| Study characteristics |
| Methods |
Randomized, double‐blind, multicenter (16 participating NICUs), placebo‐controlled trial |
| Participants |
42 neonates born at 23 to 32 weeks of gestation, intubated before 72 hours of age and ventilated for < 8 hours at inclusion.
Exclusion criteria: congenital anomalies, birth asphyxia, intrauterine growth retardation, maternal opioid addiction and participation in other clinical trials.
Morphine group (n = 21; mean GA 27.2 SD 1.7 weeks; mean BW 947 SD 269 g)
5% dextrose (placebo) group (n = 21; mean GA 27.3 SD 1.8 weeks; mean BW 972 SD 270 g) |
| Interventions |
Morphine group: 100 μg/kg loading dose, infused intravenously in 1 hour and 10 to 30 μg/kg/h continuous infusion (intravenously)
5% dextrose (placebo) group (n = 21; mean GA 27.3 SD 1.8 weeks; mean BW 972 SD 270 g) |
| Outcomes |
Pain assessment by DAN and PIPP‐R scale during heel stick before the loading dose, the heel stick 2 to 3 hours after the loading dose, and the heel stick after 20 to 28 hours of morphine infusion |
| Funding sources |
Grant funds from the Fondation CNP (Paris, France) and National Institute for Child Health and Human Development grants HD36484 and HD36270 |
| Declaration of interest among the primary researchers |
No conflict of interest declared. |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Quote: "Randomization to the morphine and placebo groups occurred with an automated telephone response system located in the United States, followed by faxed confirmation of the coded treatment assignment to the NICU and the hospital pharmacy. Neonates were randomized to 8 study drug codes, with 4 codes each for the morphine and placebo groups." |
| Allocation concealment (selection bias) |
Low risk |
Quote: "parents of each enrolled infant. Assignment Randomization to the morphine and placebo groups occurred with an automated telephone response system located in the United States, followed by faxed confirmation of the coded treatment assignment to the NICU and the hospital pharmacy. Neonates were randomized to 8." |
| Blinding of participants and personnel (performance bias)
All outcomes |
Low risk |
Quote: "Physicians and nurses in charge of neonates were blinded to the treatments received by the patients. Study drug syringes were dispensed by a research pharmacist who did not participate in the routine care of neonates." |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Quote: "Pain assessments were conducted by an independent observer, who did not participate in the procedure" |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Outcomes are reported for all randomized infants—see Fig 1. Trial profile and participant flow. |
| Selective reporting (reporting bias) |
Unclear risk |
Protocol not available. |
| Other bias |
Low risk |
None |
