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June - 2017


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Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery

S Deiner, X Luo, H Lin, and the Dexlirium Writing Group JAMA Surg, 2017, online first 7th June


This multi-centre double-blind RCT investigates the effect of intra-operative dexmedetomidine (0.5 ug/kg/hr on entry to OR and continuing to 2-hrs postop) compared to placebo on the incidence post-operative delirium (daily CAM-ICU until day-5) in over 70-year old patients undergoing major non-cardiac elective surgery. They also examined the effect on cognitive function changes at 3 and 6-months. They report;

  • A sample size of 706 participants was calculated for 80% power to detect a 50% reduction in delirium from a baseline of 15%. The study was stopped for futility after 429 participants enrolled. 
  • Well matched at baseline, median age of 74.0 years
  • Postop delirium occurred 11.8% (dex) vs 11.4% (placebo), RR 1.06, 95% CI 0.79-1.41, p=0.77), no difference in severity
  • No significant difference in cognition at 6-months
  • No difference in adverse events, with exception of more intraoperative bradycardia in dex group

Overall intraoperative dexmedetomidine was not associated with differences in postoperative delirium or other secondary outcomes. This is not overly surprising, as delirium is multifactorial and complex, and it seems unlikely an intervention for the intraoperative period alone would resolve these issues.  It is a well designed and conducted study, and it does provide valuable information about the incidence and outcomes of psotop delirium in the non-critically ill population, and provides evidence that argues against the use of dexmedetomidine as a prophylactic agent.



Importance  Postoperative delirium occurs in 10% to 60% of elderly patients having major surgery and is associated with longer hospital stays, increased hospital costs, and 1-year mortality. Emerging literature suggests that dexmedetomidine sedation in critical care units is associated with reduced incidence of delirium. However, intraoperative use of dexmedetomidine for prevention of delirium has not been well studied.

Objective  To evaluate whether an intraoperative infusion of dexmedetomidine reduces postoperative delirium.

Design, Setting, and Participants  This study was a multicenter, double-blind, randomized, placebo-controlled trial that randomly assigned patients to dexmedetomidine or saline placebo infused during surgery and for 2 hours in the recovery room. Patients were assessed daily for postoperative delirium (primary outcome) and secondarily for postoperative cognitive decline. Participants were elderly (>68 years) patients undergoing major elective noncardiac surgery. The study dates were February 2008 to May 2014.

Interventions  Dexmedetomidine infusion (0.5 µg/kg/h) during surgery and up to 2 hours in the recovery room.

Main Outcomes and Measures  The primary hypothesis tested was that intraoperative dexmedetomidine administration would reduce postoperative delirium. Secondarily, the study examined the correlation between dexmedetomidine use and postoperative cognitive change.

Results  In total, 404 patients were randomized; 390 completed in-hospital delirium assessments (median [interquartile range] age, 74.0 [71.0-78.0] years; 51.3% [200 of 390] female). There was no difference in postoperative delirium between the dexmedetomidine and placebo groups (12.2% [23 of 189] vs 11.4% [23 of 201], P = .94). After adjustment for age and educational level, there was no difference in the postoperative cognitive performance between treatment groups at 3 months and 6 months. Adverse events were comparably distributed in the treatment groups.

Conclusions and Relevance  Intraoperative dexmedetomidine does not prevent postoperative delirium. The reduction in delirium previously demonstrated in numerous surgical intensive care unit studies was not observed, which underscores the importance of timing when administering the drug to prevent delirium.


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