High dose glucocorticoids for treatment of postoperative pain: A systematic review of the literature and meta-analysis

STUDY OBJECTIVE: Glucocorticoids as a component of multimodal analgesia have been studied for many years and their post-operative analgesic effects appear to be dose-dependent. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the evidence of peri-operative high dose corticosteroid therapy in comparison to placebo (placebo drug) or control group (no treatment) for improving the quality of post-operative analgesia as indicated by a reduction of 10 mm in 100 mm Visual Analogue Scale (VAS) or reduction of 1 point in a 0-10 point VAS scale, or a reduction of 1 point in an 11-point Numerical Rating Scale (NRS) score, or reduction of rescue opioid analgesia, in patients undergoing all types of surgery. DESIGN: Systematic review of RCTs with meta-analysis. SETTING: Acute postoperative pain treatment in non-obese adult population. INTERVENTIONS: Perioperative administration of high dose of Dexamethasone (≥ 0,2 mg/Kg or ≥ 15 mg), or a corresponding dose of a systemic glucocorticoid. MEASUREMENTS: Primary outcomes were postoperative pain measured in 0-100 mm VAS score at 24 h after surgery upon rest and movement. Secondary outcomes were postoperative pain 0-100 mm VAS score 48 h after surgery, postoperative rescue analgesic requirement, postoperative nausea and vomiting (PONV), relevant adverse events. MAIN RESULTS: 47 RCT's were included (3943 patients). The Mean Difference (MD) of 100 mm VAS scores for pain at rest 24 h after surgery was -6.18 mm 95% CI [-8.53, -3.83], at motion -8.86 mm 95% CI [-11.82, -5.89]. Opioid analgesic requirements evaluated in Oral Morphine Equivalents (OME) was -10.00 mg 95% CI [-13.65, -6.34]. PONV events Odds Ratio of 0.29 95%CI [0.24, 0.36]. Major adverse events OR was 0.88 95% CI [0.65, 1.19]. Minor adverse events OR 1.29 95% CI [0.86, 1.92]. CONCLUSION: High doses of glucocorticoids are one of the many possible tools available in multimodal postoperative analgesia, possibly reducing opioids consumption and recurrence of PONV but with no relevant effects in terms of reduction of postoperative VAS score. Available data show a safe therapeutic profile, without increase adverse events. PROTOCOL REGISTRATION: CRD42020137119.