Delirium in ICU Characteristic, Diagnosis and Prevention
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Delirium in ICU Characteristic, Diagnosis and Prevention Presentation Transcript

  • 1. Delirium in ICU Characteristic, Diagnosis and  Prevention Marcelo G. Rocha, M.D. Marcelo G. Rocha, M.D. ICU Pav. Pereira Filho Santa Casa Porto Alegre  S t C P t Al RGS Brazil
  • 2. OUTLINE OF THE TALK • Definitions – types/prevalence/importance – risk factors/pathoetiology of delirium risk factors/pathoetiology of delirium • What can we do to prevent delirium: a. Monitoring p g b. Non pharmacolgical interventions c. Reduction in deliriogenic medications • Use of Protocols and  less is more Use of Protocols and “less is more” d. Pharmacological interventions a. Antipsychotics a Antips chotics b. Dexmedetomidine
  • 3. Definition of Delirium Definition of Delirium • derived from Latin: derived from Latin: – de “away from” – lira “ furrow in field”  – ium (Latin for singular) (Latin for singular)
  • 4. Delirium • Delirium is  li i i (1) fluctuation/change in mental status fluctuation/change in mental status  (2) inattention either/or (3) disorganized thinking disorganized thinking  (4) altered level of consciousness ( ) DSM IV and CAM‐ICU
  • 5. Delirium – a brain organ dysfunction Morandi et al ICM 2008;34:1907‐1915
  • 6. Delirium Subtypes yp • Hyperactive delirium ‐ agitation, restlessness, pulling catheters or tubes,  agitation restlessness pulling catheters or tubes hitting, biting, and emotional lability. (At risk for self‐ extubation and subsequent reintubation) q ) • Hypoactive delirium – yp withdrawal, flat affect, apathy, lethargy and perhaps  even unresponsiveness; often unrecognized due to  these “quiet” symptoms; (At risk for aspiration,  h “ i ” ( i kf i i pulmonary embolism, decubitus ulcers, and other  complications related to immobility) complications related to immobility) • Mixed ‐ combination Mixed 
  • 7. Delirium versus Cognitive Impairment D li i C iti I i t • Delirium • Cognitive impairment – rapid onset – variable to insidious onset – fluctuation – not fluctuating not fluctuating – clouded consciousness – no clouding of  – Inattention, disorganized  consciousness thought – many domains impaired – not chronic – persistent/chronic (?) Gordon SM, Intensive Care Med 30:1997‐2008, 2004 Jackson JC, Intensive Care Med 30:2009‐2016, 2004
  • 8. Prevalence of ICU Delirium Prevalence of ICU Delirium • Occurs in up to 80% MICU/SICU MVpatients • 20 50% of lower severity ICU patients develop 20‐50% of lower severity ICU patients develop • Hypoactive or mixed forms most common • 65‐70% goes undiagnosed if routine monitoring is  p not implemented Roberts B. Aust Roberts B Aust Crit Care 2005;18:6 8‐9 Care. 2005;18:6,8‐9. Ely EW. ICM. 2001;27:1892‐1900. Thomason J. Crit Care. 2005;9:375‐381. Ely EW. JAMA. 2001;286,2703‐2710. Ely EW. CCM. 2004;32:106‐112. Pandharipande. J Trauma. 2008;65:34‐41. Peterson. JAGS. 2006;54:479‐484. Ely EW. CCM. 2001;29:1370 1379. Ely EW CCM 2001;29:1370‐1379 Ouimet S. ICM. 2007;33:66‐73. Pandharipande. ICM. 2007;33:1726‐1731. Spronk P. Neth J Med.2009;67:296‐300 Lat I. CCM.2009;37:1898‐1905 Slooter A. CCM.2009. 37 (6):1881‐1885, 2009
  • 9. “Invisible” Organ Dysfunction “I i ibl ” O D f ti • Delirium is not routinely monitored in the ICU 1 • Validated tools – ICU‐DSC 2 or CAM‐ICU 3‐4 • “ICU Psychosis” traditionally an expected outcome • In non ICU settings, delirium has been associated with  In non‐ICU settings delirium has been associated with prolonged stay, institutionalization, and death 5‐7 1 Ely EW CCM 2004;32:106‐112 4 Ely EW CCM 2001;29,1370‐79 5 Inouye, Am J Med 1999;106:565‐573 2 Bergeron, ICM 2001;27:859‐64 g , ; 6 Lawlor, Arch Intern Med 2000;160:786‐794 3 Ely EW JAMA 2001;286,2703‐2710 7 McCusker, Arch Intern Med 2002;162:457‐463
  • 10. ICU Delirium ‐ i li ti ICU D li i implications • 3 times higher risk of death by 6 months 3 i hi h i k f d h b 6 h • $15k to $25k higher hospital costs • Estimated national $4 to $16 billion associated costs  • 5 fewer ventilator free days (days alive and off vent),  adjusted P=0.03 • 9 times higher incidence of cognitive impairment at  hospital discharge, adj. P=0.002 • Using similar methodology (CAM‐ICU, etc) a  Taiwanese cohort found similar mortality data Ely EW et al, JAMA 2004;291‐1753‐1762 y , ; Milbrandt E et al, Crit Care Med 2004;32:955‐962 Lin et al, Crit Care Med 2004;32:2254‐59
  • 11. Risk factors Modifiable Risk Factor Preexisting Risk Factors • Sedatives/analgesics • Sleep disturbances Sleep disturbances • Dementia • Prolonged immobilization • Cognitive dysfunction Cognitive dysfunction • Poor oxygenation Poor oxygenation • Age • Glucose • Severity of illness Severity of illness • Pain • Comorbidities • Infection • Anticholinergic  Anticholinergic Medication • Electrolyte disturbances y • Dehydratation
  • 12. Risk factors you can t control Risk factors you can’t control Age Severity  of Ilness S i f l Each year increase risk in 2% Each point increase risk in 6% Pandharipande P et all. Lorazepan is an independent risk factor for transitioning to delirium in ICU patients, Anesthesiology, 2006; 104:21‐26
  • 13. Risk factors you can control: medication Risk factors you can control: medication Pandharipande P et all. Lorazepan is an independent risk factor for transitioning to delirium in ICU patients, Anesthesiology, 2006; 104:21‐26
  • 14. Midazolam and fentanyl as risk factors for delirium Midazolam Fentanyl 100 100 Users Users Non-Users Non-Users 80 80 p=0.014 p=0.007 p=0.031 ous ous 60 60 % Days Delirio % Days Delirio p=0.936 p=0 936 6 6 40 40 20 20 0 0 Surgical Trauma Surgical Trauma Daily Midazolam Use (Exc Coma Days) (Exc. Daily Fentanyl Use (Exc Coma Days) (Exc. Pandharipande et al., J Trauma.2008:65;34‐41
  • 15. A basic pathoetiological model of delirium Maldonado J, Crit Care Clin 2008
  • 16. Hipoxemia, metabolic  Systemic Inflamation derangements Drugs Global impairment of  Activation of primed  cerebral metabolism microglia Neurotransmitter  Decreased synthesis  imbalance, disruption disruption  and release of  of synaptic  Increased cytokines  neurotransmitters communication levels in the brain delirium deliri m
  • 17. What should we do to prevent  What should we do to prevent delirium in ICU patients? p 1. Monitoring  2. Non pharmacolgical interventions 2. Non pharmacolgical interventions 3. Reduction in deliriogenic medications 4. Pharmacological interventions Dexmedetomidine Antipsychotics
  • 18. Two Step Approach to Assessing  Consciousness Step 1 Level: Arousal/Sedation Assessment (RASS, SAS) (If pt opens eyes to voice then proceed to Step 2) (f i h d ) Step 2 Content:  Delirium Assessment (CAM‐ICU)
  • 19. Confusion Assessment Method CAM‐ICU 1. Acute onset of mental status changes  1 A t t f t l t t h or a fluctuating course and 2. Inattention 2 I i and  and 3. Disorganized  or 4. Altered level of  Thinking consciousness = Delirium Ely, E.W., et al.   JAMA; 286, 2703‐2710, 2001.    Ely, E.W., et al. Crit Care Med; 29, 1370‐1379, 2001.
  • 20. ICU Delirium Screening Checklist 8 items based on DSM criteria 8 items based on DSM criteria Normal = 0,  1‐3 = subsyndromal delirium, ≥ 4 = delirium 1. Altered level of consciousness 1 2. Inattention 1 3. Disorientation 1 4. Hallucinations 4 Hallucinations 0 5. Psychomotor agitation or retardation 1 6. Inappropriate speech 0 p/ y 7. Sleep/wake cycle disturbances 1 8. Symptom fluctuation 1 Total score (0‐8) Total score (0 8) 6/8 Bergeron, et al. ICM. 2001; 27:859
  • 21. What should we do to prevent  What should we do to prevent delirium in ICU patients? p 1. Monitoring  2. Non pharmacolgical interventions 2. Non pharmacolgical interventions 3. Reduction in deliriogenic medications 4. Pharmacological interventions Dexmedetomidine Antipsychotics
  • 22. Daily Wake‐Up + Early Mobility Outcome Intervention Control P (n=49) (n=50) Funcionally independent  at  discharge (nnt=4) 29 (59%) 19 (35%) .02 ICU delirium (days) 2 (0‐6) 4 (2‐7) .03 Time in ICU with delirium (%) 33% (0‐58) 57% (33‐69) .02 Hospital delirium (days) 2 (0‐6) 4 (2‐8) .02 Hospital days with delirium (%) 28% (26) 41% (27) .01 Barthel Index score at discharge 75 (7.5‐95) 55 (0‐85) .05 ICU‐acquired paresis at discharge 15 (31%) 27 (49%) .09 Ventilator‐free days 23.5 (7.4‐25.6) 21.1 (0 – 23.8) .05 Lenght of stay in ICU (days) 5.9 (4.5‐13.2) 7.9 (6.1‐12.9) .08 LOS hospital (days) 13.5 (8‐23.1) 12.9 (8.9‐19.8) .93 Hospital Mortality 9 (18%) 14 (25%) .53 Schweickert WD – Early physical and occupational therapy in MV, critically ill patients, a RCT, Lancet 2009
  • 23. Environmental factor  E i t lf t • Extremes in sensory experience (eg. Hypothermia) • Deficits in vision or hearing f h • Immobility or decreased activity y y • Social isolation • Novel environment • Stress
  • 24. A “bundle” for delirium prevention? bu d e o de u p e e t o • Family support (all levels, kids, childrens) y pp • Allow family at bedside, 24 h/day •Oi Orientation improvements i i – Daylights – Wall clocks • Hearing aid Hearing aid • Glasses • Sleep...
  • 25. Sleep deprivation and delirium l d dd l Sleep Deprivation Delirium D li i • Daytime sleepiness D ti l i • Lethargy h • Lethargy • Agitation • Irritability • Confusion • Confusion • Inattention • Poor short term memory Poor short‐term memory • Sympathetic stimulation • Sympathetic stimulation • Anger and Frustration g • Emotional liability • Restlessness • Restlessness • Anxiety • Hallucinations 
  • 26. Sleep P t l Sl Protocol • Design behavioral protocol to reduce sleep disturbance  • Noise reduction at night • Light reduction at night (cover eyes) • Modify timing of patient/staff intervention at night y g p / g • Avoid unnecssary analgesia and sedation • Ear plugs  Ear plugs • Pharmacology (melatonin, sedatives) • Back massage, relaxation, music therapy Back massage relaxation music therapy • Record hours of sleep and discuss during round
  • 27. What should we do to prevent  What should we do to prevent delirium in ICU patients? p 1. Monitoring 2. Non pharmacolgical interventions 2. Non pharmacolgical interventions 3. Reduction in deliriogenic medications ‐ sedation protocols and “less is more” 4. Pharmacological interventions 4 Pharmacological interventions Dexmedetomidine Antipsychotics h
  • 28. Sedation Protocols: The Evidence Sedation Protocols: The Evidence Trial RCT Outcome(s) improved by Protocol Brook  AD, CCM 1999 Yes Ventilator days, ICU and HO LOS, need for tracheostomy Kress JP, O’Connor NEJM 2000 Yes Ventilator days, ICU LOS Brattebo G, BMJ 2000 G,  BMJ 2000 No Ventilator days Ventilator days Chanques G, CCM 2006 No Ventilator days, pain/agitation, infections Quenot JP, CCM 2007 No Ventilator days, extubation sucess, VAP Arias‐Rivera S, CCM 2008 , No Extubation sucess Girart TD, Lancet 2008 (ABC) Yes Ventilator days, HO LOS, survival (nnt=7) Robinson BR, J Trauma 2008 No Ventilator days, HO LOS
  • 29. What should we do to prevent  What should we do to prevent delirium in ICU patients? p 1. Monitoring 2. Non pharmacolgical interventions 2. Non pharmacolgical interventions 3. Reduction in deliriogenic medications ‐ sedation protocols and “less is more” 4. Pharmacological interventions 4 Pharmacological interventions Antipsychotics Dexmedetomidine d d
  • 30. Risperidone and Delirium Risperidone and Delirium • Double‐blind randomized trial Double blind randomized trial  • Single dose (1 mg) of risperidone administered after  cardiac surgery di • Reduced the incidence of postoperative delirium p p – 11.1% (intervention) vs. 31.7% (placebo), P=.009 – RR=0 35 95% CI=0 16 0 77 RR=0.35, 95% CI=0.16‐0.77 Prakanrattana, et al. Anaesth Intensive Care. 2007;35:714‐719
  • 31. Design: Double‐blind, placebo‐controlled • Quetiapine 50mg PO/NGT twice daily vs Placebo • PRN IV haloperidol protocolized and encouraged in each group • Primary outcome:  Time to first resolution of delirium  (first 12 hour  • Primary outcome Time to first resolution of delirium (first 12 hour period when ICDSC ≤ 3) Results: Quetiapine added to as‐needed haloperidol results in faster  delirium resolution, less agitation, and a greater rate of transfer to  home or rehabilitation. h h bili i Crit Care Med 2010 Vol. 38, No. 2
  • 32. Modyfing the Incidence of Delirium (MIND Trial) Girard T., Feasibility, efficacy, and safety of antipsychotics for ICU delirium: MIND trial ‐ CCMed 2010
  • 33. Dexmedetomidine x Haloperidol Randomised, open label, parallel‐groups pilot trial , p ,p g p p • 20 ventilated patients with agitated delirium • Randomized to haloperidol 0.5‐2mg/hr or dexmedetomidine 0.2‐0.7 μg/kg/hr • Dexmedetomidine shorter hours to extubation Dexmedetomidine shorter hours to extubation 42 (IQR 23.2‐117.8) vs 20 (IQR 7.3‐24), p=0.016 • Dexmedetomidine decreased ICU length of stay 6.5 (IQR 4 9) vs 1.5 (IQR 1 3) days, p=0.004 6 5 (IQR 4‐9) vs 1 5 (IQR 1‐3) days p=0 004 Reade MC. Critical Care 2009, 13:R75
  • 34. Dexmedetomidine x Haloperidol Randomised, open label, parallel‐groups pilot trial , p ,p g p p • 20 ventilated patients with agitated delirium • Randomized to haloperidol 0.5‐2mg/hr or dexmedetomidine 0.2‐0.7 μg/kg/hr • Dexmedetomidine shorter hours to extubation Dexmedetomidine shorter hours to extubation 42 (IQR 23.2‐117.8) vs 20 (IQR 7.3‐24), p=0.016 • Dexmedetomidine decreased ICU length of stay 6.5 (IQR 4 9) vs 1.5 (IQR 1 3) days, p=0.004 6 5 (IQR 4‐9) vs 1 5 (IQR 1‐3) days p=0 004 Reade MC. Critical Care 2009, 13:R75
  • 35. MENDS Study MICU/SICU Ventilated on Sedatives V til t d S d ti Informed Consent Control Intervention Lorazepam (GABA) L Dexmedetomidine ( 2) D d idi (α2) +/- Fentanyl +/- Fentanyl Pandharipande et al JAMA. 2007 Dec 12;298(22):2644-53
  • 36. Brain Dysfunction p .01 p=.01 p .09 p=.09 p .001 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
  • 37. SEDCOM Trial MICU Patients Ventilated & Sedated Control Intervention Midazolam (GABA) Dexmedetomidine (α2) ± Fentanyl ± Fentanyl Riker R. et all JAMA 2009 301, 5:489 ik ll
  • 38. Daily Incidence of Delirium 54% DEX vs 76.6% MDZ, p<0.001 Dexmedetomidine Midazolam † 80 75.7 * 70 ents with Delirium m 60 * 54,6 * P < 0.05 50 † P < 0.001 * 40 * Percen of Patie 30 * 20 * nt 10 0 Baseline 1 2 3 4 5 6 7 8 Total Treatment Day
  • 39. Daily Delirium ‐ CAM‐ICU Negative at Baseline Dexmedetomidine Midazolam † 60 55,3 um_ 50 rcent of Subjects with Deliriu * P < 0.05 † P < 0.001 40 * 33.3 33 3 w 30 20 10 Per 0 Baseline 1 2 3 4 5 6 7 8 Total Treatment Day
  • 40. Daily Delirium  CAM ICU Positive at Baseline Daily Delirium ‐ CAM‐ICU Positive at Baseline † Dexmedetomidine Midazolam 100 94,6 90 * atients wit Delirium m 80 * * P < 0.05 69,7 70 † P < 0.001 P < 0.001 th 60 * 50 * rcent of Pa 40 30 * * Perc 20 10 0 Baseline 1 2 3 4 5 6 7 8 Total
  • 41. SEDCOM Results Dexmedetomidine Midazolam Outcome P n=244 n=122 Time sedation target Ti d ti t t 77.3 (%) 77 3 (%) 75.1 75 1 .18 18 Delirium prevalence p 132 (54%) ( ) 93 (76%)% ( ) <0,001 Delirium free‐days 2.5 1.7 .002 Time to extubation 3,7 days 5.6 days .01 ICU LOS ICU LOS 5,9 59 7,6 76 .24 24
  • 42. Summary of MENDS & SEDCOM Summary of MENDS & SEDCOM • Two multicenter, double blind RCTs of Two multicenter, double blind RCTs of  benzodiazepines vs dexmedetomidine (GABA vs. Alpha 2  agonists) in high severity medical and surgical ICU  agonists) in high severity medical and surgical ICU patients: – R d d i id Reduced incidence and duration of delirium/coma d d ti f d li i / – Significant or trend towards shorter time to extubation and  ICU length of stay – Other very interesting hypothesis generating findings such Other very interesting hypothesis generating findings such  as reduced infection rates and improved survival in severe  sepsis p
  • 43. Conclusions • Delirium is a frequent disease in the ICU and Delirium is a frequent disease in the ICU and  associated with poor outcomes. • Delirious is under‐recognized, can be monitored and  rapidly identified. rapidly identified. • New approaches to manage and prevent delirium  are emerging every day. i d • Dexmedetomidine has a place in this new strategies.  p g
  • 44. Conclusions (6 points for DEX) ( p ) 1. GABA‐agonists increase delirium g 2. Dexmedetomidine improves outcomes compared to  GABA‐agonists GABA agonists 3. Dexmedetomidine reduces incidence of delirium 4. Dexmedetomidine facilitates clearing of delirium 5. Dexmedetomidine saves money compared to  5 Dexmedetomidine saves money compared to GABAagonists 6. Dexmedetomidine may be better than haloperidol