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Post‐operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review

In contemporary post‐operative pain management, patients are most often treated with combinations of non‐opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid‐related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well‐documented ‘gold standards’ exist. The aim of the present topical, narrative review is to provide an update of the evidence for post‐operative analgesic efficacy with the most commonly used, systemic non‐opioid drugs, paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs)/COX‐2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta‐analyses, investigating effects of non‐opioid analgesics on pain, opioid‐requirements, and opioid‐related adverse effects. Paracetamol, NSAIDs, COX‐2 antagonists, and gabapentin reduced 24 h post‐operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid‐sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine‐sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX‐2 antagonists, and gabapentin all seem to have well‐documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies.