Oliceridine vs Sufentanil for Cough During Anesthesia Induction

Overview

Sufentanil is the most widely used opioid analgesic for general anaesthesia induction; however, rapid intravenous bolus injection frequently triggers sufentanil-induced cough (SIC). In high-risk patients, SIC can cause abrupt elevation of intracranial and intraocular pressure and severe haemodynamic instability, posing a meaningful safety risk during the induction period. Oliceridine, the first G protein-biased μ-opioid receptor agonist approved by the Food and Drug Administration in 2020, provides analgesia through μ-receptor activation while substantially reducing β-arrestin-2 recruitment. This biased signalling profile is hypothesised to raise the excitation threshold of airway C-fibres and thereby reduce the incidence of cough. This prospective, single-centre, randomised, double-blind, parallel-group controlled trial directly compares oliceridine with sufentanil for general anaesthesia induction with respect to cough incidence, cough severity, haemodynamic responses, and perioperative safety, with the aim of providing evidence-based guidance for opioid selection during induction.

Rapid intravenous bolus injection of sufentanil frequently triggers sufentanil-induced cough (SIC). Although several prophylactic strategies have been described, all rely on adding a pretreatment agent on top of sufentanil - a reactive, patch-based approach that does not address the underlying cause. Oliceridine, a G protein-biased μ-opioid receptor agonist, preserves analgesic efficacy while substantially reducing β-arrestin-2 recruitment. This biased signalling profile is hypothesised to reduce cough risk at its origin by maintaining normal desensitisation of airway C-fibre transient receptor potential vanilloid 1 (TRPV1) channels and preserving β₂-adrenergic receptor-mediated bronchodilatory reserve in airway smooth muscle. Furthermore, oliceridine is formulated as a fumarate salt; because conventional fentanyl-class agents use citrate formulations, this difference eliminates a potential chemical cough stimulus at the formulation level. This prospective, single-centre, randomised, double-blind, parallel-group controlled trial directly compares oliceridine with sufentanil for general anaesthesia induction. A randomisation sequence will be generated by an independent statistician and concealed using sealed opaque envelopes; both the attending anaesthesiologist and the data recorder will remain blinded to group allocation throughout the study. Participants in the oliceridine group will receive intravenous oliceridine 0.05 mg/kg (elderly patients) or 0.06 mg/kg (younger patients) as a 2-second bolus, whereas participants in the sufentanil group will receive intravenous sufentanil 0.25μg/kg (elderly patients) or 0.3 μg/kg (younger patients) as a 2-second bolus. Cough will be observed for 2 minutes after injection, after which anaesthesia induction will be completed with propofol 2.0 mg/kg followed by rocuronium 0.6 mg/kg, and tracheal intubation will be performed. The primary outcome is the incidence of cough within 2 minutes of study drug injection. Secondary outcomes include cough severity (mild, moderate, or severe); haemodynamic variables - heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure - at time points T0 through T5; incidence of haemodynamic adverse events, including bradycardia and hypotension; and opioid-related adverse events, including chest wall rigidity, apnoea, and arterial oxygen saturation below 95%. Assuming a cough incidence of 40% in the sufentanil group and an expected reduction to 10% in the oliceridine group, with a two-sided α of 0.05 and 80% power, 30 participants per group are required; accounting for a 5% dropout rate, 31 participants will be enrolled per group, for a total of 62 participants. The trial will be conducted in the Department of Anaesthesiology, Tianmen First People's Hospital, Tianmen, Hubei, China (a tertiary Grade-A hospital).