The Role of Ultra-Low-Dose Naloxone as an Additive in Anesthesia and Nerve Block: A Systematic Review

In anesthesia and analgesia, opioids alone or in combination with local anesthetics (bupivacaine, lidocaine, and ropivacaine) have been investigated to prolong peripheral nerve blocks. Ultra-low-dose naloxone administration in local anesthetic solutions could lengthen sensory and motor blocks through enhanced opioid effects or direct antagonistic effects on the receptors. We aim to assess the role of ultra-low-dose naloxone as an additive in anesthesia duration, motor, and sensory block duration, visual analog scale (VAS) scores, opioid consumption, and the incidence of postoperative complications.

A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to November 23rd, 2023, and 840 records were retrieved and screened. Accordingly, seven randomized controlled trials met the eligibility criteria and were included for data extraction. The National Institute of Health's (NIH) Quality Assessment Tool for Clinical Trials was used for critical appraisal of the studies.

The effects of ultra-low-dose naloxone on intravenous regional anesthesia and various nerve blocks (including axillary and supraclavicular brachial plexus, peribulbar, femoral, and intercostal nerve block) were assessed. The administration of naloxone at doses of 100 and 50 ng as an additive to bupivacaine, lidocaine, and ropivacaine was associated with longer postoperative analgesia, prolonged motor and/or sensory block, lower postoperative opioid or analgesic consumption, and lower VAS pain scores in several included studies. Besides, in most studies, postoperative complications did not significantly differ between the groups.

The available evidence suggests that ultra-low-dose naloxone may be associated with prolonged postoperative analgesia and, in some studies, longer motor and/or sensory block duration and reduced postoperative opioid consumption. These findings should be interpreted as observations reported by individual studies rather than definitive treatment effects. Although no major safety concerns were identified, the available evidence is insufficient to establish the overall safety or efficacy of ultra-low-dose naloxone.