Rastogi 1994.

Methods	Blinding of randomization: no. Randomization was obtained using a table of random numbers. Blinding of intervention: no Complete follow‐up: yes. Of 11 eligible infants, informed consent was denied in 3. All of 8 enrolled infants were followed throughout the study. Blinding of outcome: no Randomized clinical trial, cross‐over design with pooled data. Washout: 72 hr before delivery; 24 hr at cross‐over
Participants	Number of patients entered into the study: n=8 Mechanical ventilation Entry criteria: history of RDS requiring mechanical ventilation at birth, postnatal age > 14 days, persistence of respiratory failure and dependence on O2 and mechanical ventilation, radiographic evidence of chronic pulmonary parenchymal disease, no drug therapy other than vitamins for at least 72 hours before the start of the study Exclusion criteria: evidence of congenital malformations, infection, congenital heart defect, or congenital heart disease. Mean birth weight was 815±297 g and mean gestational age was 27.4±1.6 weeks. At the time of the study, postnatal age was 33±13 days, postconceptional age 32.1±2.5 weeks and weight 1013±331 g. Mean peak inspiratory pressure was 19.3±1.0 cm H2O, mean airway pressure 7.9±1.5 cm, FiO2 0.45±0.17, and ventilatory rate 30±12 per minute. Blood pH was 7.33±0.07 and pCO2 was 44±8 mm Hg.
Interventions	Aerosolized furosemide 0.1 vs 0.25, 0.5 ,1 mg/kg Patients successively received in random order four different doses of aerosolized furosemide: 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg. Furosemide was made up to a final volume of 2 ml with 0.9% NaCl.
Outcomes	Compliance improved in 0/8 patients after a low dose of furosemide, compared to 7/8 at 30 minutes and 6/8 at 4 hours after a dose of 1 mg/kg. Resistance decreased in 0/8 patients after a low dose of furosemide, compared to 7/8 at 30 minutes and at 4 hours after a dose of 1 mg/kg. Tidal volume increased in 0/8 patients after a low dose of furosemide, compared to 8/8 at 30 minutes and 6/8 at 4 hours after a dose of 1 mg/kg. Urine output, urinary calcium, calcium/creatinine ratio, fractional excretion of sodium and creatinine clearance were similar after each of the 4 doses of furosemide, suggesting that aerosolized furosemide had no effect on the kidney.
Notes	There is no information about efficacy of the method of nebulization, so that the exact amount of drug reaching the distal airways is not sure. Pulmonary function was measured at baseline, then at 30 min, 1,2 and 4 hours after aerosol administration. Pulmonary mechanics were measured using the least mean square method. The FiO2 was adjusted during measurement of pulmonary mechanics to maintain hemoglobin saturation >94 %. Patients did not receive sedation; most were in quiet but active sleep state during testing. Urine was collected for 24 hours after each dose of diuretic. The authors state that doses of 0.1‐0.5 mg/kg had no effect on pulmonary function; however, no data are provided, so this information cannot be used for meta‐analysis. Furthermore, no data are provided to support that a dose of furosemide of 0.1 mg/kg had no effect on urine output. For this meta‐analysis, we assumed that 0.1 mg/kg of furosemide had no significant effect on any of the variables and thus can be considered as a placebo.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Randomization was obtained using a table of random numbers
Allocation concealment?	High risk	Blinding of randomization: no
Blinding? All outcomes	Unclear risk	Blinding of intervention: no Blinding of outcome: no
Incomplete outcome data addressed? All outcomes	Unclear risk	Complete follow‐up: yes Of 11 eligible infants, informed consent was denied in 3. All of 8 enrolled infants were followed throughout the study.
Free of selective reporting?	Low risk
Free of other bias?	Unclear risk	Randomized clinical trial, cross‐over design with pooled data. Washout: 72 hr before delivery; 24 hr at cross‐over