Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial.
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.
Pandharipande
Pratik P
PP
Department of Anesthesiology/Division of Critical Care, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. pratik.pandharipande@vanderbilt.edu
Pun
Brenda T
BT
Herr
Daniel L
DL
Maze
Mervyn
M
Girard
Timothy D
TD
Miller
Russell R
RR
Shintani
Ayumi K
AK
Thompson
Jennifer L
JL
Jackson
James C
JC
Deppen
Stephen A
SA
Stiles
Renee A
RA
Dittus
Robert S
RS
Bernard
Gordon R
GR
Ely
E Wesley
EW
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
D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D008140:Lorazepam