The Efficacy of Ramelteon to Prevent Postoperative Delirium After General Anesthesia in the Elderly: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Postoperative delirium is common and serious in elderly patients. Several drugs have been proposed as potential prophylactic agents for postoperative delirium. Studies on melatonin receptor agonists showed heterogeneity in age, cognitive function, anesthesia, surgery, interventions, methodologies for assessing outcomes, and results. Our objective was to examine the effect of ramelteon to prevent postoperative delirium in elderly patients, including those with dementia. DESIGN: A stratified, double-blind, randomized, placebo-controlled trial (UMIN000028436, jRCTs031180054). SETTING: Tertiary medical center. PARTICIPANTS: Patients aged older than or equal to 65 years undergoing elective surgery under general anesthesia. INTERVENTION: Ramelteon (8 mg orally) or placebo (lactose) for six nights (the preoperative night and five consecutive nights from postoperative day 1 to 5) at around 9 P.M. MEASUREMENTS: Patients were screened for postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit twice daily until the sixth postoperative day. Patients with positive results were referred to a consultant psychiatrist to establish the diagnosis of delirium. RESULTS: A total of 108 patients were randomly assigned to receive ramelteon (n = 55) or placebo (n = 53). Most of the patients' characteristics were reasonably well-balanced between the two groups. The stratified log-rank test showed no significant difference in preventing postoperative delirium between ramelteon and placebo (χ2 = 0.30, degrees of freedom = 1, p = 0.60). The Cox proportional hazard ratio for ramelteon compared to placebo was 1.40 (95% confidence interval: 0.40-4.85, χ2 for likelihood ratio test = 0.29, degrees of freedom = 1, p = 0.60). CONCLUSION: There was no significant difference in the incidence of postoperative delirium between ramelteon and placebo after general anesthesia in elderly patients.