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How to manage Sedation in Neuro ICU
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How to manage Sedation in Neuro ICU Presentation Transcript

  • 1. Sedation In the Neuro-ICU 2009 PJ Papadakos MD FCCM Director CCM Professor Anesthesiology, Surgery and Neurosurgery Rochester NY USA
  • 2. University of Rochester Developed the first use guidelines for evaluation of Neurosurgery patients with Propofol (Ireland et al., Proceedings American Association of Neurological Surgeons . 1992) Development of Fast Tracking for Open Heart Surgery. 1991 Development of use protocols for sedation in Critically ill patients 1993. Development of guidelines for Dexmedetomidine in Burn patients 2001
  • 3. University of Rochester Developed the first use guidelines for evaluation of Neurosurgery patients with Propofol (Ireland et al., Proceedings American Association of Neurological Surgeons . 1992) Development of Fast Tracking for Open Heart Surgery. 1991 Development of use protocols for sedation in Critically ill patients 1993. Development of guidelines for Dexmedetomidine in Burn patients 2001
  • 4. Articles on Sedation
  • 5. Several Practice Standards are in the Literature In 2001 a large conference was held: Crit Care Med 2002 Vol 30 #1
  • 6. ICU Sedation ICU sedation is a complex clinical problem Current therapeutic approaches all have potential adverse side effects Agitated patients are often hypertensive, increase stress hormones, and require more intensive nursing care
  • 7. Goals of Sedation in the ICU Patient comfort Control of pain Anxiolysis and amnesia Blunting adverse autonomic and hemodynamic responses Facilitate nursing management Facilitate mechanical ventilation Avoid self-extubation Reduce oxygen consumption
  • 8. Characteristics of an Ideal Sedation Agent for the ICU Lack of respiratory depression Analgesia, especially for surgical patients Rapid onset, titratable, with a short elimination half-time Sedation with ease of orientation and arousability Anxiolytic Hemodynamic stability
  • 9. Agitated Patients Can injure themselves or others Self-extubation, decannulation, wound dehiscence  Peripheral oxygen consumption Risks of hypoxemia, organ ischemia  Physiologic stress Change in immune response, wound healing,  coagulation, release cytokines Require more intensive nursing care Restraints  Risks of excessive sedation 
  • 10. Sedative Drugs
  • 11. Most commonly used drugs in the ICU
  • 12. Why do we use these drugs Pain Agitation Anxiety Keep patient intubated Protect Patient from Harm ?Cytokine Modulation?
  • 13. Causes of Anxiety
  • 14. Factors Provoking Anxiety Pain Fear Memory Loss Sleep Deprivation Confusion Inconsiderate Providers Loss of Control ICU Chemical/Physiologic Psychosis Surgical Stress Imbalance Medications Temperature Alarms Noises Mechanical Devices Lights Nonchanging Environment Tesar, Stern. J Intensive Care Med. 1986;1:137-148. Harvey. Am J Crit Care. 1996;5:7-16. Crippen. Crit Care Clin. 1990;6:369-392.
  • 15. To Use these drugs We need a common language to speak to all levels of care givers
  • 16. Sedation Scales Should be used in every unit.
  • 17. Faces Pain Rating Scale 0 3 4 5 1 2 0 1 2 3 4 5 6 7 8 9 10 No Worst Moderate pain possible pain pain Adapted with permission from Chambers, Craig. Pain. 1998;78:29. Sriwatanakul et al. Clin Pharmacol Ther. 1982;32:143-148.
  • 18. Ramsay Sedation Scale Score Definition 1 Anxious, agitated, or restless 2 Cooperative, oriented, and tranquil 3 Responds to commands 4 Asleep, but with brisk response to light glabellar tap or loud auditory stimuli 5 Asleep, sluggish response to light glabellar tap or loud auditory stimuli 6 Asleep, no response Adapted with permission from Ramsay et al. BMJ. 1974;2:656-659.
  • 19. SAS: Sedation-Agitation Scale Description Score Definition 7 Dangerous agitation Striking staff, thrashing 6 Very agitated Does not calm, needs restraints 5 Agitated Calms with verbal instructions 4 Calm and cooperative Follows commands 3 Sedated Difficult to arouse 2 Very sedated Does not follow commands 1 Unarousable No response to noxious stimuli .
  • 20. Drugs to Use:
  • 21. Pharmacologic Agents Opioids1 Morphine sulfate   Fentanyl and Remifentanyl Benzodiazepines1 Lorazepam   Midazolam Sedative/hypnotics1 Propofol  Butyrophenones1 Haloperidol  Agonists2 2 Dexmedetomidine 
  • 22. Benzodiazepines: Mechanisms of Action Benzodiazepines GABAA receptor modulation in CNS1  Facilitate binding of GABA1  Hyperpolarize cells, more resistant to  excitation Receptors mainly postsynaptic  1. Lerch, Park. Br Med Bull. 1999;55:76-95.
  • 23. Benzodiazepines: Pharmacodynamics Amnesia Sedation/anxiolysis Anticonvulsant Relief of muscle spasm Lerch, Park. Br Med Bull. 1999;55:89.
  • 24. Lorazepam: Clinical Effects Sedation, anxiolysis, and amnesia1 Preferred for prolonged sedation2 Slower onset of action than midazolam2,3 Propylene glycol toxicity with higher doses1 Less hypotension than with midazolam2 Retrograde and anterograde amnesia4 1. Lerch, Park. Br Med Bull. 1999;55, 90. 2. Shafer. Crit Care Med. 1998;26:952-953. 3. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:430, 434. 4. Harvey. Am J Crit Care. 1996;5:11.
  • 25. Benzodiazepines: Reversal Agents Flumazenil Transiently antagonizes the benzodiazepine  component of ventilatory depression and sedation during use with opioids Reverses CNS and circulatory side effects of  benzodiazepines within 2 minutes Useful for diagnostic evaluation  Stoelting. Pharmacology and Physiology in Anesthetic Practice. 3rd ed. 1999:138.
  • 26. Benzodiazepines Advantages Limitations • Amnesia1 • Weaning prolonged2,3 • Anxiolysis1 • Polyethylene glycol toxicity3 • Sedation1 • Respiratory depression2,4 • Hypotension2 • Lack of analgesia4 • Oversedation/deep sedation2 • Dependence/tolerance2 • Paradoxic agitation2 1. Pepperman. Care of the Critically Ill. 1989;5:197. 2. Harvey. Am J Crit Care. 1996;5:10, 11. 3. Lerch, Park. Br Med Bull. 1999;55:89, 90. 4. Crippen. Crit Care Clin. 1990;6:380.
  • 27. Propofol: Mechanisms of Action Not well-understood GABAA receptor modulation is most likely Davies. Can J Physiol Pharmacol. 1998;76:46.
  • 28. Propofol: Pharmacodynamics Sedation/anesthesia1 Decreases ICP1,2 Decreases SNS activity1,2 Cardiovascular depression1,3 Decreases ventilation time1 1. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:434, 436. 2. Harvey. Am J Crit Care. 1996;5:12. 3. Lerch, Park. Br Med Bull. 1999;55:90,
  • 29. Propofol: Clinical Effects Anesthesia and sedation1 Rapid onset of action1,2 Very short half-life2 Decrease in BP and HR from sympathetic effects1 Decreases ventilation time3,4 Time to extubation faster than with midazolam3,4 1. Lerch, Park. Br Med Bull. 1999:55:90. 2. Harvey. Am J Crit Care. 1996;5:7-16. 3. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:434. 4. Ostermann et al. JAMA. 2000;283:1457.
  • 30. Propofol Limitations Advantages • Respiratory depression (enhanced • Sedation1 by opioids)1 • Hypnosis1 • Hypotension1 • Anxiolysis1 • Decreased contractility2 • Muscle relaxation1 • Lack of analgesia3 •  ICP1 • Hypertriglyceridemia1 •  Cerebral metabolic • Preservative issues4 rate1 • Potential for infection necessitates need for regular changing of lines5 • Relief of bronchospasm1 1. Harvey. Am J Crit Care.1996;5:7-16. 2. Lerch, Park. Br Med Bull. 1999;55:90. 3. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:435. 4. Propofol [package insert]. 5. Prielipp et al. Crit Care Clin. 1995;11:986.
  • 31. The Stress Response and Immunomodulation In Sedated ICU Patients
  • 32. Crit Care Med 2006 Vol.34 #2 453-460
  • 33. Sedation May affect Patient outcome through affect on cytokine release
  • 34. Propofol with EDTA There is a difference
  • 35. Herr et al, Intensive Care Medicine; 2000; 26 In a surgical ICU Serious Adverse Events 25 vs 8% Mortality 17.5 vs 2% 11 deaths in plain propofol vs 1 among the propofol with EDTA
  • 36. Propofol with EDTA Boost lipoidal antixidant defenses in tissue Chelator of heavy metals Iron is important for cytokine secretion Decrease Trace elements Decreased Free Radicals
  • 37. What we wish to investigate Do different drugs affect levels of cytokines released by the lung Can they protect the compartment of the lung from systemic cytokine release Do they prevent the release of cytokines from the lung
  • 38. How does Propofol with EDTA Affect Cytokine Levels Erasmus MC Rotterdam Papadakos, Lachmann Haitsma ATS 2006
  • 39. Propofol with EDTA affect on electrolytes:
  • 40. Dexmedetomidine
  • 41. Physiology of alpha receptor
  • 42. Peripheral Receptors 2 A 2A B 2B 2A
  • 43. Central Sites of Action: 2 Agonists Sedation Anxiolysis Sympathetic inhibition Analgesia
  • 44. Agonists 2 Dexmedetomidine Clonidine Selectivity: 2: 1 Selectivity: 2: 1 1620:13 200:11 t1/2 10 hrs1 t1/2 2 hrs3 PO, patch, epidural2 Intravenous3 Antihypertensive1 Sedative-analgesic3 Analgesic adjunct1 Primary sedative IV formulation not Only IV 2 available for available in US use in the US
  • 45. Clinical Effects of 2 Agonists Sedation/hypnosis1 Anxiolysis1 Analgesia1 Decreased sympathetic activity1 Decreased BP and HR2 Vasoconstriction at high doses1 Kamibayashi, Maze. Anesthesiology. 2000;93:1345-1349. 2. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:426-453.
  • 46. Dexmedetomidine: Indications  Sedation of initially intubated and MV patients during treatment in the ICU Contraindications  Caution in patients with advanced heart block Drug interactions  Vagal effects can be counteracted by IV administration of anticholinergic agents Disease effecting clearance  Clearance is lower in patients with hepatic impairment
  • 47. Dexmedetomidine Advantages Limitations • Has sedative, analgesic, • May reduce HR and BP (caution in and anxiolytic effects1 hypovolemia, shock, and heart block)4 • Respiratory stability2 • Potentiates effects of opioids, • Predictable hemodynamic sedatives and anesthetics4 response1 • Dry mouth4 • Arousable and oriented patient3 • Vasoconstriction at high dose4 • No need to discontinue before extubation4 • Antishivering5 1. Aantaa et al. Drugs of the Future. 1993;18:49-56. 2. Frangoulidou et al. In: Redefining Sedation. 1998:40-50. 3. Mantz, Singer. In: Redefining Sedation. 1998:23-29. 4. Precedex™ [package insert]. 5. Kamibayashi, Maze. Anesthesiology. 2000;93:1345-1349.
  • 48. Other interesting Drugs
  • 49. COX – 2 Inhibitors Prostaglandin Modulation
  • 50. Recent Data: May have important role in treatment of Septic Patients Normalization of Endotoxin Attenuation of macrophage depression of hematopoietic proliforation Augmentation of white cell count Shoup M et al J Trauma Inj Inf Crit Care 1998;45:215-219
  • 51. Several Studies in Burn Injury Highly affective in murine burn injury 80% increase in COX-2 protein compared to control at 4 hours post injury
  • 52. COX-2 Drugs have however been recalled for increased Cardiac Risk
  • 53. Neurontin Increases GABA Levels
  • 54. Neurontin Decreases requirement of narcotics Decreases Alcohol Withdrawal
  • 55. We now use this Drug commonly in Withdrawal Syndromes
  • 56. The Fine Balance in Patient Comfort
  • 57. The Fine Balance in Patient Comfort Anxiety Agitation Hypertension Tachycardia Arrhythmias Myocardial ischemia Wound disruption Patient injury
  • 58. The Fine Balance in Patient Comfort Depersonalization Delayed emergence Delayed weaning Pressure injury Venous stasis Muscle atrophy Increased cost
  • 59. Sedation Modulates immune system Provides comfort Modulates Length of Stay Affects health care costs