Prophylactic dexmedetomidine may reduce postoperative delirium in patients ≥ 65 years old admitted to intensive care unit after non-cardiac surgery

EBM Focus - Volume 11, Issue 35

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Reference - Lancet 2016 Aug 16 early online (level 2 [mid-level] evidence)

  • Delirium is associated with increased morbidity and poorer outcomes in postoperative patients.
  • Older age, opioid analgesics, and exposure to anesthesia are among potential predisposing factors for delirium.
  • Compared to placebo, prophylactic dexmedetomidine given postoperatively significantly reduced delirium in a randomized trial of 700 elderly patients admitted to a Chinese intensive care unit (ICU) after elective noncardiac surgery.
  • The baseline differences between the two groups and the lack of data regarding the proportion of patients with delirium in each group before initiation of treatment are potential sources of bias.

Delirium in the ICU is common in postoperative patients and is associated with higher mortality, increased length of hospital stay, and persistent cognitive impairment (Neurotherapeutics 2012 Jan;9(1):158). Dexmedetomidine, a clonidine-like alpha-2 adrenoreceptor agonist, has a different mechanism of action than the commonly used agents for sedation in the ICU setting and compared to midazolam, was associated with reduced occurrence of delirium in mechanically ventilated patients (JAMA 2009 Feb 4;301(5):489). No recommendation regarding use of dexmedetomidine to prevent delirium was given in the 2013 guidelines from the Society for Critical Care Medicine due to absence of convincing data showing its efficacy (SCCM 2013 Jan PDF). To further assess the potential for using dexmedetomidine in this setting, a recent randomized trial investigated the efficacy of low-dose dexmedetomidine in 700 patients ≥ 65 years of age admitted to a Chinese ICU after elective noncardiac surgery under general anesthesia.

Patients who arrived to the ICU before 8:00 PM were randomized to dexmedetomidine 0.1 mcg/kg/hour IV vs. saline IV within 1 hour after arrival in the ICU, and the infusion was continued until 8:00 AM the following morning. Patients who still had endotracheal intubation upon arrival to the ICU first received propofol or midazolam titrated to a Richmond Agitation Sedation Scale (RASS) of -2 or higher. Morphine, nonsteroidal anti-inflammatory drugs, and/or epidural analgesia were used for pain control. The primary endpoint was occurrence of delirium over six days beginning 24 hours after surgery. Of note, there were significant differences in the baseline characteristics of the two groups, with more patients in the placebo group having preoperative renal dysfunction and intraoperative blood transfusion. Comparing dexmedetomidine vs. saline, dexmedetomidine was associated with reduced rates of delirium (9.1% vs. 22.6%, p< 0.001, NNT 8), hypertension requiring intervention (2% vs. 5.4%, p = 0.016, NNT 30), and tachycardia requiring intervention (2.6% vs. 7.1%, p = 0.005, NNT 23), as well as better sleep quality. There were no significant differences in the rates of hypotension or bradycardia requiring intervention.

There are some significant limitations to this data. Patients were excluded for a number of factors including serious neurologic or cardiac conditions, hepatic dysfunction or requirement of dialysis. There were significant differences in factors between the two groups which may have selectively favored the dexmedetomidine group. In light of the fact that adjustments for these differences were not performed in the statistical analyses, this may result in overstating the effect of dexmedetomidine. In addition, the proportion of patients with delirium before the initiation of treatment in each of the two groups is not known and, therefore, the potential influence of this factor on the results cannot be ascertained. Overall, these results suggest that low-dose dexmedetomidine may reduce postoperative delirium and may improve hemodynamic outcomes in elderly patients admitted to the ICU after general anesthesia. However, the magnitude of the benefit may be smaller than that found in this trial.

For more information, see the Delirium in hospitalized patients topic in DynaMed.