Kidney and Mortality Outcomes Associated with Ondansetron in Critically Ill Patients

Abstract

Background: Ondansetron is a preferred anti-emetic in critical care to treat 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). Methods: We interrogated the High-Density Intensive Care (HiDenIC-15) database containing intensive care data for 13 hospitals across Western Pennsylvania between Oct 2008-Dec 2014. AKI was defined using the Kidney Disease, Improving Global Outcomes 2012 guidelines. Ondansetron use was considered as receiving any form of ondansetron within 24 h of admission. The subsequent 48 h (hours 25-72 after admission) were analyzed for outcomes. Primary outcome was development of AKI; secondary outcomes included 90-day mortality and time to AKI. Propensity-matched, multivariate logistic regression was applied for both outcomes. Comparator groups were metoclopramide and prochlorperazine using the same exposure criteria. Results:AKI occurred in 965 (5.6%), 12 (3.0%), and 61 (6.5%) patients receiving ondansetron, prochlorperazine, and metoclopramide, respectively. In the adjusted analysis, no anti-emetic was associated with a significant change in the odds of developing AKI. Ondansetron was associated with a 5.48% decrease (CI −6.17–−4.79) in death within 90 days of ICU-admission, which was independent of AKI status; an effect not seen with other anti-emetics. Anti-emetic usage was not associated with a change in the time to first AKI. Conclusion:Anti-emetic usage did not alter AKI risk. Ondansetron was associated with a significant decrease in 90-day mortality that was not seen by other anti-emetics, which requires further exploration.

Early Postoperative Ondansetron Exposure is Associated with Reduced 90-Day Mortality in Patients Undergoing Cardiac Surgery

“…Our study shows that early postoperative ondansetron exposure is associated with better survival at 90 days after surgery in patients with postoperative AKI. This finding is similar to that of three other retrospective cohort studies that investigated critically ills patients with AKI and demonstrated that patients who received ondansetron had significantly lower ICU mortality, in-hospital mortality, and 90-day mortality, respectively ( 17 – 19 ). Additionally, the genes of 5-HT3 receptor were reported to be upregulated in AKI kidneys, and a molecular mechanism study by gene expression signatures demonstrated that the NF-KB and JAK-STAT pathways might be involved in the potential therapeutic effect of ondansetron in critically ill patients complicated by AKI ( 18 ).…”

“…In a retrospective study of a large COVID-19 patient cohort, the use of no less than 8 mg of ondansetron within 48 h of hospital admission was associated with a reduced risk of 30-day mortality for all hospitalized patients (Hazard ratio: 0.55, 95%CI: 0.42–0.70; P < 0.001) and those admitted to ICU (Hazard ratio: 0.52, 95%CI: 0.31–0.87; P = 0.012) after severe acute respiratory syndrome coronavirus 2 infection ( 16 ). In another retrospective cohort study using a large multicenter ICU database, ondansetron received within 24 h after ICU admission was associated with a 5.48% decrease (95%CI: −6.17–−4.79; P < 0.001) of 90-day mortality in the regression analysis of the propensity score–matched cohort ( 17 ). Additionally, this association was not seen by other anti-emetics including prochlorperazine and metoclopramide, suggesting that the beneficial effect of ondansetron on survival might be related to effects other than anti-emetic ( 17 ).…”

“…In another retrospective cohort study using a large multicenter ICU database, ondansetron received within 24 h after ICU admission was associated with a 5.48% decrease (95%CI: −6.17–−4.79; P < 0.001) of 90-day mortality in the regression analysis of the propensity score–matched cohort ( 17 ). Additionally, this association was not seen by other anti-emetics including prochlorperazine and metoclopramide, suggesting that the beneficial effect of ondansetron on survival might be related to effects other than anti-emetic ( 17 ). Furthermore, our previous study found in the MIMIC-IV database that a low-to-moderate but not a high dose of ondansetron within 48 h after ICU admission was associated with decreased in-hospital mortality in ICU patients ( 22 ).…”

“…The beneficial effects of 5-HT3 receptor antagonists have also been seen on anti-inflammation ( 9 – 12 ), renal function ( 13 – 15 ), and even mortality reduction ( 16 – 20 ). Recent retrospective studies reported an association between ondansetron use and reduced risk of mortality in critically ill patients both with and without acute kidney injury (AKI) ( 17 – 20 ). Patients undergoing cardiac surgery are also at high risk of developing AKI ( 21 ), but research on the mortality benefit of ondansetron use in cardiac surgical patients is lacking.…”

Association between early ondansetron administration and in-hospital mortality in critically ill patients: analysis of the MIMIC-IV database

“…Based on the comparison of gene expression signatures, the latest study illustrated that the advantageous effect of OND might be elicited through the NF-KB pathway and JAK-STAT pathway [ 6 , 7 ]. A recent pharmacoepidemiology study reported that OND was also associated with a significant decrease in 90-day mortality on the High-Density Intensive Care (HiDenIC-15) database containing intensive care data for 13 hospitals across Western Pennsylvania [ 17 ]. Last but not least, OND would inhibit agonist-induced platelet aggregation.…”