Effect of Sub-antagonist Doses of Naloxone as an Adjuvant to Ropivacaine on the Onset and Quality of Axillary Brachial Plexus Block in Patients Undergoing Forearm and Hand Surgery: A Randomized Double-Blind Clinical Trial.

Background: Axillary brachial plexus block (ABPB) is the preferred regional anesthetic technique for forearm and hand surgery. Naloxone at sub-antagonist doses may paradoxically enhance local anesthetic effects through selective opioid receptor modulation; however, the optimal dose and its clinical benefit in ABPB with ropivacaine remain unclear. Objectives: This study aimed to compare the effects of ultra-low-dose naloxone (0.4 µg), low-dose naloxone (4 µg), and placebo added to 0.5% ropivacaine on block onset, intensity, and postoperative analgesia in patients undergoing elective forearm and hand surgery. To our knowledge, this is the first trial to directly compare two sub-antagonist doses of naloxone as adjuvants to ropivacaine for axillary block. Methods: In this randomized, double-blind clinical trial, 120 patients with American Society of Anesthesiologists (ASA) physical status I or II were allocated equally to three groups: Group 1 (control; ropivacaine plus saline), Group 2 (ropivacaine plus low-dose naloxone, 4 µg), and Group 3 (ropivacaine plus ultra-low-dose naloxone, 0.4 µg). All blocks were performed using combined ultrasound and nerve stimulator guidance. The co-primary outcomes were sensory and motor block onset times. Secondary outcomes included block intensity, visual analog scale (VAS) pain scores during recovery, and the proportion of patients requiring pethidine within 24 hours. Results: All 120 blocks (100%) were clinically successful, with no intraoperative rescue analgesia or conversion to general anesthesia in any group. Motor block onset was significantly faster in Groups 2 and 3 than in Group 1 (P < 0.001); no patient in the naloxone groups required 9 minutes to achieve motor block, compared with 30% in Group 1. Sensory block onset did not differ significantly among groups (P = 0.163). At 30 minutes, VAS scores were lower in both naloxone groups than in Group 1; the overall analysis of variance (ANOVA) result was P < 0.001, and the reported comparison between Group 3 and Group 1 was significant (P < 0.001). The 15-minute difference was not significant after Conclusions: Ultra-low-dose naloxone (0.4 µg) significantly accelerates motor block onset and reduces postoperative pethidine requirements in patients with American Society of Anesthesiologists physical status I or II undergoing elective hand and forearm surgery with ABPB, without adverse effects. Although the 4 µg dose was associated with lower VAS scores at 30 minutes, it did not reduce pethidine requirements and was associated with a nonsignificant increase in the proportion of patients requiring pethidine, consistent with a biphasic dose-response model. These findings highlight the narrow therapeutic margin of perineural naloxone and suggest caution with doses above the ultra-low-dose range, as higher sub-antagonist doses may paradoxically antagonize endogenous analgesic mechanisms.