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Sroke continuum 2014

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  • 1. Evaluation and Management of Acute Ischemic Stroke Pooja Khatri, MD, MSc ABSTRACT Purpose of Review: This review provides an overview of emergent evaluation of the stroke patient with an emphasis on practical issues regarding ischemic stroke treatment. Recent Findings: The IV recombinant tissue-type plasminogen activator (rtPA) treatment window has been expanded from 3 to 4.5 hours from symptom onset. The evidence for better outcomes with more rapid initiation of reperfusion therapies is very strong. Adjunctive endovascular therapy has not been shown to benefit all patients with moderate or severe strokes, and investigations are underway to identify subgroups that may benefit from this approach. Endovascular therapy should be considered for patients who are ineligible for IV rtPA and can begin treatment within 6 hours of stroke onset. Summary: Effective emergent evaluation of a stroke patient requires well-organized systems that maximize speed of assessment and administration of appropriate therapies, including IV rtPA and endovascular therapies. Continuum (Minneap Minn) 2014;20(2):283–295. INTRODUCTION This article provides a practical over- view regarding the emergent evalua- tion of a patient with acute ischemic stroke, including the decision to administer acute reperfusion therapy and other acute supportive care. It should be noted that ‘‘acute re- perfusion therapy’’ refers to treat- ment aimed at emergently restoring blood flow in the acutely occluded cerebral artery, and may consist of IV thrombolysis and/or specific endovas- cular interventions such as intra- arterial thrombolysis or mechanical embolectomy. This discussion is framed around the most recent American Heart Association/American Stroke Associ- ation guidelines, which serve as use- ful and comprehensive references to the reader.1 EMERGENT EVALUATION OF THE POTENTIAL ACUTE REPERFUSION CANDIDATE Rapid evaluation and treatment is critical for the best outcomes. This has been shown both in the setting of IV thrombolysis (IV recombinant tissue-type plasminogen activator [rtPA]) and endovascular therapy. With IV rtPA, the number needed to treat to prevent one death or signifi- cant disability is 8 when treating within 3 hours of symptom onset, and 14 when treating from 3 to 4.5 hours.2,3 Figure 1-1 demonstrates the odds of good outcome with IV rtPA treatment among subjects pooled from major trials to date.4 It has also been demonstrated that every 30- minute delay in acute reperfusion leads to a 10% relative reduction in the likelihood of a good outcome.5 Address correspondence to Dr Pooja Khatri, Department of Neurology, University of Cincinnati, 260 Stetson Street, ML 0525, Cincinnati, OH 45267-0525, pooja.khatri@uc.edu. Relationship Disclosure: Dr Khatri has received research grants from the NIH and research support from Penumbra Inc and Genentech, Inc. Unlabeled Use of Products/Investigational Use Disclosure: Dr Khatri discusses the use of IV tissue plasminogen activator for minor stroke and of endovascular therapy for stroke treatment, neither of which are approved by the US Food and Drug Administration. * 2014, American Academy of Neurology. 283Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com Review Article Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 2. A patient should receive IV rtPA within 1 hour of arrival to an emergency department (and sooner is better) with the following goals.6 & Emergency department physician sees patient within 10 minutes of arrival & Stroke consultant is notified within 15 minutes of arrival & CT scan is completed within 25 minutes of arrival & CT is interpreted within 45 minutes of arrival Strategies likely to increase the speed of treatment include early stroke-team notification (preferably be- fore or concurrent with CT scan per- formance); storage of rtPA in the emergency department; recognition that glucose level is the only necessary laboratory result if no clinical suspicion for bleeding diathesis is present; and mixing of IV rtPA (1:1 ratio with sterile water or normal saline) early. DECISION TO ADMINISTER ACUTE REPERFUSION THERAPY The following information is needed from the emergency department upon initial consultation to guide clinical decision making. & Time that patient was last known to be well & Any significant medical history & A brief neurologic examination (ideally the NIH Stroke Scale [NIHSS]) & Glucose level (finger stick) and any other significant laboratory results & Current blood pressure & Results of acute brain imaging, typically CT scan, when available Each of these points and their role in decision making are described in subsequent sections. Time The patient’s ‘‘last known well’’ time determines potential treatment options. KEY POINTS h Rapid evaluation and treatment are critical for the best outcomes. h A patient should receive IV recombinant tissue-type plasminogen activator within 1 hour of arrival to an emergency department (and sooner is better). FIGURE 1-1 Odds of good outcome based on stroke onset to treatment time. Pooled analysis of European Cooperative Acute Stroke Study (ECASS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke (ATLANTIS), National Institute of Neurological Disorders and Stroke (NINDS), and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) subjects demonstrates that later onset to treatment times lead to lower odds of a treatment effect of IV rtPA compared with placebo. Treatment beyond 270 minutes appears to have no benefit. Reprinted with permission from Lees KR, et al, Lancet. 4 B 2010 Elsevier. www.sciencedirect.com/science/ article/pii/S0140673610604916. 284 www.ContinuumJournal.com April 2014 Acute Stroke Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 3. It is important to distinguish the time last known well from the time that the stroke deficits were first discovered, as demonstrated by Case 1-1. IV thrombolysis, specifically using rtPA, should be considered for patients for whom it can be administered within 4.5 hours of onset. IV rtPA (at the dose of 0.9 mg/kg, maximum dose 90 mg, with 10% given as an initial bolus) has been shown to improve clinical out- comes for patients within 3 hours of onset by two randomized trials (jointly referred to as the National Institutes of Neurological Disorders and Stroke [NINDS] tPA Stroke Study),2 and within 3 to 4.5 hours by one randomized trial (European Cooperative Acute Stroke Study III).3 Specifically, within 3 hours of onset, despite a 6% increased risk of symptomatic intracranial hemorrhage, the overall absolute benefit of treatment is a 13% lower rate of significant dis- ability (defined as a modified Rankin Scale of 0 or 1). This benefit is estimated to be as high as 33% for any improve- ment in the spectrum of independence to severe disability or death; Figure 1-27 illustrates potential treatment effects.8 Several community cohorts,9 pooled analyses of other IV rtPA trials,4 and the 3-hour subgroup of the Third Interna- tional Stroke Trial (IST-3) provide further supportive evidence.10 Of note, KEY POINT h IV thrombolysis, specifically using recombinant tissue-type plasminogen activator, should be considered for patients for whom it can be administered within 4.5 hours of onset of stroke deficits. Case 1-1 A 78-year-old woman with a history of diabetes mellitus presented to the emergency department with acute left-sided weakness at 4:00 PM. Her husband had called 9-1-1 immediately upon identifying her symptoms at 3:30 PM. Emergency medical services (EMS) had promptly evaluated the patient and brought her to the stroke-ready emergency department. En route, EMS had prenotified the hospital, where a CT scan was performed upon the patient’s arrival. The CT scan showed minimal early ischemic changes and no intracranial hemorrhage. The patient’s finger-stick glucose level was 95 mg/dL, and her examination revealed left hemiplegia and anosognosia. Her husband reported that her only medication was metformin and she had no recent surgeries or prior history of intracranial hemorrhage. However, upon further discussion regarding the time of onset with the stroke clinician, it became clear that, while the patient’s symptoms were discovered at 3:30 PM, her husband had last seen her well before he left for work at 9:00 AM. The patient reported feeling fine until her husband came home. Her cell phone was checked, and she had not spoken to anyone that day. Her neighbor was called by the husband, and the patient had not been witnessed to be well by anyone else since 9:00 AM. Thus, it was 7 hours from last known well at this point, and IV recombinant tissue-type plasminogen activator (rtPA) was not administered. Comment. In this case, if the patient had not had anosognosia, it may have been appropriate to identify the last known well time based on the patient’s own history. However, given her lack of appreciation for her deficit, her report could not be trusted. A normal CT scan has not been demonstrated to identify patients who might benefit from IV rtPA regardless of time from last known well. However, an active and promising area of investigation is to develop imaging markers that can identify patients who will benefit from IV rtPA treatment based on physiologic time. Had it not been for the unknown and potentially greater than 4.5-hour time of onset, the patient in this case would have been eligible for IV rtPA. 285Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 4. the US Food and Drug Administration has only approved the 3-hour time window for IV rtPA, whereas clinical guidelines recommend treatment up to 4.5 hours based on the current evidence.1 It should also be noted that no other lytic agent, such as reteplase or tenecteplase, has been demonstrated as an effective treatment for acute ischemic stroke. Endovascular therapy for IV re- combinant tissue-type plasminogen activatorYineligible patients. For pa- tients ineligible for IV rtPA (because of, for example, time of onset, coagulopathy, or recent surgery) who have significant stroke deficits (typically, an NIHSS score of 8 or higher), endovascular therapy should be consid- ered if treatment can be initiated within 6 hours (Case 1-2). Indirect evidence, including the Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial of recombinant prourokinase and the Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) of urokinase,11Y13 suggests that intra- arterial rtPA initiated within 6 hours of onset will lead to better clinical out- comes than supportive care alone (ie, no reperfusion therapy). More recent evidence suggests that endovascular devices open major arterial occlusions more effectively, leading to their fre- quent clinical use in this setting; spe- cifically, the most recent generation of mechanical embolectomy devices, in- cluding the Penumbra Aspiration Sys- tem, the Solitaire Stent Retriever, and the TREVO2 Stent Retriever, report revascularization rates exceeding 80%.14Y16 Comparable safety and effi- cacy between IV rtPA within 3 hours versus endovascular therapy within 6 hours in the SYNTHESIS trial also sup- ports the approach for IV rtPAYineligible patients who present early.17 Case series data also suggest reasonable safety for the use of intra-arterial thrombolysis in the nonneurosurgical postoperative set- ting.18 Devices available in the United States are shown in Figure 1-4. The role of imaging selection to identify patients beyond 6 hours from onset who will benefit from acute reperfusion therapies remains to be determined. A phase 2b study, the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) trial, tested the penum- bral hypothesis.19 A favorable CT-based or magnetic resonanceYbased penum- bral selection pattern was defined as a KEY POINT h For patients ineligible for IV recombinant tissue-type plasminogen activator who have significant stroke deficits (typically, an NIH Stroke Scale score of 8 or greater), endovascular therapy should be considered if treatment can be initiated within 6 hours. FIGURE 1-2 Changes in final outcome as a result of intravenous recombinant tissue-type plasminogen activator (IV rtPA) treatment within 3 hours of onset. Reprinted from Saver JL, Medscape. 7 emedicine. medscape.com/article/1160840-overview. 286 www.ContinuumJournal.com April 2014 Acute Stroke Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 5. Case 1-2 A 65-year-old woman who was postoperative from coronary artery bypass graft surgery was found to have right-sided weakness and confusion in the postoperative anesthesia care unit (PACU) upon regaining consciousness from general anesthesia at 3:00 PM. She was last known to be neurologically normal at 12:00 PM. The on-call neurologist, who was immediately activated by the PACU nurse, identified a left middle cerebral artery syndrome with global aphasia and right hemiparesis (NIH Stroke Scale score of 20). Given the recent surgery, she deemed the patient to be ineligible for IV recombinant tissue-type plasminogen activator (rtPA), and alerted the neurointerventional team regarding a potential endovascular case while transporting the patient to the CT scanner. The CT scan revealed no intracranial hemorrhage, no early ischemic changes, and a hyperdense left middle cerebral artery; the patient was briskly taken directly from the CT scanner to the neuroangiography suite. Groin stick was performed at 4 hours after her last time seen normal, and a left proximal middle cerebral artery thrombus was evacuated by mechanical embolectomy at 4.5 hours with complete angiographic reperfusion observed on finalangiogram, asdemonstrated inFigure 1-3. Upon reexamination after the procedure, the patient had regained strength on her right side and her aphasia (now primarily expressive) was improved. Follow-up CT scan showed a small branch middle cerebral artery infarct. Comment. Given the recent surgery, IV rtPA could not be safely administered in this patient. In this case, emergent endovascular treatment was a consideration. Rapid time to angiographic reperfusion likely contributed to the improved clinical outcome seen after the procedure. Of note, despite the observation of complete angiographic reperfusion, some infarct burden remained. This may have been due to a distal embolus or brain tissue that was irreversibly infarcted by the time angiographic reperfusion was achieved. FIGURE 1-3 Example of middle cerebral artery (MCA) infarction with hyperdense left middle cerebral artery on baseline CT scan (A). Proximal MCA (M1) occlusion on pretreatment digital subtraction angiogram in coronal (B) and sagittal (C) planes, mechanical extraction of intact thrombus (D), and complete angiographic reperfusion in coronal (E), and sagittal (F) planes. Courtesy of Aaron Grossman, MD, PhD, and Todd Abruzzo, MD, University of Cincinnati Medical Center. 287Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 6. predicted infarct core comprising 70% or more of ‘‘at-risk’’ tissue as identified by a complex voxel-by-voxel algorithm, and incorporating baseline NIHSS score for the CT-based cases as well. Patients for whom endovascular treatment could be initiated within 8 hours of symptom onset were randomized to mechanical embolectomy versus supportive care, and stratified by the presence of penum- bra. The presence of penumbra did not discriminate between subjects who would differentially benefit from mechanical em- bolectomy, but did predict better clinical outcomes among those with penumbra regardless of treatment arm. Evidence for newer definitions of penumbra, and its use beyond 8 hours from onset, are limited to nonrandomized cohort studies of treated patients only.20,21 These single- arm trials are unable to discriminate between a predictor of treatment effect and a marker of better clinical outcome regardless of treatment. This is an active area of investigation, and several planned and ongoing randomized trials will likely inform this discussion in the future.22 Medical History In addition to eligibility based on time from onset, acute reperfusion treat- ment options are further determined by eliciting key medical history. IV rtPA exclusion criteria and relative contraindications are listed in Box 1-1.1 A consensus definition of deficits that should typically be considered disabling (regardless of total NIHSS score) is shown in Table 1-1. Based on limited evidence, poten- tial eligibility for endovascular therapy in IV rtPAYineligible patients might include age younger than 85 years, NIHSS greater than or equal to 8, and treatment within 6 hours of onset.1,10,11 Brief Examination and NIHSS The examination helps the clinician determine that the patient is indeed having a stroke and gauge its severity. The NIHSS score, in particular, is a useful way to describe and follow the patient’s examination (Appendix A). All clinicians who care for stroke patients in the acute setting should be NIHSS certified KEY POINTS h Rapidly improving deficits should not be considered a contraindication unless the remaining deficit is minor. h Additional exclusion criteria for IV recombinant tissue-type plasminogen activator within the 3- to 4.5-hour time window include a history of stroke and diabetes mellitus, NIH Stroke Scale score greater than 25, age greater than 80 years, and warfarin use (regardless of international normalized ratio value). h All clinicians who care for stroke patients in the acute setting should be NIH Stroke Scale certified. FIGURE 1-4 Devices cleared by the US Food and Drug Administration for acute stroke clot removal: A, Merci Retriever; B, Solitaire stent retriever; C, Penumbra aspiration system; and D, TREVO2 stent retriever. Panel A courtesy of Concentric Medical, Inc; Panel B courtesy of Covidien; Panel C courtesy of Penumbra, Inc; Panel D courtesy of Stryker. 288 www.ContinuumJournal.com April 2014 Acute Stroke Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 7. BOX 1-1 IV rtPA Exclusion and Relative Contraindication Criteria Key IV rtPA Exclusion Criteria & Stroke or significant head trauma within 3 months & Major surgery or serious trauma within 14 days & Gastrointestinal or urinary hemorrhage within 21 days & Arterial puncture at a noncompressible site within 7 days & History of intracranial hemorrhage & Intracranial neoplasm, arteriovenous malformation, or aneurysm ) Some experts consider treating patients with remotely secured or unruptured aneurysms & Symptoms of subarachnoid hemorrhage & Active internal bleeding & Pretreatment blood pressure with systolic 9185 mm Hg or diastolic 9110 mm Hg & Clear and large hypodensity on CT scan & Current bleeding diathesis including ) International normalized ratio (INR) 91.7 ) Heparin within 48 hours resulting in abnormal partial thromboplastin time (PTT) ) Platelets G100,000/mm3 ) Direct thrombin inhibitor (eg, dabigatran) or factor Xa inhibitor (eg, rivaroxaban, apixaban) use within 48 hours h Optimal laboratory testing thresholds for safe IV recombinant tissue-type plasminogen activator (rtPA) use in this setting remain to be determined and are an area of active investigation. & Serum glucose G50 ) If persistent symptoms after correction, or infarct is verified/supported by imaging, most experts would consider IV rtPA treatment. Relative Contraindications for IV rtPA1 & Minor deficit ) Rapidly improving deficits should not be considered a contraindication unless the remaining deficit is minor.23 ) A common definition of minor deficits is an NIH Stroke Scale (NIHSS) score e5 and not clearly disabling. ) A consensus definition of deficits that should typically be considered disabling (regardless of total NIHSS score) is shown in Table 1-1. & Myocardial infarction in the past 3 months ) Some experienced centers treat this as a contraindication only if the myocardial infarction is subacute and transmural, or other signs suggest a high risk of hemopericardium, such as clinical or ECG evidence of pericarditis. ) Concurrent acute myocardial infarction may benefit from IV rtPA as well and should be considered in consultation with a cardiologist; however, only lower stroke dosing of 0.9 mg/kg (not higher cardiac dosing of approximately 1.1 mg/kg) should be used in this setting. & Seizure at presentation ) If stroke is verified by imaging, IV rtPA treatment should be considered. However, the severity of concurrent stroke must be judged in the context of ictal/postictal presentation. & Pregnancy ) Must weigh risks and benefits in the individual circumstances. Continued on next page 289Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 8. (http://nihss-english.trainingcampus. net/uas/modules/trees/windex.aspx). However, emergency physicians are not always NIHSS trained, and a de- scriptive examination can be used to estimate the NIHSS score and thereby the severity of the stroke in that circumstance. Treating a stroke mimic, such as a complicated migraine or seizure, with IV rtPA is inevitable sometimes. Fortunately, the risk of intracranial hemorrhage when treating a stroke mimic with IV rtPA inadvertently is extremely low (less than 1%) based on case series of tPA-treated stroke mimics and the cardiology literature.24 Therefore, time to treatment should not be lost with ancillary testing such as MRI or CT angiography if stroke seems likely but not definitive. The role of adjunctive endovascular treatment for severe IV rtPAYtreated ischemic strokes remains to be deter- mined. The only randomized trial of the combined IV rtPA/endovascular approach to date, the Interventional Management of Stroke (IMS) III trial, did not demonstrate its superiority over IV rtPA alone among subjects of 18 to 83 years of age with severe strokes (NIHSS score of 8 or higher), although safety parameters were comparable.25 The trial results also suggested that the clinical benefit of successful flow restoration may be lost beyond 7 hours from stroke onset in the average patient. It has been hy- pothesized that subgroups of patients may benefit from endovascular therapy, such as those with the most severe deficits (eg, an NIHSS score greater than KEY POINTS h The risk of intracranial hemorrhage when treating a stroke mimic with IV recombinant tissue-type plasminogen activator inadvertently is extremely low (less than 1%). h The combined IV/ endovascular approach in all patients with an NIH Stroke Scale score of 8 or greater is not superior to IV recombinant tissue-type plasminogen activator alone despite comparable safety. BOX 1-1 IV rtPA Exclusion and Relative Contraindication Criteria (continued) Additional Exclusion Criteria for IV rtPA Within the 3- to 4.5-Hour Time Window1 & History of stroke AND diabetes mellitus & NIHSS score 925 & Age 980 years old & On warfarin (regardless of INR value) TABLE 1-1 Proposed Operational Definition of Disabling Deficitsa,b The following typically should be considered disabling deficits: Complete hemianopsia (Q2 on NIH Stroke Scale [NIHSS] question 3), or Severe aphasia (Q2 on NIHSS question 9), or Visual or sensory extinction (Q1 on NIHSS question 11), or Any weakness limiting sustained effort against gravity (Q2 on NIHSS question 6 or 7), Any deficits that lead to a total NIHSS 95, or Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner. Clinical judgment is required. a Reprinted with permission from Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force, Stroke.23 stroke.ahajournals.org/content/44/9/2500.abstract. b All neurologic deficits present at the time of the treatment decision should be considered in the context of individual risk and benefit, as well as the patient’s baseline functional status. 290 www.ContinuumJournal.com April 2014 Acute Stroke Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 9. 20), patients with demonstrated large proximal arterial occlusions (such as internalcarotid artery terminusocclusions or occlusions that are greater than 8 mm in length), and those whose occlusions are recanalized more rapidly or effectively. Several randomized trials of more selec- tive patient subgroups are now underway. Glucose and Other Laboratory Results Testing for serum glucose level is necessary before the IV rtPA treatment decision.1 This should take minimal time when performed by finger stick and is often done by EMS en route. This test allows the clinician to exclude stroke mimics of hypoglycemia or hyperglycemia. If the hypoglycemic patient’s symptoms resolve after glu- cose administration, then IV rtPA may not be indicated. Hyperglycemia can present with choreiform movements that can be mistaken for stroke symp- toms. Experts generally believe that neither hypoglycemia nor hyperglyce- mia should preclude IV rtPA treatment if the deficits are believed to be caused by concurrent ischemia. Other laboratory results should be so- licited if available, but they are not ne- cessary. In particular, INR, PTT, and platelet count will help determine IV rtPA eligibility. However, IV rtPA administration should not be delayed for any laboratory result other than finger-stick glucose level unless a clinical suspicion for an abnormality exists. Fewer than three in 1000 patients will have unsuspected thrombocytopenia,26 and fewer than four in 1000 patients will have an unsus- pected INR greater than 1.7.27 Blood Pressure Blood pressure is generally maintained relatively high after acute ischemic stroke. In the setting of cerebral ischemia, a loss of cerebral autoregulation occurs such that systemic blood pressures directly affect cerebral perfusion pres- sure. In this setting, increased systemic blood pressure will improve blood flow to the cerebral infarct, often via collateral blood vessels, and thereby may reduce the extent of irreversible ischemia. The upper limits of blood pressure control are dictated by the decision of whether to administer acute reperfu- sion therapy. The blood pressure must be less than 185 mm Hg systolic and 110 mm Hg diastolic for IV rtPA eligibility, and must be maintained below 180/105 mm Hg during and after IV rtPA administration. Gentle blood pressure reduction can usually be achieved with labetalol 10 mg IV. If this dose is not enough, then it might be doubled. If no response occurs, a nicardipine infusion (5 mg per hour IV, titrate up by 2.5 mg per hour every 5 to 15 minutes, maximum 15 mg per hour) may be needed and typically achieves the blood pressure goals. If nicardipine is not available, or contra- indications exist for this or labetalol, another consideration is IV enalaprilat 3.25 mg to 6.5 mg. Acute Brain Imaging Imaging of the brain parenchyma serves the primary role of ruling out intracranial hemorrhage, including intracerebral, subarachnoid, and epidural/subdural lo- cations. At most centers, a noncontrast CT scan is the most rapid modality available, although some centers may use limited MRI (specifically consisting of diffusion-weighted imaging [DWI], either susceptibility-weighted [SW] im- aging or gradient echo [GRE] se- quences, and fluid-attenuated inversion recovery [FLAIR] sequences) if rapidly available. Rarely, an acute CT scan will reveal a large and clear hypodensity that will lead to questioning the time of onset of the stroke and the possibility of an undiagnosed subacute stroke, both of which would contraindicate IV KEY POINT h One should not delay IV recombinant tissue-type plasminogen activator administration for any laboratory result other than finger-stick glucose level unless a clinical suspicion for an abnormality exists. 291Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 10. rtPA. Subtle changes may also be seen on CT scan, such as loss of gray-white differentiation or sulcal effacement, to support the diagnosis of ischemic stroke. While subtle ischemic changes on CT scan are not contraindications to acute reperfusion therapy, they do portend worse outcomes compared with those with lesser acute ischemic changes on CT scan.28 Advanced imaging, specifically head and neck vascular imaging with CT angiography or magnetic resonance angiography, can be valuable in plan- ning the approach to endovascular therapy if indicated, determining the etiology of stroke for secondary pre- vention (eg, carotid endarterectomy), or obtaining supportive evidence for an ischemic stroke diagnosis. Using this as a first-line imaging approach for all ‘‘rule-out stroke patients’’ in an emergency department is likely to be inappropriate, given the additional radiation exposure to a diverse group of patients. In settings where an expert physician triages stroke patients, CT angiography or magnetic resonance angiography may be useful in selected cases (ie, IV rtPAYineligible patients who arrive in the emergency department early) to identify symptomatic occlu- sions amenable to acute endovascular therapy while the neurointerventional team is being mobilized. In all cases, advanced neuroimaging should not de- lay the administration of IV rtPA. To date, there is no known role for other forms of advanced imaging, such as perfusion studies with CT perfusion or magnetic resonance perfusion-weighted imaging, to select patients for acute reperfusion thera- pies. In particular, no data have supported the utility of identifying penumbra (ie, brain at risk for infarc- tion without reperfusion) for IV rtPA decisions, as the majority of these patients will have penumbra within 4.5 hours, and the role of penumbral imaging for selecting patients for acute reperfusion treatment beyond 4.5 hours remains to be determined (as discussed earlier in this review). POSTREPERFUSION THERAPY CARE Standard post-tPA management for the first 24 hours includes the following: & admission to a step-down or intensive care unit & maintenance of nothing-by-mouth (NPO) status until dysphagia screening is performed to avoid aspiration pneumonia & administration of isotonic IV fluids (not dextrose containing because of risk of hyperglycemia) & blood pressure and neurologic monitoring every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then every hour for 16 hours after treatment & aggressive blood pressure treatment if systolic blood pressure is greater than 180 mm Hg or diastolic blood pressure is greater than 105 mm Hg & emergent CT scan of the brain if neurologic decline, acute increase in blood pressure, nausea, vomiting, or new headache is present to rule out hemorrhagic transformation & repeat brain imaging at 24 hours to assess for asymptomatic hemorrhage and to allow initiation of antiplatelet therapy OTHER ACUTE ISCHEMIC STROKE MANAGEMENT CONSIDERATIONS Blood Pressure in Patients With No Reperfusion Therapies Data are very limited to dictate the optimal blood pressure in this set- ting. Experts generally recommend permissive hypertension if tolerated KEY POINTS h Subtle ischemic changes on CT scan are not contraindications to acute reperfusion therapy. h Standard postYtissue plasminogen activator management for the first 24 hours includes aggressive blood pressure treatment if systolic blood pressure is greater than 180 mm Hg or diastolic blood pressure is greater than 105 mm Hg. 292 www.ContinuumJournal.com April 2014 Acute Stroke Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
  • 11. (up to 220/120 mm Hg) in the non- reperfusion therapy setting and con- sideration of lowering blood pressure by 15% over the first 24 hours.1 Less commonly, blood pressure may be low in the acute setting, and stroke deficits may improve with raising the pressure. Most experts will attempt IV fluid boluses to raise blood pressure in the setting of relative hypotension and see if stroke symptoms improve with this intervention. If the stroke deficits appear to be pressure depen- dent, more aggressive blood pressure support with pressors may be consid- ered. Evidence for the role of pressors in the acute stroke setting is limited, however. Glucose in the Acute Setting Hyperglycemia (greater than 140 mg/dL) during the first 24 hours after stroke is a poor prognostic indicator. Whether acute correction will lead to better clinical out- comes after stroke is unknown. Current recommendations are to treat hyper- glycemia to achieve a level lower than 180 mg/dL, and stricter glucose control is under study in a major randomized clinical trial.1 Antithrombotic Therapy in the Acute Setting Aspirin should be initiated within 48 hours in all patients and is typically initiated in the emergency department if no acute reperfusion therapy is administered. If IV rtPA or acute endovascular therapy is administered, aspirin is initiated at approximately 24 hours and only after confirmation of no hemorrhagic transformation on the 24-hour CT scan. Early aspirin treat- ment leads to a 1% absolute reduction of stroke over the next 2 weeks.29,30 Recent evidence from a randomized trial in China of TIA and minor stroke patients who were not treated with IV tPA has suggested that short-term combined aspirin and clopidogrel admin- istration may better prevent early stroke recurrence in minor strokes or TIAs, and further randomized study is currently underway in the United States.31 It is well established that acute anticoagulation (including unfractionated and low-molecular-weight heparin) does not improve clinical outcomes after acute ischemic stroke compared with antiplatelet therapy in unselected patients. There may be a role for acute anticoagulation in specific circum- stances in which early stroke recurrence risk is high, but clinical data are lacking. SUMMARY In summary, effective emergent evalua- tion of a stroke patient requires well- organized systems that maximize speed of assessment and administration of appropriate therapies. This article pro- vides a practical overview of this pro- cess, and the reader is referred to the American Heart Association/American Stroke Association clinical guidelines for more detailed discussions. When these systems cannot appropriately be implemented at a given hospital, it is imperative that triage and bypass plans be implemented to maximize clinical outcomes after stroke. REFERENCES 1. Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44(3):870Y947. 2. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333(24): 1581Y1587. 3. Hacke W, Donnan G, Fieschi C, et al; ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators. Association of outcome with KEY POINTS h Experts generally recommend permissive hypertension if tolerated (up to 220/120 mm Hg) in the nonreperfusion therapy setting. h Current recommendations are to treat hyperglycemia to a level lower than 180 mg/dL. h Early aspirin treatment leads to a 1% absolute reduction of stroke over the next 2 weeks. h Short-term combined aspirin and clopidogrel administration may better prevent early stroke recurrence in minor strokes or TIAs. 293Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
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