Effect of ondansetron on reducing ICU mortality in patients with acute kidney injury

Guo, Xiaojiang; Qi, Xiguang; Fan, Peihao; Gilbert, Michael; La, Andrew D.; Liu, Zeyu; Bertz, Richard; Kellum, John A.; Chen, Yu; Wang, Lirong

doi:10.1038/s41598-021-98734-x

Cited by 10 publications

(8 citation statements)

References 43 publications

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“…Importantly, potentially favourable effects of OND on reduced in-hospital mortality in acute kidney injury (AKI) patients in the ICU were reported depending on the MIMIC-III database, the eICU database and 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 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the latest study found that OND could be used to decrease mortality in the coronavirus disease 2019(COVID-19) inpatients [ 4 ]. In addition, OND has been illustrated the potentially pleiotropic effect, including neuroprotection [ 5 ], renal protection [ 6 , 7 ], and anticoagulation [ 8 , 9 ]. However, research on the survival benefit of initial use of OND, particularly in the critically ill, is lacking.…”

Section: Introductionmentioning

confidence: 99%

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

2022

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Background While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose. Methods The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings. Results In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63–0.89, p < 0.001]. In the circulatory system group, the early OND administration was associated with improved in-hospital mortality in ICU patients (OR 0.48, 95% CI 0.34–0.66; P < 0.001). The risk of in-hospital mortality was also lower in early OND users than in non-OND users both in the medical admission group and the surgical ICU admission group, and ORs were 0.57 (95% CI 0.42–0.76; P < 0.001) and 0.79 (95% CI 0.62–0.91; P < 0.001), respectively. A positive role of daily low- and moderate-dose OND treatment in early-stage was showed on the in-hospital mortality in PSM cohort, and the ORs were 0.75 (95% CI 0.62–0.90; P < 0.001) and 0.63 (95% CI 0.43–0.91; P < 0.001), respectively. The relationship between the daily low- and moderate-dose of OND and in-hospital mortality was also significant in ICU patients with cardiovascular diseases, and ORs were 0.51(95% CI 0.36–0.73; P < 0.001), and 0.26(95% CI 0.11–0.65; P < 0.001), respectively. Daily low-to-moderate dose of OND was also associated with in-hospital mortality in ICU entire cohort. Conclusions Early OND use is closely associated with lower in-hospital mortality in ICU patients. Daily low-to-moderate dose of OND application is protective against in-hospital mortality. This association is more evident in the circulatory system group. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2022

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“…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 ). These findings suggest the possibility of the 5-HT3 receptor as a therapeutic target for the treatment of AKI patients.…”

Section: Discussionmentioning

confidence: 99%

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

Xiong

2022

Front. Surg.

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BackgroundOndansetron is a widely used anti-emetic for the prevention and treatment of nausea and vomiting for patients in critical care. Recent retrospective cohort studies suggest the potential beneficial effects of ondansetron in critically ill patients. In this study, we investigate the impact of ondansetron use on patient outcomes after cardiac surgery.Material and MethodsThe MIMIC-III database was used to identify two types of cardiac surgical patients: those who were administered early ondansetron and those who were not given this early medication in the first 48 h in the postoperative period. Multivariable logistic regression was used to investigate the effect of ondansetron exposure on 90-day mortality, acute kidney injury, and malignant ventricular arrhythmias. Sensitivity analyses utilizing the inverse probability of treatment weighting and covariate balancing propensity score models were conducted to test the robustness of our findings.ResultsA total of 12.4% of patients received ondansetron. Ondansetron use was associated with a lower risk of 90-day mortality in the multivariable logistic regression model (OR: 0.31, 95% CI: 0.13 to 0.72; P = 0.006) and sensitivity analyses. Additionally, ondansetron exposure was associated with less postoperative acute kidney injury (OR: 0.82, 95%CI: 0.69 to 0.96; P = 0.017) but did not increase the risk of postoperative malignant ventricular arrhythmias (OR: 0.38, 95%CI: 0.09 to 1.16; P = 0.191).ConclusionsIn a population of cardiac surgical patients, early postoperative use of ondansetron appears to be associated with decreased 90-day mortality and acute kidney injury.

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“…11 However, a recent pharmacoepidemiologic study has identified an association between ondansetron use and a decrease in the risk for acute kidney injury (AKI). 12 5-HT3 antagonists have also been found to be nephroprotective in animal models. 13 Anti-emetics are generally metabolized through conjugation and hepatic routes, and it is important to further explore the role they play on renal function since anti-emetics are often administered despite compromised renal function because of their relative safety.…”

Section: Introductionmentioning

confidence: 99%

Kidney and Mortality Outcomes Associated with Ondansetron in Critically Ill Patients

Gray

Priyanka

Kane‐Gill

et al. 2022

J Intensive Care Med

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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.

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Effect of ondansetron on reducing ICU mortality in patients with acute kidney injury

Cited by 10 publications

References 43 publications

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

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

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

Kidney and Mortality Outcomes Associated with Ondansetron in Critically Ill Patients

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