| Study characteristics |
| Methods |
Multi‐centre randomised placebo‐controlled trial |
| Participants |
898 preterm (23 to 32 weeks) babies intubated within 72 hours of birth and ventilated for < 8 hours at enrolment
Exclusion criteria: major congenital anomalies, asphyxia, intrauterine growth retardation, maternal opioid addiction, participation in other clinical trials |
| Interventions |
Morphine group (n = 449): loading dose 100 mcg/kg followed by infusion of 10, 20, or 30 mcg/kg/hour for infants of gestational ages 23 to 26, 27 to 29, and 30 to 32 weeks, respectively
Placebo group (n = 449): additional analgesia with morphine bolus doses was allowed |
| Outcomes |
Primary outcomes: a composite of neonatal death, grade III/IV IVH, and PVL
Secondary outcomes: pain response to tracheal suctioning (assessed by PIPP) ‐ scores were assessed before start of treatment, after 24 and 72 hours of infusion, and at 12 hours after treatment was discontinued; days of ventilatory support; days of oxygen supplementation; days to full volume feeding |
| Notes |
Data on PIPP scores, duration of ventilation, days to reach full enteral feeding were obtained by personal communication with the study author |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Randomisation was performed by an automated procedure, stratified by centre and groups of gestational age at birth |
| Allocation concealment (selection bias) |
Low risk |
Allocation concealment was ensured by an automated telephone response system |
| Blinding of participants and personnel (performance bias) |
Low risk |
Caregivers were blinded to treatment |
| Blinding of outcome assessment (detection bias) |
Low risk |
Assessors were blinded to treatment |
| Incomplete outcome data (attrition bias) |
Low risk |
Outcomes were reported for all patients enrolled |
| Selective reporting (reporting bias) |
Unclear risk |
Trail not registered; protocol not available |
| Other bias |
Low risk |
Study appears to be free of other sources of bias |
