Background Multimodal analgesia is the leading principle for managing postoperative pain. Recent guidelines recommend combinations of paracetamol and a non‐steroidal anti‐inflammatory drug (NSAID) for most surgeries. Glucocorticoids have been used for decades due to their potent anti‐inflammatory and antipyretic properties. Subsequently, glucocorticoids may improve postoperative analgesia. We will perform a systematic review to assess benefits and harms of adding glucocorticoids to paracetamol and NSAIDs. We expect to uncover pros and cons of the addition of glucocorticoid to the basic standard regimen of paracetamol and NSAIDs for postoperative analgesia. Method This protocol for a systematic review was written according to the The Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols guidelines. We will search for trials in the following electronic databases: Medline, CENTRAL, CDSR and Embase. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's ROB 2 tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta‐analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight‐step procedure suggested by Jakobsen et al We will present our primary findings in a ‘summary of findings’ table. We will evaluate the overall certainty of evidence using the GRADE approach. Discussion This review will aim to explore the combination of glucocorticoids together with paracetamol and NSAIDs for postoperative pain. We will attempt to provide reliable evidence regarding the role of glucocorticoids as part of a multimodal analgesic regimen in combination with paracetamol and NSAID.

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Background We hypothesized that both perineural and systemic dexamethasone as adjuncts to bupivacaine increase the duration of an ulnar nerve block compared with bupivacaine alone, and that systemic dexamethasone is non-inferior to perineural dexamethasone. Methods We performed bilateral ulnar nerve blocks with 3 ml bupivacaine 5 mg/ml in 16 healthy volunteers on two trial days. According to randomization, subjects received adjunct treatment with 1 ml dexamethasone 4 mg/ml + 1 ml of saline (perineural condition) in one arm and 2 ml saline in the other arm (systemic condition, through absorption and redistribution of the contralaterally administered perineural dexamethasone) on one trial day; and 2 ml of saline in one arm (placebo condition) and 2 ml of lidocaine in the other arm (lidocaine condition) on the other trial day. The primary outcome was the duration of the sensory nerve block assessed by temperature discrimination. Results Mean sensory block duration was 706 ± 94 minutes for the perineural condition, 677 ± 112 minutes for the systemic condition, and 640 ± 121 minutes for the placebo condition. The duration of the sensory nerve block was greater with perineural dexamethasone versus placebo (mean difference (MD) 66 minutes (95% CI 23 to 108). Block duration was similar between systemic dexamethasone and placebo (MD 36 minutes; 95% CI -30 to 103). Conclusion Perineural dexamethasone as an adjunct to bupivacaine in healthy volunteers resulted in a greater duration of an ulnar nerve block when compared with placebo. Systemic dexamethasone resulted in a similar duration as placebo.

Background: Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as the basic pain treatment regimen for most surgeries. Glucocorticoids have well-known anti-inflammatory and anti-emetic properties and may also demonstrate analgesic effects. We assessed benefit and harm of adding glucocorticoids to a combination of paracetamol and NSAIDs for post-operative pain management.Methods: We searched Embase, Medline and CENTRAL for randomised clinical trials investigating the addition of glucocorticoids versus placebo/no intervention to paracetamol and an NSAID in adults undergoing any type of surgery. We assessed three primary outcomes: cumulative opioid consumption at 24 h postoperatively, serious adverse events and pain at rest at 24 h postoperatively. We performed meta-analysis and trial sequential analysis (TSA), assessed risk of bias using the Risk of Bias 2 tool and used the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the certainty of the evidence.Results: We identified 12 relevant trials of which nine trials randomising 804 participants were included in quantitative analysis. When added to paracetamol and NSAIDs, we found no evidence of a difference of glucocorticoids versus placebo/no intervention in cumulative opioid consumption at 24 h postoperatively (mean difference [MD] À0.28, TSA-adjusted 95% confidence interval [CI] À1.90 to 1.33, p = .68, moderate certainty of evidence), serious adverse events (risk ratio (RR) 0.99, TSAadjusted 95% CI 0.27-3.63, p = .93, very low certainty of evidence) or pain on the Numeric Rating Scale at 24 h postoperatively (MD À0.39, TSA-adjusted 95% CI À0.84 to 0.17, p = .10, moderate certainty of evidence). All outcomes were assessed to be at high risk of bias and TSA showed that we had insufficient information for most outcomes. Conclusion:Glucocorticoids added to a baseline therapy of paracetamol and an NSAID likely result in little to no difference in cumulative opioid consumption and pain at rest at 24 h postoperatively. In addition, the evidence is very uncertain about the effect on serious adverse events. For most outcomes we did not have