Review on sedation for gastrointestinal tract endoscopy in children by non-anesthesiologists

Table 1 Publications from the first search (“endoscopy, gastrointestinal”, “endoscopy, digestive system” AND “sedation”, “conscious sedation”, “moderate sedation”, “deep sedation”, and “hypnotics and sedatives”; limits: publications in English, paediatric population

Ref.	Methodology	Results	Limitations	Conclusions
Bedirli et al[3]	Study type: prospective, randomised, double-blinded Patients: N = 80; 1–16 yr; ASA I, II Procedure: upper GI endoscopy Drugs: baseline: propofol (1 mg/kg; additional 0.5–1 mg/kg as needed); intervention: fentanyl (2 μg/kg) vs tramadol (2 mg/kg) Intended sedation level: deep sedation Additional interventions: spray of lidocaine 10%; infusion of 10 lactated Ringer’s solution (10 mL/kg per hour); supplemental oxygen 3–4 L/min) Administered by: anesthesiologist Outcome measures: Adverse events: HR (change for 20% from the baseline), BP (change for 20% from the baseline), SpO2 (< 90% for more than 15 s), respiratory rate, agitation score Effectiveness: Ramsey sedation score, duration of endoscopy, Steward recovery score, endoscopist’s rating of ease of procedure, total propofol consumption	Adverse events: self-limited bradycardia and transient desaturation in age group 0–2 yr, more in the fentanyl group Effectiveness: lower sedation scores in tramadol group; no difference of gastroenterologist rating	Only one dosage of drugs instead of titrating them	Propofol with tramadol or propofol provided efficient sedation; significantly less adverse effects in the tramadol group
Brecelj et al[4]	Study type: randomized, controlled, single-blinded Patients: N = 201; 1–18 yr Procedure: gastroscopy, colonoscopy Drugs: ketamine (0.75 mg/kg with additions of 0.25 mg/kg up max. to 1.5 mg/kg; repeated after 10–15 min at 0.5 mg/kg as needed) Intervention: midazolam (0.1 mg/kg; max 2.5 mg; repeated after 30–60 min at 0.05 mg/kg as needed) vs no premedication Intended sedation level: deep sedation Additional interventions: none Administered by: dedicated nurse under supervision of endoscopist Outcome measures: Adverse events: respiration rate, HR, BP, SaO2 (any drop below 92%), adverse reactions Effectiveness: ease of procedure, total ketamine consumption	Adverse events: mild self-limited laryngospasm in 3%, high rate of desaturations (approx. in 40%), vomiting in 17%, regardless of study group; more emergence reactions in ketamine group during recovery (10 vs 2) Effectiveness: high rate of sedation adequacy	Study was not double-blinded	Ketamine starting dose should be at least 1 mg/kg; more emergence reactions without midazolam premedication; same frequency of other adverse reactions
Miqdady et al[5]	Study type: retrospective cohort study Patients: N = 301; 1 (more than 10 kg) –18 yr; ASA I, II Procedure: upper, lower or combined GI endoscopy Drugs: atropine (0.01–0.02 mg/kg per minute. 0.1 mg, max. 0.4 mg); midazolam (0.05–0.2 mg/kg); ketamine (0.5–1 mg/kg) Intended sedation level: deep sedation Additional interventions: none Administered by: endoscopist Outcome measures: Adverse events: respiration rate, HR, BP, SaO2 (any drop below 94%), side effects Effectiveness: the adequacy of sedation	Adverse events: desaturation in 12.3%, in 1.2% disruption of examination due to persistent desaturation; in 1.2% respiratory distress after examination Effectiveness: effective and uneventful sedation in 79.4%	Retrospective study	Midazolam and ketamine sedation is safe and effective for diagnostic GI endoscopies in children older than 1 yr weighting more than 10 kg without comorbidities
Motamed et al[6]	Study type: prospective, randomised, double-blinded Patients: N = 150; 1–18 yr; ASA I, II Procedure: upper GI endoscopy Drugs: main sedative: midazolam (0.1 mg/kg; if needed repeated doses up to 5 mg or 0.3 mg/kg); premedication 45 min before the procedure with oral placebo (normal saline), oral ketamin (5 mg/kg), or oral fentanyl (2 μg/kg) Additional interventions: spray of lidocaine 10%; additional oxygen trough nasal cannula at 2 L/min Administered by: registered nurse supervised by anaesthesiologist Outcome measures: Adverse events: respiration rate, HR (decrease by 30% from baseline), BP (decrease or increase by 20%), SaO2 (any drop below 90%) Effectiveness: total midazolam dose, modified Ramsey sedation score, procedure time, discharge time, ease of iv catheter placement, separation from parents agitation, the adequacy of sedation	Adverse events: in total in 26% of patients (hypoxia in 7.3%, hypotension in 6.7%, dizziness in 20%, nausea in 10%, vomiting in 17.6%); mild, easily managed Effectiveness: the total recovery and procedure duration time was shorter in the ketamine-midazolam group, inadequate sedation in 10.2% in placebo-midazolam and in 8% in fentanyl-midazolam vs in 3.9% in ketamine-midazolam group; the mean administered dose of midazolam was the lowest in ketamine-midazolam group; the iv line placement and separation from parents was easier in ketamine-midazolam group; only 27.4% of patients did not remember the procedure		Sedation with oral ketamine-iv midazolam is better than placebo-midazolam or oral fentanyl-iv midazolam
Chiaretti et al[7]	Study type: retrospective (12 yr), multicentric Patients: N = 36516; 1 to > 10 yr; ASA I, II, III Procedure: different painful procedures Drugs: main sedative: propofol 2 mg/kg in children from 1 to 8 yr of age and 1 mg/kg in older children and in children younger than 1 yr; further doses of 0.5–1.0 mg/kg in the case of agitation or complain; premedication: atropine 0.010–0.015 mg/kg, ketamine (0.5 mg/kg) to avoid infusion pain in 2 centres (not in gastroscopy); additional oxygen trough nasal cannula at 6 L/min Intended sedation level: deep sedation Administered by: paediatrician (anaesthesiologist available in case of need) Outcome measures: mean arterial pressure, heart rate and SatO2, incidence, type and timing of adverse events (major and minor) and number of calls to the emergency team Effectiveness: total dosage of the sedative agents, level of sedation (Ramsay scale)	Adverse events: in 6 patients (0.02%) emergency team intervention (prolonged laryngospasm in 3 patients, bleeding in 1, intestinal perforation in 1, and 1 during lumbar puncture); milder adverse events: hypotension in 19 patients (0.05%), ventilation by face mask and additional oxygen in 128 patients (0.4%), laryngospasm in 78 patients (0.2%), bronchospasm in 15 patients (0.04%); minor complications more often in children who underwent gastroscopy; none of the children experienced severe side effects or prolonged hospitalisation.	Retrospective study	Propofol is safe and effective for paediatrician-administered procedural sedation in children; appropriate training for paediatricians is important
Gül et al[8]	Study type: randomized, controlled, double-blinded Patients: N = 64; 3-14 yr; ASA I Procedure: esophagogastroduodenoscopy Drugs: main sedative: propofol 2 mg/kg; analgesic: group R: remifentanil 0.25 μg/kg, group F: fentanyl 0.5 μg/kg; additional oxygen trough nasal cannula at 4 L/min Intended sedation level: deep sedation Administered by: anesthesiologist Outcome measures: MAP, HR, RR, and SpO2 Effectiveness: ease of gastroscopy, patient’s movements during procedure, additional doses of drugs; level of sedation (Ramsay scale); duration of PACU stay	Adverse events: prolonged apnoea in 14 (43.8%) children in group R and in 11 (33.3%) children in group F; none required endotracheal intubation; Effectiveness intraoperative respiratory rate, time to eye opening, opioid consumption, and duration of recovery were significantly shorter in group R duration of PACU stay were significantly shorter in group R than in group F		Remifentanil (combined with propofol) is an efficient and as safe as fentanyl propofol combination for esophagogastroduodenoscopy in children
Long et al[9]	Study type: retrospective analysis of prospectively collected data Patients: N = 4904; 15-90 yr; ASA I-IV Procedure: esophagogastroduodenoscopy Drugs propofol 1-100 mg and/or midazolam 1-3 mg2 mg/kg Administered by: endoscopist Outcome measures: influence of pre-existing disease and ASA score on oxygen desaturation (SpO2) < 90%	Adverse events: hypoxemia in 245 patients (5%); risk factors: high BMI (30 kg/m2), hypertension, diabetes, gastrointestinal disease, heart disease ASA score was not predictive for hypoxemia	Retrospective study	Independent risk factors for hypoxemia were high BMI, hypertension, diabetes, gastrointestinal and heart diseases and combined gastro and colonoscopy
Agostoni et al[10]	Study type: retrospective analysis of prospectively collected data Patients: N = 17999 (17524 in older than 12 yr, 457 in < 12 yr); 4-74 yr; ASA I-IV Procedure: esophagogastroduodenoscopy and in some cases different procedures (mucosectomy, hemostatic clip, percutaneous endoscopic gastrostomy, …) Drugs: propofol induction (in children 1-2 mg/kg BW) then in continous infusion Intended sedation level: deep sedation Administered by: anesthesiologist Outcome measures: adverse events (hypotension, desaturation, bradycardia, hypertension, arrhythmia, aspiration, respiratory depression, vomiting, cardiac arrest, respiratory arrest, angina, hypoglycemia, and/or allergic reaction)	Adverse events: rare in children (2.6%) and in adults (4.5%), in children were more often only bradycardia (2.1%) and hypotension (0.44%) 3 adult patients died; no death case in children	Retrospective analysis, single centre data	Deep sedation with intravenous propofol for endoscopic procedures is safe in children and adults

ASA: American Society for Anesthesiology; BP: Blood pressure; GI: Gastrointestinal; HR: Heart rate; SpO2: Oxygen saturation; BMI: Body mass index; RR: Respiratory rate.

Table 2 Gastrointestinal endoscopy sedation guidelines for adults

OrganisationRef.	Title	Year of publication
American Association for the Study of Liver Diseases; American College of Gastroenterology; American Gastroenterological Association Institute; American Society for Gastrointestinal Endoscopy; Society for Gastroenterology Nurses and Associates Vargo et al[16]	Multisociety sedation curriculum for GI endoscopy	2012
Task Force Members. European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates, and the European Society of Anaesthesiology Dumonceau et al[17]	Guideline: Non-anesthesiologist administration of propofol for GI endoscopy	2010
Society of American Gastrointestinal Endoscopic Surgeons Heneghan et al[18]	Surgeons. Society of American Gastrointestinal Endoscopic Surgeons guidelines for office endoscopic services	2009
Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy Lichtenstein et al[19]	Sedation and anesthesia in GI endoscopy	2008
Training Committee of the American Society for Gastrointestinal Endoscopy Vargo et al[20]	Training in patient monitoring and sedation and analgesia	2007
Working Group on Endoscopy, Austrian Society of Gastroenterology and Hepatology (OGGH) Schreiber[21]	Austrian Society of Gastroenterology and Hepatology (OGGH)-guidelines on sedation and monitoring during GI endoscopy	2007
Training Committee American Society for Gastrointestinal Endoscopy[22]	Training guideline for use of propofol in gastrointestinal endoscopy	2004
American Society for Gastrointestinal Endoscopy, Standards of Practice Committee Waring et al[23]	Guidelines for conscious sedation and monitoring during GI endoscopy	2003
Standards Practice Committe American Society for Gastrointestinal Endoscopy Faigel et al[24]	Guidelines for the use of deep sedation and anesthesia for GI endoscopy	2002

GI: Gastrointestinal.

Table 3 Paediatric procedural sedation guidelines

OrganisationRef.	Title	Year ofpublication
Green et al[28]	Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update	2011
National Clinical Guideline Centre (United Kingdom)[26]	Sedation in children and young people: Sedation for diagnostic and therapeutic procedures in children and young people	2010
American Academy on Pediatric Dentistry Clinical Affairs Committee-Sedation and General Anesthesia Subcommittee; American Academy on Pediatric Dentistry Council on Clinical Affairs[29]	Guideline on use of anesthesia personnel in the administration of office-based sedation/general anesthesia to the pediatric dental patient	2009
American Academy on Pediatrics; American Academy on Pediatric Dentistry[30]	Guideline for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures	2009
American Academy of Pediatrics; American Academy of Pediatric Dentistry Coté et al[25]	Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update	2006
American Academy on Pediatric Dentistry Clinical Affairs Committee-Sedation and General Anesthesia Subcommittee; American Academy on Pediatric Dentistry Council on Clinical Affairs[31]	Guideline on use of anesthesia care providers in the administration of in-office deep sedation/general anesthesia to the pediatric dental patient	2005
American Academy of Pediatric Dentistry	Guideline on the elective use of minimal, moderate, and deep sedation and general anesthesia for pediatric dental patients	2005
American Academy of Pediatric Dentistry Committee on Sedation and Anesthesia[15]
American Academy of Pediatric Dentistry[32]	Clinical guideline on the elective use of minimal, moderate, and deep sedation and general anesthesia for pediatric dental patients	2004
Green et al[27,28]	Clinical practice guideline for emergency department ketamine dissociative sedation in children	2004
UK National Clinical Guidelines in Pediatric Dentistry Hosey[33]	UK National Clinical Guidelines in Paediatric Dentistry. Managing anxious children: the use of conscious sedation in paediatric dentistry	2002

Table 4 Preparation of a child for sedation for gastrointestinal endoscopy

	Preparation of the patient	Comments
Planning of the investigation /procedure	Understanding of the investigation	Explanation of the examination: Aims of investigation Possible risks
	Informed consent	Signed by parents and/or the child (depending on the age and legislation)
	Presedation assessment	Co-morbidity ASA score (Table 5) Medicines Bleeding tendency Previous undesirable effects of sedation/anesthesia Specific contraindications for the planned sedation Previous complications of investigations Allergies The need for antibiotic prophylaxis Laboratory investigation/consultation before the investigation/procedure (e.g., tests of hemostasis in case of bleeding tendency) Additional important data
Preparation	Exact instructions (fasting time, colon cleansing etc.)
On the day of examination	Focused history: Current health state Infectious diseases Epidemiologic situation Fasting Allergy Specific contraindications for the planned sedation
	Physical examination	Complete physical examination with the focus on respiratory and cardiovascular system
	Measurement of vital signs	Arterial blood pressure Heart rate Arterial oxygen saturation
	Laboratory investigations	If needed

ASA: American Society for Anesthesiology.

Table 5 American Society of Anesthesiologists physical status classification[24]

Class	Description	Suitability for sedation
Class I	A normally healthy patient	Excellent
Class II	A patient with mild systemic disease (e.g., controlled asthma)	Generally good
Class III	A patient with severe systemic disease (e.g., a child who is actively wheezing)	Intermediate to poor
Class IV	A patient with severe systemic disease that is a constant	Poor
	threat to life (e.g., a child with status asthmaticus)
Class V	A moribund patient who is not expected to survive without the operation (e.g., a patient with severe cardiomyopathy requiring heart transplantation	Extremely poor

Table 6 Sedatives and adjuvant medicines for paediatric gastrointestinal endoscopy sedation

Generic name	Mechanism(s) of action	Main undesirable effects	Comments	Ref.
Sedatives
Fentanyl	Opioid receptors agonist; analgesia and sedation	Respiratory depression, hypotension	Due to analgesic effect only it should be combined with benzodiazepine; antagonist naloxone	[38-40]
Ketamine	Binds to the NmethylDaspartate (NMDA) receptors; anesthesia, analgesia, amnesia, sedation, immobilisation	Laryngospasm, hypertension, tachycardia, hypersalivation, vomiting, random movements, increase in intraocular pressure, emergence phenomena (floating sensations, vivid dreams, blurred vision, hallucinations, and delirium)	Beneficial respiratory properties and analgesic potency S(+) isomer has less adverse effects	[40-42]
Meperidine	Opioid receptors agonist; analgesia and sedation	Respiratory depression, pruritus, vomiting	Interaction with monoamine oxidase inhibitors	[38,43,44] [38-40]
Midazolam	GABA receptor agonist; anterograde amnesia, anxiolysis, sedation, hypnosis	Respiratory depression, hypotension, paradoxical agitation	Without analgesic effect; should be combined with analgesic (usually opioids)
			Concomitant use with opioid increases the risk of respiratory depression antagonist flumazenil
Nitrous oxide	Inhalation anaesthetic	Vomiting, dizziness, voice change, euphoria, laughter	The need of scavenging system Use mostly limited to anaesthesiologists	[38,40,45]
Propofol	GABA receptor agonist; sedation, hypnosis, amnesia	Respiratory depression, apnoea, hypotension, painful injection		[38,40,46]
Sevoflurane	Inhalation anaesthetic	Recovery agitation, bradycardia, hypotension, cough, vomiting, seizures	The need of scavenging system Use limited to anaesthesiologists	[47-49]
Antagonists
Flumazenil	Benzodiazepine antagonist	Nausea, vomiting	Contraindicated in benzodiazepine dependence, seizure disorder, cyclic antidepressant overdose, elevated intracranial pressure in patients, and in patients taking medicines known to lower the seizure threshold	[40]
Naloxone	Opioid antagonist	Nausea, vomiting, tachycardia		[40]

Table 7 The list of sedatives/analgesic, adjuvant medicines and antagonists with usual dosage regimens, and main contraindications

Medicine generic name	Route	Dose	Time to start sedation/analgesia (after iv application)	Sedation/analgesia duration	Repeating time and dose	Contraindications	Comments	Ref.
Sedative/analgesic
Fentanyl	iv	1–2 μg/kg (up to 50 μg)	0.5 s	20–40 min (30–60 min)	3 min 1–1.25 μg/kg		Due to higher clearance younger children need frequent dosing	[38,40]
Ketamine	iv slowly over 1 min; other routes have less predictive effects and different dosing – see the discussion	1–1.5 mg/kg	1–5 min	15 min	10 min	Severe cardiovascular disease, malignant hypertension, CSF obstructive states (controversial), intraocular pressure pathology; previous psychotic illness, hyperthyroidism or thyroid medicine use; porphyria	A single enantiomer S(+);	[8,40-42]
					0.5 mg/kg		the anesthetic management of seriously ill hypovolemic patients, it may be the agent of choice for managing children and burned patients; low cost
Meperidine	iv slowly over 1–2 min	0.3–2 mg/kg	3–6 min	60–180 min		Simultaneous treatment with monoamine oxidase inhibitors		[38,43,44]
Midazolam	iv slowly over 2–3 min; other routes have less predictive effects and different dosing	0.05–0.1 mg/kg in < 5 yr (max. 0.6 mg/kg); in 6–12 yr 0.025–0.05 mg/kg (max.0.4 mg/kg); in older than 12 yr 2–2.5 mg (in total not per kg BW)	2–3 min	45–60 min	Repeating doses every 2–5 min until desired effect; in children 6 mo–5 yr total dose up to 0.6 mg/kg or max. 6 mg; in 6–12 yr total dose up to 0.4 mg/kg or max. 10 mg; in older than 12 yr additional boluses of 1 mg until desired sedation	Respiratory depression, hypotension	Rarely used as a sole sedative; might be used to sedate the frightened child before iv catheter placement; mostly combined with opioids; paradoxical irritation in 1%–5% of patients	[38-40]
Nitrous oxide	Inhalation	Mostly the mixture of nitrous oxide (50%) and oxygen	0.5–1 min	5 min	Continuously or “on demand”	Pneumothorax, bowel obstruction, head injury, pregnancy	Its use limited to anaesthesiologists	[38,40,45]
Propofol	iv	2 mg/kg in infants and young children (younger than 3 yr); 1 mg/kg in children older than 3 yr	1–2 min	5–15 min	1 mg/kg (infants and children up to 3 yr); 0.5 mg/kg (children older than 3 yr) to reach the desired sedation; may be continuously infused at 100 μg/kg per min and increasing the speed of infusion by 50 μg/kg per min for prolonged procedures	Egg or soy allergy	For additional medication to alleviate infusion pain see text; alfentanil but not fentanyl increases propofol blood level; in many countries the use is limited to anaesthesiologists	[38,40,46]
Sevoflurane	Inhalation	Different concentrations according to the age				Duchenne’s muscular dystrophy, moderate to severe liver disease of unknown aetiology, history of malignant hyperthermia	Its use limited to anaesthesiologists	[47-49]
Antagonists
Flumazenil	iv	0.02 mg/kg (max. 1 mg)	1–3 min	30 min	1 min; same dose	Chronic benzodiazepine use; ingestion of drugs that increase the risk for seizures development (e.g., cyclic antidepressants, cyclosporine, and others)	Due to its shorter duration of action than most of benzodiazepines (e.g., midazolam) repeated doses may be needed	[38,40]
Naloxone	iv or i.m.	0.1 mg/kg (max. 2 mg)	2 min	20–40 min	2 min; same dose	Hypersensitivity only	Due to its shorter duration of action than most of opioids (e.g., fentanyl) repeated doses may be needed	[38,40]