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Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease
L P Brion1, R A Primhak, I Ambrosio-Perez
1Pediatrics, Division of Neonatology, Albert Einstein College of Medicine and Montefiore Medical Center, Weiler Hospital Room 725, 1825 Eastchester Road, Bronx, NY 10461, USA. brion@aecom.yu.edu
Insights
Distal diuretics may improve lung mechanics in preterm infants with chronic lung disease (CLD). However, evidence for benefits on mortality, ventilation, or long-term outcomes is limited, necessitating further research.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Pharmacology
Background:
- Preterm infants with chronic lung disease (CLD) often require respiratory support.
- Distal diuretics, acting on renal tubules, are sometimes used in managing CLD.
- The risks and benefits of these diuretics in this vulnerable population require careful evaluation.
Purpose of the Study:
- To assess the efficacy and safety of distal diuretics in preterm infants with CLD.
- Primary objectives include evaluating changes in oxygen and ventilatory support needs and long-term outcomes.
- Secondary objectives focus on pulmonary mechanics and potential therapy complications.
Main Methods:
- Systematic review following Cochrane Neonatal Review Group methodology.
- Searched Medline, Embase, and Cochrane Controlled Trials Register (CCTR) using keywords related to CLD and diuretics.
- Included randomized trials of preterm infants (≥5 days old) with CLD receiving distal diuretics, assessing predefined clinical outcomes.
Main Results:
- Limited studies assessed clinical outcomes or complications; most focused on physiological parameters.
- In preterm infants (>3 weeks) with CLD, thiazide and spironolactone improved lung compliance and reduced furosemide need.
- These diuretics decreased death risk and tended to reduce extubation failure risk in infants not on other respiratory medications; no clear benefit on ventilation, hospital stay, or long-term outcomes was found with current therapies.
Conclusions:
- Distal diuretics improve pulmonary mechanics in preterm infants (>3 weeks) with CLD.
- Further studies are needed to determine if thiazides improve mortality, oxygen/ventilator dependency, hospital stay, and long-term outcomes in infants receiving corticosteroids and bronchodilators.
- Research is also required to assess the benefits of adding spironolactone to thiazides or metolazone to furosemide.
Objectives:
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.
Search Strategy:
We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿
Selection Criteria:
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.
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:
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.
Reviewer'S 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.