Oliceridine Dose for Tracheal Intubation Hemodynamic Elevation: Up-and-Down Trial

• Study Objectives To determine the ED50 and ED95 of oliceridine in inhibiting tracheal intubation-induced hyperdynamic responses (e.g., increased blood pressure and heart rate) during general anesthesia induction, and to provide dose evidence for individualized anesthesia induction protocols.
• Study Design Type: A dynamic dose-finding clinical trial using the modified Dixon up-and-down sequential design.

Sample Size: 35 cases per group anticipated, with trial termination after 7 cross-overs between positive and negative responses (i.e., transitions in whether hemodynamic responses exceed 20% of baseline).

Grouping: Stratified by age into young group (18-65 years) and elderly group (≥65 years).

• Study Participants

Inclusion criteria

Patients undergoing elective tracheal intubation under general anesthesia; Aged ≥18 years; American Society of Anesthesiologists (ASA) physical status Ⅰ-Ⅲ; Body mass index (BMI) < 25.

Exclusion criteria

Systolic blood pressure (SBP) ≥160 mmHg, diastolic blood pressure (DBP) ≥110 mmHg, or heart rate ≥110 beats/min at rest upon admission to the operating room; Long-term use of analgesics or sedatives before surgery; Pregnancy, lactation, or planned pregnancy; Allergy to oliceridine; Mental illness or inability to communicate normally.

• Trial Procedures Screening Period (-7 to 0 days): Informed consent signed; collection of basic information (age, ASA class, etc.); baseline blood pressure and heart rate monitored.

Anesthesia Induction and Intubation:

Routine vital sign monitoring and intravenous access established upon patient admission.

Initial doses: 45 μg/kg for the young group and 42 μg/kg for the elderly group. Subsequent doses adjusted based on intubation response (increase by 3 μg/kg for positive response, decrease by 3 μg/kg for negative response).

Administration sequence: Intravenous oliceridine → propofol 2 mg/kg 2 minutes later → rocuronium 0.6 mg/kg after loss of consciousness (MOAA/S score ≤1) → tracheal intubation after neuromuscular blockade.

Anesthesia Maintenance: Propofol (4-8 mg/kg/h) and remifentanil (0.05-0.1 μg/kg/min) infused continuously; rocuronium added intermittently; protective ventilation strategy applied.

• Outcome Measures Primary Measures: ED50 and ED95 of oliceridine for inhibiting post-intubation hyperdynamic responses.

Secondary Measures:

Incidence of hyperdynamic responses within 3 minutes after intubation; Blood pressure (SBP, DBP) and heart rate at baseline, 2 minutes after drug administration, before intubation, and within 3 minutes after intubation; Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score; Adverse events (arrhythmia, coughing, allergic reactions, etc.).

• Statistical Methods Data analysis will be performed using R software. Quantitative data will be expressed as mean±standard deviation or median (interquartile range), and qualitative data as frequency (percentage). Probit analysis will be used to calculate ED50 and its 95% confidence interval. A P-value <0.05 will be considered statistically significant.

Inclusion criteria

• Elective surgery requiring general anesthesia with tracheal intubation
• Age ≥ 18 years
• American Society of Anesthesiologists (ASA) physical status I-III
• BMI<25

Exclusion criteria

• At rest in the operating room, systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 110 mmHg or heart rate ≥ 110 bpm
• Preoperative long-term use of analgesic or sedative medications
• Pregnancy, breastfeeding, known or planned pregnancy
• Known allergy or hypersensitivity to oliceridine or any study medication components
• History of psychiatric illness or inability to communicate effectively