Acetaminophen administration reduces acute kidney injury risk in critically ill patients with Clostridium difficile infection: A cohort study

Acetaminophen serves as a standard antipyretic and analgesic agent in the intensive care unit (ICU). However, the association between its administration and acute kidney injury (AKI) among critically ill patients remains controversial, particularly lacking research in patients with Clostridioides difficile infection (CDI). Our aim was to explore the potential relationship between early acetaminophen administration and AKI in critically ill patients with concurrent CDI. Using data from the Medical Information Mart for Intensive Care (MIMIC) IV version 2.2 database, we performed a retrospective cohort study. AKI within 7 days of ICU admission was the main outcome that was measured. We utilized multivariable logistic regression models adjusted for potential confounders based on statistical significance and clinical relevance, to investigate the association between acetaminophen exposure and the risk of AKI in patients with CDI. Additionally, subgroup analyses and sensitivity analysis were conducted to assess the robustness of our primary findings. The average age of 984 participants was 66.8 ± 16.5 years, and 52.7% (519) were male. The overall proportion of patients who developed AKI was 75.4% (742/984). In patients without and with acetaminophen administration, AKI rates were 79.8% (380/476) and 71.3% (362/508), respectively. Compared to the non-acetaminophen administration group, the risk of AKI was lower in the acetaminophen administration group (absolute risk difference: -8.5%, 95%CI: -13.83%∼-3.17%, P < 0.01).After adjusting for potential confounders, acetaminophen administration was associated with a 32% reduction in the risk of AKI (OR = 0.68, 95%CI:0.48∼0.96, P = 0.027). Our study suggests that early acetaminophen administration may offer renal protection by reducing the risk of AKI in critically ill patients with CDI. Prospective, multicenter randomized controlled studies are needed to verify this finding.