• Yahya Shehabi, Lucy Chan, Suhaini Kadiman, Anita Alias, Wan Nasrudin Ismail, Mohd Ali T Ismail Tan, Tien Meng Khoo, Saedah Binti Ali, Mat Ariffin Saman, Ahmad Shaltut, Cheng Cheng Tan, Cow Yen Yong, Michael Bailey, and Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators.
• Department of Intensive Care, University New South Wales Clinical School, The Prince of Wales Hospital, Randwick, NSW, Australia. y.shehabi@unsw.edu.au
• Intensive Care Med. 2013 May 1; 39 (5): 910-8.

PurposeTo ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality.MethodsWe 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.ResultsThe 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.ConclusionIrrespective 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.

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