• D Norman Buckley and W Scott Beattie.
• Department of Anesthesia, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
• Br J Anaesth. 2024 May 13.

AbstractReductionist thinking results in the bulk of anaesthesia trial designs being a single intervention to address what are in fact complex processes. The Perioperative Administration of Dexamethasone and Infection (PADDI) trial assessed the safety of a single preoperative dose of dexamethasone. Surprising to most, in the original report, a single dose of dexamethasone increased the incidence of the secondary outcome chronic postsurgical pain. Was this a chance finding or does dexamethasone increase chronic postsurgical pain? In an attempt to address this question, the PADDI investigators have now analysed this prespecified secondary outcome in two ways: as a substudy published earlier in this Journal, and as a retrospective analysis of the ENIGMA-II chronic pain database in this issue of the Journal. The PADDI investigators have now presented enough data to convince us that indeed a single dose of dexamethasone is safe and effective. However, the increase in chronic postsurgical pain seen in the original PADDI publication highlights the complexities, and the possible immunologic mechanisms, behind the genesis of chronic postsurgical pain. These publications from the PADDI group raise questions about other anti-inflammatory agents we use regularly for long-term postoperative pain management, and highlights the need for well-designed clinical trials to address this critically important patient-centred adverse functional outcome.Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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