Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial.
JAMA Surgery. Published online June 2017. doi:10.1001/jamasurg.2017.1505
Presented by: Dr B Morris
This study aims to tackle the issue of high rates of post operative delirium (POD) and post operative cognitive dysfunction (POCD) in elderly patients. There is thought to be a high incidence of POD (10-60%) and this is also thought to contribute to POCD, a more permanent alteration of mental state. Both these conditions are associated with disadvantageous features such as increased perioperative morbidity, increased length of stay and ultimately decreased life expectancy and quality of life, so it is a significant problem. The authors aimed to evaluate specifically the perioperative use of an infusion of Dexmedetomidate as this has been shown to improve delirium and cognitive dysfunction in ICU patients.
Design & Setting
A double-blind, randomized, parallel group placebo-controlled trial in 10 centres across the USA over 6 years (2008 – 2014).
Of 404 patients who were initially randomized, 390 made it through to be included in the results of the trial. These were patients selected by the following criteria: Age over 68 (adjusted from 70 in the interest of gaining more numbers), undergoing major (planned 2 day admission) elective non-cardiac surgery under GA. There was a long list of exclusory criteria, including surgical, anaesthetic and patient factors such as intracranial/emergency surgery, planned post operative intubation, life limiting conditions, preexisting cognitive conditions and ASA IV/V.
An infusion of 0.5mcg.kg-1.hr-1 of Dexmedetomidine commenced in the anaesthetic room and continued until 2 hours into recovery, vs placebo of saline.
Primary: Presence of delirium whilst hospitalised or until day 5 post operatively.
Secondary: Post operative cognitive decline up to 6 months post operatively.
The trial was stopped early due to futility and failure to find any difference between the two groups.
23 patients from the Dexmedetomidine group (12.2%) and 23 patients from the control group (11.4%) developed post operative delirium (risk ratio, 1.06; 95% CI, 0.79-1.41; P = .77). Interestingly they did isolate some other factors that made POD more likely – namely increased length of surgery, baseline mild cognitive impairment, lower number of educational years and type of surgery, general surgery being the least likely to be associated with POD.
There was found to be no statistically significant difference between the two groups in POCD at either 3 or 6 months.
Unintended adverse events:
Similarly distributed between the two groups, with more bradycardia with the Dexmedetomidine group and slightly more infections, although the overall number of infections was low.
This study contrasted with other work on administration of dexmedetomidine in the postoperative setting of 1 or more days in cardiac and non-cardiac surgical patients, which has shown an improvement in POD.
This study did show some correlation between other factors such as educational level and baseline mild cognitive impairment and POD.
Encouragingly, there was little evidence of POCD in either group, perhaps indicating that although Dexmedetomidine is not beneficial, these patients in general are not at high risk for significant POCD anyway.
Strengths and Weaknesses
The exclusion of so many patients did allow for a more robust scientific analysis of Dexmedetomidine and its effects, as the two groups being compared were homogeneous, however this did limit the study’s usefulness in real terms as it may be in many of these excluded patients interests to have POD decreased, more so than the ‘fitter’ population studied.
Whilst absolute presence of delirium was measured, a weakness of the study is that the number of episodes, severity and consequences i.e. length of stay, etc. were not.
Basically, based on this study, we should not endeavour to provide intraoperative Dexmedetomidine infusions to elderly patients undergoing major non cardiac surgery in an attempt to ameliorate POD/POCD.
Potential for impact
This is a useful piece of research in the full context of Dexmedetomidine and POD, but needs to be taken into consideration with all of the other work done in the surrounding areas of other types of surgeries, other populations and prolonged administration post operatively.
Further research should be directed at the higher risk groups that were excluded from this study, and more far-reaching measures such as improvement in patient outcomes (both clinically objective and subjective), length of stay, financial efiiciency etc. It is also still perfectly reasonable to consider providing post operative Dexmeditomidine infusions to high risk patients in HDU/ICU environments in the absence of deleterious factors.