Bouwmeester 2001.

Study characteristics
Methods	Study design: Double‐blind, randomized clinical trial Study grouping: Continuous morphine versus three‐hourly placebo or intermittent morphine with placebo infusion
Participants	Baseline Characteristics Inclusion criteria: Children aged 0 to 3 years, admitted to the pediatric surgical intensive care unit after non‐cardiac thoracic and abdominal surgery Exclusion criteria: Author excluded patients if they had received analgesic or sedative drugs less than 6 hours before surgery, if they were receiving neuromuscular blockade or if they suffered from hepatic, renal or neurological disorders or altered muscle tone. Pretreatment: Anesthesia was induced with thiopentone or by inhalation of halothane in oxygen. Fentanyl 5 mcg/kg was given before orotracheal intubation, which was facilitated with atracurium 0.5‐1 mcg/kg or suxamethonium 2 mcg/kg.
Interventions	Intervention Characteristics Continuous infusion versus bolus administration Dose regimen: Two groups (continuous morphine versus intermittent morphine) Description of procedure: One group received continuous morphine (10 mcg/kg/h) while the other group received a continuous placebo infusion combined with three‐hourly intravenous doses of 30 mcg/kg. All participants received an intravenous loading dose of morphine (100 mcg/kg).
Outcomes	Pain assessed with validated methods during the administration of selected drugs Outcome type: Continuous outcome Nurses performed regular assessments before surgery (baseline) and every 3 h up to 36 h after surgery. Nursing interventions included pain assessment using a VAS and the COMFORT scale.
Identification	Sponsorship source: The study was supported by the Dutch Research Council and the Sophia Foundation for Medical Research.  Country: The Netherlands Setting: Pediatric Intensive Care Unit Comments: None Authors names: Nancy J. Bouwmeester, K.J.S. Anand, Monique van Dijk, Wim C. J. Hop, F. Boomsma, and Dick Tibboel Institution: Department of Anesthesiology and Pediatric Surgery, Sophia Children's Hospital Email: Not provided Address: Sophia Children's Hospital, University Hospital Rotterdam, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The pharmacists prepared all study drugs, and the strata‐specific schedules for randomization". Computer‐generated
Allocation concealment (selection bias)	Low risk	Clinical staff blinded to allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Pharmacists prepared all study drugs, and the strata‐specific schedules for randomization and the clinical staff were blinded to the study group allocation until data collection was complete." Blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Clinical staff were blinded to the study group allocation until data collection was complete".
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"All enrolled patients were included in an intention‐to‐treat analysis. Nine patients dropped out during the study (five in CM, four in IM) because of the loss of arterial access (seven), the need for neuromuscular blockade (one) and one postoperative death 3 h after surgery." N in the figures did not match the size of each experimental group and reasons were not clearly stated.
Selective reporting (reporting bias)	Unclear risk	No registry stated so unable to compare to protocol
Other bias	Low risk	None