The potential effectiveness of tolvaptan independent of cardiac disease in critically ill patients: A retrospective observational study

Abstract

Abstract Background: The selective arginine vasopressin 2 receptor antagonist tolvaptan has been demonstrated to increase the urine volume of patients with cardiac issues. We investigated the potential diuretic effectiveness of tolvaptan independent of cardiac disease in critically ill patients. Patients and Methods: This was a single-center (teaching hospital) retrospective observational study. We analyzed the data of the hospital's critically ill adult patients (n=477) including non-cardiac as well as cardiac populations who had an ICU stay ≥4 days in 2019–2020 and who did not undergo permanent renal replacement therapy before their ICU admission. We investigated the independent effects of tolvaptan use on the primary endpoint (increased urine volume) and a secondary endpoint (time-course changes in patients' serum creatine [sCr] values), adjusted for confounders (patients' disease severity, comorbidities including cardiac disease, and diuretics used), by applying two statistical models: (i) a multivariate logistic regression model to estimate the predictors independent of cardiac disease for the patients whose daily urine volume had increased by >twofold compared to the minimal value, and (ii) a generalized estimating equation model to estimate tolvaptan's effect independent of cardiac disease on time-course changes in the sCr level. Results: Tolvaptan use was a significant predictor independent of cardiac disease for increased urine volume (odds ratio [OR] 1.86, 95%CI: 1.13–3.06, p=0.015). In contrast, cardiac disease was asignificant independent predictor of decreased urine volume (OR 0.58, 95%CI: 0.37–0.90, p=0.016). Tolvaptan use was not significantly associated with time-course changes in the sCr level: beta estimator [95%CI], 0.07 [−0.01 to 0.15], p=0.08. Conclusions: Tolvaptan use was a significant predictor — independent of cardiac disease — for increased daily urine volume in this critically ill population. After adjustment for cardiac disease, tolvaptan was not associated with time-course changes in the patients' sCr levels during their intensive care. Trial registration: Not applicable.