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

  • Review
  • Intervention




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


The aim of this review was 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). The primary objectives were to assess changes in need for oxygen or ventilatory support and effects on long-term outcome. The secondary objectives were to assess changes in pulmonary mechanics and potential complications of therapy.

Search strategy

The standard method of the Cochrane Neonatal Review Group were used. Initially, MEDLINE (1966 - November 2001), EMBASE (1974 - November 2001) and the Cochrane Controlled Trials Register (CCTR) (The Cochrane Library, Issue 4, 2001) were searched. In addition, several abstract books of national and international American and European Societies were hand searched. Updated searches in April 2003 and April 2007 did not yield any additional trials.

Selection criteria

Included in this analysis are trials in which preterm infants with or developing CLD and at least five days of age were 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 postmenstrual 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.

Data collection and analysis

The standard method for the Cochrane Collaboration described in the Cochrane Collaboration Handbook were used. 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. Parallel and cross-over trials were combined. Whenever possible, baseline and final outcome data measured on a continuous scale was transformed into change scores using Follmann's formula.

Main results

Of the 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 remaining intubated after eight weeks in 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.

Authors' conclusions

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.

Plain language summary

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

There is no strong evidence of benefit from routine use of distal diuretics in preterm infants with chronic lung disease. Lung disease in infants born early (preterm) is often complicated with excess of water. Medications that reduce body water (diuretics) might help the infant recover from lung disease. The review of trials analysed the effects of diuretics working on the end of the small kidney tubes (distal diuretics). It found that diuretic treatment for four weeks improved lung function. Only one study showed long term benefit (decreased rates of death and artificial ventilation). However, the infants in these trials did not receive all the medications that are currently available.