Effects of Esketamine Versus Remifentanil on Hemodynamics and Prognosis in Patients with Septic Shock Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial

Yuting Li, Hongxiang Li, Feng Zhang, Yumeng Chen, Dong Zhang Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Dong Zhang, Email [email protected]: Analgesics and sedatives may affect the hemodynamics of patients with septic shock and produce adverse reactions. The purpose of this study is to compare the hemodynamic effects and prognosis of esketamine and remifentanil in combination with propofol in patients with septic shock receiving invasive mechanical ventilation.Methods: In this single-center, prospective, randomized, controlled pilot study, patients with septic shock in the intensive care unit (ICU) receiving invasive mechanical ventilation were randomized to receive esketamine or remifentanil in combination with propofol intravenously. The target Critical-Care Pain Observation Tool (CPOT) score was < 3 points and Richmond Agitation and Sedation Scale (RASS) score was − 2~0 points. The primary outcome was dosage of norepinephrine (mg/kg). Secondary outcomes included mechanical ventilation time(hours), dosage of propofol (mg/kg), intestinal dysfunction rate, ICU length of stay(days), hospital length of stay(days), hospital mortality and 28-day survival rate. We registered the study at ClinicalTrials.gov on 23/09/2022 (https://clinicaltrials.gov/study/NCT05551910).Results: A total of 120 patients were enrolled in the study. Sixty patients were assigned to each group. The median dosage of norepinephrine of remifentanil group was 4.09(1.52,8.85) mg/kg while that of esketamine group was 1.72(1.01,3.97) mg/kg. The dosage of norepinephrine of esketamine group was less than that of remifentanil group(P=0.007). There were no significant differences between the two groups with respect to adverse event rate, intestinal dysfunction rate, dosage of propofol, mechanical ventilation time, ICU length of stay, hospital length of stay and hospital mortality(P> 0.05). Kaplan-Meier survival analysis showed that there was no significant difference in 28-day survival rate between the two groups(P=0.225).Conclusion: Esketamine may decrease the dosage of norepinephrine in patients with septic shock receiving invasive mechanical ventilation. It is beneficial for stabilizing hemodynamics and appears to be an effective and safe agent for patients with septic shock requiring invasive mechanical ventilation.Keywords: septic shock, invasive mechanical ventilation, esketamine, remifentanil, norepinephrine