ED90 of Tegileridine for Suppressing Hemodynamic Response to Tracheal Intubation: A Biased Coin Up-and-Down Trial

Tracheal intubation under general anesthesia stimulates the airway and triggers transient hypertension and tachycardia due to sympathetic excitation. Excessive hemodynamic fluctuations may trigger myocardial ischemia, arrhythmia and other adverse cardiovascular events. Traditional opioids simultaneously activate G-protein and β-arrestin pathways, often accompanied by obvious respiratory depression. As a newly marketed biased μ-opioid agonist, tegileridine exerts analgesic effects with reduced β-arrestin related side effects. Up to now, few studies have explored the effective dose of tegileridine for blunting intubation stress.

We conduct a single-center, open-label sequential dose-finding trial stratified by age. Eligible subjects are ASA I-III patients scheduled for elective surgery with tracheal intubation. Subjects receive intravenous tegileridine before anesthetic induction. The dose is adjusted according to biased coin up-and-down rule based on whether a positive cardiovascular response occurs after intubation. We adopt centered isotonic regression to calculate the 90% effective dose (ED90). Blood pressure, heart rate, induction adverse reactions and sedation scores will be recorded. All adverse events will be closely monitored throughout induction. The findings of this trial will establish a dosing reference of tegileridine for anesthesia induction and facilitate safer perioperative management.

Inclusion criteria

• American Society of Anesthesiologists (ASA) physical status I-III
• Aged 18-90 years old
• Scheduled for elective surgery requiring general anesthesia with tracheal intubation
• No predicted difficult airway

Exclusion criteria

• Resting Systolic Blood Pressure ≥ 160 mmHg, Diastolic Blood Pressure ≥ 110 mmHg, or heart rate ≥ 110 beats/min on admission to endoscopy room
• Continuous opioid medication use for more than 2 weeks within 6 months before the procedure
• Known hypersensitivity or allergic reaction to tegileridine, propofol or any excipients of the two drugs
• Diagnosed psychiatric disorders or inability to communicate and cooperate with study assessment