Effect of esketamine on the EC50 of remifentanil for blunting cardiovascular responses to endotracheal intubation in female patients under general anesthesia: a sequential allocation dose-finding study

Abstract

Background: This study aimed to investigate the effect of esketamine on the dose–effect relationship between remifentanil and the cardiovascular response to endotracheal intubation during target-controlled infusion (TCI) of propofol. Methods: Patients underwent elective gynecological laparoscopic surgery under general anesthesia with endotracheal intubation, aged 18–65 years, American Society of Anesthesiologists class I or II, 18 kg/m2 ≤ body mass index ≤ 30 kg/m2, were randomly divided into the control (group C) and esketamine groups (group E). Before anesthesia induction, group E received an intravenous injection of 0.3 mg/kg of esketamine, while group C received an equal dose of physiological saline. TCI of propofol to the effect-site concentration (EC) of 3.0 μg/mL, and then TCI of remifentanil to the effect room and intravenous injection of rocuronium 0.6 mg/kg after MOAA/S was 0. Endotracheal intubation was performed after 2 min. Dixon’s modified sequential method was used, and the initial EC of remifentanil was 3.0 ng/mL. The EC of remifentanil was determined according to the intubation response of the previous patient, with an adjacent concentration gradient of 0.3 ng/mL. The EC50 and EC95 values and their 95% confidence intervals (CIs) were determined using probit regression analysis. Results: The EC50 for cardiovascular response inhibition to endotracheal intubation using remifentanil was 3.91 ng/mL (95% CI: 3.59–4.33 ng/mL) and EC95 was 4.66 ng/mL (95% CI: 4.27–6.23 ng/mL) with TCI of propofol 3.0 μg/mL. After intravenous administration of 0.3 mg/kg of esketamine, the EC50 of remifentanil was 3.56 ng/mL (95% CI: 3.22–3.99 ng/mL) and EC95 was 4.31 ng/mL (95% CI: 3.91–5.88 ng/mL). Conclusions: Combined with TCI of propofol 3.0 μg/mL for anesthesia induction, esketamine significantly reduced the EC50 and EC95 of remifentanil to inhibit the cardiovascular response to endotracheal intubation. Trial registration: The trial was registered in the Chinese Clinical Trials Registry (www.chictr.org.cn; registration number: ChiCTR2200064932; date of registration:24/10/2022).