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Original Investigation
July 2018

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

Author Affiliations
  • 1Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 3Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
  • 4Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 5Cardiovascular Perfusion Technology Program, Vanderbilt University Medical Center, Nashville, Tennessee
  • 6Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 7Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 8Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
JAMA Pediatr. 2018;172(7):655-663. doi:10.1001/jamapediatrics.2018.0614
Key Points

Question  Does early postoperative acetaminophen exposure reduce the incidence of acute kidney injury in children who undergo cardiac surgery?

Findings  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.

Meaning  Postoperative use of acetaminophen may protect pediatric cardiac surgery patients from acute kidney injury.

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 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.

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 ≥0.3 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.

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 < .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 (P = .03), with an adjusted odds ratio of 0.91 (95% CI, 0.84-0.99) for each additional 10 mg/kg.

Conclusions and Relevance  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.

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