title: Cognitive improvement during continuous sedation in critically ill, awake and responsive patients: the Acute Neurological ICU Sedation Trial (ANIST).
abstract: BACKGROUND
  Most anxiolytics and sedative regimens in the intensive care unit (ICU) impair intellectual function, reducing patient autonomy, and often add to patient morbidity. Using an ICU-validated cognitive assessment tool Adapted Cognitive Exam (ACE), we performed a comparison between dexmedetomidine (DEX) and propofol (PRO) to evaluate which sedative regimen offered the least decrement in intellectual capacity.
  
  
  METHODS
  This was a prospective, randomized, double-blinded study of 30 awake and intubated brain-injured (BI, n = 18) and non-BI (12) ICU patients. Each patient received fentanyl/PRO and fentanyl/DEX titrated to a calm, awake state using a crossover design. Cognitive testing was performed at each study period using the validated 100-point Hopkins ACE cognitive battery.
  
  
  RESULTS
  Sedation with PRO diminished adjusted ACE scores (100-point exam) by a mean of -12.4 (95% CI -8.3 to -16.5, p < 0.001) while DEX, in contrast, improved ACE scores (6.8, 95% CI 1.2-12.4, p < 0.018). The difference in the change of ACE score between DEX versus PRO, our primary endpoint, was 19.2 (95% CI 12.3-26.1 p < 0.001) in favor of an improved ACE score on DEX. Patients with BI required less sedative, but effects of PRO and DEX on cognition were not changed. No serious adverse events occurred. Modest bradycardia was noted post hoc with DEX (-7.7 bpm, p < 0.01).
  
  
  CONCLUSIONS
  ICU patients may be offered sedation without necessarily compromising arousal or cognition. Alleviation of anxiety and agitation can singly and effectively improve mental engagement and performance if overt forebrain dysfunction is avoided. Higher ACE scores with DEX may be a consequence of the intellect-sparing yet calming effect of this drug.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine, 600 N. Wolfe Street, Meyer 8-140, Baltimore, MD 21287, USA. mmirski1@jhmi.edu
authors.forename: Marek A
authors.initials: MA
authors.lastname: Mirski
authors.forename: John J
authors.initials: JJ
authors.lastname: Lewin
authors.forename: Shannon
authors.initials: S
authors.lastname: Ledroux
authors.forename: Carol
authors.initials: C
authors.lastname: Thompson
authors.forename: Peter
authors.initials: P
authors.lastname: Murakami
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Zink
authors.forename: Michael
authors.initials: M
authors.lastname: Griswold
mesh_terms: D000179:Acrylates / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D003071:Cognition / Q000187:drug effects*; D016292:Procedural Sedation / Q000379:methods*; D016638:Critical Illness; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012121:Respiration, Artificial; D016896:Treatment Outcome
chemical_list: C110594:3-(4-hydroxy-3-(3-oxo-but-1-enyl)-phenyl)-acrylic acid; D000179:Acrylates; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D005283:Fentanyl