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Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Furosemide versus ethacrynic acid in pediatric patients undergoing cardiac surgery: a randomized controlled trial

Authors: Zaccaria Ricci, Roberta Haiberger, Chiara Pezzella, Cristiana Garisto, Isabella Favia, Paola Cogo

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

Clinical effects of furosemide (F) and ethacrynic acid (EA) continuous infusion on urine output (UO), fluid balance, and renal, cardiac, respiratory, and metabolic function were compared in infants undergoing surgery for congenital heart diseases.

Methods

A prospective randomized double-blinded study was conducted. Patients received 0.2 mg/kg/h (up to 0.8 mg/kg/h) of either F or EA.

Results

In total, 38 patients were enrolled in the F group, and 36, in the EA group. No adverse reactions were recorded. UO at postoperative day (POD) 0 was significantly higher in the EA group, 6.9 (3.3) ml/kg/h, compared with the F group, 4.6 (2.3) ml/kg/h (P = 0.002) but tended to be similar in the two groups thereafter. Mean administered F dose was 0.33 (0.19) mg/kg/h compared with 0.22 (0.13) mg/kg/h of EA (P < 0.0001). Fluid balance was significantly more negative in the EA group at postoperative day 0: −43 (54) ml/kg/h versus −17 (32) ml/kg/h in the F group (P = 0.01). Serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels and incidence of acute kidney injury did not show significant differences between groups. Metabolic alkalosis occurred frequently (about 70% of cases) in both groups, but mean bicarbonate level was higher in the EA group: 27.8 (1.5) M in the F group versus 29.1 (2) mM in the EA group (P = 0.006). Mean cardiac index (CI) values were 2.6 (0.1) L/min/m2 in the F group compared with 2.98 (0.09) L/min/m2 in the EA group (P = 0.0081). Length of mechanical ventilation was shorter in the EA group, 5.5 (8.8) days compared with the F group, 6.7 (5.9) (P = 0.06). Length of Pediatric Cardiac Intensive Care Unit (PCICU) admission was shorter in the EA group: 14 (19) days compared with 16 (15) in the F group (P = 0.046).

Conclusions

In cardiac surgery infants, EA produced more UO compared with F on POD0. Generally, a smaller EA dose is required to achieve similar UO than F. EA and F were safe in terms of renal function, but EA caused a more-intense metabolic alkalosis. EA patients achieved better CI, and shorter mechanical ventilation and PCICU admission time.

Trial registration

Clinicaltrials.gov NCT01628731. Registered 24 June 2012.
Literature
1.
go back to reference Eades SK, Christensen ML. The clinical pharmacology of loop diuretics in the pediatric patient. Pediatr Nephrol. 1998;1998:603–16.CrossRef Eades SK, Christensen ML. The clinical pharmacology of loop diuretics in the pediatric patient. Pediatr Nephrol. 1998;1998:603–16.CrossRef
2.
go back to reference van der Vorst MM, van Heel Ruys-Dudok I, Kist-van Holthe tot Ech-ten JE, den Hartigh J, Schoemaker RC, Cohen AF, et al. Continuous intravenous furosemide in haemodynamically unstable children after cardiac surgery. Intensive Care Med. 2001;27:711–5.CrossRef van der Vorst MM, van Heel Ruys-Dudok I, Kist-van Holthe tot Ech-ten JE, den Hartigh J, Schoemaker RC, Cohen AF, et al. Continuous intravenous furosemide in haemodynamically unstable children after cardiac surgery. Intensive Care Med. 2001;27:711–5.CrossRef
3.
go back to reference Ricci Z, Iacoella C, Cogo P. Fluid management in critically ill pediatric patients with congenital heart disease. Minerva Pediatr. 2011;63:399–410.PubMed Ricci Z, Iacoella C, Cogo P. Fluid management in critically ill pediatric patients with congenital heart disease. Minerva Pediatr. 2011;63:399–410.PubMed
4.
go back to reference 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;13:253–8.CrossRef 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;13:253–8.CrossRef
5.
go back to reference Hassinger AB, Wald EL, Goodman DM. Early postoperative fluid overload precedes acute kidney injury and is associated with higher morbidity in pediatric cardiac surgery patients. Pediatr Crit Care Med. 2014;15:131–8.CrossRef Hassinger AB, Wald EL, Goodman DM. Early postoperative fluid overload precedes acute kidney injury and is associated with higher morbidity in pediatric cardiac surgery patients. Pediatr Crit Care Med. 2014;15:131–8.CrossRef
6.
go back to reference Seguin J, Albright B, Vertullo L, Lai P, Dancea A, Bernier PL, et al. Extent, risk factors, and outcome of fluid overload after pediatric heart surgery. Crit Care Med. 2014 Jul 28. [Epub ahead of print]. Seguin J, Albright B, Vertullo L, Lai P, Dancea A, Bernier PL, et al. Extent, risk factors, and outcome of fluid overload after pediatric heart surgery. Crit Care Med. 2014 Jul 28. [Epub ahead of print].
7.
go back to reference Hazle MA, Gajarski RJ, Yu S, Donohue J, Blatt NB. Fluid overload in infants following congenital heart surgery. Pediatr Crit Care Med. 2013;14:44–9.CrossRef Hazle MA, Gajarski RJ, Yu S, Donohue J, Blatt NB. Fluid overload in infants following congenital heart surgery. Pediatr Crit Care Med. 2013;14:44–9.CrossRef
8.
go back to reference Kellum JA, Lameire N, KDIGO AKI. Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013;17:204.CrossRef Kellum JA, Lameire N, KDIGO AKI. Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013;17:204.CrossRef
9.
go back to reference Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805.CrossRef Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805.CrossRef
10.
go back to reference Klinge J. Intermittent administration of furosemide or continuous infusion in critically ill infants and children: does it make a difference? Intensive Care Med. 2001;27:623–4.CrossRef Klinge J. Intermittent administration of furosemide or continuous infusion in critically ill infants and children: does it make a difference? Intensive Care Med. 2001;27:623–4.CrossRef
11.
go back to reference Luciani GB, Nichani S, Chang AC, Wells WJ, Newth CJ, Starnes VA. Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations. Ann Thorac Surg. 1997;64:1133–9.CrossRef Luciani GB, Nichani S, Chang AC, Wells WJ, Newth CJ, Starnes VA. Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations. Ann Thorac Surg. 1997;64:1133–9.CrossRef
12.
go back to reference Reilly RF, Jackson EK. Regulation of renal function and vascular volume. In: Chabner BA, Brunton LL, Knollmann BC, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill; 2011. Reilly RF, Jackson EK. Regulation of renal function and vascular volume. In: Chabner BA, Brunton LL, Knollmann BC, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill; 2011.
13.
go back to reference Akan-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;71:1028–35.CrossRef Akan-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;71:1028–35.CrossRef
14.
go back to reference Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010;11:234–8.CrossRef Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010;11:234–8.CrossRef
15.
go back to reference Garisto C, Favia I, Ricci Z, Romagnoli S, Haiberger R, Polito A, et al. Pressure recording analytical method and bioreactance for stroke volume index monitoring during pediatric cardiac surgery. Paediatr Anaesth. 2014. [Epub ahead of print] Garisto C, Favia I, Ricci Z, Romagnoli S, Haiberger R, Polito A, et al. Pressure recording analytical method and bioreactance for stroke volume index monitoring during pediatric cardiac surgery. Paediatr Anaesth. 2014. [Epub ahead of print]
16.
go back to reference Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update: ACCF/ AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/ American Heart Association task force on practice guidelines: developed in collaboration with the International Society forHeart and Lung Transplantation. Circulation. 2009;119:1977–2016.CrossRef Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update: ACCF/ AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/ American Heart Association task force on practice guidelines: developed in collaboration with the International Society forHeart and Lung Transplantation. Circulation. 2009;119:1977–2016.CrossRef
17.
go back to reference Wittner M, Stefano AD, Wangemann P. How do loop diuretics act? Drugs. 1991;41:1–13.CrossRef Wittner M, Stefano AD, Wangemann P. How do loop diuretics act? Drugs. 1991;41:1–13.CrossRef
18.
go back to reference Martin S, Danziger LH. Continuous infusion of loop diuretics: pharmacodynamic concepts and clinical applications. Clin Trends Pharm Pract. 1994;8:10–3. Martin S, Danziger LH. Continuous infusion of loop diuretics: pharmacodynamic concepts and clinical applications. Clin Trends Pharm Pract. 1994;8:10–3.
19.
go back to reference Singh NC, Kisson N, Al Mofada S, Bennett M, Bohn DJ. Comparison of continuous versus intermittent furosemide administration in postoperative pediatric cardiac patients. Crit Care Med. 1992;20:17–21.CrossRef Singh NC, Kisson N, Al Mofada S, Bennett M, Bohn DJ. Comparison of continuous versus intermittent furosemide administration in postoperative pediatric cardiac patients. Crit Care Med. 1992;20:17–21.CrossRef
20.
go back to reference van der Vorst MM, Kist JE, van der Heijden AJ, Burggraaf J. Diuretics in pediatrics: current knowledge and future prospects. Paediatr Drugs. 2006;8:245–64.CrossRef van der Vorst MM, Kist JE, van der Heijden AJ, Burggraaf J. Diuretics in pediatrics: current knowledge and future prospects. Paediatr Drugs. 2006;8:245–64.CrossRef
21.
go back to reference Sparrow AW, Friedberg DZ, Nadas AS. The use of ethacrynic acid in infants and children with congestive heart failure. Pediatrics. 1968;42:291–302.PubMed Sparrow AW, Friedberg DZ, Nadas AS. The use of ethacrynic acid in infants and children with congestive heart failure. Pediatrics. 1968;42:291–302.PubMed
22.
go back to reference Scalais E, Papageorgiou A, Aranda JV. Effects of ethacrynic acid in the newborn infant. J Pediatr. 1984;104:947–50.CrossRef Scalais E, Papageorgiou A, Aranda JV. Effects of ethacrynic acid in the newborn infant. J Pediatr. 1984;104:947–50.CrossRef
23.
go back to reference Brown DM, Reynolds JW, Alfred FM, Ulstrom RA. The use and mode of action of ethacrynic acid in nephrogenic diabetes insipidus. Pediatrics. 1966;37:447–55.PubMed Brown DM, Reynolds JW, Alfred FM, Ulstrom RA. The use and mode of action of ethacrynic acid in nephrogenic diabetes insipidus. Pediatrics. 1966;37:447–55.PubMed
24.
go back to reference James JA. Ethacrynic acid in edematous states in children. J Pediatr. 1967;71:881–6.CrossRef James JA. Ethacrynic acid in edematous states in children. J Pediatr. 1967;71:881–6.CrossRef
25.
go back to reference Taketomo CK, Hodding JH, Kraus DM. Ethacrynic acid. In: Pediatric and neonatal dosage handbook. 20th ed. Hudson, Ohio: Lexi-Comp, Inc; 2013. Taketomo CK, Hodding JH, Kraus DM. Ethacrynic acid. In: Pediatric and neonatal dosage handbook. 20th ed. Hudson, Ohio: Lexi-Comp, Inc; 2013.
26.
go back to reference Miller JL, Schaefer J, Tam M, Harrison DL, Johnson PN. Ethacrynic acid continuous infusions in critically ill pediatric patients. J Pediatr Pharmacol Ther. 2014;19:49–55.PubMedPubMedCentral Miller JL, Schaefer J, Tam M, Harrison DL, Johnson PN. Ethacrynic acid continuous infusions in critically ill pediatric patients. J Pediatr Pharmacol Ther. 2014;19:49–55.PubMedPubMedCentral
27.
go back to reference Mehta RL, Pascual MT, Soroko S, Chertow GM, PICARD Study Group. Diuretics, mortality, and non recovery of renal function in acute renal failure. JAMA. 2002;288:2547–53.CrossRef Mehta RL, Pascual MT, Soroko S, Chertow GM, PICARD Study Group. Diuretics, mortality, and non recovery of renal function in acute renal failure. JAMA. 2002;288:2547–53.CrossRef
28.
go back to reference Uchino S, Doig GS, Bellomo R, Morimatsu H, Morgera S, Schetz M, et al. Diuretics and mortality in acute renal failure. Crit Care Med. 2004;32:1669–77.CrossRef Uchino S, Doig GS, Bellomo R, Morimatsu H, Morgera S, Schetz M, et al. Diuretics and mortality in acute renal failure. Crit Care Med. 2004;32:1669–77.CrossRef
29.
go back to reference Zappitelli M, Bernier PL, Saczkowski RS, Tchervenkov CI, Gottesman R, Dancea A, et al. A small post-operative rise in serum creatinine predicts acute kidney injury in children undergoing cardiac surgery. Kidney Int. 2009;76:885–92.CrossRef Zappitelli M, Bernier PL, Saczkowski RS, Tchervenkov CI, Gottesman R, Dancea A, et al. A small post-operative rise in serum creatinine predicts acute kidney injury in children undergoing cardiac surgery. Kidney Int. 2009;76:885–92.CrossRef
30.
go back to reference Aydin SI, Seiden HS, Blaufox AD, Parnell VA, Choudhury T, Punnoose A, et al. Acute kidney injury after surgery for congenital heart disease. Ann Thorac Surg. 2012;94:1589–95.CrossRef Aydin SI, Seiden HS, Blaufox AD, Parnell VA, Choudhury T, Punnoose A, et al. Acute kidney injury after surgery for congenital heart disease. Ann Thorac Surg. 2012;94:1589–95.CrossRef
31.
go back to reference Ricci Z, Di Nardo M, Iacoella C, Netto R, Picca S, Cogo P. Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study. Pediatr Cardiol. 2013;34:1404–8.CrossRef Ricci Z, Di Nardo M, Iacoella C, Netto R, Picca S, Cogo P. Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study. Pediatr Cardiol. 2013;34:1404–8.CrossRef
32.
go back to reference Lex DJ, Tóth R, Cserép Z, Alexander SI, Breuer T, Sápi E, et al. A comparison of the systems for the identification of postoperative acute kidney injury in pediatric cardiac patients. Ann Thorac Surg. 2014;97:202–10.CrossRef Lex DJ, Tóth R, Cserép Z, Alexander SI, Breuer T, Sápi E, et al. A comparison of the systems for the identification of postoperative acute kidney injury in pediatric cardiac patients. Ann Thorac Surg. 2014;97:202–10.CrossRef
33.
go back to reference Taylor ML, Carmona F, Thiagarajan RR, Westgate L, Ferguson MA, del Nido PJ, et al. Mild postoperative acute kidney injury and outcomes after surgery for congenital heart disease. J Thorac Cardiovasc Surg. 2013;146:146–52.CrossRef Taylor ML, Carmona F, Thiagarajan RR, Westgate L, Ferguson MA, del Nido PJ, et al. Mild postoperative acute kidney injury and outcomes after surgery for congenital heart disease. J Thorac Cardiovasc Surg. 2013;146:146–52.CrossRef
34.
go back to reference Mæhle K, Haug B, Flaatten H, Nielsen E. Metabolic alkalosis is the most common acid–base disorder in ICU patients. Crit Care. 2014;18:420.CrossRef Mæhle K, Haug B, Flaatten H, Nielsen E. Metabolic alkalosis is the most common acid–base disorder in ICU patients. Crit Care. 2014;18:420.CrossRef
Metadata
Title
Furosemide versus ethacrynic acid in pediatric patients undergoing cardiac surgery: a randomized controlled trial
Authors
Zaccaria Ricci
Roberta Haiberger
Chiara Pezzella
Cristiana Garisto
Isabella Favia
Paola Cogo
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-014-0724-5

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