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).