Intraoperative use of sodium oxybate to prevent postoperative delirium in older patients undergoing major orthopedic surgery

This matters arising article addresses the recently published article in BMC Medicine by Cui et al., titled “Prophylactic effect of intraoperative sodium oxybate on postoperative delirium in older patients undergoing major orthopedic surgery: a randomized clinical trial.” The work by Cui et al. demonstrated that intraoperative administration of sodium oxybate only significantly reduced postoperative delirium (POD) incidence in the participants undergoing morning surgery but not in those with afternoon surgery. Although this trial provided evidence that sodium oxybate may reduce POD, we raise several concerns regarding methodology and generalizability, such as incomplete control of perioperative risk factors, underestimated incidence of POD, subgroup analysis without multiple adjustments of confounding factors, and inadequate postoperative pain strategy. To verify the findings of this trial in further researches, we advocate the implementation of multi-center randomized clinical trials with large sample sizes, strict control of perioperative confounding factors, precise assessment of POD episodes, and the inclusion of subgroup analysis with multiple adjustments. This matters arising does not seek to deny the results of Cui et al.’s trial. The main purpose of the authors is to emphasize that above methodological refinements are crucial for translating this valuable evidence into generally clinical practice and improving final outcomes of patients.