Brain Resuscitation

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Brain Resuscitation

  1. 1. A previously healthy 44-year-old woman collapses at work after complaining of chest tightness – 3 min: bystander CPR initiated – 7 min: defibrillation provided by bystanders using an automated external defibrillator (AED) – 9 min: EMS arrives, intubation performed • Pulse present • Generalized seizure activity noted • Lorazepam 2 mg administered – In the ED • • • • Does not open eyes or follow commands Extensor motor response to pain Pupils minimally reactive at 3 mm Corneal and weak gag reflexes present 2
  2. 2. • • • • Triage of the cardiac arrest survivor Best outcome after ROSC Role of therapeutic hypothermia Performing therapeutic hypothermia – How to cool – Managing the complications of therapy • Outcome and prognosis 3
  3. 3. LITTLE ABILITY TO STORE SUBSTRATES 4
  4. 4. 5
  5. 5. • AT BEST - standard closed-chest CPR generates 20% to 30% normal cardiac output • 20% normal CBF is required to maintain neuronal viability 6
  6. 6. CBF with a GOOD CPR is inversely proportional to arrest time – CPR in 2 min à CBF to 50% normal – CPR after 5 min à CBF 28% normal – CPR after 10 min à CBF = 0% 7
  7. 7. VF/VT PEA/asyst 80 70 60 50 40 30 20 10 0 MOF Intensive care medicine, 2004 Neurologic complic. shock
  8. 8. Seder. Cause of death in patients surviving out of hospital cardiac arrest but dying during hospitalization. Proceedings of the American Thoracic Society 2007; 4:A792. Oddo. Effect of the implementation of a therapeutic hypothermia protocol on neurological outcome after outof-hospital VF/VT arrest. Crit Care Med. 2006;34:1865.
  9. 9. 11
  10. 10. Interruption of Cerebral Blood Flow Hypoxia-Ischemia Resuscitation Reperfusion Injury 12
  11. 11. • Pre-arrest ↓Glu à devastating neurologic outcome • Pre-arrest ↓O2 à worse outcome after ischemia • Arrest interval (pulselessness before CPR) • CPR interval • Others: Prearrest ↓Hb, ↓BP 13
  12. 12. With Low flow (10-15% of NBF) • 15 sec à LOC • 1 minà cessation of brainstem function (agonal respirations, fixed pupils) • 4-5 min à depletion of glucose and ATP (anaerobic metabolism) • 4-6 min à irreversible damage • Tolerate ~15 min of ischemia for total brain damage NBF= Normal Blood Flow 14
  13. 13. • Primary Injury ( Energy failure ) • Secondary injury – – – – – cytotoxic edema Lipid peroxidases damage membranes Neurotransmitter release causes excitotoxicity Activation of apoptotic pathways Microvascular thrombosis REPERFUSION INJURY 6 72h 15
  14. 14. • Uncontrolled seizure activity • Hypotension/hypoperfusion – Postresuscitation syndrome – ICP crisis – Autoregulatory failure • • • • Fever Re-arrest Hypoxia Derangements of glucose metabolism Neurology 2008;72:744 16
  15. 15. • “No flow” affects the most metabolically active areas of brain – Cortex – Basal ganglia – Cerebellum • “Low flow” affects the watershed areas between vascular territories 17
  16. 16. Shrunken eosinophilic neuron (anoxic neuron) Pseudolaminar necrosis http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html 18
  17. 17. 19
  18. 18. • ↓ATP à↑ intra Ca ++ àact. Phospholipase à # phospholipids à ↑ FFA ( arachidonic acid ) + act. Proteolytic enz. à hydrolyze ATP to AMP à ↑ hypoxanthine and other free radicals • ↑ extra celluar Excitatory neurotransmitters, glutamate and aspartate à exacerbating injury • ↑ excitatory amino acids àNmethyl-D-aspartate receptors, ↑ intra calcium + ↓ K to the à excitatory amino acids receptors • Total cerebral reperfusion takes up to 12 hours after systemic reperfusion occurs 20
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  21. 21. RAPID INITIATION OF NEUROPROTECTIVE THERAPY IS THE MOST IMPORTANT INTERVENTION 23
  22. 22. 1. Support the heart: • • acute coronary thrombosis à PCI shock develops ( Revascularization, Aortic counterpulsation device, Vasopressor support) 2. Protect the brain: • • 2nd neurological injury à therapeutic hypothermia Adequate cerebral perfusion 24
  23. 23. Cardiac assessment – Rhythm stabilization – BP stabilization – Evaluation and treatment of the underlying cause of the cardiac arrest – Consideration of urgent coronary angiography and revascularization Neurological assessment – Severity of HIE – CT head to rule out intracranial bleed – Institution of therapeutic hypothermia – EEG monitoring if appropriate – Maintenance of adequate cerebral blood flow 25
  24. 24. 26 Seder. Curr Opin Neurol Neurosurg. 2008;8:508-517.
  25. 25. Anesthesia and Analgesia 1959;38 (6): 423 27
  26. 26. 28
  27. 27. WARM COLD 29
  28. 28. 1. Good Cerebral Performance : Conscious, alert, able to work and lead a normal life. May have minor psychological or neurological deficits 2. Moderate Cerebral Disability : Conscious. sufficient cerebral function for part-time work in sheltered environment or independent activities of daily life (dressing, traveling by public transportation, and preparing food). 3. Severe Cerebral Disability : Conscious. Dependent on others for daily support because of impaired brain function (in an institution or at home with exceptional family effort). 4. Coma/Vegetative State : Not conscious. Unaware of surroundings, no cognition. No verbal or psychological interactions with environment. 5. Death : Certified brain dead or dead by traditional criteria. Booth. JAMA. 2004;291:870. 30
  29. 29. 31
  30. 30. N Engl J Med 2002;346:549-56 32
  31. 31. • Australian randomized clinical trial conducted 1996-1999 • Randomized on alternating days to TH or routine care • TH: good outcome 49%, routine care good outcome: 26% (p=0.046) 33
  32. 32. Risks • Infections • Bleeding • Need for sedation Benefits • • • Strongly neuroprotective Decreased mortality Better neurological outcome 34
  33. 33. • “Unconscious adult patients with ROSC after OHCA should be cooled to 32°C to 34°C (89.6°F to 93.2°F) for 12 to 24 hours when the initial rhythm was VT/VF • “Similar therapy may be beneficial for patients with non-VF arrest out of hospital or for inhospital arrest ” • In-hospital arrest 35 Circulation 2010;111:IV-84-IV-88
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  35. 35. Clinical criteria for therapeutic hypothermia – <8 hr since ROSC. – Encephalopathy is present (unable to follow verbal commands) – no life-threatening infection or bleeding. – Aggressive care is warranted and desired by the patient or the patient’s surrogate decision-maker. 37
  36. 36. INDUCTION • Rapidly bring the temperature to 32°-34°C • Sedate with propofol or midazolam during TH • Paralyze to suppress heat production MAINTENANCE • Maintain the goal temperature at 33°C • Standard 24 hours • Suppress shivering DE-COOLING (REWARMING) • Most dangerous period: hypotension, brain swelling, • Goal is to reach normal body temperature over 12-24 hours • Stop all sedation when normal body temperature is achieved 38
  37. 37. • Cold fluid – 30 cc/kg LR or 0.9% NS over 30 minutes • 2.0°-2.5°C temperature reduction • EXPOSE THE PATEINT • Monitor core temperature – Bladder, esophagus, or central venous/pulmonary arterial • Ice packs and cooling mats – Effective, but difficult to control rate of temperature change Overcooling is dangerous 39
  38. 38. External (surface cooling) systems • Hydrogel heat exchange pads • Cold water circulating through plastic “suit” • Cold water immersion – awaiting safety data Invasive (catheter-based) systems • Heat exchange catheter in SVC or IVC • Plastic or metallic heatexchange catheter Holzer. New Engl J Med 2010;363:1256-64 40
  39. 39. INDUCTION • • • Traditional cooling – Inexpensive and available – Effective – Very high incidence of overcooling Noninvasive cooling devices – Safe – no insertion, lots of clinical experience – Effective, unless patients very heavy – Expensive Invasive cooling devices – Most effective at tight temperature control – Better for heavy patients – Insertion dangers: thrombosis, infection, placement-related injury – Expensive Hoedemaekers. Crit Care. 2007;11:R91. MAINTENANCE 41
  40. 40. • More bleeding complications • More infections • But…a strong trend toward lower mortality Wolfrum. Crit Care Med. 2008;36:1780-1786. 42
  41. 41. • Maintain physiological homeostasis – Adequate blood pressure and cerebral perfusion – Head Position “ NO EVIDENCE YET ABOUT ELEVATION “ – Normal glucose level (100-140) – Normal electrolytes – Recognize and treat seizures – Suppress shivering – Adequate sedation TO IMMOBILIZ – Adequate oxygenation – Optimal volume status and cardiac output 43
  42. 42. At 24 hours after initiation of cooling, initiate rewarming to a target temperature of 36.5° C at a rate of 0.15°/hr. • Vasodilation causes hypotension – May require several liters IVF replacement • More shivering during this phase • Increased ICP and decreased CPP – Maintain adequate MAP! • Watch for hyperkalemia – Can be problematic in patients with renal failure Discontinue paralytics at the onset of warming. Control shivering with sedation, narcotics, and surface counter Warming - Lighten sedation as tolerated as rewarming 44 progresses-.
  43. 43. • Discontinue endovascular temperature control device after 48hours. (May use the device to maintain normothermia after rewarming is complete until it is removed.) • Remove or minimize sedation to allow neurologic evaluation before 72 hours to allow the best possible clinical prognostication at that time point. Neurology consultation recommended. 45
  44. 44. • • • • INFECTION ( High incidence of pneumonia) COAGULOPATHY (Mild platelet dysf. and prolonged PT, aPTT) HYPOKALEMIA (K+ may drop upto 1mg/dL during induction ) ARRHYTHMIA – Almost all patients have asymptomatic bradycardia – VT/VF: no significant increase with therapeutic hypothermia • If VT/VF, verify no overcooling or hypokalemia • DECREASED DRUG METABOLISM – At least a 7-8% decrease per degree below 36°C • Shivering 46
  45. 45. • Incidence of pneumonia 30%-50% • Neutrophil oxidative killing, T-cell function impaired at low temperature • Fever and inflammation exacerbate brain injury • When pneumonia or aspiration is suspected, consider: – Cefuroxime 1500 mg x 2 doses, or – Ampicillin/sulbactam x 3 days Sirvent. Am J Respir Crit Care Med. 1997;155:1729. Aquarolo. Intensive Care Med. 2005;31:510. 47
  46. 46. • systemic metabolic rate – ↑CO2 production – ↑ O2 consumption • cerebral oxygen consumption Prevent shivering with sedation and nondepolarizing paralytic e.g. Vecuronium bolus 0.1mg/kg prn BSAS >2. Bolus in ED. Bolus or drip in ICU Badjatia. Metabolic impact of shivering during therapeutic temperature modulation: the Bedside Shivering Assessment Scale . 48 Stroke, 2008, In Press.
  47. 47. Up to 50% patients have abnormal movements – Myoclonus (Marker of severe brain injury & poor prognosis) – Seizures (↑cerebral oxygen demand by 300% to 400%) EEG of OHCA survivor with multiple generalized epileptiform discharges discovered after therapeutic hypothermia • Convulsive seizures • Nonconvulsive seizures ( 20%, need continuous EEG 49 Hovland. Resuscitation. 2006;68:143. | Claassen. Neurology. 2004;62:1743.
  48. 48. • BLOOD GLUCOSE CONTROL - normoglycemia and mild insulin-induced hypoglycemia have been shown to improve neurologic function after focal and global ischemia. - insulin itself have a neuronal growth factor–like effect that may theoretically also be neuroprotective - BUT BECAUSE OF THE RISK OF HYPOGLYCEMIA POST ARREST 144-180 mg/dL • BLOOD PRESSURE MANIPULATION – Map ≥ 65 mmHg – Normovolemic hemodilution of hematocrit to 20-25% - promotes homogenous cerebral perfusion – Anticoagulation with low-molecular weight heparins – Low-dose thrombolytics to prevent microvascular fibrinolytic clotting • SpO2 CONTROL ≥ 94%, Quantitative waveform capnography 35-45 mmHg. 50
  49. 49. • EEG • – Nonconvulsive seizure activity is common – Continuous EEG preferred – Sedation with propofol/midazolam will suppress Bispectral index (Verify no awareness during hypothermia) • Systemic oxygen utilization (Maintain SvO2 > 60%) • Brain oxygen extraction (maintain SjvO2 > 55%) • Intracranial pressure (↑ ICP in 25% survivors, CPP< 50 in 56%) • Intracranial metabolism ( brain glu OR cerebral lactate/pyruvate ratio ) Gueugniaud. Resuscitation. 1990;20:203. Gueugniaud. Resuscitation 1991;17:392. Lemiale. Resuscitation. 2008;76:17. 51 Intensive Care Med. 1991;17:392-398.
  50. 50. • Neuro exam (24 h, 72 h, 7 day ) • Serum markers - Neuron-specific enolase - S100B protein • • • • EEG Somatosensory evoked potentials (SSEPs) Myoclonic status epilepticus MRI “Current indicators of prognosis are derived from patients not treated with hypothermia ” Wijdicks. Neurology. 2006;67:203. 52
  51. 51. • Drugs that build up during hypothermia may confound prognosis! • Verify that sedation, analgesia, and paralytics are no longer present! Wijdicks. Neurology. 2006;67:208. 53
  52. 52. 54
  53. 53. (induced cooling to eliminate deficits) 55
  54. 54. 56
  55. 55. • 125 patients randomized to prehospital vs ED cooling • Good outcome in VT pts cooled in the field – 20/29 vs 10/22 (P=0.15) • No safety concerns • Average temp at ED arrival differed by only 1ºC 57 Circulation. 2007;115(24):3064-70.
  56. 56. www.med.upenn.edu/resuscitation/hypothermia/protocols.shtml 58 58
  57. 57. • Cardiac Arrest • Hepatic encephalopathy with cerebral edema • Near hanging • Neonatal asphyxia • Elevated ICP, all causes • Severe (Hunt and Hess IV-V) SAH with cerebral edema 59
  58. 58. • • • • • • • Hydrogen peroxide Iron (from Fenton reaction) Activated neutrophils Clotting derangement Mannitol increases cerebral blood flow and is a good free-radical scavenger, but optimal doses have not been determined Etomidate is a carboxylated imidazole that depresses cerebral metabolism without cardio-toxicity, but no human studies exist confirming its usefulness Corticosteroids have been shown to stabilize vascular membranes, prevent astrocyte swelling, and improve intracranial compliance, no CLINICAL benefit has been shown • • • • • • Catalase Superoxide dismutase Deferoxamine Antineutrophil antibody Heparins, thrombolytics Allopurinol • HYPERTENSIVE FLUSH – 1 to 5 minutes of MAP >130 mm Hg – Flushes toxins out of cerebral circulation 60
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  60. 60. • Therapeutic hypothermia urgently initiated – Sedated with propofol, paralyzed with vecuronium – Cooled to 33°C over 4 hr using cold mat and ice packs – Rewarmed after 18 hr • No further seizure activity • Coronary angiography revealed spontaneous LAD dissection – Conservative management with antiplatelet therapy • Discharged with short-term memory deficits and emotional lability • Cognitively normal at 6 months after ROSC 62
  61. 61. • Neuronal injury is a dynamic process that continues for hours or days after an ischemic insult to the brain. • Hypotension, hypoperfusion, and hypoxia must be avoided during brain resuscitation. • Hyperthermia, hyperglycemia, and seizures should be treated • promptly during brain resuscitation. • Comatose survivors of out-of-hospital cardiac arrest should be rapidly cooled in the ED and maintained at 33° C in an ICU setting for 12 to 24 hours after resuscitation. 63
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  63. 63. Dr. Rashid Abdulla Abuelhassan, MBBS Resident Emergency Medicine – KFMC program King Fahad Medical City 65

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