Ramelteon for Prevention of Postoperative Delirium: A Randomized Controlled Trial in Patients Undergoing Elective Pulmonary Thromboendarterectomy.

Abstract

To assess the efficacy of ramelteon in preventing delirium, an acute neuropsychiatric condition associated with increased morbidity and mortality, in the perioperative, ICU setting. Parallel-arm, randomized, double-blinded, placebo-controlled trial. Academic medical center in La Jolla, California. Patients greater than or equal to 18 years undergoing elective pulmonary thromboendarterectomy. Ramelteon 8 mg or matching placebo starting the night prior to surgery and for a maximum of six nights while in the ICU. Incident delirium was measured twice daily using the Confusion Assessment Method-ICU. The safety outcome was coma-free days assessed by the Richmond Agitation-Sedation Scale. One-hundred twenty participants were enrolled and analysis completed in 117. Delirium occurred in 22 of 58 patients allocated to placebo versus 19 of 59 allocated to ramelteon (relative risk, 0.8; 95% CI, 0.5-1.4; p = 0.516). Delirium duration, as assessed by the number of delirium-free days was also similar in both groups (placebo median 2 d [interquartile range, 2-3 d] vs ramelteon 3 d [2-5 d]; p = 0.181). Coma-free days was also similar between groups (placebo median 2 d [interquartile range, 1-3 d] vs ramelteon 3 d [2-4 d]; p = 0.210). We found no difference in ICU length of stay (median 4 d [interquartile range, 3-5 d] vs 4 d [3-6 d]; p = 0.349), or in-hospital mortality (four vs three deaths; relative risk ratio, 0.7; 95% CI, 0.2-3.2; p = 0.717), all placebo versus ramelteon, respectively. Ramelteon 8 mg did not prevent postoperative delirium in patients admitted for elective cardiac surgery.