2. Learning Objectives Describe current guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit Use validated scales to measure sedation, pain, agitation, and delirium in critically ill patients Compare the benefits and limitations of available sedatives and analgesics in the acute care, procedural, and surgical settings

3. Goals for Sedation and Analgesia Prevent pain and anxiety Decrease oxygen consumption Decrease the stress response Patient-ventilator synchrony Avoid adverse neurocognitive sequelae –Depression –PTSD –Dementia –Anxiety Rotondi AJ, et al. Crit Care Med. 2002;30:746-752. Weinert C. Curr Opin in Crit Care. 2005;11:376-380. Kress JP, et al. Am J Respir Crit Care Med. 1996;153:1012-1018.

4. American College of Critical Care Medicine Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Guideline focus –Prolonged sedation and analgesia –Patients older than 12 years –Patients during mechanical ventilation Assessment and treatment recommendations –Analgesia –Sedation –Delirium –Sleep Update expected in 2012 Jacobi J, et al. Crit Care Med. 2002;30:119-141.

5. American College of Critical Care Medicine (ACCM) Guidelines Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Pertains to patients older than 12 years during mechanical ventilation Areas of focus –Assessment for pain, delirium –Physiological monitoring –Pharmacologic tools Most recommendations rated as grade B or C Jacobi J, et al. Crit Care Med. 2002;30:119-141.

6. Assessing Pain: FACES Scale 0–10 Wong DL, et al. Wong’s Essentials of Pediatric Nursing. 6th ed. St. Louis, MO: Mosby, Inc; 2001. p.1301. Other Scales Behavioral Pain Scale (BPS) 3-12 –Payen JF, et al. Crit Care Med. 2001;29(12):2258-2263. Critical Care Pain Observation Tool 0-8 –Gélinas C, et al. Am J Crit Care. 2006;15:420-427.

7. Managing Pain in the ICU: Opioids Hormonal changes Withdrawal symptoms Tolerance Constipation Bradycardia Hypotension Sedation Respiratory depression Analgesia Adverse EffectsClinical Effects Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S105-120. Fentanyl Morphine Remifentanil

8. What Is the ABCDE Bundle? We Need Coordinated Care Many tasks and demands on critical care staff Great need to align and support the people, processes, and technology already in ICUs ABCDE bundle is multicomponent, interdependent, and designed to: –Improve clinical team collaboration –Standardize care processes –Break the cycle of oversedation and prolonged ventilation Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.

9. What Is the ABCDE Bundle? Awakening and Breathing Trial coordination Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobility Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233.

10. Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization ABCDE

11. ICU Sedation: The Balancing Act Oversedation Prolonged mechanical ventilation Increase length of stay Increased risk of complications - Ventilator-associated pneumonia Increased diagnostic testing Inability to evaluate for delirium Undersedation Patient recall Device removal Ineffectual mechanical ventilation Initiation of neuromuscular blockade Myocardial or cerebral ischemia Decreased family satisfaction w/ care Patient Comfort and Ventilatory Optimization GOALGOAL Jacobi J, et al. Crit Care Med. 2002;30:119-141.

12. Improper Sedation Continuous sedation carries the risks associated with oversedation and may increase the duration of mechanical ventilation (MV) 1 MV patients accrue significantly more cost during their ICU stay than non-MV patients 2 –$31,574 versus $12,931, P < 0.001 Sedation should be titrated to achieve a cooperative patient and daily wake-up, a JC requirement 1,2 1. Kress JP, et al. N Engl J Med. 2000;342:1471-1477. 2. Dasta JF, et al. Crit Care Med. 2005;33:1266-1271. 3. Kaplan LJ, Bailey H. Crit Care. 2000;4(suppl 1):P190. Undersedated 3 Oversedated On Target 15.4% 54.0% 30.6%

13. Assessing Agitation and Sedation Sedation-Agitation Scale (SAS) –Riker RR, et al. Crit Care Med. 1999;27:1325-1329. –Brandl K, et al. Pharmacotherapy. 2001;21:431-436. Richmond Agitation-Sedation Scale (RASS) –Sessler CN, et al. Am J Respir Crit Care Med. 2002;166(10):1338-1344. –Ely EW, et al. JAMA. 2003;289:2983-2991.

14. Systematic Implementation of Pain and Sedation Tools: Montpellier France P < 0.01 Significant Patient Characteristics/Metrics/Outcomes PrePostP-value Mechanical Ventilation, hrs* 120650.01 Duration CIVS, hrs*84480.03 Duration CIVI Opioid, hrs* 96600.02 Nosocomial infection† 17 (17)11 (8)< 0.05 *Data presented in median hrs; †Data presented as n (%) CIVS; Continuous intravenous infusion sedation Chanques G, et al. Crit Care Med. 2006;34(6):1691-1699. P < 0.01

15. Daily Sedation Interruption Decreases Duration of Mechanical Ventilation Hold sedation infusion until patient awake and then restart at 50% of the prior dose “Awake” defined as any 3 of the following: –Open eyes in response to voice –Use eyes to follow investigator on request –Squeeze hand on request –Stick out tongue on request Kress JP, et al. N Engl J Med. 2000;342:1471-1477. Fewer diagnostic tests to assess changes in mental status No increase in rate of agitated-related complications or episodes of patient-initiated device removal No increase in PTSD or cardiac ischemia

16. To determine the efficacy and safety of a protocol linking: spontaneous awakening trials (SATs) & spontaneous breathing trials (SBTs) –Ventilator-free days –Duration of mechanical ventilation –ICU and hospital length of stay –Duration of coma and delirium –Long-term neuropsychological outcomes ABC Trial: Objectives Girard TD, et al. Lancet. 2008;371:126-134.

17. ABC Trial: Main Outcomes Outcome*SBTSAT+SBTP-value Ventilator-free days 12150.02 Time-to-Event, days Successful extubation, days 7.050.05 ICU discharge, days 1390.02 Hospital discharge, days 19150.04 Death at 1 year, n (%) 97 (58%)74 (44%)0.01 Days of brain dysfunction Coma 3.02.00.002 Delirium 2.0 0.50 * Median, except as noted Girard TD, et al. Lancet. 2008;371:126-134.

18. ABC Trial: 1 Year Mortality Girard TD, et al. Lancet. 2008;371:126-134.

19. Despite Proven Benefits of Spontaneous Awakening/Daily Interruption Trials, They Are Not Standard of Practice at Most Institutions Canada – 40% get SATs (273 physicians in 2005) 1 US – 40% get SATs (2004-05) 2 Germany – 34% get SATs (214 ICUs in 2006) 3 France – 40–50% deeply sedated with 90% on continuous infusion of sedative/opiate 4 1. Mehta S, et al. Crit Care Med. 2006;34:374-380. 2. Devlin J. Crit Care Med. 2006;34:556-557. 3. Martin J, et al. Crit Care. 2007;11:R124. 4. Payen JF, et al. Anesthesiology. 2007;106:687-695.

20. Number of respondents (%) Barriers to Daily Sedation Interruption (Survey of 904 SCCM members) Clinicians preferring propofol were more likely use daily interruption than those preferring benzodiazepines (55% vs 40%, P < 0.0001) Tanios MA, et al. J Crit Care. 2009;24:66-73. 010203040506070 Leads to PTSD Leads to cardiac ischemia No benefit Difficult to coordinate with nurse Leads to respiratory compromise Compromises patient comfort Poor nursing acceptance Increased device removal #1 Barrier #2 Barrier #3 Barrier

21. Awakening and Breathing (AB) Safety Screens Breathing Trial No active agitation Oxygen saturation ≥ 88% FiO 2 ≤ 50% PEEP ≤ 8 cm H 2 O No myocardial ischemia (24h) Normal intracranial pressure No significant vasopressor or inotrope use Girard TD, et al. Lancet. 2008;371(9607):126-134. Awakening Trial No active seizures No active alcohol withdrawal No active agitation No active paralytic use No myocardial ischemia (24h) Normal intracranial pressure

22. Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization ABCDE

23. Characteristics of an Ideal Sedative Rapid onset of action allows rapid recovery after discontinuation Effective at providing adequate sedation with predictable dose response Easy to administer Lack of drug accumulation Few adverse effects Minimal adverse interactions with other drugs Cost-effective Promotes natural sleep Ostermann ME, et al. JAMA. 2000;283:1451-1459. Jacobi J, et al. Crit Care Med. 2002;30:119-141. Dasta JF, et al. Pharmacother. 2006;26:798-805. Nelson LE, et al. Anesthesiol. 2003;98:428-436.

24. Consider Patient Comorbidities When Choosing a Sedation Regimen Chronic pain Organ dysfunction CV instability Substance withdrawal Respiratory insufficiency Obesity Obstructive sleep apnea

25. GABA Agonist Benzodiazepine Midazolam May accumulate with hepatic and/or renal failure Anterograde amnesia Long recovery time Synergy with opioids Respiratory depression Delirium Sedation, anxiolysis, and amnesia Rapid onset of action (IV) Adverse EffectsClinical Effects Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360. Riker RR, et al; SEDCOM Study Group. JAMA. 2009;301(5):489-499.

26. Clinical Effects Sedation, anxiolysis, and amnesia Commonly used for long- term sedation Adverse Effects Metabolic acidosis (propylene glycol vehicle toxicity) Retrograde and anterograde amnesia Delirium GABA Agonist Benzodiazepine Lorazepam Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):335-360. Wilson KC, et al. Chest. 2005;128(3):1674-1681.

27. GABA Agonist Propofol Sedation Hypnosis Anxiolysis Muscle relaxation Mild bronchodilation Decreased ICP Decreased cerebral metabolic rate Antiemetic Ellett ML. Gastroenterol Nurs. 2010;33(4):284-925. Lundström S, et al. J Pain Symptom Manage. 2010;40(3):466-470. Clinical Effects Adverse Effects Pain on injection Respiratory depression Hypotension Decreased myocardial contractility Increased serum triglycerides Tolerance Propofol infusion syndrome Prolonged effect with high adiposity Seizures (rare)

28.   Agonist Clonidine Bradycardia Dry mouth Hypotension Sedation Antihypertensive Analgesia Sedation Decrease sympathetic activity Decreased shivering Adverse EffectsClinical Effects Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349. Bergendahl H, et al. Curr Opin Anaesthesiol. 2005;18(6):608-613. Hossmann V, et al. Clin Pharmacol Ther. 1980;28(2):167-176.

29.   Agonist Dexmedetomidine Hypotension Hypertension Nausea Bradycardia Dry mouth Peripheral vasoconstriction at high doses Antihypertensive Sedation Analgesia Decreased shivering Anxiolysis Patient arousability Potentiate effects of opioids, sedatives, and anesthetics Decrease sympathetic activity Adverse Effects Clinical Effects Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349. Bhana N, et al. Drugs. 2000;59(2):263-268.

30. Comparison of Clinical Effects 1. Blanchard AR. Postgrad Med. 2002;111:59-74. 2. Kamibayashi T, et al. Anesthesiol. 2000;95:1345-1349. 3. Maze M, et al. Anesthetic Pharmacology: Physiologic Principles and Clinical Practice. Churchill Livingstone; 2004. 4. Maze M, et al. Crit Care Clin. 2001;17:881-897. XX Alleviate anxiety 1,2 XX Control delirium 1-4 X Facilitate ventilation during weaning 2-4 X Promote arousability during sedation 2-4 XX Analgesic properties 1-4 XXXXX Sedation Haloperidol  2 Agonists OpioidsPropofolBenzodiazepines X

31. Comparison of Adverse Effects 1. Harvey MA. Am J Crit Care. 1996;5:7-18. 2. Aantaa R, et al. Drugs of the Future. 1993;18:49-56. 3. Maze M, et al. Crit Care Clin. 2001;17:881-897. XXX Respiratory depression 1 XXfentanyl Bradycardia 1 morphine Tachycardia 1 X X X Deliriogenic X Constipation 1 XXXXX Hypotension 1-3 X *XX Prolonged weaning 1 HaloperidolOpioidsPropofolBenzodiazepines *Excluding remifentanil X  2 Agonists

32. Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) Double-blind RCT of dexmedetomidine vs lorazepam 103 patients (2 centers) –70% MICU, 30% SICU patients (requiring mechanical ventilation > 24 hours) –Primary outcome: days alive without delirium or coma Intervention –Dexmedetomidine 0.15–1.5 mcg/kg/hr –Lorazepam infusion 1–10 mg/hr –Titrated to sedation goal (using RASS) established by ICU team No daily interruption Pandharipande PP, et al. JAMA. 2007;298:2644-2653.

33. MENDS: Dexmedetomidine vs Lorazepam Pandharipande PP, et al. JAMA. 2007;298:2644-2653. Dexmedetomidine resulted in more days alive without delirium or coma (P = 0.01) and a lower prevalence of coma (P < 0.001) than lorazepam Dexmedetomidine resulted in more time spent within sedation goals than lorazepam (P = 0.04) Differences in 28-day mortality and delirium-free days were not significant Days Lorazepam n = 51 Dexmedetomidine n = 52 0 2 4 6 8 10 12 P = 0.011 Delirium/Coma-Free Days Delirium-Free Days P = 0.086P < 0.001 Coma-Free Days

34. MENDS Delirium: All Patients Pandharipande PP, et al. Crit Care. 2010;14:R38.

35. Outcome Midazolam (n = 122) Dexmedetomidine (n = 244) P- Value Time in target sedation range, % (primary EP)75.177.30.18 Duration of sedation, days4.13.50.01 Time to extubation, days5.63.70.01 Delirium prevalence93 (76.6%)132 (54%)0.001 Delirium-free days1.72.50.002 Patients receiving open-label midazolam60 (49%)153 (63%)0.02 Double-blind, randomized, multicenter trial comparing long-term (> 24 hr) dexmedetomidine (dex, n = 244) with midazolam (mz, n = 122) Sedatives (dex 0.2-1.4 μg/kg/hr or mz 0.02-0.1 mg/kg/hr) titrated for light sedation (RASS -2 to +1), administered up to 30 days All patients underwent daily arousal assessments and drug titration Q 4 hours Riker RR, et al. JAMA. 2009;301:489-499. SEDCOM: Dexmedetomidine vs Midazolam

36. Midazolam Dexmedetomidine Dexmedetomidine versus Midazolam, P < 0.001 Reduced Delirium Prevalence with Dexmedetomidine vs Midazolam SEDCOM Sample Size 118 229109 20692 17577 13457 9242 6044 34 Treatment Day 0 20 40 60 80 100 Baseline123456 Patients With Delirium, % Riker RR, et al. JAMA. 2009;301:489-499.

37. SEDCOM Trial: Safety Outcomes Outcome Midazolam (n = 122) Dexmedetomidine (n = 244) P- Value Bradycardia18.9%42.2%0.001 Tachycardia44.3%25.4% 0.001 Hypertension requiring intervention29.5%18.9%0.02 Hyperglycemia42.6%56.6%0.02 Infections19.7%10.2%0.02 Riker RR, et al. JAMA. 2009;301:489-499. Bradycardia needing treatment 0.8% 4.9% 0.07

38. MIDEX and PRODEX Trials Jakob SM, et al. JAMA. 2012;307(11):1151-1160. 2 phase 3 multicenter RCTs Dexmedetomidine vs midazolam (MDZ) or propofol ~ 250 patients per arm, MV > 24 hours Daily interruption of sedation, SBT Arm Time at RASS Target Median MV, h ICU LOS, h Arousability (total VAS) Hypo tension Brady cardia MIDEX MDZ56.6%16424330.011.6%5.2 Dex60.7%12321149.720.6%14.2 P-value0.150.03< 0.0010.007< 0.001 PRODEX Propofol64.7%11818540.113.4%10.1% Dex64.6%9716451.313.0%13% P-value0.970.24< 0.001

39. Analgosedation Analgesic first (A-1), supplement with sedative Acknowledges that discomfort may cause agitation Remifentanil-based regimen –Reduces propofol use –Reduces median MV time –Improves sedation-agitation scores Not appropriate for drug or alcohol withdrawal Park G, et al. Br J Anaesth. 2007;98:76-82. Rozendaal FW, et al. Intensive Care Med. 2009;35:291-298.

40. Analgosedation 140 critically ill adult patients undergoing mechanical ventilation in single center Randomized, open-label trial –Both groups received bolus morphine (2.5 or 5 mg) –Group 1: No sedation (n = 70 patients) - morphine prn –Group 2: Sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n = 70, control group) Endpoints –Primary  Number of days without mechanical ventilation in a 28-day period –Other  Length of stay in ICU (admission to 28 days)  Length of stay in hospital (admission to 90 days) Strøm T, et al. Lancet. 2010;375:475-480.

41. Analgosedation Results Patients receiving no sedation had –More days without ventilation (13.8 vs 9.6 days, P = 0.02) –Shorter stay in ICU (HR 1.86, P = 0.03) –Shorter stay in hospital (HR 3.57, P = 0.004) –More agitated delirium (N = 11, 20% vs N = 4, 7%, P = 0.04) No differences found in –Accidental extubations –Need for CT or MRI –Ventilator-associated pneumonia Strøm T, et al. Lancet. 2010;375:475-480.

42. Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization ABCDE

43. Morandi A, et al. Intensive Care Med. 2008;34:1907-1915. Cardinal Symptoms of Delirium and Coma

44. ICU Delirium Vasilevskis EE, et al. Chest. 2010;138(5):1224-1233. Develops in ~2/3 of critically ill patients Hypoactive or mixed forms most common Increased risk –Benzodiazepines –Extended ventilation –Immobility Associated with weakness Undiagnosed in up to 72% of cases

45. Patient Factors Increased age Alcohol use Male gender Living alone Smoking Renal disease Environment Admission via ED or through transfer Isolation No clock No daylight No visitors Noise Physical restraints Predisposing Disease Cardiac disease Cognitive impairment (eg, dementia) Pulmonary disease Acute Illness Length of stay Fever Medicine service Lack of nutrition Hypotension Sepsis Metabolic disorders Tubes/catheters Medications: - Anticholinergics - Corticosteroids - Benzodiazepines Less Modifiable More Modifiable DELIRIUM Van Rompaey B, et al. Crit Care. 2009;13:R77. Inouye SK, et al. JAMA.1996;275:852-857. Skrobik Y. Crit Care Clin. 2009;25:585-591.

46. Mechanisms for Delirium in the Critically Ill Are Numerous and Not Clearly Understood Maldonado JR. Crit Care Clin. 2008;24(4):789-856. Pandharipande PP. Intensive Care Med. 2009;35(11):1886-1892. Adams-Wilson JR, et al. Crit Care Med. 2012 (in press) Neurotransmitter imbalance Neuroinflammation Blood brain barrier permeability Impaired oxidative metabolism Microglial activation Abnormal levels of large neutral amino acids (eg, tryptophan) and their metabolism (eg, kynurenine pathway)

47. After Hospital Discharge During the ICU/Hospital Stay Sequelae of Delirium Increased mortality Longer intubation time Average 10 additional days in hospital Higher costs of care Increased mortality Development of dementia Long-term cognitive impairment Requirement for care in chronic care facility Decreased functional status at 6 months Bruno JJ, Warren ML. Crit Care Nurs Clin North Am. 2010;22(2):161-178. Shehabi Y, et al. Crit Care Med. 2010;38(12):2311-2318. Rockwood K, et al. Age Ageing. 1999;28(6):551-556. Jackson JC, et al. Neuropsychol Rev. 2004;14:87-98. Nelson JE, et al. Arch Intern Med. 2006;166:1993-1999.

48. Delirium Duration and Mortality Pisani MA. Am J Respir Crit Care Med. 2009;180:1092-1097. Kaplan-Meier Survival Curve Each day of delirium in the ICU increases the hazard of mortality by 10% P < 0.001

49. Worse Long-term Cognitive Performance Duration of delirium was an independent predictor of cognitive impairment –An increase from 1 day of delirium to 5 days was associated with nearly a 5-point decline in cognitive battery scores Patient testimony “One quite literally loses one’s grip on what is true and what is false because the true and the false are mixed together in a mess of experience.” Girard TD, et al. Crit Care Med. 2010;38:1513-1520. Misak CJ. Am J Respir Crit Care Med. 2004;170(4):357-359.

50. Risk Factors Specific for ICU Delirium Benzodiazepine use 4,10 Coma (medical vs. pharmacologic) 4,9 Morphine use ( ?data unclear ) 1.Pisani MA, et al. Crit Care Med. 2009;37:177-183 2.Pisani MA, et al. Arch Intern Med. 2007;167:1629-1634. 3.Van Rompaey B, et al. Crit Care. 2009;13:R77. 4.Ouimet S, et al. Intensive Care Med. 2007;33:66-73. 5.Dubois MJ, et al. Intensive Care Med. 2001;27:1297-1304. 6.Pandharipande PP, et al. Anesthesiology. 2006;104:21-26. 7.Pisani MA, et al. Crit Care Med. 2009;37:177-183. 8.Pandharipande PP, et al. Intensive Care Med. 2009;35:1886-1892. 9.Ely EW, et al. Crit Care Med. 2007;35:112-117. 10.Pandharipande PP, et al. J Trauma. 2008;65:34-41. Dementia 1,2,3 Hypertension history 4,5 Alcoholism 3,4 Severity of illness 1,4,6,7,8 Age (?pos 6,8 /neg 2,3,4,9 )

51. Delirium After Stroke Shi Q, et al. Stroke. 2012;43(3):645-649. Increased 12-month mortality risk Stroke patients +/- delirium Will delirium treatment change outcome?

52. Delirium Assessment Tools Confusion Assessment Method for the ICU (CAM- ICU) –Ely EW, et al. Crit Care Med. 2001;29:1370-1379. –Ely EW, et al. JAMA. 2001;286:2703-2710. Intensive Care Delirium Screening Checklist (ICDSC) –Bergeron N, et al. Intensive Care Med. 2001;27:859-864. –Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013.

53. Confusion Assessment Method (CAM-ICU) or 3. Altered level of consciousness 4. Disorganized thinking = Delirium Ely EW, et al. Crit Care Med. 2001;29:1370-1379. Ely EW, et al. JAMA. 2001;286:2703-2710. 1. Acute onset of mental status changes or a fluctuating course 2. Inattention and

54. Intensive Care Delirium Screening Checklist 1. Altered level of consciousness 2. Inattention 3. Disorientation 4. Hallucinations 5. Psychomotor agitation or retardation 6. Inappropriate speech 7. Sleep/wake cycle disturbances 8. Symptom fluctuation Bergeron N, et al. Intensive Care Med. 2001;27:859-864. Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013. Score 1 point for each component present during shift Score of 1-3 = Subsyndromal Delirium Score of ≥ 4 = Delirium

55. Pediatric CAM-ICU Smith HA, et al. Crit Care Med. 2011;39(1):150-157. 146 paired assessments Mean age = 12.2 years 2 critical care clinicians vs. pediatric psychiatrist Sensitivity = 83% (95% CI, 66-93%) Specificity = 99% (95% CI, 95-100%) Inter-rater reliability κ = 0.96

56. Predicting Delirium in the ICU PRE-DELIRIC Development of model –1613 ICU patients –Delirium defined as +CAM-ICU or haloperidol use –10 variables Age APACHE-II score Admission group Coma Infection Validation of model –549 ICU patients –Area under ROC PRE-DELIRIC0.85 Nurses 0.59 Physicians 0.59 Metabolic acidosis Use of sedatives Use of morphine Urea concentration Urgent admission van den Boogaard M, et al. BMJ. 2012;344:e420. Sensitivity 1 - Specificity Pooled ROC

57. Delirium Assessment Implementation Strategies Case-based scenarios 1 –Before-and-after case studies –This strategy increased usage of the ICDSC by 70% and accuracy of assessment by 54% –http://www.biomedcentral.com/content/supple mentary/cc6793-S2.doc Spot-checking 2,3 –Systematically uses expert raters –Identifies areas for fine tuning education 1. Devlin JW, et al. Crit Care. 2008;12(1):R19. 2. Pun BT, et al. Crit Care Med. 2005;33(6):1199-1205. 3. Soja SL, et al. Intensive Care Med. 2008;34(7):1263-1268.

58. Helpful Approach to Delirium Management 1.Stop 2.THINK 3.Lastly medicate

59. Stop and THINK Do any meds need to be stopped or lowered? Especially consider sedatives Is patient on minimal amount necessary? –Daily sedation cessation –Targeted sedation plan Do sedatives need to be changed? T oxic Situations CHF, shock, dehydration Deliriogenic meds (tight titration) New organ failure (liver/kidney) H ypoxemia I nfection/sepsis (nosocomial) I mmobilization N onpharm interventions Hearing aids, glasses, reorient, sleep protocols, music, noise control, ambulation K + or electrolyte problems

60. Delirium Nonpharmacologic Interventions Early mobility – the only nonpharmacologic intervention shown to reduce ICU delirium 1 Other interventions: –Environmental changes (eg, noise reduction) –Sensory aids (eg, hearing aids, glasses) –Reorientation and stimulation –Sleep preservation and enhancement Schweickert WD, et al. Lancet. 2009;373:1874-1882.

61. Sleep Abnormalities in the ICU More time in light sleep Less time in deep sleep More sleep fragmentation Friese R. Crit Care Med. 2008;36:697-705. Weinhouse GL, Watson PL. Crit Care Clin. 2009;25:539-549. There is little evidence that sedatives in the ICU restore normal sleep

62. Boosting Sleep Quality in ICU Optimize environmental strategies –Day/night variation, reduce night interruptions, noise reduction Avoid benzodiazepines (↓ SWS & REM) Consider dexmedetomidine (↑ SWS) GABA receptor agonists (eg, zolpidem) Sedating antidepressants (eg, trazodone) or antipsychotics Melatonin –Pilot: may improve sleep quality of ICU COPD patients Weinhouse GL, Watson PL. Crit Care Clinics. 2009;25:539-549. Faulhaber J, et al. Psychopharmacology. 1997;130:285-291. Shilo L, et al. Chronobiol Int. 2000;17:71-76.

63. Effect of Common Sedatives and Analgesics on Sleep There is little evidence that administration of sedatives in the ICU achieves the restorative function of normal sleep Benzodiazepines ↑ Stage 2 NREM ↓ Slow wave sleep (SWS) and REM Propofol ↑ Total sleep time without enhancing REM ↓ SWS Analgesics Abnormal sleep architecture Dexmedetomidine ↑ SWS Weinhouse GL, et al. Sleep. 2006;29:707-716. Nelson LE, et al. Anesthesiology. 2003;98:428-436.

64. Differences in BOLD activities/NREM sleep (fMRI) Contribution of Sedative-Hypnotic Agents to Delirium Via Modulation of the Sleep Pathway Sanders RD, Maze M. Can J Anesth. 2011;58:149-156.

65. A Multicomponent Intervention to Prevent Delirium in Hospitalized Older (Non-ICU) Patients 852 patients ≥ 70 years old on general medicine service, no delirium at time of admission Intervention –Standardized protocol for management of 6 delirium risk factors (n = 426) Usual care –Standard hospital services (n = 426) Primary Outcome –Delirium incidence and prevalence Inouye SK, et al. N Engl J Med. 1999;340:669-676.

66. Elder Life Program Targeted Risk FactorStandardized Intervention Cognitive impairment Orientation & therapeutic activity protocol (discuss current events, word games, reorient, etc) Sleep deprivation Sleep enhancement & nonpharm sleep protocol (noise reduction, back massages, schedule adjustment) Immobility Early mobilization protocol (active ROM, reduce restraint use, ambulation, remove catheters) Visual impairment Vision protocol (glasses, adaptive equipment, reinforce use) Hearing impairment Hearing protocol (amplification devices, hearing aids, earwax disimpaction) Dehydration Dehydration protocol (early recognition of dehydration & volume repletion) Inouye SK, et al. N Engl J Med. 1999;340:669-676.

67. Results OutcomeInterventionControlP-value Incidence of delirium, N (%)42 (9.9)64 (15)0.02 Total days of delirium1051610.02 Episodes of delirium62900.03 ↓ delirium incidence in patients with intermediate baseline risk Improved orientation score with targeted intervention (P = 0.04) Reduced rate of sedative use for sleep (P = 0.001) 87% overall adherence to protocol Inouye SK, et al. N Engl J Med. 1999;340:669-676.

68. Survey: First-Choice Delirium Treatment Options % Delirium should always be managed with a medication: 85% Use ≥ 2 medications to treat delirium: 68% Characteristics of Haloperidol Use (always or frequently) Oral: 23%; IV 93% As needed: 93%; Scheduled: 61%; Infusion: 0% ≤ 4 mg/d: 47%; 5-10 mg/d: 56%; 11-20 mg/d: 38%; ≥ 21 mg/d: 9% Devlin JW, et al. Ann Pharmacother. 2011;45(10):1217-1229. Haloperidol Atypical Antipsychotic Benzodiazepine Dexmedetomidine

69. Dopamine Antagonist Haloperidol Adverse CV effects include QT interval prolongation Extrapyramidal symptoms, neuroleptic malignant syndrome (rare) 1 Does not cause respiratory depression 1 Dysphoria 2 Hypnotic agent with antipsychotic properties 1 Adverse EffectsClinical Effects 1. Harvey MA. Am J Crit Care. 1996;5:7-16. 2. Crippen DW. Crit Care Clin. 1990;6:369-392. –For treatment of delirium in critically ill adults 1 Metabolism altered by drug-drug interactions 2

70. But…Use of Haloperidol Is an Independent Predictor for Prolonged Delirium Pisani MA, et al. Crit Care Med. 2009;37:177-183.

71. Atypical Antipsychotics Receptor adherence is variable between agents Use has increased substantially Possible safety benefits –Decreased extrapyramidal effects –Little effect on the QTc interval (except ziprasidone) –Less hypotension/fewer orthostatic effects –Less likely to cause neuroleptic malignant syndrome Possible limitations –No IV formulations available –Little published experience in ICU patients –Troublesome reports of adverse events but most associated with prolonged use in non-delirium patients Devlin JW, et al. Harv Rev Psychiatry. 2011;19:59-67.

72. Use of Atypical Antipsychotic Therapy Is Increasing Ely EW, et al. Crit Care Med. 2004;32:106-112. Patel RP, et al. Crit Care Med. 2009;37:825-832. 0 10 20 30 40 50 60 70 80 90 Atypical Antipsychotics Benzodiazepines Haloperidol Propofol 2001 2007 Respondents, %

73. The MIND Study Modifying the INcidence of Delirium (MIND) Randomized and double-blind Multisite (6 centers) 103 MV patients PO/IM delivery of study drug Doses –Haloperidol 5-20 mg –Ziprasidone 40-160 mg HaloperidolZiprasidonePlacebo Girard TD, et al. Crit Care Med. 2010;38(2):428-437. n = 35n = 32n = 36

74. MIND Study Results Outcome* Haloperidol (n = 35) Ziprasidone (n = 32) Placebo (n = 36)P Delirium/coma-free days 14 [6-18]15 [9-18]13 [2-17]0.65 Ventilator-free days 8 [0-15]12 [0-19]12 [0-23]0.33 Length of stay ICU12 [5-16]10 [4-15]8 [5-13]0.70 Hospital14 [10-NA † ] 16 [9-NA † ]0.67 Mortality, %1112170.80 Extrapyramidal side effects Daily EPS score0 [0-0.2]0 [0-0] 0.56 Cognition at discharge Mean T-score27 [25-31]28 [24-35]33 [23-36]0.50 *Median [interquartile range] except as noted Girard TD, et al. Crit Care Med. 2010;38(2):428-437.

75. Prophylactic Haloperidol RCT of short-term low-dose IV haloperidol Patients –N = 457 –Age > 65 years –ICU after noncardiac surgery Intervention –Haloperidol  0.5 mg IV bolus then  Infusion 0.1 mg/h for 12 hrs –Placebo Primary endpoint –Incidence of delirium within the first 7 days after surgery Wang W, et al. Crit Care Med. 2012;40(3):731-739.

76. Prophylactic Haloperidol Wang W, et al. Crit Care Med. 2012;40(3):731-739. Haloperidol (n = 229) Placebo (n = 229) P-value 7 day delirium incidence (%) 15.323.20.031 Mean time to delirium onset (days) 6.25.70.021 Mean time delirium-free (days) 6.86.70.027 Median ICU LOS (hours) 21.323.00.024 All-cause 28-day mortality (%) 0.92.60.175

77. Quetiapine vs. Placebo Randomized, double-blind, placebo-controlled Multisite (3 centers) 36 ICU patients PO delivery of study drug Quetiapine dose: 50-200 mg q12h Primary outcome: time to first resolution of delirium (ie, first 12-hour period when ICDSC ≤ 3) Quetiapine (n = 18)Placebo (n = 18) Delirium + Haloperidol PRN Devlin JW, et al. Crit Care Med. 2010;38(2):419-427.

78. Placebo Quetiapine Proportion of Patients with Delirium Day During Study Drug Administration Log-Rank P = 0.001 Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation. Devlin JW, et al. Crit Care Med. 2010;38:419-427. Patients with First Resolution of Delirium

79. Impact of Quetiapine on the Resolution of Individual Delirium Symptoms Median ICDSC and individual delirium symptoms similar at study baseline QuetiapinePlaceboP value Median time to symptom resolution Log rank Inattention3 hrs8 hrs0.10 Disorientation2 hrs10 hrs0.10 Symptom fluctuation 4 hrs14 hrs0.004 Agitation5 hrs1 hrs0.04 Time with each symptom [median (IQR)] Comparison of Proportions Inattention47 (0-67)%78 (43-100)%0.02 Hallucinations0 (0-17)%28 (0-43)%0.10 Symptom fluctuation 47 (19-67)%89 (33-100)%0.04 Devlin JW, et al. Crit Care. 2011;15(5):R215.

80. http://www.accessdata.fda.gov. Accessed March 2012. Van Eijk MM, et al. Lancet. 2010;376(9755):1829-1837. Rivastigmine for Delirium? FDA approved for dementia of Alzheimer’s or Parkinson’s Cholinesterase inhibitor Result −Mortality (vs placebo): 22% vs 8%, P = 0.07 −Delirium (vs placebo): 5 vs 3 days, P = 0.06 Conclusion: −Need RCTs for delirium as endpoint −Don’t use rivastigmine for ICU delirium Time (days after inclusion) Survival (%)

81. Impact of Pain-Sedation-Delirium Protocol on Subsyndromal Delirium P = 0.009 P < 0.001 P = 0.01 Significant Patient Characteristics/Metrics/Outcomes ProtocolPREP-value Delirium † (34.2)(34.7)0.9 Subsyndromal Delirium † (24.6)(33)0.009 Lorazepam equivalents, mg* 2.75 ± 7.94 5.79 ± 31.78 0.02 MSO4 equivalents, mg* 22.3 ± 40.1 103.5 ± 239.2 < 0.001 *Data presented in mean; † Data presented as n (%) Subsyndromal delirium; max ICDSC 1-2 in ICU Skrobik Y, et al. Anesth Analg. 2010;111(2):451-463.

82. Before Considering a Pharmacologic Treatment for Delirium… Does your patient have delirium? –Assessed with scale? Which type of delirium? –Hyperactive –Hypoactive –Mixed hyperactive-hypoactive Have the underlying causes of delirium been identified and reversed/treated? Have non-pharmacologic strategies been optimized? Inouye SK, et al. N Engl J Med. 1999;340:669-676.

83. Antipsychotics. http://www.canhr.org/ToxicGuide/Media/Articles/FDA%20Alert%20on%20Antipsychotics.pdf. Accessed March 2012. Antipsychotic Therapy Rule Out Dementia Antipsychotic drugs are not approved for the treatment of dementia-related psychosis –No drug is approved for dementia-related psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death Physicians considering antipsychotics for elderly patients with dementia-related psychosis should discuss this increased risk of mortality with their patients, patients’ families, and caregivers

84. Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization ABCDE

85. Early Mobilization Patient Selection Inclusion criteria −Medical ICU −Adults (≥ 18 years of age) −On MV < 72 h, expected to continue for at least 24 h −Met criteria for baseline functional independence (Barthel Index score ≥ 70) Exclusion criteria −Rapidly developing  Neuromuscular disease  Cardiopulmonary arrest  Irreversible disorders with estimated 6-month mortality > 50%  Raised intracranial pressure  Absent limbs  Enrolment in another trial Schweickert WD, et al. Lancet. 2009;373:1874-1882.

86. Early Mobilization Trial Design 104 sedated patients with daily interruption –Early exercise and mobilization (PT & OT; intervention; n = 49) –PT & OT as ordered by the primary care team (control; n = 55) Primary endpoint: number of patients returning to independent functional status at hospital discharge –Ability to perform 6 activities of daily living –Ability to walk independently Assessors blinded to treatment assignment Secondary endpoints –Duration of delirium during first 28 days of hospital stay –Ventilator-free days during first 28 days of hospital stay Schweickert WD, et al. Lancet. 2009;373:1874-1882.

87. Perform Safety Screen First Schweickert WD, et al. Lancet. 2009;373:1874-1882. PassFail Exercise/Mobility Therapy Too Ill for Exercise/Mobility *Range of motion may be started in comatose patients, but not considered Early Exercise/Mobility

88. Early Mobilization Protocol: Result Schweickert WD, et al. Lancet. 2009;373:1874-1882. Return to independent functional status at discharge –59% in intervention group –35% in control group (P = 0.02)

89. Early PT and OT in Mechanically Ventilated ICU Patients Schweickert WD, et al. Lancet. 2009;373(9678):1874-1882. P = 0.02 P = 0.08 P = 0.02 P = 0.93 All Patients

90. Protocol for Early Mobility Therapy Acute Respiratory Failure Patients Morris PE, et al. Crit Care Med. 2008;36(8):2238-2243.

91. Early Mobility Therapy Results Morris PE, et al. Crit Care Med. 2008;36(8):2238-2243. Usual Care* (n = 135) Protocol* (n = 145) P-Value Days to first out of bed 11.35.00.001 Ventilator days 10.28.80.163 ICU LOS days 6.95.50.025 Hospital LOS days 14.511.20.006 Primary Endpoint: more protocol patients received PT than did usual care (80% vs. 47%, P ≤ 0.001) *Values adjusted for BMI, Acute Physiology and Chronic Health Evaluation II, and vasopressors

92. Early Mobility Resources Agency for Healthcare Research and Quality (AHRQ) website has a description of LDS Hospital’s (Salt Lake City, UT) Early Mobility Program implementation process. Helpful points on how to get started: –http://www.innovations.ahrq.gov/content.aspx?id=2442 Overview of the implementation of a Early Mobility Quality Improvement Program in the ICUs at Johns Hopkins University in Baltimore, MD –Needham DM, Korupolu R. Rehabilitation Quality Improvement in an Intensive Care Unit Setting: Implementation of a Quality Improvement Model. Top Stroke Rehabil. 2010;17(4):271-281. This video highlights the patient’s perspective; watch the patient ambulating in the ICU while mechanically ventilated –http://www.youtube.com/watch?v=0jycOFVE624 (Full version: 9 minutes) –http://www.youtube.com/watch?feature=player_detailpage&v=aobZTnhMK1g (Shorter version: 2 minutes) Dale Needham, MD, PhD, talks about the Early Mobility Program at Johns Hopkins University (2.5 minutes) –http://www.youtube.com/watch?v=D53gygWRhLM

93. Morandi A, et al. Curr Opin Crit Care. 2011;17:43-49. Benefits of ABCDE Protocol

94. Ely EW, et al. N Engl J Med. 1996;335(25):1864-1869. Kress JP, et al. N Engl J Med. 2000;342(20):1471-1477. Girard TD, et al. Lancet. 2008;371(9607):126-134. Strøm T, et al. Lancet. 2010;375(9713):475-480. Pandharipande PP, et al. JAMA. 2007;298(22):2644-2653. Riker RR, et al. JAMA. 2009;301(5):489-499. Schweickert WD, et al. Lancet. 2009;373(9678):1874-1882. Liberation and Animation Summary of RCT Literature SBT SAT Remove (A+B) Remove Sedation Sedation Choice Early Mobility

95. Post-Intensive Care Syndrome SCCM Task Force on Long-Term Outcomes “Post-intensive care syndrome (PICS) was agreed upon as the recommended term to describe new or worsening problems in physical, cognitive, or mental health status arising after a critical illness and persisting beyond acute care hospitalization. The term could be applied to either a survivor or family member- PICS-F.” Needham DM, et al. Crit Care Med. 2012;40(2):502-509.

96. Post Intensive Care Syndrome (PICS) Family (PICS-F) Mental Health Anxiety/ASD PTSD Depression Complicated Grief Survivor (PICS) Mental Health Anxiety/ASD PTSD Depression Cognitive Impairments Executive Function Memory Attention Physical Impairments Pulmonary Neuromuscular Physical Function Needham DM, et al. Crit Care Med. 2012;40(2):502-509. Desai SV, et al. Crit Care Med. 2011;39(2):371-379. Davidson JE, et al. Crit Care Med. 2012;40(2):618-624. PICS Consequences

97. PICS Checklist: Have We…. Limited sedation? Changed goals from "arouseable" to "cognitively engaged“ Promoted early physical and cognitive activity to engage the brain? Treated pain first and used benzodiazepines only when necessary? Limited drugs that block memory (exception: AWS)? Assessed and treated pts with alcohol dependency? Encouraged family involvement (for both the health of the pt and the family)? Performed a thorough medication reconciliation?

98. Communicated with the pt and family to support psychological well- being? Offered pt care conferences when indicated? Translated/interpreted when indicated? Maintained glycemic control without causing hypoglycemia? Encouraged uninterrupted sleep at night and for at least 2 hours in the afternoon? Assured that the pt who has dentures and glasses wears them when conscious? Assessed for delirium? Noted the presence of delirium in the progress notes for coding and communication? Considered maintaining a pt diary of key events to share with the family? PICS Checklist: Have We….

99. PICS Hand-Off Checklist Have we coordinated care prior to transfer? –Referred cognitive issues to speech therapy/OT (taught pt/family cognitive recovery exercises) –Referred psychiatric issues to psych consult (taught pt/family coping strategies) –Referred physical issues to PT (promoting physical activity that engages the brain) –Discussed with family lasting effects of illness and the possible need for continued care (assured them that this is common, and will take time to resolve) –Recorded current physical, cognitive and psychological issues, informed next provider?

100. Introducing ABCDE in the ICU: Practical Advice for Implementing Protocols

101. How to Identify Barriers The ABCDE Bundle focuses on aligning and supporting: –People –Processes –Technology These are three key areas to evaluate when identifying barriers to adoption and implementation

102. People: Who Is on Your Team? Nurses Doctors Pharmacists Respiratory therapists PT/OT Administration

103. Processes: What Does Your Team Have in Place? What do you do well? (ABCDEs) Where do you need help? What is in motion? What has not started?

104. What Is the Role of Technology? Computerized charting Computerized order entry Keep it simple Size of the institution Measure outcomes

105. Tendency to maintain the status quo Resistance of independent groups to alter their behaviors and relinquish some autonomy Perceived disproportionality of outcomes from the proposed change to the efforts required for change Lack of significant prioritization Insufficient personal accountability for completing change Inadequate knowledge about clinical outcomes General Barriers to Changing the ICU Culture Hatler CW, et al. Am J Crit Care. 2006;15:549-555.

106. Nursing-Implemented Sedation Protocol: Barnes Jewish Pilot United States P = 0.13 P < 0.001 P = 0.003 Significant patient characteristics/metrics/outcomes ProtocolRoutineP value CIVS†66 (40)66 (42)0.9 Duration CIVS, hrs*3.5 ± 45.6 ± 6.40.003 Bolus † 118 (72)127 (80)0.14 Reintubated † 14 (8.6)21 (13)0.2 Trached † 10 (6.2)21 (13.2)0.04 *Data presented in median; † Data presented as n (%) CIVS: continuous intravenous infusion sedation Brook AD, et al. Crit Care Med. 1999;27(12):2609-2615. Single center, prospective, trial of 332 consecutive ICU patients requiring mechanical ventilation randomized to protocolized sedation (n = 162) or routine care (n = 159) at Barnes Jewish Hospital from 8/97 to 7/98. Protocol used goal orientated sedation to target Ramsay with bolus requirements before initiation of continuous infusion and uptitration of opioids and benzodiazepines.

107. Nursing-Implemented Sedation Protocol: Bocage University Hospital France P = 0.004 P = 0.003 P = 0.001 Significant patient characteristics/metrics/outcomes ProtocolControlP value Daily midazolam, mg* 44 ± 3192 ± 590.001 Duration midazolam, hrs** 350.18 Reintubated†11 (6)29 (13)0.01 VAP diagnosis † 12 (6)34 (15)0.005 *Data presented in mean; ** Data presented in median † Data presented as n (%) Single center, prospective, before-after trial of 423 ICU patients requiring mechanical ventilation for > 48 hours before (n = 226) and after (n = 197) implementation of sedation protocol at Bocage University Hospital from 5/99 to 12/03. Protocol used goal orientated sedation to target Q3hr Cambridge scale with bolus requirements before initiation of continuous infusion and uptitration of midazolam Quenot JP, et al. Crit Care Med. 2007;35(9):2031-2036.

108. Pharmacist Enforced Adherence to an ICU Sedation Guideline: Boston Medical Center MICU P = 0.002 P = 0.001 P = 0.0004 Significant patient characteristics/metrics/outcomes RPhControlP value Alcohol/drug overdose † 15 (19.2)6 (7.7)0.03 Lorazepam equivalents/vent day, mg* 65.2 ± 114.1 74.8 ± 76.1 0.54 Fentanyl equivalents/vent day, mcg* 102.5 ± 328 400 ± 1026 0.02 *Data presented in mean ; † Data presented as n (%) Single center trial of 156 adult MICU patients requiring mechanical ventilation before (n = 78) and after (n = 78) implementation of RPh enforced guideline sedation management at Boston Medical Center. Guideline addressed use of agent selection, goal oriented therapy, and dose limitation strategies. Marshall J, et al. Crit Care Med. 2008;36(2):427-433.

109. Quality Improvement Project: Implementing ABCDE Multidisciplinary team focused on reducing heavy sedation, using SAT-SBT protocol and increasing MICU staffing to include full-time physical and occupational therapists with new consultation guidelines Results: –Delirium decreased –Sedation use decreased –Physical mobility improvement –Decrease hospital length of stay –Increased MICU admissions Needham DM, et al. Arch Phys Med Rehabil. 2010;91(4):536-542. Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.

110. QI Program for Changing the ICU Culture Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281. Summarize the Evidence Identify Local Barriers to Implementation Measure Performance Ensure All Patients Receive the Interventions

111. Barriers to Changing the ICU Culture Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.

112. Barriers to Changing the ICU Culture (cont) Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.

113. Results of ICU Quality Initiative Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.

114. Results of ICU Quality Initiative (cont) Needham DM, et al. Top Stroke Rehabil. 2010;17(4):271-281.

115. Developing and Implementing ICU Sedation Protocols and Guidelines Phase I: Development Phase II: Implementation Phase III: Continuous Quality Improvement (CQI) 1.Creation of the “physical champion(s)” 2.Multidisciplinary Committee 3.Data synthesis 4.Protocol drafting 1.Periodic Metric Assessment 2.Guideline update with current literature 3.Publication of efficacy, safety, and compliance data Benchmarking against other institutions Assistance in guideline development 1.Pilot Analysis Efficacy, Safety, Adherence 2.Endorsement of protocol from institutional credible bodies 3.Education to all ICU clinicians 4.Integration with electronic documentation and clinical monitoring systems

116. Key Steps for Effective Change Wheelan SA, et al. Am J Crit Care. 2003;12:527-534. Durbin CG. Crit Care Med. 2006;34(3 Suppl):S12-S17. Linking effective care processes with hospital and long-term patient outcomes Creating a strategy to improve teamwork and collaboration Creating a process for early mobilization Recognizing that current practice patterns may interfere with mobility Agreeing on a need to change Identification of a local champion

117. Conclusions Oversedation in the ICU is common; associated with negative sequelae Analgosedation has been shown to improve outcomes; consider sedation only if necessary Use the ABCDE protocol Titrate all sedative medications using a validated assessment tool to keep patients comfortable and arousable if possible Use of benzodiazepines should be minimized

118. Conclusions Consider nonpharmacological management of delirium and reduce exposure to risk factors Typical and atypical antipsychotic medications may be used to treat delirium if nonpharmacological interventions are not adequate Early mobility in ICU patients decreases delirium and improves functional outcomes at discharge