Oliceridine for postoperative pain and opioid-related complications: The intravenous oliceridine and opioid-related complications (VOLITION) prospective cohort study.

BACKGROUND

Oliceridine is a G protein-selective μ-opioid receptor agonist with reduced β-arrestin activation that may produce fewer opioid-related adverse effects (ORAEs) than traditional opioids. The VOLITION prospective cohort study evaluated oliceridine for management of postoperative pain and evaluated ORAEs.

METHODS

We enrolled 204 patients scheduled for major noncardiac surgery. Our primary aim was to quantify the proportion of patients having respiratory compromise over the initial two postoperative days. Cardiorespiratory function was continuously monitored with pulse oximetry, capnography, and plethysmography. Our composite of clinically meaningful respiratory events was defined by an end-tidal (Et) CO ≤ 15 mmHg for ≥3 min, respiratory rate ≤ 5 breaths/min for ≥3 min, oxygen saturation ≤ 85 % for ≥3 min, apnea lasting >30 s, or any life-threatening respiratory events. All potential respiratory events were adjudicated by two independent expert reviewers. On an exploratory basis we evaluated the proportion of patients achieving a complete gastrointestinal response (no vomiting and no rescue antiemetic use). Central nervous system compromise was evaluated with the Richmond Agitation-Sedation Scale, the Pasero Opioid-Induced Sedation Scale, and the 3-min Diagnostic Confusion Assessment Method.

RESULTS

Among 203 patients in the safety population (mean age 57 years, 52 % women; mean duration of surgery: 5 h), 197 patients had cardiorespiratory data available for analysis. The median cumulative oliceridine dose was 33 mg (range 1.5-75 mg). There were 174 adjudicated episodes of respiratory compromise in 45 patients (23 %) but no deaths or oliceridine-related serious adverse events. Naloxone opioid reversal was never required. There were 107 (53 %) patients who had a complete gastrointestinal response, and eight met screening criteria for delirium.

CONCLUSION

Nearly one quarter of patients experienced a respiratory compromise with oliceridine analgesia, none of which was life-threatening. A randomized trial needs to determine whether oliceridine produces fewer overall ORAEs than conventional opioids. The study was registered at ClinicalTrials.gov (NCT04979247).