| Study characteristics |
| Methods |
Multicentre randomised, placebo controlled trial. Randomisation was performed by an automated procedure in blocks, stratified by centre. Allocation concealment was ensured by an automated telephone response system. Carers and assessors were blinded to the treatment. Outcomes were reported for all patients enrolled. |
| Participants |
67 preterm infants (24‐32 weeks) on ventilator by < 8 h were eligible for inclusion. Exclusion criteria: postnatal age >72 h, positive pressure ventilation >=8 h, major congenital anomalies, severe intrapartum asphyxia (Apgar score<=3 at 5 min), and participation in other studies interfering with the NOPAIN trial procedures criteria: postnatal age >72 h, positive pressure ventilation >=8 h, major congenital anomalies, severe intrapartum asphyxia (Apgar score<=3 at 5 min) |
| Interventions |
Morphine group (n=24): loading dose 100 mcg/kg for all gestational ages.
Midazolam group (n=22): loading dose 200 mcg/kg followed by an infusion of 20, 40 or 60 mcg/kg/h for infants of gestational ages 24‐26, 27‐29 and 30‐32 weeks respectively.
Placebo group (n=21): dextrose 10%
treatment continued as long as necessary (written protocol for stopping drugs), max 14 days. Additional analgesia with morphine bolus doses was allowed. The amount and frequency of additional morphine was recorded as an outcome measure. |
| Outcomes |
Primary outcome: incidence of adverse neurological events (neonatal death, grade III/IV intraventricular haemorrhage, periventricular leucomalacia). Secondary outcomes: level of sedation (measured by the COMFORT score); and pain response to tracheal suctioning (assessed by the PIPP) ‐ all scores assessed before starting treatment, after 24 h of infusion, and at 10‐12 h after treatment was discontinued;. incidence of pneumothorax; days of ventilatory support; continuous positive airway pressure and oxygen; length of intensive care unit and hospital stay; and neurodevelopmental outcome (measured by Neurobehavioral Assessment of the NAPI cluster scores at 36 weeks corrected for gestational age). |
| Notes |
|
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment (selection bias) |
Low risk |
A ‐ Adequate |
