Arya 2001.

Methods	Randomised, double‐blind, placebo‐controlled trial 1. Blinding of randomisation ‐ yes 2. Blinding of intervention ‐ yes 3. Complete follow‐up ‐ yes 4. Blinding of outcome measure ‐ yes Study location: neonatal unit of a tertiary hospital, New Dehli, India Study period: not stated
Participants	Newborn infants < 2000 grams needing mechanical ventilation during first week of life were eligible for inclusion. Exclusion criteria: encephalopathy, birth asphyxia, major malformation, maternal benzodiazepine use before delivery 33 infants were randomised. 3 in each group did not complete the first 24 hours of the study; 4 in each group did not complete the first 48 hours of the study Reasons for withdrawal: death (13) and extubation (1) Demographic data: values presented as means (SDs), unless indicated Midazolam group (n = 17) Gestational age: 31.5 weeks (2.4 weeks) Birth weight: 1263 grams (326 grams) Male: 58.8% PIP at baseline: 19.9 cmH2O (5.5 cmH2O) MAP at baseline: 8.7 cmH2O (3.2 cmH2O) Median (range) OI at baseline: 5 (1 to 22) Median (range) AaDO2 at baseline: 205 (13 to 619) Placebo group (n = 16) Gestational age: 32.3 weeks (2.2 weeks) Birth weight: 1337 grams (297 grams) Male: 75.0% PIP at baseline: 21.2 cmH2O (7.1 cmH2O) MAP at baseline: 9.8 cmH2O (4.3 cmH2O) Median (range) OI at baseline: 5 (2 to 55) Median (range) AaDO2 at baseline: 234.5 (59 to 553)
Interventions	Midazolam was given as 200 microgram/kg loading dose followed by infusion of 60 microgram/kg/h. Duration of infusion and method of weaning were not specified. Infants in both groups received morphine infusion at 10 microgram/kg/h during the study. Study consisted of 48 hours of infusion.
Outcomes	Primary outcome Adequacy of sedation was measured every 6 hours by a 5‐item behavioural scale (facial expression, sucking, continuous motor activity, excitability and response to stimulation, excessive flexing) (Barrier 1989); physiological measures of sedation level included mean daily values of heart rate and blood pressure. Secondary outcomes Intracranial haemorrhage and epileptiform movement, haemodynamic instability (hypotension, tachycardia, oliguria) with the need for volume expansion or vasoactive drugs, or both, ventilation requirement (peak inspiratory and PEEP, MAP and rate), days of ventilation, incidence of pulmonary air leak
Notes	Randomisation was performed with opaque envelopes containing computer‐generated random numbers. Ranbaxy Laboratoried Ltd provided drugs and placebo for the study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random numbers were placed in opaque envelopes.
Allocation concealment (selection bias)	Low risk	Opaque envelopes contained computer‐generated random numbers.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo was manufactured with colour and vial volume similar to those of study drug.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Sedation score was determined by an investigator who was blinded to allocation of infants.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Three patients each in midazolam and placebo groups did not complete 24 hours of follow‐up after enrolment. Additionally, 4 patients in the midazolam group and 4 in the placebo group did not complete 48 hours of follow‐up. Reasons for withdrawal included death (6 in midazolam group and 7 in placebo group) and cessation of mechanical ventilation (1 in midazolam group).
Selective reporting (reporting bias)	Unclear risk	The protocol for the study was not available to us, so we cannot ascertain whether deviations from the protocol occurred.
Other bias	Low risk	Trial appears free of other bias.