Sleep in the ICU The Next Delirium Frontier?

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Sleep in the ICU The Next Delirium Frontier?

  1. 1. Sleep in the ICU The Next Delirium Frontier? Paula L. Watson, M.D. Assistant Professor Pulmonary/Critical Care/Sleep Medicine Vanderbilt University Medical Center NIH AG027472-01A1, VA-GRECC,CTSA 1 UL1 RR024975, ASPECT
  2. 2. Presenter Disclosures Paula L. Watson, MD The following relationships with commercial interests related to this presentation existed during the past 12 months: Industry sponsored grant: Aspect
  3. 3. Risk Factors for ICU Delirium Aging Sleep Deprivation Baseline dementia Underlying illness Psychoactive – Inflammation Medications (sedatives) – Coagulation Metabolic Disturbances Hypoxemia Inouye, JAMA 1996;275:852-57 Dubois, Intens Care Med 2001;27:1297-1304 Pain / pain Inouye, NEJM 1999;340:669-676 Jacobi, Crit Care Med 2002;30:119-141 management Vaurio, Anesth Analg 2006; 102:1267-1273 Milbrandt, Crit Care Med. 2005;33:226-9
  4. 4. Perception of problems during ICU stay Pain relief 94% problems Anxiety 62% Sleep 61% deprivation Simini, Lancet 1999;354:571-572
  5. 5. Characteristics of Sleep in the ICU Severely fragmented – (>80 arousals/ hour) Increased stage 1 Decreased or absent Slow Wave & REM Distributed over day and night Aurell et al., BMJ 1985;290:1029-32 Cooper et al., Chest 2000;117:809-18 Orr et al., Am J Card 1977;39:196-201 Freedman et al., AJRCCM 2001;163:451-7
  6. 6. Sleep Deprivation Delirium
  7. 7. Sleep Deprivation and Delirium Common Neurocognitive Traits Inattention Fluctuating mental status Altered level of consciousness Cognitive slowing Incoordination Irritability Forest & Godbout, Sleep Deprivation: Basic Science, Physiology, and Behaviour 2005:199-222 Durmer & Dinges, Sem Neuro 2005;25:117-129
  8. 8. The Psychosis of Sleep Deprivation Case reports of hallucinations and persecutory delusions On the 4th and 5th day, he began to experience “waking dreams” Heightened suspiciousness, feeling of Randy Gardner, 264 hours resentment Patrick & Gilbert, Psychol Rev 1896;3:469-83 Katz & Landis, Arch Neurol Psychiat 1935;34:307-16 Luby et al., Psychosom Med 1960;22:182-92 West, Ann NY Acad Sci 1962;96:66-70 Gulevich & Dement Arch Gen Psychiat 1966;15:29-35
  9. 9. Sleep Deprivation Preferentially Affects the Pre-frontal Cortex Pre- Cerebral Blood Flow Harrison et al. Sleep 2000;23:1-7 Tabor & Hurley J Neuropsych Clin Neurosci 2006;18:1-5
  10. 10. Neurotransmitters Sleep Deprivation & Delirium histamine GABA melatonin Dopaminergic orexin Cholinergic activation deficiency serotonin dopamine adenosine norepinephrine acetylcholine Espana & Scammell, Sleep 2004;27:811-20 Trzepacz, Sem Clin Neuropsych 2000;5:132-48 Camarini, Braz J Med Biol Res 1997;30:641-47 Ebert, Adv Biol Psych 1998;153-69
  11. 11. Investigating the relationship of sleep deprivation and ICU delirium
  12. 12. Sleep Deprivation and ICU Delirium 50 45 40 35 % Patients 30 Mental Status 25 Changes 20 15 10 N = 62 5 0 None Moderate Severe Severity of Sleep Deprivation Helton et al., Heart & Lung 1980;9:464-68
  13. 13. Sleep disturbances associated with delirium ICU patients with delirium: – Longer REM latency – Shorter REM duration – Fewer REM periods Trompeo, Ranieri, 2005 Int Care Med Abstract Study designed to investigate sleep quality on noninvasive ventilation failure – circadian abnormalities, ↓ REM associated with development of delirium Campo, Brochard, Crit Care Med 2010;38
  14. 14. Measuring Sleep in the ICU Polysomnography: – Labor intensive – Expense – Difficulty interpreting Medications Metabolic effects Delirium
  15. 15. Decreased Spindles & K complexes Effect of primary illness or sedatives/analgesics? Scored as stage 1 due to lack of Spindles and K-complexes
  16. 16. EEG findings in the critically ill Polymorphic delta Burst suppression Isoelectric
  17. 17. The EEG and Delirium RASS -2, CAM-ICU + Consent to show full photo provided by patient Delta waves
  18. 18. Approach to Scoring in ICU Patients Assess Behavioral Sleep State Sleep Wake Classic Atypical Assess Sleep Stage Using Revised PSG Criteria Watson & Gehlbach -manuscript in progress
  19. 19. Sedatives in Sleep & Delirium
  20. 20. Sedation ≠ Sleep Sleep Essential biologic function Easily reversed by stimuli Circadian rhythm Cyclic progression of sleep stages RASS -5 (unresponsive) Weinhouse & Watson, Crit Care Clinics 2009;25:539-49
  21. 21. Lorazepam and Midazolam are associated with increased risk of delirium Delirium Risk- lorazepam Pandharipande et al., Anesthesiology 2006;104:21-6 Pandharipande et al., J Trauma 2008;65(1):34-41
  22. 22. Benzodiazepines and the EEG Normal Stage 2 Sleep lorazepam Benzodiazepines and opioids suppress REM and Slow Wave Sleep. Does sedation deprive patients of true sleep? What restorative benefits of natural sleep are provided by sedation? Bourne and Mills, Anaesthesia 2004;59:374-84 Kuehn, JAMA 2006;296:2427-2428 Tung et al., Anesthesiology 2004;100:1419-26
  23. 23. Benzodiazepine & propofol - GABA receptor in ventrolateral preoptic nucleus Dexmedetomidine – α2adrenoreceptor in the locus coerulus Nelson et al., Nature 2002;5:979-84 Nelson et al, Anesthes 2003;98:428-36
  24. 24. Dexmedetomidine Properties similar to natural sleep – Clinically sedated but arousable EEG activity similar to stage 2 sleep Nelson, Maze et al., Anesthesiology 2003;98:428-36 Huupponen et al., Acta Anaesthesiol Scand 2008; 52:289-94 Mason et al., Pediatric Anesthesia 2009;19:1175-83
  25. 25. Daily Prevalence of Delirium Prevalence of delirium similar prior to starting study drug Dexmedetomidine resulted in 24.9% ↓ in delirium during treatment phase (54% dex vs. 76.6% mdz) Riker et al., JAMA 2009;301(5):489-99 2009;301(5):489-
  26. 26. Summary Sleep deprivation and delirium – epidemiologic, biochemical, anatomic similarities Investigating the relationship of sleep deprivation and ICU delirium – measuring sleep, not an easy task Sleep and sedation – not the same and not equal
  27. 27. Future Research The Unanswered Questions Is sleep deprivation a cause of ICU delirium? Does sleep deprivation lower the threshold for developing delirium? Does sedation provide benefits of natural sleep?
  28. 28. Educational Delirium Website www.ICUdelirium.org
  29. 29. ICU Recall N = 146 Pain 28% Short of breath while on mech vent 20% Being terrified about my situation 38% Had hallucinations or nightmares 51% Think that some memories were from Situations that never really happened 49% Weinert & Sprenkle Int Care Med 2008;34:82-90
  30. 30. Memories of Critical Care “I have memories of jumbled thoughts…..it was petrifying. I could hardly tell what was real and what wasn’t. This sounds like some kind of a novel doesn’t it? Was I dreaming it all?” Illustration by Steven Stahlberg Cox et al., Crit Care Med 2009;37:2702-2708
  31. 31. The Psychosis of Sleep Deprivation Case reports of hallucinations and persecutory delusions “inevitable” if sleep deprivation continued longer than 100 hours Photo by Peter Tonningsen Patrick & Gilbert, Psychol Rev 1896;3:469-83 Katz & Landis, Arch Neurol Psychiat 1935;34:307-16 Luby et al., Psychosom Med 1960;22:182-92 West, Ann NY Acad Sci 1962;96:66-70
  32. 32. Randy Gardner Case of Prolonged (264 hrs) Wakefulness On the 4th and 5th day, he began to experience “waking dreams” Heightened suspiciousness, feeling of resentment Gulevich & Dement Arch Gen Psychiat 1966;15:29-35 Irritability Memory losses, difficulty concentrating Hallucinations, paranoia Ross Arch Neuro 1966;12:399-403
  33. 33. Sleep in Critically ill Patients Requiring Mechanical Ventilation N=20, Disrupted sleep (8 pts) – PSG features of NREM and REM sleep Atypical sleep (5 pts) – virtual absence of stage 2 – no K Complex’s or sleep spindles – higher dose of sedative medications Coma (7 pts) Cooper et al., Chest 2000;117:809-818
  34. 34. Sedation ≠ Sleep RASS – 5 (unresponsive)
  35. 35. Severe Sleep Fragmentation RASS -5 Watson, Crit Care Clinics 2009;25:539-49
  36. 36. Natural Sleep Dexmedetomidine Benzo / Propofol sleep sleep convergence hypnosis Cortex & Subcortical X X X areas histamine histamine histamine TMN TMN TMN tuberomammillary (-) (-) (-) +galanin & GABA +galanin & GABA ventrolateral VLPO VLPO VLPO preoptic nucleus X X X norepinephrine norepinephrine + norepinephrine locus ceruleus LC (-) LC LC Peruzzi, Pharmacotherapy 2005;25(5pt 2):34S-39S
  37. 37. Delirium is Associated with a Malfunction of the Pre-frontal Cortex Pre- Pilot fMRI data: Depressed activation - dorsolateral pre-frontal cortex on testing working memory in previously delirious vs. non- delirious ICU patients Gunther et al., Crit Care Med 2008;36:12 Mesulam et al., J Neurol Neurosurg Psych 1979;39:84-89 Koponen et al., J Nerv Men Dis 1989;177:226-31 Doyle & Warden Am J Psych 1996;153:838-9
  38. 38. Sedatives in Sleep & Delirium
  39. 39. Probability of transitioning from normal to delirium after lorazepam 1 0.9 0.8 Delirium Risk 0.7 0.6 0.5 No Drug 0-1 1-2 2-3 3-4 4+ Log scale 0-2.7 2.7-7.4 7.4-20 20-55 55+ Original scale Lorazepam Dose (mg) Pandharipande PP, et al. Anesthesiology 206;104:21-6
  40. 40. Sleep Deprivation It doesn’t end at hospital discharge Patient 1 Patient 2 Watson, unpublished data
  41. 41. Brain Dysfunction p=.01 p=.09 p=.001 12 10 8 6 4 2 Dexmedetomidine Lorazepam 0 Delirium/Coma-Free Days Delirium-Free Days Coma-Free Days Pandharipande PP, et al. JAMA 2007;298:2644-53
  42. 42. Delirium Acute confusional state – Fluctuating mental status – Inattention – Cognitive dysfunction Incidence – lower severity ICU patients – 60-80% of ventilated patients 60- Delirium is associated with: – $15k- $25k higher hospital $15k- costs – 3 times higher risk of death by 6 months Pun & Ely, Chest 2007;132
  43. 43. Flip- Flip-Flop Switch Model Saber et al, Nature 2005;247:1257-63
  44. 44. Neural Pathways of Sleep and Sedation Peruzzi, Pharmacotherapy 2005;25(5pt 2):34S-39S
  45. 45. Ayptical Sleep and Delirium Watson, 2007 ATS abstract

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