Identifying the lowest effective opioid dose that achieves rapid pain relief while minimizing side effects is a principal objective in postoperative multimodal analgesia strategies. This study aims to determine the optimal analgesic regimen and dosage by assessing the clinical efficacy of oliceridine for postoperative pain management. It also evaluates oliceridine's contribution to accelerated postoperative recovery, examining aspects such as postoperative pulmonary complications, gastrointestinal function, nausea and vomiting, cognitive function, and emotional distress. Furthermore, the study integrates microbiomics and metabolomics to investigate the underlying molecular mechanisms by which oliceridine promotes rapid postoperative recovery. This research will broaden the clinical data and potential applications of oliceridine, addressing gaps in the field and enhancing practical knowledge. Moreover, this is the first time a clinical study combining multiple omics approaches will provide a comprehensive theoretical foundation for its clinical benefits.

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:

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

Exclusion Criteria:

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