Intraoperative dexmedetomidine to prevent postoperative delirium: in search of the magic bullet

Abstract

Agitation and delirium are important targets for quality improvement across inpatient healthcare settings because of the timeand resource-intensive nature of the screening, diagnosis, and management processes. In the general patient population, no prophylactic pharmacologic treatment has shown widespread effectiveness in preventing delirium. Several studies have failed to find a magic pharmacologic bullet for preventing delirium—ketamine and haloperidol have recently failed to impress. Dexmedetomidine is an attractive pharmacologic option because of its biologic plausibility in modifying several known contributors to delirium, including attenuating inflammatory mediators and catecholamines, providing analgesia, reducing deliriuminducing medications, and promoting natural sleep-wake cycles, among other plausible neuroprotective mechanisms. Data on postoperative delirium after intraoperative dexmedetomidine administration are conflicting, and the diverse mechanisms by which it may act have prompted trials in a variety of populations, with a variety of doses and administration schema. If providing dexmedetomidine intraoperatively to a diverse group of patients otherwise receiving usual care has not been effective, could its use in a highly protocolized, homogenous setting reveal an effect? In this month’s edition of the Journal, Kim et al. report the results of a double-blind randomized efficacy trial of 143 patients undergoing thoracoscopic lung resection surgery. Patients were randomized to receive general anesthesia with either sevoflurane plus dexmedetomidine at 0.5 lg kg hr (started immediately prior to anesthesia induction and continued until the end of surgery) or sevoflurane plus placebo. Anesthetic depth was titrated to maintain a bispectral index of 45 ± 5 and a blood pressure within 20% of the baseline. Emergence agitation was measured with the Riker sedation agitation scale at one minute after extubation, then every 15 min until discharge from the postanesthesia recovery unit (PACU). Patients were then assessed for postoperative delirium with either the Confusion Assessment Method (CAM) or CAM-ICU starting after PACU discharge and every four hours for intensive care unit (ICU) patients or three times daily for ward patients until postoperative day 3. The authors showed a decrease in emergence agitation in the dexmedetomidine group (13% vs 35%; relative risk, 0.38; 95% confidence interval (CI), 0.18 to 0.79; P = 0.011) without a corresponding increase in oversedation but, disappointingly, no difference in postoperative delirium (25% vs 25%). There were reasons for optimism. Studies comparing the incidence of delirium and other adverse neurocognitive outcomes based on particular sedation strategies in the ICU setting have found significant benefit with use of dexmedetomidine compared with benzodiazepines and propofol. Not surprisingly, focus has turned to investigation of whether intraoperative use of dexmedetomidine may also prove effective as a delirium prevention measure. Results were encouraging in focused surgical groups—for example, in cardiac and orthopedic surgery— where significant tissue trauma is expected. In a recent meta-analysis, Wu et al. found a significant reduction in postoperative delirium with A. L. Donovan, MD Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine, University of California, 500 Parnassus Avenue, Box 0648, San Francisco, CA 94143, USA