Dexmedetomidine for Reduction of Mortality in Septic Shock: a Protocol for a Randomized Controlled Trial (DecatSepsis)

Abstract

Abstract Introduction: Sepsis is a global problem, which has a high mortality in cases of shock. Sepsis and its complications have been linked to acute stress response. Therefore, we hypothesized that decatecholaminization (i.e., reducing adrenergic stress) with dexmedetomidine would reduce mortality and improve the outcomes of septic shock. Methods and Analysis: This is a protocol for an open-label randomized controlled trial that aims to study the impact of heart rate (HR)-calibrated dexmedetomidine infusion on inhospital mortality, which is the study primary outcome, in cases of septic shock. We will use a dose range of 0.2–0.7 mcg/kg/h for 48 hours to keep the HR between 60 and 90 beats per minute (bpm). In ventilated patients, we will use the least conventional sedation that will enable the patients in both groups to tolerate the tube and ventilation. We plan to include 90 patients with sepsis and HR of > 90 bpm while on norepinephrine infusion. The main secondary outcomes are the mean dose of norepinephrine and the mean hemodynamic parameters over the first three days of inclusion or death. We will perform per-protocol and intension-to-treat analyses. The primary outcome will be analyzed using the Chi-square test, and we will report the risk ratio and 95% confidence interval. Thereafter, we will adjust for the confounders (i.e., age, sex, mechanical ventilation, and comorbidities) in a logistic regression. The level of statistical significance will be a p-value ≤ 0.05. Ethics and dissemination: We obtained the institutional review board approval (MS:22.02.1889) on March 19, 2022 at the Mansoura University, Faculty of Medicine. Written informed consent will be obtained from all patients or their relatives. We will publish the study results in a preprint registry and in conferences, with attempt to publish the report in a peer-reviewed journal. Trial registration: Clinical trial registration (https://clinicaltrials.gov/ct2/show/NCT05283083) on March 16, 2022