The Effects of Perineural Dexamethasone on Preventing Post-Surgical Rebound Pain and Effects on Hyperglycaemia: A Meta-Analysis, Meta Regression and Trial Sequential Analysis

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Aims/Background: Rebound pain is extreme pain occurring once the effects of a regional nerve block have subsided. We undertook a meta-analysis to assess the impact of perineural dexamethasone, as an adjunct to peripheral nerve block, on post-surgical rebound pain compared to local anaesthetic alone. Methods: The databases PubMed, Scopus and Cochrane Library were searched for randomised controlled trials, reporting rebound pain with perineural dexamethasone used as an adjunct to peripheral nerve blocks (from inception to 28 October 2025). The primary outcome was the incidence of rebound pain post-surgically; the secondary outcomes were onset of rebound pain (hours), pain scores at 24 and 48 hours, time until first analgesic request (hours), and incidence of hyperglycaemia. Results: Nine studies with 764 participants were included. Perineural dexamethasone significantly reduced the incidence of rebound pain (odds ratio [OR] = 5.00, 95% confidence interval [CI] 2.69–9.29, p < 0.00001, I2 = 41%). The time to the first analgesic request was prolonged in the dexamethasone group (standardised mean differences [SMD] = –2.37, 95% CI –3.38– –1.36, p < 0.00001, I2 = 77%). Perineural dexamethasone did not delay the onset of rebound pain, reduce pain scores at 24 and 48 hours, nor did it significantly alter blood sugar levels. Conclusion: This meta-analysis demonstrated that perineural dexamethasone is more effective than local anaesthetic alone in reducing the incidence of rebound pain and extending the time to the patients’ first analgesic request. There was no significant difference in the onset of rebound pain, pain scores at 24 and 48 hours, nor alteration of blood sugar levels. Systematic Review Registration: PROSPERO (CRD42024545072).