Comparative effective dose of ciprofol and propofol in suppressing cardiovascular responses to tracheal intubation

Abstract

Ciprofol, a novel γ-aminobutyric acid receptor agonist, outperforms propofol with minimal cardiovascular effects, higher potency, reduced injection pain, and a broader safety margin. Despite these advantages, ciprofol's clinical research is still emerging. This study compares the median effective dose (ED₅₀) and adverse reactions of ciprofol and propofol, in conjunction with sufentanil, for suppressing cardiovascular responses during tracheal intubation. Fifty-three adult patients scheduled for tracheal intubation under general anesthesia were enrolled and randomly assigned to receive either ciprofol (Group C) or propofol (Group P), according to a random number table. Tracheal intubation was performed using a standardized laryngoscope and endotracheal tube. The Dixon's up-and-down method was employed to determine the ED₅₀ and 95% effective dose (ED₉₅) of ciprofol and propofol in inhibiting cardiovascular responses during tracheal intubation. Based on the pilot study, the initial dose for ciprofol was set at 0.35 mg/kg (with a 0.01 mg/kg increment) and for propofol at 2.0 mg/kg (with a 0.1 mg/kg increment). Probit analysis was applied to derive dose-response curves, while adverse reactions were continuously monitored. A total of 54 participants were included, with 24 in group C (1 excluded) and 30 in group P. Probit analysis revealed that the ED₅₀ of ciprofol for inhibiting cardiovascular responses to tracheal intubation were 0.326 mg/kg (95% CI 0.304-0.337 mg/kg), and for propofol, 1.541 mg/kg (95% CI 1.481-1.599 mg/kg). The heart rate in group P was significantly higher than the group C at 1 minute (p = 0.026) and 3 minutes (p = 0.016) post-intubation. Systolic and diastolic blood pressures (SBP and DBP) decreased significantly before and after intubation compared to baseline values in both groups (p< 0.05). Group C experienced significantly less injection pain (p = 0.001), although the incidence of other adverse effects was not statistically different between groups (p > 0.05).Clinical Trial Registration: hppts://ClinicalTrials.gov; Identifier: NCT06095570(18/10/2023).

Keywords: Cardiovascular response; Ciprofol; Dose-response relationship; Propofol; Tracheal intubation.

Fig. 1

Flowchart of study participant enrollment.

Fig. 2

The sequential plots of ciprofol and propofol. Panel A represents the propofol group, panel B represents the ciprofol group. White circles indicate positive tracheal intubation response, while black circles indicate negative tracheal intubation response.

Fig. 3

Dose-response curves of propofol and ciprofol. Panel A shows the dose-response curve of propofol, with ED50 and ED95 for inhibiting cardiovascular responses to tracheal intubation being 1.541 mg/kg (95% CI 1.481–1.599 mg/kg) and 1.656 mg/kg (95% CI 1.599–1.943 mg/kg). Panel B shows the dose-response curve of ciprofol, with ED50 and ED95 for inhibiting cardiovascular responses to tracheal intubation being 0.326 mg/kg (95% CI 0.304–0.337 mg/kg) and 0.349 mg/kg (95% CI 0.337–0.470 mg/kg). CI = confidence interval, ED = effective dose.

Fig. 4

Comparison of BP and HR during induction in Group C and Group P. T1: the average values of three measurements after entering the room as baseline, T2: after intravenous administration of study drug, T3: after complete injection of all drugs, T4: immediately before intubation, immediately after intubation, T5: 1 min after intubation, T6: 2 min after intubation, and T7: 3 min after intubation. * Compared to Group P, Group C showed a p ≤ 0.05 for blood pressure or heart rate at the corresponding time point. ** Group C showed a p ≤ 0.01 for blood pressure or heart rate at the corresponding time point when compared to Group P.