Efficacy of sequential nephron blockade with intravenous chlorothiazide to promote diuresis in cardiac intensive care infants

Cardiol Young. 2017 Aug;27(6):1104-1109. doi: 10.1017/S1047951116002122. Epub 2016 Nov 11.


Background: Sequential nephron blockade using intravenous chlorothiazide is often used to enhance urine output in patients with inadequate response to loop diuretics. A few data exist to support this practice in critically ill infants.

Methods: We included 100 consecutive patients <1 year of age who were administered intravenous chlorothiazide while receiving furosemide therapy in the cardiac ICU in our study. The primary end point was change in urine output 24 hours after chlorothiazide administration, and patients were considered to be responders if an increase in urine output of 0.5 ml/kg/hour was documented. Data on demographic, clinical, fluid intake/output, and furosemide and chlorothiazide dosing were collected. Multivariable regression analyses were performed to determine variables significant for increase in urine output after chlorothiazide administration.

Results: The study population was 48% male, with a mean weight of 4.9±1.8 kg, and 69% had undergone previous cardiovascular surgery. Intravenous chlorothiazide was initiated at 89 days (interquartile range 20-127 days) of life at a dose of 4.6±2.7 mg/kg/day (maximum 12 mg/kg/day). Baseline estimated creatinine clearance was 83±42 ml/minute/1.73 m2. Furosemide dose before chlorothiazide administration was 2.8±1.4 mg/kg/day and 3.3±1.5 mg/kg/day after administration. A total of 43% of patients were categorised as responders, and increase in furosemide dose was the only variable significant for increase in urine output on multivariable analysis (p<0.05). No graphical trends were noted for change in urine output and dose of chlorothiazide.

Conclusions: Sequential nephron blockade with intravenous chlorothiazide was not consistently associated with improved urine output in critically ill infants.

Keywords: Diuretic resistance; chlorothiazide; furosemide; intensive care; loop diuretics; paediatrics.

MeSH terms

  • Chlorothiazide / administration & dosage*
  • Critical Care / methods*
  • Critical Illness / therapy*
  • Diuresis / drug effects*
  • Diuretics / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Furosemide / administration & dosage
  • Humans
  • Infant
  • Infant, Newborn
  • Injections, Intravenous
  • Male
  • Nephrons / drug effects*
  • Retrospective Studies


  • Diuretics
  • Chlorothiazide
  • Furosemide