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Guidelines For Sedation in Gastroenterological Endoscopy (Second Edition)
Guidelines For Sedation in Gastroenterological Endoscopy (Second Edition)
13882
Guidelines
Sedation in gastroenterological endoscopy has become an benzodiazepine drugs primarily used for sedation during
important medical option in routine clinical care. Here, the gastroenterological endoscopy are not approved by national
Japan Gastroenterological Endoscopy Society and the Japanese health insurance in Japan, and investigations regarding
Society of Anesthesiologists together provide the revised expense-related disadvantages have not been conducted.
“Guidelines for sedation in gastroenterological endoscopy” as Furthermore, including the perspective of beneficiaries (i.e.,
a second edition to address on-site clinical questions and issues patients and citizens) during the creation of clinical guidelines
raised for safe examination and treatment using sedated should be considered. These guidelines are standardized based
endoscopy. Twenty clinical questions were determined and on up-to-date evidence quality (strength) and supports on-site
the strength of recommendation and evidence quality clinical decision-making by patients and medical staff. There-
(strength) were expressed according to the “MINDS Manual fore, these guidelines need to be flexible with regard to the
for Guideline Development 2017.” We were able to release up- wishes, age, complications, and social conditions of the patient,
to-date statements related to clinical questions and current as well as the conditions of the facility and discretion of the
issues relevant to sedation in gastroenterological endoscopy physician.
(henceforth, “endoscopy”). There are few reports from Japan in
Key words: gastroenterological endoscopy, patient
this field (e.g., meta-analyses), and many aspects have been
monitoring, pre-sedative assessment, sedation, training
based only on a specialist consensus. In the current scenario,
safety and efficacy in sedative usage, as well as the selection the JGES guideline committee, and the guidelines were
of appropriate sedatives. created with the participation of the Japanese Society of
Anesthesiologists as well. First, a key clinical issue
addressed by the clinical guidelines was whether improved
TASK FORCE MEMBERS AND CONSULTANTS
examination/treatment success rate and elimination of pain
or anxiety can be achieved with the “benefits” of sedative
E LEVEN GASTROINTESTINAL ENDOSCOPISTS
were commissioned as task force members of the Japan
Gastroenterological Endoscopy Society (JGES) committee
usage. Furthermore, the possibility of increased adverse
events due to sedative usage was considered as an outcome.
for creating the guidelines, with a single anesthesiologist as Disadvantages such as financial burdens were not included
an external committee member. Furthermore, five gastroin- in assessments in the creation of these guidelines. The
testinal endoscopists and a single anesthesiologist were reason for this is because in Japan, dexmedetomidine
assigned as assessment consultants, and a single specialist in hydrochloride is the only sedative among those used in
charge of guideline creation was included as an external endoscopy that can be reimbursed, while no other sedatives
assessment consultant (Table 1). are covered by national health insurance in Japan. Further-
more, there were regional differences in the assessment
conditions of the sedatives used, and it was difficult to
BASIC PRINCIPLES FOR GUIDELINE CREATION
conduct a unified assessment.
Table 1 Members of the committee for guidelines for sedation in gastroenterological endoscopy (second edition)
Table 2 Strength of recommendation and evidence quality participation like that of the National Institute for Health
(strength) and Care Excellence in the U.K. and support participation in
Strength of recommendation the creation of such clinical guidelines.
1: Strongly recommended
2: Weakly recommended (proposed) SUBJECTS AND GUIDELINE USERS
None: No clear recommendations can be made, or the
strength of recommendation cannot be determined
Evidence quality (strength)
A: Based on strong grounds
T HE SUBJECTS OF these guidelines are patients who
undergo investigation and treatment using endoscopy.
Children are excluded from the subjects of these guidelines.
B: Based on moderate grounds The users of these guidelines include clinical physicians
C: Based on weak grounds who conduct endoscopy and all medical staff involved in
D: Based on very weak grounds
endoscopy. The guidelines are standardized based on current
evidence and support on-site clinical decision-making
Furthermore, most of the drugs used in endoscopy are not between the patient and medical staff. As such, these
eligible for insurance approval. In other words, these drugs are guidelines need to be flexible with regard to the wishes, age,
just widely used in general clinics as well-known options. complications, and social conditions of the individual
Regional differences interfere with whether the sedatives used patient, as well as the conditions at the facility and the
are inspected, and it is unclear who shoulders the responsibility discretionary powers of the physician.
when adverse events occur as a result of the sedative. This was
also made clear with the creation of these guidelines, but the
CONFLICT OF INTEREST
use of these drugs cannot be avoided since the disadvantages to
the patient during endoscopy treatment without sedatives or
general anesthesia are too high, and comparison trials between
sedative use and non-use are not available.
E ACH OF THE task force members of the guideline
creation and assessment committee declared the fol-
lowing content with regard to conflict of interest.
In Japan, even if sedative use is shown to be a “benefit” for Takuji GOTODA (lecturer’s fee: Fujifilm), Seiichiro ABE
the patient (i.e., beneficiary), this is disadvantageous to the (lecturer’s fee: Boston Scientific Japan; research expenses/
medical provider (i.e., facility, endoscopist), and the patient scholarship: Olympus, Fujifilm), Naoki HOSOE (research
will be held responsible for the financial burden or for serious expenses/scholarship: Olympus), Yoshimasa MIURA (en-
incidents. These guidelines are for endoscopy, a general dowed lecture: Fujifilm Medical), Hajime ISOMOTO
medical procedure, and all Japanese citizens become bene- (lecturer’s fee: Takeda Pharmaceutical Company, Daiichi
ficiaries. Even with regard to expenses, it is unlikely that this Sankyo Company; scholarship contributions: Otsuka Phar-
would require vast expenses that affect the national budget of maceutical, Eli Lilly Japan), Atsushi IRISAWA (scholarship
Japan. The “individual and social aspects to be gained and its contributions: Takeda Pharmaceutical Company, EA
considerations,” and the consideration of medical regulation Pharma, AbbVie), Kazuma FUJIMOTO (lecturer’s fees:
and policy decisions (e.g., medical insurance regulations) Tsumura & Co., EA Pharma, AstraZeneca, Daiichi Sankyo;
from the perspective of safety in sedative use are issues that scholarship contributions: AstraZeneca, Daiichi Sankyo,
should be addressed in the future. Astellas Pharma, Takeda Pharmaceutical Company, EA
The present guidelines are designed for medical providers Pharma, Asahi Kasei Medical), Haruhiro INOUE (patent
who have the opportunity to conduct examinations and fees: Olympus; lecturer’s fees: Olympus, Takeda Pharma-
treatment using endoscopy. However, it is extremely ceutical Company; scholarship contributions: Olympus,
important to reflect the patient and citizen perspective Boston Scientific Japan, Takeda Pharmaceutical Company).
(Patients and Public Involvement) in addition to that of the Takuji GOTODA and Hajime ISOMOTO are Deputy
medical staff when creating the clinical guidelines. The need Editors‐in‐Chiefs of Digestive Endoscopy, and Yousuke
for patient/citizen participation for creating the guidelines NAKAI, Atsushi IRISAWA and Naohisa YOSHIDA are
has also been clearly stated in the “MINDS Manual for Associate Editors of Digestive Endoscopy.
Guideline Development 2017”,3 but the incorporation of the
guideline subject group’s values and hopes to the extent
FUNDING INFORMATION
possible is thought to be an issue to be addressed in the next
revision. This requires preparation for patient participation,
including education and training. The Society will also need
to provide a program that brings about patient/citizen
E XPENSES RELATED TO the creation of these guide-
lines were covered by the JGES, and no funds were
provided from other businesses.
CQ1 Are pre-sedative assessments recommended for Clinical history and physical status (PS) assessments prior to sedation are 1 C
suitable and safe sedation? recommended for utilizing the suitable depth of sedation and preventing
adverse events
CQ2 Are sedated endoscopy examinations safe for Sedated endoscopy examinations can be safely conducted if sufficient pre- 2 D
patients with complications (e.g., COPD, heart operation assessments are conducted, including consultations with
disease, chronic renal failure, hepatic cirrhosis, anesthesiology departments and other clinical departments, and a sedative
psychotropic drug administration, myasthenia suitable for the underlying disease is selected
gravis), seniors, and pregnant patients?
Digestive Endoscopy 2021; 33: 21–53
CQ3 What constitutes suitable monitoring during Suitable monitoring during sedation constitutes continuous monitoring of a 1 B
sedation? patient’s consciousness level, respiratory dynamics, and circulatory
dynamics
CQ4 Is a monitoring supervisor necessary when A single monitoring supervisor should be present for minimal or moderate 2 D
conducting sedated endoscopy? sedation, and more than one monitoring supervisor should be present for
high-risk endoscopy
CQ5 How should monitoring release during sedated Monitoring release (discharge) standards have not been established, but this 2 D
endoscopy be ascertained? should be determined upon assessment of the patient’s consciousness level,
respiratory dynamics, and circulatory dynamics
CQ6 Is sedation training for endoscopists and Sedation training should be proposed to endoscopists and endoscopy staff 2 D
endoscopy staff recommended? who provide sedation
CQ7 What are suitable sedation methods during Secure monitoring should be conducted, and antagonist sedatives or those 2 D
emergency endoscopy? with a short half-life should be used under an environment where emergency
treatment can be conducted
CQ8 Do sedatives contribute to transoral endoscopy? Sedatives improve the receptivity and satisfaction of transoral endoscopy 2 A
and contribute to improved examination/treatment performance
CQ9 Do sedatives contribute to transanal endoscopy? Sedatives reduce anxiety and pain during transanal endoscopy and 2 C
contribute to increased satisfaction and improved examination/treatment
performance
CQ10 What is a suitable benzodiazepine drug for Among midazolam, diazepam, and flunitrazepam, midazolam usage is 2 C
transoral endoscopy examinations? proposed for its sedative effects and patient satisfaction
CQ11 What is a suitable benzodiazepine drug for Among midazolam, diazepam, and flunitrazepam, midazolam usage is 2 C
transanal endoscopy examinations? proposed for its sedative effects and patient satisfaction
CQ12 What is a suitable benzodiazepine drug when There is no evidence related to benzodiazepine drug selection, and no None D
undergoing transoral endoscopy treatment? suitable drugs have been established
CQ13 What is a suitable benzodiazepine drug when There is no evidence related to benzodiazepine drug selection, and no None D
undergoing transanal endoscopy treatment? suitable drugs have been established
Sedation for GI endoscopy
25
CQ14 What should be done when a suitable depth of The addition of analgesics (e.g., pethidine hydrochloride, pentazocine) should 2 D
sedation cannot be obtained even when more be considered when using only benzodiazepine drugs. Patients suspected of
T. Gotoda et al.
than the recommended amount of disinhibition should be administered antagonists, and the procedure should
benzodiazepine drug is administered during be conducted while awake or the examination/treatment should be extended
sedated endoscopy?
CQ15 Is the use of analgesics in addition to sedatives The use of analgesics in addition to sedatives is effective for ERCP. There are 2 B
effective during transoral endoscopy? cases with other endoscopies where the use of analgesics in addition to
sedatives is effective
CQ16 Is the use of analgesics in addition to sedatives There are cases where the use of analgesics in addition to sedatives is 2 C
effective during transanal endoscopy? effective in transanal endoscopy
CQ17 What is the efficacy of propofol in endoscopy? Adverse outcomes do not increase if propofol is used under suitable 2 A
monitoring conditions, and it has the advantages of short duration of
recovery/confinement, low interruption rate of long-term surgical
Table 4 Extent of consent based on the modified Delphi auscultation of the heart and lungs, baseline consciousness
method level, and the airway are similarly recommended for
1–3 Disagree physical findings. The modified Mallampati score5,6 is often
4–6 Dissatisfied used for airway assessment (Table 6). Previous reports have
7–9 Agree indicated the efficacy of the ASA pre-procedure assessment
classification “ASA physical status (PS) classification”
(Table 7) for PS assessment. Anesthesiologist consultations
REFERENCES are recommended for patients with an ASA-PS classification
of IV and above according to ASGE3 and ASA4 guidelines
1 Obara K, Haruma K, Irisawa A et al. Guidelines for sedation in
and ASA-PS classification of III and above according to the
gastroenterological endoscopy. Dig Endosc 2015; 27: 435–49.
European Society of Anaesthesiology (ESA) guidelines,7
2 American Society of Anesthesiologists Task Force on Sedation
and Analgesia by Non-Anesthesiologists. Practice guidelines given their higher risk of adverse events. Other risk factors
for sedation and analgesia by non-anesthesiologists. Anesthe- for sedation-related adverse events in the ESA guidelines7
silogy 2002; 96: 1004–17. include patients with cardiovascular diseases, obstructive
3 https://minds.jcqhc.or.jp/english/english.php. Accessed 6 sleep apnea, obesity, renal failure, liver failure, and old age.
March 2020. The ASGE requires careful administration of sedation in
4 Fink A, Kosecoff J, Chassin M et al. Consensus methods: elderly patients but does not provide a clear definition for
Characteristics and guidelines for use. Am J Public Health elderly patients. ESA guidelines7 state that anesthesiologist
1984; 74: 979–83. consultations are recommended for patients over the age of
70 due to their higher risk of sedation-related adverse
CQS AND STATEMENTS events.
CQ 1: Are pre-sedative assessments The databases used for this reference extraction were
recommended for suitable and safe PubMed, Cochrane Library database, and Japan Medical
sedation? Abstract Society. A search using the keywords “endoscopy”
and “sedation” and (“training” or “assessment”) yielded 177
articles, of which 22 were meta-analyses/systematic
x reviews/clinical guidelines, 40 were clinical trials, 99 were
Statement 1:
miscellaneous clinical research/epidemiological research,
and 16 were controlled trials. Manual searching added
Clinical history and physical status (PS) assessments seven articles, and screening results yielded seven related
prior to sedation are recommended for utilizing the references, including two clinical guidelines.
appropriate level of sedation and preventing adverse
events.
Assessment based on the modified Delphi method:
Table 5 Items for pre-sedative assessments
median, 9; minimum, 5; maximum, 9
Strength of recommendation: 1, Evidence quality Clinical history
(strength): C Presence of serious cardiopulmonary conditions
A history of stridor, snoring, sleep apnea
Drug allergies
Prior sedation- or anesthesia-related adverse reactions
Textual explanation Current medications
History of smoking and alcohol consumption
Suitable sedation requires the determination of the target Pregnancy/lactation
level of sedation for the planned procedure, as well as the Time and contents of the last oral intake
patient’s PS, clinical history, and pre-existing medical Physical examinations
conditions, which are thought to be correlated with Physical status (PS) assessment (ASA-PS classification)
sedation-related adverse events.1,2 Parameters similar to Vital signs
those shown in the American Society for Gastrointestinal Auscultation of the heart and lungs
Endoscopy (ASGE)3 and the ASA4 and to be assessed in Baseline consciousness level
Airway assessment
advance are shown in Table 5. Assessments of vital signs,
Table 6 Modified Mallampati score for airway assessment endoscopic examinations. For respiratory muscle examina-
tion, sedated endoscopy is not recommended under condi-
Class I Full visibility of the tonsils, uvula, and soft palate
Class II Visibility of the hard and soft palate, upper portion of tions where negative expiratory pressure and forced vital
the tonsils, and uvula capacity are used in lung function examinations and spare
Class The soft and hard palate and base of the uvula are respiratory functions are virtually non-existent.13 Benzodi-
III visible azepine drugs like midazolam and diazepam have muscle
Class Only the hard palate is visible relaxation effects and are contraindicated due to their
IV tendency to exacerbate symptoms. Reports have indicated
the efficacy of propofol due to its short-acting effects, which
do not influence the neuromuscular junction.13
heart disease, as they can cause anginal attacks or heart
failure.2 Seniors. Prior assessments should be conducted for seniors,
because age-related functional decreases in the heart, lungs,
Chronic renal failure. Reports have indicated that patients kidney, liver, endocrine system, and nerves increase the risk
with renal function lower than GFR 60 mL/min/1.73 m2 are of sedation-related adverse events.14,15
at higher-than-normal risk of hypoxemia or respiratory Closer attention should be paid to hypotension, hypoxemia,
insufficiency. Therefore, short-acting and liver-metabolizing arrhythmia, and pulmonary aspiration in seniors than in
drugs (e.g., propofol) are recommended.7 younger patients.16–18 Furthermore, seniors are known to
have a higher sensitivity to sedatives like midazolam, and the
Liver cirrhosis. Benzodiazepine drugs, which are often used appropriate dose for them is lower than that for younger
for sedation, have variable durations of action depending on patients.19,23 It is therefore important to avoid overdosing and
the drug type, but since they are deactivated through to conduct management during and after surgery carefully;
glucuronic acid conjugation, decreased liver function influ- reduced post-procedural onset of hypoxemia during rest can
ences the liver metabolism of the sedative and increases the be expected by selecting a short-acting drug.24
frequency of adverse events.8,9 Short-acting drugs (e.g.,
midazolam) can be considered, but care must be taken Pregnant patients. Sedative use should be prolonged if
against the prolonged half-life of these drugs.2 Furthermore, possible, given its effects on the fetus (e.g., hypoxemia,
deep sedation is a risk factor for the onset of hepatic hypotension, teratogenesis). Elective administration is rec-
encephalopathy; thus, moderate sedation is recommended.10 ommended in the second trimester (14–27 weeks). With
regard to sedative safety assessments on pregnant women,
Psychotropic drug administration. The necessary sedative anesthesiologist-administered propofol and midazolam have
dose during endoscopic examination increases when benzo- been classified as category B (relatively safe) and D,
diazepine drugs, opioid analgesics, or psychotropic drugs are respectively, by the U.S. Food and Drug Administration.
regularly used, and patient satisfaction also decreases.11,12 Diazepam is not recommended due to reports indicating its
correlations to infants being born with a cleft palate.25
Myasthenia gravis. Myasthenia gravis is an autoimmune Breast-feeding after sedation is not recommended, con-
disease that disrupts synapse transmission at the neuromus- sidering reports indicating the transfer of sedatives through
cular junction. Assessments of the voluntary and respiratory breast milk (e.g., midazolam breast milk/blood plasma ratio,
muscles are conducted in order to safely conduct sedated 0.15) and variable half-life of drugs between adults and
Table 7 American Society of Anesthesiologists physical status classification (ASA-PS classification; adapted from the ASA website)
children (e.g., midazolam half-life in adults, approximately 6 Hirose S, Sato T, Yamaguchi T et al. Endoscopy for high-risk
1.9 h; in children, 6.5–23 h), with a particularly large patients with serious comorbidities. Endoscopia Dig 2018; 30:
number of reports indicating adverse outcomes in infants 831–7. (Article in Japanese with English summary).
within 2 months of birth.26 Sedatives with a short half-life 7 Lee SM, Kim GH, Lee JJ et al. Does propofol and alfentanil-
induced sedation cause periodic apnoea in chronic renal failure
need to be selected when breast-feeding after awakening
patients? Int J Clin Pract 2010; 64: 1–5.
from sedation, but the discharge amount is thought to
8 Jensen DM. Endoscopic screening for varices in cirrhosis:
accumulate up to 87.8% even with midazolam up to 24 h Findings, implications, and outcomes. Gastroenterology 2002;
after drug administration. Safety measures such as infant 122: 1620–30.
monitoring are necessary even after awakening since the 9 Thuluvath PJ. Toward safer sedation in patients with cirrhosis:
drug type used for sedation and the metabolic functions of Have we done enough? Gastrointest Endosc 2009; 70: 269–71.
the mother and infant all influence the infant. 10 Mao W, Wei XQ, Tao J et al. The safety of combined sedation
The databases used for this reference extraction were with propofol plus fentanyl for endoscopy screening and
PubMed, Cochrane Library database, and Japan Medical endoscopic variceal ligation in cirrhotic patients. J Dig Dis
Abstract Society. A search including the keywords (“en- 2014; 15: 124–30.
doscopy” or “digestive system”) and (“sedation” or “anes- 11 Papachristou GI, Gleeson FC, Papachristou DJ et al. Endo-
scopist administered sedation during ERCP: Impact of chronic
thesia” or “analgesia”) and (“elderly” or “cirrhosis” or
narcotic/benzodiazepine use and predictive risk of reversal
“pulmonary” or “cardiac” or “renal disease” or “high risk”
agent utilization. Am J Gastroenterol 2007; 102: 738–43.
or “pregnancy”) yielded 404 articles, of which 18 were 12 Pe~na LR, Mardini HE, Nickl NJ. Development of an
meta-analyses/systematic reviews/clinical guidelines, 96 instrument to assess and predict satisfaction and poor tolerance
were clinical trials, 273 were miscellaneous clinical among patients undergoing endoscopic procedures. Dig Dis
research/epidemiological research, and 17 were controlled Sci 2005; 50: 1860–71.
trials. After manual searching added 21 articles (including 13 Abel M, Eisenkraft JB. Anesthetic implications of myasthenia
four clinical guidelines), screening results yielded 26 related gravis. Mt Sinai J Med 2002; 69: 31–7.
references, including four randomized controlled trials 14 Ekstein M, Gavish D, Ezri T et al. Monitored anaesthesia care
(RCTs) and four clinical guidelines. in the elderly: Guidelines and recommendations. Drugs Aging
2008; 25: 477–500.
15 Travis A, Pievsky D, Saltzman J. Endoscopy in the elderly.
Am J Gastroenterol 2012; 107: 1495–501.
REFERENCES
16 Fritz E, Kirchgatterer A, Hubner D et al. ERCP is safe and
1 Smith ZL, Mullady DK, Lang GD et al. A randomized effective in patients 80 years of age and older compared with
controlled trial evaluating general endotracheal anesthesia younger patients. Gastrointest Endosc 2006; 64: 899–905.
versus monitored anesthesia care and the incidence of 17 Katsinelos P, Kountouras J, Chatzimavroudis G et al. Outpa-
sedation-related adverse events during ERCP in high-risk tient therapeutic endoscopic retrograde cholangiopancreatog-
patients. Gastrointest Endosc 2019; 89: 855–62. raphy is safe in patients aged 80 years and older. Endoscopy
2 Practice guidelines for moderate procedural sedation and 2011; 43: 128–33.
analgesia 2018. A report by the American Society of 18 Salminen P, Gr€ onroos JM. Anesthesiologist assistance in
Anesthesiologists Task Force on Moderate Procedural Seda- endoscopic retrograde cholangiopancreatography procedures
tion and Analgesia, the American Association of Oral and in the elderly: Is it worthwhile? J Laparoendosc Adv Surg
Maxillofacial Surgeons, American College of Radiology, Tech A 2011; 21: 517–9.
American Dental Association, American Society of Dentist 19 Liu LL. Conscious sedation in the elderly. In: Wiener-Kronish
Anesthesiologists, and Society of Interventional Radiology. JP, Gropper MA (eds). Conscious Sedation. Philadelphia, PA:
Anesthesiology 2018; 128: 437–79. Hanley & Belfus, 2001; 105–17.
3 Hinkelbein J, Lamperti M, Akeson J et al. European Society of 20 Schnider TW, Minto CF, Shafer SL et al. The influence of age
Anaesthesiology and European Board of Anaesthesiology on propofol pharmacodynamics. Anesthesiology 1999; 90:
guidelines for procedural sedation and analgesia in adults. Eur 1502–16.
J Anaesthesiol 2018; 35: 6–24. 21 Bell GD, Spickett GP, Reeve PA et al. Intravenous midazolam
4 ASGE Standards of Practice Committee, Early DS, Lightdale for upper gastrointestinal endoscopy: a study of 800 consec-
JR et al. Guidelines for sedation and anesthesia in GI utive cases relating dose to age and sex of patient. Br J Clin
endoscopy. Gastrointest Endosc 2018; 87: 327–37. Pharmacol 1987; 23: 241–3.
5 American Society of Anesthesiologists Task Force on Sedation 22 Christe C, Janssens JP, Armenian B et al. Midazolam sedation
and Analgesia by Non-Anesthesiologists. Practice guidelines for upper gastrointestinal endoscopy in older persons: a
for sedation and analgesia by non-anesthesiologists. Anesthe- randomized, double-blind, placebo-controlled study. J Am
silogy 2002; 96: 1004–17. Geriatr Soc 2000; 48: 1398–403.
23 Heuss LT, Schnieper P, Drewe J et al. Conscious sedation with assessment of the patient’s consciousness level and vital
propofol in elderly patients: a prospective evaluation. Aliment signs at the very least prior to anesthesia and must regularly
Pharmacol Ther 2003; 17: 1493–501. and continuously conduct this at least every 5 min once
24 Riphaus A, Stergiou N, Wehrmann T. Sedation with propofol securing the blood vessels, administering the sedative, and
for routine ERCP in high-risk octogenarians: a randomized,
conducting endoscopy until the examination/treatment is
controlled study. Am J Gastroenterol 2005; 100: 1957–63.
completed and the patient awakens.4 The physician in
25 ASGE Standard of Practice Committee, Shergill AK, Ben-
Menachem T et al. Guidelines for endoscopy in pregnant and
charge of the anesthetic can perform short-term treatments
lactating women. Gastrointest Endosc 2012; 76: 18–24. for moderate sedation, but should be focused on continuous
26 Dalal PG, Bosak J, Berlin C. Safety of the breast-feeding monitoring for deep sedation.1,6
infant after maternal anesthesia. Pediatr Anesth 2014; 24: With regard to respiratory system monitoring, direct
359–71. monitoring of respiratory status is extremely important, and
auscultation/respiratory rate measurements should also be
conducted as needed. Furthermore, a pulse oximeter is an
CQ 3: What constitutes suitable monitoring
important respiration monitor since it can accurately digitize
during sedation?
hypoxemia.7 The ASGE recommends the use of a pulse
Statement 3: oximeter in all endoscopy treatments,4 being particularly
essential during sedated endoscopy. Oxygen administration
should be considered under moderate sedation to prevent
hypoxemia, and it is essential under deep sedation.
Suitable monitoring during sedation constitutes contin-
Capnography measures the gaseous carbonic acid con-
uous monitoring of a patient’s consciousness level,
centration during expiration and has been shown to detect
respiratory dynamics, and circulatory dynamics.
insufficient ventilation and hypoxemia at an early stage,8,9
Assessment based on the modified Delphi method:
but the relationship between temporary hypoxemia and
median, 9; minimum, 7; maximum, 9
serious cardiopulmonary events during sedated endoscopy
Strength of recommendation: 1, Evidence quality
has not been clarified.10 A report has indicated that
(strength): B
capnography was not able to reduce hypoxemia incidence
during upper and lower endoscopic examinations on healthy
individuals under mild sedation,11 while an RCT reported
Textual explanation that capnography-based monitoring was able to significantly
reduce hypoxemia during lower gastrointestinal endoscopic
Moderate sedation (conscious sedation) is primarily recom- examinations with deep sedation.12 Therefore, capnography-
mended for sedation conducted for the purposes of endo- based monitoring should be used during deep sedation.
scopic examination and treatment,1 and deep sedation may With regard to the circulatory system, it is important to
be necessary depending on the sedation type, treatment monitor arrhythmia and measure blood pressure under deep
difficulty, treatment duration, and patient conditions2 sedation,1,13 and both ASA and ASGE guidelines particu-
(Table 8). larly recommend continuous electrocardiogram-based mon-
Visual examinations and suitable/continuous observations itoring for patients with serious cardiovascular diseases or
of respiratory/circulatory dynamics are important with arrhythmia and cases where endoscopy extends over long
regard to patient monitoring.3 The frequency of adverse periods of time.1,3 Monitoring with higher-accuracy devices,
events is somewhat variable depending on the drug used for including blood pressure monitors and electrocardiography
sedation and the depth of sedation, but the basic parameter devices, is recommended for sedated endoscopy conducted
needed for monitoring include the consciousness level, pulse in high-risk patients.
rate, blood pressure, and degree of SpO2.2,4 In addition, Bispectral index monitoring and brainwave
The ASA Clinical Outcomes Research Initiative database monitors, both of which measure and objectively quantify
showed that cardiopulmonary events during endoscopy were brainwaves, have been used for deep sedation during
the most important fatal adverse events.5 Suitable patient endoscopy treatment primarily using propofol. This has
monitoring, particularly that of respiratory and circulatory been shown to minimize the risk of over-sedation during
dynamics, is needed for sedated endoscopy in an endoscopy endoscopy treatment14,15 and to reduce the administered
facility. dose of propofol.16,17
With regard to both moderate and deep sedation, the Safer sedated endoscopy should be pursued through the
physician in charge of the anesthetic needs to begin combination of visual examination of the patient,
Responsiveness Normal response to Purposeful response to verbal Purposeful response after Unarousable even
verbal stimulation or tactile stimulation repeated or painful stimulation with painful stimulus
Airway Unaffected No intervention required Intervention may be required Intervention often
required
Spontaneous Unaffected Adequate May be inadequate Frequently
ventilation inadequate
Cardiovascular Unaffected Usually maintained Usually maintained May be impaired
function
appropriate monitoring of consciousness level and respira- Association Institute et al. Multisociety sedation curriculum for
tory/circulatory dynamics, and the use of various monitoring gastrointestinal endoscopy. Gastrointest Endosc 2012; 76: e1–
devices. 25.
The databases used for this reference extraction were 7 Cohen LB, Delegge MH, Aisenberg J et al. AGA Institute
review of endoscopic sedation. Gastroenterology 2007; 133:
PubMed, Cochrane Library database, and Japan Medical
675–701.
Abstract Society. A search using the keywords “monitor-
8 Lightdale JR, Goldmann DA, Feldman HA et al. Microstream
ing”[TIAB] AND “sedation”[TIAB] AND (“Endoscopy, capnography improves patient monitoring during moderate
Digestive System”[MeSH Terms]) AND (English[LA] OR sedation: a randomized, controlled trial. Pediatrics 2006; 117:
Japanese[LA]) AND “humans”[MeSH Terms]) yielded 365 e1170-8.
articles, of which 43 were meta-analyses/systematic reviews/ 9 Qadeer MA, Vargo JJ, Dumot JA et al. Capnographic
clinical guidelines, 164 were clinical trials, 104 were monitoring of respiratory activity improves safety of sedation
miscellaneous clinical research/epidemiological research, for endoscopic cholangiopancreatography and ultrasonogra-
one was a Cochrane review, and 16 were controlled trials. phy. Gastroenterology 2009; 136: 1568–76.
Manual searching added seven articles (including three 10 Vargo JJ 2nd. Sedation-related complications in gastrointestinal
clinical guidelines), and screening results yielded 17 related endoscopy. Gastrointest Endosc Clin N Am 2015; 25: 147–58.
11 Mehta PP, Kochhar G, Albeldawi M et al. Capnographic
references, including six RCTs and five clinical guidelines.
monitoring in routine EGD and colonoscopy with moderate
sedation: a prospective, randomized, controlled trial. Am J
Gastroenterol 2016; 111: 395–404.
REFERENCES
12 Friedrich-Rust M, Welte M, Welte C et al. Capnographic
1 American Society of Anesthesiologists Task Force on Sedation monitoring of propofol-based sedation during colonoscopy.
and Analgesia by Non-Anesthesiologists. Practice guidelines Endoscopy 2014; 46: 236–44.
for sedation and analgesia by non-anesthesiologists. Anesthe- 13 Maurer WG, Walsh M, Viazis N. Basic requirements for
silogy 2002; 96: 1004–17. monitoring sedated patients: Blood pressure, pulse oximetry,
2 ASGE Ensuring Safety, in the Gastrointestinal Endoscopy Unit and EKG. Digestion 2010; 82: 87–9.
Task Force, Calderwood AH, Chapman FJ et al. Guidelines for 14 Imagawa A, Fujiki S, Kawahara Y et al. Satisfaction with
safety in the gastrointestinal endoscopy unit. Gastrointest bispectral index monitoring of propofol-mediated sedation
Endosc 2014; 79: 363–72. during endoscopic submucosal dissection: a prospective,
3 Standards of Practice Committee of the American Society for randomized study. Endoscopy 2008; 40: 905–9.
Gastrointestinal Endoscopy, Lichtenstein DR, Jagannath S 15 Paspatis GA, Chainaki I, Manolaraki MM et al. Efficacy of
et al. Sedation and anesthesia in GI endoscopy. Gastrointest bispectral index monitoring as an adjunct to propofol deep
Endosc 2008; 68: 815–26. sedation for ERCP: a randomized controlled trial. Endoscopy
4 ASGE Standards of Practice Committee, Early DS, Lightdale 2009; 41: 1046–51.
JR et al. Guidelines for sedation and anesthesia in GI 16 Gotoda T, Okada H, Hori K et al. Propofol sedation with a
endoscopy. Gastrointest Endosc 2018; 87: 327–37. target-controlled infusion pump and bispectral index monitor-
5 Metzner J, Posner KL, Domino KB. The risk and safety of ing system in elderly patients during a complex upper
anesthesia at remote locations: The US closed claims analysis. endoscopy procedure. Gastrointest Endosc 2016; 83: 756–64.
Curr Opin Anaesthesiol 2009; 22: 502–8. 17 Park SW, Lee H, Ahn H. Bispectral index versus standard
6 American Association for Study of Liver Diseases, American monitoring in sedation for endoscopic procedures: a system-
College of Gastroenterology, American Gastroenterological atic review and meta-analysis. Dig Dis Sci 2016; 61: 814–24.
sedation/analgesia levels. The Aldrete score,3 postanesthetic The databases used for this reference extraction were
discharge scoring system (PADSS),4 and the modified post- PubMed, Cochrane Library database, and Japan Medical
anesthesia discharge scoring system (MPADSS)5 are scores Abstract Society. A search using the keywords (“en-
often used as standards for monitoring release (discharge) in doscopy”) and (“sedation”) and (recovery assessment)
endoscopy. Table 9 shows the Aldrete score, which yielded 148 articles, of which nine were meta-analyses/
comprises five parameters (respiration, SpO2, consciousness systematic reviews/clinical guidelines, 88 were clinical
level, circulation, activity), and where discharge standards trials, 49 were miscellaneous clinical research/epidemiolog-
are satisfied with a score of 9 or higher. These standards are ical research, and two were controlled trials. After manual
used when assessing the recovery time from sedation in searching added six articles (including RCTs), screening
RCTs assessing sedative efficacy. The efficacy of these results yielded seven related references.
scores has only been verified with a relatively small number
of prospective trials.6 As such, further investigations are REFERENCES
needed to assess the efficacy of these scores.
Willey et al.7 used the Aldrete score to assess the 1 Chernik DA, Gillings D, Laine H et al. Validity and reliability
of the observer’s assessment of alertness/sedation scale: Study
discharge standards of 31 patients who underwent sedated
with intravenous midazolam. J Clin Psychopharmacol 1990;
upper gastrointestinal endoscopy during outpatient care.
10: 244–51.
Results showed that of the patients whose discharge 2 Ramsay MA, Savege TM, Simpson BR et al. Controlled
standards were satisfied, 60–70% showed a recovery of sedation with alphaxalone-alphadolone. Br Med J 1974; 2:
psychomotor function. 656–9.
Based on the above findings, it must be stated that 3 Aldrete JA, Kroulik D. A postanesthetic recovery score.
monitoring release (discharge) standards following sedated Anesth Analg 1970; 49: 924–34.
endoscopy have not been established, but monitoring release 4 Chung F, Chan VW, Ong D. A post-anesthetic discharge
should be determined by assessing the patient’s conscious- scoring system for home readiness after ambulatory surgery. J
ness level, respiration dynamics, SpO2, circulation, and Clin Anesth 1995; 7: 500–6.
activity (motor function), and assessments at the time of 5 Chung F. Discharge criteria–a new trend. Can J Anaesth 1995;
42: 1056–8.
determination should be written in clinical records.
Table 9 Aldrete score 6 Amornyotin S, Chalayonnavin W, Kongphlay S. Recovery
pattern and home-readiness after ambulatory gastrointestinal
Parameter Standard Points endoscopy. J Med Assoc Thai 2007; 90: 2352–8.
Respiration Able to breathe deeply and cough 2 7 Willey J, Vargo JJ, Connor JT et al. Quantitative assessment of
Dyspnea or shallow breathing 1 psychomotor recovery after sedation and analgesia for outpa-
Apnea 0 tient EGD. Gastrointest Endosc 2002; 56: 810–6.
Oxygen Maintains >92% on room air 2
saturation Needs O2 inhalation to maintain O2 1
CQ 6: Is sedation training for endoscopists
(SpO2) saturation ≧90%
SpO2 <90% (with supplemental 0
and endoscopy staff recommended?
oxygen administered) Statement 6:
Consciousness Fully awake 2
level Arousable upon calling 1
Not responding 0
Circulation Blood pressure 20 mmHg 2 Sedation training is recommended for endoscopists and
(relative to pre-operation standard endoscopy staff who perform sedation.
value) Assessment based on the modified Delphi method:
Blood pressure 20–50 mmHg 1 median, 7.5; minimum, 5; maximum, 9
(relative to the pre-procedural
Strength of recommendation: 2, Evidence quality
standard value)
(strength): D
Blood pressure 50 mmHg 0
(relative to the pre-procedural
standard value)
Activity Able to move the four extremities 2
Able to move two extremities 1 Textual explanation
Cannot move the four extremities 0 To provide safe and appropriate endoscopic sedation,
Discharge standards satisfied if score is 9 or above. knowledge of the level of sedation appropriate for each
endoscopic procedure, as well as the management of administered propofol sedation for gastrointestinal endoscopy.
sedation-related adverse events (even though they have a Scand J Gastroenterol. 2016; 51: 872–9.
low frequency), is required. Sedation training should
involve basic knowledge on pre-sedative assessment, the CQ 7: What are suitable sedation methods
level of sedation appropriate for endoscopic procedures, during emergency endoscopy?
sedative drug/monitoring, recovery care and discharge, and
sedative antagonists, as well as basic life support (BLS) and Statement 7:
advanced cardiovascular life support (ACLS) certifications
to provide emergency management of cardiopulmonary
events. The training curriculum for sedation for endoscopic
Secure monitoring should be conducted, and antagonist
procedures has been published by the Multisociety Sedation
sedatives or those with a short half-life should be used
Curriculum for Gastrointestinal Endoscopy (MSCGE)1 and
under an environment where emergency treatment can be
the European Society of Gastrointestinal Endoscopy/Euro-
conducted.
pean Society of Gastroenterology and Endoscopy Nurses
Assessment based on the modified Delphi method:
and Associates (ESGE/ESGENA).2 There is some variation
median, 8; minimum, 7; maximum, 9
in the content of the two documents, but each curriculum
Strength of recommendation: 2, Evidence quality
includes BLS or ACLS as an item for the training
(strength): D
curriculum to manage adverse events during sedation. Some
research has shown the improvement of sedation-related
knowledge through the use of training curricula,3 but to
date, no reports have demonstrated that these resulted in Textual explanation
improvement in sedation safety or efficacy itself. However,
considering safety aspects such as the management of Sedation is thought to be effective for conducting safe and
adverse events, endoscopists or endoscopy staff who secure emergency treatment if vital signs are stable, partic-
provide sedation are recommended to undergo training. ularly when the patient is in an agitated or anxious state,1 but
The databases used for this reference extraction were sedation may not be effective depending on the patient’s PS
PubMed, Cochrane Library database, and Japan Medical or extent of symptoms.2 Sedation control or monitoring by
Abstract Society. A search using the keywords “endoscopy” anesthesiologists, emergency physicians, or intensive treat-
and “sedation” and (“preoperative care” or “preprocedural ment physicians is particularly recommended for emergency
assessment” or “risk assessment” or “patient evaluation”) endoscopy similar to that conducted under intubation.
yielded 65 articles, of which eight were meta-analyses/ When performing sedation, it is desirable to secure blood
systematic reviews/clinical guidelines, five were clinical vessels and to confirm oxygen saturation, blood pressure,
trials, 40 were miscellaneous clinical research/epidemiolog- heart rate, respiration rate, etc., with a biological monitor to
ical research, and 12 were controlled trials. After manual ensure safety.3,4 It is also important that the sedation
searching added three articles, screening results yielded supervisor name, supervisory nurse name, sedative name,
three related references, including verification research. administered dose, administration route, administered dose
of oxygen, etc., all be recorded.
Recently, endoscopy treatment using CO2 supply insuf-
REFERENCES flation under sedation has been widely performed, but this
1 American Association for Study of Liver Diseases, American poses a risk of CO2 accumulation; hence, capnography-
College of Gastroenterology, American Gastroenterological based monitoring and non-invasive continuous transcuta-
Association Institute et al. Multisociety sedation curriculum neous CO2 partial pressure monitors have been considered
for gastrointestinal endoscopy. Gastrointest Endosc 2012; 76: useful for early-stage detection of hypercapnia.5,6
e1–25. Commonly used drugs include diazepam, midazolam, and
2 Dumonceau JM, Riphaus A, Beilenhoff U et al. European flunitrazepam for sedatives with antagonists, and pethidine
curriculum for sedation training in gastrointestinal endoscopy: hydrochloride and pentazocine for analgesics. The adminis-
Position statement of the European Society of Gastrointestinal tered dose should be carefully determined by considering the
Endoscopy (ESGE) and European Society of Gastroenterology
clinical conditions, including the patient’s PS, age, weight,
and Endoscopy Nurses and Associates (ESGENA). Endoscopy
type of treatment, and the predicted treatment duration.
2013; 45: 496–504.
3 Jensen JT, Savran MM, Møller AM et al. Development and Recently, it has been reported that drugs such as propofol
validation of a theoretical test in non-anaesthesiologist- have an equivalent or greater effect and safety than sedation
caused by small doses of benzodiazepine drugs,6–15 and that prospective, randomized, double-blind study. Endoscopy
safe endoscopy treatment with minimal respiratory suppression 2000; 32: 677–82.
or rough body movements can be conducted with dexmedeto- 8 Vargo JJ, Zuccaro G Jr, Dumot JA et al. Gastroenterologist-
midine hydrochloride sedation,16,17 and these drugs may be administered propofol versus meperidine and midazolam for
advanced upper endoscopy: a prospective, randomized trial.
effective for emergency endoscopy as well. However, care
Gastroenterol 2002; 123: 8–16.
must be taken with regard to bradycardia arrhythmia or
9 Tohda G, Higashi S, Sakumoto H et al. Efficacy and safety of
respiratory suppression/hypotension caused by dexmedeto- nurse-administered propofol sedation during emergency upper
midine hydrochloride or propofol, respectively. Accordingly, endoscopy for gastrointestinal bleeding: a prospective study.
monitoring supervisors need to be present to conduct suitable Endoscopy 2006; 38: 684–9.
monitoring and circulatory dynamics management, and seda- 10 Imagawa A, Fujiki S, Kawahara Y et al. Satisfaction with
tion should be conducted while rapidly ensuring airway bispectral index monitoring of propofol-mediated sedation
maintenance and conducting airway intubation. during endoscopic submucosal dissection: a prospective,
The databases used for this reference extraction were randomized study. Endoscopy 2008; 40: 905–9.
PubMed, Cochrane Library database, and Japan Medical 11 Paspatis GA, Manolaraki MM, Vardas E et al. Deep sedation
Abstract Society. A search using the keywords (“emergency for endoscopic retrograde cholangiopancreatography: Intra-
venous propofol alone versus intravenous propofol with oral
endoscopy” or “urgent endoscopy”) and (“appropriate
midazolam premedication. Endoscopy 2008; 40: 308–13.
sedation” or “analgesia” or “anesthesia”) and “safety” and
12 Thanvi BR, Munshi SK, Vijayakumar N et al. Acceptability of
(“utility” or “availability”) yielded 271 articles, of which 18 oesophagogastroduodenoscopy without intravenous sedation:
were meta-analyses/systematic reviews/clinical guidelines, Patients’ versus endoscopist’s perception with special refer-
83 were clinical trials, 116 were miscellaneous clinical ence to older patients. Postgrad Med J 2003; 79: 650–1.
research/epidemiological research, two were Cochrane 13 Horiuchi A, Nakayama Y, Tanaka N et al. Propofol sedation
reviews, and 52 were controlled trials. After manual for endoscopic procedures in patients 90 years of age and
searching added 17 articles (including six RCTs relating to older. Digestion 2008; 78: 20–3.
adverse outcomes), screening results yielded 19 related 14 Schilling D, Rosenbaum A, Schweizer S et al. Sedation with
references, including six RCTs and one clinical guideline. propofol for interventional endoscopy by trained nurses in
high-risk octogenarians: a prospective, randomized, controlled
study. Endoscopy 2009; 41: 295–8.
REFERENCES 15 Aviv JE. Effects of aging on sensitivity of the pharyngeal and
supraglottic areas. Am J Med 1997; 103: 74S–S76.
1 Waye JD. Intubation and sedation in patients who have
16 Yin S, Hong J, Sha T et al. Efficacy and tolerability of
emergency upper GI endoscopy for GI bleeding. Gastrointest
sufentanil, dexmedetomidine, or ketamine added to propofol-
Endosc 2000; 51: 768–71.
based sedation for gastrointestinal endoscopy in elderly
2 Duch P, Haahr C, Møller MH et al. Anaesthesia care for
patients: A prospective, randomized, controlled trial. Clin
emergency endoscopy for peptic ulcer bleeding. A nationwide
Ther 2019; 41: 1864–77.
population-based cohort study. Scand J Gastroenterol 2016;
17 Chang ET, Certal V, Song SA et al. Dexmedetomidine versus
51: 1000–6.
propofol during drug-induced sleep endoscopy and sedation: a
3 Berg JC, Miller R, Burkhalter E. Clinical value of pulse
systematic review. Sleep Breath 2017; 21: 727–35.
oximetry during routine diagnostic and therapeutic endoscopic
procedure. Endoscopy 1991; 23: 328–30.
4 Iber FL, Sutberry M, Gupta R et al. Evaluation of complica- CQ 8: Do sedatives contribute to transoral
tions during and after conscious sedation for endoscopy using endoscopy?
pulse oximetry. Gastrointest Endosc 1993; 39: 620–5.
5 Jopling MW, Qiu J, Capnography sensor use is associated with Statement 8:
reduction of adverse outcomes during gastrointestinal endo-
scopic procedures with sedation administration. BMC Anes-
thesiol 2017; 17: 157.
6 Miyoshi H, Shimatani M, Kato K et al. Transcutaneous Sedatives improve the receptivity and satisfaction of
monitoring of partial pressure of carbon dioxide during transoral endoscopy and contribute to improved exam-
endoscopic retrograde cholangiopancreatography using a ination/treatment performance.
double-balloon endoscope with carbon dioxide insufflation Assessment based on the modified Delphi method:
under conscious sedation. Dig Endosc 2014; 26: 436–41. median, 9; minimum, 8; maximum, 9
7 Krugliak P, Ziff B, Rusabrov Y et al. Propofol versus Strength of recommendation: 2, Evidence quality
midazolam for conscious sedation guided by processed EEG (strength): A
during endoscopic retrograde cholangiopancreatography: a
patient’s decision, but there are regions or facilities where dissection: a prospective double-blind randomized controlled
sedation cannot always be safely administered. With regard study. Clin Transl Gastroenterol 2018; 9: e167.
to adverse events, it is important to maintain suitable 3 Takahashi Y, Tanaka H, Kinjo M et al. Sedation-free
observations and an appropriate depth of sedation since the colonoscopy. Dis Colon Rectum 2005; 48: 855–9.
4 Park DI, Kim HJ, Park JH et al. Factors affecting abdominal
frequency of hypoxemia and hypotension increases with
pain during colonoscopy. Eur J Gastroenterol Hepatol 2007;
sedation. Recent reports have indicated that the incidence of
19: 695–9.
adverse outcomes like aspiration pneumonia increased 5 Eckardt AJ, Swales C, Bhattacharya K et al. Open access
during transanal endoscopic examinations under general colonoscopy in the training setting: Which factors affect
anesthesia or anesthetic assistance compared to other patient satisfaction and pain? Endoscopy 2008; 40: 98–105.
examinations under sedation,7,8 and care should be taken 6 Paggi S, Radaelli F, Amato A et al. Unsedated colonoscopy:
on this aspect. An option for some but not for all. Gastrointest Endosc 2012;
From the perspective of the endoscopist, sedation 75: 392–8.
increases endoscopist satisfaction during transanal endo- 7 Wernli KJ, Brenner AT, Rutter CM et al. Risks associated with
scopy.2,9 Western guidelines also indicate that sedation is anesthesia services during colonoscopy. Gastroenterology
effective in improving diagnosis quality and achieving 2016; 150: 888–94.
8 Bielawska B, Hookey LC, Sutradhar R et al. Anesthesia
treatment objectives,10,11 and that the cecal intubation rate
assistance in outpatient colonoscopy and risk of aspiration
during transanal endoscopic examination is particularly
pneumonia, bowel perforation, and splenic injury. Gastroen-
better in women.12 Meanwhile, sedation has been shown to terology 2018; 154: 77–85.e3.
not improve intubation difficulties, reduce the cecal intuba- 9 Kashiwagi K, Hosoe N, Takahashi K et al. Prospective,
tion time, or improve polyp discovery rates during exam- randomized, placebo-controlled trial evaluating the efficacy
ination.12,13 and safety of propofol sedation by anesthesiologists and
The frequency with which sedation will be used in transanal gastroenterologist-led teams using computer-assisted person-
endoscopy is expected to continue increasing in the future. alized sedation during upper and lower gastrointestinal
Regional and facility-based conditions need to be considered endoscopy. Dig Endosc 2016; 28: 657–64.
in sedation use, but medical staff should investigate adjust- 10 Cohen LB, Ladas SD, Vargo JJ et al. Sedation in digestive
ments based on sedation efficacy and adverse outcomes and endoscopy: The Athens international position statements.
Aliment Pharmacol Ther 2010; 32: 425–42.
sufficiently respect the decision of patients with regard to
11 Cohen LB, Delegge MH, Aisenberg J et al. AGA Institute
sedation use after considering clinical safety.
review of endoscopic sedation. Gastroenterology 2007; 133:
The databases used for this reference extraction were 675–701.
PubMed, Cochrane Library database, and Japan Medical 12 Bannert C, Reinhart K, Dunkler D et al. Sedation in screening
Abstract Society. A search using the keywords (“colono- colonoscopy: Impact on quality indicators and complications.
scopy” or “enteroscopy”) and (“routine” or “diagnosis” or Am J Gastroenterol 2012; 107: 1837–48.
“therapy” or “therapeutics”) and (“sedation” or “anesthesia” 13 Ristikankare M, Hartikainen J, Heikkinen M et al. Is routinely
or “analgesia”) and (“quality” or “efficacy” or “time” or given conscious sedation of benefit during colonoscopy?
“acceptance” or “tolerance” or “satisfaction” or “pain” or Gastrointest Endosc 1999; 49: 566–72.
“detection” or “complication”) yielded 514 articles, of
which 32 were meta-analyses/systematic reviews/clinical CQ 10: What is a suitable benzodiazepine
guidelines, 163 were clinical trials, 196 were miscellaneous drug for transoral endoscopy?
clinical research/epidemiological research, and 123 were
controlled trials. After manual searching added six articles Statement 10:
(including two national reports relating to adverse out-
comes), screening results yielded 15 related references,
including three RCTs and one clinical guideline.
Among midazolam, diazepam, and flunitrazepam, mida-
zolam is proposed for its sedative effects and patient
REFERENCES satisfaction.
Assessment based on the modified Delphi method:
1 Baudet JS, Aguirre-Jaime A. The sedation increases the
median, 8; minimum, 6; maximum, 9
acceptance of repeat colonoscopies. Eur J Gastroenterol
Hepatol 2012; 24: 775–80.
Strength of recommendation: 2, Evidence quality
2 Kinugasa H, Higashi R, Miyahara K et al. Dexmedetomidine (strength): C
for conscious sedation with colorectal endoscopic submucosal
should be administered antagonists, and the procedure local anesthesia” and also induces minimal respiratory
should be conducted while awake or the examination/ suppression. Its use during endoscopy examinations is
treatment should be extended. thought to be difficult due to the high cost of the drug and its
Assessment based on the modified Delphi method: need for continuous administration.
median, 8; minimum, 7; maximum, 9 Next, propofol use needs to be carefully selected since it
Strength of recommendation: 2, Evidence quality is not covered by insurance. As a general rule, the drug
(strength): D should be continuously administered, because single admin-
istrations are thought to easily induce unstable sedation
conditions. In either case, the combined use of benzodi-
azepine drugs and other sedatives might increase the risk of
Textual explanation over-sedation-related adverse events, and the reversal of
benzodiazepine drugs using flumazenil should consistently
It is standard practice overseas for anesthesiologists or nurse
be considered. Patients in whom sedation is difficult
anesthetists to conduct sedation control during invasive
(particularly those who have circulatory or respiratory
endoscopy. However, currently in Japan, there is little
complications) should also consider consulting with anes-
treatment compensation for independently ensuring human
thesiologists for appropriate selection of the drugs to be used
resources for conducting these procedures, and that the only
in sedation and decide whether to undergo general anesthe-
drug covered by insurance is dexmedetomidine hydrochlo-
sia with intubation.
ride, thus making these procedures difficult.
The databases used for this reference extraction were
Most sedation problems are caused by insufficient
PubMed, Cochrane Library database, and Japan Medical
measures against discomfort/pain during endoscopic exam-
Abstract Society. A search using the keywords (“en-
ination/treatment. Many reference investigations that com-
doscopy” or “endoscopic”) and “benzodiazepine” and
pared sole use of benzodiazepine versus benzodiazepine
“insufficient sedation” and ( “disinhibition” or “paradoxical
with analgesics like pethidine hydrochloride or pentazocine
reaction” or “paradoxical effect”) yielded 92 articles, of
showed that the combined analgesic use was effective.1–3
which 10 were meta-analyses/systematic reviews/clinical
However, sedative and analgesic overdosing can cause
guidelines, 26 were clinical trials, 51 were miscellaneous
upper airway obstruction and respiratory suppression,
clinical research/epidemiological research, and five were
warranting intermittent monitoring of respiratory conditions
controlled trials. Screening results yielded six related
before and after additional drug administration.
references, including four RCTs.
Besides analgesics, reports have indicated that combining
droperidol with midazolam/pethidine hydrochloride
improves sedation quality in upper endoscopic examina- REFERENCES
tion/treatment.4,5 However, side effects related to the
1 Terui T, Inomata M. Administration of additional analgesics
circulatory system (e.g., QT extension) have been found, can decrease the incidence of paradoxical reactions in patients
and droperidol use for sedation in Japan is not standard under benzodiazepine-induced sedation during endoscopic
practice, with its usage being difficult even when drug transpapillary procedures: Prospective randomized controlled
conditions are ideal. There are no other references for drugs trial. Dig Endosc 2013; 25: 53–9.
that can be recommended for simultaneous use with 2 Y€uksel O, Parlak E, K€okl€
u S et al. Conscious sedation during
benzodiazepine drugs. endoscopic retrograde cholangiopancreatography: Midazolam
Benzodiazepine drug-based sedation should be sus- or midazolam plus meperidine? Eur J Gastroenterol Hepatol
pended, and antagonists should be promptly used when 2007; 19: 1002–6.
disinhibition occurs.6 The possibility of continuing the 3 Dzeletovic I, Harrison ME, Crowell MD et al. Impact of
fentanyl in lieu of meperidine on endoscopy unit efficiency: a
examination/treatment should be investigated while the
prospective comparative study in patients undergoing EGD.
patient is awake, and temporarily suspending the procedure
Gastrointest Endosc 2013; 77: 883–7.
and postponing it to another date might be safer if a separate 4 Cohen J, Haber GB, Dorais JA et al. A randomized, double-
sedation method needs to be conducted. blind study of the use of droperidol for conscious sedation
Sedatives that should be investigated as substitutes to during therapeutic endoscopy in difficult to sedate patients.
benzodiazepine drugs include dexmedetomidine hydrochlo- Gastrointest Endosc 2000; 51: 546–51.
ride and propofol. First, dexmedetomidine hydrochloride 5 Barthel JS, Marshall JB, King PD et al. The effect of
additionally includes the additional insurance-covered use of droperidol on objective markers of patient cooperation and
“sedation during non-intubated surgery and treatment under vital signs during esophagogastroduodenoscopy: a
randomized, double-blind, placebo-controlled, prospective with analgesics was effective in ERCP due to less pain
investigation. Gastrointest Endosc 1995; 42: 45–50. in the combined drug group, higher possibility of
6 Tae CH, Kang KJ, Min BH et al. Paradoxical reaction to patient and operator satisfaction, and minimal costs.
midazolam in patients undergoing endoscopy under sedation: Meanwhile, many RCT participants were under the
Incidence, risk factors and the effect of flumazenil. Dig Liver
age of 80 and had an ASA-PS classification of II or
Dis 2014; 46: 710–5.
below (Table 77); thus, careful measures are required
for patients with extremely advanced age or those with
CQ 15: Is the use of analgesics in addition to an ASA-PS classification of III or higher.There are no
sedatives effective during transoral controlled trials between sedatives and seda-
endoscopy? tives + analgesics that focus on examination/treatment
other than ERCP. Combined use with analgesics in
Statement 15:
addition to sedatives is an option for endoscopies
involving high levels of pain or discomfort or which
are long in duration.
The use of analgesics in addition to sedatives is effective b Controlled trials between different analgesics
for ERCP. There are cases with other types of endoscopy An RCT that compared different analgesics under
where the use of analgesics in addition to sedatives is conditions where sedatives + analgesics were used,
effective. specifically propofol + pethidine hydrochloride and
Assessment based on the modified Delphi method: propofol + fentanyl, has been conducted.5 The success
median, 8; minimum, 5; maximum, 9 rate, required time, duration of recovery room stay,
Strength of recommendation: 2, Evidence quality cardiopulmonary system-related adverse events, patient
(strength): B satisfaction, and operator satisfaction were all equiv-
alent. The administered dose of propofol was low in
the combined propofol + fentanyl group. From the
perspective of administered doses of propofol, fentanyl
Textual explanation is potentially thought to be safer. There are no
controlled trials comparing pentazocine with other
drugs.
2. Moderately invasive transoral endoscopy: esophagogas-
1. Highly invasive transoral endoscopy: ERCP, esophageal tric EMR, esophageal stenting, esophagogastric varicose
dilation, esophago-gastro-duodenal ESD, gastrostomy, vein treatment, gastrointestinal hemostasis, cauteriza-
transoral enteroscopy, interventional EUS, enteroscopic tion, EUS-FNA, etc.
ERCP, etc. There have been no controlled trials comparing sedatives
and sedatives + analgesics for these procedures. Short-
a Controlled trials between sedatives and seda- duration and minimally painful examination/treatment can
tives + analgesicsFour RCTs have been reported for be conducted with only sedatives, but combined use with
controlled trials between sedatives and seda- analgesics is also an option.
tives + analgesics in ERCP,1–4 with one comparing 3. Minimally invasive transoral endoscopy: upper endo-
midazolam and midazolam + pethidine hydrochlo- scopy examinations (including biopsy), diagnostic
ride,1 one comparing midazolam and midazo- EUS.
lam + pentazocine,2 and two comparing propofol
and propofol + fentanyl.3,4 The success rate and depth a Controlled trials between sedatives and seda-
of sedation were equivalent in both groups,1–4 and tives + analgesics.
adverse outcomes related to the circulatory system1,3,4 There have been five RCTs that compared sedatives
and respiratory system1–4 were also equivalent in both and sedatives + analgesics for upper endoscopy
groups. Pain was lower in the combined drug examination,6–10 with three comparing midazolam
group,1,3,4 and patient satisfaction was either equiva- and midazolam + pethidine hydrochloride,6–8 one
lent1464 or higher in the combined drug group.1 comparing midazolam and midazolam + fentanyl,9
Operator satisfaction was also either equivalent3,4 or and one comparing midazolam and midazolam + nal-
higher in the combined drug group.1,2 Combined use buphine.10 No RCTs have used propofol as a sedative
10 Chin KW, Tan PK, Chin MK. Sedation for gastroscopy: A a Controlled trials between sedatives and seda-
comparison between midazolam and midazolam with nal- tives + analgesicsSeven RCTs have compared seda-
buphine. Ann Acad Med Singapore 1994; 23: 330–2. tives and sedatives + analgesics for colonoscopy
11 Chokhavatia S, Nguyen L, Williams R et al. Sedation and examination,1–7 with two comparing midazolam and
analgesia for gastrointestinal endoscopy. Am J Gastroenterol
midazolam + pethidine hydrochloride,1,2 one compar-
1993; 88: 393–6.
ing midazolam and midazolam + fentanyl,3 one com-
12 Robertson DJ, Jacobs DP, Mackenzie TA et al. Clinical trial: a
randomized, study comparing meperidine (pethidine) and
paring diazepam and diazepam + pethidine
fentanyl in adult gastrointestinal endoscopy. Aliment Pharma- hydrochloride,4 one comparing propofol and propo-
col Ther 2009; 29: 817–23. fol + pethidine hydrochloride,5 and two comparing
13 Dzeletovic I, Harrison ME, Crowell MD et al. Impact of propofol and propofol + fentanyl.6,7 There have been
fentanyl in lieu of meperidine on endoscopy unit efficiency: a no trials using pentazocine as an analgesic. The success
prospective comparative study in patients undergoing EGD. rate and patient satisfaction were equivalent in both
Gastrointest Endosc 2013; 77: 883–7. groups.1–7 Many reports indicated that the rate of
adverse events related to the circulatory system was
CQ 16: Is the use of analgesics in addition to equivalent in both groups,1–3,5,6 whereas those related
sedatives effective during transanal to the respiratory system were either equivalent in both
endoscopy? groups2,3,5,6 or lower in the combined drug group.1,7
Operator satisfaction was equivalent in both
Statement 16: groups1,4,6,7 or higher in the combined drug group.3,5
The administered dose of sedatives was either equiv-
alent4 or lower in the combined drug group,5–7 and the
duration of recovery room stay was either equivalent2
There are cases where the use of analgesics in addition to
or shorter in the combined drug group.5,6 There are
sedatives is effective in transanal endoscopy.
many cases where colonoscopy examinations could be
Assessment based on the modified Delphi method:
conducted with only sedatives, but combined use with
median, 8; minimum, 7; maximum, 9
analgesics is an option due to the increased frequency
Strength of recommendation: 2, Evidence quality
of pain, potentially higher operator satisfaction, higher
(strength): C
examination facility turnaround rate, and minimal
costs. Meanwhile, many RCT participants were below
the age of 80 and had an ASA-PS classification of II or
Textual explanation below (Table 77), necessitating careful measures for
patients with extremely advanced age or those with an
ASA-PS classification of III or higher.
There have been no controlled trials comparing the use
1. Highly invasive transanal endoscopy: colon ESD, colonic of sedatives only and sedatives + analgesics for colon
stenting, EBD, enteroscopy (including treatment), EUS (including FNA). There might be cases where
etc.There have been no trials comparing the use of endoscopic examination can be conducted with only
sedatives only and sedatives + analgesics for these pro- sedatives, but combined use with analgesics is also an
cedures. Combined use of analgesics and sedatives is an option.
option for endoscopies causing high levels of pain or b Controlled trials between analgesicsThree trials had
discomfort or that are long in duration. pethidine hydrochloride and fentanyl comparison arms
2. Moderately invasive transanal endoscopy: colon EMR, under conditions where sedatives + analgesics were
gastrointestinal hemostasis, cauterization, etc.No trials used for colonoscopy examinations.8–10 There have
have compared the use of sedatives only and seda- been no trials comparing pentazocine with other drugs.
tives + analgesics for these procedures. Endoscopy treat- Some trials have compared analgesics that are not in
ment that is short in duration and causes relatively little standard use in colonoscopy examinations in Japan,
pain can be conducted with only sedatives, but combined e.g., sufentanil,11,12 alfentanil,13–17 remifentanil,18,19
use with analgesics is also an option. ketamine,13,20 nalbuphine,11 paracetamol,21 and tra-
3. Minimally invasive transanal endoscopy: colonoscopy madol.19,22 In three RCTs that compared midazo-
examinations (including biopsy, polypectomy), colon lam + pethidine hydrochloride and
EUS (including FNA) midazolam + fentanyl,8–10 safety and operator
satisfaction were equivalent between the two groups. cognitive functions: Randomized controlled trial. Turk J
Patient pain was reported as either equivalent in both Gastroenterol 2017; 28: 453–9.
groups8,10 or lower in the pethidine hydrochloride 8 Chokhavatia S, Nguyen L, Williams R et al. Sedation and
group.9 The duration of recovery room stay was shorter analgesia for gastrointestinal endoscopy. Am J Gastroenterol
1993; 88: 393–6.
in the fentanyl group for all studies. Based on these
9 Robertson DJ, Jacobs DP, Mackenzie TA et al. Clinical trial: a
findings, safety, patient satisfaction, and operator
randomized, study comparing meperidine (pethidine) and
satisfaction are thought to be virtually equivalent for fentanyl in adult gastrointestinal endoscopy. Aliment Pharma-
pethidine hydrochloride and fentanyl. The examina- col Ther 2009; 29: 817–23.
tion facility turnaround rate might be higher with the 10 Hayee B, Dunn J, Loganayagam A et al. Midazolam with
administration of fentanyl.The databases used for this meperidine or fentanyl for colonoscopy: Results of a random-
reference extraction were PubMed, Cochrane Library ized trial. Gastrointest Endosc 2009; 69: 681–7.
database, and Japan Medical Abstract Society. A 11 Deng C, Wang X, Zhu Q. Comparison of nalbuphine and
search using the keywords (“endoscopy” or “colono- sufentanil for colonoscopy: A randomized controlled trial.
scopy” or “endoscopic” or “EMR” or “ESD” or “EUS” PLoS One 2017; 12: e0188901.
or “endoscopic therapy”) and (“sedation” or “anesthe- 12 Akarsu Ayazo glu T, Polat E, Bolat C et al. Comparison of
propofol-based sedation regimens administered during colo-
sia” or “benzodiazepine” or “midazolam” or “propo-
noscopy. Rev Med Chil 2013; 141: 477–85.
fol” or “dexmedetomidine”) and (“analgesia” or €
13 T€urk HS ß , Aydogmusß M, Unsal O et al. Ketamine versus
“opioid” or “opiate” or “narcotic”) and (“meta-analy- alfentanil combined with propofol for sedation in colonoscopy
sis” or “randomized controlled” or “RCT”) not procedures: a randomized prospective study. Turk J Gastroen-
(“ERCP”) yielded 468 articles, of which 33 were terol 2014; 25: 644–9.
meta-analyses/systematic reviews/clinical guidelines, 14 T€urk HSß , Aydo €
gmusß M, Unsal O et al. Sedation-analgesia in
221 were clinical trials, 186 were miscellaneous elective colonoscopy: Propofol-fentanyl versus propofol-
clinical research/epidemiological research, and 28 alfentanil. Braz J Anesthesiol 2013; 63: 352–7.
were controlled trials. Screening results yielded 22 15 Ho WM, Yen CM, Lan CH et al. Comparison between the
related references. recovery time of alfentanil and fentanyl in balanced propofol
sedation for gastrointestinal and colonoscopy: a prospective,
randomized study. BMC Gastroenterol 2012; 12: 164.
16 Usta B, T€ urkay C, Muslu B et al. Patient-controlled analgesia
and sedation with alfentanyl versus fentanyl for colonoscopy:
REFERENCES A randomized double blind study. J Clin Gastroenterol 2011;
1 Froehlich F, Thorens J, Schwizer W et al. Sedation and 45: e72–e75.
analgesia for colonoscopy: Patient tolerance, pain, and 17 Holloway AM, Logan DA. Pain relief for outpatient colono-
cardiorespiratory parameters. Gastrointest Endosc 1997; 45: scopy: a comparison of alfentanil with fentanyl. Anaesth
1–9. Intensive Care 1990; 18: 210–3.
2 Cinar K, Yakut M, Ozden A. Sedation with midazolam versus 18 Fanti L, Agostoni M, Gemma M et al. Remifentanil vs.
midazolam plus meperidine for routine colonoscopy: a meperidine for patient-controlled analgesia during colono-
prospective, randomized, controlled study. Turk J Gastroen- scopy: A randomized double-blind trial. Am J Gastroenterol
terol 2009; 20: 271–5. 2009; 104: 1119–24.
3 Wang F, Shen SR, Xiao DH et al. Sedation, analgesia, and 19 Arici G, Kayacan N, Dincer D et al. Remifentanil/midazolam
cardiorespiratory function in colonoscopy using midazolam versus tramadol/midazolam use for colonoscopy. Hepatogas-
combined with fentanyl or propofol. Int J Colorectal Dis 2011; troenterology 2003; 50(Suppl 2): cclxxxiii-vi.
26: 703–8. 20 Khajavi M, Emami A, Etezadi F et al. Conscious sedation and
4 Rembacken BJ, Axon AT. The role of pethidine in sedation for analgesia in colonoscopy: Ketamine/propofol combination has
colonoscopy. Endoscopy 1995; 27: 244–7. superior patient satisfaction versus fentanyl/propofol. Anesth
5 Hsieh YH, Chou AL, Lai YY et al. Propofol alone versus Pain Med 2013; 3: 208–13.
propofol in combination with meperidine for sedation during 21 Ahmadi A, Amri P, Shokri J et al. Comparison of the analgesic
colonoscopy. J Clin Gastroenterol 2009; 43: 753–7. effect of intravenous paracetamol/midazolam and fentanyl in
6 VanNatta ME, Rex DK. Propofol alone titrated to deep preparation of patients for colonoscopy: A double blind
sedation versus propofol in combination with opioids and/or randomized clinical trial. Caspian J Intern Med 2015; 6: 87–
benzodiazepines and titrated to moderate sedation for colono- 92.
scopy. Am J Gastroenterol 2006; 101: 2209–17. 22 Hirsh I, Vaissler A, Chernin J et al. Fentanyl or tramadol, with
7 Doganay G, Ekmekcßi P, Kazbek BK et al. Effects of alfentanil midazolam, for outpatient colonoscopy: Analgesia, sedation,
or fentanyl added to propofol for sedation in colonoscopy on and safety. Dig Dis Sci 2006; 51: 1946–51.
comparing propofol-based sedation with NAAP that used a gastrointestinal endoscopy: The first double blind randomized
target-controlled infusion (TCI) pump and midazolam-based controlled trial. Dig Liver Dis 2015; 47: 566–71.
sedation during colonoscopy and upper endoscopy examina- 6 Klare P, Reiter J, Meining A et al. Capnographic monitoring of
tion has been reported.5 The propofol group in the colono- midazolam and propofol sedation during ERCP: a randomized
controlled study (EndoBreath Study). Endoscopy 2016; 48: 42–
scopy examination had a significantly shorter hospital
50.
discharge time and a significantly higher physician/patient
satisfaction. The propofol group in upper endoscopy exam-
ination had significantly higher patient/physician satisfaction CQ 19: Is dexmedetomidine hydrochloride
but showed no significant differences in hospital discharge effective in sedation during endoscopy
time, and the propofol sedation group was reported to request treatment with long sedation times?
the same sedative for their next session. These results suggest
Statement 19:
that there are differences in propofol- based sedation with
NAAP that uses a TCI pump, depending on transoral or
transanal intubation. There is also an RCT that investigated
the efficacy of capnography. There was no difference in Dexmedetomidine hydrochloride is effective in sedation
decreased SpO2 when the groups with or without capnogra- during endoscopy treatment with long sedation times.
phy in ERCP were compared, but the detection rate of apnea Assessment based on the modified Delphi method:
lasting longer than 15 s was significantly higher in the median, 8; minimum, 7; maximum, 9
capnography group (64.5% vs. 6.0%, P < 0.001).6 Strength of recommendation: 1, Evidence quality
Based on the above findings, (i) propofol management by (strength): B
either non-anesthesiologists or anesthesiologists is equiva-
lent for patients with an ASA-PS classification of I or II, and
(ii) the administered dose of propofol is larger with
anesthesiologists, but this is superior for deep sedation. Textual explanation
Propofol management by anesthesiologists is particularly There are numerous procedures for endoscopy treatment,
recommended for patients with an ASA-PS classification of and the necessity of sedation varies according to the
III or higher. endoscopy treatment type since the treatment time also
This reference extraction used the search results shown in varies according to the frequency of pain and the difficulty
CQ 17. Following the screening of 538 articles, seven of treatment. Short-duration endoscopy treatments such as
related references were used, including two RCTs, two colonic polypectomy can be conducted without sedation.
clinical guidelines, and three meta-analyses. Meanwhile, esophageal and gastric ESD and ERCP are
painful procedures, warranting sedation to safely and
REFERENCES securely conduct treatment. Moderate sedation is the
standard sedation level, but general anesthesia is also an
1 Vargo JJ, Cohen LB, Rex DK et al. Position statement:
option when the patient needs to be immobilized and stable
Nonanesthesiologist administration of propofol for GI endo-
for long periods of time during treatment.
scopy. Gastroenterology 2009; 137: 2161–7.
2 Daza JF, Tan CM, Fielding RJ et al. Propofol administration Dexmedetomidine hydrochloride is an a2 adrenaline
by endoscopists versus anesthesiologists in gastrointestinal receptor agonist and expresses its sedative effects by acting
endoscopy: A systematic review and meta-analysis of patient on the locus coeruleus and spinal cord of the pons.1–3 Unlike
safety outcomes. Can J Surg 2018; 61: 226–36. GABA agonists (e.g., midazolam), dexmedetomidine
3 Goudra BG, Singh PM, Gouda G. Safety of non-anesthesia hydrochloride has virtually no respiratory suppression and
provider-administered propofol (NAAP) sedation in advanced has sedative, analgesic, and sympathetic nerve suppression
gastrointestinal endoscopic procedures: Comparative meta- effects.4
analysis of pooled results. Dig Dis Sci 2015; 60: 2612–27. The use of this drug for sedation during non-intubated
Erratum in: Dig Dis Sci 2015; 60: 3151. treatment under local anesthesia in Japan is covered by
4 Wadhwa V, Issa D, Garg S et al. Similar risk of cardiopulmonary
insurance. It is clearly stated that physicians who are trained
adverse events between propofol and traditional anesthesia for
in patient management during non-intubated sedation are to
gastrointestinal endoscopy: A systematic review and meta-
analysis. Clin Gastroenterol Hepatol 2017; 15: 194–206. accurately understand the pharmacological effects of this
5 Fanti L, Gemma M, Agostoni M et al. Target Controlled drug and to carefully and continuously manage the patient’s
Infusion for non-anaesthesiologist propofol sedation during sedation level and physical status. It also clearly states that
physicians are to be prepared to conduct airway mainte- Terms] NOT “laparoscopy”[MeSH Terms] NOT “ureteros-
nance, oxygen inhalation, artificial respiration, and circula- copy”[MeSH Terms] AND (English[LA] OR Japanese[LA])
tion management. AND “humans”[MeSH Terms] yielded 126 articles, of which
A meta-analysis of dexmedetomidine hydrochloride and 12 were meta-analyses/systematic reviews/clinical guideli-
midazolam in endoscopy1 showed that the percentage of body nes, 56 were clinical trials, 20 were miscellaneous clinical
movement that resulted in the suspension of treatment was research/epidemiological research, and 38 were controlled
significantly lower in the dexmedetomidine hydrochloride trials. After manual searching added four articles (including
group relative to the midazolam group. The Ramsay sedation two RCTs), screening results yielded 14 related references,
score was significantly higher in the dexmedetomidine group including six RCTs and one meta-analysis.
compared to the midazolam group. There were no significant
differences in the frequency of adverse events like hypox-
emia, hypotension, and bradycardia between the two groups. REFERENCES
There were also no significant differences in the onset of body
1 Nishizawa T, Suzuki H, Sagara S et al. Dexmedetomidine
movement during upper endoscopy and colonoscopy exam- versus midazolam for gastrointestinal endoscopy: A meta-
ination, but body movement was suppressed with dexmedeto- analysis. Dig Endosc 2015; 27: 8–15.
midine hydrochloride during endoscopy treatment, which 2 Hashiguchi K, Matsunaga H, Higuchi H et al. Dexmedeto-
required longer periods of time (e.g., ESD, ERCP). midine for sedation during upper gastrointestinal endoscopy.
Comparisons between dexmedetomidine hydrochloride, Dig Endosc 2008; 20: 178–83.
midazolam, and propofol groups in gastric ESD showed that 3 Hayashi Y, Guo TZ, Maze M. Desensitization to the behav-
the dexmedetomidine hydrochloride group had significantly ioral effects of alpha 2-adrenergic agonists in rats. Anesthe-
lower body movement, treatment time, and additional siology 1995; 82: 954–62.
administered doses of midazolam.5 There were no patients 4 Riker RR, Shehabi Y, Bokesch PM et al. Dexmedetomidine vs
midazolam for sedation of critically ill patients : a randomized
whose examination was suspended due to respiratory
trial. JAMA 2009; 301: 489–99.
suppression in the dexmedetomidine hydrochloride group.
5 Takimoto K, Ueda T, Shimamoto F et al. Sedation with
Reports indicated that the combined use of dexmedeto- dexmedetomidine hydrochloride during endoscopic submu-
midine hydrochloride with sedatives/analgesics reduced the cosal dissection of gastric cancer. Dig Endosc 2011; 23: 176–
additional administration and total administered dose of 81.
sedatives, as well as the frequency of SpO2 decrease.6–8 6 Lee BS, Ryu J, Lee SH et al. Midazolam with meperidine and
Based on these reports, dexmedetomidine hydrochloride dexmedetomidine vs. midazolam with meperidine for sedation
was shown to have superior sedation effects during during ERCP: Prospective, randomized, double-blinded trial.
endoscopy (particularly with ESD and ERCP, which Endoscopy 2014; 46: 291–8.
requires over 30 min for the procedure) without increasing 7 Sethi P, Mohammed S, Bhatia PK et al. Dexmedetomidine
respiratory suppression. versus midazolam for conscious sedation in endoscopic
retrograde cholangiopancreatography: An open-label ran-
However, there are a number of drawbacks to dexmedeto-
domised controlled trial. Indian J Anaesth 2014; 58: 18–24.
midine hydrochloride. Side effects influencing circulatory
8 Lu Z, Li W, Chen H et al. Efficacy of a dexmedetomidine-
dynamics (e.g., bradycardia, hypotension) can occur due to remifentanil combination compared with a midazolam-rmifen-
sympathetic nerve blocking effects,9 and dexmedetomidine tanil combination for conscious sedation during therapeutic
hydrochloride-administered groups were shown to have a endoscopic retrograde colangio-pancreatography: A prospec-
higher frequency of hypotension and bradycardia during tive, randomized, single-blinded preliminary trial. Dig Dis Sci
ERCP and esophageal/gastric ESD; hence, sufficient care 2018; 63: 1633–40.
must be given to circulatory dynamics during drug admin- 9 Venn RM, Grounds RM. Comparison between dexmedeto-
istration.2,10,11 The administration method is also somewhat midine and propofol for sedation in the intensive care unit:
complicated, requiring a 10 min initial loading period; Patient and clinician perceptions. Br J Anaesth 2001; 87: 684–
furthermore, single drug administration can destabilize 90.
10 Nonaka T, Inamori M, Miyashita T et al. Feasibility of deep
circulatory dynamics,12 and it has a higher cost than other
sedation with a combination of propofol and dexmedeto-
drugs.
midine hydrochloride for esophageal endoscopic submucosal
The databases used for this reference extraction were dissection. Dig Endosc 2016; 28: 145–51.
PubMed, Cochrane Library database, and Japan Medical 11 Nonaka T, Inamori M, Miyashita T et al. Can sedation using a
Abstract Society. A search using the keywords “dexmedeto- combination of propofol and dexmedetomidine enhance the
midine”[MeSH Terms] AND “sedation”[TIAB] AND “en- satisfaction of the endoscopist in endoscopic submucosal
doscopy”[MeSH Terms] NOT “bronchoscopy”[MeSH dissection?Endosc Int Open 2018; 6: E3–10.
12 Muller S, Borowics SM, Fortis EA et al. Clinical efficacy of have indicated flumazenil administration to be effective in
dexmedetomidine alone is less than propofol for conscious greatly reducing patient observation time following exam-
sedation during ERCP. Gastrointest Endosc 2008; 67: 651–9. ination.7 As regards the timing of flumazenil administration,
trials comparing two groups where the drug was adminis-
CQ 20: Is the use of antagonists tered immediately after or 15 min after endoscopy showed
recommended for sedation/pain relief cases? that the latter group had higher patient satisfaction.8 This
suggests that flumazenil administration was effective not
Statement 20: only in the prompt elimination of respiratory suppression
but also in the prompt recovery from sedation or amnesia.
Issues relating to flumazenil use involve the possibility of
The use of flumazenil and naloxone hydrochloride is requiring re-sedation due to flumazenil having a shorter
recommended as antagonists for respiratory suppression duration of action than that of midazolam1–3 and patients
induced by benzodiazepine drugs and opioid analgesics, sometimes having convulsive or anxiety attacks (for those
respectively. who take anti-anxiety medication) due to flumazenil
Assessment based on the modified Delphi method: administration.3
median, 8; minimum, 5; maximum, 9 Naloxone hydrochloride is an opioid receptor antagonist,
Strength of recommendation: 2, Evidence quality which is metabolized in the liver into naloxone-3-glu-
(strength): B curonide, and it can diminish or eliminate sedation,
respiratory suppression, delayed gastric discharge, papilla
sphincter muscle contraction, and analgesic effects by
expressing its opioid receptor antagonist effects.9 Issues
Textual explanation relating to naloxone hydrochloride use involve eliciting
acute withdrawal syndrome in opioid-dependent patients
Flumazenil is a benzodiazepine antagonist and is effective and inducing hypertension, tachycardia, ventricular fibrilla-
in avoiding respiratory suppression induced by benzodi- tion, pulmonary edemas, hyperventilation, nausea, vomiting,
azepine drugs under emergency situations and the early and convulsions, and naloxone hydrochloride itself can
confirmation of PS during patient arousal. Antagonist induce respiratory suppression and sedation.9 Arbitrary use
effects against respiratory suppression induced by mida- of naloxone hydrochloride is not recommended since its
zolam are expressed in 120 s of intravenous injections of adverse effects can be potentially life-threatening.
flumazenil, immediately reducing and eliminating respira- The databases used for this reference extraction were
tory suppression.1–3 However, flumazenil has a short PubMed, Cochrane Library database, and Japan Medical
duration of action due to its prompt metabolism in the Abstract Society. A search using the keywords (“en-
liver, necessitating re-sedation. doscopy” or “digestive system”) and (“sedation” or “anal-
When flumazenil or a placebo was administered in 50 gesia”) and (“antagonist” or “reversal agent” or “flumazenil”
patients who underwent upper endoscopy examinations or “naloxone”) and (“usefulness” or “utility” or “availabil-
under midazolam-based sedation, significant improvements ity”) yielded 132 articles, of which nine were meta-analyses/
in memory, psychomotor functions, and regulatory functions systematic reviews/clinical guidelines, 59 were clinical
were seen in the flumazenil-administered patients 5 min trials, 52 were miscellaneous clinical research/epidemiolog-
after its administration, but no differences were seen ical research, and 12 were controlled trials. After manual
between the two groups during re-assessments after searching added three articles (including RCTs), screening
3.5 h.4 When flumazenil or a placebo was administered results yielded nine related references, including seven
10 min after the end of upper GI endoscopy examination, RCTs and one meta-analysis.
the duration of recovery room stay was significantly shorter
in the flumazenil-administered group, but there were no
significant differences in other factors (satisfaction, treat- REFERENCES
ment memory, psychological status, discomfort on the day 1 Carter AS, Bell GD, Coady T et al. Speed of reversal of
of the procedure and the following day, all based on the midazolam-induced respiratory depression by flumazenil-a
pain/visual analog scale (VAS)) between the two groups.5 study in patients undergoing upper GI endoscopy. Acta
Flumazenil has been shown to have stronger antagonistic Anaesthesiol Scand Suppl 1990; 92: 59–64.
effects against benzodiazepine-based sedation and amnesia 2 Saletin M, Malchow H, M€ uhlhofer H et al. A randomized
rather than against respiratory suppression,6 and reports controlled trial to evaluate the effects of flumazenil after
midazolam premedication in outpatients undergoing colono- 6 Mora CT, Torjman M, White PF. Sedative and ventilatory
scopy. Endoscopy 1991; 23: 331–3. effects of midazolam infusion: Effect of flumazenil reversal.
3 Kankaria A, Lewis JH, Ginsberg G et al. Flumazenil reversal Can J Anaesth 1995; 42: 677–84.
of psychomotor impairment due to midazolam or diazepam for 7 Chang AC, Solinger MA, Yang DT et al. Impact of flumazenil
conscious sedation for upper endoscopy. Gastrointest Endosc on recovery after outpatient endoscopy: a placebo-controlled
1996; 44: 416–21. trial. Gastrointest Endosc 1999; 49: 573–9.
4 Andrews PJ, Wright DJ, Lamont MC. Flumazenil in the 8 Chung HJ, Bang BW, Kim HG et al. Delayed flumazenil injection
outpatient. A study following midazolam as sedation for upper after endoscopic sedation increases patient satisfaction.ction
gastrointestinal endoscopy. Anaesthesia 1990; 45: 445–8. compared with immediate flumazenil injectionGut. Liv. 2014; 8:
5 Lee SP, Sung IK, Kim JH et al. Efficacy and safety of 7–12.
flumazenil injection for the reversal of midazolam sedation 9 Gowing L, Ali R, White JM. Opioid antagonists under heavy
after elective outpatient endoscopy. J Dig Dis 2018; 19: 93– sedation or anesthesia for opioid withdrawal. Cochrane
101. Database Syst Rev 2010; 20: CD002022.