Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study.
OBJECTIVE
To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality.


METHODS
We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤-3.


RESULTS
The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7%) and 110/237 (46.4%). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93%) versus 72 (28%) patients (P < 0.0001) for 966 (39.6%) versus 183 (7.5%) study days respectively. Deep sedation occurred in (182/257) 71% patients at first assessment and in 159 (61%) patients and 1,658 (59%) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.97, P = 0.003], hospital death (HR 1.11, 95% CI 1.05-1.18, P < 0.001) and 180-day mortality (HR 1.09, 95% CI 1.04-1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44%) of patients.


CONCLUSIONS
Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.
Department of Intensive Care, University New South Wales Clinical School, The Prince of Wales Hospital, Randwick, NSW, Australia. y.shehabi@unsw.edu.au
Yahya
Y
Shehabi
Lucy
L
Chan
Suhaini
S
Kadiman
Anita
A
Alias
Wan Nasrudin
WN
Ismail
Mohd Ali T Ismail
MA
Tan
Tien Meng
TM
Khoo
Saedah Binti
SB
Ali
Mat Ariffin
MA
Saman
Ahmad
A
Shaltut
Cheng Cheng
CC
Tan
Cow Yen
CY
Yong
Michael
M
Bailey
D018806:APACHE; D016009:Chi-Square Distribution; D016638:Critical Illness / Q000401:mortality*; D054810:Deep Sedation / Q000401:mortality*; D003693:Delirium / Q000175:diagnosis; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage; D007362:Intensive Care Units; D008137:Longitudinal Studies; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012121:Respiration, Artificial
D006993:Hypnotics and Sedatives