EC50 of Remifentanil for Inhibiting Cardiovascular Responses to Tracheal Intubation in Patients Treated by Different Doses of Oliceridine: A Randomized Controlled Trial Using Up-and-Down Sequential Allocation Methodology

Zhenzhen Zhao,* Lingling Ge,* Xiaolin Wang,* Xiandong Wang, Jie Huang, Yaqin Xiao, Ying Zhang, Yan Zhou, Rui Bao, Jia-feng Wang Faculty of Anesthesiology, Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Bao, Faculty of Anesthesiology, Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China, Tel +86 13816947847, Email [email protected] Jia-feng Wang, Faculty of Anesthesiology, Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China, Tel +86 13774286926, Email [email protected]: The aim was to evaluate its antinociceptive potency by comparing the effect of oliceridine and sufentanil on the half maximal effective concentration (EC50) of remifentanil in suppressing the cardiovascular response to endotracheal intubation under general anesthesia.Patients and methods: A total of 120 patients scheduled for thyroid nodulectomy were randomized into four groups: (i) control group, (ii) sufentanil group, (iii) oliceridine 0.015 mg/kg group, and (iv) oliceridine 0.03 mg/kg group. The initial dosage of remifentanil for induction of general anesthesia was 3 ng/mL. The subsequent infusion dosage of remifentanil was adjusted based on the response to endotracheal intubation in the previous patient in the group, defined as a ≥ 15% change in heart rate (HR) or mean arterial pressure (MAP) before and after intubation. Adjustments were made in increments or decrements of 0.2 ng/mL. The control group received no additional medication, whereas the sufentanil group was administered a 0.15 μg/kg intravenous (IV) bolus of sufentanil. The two oliceridine groups received IV boluses of oliceridine either 0.015 mg/kg or 0.03 mg/kg respectively. Postoperative airway complications, encompassing hoarseness, sore throat, and dysphonia, were also documented.Results: The EC50 values of remifentanil was 3.728 ng/mL (95% CI: 3.536– 3.943 ng/mL), 2.824 ng/mL (95% CI: 2.620– 3.015 ng/mL), 3.045 ng/mL (95% CI: 2.852– 3.239 ng/mL) and 2.887 ng/mL (95% CI: 2.689– 3.085 ng/mL) in the control, sufentanil, oliceridine 0.015 mg/kg group and oliceridine 0.03 mg/kg group, respectively.Conclusion: The effect of 0.03 mg/kg oliceridine is similar to 0.15 μg/kg sufentanil in reducing the EC50 of remifentanil in inhibiting the cardiovascular responses induced by trachea intubation.Keywords: oliceridine, EC50, hemodynamic response to trachea intubation, the sequential method