title: Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation.
abstract: OBJECTIVE
  Sleep is regulated by circadian and homeostatic processes and is highly organized temporally. Our study was designed to determine whether this organization is preserved in patients receiving mechanical ventilation (MV) and intravenous sedation.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Academic medical intensive care unit.
  
  
  METHODS
  Critically ill patients receiving MV and intravenous sedation.
  
  
  METHODS
  Continuous polysomnography (PSG) was initiated an average of 2.0 (1.0, 3.0) days after ICU admission and continued ≥ 36 h or until the patient was extubated. Sleep staging and power spectral analysis were performed using standard approaches. We also calculated the electroencephalography spectral edge frequency 95% SEF₉₅, a parameter that is normally higher during wakefulness than during sleep. Circadian rhythmicity was assessed in 16 subjects through the measurement of aMT6s in urine samples collected hourly for 24-48 hours. Light intensity at the head of the bed was measured continuously.
  
  
  RESULTS
  We analyzed 819.7 h of PSG recordings from 21 subjects. REM sleep was identified in only 2/21 subjects. Slow wave activity lacked the normal diurnal and ultradian periodicity and homeostatic decline found in healthy adults. In nearly all patients, SEF₉₅ was consistently low without evidence of diurnal rhythmicity (median 6.3 [5.3, 7.8] Hz, n = 18). A circadian rhythm of aMT6s excretion was present in most (13/16, 81.3%) patients, but only 4 subjects had normal timing. Comparison of the SEF₉₅ during the melatonin-based biological night and day revealed no difference between the 2 periods (P = 0.64).
  
  
  CONCLUSIONS
  The circadian rhythms and PSG of patients receiving mechanical ventilation and intravenous sedation exhibit pronounced temporal disorganization. The finding that most subjects exhibited preserved, but phase delayed, excretion of aMT6s suggests that the circadian pacemaker of such patients may be free-running.
authors.affiliation: Division of Pulmonary, Critical Care, and Occupational Medicine, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA. brian-gehlbach@uiowa.edu
authors.forename: Brian K
authors.initials: BK
authors.lastname: Gehlbach
authors.forename: Florian
authors.initials: F
authors.lastname: Chapotot
authors.forename: Rachel
authors.initials: R
authors.lastname: Leproult
authors.forename: Harry
authors.initials: H
authors.lastname: Whitmore
authors.forename: Jason
authors.initials: J
authors.lastname: Poston
authors.forename: Mark
authors.initials: M
authors.lastname: Pohlman
authors.forename: Annette
authors.initials: A
authors.lastname: Miller
authors.forename: Anne S
authors.initials: AS
authors.lastname: Pohlman
authors.forename: Arlet
authors.initials: A
authors.lastname: Nedeltcheva
authors.forename: John H
authors.initials: JH
authors.lastname: Jacobsen
authors.forename: Jesse B
authors.initials: JB
authors.lastname: Hall
authors.forename: Eve
authors.initials: E
authors.lastname: Van Cauter
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D016638:Critical Illness; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000494:pharmacology*; D007362:Intensive Care Units; D008029:Lighting; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D008875:Middle Aged; D017286:Polysomnography; D012121:Respiration, Artificial; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D006993:Hypnotics and Sedatives; C054513:6-sulfatoxymelatonin; D008550:Melatonin