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Meta-Analysis
. 2006 Jul 19;2006(3):CD001694.
doi: 10.1002/14651858.CD001694.pub2.

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease

L P Brion  1 , R A Primhak, W Yong
Affiliations
Meta-Analysis

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease

L P Brion et al. Cochrane Database Syst Rev. .

Abstract

Background: Lung disease in preterm infants is often complicated with lung edema.

Objectives: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy.

Search strategy: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: {<bronchopulmonary dysplasia> or <chronic lung disease>} and <explode diuretics>, limited to <human> and limited to <infant, newborn> or <infant>. We searched MEDLINE (1966 - 1998), EMBASE (1974 - 1998) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006). In addition, we hand searched several abstract books of national and international American and European Societies. The search of MEDLINE and of CENTRAL was last updated in March 2006.

Selection criteria: For the purpose of this analysis, we included trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included need for ventilator support, chronic lung disease, mortality and other important clinical outcomes. Secondary outcome variables included pulmonary mechanics and potential complications of therapy.

Data collection and analysis: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula.

Main results: We identified eight studies that met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics.

Authors' conclusions: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence.More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g., washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

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Conflict of interest statement

None

Figures

1.1
1.1. Analysis
Comparison 1 Aerosolized furosemide vs. control, Outcome 1 Change in transcutaneous pO2 (mm Hg), patients > 3 weeks of age.
1.2
1.2. Analysis
Comparison 1 Aerosolized furosemide vs. control, Outcome 2 Change in blood pH, 1 hour after 1 dose, patients > 3 weeks of age.
1.3
1.3. Analysis
Comparison 1 Aerosolized furosemide vs. control, Outcome 3 Change in compliance (ml/cm H2O/kg).
1.4
1.4. Analysis
Comparison 1 Aerosolized furosemide vs. control, Outcome 4 Change in resistance (cm/L/sec).
1.5
1.5. Analysis
Comparison 1 Aerosolized furosemide vs. control, Outcome 5 Change in tidal volume (ml/kg).
1.6
1.6. Analysis
Comparison 1 Aerosolized furosemide vs. control, Outcome 6 Change in minute ventilation (ml/kg/min) 20 min after dose, on 2nd day, > 3 weeks of age.
2.1
2.1. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 1 Change in % inspiratory O2 2 hours after 1 dose.
2.2
2.2. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 2 Change in transcutaneous O2 saturation (%) 2 hours after 1 dose.
2.3
2.3. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 3 Change in peak inspiratory pressure (cm H2O) 2 hours after 1 dose.
2.4
2.4. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 4 Change in positive end expiratory pressure (cm H2O) 2 hours after 1 dose.
2.5
2.5. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 5 Change in ventilator rate (cycles per minute) 2 hours after 1 dose.
2.6
2.6. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 6 Change in compliance (ml/cm H2O/kg).
2.7
2.7. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 7 Change in resistance (cm/L/sec).
2.8
2.8. Analysis
Comparison 2 Aerosolized furosemide vs. intravenous furosemide, Outcome 8 Change in tidal volume (ml/kg).
3.1
3.1. Analysis
Comparison 3 1 mg/kg aerosolized furosemide (Treatment) vs. lower dose (Control), Outcome 1 Failure to improve compliance.
3.2
3.2. Analysis
Comparison 3 1 mg/kg aerosolized furosemide (Treatment) vs. lower dose (Control), Outcome 2 Failure to improve resistance.
3.3
3.3. Analysis
Comparison 3 1 mg/kg aerosolized furosemide (Treatment) vs. lower dose (Control), Outcome 3 Failure to improve tidal volume.
3.4
3.4. Analysis
Comparison 3 1 mg/kg aerosolized furosemide (Treatment) vs. lower dose (Control), Outcome 4 Urinary calcium (mg/kg/day) over 24 hours.
3.5
3.5. Analysis
Comparison 3 1 mg/kg aerosolized furosemide (Treatment) vs. lower dose (Control), Outcome 5 Calcium:creatinine ratio (mg:mg).
4.1
4.1. Analysis
Comparison 4 2 mg/kg aerosolized furosemide (Treatment) with 1 mg/kg (Control), Outcome 1 Change in compliance (ml/cm H2O/kg).
4.2
4.2. Analysis
Comparison 4 2 mg/kg aerosolized furosemide (Treatment) with 1 mg/kg (Control), Outcome 2 Change in resistance (cm/L/sec).
4.3
4.3. Analysis
Comparison 4 2 mg/kg aerosolized furosemide (Treatment) with 1 mg/kg (Control), Outcome 3 Change in tidal volume (ml/kg).
4.4
4.4. Analysis
Comparison 4 2 mg/kg aerosolized furosemide (Treatment) with 1 mg/kg (Control), Outcome 4 Change in urine output.
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Brion 1999d
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