Skip to main content Accessibility help

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

  • Brady S. Moffett (a1) (a2), Rocky Tsang (a2), Curt Kennedy (a2), Ron A. Bronicki (a2), Ayse Akcan-Arikan (a2) and Paul A. Checchia (a2)...



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.


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.


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.


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


Corresponding author

Correspondence to: B. S. Moffett, PharmD, MPH, Department of Pharmacy, Texas Children’s Hospital, 6621 Fannin Street, Suite WB1120, Houston, TX 77030, United States of America. Tel: +832 824 6087; Fax: +832 825 5261; E-mail:


Hide All
1. Dettli, L, Spring, P. Therapy with combinations of diuretic agents: comparative studies. Ann NY Acad Sci 1966; 139: 471480.
2. Kissling, KT, Pickworth, KK. Comparison of the effects of combination diuretic therapy with oral hydrochlorothiazide or intravenous chlorothiazide in patients receiving intravenous furosemide therapy for the treatment of heart failure. Pharmacotherapy 2014; 34: 882887.
3. Eades, SK, Christensen, ML. The clinical pharmacology of loop diuretics in the pediatric patient. Pediatr Nephrol 1998; 12: 603616.
4. Jentzer, JC, DeWald, TA, Hernandez, AF. Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol 2010; 56: 15271534.
5. Schwartz, GJ, Brion, LP, Spitzer, A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34: 571590.
6. Akcan-Arikan, A, Zappitelli, M, Loftis, LL, Washburn, KK, Jefferson, LS, Goldstein, SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 2007; 71: 10281035.
7. Arikan, AA, Zappitelli, M, Goldstein, SL, Naipaul, A, Jefferson, LS, Loftis, LL. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 2012; 13: 253258.
8. Selewski, DT, Cornell, TT, Blatt, NB, et al. Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy. Crit Care Med 2012; 40: 26942699.
9. Selewski, DT, Cornell, TT, Lombel, RM, et al. Weight-based determination of fluid overload status and mortality in pediatric intensive care unit patients requiring continuous renal replacement therapy. Intensive Care Med 2011; 37: 11661173.
10. Segar, JL, Robillard, JE, Johnson, KJ, Bell, EF, Chemtob, S. Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia. J Pediatr 1992; 120: 966973.
11. De Vecchis, R, Ariano, C, Esposito, C, Giasi, A, Cioppa, C, Cantatrione, S. In right or biventricular chronic heart failure addition of thiazides to loop diuretics to achieve a sequential blockade of the nephron is associated with increased risk of dilutional hyponatremia: results of a case-control study. Minerva Cardioangiol 2012; 60: 517529.
12. Sica, DA, Gehr, TW. Diuretic combinations in refractory oedema states: pharmacokinetic-pharmacodynamic relationships. Clin Pharmacokinet 1996; 30: 229249.
13. Thomas, CA, Morris, JL, Sinclair, EA, Speicher, RH, Ahmed, SS, Rotta, AT. Implementation of a diuretic stewardship program in a pediatric cardiovascular intensive care unit to reduce medication expenditures. Am J Health Syst Pharm 2015; 72: 10471051.
14. Valente, MA, Voors, AA, Damman, K, et al. Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 2014; 35: 12841293.
15. Harrison, AM, Davis, S, Eggleston, S, Cunningham, R, Mee, RB, Bokesch, PM. Serum creatinine and estimated creatinine clearance do not predict perioperatively measured creatinine clearance in neonates undergoing congenital heart surgery. Pediatr Crit Care Med 2003; 4: 5559.
16. Piggott, KD, Soni, M, Decampli, WM, et al. Acute kidney injury and fluid overload in neonates following surgery for congenital heart disease. World J Pediatr Congenit Heart Surg 2015; 6: 401406.
17. Miller, JL, Thomas, AN, Johnson, PN. Use of continuous-infusion loop diuretics in critically ill children. Pharmacotherapy 2014; 34: 858867.
18. Moranville, MP, Choi, S, Hogg, J, Anderson, AS, Rich, JD. Comparison of metolazone versus chlorothiazide in acute decompensated heart failure with diuretic resistance. Cardiovasc Ther 2015; 33: 4249.


Related content

Powered by UNSILO

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

  • Brady S. Moffett (a1) (a2), Rocky Tsang (a2), Curt Kennedy (a2), Ron A. Bronicki (a2), Ayse Akcan-Arikan (a2) and Paul A. Checchia (a2)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.