| Study characteristics |
| Methods |
Single‐centre double‐blind randomised controlled trial |
| Participants |
163 babies mechanically ventilated during the first day of life fulfilled study entry criteria: 24 weeks' or longer GA, estimated duration of MV ≥ 1 day, with indwelling arterial line
Exclusion criteria: chromosomal aberrations; major anomalies |
| Interventions |
Fentanyl group (n = 83): loading dose of 10.5 mcg/kg in 1 hour, followed by maintenance rate of 1.5 mcg/kg/hour for ≥ 24 hours
Morphine group (n = 80): loading dose of 140 mcg/kg in 1 hour, followed by maintenance dose of 20 mcg/kg/hour for ≥ 24 hours
Additional analgesia with opioid boluses was allowed. The bolus, equal to a 1‐hour maintenance infusion dose, could be given 4 times a day at the most. Muscle relaxation could be used if the infant was struggling against the ventilator despite analgesia |
| Outcomes |
Primary outcome (used for sample size calculation): gastrointestinal motility and urinary retention
Secondary outcomes: duration of MV; beginning of enteral feeding (days); duration of opioid infusion (hours); administration of opioid boluses; pancuronium relaxation; surfactant treatment; RDS; infection; PPHN; NEC; IVH (grades 3 + 4); mortality; severity of pain assessed with (i) physiological parameters (heart rate, arterial blood pressure, and oxygen saturation); (ii) behavioural pain responses before, during, and after tracheal suction assessed with a pain score adapted from the Neonatal Infant Pain Scale of the Children´s Hospital of East Ontario Pain Scale; (iii) stress hormone concentrations (noradrenaline, adrenaline, and beta‐endorphin) before and 2 and 24 hours after the start of treatment |
| Notes |
Power calculation was made on urinary retention and decreased gastrointestinal motility |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Infants were randomised in 5 blocks with closed envelopes. Sequence generation was not specified |
| Allocation concealment (selection bias) |
Unclear risk |
Allocation concealment was not specified |
| Blinding of participants and personnel (performance bias) |
Low risk |
Carers were blinded |
| Blinding of outcome assessment (detection bias) |
Low risk |
Assessors were blinded |
| Incomplete outcome data (attrition bias) |
Low risk |
2 infants in the fentanyl group did not receive the infusion; their data are included in an ITT analysis. Data on plasma catecholamine and endorphin levels were not available for all infants; however loss to follow‐up seems similar in the 2 groups |
| Selective reporting (reporting bias) |
Unclear risk |
Trial not registered; protocol not available |
| Other bias |
Low risk |
Study appears to be free of other sources of bias |
