| Study characteristics |
| Methods |
Single‐centre randomised double‐blind controlled trial |
| Participants |
95 preterm newborns (57, excluding those receiving only morphine)
Entry criteria: newborns with hyaline membrane disease who were fighting against the ventilator (on clinical impression); postnatal age > 4 hours and < 48 hours; no prior treatment with narcotic analgesic or neuromuscular blocking agent |
| Interventions |
Morphine group (n = 29): 50 mcg/kg/hour by continuous infusion, increased to 100 mcg/kg/hour if the newborn was still struggling after 2 hours. Babies in this group were allowed to receive pancuronium if still fighting the ventilator after 4 hours (n = 7)
Pancuronium group (n = 28): 100 mcg/kg per dose given as required to inhibit breathing. Babies in this group were given morphine for painful procedures (n = 4)
Morphine + pancuronium group (n = 38): continuous morphine at 50 mcg/kg/hour + intermittent pancuronium at 100 mcg/kg as required; morphine not increased above 50 mcg/kg/hour
We extracted data from the morphine + pancuronium group and the pancuronium group (i.e. pancuronium was a co‐intervention); we did not include the group receiving only morphine
Drug therapy continued until FiO₂ < 0.45. 1 baby stopped treatment within 24 hours because FiO₂ fell below 0.45 |
| Outcomes |
Catecholamines; plasma levels; blood pressure; heart rate; peak inspiratory pressure; FiO₂ on entry to the study and after 6 hours' treatment; days on ventilator; air leaks; intraventricular haemorrhage; PDA; death
5 to 6 years' follow‐up outcomes: IQ (by Weschler Preschool and Primary Scale of Intelligence); motor impairment (by Movement Assessment Battery for Children); behaviour problems (by Child Behaviour Checklist completed by a parent); blood thyroid‐stimulating hormone level |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Study authors stated that randomisation was performed by drawing a sealed envelope. These authors did not state how the list of randomisation was generated |
| Allocation concealment (selection bias) |
High risk |
Allocation concealment was inadequate |
| Blinding of participants and personnel (performance bias) |
High risk |
Blinding of interventions and outcomes was not clearly ensured |
| Blinding of outcome assessment (detection bias) |
High risk |
Blinding of interventions and outcomes was not clearly ensured |
| Incomplete outcome data (attrition bias) |
Unclear risk |
Clinical outcomes were reported for 28 of the 38 randomised infants to morphine and for 28 of 28 in the control group. Unclear if due to a typo in the manuscript or attrition bias. A power calculation was made for differences in catecholamine levels. Analysis of clinical data was performed on an intention‐to‐treat basis |
| 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 |
