title: Early intensive care sedation predicts long-term mortality in ventilated critically ill patients.
abstract: BACKGROUND
  Choice and intensity of early (first 48 h) sedation may affect short- and long-term outcome.
  
  
  OBJECTIVE
  To investigate the relationships between early sedation and time to extubation, delirium, and hospital and 180-day mortality among ventilated critically ill patients in the intensive care unit (ICU).
  
  
  METHODS
  Multicenter (25 Australia and New Zealand hospitals) prospective longitudinal (ICU admission to 28 d) cohort study of medical/surgical patients ventilated and sedated 24 hours or more. We assessed administration of sedative agents, ventilation time, sedation depth using Richmond Agitation Sedation Scale (RASS, four hourly), delirium (daily), and hospital and 180-day mortality. We used multivariable Cox regression to quantify relationships between early deep sedation (RASS, -3 to -5) and patients' outcomes.
  
  
  RESULTS
  We studied 251 patients (mean age, 61.7 ± 15.9 yr; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 20.8 ± 7.8), with 21.1% (53) hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed 14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4 hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium occurred in 111 (50.7%) patients with median (interquartile range) duration of 2 (1-4) days. After adjusting for diagnosis, age, sex, APACHE II, operative, elective, hospital type, early use of vasopressors, and dialysis, early deep sedation was an independent predictor of time to extubation (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.94; P < 0.001), hospital death (HR, 1.11; 95% CI, 1.02-1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01-1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19).
  
  
  CONCLUSIONS
  Early sedation depth independently predicts delayed extubation and increased mortality, making it a potential target for interventional studies.
authors.affiliation: University of New South Wales Clinical School and Prince of Wales Hospital, Program of Acute Care, Department of Intensive Care Services, Barker Street, Randwick, NSW 2031, Australia. y.shehabi@unsw.edu.au
authors.forename: Yahya
authors.initials: Y
authors.lastname: Shehabi
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reade
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Frances
authors.initials: F
authors.lastname: Bass
authors.forename: Belinda
authors.initials: B
authors.lastname: Howe
authors.forename: Colin
authors.initials: C
authors.lastname: McArthur
authors.forename: Ian M
authors.initials: IM
authors.lastname: Seppelt
authors.forename: Steve
authors.initials: S
authors.lastname: Webb
authors.forename: Leonie
authors.initials: L
authors.lastname: Weisbrodt
mesh_terms: D060666:Airway Extubation; D001315:Australia; D016638:Critical Illness / Q000401:mortality*; D054810:Deep Sedation / Q000009:adverse effects; D003693:Delirium / Q000453:epidemiology*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects*; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009520:New Zealand; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000379:methods*; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives