Intraoperative dexamethasone and chronic postsurgical pain: a propensity score-matched analysis of a large trial

Background: Dexamethasone has been shown to reduce acute pain after surgery, but there is uncertainty as to its effects on chronic postsurgical pain (CPSP). We hypothesised that in patients undergoing major noncardiac surgery, a single intraoperative dose of dexamethasone increases the incidence of CPSP. Methods: We devised a propensity score-matched analysis of the ENIGMA-II trial CPSP dataset, aiming to compare the incidence of CPSP in patients who had received dexamethasone or not 12 months after major noncardiac surgery. The primary outcome was the incidence of CPSP. We used propensity score matching and inverse probability weighting to balance baseline variables to estimate the average marginal effect of dexamethasone on patient outcomes, accounting for confounding to estimate the average treatment effect on those treated with dexamethasone. Results: We analysed 2999 patients, of whom 116 of 973 (11.9%) receiving dexamethasone reported CPSP, and 380 of 2026 (18.8%) not receiving dexamethasone reported CPSP, unadjusted odds ratio 0.76 (95% confidence interval 0.78 - 1.00), P = 0.052. After propensity score matching, CPSP occurred in 116 of 973 patients (12.2%) receiving dexamethasone and 380 of 2026 patients (13.8%) not receiving dexamethasone, adjusted risk ratio 0.88 (95% confidence interval 0.61 - 1.27), P = 0.493. There was no difference between groups in quality of life or pain interference with daily activities, but 'least pain ' (P = 0.033) and 'pain right now ' (P = 0.034) were higher in the dexamethasone group. Conclusions: Dexamethasone does not increase the risk of chronic postsurgical pain after major noncardiac surgery. Clinical trial registration: Open Science Framework Registration DOI https://doi.org/10.17605/OSF.IO/ZDVB5.