David M Axelrod1, Scott M Sutherland, Andrew Anglemyer, Paul C Grimm, Stephen J Roth. 1. 1Department of Pediatrics (Cardiology), Stanford University Medical Center, Stanford, CA. 2Department of Pediatrics (Nephrology), Stanford University Medical Center, Stanford, CA. 3Department of Clinical Pharmacy, School of Pharmacy, University of California-San Francisco, San Francisco, CA.
Abstract
OBJECTIVES:Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Single-center, double-blinded, placebo-controlled, randomized clinical trial. SETTING: Tertiary center, pediatric cardiovascular ICU. PATIENTS: A total of 144 children after congenital heart surgery with cardiopulmonary bypass. INTERVENTIONS:Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). CONCLUSIONS: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.
RCT Entities:
OBJECTIVES:Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Single-center, double-blinded, placebo-controlled, randomized clinical trial. SETTING: Tertiary center, pediatric cardiovascular ICU. PATIENTS: A total of 144 children after congenital heart surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). CONCLUSIONS: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.
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