Alpha(2)-receptor agonists as adjuvants for brachial plexus nerve blocks-A systematic review with meta-analyses

Background We review the efficacy and safety of dexmedetomidine and clonidine as perineural or systemic adjuvants for brachial plexus blocks (BPB). Methods We included randomised controlled trials on upper limb surgery with BPBs in adults, comparing dexmedetomidine with clonidine or either drug with placebo. The primary outcome was duration of analgesia. Secondary outcomes included adverse and serious adverse events. The review was conducted using Cochrane standards, trial sequential analyses (TSA) and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results We included 101 trials with 6248 patients. Overall, duration of analgesia was prolonged with both clonidine (176 min [TSA adj. 95% CI: 118, 205, p < .00001; 33 trials]) and dexmedetomidine (292 min [TSA adj. 95% CI: 245 329, p < .00001; 53 trials]), but was longer for dexmedetomidine than clonidine (205 min [TSA adj. 95% CI: 157, 254, p < .00001; 19 trials]). Compared with placebo, dexmedetomidine was associated with bradycardia (RR 4.2 [95% CI 2.2, 8.3]), and both clonidine (RR 4.5 [95% CI 1.1, 18.3]) and dexmedetomidine (RR 3.9 [95% CI 2.0, 7.5]) were associated with hypotension. Serious adverse events were mostly related to block technique. GRADE-rated quality of evidence was low or very low. Conclusion Alpha2-receptor agonists used as adjuvants for BPBs lead to a prolonged duration of analgesia, with dexmedetomidine as the most efficient. Alpha2-receptor agonists were associated with increased risk of cardiovascular adverse events. The quality of evidence was low to very low.