Delirium in Neuro ICU 2011


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  • 222 Excluded 46 Prior antipsychotic use within 30 days 38 Not receiving enteral nutrition 28 Primary neurological condition 16 Encephalopathy or end-stage liver disease 12 Alcohol withdrawal 12 Inability to conduct ICDSC 11 No delirium 11 Inability to obtain informed consent 10 Moribund 8 Irreversible brain disease (e.g. dementia) 5 Baseline QTc interval ≥ 500msec 5 Attending physician refusal for enrollment 7 Other
  • Delirium in Neuro ICU 2011

    1. 1. Delirium In Neuro-ICU 2011 PJ Papadakos MD Director CCM University of Rochester Rochester NY.
    2. 2. Assessing and Managing Sedation
    3. 3. Predisposing and Causative Conditions Anxiety Pain Delirium Interventions Management of predisposing & causative conditions Sedative, analgesic, antipsychotic, medications Calm Alert Free of pain and anxiety Lightly sedated Deeply sedated Unresponsive Pain, anxiety Agitation, vent dyssynchrony Dangerous agitation Spectrum of Distress/Comfort/Sedation ICU Environmental Influences Hospital Acquired Illness Medications Invasive, Medical, & Nursing Interventions Underlying Medical Conditions Acute Medical or Surgical Illness Mechanical Ventilation Agitation Sessler CN, Varney K. Chest. 2008;133(2):552-565.
    4. 4. Need for Sedation and Analgesia <ul><li>Prevent pain and anxiety </li></ul><ul><li>Decrease oxygen consumption </li></ul><ul><li>Decrease the stress response </li></ul><ul><li>Patient-ventilator synchrony </li></ul><ul><li>Avoid adverse neurocognitive sequelae </li></ul><ul><ul><li>Depression, PTSD </li></ul></ul>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.
    5. 5. Need for Sedation and Analgesia <ul><li>Prevent pain and anxiety </li></ul><ul><li>Decrease oxygen consumption </li></ul><ul><li>Decrease the stress response </li></ul><ul><li>Patient-ventilator synchrony </li></ul><ul><li>Avoid adverse neurocognitive sequelae </li></ul><ul><ul><li>Depression, PTSD </li></ul></ul>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.
    6. 6. American College of Critical Care Medicine Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult <ul><li>Guideline focus </li></ul><ul><ul><li>Prolonged sedation and analgesia </li></ul></ul><ul><ul><li>Patients older than 12 years </li></ul></ul><ul><ul><li>Patients during mechanical ventilation </li></ul></ul><ul><li>Assessment and treatment recommendations </li></ul><ul><ul><li>Analgesia </li></ul></ul><ul><ul><li>Sedation </li></ul></ul><ul><ul><li>Delirium </li></ul></ul><ul><ul><li>Sleep </li></ul></ul>Jacobi J, et al. Crit Care Med . 2002;30:119-141.
    7. 8. Identifying and Treating Pain
    8. 10. Maintaining Patients at the Desired Sedation Goal
    9. 11. Sedation-Agitation Scale (SAS) Riker RR, et al. Crit Care Med. 1999;27:1325-1329. Brandl K, et al. Pharmacotherapy. 2001;21:431-436.
    10. 12. Richmond Agitation Sedation Scale (RASS) Ely EW, et al. JAMA . 2003;289:2983-2991. Sessler CN, et al. Am J Respir Crit Care Med. 2002;166(10):1338-1344. Verbal Stimulus Physical Stimulus
    11. 13. The Importance of Preventing and Identifying Delirium
    12. 14. ICU Delirium Vasilevskis EE, et al. Chest . 2010;138(5):1224-1233. <ul><li>Develops in ~2/3 of critically ill patients </li></ul><ul><li>Hypoactive or mixed forms most common </li></ul><ul><li>Increased risk </li></ul><ul><ul><li>Benzodiazepines </li></ul></ul><ul><ul><li>Extended ventilation </li></ul></ul><ul><ul><li>Immobility </li></ul></ul><ul><ul><li>Associated with weakness </li></ul></ul><ul><ul><li>Undiagnosed in up to 72% of cases </li></ul></ul>
    13. 15. 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 Use of physical restraints Predisposing Disease Cardiac disease Cognitive impairment (eg, dementia) Pulmonary disease <ul><li>Acute Illness </li></ul><ul><li>Length of stay </li></ul><ul><li>Fever </li></ul><ul><li>Medicine service </li></ul><ul><li>Lack of nutrition </li></ul><ul><li>Hypotension </li></ul><ul><li>Sepsis </li></ul><ul><li>Metabolic disorders </li></ul><ul><li>Tubes/catheters </li></ul><ul><li>Medications: </li></ul><ul><li>Anticholinergics </li></ul><ul><li>Corticosteroids </li></ul><ul><li>- Benzodiazepines </li></ul>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.
    14. 16. Sequelae of Delirium After Hospital Discharge During the ICU/Hospital Stay <ul><li>Increased mortality </li></ul><ul><li>Longer intubation time </li></ul><ul><li>Average 10 additional days in hospital </li></ul><ul><li>Higher costs of care </li></ul><ul><li>Increased mortality </li></ul><ul><li>Development of dementia </li></ul><ul><li>Long-term cognitive impairment </li></ul><ul><li>Requirement for care in chronic care facility </li></ul><ul><li>Decreased functional status at 6 months </li></ul>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.
    15. 17. Delirium Duration and Mortality Pisani MA. Am J Respir Crit Care Med . 2009;180:1092-1097. Kaplan-Meier survival curve for 1- year mortality post–ICU admission P < 0.001
    16. 18. 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 and
    17. 19. Intensive Care Delirium Screening Checklist <ul><li>1. Altered level of consciousness </li></ul><ul><li>2. Inattention </li></ul><ul><li>3. Disorientation </li></ul><ul><li>4. Hallucinations </li></ul><ul><li>5. Psychomotor agitation or retardation </li></ul><ul><li>6. Inappropriate speech </li></ul><ul><li>7. Sleep/wake cycle disturbances </li></ul><ul><li>8. Symptom fluctuation </li></ul>Bergeron N, et al. Intensive Care Med . 2001;27:859-864. Ouimet S, et al. Intensive Care Med. 2007;33:1007-1013. <ul><li>Score 1 point for each component present during shift </li></ul><ul><ul><li>Score of 1-3 = Subsyndromal Delirium </li></ul></ul><ul><ul><li>Score of ≥ 4 = Delirium </li></ul></ul>
    18. 20. What to THINK When Delirium Is Present <ul><ul><ul><li>T oxic Situations </li></ul></ul></ul><ul><ul><ul><ul><li>CHF, shock, dehydration </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Deliriogenic meds ( T ight Titration ) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>New organ failure, eg, liver, kidney </li></ul></ul></ul></ul><ul><ul><ul><li>H ypoxemia; also, consider giving H aloperidol or other antipsychotics? </li></ul></ul></ul><ul><ul><ul><li>I nfection/sepsis (nosocomial), I mmobilization </li></ul></ul></ul><ul><ul><ul><li>N onpharmacologic interventions </li></ul></ul></ul><ul><ul><ul><ul><li>Hearing aids, glasses, reorient, sleep protocols, music, noise control, ambulation </li></ul></ul></ul></ul><ul><ul><ul><li>K + or Electrolyte problems </li></ul></ul></ul>See Skrobik Y. Crit Care Clin. 2009;25:585-591.
    19. 21. What to THINK When Delirium Is Present <ul><ul><ul><li>T oxic Situations </li></ul></ul></ul><ul><ul><ul><ul><li>CHF, shock, dehydration </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Deliriogenic meds ( T ight Titration ) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>New organ failure, eg, liver, kidney </li></ul></ul></ul></ul><ul><ul><ul><li>H ypoxemia; also, consider giving H aloperidol or other antipsychotics? </li></ul></ul></ul><ul><ul><ul><li>I nfection/sepsis (nosocomial), I mmobilization </li></ul></ul></ul><ul><ul><ul><li>N onpharmacologic interventions </li></ul></ul></ul><ul><ul><ul><ul><li>Hearing aids, glasses, reorient, sleep protocols, music, noise control, ambulation </li></ul></ul></ul></ul><ul><ul><ul><li>K + or Electrolyte problems </li></ul></ul></ul>See Skrobik Y. Crit Care Clin. 2009;25:585-591.
    20. 22. ICU Sedation: The Balancing Act Undersedation <ul><li>Patient recall </li></ul><ul><li>Device removal </li></ul><ul><li>Ineffectual mechanical ventilation </li></ul><ul><li>Initiation of neuromuscular blockade </li></ul><ul><li>Myocardial or cerebral ischemia </li></ul><ul><li>Decreased family satisfaction w/ care </li></ul>Patient Comfort and Ventilatory Optimization G O A L Jacobi J, et al. Crit Care Med. 2002;30:119-141. Oversedation <ul><li>Prolonged mechanical ventilation </li></ul><ul><li>Increase length of stay </li></ul><ul><li>Increased risk of complications </li></ul><ul><li>- Ventilator-associated pneumonia </li></ul><ul><li>Increased diagnostic testing </li></ul><ul><li>Inability to evaluate for delirium </li></ul>
    21. 23. Consequence of Improper Sedation <ul><li>Continuous sedation carries the risks associated with oversedation and may increase the duration of mechanical ventilation (MV) 1 </li></ul><ul><li>MV patients accrue significantly more cost during their ICU stay than non-MV patients 2 </li></ul><ul><ul><li>$31,574 versus $12,931, P < 0.001 </li></ul></ul><ul><li>Sedation should be titrated to achieve a cooperative patient and daily wake-up, a JC requirement 1,2 </li></ul>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):S110. Undersedated 3 Oversedated On Target 15.4% 54.0% 30.6%
    22. 24. Analgosedation <ul><li>Analgesic first (A-1), supplement with sedative </li></ul><ul><li>Acknowledges that discomfort may cause agitation </li></ul><ul><li>Remifentanil-based regimen </li></ul><ul><ul><li>Reduces propofol use </li></ul></ul><ul><ul><li>Reduces median MV time </li></ul></ul><ul><ul><li>Improves sedation-agitation scores </li></ul></ul><ul><li>Not appropriate for drug or alcohol withdrawal </li></ul>Park G, et al. Br J Anaesth. 2007;98:76-82. Rozendaal FW, et al. Intensive Care Med. 2009;35:291-298.
    23. 25. Consider Patient Comorbidities When Choosing a Sedation Regimen <ul><li>Chronic pain </li></ul><ul><li>Organ dysfunction </li></ul><ul><li>CV instability </li></ul><ul><li>Substance withdrawal </li></ul><ul><li>Respiratory insufficiency </li></ul><ul><li>Obesity </li></ul><ul><li>Obstructive sleep apnea </li></ul>
    24. 26. Risk of Delirium With Benzodiazepines Pandharipande P, et al. J Trauma. 2008;65:34-41. Pandharipande P, et al. Anesthesiol. 2006:104:21-26. Lorazepam Dose, mg Delirium Risk
    25. 27. Propofol Has Greater Sedation Efficacy Than Continuous Midazolam Walder B, et al. Anesth Analg. 2001;92:975-983. Efficacy of Sedation* Duration of Adequate Sedation * Avg adequate sedation time avg total sedation time n = 18 trials n = 15 trials
    26. 28. DEX
    27. 29. ?  2A  2C  2A  2A Anxiolysis  2B  2B X  2B X Adapted from Kamibayashi T, Maze M. Anesthesiology . 2000;93:1346-1349. Physiology of   Adrenoceptors  2A
    28. 30.   Agonist Clonidine <ul><li>Bradycardia </li></ul><ul><li>Dry mouth </li></ul><ul><li>Hypotension </li></ul><ul><li>Sedation </li></ul><ul><li>Antihypertensive </li></ul><ul><li>Analgesia </li></ul><ul><li>Sedation </li></ul><ul><li>Decrease sympathetic activity </li></ul><ul><li>Decreased shivering </li></ul>Adverse Effects Clinical 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. 31.   Agonist Dexmedetomidine <ul><li>Hypotension </li></ul><ul><li>Hypertension </li></ul><ul><li>Nausea </li></ul><ul><li>Bradycardia </li></ul><ul><li>Dry mouth </li></ul><ul><li>Peripheral vasoconstriction at high doses </li></ul><ul><li>Antihypertensive </li></ul><ul><li>Sedation </li></ul><ul><li>Analgesia </li></ul><ul><li>Decreased shivering </li></ul><ul><li>Anxiolysis </li></ul><ul><li>Patient arousability </li></ul><ul><li>Potentiate effects of opioids, </li></ul><ul><li>sedatives, and anesthetics </li></ul><ul><li>Decrease sympathetic activity </li></ul>Adverse Effects Clinical Effects Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349. Bhana N, et al. Drugs . 2000;59(2):263-268.
    30. 32. MENDS Delirium: All Patients Pandharipande PP, et al . Crit Care . 2010;14:R38.
    31. 33. MENDS: Survival in Septic ICU Patients Pandharipande PP, et al . Crit Care . 2010;14:R38.
    32. 34. Costs of Drug Therapy <ul><li>Acquisition </li></ul><ul><li>Waste disposal </li></ul><ul><li>Preparation </li></ul><ul><li>Distribution </li></ul><ul><li>Administration (Nursing time) </li></ul><ul><li>Toxicity cost (ADRs) </li></ul><ul><li>Monitoring (Time, lab, and diagnostic tests) </li></ul><ul><li>Downstream issues (infections, adverse events, ICU stay, ventilator time, etc) </li></ul>Dasta JF, Kane-Gill S. Crit Care Clin . 2009;25:571-583.
    33. 35. Strategies to Reduce the Duration of Mechanical Ventilation in Patients Receiving Continuous Sedation
    34. 36. Daily Sedation Interruption Decreases Duration of Mechanical Ventilation <ul><li>Hold sedation infusion until patient awake and then restart at 50% of the prior dose </li></ul><ul><li>“ Awake” defined as 3 of the following 4: </li></ul><ul><ul><li>Open eyes in response to voice </li></ul></ul><ul><ul><li>Use eyes to follow investigator on request </li></ul></ul><ul><ul><li>Squeeze hand on request </li></ul></ul><ul><ul><li>Stick out tongue on request </li></ul></ul>Kress JP, et al. N Engl J Med. 2000;342:1471-1477. <ul><li>Fewer diagnostic tests to assess changes in mental status </li></ul><ul><li>No increase in rate of agitated-related complications or </li></ul><ul><li>episodes of patient-initiated device removal </li></ul><ul><li>No increase in PTSD or cardiac ischemia </li></ul>
    35. 37. Despite Proven Benefits of Spontaneous Awakening/Daily Interruption Trials, They Are Not Standard of Practice at Most Institutions <ul><li>Canada – 40% get SATs (273 physicians in 2005) 1 </li></ul><ul><li>US – 40% get SATs (2004-05) 2 </li></ul><ul><li>Germany – 34% get SATs (214 ICUs in 2006) 3 </li></ul><ul><li>France – 40 – 50% deeply sedated with 90% on </li></ul><ul><li>continuous infusion of sedative/opiate 4 </li></ul>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.
    36. 38. 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. 0 10 20 30 40 50 60 70 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
    37. 39. Prevention and Treatment of Delirium in the ICU
    38. 40. Before Considering a Pharmacologic Treatment for Delirium… <ul><li>Have the underlying causes of delirium been identified and reversed/treated? </li></ul><ul><li>Have non-pharmacologic treatment strategies been optimized? </li></ul><ul><li>Does your patient have delirium? </li></ul><ul><ul><li>Hyperactive </li></ul></ul><ul><ul><li>Hypoactive </li></ul></ul><ul><ul><li>Mixed hyperactive-hypoactive </li></ul></ul>Inouye SK, et al. N Engl J Med. 1999;340:669-676.
    39. 41. Dopamine Antagonist Haloperidol <ul><li>Adverse CV effects include QT interval prolongation </li></ul><ul><li>Extrapyramidal symptoms, neuroleptic malignant syndrome (rare) 1 </li></ul><ul><li>Does not cause respiratory depression 1 </li></ul><ul><li>Dysphoria 2 </li></ul><ul><li>Hypnotic agent with antipsychotic properties 1 </li></ul>Adverse Effects Clinical Effects 1. Harvey MA. Am J Crit Care. 1996;5:7-16. 2. Crippen DW. Crit Care Clin. 1990;6:369-392. <ul><li>For treatment of delirium in critically ill adults 1 </li></ul><ul><li>Metabolism altered by drug-drug interactions 2 </li></ul>
    40. 42. Potential Advantages of Atypical Antipsychotics vs Conventional Antipsychotics <ul><ul><li>Decreased extrapyramidal effects </li></ul></ul><ul><ul><li>Little effect on the QTc interval (with the exception of ziprasidone) </li></ul></ul><ul><ul><li>Less hypotension/fewer orthostatic effects </li></ul></ul><ul><ul><li>Less likely to cause neuroleptic malignant syndrome </li></ul></ul><ul><ul><li>Unlikely to cause laryngeal dystonia </li></ul></ul><ul><ul><li>Lower mortality when used in the elderly to treat agitation related to dementia </li></ul></ul>Tran PV, et al. J Clin Psychiatry. 1997;58:205-211. Lee PE, et al. J Am Geriatr Soc. 2005;53:1374-1379. Wang PS, et al. N Engl J Med. 2005;353:2235-2341.
    41. 43. 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 anti-psychotics Benzodiazepines Haloperidol Propofol 2001 2007
    42. 44. <ul><li>Double-blind, placebo-controlled, randomized trial </li></ul><ul><li>3 academic medical centers </li></ul><ul><li>Intervention </li></ul><ul><ul><li>Quetiapine 50 mg PO/NGT twice daily titrated to a maximum of 200 mg twice daily) vs placebo </li></ul></ul><ul><ul><li>PRN IV haloperidol protocolized and encouraged in each group </li></ul></ul><ul><ul><li>Oversedation: hold study drug when SAS ≤ 2 (after holding sedation therapy) </li></ul></ul><ul><li>Primary outcome </li></ul><ul><ul><li>Time to first resolution of delirium (ie, first 12-hour period when ICDSC ≤ 3) </li></ul></ul>Devlin JW, et al. Crit Care Med . 2010;38:419-427. Quetiapine for Delirium Study Design
    43. 45. 222 patients excluded 36 subjects randomized Quetiapine 50 mg NG bid (n = 18) Placebo 50 mg NG bid (n = 18) As-needed haloperidol, usual sedation and analgesia therapy at physician’s discretion Dose Titration Increase quetiapine or placebo dose by 50 mg every 12 hours daily if the subject received ≥ 1 dose of as needed haloperidol in prior 24 hours. (Maximum dose = 200 mg every 12 hours) 258 patients with delirium (ICDSC ≥ 4) tolerating enteral nutrition <ul><li>Discontinuation of study drug </li></ul><ul><li>No signs of delirium </li></ul><ul><li>10 days of therapy had elapsed </li></ul><ul><li>3. ICU discharge prior to 10 days of therapy </li></ul><ul><li>4. Serious adverse event potentially attributable to the study drug </li></ul>Devlin JW, et al. Crit Care Med. 2010;38:419-427.
    44. 46. 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
    45. 47. The Interaction Between Sedation, Critical Illness and Sleep in the ICU
    46. 48. Effect of Common Sedatives and Analgesics on Sleep <ul><li>There is little evidence that administration of sedatives in </li></ul><ul><li>the ICU achieves the restorative function of normal sleep </li></ul><ul><li>Benzodiazepines </li></ul><ul><ul><li>↑ Stage 2 NREM </li></ul></ul><ul><ul><li>↓ Slow wave sleep (SWS) and REM </li></ul></ul><ul><li>Propofol </li></ul><ul><ul><li>↑ Total sleep time without enhancing REM </li></ul></ul><ul><ul><li>↓ SWS </li></ul></ul><ul><li>Analgesics </li></ul><ul><ul><li>Abnormal sleep architecture </li></ul></ul><ul><li>Dexmedetomidine </li></ul><ul><ul><li>↑ SWS </li></ul></ul>Weinhouse GL, et al. Sleep. 2006;29:707-716. Nelson LE, et al. Anesthesiology. 2003;98:428-436.
    47. 49. Strategies to Boost Sleep Quality in the ICU <ul><li>Optimize environmental strategies </li></ul><ul><li>Avoid benzodiazepines </li></ul><ul><li>Consider dexmedetomidine </li></ul><ul><li>Zolpidem and zopiclone are GABA receptor agonists but do not decrease SWS like the benzodiazepines </li></ul><ul><li>Sedating antidepressants (eg, trazodone) or antipsychotics may offer an option in non-intubated patients </li></ul><ul><li>Melatonin may improve sleep of COPD patients in medical ICU (1 small RCT) </li></ul>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.
    48. 50. Conclusions <ul><li>Oversedation in the ICU is common; associated with negative sequelae </li></ul><ul><li>Monitor and treat pain and delirium prior to administering sedation therapy </li></ul><ul><li>Analgosedation has been shown to improve outcomes; consider sedation only if necessary </li></ul><ul><li>Titrate all sedative medications using a validated assessment tool to keep patients comfortable and arousable if possible </li></ul><ul><li>Monitor for adverse events </li></ul>
    49. 51. Conclusions <ul><li>ICU sedation should use protocols that include a down-titration and/or daily interruption strategy coupled with a spontaneous breathing trial </li></ul><ul><li>Multiple sedatives are available </li></ul><ul><li>Propofol and dexmedetomidine will liberate patients from mechanical ventilation faster than benzodiazepine therapy (even when administered intermittently) and are associated with less delirium </li></ul><ul><li>Use of benzodiazepines should be minimized </li></ul>
    50. 52. Conclusions <ul><li>Cost of care calculations should consider the overall costs, not just drug acquisition costs </li></ul><ul><li>Early mobility in ICU patients decreases delirium and improves functional outcomes at discharge </li></ul><ul><li>Consider non-pharmacological management of delirium and reduce exposure to risk factors </li></ul><ul><li>Typical and atypical antipsychotic medications may be used to treat delirium if non-pharmacological interventions are not adequate </li></ul>