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Design, Setting, Patients, and Intervention Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006.

Objective To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam.

Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction.

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Wesley Ely, MD, MPHAuthor Affiliations: Department of Anesthesiology/Division of Critical Care (Dr Pandharipande), Department of Medicine, Center for Health Services Research (Drs Girard, Stiles, Jackson, Dittus, and Ely), and Division of Allergy/Pulmonary/Critical Care Medicine (Ms Pun and Drs Girard, Miller, Bernard, and Ely), Department of Biostatistics (Dr Shintani and Ms Thompson), Department of Accreditation and Standards (Mr Deppen), Vanderbilt University Schools of Medicine and Nursing, Nashville, Tennessee; the VA Tennessee Valley Geriatric Research, Education and Clinical Center (GRECC), Nashville, Tennessee (Drs Jackson, Dittus, and Ely); Department of Surgery and Surgical Critical Care at Washington Hospital Center, Washington, DC (Dr Herr); and the Department of Anaesthetics, Pain Medicines, and Intensive Care, Imperial College London, London, England (Dr Maze).for the sustained sedation of mechanically ventilated ICU patients.Although recent trials have shown that protocols with patient-targeted sedation and the daily interruption of sedatives improve patient outcomes, no study to date has compared benzodiazepine drugs with novel sedative medications that act on different central nervous system receptors in reducing brain organ dysfunction (delirium and coma) and providing efficacious sedation. Trial Registration Identifier: NCT00095251Sedative and analgesic medications are routinely administered to mechanically ventilated patients to reduce pain and anxiety and to allow patients to tolerate invasive procedures in the intensive care unit (ICU). Conclusion In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion.

The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group ( = .48). Results Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. Main Outcome Measures Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal. Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours.