Early Postoperative Acetaminophen Administration and Severe Acute Kidney Injury After Cardiac Surgery

Am J Kidney Dis. 2022 Dec 28;S0272-6386(22)01093-9. doi: 10.1053/j.ajkd.2022.11.009. Online ahead of print.


Rationale & objective: Oxidative stress may contribute to the development of acute kidney injury (AKI) after cardiac surgery. Acetaminophen can be considered an antioxidant as it inhibits hemoprotein-catalyzed lipid peroxidation. We hypothesized that perioperative acetaminophen administration is associated with reduced AKI after cardiac surgery.

Study design: Retrospective observational cohort study.

Setting & participants: Patients aged ≥18 years who had cardiac surgery were identified from two publicly available clinical registries: the Medical Information Mart for Intensive Care (MIMIC)-III and the eICU Collaborative Research Database (eICU).

Exposure: Administration of acetaminophen in the first 48 hours after surgery.

Outcomes: Severe AKI in the first 7 days after surgery, defined as stage 2 or stage 3 AKI according to KDIGO criteria.

Analytic approach: Multivariable cause-specific hazards regression analysis.

Results: We identified 5,791 patients from the MIMIC-III and 3,840 patients from the eICU registries. The overall incidence of severe AKI was 58% (3,390 patients) in the MIMIC-III cohort and 37% (1,431 patients) in the eICU cohort. Acetaminophen was administered in the early postoperative period to 4,185 patients (72%) and 2,737 patients (71%) in these two cohorts, respectively. In multivariable regression models, early postoperative use of acetaminophen was associated with a reduced risk of severe AKI in both the MIMIC-III (adjusted hazard ratio, 0.86 [95% CI, 0.79 to 0.94]) and eICU (adjusted hazard ratio, 0.84 [95% CI, 0.72 to 0.97]) cohorts. The benefit was consistent across sensitivity and subgroup analyses.

Limitations: No data on acetaminophen dose.

Conclusions: Early postoperative acetaminophen administration was independently associated with a lower risk of severe AKI in adults recovering from cardiac surgery. Prospective trials are warranted to assess the extent to which the observed association is causal and estimate the extent to which acetaminophen administration might prevent or reduce the severity of AKI.

Keywords: Acetaminophen; Acute kidney injury; Anesthesia; Cardiac surgery.