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

ABSTRACT: The purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients' baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug's molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.

SUBMITTER: Guo X

PROVIDER: S-EPMC8484575 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Guo Xiaojiang X Qi Xiguang X Fan Peihao P Gilbert Michael M La Andrew D AD Liu Zeyu Z Bertz Richard R Kellum John A JA Chen Yu Y Wang Lirong L

Scientific reports 20210930 1

The purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients' ...[more]

PMID: 34593872

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Project description:BackgroundOndansetron is widely used for prophylaxis of postoperative nausea and vomiting (PONV) after general anesthesia. While previous studies have emphasized its early use, the effects of ondansetron in intensive care unit (ICU) patients following cardiac surgery remain unclear. This study investigates the association between postoperative ondansetron exposure and the risk of mortality, acute kidney injury (AKI), and postoperative atrial fibrillation (POAF) in ICU patients after cardiac surgery.MethodsWe conducted a retrospective cohort study utilizing data from the MIMIC-IV database. Adult patients who underwent cardiac surgery and were subsequently admitted to the ICU were included. Cox proportional hazards models were employed to assess the effect of ondansetron exposure on ICU and 28-day mortality. Multivariable logistic regression analyses examined the associations between ondansetron exposure and the incidence of AKI (2-day and 7-day) and POAF. Sensitivity analyses included Propensity Score Matching (PSM) and the inclusion of patients with ICU stays of less than 24 h to ensure robustness of results. Subgroup analyses explored the effects of age and other clinical factors, with interaction tests to examine differential impacts.ResultsA total of 7,170 were included. The incidence of AKI was 74.4% at 2 days and 76.7% at 7 days post-surgery. The 28-day postoperative mortality rate was 1.4%, while the ICU mortality rate was 1.0%. POAF occurred in 17.4% of the patients. Ondansetron exposure was not associated with 28-day mortality or ICU mortality (p > 0.05). However, after PSM, ondansetron exposure was significantly associated with an elevated risk of AKI at 2 days (OR 1.28, 95% CI 1.13-1.45, p < 0.001] and 7 days (OR 1.25, 95% CI 1.15-1.45, p < 0.001), as well as POAF (OR 1.20, 95% CI 1.04-1.39, p = 0.014).Subgroup analysis revealed a stronger association in patients aged over 65 years, where ondansetron was linked to an increased risk of 7-day AKI (OR 1.51, 95% CI 1.29-1.78, p < 0.001) and POAF (OR 1.31, 95% CI 1.12-1.53, p = 0.001). Interaction tests showed a significant interaction between ondansetron exposure and age (P for interaction = 0.018 for AKI and P for interaction = 0.02 for POAF). Sensitivity analyses, including patients with ICU stays of less than 24 h, confirmed the robustness of these findings.ConclusionIn ICU patients following cardiac surgery, postoperative use of ondansetron is associated with an increased risk of both 7-day AKI and POAF, particularly in patients aged 65 years and older. These findings suggest that the use of ondansetron in this population should be approached with caution, especially in elderly patients who may be more susceptible to these complications. Further research is needed to explore the mechanisms underlying the association between ondansetron and these adverse outcomes.

Project description:Background: Aspirin, with its pleiotropic effects such as anti-inflammatory and anti-platelet aggregation, has been widely used for anti-inflammatory, analgesic, and cardiovascular diseases. However, the association between the use of aspirin before the intensive care unit (ICU) and clinical outcomes in critically ill patients with acute kidney injury (AKI) is unknown. Methods: Patients with AKI in this retrospective observational study were selected from the Marketplace for Medical Information in Intensive Care IV (MIMIC-IV). The association between aspirin intervention and 30-day mortality was assessed using Cox proportional hazards model. Logistic regression models were used to assess the association of aspirin intervention with the risks of intracranial hemorrhage, gastrointestinal bleeding and blood transfusion. The propensity score matching (PSM) method was adopted to balance the baseline variables. Sensitivity analysis was performed to validate the results by multiple interpolations for the missing data. Results: The study included 4237 pre-ICU aspirin users and 9745 non-users. In multivariate models, we found a decreased risk of mortality in those who received aspirin before ICU compared to those who did not (30-day:hazard ratio [HR], 0.70; 95% CI, 0.62-0.79; p < 0.001; 90-day:HR, 0.70; 95% CI, 0.63-0.77, p < 0.001; 180-day:HR, 0.72; 95%CI,0.65-0.79, p < 0.001). This benefit was consistent in the post-PSM analyses, sensitivity analyses, and subgroup analyses. Moreover, aspirin intervention was associated with a reduced risk of intracranial hemorrhage and gastrointestinal bleeding (HR, 0.16; 95% CI, 0.10-0.25; p < 0.001; HR, 0.59; 95% CI, 0.38-0.88, p = 0.012) after being adjusted by relating covariates, whereas with a increased risk of blood transfusion (HR, 1.28; 95% CI, 1.16-1.46; p < 0.001). Conclusion: Patients with AKI treated with aspirin before ICU admission might have reduced 30-day, 90-day and 180-day mortality without increasing the risk of intracranial hemorrhage (ICH) or gastrointestinal bleeding, but may increase the risk of transfusion.

Project description:BackgroundSepsis is a systemic inflammatory response syndrome, with sepsis-associated acute kidney injury (SA-AKI) being a common complication. Insulin resistance (IR) is closely related to the stress response, inflammatory response, and severity of critical illness. The triglyceride-glucose body mass index (TyG-BMI) is a valuable tool for assessing IR. However, the relationships between TyG-BMI and clinical outcomes in patients with SA-AKI remain unclear.MethodsWe conducted a retrospective analysis of ICU patients with SA-AKI using data from the MIMIC-IV database. The Boruta algorithm was employed to select significant features for predicting short-term mortality in SA-AKI patients. Multivariate Cox proportional hazards regression, sensitivity analysis, restricted cubic spline (RCS) models, and Kaplan-Meier (K-M) survival analysis were used to assess the relationship between TyG-BMI and short-term mortality in SA-AKI patients. Subgroup analyses considered the effects of age, sex, ethnicity, comorbidities and septic shock.ResultsThis study included 3,349 patients, with males accounting for 60.5% of the patients. The Boruta analysis identified the TyG-BMI as an important clinical feature. Higher TyG-BMI values were significantly associated with reduced short-term mortality rates (28, 90, and 180 days) in patients with SA-AKI; for each standard deviation increase in TyG-BMI, the risk of all-cause death decreased by 0.2% (p < 0.0001). Kaplan-Meier analysis demonstrated that patients with high TyG-BMIs had significantly lower mortality rates than did those with low TyG-BMIs. The RCS model revealed an L-shaped nonlinear relationship between the TyG-BMI and mortality. Sensitivity analyses indicated that the association remained significant even after excluding patients with myocardial infarction, congestive heart failure, or those who were hospitalized in the ICU for less than 2 days. Subgroup analyses revealed a significant interaction effect on short-term mortality in CRRT patients (p < 0.05).ConclusionThe relationship between the TyG-BMI and short-term mortality in ICU patients with SA-AKI is significant, indicating its potential value for early risk assessment and clinical intervention.

Dataset Information

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

Publications

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

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