Brain Resuscitation
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A 44-year-old woman collapsed at work and received bystander CPR and defibrillation. She was intubated by EMS and taken to the ED with a pulse but exhibiting seizure activity and a minimally responsive neurological exam. The document then discusses therapeutic hypothermia for cardiac arrest survivors including how to induce and maintain cooling, potential complications, and prognostic factors.
Brain Resuscitation
- 2. 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
- 3. • • • • 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
- 4. LITTLE ABILITY TO STORE SUBSTRATES 4
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- 6. • AT BEST - standard closed-chest CPR generates 20% to 30% normal cardiac output • 20% normal CBF is required to maintain neuronal viability 6
- 7. 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
- 8. VF/VT PEA/asyst 80 70 60 50 40 30 20 10 0 MOF Intensive care medicine, 2004 Neurologic complic. shock
- 9. 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.
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- 11. Interruption of Cerebral Blood Flow Hypoxia-Ischemia Resuscitation Reperfusion Injury 12
- 12. • 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
- 13. 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
- 14. • 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
- 15. • Uncontrolled seizure activity • Hypotension/hypoperfusion – Postresuscitation syndrome – ICP crisis – Autoregulatory failure • • • • Fever Re-arrest Hypoxia Derangements of glucose metabolism Neurology 2008;72:744 16
- 16. • “No flow” affects the most metabolically active areas of brain – Cortex – Basal ganglia – Cerebellum • “Low flow” affects the watershed areas between vascular territories 17
- 17. Shrunken eosinophilic neuron (anoxic neuron) Pseudolaminar necrosis http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html 18
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- 19. • ↓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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- 22. RAPID INITIATION OF NEUROPROTECTIVE THERAPY IS THE MOST IMPORTANT INTERVENTION 23
- 23. 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
- 24. 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
- 25. 26 Seder. Curr Opin Neurol Neurosurg. 2008;8:508-517.
- 26. Anesthesia and Analgesia 1959;38 (6): 423 27
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- 28. WARM COLD 29
- 29. 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
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- 31. N Engl J Med 2002;346:549-56 32
- 32. • 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
- 33. Risks • Infections • Bleeding • Need for sedation Benefits • • • Strongly neuroprotective Decreased mortality Better neurological outcome 34
- 34. • “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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- 36. 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
- 37. 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
- 38. • 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
- 39. 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
- 40. 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
- 41. • More bleeding complications • More infections • But…a strong trend toward lower mortality Wolfrum. Crit Care Med. 2008;36:1780-1786. 42
- 42. • 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
- 43. 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-.
- 44. • 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
- 45. • • • • 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
- 46. • 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
- 47. • 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.
- 48. 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.
- 49. • 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
- 50. • 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.
- 51. • 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
- 52. • 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
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- 54. (induced cooling to eliminate deficits) 55
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- 56. • 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.
- 58. • 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
- 59. • • • • • • • 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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- 61. • 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
- 62. • 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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- 64. Dr. Rashid Abdulla Abuelhassan, MBBS Resident Emergency Medicine – KFMC program King Fahad Medical City 65