Acetaminophen may protect against acute kidney injury after pediatric heart surgery

Acetaminophen after pediatric heart surgery was associated with an increasingly protective effect against acute kidney injury (AKI), according to an analysis of separate cohorts at two children’s hospitals.

Researchers retrospectively studied children older than 28 days who were admitted for cardiac surgery between July 2008 and June 2016 at hospitals associated with Vanderbilt and Duke universities. The primary cohort from Vanderbilt included 666 patients a median of 6.5 months old while the validation cohort from Duke included 333 patients a median of 14.1 months old. About half of the patients at each center had AKI, a common complication of pediatric cardiac surgery.

However, when analyzing the relationship between AKI and cumulative acetaminophen exposure in the first 48 hours after surgery, the authors found each 10 mg/kg increase in acetaminophen was associated with an adjusted 14 percent decrease in the odds of AKI among the primary cohort. The adjusted risk decrease was 9 percent for each incremental dose increase in the smaller, validation group.

When stratified by AKI stage, higher doses of the drug were associated with less severe stages (or no AKI at all), while patients who received no acetaminophen had the highest rates of AKI. 

“In tow independent cohorts of children undergoing cardiac surgery, we observed a dose-dependent inverse association between postoperative receipt of acetaminophen and development of AKI,” lead author Sara L. Van Driest, MD, PhD, and colleagues wrote in JAMA Pediatrics. "Taken together with other retrospective and prospective studies showing protective associations of acetaminophen against AKI in several conditions associated with release of cell-free hemoglobin, these findings provide a compelling rationale to justify prospective evaluation of acetaminophen for prevention of AKI in children undergoing CPB (cardiopulmonary bypass).”

The researchers suggested acetaminophen’s ability to reduce the oxidation state of free hemoglobin may help prevent AKI. However, they said randomized trials are needed to prove a causative effect and establish acetaminophen as a protective agent following pediatric heart operations.