| Methods |
Blinding of randomization: yes
Blinding of intervention: yes
Complete follow up: no. Of 16 eligible infants, 13 were enrolled (consent signed); two patients were later excluded because of documented infection.
Blinding of outcome: yes
Randomized controlled trial, cross‐over design with pooled data
Washout 24 hours before the study, 48 hours at cross‐over |
| Participants |
Patients entered into the study: n=13
No mechanical ventilation.
Entry criteria: (1) History of respiratory failure requiring O2 and mechanical ventilation at birth, (2) postnatal age > 28 days, (3) persistence of respiratory symptoms and O2 requirement to maintain hemoglobin O2 saturation > 92%, (4) radiographic evidence of parenchymal CLD, (5) no mechanical ventilation at time of enrolment, (6) no drug therapy except for vitamins, (7) no evidence of congenital malformations, infection or congestive heart failure, (8) > 75% enteral feedings.
Eleven patients were analyzed. Average birth weight was 962±328 g, mean gestational age 28.0±2.3 weeks, postnatal age 9.4±3.5 weeks, postconceptional age 37.4±4.2 weeks and FiO2 0.45±0.13. Baseline compliance during the furosemide week tended to be 20% lower than that during the placebo week (0.61±0.32 ml/cm/kg vs 0.75±0.67 ml/cm/kg, respectively, NS). |
| Interventions |
Alternate day oral furosemide vs placebo.
Patients were randomly allocated to receive either (1) alternate day furosemide (4 mg/kg orally in 2 divided doses) for 8 days followed by a 48‐hour washout period and then alternated day placebo (in 2 divided doses) for 8 days, or (2) placebo followed by a washout period and then furosemide. Fluid intake and caloric intake were identical during furosemide administration and during placebo administration: 134.4±14.0 ml/kg/day vs 135.7±19.8 ml/kg/day, and 106.3±6.8 kcal/kg/day vs 107.2±4.6 kcal/kg/day, respectively). |
| Outcomes |
Main outcome: pulmonary function including compliance, resistance and FiO2 required to maintain pulse oximetry 92‐94% when quiet and awake. Improvement was defined as a 20% increase in compliance, a 20% decrease in resistance, or both, between baseline and day 8.
Secondary outcome: body weight, electrolyte and mineral balance.
After 8 days of therapy, dynamic compliance on diuretic therapy was 1.01±0.72 ml/cm/kg compared to 0.50±0.32 ml/cm/kg on placebo (p<0.05), and total pulmonary resistance on diuretic was 0.61±0.26 cm/L/sec, compared to 1.02±0.27 cm/L/sec on placebo (<0.01). One infant improved during both periods, 8 improved with furosemide but not with placebo, 1 improved with placebo but not furosemide and 1 did not improve during either treatment (p<0.04 for unmatched pairs, McNemar test). Oxygen requirement decreased by 7±2% during furosemide administration compared to 4.5±2% during placebo administration (furosemide vs placebo, p<0.01).
The average weight gain was lower during treatment than during placebo, 16.6±8.6 g/day vs 25.6±6.9 g/day, p<0.04. Urine output did not increase anytime during furosemide administration, and was similar during diuretic treatment and during placebo treatment (79.0±17.4 ml/kg/day vs 72.3±10.6 ml/kg/day). Furosemide treatment did not significantly affect the calcium/creatinine ratio (p>0.10) nor serum electrolytes; serum sodium tended to increase less with furosemide than with placebo (0.1±5.0 vs 3.4±4.0 mEq/L, p=0.07). |
| Notes |
All variables were obtained 12‐18 hours after drug administration. Dynamic pulmonary function tests were obtained at baseline and after 2,4,6, and 8 days. Urine output, weight gain and serum electrolytes concentrations were obtained at baseline and after 8 days.
No infant received Na, K or Cl supplementation for correction of serum electrolyte anomalies.
There was no difference in fluid and electrolyte variables (blood and urine) between the fist and the second part of the study, suggesting there was no carry‐over effect on fluid balance. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Randomized controlled trial, cross‐over design with pooled data |
| Allocation concealment (selection bias) |
Low risk |
Blinding of randomization: yes |
| 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 16 eligible infants, 13 were enrolled (consent signed); two patients were later excluded because of documented infection |
