Association between early postoperative acetaminophen exposure and acute kidney injury in pediatric patients undergoing cardiac surgery

Abstract

Importance: Acute kidney injury (AKI) is a common and serious complication for pediatric cardiac surgery patients associated with increased morbidity, mortality, and length of stay. Current strategies focus on risk reduction and early identification because there are no known preventive or therapeutic agents. Cardiac surgery and cardiopulmonary bypass lyse erythrocytes, releasing free hemoglobin and contributing to oxidative injury. Acetaminophen may prevent AKI by reducing the oxidation state of free hemoglobin. Objective: To test the hypothesis that early postoperative acetaminophen exposure is associated with reduced risk of AKI in pediatric patients undergoing cardiac surgery. Design, Setting, and Participants: In this retrospective cohort study, the settingwas 2 tertiary referral children's hospitals. The primary and validation cohorts included children older than 28 days admitted for cardiac surgery between July 1, 2008, and June 1, 2016. Exclusion criteria were postoperative extracorporeal membrane oxygenation and inadequate serum creatinine measurements to determine AKI status. Exposures: Acetaminophen exposure in the first 48 postoperative hours. Main Outcomes and Measures: Acute kidney injury based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (increase by ≥0.3mg/dL from baseline or at least 1.5-fold more than the baseline [to convert to micromoles per liter, multiply by 88.4]) in the first postoperative week. Results: The primary cohort (n = 666) had a median age of 6.5 (interquartile range [IQR], 3.9-44.7) months, and 341 (51.2%) had AKI. In unadjusted analyses, those with AKI had lower median acetaminophen doses than those without AKI (47 [IQR, 16-88] vs 78 [IQR, 43-104] mg/kg, P