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.