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  1. Drugs, Delirium and Daily Interruptions of Sedation Noel Baldwin BSN, RN University of Michigan Critical Care Medicine Unit

  2. Points of Discussion • Review of sedatives commonly used in the ICU • Describe the need to identify and assess for delirium in the ICU • Describe current recommendations to improve outcomes

  3. Common ICU sedatives & analgesia • Benzodiazepines: ativan, versed, valium • Hypnotic: propofol • Alpha 2 agonist: dexmedetomidine (Precedex) • Analgesia: morphine, fentanyl, dilaudid

  4. Benzodiazepines: enhance the effect of the GABA neurotransmitter thereby decreasing neuron excitability • Versed: short acting with 1.5 to 5 minute onset of action, effects last an average of 2 hours, half life of 2.5 hours • Ativan: intermediate acting with 15 to 30 minute onset, effects last an average of 6-8 hours, half life is 9.5-19 hours • Valium: long acting with rapid IV onset of 1-5 minutes, half life is 20-50 hours Wake up time after continuous infusions unpredictable

  5. Propofol: several mechanisms of action both through potientiation of GABA receptors and also acts as a sodium channel blocker • A short acting hypnotic agent with rapid onset of less than 1 minute. Wake up time is usually minutes, but if used for prolonged period, build up in tissues will lead to longer wake up. • Artificial airway required due to apnea (unless MD with deep sedation privelages) • Monitor for hypotension • Lipid based solution, monitor triglycerides

  6. Dexmedetomidine: agonist of the α2 adrenergic receptor. It produces sedative, analgesic and anxiolytic effects • Bolus dose followed by continuous infusion. Onset of action is 30-60 minutes with a duration of 4 hours. Half life is 2-3 hours. • NO RESPIRATORY SUPPRESSION • Bradycardia is most common side effect • Expensive. Still under patent.

  7. More alert, cooperative patients: PT ready? Jakob et al. JAMA 2012; 307(11): 1151-1160

  8. Analgesia • Morphine: gold standard for treating pain. • Fentanyl: potent, synthetic narcotic with rapid onset and short acting. 100 times more potent than morphine. • Dilaudid: semi-synthetic narcotic. 6-8 times more powerful than morphine but with a lower risk of dependency.

  9. Sedation Scales Richmond Agitation Sedation Scale Ramsay Scale 1 anxious, agitated or restless 2 cooperative, oriented, tranquil 3 Responding only to verbal commands 4 brisk response to light glabella tap or loud auditory stimulus 5 sluggish response to light glabella tap or loud auditory stimulus 6 no response to light glabella tap or loud auditory stimulus +4 Combative, violent, danger to staff +3 Aggressive, pulls or removes tubes +2 Frequent nonpurposeful movements +1 Anxious, apprehensive 0 Alert and calm -1 Verbal stimulation, eye contact >10sec -2 Verbal stimulation, eye contact < 10sec -3 Verbal stimulation, no eye contact -4 Physical stimulation, responds -5 Physical stimulation, no response

  10. What is Delirium?

  11. di-’lir-E-&m “a disturbanceof consciousness that is accompanied by a changein cognition that cannot be better accounted for by a preexisting dementia” “incontrast to dementia which develops slowly and persists over time, delirium symptoms develop rapidly and often fluctuate over a period of hours to days “ American Psychiatric Association

  12. Perception v. Reality ■Perception: delirium in the ICU is “part of the scenery,” or an expected and inconsequential outcome of mechanical ventilation and other therapies necessary to save lives. • Reality: delirium is an acute organ dysfunction that needs to be treated with medical urgency.

  13. Estimated delirium rates Mechanically ventilated ICU patients 26%-50% Non-ventilated ICU patients 10%-25%

  14. Looking Deeper….

  15. Subtypes of Delirium • Hyperactive: agitation, restlessness, and hyper-vigilance; patient often displays frequent non-purposeful movement or makes attempts to discontinue treatment • Hypoactive: withdrawal, flat affect and decreased responsiveness • Mixed: a fluctuation between both subtypes

  16. Delirium Prevalence 614 critically ill medical ICU patients at a tertiary care center • Hyperactive: 1.6% • Mixed 55% • Hypoactive 43.5% Peterson JF et al. J Am Geriatr Soc 2006; 54: 479-84

  17. Hypoactive delirium patients seem to be the ideal patient: quiet and peaceful. However, hypoactive delirium carries with it a worse prognosis than hyperactive delirium. Their delirium is often not recognized. Hyperactive delirium may lead to more sedatives. More sedatives may lead to prolonged, worsening of delirium. Sedatives should be reserved for utilization only if patient is at risk of harm to self. Quiet is not always good.

  18. How do I know if my patient is delirious?

  19. Commonly Utilized Delirium Assessment Tools • Intensive Care Delirium Screening Checklist (ICDSC) • Confusion Assessment Method for the ICU (CAM-ICU • Both proven sensitive and reliable

  20. ICDSC Completed throughout the day/shift ≥ 4 = delirium

  21. CAM-ICU Approximately 2 minutes to complete Objective Patient must be able to open eyes to voice for

  22. CAM-ICU content

  23. Why do we care?

  24. It is expensive! ICU delirium is associated with costs ranging from $4 to $16 billion annually in the US alone, not including added cost of lost workdays, caregiver burden or cognitive rehabilitation Pun et al 2007. CHEST 132(2): 624-636

  25. 2X Longer LOS Ely et al JAMA 2004; 291(14): 1753-1762

  26. 5X Self-Extubation Dubois, MJ et al. Intensive Care Med 2001; 27: 1297-1304

  27. More Cognitive Impairment • Jackson and coworkers reviewed nine prospective studies, nearly 1900 patients, and found delirium was associated with long term cognitive decline over 1-3 years after discharge • The relationship between long term cognitive impairment and delirium is still being studied but preliminary data suggests the association is significant. Jackson et al. Neuropsychol Review 2004; 14: 87-98

  28. Cognitive outcomes for delirious patients 126 patients, 99 survived ≥ 3 months • At 3 mos: 21% (16/76) with no impairment 17% (13/76) with mild/moderate impairment 62% (47/76) with severe impairment • At 12 mos: 29% (15/52) with no impairment 35% (18/52) with mild/moderate impairment 36% (19/52) with severe impairment • Duration of delirium was an independent predictor of worse cognitive performance Girard et al, Crit Care Med 2010; 38: 1513-1520

  29. People Die!3X more likely to be dead in 6 months Ely et al. JAMA 2004; 291: 1753-1762

  30. Delirium duration and mortality: 1 day = 10% higher risk Pisani et al. Am J Respir Crit Care Med 2009; 180: 1092-1097

  31. What to think if your patient is delirious! • Toxic situations: CHF, shock, dehydration, deliriogenic medicines, new organ failure • Hypoxemia • Infection or Immobility • Non-pharmacologic efforts: hearing aids, eyeglasses, reorientation, noise reduction, sleep, ambulation • K+ or Electrolyte problems

  32. Predisposing Risk Factors • Age > 70yrs • Depression • Polypharmacy • Anemia • CHF • Renal Failure • HTN • Tobacco use • Pain • Visual/hearing impairment • Malnutrition • Dementia Evaluate risk factors on admit!

  33. Are the restraints necessary?

  34. The problem with benzos

  35. What can I do to help my delirious patient?

  36. Prevention • Use of eyeglasses and hearing aides • Blinds open and lights on during daytime hours • Allow for sleep at night (is that 2 a.m. bath really necessary?) • Cognitive stimulation • Familiar objects in the room (picture of family) • Monitor hydration • Early mobility • Treat pain • Limit deliriogenic drugs (benzos)

  37. Pharmacological Approach • Zero approved agents for delirium • Common treatment protocols include haloperidol, resperidone, olanzapine and quetiapine • Delirium protocols not well validated • STOP deliriogenic medications!

  38. MIND Trial Girard TD, et al. Crit Care Med 2010; 38:428-437

  39. What about Dexmedetomidine? SEDCOM Trial MENDS Trial Pandharipande PP, et al. JAMA 2007; 298: 2644-2653 Riker RR, et al. JAMA 2009: 301:489-499

  40. Quetiapine (Seroquel)- Resolution of delirium Devlin et al. Crit Care Med 2010; 38: 419-427

  41. ABCDE Approach: Modifying Risk Factors in the ICU Combine awakening with breathing trials

  42. Daily Awakening Trials • Decreased days on ventilator • Decreased ICU LOS • Decreased hospital LOS • Less diagnostic testing Kress et al. NEJM 2000; 342(20): 1471-1477

  43. Daily awakening trial paired with breathing trials • Duplicated daily awakening trial data • PLUS, demonstrated a mortality benefit. For every seven patients treated, one life saved Girard et al. Lancet 2008; 371: 126-134

  44. Daily Awakening and Delirium

  45. Stop Sedation?! What about the Emotional Trauma? Kress et al. AJRCCM(2003);168: 1457-1461

  46. Early Mobility

  47. Best Patient Care • Is the sedated patient stable?

  48. The Lasting Legacy of ICU Survivorship:Evidence for Practice Change • Physical Impairments • Cognitive Decline • Mental Health Issues • Caregiver/Family Strain More to come on these issues later today

  49. “It is no longer a matter how we keep them alive, but rather how well we keep them alive.”--Wes Ely, M.D, M.P.H