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

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

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/m(2) in the F group compared with 2.98 (0.09) L/min/m(2) 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.

Figures

Figure 1
Figure 1
Urine output (UO) levels expressed in ml/kg/h in the furosemide (F) and ethacrynic acid (EA) groups. In (A) Absolute UO levels.are depicted. In (B), UO indexed on diuretic dose are indicated. *P < 0.05. POD, postoperative day. Data are expressed as average and standard deviation.
Figure 2
Figure 2
Fluid balance (FB) per kilogram of patient body weight in the three study days in the furosemide (F) and ethacrynic acid (EA) groups. *P < 0.05. POD, postoperative day. Data are expressed as average and standard deviation.
Figure 3
Figure 3
Serum creatinine (SCr) levels in the furosemide (F) and ethacrynic acid (EA) groups: although significant increase was evident from preoperative (PRE-OP) to Pediatric Cardiac Intensive Care Unit admission (PCICU admiss) levels, no difference was evident between the two study groups over time. *P < 0.05. POD, postoperative day. Data are expressed as average and standard deviation.

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