1. ABCDE ICU Delirium Bundle From Diagnosis to Treatment Timothy D. Girard, MD, MSCI ICU Delirium and Cognitive Impairment Study Group Division of Allergy, Pulmonary, & Critical Care Medicine Center for Health Services Research Vanderbilt University School of Medicine VA Tennessee Valley GRECC Nashville, Tennessee

2. Disclosures Grant monies –NIH Honoraria (for non-promotional presentation) –Hospira, Inc. Research product/procedure/technique –None

4. What’s ahead 1.ABCDEs of critical care 2.Delirium diagnosis 3.Delirium management

5. 1 1 ABCDEs of Critical Care

6. A A Awakening trials B B Breathing trials C C Coordination D D Delirium management E E Exercise & mobility

8. 0 20 40 60 80 100 Patients Receiving Mechanical Ventilation (%) 030201015525 Control (n=60) Protocol (n=68) Adjusted p<. 001 Time (Days) Kress JP, et al. N Engl J Med 2000;342:1471-7 Ventilator time reduced by 2 days Awakening – Daily Interruption of Sedatives

10. 014846212 0 20 40 60 80 100 Patients Liberated from Mechanical Ventilation (%) 10 Intermittent SBTs (n=33) Daily SBTs (n=31) Pressure support vent (n=37) Intermittent mandatory vent (n=29) Weaning Time (Days) Esteban A, et al. N Engl J Med 1995;332:345-50 Breathing – Spontaneous Breathing Trials

12. Ely EW, et al. N Engl J Med 1996;335:1864-9 0 20 40 60 80 100 Patients Receiving Mechanical Ventilation (%) 030201015525 Control (n=151) Protocol (n=149) p<.001 Weaning Time (Days) Breathing – SBT Protocols Ventilator time reduced by 2 days

13. Days before Weaning Begins 0642315 Days after Intubation 7 SBTs begin (Esteban 1995) Intubation SBTs begin (Ely 1996) Sedation

15. Duration of Mechanical Ventilation 0 Days 7 0 20 40 60 80 100 Patients Successfully Extubated (%) 142128 SAT+SBT (n=167) Control (n=168) Girard TD, et al. Lancet 2008;371:126-34 Ventilator time reduced by 3 days

16. 0 Days 7 0 20 40 60 80 100 Patients Discharged from the ICU (%) 142128 SAT+SBT (n=167) Control (n=168) p=.01 ICU Length of Stay Girard TD, et al. Lancet 2008;371:126-34

17. 0 Days 7 0 20 40 60 80 100 Patients Discharged from the Hospital (%) 142128 SAT+SBT (n=167) Control (n=168) p=.04 Hospital Length of Stay Girard TD, et al. Lancet 2008;371:126-34

18. Patients Alive (%) 0 0 20 40 60 80 100 60120180240300360 Days Control (n=168) SAT+SBT (n=167) One-Year Survival p=.01 NNT=7 Girard TD, et al. Lancet 2008;371:126-34

20. 80 60 40 20 0 0721285010014 Hospital Days Patients with Functional Independence (%) Early PT/OT (n=49) Control (n=55) p=.05 Schweickert WD, et al. Lancet 2009;373:1874-82 Return to Functional Independence

21. Outcome*Early PT/OTControlp Independent functional status at discharge, % 59%35%0.02 Barthel Index score at discharge 75 [7.5-95]55 [0-85]0.05 ICU-acquired paresis at discharge 31%49%0.09 Ventilator-free days 23.5 [7.4-25.6]21.1 [0-23.8]0.05 ICU delirium, days 2.0 [0-6.0]4.0 [2.0-7.0]0.03 ICU length of stay, days5.9 [4.5-13.2]7.9 [6.1-12.9]0.08 Hospital length of stay, days 13.5 [8.0-23.1]12.9 [8.9-19.8]0.93 In-hospital mortality18%25%0.53 *Median [IQR] or % Schweickert WD, et al. Lancet 2009;373:1874-82 Secondary Outcomes

22. 2 2 Delirium Diagnosis

23. ConsciousnessCognition

24. “a disturbance of consciousness that is accompanied by a change in cognition that cannot be better accounted for by a preexisting or evolving dementia” – American Psychiatric Association di-'lir-E-&m

25. 020406080100 Bergeron, ‘01 Skrobik, ‘04 Ouimet, ‘07 Pandharipande, ‘07 Ely, ‘01 McNicoll, ‘03 Ely, ‘04 McNicoll, ‘05 Micek, ‘05 Thomason, ‘05 Actual Prevalence of Delirium Medical ICUs (40%-80%) Mixed ICUs (10%-40%) Plaschke, ‘07 Pisani, ‘07 Lat, ‘09 Guenther, ‘09 Riker, ‘09 Girard, ‘08

26. Recognition of Delirium in the ICU Spronk PE, et al. Intensive Care Med 2009;35:1276-80 MDs recognized 28%RNs recognized 35%

27. 0 20 40 60 80 100 HypoactiveMixedHyperactive % Delirium Subtypes in the ICU Peterson JF, et al. J Am Geriatr Soc 2006;54:479-84

28. 1 2

29. Which diagnostic method? 41% - none 37% - clinical assessment 14% - Confusion Assessment Method-ICU 2% - Delirium Rating Scale 2% - Mini Mental State Examination 1% - Delirium Screening Checklist 14% - Confusion Assessment Method-ICU 01% - Delirium Screening Checklist Patel R, et al. Crit Care Med 2009;37:825-32

30. Feature 1 Feature 3 Feature 2 Feature 4 and and either or Ely EW, et al. JAMA 2001; 286:2703-10 Confusion Assessment Method-ICU Acute onset of changes or fluctuations in the course of mental status Acute onset of changes or fluctuations in the course of mental status Inattention Altered level of consciousness Altered level of consciousness Disorganized thinking

31. Bergeron N, et al. Intensive Care Med 2001; 27:1297-1304 Intensive Care Delirium Screening Checklist (ICDSC) Altered level of consciousness Inattentiveness Disorientation Hallucination-delusion-psychosis Psychomotor agitation or retardation Inappropriate speech or mood Sleep/wake cycle disturbance Symptom fluctuation ≥4 = delirium

32. Symptoms Rating (0, 1, or 2) Disorientation Inappropriate behavior Inappropriate communication Illusions/hallucinations Psychomotor retardation Total score Gaudreau JD, et al. J Pain Symptom Manage;29:368-75 Nursing Delirium Screening Scale (NuDESC) ≥2 = delirium

33. 0 20 40 60 80 100 CAM-ICU % Luetz A, et al. Crit Care Med 2010;38:409-18 Validity of ICU Delirium Assessment Tools Nu-DESCDDS ICDSC* Sensitivity Specificity *Van Eijk MM, et al. Crit Care Med 2009;37:1881-5

34. Brain Road Map 3. How did they get there? Drugs 1. Where is the patient going? Target RASS 2. Where is the patient now? Current RASS Current CAM-ICU © Brian Sloan via Flickr

35. 3 3 Delirium Management

37. Toxic Situations CHF, shock, dehydration CHF, shock, dehydration Deliriogenic medications Deliriogenic medications New organ failure, eg, liver, kidney New organ failure, eg, liver, kidney Hypoxemia Infection or Immobilization Nonpharmacologic efforts Hearing aids, eye glasses, reorientation, noise reduction, sleep, ambulation K+ or Electrolyte problems What to THINK When Delirium Is Present

38. Study Day Daily Dose of Benzodiazepines 123456789101112131415161718192021 0 10 20 30 40 50 60 70 ABC Trial - Benzodiazepines Control Protocol

39. 50 60 70 80 90 100 No Drug Lorazepam Dose (mg) Log scale Original scale 0-11-22-33-44+ 0-2.7 -7.4 -20 -5555+ Probability of Delirium (%) Pandharipande PP, et al. Anesthesiology 2006;104:21-6 Benzodiazepines and Delirium

40. Duration of Delirium ControlSAT+SBT 0 2 4 6 8 10 12 14 16 Days p=.50 Girard TD, et al. Lancet 2008;371:126-34

41. Effect of Wake Up and Breathe on Coma Girard TD, et al. Unpublished data from the ABC Trial.

42. Effect of Wake Up and Breathe on Delirium Girard TD, et al. Unpublished data from the ABC Trial.

44. Daily Risk of Delirium in MENDS Pandharipande PP, et al. Crit Care 2010;14:R38 p=0.02

45. Daily Risk of Delirium in SEDCOM p<0.001 Riker RR, et al. JAMA 2009;301:489-499

46. Which drug for delirium? 86% - haloperidol 37% - atypical antipsychotics 35% - benzodiazepines 13% - propofol 8% - opiates 5% - dexmedetomidine Patel R, et al. Crit Care Med 2009;37:825-32

48. Antipsychotics – Delirium and Coma 15101520 Day Patients without Delirium or Coma (%) 0 20 40 60 80 100 Girard TD, et al. Crit Care Med 2010;38:428-37 Haloperidol (n=35) Ziprasidone (n=32) Placebo (n=36) p=0.66

49. Quetiapine – Resolution of Delirium 024610 Day Patients with Delirium (%) 0 20 40 60 80 100 Devlin JW, et al. Crit Care Med 2010;38:419-27 Quetiapine (n=18) Placebo (n=18) 8 p=0.001

50. Reade MC, et al. Crit Care 2009;13:R75 Dexmedetomidine in Agitated Patients 0 20 40 60 80 100 Hours 0 268 Patients Intubated (%) p=.001 Dexmedetomidine Haloperidol

51. Modifying the Impact of ICU-Associated Neurological Dysfunction MIND-USA

52. Photo by Chris Hartlove for The New York Times Reduce immobility Promote consciousness

53. Outcome*Early PT/OTControlp Independent functional status at discharge, % 59%35%0.02 Barthel Index score at discharge 75 [7.5-95]55 [0-85]0.05 ICU-acquired paresis at discharge 31%49%0.09 Ventilator-free days 23.5 [7.4-25.6]21.1 [0-23.8]0.05 ICU delirium, days 2.0 [0-6.0]4.0 [2.0-7.0]0.03 ICU length of stay, days5.9 [4.5-13.2]7.9 [6.1-12.9]0.08 Hospital length of stay, days 13.5 [8.0-23.1]12.9 [8.9-19.8]0.93 In-hospital mortality18%25%0.53 *Median [IQR] or % Schweickert WD, et al. Lancet 2009;373:1874-82 Secondary Outcomes

54. Looking back 1.ABCDEs of critical care 2.Delirium diagnosis 3.Delirium management