(P-399) Association of Ondansetron Use and Subsequent Acute Kidney Injury in Critical Care

Background: Ondansetron is a preferred option in critical care to treat and prevent nausea and vomiting, and has historically been considered a largely safe option. A recent pharmacoepidemiology study reported that ondansetron may be associated with an increased risk for acute kidney injury (AKI).

Objectives: Determine the association between ondansetron use and subsequent risk of AKI using a retrospective cohort design

Methods: High-Density Intensive Care-15 database, containing intensive care data for 13 hospitals across Pennsylvania between Oct 2008 - Dec 2014 was used. Patients were excluded if under age 18, developed AKI or death within 24 hours of admission, or a history of ECMO, transplant, immunosuppression, or ESKD. AKI was defined using the Kidney Disease, Improving Global Outcomes 2012 guidelines. The first ICU admission for each patient was included. Ondansetron use was considered as receiving any form of ondansetron within 24 hours of admission. The subsequent 48 hours (hours 25-72 after admission) were analyzed for outcomes. Primary outcome was development of AKI; secondary outcomes included 90-day mortality. Multivariate logistic regression was applied for both outcomes. Independent variables include reference serum creatinine, age, sex, history of hypertension or chronic kidney disease, sofa score, and apache score. Comparator groups were metoclopramide and prochlorperazine using the same exposure criteria.

Results: Ondansetron, prochlorperazine, and metoclopramide was used in 31745, 2183, and 2647 patients, respectively. AKI occurred in 1493 (4.70%), 70 (3.21%), and 120 (4.53%) patients receiving ondansetron, prochlorperazine, and metoclopramide, respectively. In adjusted analysis, ondansetron was associated with a 7% decrease in the odds of developing AKI (OR 0.933; CI 0.876 – 0.996). Prochlorperazine (OR 0.765; CI 0.599 – 0.976) showed similar decreases in AKI, but metoclopramide (OR 0.943; CI 0.782 – 1.140) did not. In respect to 90-day mortality, ondansetron was associated with a 46% decrease (OR 0.536; CI 0.511 – 0.563) in the odds of dying within 90 days of ICU-admission. Neither metoclopramide (OR 0.942; CI 0.824 – 1.076) or prochlorperazine (OR 0.897; CI 0.763 – 1.055) showed this decrease in mortality.

Conclusions: Ondansetron was associated with a statistically significant decrease in the development of AKI. However, prochlorperazine showed similar results, and may suggest residual indication bias. Ondansetron was associated with a significant decrease in 90-day mortality that was not seen by other anti-emetics. Our results contrast previous findings, and suggest that ondansetron may be associated with decreased risk of AKI and 90-day mortality.