title: Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.
abstract: 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.
authors.affiliation: Department of Anaesthesia 4231, Centre of Head and Orthopaedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Dahl
authors.forename: R V
authors.initials: RV
authors.lastname: Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Wetterslev
authors.forename: L
authors.initials: L
authors.lastname: Nikolajsen
authors.forename: K
authors.initials: K
authors.lastname: Hamunen
authors.forename: V K
authors.initials: VK
authors.lastname: Kontinen
authors.forename: M S
authors.initials: MS
authors.lastname: Hansen
authors.forename: J J
authors.initials: JJ
authors.lastname: Kjer
authors.forename: O
authors.initials: O
authors.lastname: Mathiesen
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D000588:Amines / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004338:Drug Combinations; D000077206:Gabapentin; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D010149:Postoperative Pain / Q000150:complications / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003509:Cyclohexanecarboxylic Acids; D004338:Drug Combinations; D005938:Glucocorticoids; D000082:Acetaminophen; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin