| Study characteristics |
| Methods |
Single‐centre double‐blind randomised placebo‐controlled trial |
| Participants |
60 premature newborns (< 32 weeks' GA) mechanically ventilated in the first 72 hours after birth
Exclusion criteria: serious birth injury; serious malformation; significant parenchymal brain injury (grade IV IVH or PVL); treatment with analgesics or sedatives |
| Interventions |
Fentanyl group (n = 30): intravenous loading dose of 1 mcg/kg in 30 minutes, followed by continuous intravenous infusion of 1 mcg/kg/hour immediately after MV
Placebo group (n = 30): 5% glucose at the same rate as fentanyl
Dose of fentanyl/glucose was decreased to 0.5 mcg/kg/hour when default parameters for MV were as follows: FiO₂ < 25%, RR < 25 bpm, and MAP < 7 cmH₂O. 30 minutes later, MV was stopped after discontinuation of infusion |
| Outcomes |
PIPP; cerebral blood flow velocity (by transcranial Doppler at 1, 3, and 7 days after MV); neuron‐specific enolase (NSE) concentrations in plasma samples (immediately before and after MV); cerebral function monitoring (CFM) recordings (obtained at 37 weeks' GA)
Also, pH, PaO₂, PaCO₂, MAP, heart rate, cardiac output, PIP, PEEP, mean airway pressure, and FiO₂ were recorded immediately before administration and at 1, 12, 24, 48, and 72 hours after the start of the infusion |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Randomisation was done with a random numbers table |
| 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) |
Unclear risk |
3 neonates in the fentanyl group and 4 neonates in the control group were excluded after randomisation because they were discharged within 2 weeks; they were not included in the analysis |
| 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 |
