McCann 1985.

Methods	Blinding of randomization: yes. Medications were prepared in the pharmacy. Blinding of intervention: yes Complete follow up: no. Of 24 infants entered into the study, 7 were removed from the analysis. In the control group, 2 infants had clinical deterioration. In the treatment group, 1 had severe hypochloremia, 2 had sepsis, 1 had a surgical shunt for hydrocephalus, and 1 had CLD following meconium aspiration syndrome. Blinding of outcome: yes Randomized controlled trial, parallel design Washout period: 72 hours
Participants	Patients entered into the study: n=24 (12 in each group) The need for mechanical ventilation was not used as a criterion. Entry criteria: (1) CLD defined as >30% O2 and chest radiograph findings of coarse interstitial markings with areas of hyperaeration (2) following mechanical ventilation for respiratory distress. Exclusion criteria: renal failure, sepsis, necrotizing enterocolitis, hyperbilirubinemia, current administration of aminoglycoside, administration of diuretics within 72 hours. A final number of 17 patients were available for this analysis, including 7 in the furosemide group and 10 in the placebo group. The average birth weight was 947 g (range 620‐1510) in the treatment group and 859 g (650‐1030) in the placebo group. The average gestational age was 27 weeks (24‐32) and 27 weeks (range 24‐29), respectively. Postnatal age was 49 days (36‐72) and 38 days (23‐82), respectively, and postconceptional age 34.0 and 32.4 weeks, respectively. The two groups had similar severity of respiratory distress, history of PDA, history of pulmonary interstitial emphysema, serum electrolytes, alveolar ventilation, minute ventilation, venous admixture, blood pH and pCO2, and urine output. Patients in the furosemide group tended to have a 90% higher dead space than those in the control group and lesser trends for other pulmonary function measurements. Five of 7 patients in the treatment group and 8 of 10 in the control group were on mechanical ventilation at the time of recruitment. Mean FiO2 was 0.45±0.10 in the treatment group and 0.45±0.11 in the control group.
Interventions	Furosemide vs placebo. Patients were randomly allocated to receive, either furosemide (1 mg/kg iv or 2 mg/kg orally q 12 hours) and KCl for 7 days, or similar placebo solutions. The dose of furosemide was doubled if no diuretic response (50% increase in urine output over 12 hours) was observed after 48 hours. The KCl dose was adjusted to keep serum K > 3.5 mEq/L and serum Cl > 95 mEq/L. Fluid intake was limited to 100‐150 ml/kg/day. Six of seven infants received furosemide orally.
Outcomes	Main outcome: risk and benefits of furosemide including physical findings, fluid and Na balance, serum electrolytes, ventilator and O2 requirements, blood gases, and pulmonary function. One patient in the furosemide group had no detectable diuresis after the first dose and the dose was doubled. In the furosemide group, 3 infants were extubated and 2 infants needed less ventilatory support after therapy; in the control group, 2 were extubated and 6 were not weaned. Six patients in the furosemide group had clinical improvement (chest examination) compared with 2 in the control group. Similarly, 6 patients in the furosemide group had an improvement in lung aeration on the chest radiograph compared with 2 in the control group. The authors analyzed the results based on a total number of 7 patients in the furosemide group and 10 in the control group and found significant differences between groups. However, analysis of relative risk showed no significant difference, whether using the same total numbers as the authors did, or whenever possible using an intention‐to treat basis (11 furosemide‐treated patients and 12 controls). The authors reported that after 7 days patients in the furosemide group, but not those in the control group, had significant improvements in minute ventilation, alveolar ventilation, dynamic compliance, ventilator peak pressure and ventilator frequency. Nevertheless, there was no significant difference between the 2 groups in any of these variables by Student t‐test (using numbers provided by the authors for ventilated patients). Comparison of change scores showed a significant difference only for % inspired O2, compliance and minute ventilation after 1 week of treatment. Patients in the furosemide group had a transient increase in urine output and a decrease in serum chloride concentration; their urine output was higher than that in controls on the first day of therapy (p<0.01) and their serum chloride concentration was lower (p<0.05) after 48 hours of therapy.
Notes	One infant in the furosemide group received the medication for 5 days only; study medication was stopped when serum creatinine concentration increased to 2.5 mg/dl. The authors did not provide any additional information about this patient's renal failure (e.g., pre‐renal vs intrinsic renal), nor about the potential role of furosemide. Pulmonary function was measured at baseline, after 2 days and after 7 days; they were obtained at variable times (range 1.5‐7 hours) after furosemide administration. The authors measured dynamic compliance and resistance using an esophageal balloon.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomized controlled trial, parallel design
Allocation concealment (selection bias)	Low risk	Blinding of randomization: yes. Medications were prepared in the pharmacy.
Blinding (performance bias and detection bias) All outcomes	Low risk	Blinding of intervention: yes Blinding of outcome: yes
Incomplete outcome data (attrition bias) All outcomes	High risk	Complete follow up: no. Of 24 infants entered into the study, 7 were removed from the analysis. In the control group, 2 infants had clinical deterioration. In the treatment group, 1 had severe hypochloremia, 2 had sepsis, 1 had a surgical shunt for hydrocephalus, and 1 had CLD following meconium aspiration syndrome.