Dexamethasone Injected Perineurally is More Effective than Administered Intravenously for Peripheral Nerve Blocks

Introduction: Peripheral nerve blocks (PNBs) are widely and increasingly used for better acute perioperative pain control for a variety of procedures. Clinically preservative-free dexamethasone is arguably the most commonly used adjuvant and offers the most optimization effects on PNBs yet with the least side-effects noted. Our aim was to compare the effectiveness of intravenous versus perineural dexamethasone on the effectiveness and safety of PNBs. Methods: Major databases (PubMed, EMBASE, Cochrane library, ISI Web of Science, Google Scholar) were systematically searched for randomized controlled trials comparing the effectiveness of intravenous versus perineural dexamethasone on PNBs. Study characteristics, intraoperative events, and postoperative outcomes including duration of analgesia, duration of sensory block, duration of motor block, pain score at 24 hours, opioid consumption, and postoperative nausea and vomiting, were extracted from the articles. Meta-analysis was performed using random-effect models. Results: Thirteen randomized controlled trials comprising a total of 937 patients (intravenous: 464 patients; perineural: 473 patients) were included in this meta-analysis. Perineural dexamethasone significantly prolonged the duration of analgesia (standardized mean difference [SMD], 0.48 h; 95% confidence interval [CI], 0.18-0.79) and sensory block (SMD, 0.74; 95% CI, 0.53-0.94). In subgroup of studies that used 4 to 5 mg we found that perineural dexamethasone was universally more effective to prolong analgesia as compared with intravenous dexamethasone (SMD, 0.48 h; 95% CI, 0.24-0.72), but there was no significant difference between intravenous versus perineural dexamethasone when using a dose of dexamethasone ≥8 mg (SMD, 0.33 h; 95% CI, −0.11 to 0.77). Perineural dexamethasone had similarly more benefits in terms of prolongation of motor block duration, decreasing pain score, reducing opioid consumption, and less postoperative nausea and vomiting. Conclusions: This investigation not only confirmed the better analgesic effects of perineurally administered dexamethasone as compared with its intravenous injection, but also implicitly supported the hypothesis of local interaction between dexamethasone and the nerve as one of the pain modulation mechanisms of dexamethasone, because systemic absorption alone could not explain the superior quality of PNBs.