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Short-Term Effects of Spironolactone/Hydrochlorothiazide on Respiratory Support in Preterm Infants with

Osman Selçuk Duysak¹, Murat Konak¹, Muhammed Yaşar Kılınç¹

¹Division of Neonatology, Department of Pediatrics, Selçuklu Medical Faculty, Selçuk University, Konya 42000, Turkey.

Journal of Clinical Medicine

|March 28, 2026

Insights

Combined spironolactone and hydrochlorothiazide (SP/HCTZ) therapy in preterm infants with bronchopulmonary dysplasia (BPD) was associated with reduced respiratory support needs. However, this treatment also increased the risk of hyponatremia, necessitating careful monitoring.

Area of Science:

Neonatology
Pediatric Pulmonology
Pharmacology

Background:

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm infants.
Diuretics are frequently used in BPD management, but their short-term effects are not well-documented.
Limited evidence exists on the early physiological impacts of combined oral spironolactone and hydrochlorothiazide (SP/HCTZ) in BPD.

Purpose of the Study:

To evaluate the early changes in respiratory support parameters after initiating SP/HCTZ in preterm infants with BPD.
To assess safety outcomes, specifically serum electrolyte levels, during the initial phase of SP/HCTZ therapy.
To determine the clinical response rate to SP/HCTZ based on predefined respiratory support criteria.

Main Methods:

Retrospective, single-center before-after observational study design.
Inclusion of preterm infants diagnosed with BPD who started SP/HCTZ.
Comparison of respiratory parameters (FiO2, PEEP, flow rate) and serum electrolytes on Day 1 versus Day 3 of treatment.

Main Results:

A significant decrease in mean FiO2 from 26.2% to 22.4% (p < 0.001) was observed after 72 hours of SP/HCTZ.
Significant reductions in PEEP (p = 0.004) and cannula flow rates (p = 0.003) were also noted.
69.6% of infants met the clinical response criteria; however, hyponatremia prevalence increased from 7.1% to 25.0% (p = 0.039).

Conclusions:

Initiation of SP/HCTZ showed a temporal association with reduced short-term respiratory support requirements in preterm infants with BPD.
These observed reductions should be considered associations, not definitive treatment effects.
Increased hyponatremia by Day 3 highlights the need for vigilant electrolyte monitoring during early SP/HCTZ therapy.

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Abstract:

Objectives: Diuretics are frequently used in bronchopulmonary dysplasia (BPD), yet evidence describing their short-term physiological effects remains limited. This study aimed to describe early changes in respiratory support parameters and safety outcomes following combined oral spironolactone and hydrochlorothiazide (SP/HCTZ) therapy in preterm infants with BPD. Methods: A retrospective, single-center before-after observational study was conducted. Preterm infants diagnosed with BPD who initiated SP/HCTZ therapy were included. Respiratory parameters (FiO₂, PEEP, and flow rate) and serum electrolytes were compared between Day 1 (initiation) and Day 3 of treatment. A predefined clinical response was defined as either a ≥10% reduction in FiO₂ or a step-down in respiratory support modality. Results: Fifty-six infants (mean gestational age 27.7 ± 2.3 weeks) were analyzed. After 72 h of SP/HCTZ therapy, mean FiO₂ decreased from 26.2 ± 6.3% to 22.4 ± 3.4% (p < 0.001). Significant reductions were also observed in PEEP and cannula flow rates (p = 0.004 and p = 0.003, respectively). Overall, 39 infants (69.6%) met the predefined clinical response criteria. The prevalence of hyponatremia (Na < 133 mmol/L) increased from 7.1% at baseline to 25.0% on Day 3 (p = 0.039). Conclusions: Initiation of SP/HCTZ was temporally associated with short-term reductions in respiratory support parameters; however, these findings should be interpreted as associations rather than treatment effects. Given the increased frequency of hyponatremia by Day 3, close electrolyte monitoring appears warranted during the early phase of therapy.

Keywords:

bronchopulmonary dysplasia diuretics hydrochlorothiazide oxygen requirement preterm infant spironolactone

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