Alternative to Lorazepam May Improve Outcome for ICU Ventilated Patients

A new study has found that patients receiving mechanical ventilation in an intensive care unit (ICU) who were given dexmedetomidine for sedation had more days without delirium or coma and significantly more time at the desired level of sedation, compared to patients who received the standard sedative, lorazepam.

Researchers at the Vanderbilt University Medical Center (Nashville, TN, USA) conducted a double-blind trial that enrolled 106 adult patients in an ICU who needed mechanical ventilation between August 2004 and April 2006. The patients were randomized to receive sedation with either dexmedetomidine (52 patients) or lorazepam (51 patients) for as long as 120 hours. Nurses treated pain with doses of fentanyl based on physiological parameters including blood pressure, heart and respiratory rates, facial expression, and limb movement. Patients were categorized as having brain dysfunction, defined as delirium or coma, if they had a Richmond Agitation-Sedation Scale (RASS) score of –3 or greater (delirium), and coma was defined as a RASS score of –4 (responsive only to physical touch) or –5 (unresponsive to physical stimulus).

The researchers found that approximately 30% fewer patients experienced coma in the dexmedetomidine group compared to the lorazepam group (63% vs. 92%) and that the patients receiving dexmedetomidine had more days alive without delirium or coma. Also, patients sedated with dexmedetomidine spent more time at the level of sedation targeted by both nurses and physicians, and although this was not statistically significant, they had more ventilator-free days than patients receiving the standard drug. Patients treated with dexmedetomidine received more fentanyl for pain control than those treated with lorazepam, possibly because they were less likely to be delirious or in a coma and thus were more able to communicate their need for an analgesic, or because the pain drug was being used for its sedating properties. The study was published in the December 12, 2007 issue of the Journal of the American Medical Association (JAMA).

"We found that in a 12-day evaluation period . . . even though the groups were balanced as far as their age, demographics, etc., were concerned, patients on dexmedetomidine had a median or an average duration of being free of delirium and coma about 4 days more than the lorazepam group,” said lead author Pratik P. Pandharipande, M.D., an assistant professor of anesthesiology and critical care.

Lorazepam, which acts on gamma-aminobutyric acid receptors, is the medication currently recommended for sustained sedation in patients in the ICU, but this and other benzodiazepines may contribute to acute brain dysfunction. Dexmedetomidine is a highly selective alpha-2-adrenergic receptor agonist and an alternative to lorazepam that may be associated with less organic brain dysfunction.


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Vanderbilt University Medical Center