Ceelie 2013

Methods	Randomised controlled trial
Participants	71 neonates or infants; PMA of 36 1/7 weeks or older to 1 year of age with body weight > 1500 grams undergoing major thoracic (non‐cardiac) or abdominal surgery. We obtained unpublished data on 41 infants who were ≤ 30 days of age and fulfilled our inclusion criteria. These infants are included in our review. Infants were admitted to a level III paediatric intensive care unit in Rotterdam, The Netherlands, between March 2008 and July 2010
Interventions	All participants received a loading dose of morphine 30 minutes before the end of surgery, followed by continuous morphine or intermittent intravenous paracetamol up to 48 hours post surgery. Infants in both study groups received morphine (boluses and/or continuous infusion) as rescue medication on the guidance of the validated pain assessment instruments. Participants were randomly assigned to receive morphine or paracetamol postoperatively. When participants were randomly assigned to receive paracetamol (30 mg/kg per day in 4 doses), a placebo infusion of normal saline was administered continuously at the same rate as an equivalent morphine infusion. When randomly assigned to receive morphine (participants ≤ 10 days of age, 2.5 µg/kg1.5 per hour; participants 11 days to 1 year of age, 5 µg/kg1.5 per hour), normal saline was administered 4 times daily as placebo in a volume similar to the intravenous paracetamol dose
Outcomes	Primary outcome was cumulative morphine dose (study and rescue dose). Secondary outcomes were pain scores and morphine‐related adverse effects
Notes	We wrote to Dr Saskia N de Wildt, and she provided us with unpublished information on 41 infants who were ≤ 30 days of age and fulfilled our inclusion criteria
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A hospital pharmacist carried out computer randomisation in advance
Allocation concealment (selection bias)	Low risk	Only the pharmacist had access to group allocation during the study period, for preparation of study medication
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Only the pharmacist had access to group allocation during the study period, for preparation of study medication. No other information was provided
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All staff were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcomes were reported for all randomly assigned infants
Selective reporting (reporting bias)	Low risk	This study was entered into a trials registry ‐ trialregister.nl Identifier: NTR1438 in The Netherlands. No deviations from the protocol are apparent
Other bias	Low risk	Study appears free of other bias