Acute Ischemic Stroke - ACCP
Acute Ischemic Stroke By Steven H. Nakajima, Pharm.D., BCCCP; and Katleen Wyatt Chester, Pharm.D., BCCCP, BCGP Reviewed by Dennis Parker, Jr., Pharm.D.; Abigail M. Yancey, Pharm.D., FCCP, BCPS; and Marcus Patrick, Pharm.D., BCPS LEARNING OBJECTIVES 1. Design a patient-specific pharmacotherapeutic regimen to treat adverse events associated with intravenous alteplase, including hemorrhage and angioedema. 2. Distinguish key differences between the most recent guidelines for early management of acute ischemic stroke and the previous guidelines. 3. Assess a patient’s candidacy for intravenous fibrinolytic therapy on the basis of updated inclusion and exclusion recommendations. 4. Evaluate the role of thrombolysis and thrombectomy with respect to eligibility criteria, efficacy, complications, and post-intervention considerations. 5. Devise an evidence-based, patient-specific antiplatelet plan for early secondary prevention after minor ischemic stroke or high-risk transient ischemic attack. 6. Justify the pharmacist’s role as an integral part of the stroke response team for acute ischemic stroke. ABBREVIATIONS IN THIS CHAPTER AIS DAPT DTN EVT ICH LVO MCA mRS NIHSS NINDS TIA TICI Acute ischemic stroke Dual antiplatelet therapy Door-to-needle time Endovascular therapy Intracranial hemorrhage Large vessel occlusion Middle cerebral artery Modified Rankin Scale National Institutes of Health Stroke Scale National Institute of Neurological Disorders and Stroke Transient ischemic attack Thrombolysis in Cerebral Infarction Table of other common abbreviations. PSAP 2020 Book 1 Critical and Urgent Care INTRODUCTION Stroke is the leading cause of serious long-term disability and the fifth leading cause of death for Americans. On average, someone in the United States has a stroke every 40 seconds, resulting in about 795,000 strokes per year. Ischemic strokes account for 87% of cases, whereas 10% are intracerebral hemorrhage and 3% are subarachnoid hemorrhage. The burden of stroke in the United States resulted in direct and indirect costs that averaged 33.9 billion annually in 2013 (Benjamin 2017). Acute ischemic stroke (AIS) can affect the anterior circulation, the posterior circulation, or both. The internal carotid arteries supply oxygenated blood to the anterior circulation of the brain (i.e., middle cerebral arteries [MCAs] and anterior cerebral arteries), and the posterior circulation is supplied by the vertebral arteries that merge into the basilar artery, which feeds into the posterior cerebral and posterior communicating arteries. These anterior and posterior arteries that make up the circle of Willis (Figure 1) are called proximal arteries, given their proximity to the circle itself. Anterior circulation strokes involving the internal carotid artery and MCA are more common than posterior infarcts. The vascular territory and the volume of ischemic brain tissue determine the type and severity of deficits. Patients with anterior strokes may present with focal deficits such as aphasia, neglect, hemiplegia, hemisensory loss, or visual field deficits. Patients with posterior strokes usually have a broad range of symptoms, including gait disturbances, unilateral or bilateral ataxia, visual field disturbances, optic ataxia, nystagmus, and even unresponsiveness and 7 Acute Ischemic Stroke
respiratory arrest in the case of a complete, proximal basilar artery occlusion. Proximal arterial occlusions tend to result in larger volumes of ischemic brain tissue (and therefore a broader array and increased severity of stroke symptoms), whereas occlusions more distally or in small arteries typically produce an isolated deficit of lower severity. Acute ischemic stroke can be categorized into five subtypes depending on the cause, as described by the TOAST investigators (Adams 1993). These subtypes are large- artery atherosclerosis, cardioembolic, small vessel occlusion (lacunar), stroke of other determined cause, and stroke Ant. communicating Int. carotid Ant. cerebral A.M. Basilar BASELINE KNOWLEDGE STATEMENTS Pontine Readers of this chapter are presumed to be familiar with the following: General knowledge of the pathophysiology of AIS Knowledge of pharmacotherapy for secondary prevention of stroke P.L. Anterior Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50:e344-e418. Posterior inferior cerebellar Figure 1. Arterial circulation at the base of the brain, “the circle of Willis.” A.L. anterolateral ganglionic branches; A.M. anteromedial ganglionic branches; Ant. anterior; Int. internal; arterial circle “the circle of Willis”; P.L. posterolateral ganglionic branches; P.M. posteromedial ganglionic branches; Post posterior. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2016;47:581-641. Image reprinted from: Gray H. Anatomy of the Human Body. Philadelphia: Lea & Febiger, 1918; Figure 519. of undetermined cause. Table 1 outlines the definitions, incidence, and survival rates from a population-based epidemiology study (Kolominsky-Rabas 2001). The TOAST categorization is useful to both clinicians and researchers. For clinicians, this categorization helps classify the cause in order to formulate a therapeutic plan to mitigate risk factors and potentially prevent future stroke events. For researchers, this classification defines different stroke subtypes to more clearly identify risk factors and to evaluate the safety and efficacy of potential new therapies. Yaghi S, Willey JZ, Cucchiara B, et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2017;48:e343-e61. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016;24:6-46. PSAP 2020 Book 1 Critical and Urgent Care Spinal Ve rte br al The following free resources have additional background information on this topic: Post communicating Understanding of the pharmacology of aspirin, fibrinolytics, and P2Y12 receptor inhibitors ADDITIONAL READINGS . A.L Internal auditory Table of common laboratory reference values M Arterial circle P.M. l bra ere c id. 8 Acute Ischemic Stroke
Table 1. TOAST Classifications TOAST Classification Incidence Definition Support for Diagnosis 2-Yr Survival 2-Yr Recurrence Undetermined causes 31% a. Two or more causes identified, b. Negative evaluation, OR c. Incomplete evaluation Diagnosis of exclusion 61% 14% Cardioembolic 29% Arterial embolism of cardiac origin High-risk cardiac sources: Mechanical prosthetic valve, atrial fibrillation, left atrial appendage thrombus, left ventricular thrombus, and dilated cardiomyopathy 55% 22% Small-artery “lacunar” 21% No recognizable lesion on CT or MRI or a subcortical or brain stem lesion 1.5 cm diameter Lacunar syndrome (e.g., pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, or ataxic hemiparesis) History of diabetes mellitus and/or hypertension 85% 11% Large-artery atherosclerosis 15% 50% stenosis of a large artery with a 1.5-cm atherosclerotic lesion, no cardioembolic source History of intermittent claudication, carotid bruit, TIAs, or diminished pulses 58% 10% Stroke of other cause 5% Identified source of stroke different fromearlier classifications Examples include hypercoagulable states, vasculopathies, hematologic disorders Variable Variable CT computed tomography; TIA transient ischemic attack. Information from: Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41; Kolominsky-Rabas PL, Weber M, Gefeller O, et al. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and longterm survival in ischemic stroke subtypes: a population-based study. Stroke 2001;32:2735-40; Krishnamurthi RV, Barker-Collo S, Parag V, et al. Stroke incidence by major pathological type and ischemic subtypes in the Auckland Regional Community Stroke Studies: changes between 2002 and 2011. Stroke 2018;49:3-10. THERAPEUTIC GOALS and 42 representing the highest severity of deficits (Table 2). The NIHSS is rapidly performed and is valuable for its ability to determine stroke severity while serving as a tool for measuring changes in clinical status (Table 3). Varying definitions of stroke severity have been defined in the literature, with severe strokes usually identified as an NIHSS score of more than 15 to 20 points. Although clinicians and researchers also use varying thresholds for defining clinically relevant changes in the NIHSS, differences in NIHSS scores of 1, 4, or 8 are used most in thrombolytic trials (Kwah 2014; Schlegel 2003). Besides stroke severity, the NIHSS score also predicts long-term outcomes. Despite some limitations, the NIHSS is the most widely used rating scale for identifying candidates for reperfusion therapies such as thrombolysis and thrombectomy. The modified Rankin Scale (mRS) is the gold standard tool for categorizing functional status in patients with stroke (van Swieten 1988). The mRS ranges from 0 to 6, with 0 representing the absence of disability and 6 representing death Therapeutic goals for ischemic stroke can be categorized as acute versus chronic. Although chronic management goals focus towards secondary prevention of ischemic events, initial acute treatment goals focus on reducing infarct size and stroke severity to ultimately return a patient to baseline functional status. Acute treatment aims for timely restoration of blood flow to ischemic areas to limit the volume of unsalvageable brain tissue, known as the ischemic core. Acute treatment also focuses on preserving the penumbra, which is an area of salvageable, ischemic neurons surrounding the core infarct that can be recovered by timely reperfusion. Outcomes from landmark AIS trials focus on eliminating or reducing the severity of stroke-related deficits and improving functional status at 90 days. The 2019 guidelines prefer the National Institutes of Health Stroke Scale score (NIHSS), a validated scoring tool for measuring stroke deficits (Brott 1989, Powers 2019). The NIHSS generates a value of 0–42, with 0 representing the absence of ischemic stroke deficits PSAP 2020 Book 1 Critical and Urgent Care 9 Acute Ischemic Stroke
Table 2. NIHSS Score Category Score/Description Category Score/Description 1a. LOC 0 Alert 1 Drowsy 2 Stuporous 3 Coma 6a. Motor leg – Left 6b. Motor leg – Right 1b. LOC questions 0 Answers both correctly 1 Answers one correctly 2 Incorrect 0 No drift 1 Drift 2 Cannot resist gravity 3 No effort against gravity 4 No movement X Untestable 1c. LOC commands 0 Obeys both correctly 1 Obeys one correctly 2 Incorrect 7. Limb ataxia 0 No ataxia 1 Present in one limb 2 Present in two limbs 2. Gaze 0 Normal 1 Partial gaze palsy 2 Forced deviation 8. Sensory 0 Normal 1 Partial loss 2 Severe loss 3. Visual fields 0 No visual loss 1 Partial hemianopia 2 Complete hemianopia 3 Bilateral hemianopia 9. Language 0 No aphasia 1 Mild to moderate aphasia 2 Severe aphasia 3 Mute X Untestable 4. Facial paresis 0 Normal 1 Minor 2 Partial 3 Complete 10. Dysarthria 0 Normal articulation 1 Mild to moderate slurring of words 2 Near to unintelligible or worse X Intubated or other physical barrier 5a. Motor arm – Left 5b. Motor arm – Right 0 No drift 1 Drift 2 Cannot resist gravity 3 No effort against gravity 4 No movement X Untestable 11. Extinction/ inattention 0 No neglect 1 Partial neglect 2 Complete neglect LOC level of consciousness; NIHSS National Institutes of Health Stroke Scale. Information from: Richardson J, Murray, D, House CK, et al. Successful implementation of the National Institutes of Health Stroke Scale on a stroke/neurovascular unit. J Neurosci Nurs 2006;38:309-15. (Table 4). Disability status, as measured by the mRS, is generally determined at discharge and again at 90 days because most patients who achieve functional recovery do so within this timeframe (Duncan 2000). The clinical significance of a 1-point change in mRS depends on the baseline value of the mRS. For example, a change from 0 to 1 indicates a low impact on daily activities, whereas a change in mRS from 3 to 4 indicates that the patient can no longer ambulate without assistance. protease enzyme that cleaves the cross-links between fibrin molecules, thus disrupting the mesh-like structure of a fibrin-based blood clot. Alteplase’s FDA-approved labeling includes treatment of AIS at a dose of 0.9 mg/kg intravenously once with a maximum total dose of 90 mg. Ten percent of the dose (0.09 mg/kg) is given as a bolus over 1 minute, with the remaining 90% (0.81 mg/kg) infused over 1 hour. The biggest concern with administering intravenous alteplase for AIS is the risk of symptomatic intracranial hemorrhage (ICH), which occurs in 2 to 7 percent of patients (Frontera 2016). ICH is usually the result of hemorrhagic conversion within the infarcted territory. Providing broad clinical guidance on alteplase use is a delicate balance. Liberal interpretation of relative contraindications may increase the risk of ICH, whereas conservative approaches may limit how many patients benefit from this therapy. INTRAVENOUS FIBRINOLYTICS Alteplase Alteplase is a recombinant tissue-type plasminogen activator (rtPA) that exerts its therapeutic effect through initiating fibrinolysis (also referred to as thrombolysis). Specifically, rtPA cleaves plasminogen at the Arg561-Val562 peptide bond, forming plasmin. Plasmin is an endogenous PSAP 2020 Book 1 Critical and Urgent Care 10 Acute Ischemic Stroke
state it may be reasonable to lower the blood pressure by fifteen percent in the first 24 hours after onset of strokes in this select population. Ideal agents for acute control of blood pressure have a rapid onset, are available for intravenous administration, have a short half-life, and have a predictable blood pressure lowering to dose response. There is no evidence that one antihypertensive is preferred to another in the setting of AIS. Common blood pressure–lowering agents are labetalol, nicardipine, clevidipine, and hydralazine (Table 5). The optimal target for blood pressure during and after intravenous alteplase was recently evaluated. Published in February 2019, the ENCHANTED trial randomized 2196 patients with hypertension receiving alteplase to a systolic blood pressure (SBP) goal of 130–140 mm Hg within 1 hour (intensive blood pressure–lowering cohort) or to a goal SBP of less than 180 mm Hg (guideline-based blood pressure cohort) (Anderson 2019). Functional outcome (shift in mRS) at 90 days was the primary efficacy end point, and the primary safety outcome was any ICH. The incidence of ICH was lower in the intensive-lowering group (14.8% vs. 18.7%; OR 0.75; 95% CI, 0.60–0.94; p 0.0137); however, the primary outcome of functional status at 90 days did not differ between the groups (unadjusted OR 1.01; 95% CI, 0.87–1.17; p 0.8702). Despite reduced rates of ICH, no change in functional outcome was shown. These findings call into question the benefit of intensive blood pressure lowering, and subsequent editorials from stroke experts, including the authors of this study, advise caution in interpreting the lower rates of ICH as a positive indicator of this therapy. The positive outcomes associated with the lower rate of ICH could have been negated by the negative impact on cerebral perfusion with intensive blood pressure lowering, possibly leading to the net neutral effect on functional outcomes at 90 days. According to this study alone, intensive blood pressure lowering postalteplase may not be necessary or beneficial. Table 3. NIHSS Definitions of Severity and Relationship with Hospital Discharge Disposition NIHSS Score Stroke Severity 0 or 1 Normal 1–4 Mild 5–14 Mild to moderately severe 15–25 Severe 25 Very severe Discharge Disposition Discharge home Acute inpatient rehabilitation Long-term acute care NIHSS National Institutes of Health Stroke Scale. Information from: Schlegel D, Kolb SJ, Luciano JM, et al. Utility of the NIH Stroke Scale as a predictor of hospital disposition. Stroke 2003;34:134-7. Acute Blood Pressure Management About 70% of patients presenting with stroke have a blood pressure of 170/110 mm Hg or greater (Britton 1986). Severe hypertension must be managed acutely if a patient is otherwise eligible to receive intravenous alteplase. The goal of acute management of blood pressure is to achieve a blood pressure less than 185/110 mm Hg to initiate alteplase and maintain a blood pressure of less than 180/105 mm Hg while alteplase is being infused and for the 24 hours after administration (Powers 2019). If the patient is not a candidate for intravenous fibrinolysis or mechanical thrombectomy, permissive hypertension, up to 220/120 mm Hg, is recommended to maintain cerebral perfusion to the penumbra. In these patients with no other indication for urgent hypertension treatment, the benefit of treatment of hypertension in the first 48 to 72 hours is uncertain (Powers 2019). The guidelines Table 4. Modified Rankin Scale Value Independent Dependent Description 0 No symptoms 1 No significant disability despite symptoms; able to carry out all usual duties and activities 2 Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3 Moderate disability; requiring some help, but able to walk without assistance 4 Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5 Severe disability; bedridden, incontinent, and requiring constant nursing care and attention 6 Dead Information from: van Swieten JC, Koudstaal PJ, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604-7. PSAP 2020 Book 1 Critical and Urgent Care 11 Acute Ischemic Stroke
Table 5. Options for Antihypertensive Agents in Acute Stroke Medication Dose Onset Duration Labetalol 10–20 mg slow IV push q5min, doubling dose until effect. May follow with an IV infusion at 2 mg/min. Titrate to max of 8 mg/min. Within 5 min 16–18 hr (dose dependent) Nicardipine 5 mg/hr IV continuous, titrate by 2.5 mg/hr q5–15min. Max 15 mg/hr Within 5 min; 50% of max effect at 45 min with continuous infusion 50% decrease in effect by 30 min after discontinuation Clevidipine 1–2 mg/hr IV continuous, titrate by doubling dose q2–5min. Max 21 mg/hr 2–4 min 5–15 min Hydralazine 10–20 mg IV push q4–6hr, max single dose 40 mg 10–80 min Up to 12 hr Enalaprilat 1.25 mg slow IV push over 5 min q6hr 6 hr Within 15 min, peak effect 1–4 hr IV intravenous(ly); q every. Information from: Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50:e344-e418. Management of Adverse Events concentrations by about 70 mg/dL after 10 units given to a patient weighing 70 kg), administration of this blood product to target a fibrinogen concentration of greater than 150 mg/dL is theorized to decrease the risk of further expansion. This theory, however, has never been prospectively evaluated, and retrospective studies have been underpowered to detect a treatment benefit. Antifibrinolytics such as tranexamic acid and ε-aminocaproic acid have less efficacy data in the setting of ICH after alteplase administration. Mechanistically, these agents competitively bind to plasminogen, blocking its conversion to plasmin and inhibiting fibrin degradation (Frontera 2016). Supporting data analyses for recommending these agents are limited to case reports and small, retrospective case series. Given the slightly stronger evidence for cryoprecipitate, the NCS guidelines recommend cryoprecipitate over antifibrinolytics unless there is a contraindication to using or significant delay in obtaining this product. The authors state that an antifibrinolytic such as tranexamic acid or ε-aminocaproic acid can be used as an alternative to cryoprecipitate if these conditions exist. Alternatively, the 2019 AHA/ASA guidelines for the early treatment of patients with AIS are less direct about this recommendation, suggesting that using both agents together could be considered, but certainly antifibrinolytics would have a specific benefit in situations where cryoprecipitate was unavailable or otherwise contraindicated. Transfusing platelets for the treatment of ICH associated with alteplase remains controversial as well. No data have supported the use of platelet transfusion, regardless of Plt. In fact, in one retrospective study, platelet transfusion was associated with a risk of hematoma expansion; however, given the study’s retrospective design, the authors could not The incidence of ICH after alteplase administration for AIS depends on several factors, including age, weight, history of hypertension, current antiplatelet therapy, baseline NIHSS score, blood glucose, SBP, and time since symptom onset (Mazya 2012). This complication can be devastating, with rates of hematoma expansion of up to 40% and 3-month mortality as high as 60%. “Reversal” of intravenous thrombolytics is usually indicated for symptomatic ICH with decline in neurologic function within the first 24 hours after administration. This may seem counterintuitive, given that the plasma half-life of alteplase is only 4 minutes; however, the terminal half-life is 72–100 minutes, and studies have noted a decrease in fibrinogen concentrations at 24 hours after administration. Treatment of thrombolytic-related ICH has great uncertainty, and guidance is limited to theoretical mechanisms, a heterogeneous mix of case series, and a few small, underpowered retrospective studies. Recommendations for managing ICH after alteplase in patients with AIS are available from the 2019 American Heart Association/American Stroke Association (AHA/ASA) guidelines for the early treatment of patients with AIS (Powers 2019) and the Neurocritical Care Society (NCS) guideline for reversal of antithrombotics in ICH (Frontera 2016). A summary of these recommendations is listed in Table 6. The recommendation for cryoprecipitate administration after alteplase-related ICH is based on a single, multicenter, retrospective study. This trial evaluated risk factors for patients with symptomatic ICH after receiving alteplase for AIS (Yaghi 2015). In this study, a fibrinogen concentration of less than 150 mg/dL was the only statistically significant predictor of hematoma expansion. Because cryoprecipitate contains fibrinogen 200 mg/unit (and can increase fibrinogen PSAP 2020 Book 1 Critical and Urgent Care 12 Acute Ischemic Stroke
Table 6. Management of Symptomatic ICH Within 24 Hr After IV Thrombolytic Administration AHA/ASA 2019 NCS 2016 Discontinue alteplase Discontinue thrombolytic infusion when ICH is present or suspected Obtain CBC, PT (INR), PTT, fibrinogen concentration, type, and cross-match No recommendation made for pretreatment laboratory tests Cryoprecipitate 10 units infused over 10–30 min. Administer additional dose if fibrinogen concentration 200 mg/dL Cryoprecipitate 10 units initially for patients with thrombolytic administration within previous 24 hr. Administer additional dose if fibrinogen concentration 150 mg/dL Tranexamic acid 1000 mg IV over 10 min OR ε-aminocaproic acid When cryoprecipitate contraindicated or unavailable in a 4–5 g IV over 1 hr, followed by 1 g IV until bleeding controlled timely fashion, suggest tranexamic acid 10–15 mg/kg IV over (Potential for benefit in all patients, but particularly when blood 20 min or ε-aminocaproic acid 4–5 g IV as an alternative to products are contraindicated or declined by patient/family or if cryoprecipitate cryoprecipitate is not available in a timely manner) No recommendation for platelet transfusion Unclear whether platelet transfusion is useful; therefore, no recommendation offered Hematology and neurosurgery consultation and supportive therapy, BP management, ICP, CPP, MAP, temperature, and glucose control No recommendation made for consultations or supportive therapies AHA/ASA American Heart Association/ American Stroke Association; BP blood pressure; CPP cerebral perfusion pressure; ICH intracranial hemorrhage; ICP intracranial pressure; MAP mean arterial pressure; NCS Neurocritical Care Society. Information from: Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50:e344-e418; Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for health-care professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016;24:6-46. conclude whether this finding was because of selection or even outcome bias (Yaghi 2015). Regardless, given the paucity of data with this intervention in ICH after alteplase, the NCS guidelines recommend against the routine use of platelets and make no recommendation about platelet transfusion in known thrombocytopenia. Additional supportive therapy for ICH after thrombolysis is essentially extrapolated from the management of spontaneous ICH. In-depth discussion is beyond the scope of this chapter. Briefly, SBP should be lowered to a target of less than 160 mm Hg to decrease the risk of further hematoma expansion. Administration of anticoagulation reversal agents such as 4-factor prothrombin complex concentrate and vitamin K should be reserved for patients who were receiving anticoagulants at the time of alteplase administration (Frontera 2016). Administration of hyperosmolar solutions such as hypertonic saline or mannitol may be necessary if cerebral edema or increased intracranial pressure is present or if the patient has signs of impending herniation. Orolingual angioedema is a rare but important adverse reaction associated with alteplase therapy after AIS. Alteplase is thought to cause angioedema in AIS through several pathways activated by the conversion of plasminogen PSAP 2020 Book 1 Critical and Urgent Care into plasmin, resulting in both histamine release and an increase in circulating bradykinin (Hill 2000). The 2019 AHA/ ASA guidelines provide treatment recommendations for alteplase-induced angioedema as outlined in Figure 2. The incidence of orolingual angioedema is 1%–5%, and concurrent use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with up to 65% of cases. This is thought to be propagated by an already elevated bradykinin in patients receiving ACEI therapy. In most cases associated with alteplase, angioedema is self-limiting and typically does not require an advanced airway. A recent, prospective analysis of 923 patients treated with intravenous alteplase for AIS in a single center in France found an overall incidence of angioedema of 2.2%, with no patients requiring an advanced airway or epinephrine (Myslimi 2016). Outcomes, including 90-day mRS and ICH, did not differ between those who had angioedema and those who did not. The risk of angioedema increased significantly in those receiving ACEI therapy (OR 3.8; 95% CI, 1.6–9.3). No single anatomic site of stroke was linked to the development of angioedema. The AHA/ASA guidelines recommend blood pressure checks, neurologic examinations, and angioedema screenings every 15 minutes for the first 2 hours after initiating 13 Acute Ischemic Stroke
Discontinue alteplase and hold ACEIs Maintain the airway Involvement of the larynx, palate, floor of mouth, or oropharynx with progression within 30 minutes may pose a higher risk of requiring intubation Treat histamine related angioedema Administer methylprednisolone 125 mg intravenously, diphenhydramine 50 mg intravenously, and ranitidine 50 mg or famotidine 20 mg intravenously May consider epinephrine 0.3 mg IM or 0.5 mg nebulized if angioedema continues despite above treatment Consider alternative therapies Consider icatibant (a selective bradykinin B2 receptor antagonist), 30 mg subcutaneously or plasma-derived C1 esterase inhibitor 20 IU/kg intravenously Figure 2. Treatment of alteplase-induced angioedema. C1 complement 1; IM intramuscular(ly). Information from: Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50:e344-e418. alteplase and then every 30 minutes for the next 6 hou
PSAP 2020 Book 1 Critical and Urgent Care 7 Acute Ischemic Stroke Acute Ischemic Stroke By Steven H. Nakajima, Pharm.D., BCCCP; and Katleen Wyatt Chester, Pharm.D., BCCCP, BCGP INTRODUCTION Stroke is the leading cause of serious long-term disability and the
Green et al Care of the Patient With Acute Ischemic Stroke Stroke. 2021;52:00-00. DOI: 10.1161/STR.0000000000000357 TBD 2021 e3 patient was cared for in an acute stroke unit. Care in a stroke unit resulted in an increased chance of func-tional recovery from acute stroke assessed with Barthel
enoxaparin, warfarin, NOAC) depends on stroke etiology Do not routinely use heparin drips for acute ischemic stroke Recent Cochrane Review: Anticoagulation within 48 hours of stroke Decreased risk of recurrent ischemic stroke, PE Significant
stroke-related deaths than white Americans (1,12). Reflecting this ethnic disparity, stroke mortality is 20% higher in the Southeast stroke belt of the US (13). Pathophysiology More than 85% of strokes are ischemic with the remainder being hemorrhagic (1). The Trial of ORG 10172 in the Acute Stroke Treatment
number of stroke patients continues to enlarge because of the ageing population [3]. Of those, acute ischemic stroke as the dominant type of stroke, account for 85 % of all strokes [4]. Currently, rapid assessment and early intervention for patients suffering an acute ischemic stroke is of top pri-ority [5, 6]. There is as yet no routine .
1994, Bragoni 44, F Ischemic stroke 1994, Urban 41, F Venous sinus thrombosis 1995, Giordano 55, F SAH 1996, Nagahiro 17, F Ischemic stroke 2002, Koh 50, F Ischemic stroke 2009, Klingler 46, F SAH 2010, Hayashi 54, F SAH 2012, Asai 52, F Thalamic hemorrhage 2012, Ishizaka 66, F SAH 2013, Wang 39, F ICH 2013, Mercurio 43, F Venous sinus thrombosis
from the American College of Chest Physicians (ACCP) (Geerts 2004). National guidelines are also available, such as those published by the Scot-tish Intercollegiate Guidelines Net-work (SIGN 2003). The first ACCP recommendations were published in 1986 (ACCP/NHLBI 1986). Since then,the ACCP
Call an ACCP customer service rep-resentative at (913) 492-3311, 8 a.m. 5 p.m. (Central Time) Monday through Friday. 3. ACCP Ambulatory Care Pharmacist's . NEW ACCP PUBLICATIONS. The second edition of Clinical Pharmacy in the United States: Transformation of a Profession
The modern approach is fact based and lays emphasis on the factual study of political phenomenon to arrive at scientific and definite conclusions. The modern approaches include sociological approach, economic approach, psychological approach, quantitative approach, simulation approach, system approach, behavioural approach, Marxian approach etc. 2 Wasby, L Stephen (1972), “Political Science .
