Oliceridine-Enhanced Analgesia and Recovery: A G-Protein Biased μ-Opioid Study

This study selects 80 elective patients slated for upper abdominal laparoscopic surgery under general anesthesia, classified as ASA I-II. These patients are randomly allocated into four groups: Oliceridine low dose (OⅠ), medium dose (OⅡ), and high dose (OⅢ), and a Morphine (M) group. The postoperative analgesic protocol includes a universal loading dose of 1.5 mg for all groups. Depending on the group, the PCA doses are set at 0.1 mg, 0.35 mg, or 0.5 mg, with a lockout interval of 6 minutes. After the initial dose, patients may receive an additional 0.75 mg per hour as needed, with a daily ceiling of 27 mg for Oliceridine. In the Morphine group, the loading dose is 4 mg with a PCA dose of 1 mg and similar lockout, allowing 2 mg per hour post-loading, capped at 60 mg daily. Outcomes to monitor include systolic and diastolic blood pressures, heart rate, oxygen saturation, and respiratory rate at 6, 24, and 48 hours postoperatively; pain levels using the NRS scale; nausea and vomiting via the VAS score; and pulmonary complications evaluated by EPCO standards at specified intervals. Gastrointestinal function is assessed using the I-FEED score, and mental health through the HADS scale preoperatively and 48 hours post-surgery. Cognitive function is evaluated using the MMSE scale preoperatively and 72 hours postoperatively. Patient fecal samples are collected pre- and 48 hours post-surgery for microbial and metabolomic analyses to identify potential molecular benefits of Oliceridine, informed by its G-protein biased pharmacology. The study also uses statistical methods to compare microbiological outcomes and correlate these with clinical presentations.

Inclusion criteria

• ASA grades 1-2
• Age > 18 years and < 70 years
• Laparoscopic upper abdominal surgery under general anesthesia is planned, and the operation time is not more than 4 hours
• Voluntarily receive postoperative controlled intravenous analgesia
• Subjects understand and can cooperate with this study
• Subjects can provide and sign written informed consent prior to conducting investigation-related screening procedures

Exclusion criteria

• BMI>30 kg/m2 or < 19 kg/m2
• Patients with preoperative use of opioids, acute and chronic pain or hyperalgesia
• Patients with coronary atherosclerotic heart disease, significant ischemic heart disease, severe angina, heart failure, valvular disease or other heart disease
• More severe hepatic and renal insufficiency
• A history of mental illness or alcoholism
• A history of alcohol or drug abuse
• Combined with cranial pressure, intraocular pressure or glaucoma
• Poorly controlled or untreated hypertension before surgery
• Preeclampsia or eclampsia
• Untreated and undertreated hyperthyroidism
• Combined with autoimmune disease
• Unable to use the numerical rating scale
• History of chronic cough
• Surgery is expected to take more than 4 hours Patients enrolled in other clinical trials within 3 months