Glucocorticoids added to paracetamol and NSAIDs for post-operative pain: A systematic review with meta-analysis and trial sequential analysis

BackgroundParacetamol 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. MethodsWe 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. ResultsWe 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] -0.28, TSA-adjusted 95% confidence interval [CI] -1.90 to 1.33, p = .68, moderate certainty of evidence), serious adverse events (risk ratio (RR) 0.99, TSA-adjusted 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 -0.39, TSA-adjusted 95% CI -0.84 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. ConclusionGlucocorticoids 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 sufficient information to draw firm conclusions and the certainty of the evidence varied from moderate to very low. Editorial CommentMultimodal approaches for post-operative analgesia are favoured, including paracetamol and nonsteroidal anti-inflammatory drugs. In this meta-analysis, pooled results from clinical trials are assessed to describe possible benefit of addition of glucocorticoid treatment for analgesia. The findings did not identify additional benefit, though the certainty of the evidence was not high.