Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.
BACKGROUND
Lung disease in preterm infants is often complicated with lung edema.


OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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.


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.


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.
Brion
L P
LP
Albert Einstein College of Medicine, Children's Hospital at Montefiore, Pediatrics, Section of Neonatology, Weiler Hospital Room 725, 1825 Eastchester Road, Bronx, NY 10461-2373, USA. lbrion@montefiore.org
Primhak
R A
RA
Yong
W
W
D000336:Aerosols; D002908:Chronic Disease; D004232:Diuretics / Q000008:administration & dosage*; D005665:Furosemide / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008171:Lung Diseases / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
D000336:Aerosols; D004232:Diuretics; D005665:Furosemide