Sedation in gastrointestinal endoscopy: Current issues

Table 1 Percentage of sedation use in different countries

Country	Sedation	Propofol use	Benzodia-zepines alone use	Benzodiaze-pines plus opioids use	No. of nurses present during endoscopy	Pulse oximetry use	Supplemental oxygen use
Canada	90%	12%		always	1
Italy		42.30% for ERCP (by anaesthesiologists)	50.80%	39.50%		100%	By 39.3% of endoscopists
Greece	EGD: 64%; Colonoscopy: 78%; ERCP: 100%; EUS: 100%	33.80% (in selected cases and only by anaesthesiologists)	35.30%	62.10%		96%
United States	98%	25.70%		74.30%		98.60%	By 72.7% of endoscopists (in all EGDs)
Switzerland	78%	43% (regular use with or without the help of an anaesthesiologist)	Midazolam for the majority of endoscopies		1	95%
Spain	EGD: 20%; Colonoscopy: 20%; ERCP: 100%; EGD: 74%	Only by anaesthesiologists	Only for EFD	Only for colonoscopies	1	77%
Germany	Colonoscopy: 87%	74%	82%	35%		97%	34%

ERCP: Endoscopic retrograde cholangiopancreatography; EGD: Esophagogastroduodenoscopy; EUS: Endoscopic ultrasound; EFD: Energy flux density.

Table 2 Characteristics of the pharmacological agents used to achieve a moderate level of sedation in gastrointestinal endoscopy (i.v. administration)¹

Agent	Chemical structure	Molecular weight (g/moL)	Onset of action (min)	Duration of action	Elimination half-life	Metabolism/excretion
Midazolam	C18H13ClFN3	325.78	1.0-2.5	2-6 h	1.8-6.4 h	Hepatic and intestinal; excreted in urine
Propofol	C12H18O	178.27	< 1	3-10 min	Triphasic: 2.2 min, 20 min, 8 h	Hepatic; excreted in urine
Fentanyl	C22H28N2O	336.471	≤ 1.5	1-2 h	2-7 h	Hepatic; excreted in urine
Meperidine	C15H21NO2	247.33	5	2-4 h	2-7 h	Hepatic; excreted in urine

¹Modified from Manolaraki et al[14].

Table 3 Currently used drugs for sedation and drugs under investigation

Drugs currently used for sedation	Drugs and other practices under investigation
Midazolam	Nitrous oxide gas (N2O)
Fentanyl	Remimazolam
Propofol	Fospropofol
	Dexmedetomidine
	Alfentanyl
	Remifentanil
	Music

Table 4 Main adverse events related to sedation occurring during endoscopy in clinical trials

Ref.	Drug regimen	Percentage of side effects	Severe hypotension (< 60 mmHg)	Severe desaturation (< 90%)
Ljubicić et al[98]	Propofol	17.3% (including bradycardia: 11.8%)		5.5%
Conigliaro et al[95]	Midazolam	0.47%
Gasparović et al[28]	Propofol	2.9%	0.5%	2.4%
Sharma et al[97]	Cardiopulmonary events	EGD: 0.6%; Colonoscopy: 1.1%;ERCP: 2.1%; EUS: 0.9%
Nayar et al[96]	Propofol deep sedation vs moderate sedation	0.6% vs 1.0%	0.1%	0.1% (apnoea: 0.3%)
Correia et al[69]	Midazolam plus propofol vs midazolam plus fentanyl	14% vs 7.3%
Amornyotin et al[87]	Diluted vs undiluted propofol for deep sedation	18.2% vs 42.9%	11.4% vs 31.0%	0 vs 2.4%
Wang et al[32]	Midazolam vs midazolam combined with either fentanyl or propofol		Midazolam combined with propofol resulted in hypotension and bradycardia more significantly than a combination with fentanyl or midazolam alone

EUS: Endoscopic Ultrasound; EGD: Esophagogastroduodenoscopy; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 5 Side effects related to the administration of drugs used for sedation in gastrointestinal endoscopy

Side effect	Midazolam	Propofol	Fentanyl
Hypotension	Yes	Yes
Hypertension		Yes
Heart rate alterations	Arrhythmia	Decrease	Arrhythmia
Respiratorydepression	Yes	Yes	Yes (particularly in the elderly)
Apnoea	Yes (in combination with fentanyl)	Yes	Yes (in combination with Midazolam)
Dystonia		Yes	Yes
Priapism		Yes	Yes (very rarely)
Pain on injection		Yes
Lactic acidosis		Yes
Intraocular pressure changes		Decrease
Myoclonic movements		Yes
Nervous system side effects	Yes (especially in the elderly)	Rare	Yes
Unusual dreams		Yes
Hypersensitivity	Yes	Yes	Yes (rarely)
Liver damage		Yes
Amnesia	Yes
Impairment of cognitive functions - inability to drive safely	Yes
Paradoxical behaviour	Yes	Yes
Gastrointestinal effects (nausea, vomiting, hiccups, diarrhoea)	Yes	Yes	Yes
Sexual disinhibition	Yes
Potential for abuse			Yes
Haemolysis			Yes (slow injection rates and/or mixture in isotonic fluid)