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Analgesia and Sedation in Hospitalized Children: by Elizabeth J. Beckman, Pharm.D., BCPS, BCCCP, BCPPS
Analgesia and Sedation in Hospitalized Children: by Elizabeth J. Beckman, Pharm.D., BCPS, BCCCP, BCPPS
in Hospitalized Children
By Elizabeth J. Beckman, Pharm.D., BCPS, BCCCP, BCPPS
Reviewed by Julie Pingel, Pharm.D., BCPPS; and Brent A. Hall, Pharm.D., BCPPS
Learning Objectives
1. Evaluate analgesics and sedative agents on the basis of drug mechanism of action, pharmacokinetic principles, adverse
drug reactions, and administration considerations.
2. Design an evidence-based analgesic and/or sedative treatment and monitoring plan for the hospitalized child who is
postoperative, acutely ill, or in need of prolonged sedation.
3. Design an analgesic and sedation treatment and monitoring plan to minimize hyperalgesia and delirium and optimize
neurodevelopmental outcomes in children.
Introduction
Abbreviations in This Chapter
Pain, anxiety, fear, distress, and agitation are often experienced by
GABA γ-Aminobutyric acid
children undergoing medical treatment. Contributory factors may
ICP Intracranial pressure
include separation from parents, unfamiliar surroundings, sleep dis-
PAD Pain, agitation, and delirium turbance, and invasive procedures. Children receive analgesia and
PCA Patient-controlled analgesia sedatives to promote comfort, create a safe environment for patient
PICU Pediatric ICU and caregiver, and increase patient tolerance to medical interven-
PRIS Propofol-related infusion tions such as intravenous access placement or synchrony with
syndrome
mechanical ventilation. However, using these agents is not without
Table of other common abbreviations. risk. Many of the agents used for analgesia and sedation are con-
sidered high alert by the Institute for Safe Medication Practices
because of their potential to cause significant patient harm, given
their adverse effects and the development of tolerance, dependence,
and withdrawal symptoms. Added layers of complexity include the
ontogeny of the pediatric patient, ongoing disease processes, and
presence of organ failure, which may alter the pharmacokinetics and
pharmacodynamics of these medications. Therefore, the pharma-
cist’s role is vital in forming the best and safest comfort plan and
environment for the patient and provider.
Review of Medications
The primary pillars for safe and effective analgesia and sedation in
children are using the lowest effective dose (Table 1-1) with the wid-
est therapeutic index and minimizing adverse effects (Table 1-2). In
addition, the pharmacokinetic changes that children undergo across
the developmental spectrum must be considered, as must how these
will affect each child’s drug exposure.
Opioid Analgesics
Fentanyl, morphine, and hydromorphone are the most commonly
used parenteral opioid agents in the hospital. Other synthetic
PedSAP 2017 Book 3 • Sedation and Analgesia 7 Analgesia and Sedation in Hospitalized Children
a
Actual infusion rates may exceed listed values as infusions are titrated to effect.
b
Higher loading doses (5–10 mg/kg) may be used to induce pentobarbital coma.
IM = intramuscularly; IN = intranasally; IV = intravenously; N/A = not applicable; PO = orally; PR = rectally.
parenteral opioids such as sufentanil and remifentanil are and peripheral nervous system. However, these opioids, even
also used, but typically not outside the operating room. when used at high doses, do not induce the deep level of
Meperidine is another synthetic opioid with a long history unconsciousness or amnesia necessary for general anes-
of use in analgesia. However, data do not support the supe- thesia, but they may cause transient euphoria and sedation
riority of meperidine to any other opioid for analgesia, and (Butterworth 2013b). Analgesia-based sedation is gaining
meperidine may place the patient at risk of exposure to momentum as a sedation strategy in adult ICUs because it
the neurotoxin normeperidine (Buck 2011). The American is recommended by the American College of Critical Care
Academy of Pediatrics (AAP), American Pain Society, and Medicine publication titled “Clinical Practice Guidelines for
Institute for Safe Medication Practices have recommended on the Management of Pain, Agitation, and Delirium [PAD] in
against the routine use of meperidine for analgesia (ISMP Adult Patients in the Intensive Care Unit” (Barr 2013).
2007; AAP 2001). Oral opioid analgesics are also used for Opioid adverse effects include respiratory depression,
analgesia in the hospital setting. These agents are often used constipation, nausea, vomiting, and pruritus. Pruritus is
in the less critically ill patient (e.g., hemodynamically stable) more likely with morphine because histamine release is not
when it is clinically appropriate to transition to the enteral commonplace with synthetic and semisynthetic opioids like
route and a longer-acting analgesic option is desired. fentanyl and hydromorphone. In addition, histamine release
Fentanyl, morphine, and hydromorphone are μ-opioid from morphine may induce hypotension and potentially exac-
receptor agonists that produce analgesia through the central erbate reactive airway disease in susceptible patients. Rigid
PedSAP 2017 Book 3 • Sedation and Analgesia 8 Analgesia and Sedation in Hospitalized Children
Chloral hydrate X X
Clonidine X X X
Dexmedetomidine X X X X
Etomidate X
Fentanyl X Xa X
Hydromorphone X Xa X
Ketamine X X X Xb X
Lorazepam X X X X X
Midazolam X X X X X
Morphine X X a
X X
Pentobarbital X X X X
Propofol X X X X
a
Opioids have transient sedating properties.
b
Ketamine may induce hypoventilation with high intravenous doses.
chest syndrome is a rare phenomenon that has been associ- spasms of the respiratory muscles leading to insufficient res-
ated with the rapid infusion of high-dose fentanyl (e.g., greater pirations and inability to ventilate the patient through artificial
than 5 mcg/kg) in adults, but rigid chest syndrome has also means. To reverse this syndrome, neuromuscular blockade
been reported at lower fentanyl doses in neonates and infants must be introduced to paralyze the chest wall muscles and
(Dewhirst 2012). Rigid chest syndrome is characterized by allow for effective respirations (Weaver 2016). Case reports
have also described success with naloxone in reversing this
syndrome (Coruh 2013). Naloxone is a competitive opioid
antagonist that reverses the effects of opioids. Naloxone’s
Baseline Knowledge Statements
effects are dose-dependent, in which low doses (less than
Readers of the chapter are presumed to be familiar 0.05 mg/kg) are used for opioid-induced pruritus and partial
with the following: reversal and larger doses (0.1 mg/kg) are used for full opioid
• Pharmacokinetic and pharmacodynamic changes reversal for intoxication.
in children
Sedatives
Table of common laboratory reference values.
Benzodiazepines
Benzodiazepines potentiate the binding of the inhibitory neu-
Additional Readings
rotransmitter γ-aminobutyric acid (GABA), which promotes
The following free resources have additional back- GABA A postsynaptic receptor opening to chloride ions, thus
ground information on this topic: hyperpolarizing the cell membrane and preventing the gen-
• American Academy of Pediatrics (AAP). Guidelines eration of an action potential. Sedation, hypnosis, muscle
for Monitoring and Management of Pediatric relaxation, anxiolysis, and anticonvulsant effects are medi-
Patients Before, During, and After Sedation for ated through this mechanism.
Diagnostic and Therapeutic Procedures: Update Midazolam is a short-acting benzodiazepine that is com-
2016. monly used as both procedural and long-term sedation. With
• ICU Delirium and Cognitive Impairment Study continuous exposure to midazolam, the half-life and dura-
Group. ABCDEFs of Prevention and Safety [home-
tion of action become prolonged (Patel 2011). The anxiolytic
page on the Internet].
effect is ideal for treating the anxious and uncooperative
• Society of Critical Care Medicine. ICU Liberation child and allows for anterograde amnesia, thus inhibiting the
Collaborative [homepage on the Internet].
formation of memory after administration. This property may
PedSAP 2017 Book 3 • Sedation and Analgesia 9 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 10 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 11 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 12 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 13 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 14 Analgesia and Sedation in Hospitalized Children
FLACC = Face, Legs, Activity, Cry, and Consolability scale; FPS-R = Faces Pain Scale Revised; N-PASS = Neonatal Pain, Agitation, and
Sedation Scale; NRS = numeric rating scale; NVPS = Nonverbal Pain Scale; VAS = visual analog scale.
PedSAP 2017 Book 3 • Sedation and Analgesia 15 Analgesia and Sedation in Hospitalized Children
duration of action, and adverse effect profile must be con- more-frequent arrhythmias, suggesting that atropine admin-
sidered. The level of sedation desired is another important istration provides a safer intubation environment (Jones
element in agent selection (Table 1-4). 2013). Intravenous lidocaine is used as an adjuvant in intubat-
ing a patient with neurological injury. Intravenous lidocaine is
thought to blunt the sympathomimetic response from intu-
Indications for Use
bation and preserve cerebral perfusion. A systematic review
Rapid Sequence Intubation
has shown equivocal results when comparing intravenous
Rapid sequence intubation originated in the ED as a way to lidocaine-pretreated and lidocaine-untreated patients with
handle the airway of a patient in extremis with an unknown traumatic brain injury in hemodynamics, ICP reduction, or
aspiration risk. The goal is to induce unresponsiveness and overall neurological outcome (Bucher 2015). At this time, no
muscular relaxation as quickly as possible in order to con- data support intravenous lidocaine as an intubation adjuvant
trol the airway (Bledsoe 2004). Benzodiazepines, ketamine, in a neurologically injured patient.
etomidate, quick-acting opioids (e.g. fentanyl), and rapid-
acting neuromuscular blocking agents are preferred because Non-painful Procedures
of their favorable pharmacodynamic profiles of quick onset Procedural sedation is used for non-painful procedures such
and short duration of action. Hemodynamic stability will as radiologic imaging, echocardiograms, and auditory testing.
contribute to the selection of agents, and the agents with car- Previously, agents such as benzodiazepines and barbiturates
diovascular neutrality (e.g., ketamine, etomidate, fentanyl) were the only available medication, leading to delayed recov-
will likely be preferred for a patient with compromised hemo- ery periods. With the introduction of dexmedetomidine and
dynamics. The NEAR III investigators reported the intubation propofol, recovery time has been shortened.
practices in children younger than 16 years and described Because imaging is being pushed to the outpatient areas,
etomidate (64%) and succinylcholine (53%) as the most com- children undergoing these procedures most likely do not
mon induction agent and paralytic used, though there was have an artificial airway for mechanical ventilation; therefore,
a trend toward not using a neuromuscular blocking agent using an agent that allows spontaneous respirations such
in children younger than 2 years (39%). Premedication with as dexmedetomidine is a favorable choice for sedation. A
the intubation adjuvants atropine or lidocaine had decreased 2015 meta-analysis compared dexmedetomidine with propo-
from previous years (Pallin 2016). fol for procedural sedation in 337 children undergoing MRIs.
Although little evidence supports adjuvants to blunt Children who received dexmedetomidine had a longer mean
hemodynamic response with intubation, these adjuvants recovery time with a pooled mean difference of 10.7 minutes
may be used in some institutions and in certain patient between the groups (95% CI, 4.26–17.13; p<0.05). The dex-
populations. Use of intravenous atropine during intubation medetomidine group had a delayed discharge time weighted
conserves the heart rate by antagonizing acetylcholine in mean difference of 12.7 minutes (95% CI, 8.1–17.37; p<0.05)
the sinoatrial node, which helps combat the vagal-mediated compared with the propofol group. However, despite the
bradycardia that can be induced by inserting a laryngo- delays in the dexmedetomidine group, both groups had sim-
scope or using succinylcholine. The anticholinergic effects ilar duration of sedation for the procedure. As for effects on
of atropine can help curtail secretions from succinylcho- the respiratory and cardiovascular system, minimum heart
line or ketamine (Bledsoe 2004). The expert opinion from rate did not differ between the two groups, but the dexmede-
the pediatric shock group recommends using ketamine tomidine group had higher minimum mean arterial pressure
with adjuvant atropine for intubation of critically ill children and respiratory rates (Fang 2015). Concurrent use of dex-
(Brierley 2009). More recently, in a study of over 300 neona- medetomidine and midazolam was compared with propofol
tal and pediatric intubations, fewer bradyarrhythmias were for maintaining anesthesia in a small group of children (n=40)
noted with atropine administration (OR 0.14; 95% CI, 0.06– undergoing an MRI. Dexmedetomidine/midazolam resulted in
0.35; p<0.05). Lack of atropine administration resulted in a delayed time to full responsiveness compared with propofol
PedSAP 2017 Book 3 • Sedation and Analgesia 16 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 17 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 18 Analgesia and Sedation in Hospitalized Children
Answer
Several options can be used for analgesia and seda- which would explain its success in patients with asthma.
tion in this child. However, morphine should be avoided. Dexmedetomidine, because of its lack of interference with
Morphine should not be used because of the potential for the respiratory drive, may prove advantageous as a sed-
histamine release exacerbating airway bronchospasm. ative in a patient with asthma and allowance for native
Fentanyl or hydromorphone would be reasonable options respiratory drive to stay intact. Midazolam and prop-
for analgesia in a patient with asthma. Fentanyl might ofol would be options in this child as well because they
be the best choice because of its shorter half-life, but its would provide titratable sedation (e.g., from light to deep)
high volume of distribution and lipophilicity may not be if the situation continued to deteriorate (e.g., continuous
desirable in this child with obesity. As for sedatives, dex- neuromuscular blockade is introduced). Midazolam and
medetomidine, midazolam, ketamine, and propofol are all propofol are not without risks; both adversely affect the
reasonable options. Ketamine is the only drug with data cardiorespiratory system, and propofol has the risk of
to support its use for sedating patients with asthma. One PRIS with high doses and long durations of use. One other
retrospective study reported that intravenous ketamine layer of complexity in this sedation conundrum is the
given at 2 mg/kg × 1, followed by an infusion at 20–60 mcg/ dosing of these agents in a child with obesity. Ketamine,
kg/minute, improved ventilation (e.g., improved partial dexmedetomidine, and midazolam should be dosed on
pressure of oxygen/fraction of inspired oxygen ratio, lung ideal body weight, whereas fentanyl uses an adjusted
compliance). Ketamine has bronchodilator properties, body weight for dosing.
1. Youssef-Ahmed MZ, Silver P, Nimkoff L, et al. Continuous infusion of ketamine in mechanically ventilated children with refractory
bronchospasm. Intensive Care Med 1996;22:972-6.
2. Ross EL, Heizer J, Mixon MA, et al. Development of recommendations for dosing of commonly prescribed medications in critically ill
obese children. Am J Health Syst Pharm 2015;72:542-56.
PedSAP 2017 Book 3 • Sedation and Analgesia 19 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 20 Analgesia and Sedation in Hospitalized Children
± ventilator
COMFORT-B Newborn – 18 yr X X X X
± sedatives
± ventilator
Ramsay Adults X X
+ sedatives
Adults ± ventilator
RASS X X X
2 mo – 21 yr ± sedatives
+ ventilator
SBS 6 wk – 6 yr X X X
+ sedatives
UMSS 4 mo – 5 yr + sedatives X X
COMFORT-B = COMFORT-behavior; RASS = Richmond Agitation-Sedation Scale; SBS = State Behavioral Scale; UMSS = University of
Michigan Sedation Scale.
the evaluation for the Ramsay scale and SBS. However, the that tolerance has a decreasing clinical effect with pro-
provocation may not be desirable, especially if assessing an longed exposure. In addition, opioid-induced hyperalgesia
already agitated or hemodynamically tenuous patient. differs from allodynia because allodynia describes a painful
response induced by normally innocuous stimuli (Roeckel
Untoward Effects of 2016). There is only one published report of opioid-induced
Analgesia and Sedation hyperalgesia in a child. The patient with polyarticular juve-
When recalling the untoward effects of analgesia and seda- nile idiopathic arthritis was experiencing refractory pain
tion, hemodynamic compromise, respiratory depression, with escalating opioid doses and allodynia. With a taper and
opioid-induced constipation, and nausea and vomiting eventual discontinuation of the opioids, pain alleviation was
come to mind. Iatrogenic withdrawal syndrome is also of reported (Vijayan 2012).
concern with prolonged, continuous exposure to these Prevention and treatment of hyperalgesia is not well
agents (e.g., opioids, benzodiazepines, barbiturates, and understood. Some approaches to relieve symptoms have
dexmedetomidine). Abrupt discontinuation after such been documented in case reports. Removing the offend-
exposure may activate this withdrawal syndrome. Other ing opioid, rotating to a different opioid, and using a
chapters in this series will examine iatrogenic withdrawal longer-acting opioid have been executed with success.
syndrome. Other than acute adverse drug events and with- Adding low-dose ketamine (0.25–5 mg/kg), an N-methyl-d-
drawal, exposure to analgesics and sedatives has many aspartate (glutamate) receptor antagonist, has also been
protracted effects. successful in some cases (Anand 2010). With the paucity
of pediatric hyperalgesia literature, this phenomenon is
Hyperalgesia not currently recognized as an issue in pediatric patients.
However, with its increased recognition in adult patients
Opioid-induced hyperalgesia has been described in both
and the changing landscape for analgesia and analgoseda-
human and animal models with various types of pain.
tion, the conversation about opioid-induced hyperalgesia
Hyperalgesia is an increased sensitivity to pain, and in opioid-
will likely increase.
induced hyperalgesia, opioids are thought to worsen pain
through a paradoxical response to painful stimuli (Roeckel
2016). The mechanism is theorized to be from sensitization Delirium
of the primary afferent neurons, enhanced glutamate release Delirium is acute brain dysfunction manifested by changes
at the primary afferent neurons, hyperexcitability of the neu- and fluctuations in cognition and attention. Symptoms mani-
rons, and release of excitatory neurotransmitters (Anand fest as hyperactive (e.g., restless, agitated, emotional liability),
2010). Hyperalgesia is a clinical diagnosis of increased hypoactive (e.g., somnolence, withdrawal from environment),
pain perception despite increasing opioid exposure. Opioid- or mixed delirium. Delirium is recognized as an adverse con-
induced hyperalgesia differs from opioid tolerance, given sequence of critical illness in adults and children alike. The
PedSAP 2017 Book 3 • Sedation and Analgesia 21 Analgesia and Sedation in Hospitalized Children
largest pediatric delirium study had a point prevalence of cost reflecting this trend as well (median $2645 vs. $1701;
25% across all studied institutions and a median institutional p<0.05) (Traube 2016). Delirium significantly affects the
prevalence of 23.3% (interquartile ratio 20%–35.4%, p=0.038) health care system.
(Traube 2017). Several risk factors have been identified (e.g., To prevent or treat delirium, a clinician must be able to
severity of illness, exposure to certain medications, and dis- recognize the signs and symptoms. The gold standard for
ruption of sleep-wake cycles) (Silver 2015) (Figure 1-1). In the diagnosing delirium is an evaluation completed by a psychi-
point prevalence study, medications appeared to contribute atrist. However, psychiatry resources are not available in all
to delirium, with narcotics, benzodiazepines, and antiepileptic locations at all times. Therefore, bedside tools were devel-
drugs identified. Age younger than 2 years (adjusted OR 0.7; oped to allow non-psychiatry clinicians to complete the
95% CI, 0.5–1), use of physical restraints (adjusted OR 4; 95% CI, delirium assessment (Table 1-6). The Delirium Rating Scale,
2–7.7), and use of vasopressors (adjusted OR 2.4; 95% CI, 1.5– 1988 (DRS-88) was the first tool for hospitalized patients to
3.8) were also identified as contributing factors. After 5 days detect hyperactive delirium symptoms (Trzepacz 1988). This
in the PICU, prevalence increased from 20% to 37% (p<0.001) scale was revised in 1998 to help discern between delirium
(Traube 2017). and psychiatric disorders (Trzepacz 2001). The Pediatric
Adult delirium data analyses have shown negative Anesthesia Emergence Delirium (PAED) tool was created to
long-term consequences in critical care survivors result- detect postoperative emergence delirium in children but was
ing in cognitive dysfunction, increased length of stay, and not applied to other hospitalized children (Sikich 2004). In
even mortality, as well as an increased financial burden to 2008, the adult confusion assessment method for ICU (CAM-
the health care system (Barr 2013). In a recent study, total ICU) tool was adapted for critically ill pediatric patients and
costs of a PICU stay were higher in children who had delir- renamed the pediatric confusion assessment method for
ium at any time during admission than in those who did not ICU (pCAM-ICU). This was the first pediatric bedside tool
(median $18,831 vs. $4802; p<0.05), with the daily PICU that could detect symptoms of delirium in patients 5 years
PedSAP 2017 Book 3 • Sedation and Analgesia 22 Analgesia and Sedation in Hospitalized Children
Include mechanical
No No No Yes Yes Yes
ventilation?
a
Included postoperative patients, not PICU patients.
b
Bedside provider includes nurse, advanced practice provider, and physician.
CAPD = Cornell Assessment of Pediatric Delirium; DRS-88 = Delirium Rating Scale, 1988; DRS-R-98 = Delirium Rating Scale, Revised,
1998; IRR = interrater reliability; PAED = Pediatric Anesthesia Emergence Delirium; pCAM-ICU = pediatric confusion assessment
method for the ICU; psCAM-ICU = preschool confusion assessment method for the ICU.
and older (Smith 2011). To fill the age gap left by the first ver- literature; however, well-designed, well-controlled trials are
sion of the pCAM-ICU, the preschool confusion assessment lacking to support the safe and effective use of these agents.
tool for ICU (psCAM-ICU) was validated in children 6 months These medications are not without acute risk, most notably
to 5 years of age (Smith 2016). The Cornell Assessment of QT prolongation, dystonic reactions, and neuroleptic malig-
Pediatric Delirium (CAPD) is an adaption of the PAED with nant syndrome. Therefore, if pharmacologic treatment of a
additional questions to detect hypoactive delirium. The pediatric patient for delirium becomes an intention, this deci-
CAPD includes developmental anchor points for all ages, sion should be entered into thoughtfully and with a specific
negating an age limitation (Traube 2014). A recent publica- monitoring plan outlined.
tion showed much overlap in the symptoms of delirium and
iatrogenic drug withdrawal syndrome in children. Although Neurodevelopmental Outcomes
these screening tools help assign objectivity to the assess- Currently, neurodevelopmental outcomes of children exposed
ment, the syndromes are not mutually exclusive, and the to short- and long-term analgesics and sedatives are unknown.
authors warn providers not to overlook the clinical context A growing body of literature aims to describe the effect of
(Madden 2017). drug exposure on a child’s motor and cognition development.
Prevention and treatment of delirium are evolving. The In a study of infants younger than 8 weeks with periopera-
adult PAD guidelines recommend normalizing patient tive analgesia and sedation exposure, drug exposure was
environments, promoting sleep, and performing early mobi- not associated with negative neurodevelopmental outcomes
lization. One center showed that the incidence of delirium in 2 years after cardiac surgery (Guerra 2011). Mechanically ven-
the PICU decreased from 19.3% to 11.8% with the successive tilated preterm infants with a median gestational age of 29
rollout of delirium screening, sedation, and early-mobilization weeks who received morphine had a decreased IQ early in life,
protocols (Simone 2017). The PAD guidelines recommend but by 5 years of age, this effect had disappeared (de Graaf
against pharmacologic therapy for preventing or treating 2011). In a neuropsychological follow-up study of childhood
delirium because data are sparse to support medication use meningococcal survivors exposed to analgesia and seda-
(Barr 2013). Prevention of delirium has been investigated in tion in the PICU, the children had poor test outcomes at least
the pediatric anesthesia literature with respect to anesthesia 4 years after admission. Full-scale IQ, verbal and vocabulary
emergence, as well in the adult critically ill population with IQ, and visual attention and executive functioning were all
dexmedetomidine use. Treating the symptoms of delirium adversely affected (p<0.05). A multivariate analysis showed
with typical antipsychotics (e.g., haloperidol) and atypical that opioids were associated with the poor cognitive out-
antipsychotics (e.g., risperidone, quetiapine, olanzapine) has comes after controlling for many confounding factors (van
been reported in both the adult and the pediatric delirium Zellem 2014).
PedSAP 2017 Book 3 • Sedation and Analgesia 23 Analgesia and Sedation in Hospitalized Children
One limitation to studying neurocognitive outcomes is understanding the ontogeny of the disposition and clearance
the heterogeneity of the pediatric population, which may mechanisms in pediatric patients as well as how obesity and
preclude classifying patients into homogeneous groups for other illnesses contribute to medication pharmacokinetics.
more in-depth investigation. In addition, follow-up may be Analgesics and sedatives carry a high risk of patient harm
more difficult because many childhood hospitalizations are
acute and limited and do not require recurring care. There
is a growing interest in the pediatric critical care discipline
Practice Points
to address the unanswered questions of growth and devel-
• Each analgesic and sedative medication has a unique phar-
opment after critical illness and interventions, including
macokinetic profile. The agent-specific adverse events with
prolonged analgesia and sedation. Some children’s hospitals administration (e.g., fentanyl and rigid chest syndrome,
are responding to this need by creating longitudinal clinics to propofol and PRIS) and the ways in which to alleviate and
assist with follow-up. avoid them must be understood and appreciated.
Another initiative that is growing to address neurocogni- • Appreciation of the developmental changes in children is
important in order to optimize analgesia and sedation and
tive patient outcomes is the development of the ABCDEF care
avoid toxicities that may lead to serious adverse effects.
bundle in the ICU setting (Figure 1-2). Each arm of bundle can
• Obesity complicates drug dosing of these high-risk med-
help to reduce and prevent delirium, and enhance rehabilita- ications; thus, dosing on the basis of ideal, adjusted, or
tion of the adult ICU patient. The combination of all the arms total body weight must be considered.
of ABCDEF care bundle is thought to optimize the climate • Combination or multimodal analgesic therapy is preferred
for successful ICU liberation. Pediatric centers are actively for postoperative analgesia.
• Self-reported pain assessment is preferred to observa-
working to implement similar bundles; therefore, pediatric
tional pain assessment tools.
data supporting ABCDEF care bundles are forthcoming.
• When choosing sedatives for procedural sedation, onset
and duration of action are important, as are the adverse
Conclusion effects on the cardiorespiratory system. If there is a poten-
tial to adversely affect hemodynamics, respiratory drive, or
Providing hospitalized children with safe, effective, and
airway patency, patients must be sedated in a safe environ-
appropriate analgesia and sedation is complex. However, ment with appropriate rescue equipment and providers who
provision of analgesia and sedation is necessary to meet are skilled in managing cardiorespiratory emergencies.
the expectations of the patient and caregiver in pain relief • Sedation and delirium assessments are available for
and level of sedation as well as to optimize the healing children. Practitioners must understand the limitations of
these tools to make appropriate assessments.
environment. Challenges with providing this care include
PedSAP 2017 Book 3 • Sedation and Analgesia 24 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 25 Analgesia and Sedation in Hospitalized Children
Coté CJ, Wilson S. Guidelines for monitoring and man- Ghai B, Jain K, Saxena AK, et al. Comparison of oral midazo-
agement of pediatric patients before, during, and after lam with intranasal dexmedetomidine premedication for
sedation for diagnostic and therapeutic procedures: children undergoing CT imaging: a randomized,
update 2016. Pediatrics 2016;138:e1-31. double-blind, and controlled study. Paediatr Anaesth 2016.
Cray SH, Holtby HM, Kartha VM, et al. Early tracheal extuba- Grant MJ, Schneider JB, Asaro LA, et al. Dexmedetomidine
tion after paediatric cardiac surgery: the use of propofol to use in critically ill children with acute respiratory failure.
supplement low-dose opioid anaesthesia. Paediatr Pediatr Crit Care Med 2016;17:1131-41.
Anaesth 2001;11:465-71.
Grunwell JR, Travers C, McCracken CE, et al. Procedural
Curley MA, Wypij D, Watson RS, et al. Protocolized sedation sedation outside of the operating room using ket-
vs usual care in pediatric patients mechanically ventilated amine in 22,645 children: a report from the Pediatric
for acute respiratory failure: a randomized clinical trial. Sedation Research Consortium. Pediatr Crit Care Med
JAMA 2015;313:379-89. 2016;17:1109-16.
Curley MAQ, Harris SK, Fraser K, et al. State Behavioral Scale Guerra GG, Robertson CM, Alton GY, et al. Western
(SBS): a sedation assessment instrument for infants and Canadian Complex Pediatric Therapies Follow-up Group.
young children supported on mechanical ventilation. Neurodevelopmental outcome following exposure to sed-
Pediatr Crit Care Med 2006;7:107-14. ative and analgesic drugs for complex cardiac surgery in
infancy. Paediatr Anaesth 2011;21:932-41.
Deasy C, Babl FE. Intravenous vs intramuscular ketamine
for pediatric procedural sedation by emergency medicine Hartman ME, McCrory DC, Schulman SR. Efficacy of seda-
specialists: a review. Paediatr Anaesth 2010;20:787-96. tion regimens to facilitate mechanical ventilation in the
pediatric intensive care unit: a systematic review. Pediatr
Deeter KH, King MA, Ridling D, et al. Successful implemen- Crit Care Med 2009;10:246-55.
tation of a pediatric sedation protocol for mechanically
ventilated patients. Crit Care Med 2011;39:683-8. Heard C, Burrows F, Johnson K, et al. A comparison of dex-
medetomidine-midazolam with propofol for maintenance
de Graaf J, van Lingen RA, Simons SH, et al. Long-term of anesthesia in children undergoing magnetic resonance
effects of routine morphine infusion in mechanically imaging. Anesth Analg 2008;107:1832-9.
ventilated neonates on children’s functioning: five-
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procedures. Paediatr Anaesth 2009;19:500-6. mulation in critically ill patients receiving continuous
intravenous lorazepam infusions. Ann Pharmacother
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agonists. Anesthesiology 2000;93:1345-9. American pediatric anesthesiologists: patient-controlled
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(acetaminophen) with nonsteroidal anti-inflamma-
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drome: a structured review of experimental studies and efficacy for acute postoperative pain. Anesth Analg
153 published case reports. Crit Care 2015;19:398. 2010;110:1170-9.
Krauss B, Green SM. Procedural sedation and analgesia in Pallin DJ, Dwyer RC, Walls RM, et al. Techniques and
children. Lancet 2006;367:766-80. trends, success rates, and adverse events in emergency
Kudchadkar SR, Yaster M, Punjabi NM. Sedation, sleep pro- department pediatric intubations: a report from the
motion, and delirium screening practices in the care of National Emergency Airway Registry. Ann Emerg Med
mechanically ventilated children: a wake-up call for 2016;67:610-5.
the pediatric critical care community. Crit Care Med Pasero C. Assessment of sedation during opioid admin-
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Lam J, Baello S, Iqbal M, et al. The ontogeny of P-glycoprotein 2009;24:186-90.
in the developing human blood-brain barrier: implication for Patel P, Patel H, Roth D. General anesthetics and therapeutic
opioid toxicity in neonates. Pediatr Res 2015;78:417-21. gases. In: Brunton L, Chabner B, Knollmann B, eds. Goodman
Leeder JS, Kearns GL, Spielberg SP, et al. Understanding & Gilman’s The Pharmacological Basis of Therapeutics, 12th
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pediatric drug development and regulatory science. J Clin Phan H, Nahata MC. Clinical uses of dexmedetomidine in
Pharmacol 2010;50:1377-87. pediatric patients. Paediatr Drugs 2008;10:49-69.
Lee-Jayaram JJ, Green A, Siembieda J, et al. Ketamine/ Ramsay MA, Savege TM, Simpson BR, et al. Controlled seda-
midazolam versus etomidate/fentanyl: procedural seda- tion with alphaxalone-alphadolone. Br Med J 1974;2:656-9.
tion for pediatric orthopedic reductions. Pediatr Emerg
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induced hyperalgesia: cellular and molecular
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reliability of the University of Michigan Sedation Scale Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond
(UMSS). Br J Anaesth 2002;88:241-5. Agitation-Sedation Scale: validity and reliability in adult
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PedSAP 2017 Book 3 • Sedation and Analgesia 28 Analgesia and Sedation in Hospitalized Children
PedSAP 2017 Book 3 • Sedation and Analgesia 29 Analgesia and Sedation in Hospitalized Children
cin for treatment of a UTI, intravenous famotidine for J.M. is an 8-year-old, mechanically ventilated boy with trisomy
stress-related mucosal disease, and intravenous ondan- 21. He is admitted to the PICU with acute respiratory failure.
setron as needed for nausea and vomiting (one dose in The nurse reports increased agitation despite escalating con-
24 hours). She is awake in the evenings, asleep through- tinuous infusion of both the opioid and the benzodiazepine,
out the daytime, and less engaged with her environment with extra bolus doses given of each.
and her family. She becomes combative with the bedside 13. J.M.’s medical team has high suspicion for delirium.
caregivers at times. The medical team is concerned for Which delirium screening tool would be most appropri-
delirium. Which one of the following is best to recom- ate for J.M.?
mend for this patient?
A. PAED (Pediatric Anesthesia Emergence Delirium)
A. Provide an atypical antipsychotic B. Cornell Assessment of Pediatric Delirium (CAPD)
B. Institute day- and nighttime activity schedule C. Preschool confusion assessment method for ICU
C. Add a dexmedetomidine infusion (psCAM-ICU)
D. Add lorazepam intravenously as needed D. Delirium Rating Scale, 1988 (DRS-88)
10. A patient has opioid-induced pruritus with intravenous 14. Which one of the following pain scales would be most
morphine for postoperative pain management. Which appropriate for J.M.?
one of the following is best for this patient?
A. VAS
A. Initiate diphenhydramine B. FACES
B. Change to intravenous fentanyl C. N-PASS
C. Change to enteral morphine D. FLACC
D. Initiate a dexmedetomidine infusion
15. Which one of the following sedation scales would be
11. A 16-year-old male adolescent is admitted to the PICU most appropriate for J.M.?
after a motor vehicle crash with a traumatic brain injury.
A. University of Michigan Sedation Scale
He is 24 hours into sedation with propofol so that fre-
B. Richmond Agitation-Sedation Scale (RASS)
quent neurological examinations can be done. Which
C. State Behavioral Scale (SBS)
one of the following monitoring values would be most
D. N-PASS
appropriate to detect the life-threatening adverse event
of propofol-related infusion syndrome at this time?
A. Serum phosphorus
B. Arterial blood gas
C. Creatine phosphokinase
D. Serum triglycerides
PedSAP 2017 Book 3 • Sedation and Analgesia 30 Analgesia and Sedation in Hospitalized Children