title: Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial.
abstract: Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery.
  
  
  
  We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn, number ChiCTR-TRC-10000802.
  
  
  
  Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22-0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0·50, 0·32-0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0·44, 0·26-0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups.
  
  
  
  For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe.
  
  
  
  Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Zhao-Ting
authors.initials: ZT
authors.lastname: Meng
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Xin-Hai
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Cui
authors.affiliation: Department of Critical Care Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China. Electronic address: wangdongxin@hotmail.com.
authors.forename: Dong-Xin
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Biostatistics, Peking University First Hospital, Beijing, China.
authors.forename: Sai-Nan
authors.initials: SN
authors.lastname: Zhu
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.affiliation: Section of Anaesthetics, Pain Management and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, UK. Electronic address: d.ma@imperial.ac.uk.
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D002681:China / Q000453:epidemiology; D003221:Confusion / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D003422:Critical Care / Q000379:methods*; D003693:Delirium / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention / Q000379:methods*; D012121:Respiration, Artificial / Q000009:adverse effects; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D020927:Dexmedetomidine