Association Between Early Postoperative Acetaminophen Exposure and Acute Kidney Injury in Pediatric Patients Undergoing Cardiac Surgery

Abstract

<div class="section"> <a class="named-anchor" id="ab-poi180016-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e415">Question</h5> <p id="d1982176e417">Does early postoperative acetaminophen exposure reduce the incidence of acute kidney injury in children who undergo cardiac surgery? </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e420">Findings</h5> <p id="d1982176e422">In this cohort study, acetaminophen exposure in the first postoperative 48 hours was associated with a lower rate of acute kidney injury in pediatric patients who underwent cardiac surgery in primary and validation cohorts from 2 tertiary referral children’s hospitals. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e425">Meaning</h5> <p id="d1982176e427">Postoperative use of acetaminophen may protect pediatric cardiac surgery patients from acute kidney injury. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e431">Importance</h5> <p id="d1982176e433">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e436">Objective</h5> <p id="d1982176e438">To test the hypothesis that early postoperative acetaminophen exposure is associated with reduced risk of AKI in pediatric patients undergoing cardiac surgery. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e441">Design, Setting, and Participants</h5> <p id="d1982176e443">In this retrospective cohort study, the setting was 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. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e446">Exposures</h5> <p id="d1982176e448">Acetaminophen exposure in the first 48 postoperative hours.</p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e451">Main Outcomes and Measures</h5> <p id="d1982176e453">Acute kidney injury based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (increase by ≥0.3 mg/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. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e456">Results</h5> <p id="d1982176e458">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, <i>P</i> &lt; .001). In logistic regression analysis adjusting for age, cardiopulmonary bypass time, red blood cell distribution width, postoperative hypotension, nephrotoxin exposure, and Risk Adjustment for Congenital Heart Surgery score, acetaminophen exposure was protective against postoperative AKI (odds ratio, 0.86 [95% CI, 0.82-0.90] per each additional 10 mg/kg). Findings were replicated in the validation cohort (n = 333), who had a median age of 14.1 (IQR, 3.9-158.2) months, and 162 (48.6%) had AKI. Acetaminophen doses were 60 (95% CI, 40-87) mg/kg in those with AKI vs 70 (95% CI, 45-94) mg/kg in those without AKI ( <i>P</i> = .03), with an adjusted odds ratio of 0.91 (95% CI, 0.84-0.99) for each additional 10 mg/kg. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180016-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d1982176e467">Conclusions and Relevance</h5> <p id="d1982176e469">These results indicate that early postoperative acetaminophen exposure may be associated with a lower rate of AKI in pediatric patients who undergo cardiac surgery. Further analysis to validate these findings, potentially through a prospective, randomized trial, may establish acetaminophen as a preventive agent for AKI. </p> </div><p class="first" id="d1982176e472">This study tests the hypothesis that early postoperative acetaminophen exposure is associated with reduced risk of acute kidney injury in pediatric patients undergoing cardiac surgery. </p>