The Effectiveness of Dexmedetomidine as a Prophylactic Treatment for Emergence Delirium Among Combat Veterans With High Anxiety: A Randomized Placebo-Controlled Trial

Introduction Emergence delirium (ED) is characterized by agitation, confusion, and violent physical and verbal behavior associated with awakening from general anesthesia. Combat exposure among U.S. military veterans has been identified as a risk factor for ED. Preoperative baseline anxiety was shown to be a predictor of ED, and combat veterans are known to be at high risk for anxiety as well as depression and PTSD. Dexmedetomidine is an alpha-2 receptor agonist proven to mitigate ED in several patient populations. Perioperative use of dexmedetomidine demonstrated promising benefits in pediatric ED but has not been evaluated in combat veterans. Materials and Methods This study was a multi-site, prospective, randomized controlled investigation of 369 patients with a history of military combat exposure who were scheduled for elective surgery with a general anesthetic as the primary means of anesthesia. The trial was funded by the Tri-Service Nursing Research Program Grant HU0001-14-TS05 (N14-PO3) and approved by the Institutional Review Boards at the Naval Medical Center San Diego, Womack Army Medical Center, Walter Reed National Military Medical Center, and the Uniformed Services University of the Health Sciences, Bethesda, MD. All subjects were administered the State-Trait Anxiety Inventory (STAI) to evaluate baseline anxiety. Those enrolled subjects with a low anxiety level (STAI Results The central tendencies of demographics and clinical characteristics are reported. PAED among those randomized to dexmedetomidine (median 7, interquartile interval (IQI) 5.2-9.2) tended to be less (P Conclusions Dexmedetomidine was effective at reducing PAED among combat veterans who were experiencing symptoms of pre-operative anxiety (i.e., STAI-State ≥39). Although psychological morbidity is not unique to the military population, combat veterans carry some of the highest rates of anxiety, PTSD and depression compared to the general population. Dexmedetomidine can be safety employed by anesthesia providers to reduce symptoms of ED in the perioperative period. The double-blind randomized, controlled study design strengthens our analyses; however, this study did not control for the type of surgical procedure or the duration of anesthetic. Furthermore, we only enrolled patients with combat exposure experiencing symptoms of anxiety and did not investigate the role of dexmedetomidine in combat veterans with less anxiety. Further study of the relationship between psychological comorbidities, ED, and dexmedetomidine is warranted.