Background/importance The effects of combining dexamethasone and dexmedetomidine on block duration are unclear.

Objective To investigate the effects of combining dexamethasone and dexmedetomidine on block duration.

Evidence review Systematic review of randomized controlled trials (RCTs) from Medline, Embase, CENTRAL, CINAHL, the Web of Science, and BIOSIS until June 8, 2023. RCTs with adults undergoing surgery with a peripheral nerve block randomized to combined dexamethasone and dexmedetomidine versus placebo or other adjuncts were eligible. Primary outcome was duration of analgesia. We performed meta-analysis, trial sequential analysis, risk of bias-2, and Grading Recommendations Assessment, Development, and Evaluation assessment.

Findings We included 9 RCTs with 14 eligible comparisons. The combination of dexamethasone and dexmedetomidine was compared with placebo in three RCTs (173 participants), dexamethasone in seven (569 participants), and dexmedetomidine in four (281 participants). The duration of analgesia was likely increased with the combination versus placebo (mean difference 460 min, 95% CI 249 to 671) and versus dexmedetomidine (mean difference 388 min, 95% CI 211 to 565). The duration was likely similar with the combination versus dexamethasone (mean difference 50 min, 95% CI −140 to 239). The certainty of the evidence was moderate because most trials were at high risk of bias.

Conclusions Combined dexamethasone and dexmedetomidine likely increased the duration of analgesia when compared with placebo and dexmedetomidine. The combination likely provided a similar duration of analgesia as dexamethasone. Based on this systematic review, it seems reasonable to use dexamethasone as the sole adjunct if the goal is to increase the duration of analgesia.