PT2 IDM2 2022 Stroke_students slides 1pp-1.pdf

Jennifer Steinberg, PharmD, BCPS Assistant Professor NSU College of Pharmacy [email protected] 1. Differentiate between stroke sub-types, including TIA, ischemic and hemorrhagic 2. Identify modifiable and non-modifiable risk factors for development of stroke and estimate risk based on e...

Jennifer Steinberg, PharmD, BCPS Assistant Professor NSU College of Pharmacy [email protected] 1. Differentiate between stroke sub-types, including TIA, ischemic and hemorrhagic 2. Identify modifiable and non-modifiable risk factors for development of stroke and estimate risk based on established risk stratification tools 3. Apply eligibility criteria and patient selection to determine appropriateness of reperfusion therapy with tPA 4. Describe appropriate use of oral anticoagulants in stroke based on current indications, contraindications, place in therapy, and proper initiation 5. Select appropriate primary and secondary stroke prevention strategies 6. Recommend an appropriate therapeutic regimen (drug, dose, route, frequency and duration) for acute management and secondary prevention of stroke, based on subtype 7. Identify appropriate efficacy and safety monitoring parameters for medications used in stroke ¡ Guidelines for the Early Management of Patients With Ischemic Stroke. 2019 Update Stroke. 2019;50:e344-e418. ¡ Guidelines for the Primary Prevention of Stroke. Stroke 2014;45;3754-3832. ¡ 2021 Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. Stroke. 2021 Jul;52(7):e364-e467. ¡ 2022 Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2022 Jul;453(7):2e282-e361. ¡ Guidelines for the management of aneurysmal subarachnoid hemorrhage. Stroke 2012 Jun;43(6):1711-37.  IHD Veins VTE ACS Coronary Stroke Cerebral Vascular disease Arteries TIA Peripheral Renal Lymphatic Mesenteric system Aorta  Arterial Venous “White clots” “Red clots” High pressure Low pressure Platelet rich Red blood cells Antiplatelet agents Anticoagulant agents Pharmacist's Letter/Prescriber's Letter 2009;25(9):250901. ¡ Ischemic stroke = clot § Neurologic dysfunction caused by reduced blood flow to the CNS leading to local tissue damage ¡ Transient Ischemic Attack (TIA): § Temporary episode of focal neurologic dysfunction due to vascular causes - No evidence of infarct § Warning sign of a future stroke ¡ Hemorrhagic Stroke = bleeding § Leakage of blood into brain or other areas of CNS ¡ 5th leading cause of death in the United States ¡ ~795,000 new or recurrent strokes annually § 15% of strokes have a prior TIA ¡ Over 7.2 million adult Americans self-report having had a stroke ¡ Leading cause of disability among adults  3% 10% Ischemic ICH SAH 87%  Non-Modifiable Risk Factors Modifiable Risk Factors Age Hypertension (HTN) Sex (M > F) Cigarette smoking Race (AA > Hispanic > Diabetes (DM) Caucasian) Dyslipidemia Genetic factors Cariovascular disease – Family history AFib, CAD, HF, PAD, LVH, carotid stenosis Sickle cell disease Lifestyle factors Hormone replacement therapy (HRT) ¡ Hormonal contraceptives (estrogen) ¡ Migraine (especially with aura) ¡ Drugs/alcohol abuse ¡ Hypercoaguable states ¡ Hyperhomocysteinemia ¡ Inflammation ¡ Sleep apnea ¡ Large vessel atherosclerosis § Extracranial § Intracranial ¡ Cardiogenic embolism ¡ Penetrating artery disease ¡ Unusual causes § Dissection § Hypercoagulable states § Sickle cell disease ¡ Cryptogenic Thrombosis Embolism Arterial Occlusion Ischemia → Infarction Time=Tissue ¡ Penumbra § Ischemic tissue surrounding infarction § Able to be salvaged through therapeutic intervention Retrieved from http://stroke.nih.gov/images/StrokeChallenge_Vessel.jpg. Accessed Feb 21, 2012 Up to 80% of strokes are preventable ¡ Major risk factor for ischemic stroke ¡ Target BP reduction to meet current guidelines recommendations ¡ Lifestyle modification and pharmacologic therapy § Consider compelling indications ¡ Association between high cholesterol levels and increased risk of ischemic stroke ¡ Use treatment approach in current cholesterol guidelines § Statin + therapeutic lifestyle changes § Nonstatin therapies – no established evidence to support primary stroke prevention  Risk factor(s) + 10-year risk Recommendation Individuals with clinical ASCVD Individuals with primary elevations of LDL-C Moderate – High intensity ≥190 mg/dL statin therapy Individuals 40 to 75 years of age with (based on age, tolerability, and/or estimated 10-yr risk) diabetes ± other cholesterol lowering agents Individuals without clinical ASCVD or according to guidelines diabetes , 40 to 75 years of age with LDL-C 70-189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher Grundy SM, et al. Circulation. 2018 Nov 10. Epub ahead of print. https://doi.org/10.1161/CIR.0000000000000625 ¡ Low dose aspirin to reduce risk of overall CV events (not specific to stroke) § High risk; 10-year risk of CV events of >10% § No evidence favors one dose over another ¡ Not useful in primary stroke prevention for: § Low risk § DM or DM + PAD with no evidence/low risk of CVD ¡ Diabetes § Use current guidelines for glycemic control, BP control and lipid lowering ¡ Cigarette smoking § Abstain or cease § Avoid environmental smoke ¡ Lifestyle § Balanced diet, lower sodium intake § Increased physical activity; weight reduction § Limit alcohol intake ¡ Hormonal contraceptives § Avoid in smokers, migraine with aura, age > 35, prior thrombotic events ¡ HRT § Should not be used for primary prevention of stroke § Timing issue unclear ¡ Migraines § Treat to reduce frequency → no evidence this reduces risk of stroke ¡ Risk of stroke regardless of strategy used to treat arrhythmia (rate vs rhythm control) ¡ Approach to atrial flutter is the same ¡ Efficacy § Oral anticoagulation > clopidogrel + ASA > ASA § Benefit is limited by potential for major bleeding complications – HAS-BLED score ¡ “Valvular AF” à anticoagulation w/ warfarin § Moderate to severe mitral stenosis § Mechanical heart valve ¡ “Non-valvular AF” à risk assessment § Absence of mitral stenosis/mechanical valve § May have other valve-related conditions CHADS2Risk Factor Score CHA2DS2VAScRisk Factor Score Congestive Heart 1 Congestive Heart Failure/LV Dysfunction 1 Failure Hypertension 1 Hypertension 1 Age ≥ 75 2 Age ≥ 75 1 Diabetes 1 Diabetes 1 Stroke/TIA 2 Stroke/TIA 2 Vascular Disease 1 (MI, PAD, aortic plaque) CHADS2 Total 6 Age 65 - 74 1 Sex Category (female) 1 CHA2DS2VASc Total 9  Risk CHADS* CHEST AHA/ACC/HRS Category Score 0 Low Risk (not including None None (IIa) point for female) Moderate 1 Oral AC Oral AC may be (not including Risk point for female) (DOACs recommended as first line) considered (IIb) ≥2 Oral AC High Risk (not including Oral AC (I) point for female) (DOACs recommended as first line) Circulation 2019 Jul 9;140(2):e125-e151. AC = anticoagulant Chest 2018;154(5);1121-1201 *CHA2DS2VASc Stroke 2014;45;3754-3832. ¡ Warfarin with goal INR 2-3 ¡ Choice varies: ¡ Dabigatran (Pradaxa®) § Risk factors ¡ Rivaroxaban (Xarelto®) § Black box warnings ¡ Apixaban (Eliquis®) § Tolerability ¡ Edoxaban (Savaysa®) § Drug interactions § Patient preference ¡ Indicated to reduce risk of § Cost stroke and systemic § Conversion among agents embolism in patients with § Others nonvalvular AF ¡ Primary and secondary prevention ¡ Direct thrombin inhibitor ¡ Pharmacokinetics: § Oral pro-drug § Substrate of efflux transporter P-glycoprotein (P-gp) § 80% renally excreted ¡ Routine monitoring of anticoagulant effects not required § If needed, aPTT or ECT may be useful § PT/INR not sensitive ¡ Dosing CrCl > 30 ml/min: 150 mg PO BID (*different from VTE prophylaxis*) CrCl 15-30 mL/min: 75 mg PO BID (*different from VTE*) CrCl < 15 mL/min: dosing recommendations cannot be provided Concomitant use with P-gp inhibitors may warrant dose reduction or avoidance of co-administration ¡ Adverse effects: bleeding, dyspepsia, gastritis ¡ Reversal § Praxbind® (idarucizumab) § Activated charcoal, dialysis may be helpful § Mixed results with other tested antidotes ¡ Contraindicated in patients with mechanical prosthetic heart valve ¡ Keep in original container and use within 4 months of opening ¡ Factor Xa inhibitor ¡ Pharmacokinetics § CYP3A4 and p-glycoprotein substrate § Avoid concomitant use with: ▪ P-gp inhibitors and strong CYP3A4 inhibitors- ketoconazole, itraconazole, ritonavir, indinavir, conivaptan ▪ P-gp inducers and strong CYP3A4 inducers- carbamazepine, phenytoin, rifampin, St. John’s wort § Bioavailability is dose dependent; doses ≥15 mg should be taken with food ¡ *Different dosing compared to use in VTE* CrCl > 50 mL/min: 20mg PO daily with evening meal CrCl 15 - 50 mL/min: 15mg PO daily with evening meal CrCl < 15 mL/min: Avoid use ¡ Routine monitoring of anticoagulant effects not required § PT, INR, aPTT, Anti-factor Xa are limitedly affected ¡ Reversal § Supportive care if bleeding § Activated charcoal; not dialyzable § Andexanet alfa (Andexxa®) ¡ Factor Xa inhibitor ¡ Pharmacokinetics: § Prolonged absorption, t1/2 = 8-15 hours § Metabolized via CYP3A4 § Substrate of P-gp ¡ Predictable effects without need for routine monitoring of anticoagulant effects § Prolongs PT, INR, aPTT– not useful for monitoring effects  ¡ Dosing: Recommended dose (*different from VTE dosing*) 5 mg PO BID Patient with ≥2 of the following: - age ≥80 years 2.5 mg PO BID - body weight ≤60 kg - serum creatinine ≥1.5 mg/dl Concomitant CYP 3A4 and P-gp inhibitors Reduce to 2.5 mg PO BID (ketoconazole, itraconazole, ritonavir, clarithromycin) Avoid if already at lower dose CYP3A4 and P-gp inducers Avoid concomitant use ¡ Reversal ¡ Supportive care if bleeding ¡ Activated charcoal; not dialyzable ¡ Andexanet alfa (Andexxa®) ¡ Factor Xa inhibitor ¡ Dosing: CrCl > 95 mL/min: Do not use CrCl 50 - 95 mL/min: 60 mg PO daily CrCl 15-50 mL/min: 30 mg PO daily CrCl < 15 mL/min: not recommended (limited clinical data) ¡ Avoid use with P-gp inducer rifampin ¡ No established reversal agent; not dialyzable ¡ Cannot be reliably monitored with standard lab tests - small variable changes in PT, INR, and aPTT ¡ Depends on area of the brain affected § Hemiparesis § Hemiplegia § Dysarthria/Aphasia § Vertigo § Falling § May present with headache Retrieved at http://www.strokeassociation.org/STROKEORG/WarningSigns/Warning- Signs_UCM_308528_SubHomePage.jsp. Jan 23, 2011 Balance Eyes Face Arm Speech Time to call 9-1-1 FAST ¡ History § Symptom onset § Recent PMH and comorbidities § Medications ¡ Physical Examination § Assessment of ABCs, pulse oximetry § Signs of trauma or seizures § Identification of comorbidities ¡ Neurological examination § Validated prognostic tool to quantify effect of acute cerebral ischemia (Score 0-42) Tested Items a) Level of Consciousness Motor function (leg) b) Orientation questions Limb Ataxia c) Response to commands Sensory loss Gaze Language Visual fields Articulation Facial movement Extinction and Inattention Motor function (arm) ¡ Imaging of the brain § Prior to beginning acute therapy § Non-contrast CT scan or MRI of brain § Looking for evidence of hemorrhage/brain tumor ¡ Labs and other testing § Glucose § PT/INR, platelets § ECG § Others ¡ Minimize ongoing neurologic injury and long- term disability § Intravenous thrombolysis § Endovascular intervention § Early anticoagulation § Early antiplatelet therapy § Management of hypertension § Supportive care ¡ Recombinant tissue Tissue plasminogen activator plasminogen activator (tPA) (tPA) ¡ Conversion of plasminogen to plasmin Plasminogen Plasmin § Activated local fibrinolysis ¡ Major adverse reaction: bleeding Fibrinolysis ¡ Patients with ischemic stroke given placebo or tPA (0.9 mg/kg IV, maximum 90 mg) within 3 hrs of symptom onset § Extensive inclusion/exclusion criteria § Two part study (n = 624) § Part 1: Neurological improvement at 24 hours § Part 2: Clinical outcome at 3 months N Engl J Med. 1995;333:1581-7. ¡ Results: § Part 1: No statistical difference seen at 24 hours § Part 2: Improvement seen at 3 months ▪ OR 1.7 (95% CI 1.2 to 2.6; p=0.008) ▪ 12% absolute increase in patients with no/minimal disability ¡ No difference in mortality between groups § tPA group (17%) vs. placebo group (21%); p=0.30 ¡ Symptomatic ICH § tPA (6.4%) vs. placebo (0.6%); p 80 years, oral anticoagulants, NIHSS score > 25, h/o stroke + DM ¡ Results § Primary outcome: 52.4% vs. 45.2%; OR 1.34; 95% CI 1.02 to 1.76; p=0.04 § Symptomatic ICH: 2.4% vs. 0.2%; p=0.008 ¡ Conclusion: IV recombinant tPA can be given safely 3 to 4.5 hours after stroke and may improve outcomes after stroke N Engl J Med. 2008;359(13):1317-29. 1. Activation of stroke team 2. Onset of symptoms within 3 or 4.5 hours 3. CT scan r/o hemorrhage 4. Assessment of inclusion/exclusion criteria 5. Administer tPA (alteplase) 0.9 mg/kg (maximum 90 mg) § 10% bolus over 1 minute § Remainder over 60 minutes 6. Avoidance of anticoagulants/antiplatelets for 24 hours after treatment 7. Monitor for response and hemorrhage (ongoing neurological assessments) Indications (Class I/Strong recommendation) ü Age ³ 18 years ü Ischemic stroke w/ neurological deficit ü Onset less than 3 hours before treatment begins ü 3 to 4.5 hr window recommended for: ü 50 mg/dl Powers EJ, et al. Stroke. 2018; 49(2):e46-e99. Contraindications (Class III: No Benefit/ Class III: Harm) Ò Unclear time of symptom onset or outside of time window Ò Acute or history of intracranial hemorrhage Ò Ischemic stroke or severe head trauma within 3 months Ò Intracranial/spinal surgery within 3 months Ò Symptoms suggestive of subarachnoid hemorrhage Ò GI malignancy or GI bleed within 21 days Ò Coagulopathy or acute bleeding risk: Ò Platelets 1.7, aPTT >40s, or PT >15s Ò LMWH treatment dose within previous 24 hrs Ò Direct thrombin or Xa inhibitor use with elevated assays/within past 48 Ò Infective endocarditis Ò Aortic arch dissection Ò Some kinds of intracranial neoplasms Powers EJ, et al. Stroke. 2018; 49(2):e46-e99. Risk to Benefit assessment (Class II: may be reasonable to consider) ´ Wake-up or unknown time since symptom onset ´ History of coagulopathy ´ Recent major trauma not involving head ´ Recent major surgery ´ Past GI/GU bleeding ´ Unruptured intracranial aneurysm ´ Acute/recent myocardial infarction ´ Pregnancy ´ Several others included in guidelines Powers EJ, et al. Stroke. 2018; 49(2):e46-e99. ¡ Tenecteplase (0.4 mg/kg IV bolus) might be considered as alternative to alteplase in minor neurological impairment and no major intracranial occlusion § NOT proven superior or non-inferior to alteplase § Similar safety as alteplase ¡ sICH within 24 hours of alteplase might be a reasonable indication for treatment § 85-90% of hemorrhagic transformations occur within 24 hours of thrombolytic § Detected through neurologic monitoring; diagnosed by post-treatment CT/MRI showing hemorrhage § Limited data to support treatment in asymptomatic bleeding, but it may be considered Yaghi S, et al. Stroke. 2017 Dec; 48:e343-e361 Reversal Agent Potential for Benefit Cryoprecipitate Potential benefit in all sICH Platelets Thrombocytopenia (platelets 220 or DBP >120 mmHg or if required due to comorbid conditions § Goal reduction of ~15% over the first 24 hrs ¡ Oxygenation and airway support ¡ Antipyretics for fever ¡ Cardiac monitoring for arrhythmias ¡ Correction of hypovolemia ¡ Maintenance of normoglycemia § Hyperglycemia associated with poor outcomes § Target BG range of 140-180 mg/dl ¡ Early mobilization if possible ¡ Intermittent compression devices ¡ Pharmacologic prophylaxis § Ideal time to start is not known § LMWH or UFH § Recent meta-analysis showed fewer PE but increase in sICH and other bleeding ¡ In patients with hypertension: § Office BP goal of < 130/80 is recommended for most patients § Thiazide diuretic, ACE-inhibitor, or ARB may be beneficial for reducing stroke risk ¡ Tailor therapeutic regimen to patient § Magnitude of BP reduction seems more important for risk reduction than specific class of medication § Include lifestyle modifications ¡ Statins recommended to reduce risk of stroke and CV events in patients with: § Ischemic stroke/TIA of atherosclerotic origin § LDL-C> 100 mg/dL § ± other ASCVD ¡ Intensive lipid-lowering effects according to 2018 ACC/AHA cholesterol guidelines and other supporting recommendations  Risk factor(s) + 10-year risk Recommendation Individuals with clinical ASCVD Individuals with primary elevations of LDL-C Moderate – High intensity ≥190 mg/dL statin therapy (based on statin benefit group, tolerability, Individuals 40 to 75 years of age with and/or estimated 10-yr risk) diabetes ± other cholesterol lowering agents Individuals without clinical ASCVD or according to guidelines (ezetimibe, diabetes , 40 to 75 years of age with LDL-C PCSK9 inhibitor) 70-189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher Grundy SM, et al. Circulation. 2018 Nov 10. Epub ahead of print. https://doi.org/10.1161/CIR.0000000000000625 ¡ Diabetes § Refer to current guidelines (ADA, AACE) for glycemic control § Individualize goal based on risk for adverse events, patient characteristics, etc ¡ Cigarette smoking § Abstain or cease § Avoid environmental smoke ¡ Salt restriction ¡ Weight loss ¡ Consumption of a diet rich in fruits, vegetables, and low-fat dairy products ¡ Regular moderate-intensity physical activity ¡ Limited alcohol consumption Non-Cardioembolic Cardioembolic dabigatran/ rivaroxaban/apixaban/ ASA edoxaban (indicated in non-valvular afib only) ASA + extended release dipyridamole Warfarin clopidogrel  ¡ Antiplatelets Non-Cardioembolic recommended over oral anticoagulation ASA ASA + extended- release dipyridamole clopidogrel Stroke. 2014;45:2160-2236. ¡ Antiplatelet effects through inhibition of thromboxane A2 ¡ Reduced risk of stroke, MI and vascular death § 23% among high risk atherosclerosis patients § 16% among stroke/TIA patients ¡ Aspirin 50 – 325 mg daily § Similar efficacy with both high and low dose § Lower doses associated with less bleeding events Stroke. 2006 Feb; 37(2):577-617 Chest. 2004 Sep; 126(3 Suppl): 483S-512S ¡ Inhibit platelet activation and aggregation by irreversibly binding to ADP P2Y12 receptor ¡ Clopidogrel § 75 mg daily § Pro-drug: Must be metabolized (CYP 2c19) to active form ▪ Clopidogrel resistance ▪ Potential for drug interactions § Similar safety to aspirin with lower risk of GI hemorrhage ¡ ASA 25 mg + extended-release dipyridamole 200 mg BID ¡ Dipyridamole component inhibits platelet activation and aggregation by inhibiting phosphodiesterase ¡ Less well-tolerated than aspirin or clopidogrel § Headaches, GI upset ¡ May consider dual antiplatelet therapy (DAPT) within 24 hours for minor stroke or high-risk TIA that did not receive alteplase § Clopidogrel + ASA for 21 to 90 days followed by single antiplatelet therapy (SAPT) ¡ Ticagrelor (Brilinta®) + aspirin might be considered for up to 30 days in recent minor stroke/high-risk TIA with certain intracranial/extracranial large artery atherosclerosis (Class 2b recommendation)  ¡ Antiplatelets Non-Cardioembolic recommended over oral anticoagulation ASA ¡ Choice based on: ASA + extended- § Effectiveness release dipyridamole § Safety and tolerability § Cost clopidogrel § Patient factors Stroke. 2014;45:2160-2236.  ¡ Cardioembolic causes: § Atrial fibrillation Cardioembolic* § Acute MI and LV thrombus § Native valvular disease dabigatran/ § Cardiomyopathy rivaroxaban/apixaban/ [edoxaban] § Prosthetic heart valves (indicated in non-valvular afib only) *Agent selection, INR goals, and concomitant antiplatelets vary by Warfarin indication. Refer to appropriate guidelines for specific recommendations and level of evidence Stroke. 2014;45:2160-2236. CHADS2Risk Factor Score CHA2DS2VAScRisk Factor Score Congestive Heart 1 Congestive Heart Failure/LV Dysfunction 1 Failure Hypertension 1 Hypertension 1 Age ≥ 75 2 Age ≥ 75 1 Diabetes 1 Diabetes 1 Stroke/TIA 2 Stroke/TIA 2 Vascular Disease 1 (MI, PAD, aortic plaque) CHADS2 Total 6 Age 65 - 74 1 Sex Category (female) 1 CHA2DS2VASc Total 9  Risk CHADS* CHEST AHA/ACC/HRS Category Score 0 Low Risk (not including None None (IIa) point for female) Moderate 1 Oral AC Oral AC may be (not including Risk point for female) (DOACs recommended as first line) considered (IIb) ≥2 Oral AC High Risk (not including Oral AC (I) point for female) (DOACs recommended as first line) AC = anticoagulant Circulation 2019 Jul 9;140(2):e125-e151. *CHA2DS2VASc Chest 2018;154(5);1121-1201 Stroke 2014;45;3754-3832. ¡ Other etiologies addressed in secondary prevention guidelines: § Hypercoagulable states § Carotid web § Malignancy § Fibromuscular dysplasia § Sickle cell disease § Dolichoectasia § Vasculitis § Others ¡ Carotid endarterectomy (CEA) § When combined with medical therapy, more efficacious than medical therapy alone for atherosclerotic carotid stenosis> 70% § Not indicated for carotid stenosis< 50% ¡ Carotid angioplasty and stenting (CAS) § Alternative for patients considered to be at high- risk for CEA Stroke 2011, 42:227-276. Category Focused items* Patient characteristics Age, sex, race Medication allergies Past medical / family Previous stroke/TIA, AF, stroke or CV risk factors, etc history Social history Tobacco, alcohol, drug use Current medications ASA, NSAIDs, antiplatelet/anticoagulant use, hormonal contraceptives, etc Objective BP, HR, RR, Ht/Wt Labs: H/H, SCr, aPTT, PT/INR, BG, troponin Neuro exam (e.g. NIHSS score) Brain imaging (e.g. CT scan) ECG, TEE *may not be all-inclusive or all items may not be applicable to all patients Category Details Stroke etiology Cardioembolic or noncardioembolic Blood pressure Eligibility for alteplase (tPA), need for antihypertensive or vasopressor agents Blood glucose Stroke mimic, need for treatment (180 mg/dL) Bleeding risk Active bleeding or significant risk factors present tPA eligibility Inclusion and exclusion criteria Thrombectomy Inclusion and exclusion criteria eligibility (not presented in this lecture)  Plan items Alteplase (tPA) if eligible ASA within 24-48 hrs unless contraindicated; delay 24 hrs if tPA given Acute VTE prophylaxis Nutrition plan Secondary Prevention Antiplatelet or anticoagulant regimen based on stroke etiology Evaluation for carotid artery stenosis and need for intervention Manage/treat stroke risk factors (e.g. HTN, DM, etc) Educate patient including self-monitoring parameters Referral for additional services when appropriate Implementation items Communicate care plan to patient and healthcare team Provide patient/caregiver education Confirm orders and access to medications Schedule follow-up and referral appointments Category Potential monitoring parameters Efficacy Improvement of symptoms, neurologic exam Adverse effects, bleeding, symptoms, relevant labs, Safety neurologic exam Adherence Use multiple sources of information Recurrence New/worsening symptoms Intracranial Hemorrhage 1. Intracerebral Hemorrhage 2. Subarachnoid Hemorrhage Intracerebral (ICH) Subarachnoid (SAH) ¡ Hypertension ¡ Cerebral aneurysm ¡ Trauma ¡ Trauma ¡ AV malformations ¡ Blood clotting deficiencies ¡ Tumors ¡ Not as well studied as ischemic stroke ¡ Bleeding within the brain § Mechanical/compression injury § Increased intracranial pressure § Neurotoxicity of blood components ¡ Risk factors: HTN, warfarin, platelet abnormalities, coagulation factor deficiencies, trauma ¡ Clinical Presentation § Onset of sudden focal neurological deficit § Progressive over minutes to hours § Headache, vomiting ¡ Management of anticoagulant-related hemorrhage § Warfarin (varies by INR value) ▪ Prothrombin complex concentrate (PCC) ▪ IV Vitamin K § Dabigatran / Factor Xa inhibitors ▪ Activated charcoal if last dose < 2 hours ▪ Idarucizumab / andexanet alfa ▪ PCC § UFH or LMWH ▪ Protamine ¡ VTE prophylaxis § Mechanical devices § Pharmacological therapy if needed once bleeding stops ¡ Management of hypertension ¡ ICU care with neuroscience experience ¡ Maintenance of normoglycemia ¡ Dysphagia screening ¡ Treatment of clinical or EEG-detected seizures ¡ Intracranial pressure (ICP) monitoring and treatment as needed ¡ Use of surgical interventions for select cases ¡ Risk factors: smoking, HTN, cocaine/heavy alcohol use ¡ Typical Presentation: § Sudden onset severe headache with N/V § Stiff neck § Focal neurological deficit § Loss of consciousness § May have history of a “sentinel” or warning leak ¡ Hypertension management § Exact goal has not been established; reduction in SBP to