| Methods |
Blinding of randomization: no
Blinding of intervention: no
Complete follow‐up: no. Two of twelve patients randomized to furosemide were subsequently removed from the study because they did not have typical RDS. All ten control patients were kept in the study.
Blinding of outcome: no
Randomized controlled trial, parallel design.
No washout period documented |
| Participants |
Patients entered into the study: n=22
Mechanical ventilation or oxygen requirement.
Entry criteria included: prematurity, RDS, 7th postnatal day, either FiO2 > 0.30 for last 24 hours or continued ventilatory assistance.
Exclusion criteria: cardiac failure, renal disease, clinically significant PDA by echocardiography (left atrium/aorta ratio <1.0).
A total of 20 patients were available for the analysis, 10 in each group. The average birth weight was 1019±269 g in the treatment group and 1271±553 g in the control group. The average gestational age was 29±1.4 weeks and 30±2.9 weeks, respectively. The postnatal age was 7‐13 days and 6‐11 days, respectively, and postconceptional age 30.4 and 31.2 weeks, respectively. Baseline FiO2 was 0.43±0.09 and 0.40±0.22, respectively. Baseline A‐aDO2 gradient and PCO2 were similar in both groups. Average compliance tended to be 32% lower in the treatment group than in controls. Four infants in the furosemide group were ventilated. |
| Interventions |
Furosemide vs no medication.
Patients were randomly allocated to receive either furosemide at a dose of 1 mg/kg/day intravenously for 4 days or no treatment.
Average fluid intake was similar in both groups (147 ml/kg/day, range 86‐280 in treatment group, vs 153 ml/kg/day, range 97‐243 in control group). |
| Outcomes |
The authors report that 1) compliance improved more often in the treatment group than in controls, and that compliance improved significantly in 4 ventilated patients treated with furosemide. 2) AaDO2 improved more in the treatment group than in the controls, and 3) urine output did not increase.
Using the original data but with a total n equalling the number of enrolled infants, we found no difference in AaDO2 between the groups on days 1, 3 and 4, but a significant difference on day 2 (‐11.1±12.06 mm Hg in treatment group vs +4.9±17.51 mmHg in controls, p<0.05); identical results were obtained using either Student t‐test or Wilcoxon test. Urine output was similar on day 1 in both groups, but was higher in the treatment group than in controls on day 4 (28±7 ml/kg/6 hr vs 21±6 ml/kg/6 hr, respectively, p<0.05, unpaired Student t‐test). |
| Notes |
Measurements were obtained each of the 4 days of the study. Dynamic compliance was measured using an esophageal balloon in the furosemide group at 1,2,4, and 6 hours after furosemide but is not reported in the control group. The AaDo2 was measured 2 hours after furosemide, and urine output was measured for 6 hours after furosemide.
Unfortunately, for most of the outcomes, data cannot be used for meta‐analysis for one of the following reasons: Only mean values are given, only data in the treatment group are provided, or more than one test was reported per baby and used for statistical analysis (n=30‐39 for 10 infants). Statistics were recalculated using a total n of 10 (1 data per patient per day). |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
High risk |
Randomized controlled trial, parallel design. |
| Allocation concealment (selection bias) |
High risk |
Blinding of randomization: no |
| Blinding (performance bias and detection bias)
All outcomes |
High risk |
Blinding of intervention: no
Blinding of outcome: no |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Complete follow‐up: no. Two of twelve patients randomized to furosemide were subsequently removed from the study because they did not have typical RDS. All ten control patients were kept in the study |
