title: Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00095251.
authors: Department of Anesthesiology/Division of Critical Care, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. pratik.pandharipande@vanderbilt.edu
authors: Pratik P
authors: PP
authors: Pandharipande
authors: Brenda T
authors: BT
authors: Pun
authors: Daniel L
authors: DL
authors: Herr
authors: Mervyn
authors: M
authors: Maze
authors: Timothy D
authors: TD
authors: Girard
authors: Russell R
authors: RR
authors: Miller
authors: Ayumi K
authors: AK
authors: Shintani
authors: Jennifer L
authors: JL
authors: Thompson
authors: James C
authors: JC
authors: Jackson
authors: Stephen A
authors: SA
authors: Deppen
authors: Renee A
authors: RA
authors: Stiles
authors: Robert S
authors: RS
authors: Dittus
authors: Gordon R
authors: GR
authors: Bernard
authors: E Wesley
authors: EW
authors: Ely
mesh_terms: D000368:Aged; D003128:Coma / Q000139:chemically induced* / Q000175:diagnosis; D016292:Procedural Sedation / Q000191:economics; D003693:Delirium / Q000139:chemically induced* / Q000175:diagnosis; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D007362:Intensive Care Units / Q000191:economics; D008140:Lorazepam / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012121:Respiration, Artificial / Q000191:economics
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D008140:Lorazepam