The effect of peri‐operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non‐cardiac surgical patients: a randomised, double‐blind placebo‐controlled trial

Abstract

Summary Delirium occurs commonly following major non‐cardiac and cardiac surgery and is associated with: postoperative mortality; postoperative neurocognitive dysfunction; increased length of hospital stay; and major postoperative complications and morbidity. The aim of this study was to investigate the effect of peri‐operative administration of dexmedetomidine on the incidence of postoperative delirium in non‐cardiac and cardiac surgical patients. In this randomised, double‐blind placebo‐controlled trial we included 63 patients aged ≥ 60 years undergoing major open abdominal surgery or coronary artery bypass graft surgery with cardiopulmonary bypass. The primary outcome was the incidence of postoperative delirium, as screened for with the Confusion Assessment Method. Delirium assessment was performed twice daily until postoperative day 5, at the time of discharge from hospital or until postoperative day 14. We found that dexmedetomidine was associated with a reduced incidence of postoperative delirium within the first 5 postoperative days, 43.8% vs. 17.9%, p = 0.038. Severity of delirium, screened with the Intensive Care Delirium Screening Checklist, was comparable in both groups, with a mean maximum score of 1.54 vs. 1.68, p = 0.767. No patients in the dexmedetomidine group died while five (15.6%) patients in the placebo group died, p = 0.029. For patients aged ≥ 60 years undergoing major cardiac or non‐cardiac surgery, we conclude that the peri‐operative administration of dexmedetomidine is associated with a lower incidence of postoperative delirium.

The use of dexmedetomidine to prevent delirium after major cardiac and non‐cardiac surgery

“…In the peri-operative period, accumulating evidence suggests that systemic inflammation associated with surgery and bleeding leads to delirium, potentially leading to disruption of the bloodbrain barrier, influx of immune mediators with subsequent changes in neuronal metabolism and excitability. Hence, while van Norden et al [10] hypothesise that dexmedetomidine may act to reduce inflammation to prevent delirium, it is a shame they did not validate their hypothesis by measurement of inflammatory changes. This sort of mechanistic approach would be valuable in the context of a small trial and would enhance the plausibility of the results.…”

“…One can also imagine that the impact of anti-inflammatory therapies may vary based on the extent to which pre-surgery cognition is impaired in an individual. For this reason, it is commendable that van Norden et al [10] reported pre-operative cognitive data as part of their study.…”

“…In this issue of Anaesthesia , van Norden et al. [10] report on the results of a small randomised controlled trial (60 patients analysed) comparing dexmedetomidine vs. saline placebo. However, to appreciate how dexmedetomidine may benefit, it is useful to review the mechanistic pathways implicated in delirium.…”

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial

“…The relative risk and 95% CI was 0.52 (0.39 to 0.70) when compared with placebo 25. Among newer studies in cardiac surgery, some,29–32 but not all,33 34 have found a beneficial short time effect on the incidence of delirium. A meta-analysis in cardiac surgery patients showed that dexmedetomidine could reduce the risk of postoperative delirium (OR 0.56, 95% CI 0.36 to 0.89) 35.…”

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method

“…Dexmedetomidine is a potent and highly selective 2-adrenoceptor agonist displaying anxiolytic, sedative, sympatholytic, and analgesic effects with minimum cardiovascular and respiratory depression [1]. Neurophysiologically, sedation using dexmedetomidine approximates stage 2 non-rapid eye movement sleep and reduces the incidence of delirium [2][3][4].…”