlordiazepoxide (Librium) 25mg 5-30 (oral peak 0.5-4) usage bc most
commonly prescribed
Clonazepam (Klonopin)* 0.25mg 18-50 (oral peak 1-2)
Diazepam (Valium)* 5mg 20-50 (oral peak 0.5-1)
Lorazepam (Ativan)* 1mg 10-20 (oral peak 2-4)
Temazepam (Restoril) 10mg 3-19 (oral peak 1-2)
Triazolam (Halcion) 0.25mg 2-3 (oral peak 0.7-2)
Spice/K2/Bath Salt Intoxication: agitation/violence, hallucination/paranoia, anxiety, tachycardia, arrhythmia, myoclonus, diaphoresis.
• Tx: low stimulation environment, IVF, consider IV BZDs to reduce agitation and prevent seizure (Curr Psychiatry Rep 2016;18:52)
THC Intoxication: euphoria followed by relaxation; tachycardia; hallucinations (especially w/ high potency THC, e.g., wax/dab)
• Cannabinoid hyperemesis syndrome: chronic user with recurrent n/v, abd pain; sx relief w/ hot showers; mild leukocytosis. Tx:
IVF, antiemetic, and THC cessation; consider BZD, followed by antipsychotic and capsaicin (J Med Toxicol 2017;13:71)
Alexandra Wick

201
TOC

Primary Care Health Screening & Maintenance

GENERAL SCREENING GUIDELINES [Evidence Grade] (aUSPSTF, bADA, cAACE, dACC/AHA, eACCP, fCDC, gACS)
Age 18 19 20 21 25 30 35 40 45 50 55 60 65 70 75+
Cardiovascular Screening / Preventative Health Recommendations
Assess RFs q4-6y [B]d Estimate risk w/ ASCVD calculator q4-6y [B]d
CVD Risk
(age, sex, total chol/HDL, SBP, DM, smoking, FHx) If ASCVD risk ≥20% consider high intensity statin* [B]a
Not
ASA for 1° Low dose ASA in adults 40-70 with higher
recommended for
ppx∆ ASCVD risk but not higher bleeding riskδ [A]d
adults > 70 [B]d
Diabetes If HTN or BMI ≥25 (>23 Asian) w/ ≥1 DM RF^ [B]b A1c Q3y. interval if abnl result,  annually in pre-DMb
HTN Q3-5y; Q1y if BP >135/90, obese, AA [A]a Q1y [A]a
One-time Men >45, women >55
Men 20-45, women 20-55: screen Q5yr,  if RF [C]c
HLD screening age Q1-2y if no RF* [A]c, Screen Q1y [A]c
Q 3-5y in DM if wnl at dx
<20 Q1y in DM [B] c

Obesity Annual BMI  refer for or offer comprehensive lifestyle program if ≥25 (overweight) [B]d
Diet Intensive behavioral counseling if CVD RF* [B]a
Exercise 150 min/wk mod exercise or 75 min/wk intense exercise & 2 days of muscle strengthening activityf
Universal Cancer Screening
Colorectal CA Start 10 years prior to age of affected family member at dx*** Colo Q10y, flex sig q5y, FIT q1y [A]a +/-***
Q1y low-dose CT if 30 pack-yrs & current
Lung CA
smoker or quit w/in last 15y [B]a
Skin CA Insufficient evidence for routine skin exams by clinicians [I]a
Infectious Disease Screening
HIV Screen at least once; repeat based on risk assessment [A]a
HCV Screen all 18-79 at least once; repeat based on risk assessment [B]a
HBV Born in endemic region, getting HD, or immunosuppression, HIV+, IVDU, MSM, close contact w/ HBV+ person [B]a
Latent TB Screen if born or lived in high risk country (see CDC website) or high risk setting (homeless, jail) in last 2 years [B]a
Psych/SUD/Social Risk Factor Screening
Depression Q1y [B]a; PHQ-2: in 2 wk how often (a) little interest/pleasure doing things & (b) down/depressed/hopeless
EtOH Misuse Screen regularly with AUDIT-C [B]a
Tobacco Every encounter [A] . Advise to quit, Assist doing so (plan, quit date, QuitWorks, meds), Arrange f/u.
a

Intimate
Screen regularly in women of reproductive age [B]a. HITS screen well- No data but consider ongoing IPV, elder abuse
Partner
validated. Assess immediate safety & consider HAVEN referral. screening
Violence
Fall Risk PT, Vit D [B]a
* If ASCVD borderline risk (5%-7.5%) or intermediate risk (7.5%-20%) use risk-enhancing factors (i.e. FHx, metabolic syndrome, CKD,
race/ethnicity, CKD, chronic inflammatory disease) or CA calcium scanning to guide decision about preventative interventions
δ history of previous GIB or PUD, or bleeding from other sites, thrombocytopenia, coagulopathy, CKD, and concurrent use of other

medications that increase bleeding risk (NSAID, steroids, NOACs, Warfarin)

^DM RFs: prior abnl testing (A1c≥5.7), FHx, AA/Latinx/Asian/NA ancestry, Hx GDM, PCOS, CVD, HDL<35 or TG>250, physical inactivity
***Age 40: ≥1st degree relative dx<65; Age 45: AA/ 1st degree relative dx<65; Age 50: expected to live >10y; 75+: based on life expectancy
ADDITIONAL SCREENING GUIDELINES FOR MEN [Evidence grade] (aUSPSTF, gACS)
Age 18-40 40 45 50 55 60 65 70 75+
AAA If +tobacco hx [B]a
FHx** Q2yg FHx, AA Q2yg Screen all men Q2y if life expectancy ≥ 10-15 yrsg
Prostate CA* PSA 55-69yo if pt preference [C]a,
recommend against if >70yo [D]a
Testicular CA Recommend against routine screening in all men[D]a
* All patients should be informed of the uncertainties, risks, and potential prior to deciding if they would like to be screened
** >1 first-degree relative with history of prostate cancer
ADDITIONAL SCREENING GUIDELINES FOR NON-PREGNANT WOMEN [Evidence grade] (aUSPSTF)
Age 18 19 20 21 25 30 3540 45 50 55 60 65 70 75+
Individualized Q2y mammography age 50-74.
Consider BRCA counseling if +FHx. Screening
Breast CA screen by risk Stop if <10yrs life expectancy.
tools available. [B]a
(Gail Model) [B]a
Cervical CA Q3y [A] a Q3y or Q5y + HPV co-testing [A] a Stop∑
STIs ≤24: GC/CT annually [B] a Screen based on risk assessment
Contraception Discuss with everyone. Start folic acid at reproductive age if planning/capable of pregnancy [A]a
Osteoporosis Consider earlier screening based on FRAX assessment [B]a DEXA [B]a
∑
Stop if 3 consecutive neg paps or 2 consecutive neg co-tests within 10 years w/ most recent test within 5 years. Continue x20 yrs s/p dx
pre-cancerous lesion regardless of age. Do not resume age ≥65 for new sexual partner only.
Jiby Yohannan
202
TOC

Primary Care Health Screening & Maintenance

ADDITIONAL SCREENING GUIDELINES FOR SPECIAL POPULATIONS
• MSM (men who have sex with men) and SMW (sexual minority women): see LGBTQ Health
• Immigrants and refugees: see Immigrant & Refugee Health
Note that there is considerable discrepancy between societal guidelines created using the same evidence.
Ex: Breast Cancer – USPSTF: biannual screening age 50-74 [B]; discussion of risks/benefits age 40-49 [C]; no
recommendation for women >75 [I]. ACS: annual mammography age 45-55; discuss transitioning to biennial screening at
55 until life expectancy <10 years; discuss initiation of annual screening at age 40. ACOG: offer mammography at 40; start
screening at 50; discuss cessation at 75; screen Q1-2 years.

MANAGEMENT OF ABNORMAL PAP SMEAR (ASCCP Consensus Guidelines, 2012)

Abnormal Pap Cytology Results
ASCUS LSIL HSIL AGC
Repeat cytology at 1 & 2 yrs: Colpo w/ For AGC-NOS, AGC-
Preferred: mgmt as per
Yr 1: ⊝, ASC-US, or LSIL  endocervical endocervical, or
LSIL (annual cytology)
repeat in 12 months; if >LSIL  curettage. May also adenocarcinoma in situ (AIS)
Alternative: HPV reflex. If
Age 21-24 colpo choose monitoring  will need gyn follow up
HPV⊝, resume regular
w/ colpo & cytology for colpo w/ biopsy &
screening; if HPV⊕, Yr 2: if ⊝ x2 resume regular q6mos for up to 24 endocervical sampling, w/
manage as LSIL screening; if ≥ ASC-US  colpo mos before tx
additional sampling if ≥ 35yo
Age 25- Preferred: HPV reflex; if Colposcopy, even if have HPV- or younger w/ endometrial
Option 1: colpo w/
menopause HPV⊕  colpo. If HPV⊝ result neoplasia RFs (unopposed
endocervical
repeat co-testing in 3 3 options: curettage estrogen, tamoxifen, early
years. - HPV reflex: if ⊕ colpo; if menarche, late menopause,
Post- Alternative: Repeat Option 2: immediate PCOS, DM, obesity)
HPV⊝, repeat pap in 1 yr OR
menopausal cytology in 1 year. If ⊝, LEEP (not if For AGC-endometrial 
- Repeat pap in 6 & 12 months:
resume routine screening. pregnant or desiring endometrial & endocervical
≥ ASC-US  colpo OR
If ≥ ASC-US  colpo pregnancy) sampling
- Refer for colpo
VACCINES (CDC)
Standard Immunizations 19-21 22-26 27-49 50-64 ≥65
Influenza 1 dose annually
Tdap/Td 1 dose Tdap then Td booster every 10 years
MMR 1-2 doses based on indication (if born in 1957 or later)
Varicella 2 doses (if born in 1980 or later)
Zoster 2 doses (recombinant)
HPV 3 doses
1 dose PPSV23. Shared decision
PCV13/PPSV23 Based on indication (see below)
making re PCV13. If both, give 1yr apart
Vaccine Special Indications
Influenza No live vaccine (intranasal) if immunocompromised or pregnant
TDaP / Td Extra dose of Tdap during each pregnancy
Special pops: CSF leak, cochlear implant, functional asplenia, immunocompromised, HIV, CKD, nephrotic
syndrome, malignancy, solid organ transplant, full list at CDC):
PCV13/ PPSV23 - Age >18: give PCV13 x1 followed by PPSV23 8 wks later followed by PPSV23 re-dose x1 at 5 yrs &
again at age 65 (if >5yrs from most recent)
- Age 19-64 w/ chronic heart, lung, or liver disease, diabetes, alcoholism, or cigarette smoking: 1 dose PPSV23
Varicella* Consider 2 doses in pts with HIV w/ CD4≥200
2 doses RZV 2-6 mo apart if >50yo (if received ZVL, at least 2 mo after dose). If >60, give RZV (preferred) or
Zoster*
ZVL.
HPV If MSM, transgender persons, or M with HIV vaccinate through age 26; Not recommended during pregnancy
1 dose in women of childbearing age; 2 doses if HIV & CD4≥200 OR health care personnel born in 1957 or
MMR*
later.
2 doses for travel to endemic countries, MSM, any drug use (not just IVDU), liver dz, clotting disorder,
Hep A
undomiciled, contacts of those at risk
3 doses for those w/ HCV, sexual exposure risk, IVDU, DM, ESRD, any chronic liver dz, HIV, health
Hep B worker/occupational exposure, travel to endemic country, household contacts, incarcerated persons
Meningococcus 1-3 doses depending on type for living in dorms, asplenia, HIV, MSM, complement def, military, occupational
(MenACWY/ MenB) exposure, travel in endemic country
Hib 1 dose if not immune for asplenia, 3 doses after HSCT regardless of vaccination history
* Hold in pregnancy, malignancy, immunocompromised (i.e. CD4 < 200)

Jiby Yohannan
203
TOC

Primary Care Women’s Health

V U L V A R / V A G I N A L C O M P L A I N T S (Obstet Gynecol 2008;5:1243)
Vaginal discharge: ask about amount, color, odor, pain, pruritus; infectious vaginitis is more likely to present acutely
• Bacterial vaginosis (BV): malodorous discharge, most common, most pts asymptomatic, high prevalence in WSW
o Dx: Amsel criteria (≥3): 1) homogenous, thin, grey-white discharge smoothly coating vaginal walls; 2) clue cells; 3) fishy
smell on KOH; 4) pH >4.5 (less reliable if post-menopause)
 Order “Genital culture female”, collected with rayon swab. GS assesses for clue cells (7-10 = BV)
o Tx: Metronidazole 500mg BID x7d, clinda 300mg BID x7d (vaginal gels also available w/less systemic effects), or secnidazole
2gm x 1; can opt not to tx if not pregnant
• Candida: curd-like discharge, pruritus, physical signs (vulvar erythema, edema may occur)
o Dx: pH normal, order “Genital culture female”, add on anti-fungal sens. if recurrent
o Complicated infxn: recurrent (≥4x/yr, severe symptoms, non-C. albicans, comorbid dz (DM, immunosuppression)
o Tx: miconazole 2% x 7d (pregnancy) or fluconazole 150mg PO x1; longer PO course for complicated infxn
• Trichomonas: purulent, malodorous, thin discharge, inflammation on exam, postcoital bleeding (DDx gonorrhea/chlamydia)
o Dx: if ⊕ pear-shapes on wet mount, don’t need NAAT test. If ⊝, order “Trichomonas vaginalis antigen”
o Tx: metronidazole 2g x1 for patient and sexual partners (tinidazole is better tolerated but more expensive)
Dermatoses: more likely to present chronically, often require GYN referral and vulvar punch biopsy to confirm diagnosis
• Contact dermatitis: erythema, swelling, fissures, erosions  r/o Candida, remove offending agent
• Vulvar atrophy: 50% postmenopausal ♀ 2/2 less secretions, Δ flora  lubricants, topical estradiol
• Lichen simplex chronicus: intense pruritis + lichenified plaque in pt w/ atopic dermatitis hx  antihistamines, steroids
• Lichen sclerosus: onset 50-60s, cigarette paper skin + porcelain white papules in pt w/ autoimmune dz. May lead to labia minora
fusion, clitoral hood phimosis, fissures, perianal dz. 5% incidence of malignancy  high potency steroids x4 wks
• Lichen planus: “purple, papular, pruritic,” white lacy striae, also involves vagina  high potency steroids, monitor for SCC
U R I N A R Y I N C O N T I N E N C E : very common (25% young women, 75% of older women); most women do not seek help
• Types: stress (leakage w/ coughing, laughing w/out bladder contraction), urge (urination preceded/accompanied by urge), mixed
(stress + urge), overflow (incomplete emptying), & functional (impaired mobility/cognition/neurologic); other (UTI, vaginal atrophy)
• History: systemic sx (fevers, dysuria, pain), meds (anticholinergics, diuretics, etc.), bowel habits, caffeine/EtOH use, voiding diary.
• Exam: check for prolapse, fistula, diverticulum; cough stress test (can be supine, but standing w/ full bladder sensitivity); urethral
mobility; rectal exam (fecal impaction, sphincter tone); neuro exam.
• Dx: UA/Cx, PVR (abnl >150cc), bladder stress test; urodynamic studies not indicated in initial eval of uncomplicated UI.
• Tx: bladder training (timed voiding; use PCOI handout), lifestyle interventions (e.g. wt loss, fluid/caffeine intake), pelvic floor
muscle exercises (e.g. Kegels; use PCOI handout, can refer to pelvic floor PT). Stress/mixed: pessaries (best if wish to avoid
therapy, refer to urogyn for fitting), vaginal estrogen (post-menopausal w/ vaginal atrophy), and procedures (midurethral sling,
urethral bulking agents). Urgency: antimuscarinics (numerous side effects), β-agonists (e.g. mirabegron, avoid w/uncontrolled HTN,
ESRD, liver disease), and intravesicular botox
A M E N O R R H E A (AFP 2013;187:781)
• Initial labs: HCG, FSH, LH, TSH, PRL
• In adults, most commonly 2° amenorrhea: cessation of regular menses for 3 mos or cessation of irregular menses for 6 mos
• Ddx: functional hypothalamic hypogonadism (weight Δ, eating disorder, excessive exercise, stress, prolonged illness), pituitary
dysfunction (hyperprolactinemia, mass effect from non-functioning adenoma, apoplexy), 1° ovarian insufficiency, PCOS,
hypo/hyperthyroidism, poorly controlled DM, exogenous androgen use, h/o uterine instrumentation (Asherman Syndrome)
• Progestin challenge: medroxyprogesterone acetate 10 mg x10 days. If ⊕ withdrawal bleeding  anovulation
o If ∅ withdrawal bleeding  E/P challenge  ⊕ bleeding = hypoestrogen state (nml/FSH = hypothalamic; FSH = ovarian
failure). ∅ bleeding = outflow tract obstruction (hysterosalpingogram/hysteroscopy)
POLYCYSTIC OVARY SYNDROME ( P C O S ) (J Clin Endo Met 2013;98:4565; NEJM 2016;375:54)
• Affects 5-10% of women of reproductive age
• Rotterdam Criteria 2/3: 1) oligo/anovulation, 2) clinical/ biochemical hyperandrogenism, 3) polycystic ovaries on pelvic U/S
• Workup: testosterone; exclude other dx (hCG, FSH, 17-OHP [pre-8AM], prolactin, TSH), metabolic d/o, OSA, mood d/o (depression)
• Tx: weight loss, exercise, OCP (1st line), spironolactone, metformin (if insulin resistant), fertility referral for pregnancy (clomiphene)
I N F E R T I L I T Y (Fertil Steril 2015;103:e44)
• Evaluate after 12 mo unprotected intercourse in <35 yo, 6 mo in >35 yo
• DDx: ovulatory dysfunction, fallopian tube or uterine abnormalities, cervical factors, endometriosis
• Hx: duration of infertility, prior OB/GYN hx (menstrual hx, pregnancies, PID, fibroids, cervical dysplasia, endometriosis, contraceptive
use, DTE exposure), sexual hx (timing, frequency, lubrication, dyspareunia), meds, prior chemo/XRT, substance use, FHx
• Dx: 1) Test ovulation: mid-luteal progesterone (day 21, 1wk before expected menses, goal >3), home kit to check for LH surge.
2) Test ovarian reserve: FSH/estradiol (day 3, goal FSH <10, estradiol <80), clomiphene challenge test
3) Additional workup: chlamydia PCR, hysterosalpinogram & saline infusion sonohysterography (tubal patency), pelvic U/S (uterine
myomas/ovarian cysts), TSH, semen analysis of partner, laparoscopy if strong suspicion of endometriosis
• Tx: correct reversible etiologies, refer to reproductive endocrinology for aggressive induction of ovulation, IVF, or donor oocytes

Zoe Memel and Natasha Merali

204
TOC

Primary Care Women’s Health

MENOPAUSE
• Amenorrhea x12 mo w/o alt etiology (no need to labs), avg onset at 51, suspect 1° ovarian insuff if <40 (Obstet Gyn 2014;123:202)
• Vasomotor sx (hot flashes):
o Systemic hormone tx (estrogen + progestin, estrogen mono tx if hysterectomy) most effective tx but only recommended if <60 yo
& for <5 yrs duration (don’t use if CVD >10% or high risk for breast CA) (J Clin Endocrinol Metab 2015;100:3975). Side effects: breast
tenderness, vaginal bleeding; CRC, fracture risk; breast CA, CVD, VTE; Ø risk of mortality after 5-7 yrs (JAMA 2017;318:927).
o Try alternatives first: paroxetine, venlafaxine, gabapentin, clonidine
• Vaginal sx: dryness, burning, pain w/ intercourse
o Lubricants (KY): prior to intercourse; moisturizers (Replens) = longer-term relief
o Topical estrogen therapy: ring, tablet, cream; start at 0.3 mg/day; Ø  risk of endometrial hyperplasia
o SERM (ospemifene): for sx atrophy not relieved by non-pharm tx or not amenable to topical tx; side effects incl hot flashes
C O N T R A C E P T I O N (Quick Start Algorithm, CDC USMEC 2016, CDC 2020 Update)
• 45% of pregnancies are unplanned  rule out pregnancy before initiating contraception  LARCs (IUD, implant) are first line
• Hormonal methods take ~1 wk to work  use backup method for 7 days
1yr Failure
Use Pros/Cons Contraindications
Rate*
Estrogen-progestin
Pill Daily 9% (0.3%) - Pros: menses, PMS, cramps, acne, - VTE, thrombogenic mutation
Ring (Nuva-Ring) 3 wks in, 1 wk out 9% (0.3%) endometrial/ovarian CA - Active breast or liver CA
- Cons: n/v, breast tenderness, can - Migraine w/ aura, >35 yo + any migraine
Weekly x3 wks, 1
HTN/TGs, libido, spotting for first - Uncontrolled HTN, DM w/ vasc
wk off; apply to
Patch (Xulane) 9% (0.3%) few months, cannot start if < 21 days complications, CVD, valvular dz
arm, torso, or
post-partum (VTE risk), requires - >35 yo + >15 cig/day
buttock
patient adherence - ESLD
Progestin-only
IUD (hormone Mirena Q7Y - Pros: effective, long-acting, lighter - Abnl uterine cavity, G/C at time of insertion,
content Mirena > Kyleena Q5Y 0.2% periods, may reduce cramping PID, endometrial/cervical/ breast/liver Ca,
Kyleena > Skyla) Skyla Q3Y - Cons: irregular bleeding, physical APLAS, pregnancy, ESLD
Implant Q3Y to upper complications (rare) - Unexplained vaginal bleeding
0.05%
(Nexplanon) inner arm - Breast/liver CA, APLAS, ESLD
- Pros: long-acting - Unexplained vaginal bleeding
Injection (Depot- Q3mo IM/SQ to - Cons: irregular bleeding, weight - Breast/liver CA, APLAS, ESLD
4% (0.2%)
Provera) buttock gain (<5 lb), BMD, prolonged return - CV risk factors, uncontrolled HTN, DM w/
to fertility (1 yr) vasc comp, iCMP, CVA, vasc disease
- Pros: few contraindications
- Bariatric surgery
Pill (Micronor) Daily 8% (0.3%) - Cons: irregular bleeding, must take
- Breast/liver CA, APLAS, ESLD
at same time daily
Hormone-free
- Pros: effective, long-acting, safe in - Abnl uterine cavity, endometrial/cervical CA
Copper IUD
Q12Y 0.8% ESLD, emergency contraceptive - G/C at time of insertion, PID,
(Paraguard)
- Cons: heavier bleeding, cramping - Pregnancy
- Pros: STI prevention
Male condom Every encounter 13% (2%) - Oil based lubricant w/ latex condom
- Cons: require patient adherence
- Pros: effective, long-acting
Sterilization Permanent 0.5% - Surgical risk, patient unsure of decision
- Cons: irreversible
* Typical use – i.e. % women who will have unplanned pregnancy in 1 year on this method; (perfect use not realistic for most)
Oral Contraceptives (OCPs) (CDC MMWR 2013;62:1)
• Types: monophasic vs multiphasic/ triphasic; combined (estrogen + progestin) vs progestin-only
• OCP selection: 2nd gen progestin-containing (levonorgestrel, norethindrone):  VTE risk. 3rd gen progestin-containing (norgestimate,
desogestrel):  androgenic SE, higher VTE risk. Progestin-only (norethindrone 0.35 mg): if breastfeeding or if contraind. to estrogen
Emergency Contraception (Obstet Gynecol 2010;115:1100)
• Plan B (levonorgestrel 1.5mg x1 or 0.75mg x2): OTC, use <72 hrs, less reliable if BMI >30. Ella (ulipristal acetate 30 mg): requires Tx,
use <120 hrs, more reliable in higher BMI. Paragard (copper IUD): ideally placed within 120 hrs (okay up to 160hrs), most effective
• In cases of sexual assault: refer pt to the ED for an exam by a trained SANE RN. If IPV: ask if partner has access to online medical
records prior to detailed documentation and prepare safety plan. MGH HAVEN referral: 617-724-0054
A B O R T I O N (Guttmacher Institute Fact Sheet; Am J Public Health 2017;107:1904; Obstet Gynecol 2014;123:676)
• See PCOI for list of providers in MA. Avg cost ~$500, 50% pay out of pocket. Counseling: 1-866-4-EXHALE
• Workup: confirm pregnancy with LMP and pelvic U/S, check CBC/Rh, offer STI testing and immediate post-abortion contraception
• Medical abortion (<10 wks gestation, 92% effective): mifepristone x1  buccal misoprostal in 24-48 hr  pt passes pregnancy at
home over hrs. A/w cramping and bleeding. Tx with NSAIDs. F/u bHCG or pelvic U/S usually in 14d
• Surgical abortion (<24 wks gestation, 99% effective): same-day office procedure  no f/u unless complications
Zoe Memel and Natasha Merali
205
TOC

Primary Care LGBTQ Health

General Considerations
LGBTQ individuals are at higher risk of depression, anxiety, suicide attempts, medical mistreatment, and lacking health insurance
compared to cisgender heterosexual individuals (Am J Prev Med 2018;55:336, BMC Psych 2008;18:70)
• When in doubt, ask your patient! Use open ended questions, ask for pronouns, focus on patient’s health behavior rather than
assumptions about orientation/identity, provide anatomy-based screenings, learn from your patients’ lived experiences
• Gender Terminology
o Sex assigned at birth: based on external anatomy vs gender identity: internal sense of one’s gender
o Transgender/trans: when one’s assigned sex at birth and gender are not congruent
o Cisgender: when one’s assigned sex at birth and gender identity are congruent
o Non-binary, gender non-conforming, genderqueer: gender identity not w/in society’s M/F binary
Preventive Health Care for MSM (NEJM 2015;373:854)
• Health Inequities:
o HIV/AIDS (In U.S. 63% of all new HIV infxn, 50% of all persons living with HIV), STIs, cancer screening, immunizations,
substance & tobacco use, mental health, childhood sexual abuse, domestic violence (IOM 2011) (CDC 2018)
• Recommendations:
o Annual STI Screening: HIV; TrepAb for syphilis; site-specific GC/CT NAAT based on sexual history (urine, rectal, pharyngeal);
urine NAAT as sensitive as urethral; self-collected rectal swabs as sensitive as provider-collected rectal swabs; testing
pharyngeal swabs for CT not recommended
 Screen q3-6mo if multiple/anonymous partners, sex in conjunction w/ drug use
o Immunizations:
 HAV vaccine (fecal-oral transmission, don’t need to check immunity); HBV SAg & SAb once, vaccinate if non-immune;
HCV Ab once if born 1945-1965 & check HCV Ab q1y if high risk
 Meningococcal vaccine, HPV vaccine if <27 (NEJM 2011;364:401)
o Anal Pap: if HIV- consider q2-3y; if HIV+, perform q1y (high-grade AIN 29%) (Lancet Oncol 2012;12:487)
o PrEP: Consider if high-risk sexual activity, HIV-, nml Cr, able to take daily. TDF-FTC or TAF-FTC QD are both FDA approved
options that have been studied in MSM populations (CDC 2019); see HIV section.
o Educate on how to access PEP within 72h of high-risk exposure – can page 36222 at MGH
Guidelines for Sexual Minority Women (SMW) (ACOG 2012;119:1077)
• Higher prevalence of obesity, EtOH use, and tobacco use → Increased risk of cardiovascular disease and DM
• Still at risk for HPV infection although lower rates of screening reported (Arch Fam Med 2000;9:843).
• Discuss conception options, intimate partner violence (using gender neutral language), and substance abuse
Transgender Medicine: 0.6% of adults in the U.S. identify as transgender or gender non-conforming (NEJM 2019;381:2451)
• Health inequities: mental illness (suicide attempts, depression, anxiety) cervical cancer (counsel that less likely to obtain adequate
sample), HIV (trans women w/ 22% HIV infection rate vs 10% of MSM in the US) (J Adolesc Health 2015;56:274; JGIM 2014;29:778; Lancet
Infect Dis 2012;13:214)
• Gender-affirming care: see WPATH Standards of Care, UCSF Center for Excellence in Transgender Health, Fenway Guide
o Informed consent and well documented gender dysphoria/incongruence is needed to initiate hormone therapy
o Discuss fertility preservation needs prior to starting hormones
o Feminizing hormone therapy cornerstones: estradiol + concomitant androgen blocker
 Estradiols: oral/sublingual, transdermal patch, estradiol valerate/estradiol cypionate IM
 Androgen blockers: spironolactone, GnRH agonist; can decrease required estrogen dose
o Masculinizing hormone therapy cornerstones:
 Testosterone (T) (testosterone cypionate/enanthate IM/SQ or testosterone topical gel/transdermal patch)
(J Clin Endo Metab Potential Risks Irreversible changes Reversible changes Monitoring
2017;102:3869)
- CBC, lipids, BP q3mos first
- Deepening of voice - Cessation of menses
- Breast or uterine cancer year then q6-12 mos
Masculinizing - Facial and body hair -  sex drive
- Erythrocytosis - Regular pap tests if
Therapy - Possible male -  muscle mass
- HTN, HLD cervical tissue present
(testosterone) pattern baldness - Possible acne, mood
- Sleep apnea - Serum T q3 mos until in
- Clitoromegaly changes
normal physiologic M range
- Infertility, erectile dysfunction - If on spironolactone,
- Breast growth -  muscle mass
Feminizing - Breast cancer BUN/Cr and K q3mos first
- Testicular atrophy - Weight gain
Therapy - Blood clots (DVT, PE) year then annually
- Redistribution of fat - Hair/skin softens
(estrogen, - Increased risk of CAD, HTN, - Yearly prolactin
mass -  sex drive
spironolactone) stroke, liver dz - Serum T and estradiol
- Infertility -  libido, erections
- Migraines levels q3 mos
• Pregnancy prevention for transmasculine pts: T suppresses period but may not prevent pregnancy
• Additional practices to alter appearance: binding, tucking, hair removal, silicone injections

Jiby Yohannan
206
TOC

Primary Care Immigrant & Refugee Health

Interpreter Services:
• In-person MGH Interpreter Services: x66966 or pager 27403 (Mon-Fri 6a-8p; Sat/Sun 8a-6:30p)
• CyraCom Phone Interpreter: 617-643-3344 Pin #1050
Medical Examination (CDC checklist)
History: obtain prior medical records if possible
• Country of origin, transit countries, residence in refugee camps or detention centers, amount of time living in US
• Family structure, food security, housing stability, safety in home/neighborhood
• Chronic diseases: HTN, DM, tobacco/substance use, kidney disease, chronic pain, age-appropriate cancer screening
• Mental health: PTSD, anxiety, depression; RHS-15 (screen at 2nd visit to minimize effect of re-traumatization)
Physical Exam:
• Vision, dental, hearing, BMI, BP screenings. See PCOI for low-cost referral options “Patient Education”  “Health Care Access”
• Complete skin exam: rashes, signs of trauma, signs of micronutrient deficiencies.
Vaccinations: if no vaccine documentation, assume pt not vaccinated (CDC Adult Schedule). For varicella and HBV, check titers first
Screening and Labs: (see CDC regional profiles)
• General screening: CBC/diff (eos, anemia), U/A (hematuria), BMP (glucose, Infection Signs and Symptoms
renal dz), ♀ hCG Strongyloidiasis,
Peripheral eosinophilia
• Tuberculosis: ask every year about sx, recent travel, sick contacts; IGRA filariasis, schistosomiasis
preferred to PPD (see TB section)  CXR  induced sputum Hematuria, ♀ infertility,
Schistosomiasis
• STIs: syphilis (Trep Ab at MGH, VDRL/RPR elsewhere); HIV; GC/CT if ♀ ≤25 chronic pelvic pain
& sexually active or ♀ > 25 + risk factor Malaria, schistosomiasis Splenomegaly
• HBV serologies: if from Asia, Africa, Middle East Mycetoma,
• Malaria: treat if from SSA and did not receive pre-departure Tx, or from onchocerciasis, other Chronic rash or itching
endemic country +sx. If pregnant or breastfeeding, test first (do not treat filarial diseases
empirically). Obtain thick/thin blood smears or PCR (more sensitive if no sx) Esophageal
• Intestinal and tissue invasive parasites: depends on country of origin and pre- Chagas disease dysmotility, HF,
departure treatment. See CDC guidelines for details on diagnosis and conduction dz
treatment. Do not give empiric ivermectin if pt from Loa loa-endemic country. Neurocysticercosis Seizures, CNS sxs
• Micronutrients (Fe, D, B12, etc): if malnutrition, anemia, h/o food insecurity
Type Details
Legal Considerations
Lawful Permanent Resident: Green card recipient;
• Do not document immigration status in EMR.
LPR pathway to citizenship. Family members can get
• In MA, MassHealth eligibility is NOT contingent on
green card through “family based” immigration.
immigration status. Refer all pts to PFS; PCOI page
Eligible if victim of human trafficking (T) or victim of
“Patient Education”  “Health Care Access”  “Help
U-Visa, T-Visa certain types of crime (U). Violence Against
Uninsured Patients Access Medical Care.” Videos for
VAWA Women Act: Eligible if abused by spouse, child or
patients on the ACA
parent who is LPR/citizen.
• Know your Rights: handouts re: ICE (English) (Spanish);
Temporary Protected Status: Short list of countries,
Red Cards (rights cards in different languages)
TPS where conditions preclude safe return. Cannot be
• Legal services available for patients in the Boston area; deported while country of origin on list.
consider referral to LINC at MGH Chelsea
Based on exception hardship to self or LPR/citizen
• For the latest on public charge and other legal changes Cancellation of
spouse, parent, child if deported; ineligible with
that may affect immigrant patients, refer to: Removal
certain criminal convictions.
o Protecting Immigrant Families (PIF)
Well-founded fear of being persecuted based on
o Massachusetts Immigrant and Refugee Advocacy
race, religion, nationality, membership in social
Coalition (MIRA)
Asylum group or political opinion. Application due within
• Asylum screening questions: 1yr date of entry. If granted, may also apply to
o What led you to leave your home country? spouse and children if in United States.
o Were you ever a victim of violence or abuse there?
Same legal standard as Asylum, based on
(verbal, sexual, physical)
persecution or well-founded fear, but granted prior
o If so, was it due to your religion, race, political Refugee
to arrival in US. Maximum set annually by
beliefs, nationality, or particular social group
President (no limit to Asylum).
(including gender, sexual identity)?
Temporary reprieve from deportation for
o If so, did you face violence from anyone working for Medical Deferred
immigrants facing life-threatening medical
the government, military, or police? Action
conditions and other humanitarian circumstances
o If yesrefer to legal org above, to PAIR, or to the
MGH asylum clinic ([email protected]) Asylum/CAT/Withholding all part of same
Withholding of
application. No 1yr rule; may apply at any time.
• Resources on conducting asylum evaluations and Removal
Ineligible with certain criminal convictions.
working with asylum seekers
Convention Against Torture: similar to Withholding,
CAT
but still eligible with criminal convictions.
Patients should seek legal counsel to ensure no
Undocumented
options to apply for alternative statuses.
Hazel Lever and Miranda Ravicz
207
TOC

Primary Care Musculoskeletal Pain

Knee Pain
• History: trauma, acute vs chronic, association with activity, constitutional sx, swelling, stiffness, instability, popping or catching
sensation, sensory/motor changes, BMI, orthopedic or rheumatologic hx. Have pt point to area of pain with one finger.
Location Traumatic Related to Activity Atrauamatic
Patellofemoral syndrome, Osgood-Schlatter
Anterior Quadriceps or patellar injury RA, gout, pseudogout, septic joint
Bursitis, Quadriceps/patellar tendinopathy
Lateral Lateral meniscal tear, LCL injury Iliotibial band syndrome Lateral OA
Medial meniscal tear, MCL injury, tibial Medial OA, Saphenous nerve
Medial Anserine bursitis
plateau fracture entrapment
Popliteal PCL injury Popliteal artery entrapment, Baker cyst Popliteal artery aneurysm, DVT
Knee Exam
Test Maneuver Positive in
Lachman (sim. to Pt supine with knee flexed, one hand on pt’s femur, just above knee. Other hand on pt’s tibia. Apply
ACL injury
anterior drawer) slight flexion and pull sharply towards your abdomen. If tibia feels less restrained, ⊕ test
Pt supine with knee flexed, can stabilize foot by sitting on it. Place hands around tibia, apply pressure
Posterior drawer PCL injury
backward in place parallel to femur. If less restrained motion, ⊕ test.
One hand over medial joint line with knee fully flexed. Externally rotate foot/tibia, apply valgus stress Meniscal
McMurray
and gently flex/extend knee. If clicking around medial joint line, ⊕ test. injury
• XR imaging: if trauma <1wk old & c/f fracture, follow Ottawa Rules (Sn 98%, Sp 49%; Annals 2004;140:121)
o Obtain if any of the following: >55yo, isolated patellar tenderness, tenderness at head of fibula, cannot flex to 90°, or cannot bear
weight for 4 steps (limp doesn’t count).
o If eval of chronic OA, get weightbearing views of both knees; patellar view for patellar problems.
• Reserve MRI until 4 weeks conservative care unless suspect fracture, infection, or internal derangement (e.g. ACL, meniscal tear in
younger patients). Asymptomatic meniscal tears: 13% <45 yo, 36% >45 yo (Clin Ortho Rel Res 1992;282:177)
• Meniscal tear treatment: limited benefit of arthroscopy, esp. in degenerative meniscal tears in >45, pts with OA (BMJ 2017;357:j1982).
Start with NSAIDs, PT, wt loss. Consider glucosamine+chondroitin or platelet-rich-plasma (AHRQ 2017)

Shoulder Pain
• Rule out neck etiology: neck pain, pain radiation beyond elbow, numbness, tingling
• History: trauma, acute vs chronic, constitutional sx, orthopedic history, day/night, provoking activity, loss of ROM, weakness
o Get precise pain location
Etiology History & Physical Exam Findings
Subacromial Bursitis Ref. pain to deltoid. Pain w/ arc 60°-120° abduction +/- impingement. Overuse, heavy lifting. No imaging.
Acute=trauma. Chronic=age, acromial spurring, overuse. Can be tendonopathy, partial or full thickness tears.
Rotator Cuff
Pain & weakness,  ROM, ⊕ internal/external lag test, painful arc, impingement. Ortho referral, MRI if tear.
Glenohumeral OA / Aching, stiff; chronic loss of active and passive motion in all planes. OA: crepitus, age >60 yo.
Adhesive Capsulitis Capsulitis:  risk with diabetes, thyroid disease, immobilization, often 40-60 yo. Plain films for OA
Young athletes. “Click, pop, catch.” Ant inferiorshot-blocking arm pulled back. Posteriorpush-up.
Labral Tears & Instability
SLAP (Superior Labrum Anterior Posterior) baseball pitching, swimming. Crepitus/catching w/ ROM. MRI
Young: traumatic sprain, fall with separation. Older: AC evolves into OA (can contribute to impingment)
AC Joint Pain
Pain, tenderness, swelling over AC joint, ⊕ cross arm test. Plain films (w/ “stress views” for trauma)
Shoulder Exam
Test Maneuver
Drop Arm (RTC) Ask patient to abduct arm at 90°. ⊕ if cannot smoothly adduct shoulder to waist-level.
Bring dorsum of patient’s hand against lumbar region of back. Take forearm and hand away from
Internal Lag Test (RTC)
the back (~20°). Ask pt to maintain position while supporting elbow. ⊕ if not maintained.
External Lag Test (RTC) Externally rotate shoulder 90°, flex elbow 90°. Ask pt to maintain position. ⊕ if not maintained.
Neer (subacromial/RTC) Fully pronate forearm (thumbs point backwards), bring shoulder to full forward flexion. ⊕ if pain.
Hawkins (subacromial/RTC) Forward flex shoulder to 90°, flex elbow to 90°, and internally rotate the shoulder. ⊕ if pain.
Ext. Rotation (teres minor & infraspin.) Flex elbow 90°. Pt externally rotates shoulder while examiner provides resistance. ⊕ if pain.
Empty Can (supraspinatus) Flex shoulder 90°, internally rotated forearm. ⊕ if pain w/ resistance of downward push
• Imaging: x-ray if h/o trauma c/f fracture or dislocation, gross deformity, exam concerning for RTC tear or joint involvement; true AP of
glenohumeral joint, axillary lateral, & “Y view” of AC joint. MRI w/o contrast in pts with ⊕ internal/external lag tests, r/o full thickness
RTC tear, previous abnormal radiograph, persistent pain despite 2-3 mos of conservative therapy (see below)
• Treatment: bursitis/capsulitis/tendinopathy/impingement/OA/partial thickness RTC tear: conservative therapy (e.g. activity avoidance,
NSAIDs, PT/home exercises +/- steroid injections short-term); surgery for refractory instability, labral/full RC tear, AC joint seperation

Nate Alhalel
208
TOC

Primary Care Musculoskeletal Pain

Low Back Pain:
• 84% lifetime acute back pain, 50% sciatica (Mayo Clin Proc 2015;90:1699); 75-90% improve over 4 weeks
Definition Signs and Symptoms Etiologies
85% of acute low back pain in primary care is nonspecific
Disc: young &  w/ spine loading (i.e. sitting) Muscle/ligament injury,
Originates from Facet: > 40 yo,  in extension and  by sitting. facet, DJD, vertebral
muscles, discs, SI pain: MVA/falls, rheum compression fx, cancer,
Axial
endplates, facet joints, Compression fx: older, trauma, osteopenia, steroids spondyloarthropathies,
SI joints. Cancer: PMH, weight loss, night pain discitis/osteo/epidural
Inflammatory back pain: AM stiffness, night pain abscess
Infection: fever, night sweats, immunosuppression, IVDU
Originates from disc Sciatica is 95% Sn / 88% Sp for herniation Disk herniation,
herniation w/ nerve Leg > back pain w/ dermatomal distrib. of lancinating/burning pain spinal/foraminal stenosis,
Radicular
compression (90% L4- Straight leg raise ⊕ can’t miss cauda equina
S1), spinal stenosis L4-5: foot dorsiflex. L5-S1: foot plantarflex and ankle reflex. (bladder/bowel involv.)
• Physical exam: palpation of midline, ROM spine/hip, strength/reflexes of LEs, rectal tone (if c/f cauda equina), SLR
• Imaging
o Early MRI / x-rays if RED FLAGS:
 Focal severe/progressive neuro deficits, cauda equina sx; trauma; suspect fracture, osteopenia risk (age >50 or <20, PMH,
steroids); major risk factors/hx of cancer; fevers/wt loss/IVDU (Spine 1996;21:2885)
o Otherwise, defer imaging until after initial 4-6wk tx (Annals 2007;147:478; Choosing Wisely guidelines) as herniated disks, disc
bulging, and degenerative discs are common findings (Am J Neuroradiol 2015;36:811)
o Always explore potential poor coping, fear/avoidance, social/psychological stressors. Tx: depression, anxiety, SUD
o See STarT Back Screening tool for further guidance
• Possibly effective and lower-risk therapies:
o Avoid bed rest! Activity as tolerated.
o PT & exercise w/ progressive home exercise (no demonstrated benefit in acute LBP, modest benefit for subacute/chronic)
o Non-pharmacologic therapies: acute LBP  heat/cold, massage, manipulation, acupuncture; chronic LBP  yoga, cognitive
behavioral therapy, mindfulness, multidisciplinary rehabilitation (Annals 2017;166:514)
o NSAIDs (ibuprofen 400-800 TID or naproxen 200 to 400 BID) are first line for limited duration if no contraindication
o Muscle relaxants: combo tx w/ NSAIDs may give add’l benefit acutely if NSAIDs alone ineffective (JAMA 2015;314:1572)
o Duloxetine and tramadol for chronic LBP (no benefit in acute); second line after NSAIDs (Annals 2017;166:480)
o Radicular pain: if no improvement despite 6+wks of non-invasive tx, consider referral to Pain Med or PM&R for trial of epidural
steroids (limited evidence, benefits likely limited and short-term). Not recommended for acute or nonradicular pain.
• Therapies with questionable evidence and/or higher risk of harm:
o Acetaminophen: if NSAIDs contraindicated; but little e/o effectiveness (Lancet 2014;384:1586)
o Oral prednisone taper for acute sciatica: inconclusive evidence (Annals 2017;166:480)
o Gabapentin, pregabalin: option for sciatica though efficacy inconclusive (NEJM 2017;376:1111)
o Opioids: limited evidence of effectiveness, & higher risk of harm (JAMA 2018;319:872). Before prescribing, review potential benefits
vs. risks. MA law: Must check PMP and limit 7 days for initial opioid prescription. Plan to d/c in 6-8 weeks if no benefit

LONG-TERM OPIOIDS FOR MSK PAIN

• Limited evidence for chronic MSK pain. High risks of hyperalgesia, tolerance, dependence, addiction.
• Before prescribing longer-term opioids:
o Exhaust non-opioid options. Avoid benzodiazepines, hypnotics. Screen for sleep apnea, SUD, mental health. Stress that pain
control is a mutual goal, complete pain relief is unlikely, set functional goals.
o Perform a risk assessment (Screener & Opioid Assessment for Patients with Pain (SOAPP)-Revised). Check MassPAT (also
linked in Epic). Obtain prior records & speak to prior prescribers. Agree that single prescriber will provide scripts.
o Create a pain agreement with the patient: discuss 6-8 week initial trial, safe use, secure storage and disposal of opioids.
Educate that random UTox and toxicology, random pill counts are for pt safety. Rx on 28-day cycle ending on weekday to
facilitate refills. Prescribe the patient naloxone to be used in case of overdose risks.
o Discontinue opioids if no significant benefit at 6-8 wks, significant side effects, risk > benefit, non-adherence.
o Caution prescribing > 50 mg/day morphine equivalents (MME), avoid > 90 MME (obtain pain consult).
• Follow-up for longer-term opioids:
o See patients in office at least q1-3 months to review pain, function, side effects, compliance, and re-evaluate plan.
o Early refill requests should trigger an appointment to assess reason, obtain tox screen, discuss use.

Nate Alhalel
209
TOC

Primary Care Respiratory Complaints

C H R O N I C C O U G H (Am Fam Phys 2017;96:575, NEJM 2016;375:1544)
• Acute (≤3 weeks) vs. subacute (3-8 weeks) vs. chronic (>8 weeks)
• Most common causes: upper airway cough syndrome (UACS), asthma, GERD; 18-62% pts have combo
o Other causes: post-infxn (self-limiting; can last up to 3+ months, treat sxs), nonasthmatic eosinophilic bronchitis, chemical irritant
(eg. cigarette smoke), laryngopharyngeal bronchitis, psychogenic/habitual cough, bronchiectasis, CA, TB, sarcoid.
o Normal CXR usually excludes bronchiectasis, persistent PNA, sarcoidosis, TB.
• General approach: 1) obtain good history (smoking status, URI hx, ACE-i use); consider CXR if no ACE-i or irritant exposure (except
smoking) and  suspicion for UACS/asthma/GERD; consider spirometry; 2) remove possible offending agent; 3) start empiric tx for
UACS/asthma/GERD sequentially until resolution  tx should be added to initial regimen; 4) consider PFTs, esophageal pH
monitoring, chest CT, sputum tests, cardiac studies if sxs persist despite treatment of usual causes.
Etiology Characteristics Treatment
Upper Airway Formerly post-nasal drip syndrome. Most common cause of Avoid environmental triggers of allergic rhinitis.
Cough subacute/chronic cough. Exam of throat/nose may reveal Intranasal steroids, antihistamine nasal spray, oral
Syndrome cobblestoning. Can be absent of symptoms other than cough. antihistamine, oral decongestants, or saline nasal
(UACS) Common causes: allergic/non-allergic rhinitis, sinusitis. rinse can be used for symptom relief
Typically w/ episodic wheezing & dyspnea. Cough variant
PRN bronchodilators +/- inhaled corticosteroids.
asthma p/w only cough. Pt may have h/o atopy. Exam: may
Asthma Some pts may use only seasonally. See “Asthma”
have nasal polyps. Need spirometry w/ bronchodilator response
in Pulmonology section for stepwise therapy.
& bronchoprovocation (e.g. metacholine challenge) for dx.
30-40% of chronic cough. Epigastric burning sensation, sour Lifestyle modifications, moderate dose PPI/H2
GERD
taste in mouth, but sxs absent in >40% of patients. blocker. Consider H pylori testing.
H/o recent viral illness. 2/2 postnasal drip/UACS or direct effect UACS tx as above. 2nd gen (cetirizine) or 3rd gen
Respiratory
of virus on bronchial reactivity/cough receptors. Pts have been (fexofenadine) antihistamine. If bronchial
tract infection
shown to experience transient bronchial hyperreactivity as well. hyperreactivity, tx w/ usual asthma care.
Produces cough in 3-20% of pts. 2/2 ACEi mediated increase in Withdraw ACEi (resolves within 1-4 weeks),
ACE Inhibitor
bradykinin. Sxs can occur 1 wk to 6 mos after starting. change to ARB (not associated with cough).

R H I N O S I N U S I T I S (Otolaryngol Head Neck Surg 2015;152:598, NEJM 2016;375:962)

• Acute (<1mo) vs. subacute (1-3mo) vs. chronic (>3mo, usually w/ anaerobes); recurrent (4 or more annual episodes)
• Dx: rhinorrhea (viral=clear, bact=purulent) + nasal obstruction or facial pressure/pain/fullness. A/w anosmia, ear fullness, cough, H/A
• Acute rhinosinusitis is infectious while chronic is inflammatory (atopy, asthma, granulomatous disease, immunodeficiency, CF)
Etiology Time Frame Treatment
Bacterial: only 0.5-2% of >10 days, or worsening Watchful waiting in pts w/ follow-up • NSAIDs/Tylenol for pain
acute rhinosinusitis S. within 10d after initial vs. Augmentin 875mg BID** or Doxy • Saline irrigation/Netipot
pneumo (41%), H. flu (35%) improvement 100mg BID x 5-7d • Topical nasal steroids,
Viral: most common cause 7-10 days Symptom control, oral decongestant decongestant, expectorants
Fungal: mucor (invasive) in Acute (invasive) to more Surgical removal of fungal mucin or “fungal ball” (mycetoma). ENT
DM, immunocompromised chronic (>3mo) emergency if invasive (destruction of sinus, erosion into orbit or brain)
** Higher dose Augmentin (2g BID or 90 mg/kg/d BID) in pts w/ RFs for resistance (regional resistance pattern, age 65+, hospitalized in last 5d, abx use in
last month, immunocompromised, DM/cardiac/renal/hepatic disease, severe infxn (fever >102F, suppurative complication)
• Chronic rhinosinusitis: confirm diagnosis w/ CT or endoscopy; treatment varies by presence of absence of nasal polyps
o W/out polyps  trial saline irrigation/intranasal steroid; ⊕ polyps  add short course of PO steroid +/- ASA desens. if concern
for ASA-exacerbated respiratory disease
• Complications: meningitis, periorbital/orbital cellulitis (pain, edema, proptosis, painful eye movement, diplopia),
subperiosteal/intracranial/epidural abscess, osteomyelitis of the sinus bones, septic cavernous sinus thrombosis.
• Alarm symptoms: persistent fevers >102F; periorbital edema, inflammation, or erythema; CN palsies; abnormal extraocular
movements; proptosis; vision changes (diplopia, impaired vision); severe headache; AMS; meningeal signs
P H A R Y N G I T I S (JAMA 2012;308:1307, NEJM 2011;364:648)
• Most cases are viral (suspect if + conjunctivitis, coryza, cough, diarrhea, hoarseness, discrete ulcerative stomatitis, viral exanthema).
Only 5-15% of adult sore throat visits are Group A Strep (GAS).
• Exclude dangerous etiologies: epiglottitis, peritonsillar abscesses, infx in submandibular or retropharyngeal space, primary HIV
• Identify & treat GAS to  risk of suppurative complications (peritonsillar abscess, cervical lymphadenitis, mastoiditis), prevent
rheumatic fever (lower risk in adults),  transmission, & improve sx. ASO titers useful only in dx of non-suppurative sequelae of GAS.
o Centor Criteria: 1 pt for each: tonsillar exudates, tender ant. cervical LAD, fever, ∅ cough; (-1pt if age ≥45)
 0-2: no testing, treat sx. 3-4: send Rapid Strep antigen detection test (Sn 70-90% / Sp 95%) + throat culture (if neg rapid but
 clinical suspicion; not indicated for routine use in adults w/ neg rapid)
o Tx: PO Penicillin V 250mg QID vs 500mg BIDx10d; amoxicillin 500mg BIDx10d; IM Pencillin G benzathine 1.2 mill Ux1
 PCN-allergic: cephalexin 500mg BIDx10d
 β-lactam sensitivity: clinda 300mg TIDx10d; azithromycin 500 mg QDx1d, then 250 mg QDx4d
• Symptomatic Tx: OTC lozenges (e.g. Sucrets, Cepacol), throat sprays, NSAIDs/Tylenol for pain relief. No PO steroids.
• Follow-up: if no improvement in sx in 5-7 days, evaluate for other infectious causes (e.g. mono, primary HIV, GC/chlamydia) or
suppurative complications such as tonsillopharyngeal cellulitis or abscess or otitis acute media.
Hazel Lever
210
TOC

Primary Care Eye & Ear Complaints

Red Eye (Am Fam Physician 2010;81:137):
• DDx: ⊕ discomfort: conjunctivitis, corneal abrasion, acute angle closure glaucoma, iritis/uveitis, scleritis,
endophthalmitis, dry eye. ⊝ discomfort: subconjunctival hemorrhage, episcleritis, mild dry eye syndrome
• H&P: assess for red flags: recent eye surgery, trauma, severe foreign body sensation, severe HA/nausea, chemical
injury, immunocompromise, decreased vision, colored haloes, mod-severe pain, proptosis, ciliary flush, corneal opacity,
fixed pupil  urgent ophtho referral
Conjunctivitis (JAMA 2013;310:1721)
• Viral: most common cause (80%), higher prevalence in summer, most commonly adenovirus, highly contagious
o Presentation: sero-mucoid discharge (more watery than bacterial), gritty sensation, intense and diffuse injection, +/-
itching, +/- periauricular lymphadenopathy (more prevalent in viral cases)
o Dx: clinical, PCR/culture rarely needed
o Tx: supportive, cool compress, artificial tears, strict hand hygiene, refrain from work as long as discharge present;
self-limiting course 1-2 weeks; HSV (1.3-4.8% cases)/VZV require topical/oral therapy/ophtho referral
• Bacterial: common pathogens include S.aureus in adults vs. S.pneumo/h.influ in children; highly contagious
o Presentation: mucopurulent discharge, diffuse injection, eyelid edema, pain/stinging, foreign body sensation
(bilateral discharge, eyelids adhering, lack of itching, or prior episodes strong predictor of bacterial conjunctivitis)
o Dx: GS/Cx if pt immunocompromised, wears contacts, fails tx, severe purulence, c/f gonococcal/chlamydial infection;
If gonococcal ⊕: warrants systemic abx and ophtho referral
o Tx: no single abx class superior; trimethoprim-polymixin B 1-2 drops QID or erythromycin ointment 0.5” QID for
5-7d; tx decreases recovery time but observation reasonable; usual course 7-10d
• Allergic: chronic or seasonal (90% of cases), hx of atopy
o Presentation: bilateral, intense itching, painless tearing
o Tx: cold compress, artificial tears; try antihistamine/mast-cell stabilizer drops like olopatadine/ketotifen BID; limit
OTC vasoconstrictor/anti-H1 combos (e.g. Visine-A), as can cause rebound hyperemia; +/- PO anti-H1
In general, pts should NOT wear contacts for duration of symptoms; avoid topical corticosteroids, vasoconstrictors, analgesics
Cellulitis: also see Viral Respiratory & Head & Neck Infections (Am Fam Physician 2016;93:991, Am Fam Physician 2015;92:106)
Orbital Cellulitis Preseptal/Periorbital Cellulitis
Infection of soft tissues of orbit, a/w paranasal sinusitis; Infection of preseptal tissues, often a/w local skin
deficit; red/swollen eyelid, NO pain w/ EOM, NO
red/swollen eyelid, ⊕ orbital pain w/ EOM, restricted mobility,
vision changes
vision changes/ diploplia, can have subtle proptosis
*CT w/ contrast can help distinguish from orbital if
*Requires admission and ophtho consult hx/exam concerning
Tx: empiric vanc/CTX; add flagyl if cannot r/o CNS involvement Tx: Bactrim or clindamycin PLUS amoxicillin or amox-
or if a/w sinus/dental source clav or cefpodoxime or cefdinir
Ear Pain (Am Fam Physician 2018;97:20)
• History: previous episodes, smoking status, alcohol abuse, hearing loss, otorrhea, TM fullness, vertigo suggest 1°otalgia;
pain w/ chewing, sinusitis, dental work, GERD suggest 2° otalgia
• 1° causes: otitis media and externa, foreign object, eustachian tube dysfunction, barotrauma; less common causes
include auricular cellulitis, cholesteatoma, mastoiditis, Ramsay Hunt Syndrome (HSV)
Otitis Media Otitis Externa
History Recent URI, smoking, hx eustachian tube dysfunction, Water exposure, DM2, discharge, itching, erythematous
& Exam conductive HL, bulging TM w/ reduced mobility canal, ⊕ pain with retraction of pinna
Amox-clav or 3G cephalosporins for 5-7d for mild- Cleanse w/ water + hydrogen peroxide or acetic acid;
mod case topical tx: abx-steroid drops (like cipro-hydrocort) +
Tx
*If ruptured TM, can add antibiotic drops, but NO acetic acid drops; if c/f fungal, clotrimazole drops
steroids, refer to ENT if does not close in 6 weeks
• 2° causes: TMJ syndrome, dental/sinus infxn, GERD, neuralgias, Bell’s Palsy, zoster (Ramsay Hunt), tumor; less
common but emergent causes include temporal arteritis, MI, thoracic aneurysms
Tinnitus (NEJM 2018;378:1224 Am Fam Physician 2014;89:106)
• History: ask about dizziness/vertigo (suggests Meniere’s), hearing loss and laterality (can suggest schwannoma), meds
(ASA, loops, abx), hx trauma, CVA, HA, depression/anxiety
• Dx: audiometry (esp if unilateral, >6mo), imaging if unilateral, pulsatile, asymmetric hearing loss, focal neuro deficits
• Sensorineural hearing loss: most common cause of persistent tinnitus; Tx: hearing aids, acoustic stimulation, CBT,
patient education, noise cancelling devices; no meds/supplements have been shown to significantly reduce tinnitus

Nicole Curatola
211
TOC

Primary Care Nodules

Adrenal Nodules (>1cm) (Endocr Pract 2009;15:450, Eur J Endocr 2016;175:G1)
• Is it malignant? (<5% primary, <2.5% mets): risk: diameter >4 cm, >20 HU, heterogeneous, irregular shape, calcification,
high T2 signal on MRI, delayed contrast washout
• Is it functionally active? (10-15%): clinical exam & lab testing for all nodules >1cm (unless obvious myelolipoma) to r/o
pheo & Cushing’s (see table). Also test for hyperaldo if HTN, hypokalemia. Only test for production of excess sex
hormones if clinical stigmata. AVOID testing inpatients due to high false positive rates.
Diagnosis Suggestive Clinical Features Laboratory Tests
Cushing's syndrome HTN, metabolic syndrome, central obesity, 1mg o/n dex suppression test, serum DHEAS (if
(~6-10%) prox muscle weakness, facial plethora ⊕ send ACTH, 24H urine cort, 8mg o/n DST)
Pheochromocytoma HTN, palpitations, headache, diaphoresis; Serum fractionated metanephrines, 24H urine
(~3-5%) CT: ≥10 HU, vascularity, cystic changes fractionated metanephrines and catecholamines
Hyperaldosteronism HTN, hypokalemia Plasma aldo & renin activity (d/c aldo antagonists
(~1%) before testing). May req. adrenal vein sampling
Hyperandrogenism Virilization, hirsutism, irregular periods DHEAS, total testosterone, 17-OHP
• Consider adrenalectomy: if  risk characteristics, >4cm, malignant, or hormonally active; surgery after hormonal eval
• Consider FNA: if c/f adrenal met from another primary without known metastatic disease (only after excluding pheo)
• Follow up: repeat CT scan in 12 mos. Consider annual DHEAS/1mg DST x4-5y (unknown effectiveness, EJE guidelines
don’t recommend). Adrenalectomy if nodule grows >1 cm, reaches 4cm, or becomes functional

Thyroid Nodules (Thyroid 2016;26:1, Endocr Pract 2016;22:622)

• Is it malignant?  risk: h/o irradiation to head/neck, +family hx, or h/o thyroid cancer syndromes (i.e. MEN 2), age <30
• Workup: obtain thyroid ultrasound and check TSH ( TSH = more likely CA)
o Low TSH: measure FT4 and FT3, obtain Thyroid radionuclide (123I) scan
▪ If “hot nodule,” consider Tx for hyperthyroidism if symptomatic. No biopsy necessary.
▪ If “cold nodule,” refer for U/S-guided FNA if U/S criteria met
o If normal or high TSH, r/o hypothyroid (FT4, TPO antibody) and refer for U/S-guided FNA if U/S criteria met
• FNA: any nodule w/ extrathyroidal extension, extrusion through rim calcs, abnormal cervical LNs, adjacent to laryngeal
nerve/trachea OR >1cm w/ irregular margins with microcalcs, rim calc, or solid/hypoechoic. No FNA for purely cystic
nodules.
• Follow up (benign): based on U/S characteristics. If highly suspicious U/S findings, repeat US and FNA within 12 mo. If
low-moderate suspicious U/S findings, repeat U/S 12-24 mo., consider FNA if >1-2cm change. Stop f/u after 2 neg FNAs.

Incidental Pulmonary Nodules (<3cm) (Radiology 2017;284:228, Chest 2013;143:e93S, Thorax 2015;70 Suppl 2:ii1)
NB: these guidelines are for incidental findings; recommendations for f/u of nodules found on LDCT for lung cancer
screening are different as that population is high risk (see Lung-RADS classification tables online)
• Ddx: malignant (primary, met, carcinoid) or benign (majority; infectious granuloma, hamartoma, AVM, inflammatory)
• Is it malignant? Pt characteristics:  risk w/ h/o smoking, emphysema, pulmonary fibrosis, extra-thoracic cancer,
asbestos exposure, age. Nodule characteristics: density (part-solid/ground glass>solid), larger size, faster rate of growth
(increase >2mm on repeat CT), borders (irregular/spiculated>smooth), location (upper>lower lobe).
• Is it benign? demonstrates fat (pulmonary hamartoma) or characteristic calcification pattern (granuloma, hamartoma) or if
it is stable on CT for a defined period of time (>2 years for solid and >5 years for subsolid nodules)
• Follow up: tailored to patient and type of nodule. Subsolid (entirely ground glass): if <6 mm, no routine f/u. If >6 mm, CT at
6-12 months, then CT every 2 yrs until 5 yrs. Part solid: if <6mm, no routine f/u. If >6 mm, CT at 3-6 mos, then annual CT
for 5 yrs if unchanged and solid component <6 mm. Solid nodules: see below.
Nodule type < 6 mm 6-8 mm > 8 mm
Single solid nodule
CT at 6-12 months, then consider CT Consider CT at 3 months, PET/CT,
Low risk No routine follow up
at 18-24 months or tissue sampling
CT at 6-12 months, then CT at 18-24 Consider CT at 3 months, PET/CT,
High risk Optional CT at 12 months
months or tissue sampling
Multiple solid nodules
CT at 3-6 months, then consider CT CT at 3-6 months, then consider CT
Low risk No routine follow up
at 18-24 months at 18-24 months
CT at 3-6 months, then at 18-24 CT at 3-6 months, then at 18-24
High risk Optional CT at 12 months
months months
• Consider referral to the Pulmonary Nodule Clinic: refer in Epic or call x38728 for appointment

Radhika Jain
212
TOC

Consultants Calling Consults

TIPS FOR CALLING CONSULTS
• To do BEFORE you call:
o Place order in Epic for consult
o Know your patient: you may be asked to provide additional information (current status, exam, workup). Review the H&P/chart
and briefly see/examine the patient if you have not done so previously.
 GI: melena/hematochezia, current/prior Hct, plts, coags, transfusions, past EGD/colo, vitals, IV access, NSAID/ASA use
 Cards: EKG/tele, prior stress/echo/cath (know anatomy), dry weight, biomarkers, current cardiac meds, outpt cardiologist
 Renal: baseline Cr, CKD stage, on/off HD, dialysis access, electrolyte mgmt, current UOP, nephrotoxins, outpt nephrologist
 Onc: known cancers w/ stage/tx history, biopsy results (for new dx), current anticoagulants, special slide, outpt oncologist
 ID: current/past micro data, possible sources, current/prior abx (incl # of days), fever curve, hardware, travel, exposures
o Know your question – Bigelow JAR should specify consult question in task list. If not there, ASK. It is always OK to clarify.
• To do DURING the page/call:
o Call as early in the day as possible (ideally before noon), find out how to page using the paging directory
o In your page to consulting team, include: pt name, MRN, location, call back #, brief consult question +/- level of urgency
o Avoid “curbside” questions. If there is a specific question about management, call a formal consult.
o Tell the consultant a brief HPI, a clear explanation of the team’s thinking, and a clear and specific question
• To do AFTER the call:
o Invite the consultant to find you to relay their recommendations or tell them who will be covering for you

CALLING EMERGENT CONSULTS

• Surgery: STAT to surgeon means life-threatening emergency (e.g. hemorrhage, lost airway, perforated or ischemic bowel). Include
reason for consult in your page to help surgeon triage urgency
o Page ”Senior Resident on call” under Emergency Surgery/Trauma (Churchill) Team
• Psychiatry (e.g. pt actively trying to leave AMA w/ unclear capacity; security concerns, major behavioral issues)
o 8am-6pm: p33061 (Emergency Consult Resident). If weekend/Holiday: p17911 (weekend rounding psychiatrist)
o 6pm-8am: Call APS (6-2994) or page APS resident at 27792
• Ophtho: page p21004 for all consults. Backup/emergency number is 617-573-4063 (MEEI ED back desk).
• Toxicology (ingestions/overdoses/exposures/interactions): call Poison Control Massachusetts (617-355-6607 or 800-222-1222).
• Cardiac Surgery: call “In-House fellow”

CALLING SURGICAL CONSULTS AT MGH

• All surgical consults are considered urgent. For a non-urgent consult overnight, wait to page until AM.
• In the ED: speak directly to (do not page) the surgery team that sits in Acute. Once patient on the floor, page intern on the consulting
team. Do NOT page the ED Surgery resident who placed initial consult note. Do NOT page surgery attending.
• New ward consult  page ”Senior Resident on call” under Emergency Surgery/Trauma (Churchill) Team.
o Existing ward consults, page the intern for that Churchill service, not the team on call that day
• New private consult (patient had prior operation by MGH surgeon)  page “Senior Resident on call” for new consult on Baker
surgery services; team depends on which surgery attending is requested.
• Thoracic Surgery consult  page “Consult resident” under “Thoracic Surgery” or “Surgery”
• Vascular Surgery consult  page “Consult resident” under “Vascular Surgery” or “Surgery”
• Cardiac Surgery consult  if non-emergent (8:30am-5pm) place order and call referral coordinator 617-724-4833. Can page NP at
30010. All other times (5pm-8:30am, weekends) call “In-House fellow”
• Ortho consult  page “Floor resident” at 20296 under “Orthopedics” or if ED consult, page 22566
• Transplant Surgery consult  page “Intern” (6a-6p) or “House officer on call (6p-6a)” under “Transplant Surgery”

CALLING OTHER SUBSPECIALTY CONSULTS

• ACT (Addiction Consult Team): place consult in Epic (no need to call), for EtOH or other substance use disorders, suboxone, etc.
• AMS (Anticoagulation Management Service): for established pts: p30104, or click AMS icon in Epic to determine existing AMS RN.
For discharge – place Epic consult; if urgent or questions, page Discharge Pathway Service: p30103
• Cardiology: login to Amion under “mghcardiology” to identify appropriate fellow (link also in paging directory)
• Chronic pain (cancer pain, pain in addiction): p17246
• Acute pain service (epidurals and periop pain): p27246
• Diabetes nurse educator: service NP p20737; MD p14364
• ENT: page 22220. Backup/emergency number is 617-523-7900 (MEEI operator) and ask them to page ENT resident on call.
• Optimum Care Committee (“OCC,” Ethics): page ethics support pager: p32097 (Mon-Fri, 8am-4pm, except holidays)
• Ophtho: for all consults p21004. Backup/emergency number is 617-573-4063 (MEEI ED back desk). Determine whether patient can
travel to MEEI for an exam and if ok to dilate prior to calling consult.
• Psychiatry: for non-emergent floor consult: order psych consult in Epic
o Weekday, Weekend Night, Holiday Night: Call CL coordinators (6-2984). These consults will be seen within 24 hours.
o Weekend or Holiday 8am-5pm: p17911 (weekend rounding psychiatrist)
• Transfusion reactions: page blood bank resident at 21829

Alexandra Wick
213
TOC

Consultants Perioperative Medicine

Peri-Operative Cardiac Risk Stratification and Risk Reduction
GOAL: to estimate and optimize risk of peri-operative cardiac events, NOT to “clear for surgery”
• Peri-op cardiac events: MI (usually clinically silent, NSTEMI>STEMI, POD#0-3, not intraop), CHF, VT/VF, cardiac arrest, death
o Major determinants include: (1) condition of patient (2) risk of procedure (3) functional capacity
• Emphasis on risk stratification. Very few patients need non-invasive/invasive testing unless testing would change management in
the absence of surgery.
Peri-Operative Cardiovascular Evaluation for Non-Cardiac Surgery (JACC 2014;64:e77)
Emergency non- Active Cardiac Conditions
cardiac surgery?
- Unstable Coronary Syndromes:
unstable/severe angina, acute (<7d) or
Yes No recent (<30d) MI
- Decompensated HF
Active cardiac condition that - Significant Arrhythmias:
Proceed symptomatic/new ventricular
with surgery requires eval/tx before
surgery? arrhythmias, SVT with HR >100 at rest,
symptomatic bradycardia, high-grade
AVB
Yes No - Severe Valvular Disease: severe sx
AS (mean grad >40, AVA < 1.0 cm2),
sx MS (progressive DOE, presyncope,
Treat/Test/Stabilize Estimated periperative HF)
and reassess risk- risk of major adverse
benefit of surgery cardiac events based
on combined
clinical/surgical risk
2 Surgical Risk Calculators
(1) Revised Cardiac Risk Index
Low risk (<1% per NSQIP calculators or *4+ METs:
(2) Gupta MICA NSQIP Risk Prediction RCRI score 0-1) Elevated risk
2 flights stairs;
walk 4 blocks;
Proceed to
surgery Able to achieve golf, bowl, dance
≥4 METs*?

No/unknown Yes
Operative Risk without Adjustment for Patient Factors
Intermediate
High Risk >5% Low Risk <1% Utilize RCRI and
Risk 1-5% Proceed to surgery
- Emergent major - HEENT, CEA - Superficial, Gupta surgical
risk calculators to
surgery, especially - Intrathoracic, cataract, breast assess clinical
in elderly intraperitoneal, - Endoscopy risk factors,
- Aortic, peripheral, prostate - Ambulatory consider stress
or major vascular - Orthopedic testing, and
reduce risk

Revised Goldman Cardiac Risk Index (RCRI) (Circ 1999;100:1043)

• Six independent predictors (risk factors) of major cardiac complications
1. High-risk noncardiac surgery (not a clinical RF but Rate of cardiac death, MI, pulm edema, CHB, cardiac
incorporated elsewhere in algorithm): OR 2.6 arrest/VF according to # predictors (data from cohorts in RCRI)
2. CAD (MI, PCI, CABG, angina, nitrate use, EKG with #RCRI Predictors Rates of event (95% CI)
pathologic Q waves, or ⊕ exercise stress test: OR 3.8 0 0.4-0.5% or ~0.5% (0.05-1.5)
3. HF (CHF, pulm edema, bilateral rales, or S3): OR 4.3 1 0.9-1.3% or ~1% (0.3-2.1)
4. Cerebrovascular disease (stroke or TIA): OR 3.0 2 3.6-6.6% or ~5% (2.1-10.3)
5. Diabetes mellitus with preop insulin therapy: OR 1.0! ≥3 9.1-11.0% or ~10% (5.5-18.4)
6. Renal insufficiency with preop Cr >2.0 mg/dL: OR 0.9!
Alternative Cardiac Risk Assessment: Gupta Perioperative Cardiac Risk (Circ 2011;124:381)
• Identified 5 risk factors predictive of risk of STEMI or cardiac arrest w/in 30 days of surgery:
1) Type of surgery/procedure, 2) preoperative functional status, 3) serum Cr >1.5, 4) ASA class, 5) increasing age
• Compared to RCRI, better discriminative predictive value
• Limitations: likely underestimates actual risk because MI was defined in the study based on only ECG changes: STEMI or new
LBBB; biomarkers were NOT monitored post-op, which is necessary to detect more than 50% of perioperative MIs.

Alexandra Wick
214
TOC

Consultants Perioperative Medicine

Preoperative Coronary Revascularization (NEJM 2004;351:2795)

• CARP: multicenter RCT of 510 high-risk vascular surgery patients, showed prophylactic revascularization w/ BMS/CABG conferred no
survival benefit; data extrapolated to lower risk non-vascular/non-cardiac surgeries.
o Exclusion criteria: EF<20%, unstable angina, LMCA disease >50%, severe AS
Peri-operative β-Blockade and Other Cardiac Drugs
• Evaluate for peri-operative β-blockade (Circ 2009;120:e169)
o Continue β-blocker: if already taking for other indication (e.g. CAD, arrhythmia, HTN) for goal HR 55-65 (Class I, LOE C)
o Initiate β-blocker: ≥3 RCRI risk factors or if pt has indication for βB otherwise (Class IIa, LOE B). Never start on day of surgery!
o Uncertain role of β-blocker: if no known CAD but either ⊕stress test or significant risk factors
• Anti-platelet: (POISE-2 NEJM 2014;370:1494; Anesth Analg 2015;120:570)
o 1° prevention: can generally be held prior to surgery
o 2° prevention: continue ASA 81mg unless high risk of bleeding (intramedullary spine, intracranial, hip, knee, possibly prostate)
o DAPT post PCI: POBA <14d, BMS <30d, DES <6-12mo  delay elective surgery. If urgent, continue ASA, hold P2Y12i x5d.
• ACEi/ARB: pts have more transient peri- and post-op episodes of HoTN; no diff in death, post-op MI, stroke;  or  AKI unclear
o Discontinue ACEi/ARB night before surgery (unless used for HF and BP ok). At MGH hold prior to cardiac surgery.
o Failure to restart ARB within 48h  30d mortality (Anesthes 2015;123:288).
• Other: all other anti-hypertensives should be continued perioperatively to goal BP <180/100 to avoid bleeding
• Anticoagulation: recommendations for bridging in patients using VKAs stratified by risk (Chest 2012;141:e152S, JACC 2017;69:871)
o BRIDGE: notably ~90% were low-risk/outpatient surgeries. Exclusion criteria included: mechanical valves, stroke/TIA w/in 12
weeks, major bleeding w/in 6 weeks, CrCl <30, Plt <100k (NEJM 2015;373:823)
o More data needed on DOACs but generally do not bridge; see ACC guidelines re: timing of interruption and re-initiation
Risk
Risk Factors for Thromboembolism Recommendations
Levels
- AF w/ CHA2DS2-VASc ≤ 4, no prior embolism - No bridging recommended due to increased risk of
Low - VTE >1 year ago and no additional risk factors bleeding from BRIDGE trial (note exclusion criteria)
- Bileaflet AVR w/ out risks for stroke and no history of AF
- AF w/ CHA2DS2-VASc 5-6 or prior embolism (≥ 3 mo. ago) - Consider bridging based on individualized patient
- VTE w/in 3-12 months, recurrent VTE, non-severe bleeding/embolism risk and procedure
Moderate
thrombophilia, active malignancy
- Bileaflet AVR w/ risk factors for stroke
- AF w/ CHA2DS2-VASc ≥ 7, recent embolism, valvular AF - Bridge with LMWH or UFH
- VTE w/in 3mos, or antiphospholipid antibody syndrome - Enoxaparin should be stopped ~24h prior to surgery
High - All mitral valves, caged ball/tilt disc AVR, or any - UFH should be stopped 4-6h prior to surgery
mechanical valve w/ CVA ≤ 6 months - Ideal to resume ≤ 24 h post-op if bleeding stabilized

See Hematology: Anticoagulation Management for more details.

VTE Prophylaxis (Mayo Clin Proc 2014;89:394)
• Postop VTE risk assessment: Caparini Score
• Non-orthopedic surgeries: those undergoing general or abdominal/pelvic surgery are at highest risk
• Orthopedic surgeries: all pts at high VTE risk 2/2 tourniquet time + immobilization; minimum duration 10-14d (35d if higher risk)
Peri-operative Monitoring and Considerations (NEJM 2015;373:2258)
• ACS: most MIs occur w/in 48h while patients are on analgesics that mask pain  some data show benefit of troponin monitoring
(JAMA 2012;307:2295). Elevated post-op NT-proBNP can be used as a predictor of post-op MI and death (JACC 2014;63:170)
• AF: may be a more important risk factor than CAD for 30d post-op mortality (Circ 2011;124:289)
• Post-operative PNA: ~20% mortality; pre-op CXR or PFTs not recommended because rarely change management
o Risk factors: COPD, age >60, ASA class ≥II, albumin <3.5, poor functional dependence, weight loss >10% over previous 6
months (Annals 2006;144:575)
• Renal dysfunction: increased risk of complications in ESRD; AKI also a/w high morbidity and mortality (Ann Surg 2009;249:851)
• ESLD: high risk of peri-op death; MELD predicts survival (>15 median survival ~2 months); Child-Pugh C very high risk (>60% in-
hospital mortality) (J Gastroenterol Hepatol 2012;27:1569)
• Low albumin: independent predictor of 30d post-op morbidity and mortality (Arch Surg 1999;134:36)

Alexandra Wick
215
TOC

Consultants Dermatology
Before Consulting Dermatology: Upload photo of rash (ideally pretreatment) to media tab of EPIC using Haiku
• If consulting for drug rash, note exact timing of rash development and administration of suspect medications
Quick Steroid Guide MGH topical steroid formulary by level of potency
• Face/intertriginous areas: hydrocort. 2.5% Super-potent clobetasol 0.05%, betamethasone dipropionate 0.05%
cream, hydrocort. valerate 0.2% cream Potent fluocinonide-emollient 0.05%
• Body: fluocinolone 0.025% cream if mild, Upper-mid strength betamethasone valerate ointment 0.1%
clobetasol 0.05% ointment if severe  mid Mid-strength fluocinolone ointment 0.025%
strength to super potent depending on Lower mid-strength fluocinolone cream 0.025%, betamethasone valerate
severity cream 0.1%
• Scalp: 0.01% fluocinolone scalp solution or Mild hydrocortisone valerate 0.2%, fluocinolone scalp oil
oil (dermasmoothe); oil better for dry scalp 0.01%
Counsel patients: Use daily x2 wks then 1 wk Least potent hydrocortisone 2.5%, hydrocortisone ointment 1.0%
“off”, avoid face (risk = skin thinning) Over the counter hydrocortisone cream 0.5%, 1.0%

Common Dermatologic Conditions

• Allergic contact dermatitis: localized, but may generalize 2/2 autoeczematization (a.k.a. “id reaction”, may also occur 2/2 tinea
anywhere on the body). Identify and remove suspected trigger. Tx w/ high potency topical steroid for limited BSA (low to mid potency
for face). Pred taper (>1wk) for more extensive BSA involvement
• Eczema/atopic dermatitis: tx depends on severity. Intense BID/TID moisturization (plain hydrated petrolatum, Cetaphil®, CeraVe®).
For affected areas, use mid-strength to super-potent topical steroids BID x 2wks. For face, use least potent to lower mid-
strength steroids BID x 1-2wks. Scalp: mid- to high-potency steroid in solution, foam, or oil vehicles. Erosions/fissures: petrolatum or
mupirocin ointment BID x 1-2wks
• Cellulitis: consider derm consult if not improved in 48h to distinguish cellulitis mimickers (30% of cases).
o Calculate ALT-70. 5-7 = 82.2% likely cellulitis; 3-4 = consider derm c/s if no improvement by 48h with abx. Consult reduces abx
use + duration (JAAD 2017;76:618, JAMA Derm 2018;154:529). Bilateral LE cellulitis is rare.
• Pressure injury/ulcers: document in H&P with Haiku pics.
o NPUAP Staging: 1) non blanchable erythema of intact skin, 2) partial thickness skin loss with exposed dermis, 3) full thickness
skin loss, 4) full thickness skin and tissue loss
o Wound Nurse consult for: stage 3-4 pressure injury, device related injuries, moisture associated skin damage, edema drainage
management, special bed surfaces (i.e. clinitron, bariatric). Wound Service consult (Plastics/Vascular collab) for: acute wound
issues such as limb ischemia, wet gangrene, any wound requiring OR debridement. Consider derm c/s to confirm etiology.
Other Dermatologic Conditions
• Calciphylaxis: extreme pain (may precede lesion), violaceous retiform patch/plaque  necrosis, ulcer, eschar.
o Risk Factors: ESRD on dialysis (most common), warfarin, 1º hyperPTH, malignancy.
o Dx: skin biopsy (gold standard, not always needed); Ca2+ x phos product, PTH; bone scan w/ increased uptake
o Tx: Normalize serum Ca2+, phos, PTH via non-calcium based phos binders (i.e. sevelamer) and cinacalcet; IV sodium
thiosulfate; treat 2° infections (death from sepsis), pain control, wound care (Medihoney). D/c warfarin if possible; consider AC if
appropriate. Calciphylaxis = indication for HD in CKD pts
• Cutaneous GVHD: skin pain/pruritus can precede eruption, acral  central; acute vs. chronic based on morphology, not time course.
o Acute: follicular erythematous papules. Chronic: asteatotic, LP-like, eczematous, sclerodermoid, poikilodermatous.
o Stage 1: <25% BSA, stage 2: 25-50% BSA, stage 3: >50% BSA, stage 4: erythroderma w/ bullae (TEN-like).
o Tx: immunosuppression with corticosteroids +/- cyclosporine or tacrolimus, supportive care
• Herpes simplex virus 1/2: always confirm w/ DFA or PCR from vesicle base; cx possible but takes long to result
o Uncomplicated orolabial: primary is usually gingivostomatitis  acyclovir 400mg TID x7-10d; if recurrent  valacyclovir 2000 mg
PO q12h x 1d or famiciclovir 1500mg PO x1 at sx onset; periocular skin involvement warrants ophtho c/s to r/o herpetic keratitis
o Uncomplicated genital (immunocompetent): 1º episode (<72 hr after onset)  valacyclovir 1000mg PO BID x 10d, acyclovir
400mg PO TID x10d, or famciclovir 250mg TID; recurrent episodes (<24hr onset)  valacyclovir 500mg PO BID x 3-5d or
acyclovir 400mg PO TID x 5d.
o Complications: sacral radiculitis (acute urinary retention), proctitis (MSM).
• Herpes zoster (shingles):
o Uncomplicated, <72 hr (immunocompetent): valacyclovir 1000mg PO Q8H x7d or acyclovir 800 mg PO 5x/d x7-10d.
o Disseminated: >20 vesicles outside two 1º (non-adjacent) dermatomes; acyclovir 10mg/kg IV q8h; consider immunodeficiency
w/u; droplet precautions.
o Immunosuppressed: acyclovir 10 mg/kg IV q8h; IVFs if hypovolemic/CKD to decrease risk of crystalline nephropathy; obtain
DFA/viral culture; monitor for complications (PNA, encephalitis, aseptic meningitis, hepatitis).

Kevin Patel, Daniel Schlessinger, Daniela Kroshinsky

216
TOC

Consultants Dermatology
o Zoster ophthalmicus: urgent ophtho consult if c/f ocular involvement (“Hutchinson sign” = vesicle on nasal tip).
o Post-herpetic neuralgia: risk  w/ early antiviral treatment (<72 hr); if higher risk (>50yo w/ mod-to-severe acute pain) consider
preventive tx w/ gabapentin 300mg PO QD, titrate up to 3600mg QD, divided TID as tolerated.
o Consider high lysine, low arginine diet + post-episode vaccination to prevent HSV recurrence.
• Erythema multiforme: target lesions (well-defined, circular erythematous macules/papules w/ 3 distinct color zones + central bulla or
crust) on palms/soles +/- mucosal involvement occurs within 24-72 hours; persist for 2wks;
o 90% triggered by infection (HSV, mycoplasma, GAS, EBV); less commonly drug rxn
o Tx: treat underlying infxn, NSAIDs, cool compresses, topical steroids, antihistamines; systemic steroids only if severe
• Erythroderma: diffuse redness >90% BSA.
o Causes: psoriasis, atopic derm, cutaneous T-cell lymphoma (incl. Sezary), pityriasis rubra pilaris (islands of sparing), drugs
o Work-up: detailed med rec, +/- HIV. Tx: derm c/s; liberal emollients, mid-potency topical steroids, antihistamines; fluids/lytes;
monitor for 2º infections; d/c offending meds.
• Purpura fulminans: “DIC in skin” = true emergency; consult Hematology for possible factor replacement;
o Microvascular skin occlusion w/ platelet-fibrin thrombi  retiform purpura
o Causes: infection (Strep, Staph, H. flu, N. meningitidis, Capnocytophaga, VZV, CMV, Babesia); catastrophic APLAS, CTD,
malignancy, protein C/S deficiency
o Work-up: DIC labs, blood cultures, skin bx w/ GS and culture. Tx: broad-spectrum abx + supportive care.
• Stasis dermatitis: LE compression (ACE wraps, stockings) with elevation; mid-strength to super potent corticosteroid ointment BID x
1-2wks +/- occlusion with plastic wrap; mupirocin ointment BID x1-2wks to erosions; intensive moisturization (hydrated petrolatum);
can be unilateral or bilateral
• Psoriasis: depends on severity; Short-term tx includes topical steroids, calcipotriene, intense moisturization +/- occlusion w/ plastic
wrap; Long-term tx includes phototherapy, acitretin, MTX, biologics w/ outpt derm f/u (JAAD 2011;65:137)
• Seborrheic dermatitis: Face: least potent to lower mid-strength topical steroid BID x 1wk and/or ketoconazole 2% cream BID x4wks,
then 1-2x/wk for maintenance; Alternative: pimecrolimus cream, tacrolimus 0.03 or 0.1% ointment. Scalp: ketoconazole 2%
shampoo QHS
• Tinea pedis: “moccasin distribution”; apply topical imidazole (econazole 1% cream QD or clotrimazole 1% cream BID x 2-4 wks) or
allylamine (terbinafine 1% cream BID x 2 wks) to entire foot and webbed spaces between toes
Allergic Contact
Calciphylaxis Erythema Multiforme HSV Purpura fulminans
Dermatitis

Drug Eruptions
• Step 1: Make timeline to determine time course of drug initiation and development of rash
• Step 2: Discontinue offending agent. Common drugs for each eruption listed, but any drug can be a culprit at any time

Time Course Rash Signs/Sx Common Drugs Treatment

Pruritic, well-circumscribed, - Antihistamines

Immediate erythematous (benadryl + H2)
(min-hr) – papules/plaques with central + steroids if severe
Urticaria/ Any
delayed pallor. + IM epi if s/s
Anaphylaxis
(days) +/- angioedema, wheezing, anaphylaxis
GI sx, tachycardia, HoTN - Allergy c/s

Kevin Patel, Daniel Schlessinger, Daniela Kroshinsky

217
TOC

Consultants Dermatology
Solitary sharply demarcated
round red-brown patch or
edematous plaque recurring
Abx (sulfa, TMP,
in same location each time
FQs, TCNs), -Topical steroids if
Fixed Drug Minutes-hours drug ingested. Can evolve to
NSAIDs, symptomatic
Eruption bullae. Oral/anogenital
barbiturates
mucosa common sites but
can occur anywhere.
Usually asx.

Small non-follic. pustules on

erythem./edematous
plaques, begin on face or
Acute Abx (PCN,
intertriginous areas then
Generalized macrolides) -Anti-pyretic
widespread. Usually w/in 24-
Exanthematous 2-14 days Can occur after -Topical steroids
48hrs of med exposure.
Pustulosis only one
Burning, pruritus common.
(AGEP) exposure
Fever, marked neutrophilia
+/- oral mucosal erosions,
facial edema

Pruritic, erythematous
4-14d (if prev. macules/papules. Start on Abx (PCN, sulfa), -Topical steroids,
exposed to trunk, spread centrifugally to allopurinol, antihistamines
Exanthematous/ the drug, symmetric extremities. May phenytoin, (Note: may take 7-
Morbilliform could be lead to erythroderma. requires repeat 14d after stopping
sooner) +/- low grade fever exposures drug to resolve)

Fevers, malaise, myalgias,

arthralgias. Pruritic atypical
-Cyclosporine
targetoid (amorphous, 2 color
(preferred at MGH)
zones) macules
-Steroids possible
bullae desquamation; Abx (esp.
mortality
<10% = SJS, 10-30% = sulfa), AED,
benefit (JAMA Derm
4-21 days SJS/TEN overlap, >30% = NSAIDs,
SJS/TEN 2017;153:514) but
TEN. Mucosal bullae, allopurinol,
controversial
erosions & crusting, phenobarb.
-IVIG, anti-TNF
conjunctivitis. + Nikolsky.
-Burn level care if
Complications: 2° infection,
>30% BSA
resp. compromise, GIB,
visual impairment

Morbilliform; spreads down

symmetric. from face; can
see SJS/TEN-like lesions & -Supportive care
mucosal involv. Face often Abx, AEDs, -IV Solumedrol
swollen/painful (can help diff. carbamazepine, (decreased risk of
DRESS 3-6 wks
from morbilliform drug) ARTs (nevirapine, bowel edema vs.
Fever, arthralgias, eos, abacavir) PO), SLOW taper (3-
internal organ involv. (liver, 6 wks)
kidney; rarely lung, heart),
LAD

Kevin Patel, Daniel Schlessinger, Daniela Kroshinsky

218
TOC

Consultants Surgery
See Calling Consults for details on how to call the appropriate surgical service.

Small Bowel Obstruction: (J Trauma Acute Care Surg 2015;79:661)

• Causes: adhesions from any previous abd surgery, hernias, cancer >> intussusception, volvulus, foreign bodies, stricture
• Dx: abd distension, vomiting, obstipation. Labs normal or hypoK/hypoCl metabolic alkalosis from repeated emesis. Examine for
evidence of hernias and prior abdominal scars. If severe pain, consider ischemia from strangulation (lactate, leukocytosis).
• Imaging: KUB - air-fluid levels; CT A/P + PO contrast - dilated bowel proximal to & decompressed bowel distal to obstruction
• Tx: NPO, large bore NGT (18Fr) to continuous low wall suction; consider surgical exploration if signs of strangulation/bowel
ischemia, s/p gastric bypass (high risk of internal hernia), closed loop obstructions, or if no improvement in 72 hours

Necrotizing Fasciitis: (CID 2007;44:705, Front Surg 2014;1:36)

• Definition: progressive, rapidly spreading infection in deep fascia with secondary necrosis of skin and subcutaneous tissues
• Microbiology: 70-90% of cases are polymicrobial (anaerobes, group A strep, S. Aureus, Clostridium, Peptostreptococcus,
Enterobacteriaceae, Proteus, Pseudomonas, Klebsiella, Vibrios spp.), less commonly mono-microbial.
• Clinical signs: rapidly spreading erythema (hrs to days)  evidence of soft tissue necrosis; pain disproportionate to exam.
o Suggestive features: rapid expansion of erythema on serial exams, pain extending beyond border(s) of erythema,
dusky/violaceous skin, undermining of skin and subcutaneous tissues, turbid (“dishwater”) discharge, palpable crepitus
• Dx: CT + contrast helpful, has a ~95-100% NPV. Labs for LRINEC (CRP, WBC, Hg, Na, Cr, Gluc) – score ≥ 6 has a 96% NPV.
• Tx: IV abx ([Vanc or Linezolid] + [Pip/Tazo or meropenem] + Clinda to inhibit toxin production) + urgent surgical consultation

Ischemic Limb: (NEJM 2012; 366:2198)

• 6 P’s Pain, Poikilothermia (cool), Paresthesia, Pallor, Pulselessness, Paralysis suggest arterial thrombotic/embolic occlusion
Stage Description Sensory Loss Motor Loss Arterial Doppler Venous Doppler
I Viable None None Audible Audible
II (a/b) Threatened Minimal, painful None or Mild Variably inaudible Audible
III Irreversible Profound Profound Inaudible Inaudible
• Dx: check and document pulses and/or Doppler signals
o Obtain ankle-brachial indices, Dopplers at bedside—if stage I, non-urgent, obtain formal studies
• Tx: consider IV heparin; surgical emergency: consult Vascular Surgery immediately

Compartment Syndrome (Extremity): (Lancet 2015;386:1299, Musc Lig Tend J 2015;5:18)

• Definition: excessive pressure within a muscle compartment, impairing perfusion
• Etiology: crush injury, ischemia  edema, bleed, etc.
• Clinical signs: tight, tender skin; pain out of proportion to known injuries; pain with passive ROM;  lactate or CPK
• Dx: measurement of compartment pressures at bedside using Stryker transducer needle (call Churchill Service for assistance)
o Arterial flow diminished once compartment pressure within 30 mmHg of DBP, 20 mmHg in hypotensive patients
o Nevertheless, compartment syndrome is a clinical diagnosis, regardless of measured compartment pressure(s)
• Tx: surgical emergency (fasciotomy/decompression); consult Churchill Surgery immediately

Abdominal Compartment Syndrome and Intra-Abdominal Hypertension (IAH): (Intens Care Med 2013;39:1190)
• Definition: IAH = IAP >12. Abdominal Compartment Syndrome = IAP > 20 AND clinical evidence of organ dysfunction (e.g. high
airway pressures, decreased venous return, elevated CVP/PCWP, UOP/AKI, elevated lactate, acidemia). IAP measured via
bladder pressure (most reliable if paralyzed, only done in ICU)
• Typically occurs after massive resuscitation in ICU patients with trauma, burns, s/p liver tx, severe ascites, pancreatitis, sepsis
• Tx: True Abdominal Compartment Syndrome (IAP >20, organ dysfunction despite medical management): surgical
decompression provides definitive management
o If IAP 12-20 w/o clinical instability:
 Evacuate lumenal contents (NGT/rectal tube/enema)
 Increase pain control/sedation (to level of paralysis if necessary)
 Head of bed tilted up
 LVP if ascites
 Decrease tidal volume, permissive hypercapnia
 Avoid over-resuscitation

Jacqueline Henson
219
TOC

Consultants Urology
Symptomatic Urolithiasis (kidney stones)
• Evaluation/management:
o Imaging: CT Stone Protocol non-con (I–, O–): evaluates position, hydronephrosis, hints at composition
 Alternative is KUB and ultrasound (requires both), with non-diagnostic studies prompting CT
o UA/UCx: in all patients except those with urostomies. If positive Cx, need decompression with stent by urology or percutaneous
nephrostomy (PCN) by IR
o Rehydration: NS @ 150 mL/hr if tolerated →  ureteral peristalsis
o Alpha-Blockers: tamsulosin 0.4mg PO QD (hold for SBP < 90) → ureteral relaxation
o Analgesia: opioids preferred. NSAIDs/Ketorolac more effective but risk of bleeding and AKI
o Preoperative workup if requiring intervention: NPOpMN, EKG, Coags, T&S
• Consider urology consult: solitary or transplanted kidney, DM, immunosuppression, AKI, +UA/UCx, sepsis, inadequate pain control
• Urosepsis management: image ASAP, BCx/UCx, urgent Urology consult; IV abx to cover GNRs + enterococcus
• Clinical Pearl: patients with an acute abdomen lie still, pts with renal colic writhe in pain
Hematuria / Obstructed Catheter
• DDx: UTI, INR>3, traumatic catheter placement, bladder CA (5th most common neoplasm), upper urinary tract CA, prostate CA
• Workup: “The three C’s”: 1) hematuria protocol CT (3-phase: non-con, arterial phase, delays to assess ureters); 2) urine cytology
once hematuria clears (blood interferes with test); 3) outpatient cystoscopy
• Tx: If obstructed (can’t void or catheter not draining / “clot retention”) or significant hematuria: irrigate bladder via Whistle-Tip
catheter using a 60 cc catheter-tipped syringe – flush in and out with saline to remove clots until urine is clear. Then place 3-Way foley
on continuous bladder irrigation (CBI, AKA Murphy drip)
o Start CBI after clot extraction; titrate to keep urine cranberry juice color or lighter
Urinary Retention
• Urethral/bladder pathology:
o Etiology: BPH, UTI, constipation, neurogenic (MS, SC injury), DM, immobility, anticholinergics, opioids, benzos, pelvic surg
o Treatment (improvement may take 3-12 months):
 Aggressive bowel regimen, treat UTI, minimize narcotics and anticholinergics, encourage ambulation
 Alpha blockers (finasteride does not help acute retention, takes 4-6 months to work)
 Clean intermittent catheterization (CIC) with bladder scans to ensure low residual volume vs chronic Foley/SPT
• Ureteral pathology: typically external compression on ureter by mass or LN  hydronephrosis. Often due to underlying malignancy,
portends poor prognosis. Management depends on GOC, prognosis, GFR, need for nephrotoxic chemo. Options: PCN, ureteral stent.
Urinary Incontinence
• Classifications: stress (leakage w/ coughing, etc.), urge (proceeded by urgency), mixed (most common), overflow (PVR >150),
functional (neurologic, impaired mobility/cognition)
• Treatment:
o All types: lifestyle interventions, bladder training (timed voiding), Kegel pelvic floor exercises
o Stress: vaginal estrogen (post-menopausal women w/ vaginal atrophy), pessaries (mixed data), surgery (midurethral sling)
o Urge: antimuscarinics (oxybutynin, tolerodine, beware of side effects), beta agonists (mirabegron, avoid w/ uncontrolled HTN,
ESRD, liver disease), intravesicular botox
Tubes and Drains: see Tube Management for placement and management
• Foley catheter: externally placed tube which travels through urethra and into bladder
o Call urology if difficulty with placement
o Foley size: Hx instrumentation or urethral stricture  small Foley (14 Fr or smaller). If elderly man/BPH or difficulty placement 
large Foley (18 Fr Coudé or larger). Coudé catheter has a gentle upward curve to pass through the prostate
o Urethral trauma: leave catheter in for at least 5 days to allow for urethral healing
• Suprapubic tubes (SPT): externally placed tube which travels through the overlying skin and directly into the bladder
o Placed by GU IR. Once tract formed (after 1-2 changes by IR), change q6-12wks similar to Foley
o Staph aureus becomes a more common organism involved in infections
• Percutaneous nephrostomy tube (PCN): externally placed tube which travels through the overlying skin directly into the renal pelvis
o Placed by GU IR usually under local anesthesia. Cannot be coagulopathic, thrombocytopenic, or on ASA/Plavix
o Urine collects in external bag. If low UOP into bags, passage of blood or concern for malposition - obtain CT A/P, call GU IR
• Ureteral stent: internally placed stent which maintains ureteral patency from level of renal pelvis to bladder
o Placed by Urology in OR with general anesthesia, requires change every 3-6 months. May cause urinary urgency. Is NOT
changed in setting of infection
• Note: If stents/PCNs/Chronic Foley or SPT/ileal conduit or neobladder – UTIs should be treated only if symptomatic, NOT based on
UA/UCx

Jacqueline Henson
220
TOC

Consultants ENT
To call an ENT consult: page the ENT consult resident p22220. To transfer a patient to MEEI: call MEEI ED at 617-573-3431.

Epistaxis (nosebleed)
• Acute management:
o Have pt lean forward, pinch nostrils, hold pressure for 20 min
 Do not lean head back or hold bony part of nose
 Hold over basin, measure blood loss as possible
 Do NOT “peek” – hold continuous pressure for 20 min
 Usually a patient will not pinch hard enough – best for RN/MD to
do so
o Afrin (oxymetazoline 0.025%) nasal spray (after gently clearing
clots)
o Control SBP (goal < 120) if much > baseline
o Correct coagulopathy if present
o Consult ENT if continued bleed
 If bleed visualized, silver nitrate cauterization, nasal packing,
or Neuro IR embolization
YES NO
 Nasal packing: risk of Toxic Shock very low but may prescribe prophylactic cephalexin or clindamycin; packing typically
removed after 5d by ENT (whether inpt or outpt)
• Location: most are anterior bleeds; posterior are more rare/serious/difficult to manage
• Hx: side, duration, EBL, prior episodes (and txs), trauma (fingers, fists, foreign body, etc), prior nasal surgery, nasal trauma hx, FHx or
PMHx coagulopathy, nasal tumors, HTN, anticoagulant meds, nasal steroid spray use
• Exam: rapidity of bleeding, inspect nasal septum and oropharynx for originating site; suction clots from OP to protect airway
• Tests: coags, CBC, type & screen; crossmatch pRBC if brisk bleed
• Epistaxis prevention: after resolution, x 2 weeks: petroleum jelly (or bactroban if cautery used) inside rims; no nose
blowing/touching, no exercise, keep head higher than heart (use pillows), sneeze with mouth open, use humidification (saline nasal
spray BID), oxymetazoline spray PRN if re-bleeding

Stridor
• Acute management:
o IV access, 100% O2 by non-rebreather
o Racemic epinephrine neb x1 STAT if concern for supraglottic source, 10 mg dexamethasone IV x1 STAT
o Consider IM/IV epinephrine and Benadryl if allergy suspected (see Angioedema & Anaphylaxis), consider Heliox
o If unstable  Call RICU & trauma surgery (x6-3333) for possible surgical airway
o If stable  Call ENT for airway evaluation
• Epinephrine dosing: if allergic reaction suspected: 0.3mg IM (1:1,000 solution) or 0.1mg IV (1:10,000 solution)
• Hx: timing/evolution, inspiratory/expiratory/biphasic, inciting events, prior episodes, evidence of infection, allergy, hx EtOH/tobacco
(cancer risks), hx of known cancer of head and neck, radiation
• DDx (in adults): iatrogenic/post-intubation (laryngeal/vocal cord edema/praxis of the recurrent laryngeal nerve from ET tube);
infectious (epiglottitis, laryngitis, laryngotracheitis [croup], bacterial tracheitis, Ludwig’s angina); allergic; tumor/mass of larynx or
trachea; neurological (vocal cord spasm or immobility); foreign body/trauma
• Imaging: if stable, CT with contrast of head/neck/chest to localize source

Acute Sinusitis (Otolaryngol Head Neck Surg 2007;137:S1)

• See Respiratory Complaints for outpatient management
• Primarily a clinical diagnosis: CT usually not necessary, and CT findings alone (usually) not sufficient as 40% of asymptomatic
people have CT abnormalities of sinuses (Otolaryngol Head Neck Surg 1991;104:480)
• Signs/symptoms:
o Uncomplicated (confined to sinuses): Major Sx: facial pressure/pain, purulent nasal discharge, nasal obstruction; Minor Sx: fever,
cough, malaise, anosmia, dental pain, ear fullness.
o Complicated (extra-sinus extension): vision changes, proptosis, mental status changes, severe HA, facial soft tissue changes on
exam. In immunocompromised or critically ill, consider invasive fungal sinusitis, a surgical emergency. (See Invasive Fungal
Infections)
• Workup: uncomplicated  no testing required; complicated  CT w/ contrast +/- nasal endoscopy to look for evidence of purulence
o If needing to rule out invasive fungal sinusitis, nasal biopsy with STAT pathology required
• Inpatient treatment:
o If requires hospitalization, use levofloxacin or amp/sulbactam IV +/- surgery if complicated / drainable extra-sinus collection
o Invasive fungal sinusitis: liposomal amphotericin, surgical debridement, ID consultation

Jacqueline Henson
221
TOC

Consultants Ophthalmology
Basic Eye Exam: “Ocular Vital Signs”
- Visual Acuity (e.g. 20/200, CF) - Extra Ocular Movements
- Pupils (4mm  2mm OD, No APD) - Intraocular pressure
- Visual Fields - Color vision testing (Ishihara cards)
Common Abbreviations:
APD Afferent pupillary defect NLP No light perception (VA)
AT Artificial tears NPDR Non-prolif. diabetic retinopathy
cc/sc With/without refractive corr. NS Nuclear sclerosis (i.e. cataract)
CE Cataract extraction OD/OS Right eye, left eye
Uvea = iris + ciliary body + choroid CF Count fingers (VA) OU Both eyes
CWS Cotton wool spot PDR Prolif. diabetic retinopathy
DES Dry eye syndrome PF Pred Forte gtt (prednisolone)
EOM Extraocular movement PFAT Preservative-free artificial tears
HM Hand motion (VA) PVD Posterior vitreous detachment
IOL Intraocular lens RD Retinal detachment
IOP Intraocular pressure SLE Slit lamp exam
LP Light perception (VA) SPK Superficial punctate keratitis/dry eye
MGD Meibomian gland dysfunction VA, VF Visual acuity, fields

To call an Ophtho consult: check vision using vision card and pupils prior to calling consult!
General inpatient consult: page 21004; can also call MEEI ED back desk 617-573-4063

High-Yield Pearls for the Wards

• Vision loss: acute (requires urgent evaluation) vs. chronic (outpt referral) – assess patient with their glasses on!!
• Glaucoma drops: prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, or alpha 2 agonists – all lower IOP
o If brand-name drops unavailable, fractionate combo meds, ask pharm for substitution advice, or have pt bring in home meds
• Ophthalmoscope: available on most floors. Tropicamide (dilating drop) is available to order. Can make pt light-sensitive for 4 hours.
• Dilating drops: 0.5% tropicamide (parasympathetic antagonist), 1-2 drops placed 15-20 minutes before exam
• Finding the retina: dilate the eye and use the ophthalmoscope as in http://stanfordmedicine25.stanford.edu/the25/fundoscopic.html
Common Eye Pathology
• Red Eye: typically benign; refer to ophtho if no improvement or any ”ocular vital sign” changes (see above)
o Viral conjunctivitis: eyes “stuck shut” in AM, itchy, crusty discharge, ± URI symptoms, ± pre-auricular nodes, winter time
 Tx: supportive/isolation (typically adenovirus, highly infectious). Wash hands thoroughly if you suspect this!
o Allergic conjunctivitis: olopatadine 0.1% gtt bid x 5d. Clear Eyes/Visine not rec’d (rebound redness 2/2 alpha agonism)
o Anterior uveitis: pain and true photophobia must be present ± eye injection. Refer to MEEI ED.
o Contact lens keratitis: have patients remove contact lens when admitted! Use glasses. P/w red/uncomfortable eye; infection
until proven otherwise. Refer to MEEI ED.
• Blepharitis (inflammation of eyelids): p/w crusting/red eye/gritty feeling
o Tx: baby shampoo, warm compresses, abx ointments x 2 weeks, then daily lid hygiene. Tx for hordeolum ("stye") is same.
• Dry Eye Syndrome (DES): p/w eye pain or “grit”/paradoxical tearing ± vague “blurriness.”
o Tx: artificial tears q1h prn first line tx, refer if no improvement
• Corneal abrasion/exposure keratopathy: unilateral, redness, mild light sensitivity, common after sedation
o Dx: apply fluorescein (order in Epic) to the affected eye, illuminate with a blue light (e.g. ophthalmoscope, smartphone screen
with Eye Handbook App). Abrasion will light up green; keratopathy will look like “sandpaper” instead of smooth glass.
o Tx: abx ointment (Erythromycin 0.5%/bacitracin ophthalmic QID) + Lacrilube qhs. Consult if no improvement after 24 hrs.
• Anisocoria (unequal pupils): old (20% population has at baseline) vs. new (can be trivial 2/2 anticholinergic vs. catastrophic from
herniation). Always ask for h/o ocular surgery as surgical pupil is a common benign cause.
Miosis (Constricted Pupil) Mydriasis (Dilated Pupil)
 Cholinergic (e.g. morphine, pilocarpine)  Sympathetic (e.g. atropine, CNIII paralysis)
 Sympathetic (e.g. Horner’s)  Cholinergic (e.g. epinephrine, cocaine)
o If clinical suspicion for herniation (known bleed, CN3 palsy, obtundation, hemiparesis)  STAT head CT
o Horner’s Syndrome: ptosis, miosis, ± anhidrosis. Wide ddx along pathway from posterior hypothalamus  C8-T2  superior
cervical ganglion  up sympathetic chain along internal carotid and into orbit. Requires head and neck angiographic imaging to
r/o potential carotid dissection.
• Retinal detachment: presents with flashes/floaters/curtain coming over vision. Risk factors: myopia (near-sighted), trauma, diabetic
retinopathy, prior eye surgery.
o Tx: Refer to MEEI ED. Will likely require vitreoretinal surgery.
• Subconjunctival hemorrhage: blood between conjunctiva and sclera from ruptured vessel. No vision changes, not painful. Can be
2/2 associated blood dyscrasia, valsalva, trauma, spontaneous. Will resolve spontaneously. No need to consult ophtho.
• Endophthalmitis: infection within globe. Can be 2/2 trauma, surgery, or endogenous source (bacteremia/fungemia).
o Tx: Ophtho c/s, antibiotics/antifungals that will penetrate blood-brain barrier. May require vitrectomy (surgery).

Alexandra Wick
222
TOC

Consultants OB/GYN
How to Consult
• Obstetrics: if pt has pregnancy >20wk or has established MGH OB provider. If hCG⊕ but no confirmed intrauterine pregnancy,
should be followed on ectopic list
• GYN Onc: if pt has biopsy confirmed GYN malignancy or established GYN onc provider
• GYN: everyone else (e.g. pregnancy <20wk, undifferentiated ovarian mass)

Abnormal Uterine Bleeding

• Postmenopausal bleeding is never normal. If premenopausal, rule out pregnancy and its complications (e.g. ectopic,
miscarriage)
• History: verify source of bleeding is vaginal, duration and quantity (#soaked pads), associated sx (pain, dizziness), triggers
(e.g. postcoital), trauma hx
o LMP/menstrual hx, full pregnancy hx, known GYN conditions (e.g. fibroids), meds (hormones, AC), h/o coagulopathy
o Heavy bleeding = soaking through 1 pad per hour, symptomatic, ∆ VS,  Hgb
• Exam: external vulvar exam, speculum exam (note how many scopettes required to clear bleeding, volume of blood in vault,
cervical lacerations, blood actively coming from cervix). Do NOT do digital exam if pregnant.
Differential Diagnosis for Abnormal Uterine Bleeding
Ectopic pregnancy, miscarriage, implantation of pregnancy, subchorionic hematoma, placental abruption,
Pregnant
placenta previa/accreta, vasa previa, trophoblastic disease, cervical/vaginal/uterine pathology (e.g. polyp)
Not Endometrial/cervical polyp, adenomyosis, fibroids, endometrial hyperplasia/cancer, coagulopathy,
pregnant ovulatory dysfunction, cervical cancer, thyroid disease, vaginal/vulvar etiologies (e.g. laceration, atrophy)
• Workup:
o CBC, T&S, coags, pad count (Epic order, monitors bleeding quantity)
o If premenopausal, first step is urine hCG
 If ⊕, obtain serum quant. hCG (more sensitive for early pregnancy) and pelvic U/S (must rule out ectopic
pregnancy in all pregnant women with bleeding)
 If U/S nondiagnostic (i.e. intrauterine pregnancy not confirmed), measure serial serum hCG q48h (should increase
35-50% in 48h) and repeat pelvic U/S
o If postmenopausal, endometrial biopsy (difficult to do inpatient) or pelvic U/S (biopsy if endometrial lining >4mm)

Pregnancy and Its Complications

• Nomenclature: gravida/para (GP), G= #pregnancies, P= #births; TPAL (T=term births, P=preterm births, A=abortions, L=living
children)
• Preeclampsia: new onset HTN + significant end-organ dysfunction +/- proteinuria after 20 wks gestation
o Preeclampsia with severe features: BP >160/110 OR BP >140/90 with one of following: 1) new onset cerebral/visual sx
(photophobia, severe HA, AMS), 2) RUQ/epigastric pain, 3) plt <100k, 4) Cr >1.1, 5) pulmonary edema
o Eclampsia = preeclampsia + grand mal seizures
o Labs: BMP, LFTs, CBC with diff, LDH, smear, urine protein/Cr ratio or 24hr urine protein
o Can develop postpartum (2 days - 6 weeks)
o Stroke is the most serious complication (most commonly hemorrhagic stroke)
o Treatment: delivery = definitive; antihypertensives only if BP >150/100 (IV labetalol, hydralazine)
 Magnesium sulfate for seizure prophylaxis (Lancet 2002;359:1877) initiated at onset of labor
- Contraindicated in myasthenia gravis, use cautiously in pulm edema
- 6g load + 2g/hr gtt (goal 4.8-8.4), reduce maintenance dose if renal insufficiency
- Monitor for Mg toxicity q1-2h (loss of reflexes, RR, somnolence, HoTN, bradycardia, ECG changes); antidote =
calcium gluconate
• HELLP syndrome:
o Symptoms: rapid onset abdominal pain (epigastric, RUQ), n/v, HA in pt >28 weeks gestation
o Many patients also have HTN and proteinuria
o Labs: BMP, LFTs, CBC with diff, LDH, haptoglobin, smear, urine protein/Cr ratio, coags
o Dx: hemolysis (at least 2: smear w/ schistos and burr cells, bilirubin >1.2, low hapto or  LDH 2x ULN, severe anemia not
related to blood loss), elevated liver enzymes (AST or ALT >2x ULN), low platelets (<100k)
o Treatment: delivery = definitive; magnesium (as above) for seizure prophylaxis; blood/plt transfusion if bleeding

Miranda Ravicz
223
TOC

Radiology Contact Information

Main Number Technologists
617 – (643 / 724 / 726) – XXXX CT Blake 2 48518
CT ED 66760
Reading Rooms ED Radiology 63050
Dodd Reception 44212 GI Fluoro 44295
Teleradiology 44270 Mammography 63092
Cardiac CT 47132 MRI ED 49867
Cardiac MRI 66947 MRI Inpatient 85692
Chest CT 33899 Nuclear Medicine 68350
CXR Inpatient 42051 Pediatrics 61367
CXR Outpatient 62197 PET 64209
ED 41533 Scheduling 4XRAY
ED Neuro 68188 US White 2 53074
GI CT 65162
GI Fluoro/KUB 32605 On Call Pagers
GI MR 49919 Cardiac CT 22122
GI US White 2 60595 Cardiac MRI 33133
GI US Yawkey 6 31577 IR GI/GU 34071
IR (GI & VIR) 34723 IR Neuro Spine 33722
Mammography 40228 IR Neuro Vascular 21154
MSK 40516 IR Vascular 38553
Neuroradiology 41931 Mammography 20022
Nuclear Cardiology 43600 MSK/MSK IR 36321
Nuclear Medicine 61404 Neuro ED 39991
Pediatrics 42119 Neuro Inpatient 32535
PET 66737 Nuclear Medicine Resident On call
Vascular 47115 Pediatrics On call

Consults – Weekdays
8am 12pm 5pm 7pm 8am
Cardiac CT Dodd XXXXXXXXXXXXXXXXXXXXXX
Chest Dodd ED
GI Dodd ED
Neuro Neuro Consult (730am – 430pm) Neuro ED
Vascular Dodd ED
Other Reading Room ED

Consults – Weekends & Holidays

8am 12pm 5pm 7pm 8am
Cardiovascular Dodd ED
Chest Dodd ED
GI Dodd ED
Neuro Neuro ED
Other ED

• Life Images
o Upload images to lifeIMAGE and Epic: Partners Applications  utilities  MGH Upload Image to Radiology
(LifeImage)  Access LifeImage  find exam on CD/DVD  upload images
o Send images to MGH PACS: upload to MGH  request read
o Retrieve images from The Cloud: ISDrequests.partners.org  file an urgent ticket
o Additional information:
 Urgent reads: contact ISD (p34188, x30003)
 Multiple body parts: interpretations only given for selected body parts
 Multiple LifeImages of the same body part: upload all images  request a read only on the most recent
 Exams will not be read if: requisition was for a different body part than the uploaded images; study >6 months
old; a more recent LifeImage is available; US, fluoroscopy, or mammography
Sam Cartmell
224
TOC

Radiology Radiology Basics

• X-ray:
5 Radiographic Densities Silhouette Sign: loss of the margin between two opposing structures of the
same radiographic density
• RUL – right paratracheal stripe • LUL – aortic arch
• RML – right heart border • Lingula – left heart border
• RLL – right hemidiaphragm • LLL – left hemidiaphragm

• Computed Tomography (CT):

o Hounsfield Units (HU): measurement of CT attenuation Substance HU
o Windowing and leveling: adjusting contrast and brightness to highlight structures Air -1000
 Window (contrast): range of Hounsfield units displayed across the grayscale Fat -100
• Wide window – best for large differences in attenuation Water 0
• Narrow window – best for subtle differences in attenuation Blood 50
 Level (brightness): HU that corresponds to mid-gray Soft tissue 100
• High level – best for structures with high attenuation Bone 1000
• Low level – best for structures with low attenuation Metal >2000

o Phases of contrast:
Phase Time After Injection Structures Evaluated
CTPE 15 s Pulmonary arteries
Arterial (CTA) 30 s Aorta, systemic
arteries, renal cortices
Late arterial 60 s Routine chest
Portal Venous 70 s Routine abdomen
Nephrographic 100 s Renal medulla
Venous 120 s Peripheral veins
Delayed (Urogram) 10-15 min Ureters, bladder

• Magnetic Resonance Imaging (MRI):

T1 & T2 Signal Evolution of Blood Protein Signal

o MRI safety:
 Device compatibility: www.mrisafety.com

Sam Cartmell
225
TOC

Radiology Contrast
• Indications:
o IV: whenever possible, particularly for infection, tumors, and vessel imaging
o PO positive (hyperdense): bowel obstruction, bowel wall pathology, differentiate bowel from other abd. structures
o PO negative (hypodense): inflammatory bowel disease, GI bleed, mesenteric ischemia
o Rectal: appendicitis, penetrating abdominal trauma
• Pregnancy and breast feeding: (ACR 2020)
o Pregnancy:
 Iodinated: no need to withhold contrast (no data to suggest potential harm to fetus)
 Gadolinium: unknown risk to fetus  consider noncontrast or alternative study
o Breast feeding: mother’s informed decision to “pump and dump” for 12-24 h after scan
• Renal function: (ACR 2020, MGPO 2020)
Contrast Induced Nephropathy Nephrogenic Systemic Fibrosis
Age >60 years, dialysis, kidney transplant, single
Dialysis, kidney transplant, single kidney, renal
Risk factors kidney, renal cancer, renal surgery, HTN on
cancer, renal surgery, HTN on medication, DM
medication, DM, metformin
Outpatient:
Screening
Outpatient: GFR within 30 d • GFR 45-59: GFR within 6 wks
(At risk pts
Inpatient: GFR within 24 h • GFR <45: GFR within 2 d
only)
Inpatient: GFR within 2 d
GFR ≥ 30: contrast per protocol (NO GFR ≥ 30: gadolinium per protocol
PREHYDRATION RECOMMENDED) GFR < 30: non-contrast or alternative study
Prevention
GFR < 30: non-contrast or alternative study • If necessary  consult radiology and
• If necessary  consult radiology nephrology, obtain informed consent
Dialysis pts HD within 72 h after scan Prompt post-scan HD (PD inadequate)
Decision is clinical and subjective No risk factors: proceed
Repeat studies
Insufficient evidence to hold contrast for 24 h At risk pts: consult radiology
GFR ≥ 30: continue metformin
Metformin No need to hold metformin
GFR < 30 or AKI: hold for 48 h after scan
• MGH prehydration protocol (prophylaxis only indicated when GFR < 30): (MGPO 2020)
o PO (preferred): 1-2 L PO non-caffeinated beverage 12-24 h prior to scan
o IV (outpatient): NS 250 mL IV bolus @ 1 h prior to scan
o IV (inpatient): NS 100 mL/h IV 6-12 h before and 4-12 h after scan (ACR 2020)
• Contrast reactions: (ACR 2020)
Allergic Physiologic Indications for Premedication
Limited urticaria N/V, flushing/warmth • Prior mild-moderate allergic reaction
Itchy throat HA/dizziness • None for prior physiologic reactions
Mild

Nasal congestion Mild HTN • None for shellfish allergies

URI symptoms Transient vasovagal reaction • No cross-reactivity between iodinated
Diffuse urticaria Protracted N/V contrast and gadolinium
Moderate

Facial/laryngeal edema w/o HTN urgency

dyspnea or hoarseness Isolated CP
Bronchospasm w/o hypoxia Vasovagal reaction requiring tx
Anaphylaxis HTN emergency
Severe

Facial/laryngeal edema w/ Arrhythmia

dyspnea or hoarseness Seizure
Bronchospasm w/ hypoxemia Protracted vasovagal reaction
• Adult premedication protocol: (ACR 2020)
o Elective (13 h protocol) Corticosteroid Dose Equivalents
 Prednisone 50 mg PO @ 13, 7, and 1 h prior, AND Prednisone 50 mg PO
 Diphenhydramine 50 mg PO @ 1 h prior Hydrocortisone 200 mg
o Accelerated (4-5 h protocol) Methylprednisolone 40 mg
 Methylprednisolone 40 mg IV now and q4h until scan, AND Dexamethasone 7.5 mg
 Diphenhydramine 50 mg IV @ 1 h prior PO:IV 1:1
o Emergent (1 h protocol) – no evidence of efficacy, only if no alternatives
 Methylprednisolone 40 mg IV @ 1 h prior, AND
 Diphenhydramine 50 mg IV @ 1 h prior
Sam Cartmell
226
TOC

Radiology Protocols
Ordering Studies:
• All cross-sectional studies are protocoled by radiology – simply provide the necessary information:
o Body part and modality
o Indication: clinical history relevant to the study (GOOD HISTORIES IMPROVE INTERPRETATIONS)
o Contrast: “per radiology discretion” unless specific reason otherwise
o Contraindications for contrast: kidney injury or prior allergic reaction (see Contrast)
o Questions: call the appropriate division or page the appropriate on-call radiologist (see Contact Information)
• Level of Urgency:
o Routine: order of interpretation depends on acquisition time
o Urgent: takes priority over routine studies
o STAT: means NOW, high acuity/life threatening emergencies
 Patient must be ready for immediate transport
 Patient must be accompanied by a responding clinician capable of providing emergency care
 Responding clinician must be present for the entire exam
 Radiology will provide preliminary read: phone call for XR/US, at the scanner for cross-sectionals
Overnight Reads:
• Studies with full interpretations overnight: all ED studies, STAT studies, and acute CT PEs
• Verbal preliminary reads:
o Typically done for ICU studies only
 Inpatient studies are only reviewed overnight if there is an urgent clinical question (i.e. one that would alter
overnight management). Consider face-to-face consult in ED.
o After communication w/ the primary team, all verbalized prelim reads will be documented in the chart
o A full interpretation will be generated the following morning for all prelim reads
ED Protocols:
• Trauma: I+, single phase (arterial for chest, portal venous for abdomen/pelvis – images checked at the scanner by
radiology for possible delays)
o Blunt trauma: includes bone kernel reformats for improved visualization of bones
o Penetrating trauma: O+R+ for increased sensitivity of bowel injury
• Cervical spine: I-, need for CTA determined by radiology, bone kernel reformats in all 3 planes
o Images checked at the scanner by radiology only if IV contrast is required for another body part
• Appendicitis: I+ and O+/R+ (please specify PO or PR), kidneys through pelvis only
• Neuro ED: call reading desk @ x68188
Cardiovascular Protocols:
• DVT imaging: U/S (LENI) is initial test of choice (Cardiovascular Diagnosis and Therapy 2016;6:493)
o CTV/MRV: primarily used for central venous thrombosis when initial U/S is equivocal or non-diagnostic
• Arterial imaging:
o CTA: three phases (noncontrast, arterial, delays)  stenosis, dissection, aneurysm
o Requisition: specify vessel of interest, field of view, and indication
• Coronary CTA:
o ECG-gated study of the heart  only performed by CV CT on-call radiologist during normal hours
o Specify if body parts other than the heart should be imaged (thoracic aorta, CABG grafts, etc.)
• Other EKG-gated CTAs:
o Indications: any evaluation of the heart or ascending aorta
o EKG-gating is unnecessary for the descending thoracic aorta, abdominal aorta, and pulmonary arteries
• Noncontrast vascular studies:
o RP hematoma, pre-op aortic calcifications, coronary calcium score, follow-up aortic size
Thoracic Protocols:
• All chest CTs are high resolution – traditional “high res chest CT” is now the diffuse lung disease CT (see below)
• Routine chest vs CT PE vs CTA chest:
o Routine chest: single phase (late arterial)  workhorse protocol
o CT PE: single phase (pulmonary arterial)  pulmonary arteries
o CTA chest: three phases (noncontrast, arterial, delays)  systemic arteries
• Double rule out studies:
o Clinical concern for PE and aortic dissection
o Contrast can only be optimized for one (must pick CT PE or CTA)

Sam Cartmell
227
TOC

Radiology Protocols
• Diffuse lung disease (a.k.a. misnomer “high res CT”):
o Indications: ILD, lung transplant, air trapping
o Inspiratory and expiratory images, plus prone images to differentiate between atelectasis and fibrosis
• Nodule follow-up: (Radiology 2017;284:228)
o Indications: incidental nodule on prior CT, age >35 y, AND no history of malignancy or recent infection
o Fleischner Society 2017 Guidelines
GI/GU Protocols:
• Stone protocol: I-O-, low dose
o Order contrast-enhanced CT if there is concern for ANYTHING else (stones may still be visualized)
• Routine abdomen/pelvis vs renal mass vs bladder cancer vs hematuria:
o Routine abdomen/pelvis: I+O+, single phase (portal venous)  workhorse protocol
o Renal mass: I+O+, two phases (noncontrast, nephrographic), abdomen only  renal masses or cysts
o Bladder cancer: I+O+, two phases (portal venous, delayed)  workup or monitoring of GU malignancy
o Hematuria: I+O-, “three” phases (noncontrast, nephrographic, urogram)  hematuria, hydronephrosis
• CT urogram vs CT cystogram:
o Urogram: antegrade filling of ureters and bladder with IV contrast (delayed phase)
o Cystogram: retrograde filling of bladder with contrast via Foley catheter  evaluation of bladder rupture
• Arterially-enhancing tumors:
o MR CHIT: melanoma, RCC, choriocarcinoma, HCC, islet cell (neuroendocrine) tumors, thyroid
• Does my patient need to be NPO?
o IV contrast CT: 2 h Abdomen/pelvis CT: 8 h Non-contrast CT: no NPO
• Fluoroscopy protocols:
o Requisition: specify indication, h/o surgery or aspiration
o Barium swallow vs modified barium swallow vs UGI series vs SB follow-through:
 Barium swallow: esophagus, GE junction, proximal stomach  dysphagia, GERD
 Modified barium swallow: mouth, pharynx, upper esophagus  dysphagia, aspiration
 UGI series: barium swallow plus stomach, pylorus, and duodenal bulb  bariatric surgery
 SB follow-through: small bowel, terminal ileum, and proximal LB +/- UGI series beforehand
Neuroradiology Protocols:
• Inpatients: page Neuro IP on-call radiologist @ p32535
• Acute stroke:
o Inpatients/ICU: page acute stroke consult fellow @ p21723
o ED: activate ED2CT via the group pager
• Head CT: typically noncontrast
o Indications for contrast-enhanced head CT: infection and/or tumor AND contraindication for brain MRI
• Spine MRI: for more than 1 segment, please order total spine and specify indication
o Separate MRIs should not be ordered prior to neurology/NSGY consult
• Fluoroscopy-guided LPs: performed by neuroradiology fellows, NOT neuro IR
o Indications: difficult anatomy, and only after LP is attempted on floor
 Not to be used as an anesthesia service for unruly patients (typically performed without conscious sedation,
although this can be arranged if required for patient safety)
Musculoskeletal Protocols: if questions: page MSK IR on-call radiologist @ p36321
Nuclear Medicine Protocols:
• Overnight studies:
o Tagged RBC study: BRBPR (NOT guaiac positive stools, melena, or massive bleeding)
 Requirements: consult IR first for possible angiogram if study is positive
o VQ scan: acute PE (NOT chronic PE), ONLY if results will alter management (i.e. AC tonight)
 Requirements: CXR within 24 h, patient stable for duration of scan (~4 h)
o HIDA scan: acute cholecystitis, ONLY if results will alter management (i.e. OR tonight)
 Requirements: NPO 4-24 h prior to study, no opiates 12-24 h prior to study, bilirubin <10
• PET:
o Fasting: hold everything but meds and water
 Overnight is ideal, but AT LEAST 6 hours for non-DM patients
 AT LEAST 4 hours for DM patients
- Continue long-acting insulin, hold short-acting insulin 4 h prior to scan
o Blood sugar thresholds: FDG-PET brain < 175 mg/dL, FDG-PET whole body < 250 mg/dL
Sam Cartmell
228
TOC

Radiology Interpretation of Common Studies

Chest X-Ray
1. Line placement:
o SVC: between right tracheobronchial angle and right heart border (Chest 1998;114:820)
o Cavoatrial junction: two vertebral bodies below the carina (JVIR 2008;19:359)
o Line positioning:
 Central line: tip in the SVC or at the cavoatrial junction
 HD catheter: tip in the right atrium
o Post placement: check for pneumothorax (see below)
2. Pneumothorax:
o Sensitivities:
Imaging Position Detectable PTX Size Imaging Findings
Supine/Portable 500 cc Deep sulcus sign, lucency along mediastinal border
Upright 50 cc Sharp visceral pleural line, absence of distal lung vessels
Lateral decubitus 5 cc Nondependent collection of air
o Tension: contralateral mediastinal shift, collapse of ipsilateral lung, flattening of ipsilateral hemidiaphragm, widening
of ipsilateral rib spaces
o Artifacts that mimic visceral pleural lines: (BMJ 2005;330:1493)
 Medial border of scapula: in continuity with rest of bone
 Skin folds: form an interface (not a line), extension beyond rib cage, presence of distal lung vessels
3. Pulmonary edema:
o Vascular redistribution (first sign): increased caliber of pulmonary vessels in upper lobes (cephalization)
o Interstitial edema: increased interstitial opacities, indistinctness of pulmonary vasculature, Kerley B lines,
peribronchial cuffing
o Alveolar edema: perihilar/central opacities, pleural effusions, cardiomegaly
o Pearls: typically bilateral and symmetric, rapid appearance/resolution of radiographic findings
o Pitfalls: low lung volumes can mimic increased interstitial opacities
Abdominal X-Ray (KUB)
1. Line placement: (Pediatric Radiology 2011;41:1266)
o GE junction: within 1 vertebral body of the T10-T11 disc space, <16 mm from left spine border
o Pylorus: C-loop of duodenum is only reliable indicator of post-pyloric placement
 Right side of spine is unreliable
o Line positioning:
 Decompression: gastric fundus or dependent portion of stomach
 Feeding: distal duodenum or proximal jejunum
o Post placement: check for endobronchial placement
2. Small bowel obstruction: (RadioGraphics 2009;29:423)
o KUB: preferred initial examination
 Assess for: small bowel dilatation >3 cm, air-fluid levels, stacked loops of bowel, transition point
o CT: equivocal cases or for further evaluation
 Assess for: SB dilatation, collapse of distal bowel loops, transition point
 Severity:
- Partial: passage or air or contrast beyond the obstruction
- High grade partial: 50% difference in caliber between dilated and collapsed SB loops
- Complete: no passage of air or contrast beyond the obstruction
 Transition point: look for small-bowel feces sign (fecal material mixed with gas bubbles in small bowel)
 Cause: adhesions, Crohn’s, malignancy, hernias
 Complicated SBO:
- Closed loop obstruction: radially oriented bowel loops, engorged mesentery, whirl sign
- Strangulation: bowel wall thickening, lack of bowel wall enhancement, pneumatosis intestinalis, portal
venous gas
4. Pneumoperitoneum: (AJEM 2009;27:320)
o Upright: air beneath the diaphragm
o Left lateral decubitus: air over the liver
o Supine (insensitive):
 Anterior superior oval sign: gas bubbles projecting over liver
 Hyperlucent liver sign: free air overlying liver
 Rigler’s sign: air on both sides of the bowel wall
Sam Cartmell
229
TOC

Radiology Interpretation of Common Studies

 Falciform ligament sign: linear density projecting over liver
Ultrasound
1. Cholecystitis: (AJR 2011;196:W367)
o U/S is preferred initial examination
o Gallstones: echogenic foci with posterior shadowing
o Common findings: gallbladder wall thickening >3 mm, gallbladder distension >40 mm, peri-cholecystic fluid
o Sonographic Murphy’s sign: 92% sensitivity (analgesics reduce sensitivity)
o Gallstones and gallbladder wall thickening: 95% positive predictive value for acute cholecystitis
2. Deep venous thrombosis: (Cardiovascular Diagnosis and Therapy 2016;6:493)
o Compression U/S: noncompressibility of vein, echogenic thrombus within vein, venous distension
o Venous duplex U/S: absence of color Doppler signal within vein, loss of flow phasicity, loss of response to
augmentation maneuvers
o CT venogram:
 Alternative to U/S in critically ill patients who have undergone CT PE
 Pros: evaluation of pelvic veins and IVC, which are difficult to assess on U/S
 Cons: invasive, requires contrast, radiation, possible streak or mixing artifacts
Cross sectional imaging: For anatomy, http://www.radiologyassistant.nl/.
CT Head MRI Brain
1. Brain parenchyma 1. Brain parenchyma
a. Mass lesion: brain windows a. Mass lesion: T1, T2, FLAIR
b. Intracranial hemorrhage: brain and subdural b. Intracranial hemorrhage: SWI, T1, T2
windows c. Infarction: DWI, ADC
c. Infarction: stroke windows 2. Vessels: T2 for flow voids, T1 post-contrast, TOF if
2. Vessels noncontrast MRA
3. CSF spaces: ventricles, sulci, cisterns 3. CSF spaces: T2
4. Midline shift or herniation 4. Midline shift or herniation: coronals helpful
5. Soft tissues (great place to start for trauma head CTs) 5. Soft tissues
6. Bones/sinuses 6. Bones/sinuses

CT Chest MRCP
1. Lines and tubes (scout can be very helpful) 1. Choledocholithiasis: hypointense filling defect
2. Abdomen within CBD surrounded by hyperintense bile
3. Soft tissues
4. Bones
5. Heart and mediastinum: thyroid, lymph nodes, heart
and pericardium, major vessels, esophagus
6. Pleura: pleural effusion, pneumothorax
7. Lungs: secondary pulmonary lobule is the key
a. Radiology Assistant  Lung HRCT Basics

CT Abdomen/Pelvis
1. Lung bases
2. Liver/gallbladder: focal lesions, biliary ductal dilatation
3. Spleen
4. Pancreas: focal lesions, pancreatic ductal dilatation
5. Adrenals
6. Kidneys/ureters: hydronephrosis, stones, focal lesions
7. Bladder/pelvic organs
8. Peritoneum: free air or fluid
9. Lymph nodes
10. Vessels
11. GI tract: bowel distension, bowel wall thickening
12. Soft tissues
13. Bones

Sam Cartmell
230
TOC

Procedures Ultrasound Basics

Equipment (NEJM 2011;364:749)
Basic Terminology:
• Frequency: 1Hz = 1cycle/sec; medical U/S typically between 2-15MHz (derm U/S up to 100MHz)
- High frequency (>5MHz):  resolution, shallow tissue penetration. Ideal for vascular, skin, breast, thyroid.
- Low frequency (2–5MHz):  resolution, deeper tissue penetration. Ideal for abdominal, OB/GYN, cardiac.
• Gain: signal amplification; similar to brightness control
• Depth: depth of field of view (FOV). Excessively large FOV  spatial resolution; tight FOV limits view of nearby structures.
• Attenuation: reduced signal transduction through a medium =  signal intensity behind it (bone/air have high attenuation)

Transducer (probe): converts electricity into sound waves  transmits sound wave into tissue  receives sound waves echoed
back from tissue. Indicator (denoted by light or notch on probe) displays on left of the screen. Exception: echocardiography 
indicator displays on right side. Ensure have probe positioned appropriately.
• PHASED-ARRAY (cardiac) probe: good for looking in small windows (i.e. between intercostal
spaces for cardiac or pulm imaging); low resolution, produces fan-like image. Cardiac Linear Curved
• LINEAR (vascular) probe: good for shallow structures (i.e. vascular, soft tissue). Uses high
frequency with good resolution, produces rectangular image.
• CURVED (abdominal) probe: good for deeper structures (i.e. intra-abdominal). Uses lower
frequency; combines linear and sector probe image qualities.

Commonly Used Modes

• B-mode (brightness mode): standard 2D gray-scale image. B mode
• D-mode (doppler): detects flow to or away from transducer. Useful to find and define
vessels, flow across valves
o Color  direction and velocity are color coded and superimposed on B-mode
image. “BART” (Blue is Away from probe, Red is Towards)
o Power  detects very low flow but not direction, useful in vascular compromise
o Spectral  velocity presented graphically on a timeline
• M-mode (motion mode): takes a slice of a B-mode image over time. Often used in M mode
TTE. Useful to assess lung sliding for pneumothorax.

General Imaging Concepts

Typical Appearance of Normal Tissue: Indicator Fascia
• Skin and pleura are smooth and brighter than surrounding tissue (echogenic or
hyperechoic) Muscle
• Fat and muscle are dark, though varies depending on the tissue (hypoechoic)
• Fluid (e.g. blood, effusion) appears black on ultrasound (anechoic), though thick
fluids (pus) can be brighter than typical fluid
• Tendons and nerves are bright / hyperechoic when perpendicular to probe, but
Rib Rib
dark / hypoechoic when angle is changed (anisotropy) Pleura
• Bone has a bright hyperechoic rim (due to reflection) around a black / anechoic
image with a shadow beyond it Lung

Artifacts: elements seen on ultrasound image that do not exist in reality

• Reflection: proportional to the difference in acoustic impedance between two tissues
( difference =  reflection)
Relative acoustic impedance: bone >> solid organ > fat >> lung >> air.
• Shadowing:  signal beyond a strongly attenuating OR
reflecting structure (e.g. stones, bone)
• Enhancement:  signal posterior to weakly attenuating
(hypo or anechoic) structure (e.g., cysts)
• Mirror image: structures in front of strong reflector (e.g.
Shadowing Enhancement
diaphragm) appear to lie behind it as well
• Reverberation: evenly spaced lines at various depths
beyond a strong reflector (e.g. A lines beyond pleura)
• Comet tail: tiny, narrow reverberations beyond very
strong reflector (e.g. metal pellet) blending into a line

Sean Mendez
231
TOC

Procedures Ultrasound Basics

Imaging and Tips Seashore Sign
Diagnostic Use:
• Pneumothorax: use LINEAR (vascular) probe. With patient supine, look in the 3rd Waves
intercostal space on the anterior chest. Identify the hyperechoic rims of the ribs with
posterior shadowing; within the intercostal space identify the hyperechoic stripe that is the Sand
pleura. A normal lung will slide along the pleural line with respiration, a pneumothorax will
not. If ambiguous, use M mode to confirm. A lack of lung sliding will change the normal
‘seashore’ sign to a static ‘barcode’ sign. Sn 91% / Sp 98%, superior to CXR. A lung point Pneumothorax
is not sensitive but is 100% specific (J Emerg Trauma Shock 2012;5:76, Ann Emerg Med Barcode Sign
2013;61:207)

• Pulmonary embolism: use PHASED-ARRAY (cardiac) probe. Bedside ultrasound can be

used to identify right heart strain. Look for RV size ≥ LV size, septal bowing, though note
Sn/Sp for PE 53%/83%. RV/LV ratio is most easily visualized in the apical 4 chamber view
but can be misleading based upon slight changes in plane. Assess with septum vertical in
line with midpoint of probe. Combine with the parasternal axes for better reliability (J Am
Pulmonary Edema
Soc Echocardiogr 2017;30:714)

• Pulmonary edema: use PHASED-ARRAY (cardiac) or CURVED (abdominal) probe to

evaluate the lung between rib spaces as above, across lung fields as for auscultation. B lines
Look for B-lines: comet like artifacts that shine perpendicular from the pleural line and
obliterate A-lines. ≥3 in one interspace is consistent with interstitial fluid, and bilaterally
suggests pulmonary edema. Operator dependent but can outperform CXR. (Am J Emerg
Med 2015;33:620)
Pericardial Effusion
• Pericardial effusion: use PHASED-ARRAY (cardiac) probe. Look for an anechoic stripe
Effusion
between the heart and the hyperechoic pericardium, though hemorrhagic or purulent
effusions can appear more complex. On parasternal long axis this will be anterior to the
descending aorta, while a pleural effusion would be posterior. All four views are important,
but often only subxiphoid used in emergencies. Look for chamber collapse indicating
tamponade: RA is more sensitive; RV is more specific (Resuscitation 2011;82:671) RA Collapse
• Volume status: use the PHASED-ARRAY (cardiac) probe. IVC collapsibility has been Volume Status
proposed as a proxy for CVP and fluid responsiveness, though data is mixed and there Liver
are no consensus guidelines. Start with subcostal view of RA/RV, then rotate probe to the RA
sagittal plane to find the IVC draining into RA and abutting the liver. Look at IVC 2cm from
IVC
RA: fluid responsiveness or an underfilled IVC is suggested by 1) IVC diameter ≤2.1cm
and 2) IVC collapses ≥½ its diameter. Can use M mode to track variation, cycles are
inverted if spontaneously breathing vs mechanical ventilation, more accurate in the latter.
(Crit Care 2012;16:R188, CCM 2013;41:833, Shock 2017;47:550)
Procedural Use: refer to pages on specific procedures for more details
Ascites Abd wall
• Paracentesis: use CURVED (abdominal) probe. Locate largest fluid collection, often in
LLQ. Try rolling patient to side to increase pocket size. LINEAR (vascular) probe can help
identify any overlying vessels to your approach, particularly the inferior epigastrics. Bowel
appears as hyperechoic finger-like projections within the anechoic ascites. Measure the
depth of the abd wall and compare to your needle to determine when to expect flash,
though with tenting this will be a slight underestimation. Bowel

• Central venous access: use LINEAR (vascular) probe. Reduces complications and
quality of placement compared to landmark approach (Crit Care 2017;21:225)
o In-plane (long axis): can view entire tip, but harder to keep needle in view
o Out-of-plane (short axis): easier to center needle, may underestimate depth

• Peripheral IV: use LINEAR (vascular) probe. Most of your time should be spent finding
the best vein to go for, often in the medial groove between biceps/triceps or anterior
forearm. Track along vessel length to determine trajectory, look for large, superficial,
compressible vessels that are not adjacent to pulsatile, non-compressible arterial vessels.

Sean Mendez
232
TOC

Procedures Ultrasound-Guided Peripheral IV

General Considerations
Indications: non-emergent access in a patient with difficult access. If emergent, obtain IO or central access.
Locations: AC, basilic, brachial, cephalic; larger veins offer higher chance of success than smaller veins
Contraindications: relative: sensory/motor deficits (clot risk), HD fistula, hx of LN dissection
Materials: angiocath (18 or 20G best; small IVs not well visualized on U/S), vascular probe, gel/sterile lubricant, tourniquet, alcohol
wipe/chlorhexidine, tegaderm, extension tubing, saline flush, +/- vacutainer adapter and tubes (for labs)
• Angiocath selection: standard length (30mm) good for vein <0.8cm deep; long needle (48mm) preferred for ≥0.8 cm (48mm 18G
[green] stocked in most supply rooms, but 48mm 20G [pink] more difficult to find)

Transverse Technique
NEJM 2012;366:e38: choosing a vein (8:45), transverse (10:05), longitudinal (12:28)
1) Setup: positioning is very important. Place U/S on opposite side of pts bed, adjust
bet to appropriate height, obtain seat if needed, abduct & externally rotate pts arm.
2) Place tourniquet: place tourniquet as proximal as possible, near axilla if possible.
Can stack two tourniquets for extra compression.
3) Confirm anatomy: use vascular probe on U/S at minimum depth to locate adequate
superficial veins.
o Find vessels: start at AC and move proximal and distal. Key is to find LARGE
vessels (>0.4cm) that are CLOSE to the surface (depth between 0.3cm –
1.5cm) (J Emerg Med 2010;39:70). Common veins: basilic, cephalic > deep
brachial
o Confirm venous circulation: gentle pressure differentiates veins (fully compressible, non-pulsatile) and arteries (pulsatile); color
doppler can confirm
o Trace vessel course: follow the vessel course proximally and distally; recognize and avoid branch points, diving veins, and
irregular coursing veins
4) Sterility: use alcohol pad or chlorhexidine swabs to sterilize proposed venipuncture site; clean U/S probe then cover with tegaderm;
use sterile lubrication (or sterile U/S gel) as conduction medium for probe
5) Orient ultrasound: center target vein on U/S screen, confirm with compression, confirm vein course is in line with proposed needle
course, stabilize probe by anchoring hand on patient
6) Insert angiocath: with bevel up, puncture skin and advance angiocath 2-3 mm at a 45° angle
o Angiocath needle tip should be centered on U/S probe – this will be directly over the
vein if vein is centered on screen
o Insertion site at skin is distal to the planned site of insertion into vein
o At insertion, eyes should be on the site of venipuncture, not on the U/S screen, though
after puncture, should be watching screen and not hand
7) Find tip and advance: as insert, needle tip (and shadow) should appear on screen 
advance PROBE until you lose needle tip  advance NEEDLE tip until it reappears on U/S
screen; continue to advance until tip is “tenting” the roof of the vein
8) Enter vein: a quick short jab will allow you to enter vein; visualize needle tip as “target sign”
9) Drop angle and advance: drop your hand to flatten needle angle; continue to advance as above, keep needle in center of vein.
10) Slide off catheter: once 3-5mm into vein, can slide catheter off needle into vein and hub, and retract needle.
Optional: continue to advance needle until angiocath is hubbed to skin
11) Flush: attach extension tubing, REMOVE TOURNIQUET, pull back on saline flush (ensure drawback), THEN FLUSH with saline
12) Secure: secure catheter and tubing with tegaderm; floor and ICU nurses may redress IV

Longitudinal Technique: use the following adjustments to the above technique

1) Identify target vein in the transverse view
2) Rotate the probe to obtain a longitudinal view with the indicator towards your needle
3) Align needle in the plane of the probe; puncture skin at 45 degrees, visualize needle tip
4) Advance needle until you can see that the tip of the catheter itself is fully within the vein
5) Do not to go through the back wall. Advance the catheter under direct visualization.

Technique Pros Cons

- Faster, requires less finesse with U/S probe - Harder to visualize the needle tip
Transverse (short axis)
- Allows visualization of adjacent structures - Risk of “through and through”
- Improved visualization of the needle tip - Challenging to maintain probe/vein/needle in plane
Longitudinal (long axis)
- Can advance catheter under direct visualization - Cannot see adjacent structures.
Troubleshooting (Transverse Video; Longitudinal Video; written guide: West J Emerg Med 2017;18:1047)
• Can’t see needle: gently bounce the needle tip to generate artifact
• Too much loose tissue: use tape or have someone assist by putting tension on the tissue w/o applying pressure over target vein
• Vein rolls: reposition directly over the middle of vein, use a slightly steeper angle to take advantage of the sharp edge of the needle
• Trouble finding any veins: try using a blood pressure cuff high in the axilla instead of a tourniquet, but give the patient frequent breaks

Ryan Dodge
233
TOC

Procedures Central Line

General Considerations
Indications: hemodynamic monitoring (CVP, CVO2); admin. of noxious meds (pressors, chemo, hypertonic solution, TPN); rapid large
volume resuscitation; inadequate peripheral access; HD/CVVH/pheresis); to introduce other devices (PA line, temp wire)
Contraindications: vein thrombosis or stenosis should prompt another site. Coagulopathy/thrombocytopenia are relative
contraindications, if severe coagulopathy, avoid subclavian (not a compressible site + difficult to effectively monitor for bleed)
Site selection: general preference at MGH is RIJ > LIJ > subclavian, femoral due to historical concern for infection. However, more recent
data suggests no difference between these sites with proper attention to sterile technique
Catheter selection: select based on number of lumens and speed of infusion; if rapid infusion required  large bore, short length Cordis
Alternatives: PICC (if no concern for bacteremia) or IO (should not be used for > 24h, but in extreme circumstances OK for 48h)
Scheduled exchange of catheters without evidence of infection is NOT indicated
Cultures drawn from indwelling catheter have  false ⊕ rate; generally not done aside from time of sterile placement
(NEJM 2003;348:1123)

Internal Jugular Vein Video https://www.nejm.org/doi/full/10.1056/NEJMvcm0810156

Ad v ant ag es D i sad v ant age s
Compressible vein Carotid artery puncture 2-10%
Lower risk of pneumothorax (< 1%) than subclavian Less patient comfort
Ability to use real-time ultrasound Anatomy not as consistent as subclavian
All IJ CVCs placed with real-time U/S guidance @ MGH:  first attempt failure, procedure time, and failure / complication rate.
Positioning: supine + Trendelenburg to engorge veins, maximize target,  risk of air embolus
Site selection: Transverse ultrasound
• Locate triangle formed by medial and lateral portions of SCM with the clavicle as base view showing RIJ
• Find IJ  superficial and lateral to carotid, compressible, larger, thinner anterior & lateral to
• RIJ generally preferred (direct course to SVC; LIJ  risk of PTX and thoracic duct injury)
Entry: bevel up at the apex of SCM / clavicle triangle, about 4-5 cm above suprasternal notch
carotid artery
Target: aim at ipsilateral nipple, 45 degrees (map out trajectory of vessel using ultrasound)
1) Preparation and positioning are essential; ensure someone is always available to help
2) Obtain consent; perform TIME-OUT; complete checklist (usually RN)
3) Use 2% chlorhexidine solution to prep (in the kit); drape the entire patient in sterile field
4) Place caps on CVC, flush all lines with sterile saline, remove cap from brown port; ensure RIJ
Medial head of SCM

guide wire advances easily and syringe comes off needle easily
5)
6)
Locate IJ vein & carotid artery using ultrasound
Anesthetize with lidocaine; can make wheal & inject along tract (aspirate before injecting!)
ICA IJ
CA
7) Insert and advance the large bore needle bevel up, 45°, towards ipsilateral nipple, visualizing
tip with US; apply negative pressure. Once flash of blood is obtained  stop advancing the
needle, continue to draw back venous flow (dark, non-pulsatile)
• If arterial flow seen, remove needle and compress ~10 min
• If air drawn back, suspect PTX  STAT CXR, 100% FiO2, decompress if tension
8) Once flow obtained, stabilize needle with your non-dominant hand, remove syringe from
locator (occlude hub with thumb to minimize risk of air embolism in non-ventilated patients)
9) Feed the curved end of the wire into the needle (never feed the opposite end)
NEVER LET GO OF THE WIRE.
• If any resistance, remove wire, assess for flow w/ syringe; If good blood flow, try
twisting wire or flattening angle of needle
ICA RIJ
• For R-sided IJ  feed ~25cm of wire (between two and three dark lines)
 watch for ectopy (suggests wire in RV  withdraw)
SCM
NB: catheter length = 14cm (usually), so need at least this distance of wire in vessel.
10) Remove needle
11) Confirm wire is in vein using U/S in transverse and longitudinal planes
12) Perform manometry confirmation  advance angiocath from kit over wire, remove wire,
connect manometer tubing  venous blood should be non-pulsatile, dark, and rise < 20cm (can directly visualize fill in tubing or
connect tubing to manometer)  replace wire through angiocath, remove angiocath
13) Extend puncture site with scalpel by inserting along path of wire (face cutting edge away from wire to prevent cutting wire)
14) Thread dilator over wire (using twisting motion) until about 1/3 is inserted, then remove; goal is to dilate skin/subcutaneous tissue,
NOT the vessel itself (increased bleeding); ensure the wire moves back and forth freely while dilating (may otherwise be kinked)
15) Advance catheter over wire (wire comes out brown port, which is why it must be uncapped); remove wire
16) Draw back off all ports through caps using saline flush (only need to see small amount of flash), flush all lines clean, clamp ports
17) Secure with sutures; place Biopatch prior to securing with dressing
18) Order CXR (ASAP) to assess position, rule out PTX and hemothorax; look at the CXR yourself; catheters should terminate in
superior vena cava or cavo-atrial junction; may need to pull back if in RA ( ectopy). If adequate position, put in order “OK to use.”
Sean Mendez
234
TOC

Procedures Central Line Placement

Subclavian Vein Video: http://www.nejm.org/doi/full/10.1056/NEJMvcm074357

Ad v ant ag es D i sad v ant age s

Anatomy is more reproducible, even in obese patients, given Risk of PTX (1-8%), L side slightly > R due to higher dome of L
bony landmarks pleura
Improved patient comfort; easier to dress and maintain Not easily compressible; more risk a/w bleed if coagulopathic
Risk of subclavian artery puncture / hemothorax (0.5-1%)
Positioning: some place a roll of towels between scapula to expose subclavicular area… others
say this distorts anatomy; place in Trendelenberg to engorge vein
Entry: @ MGH  infraclavicular approach (as opposed to supraclavicular); puncture skin 1cm
caudal to junction of medial 1/3 and middle 1/3 of clavicle (where vein flows just under the bone)
Target: bevel up and aim toward sternal notch, 30° to the skin; needle should advance just on the
underside of the clavicle (~3-5cm depending on anatomy); some people “walk down” the clavicle to clavicle
ensure this, but may lead to dulling or bending of needle as well as periosteal pain
Pearls:
• Turning head to ipsilateral side will kink IJ and facilitate wire going down the SVC
• Rotate bevel 90° caudal after needle is in the vein to help direct wire into the SVC
• Ultrasound not always helpful (given acoustic shadowing from bone) SC a. & v.
• Subclavian vessels may be compressed with two fingers squeezing around the clavicle
• Guidewire usually only needs to advance 20cm (two dark lines)

Femoral Vein Video: http://www.nejm.org/doi/full/10.1056/NEJMvcm0801006

Ad v ant ag es D i sad v ant age s

Compressible Femoral artery puncture 5-10%
No risk of PTX Risk of development of deep venous thrombosis
Can be cannulated more easily during CPR Less patient comfort in hip flexion, requires immobility
Large caliber vein technically easier to cannulate May occlude flow if patient is obese
Caution in patients with inferior vena cava filters
Positioning: head of bed flat; abduct lower extremity and externally rotate the hip
Entry: bevel up, 2-3 cm below inguinal ligament, 1cm medial to palpated pulse  femoral vein lies medial & inferior to the femoral artery
• If non-urgent use ultrasound to visualize
• “NAVEL toward the NAVEL”  Nerve, Artery, Vein, Empty, Lymphatics
(alternative: venouspenis)
• Two fingerbreadths lateral to pubic tubercle if pulse not palpable
• DO NOT approach vein above inguinal ligament  risk for RP bleed & peritoneal perforation
Target: directly superior at 30-45°.
medial
Cordis (aka venous introducer sheath)
Combined dilator and sheath w/ side port for IV access
Indications:
• Rapid resuscitation (shorter length, wider diameter)
• Introducer sheath for PA catheter
• Introducer for temp wire placement.
Sites: IJ (R preferred for PA line), subclavian vein, femoral vein
Placement technique: uses Seldinger technique (advance catheter over a wire) but dilator and sheath are advanced over wire together as
unit; dilator and wire then removed together; side port aspirated and irrigated prior to use.

CVC Complications
Arterial puncture: hold pressure x 10 mins; compress 1 inch inferior (IJ) or 2 inches superior (femoral) to puncture mark
Dilation / line placement in an artery: consult vascular surgery BEFORE removing line; consider CT if pt stable
Pneumothorax (IJ & subclavian): suspect if hypoxemia, hypoTN, difficult stick; obtain STAT CXR  thoracic surgery consult if PTX or
hemoTX; if tension physiology (shock)  immediate decompression with 16G angiocath @ 5th ICS, mid-axillary line (enter above the rib)
Retroperitoneal bleed (femoral): suspect if hematoma or hypotension; STAT CT  vascular medicine consult
Loss of wire or wire stuck in vessel: DO NOT use excessive force to pull out wire if it is stuck  leave in place, hold pressure to prevent
exsanguination  STAT KUB / CXR if wire loss  vascular medicine consult

Sean Mendez
235
TOC

Procedures Arterial Line

General Considerations
Indications: real-time BP monitoring (pressors, HTN emergency, CVA); frequent ABGs, lab draws (≥3 per day)
Locations: radial > femoral > dorsalis pedis > axillary; brachial not recommended given lack of collaterals unless placed by anesthesia
Contraindications: lack of collaterals (abnormal Allen test), h/o arterial grafts/stents, Raynaud’s/scleroderma
Risks: pain, infection, bleeding, ischemia, vasospasm, arterial dissection, embolization,
necrosis, loss of limb
Materials: arm board, tape, Chux, chlorhex prep, 4 x 4 sterile gauze, pack of sterile
towels, sterile gloves, mask, eye protection, bouffant, 20G angiocaths, guide wire,
Tegaderm, U/S probe cover (if needed)
• If pt awake  consider lidocaine (w/o epi), small syringe and 25G needle
• Use PINK SOLID STRIPE angiocath; do NOT use pink interrupted stripes, which has
a one-way valve so can’t pass wire
• Alt: use Arrow arterial line kit; the kit’s longer catheter is preferable for femoral site
Radial Technique Video: http://www.nejm.org/doi/full/10.1056/NEJMvcm044149
1) Obtain consent and perform TIME-OUT; ask RN to prepare for A line
2) Confirm anatomy by palpating pulses or with U/S. Test for collateral circulation of the hand:
• Allen test: make fist for ~30 sec, then occlude ulnar & radial arteries; pt opens hand (palm should be blanched); then release
pressure from ulnar artery  palm should regain color within ~5 sec
• Modified Allen test: place sat probe on index finger or thumb; occlude radial and ulnar arteries until wave form lost; release
ulnar artery  should get arterial tracing if good collateral flow.
3) Proper positioning is key to successful placemen: adjust bed to appropriate height
• Put Chux under wrist; extend pt’s wrist; secure arm board (bendable arm boards in CCU and MICU)
• Consider taping hand to bed/table to stabilize; mark course of artery w/ pen or indent with top of pen or use U/S / doppler PRN
4) Sterilize wrist widely with 2% chlorhexidine swabs; open towel packet to create sterile field
5) Prepare field: drop angiocath & guide wire on sterile field; don sterile gloves and drape widely w/ sterile towels
6) Prepare angiocath/guidewire: check angiocath to ensure catheter slides easily off needle; pull one side of wire slightly out of paper
7) Pick your target: palpate radial artery with non-dominant hand; plan to puncture distal to the pulse you palpate, aim towards that pulse
8) Insert angiocath: with bevel up, advance angiocath needle at a 45° angle toward pulse until flash is obtained (similar to ABG)
9) Once flash obtained, go "through-and-through”: advance ~0.5cm through artery; hold the top of the plastic catheter with non-
dominant hand; push button to retract needle, while steadying the catheter (should be no blood flow)
10) Hold guide wire close to head of angiocath w/ dominant hand
11) Pull back slowly: lower angiocath as parallel to skin as possible and SLOWLY pull it back until pulsatile blood flow is obtained
12) Advance wire: inset the wire into the angiocath; should not feel resistance; if unable to advance wire, DO NOT LET GO OF GUIDE
WIRE; TRY SPINNING THE WIRE!  avoids side branches of artery (where wire commonly gets caught)
13) Advance angiocath into the artery over the wire (Seldinger technique)
14) Remove guidewire: apply pressure to radial artery proximal to cath; remove guide wire; occlude opening of the angiocath with finger
15) Connect transducer: ask RN for A-line setup and connect transducer to angiocath; RN will flush; confirm placement w/ art. waveform
16) Dress the area with a Tegaderm; MICU RNs will often re-dress afterwards,
so ask their preference; in ED, suture to the wrist; NWH has snap dressings.

Daily  for ischemia (cool, white, purple) & infection (need for removal)
Troubleshooting and Alternatives
• If using Doppler, mark out course of artery with marking pen or indentations.
• If using U/S, can try advance needle/catheter under U/S guidance and once
firmly in vessel, advance catheter over wire (no guide wire; similar to PIV).
• If unable to thread guide wire AFTER ATTEMPTING TO SPIN during
insertion, consider micropuncture wire (cardiac cath lab or MICU med room).
May help with atherosclerotic arteries at the price of  risk of perforation
• After multiple attempts, the artery may spasm. Pursue alternative site.
• Femoral artery access can be considered in difficult cases. Use the long
catheter in the Arrow arterial line kit. Puncture must occur distal to the
inguinal ligament to prevent RP bleed. Too distal, however, and the femoral Proper femoral puncture site (Interventional Cardiac
artery will bifurcate into superficial and deep femoral vessels. The femoral Catheterization Handbook, 3rd Ed. 2013)
artery usually transverses the inguinal ligament ~1/3 distance from pubic
symphysis to the ASIS. Optimal point of skin puncture is 1-2 cm below the inguinal ligament at point where pulse is palpated (see
above)
Ryan Dodge
236
TOC

Procedures Intraosseous Line

General Considerations Video: If you have 15 min; If you have 1 min
• Anatomy: veins that drain medullary sinuses of bones; veins supported by bones do not collapse in patients in shock.
• Indication: patients without available IV access with urgent need (arrest, shock, status epilepticus, trauma, etc). Used for delivery of
fluids/medications; labs (but tenuous – clots off quickly). Faster access than CVC, low complication risk (Resuscitation 2012;83:40)
• Contraindications: fractured or penetrated bone (fluids exit site), local vascular compromise (e.g. trauma or cutdown). Should be
avoided in areas of cellulitis, burns, osteomyelitis, bone disease (e.g. osteogenesis imperfecta), RL intracardiac shunts (TOF, pulm
atresia) due to risk of fat emboli, failed IO insertion within 24h at same site
• Complications: extravasation, compartment syndrome, fracture, growth plate injury, infection, fat emboli, osteomyelitis (rare)
• Note:
• Infusion rate roughly 160mL/min at tibia or humerus with use of pressure bag, half of that rate without
• IO samples only accurate for some studies (Hgb, T&S, drugs, Cx). NOT for PaO2, WBC, K, AST/ALT, iCal, after drug admin
Set-Up
• Materials: ALL IN KIT  EZ-IO Power Driver, IO needle-set,
connector tubing, 10 cc syringe with saline flush,
chlorhexidine/povidone iodine, sterile gloves. If awake, 3cc syringe
with 1% lidocaine via 25G needle
• Location:
• Proximal tibia (preferred): find the flat surface 2cm below tibial
tuberosity, 1-2cm medial along tibia
• Proximal humerus: position pt palm on abdomen (elbow flexed,
shoulder internally rotated) greater tubercle 2cm below
acromion process
• Other sites: distal tibia, distal femur, iliac crest
Procedure (Crit Care 2016; 20:102)
1. Don surgical mask, eye protection, sterile gloves
2. Flush connector tubing with NS or cardiac lidocaine if patient is awake
3. Identify injection site
4. Clean injection site with antiseptic (chlorhexidine or iodine)
5. If patient is awake, create wheal with 1% lidocaine
6. Choose proper needle size: generally blue (25mm); yellow (45mm) is for excess tissue or
for humerus approach
7. Magnetic pole holds the needle in place on the drill; turn the safety cap clockwise for
removal
8. Hold drill perpendicular to bone; manually press the needle through the skin until it
touches the bone
9. Confirm you see one black line on the needle (5mm mark); if not, use a longer needle
10. Apply gentle, steady, downward pressure while holding the trigger; allow drill to do the work
11. Release trigger when decreased resistance felt (“give” or “pop”) as you enter
into medullary space
12. While holding catheter in place, pull straight up to remove driver
13. Unscrew the needle stylet by rotating counterclockwise (both stylet and
needle are encased in colored plastic)
14. Aspirate marrow to confirm placement. Prior to attaching tubing, send labs;
blood samples may only be obtained in patients with spontaneous cardiac
activity or during initial CPR before drug and fluid infusion through the IO.
15. Attach connector tubing and flush IO w/ NS or 1% lidocaine over 45s if the
patient is awake (IO infusions are VERY painful); if the patient is
unconscious, rapid 10mL NS. Look for superficial swelling and note that no
flush means no flow!
16. Apply IO dressing stabilizer – FYI each size needle has a different dressing,
will not fit if dressing for other size
17. Administer rapid NS bolus, blood product, pressor, etc. with a pressure bag or syringe
18. Always return the IO kit to the CCU resource nurse to refill
Removal
• Remove within 24 hours of insertion once other access is obtained, or if signs of erythema, swelling or extravasation
Sean Mendez
237
TOC

Procedures Paracentesis
Indications: Video: http://www.nejm.org/doi/full/10.1056/NEJMvcm062234
• Diagnostic: new-onset ascites, unknown etiology of ascites, rule out SBP. Low threshold for inpatients with cirrhosis and often helpful
to obtain concurrent RUQUS with Doppler to rule out hepatic or portal vein thrombosis
• Therapeutic: large volume paracentesis (>5L)  performed for abdominal pain/discomfort, diuretic-refractory ascites, respiratory
compromise, abdominal compartment syndrome, adjunctive treatment of esophageal variceal bleeding (can lower portal pressures)
Contraindications: overlying infection (i.e. cellulitis), inability to demonstrate ascitic fluid on U/S, bowel obstruction/distention, acute surgical
abdomen, 2nd or 3rd trimester pregnancy
•  INR /  plts are NOT contraindications (INR in patients with cirrhosis is NOT reflective of the risk of bleeding). There is no need to
correct coagulopathy w/ FFP or platelets unless severe DIC (Hepatology 2013;57:1651)
Materials: sterile gloves, bouffant, face shield, chlorhex, sterile towels, ultrasound, 1% lidocaine (10cc syringe, SQ 25G needle, 1.5 inch 20-
22G needle), two 18G needles, 60cc syringe, diagnostic assay tubes as below, gauze, bandage or Tegaderm dressing
• Diagnostic: 20G two-way (pink box) angiocath or 18–22G 1.5-inch needle. In obese pts, may use angiocath from femoral art line kit.
Purple and green top tube, black top tube (for micro). Technically DO NOT need to inoculate blood culture bottles at the bedside.
• Therapeutic: safe-T-Centesis kit (preferred, pigtail minimizes perforation risk) or paracentesis kit (straight rigid needle), 1L vacuum
bottles, 25% albumin dosed 6-8g per liter of fluid removed if >5L (Hepatology 2013;57:1651)
Site Selection/Positioning:
• Position patient supine, turned slightly toward the side of the paracentesis, and angled upright at 30°
• Use abdominal probe to identify fluid pocket at least 2-3cm in all dimensions by rotating/fanning probe
and ensure absence of bowel loops
• Avoid superficial veins or prior surgical incisions and use vascular probe with Doppler to avoid SQ vessels 1 2 1
• Approaches:
o LLQ (1): more commonly used; LLQ  risk of bowel perf, use caution if pt with splenomegaly; avoid
inferior epigastric vessels that run along lateral borders of rectus muscles
o Infraumbilical (2): midline, 2cm below umbilicus; lowest risk of bleeding but must ensure bladder empty
Instructions:
1. Identify best site with abdominal U/S probe and mark site with pen or round base of needle Approaches
2. Open sterile OR towels package and use light blue covering as sterile field to drop sterile supplies. Don sterile protective equipment
(technically only need gloves, mask, bouffant cap) and clean skin vigorously with chlorhexidine. Create sterile field over patient with
OR towels or open kit and use dressing provided
3. Anesthetize overlying skin using ~0.5cc lidocaine (SQ 25G needle) to make a wheal. For LVP, use 1.5 inch 20-22G to anesthetize
deeper tissues with lidocaine in 10cc syringe. Use Z-line technique (below) and aspirate while advancing needle. Once ascitic fluid
begins to fill syringe, stop advancing the needle & inject remainder of lidocaine to anesthetize the highly sensitive parietal peritoneum

Z-line technique: reduces risk of ascites leak. With non- Therapeutic paracentesis instructions:
dominant hand, pull skin ~2cm caudad to deep abdominal wall a) Prepare Safe-T-Centesis kit: place catheter on needle,
while para needle is being slowly inserted attach syringe, and prep tubing
b) Use scalpel to make small superficial incision (enlarge PRN)
Diagnostic paracentesis instructions:
c) Advance needle/catheter while pulling back on syringe until
a) Insert 20G two-way (pink) angiocath through wheal at same
ascitic fluid return is visualized, then advance 0.5 cm
angle as U/S probe and advance until slightly past when flash seen
d) Advance catheter until hubbed (only with Safe-T Centesis
b) Advance the catheter without moving the needle
kit!), hold rigid needle in place
c) Retract needle, attach 60cc syringe, and fill syringe
e) Retract needle, attach 60cc syringe for dx sample PRN
d) Withdraw the catheter and apply pressure with sterile gauze
f) Connect tubing to catheter and puncture vacuum bottles
e) Apply dressing using folded gauze under Tegaderm
g) Withdraw catheter and apply gauze/Tegaderm dressing
f) Attach 18G needle to 60cc syringe and fill diagnostic tubes
h) Give 25% albumin (6-8g/L removed) if >5L removed
Diagnostic Assays:
Tube Lab Tests
Green top Chem Fluid albumin (send serum albumin to calculate SAAG), fluid total protein (to determine need for SBP ppx)
Purple top Heme Fluid cell count
Blood culture bottles Micro Can send for aerobic & anaerobic fluid culture, clean top with alcohol and inoculate at bedside for max yield
Black top Micro Gram stain and culture plates
Other tests to consider: glucose, amylase, LDH, bilirubin, triglyceride, AFB smear, mycobacterial culture, adenosine deaminase, pH, cytology

Complications:
• Flow stops/slows: roll patient slightly to side of para, rotate catheter, slightly withdraw catheter, flush catheter, new vacuum container
• Flash of blood in catheter: use vascular probe to avoid SQ vessels  withdraw & insert new catheter at different site
• BRB return: injury to mesentery or inferior epigastrics  stop, assess for hematoma w/ U/S, IR or surgery consult if HD unstable
• Hypotension: likely vasovagal or fluid shift (>1500cc tap)  Trendelenburg, hydrate, and consider 25% albumin
• Bowel perforation: may lead to polymicrobial bacterascites/sepsis  surgery consult for potential laparotomy
• Fluid leak: prevent with Z-line technique  apply pressure dressing, seal w/ Dermabond or single stitch (4-0 non-absorbable suture)

Sean Mendez
238
TOC

Procedures Arthrocentesis
Indications
Diagnostic: evaluation of inflammatory mono/oligoarthritis or uncharacterized joint effusion. A single inflamed joint should always have
diagnostic aspiration to differentiate septic arthritis, crystalline arthopathy, inflammatory arthritis, and hemarthrosis
• Avoid if overlying cellulitis or periarticular infection; prosthetic joints should prompt Ortho/Rheum consult; safe to perform if on
warfarin (Am J Med 2012;125:265) or DOAC (Mayo Clin Proc 2017;92:1223) but consider smaller needle
• Ultrasound may be used to guide needle insertion and can also offer diagnostic information with complexity of fluid
• Hip joint aspiration should be performed by interventional radiology

Therapeutic: injection of corticosteroid/anesthetic in autoimmune arthritis (RA/JIA, spondyloarthropathies) or single-joint gout flare
(especially when systemic therapy is contraindicated); drainage of large effusion, pus, or blood
• Avoid if overlying cellulitis, periarticular infection, septic arthritis, periarticular fracture, joint instability
• Use of intra-articular steroids in OA is falling out of favor due to progressive cartilage damage (JAMA 2017;317:1967)

Complications: iatrogenic infection (1/3500, >48h after procedure, may see systemic signs of infection), post-injection flare (mirrors
infection and occurs within 24-48h of procedure), hemarthrosis, leakage of joint fluid, local or systemic steroid effects

Technique: Knee NEJM Video: http://www.nejm.org/doi/full/10.1056/NEJMvcm051914

Materials: sterile gloves, chlorhexidine/iodine, 5cc 1-2% lidocaine 5cc w/o Epi (25G needle, 5cc syringe) or ethyl chloride spray, 18-22G
needle, 20-60 mL syringe, diagnostic tubes (purple/green top, aerobic/anaerobic bottles), sterile towels/sheet, bandage

Positioning/Approach: position the knee in extension or 15-20° flexion. Approaches described below:
• Lateral (see image): 1cm lateral and 1cm superior to the superior 1/3 of the lateral patella. Angle the needle approximately 45°
toward the feet and insert behind the patella at a 45° angle to the skin. More likely to yield fluid in difficult cases
• Medial: 1cm medial to the superior 1/3 of the medial patella. Angle the needle perpendicular to the leg and at a 45° angle to the skin
Lateral Approach
Protocol:
• Identify landmarks as above and mark point of entry with the base of a needle
cap or pen. Sterilize the site. A sterile field is not technically required but may
drape the area w/ a sterile sheet or towels. Prep needles and syringes.
• Anesthetize overlying skin using ~0.5cc lidocaine (SQ 25G needle, 5cc syringe)
to make a wheal. May use remaining lidocaine along procedure tract.
• Attach 18-20G needle to 30cc syringe and position needle according to approach.
Advance needle slowly (avg 1-1.5 in) and aspirate while advancing.
• Once fluid is visualized, aspirate joint fluid to fill syringe. May attach a 2nd 30cc
syringe to drain additional fluid for sx relief pending size of effusion.
• Withdraw needle and apply bandage. Fill diagnostic tubes (purple top
for cell count/diff and crystal eval, aerobic/anaerobic cx bottles).

Diagnostic Assays: cell count/diff, crystal analysis, gram stain/culture AND blood cultures (Am Fam Physician;2003;68:1)
• Septic arthritis: most common locations: knee > hip > shoulder > elbow
o If patient HDS, hold antibiotics prior to tap; 70% Staph, 17% Strep, 8% GNR (H. flu child > adult)
o WBC count usually 50-150K but can be lower (e.g. <20K in disseminated gonorrhea); WBC =  risk of infection
o Presence of crystals does not rule out septic arthritis (up to 5% of pts with crystals also have septic joint)
o Gram stain: sens 75% for Staphylococcus, 50% for GNR, < 25% for Gonococcus
o Joint cx usually positive but only 50% sensitive in gonococcal arthritis (swab genitalia & pharynx for diagnosis)
• Gout: negatively birefingent needle-shaped urate crystals (yellow) on polarized microscopy (Sn 63-78% / Sp 93-100%)
• Pseudogout: positively birefringent CPPD rhomboid crystals (blue) on polarized microscopy (Sn 12-83% / Sp 78-96%)

Sean Mendez
239
TOC

Procedures Lumbar Puncture

Indications
Diagnostic: suspicion for CNS infection (most common), CNS malignancy/mets, SAH, or CNS demyelinating/inflammatory process
Therapeutic: idiopathic intracranial hypertension, NPH, ICP in cryptococcal meningitis, intrathecal meds/chemotherapy/anesthesia
Contraindications: no absolute contraindications; high risk if skin infection over puncture site, epidural abscess, ICP 2/2 mass lesion or
obstruction (risk of brain herniation), spinal cord tumor or AVM, thrombocytopenia (<50K) or coagulopathy (INR > 1.5)
Preparation:
• Hold AC: time frame needed to hold AC prior to procedure: IV heparin (4hrs, PTT<35), LMWH therapeutic (24hrs), LMWH ppx
(12hrs), Plavix (5-7 days), DOAC (3 days), warfarin (3 days, goal INR <1.5). OK to proceed if on SQ heparin daily dose <10,000U,
ASA, or NSAIDS. If urgent, weigh risks and benefits. For details (including when to restart AC), DOM policy can be found in Ellucid.
• Head CT: only obtain head CT if ≥1 of the following: age > 60, hx CNS disease, seizure in last 7d, immunocompromised, AMS,
aphasia, cranial nerve deficit; if none of these, then 97% NPV for no mass lesion (NEJM 2001; 345:1727)
Technique (NEJM 2006;355:e12) NEJM video: http://www.nejm.org/doi/full/10.1056/NEJMvcm054952
Equipment: LP kit, sterile towels, sterile gloves, face shield, pillows to position patient
• LP kit: 1% lidocaine (25G needle, 5cc syringe), sterile drape, iodine/chlorhex, 20-22G needle/stylet, 4 collection tubes, manometer
Positioning: proper positioning is the key to a successful and smooth LP!
• Use L4–L5 (level of iliac crests), L5–S1, or L3–L4 interspaces (conus medullaris at L1–L2)
• Lateral (if measuring opening pressure): place pt in fetal position (maximize neck and
hip flexion), no hip / shoulder rotation; keep back parallel to edge of bed
• Upright (easier if obese): sit on bed, head / arms rest on table, spine flexed
• To identify target, place a hand firmly on each iliac crest and mark where your thumbs
meet at the midline or draw a line between the iliac crests. Before inserting the needle,
place your thumb and pointer finger on either side of the spine to ensure needle is midline
• Sitting while performing the procedure is often easier than standing, as the needle is in your line of sight
Protocol: (JAMA 2006;296:2012)
1) Prep: sterilize and drape widely. Re-identify target. Make lidocaine wheal w/ 25G, then inject track (aspiration before injecting, goal is
not spinal anesthesia). Keep CSF collection tubes in order nearby. If checking pressure, have manometer connected and ready.
2) Tap: check needle / stylet mobility. Bevel should face ceiling when pt is lateral. Needle angles slightly toward the head (as if aiming
to umbilicus), straight at the back. Stabilize with your hand against the skin and advance with your dominant hand. Remove stylet
frequently to check for CSF flow but always keep stylet in place when advancing.
3) Troubleshoot: if hitting bone, partially withdraw, adjust angle, and re-advance. Try another space below if no luck. If patient has pain,
DO NOT withdraw  ASK “where?” If pain is shooting down the left side, withdraw slightly and go slightly more to the right. If hitting
bone early, more likely to be superior or inferior; if hitting bone late, more likely to be too lateral.
4) Measure OP: once flow is established, remove stylet and connect manometer to measure opening pressure (must be in lateral
decubitus position). Pt must extend legs to obtain accurate pressure. If performing therapeutic LP, drain until pressure normal.
5) Collect: collect CSF tubes 1 to 4; if flow slows, try rotating needle or minimally advancing or withdrawing with stylet in place.
6) Finish: re-insert stylet prior to needle removal (associated w/  post-LP headache).

Diagnostic Assays
Tube Lab Tests
1 (1 mL) Heme CSF cell count
2 (1 mL) Chem Total protein, glucose
Gram stain/culture. Consider HSV PCR, VZV PCR, cryptococcal antigen, viral culture,
3 (3-5+ mL, depending
Micro AFB stain, VDRL. Ask lab to save extra CSF. If you may need flow cytometry, DO NOT
on number of tests)
FREEZE CSF!
4 (1 ml) Heme CSF cell count (should have fewer RBCs than tube 1 unless hemorrhage)
Additional tests: cytology & flow cytometry (meningeal carcinomatosis), oligoclonal bands (multiple sclerosis), paraneoplastic
antibodies, 14–3–3 & RT-QuIC (prion disease); may want to collect extra black top tubes for these purposes; if c/f prion disease,
contact materials management for instruction on special disposal of materials (highly contagious!)

Complications
Cerebral herniation (acute AMS, Immediately replace stylet and do not drain more CSF beyond what is in manometer. STAT
fixed pupils,  BP, brady, arrest) consult neurosurgery and treat with ICP-lowering agents (e.g. mannitol)
Shooting pains during procedure usually transient. Withdraw slightly and adjust position away from
Nerve root injury
direction of pain. Consider dexamethasone if pain is persistent.
Post-LP headache (10-30% Onset 72h, lasts 3-14 days. Give pain meds that do not affect plt. No evidence for bed rest. If
incidence; likely 2/2 dural leak) persistent, c/s anesthesia for epidural blood patch (65-98% success, usually immediate relief).
Spinal hematoma Suspect if on AC w/ persistent back pain or neuro sx  urgent MRI  IV dexamethasone +
NSGY c/s

Xavier Guell Paradis

240
TOC

Procedures Thoracentesis
Indications
Diagnostic: to establish etiology of ≥1cm pleural effusion visualized by U/S (not necessary for small effusions w/ probable alternative dx)
• NB: pleural effusions are visible on CXR when > 200mL of fluid is present
Therapeutic: large effusions  resp compromise or sx (e.g., dyspnea), hemothorax, empyema, complicated parapneumonic effusion
Contraindications (relative, not absolute) (Chest 2013;144:456)
• Consider reversing coagulopathy (INR >1.5, recent LMWH) or thrombocytopenia (plt < 50k), but no data to support
• Skin infection (cellulitis or herpes zoster) over site of entry  risk of pleural space infection
• Positive pressure ventilation  risk of PTX by 1-7% but is not a contraindication (Crit Care 2011;15:R46)

Preparation
• Materials: skin cleansing agent, gauze, sterile gloves/drape, hemostat, 1-2% lidocaine, 10mL syringe with 22 & 25 gauge needle,
thoracentesis kit with 18-20g over-the-needle catheter, 60cc syringe, 3way stopcock, drainage tubing, specimen tube, evacuation
container, occlusive dressing
• Attending MUST be present for thoracentesis: page IP (p23710), pulm, or call MICU x68048 to see who is on service

Technique (NEJM 2006;355:e16), Video

• Position: patient at edge of bed, leaning forward with arms resting on table
• Identify: height of effusion determined by auscultation & percussion of chest
wall. Use ultrasound to confirm location of effusion.
o Mark 5-10 cm lateral to spine & 1-2 ICS below effusion. Lowest level
recommended is 8th ICS (above diaphragm)
o In patients who cannot sit upright  mid-axillary approach (patient
supine) or posterior axillary with patient lateral decubitus
• Prep & drape: set up thoracentesis kit, put on sterile gown and gloves,
sterilize patient w/ chlorhexidine, then drape
• Using 25G needle, place wheel 1% lidocaine over superior edge of the rib
• Using 22G needle, walk the needle over superior aspect of the rib while
intermittently aspirating and injecting perpendicular to the pleural space
• When pleural fluid aspirated, withdraw slightly then anesthetize the parietal
pleura (highly sensitive) with 2-3cc of lidocaine. Note penetration depth.
• Attach 18G over-the-needle catheter to syringe & advance over superior
aspect of the rib, pulling back while advancing
• When fluid aspirated, stop advancing & guide plastic catheter over needle
Catheter has valve preventing fluid or air from entering the pleural space,
so may use both hands to prepare for your next step
• Attach 60 cc syringe to 3-way stopcock connected to catheter, withdraw full
syringe of fluid, and put in appropriate tubes for lab & micro studies
• Attach tubing to 3-way stopcock, affixing longer tube to large evacuation
container & shorter tube to the syringe. Tubing is all one-way.
• Aspirate fluid slowly into the syringe and inject back into bag, never fully
empty the syringe as it can lead to difficulty on repeat aspiration.
Stop if patient experiences chest pain, dyspnea, cough. Do not remove
more than 1.5L fluid as  risk of post-expansion pulm edema.
• When done, withdraw catheter while patient is humming (to avoid air entry
into pleural space); cover site with occlusive dressing
• Obtain post-procedure CXR to assess for pneumothorax or hemothorax
Diagnostic Assays
• Send fluid for: TP, LDH, chol, glucose, pH, cell count, culture and Gram stain, anaerobic culture, fungal wet prep with culture.
• Consider: TG (chylothorax), Cr (urinothorax), amylase (pancreatitis, esophageal rupture), ADA (TB), AFB culture, modified AFB culture,
cytology
Complications
1. Hemothorax/intercostal vessel injury:  risk if inferior approach to rib or elderly (tortuous vessels). CXR, H&H. Consider chest tube.
2. PTX: 5-20% risk; most can be monitored with serial CXR; monitor for signs of tension PTX and obtain STAT expiratory CXR; if PTX is
large / patient is symptomatic and/or in distress  needle decompression with 16G angiocath at 5th ICS mid-axillary line (always above
nipple); chest tube indicated in 20% of cases  consult IP (p23710) or thoracic surgery
3. Vasovagal syncope/pleural shock: caused by needle penetrating parietal pleura; supportive care
4. Re-expansion pulmonary edema: to avoid, stop thoracentesis if cough, CP, or dyspnea, limit volume removal (<1.5L). Do not attach
to vacuum, remove fluid slowly without excessive negative pressure; treat w/ O2, diuretics, BiPAP.

Ramya Chitra Mosarla

241
TOC

Procedures Pericardial Drain

Indications:
• Pericardial effusion with tamponade physiology (or if at high risk for development of tamponade physiology)
• Diagnostic or palliative drain of stable pericardial effusion

Relative Contraindications: no absolute contraindications

• Coagulopathy: INR>1.7, platelets<20, PTT>60 or on heparin gtt. Consider FFP/platelets when on call for procedure
• Effusion associated with aortic dissection or myocardial rupture, as decompression could lead to extension of injury
• Effusion associated with severe pHTN (controversial), as decompression could lead to RV dilation and acute RV failure
(Pulm Circ 2013;3:467)

Management Overview: if in doubt about management, page the cardiology team that placed the drain
• Pericardiocentesis does not completely evacuate a pericardial effusion. A pericardial pigtail catheter is often left in for 24-
72h to allow for serial drainage, preventing re-accumulation and repeated procedures.
• Frequency of drainage depends on chronicity and size of the effusion, usually q6-q12h. Recommendations are often
found in the report from the cath lab when the drain was initially placed.
• Give cefazolin 1g q8h (or vancomycin if PCN allergy) for prophylaxis while drain is in place.
• Monitor effusion resolution and recurrent tamponade. Check serial hemodynamics/pulsus paradoxus.
• If >100cc output/day for 3 days s/p drain placement, aggressive therapy may be indicated (i.e. pericardial window,
sclerosing agents, etc.)
• Consider removal of pericardial drain if <50cc output over 24 hours. Obtain approval from cardiology prior.

Materials:
• Sterile technique: gloves, mask, hat
• Sterile towels
• Chlorhexidine swabs (at least 3)
• 60cc Leur lock (screw-on) syringe (x2-3 if high output)
• New blue cap for 3-way stopcock
• Heparin (10U/mL) pre-mixed syringe (in MICU/CCU med rooms)

Technique:
1. Put on, gloves, mask and hat (gown is optional). Open supplies onto sterile field.
2. Ask RN/assistant to lift catheter off skin by flush port. Sterilize distal exposed catheter and stopcock with chlorhex swab.
Holding the sterilized area, take catheter from RN and sterilize remaining portion
3. Place sterile towels around and underneath distal catheter and stopcock, and lay the now-sterilized catheter down
4. Ensure the stopcock is turned towards the catheter. This means the catheter line is closed.
5. Remove and throw away one blue cap (doesn’t matter which).
6. Sterilize open stopcock tip with iodine or chlorhex swab.
7. Hold up flush port; RN will connect heparin syringe (syringe itself is not sterile) to open/sterilized tip. Turn stopcock toward
the remaining capped valve (opens flush port/catheter), and infuse 2cc heparin.
8. Turn stopcock back towards catheter, remove (do not discard) heparin syringe, and connect 60cc Luer lock syringe.
9. Turn stopcock to the remaining capped valve and slowly withdraw pericardial fluid. This may require significant negative
pressure. Consider different patient positions (Trendelenberg, lateral decubitus, etc.) to mobilize pericardial effusion.
Patient may experience chest discomfort. Monitor hemodynamics
10. Save/transfer pericardial fluid if needed for analysis. Otherwise discard.
11. Can stop draining once fluid flow diminishes/ceases. Turn stopcock back towards catheter and remove syringe.
12. Ask RN to re-attach heparin syringe and infuse another 2cc heparin. Again close stopcock to the patient.
13. Remove heparin syringe and attach new blue cap to open flush port.
14. Consider re-sterilizing distal exposed catheter and stopcock with chlorhex swab.
15. Write procedure note. Be sure to deduct the 2-4cc infused heparin when calculating amount of fluid removed.

Fluid Studies:
• Gram stain and bacterial/fungal culture
• Specific viral studies/PCR
• Cytology
• AFB stain, mycobacterial culture, adenosine deaminase, IFN-gamma, or lysozyme (if considering TB pericarditis)
• Protein, LDH, glucose, red/white cell count are not helpful for fluid characterization

Ramya Chitra Mosarla

242
TOC

Procedures Fluid Analysis

LUMBAR PUNCTURE INTERPRETATION
Pressure Predominant cell Glucose
Condition WBC per mL Protein (mg/dL) Further CSF Testing
(cm H2O) type (mg/dL)
Normal 9–18 0–5 Lymph 50–75 15–40 N/A
Bacterial meningitis 20–50 <100 to >10k > 80% PMN < 40 100–1000 Culture, Gram stain

Viral meningitis Lymph; early >45; low in HSV/VZV PCR, consider

(Enteroviruses, HSV, 9–20 50–1000 echovirus / HSV can LCM and <200 further viral PCR or Ab if
VZV, arboviruses) have 80% PMN mumps clinical suspicion; d/w ID

Ab testing paired with serum ab

Lyme meningitis 9–20 10–300 Lymph Normal 50–100
(though poor sensitivity)
50-300 MTb Cx < 60% sensitive,
TB meningitis 18–30 50-300 Lymph < 50 >2000 if subarach Nucleic acid test not approved
block by FDA
Fungal wet prep + Cx, discuss
Fungal meningitis 18–30 < 300 Lymph < 50 40–300
other testing with ID
Fungal wet prep + culture,
Cryptococcal meningitis 18–30+ 5–500 Lymph < 40 >45
cryptococcal antigen
Epidural/Brain abscess 18–30 10–300 Lymph Normal 50–400 Gram stain not sensitive
WBC correction for RBCs (i.e. traumatic tap) = measured WBC – (measured RBC / 500)
PARACENTESIS INTERPRETATION
⊕ Ascites culture ⊝ Ascites culture
Spontaneous Bacterial Peritonitis (SBP)
PMN ≥ 250/µL Culture Negative Neutrocytic Ascites (CNNA)
(Secondary Peritonitis  polymicrobial)
PMN < 250/µL Non-neutrocytic Bacterascites (NNBA) Normal
CNNA: has similar clinical presentation and prognosis as SBP, thus treat for suspected SBP after diagnostic PMN count without waiting for Cx
(ddx: peritoneal carcinomatosis, tuberculosis, pancreatitis)
Calculations: # of PMNs = Total nucleated cells x % of PMNs
Correction for RBCs (RBC count > 50,000/mm3, seen in “traumatic tap”) = measured PMN – (measured RBC / 250)
Clues in Fluid Analysis for SBP vs. Secondary Peritonitis:
- If ≥2 present, increased suspicion for secondary peritonitis: 1) serum total protein >1 2) serum glucose < 50 3) serum LDH > upper limit of normal
- Consider repeat paracentesis after 48hrs of antibiotic treatment: if PMN  and only 1 org. on prior culture, likely SBP; if PMN  and multiple org.
on prior culture, then likely secondary peritonitis
SAAG ≥ 1.1 g/dL SAAG < 1.1 g/dL
(etiology related to portal HTN) (etiology NOT related to portal HTN)
Fluid total protein < 2.5 g/dL Cirrhosis Nephrotic syndrome
Pancreatitis
Heart failure
Fluid total protein ≥ 2.5 g/dL Peritoneal carcinomatosis
Budd-Chiari syndrome
TB
SAAG = Serum Albumin – Ascites Albumin (from samples obtained on the same day)

PLEURAL FLUID INTERPRETATION

Transudate (due to Starling forces) vs. Exudate (due to increased capillary leak) (NEJM 2002;346:1971)
Light’s Criteria: exudate if ≥ 1 criteria present (98% Sn / 83% Sp)* If ≥ 1 of these, it’s an exudate with 98% Sn / 70% Sp:
1. Pleural fluid protein / serum protein > 0.5  Pleural fluid protein > 2.9, LDH > 95, cholesterol > 45
2. Pleural fluid LDH / serum LDH > 0.6 More specific criteria for confirming exudate:
3. Pleural fluid LDH > 2/3 ULN of serum LDH (i.e. > 140)  Pleural fluid cholesterol > 60 (54% Sn / 92% Sp)
*Diuretics cause ~25% of transudates to be misclassified as exudates  Serum albumin – pleural albumin ≤ 1.2 (87% Sn / 92% Sp)
 Pleural NT-proBNP < 2,300pg/mL (>80% Sn / >70% Sp)
• Other tests: adenosine deaminase, amylase, triglyceride, cholesterol, Gram stain/culture, cell count, IFN-γ, NT-proBNP, pH, tumor markers
• Complicated parapneumonic effusion / empyema = ⊕ Gram Stain / Cx / purulent OR pH <7.2 OR glu <60  drainage

Ramya Chitra Mosarla

243
TOC

Procedures Tube Management

NASOGASTRIC TUBES
Indications: Contraindications:
• Decompression of SBO or minimize vomiting in ileus • Head / maxillofacial trauma, basilar skull fracture, or recent
• Enteral feeding / med administration; charcoal admin (ODs), neurosurgical intervention
oral contrast or colonoscopy prep • Esophageal stricture or ≥ grade 2 varices / recent banding
• Lactulose (hepatic encephalopathy) (discuss w/ GI if uncertainty regarding varices / banding)
Supplies:
• NGT, lubricant/viscous lidocaine (“UroJet”), Chux, emesis basin, cup of water with ice and straw, 60mL syringe, tape
• If NGT needed for decompression: use 14 to 16 Fr Salem sump NGT (larger diameter,  clogging)

NGT Placement:
• Assess patency and symmetry of nares by direct visualization TYPES OF NGTs & USES
• Consider topical anesthetic (e.g. 4% lidocaine) pre-treatment
• Position patient in upright “sniffing” position with neck flexed and chin to chest • Dobhoff: PO formula, meds
• Estimate distance of NGT insertion by measuring from xiphoid processearlobenose tip • 14, 16 Fr: Decompression
• Apply lubricant / ice to tip of NGT and/or apply viscous lidocaine directly into the nares
• Insert NGT into nares along floor & apply pressure posterior & slightly inferiomedial, not upward
• After passage of NGT into oropharynx (will feel curve &  resistance), have patient swallow water via straw while advancing rapidly
o If patient excessively coughs, gags, has change in voice or dyspnea, or increased resistance, STOP (never force) and
suspect improper location (in airway or coiled) and immediately withdraw. Look in posterior oropharynx for coiling.
• Advance to predetermined depth. Can insufflate air w/ 60cc syringe while auscultating over stomach for rush of air. May also see
return of gastric contents. Inspect oropharynx to ensure no coiling before securing tube w/ tape or bridle if risk removal (AMS)
• Confirming position: MUST confirm placement with KUB prior to feeding/meds given risk of placement in trachea/lungs.
KUB will show NGT sideport below diaphragm. Optional for KUB if bilious return when NGT for decompression (bile = stomach).
Dobhoff tube / Enteroflex: thinner, more flexible; more comfortable but  risk of placement into lung
• Requires 2-step 2-CXR placement method
1. Measure from nose to earlobe to mid-sternum  insert tube this distance  secure  obtain CXR
2. If CXR shows tip (1) past carina & (2) midline  advance into stomach  repeat CXR  remove stylette once confirmed

General Troubleshooting:
• If tube coiling repeatedly in oropharynx on insertion, soak tip in ice water to make tube more rigid prior to insertion.
• NGT to suction should “sump” – air should audibly enter blue port and exit main port; if not: (1) flush blue port with air (never
fluids), (2) flush main port with water (not NS, does not need to be sterile), (3) aspirate from main port  if not able to withdraw
flush, NGT needs to be advanced vs. withdrawn (KUB can guide)
• To prevent clogging or adherence to gastric wall, NGTs should be flushed with 30cc water & air Q8hr. If clogged, can try methods
to unclog tube as below in “Gastrostomy Tubes”
Complications ( with longer duration):
• GI: malposition, coiling, knotting anywhere along course of tube, nasal/GI tract perforation.  risk acid/stomach content reflux and
aspiration  consider PPI. Chronic suction  gastritis/pressure necrosis: consider removal if grossly bloody
• Pulm: intubation of lung  inadvertent med, contrast, TF administration  PNA, pulm abscess, tracheal perforation, PTX, death
• HEENT: nasal irritation, epistaxis, intracranial placement, skin erosion, sinusitis, alar necrosis, tracheoesophageal fistula/perf
Removal:
• If for ileus/SBO, consider removal when passing flatus or resolved n/v. Alternatively, may remove when NGT output <1L over 24
hours. Consider clamp trial before removing (clamp 4 hours, then check residual. Remove if <150 cc)
• Remove tape. Flush tube w/ 10mL air or NS. Turn OFF suction & clamp. Fold Chux around tube insertion site. Gently remove tube

Ramya Chitra Mosarla

244
TOC

Procedures Tube Management

GASTROSTOMY TUBES
Description: Troubleshooting
• Clear, soft, graduated tubing held in place • Clogging: only tube feeds and elixir meds should be given through J tube
w/ plastic mushroom-shaped ring/balloon in o Attach 3cc syringe w/ warm H2O to female Leur adaptor. Push or pulse
stomach (~3 cm deeper in obese pts) plunger to force through debris. Flush w/ 30cc warm H2O to ensure not
• May be replaced at bedside after clogged.
epithelialized track forms (~2-4 wks; o Can also try Seltzer, ginger ale, Coca-Cola. If persistent, can try
delayed by malnutrition, steroids, pancrealipase (Viokase) with sodium bicarb
immunosuppression) • Leaking: retract balloon or mushroom back to skin level; do NOT insert larger
• Gastrojejunostomy (GJ) tubes have 3 size tube (can cause stoma to enlarge), call service who placed G tube if
access ports: G tube port, J tube port and persistent
balloon port • Migration: can cause n/v (w/ or w/o feeds), dumping syndrome. Confirm
• Secured with vertical Hollister device placement w/ tube injection study (30-60 mL gastrograffin f/b KUB)
• Venting means access port is attached to a • Falling out: replace w/ similar-sized foley or feeding tube. Obtain tube study.
foley bag so contents/gas can flow out as • Local site infection: try topical abx +/- antifungal before PO (cephalexin, clinda)
needed • Granulation tissue: check tube size (not too long or short); tx w/ warm
compresses & silver nitrate (w/ barrier cream on surrounding normal skin to
protect)

FOLEY CATHETER
Choosing Catheter: (order from Central Supply, ED, or Ellison 6 if not on floor) Special Circumstances:
• Many contain Latex, use silicone if allergy; silicone also risk CAUTI • Artificial Urinary Sphincter (AUS):
• 2-way Foleys (drainage & balloon ports): men s/p prostatectomy c/b sig. urinary
16F (stock), 12F if stricture or device, 18F/20F Coudé if BPH or high bladder neck incontinence. DEACTIVATE device
 insert curve up / nub on hub pointed toward umbilicus prior to placing foley. Place smallest
• 3-way Foleys (drainage, balloon, irrigation ports): 20F/22F used for continuous catheter possible (12F) and remove
bladder irrigation (CBI) in gross hematuria ASAP.
Troubleshooting:
Placement:
• Difficulty in female patient: likely
1. Lay patient flat, prep, hold penis upright (keep on stretch while advancing)
poor positioning. Place sheets under
2. Instill 10cc 2% viscous lidocaine (“UroJet”) into urethra
hips & place pt in Trendelenburg
3. Insert Foley catheter to the hub
• Urethral trauma: blood at meatus.
4. As catheter reaches bladder neck, keeping penis on stretch, point phallus down
Leave catheter ≥3-5d
towards toes (to mimic natural curve urethra).
• Foley is leaking:
5. After urine return AND catheter hubbed, fill balloon w/ 10cc sterile H2O
o Bladder spasms 2/2 infection,
6. Gently withdraw catheter to bladder neck
mucosal irritation, overactive
7. Verify position by flushing with 60cc fluid (catheter in bladder) and withdraw.
bladder. Start anticholinergic
Inability to withdraw suggests:
(oxybutynin 5mg TID PRN)
a. Bladder empty and sucking against bladder mucosa (instill 60 cc)
o Foley obstructed 2/2 sediment,
b. Catheter in urethra or false passage
kinked, dome of bladder, clot.
c. Catheter outside bladder (undermined bladder neck in pt s/p
Flush catheter & bladder US
prostatectomy/TURP)
o Urethra patulous (women w/
8. Don’t forget to reduce foreskin (if not, may cause paraphimosis = urologic
chronic indwelling catheters)
emergency)
Suprapubic Tubes:
Continuous Bladder Irrigation (CBI): consult urology to initiate
• Many types, usually standard Foley
• Indications: gross hematuria (when you cannot see your hand through the foley due
catheter
to presence of blood) +/- with clots
• Know type & size catheter, who
• Titrate flow to “fruit punch” colored urine (should be able to see through)
exchanges, how exchanged, how
• When d/c’ing, usually start with clamp trial to ensure resolution before removal
frequently
Bladder Pressure: only done in the ICU • Is this a new tract (<7d, ask urology to
Indications: concern for intra-abdominal hypertension (≥12mmHg) or frank abdominal replace) or established (years, you can
compartment syndrome (>20mmHg) try and replace)?
1. Ensure patient position correlates between measurements (head position as flat as • If need to reinsert, decompress balloon
possible) and pressure transducer set-up is arranged and remove indwelling SPT tube. Use
2. Drain bladder and clamp drainage tube of foley foley kit, prep area, apply lubricant to
3. Inject 25cc of NS into aspiration port, wait 30-60s (allows detrusor muscle relax.) new tube, insert through tract (may
4. Connect pressure transducer to aspiration port of foley and measure pressure at have to use some force) until urine
end-expiration return, inflate balloon and ensure tube
is mobile, attach to foley bag

Ramya Chitra Mosarla

245
TOC

Procedures Tube Management

CHEST TUBES
Indications: drainage of air (PTX), blood (hemothorax), pus (empyema), or lymph (chylothorax)
Chest Tube Logistics:
• Drainage: measured by gradations in 3 columns; if significant drainage, watch for re-expansion pulmonary edema
• Suction control: adjusts negative pressure applied to pleural space
o Suction determined by setting on the device [A], NOT at the
wall; if working properly, suction verification window [E] orange
bellows will be at triangle marker
o “Suction” vs. “water seal”: if disconnected from wall suction, it
is on water seal (i.e. “to gravity”) and will allow for one-way flow
of air out of chest, [E] orange bellows not expanded
Troubleshooting:
• Air leaks: if bubbles present in the water
seal chamber [C], indicates air in pleural
space. Higher level in chamber, greater
leak. Ask patient to cough to assess for
leak if bubbles are not continuous.
o Ddx: air in pleural space (parenchymal
lung injury or BPF) vs. leak in chest
tube (check tubing and connections to
Pleur-evac)
o Note: “Tidaling” (movement w/ respiratory variation in water seal chamber) [C]) is normal – i.e. not an air leak
• Clogging: look for debris in tube, lack of tidaling, can try “stripping the tube” by compressing it with your fingers while
pulling TOWARDS the drainage system, helpful to have an alcohol prep pad for lubrication, might require tPA
(alteplase) for clot or Pulmozyme (dornase) for fibrinolysis  involve IP / surgery (whoever placed tube)
Removal:
• General criteria: no active air leak, pt off positive pressure ventilation, <150cc of drainage over 24h
• Steps to removal: place on suction (-40 mm Hg to -10 mm Hg)  place on water seal  clamp trial (clamp tube with
hemostat)
o With each step, wait 4 hours, then obtain CXR to ensure stable or improving PTX
• After stable on clamp trial, tube should be removed during exhalation (patient humming). Large chest tubes often
require surgical knot to close hole covered by occlusive dressing (xeroform, 4x4 gauze, large tegaderm) for 48 hrs.

Ramya Chitra Mosarla

246
TOC

Procedures Exposures & Needle Sticks

Please follow the steps below IMMEDIATELY in the event of an exposure to bodily fluids while on duty
1. Stop the procedure
2. Immediately clean the affected area
• Sharp stick: wash site immediately with soap/water. Alcohol-based agents are also virucidal to HBV, HCV, HIV.
• Splash to open wound: wash site immediately with soap/water
• Splash to eye(s): irrigate liberally for up to 5 minutes
• Notify your department supervisor as needed; the charge nurse is often a very helpful resource
3. Call occupational health (OHS)
• Monday-Friday 7am-5pm call 617-726-2217, located at 165 Charles River Plaza (CRP) Suite 404 (4th floor)
• Outside of normal business hours, page the on-call occupational health provider at p21272
• Have the following information available for the OHS staff member at the time of your call:
o Source patient: name, MRN, DOB, location, MD, diagnosis, known Hx, exposure to HBV/HCV/HIV meds
o Needle: brand, size, gauge, specific device, device manufacturer, safety design type, part of a kit?
4. Test the patient for HBV, HCV, and HIV
• HBV/HCV: one gold top tube
o Order HBsAg and HCV qualitative Ab; if patient known HCV+, also send HCV RNA
o If using paper form (available from OA), mark with BILLING NUMBER CL00009 so pt not charged
• HIV: another gold top tube
o By law in Massachusetts (MGL Part I Title XVI Chapter 111 Section 70F [M.G.L. c. 111, §70F])
o Written consent is required to release HIV results to a third party. In the event of an exposure, since HIV status is
being released to the exposed individual, written consent is assumed to be required.
• Send HIV tube to STAT lab (results ~60 min once received), send HBV/HCV tube to standard core lab
If the patient is CONSENTABLE If the patient is NOT CONSENTABLE
1. Obtain a special HIV occupational exposure 1. A valid and invoked health care proxy (you need paperwork!) can
consent form/lab requisition from the OA sign the occupational exposure consent form OR
2. Write STAT result in the comment section 2. Facility legal staff can assume temporary guardianship
3. Have the patient sign and then sign it
yourself If the exposure occurs to a member of the primary team, the
4. Ensure the form is marked with BILLING implication of the law is unclear, as that person is not technically a third
NUMBER CL00009 so the patient is not party. Be conservative and obtain written consent anyway. If this is not
charged possible, consider contacting Kimon Zachary (infectious disease), the
Chiefs, the program director, or the chief medical officer.
5. Decide if you will initiate post-exposure prophylaxis (PEP)
***Post-exposure prophylaxis is most effective if started within 1-2 hours of exposure***
• Transmission factors increasing risk: hollow-bore needle, lack of barrier protection/direct skin penetration, depth of
needle penetration, increased amount of blood on the needle
• Starting PEP is recommended if: patient has known HIV or testing is expected to take >2 hours
o M-F 7a-5p, PEP can be obtained at the OHS office. At all other times, you must go to the Emergency
Department (page the on-call OHS provider at p21272 to be fast-tracked in the ED for treatment)
EXPOSURE RISK
PATHOGEN POST-EXPOSURE PROPHYLAXIS (PEP)
(IF PATIENT IS POSITIVE)
PEP can vary but usually includes 3 anti-retroviral drugs:
• 2 NRTI tenofovir PLUS emtricitabine (or lamivudine) AND INSTI
Percutaneous (blood): 0.3% dolutegravir (or raltegravir)
Mucocutaneous (blood): 0.09% o INSTI can be substituted with a PI (darunavir) boosted by
ritonavir
HIV
There has only been 1 • 28 days of treatment recommended but optimal length unknown
confirmed case of occupational • Regimen usually well-tolerated, side effects include:
transmission since 1999 (CDC) o Common but mild: n/v/d, fatigue, HA
o Rare: hepatitis, hyperglycemia, fevers, rash, pancytopenia
• Serial testing at 6wk, 12wk, and 6mo if patient positive
HCV Percutaneous: 1-2% No PEP; serial testing at 4wk, 12wk, and 6mo if patient positive
Positive immune titers usually are an employment requirement
AHBV Percutaneous: 30%
Vaccine non-responders should be seen in occupational health
6. File a safety report!
Ramya Chitra Mosarla
247
TOC

Logistics Monitoring & Prophylaxis

Cardiac Monitoring (MGH Clinical Guidelines for Cardiac Monitoring)
Low Risk Moderate Risk High Risk
- Continuous cardiac monitoring
- Cardiac monitoring for
Monitoring - May be off monitor ONLY in presence - Continuous cardiac monitoring
diagnostic purposes only
of licensed clinical personnel
Pt Location General care unit General care unit Step-down or ICU
- No cardiac monitor - With cardiac monitor - With cardiac monitor
Travel
- Unaccompanied - Accomp. by MD, PA, NP, or RN - Accomp. by MD, PA, NP, or RN
- Indicated to make dx or guide - Typical chest pain syndrome - Early ACS
treatment - Acute decompensated HF - S/p cardiac arrest
- Post-op AF - Uncontrolled AF - Critical care patients
Example - Post-stroke AF - 24 hrs s/p PPM/ICD placement and - Temporary PPM/pacing pads
indications* - Routine syncope eval. not PPM-dependent - s/p PPM/ICD and PPM-dependent
- Low risk chest pain syndrome - Suspected cardiogenic syncope - Mobitz II AVB, advanced 2nd deg.
- Uncomplicated EtOH - Actual or risk for QTc prolongation HB, complete HB
withdrawal - Complicated ETOH withdrawal - Unstable arrhythmias
*Refer to 2017 AHA guidelines on ECG monitoring for more detailed indications and monitoring duration (Circ 2017;136:e273)
• How to run telemetry: click on “Patient Data”
o Events: events sorted in reverse chronological order (e.g. runs of NSVT, bradycardia)
o FD Strip: telemetry strip for a specific moment in time
o FD Page: global view useful in identifying abrupt changes that can be zoomed in on using the FD Strip view
o Graphic Trends: graphic view of HR trends over time
o Calipers: interactive calipers used to calculate intervals on telemetry strip
O2 Saturation Monitoring (MGH Clinical Guidelines for O2 Saturation Monitoring)
Low Risk Moderate Risk High Risk
- Spot check O2 sats as - Continuous O2 sat monitoring
Monitoring frequently as clinically - May be off monitor ONLY in presence of - Continuous O2 sat monitoring
indicated licensed clinical personnel
Pt Location General care unit General care unit Step-down or ICU
- No O2 sat monitor - With O2 sat monitor - With O2 sat monitor
Travel
- Unaccompanied - Accomp. by MD, PA, NP, RN, or RRT - Accomp. by MD, PA, NP, RN, or RRT
- Stable chronic - Acute respiratory distress
respiratory disease - COPD exacerbation - High-risk airway
Example
- Post-procedure - OSA not on CPAP - NIPPV
Indications
- Opioid naïve patients - PCA use - Intubation
receiving PO narcotics - Continuous narcotic infusion
DVT Prophylaxis (MGH Anticoagulation Management Stewardship Committee VTE Prophylaxis Guidelines)
Low Risk Moderate Risk High Risk
- Major surgery (>45 min, not craniotomy,
- Ambulatory - Major surgery (craniotomy, ortho,
ortho, spine, or for cancer)
Risk - Estimated LOS <48 hr spine, or for cancer)
- Acute illness; immobility w/ est. LOS >48h
factors - Not meeting moderate- - Critical illness in ICU
- H/o VTE, thrombophilia (incl. hormone tx)
or high-risk criteria - 2+ moderate risk factors
- Active malignancy
Prophylaxis Ambulation Pharmacologic OR mechanical Pharmacologic AND mechanical
• 30 / 30 / 30 Rule
o Pharmacologic prophylaxis: can be administered if platelets >30K
o Mechanical prophylaxis: SCD boots should not be off the pt for >30% of the day
o Ambulation: pts should ambulate 30 min/shift (60 min/day)
• Pharmacologic prophylaxis options:
o Enoxaparin (Lovenox): 40 mg SC q24h; default in patients with CrCl >30 and BMI <40
o Heparin (UFH): 5,000 units SC Q8h-Q12h; preferred in patients with CrCl <30 or BMI >40; Q8h pref. in cancer patients
o Fondaparinux: 2.5 mg SC q24h (can be used if concern for HIT)
o Alternatives to UFH during shortage: apixaban 2.5mg PO q12h, rivaroxaban 10mg PO q24h (avoid if CrCl <30)
 Do not use if critically ill (ICU), trauma/spinal cord injury; avoid if recent/high risk for bleeding, anticipated invasive
procedure, GI/GU CA and active intraluminal lesions, Childs B/C cirrhosis or any liver disease w/ coagulopathy
GI Prophylaxis
• Indications (Crit Care Med 2016;44:1395):
o Admitted to ICU AND one of the following: 1) mechanically ventilated >48 hr, 2) coagulopathy (plt <50, INR >1.5, PTT >2x ULN),
3) GI bleed in the last year, 4) TBI, spinal cord injury, or burns, 5) 2+ of the following: sepsis, occult GIB >6 days, steroids >60
mg prednisone daily, ICU LOS >7 days
• Prophylaxis options (PO unless contraindicated): PPI (omeprazole, esomeprazole, pantoprazole) or H2 blocker (famotidine)
Jacqueline Henson
248
TOC

Logistics Peri-Procedural Anticoagulation

General Antiplatelet & Anticoagulation Guidelines for Elective Procedures
• ASA: hold for 1 week prior if for primary prevention, continue if for secondary prevention
• P2Y12: hold clopidogrel and ticagrelor 5 days prior; prasugrel 7 days
• Warfarin: hold 5 days prior (see Hematology section for indications for and guidance on bridging)
• DOAC: hold 1-3 days prior, depending on agent, renal function, & procedural bleeding risk (see below for guidance for Cath Lab & IR)
High Bleed Risk Low Bleed Risk
CrCl >50 CrCl <50 CrCl >50 CrCl <50
Dabigatran ≥48hrs (4 doses) ≥96hrs (8 doses) ≥24hrs (2 doses) ≥48hrs (4 doses)
Rivaroxaban ≥48hrs (2 doses) ≥48hrs (2 doses) ≥24hrs (1 dose) ≥24hrs (1 dose)
Apixaban ≥48hrs (4 doses) ≥48hrs (4 doses) ≥24hrs (2 doses) ≥24hrs (2 doses)
Edoxaban ≥48hrs (2 doses) ≥48hrs (2 doses) ≥24hrs (1 dose) ≥24hrs (1 dose)

Cardiac Cath Lab Anticoagulation Guidelines

Medication Hold Pre-Procedure* Resume Post-Procedure
Therapeutic (>15k U/d): 1hr or on call to CCL
Heparin 4hrs after sheath removal; no bolus
Prophylactic: continue
Enoxaparin (Lovenox) Therapeutic (1mg/kg): 24hrs; Prophylactic (≤60 mg/d): 12hrs Next morning
Bivalirudin 1hr or on call to CCL 4hrs after sheath removal; no bolus
Argatroban 1hr or on call to CCL 4hrs after sheath removal; no bolus
Dalteparin Therapeutic: 24hrs; Prophylactic (≤5000 U/d): 12hrs Next morning
Warfarin 5 days or INR ≤1.8 Night of cath
Apixaban, rivaroxaban,
CrCl ≥30: ≥2 days; CrCl <30: ≥3 days Next morning
edoxaban
Dabigatran CrCl ≥50: ≥2 days; CrCl <50: ≥5 days Next morning
Fondaparinux CrCl ≥50: ≥4 days; CrCl <50: ≥7 days Next morning
*Guidelines for endomyocardial biopsy differ. See “MGH Cardiac Cath Lab Anticoagulation Guidelines” on Ellucid.

INR Guidelines for Cardiac Catheterization: VAD Peri-Procedural Cardiac Catheterization Guidelines:
Planned Access Site INR INR goal 1.8-2.5; continue warfarin
Femoral artery or vein ≤ 1.8 PTT goal ≤ 80; continue UFH pre-, intra-, & post-procedure
Internal jugular vein ≤ 1.8
Radial artery ≤ 2.0 Cangrelor and Antiplatelet Agents:
Subclavian vein ≤ 1.5 • See Cardiology: ACS for switching/bridging P2Y12 inhibitors
Brachial or basilic vein ≤ 2.0 • Generally, prasugrel is held on day -7, clopidogrel/ticagrelor on day -5,
Pericardiocentesis ≤ 1.5 & cangrelor is started on day -3. Cangrelor is held 1-6hrs pre-
procedure.
IR Procedures
• NPO guidance: NPO (no solid food; ok to take medications with sip of water) for 8hrs if will receive sedation (e.g. port placement,
biopsies, tube placement) or if a patient-specific need for sedation.
• Low bleeding risk procedures: para., thora., chest tube, PleurX, PICC, non-tunneled central catheter, transjugular liver biopsy, IVC
filter placement & simple removal, catheter/tube exchange, dialysis access interventions, superficial bx/aspiration (thyroid, LN, breast,
superficial bone), embolization for bleeding control
o AC goals: INR <3, plt >20k; if cirrhosis: INR <3, plt >20k, fibrinogen >100 (if cirrhosis). No need to hold AC.
• High bleeding risk procedures: tunneled central access catheter placement/removal, G- or J-tube placement, nephrostomy tube
placement, biliary interventions, TIPS, solid organ/deep tissue biopsies, LP/spine procedures, arterial interventions/angiography,
intrathoracic venous interventions (SVC/IVC), portal vein interventions, catheter-directed lysis, complex IVC filter removal
o AC goals: INR <1.8, plt >50k; if cirrhosis: INR <2.5, plt >30k, fibrinogen >100. AC management per table below.
Medication Hold Pre-Procedure** Resume Post-Procedure
Heparin Therapeutic: 4-6hrs; Prophylactic: 6hrs 6-8hrs
Enoxaparin (Lovenox) Therapeutic: 24hrs / 2 doses; Prophylactic: 12hrs / 1 dose 12hrs
Dalteparin 24hrs / 1 dose 12hrs
Fondaparinux CrCl ≥50: 2-3 days; CrCl <50: 3-5 days 24hrs
Bivalirudin 2-4hrs 4-6hrs
Argatroban 2-4hrs 4-6hrs
Day after procedure; bridge
Warfarin 5 days or INR ≤1.8
if high-risk
Apixaban, edoxaban CrCl ≥50: ≥2 days / 4 doses; CrCl <50: ≥3 days / 6 doses 24hrs
Rivaroxaban CrCl ≥30: ≥2 days / 2 doses; CrCl <30: ≥3 days / 3 doses 24hrs
Dabigatran CrCl ≥50: ≥2 days / 4 doses; CrCl <50: ≥3-4 days / 6-8 doses 24hrs
**See “MGH Interventional Radiology Periprocedural Management” guidelines on Ellucid for further details.

Jacqueline Henson
249
TOC

Logistics Senior On Encounters

CODES Code/Rapid Data to Bradycardia Hypotension
A-Access Obtain Conduction disease, R sided MI, Cardiogenic: MI, ADHF, BB/CCB
B-Backboard vagal, med effect, ICP, toxicity, acute myocarditis, valvular
C-Code Status [ ] Preceding events hypothyroidism, hypoxemia disease (AS)
D-Defib [ ] Vitals Atropine 0.5-1mg q3-5m, max 3mg Distributive:
D-Drips [ ] Exam Dopamine 2-20mcg/kg/min S-Sepsis A-Adrenal Insuff
E-Epi [ ] FSBG Epinephrine 2-10mcg/min A-Anaphylax S-Spinal Shock
E-Electricity [ ] PMH Isproterenol 2-10mcg/min L-Liver dz S-Sleeping
(150-200J; tele) [ ] Recent procedures Transcutaneous pacing T-Toxin
F-Fluids [ ] Cardiopulm. history (midaz/fentanyl or ativan/dilaudid) Hypovolemic: blood, over diuresis
F-Family [ ] Last TTE Transvenous pacing / removal w/ HD, insensible losses
G-Glucose [ ] Med list Obstructive: PE, tamponade
[ ] PRN meds received Tachycardia Acute Hypoxemia
H’s and T’s: [ ] Infusions Narrow: AVRT/AVNRT, AF/AFlutter, Aspiration
CAUSE MANAGEMENT [ ] EKG AT, MAT Mucus plug
[ ] Tele if arrhythmia Wide: MMVT, PMVT, SVT Pneumonia
Hypoxemia Intubate, ECMO [ ] Last Hgb w/aberrancy, PM mediated/tracked Pulm edema (vol., MI, HTN, tachy)
Access, crystalloid, [ ] Last K Synchronized Cardioversion PE
Hypovolemia [ ] Last Bicarb
product Narrow/regular: 50-100J PTX
[ ] ABG Narrow/irregular: 120-200J Pleural effusion
H+ (Acidemia) Bicarb
Wide/regular: 100J Hypercarbia
Tx hypoK (D50W 1-2 If Intubating: Wide/irregular: 150-200J RR: sedatives, central sleep
amp + insulin 10 units [ ] Prior intubations Medications apnea, OHS, brainstem stroke,
Hypo/hyperK
IV), calcium gluconate [ ] Difficult airway? Narrow/reg: adenosine (6, 12, 12) tumor, infection, hypothyroidism
1-2g IV [ ] Hemodynamics/Heart Wide/reg: VT: OSA, pleural effusion/fibrosis,
Hypothermia Warming [ ] Aspiration Risk? - Amio: 150mg1mg/min obesity, kyphosis/scoliosis, abd
[ ] Labs - Lido: 100mg50mg q5 x3 1-2 dist, PTX, neuropathy, NMJ
Hypoglycemia D50 mg/min disorder, myopathy,
- Procainamide: 20-50mg/min until
Tamponade Pericardiocentesis VD and/or VT: COPD, asthma,
hypoTN or QRS 50%1-4 /min
OSA, ILD, CHF, PNA, PE
Tension PTX Needle decompression - consider adenosine unless WPW
ACS AMS
Wide/irreg:
Thrombosis – ASA 325, heparin, statin, CNS: CVA, ICH, sz, infxn, PRES
PCI, ECMO - PMVT: amio, lido; tx ischemia
MI TNG, BB. Metabolic toxins: NH3, CO2,
- Torsades: Mg 2mg, HR (Isuprel)
Thrombosis – CCL if HD unstable, BUN, Na
tPA, ECMO - AF+WPW: proc, ibutilide (1mg)
PE refractory CP, VT Exogenous toxins: meds, drugs,
(adenosine, BB/CCB, dig)
Stop drugs, reversal w/d
Toxin / Drugs GIB
agents (narcan) STEMI: x6-8282 Vitals: hypoTN, hypoglycemia
2 large bore IV, T&S, IVF, pRBC, IV
Interventional attending; Misc: TTP, AI, hypothyroid
PPI 40mg. Octreotide 50mcg + CTX
Others: decides on CCL
if portal HTN. Correct coagulopathy.
CAUSE MANAGEMENT RICU if hematemesis.
Septic Shock Abx, source control PE
Mucus Plug Suction/Chest PT Large PE? PE w/ abnormal VS (tachycardia, hypotension), evidence of R heart strain (TTE, EKG, or
Auto-PEEP Disconnect vent +biomarkers), central or saddle PE  PERT x4-7378
Anaphylaxis Crystalloid, epi Order: TTE, EKG, CBC w diff, PT/PTT, BMP, LFTs, lactate, D-dimer, Trop, NT-proBNP, T&S, LENIs
tPA: Pulseless50mg/2m, 50mg in 30m | Pulse100mg/2h | Follow w/ heparin gtt
Contraindications: prior ICH, ischemic CVA <3mo., active bleeding, CNS surgery/trauma (<2-3mo.)
ACLS Seizure
Non-shockable rhythm: Epi as soon as Ativan 2-4mg IV x2, diazepam 20mg PR, or Keppra 20mg/kg
feasible Anaphylaxis
Shockable rhythm (VT/VF): Epi after initial Epi 0.3-0.5 IM (1:1000; 1mg/mL); alt: 0.1-0.3mg IV (1:10,000; 0.1mg/mL)
defib attempts are unsuccessful  repeat q5-15min; start gtt if >3 required
Other agents: diphenhydramine 50mg, methylpred 125mg IV, albuterol nebs,
IV fluids
NUMBERS
ICU Resource RN x6-6718 p25213
Post Arrest: Cardiac Access RN x4-2677 p31951
Pressors: MICU Intensivist c857-331-0741 p26955
if bradylevophed HCICU Intensivist p29151
if tachyneo ECMO c857-310-0335 p29151
BRING EPI (can STEMI x6-8282
give 100mcg) PERT x4-7378
Rapid Response, RICU, x6-2333
Epi: 1mg IV/IO q3-5m Stroke
Amiodarone
(VT/VF): 300150
mg

Jacqueline Henson and Miranda Theodore

250
TOC

Logistics Post-Acute Care

Post-Acute Care: post-hospital care of patients to help them return to baseline
• Largest source of Medicare regional variation. High cost growth (NEJM 2014;370:689) and risk of readmission (Health Aff
2010;29:57).
• Risk factors for use: living alone, impaired mobility, depression, comorbidity (JAMA Intern Med 2015;175:296)
• Note: do not have capability for rapid diagnostics (CT scanners), procedures, or significant acute issues (hypoxemia,
hypotension)

Setting Avg Therapy /

Description Patients / Diagnoses MD
(most to least intensive) LOS Ancillary Services
- Tracheostomy
Long Term Acute Care - RT
High intensity - Chemotherapy 20+ Daily MD
Hospital - PT/OT PRN
hospital-level care ≥ 3-day ICU stay days visits
(LTAC) - HD
required to qualify
- Post-stroke
2-4x/week - 3+ hours of
Inpatient Rehabilitation - Spinal cord injury
Intensive therapy for 7-21 MD visits; therapy/day (pt
Facility - Note: Specific dx
recovery of function days PM&R must be able to
(IRF, “acute rehab”) codes required to
presence participate)
qualify
“Sub-acute”
~1x/week MD
rehabilitation; - CHF, PNA, UTI
visits; - 1-2 hours of
looks/feels like - Generally older
Skilled Nursing Facility 3-21 very limited therapy/day (pt
nursing home; must patients with functional
(SNF) days capacity for must be able to
have 3-night hospital decline / unsafe at
management progress)
stay to qualify under home
changes
Medicare
- Wound care Managed by
Home-based
- IV antibiotics PCP or - 4-8 PT/OT visits
services post-
Home Health - Post-hospital N/A prescribing - RN visits as
hospitalization or via
functional decline outpatient needed
PCP referral
- Home safety eval clinician

Special Cases
• Hospice:
o Criteria: pt must have a terminal illness with prognosis of ≤6 months as certified by a physician. Depending on the
hospice agency, pt may need to forego curative treatments (i.e., chemo, expensive antibiotics, etc.)
o Home hospice: fully funded by Medicare. RNs visit, but patients need full-time caregiver support in the home, which
can be a barrier to home hospice discharge
o Inpatient hospice (SNF or dedicated inpatient hospice facility): room & board (~$400 per day) only covered by
MassHealth, but not other insurers
o GIP (in-hospital hospice care): fully funded by Medicare, patient must quality  discuss with Pall Care
• Long-term care:
o Patients residing in nursing homes with stably poor functional status and who require assistance with ADLs/IADLs,
but do not require post-acute level care
o Private pay or covered by MassHealth, but not funded by Medicare
• Patient/family refusal of SNF/rehab: recommend higher-quality SNFs in Partners Skilled Nursing Facility Network
• Alternative programs: if patient is in Partners ACO, discuss additional home-based care options with case manager

Jacqueline Henson
251
TOC

Logistics Formulas
Recommended websites for formulas: Osmolality
www.mdcalc.com Plasma Osmolality:
www.nephromatic.com glucose (mg/dL) BUN (mg/dL) EtOH (mg/dL)
calc osm = 2 × Na (mEq/L) + + +
18 2.8 4.6
Drug Dosing and Body Weights Osmolar Gap:
Actual Body Weight (ABW): actual weight recorded on OG = Posm – calc osm (normal: < 10)
admission (most commonly used weight for dosing)
Stool Osmol Gap:
Ideal Body Weight (IBW): SOG = Osmstool – 2 × (Nastool +Kstool)
Male: 50.0kg + 2.3kg for every inch over 5 feet >125: suggests osmotic diarrhea; <50: suggests secretory
Female: 45.5kg + 2.3kg per inch over 5 feet diarrhea

Adjusted Body Weight (AdjBW): Urine Osmol Gap:

AdjBW = IBW + 0.4 x (ABW – IBW); Uosm = 2(UNa + UK) + Uurea / 2.8 + Uglucose / 18 (normal: 10-100)
use for obese pts (i.e., if ABW>1.3x IBW) <150: shows impaired NH4+ excretion (type I/IV RTA)
>400: shows increased NH4+ excretion (type II RTA/diarrhea)
Electrolytes and Fluids
[Na+] in fluids (mEq/L): NS = 154, ½NS = 77, 3% = 514, Acid/Base Physiology
LR = 130 Primary metabolic acidosis (Winter’s formula):
compensated pCO2 = 1.5 × HCO3 + 8 ± 2
Total Body Water (TBW):
TBW = F x weight; F = 0.6 ♂, 0.5 ♀ (or 0.5 and 0.45 if elderly) Primary metabolic alkalosis:
Intracellular fluid (ICF) = 2/3 TBW compensated pCO2 = 0.7 × HCO3 + 20 ± 5
Extracellular fluid (ECF) = 1/3 TBW
ECF = 3/4 interstitial, 1/4 intravascular Primary respiratory acidosis:
Acute: ∆pH 0.08 for each ∆PaCO2 10 mmHg; ∆HCO3 1 for
Free Water Deficit in Hypernatremia: each ∆PaCO2 10 mmHg
 measured Na  Chronic: ∆pH 0.03 for each ∆PaCO2 10 mmHg; ∆HCO3 4 for
water deficit (L) = TBW ×  − 1 each ∆PaCO2 10 mmHg
 140 
Primary respiratory alkalosis:
∆Na based on Infusate Sodium (per 1L infusion) [use for Acute: ∆pH 0.08 for each ∆PaCO2 10 mmHg; ∆HCO3 2 for
hypoNa or hyperNa]: each ∆PaCO2 10 mmHg
infusate Na − serum Na Chronic: ∆pH 0.03 for each ∆PaCO2 10 mmHg; ∆HCO3 4-5 for
change in serum Na = each ∆PaCO2 10 mmHg
TBW (in liters) + 1
Anion Gap:
Sodium Correction in Hyperglycemia: AG = Na – (Cl + HCO3) [normal ~12]
corrected Na = measured Na + (2.4/100 mg/dL) x (glucose–100) Corrected AG = AG + 2.5 x (4 – measured alb (mg/dL))
**Needed for routine chemistries; not required for ABG
specimen** Delta-Delta Gap:
∆∆G = ∆AG* / ∆HCO3 = (AG - 12) / (24-HCO3):
Calcium Correction for Hypoalbuminemia: <1 mixed hyperchloremic and anion gap acidosis;
Corrected Ca = Ca (mg/dL) + 0.8 x (4.0 − measured alb 1-2 anion gap acidosis
(mg/dL)) >2 anion gap acidosis and metabolic alkalosis
*In lactic acidosis, use 0.6*∆AG (due to ↓ renal clearance of
Transtubular Potassium Gradient: lactate compared to other anions)
KUrine / Kserum
TTKG = accurate if UNa > 25, UOsm>SOsm Urine Anion Gap:
UOsm / SOsm
Normal TTKG = 8-9, but >11 with K load UAG = UNa + UK – UCl (normal: -20 to +20)
Hyperkalemia: <6-7 suggests hypoaldosteronism >20: Type I/IV RTA; <20: diarrhea/Type II RTA
Hypokalemia: <2 suggests extrarenal loss; >7 suggests renal
loss Cardiovascular Physiology
SaO2 and PaO2 Correlation:
Fractional Excretion of Sodium and Urea: SaO2 99 98 95 90 88 80 73 60 50 40 30
UNa × PCr UUN × PCr PaO2 149 100 80 60 55 48 40 30 26 23 18
FeNa = FeUrea =
PNa × UCr BUN × UCr
Arterial Oxygen Content (CaO2):
CaO2 = (1.34 x Hb x SaO2) + (0.003 x PaO2)

Cardiac Output: CO = HR x SV

Jacqueline Henson
252
TOC

Logistics Formulas

Cardiac Output (Fick): CO = VO2 / (CaO2 – CvO2) Gastroenterology and Hepatology

→ VO2 ≈ 3 x wt (kg) or 125 x BSA (roughly 250 ml/min; use
Maddrey’s Discriminant Function for Alcoholic Hepatitis
metabolic cart to measure precise value)
MDF = 4.6 x (PT – control PT) + total bilirubin
>32: consider treatment with glucocorticoids
Systemic Vascular Resistance (normal 800-1200):
−5 MAP (mmHg) − CVP (mmHg) MELD (Model for End-Stage Liver Disease): use online calc
SVR (dynes ⋅ sec ⋅ cm ) = × 80
CO (L/min)
Correction of Ascitic PMN for Ascitic RBC
Pulmonary Vascular Resistance (normal 150-250): Corrected PMNascites = PMNascites – (RBCascites / 250)
−5 mPAP (mmHg) − PCWP (mmHg)
PVR (dynes ⋅ sec ⋅ cm ) = × 80 Neurology
CO (L/min)
Correction of CSF WBC for CSF RBC:
Corrected WBCCSF = WBCCSF – (WBCserum x [RBCCSF /
Law of LaPlace: σ (wall stress) = P × r / 2h
RBCserum])
P = intraventricular pressure, r = radius, h = wall thickness

Pouiselle Equation: ∆P = 8μ × L × Q / πr4 Nephrology

μ = dynamic viscosity, L = length, Q = flow, r = radius Creatinine Clearance from Timed Urine Collection

Bazett Formula: QTc = QT / √RR (♀ < 460 ms; ♂ < 440 ms)
UCr (mg/dl)× Uvolume (ml/min)
CrCl =
Friedewald Formula: LDL = TC – HDL – (TG / 5) serum Cr (mg/dL)

Maximum Heart Rate: Max HR = 220 – age (if unable to eGFR: use CKD-EPI equation (if black, multiply by 1.159)
achieve >85% max HR, suggests chronotropic incompetence)
Hematology
Pulmonary Physiology
Absolute Neutrophil Count: ANC = WBC x (% PMN + %
Transpulmonary and Diastolic Pulmonary Gradient: bands)
TPG = mPAP – PCWP; >12-15 suggests pre-cap pulm HTN
DPG = PAd – PCWP; >7 mmHg suggests pre-cap pulm HTN Reticulocyte Production Index (RI) (normal: 2-3):
Alveolar-arterial (A-a) Oxygen Gradient: 
RI = %retic × 
Hct  / maturation factor (MF)
patient' s normal Hct

Calculated A-a gradient = PAO2 − PaO2  
PaCO2 PaCO2
where PAO2 = FiO2 × (Patm − PH2O) − ≈ FiO2 × 713 −
R 0.8 MF: 1.0 (Hct > 36), 1.5 (Hct 26-35), 2.0 (Hct 16-25), 2.5
FiO2 = 0.21 on RA; add 0.03 for each extra L O2/min cannula (Hct < 15)
Patm = atmospheric pressure (mmHg) = 760
PH2O = alveolar pressure of water (mmHg) = 47 RI: <2 in hypoproliferative state; >3 in hyperproliferative state
R = respiratory quotient = VCO2/VO2 ≈ 0.8
Statistics and Epidemiology
**Normal A-a gradient = 2.5 + (0.21 x age)** Sensitivity = TP / (TP + FN)

Shunt Fraction (normal: 3-8%, but ↑ 5% for every 100 mmHg Specificity = TN / (FP + TN)
drop in PaO2 below 600 mmHg):
Qs 0.0031 × (PAO2 - PaO2) Positive Predictive Value = TP / (TP + FP)
=
Qt [0.0031 × (PAO2 - PaO2)] + (Ca - vO2)
Negative Predictive Value = TN / (FN + TN)
where Qs = shunt flow, Qt = total flow, Ca-vO2 assumed 5%.
FiO2 must be 1.0 in this calculation Positive Likelihood Ratio = Sensitivity / (1 – Specificity)
R becomes 1.0 after breathing 100% O2 for 20 minutes
because of N2 wash-out Negative Likelihood Ratio = (1 – Sensitivity) / Specificity
> 15% = pathologic shunt
Number Needed to Treat = 1/absolute risk reduction (ARR)
Minute Ventilation (VE) (volume per unit time): VE = RR x Vt

Bohr Equation (i.e., dead space fraction) (normal: 0.2 – 0.4):

Vd PaCO2-PetCO2
=
Vt PaCO2

Jacqueline Henson
253
TOC

Logistics MGH Directory

Main Number White 10 – Medicine 6-3345 6-7564
617-726-2000 (MGH prefix: -724, -726, -643) White 11 – Medicine 6-3348 6-7558
857-238-XXXX (Lunder), 617-523-XXXX (MEEI) Lunder 6 – Neuro ICU 8-5600 8-5701
See Partners Paging Directory for consult pagers Lunder 7 – Neuro / NSGY 8-5700 8-5701
Emergency Numbers Lunder 8 – Neuro / NSGY 8-5800 8-5899
Senior On (Med Sr)/Bauer Room 3-1388, p22337 Lunder 9 – Oncology 8-5900 8-5999
ED Triage Sr (ED Sr) 6-2333: x75360 Lunder 10 – Oncology/BMT 8-1000 8-1089
Med Consult Pager (Code Backup) p13480 Pharmacy
RICU Team (intubation) 6-3333 Outpatient pharmacy (fax: 6-3789) 4-3100
857-310-0335, Outpatient pharmacy (private line) 6-2354
ECMO Consult
p24252 / p29151 Pharmacy – White 8 p17648
SHOCK Consult p11511 Pharmacy – White 9 p24382
STEMI Team (CCL activation) 6-8282 Pharmacy – White 10 p22527
PERT (massive PE) 4-7378 Pharmacy – White 11 p17718
IV Nurse (urgent access) 6-3631, p26571 Pharmacy – Bigelow 7 p24406
ED Radiology (STAT imaging) 6-3050 Pharmacy – Bigelow 11 p27604
Pharmacy (on call) 6-4276 Pharmacy – Blake 7 p27614
RT (on call) p24225 Pharmacy – Ellison 9 p28333
Acute Stroke (neurology) 6-3333 Pharmacy – Ellison 10 p28334
ICU Nursing Supervisor 6-6718, p25213 Pharmacy – Lunder 9 p28337
Hospital Floors Phone Fax Pharmacy – Lunder 10 (BMT) p17905
ED – Front desk 4-4100 6-7415 Pharmacy – Lunder 10 (Leuk) p28338
Acute 4-4170 Laboratories
Urgent 4-4190 General lab info 4-LABS
Fast Track 4-4134 Chemistry/Hematology 6-2345
APS 6-2994 p27792 STAT Chemistry/Hematology 4-7617/4-4734
ED Obs Bigelow 12 6-3800 Serology 4-7645
Bigelow/Gray 3 – OR 6-8910 Special coagulation 6-3900
Bigelow 7 – Medicine 6-3496 6-0997 Blood gas / STAT lab – Bigelow 5 6-3856
Bigelow 9 – HMU 4-9000 4-9999 Blood bank – Bigelow 2 6-3623
Bigelow 10 – Dialysis 6-3700 6-5876 Blood bank – Lunder 8-5280
Bigelow 11 – Medicine 4-1500 6-4202 Microbiology – Bigelow 5 6-3613
Bigelow 13 – RACU 8-1300 8-1320 After hours (blood culture room) 6-7919
Bigelow 14 – HMU 6-6100 6-7562 Parasitology 6-3861
Blake 4 – Endoscopy Suite 6-8074 4-6832 Virology 6-3820
Blake 6 – Transplant Surgery 4-8610 4-8650 Pathology lab – Blake 3 4-1449
Blake 7 – MICU 6-8048 4-0102 Immunopath (Flow, ANCA, EM) 6-8487
Blake 8 – Cardiac SICU 4-4410 4-4450 Cytology / Cytopathology – Warren 1 6-3980
Blake 11 – Psychiatry 4-9110 4-9150 Toxicology (blood/urine) 4-7618/4-7615
Blake 12 – ICU 6-8071 6-7560 CCU Fellow Back-Up – see Partners Paging Directory
Blake 14 – Labor & Delivery 4-9310 4-9450 Overnight Issues / Echo Overnight fellow
Ellison 4 – SICU 4-5100 6-7566 Access (hematoma, sheath, IABP) Access fellow
Ellison 6 – Ortho / Urology 4-4610 4-4650 Cardiology Studies
Ellison 7 – Surgery 4-4710 4-4750 Cath Lab 6-7400
Ellison 8 – Cardiac Surgery 4-4810 4-4850 Echo Lab 6-8871
Ellison 9 – CICU 4-4910 4-4950 Stress Lab 4-3600
Ellison 10 – Step Down Unit 4-5010 4-5050 Holter Lab 6-7737
Ellison 11 – Cardiac Access 4-5110 4-5150 EP Lab 6-5036
Ellison 12 – HMU 4-5210 4-5603 Pacer Interrogation (PPM) p16939
Ellison 13 – Obstetrics 4-5310 4-5350 Vascular Studies
Ellison 14 – Plast/Burn/OMFS 4-5410 6-7561 Vascular Lab – Warren 9 (PVR/ABI) 6-2034
Ellison 16 – HMU / Onc 4-5610 3-5082 Pulmonary Studies
Ellison 19 – Thoracic Surgery 4-5910 4-5950 PFTs – Cox 2 6-1200/3-9680
Phillips 20 – HMU 4-6010 4-6050 Sleep Study (inpatient/outpatient) 4-7426
Phillips 21 – HMU 4-6110 4-6150 GI Studies
Phillips 22 – GYN / Surgery 4-6210 4-3497 Endoscopy Lab – Blake 4 6-8074/6-3732
White 3 – PACU 6-2835 4-8422 Neurology Studies
White 6 – Ortho 6-6106 6-7555 EEG – Blake 12 6-3640
White 7 – Surgery 6-3336 6-7550 EMG/NCS – Blake 12 6-3644
White 8 – Medicine 6-3339 6-7551 Medical Records
White 9 – Medicine 6-3342 6-7557 Record requests 6-2470/6-2477
Jacqueline Henson
254
TOC

Logistics MGH Directory

Administration Interventional Radiology
Administrator on-call p26501 GU/GI 6-8073
Admitting (fax: 4-8409) 6-3390/6-3384 Neuro 6-8320
Finance Department 6-2171 Vascular 6-8315
MD Connect (OSH Transfer Requests) 6-3384 Nephrology 6-5050
Physician Referral Line 6-5800 Neurology
Registration 866-211-6588 Acute stroke consults 6-2333 / p34282
Registrar’s office 6-2119 Non-acute stroke & ICU consults p20202
Security 6-2121 Non-stroke floor consults p20702
IT Help Desk 6-5085 Non-stroke EW consults p20000
Primary Care Clinics Neurosurgery 6-1002
Bulfinch Medical Group 617-724-6610 Obstetrics 6-2229
IMA 1A 617-726-2370 Oncology 4-4000
IMA 1B 617-726-2374 Optimum Care Committee (Ethics) p32097
IMA 2 617-726-7930 Orthopedics 6-2784
IMA 3 617-724-8400 Pain Service (Acute) – peri-op/trauma 6-8810
IMA 4A 617-724-6200 Pain Service (Chronic) p17246
IMA 4B 617-726-2674 Palliative Care 4-4000
IMA 5 617-726-7939 Pathology (FNA service) 6-3980
IMA 6 617-726-2375 Physical Therapy 6-2961
IMA 7 617-724-2700 Podiatry 6-3487
IMA 8 617-726-2368 Poison Control (ingestion) 617-232-2120
IMA 9 617-726-8157 Psychiatry 4-5600
IMA 10 617-724-4600 Psychiatry intake (for patients) 4-7792
Massachusetts General Medical Group 617-724-8059 Pulmonary 6-1721
Medical Walk-In Unit 617-726-2707 Radiation Oncology 6-8650
MGH Back Bay 617-267-7171 Rheumatology 6-7938
MGH Beacon Hill Health Associates 617-726-4900 Thyroid Clinic 6-3872
MGH Charlestown 617-724-8315 Travel Clinic 4-6454
MGH Chelsea 100 Everett Avenue 617-887-4600 Urology 6-2797
MGH Chelsea 151 Everett Avenue 617-889-8580 Mass Eye and Ear Infirmary
MGH Downtown 617-728-6000 Page Operator 617-523-7900
MGH Everett Family Care 617-394-7500 87 + last 5 digits
Direct Dial to MGH from MEEI
MGH Primary Care Associates Waltham 781-487-4040 of MGH #
MGH Revere 300 Broadway 781-485-1000 617-523-7900
Emergency Room
MGH Revere 300 Ocean Avenue 781-485-6303 x3240
MGH Senior Health 617-726-4600 617-523-7900
11th floor (Inpatient)
MGH West (Waltham) 781-487-4300 x2480
MGH Women’s Health Associates 617-724-6700 ENT Consult (MEEI ED) 617-573-3431
North End Waterfront Health 617-643-8000 ENT Clinic 617-573-4101
Subspecialties Ophthalmology Clinic 617-573-3202
Allergy / Immunology 6-3850 p23555 or 617-
Ophthalmology Consult
Anesthesia Pre-Op Inpt Evaluation 6-3382 573-3412 opt 3
Anticoagulation (AMS) 6-2768 iPOP (Translation Service)
Boston Healthcare for the Homeless 781-221-6565 IPOP 6-6966
Brace Shop (White 10) 6-3248 IPOP Access Code 017616
Breast Center 6-9200 IPOP Pin – Blake 7 1054
Cardiology 6-1335 IPOP Pin – Ellison 9 8043
Dental 6-1076 IPOP Pin – Ellison 10 8034
Oral and Maxillofacial Surgery 6-2740 IPOP Pin – Bigelow 7 1056
Dermatology 6-2914 IPOP Pin – Bigelow 11 8059
Endocrine 6-8720 IPOP Pin – White 8 7934
Gastroenterology (Fellows) 4-6113 IPOP Pin – White 9 1050
General Surgery 6-2760 IPOP Pin – White 10 7930
Gynecology 4-6850 IPOP Pin – White 11 7931
Gyn Onc 4-4800 IPOP Pin – Lunder 9 8081
Hematology 4-4000 IPOP Pin – Lunder 10 8077
Infectious Disease 6-3906
Infection Control 6-2036 See “Radiology” Section for Radiology contact information.

Jacqueline Henson
255
TOC

Logistics NWH Directory

Main Number Miscellaneous
617-243-6000 OR 6289
PACU 6295
Key Pagers GI Unit 6151
4 Usen Admitting SAR/NF p56789 Dialysis 6203
4 West Admitting SAR/NF p56788 Pulmonary Lab 6127
Locum Tenens/Covering Intensivist p57651 EEG/EMG 6624
Hospitalist p51253 Anticoagulation Clinic 6147
Cancer Center 1230
Hospital Floors Cardiovascular Health Center 7100
ED 6193 / 6194 Infusion Clinic 6350
ICU (2nd floor) 6587 Occupational Health 6168
3 West 6363 Admissions 5500
4 Usen 6459 CareFinder (new NWH PCP) 6566
4 West 6400 MDConnect (transfer to MGH) 877-637-3337
6 Usen 6307 DOM Office (6 South) 6467
6 East 1670 Chief Medical Resident 6470
Outside Calls 617-243-6841
Laboratories
Main Lab (for add-ons) 6300
Hematology 6095
Getting to NWH (2014 Washington St, Newton, MA)
Blood Bank 6091
• You will receive transportation information prior to
Chemistry 8389
your NWH rotation
Urine Studies 6090
• Note that all transportation stipends are taxed
Microbiology 6096
• MGH Uber Account
Pathology 6140
o Use Uber for Business  MGH DOM Internal
Medicine Residency Program account
Radiology
• Driving
Main Number 6600 / 6076 o Stipend covers gas and tolls
Radiology Reading Room 6162 o On day 1, park in patient garage for ~$10
ED Radiology 6185 o Pay $15 cash/check at parking/security office for
Ultrasound 6581 pass to park in employee garage behind West
CT (main) 6725 Entrance
CT (ED and after hours) 6505 • Public transportation
MRI 6217 o Take MBTA Green Line D outbound train to
PET 6334 Riverside -> Woodland stop -> NWH is 2 blocks
Nuclear Medicine 6087 to the left
Interventional Radiology 6800 / 3761
Night Watch 617-732-5657

Cardiac Studies
ECG 6229
Echo 6231 / 2665
ETT or Nuclear Stress 5375 / 6229 /
6087

Ancillary Staff
Nursing Supervisor p57711
Pharmacy 6012
Respiratory Therapy 6213
Phlebotomy 5903
Speech Language Pathology 6548
Infection Control 6282
Case Management/Social Work 6695
Chaplain 6634
Interpreter Services 6698
Jacqueline Henson
256