Lower-Dose, Intravenous Chlorothiazide Is an Effective Adjunct Diuretic to Furosemide Following Pediatric Cardiac Surgery

J Pediatr Pharmacol Ther. 2020 Jan-Feb;25(1):31-38. doi: 10.5863/1551-6776-25.1.31.

Abstract

Objectives: Postoperative fluid overload is ubiquitous in neonates and infants following operative intervention for congenital heart defects; ineffective diuresis is associated with poor outcomes. Diuresis with furosemide is widely used, yet there is often resistance at higher doses. In theory, furosemide resistance may be overcome with chlorothiazide; however, its efficacy is unclear, especially in lower doses and in this population. We hypothesized the addition of lower-dose, intravenous chlorothiazide following surgery in patients on high-dose furosemide would induce meaningful diuresis with minimal side effects.

Methods: This was a retrospective, cohort study. Postoperative infants younger than 6 months, receiving high-dose furosemide, and given lower-dose chlorothiazide (1-2 mg/kg every 6-12 hours) were identified. Diuretic doses, urine output, fluid balance, vasoactive-inotropic scores, total fluid intake, and electrolyte levels were recorded.

Results: There were 73 patients included. The addition of lower-dose chlorothiazide was associated with a significant increase in urine output (3.8 ± 0.18 vs 5.6 ± 0.27 mL/kg/hr, p < 0.001), more negative fluid balance (16.1 ± 4.2 vs -25.0 ± 6.3 mL/kg/day, p < 0.001), and marginal changes in electrolytes. Multivariate analysis was performed, demonstrating that increased urine output and more negative fluid balance were independently associated with addition of chlorothiazide. Subgroup analysis of 21 patients without a change in furosemide dose demonstrated the addition of chlorothiazide significantly increased urine output (p = 0.03) and reduced fluid balance (p < 0.01), further validating the adjunct effects of chlorothiazide.

Conclusion: Lower-dose, intravenous chlorothiazide is an effective adjunct treatment in postoperative neonates and infants younger than 6 months following cardiothoracic surgery.

Keywords: chlorothiazide; critical care; diuresis; pediatrics; water-electrolyte balance.