Dexmedetomidine May Provide Better Sedation, Less Acute Brain Dysfunction

Key Point

In a randomized trial, sedation with dexmedetomidine resulted in more days alive without delirium or coma and higher accuracy at meeting sedation goals than did sedation with lorazepam.

ICU patients on respirators who were sedated with dexmedetomidine had more days alive without delirium or coma and better sedation, compared with patients treated with the Society of Critical Care Medicine–recommended drug lorazepam, according to a study published in the December 12, 2007, JAMA.

Lorazepam is routinely administered to mechanically ventilated patients to reduce pain and anxiety and to allow them to tolerate invasive ICU procedures. But research shows that benzodiazepines such as lorazepam may also increase patients’ mechanical ventilation time, ICU length of stay, and risk of acute brain dysfunction (ie, delirium and coma), the investigators pointed out.

Dexmedetomidine induces sedation via different central nervous system receptors than do benzodiazepines, and its use may lower the risk of acute brain dysfunction. “Unlike benzodiazepine drugs and propofol, which act directly at the level of the tuberomammillary nucleus and the ventrolateral preoptic nucleus, dexmedetomidine acts at the level of the locus ceruleus, with a different neurotransmitter profile, and preserves slow-wave sleep in its neuronal pathway,” they explained.

Upon obtaining an Investigational New Drug approval from the FDA, Pratik P. Pandharipande, MD, Assistant Professor in the Department of Anesthesiology, Division of Critical Care and Perioperative Medicine at Vanderbilt University School of Medicine in Nashville, and colleagues conducted a study to determine if dexmedetomidine was more effective than lorazepam at reducing the duration of delirium and coma while providing effective sedation to mechanically ventilated ICU patients. The randomized controlled trial included adult ICU patients who were on mechanical ventilation between August 2004 and April 2006; 52 patients were randomized to dexmedetomidine and 51 to lor-azepam. The patients were sedated for as many as 120 hours.

Patients in the dexmedetomidine group had more days alive without delirium or coma (median, seven vs three), the researchers found. About 30% fewer patients experienced coma in the dexmedetomidine group than in the lorazepam group (63% vs 92%). Nonsignificant differences were noted between the dexmedetomidine and lorazepam groups in death at 28 days (17% vs 27%) and ventilator-free days (22 vs 18 days alive and free of mechanical ventilation).

A higher but nonsignificant percentage of patients in the dexmedetomidine group were able to complete post-ICU neuropsychologic testing. Patients who were administered dexmedetomidine spent more time near the targeted level of sedation compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%). The 12-month time to death in the dexmedetomidine and the lorazepam groups were 363 and 188 days, respectively.

“[This] trial adds substantially to the available safety data regarding infusion of dexmedetomidine to critically ill patients,” the investigators contended. They also acknowledged that their results are not uniformly applicable to sedatives other than lorazepam and that their data may not apply to trauma, neurological, and burn ICUs.           

Suggested Reading
Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753-1762.
Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA. 2007;298(22):2644-2653.
Thomason JW, Shintani A, Peterson JF, et al. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care. 2005;9(4):R375-R381.

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