Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease

The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy.

We used the standard method of the Cochrane Neonatal Review Group. We searched MEDLINE (1966-November 2001), EMBASE (1974-November 2001) and the Cochrane Controlled Trials Register (CCTR) (Cochrane Library Issue 4, 2001). In addition, we hand searched several abstract books of national and international American and European Societies.

We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy.

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.

Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants who did not have access to corticosteroids, bronchodilators or aminophylline. However, there is little or no evidence to support any benefit of diuretic administration on need for ventilatory support, length of hospital stay, or long-term outcome in patients receiving current therapy. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD.

In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Studies are needed to assess (1) whether thiazide administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients exposed to corticosteroids and bronchodilators (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.