Opioids With or Without Low-Dose Naloxone During the Perioperative Period: A Systematic Review With Meta-Analysis

Objectives: The aim of this systematic review and meta-analysis from randomized controlled trials is to assess opioids with or without low-dose naloxone during the perioperative period at pain intensity and opioids-related adverse events. Methods: We searched of Medline, Embase, International Clinical Trials Registry Platform, and the Cochrane Library up to May 31, 2023. We included randomized controlled trials (RCTs) of low-dose naloxone combined with opioids in adults reporting pain intensity or opioid-related adverse event during the perioperative period. Results: A total of 18 RCTs with 1784 participants were included. We could not reach a consistent conclusion for pain intensity due to high heterogeneity. High certainty evidence showed that low-dose naloxone combined with opioids reduced the risk of nausea (relative risk (RR): 0.82 and 95% confidence interval (CI): 0.70-0.96), cough (RR: 0.52 and 95% CI: 0.30-0.90) and postoperative nausea and vomiting (RR: 0.58 and 95% CI: 0.40-0.80). Moderate certainty evidence showed that low-dose naloxone combined with opioids did not reduce vomiting, urinary retention, sedation, dizziness, respiratory depression, headache, drowsiness, shivering, skin itch, hypotension, and sweating. Conclusions: Our findings show that the use of low-dose naloxone in combination with opioids can lower the risk of somnolence and coughing, postoperative nausea, and vomiting.