STROKE SUBARACHNOID HEMORRHAGE AND HYPOTHERMIA FOR CARDIAC ARREST

STROKE, SUBARACHNOID HEMORRHAGE AND HYPOTHERMIA FOR CARDIAC ARREST -Andy Rekito Dallas Presbyterian Hospital Internal Medicine Resident Lecture August 27, 2009 Samir Shah, MD Neurology Consultants of Dallas

Quick Stroke Facts - 2009 FACT: About 795, 000 Americans suffer a new or recurrent stroke each year. That means, on average, a stroke occurs every 40 seconds. FACT: Stroke kills nearly 150, 000 people each year. That’s about 1 of every 17 deaths. It remains the #3 cause of death behind heart disease and cancer. An American dies of a stroke every 3 minutes. FACT: Americans will pay about $68. 9 billion in 2009 for stroke related medical costs and disability. American Heart Association. Heart Disease and Stroke Statistics — 2009 Update. Dallas, Tex. : American Heart Association; 2009.

FACT: Prevalence of stroke in the US is 6. 5 million people (2005). Stroke is a leading cause of serious disability. Prevalence of Stroke by Age and Sex NHANES: 1999 -2002 Source: CDC/NCHS and NHLBI.

Definitions – So We’re All on the Same Page An established and universally accepted definition for stroke by the World Health Organization is "acute neurologic dysfunction of vascular origin. . . with symptoms and signs corresponding to the involvement of focal areas of the brain. " Stroke. 1989 Oct; 20(10): 1407 -31.

TIA BEFORE Stroke has also been described as the rapid onset of neurological deficits that persist for at least 24 hours and are caused either by intracerebral or subarachnoid hemorrhage or by partial or complete blockage of a blood vessel supplying or draining a part of the brain, leading to the infarction of brain tissue. A stroke is distinguished from a transient ischemic attack (TIA) by the fact that neurological deficits in TIAs clear spontaneously within 24 hours.

NOW Clinical, experimental, and imaging data have shown that the 24 -hour criterion is inaccurate in suggesting an absence of brain injury and often results in uncertainty — on the part of patients and practitioners alike — about what to do when a TIA occurs. In short, the 24 -hour definition of TIA is outdated, confusing, and potentially misleading…

NEW DEFINITION a TIA is a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction. The corollary is that persistent clinical signs or characteristic imaging abnormalities define infarction — that is, stroke (N Engl J Med 2002; 347: 1713 -1716).

THEREFORE The development of symptoms of acute brain ischemia constitutes a medical emergency and transient symptoms do not exclude the possibility of associated brain infarction. TIME=BRAIN Now, let’s talk about how we evaluate and manage stroke. We will first focus on ischemic stroke…

Consult for a 68 year-old man that has new right-sided weakness and is “talking funny. ” It started a few hours ago.

What Else Could It Be? Stroke Mimics §Abcess §Subdural and Epidural Hematomas §Tumors §Giant aneurysms §Vascular malformations (AVMs) §Hypertensive Encephalopathy §Encephalitis/cerebritis §Seizure/Todd’s paralysis §Migraine §Metabolic. Hypoglycemia/Hyperglycemia §Cerebral venous thrombosis §Psychogenic §Deficit from previous stroke made worse by general medical condition

Quickly Narrow the Differential With Imaging When presented with acute onset neurological dysfunction, stroke should always be on your differential and one of the first goals in the evaluation is differentiating hemorrhagic stroke from ischemic stroke All patients, with few exceptions should undergo STAT cranial imaging. In other words, GET A NON-CONTRAST HEAD CT (MRI if available STAT).

What Else to Ask for Over the Phone? ALL stroke patients should get immediate §CBC with platelets §Bedside glucose §PTT, PT (INR) §Chem 7 (Chem 10) §EKG, continuous cardiac monitoring §IV access, 0. 9% NS (no glucose) §NPO §? Troponin

What’s the Cardiac Workup for? §Not infrequently, patients with acute cerebral ischemia have concomitant acute myocardial ischemia §In addition cardiac evaluation helps determine etiology of the cerebral event §Several small studies have shown that patients with TIA and stroke have a high prevalence of asymptomatic CHD. These studies suggest that 20% to 40% of stroke patients may have abnormal tests for silent cardiac ischemia. § 2% to 5% of patients with acute ischemic stroke have fatal cardiac-related events in the short term after stroke. Circulation. 2003; 108: 1278.

Other Acute Studies §Urine pregnancy test §Urine toxicology §Hypercoagulable screen §CXR §Type and Screen

What are the risk factors for ischemic stroke?

Risk Factors for Ischemic Stroke Risks that cannot change §Age §Prior stroke or MI §Gender §Heredity/Ethnicity Risks that can be controlled or treated §High Blood Pressure §Smoking §Diabetes Mellitus §Prior TIA §Atrial Fibrillation §Other Heart Disease §Carotid Artery Disease or atherosclerosis in another arterial bed §Certain blood disorders §Sickle Cell Disease §Hypercholesteremia §Physical Inactivity, Obesity §Excessive alcohol §Illicit drugs §HRT

Estimated 10 -Year Stroke Risk in 55 Year-Old Adults According to Levels of Various Risk Factors - Framingham Heart Study Systolic BP Diabetes Cigarettes Prior Atrial Fib. Prior CVD A 95 -105 No No B 130 -148 No No C 130 -148 Yes No No No Source: Stroke 1991; 22: 312 -318. D 130 -148 Yes No No E 130 -148 Yes Yes No F 130 -148 Yes Yes

Estimates of Vascular Event Rates for Persons With Various Features of Atherothrombotic Cerebrovascular Disease Cerebrovascular Features General elderly male population Annual Probability(%) Stroke Vascular Death Major stroke 0. 6 1. 3 2. 2 3. 7 6. 1 9. 0 ------3. 4 3. 5 2. 3 3. 2 3. 5 Symptomatic carotid stenosis >70% 15 2. 0 Asymptomatic carotid disease Transient monocular blindness Transient ischemic attack Minor stroke Stroke. 1997; 28: 1507 -1517.

Risk Factors for Intracerebral and Subarachnoid Age Women Hemorrhage Race/ethnicity ++ indicates strong evidence; +, moderate positive evidence; ? , equivocal evidence; –, moderate inverse evidence; and 0, no relation. ICH SAH Hypertension ++ + ++ Cigarette smoking Heavy use of alcohol Anticoagulation Amyloid angiopathy Hypocholesterolemia Oral Contraceptives ? ++ ++ ? ++ 0 ? 0 0 ? Stroke. 1997; 28: 1507 -1517. + +

What Else Will You Ask? §Exact time of onset or last time the patient was last seen at baseline §History of seizures? Any seizure activity prior to onset of symptoms §Migraine headaches §Trauma or neck injury in the preceding days §Recent illnesses §Vomiting, change in level of consciousness §Allergies §Medications §Associated symptoms (? chest pain)

What to Do on Exam? §ABCs first §Vital Signs: especially notice BP and don’t forget weight §Cardiac, vascular, extremity examination §Directed and focused exam based on history - NIHSS

NIH Stroke Scale – focuses on 5 major areas § Level of consciousness § Visual function § Motor function § Sensation and neglect § Cerebellar function NIHSS is easily performed, reliable and valid. It is strongly associated with outcome with and without thrombolytics, and can predict those patients likely to develop hemorrhagic complications from thrombolytic use.

www. ferne. org

Goal of History and Physical Is to Localize Lesion and Its Vascular Supply Knowing the location of the lesion and its vascular supply allow you to begin to speculate on the underlying pathophysiology as different stroke mechanisms characteristically affect certain cerebral vessels.

Blood Supply of the Brain Anterior Circulation: Two ICAs which divide into ACA and MCA. Each ICA supplies roughly two fifths of the brain by volume. Posterior Circulation: Two Vertebrals which join to form the Basilar which then forms PCAs. The posterior circulation supplies roughly one fifth of the brain.

Source: Loyola University Neurovascular Tutorial

Four Divisions of the Vertebral Artery

Stroke Mechanisms Can simplify stroke mechanisms or etiologies into 5 categories ISCHEMIA 1. Thrombosis (60%) 2. Embolism (20%) 3. Decreased Systemic Perfusion HEMORRHAGE 4. Intracerebral Hemorrhage (12%) 5. Subarachnoid Hemorrhage (8%)

Common Stroke Mechanisms The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy STROKE 85% 15% Ischemic Stroke 20% Atherosclerotic Cerebrovascular Disease (“Large Artery”) 25% Penetrating Artery Disease (“Lacunes”) Primary Hemorrhage §Intraparenchymal §Subarachnoid 20% Cardiogenic Embolism §Atrial Fibrillation §Valve Disease §Ventricular Thrombi Hypoperfusion Arteriogenic Emboli §Many Others 30% Cryptogenic Stroke 5% Other, Unusual Causes §Prothrombotic States §Dissections §Arteritis §Migraine/vasospasm §Drug Abuse §Many More

You are done thinking of stroke mechanisms and you are almost at the ER when you get paged that the patient has a blood pressure that is “sky high” at 182/102 and that he is going to give him some oral clonidine to take care of it. What should you tell her?

Cerebral Autoregulation: It may not be working DO NOT TREAT BP IN ACUTE ISCHEMIC STROKE UNLESS BP>200 -220/100 -120

The Patient Encounter The patient’s daughter is at the bedside. She tells you that her dad had some right sided weakness yesterday that resolved in 25 minutes and that’s why she brought him in. She says his new symptoms on the right started in the hospital just 45 minutes ago. She says he has some kind of heart problem but hasn’t been taking any of his medications. She’s not sure what he was taking and is worried about his talking.

You examine the patient and with your excellent neurological skills quickly realize that his “talking funny” is actually an expressive aphasia and that he has a right facial droop, a left gaze preference, 2/5 right arm weakness and 4/5 right leg weakness. All the labs you wanted are unrevealing, and the EKG shows evidence of LVH, but otherwise ok. The nurse tells you that the monitor went off a little while ago for a rapid, irregular heart rate. You are astute enough to realize that this guy is in the usual 3 hour window for acute stroke therapy and decide to go look at the CT scan.

Now what?

Hyperdense MCA Sign

Insular Ribbon Sign Loss of Gray-White Junction

The New England Journal of Medicine ©Copyright, 1995, by the Massachusetts Medical Society Volume 333 DECEMBER 14, 1995 Number 24 TISSUE PLASMINOGEN ACTIVATOR FOR ACUTE ISCHEMIC STROKE THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE rt-PA STROKE STUDY GROUP* IV t-PA FDA approved for use in acute ischemic stroke < 3 hours from onset in 1996. As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales.

The Use of IV t-PA Eligibility §Age 18 or older §Clinical diagnosis of ischemic stroke causing a measurable neurological deficit §Time of symptom onset well established to be less than 180 minutes before treatment would begin (most now say less than 270 minutes)

Contraindications §Evidence of intracranial hemorrhage on pretreatment CT §Clinical presentation suggestive of SAH, even with normal CT §Active internal bleeding §Known bleeding diathesis, including but not limited to: Platelet count < 100, 000/mm 3 Patient has received heparin within 48 hours and has an elevated a. TT (greater than upper limit of normal for laboratory) Current use of oral anticoagulants or recent use with an elevated prothrombin time > 15 seconds (INR>1. 7) §Within 3 months any intracranial surgery, serious head trauma, or previous stroke §On repeated measurements, systolic blood pressure greater than 185 mm. Hg or diastolic blood pressure greater than 110 mm. Hg at the time treatment is to begin, and the patient requires aggressive treatment to reduce blood pressure to within these limits §History of intracranial hemorrhage §Known AVM or aneurysm

Warnings §Only minor or rapidly improving stroke symptoms §History of GI or Urinary tract hemorrhage within 21 days §Recent arterial puncture at a noncompressible site §Recent lumbar puncture §Abnormal blood glucose (<50 or >400 mg/d. L) §Post myocardial infarction pericarditis §Patient was observed to have a seizure at the same time the onset of stroke symptoms were observed

Other relative contraindications (not NINDS) §Bacterial endocarditis or CNS lesion likely to hemorrhage after t-PA §Significant trauma within 3 months §CPR with chest compressions within past 10 days §Major surgery within past 14 days, minor surgery within past 10 days §Pregnant (up to 10 days postpartum) or nursing woman §Life expectancy < 1 year from other causes §Peritoneal dialysis or hemodialysis

Additional exclusion criteria for extended time window §Age >80 §NIHSS >25 §Any oral anticoagulant use §History of both previous stroke and diabetes del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr; on behalf of the American Heart Association Stroke Council. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009; 40: 2945 -8.

What to Tell the Family After you determine your patient’s eligibility based on NINDS criteria, you go and talk with the daughter about the risks and benefits What are the risks? Bleeding and its complications (6% vs <1%) and allergic reaction (1 to 2%) She asks what is the benefit? Patient’s treated with t-PA were at least 30% more likely to have minimal or no disability at three months despite increased risk of hemorrhage. ARR=16%, NNT=6 (Similar to CEA for symptomatic carotid stenosis) (14 for extended time window)

Distribution of outcomes on NIH Stroke Scale (NIHSS) (top), Barthel index (middle), and Rankin scale (bottom) in parts 1 and 2 combined of the NINDS rt. PA Stroke Study Grotta, J. C. Stroke 1999; 30: 1722 -1728 Copyright © 1999 American Heart Association

You write to administer t-PA at 0. 9 mg/kg (max 90 mg) infused over 60 minutes with 10% of the dose administered as a bolus over 1 minute. You ensure that BPs have been consistently less than 185/110 prior to administration. You also make sure that no other antithrombotics or anticoagulants will be given in the next 24 hours and write for a Head CT in 24 hours. You also write orders for ICU admission as you know the patient will need close BP monitoring over the next 24 hours per NINDS protocol to maintain BP<180/105.

Let’s Get Serious Only a small fraction of ischemic strokes (likely 1 -3%) are treated with IV t-PA, mostly because patients arrive to medical attention after the 3 hour time window. At places without 24 hour neurointerventional capability, what do we do for a stroke acutely when the patient is not eligible for IV t-PA?

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy This CT has a clear hypodensity. This patient is not eligible for IV-t. PA given days duration of symptoms. In patients that do not receive thrombolysis: In the acute period, all ischemic stroke patients should receive 160325 mg of ASA within 48 hours of onset. (some may advocate acute anticoagulation for certain stroke subtypes).

Absolute effects in CAST and IST of early use of aspirin in 40 000 randomized patients with suspected acute ischemic stroke Chen, Z. et al. Stroke 2000; 31: 1240 -1249 For every 1000 acute strokes treated with ASA, 7 fewer early recurrent ischemic strokes were observed and 13 fewer patients will be dead or dependent at 6 months at the expense of two or more ICHs. Copyright © 2000 American Heart Association

Admit the Patient All stroke patients should be admitted to the hospital for observation, diagnostic evaluation, and determination of treatment for secondary stroke prevention. All patients should be admitted to a stroke unit or when not available to a cardiac monitored bed with staffing to perform frequent neurological checks. As already discussed, thrombolysis patients need ICU care.

Where would you admit this patient?

How about this patient?

Let’s say the patient’s symptoms resolved by the time you got there and he now feels fine and wants to go home

PATIENT IS AT HIGH RISK AND NEEDS TO BE ADMITTED TIAs carry a substantial short term risk of stroke, hospitalization for cardiovascular events, and death. Of 1, 707 TIA patients evaluated in an emergency department of a large health care plan, 180 patients or 10 percent developed stroke within 90 days. 91 patients or 5 percent did so within 2 days. Predictors of stroke: more than 60 years of age, DM, focal symptoms of weakness or speech impairment, and TIA lasting longer than 10 minutes (JAMA 2000; 284: 2901 -6).

Evaluation During Admission 1. 2. 3. 4. 5. 6. 7. Labs: LFTs, fasting lipid profile and glucose, QID bedside glucose and SSI. Consider Hypercoagulable workup, ESR, ANA, hs. CRP, Hb. A 1 c, homocysteine, LP Imaging: All patients should have MRI imaging of brain and vascular imaging of head and neck. Consider TCD, PET, SPECT or other study based on clinical findings Echocardiogram: all patient should have echo – TTE when h/o of CAD or abnormal EKG or lacunar event. All others TEE (more sensitive and cost effective in evaluation of stroke. Ann Intern Med. 1997 Nov 1; 127(9): 775 -87. ) Rehabilitation evaluation Bedside or formal swallow evaluation Medications: Home medications except BP meds. Restart or add after patient stable for >48 hrs. Again, in general do not treat BP unless >220/120 in the acute phase DVT and GI prophylaxis if indicated

Hospital Initiation of Secondary Prevention §All patients receive statin with goal LDL<100. Established evidence in patients with CAD and atherosclerotic ischemic stroke. Atorvastatin 80 mg qd SPARCL §All patients given BP meds with goal <140/90 or <130/80 with DM or renal disease. Prefer ACEI or ARB and thiazide diuretic PROGRESS (B-blocker if CAD) §Smoking Cessation §Diet and Exersice Regimen §Stroke Education

Antithrombotic / Anticoagulant Therapy §In patients who have experienced a noncardioembolic stroke or TIA, we recommend treatment with an anti-platelet agent. Aspirin at a dose of 50 to 325 mg qd; the combination of aspirin, 25 mg and extended-release dipyridamole, 200 mg bid; or clopidogrel, 75 mg qd, are all acceptable options for initial therapy §No good evidence on what to do if patient already on therapy §In patients with Afib who have suffered a recent stroke or TIA, we recommend long-term oral anticoagulation, INR range 2 -3 §? Best treatment in cryptogenic stroke, PFO, aortic disease, post-MI §? Use of IV Heparin in certain situations—brain goal PTT of 45 -65 Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

Acute Intraparenchymal Hematoma Imaged With Computed Tomography and With Magnetic Resonance Imaging Kidwell, C. S. et al. JAMA 2004; 292: 1823 -1830. Copyright restrictions may apply.

The Ischemic Penumbra Approximated by PWI-DWI MRI Mismatch and used to help guide interventional acute stroke therapies…

§IA t-PA within 6 hours of stroke onset in anterior circulation and 24+ hours in posterior circulation §Mechanical Clot removal within 8+ hours of ischemic stroke (MERCI) Stroke. 2005; 36: 1432.

Traditionally High Mortality and Limited Recovery • Mortality – 6 -month, 30%-50% – 1 -year, 50% • Only 20% of ICH patients are independent at 6 months vs 60% of ischemic stroke patients • Medical costs – US$125, 000 lifetime cost person (1990) – Direct and indirect costs (lost productivity + caregiver burden) Manno EM, et al. Mayo Clin Proc. 2005; 80: 420 -433; Mayer SA, Rincon F. Lancet Neurol. 2005; 4: 662 -672; Qureshi AI, et al. N Engl J Med. 2001; 344: 1450 -1460; Taylor TN, et al. Stroke. 1996; 27: 1459 -1466; Reed SD, et al. Neurology. 2001; 57: 305 -314.

Predictors of Outcome ● Hematoma volume ● GCS ● Intraventricular hemorrhage ● Age ● ICH location (deep) ● Increased cerebral edema (midline shift, herniation) Manno EM, et al. Mayo Clin Proc. 2005; 80: 420 -433; Garibi J, et al. Br J Neurosurg. 2002; 16: 355 -361.

Predictors of Outcome The ICH Score Component ICH score points 3 -4 2 5 -12 1 13 -15 0 >30 1 <30 0 Intraventricular hemorrhage Yes 1 No 0 Infratentorial origin Yes 1 No 0 >80 1 <80 0 GCS ICH volume (cc) Age (y) Total ICH score 30 -day Mortality 100 80 60 % 40 20 0 Overall 0 0 -6 Reproduced with permission from Hemphill JC III, et al. Stroke. 2001; 32: 891 -987. 1 2 3 ICH Score 4 5

Sites of Spontaneous ICH Lobar Subcortical Hemorrhage (25%) Putaminal Hemorrhage (35%) Thalamic Hemorrhage (20%) Pontine Hemorrhage (7%) Cerebellar Hemorrhage (8%) Reproduced with permission from Mayer SA, Rincon F. Lancet Neurol. 2005; 4: 662 -672; Qureshi AI, et al. N Engl J Med. 2001; 344: 1450 -1460.

General Management of ICH Goals Provide general supportive care in the ED and ICU/NICU to manage the primary brain injury and limit the secondary brain injury • • • Continue to support ABCs Monitoring (BP, fever, ICP, labs) Intubation BP management Seizure management Reverse anticoagulation immediately

Blood Pressure Management AHA/ASA Guidelines (2007) • Select target BP on basis of patient factors – Baseline BP – Interval since ICH onset – Cause of hemorrhage – Age – Elevated ICP • BP thresholds (limited supportive data) – SBP ≤ 180 mm Hg and/or – MAP <130 mm Hg • Closely titrate short-acting IV agents Suggested Guidelines for Elevated BP in ICH If SBP >200 mm Hg or MAP >150 mm Hg • Consider “aggressive” • • BP reduction Continuous IV Frequent BP monitoring If SBP >180 mm Hg or MAP >130 mm Hg and ↑ ICP • Monitor ICP • Intermittent/continuous IV (CPP >60 -80 mm Hg) Broderick J, et al. Stroke. 2007; 38: 2001 -2023. If SBP >180 mm Hg or MAP >130 mm Hg and no ↑ ICP • Consider “modest” BP • reduction Intermittent/continuous IV

Subarachnoid Hemorrhage Causes: §Aneurysm (80% of non-traumatic cases) §Trauma §Vascular Malformations §Tumors §Infection §Venous Thrombosis

Subarachnoid Hemorrhage (Aneurysmal) Demographics: §Mean age = 55 years §Women 1. 6 X > Men §Blacks > Whites §Average Case Fatality Rate > 50%

Subarachnoid Hemorrhage (Aneurysmal) Risk Factors: §Smoking §Hypertension §Cocaine Use §Heavy alcohol use §First degree relatives with SAH

Subarachnoid Hemorrhage Clinical Features: §Sudden severe headache (thunderclap headache) §Nausea §Vomiting §Neck Pain §Photophobia §Loss of consciousness §Retinal hemorrhages (subhyaloid hemorrhage) §Meningismus §Localizing neurological signs

Subarachnoid Hemorrhage Diagnostic Evaluation: §Head CT §Sensitivity > 90% in first 24 hours §Sensitivity drops to 50% at 1 week §Lumbar Puncture §Finding to look for is xanthochromia (12 hours to develop)

Subarachnoid Hemorrhage Treatment: §Blood Pressure §Low before aneurysm secured §High after aneurysm secured §Treat hyperglycemia and hyperthermia §DVT prophylaxis (Heparin after aneurysm secured) §Nimodipine 60 mg PO q 4 hours X 21 days §Secure aneurysm §Neurosurgical Clipping §Endovascular Coiling (favored in ISAT)

Subarachnoid Hemorrhage Complications: §Rebleeding (7%) §Vasospasm (46%) Highest incidence 3 -12 days after SAH §Screen with TCD §Treat with Hypervolemia and Induced Hypertension §Angiography §Hydrocephalus (20%) §EVD §Permanent Shunt §Seizures (30%) §Antiepileptics for 1 week to 1 month

HYPOTHERMIA Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours when the initial rhythm was ventricular fibrillation (VF). Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest. Circulation. 2003; 108: 118