Effect of Sedation With Dexmedetomidine vs Lorazepam on Acute Brain Dysfunction in Mechanically Ventilated Patients: The MENDS Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association 2007-12, Vol.298 (22), p.2644-2653
• Main Authors: Pandharipande, Pratik P, Pun, Brenda T, Herr, Daniel L, Maze, Mervyn, Girard, Timothy D, Miller, Russell R, Shintani, Ayumi K, Thompson, Jennifer L, Jackson, James C, Deppen, Stephen A, Stiles, Renee A, Dittus, Robert S, Bernard, Gordon R, Ely, E. Wesley
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Clinical trials; Coma - chemically induced; Coma - diagnosis; Conscious Sedation - economics; Delirium - chemically induced; Delirium - diagnosis; Dexmedetomidine - administration & dosage; Dexmedetomidine - adverse effects; Dexmedetomidine - economics; Double-Blind Method; Female; General aspects; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - economics; Intensive care; Intensive Care Units - economics; Lorazepam - administration & dosage; Lorazepam - adverse effects; Lorazepam - economics; Male; Medical procedures; Medical sciences; Medical treatment; Middle Aged; Neuropharmacology; Neuropsychological Tests; Patients; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Respiration, Artificial - economics; Tranquilizers
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.298.22.2644

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