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The MENDS Randomized Controlled Trial

Pratik P. Pandharipande, MD, MSCI; Brenda T. Pun, RN, MSN, ACNP; Daniel L. Herr, MD; Mervyn Maze, MB, ChB; Timothy D. Girard, MD, MSCI; Russell R. Miller, MD, MPH; Ayumi K. Shintani, MPH, PhD; Jennifer L. Thompson, MPH; James C. Jackson, PsyD; Stephen A. Deppen, MA, MS; Renee A. Stiles, PhD; Robert S. Dittus, MD, MPH; Gordon R. Bernard, MD; E. Wesley Ely, MD, MPH

JAMA. 2007;298(22):2644-2653.

Context  Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction.

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.

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. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU).

Main Outcome Measures  Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal.

Results  Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48).

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.

Trial Registration  clinicaltrials.gov Identifier: NCT00095251

Author 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).

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