7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Initial assessment and management of acute stroke : Jamary Oliveira-Filho, MD, MS, PhD, Michael T Mullen, MD : Scott E Kasner, MD, Jonathan A Edlow, MD, FACEP : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Jun 19, 2023. INTRODUCTION The subacute and long-term assessment and management of patients who have suffered a stroke includes physical therapy and testing to determine the precise etiology of the event so as to prevent recurrence. The acute management differs. Immediate goals include minimizing brain injury, treating medical complications, and moving toward uncovering the pathophysiologic basis of the patient's symptoms. Patient assessment and management during the acute phase (first few hours) of an ischemic stroke will be reviewed here. Use of thrombolytic therapy, endovascular thrombectomy, treatment of patients not eligible for reperfusion therapy, the clinical diagnosis of various types of stroke, and the subacute and long-term assessment of patients who have had a stroke are discussed separately. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack" and "Clinical diagnosis of stroke subtypes" and "Overview of the evaluation of stroke".) INITIAL ASSESSMENT Sudden loss of focal brain function is the core feature of the onset of ischemic stroke. However, patients with conditions other than brain ischemia may present in a similar fashion ( table 1). (See "Differential diagnosis of transient ischemic attack and acute stroke".) In addition, patients suffering a stroke may present with other serious medical conditions. Thus, the initial evaluation requires a rapid but broad assessment. https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 1/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate The goals in the initial phase include: Ensuring medical stability, with particular attention to airway, breathing, and circulation Quickly reversing any conditions that are contributing to the patient's problem Determining if patients with acute ischemic stroke are candidates for intravenous thrombolytic therapy ( table 2) or endovascular thrombectomy (see "Approach to reperfusion therapy for acute ischemic stroke") Moving toward uncovering the pathophysiologic basis of the patient's neurologic symptoms Time is of the essence in the hyperacute evaluation of stroke patients. The history, physical examination, serum glucose, oxygen saturation, and a noncontrast computed tomography (CT) scan are sufficient in most cases to guide acute therapy (see 'Immediate laboratory studies' below). Other tests are considered based upon individual patient characteristics, but the absence or unavailability of any additional tests need not be a reason to delay therapy if otherwise indicated. Airway, breathing and circulation Assessing vital signs and ensuring stabilization of airway, breathing, and circulation is part of the initial evaluation of all patients with critical illness, including those with stroke [1]. Patients with decreased consciousness or bulbar dysfunction may be unable to protect their airway, and those with increased intracranial pressure due to hemorrhage, vertebrobasilar ischemia, or bihemispheric ischemia can present with vomiting, decreased respiratory drive, or muscular airway obstruction. Hypoventilation, with a resulting increase in carbon dioxide, may lead to cerebral vasodilation and elevate intracranial pressure. In these cases, intubation may be necessary to restore adequate ventilation and to protect the airway from aspiration. Patients with adequate ventilation should have the oxygen saturation monitored. Patients who are hypoxic should receive supplemental oxygen to maintain oxygen saturation >94 percent [1]. Supplemental oxygen should not routinely be given to nonhypoxic patients with acute ischemic stroke. History and physical Establishing the time of ischemic stroke symptom onset is critical because it is the main determinant of eligibility for treatment with intravenous thrombolysis ( table 2) and endovascular thrombectomy [2]. For patients who are unable to provide a reliable onset time, symptom onset is defined as the time the patient was last known to be normal or at baseline neurologic status [1]. At times, information from family members, co- workers, or paramedics (who interviewed witnesses to the onset) may establish the time the patient was last known to be normal. For patients presenting within the therapeutic window for intravenous thrombolysis (less than 4.5 hours from symptom onset) or mechanical https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 2/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate thrombectomy (less than 24 hours from symptom onset), the history needs to be accurate but rapid; contraindications to thrombolytic treatment should also be assessed ( table 2). (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Rapid evaluation'.) The history and physical examination should be used to distinguish between other disorders in the differential diagnosis of brain ischemia ( table 1). As examples, seizures, syncope, migraine, hypoglycemia (see 'Hypoglycemia' below), hyperglycemia, movement disorders, or drug toxicity can mimic acute ischemia [1,3]. The most difficult cases involve patients with the combination of focal signs and altered level of consciousness. It is important to ask the patient, relative, or any reliable informant whether the patient takes insulin or oral hypoglycemic agents, has a history of epilepsy, drug overdose or abuse, or recent trauma. (See "Differential diagnosis of transient ischemic attack and acute stroke".) Diagnosing an intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) as soon as possible can be lifesaving [4,5]. The history may be helpful in this regard. The presence of acute onset headache and vomiting favor the diagnosis of ICH or SAH compared with a thromboembolic stroke ( figure 1), while the abrupt onset of impaired cerebral function without focal symptoms favors the diagnosis of SAH. Another important element of the history is whether the patient takes anticoagulant drugs. Even with these clues, diagnosing intracranial hemorrhage on clinical grounds is very imprecise, so early neuroimaging with a CT or magnetic resonance imaging (MRI) scan is critical. CT is preferred at most centers, as it can be obtained very rapidly and is effective at distinguishing between ischemic and hemorrhagic stroke (see "Neuroimaging of acute stroke"). It is important to assess and stabilize vital physiologic functions before sending the patient for an imaging study. The physical examination should include careful evaluation of the neck and retroorbital regions for vascular bruits, and palpation of pulses in the neck, arms, and legs to assess for their absence, asymmetry, or irregular rate. The heart should be auscultated for murmurs (see "Auscultation of cardiac murmurs in adults"). The lungs should be assessed for abnormal breath sounds, bronchospasm, fluid overload, or stridor. The skin should be examined for signs of endocarditis, cholesterol emboli, purpura, ecchymoses, or evidence of recent surgery or other invasive procedures, particularly if reliable history is not forthcoming. The funduscopic examination may be helpful if there are cholesterol emboli or papilledema. The head should be examined for signs of trauma. A tongue laceration may suggest a seizure. In cases where there is a report or suspicion of a fall, the neck should be immobilized until evaluated radiographically for evidence of serious trauma. Examination of the extremities is https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 3/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate important to look for evidence of systemic arterial emboli, distal ischemic, cellulitis, and deep vein thrombosis; the latter should raise the possibility that the patient is receiving anticoagulant treatment. Neurologic evaluation Ischemia in different vascular territories presents with specific syndromes ( table 3). The history should focus upon the time of symptom onset, the course of symptoms over time, possible embolic sources, possible recent trauma (which could either represent a contraindication to intravenous thrombolysis or suggest an arterial dissection as a cause), conditions in the differential diagnosis, and concomitant diseases. (See "Clinical diagnosis of stroke subtypes".) The neurologic examination should attempt to confirm the findings from the history and provide a quantifiable examination for further assessment over time. Many scales are available that provide a structured, quantifiable neurologic examination. One of the most widely used and validated scales is the National Institutes of Health Stroke Scale (NIHSS), composed of 11 items ( table 4) adding up to a total score of 0 to 42 (calculator 1); defined cutpoints for mild, moderate, and severe stroke are not well established, but cut-points of NIHSS score <5 for mild, 5 to 9 for moderate, and 10 for severe stroke may be reasonable. The three most predictive examination findings for the diagnosis of acute stroke are facial paresis, arm drift/weakness, and abnormal speech (a combination of dysarthria and language items derived from the NIHSS) [6,7]. The NIHSS score on admission has been correlated to stroke outcome ( table 5) [8,9], and its use is recommended for all patients with suspected stroke [10]. The NIHSS does not capture all stroke-related impairments, particularly with posterior circulation strokes. (See "Use and utility of stroke scales and grading systems", section on 'NIHSS'.) Immediate laboratory studies Urgent brain imaging with CT or MRI is mandatory in all patients with sudden neurologic deterioration or acute stroke. (See 'Neuroimaging' below.) All patients with suspected stroke should have the following studies urgently as part of the acute stroke evaluation [1,4]: Noncontrast brain CT or brain MRI Finger stick blood glucose Oxygen saturation Other immediate tests for the evaluation of ischemic and hemorrhagic stroke include the following [1,4]: https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 4/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate CT angiography of the head and neck with CT perfusion, or MR angiography with diffusion- weighted imaging (DWI), with or without MR perfusion-weighted imaging (PWI), for patients who may be eligible for mechanical thrombectomy MRI with DWI, to identify patients with wake-up stroke or unknown stroke onset time who have lesions that are positive on DWI but negative on fluid-attenuated inversion recovery (FLAIR), suggesting onset within 4.5 hours and eligibility for intravenous thrombolysis Electrocardiogram (this should not delay the noncontrast brain CT) Complete blood count including platelets Troponin Prothrombin time and international normalized ratio (INR) Activated partial thromboplastin time Ecarin clotting time, thrombin time, or appropriate direct factor Xa activity assay if known or suspected that the patient is taking direct thrombin inhibitor or direct factor Xa inhibitor and is otherwise a candidate for intravenous thrombolytic therapy However, thrombolytic therapy for acute ischemic stroke (see 'Acute therapy' below) should not be delayed while awaiting the results of hematologic studies unless the patient has received anticoagulants or there is suspicion of a bleeding abnormality or thrombocytopenia. The only test that is mandatory before initiation of intravenous thrombolysis is blood glucose [1]. The following laboratory studies may be appropriate in selected patients [1,4,5]: Serum electrolytes, urea nitrogen, creatinine Liver function tests Toxicology screen Blood alcohol level Pregnancy test in women of childbearing potential Arterial blood gas if hypoxia is suspected Chest radiograph if lung disease is suspected Lumbar puncture if subarachnoid hemorrhage is suspected and head CT scan is negative for blood; note that lumbar puncture will preclude administration of intravenous thrombolysis, though thrombolysis should not be given if there is suspicion for subarachnoid hemorrhage as the cause of the symptoms Electroencephalogram if seizures are suspected Chest radiography, urinalysis and blood cultures are indicated if fever is present. We also suggest blood for type and cross match in case fresh frozen plasma is needed to reverse a coagulopathy if ICH is present. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".) https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 5/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate In order to limit medication dosage errors, particularly with the use of intravenous thrombolysis with alteplase or tenecteplase, an accurate body weight should be obtained early during the urgent evaluation [11]. Neuroimaging In the evaluation of the acute stroke patient, imaging studies are necessary to exclude hemorrhage as a cause of the deficit, and they are useful to assess the degree of brain injury and to identify the vascular lesion responsible for the ischemic deficit. Advanced CT and MRI technologies may be able to distinguish between brain tissue that is irreversibly infarcted and that which is potentially salvageable, thereby allowing better selection of patients who are likely to benefit from therapy. This topic is discussed separately. (See "Neuroimaging of acute stroke".) Cardiac studies Electrocardiography (ECG) is important for detecting signs of concomitant acute cardiac ischemia. This test is particularly important in the setting of stroke, as patients with ischemic stroke frequently harbor coronary artery disease but may not be able to report chest pain. Stroke alone can be associated with ECG changes. The sympathetic response to stroke can lead to demand-induced myocardial ischemia. In large strokes, especially subarachnoid hemorrhage, there are centrally mediated changes in the ECG. The ECG and cardiac monitoring are important for the detection of chronic or intermittent arrhythmias that predispose to embolic events (eg, atrial fibrillation) and for detecting indirect evidence of atrial/ventricular enlargement that may predispose to thrombus formation. Current guidelines recommend cardiac monitoring for at least the first 24 hours after the onset of ischemic stroke to look for atrial fibrillation (AF) or atrial flutter [1]. However, paroxysmal AF may be undetected on standard cardiac monitoring such as continuous telemetry and 24- or 48-hour Holter monitors. Extended cardiac event monitoring for patients with ischemic stroke or transient ischemic attack (TIA) who present with sinus rhythm can significantly increase the detection of occult AF. Such monitoring may reduce the risk of recurrent ischemic stroke by prompting the appropriate use of long-term anticoagulation. The optimal monitoring method continuous telemetry, ambulatory electrocardiography, serial electrocardiography, transtelephonic ECG monitoring, or insertable cardiac monitors (ICMs; also sometimes referred to as implantable cardiac monitor or implantable loop recorder) is uncertain, though longer durations of monitoring are likely to obtain the highest diagnostic yield. (See "Overview of the evaluation of stroke", section on 'Monitoring for subclinical atrial fibrillation' and "Stroke in patients with atrial fibrillation", section on 'Long-term anticoagulation'.) https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 6/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Transthoracic and transesophageal echocardiography adequately detect cardiogenic and aortic sources for cerebral embolism other than atrial fibrillation (see "Echocardiography in detection of cardiac and aortic sources of systemic embolism"). However, their use can be postponed to later in the hospitalization, when the patient is in a more stable clinical condition. Exceptions include patients with a moderate or high suspicion of endocarditis, where echocardiography may provide confirmation of the diagnosis. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Echocardiography' and "Overview of the evaluation of stroke", section on 'Cardiac evaluation'.) STROKE MANAGEMENT ISSUES In addition to stabilization of airway, breathing, and circulation, and rapid neurologic evaluation discussed above, early key management issues that often arise in acute stroke include blood pressure control (see 'Blood pressure management' below), fluid management (see 'Fluids' below), treatment of abnormal blood glucose levels (see 'Hypoglycemia' below and 'Hyperglycemia' below), swallowing assessment (see 'Swallowing assessment' below), and treatment of fever and infection (see 'Fever' below). Care in a dedicated stroke unit (see 'Stroke unit care' below) is associated with better outcomes. Fluids Intravascular volume depletion is frequent in the setting of acute stroke, particularly in older adult patients [12], and may worsen cerebral blood flow. For most patients with acute stroke and volume depletion, isotonic saline without dextrose is the agent of choice for intravascular fluid repletion and maintenance fluid therapy [13]. In general, it is best to avoid excess free water (eg, as in isotonic saline) because hypotonic fluids may exacerbate cerebral edema in acute stroke and are less useful than isotonic solutions for replacing intravascular volume. In addition, it is best to avoid fluids containing glucose, which may exacerbate hyperglycemia. However, fluid management must be individualized based on cardiovascular status, electrolyte disturbances, and other conditions that may perturb fluid balance. (See "Maintenance and replacement fluid therapy in adults".) In particular, hyponatremia following subarachnoid hemorrhage may be due to inappropriate secretion of antidiuretic hormone (SIADH) or rarely, to cerebral salt wasting; these are physiologically distinct and are treated differently, as discussed separately. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Hyponatremia'.) Hypoglycemia Hypoglycemia can cause focal neurologic deficits mimicking stroke, and severe hypoglycemia alone can cause neuronal injury. It is important to check the blood sugar and rapidly correct low serum glucose (<60 mg/dL [3.3 mmol/L]) at the first opportunity [1]. https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 7/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Hyperglycemia Hyperglycemia, generally defined as a blood glucose level >126 mg/dL (>7.0 mmol/L), is common in patients with acute stroke and is associated with poor functional outcome [14-19]. In a series of 59 patients with acute ischemic stroke, admission hyperglycemia was present in 32 percent of patients without diabetes and 81 percent of patients with diabetes [20]. Stress hyperglycemia may be the most common cause [16], although newly diagnosed diabetes is also important [17]. Hyperglycemia may augment brain injury by several mechanisms, including increased tissue acidosis from anaerobic metabolism, free radical generation, and increased blood brain barrier permeability [21-23]. Hyperglycemia may also rarely present as a stroke mimic [24]. In light of these observations, it is reasonable to treat severe hyperglycemia in the setting of acute stroke. The American Heart Association/American Stroke Association guidelines for acute ischemic stroke recommend treatment for hyperglycemia to achieve serum glucose concentrations in the range of 140 to 180 mg/dL (7.8 to 10 mmol/L) [1]. The European Stroke Initiative guidelines recommend treatment for glucose >180 mg/dL (>10 mmol/L) [25]. Tighter control of glucose with intravenous insulin does not improve functional outcome in patients with acute ischemic stroke. The multicenter SHINE trial randomly assigned over 1100 adults with hyperglycemia and acute ischemic stroke to either intensive treatment of hyperglycemia (continuous insulin infusion with a target blood glucose concentration of 80 to 130 mg/dL) or standard treatment (subcutaneous insulin on a sliding scale with a target glucose of 80 to 179 mg/dL) [26]. At 90 days, there was no difference in the proportion of patients achieving a favorable functional outcome between the intensive and standard treatment groups (20.5 versus 21.6 percent). In addition, treatment withdrawal for hypoglycemia or other adverse events was more common in the intensive treatment group (11.2 versus 3.2 percent). Similarly, a 2014 systematic review identified 11 controlled trials involving nearly over 1500 adults with acute ischemic stroke who were randomly assigned to either intensively monitored insulin infusion therapy or to usual care; there was no difference between the treatment and control groups for the combined outcome of death or dependency, and no difference between groups for the outcome of final neurologic deficit [27]. In addition, the intervention group had a higher rate of symptomatic hypoglycemia. Swallowing assessment Dysphagia is common after stroke and is a major risk factor for developing aspiration pneumonia. It is important to assess swallowing function prior to administering oral medications or food. Thus, prevention of aspiration in patients with acute stroke includes initial nulla per os (NPO) status until swallowing function is evaluated. (See "Complications of stroke: An overview", section on 'Dysphagia'.) Note that aspirin, if and when indicated, can be given rectally. https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 8/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Head and body position During the acute phase of stroke, the position of the patient and the head of bed should be individualized with respect to the risk of elevated intracranial pressure and aspiration, and the presence of comorbid cardiopulmonary disease [28]. We recommend keeping the head in neutral alignment with the body and elevating the head of the bed to 30 degrees for patients in the acute phase of stroke who are at risk for any of the following problems: Elevated intracranial pressure (ie, intracerebral hemorrhage, cerebral edema >24 hours from stroke onset in patients with large ischemic infarction) Aspiration (eg, those with dysphagia and/or diminished consciousness) Cardiopulmonary decompensation or oxygen desaturation (eg, those with chronic cardiac and pulmonary disease) In the absence of these problems, we suggest keeping the head of bed in the position that is most comfortable for the patient. In addition, a cervical collar or a central intravenous line dressings, if present, should be loose enough so that they do not occlude venous outflow from the head. A number of reports suggest that cerebral perfusion is maximal when patients are in the horizontal position [29-31]. As an example, in a study involving 20 patients with moderately severe ischemic stroke in the middle cerebral artery (MCA) territory, mean flow velocity in the MCA measured by transcranial Doppler increased by an average of 20 percent when the head-of- bed elevation decreased from 30 to 0 degrees, and by an average of 12 percent when head-of- bed elevation decreased from 30 to 15 degrees [30]. Furthermore, some patients with acute ischemic stroke may develop increased ischemic symptoms upon standing, sitting, or elevating the head of the bed, due to reduction in flow through stenotic vessels or collateral pathways [32,33]. Thus, some stroke experts have favored a supine position is preferred for nonhypoxic patients with acute ischemic stroke who are able to tolerate lying flat. When done, keeping the patient flat is a temporary measure that should be discontinued in most patients after 24 to 48 hours. Nevertheless, the benefit of maintaining the head flat in this setting remains unproven [34]. In the HeadPoST controlled trial of over 11,000 subjects with acute stroke (85 percent ischemic) who were randomly assigned to either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, there was no difference between treatment groups in disability outcomes, mortality, or serious adverse events [35]. https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 9/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Mobilization of stable patients after 24 hours may lessen the likelihood of major complications such as pneumonia, deep vein thrombosis, pulmonary embolism, and pressure sores after stroke. Exceptions may include those who exhibit neurologic deterioration upon assuming more upright postures. In addition, there is a potential increased risk of aspiration if a flat position is maintained for a prolonged period [36]. However, very early mobilization, within 24 hours of symptom onset, may be harmful [37]. The multicenter randomized AVERT trial, with over 2000 patients, evaluated a protocol of very early mobilization, which was started within 24 hours of stroke onset and consisted of frequent out- of-bed activity including sitting, standing, and walking. Compared with usual care, very early mobilization and early rehabilitative therapies reduced the odds of a favorable outcome at three months [38]. Fever The source of fever should be investigated and treated, and antipyretics should be used to lower temperature in febrile patients with acute stroke. Common etiologies of fever, including aspiration pneumonia and urinary tract infection, should also be excluded. (See "Complications of stroke: An overview", section on 'Fever and infection'.) We suggest maintaining normothermia for at least the first several days after an acute stroke [39]. However, the clinical utility of this approach has not been established. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial evaluated 1400 adults no later than 12 hours after symptom onset of acute ischemic stroke or intracerebral hemorrhage [40]. Included patients had a body temperature of 36 to 39 C. Compared with placebo, paracetamol (acetaminophen) 1 g six times daily for three days did not improve outcome [40]. However, a post-hoc subgroup analysis of 661 patients with a baseline body temperature of 37 to 39 C suggested benefit for paracetamol. In a systematic review and meta-analysis of five small randomized controlled trials with a total of 293 patients, there was no benefit for pharmacologic temperature reduction for acute stroke [41]. All the trials enrolled patients within 24 hours of stroke onset, and the duration of treatment ranged from 24 hours to five days. With addition of results from the PAIS trial, the updated meta-analysis found no difference between active treatment and control for a favorable outcome (odds ratio [OR] 1.1, 95% CI 0.9-1.3) [40]. Larger trials are needed to determine if pharmacologic temperature reduction improves outcome from acute stroke, particularly for patients with temperature of 37 C, though it seems unlikely that acetaminophen will be effective by itself. In patients who are nil per os (NPO), acetaminophen is now available in the United States as an intravenous preparation. https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 10/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Induced hypothermia is not currently recommended for patients with ischemic stroke, outside of clinical trials [1]. Stroke unit care Evidence suggests that patients with acute stroke have better outcomes when admitted to a hospital unit that is specialized for the care of patients with all types of acute stroke, including ischemic, intracerebral hemorrhage, and subarachnoid hemorrhage [42-46]. The precise components of an acute stroke unit vary between centers and countries, but generally include a hospital ward with dedicated telemetry beds that is continuously staffed by a team of physicians, nurses and other personnel who specialize in stroke care, emphasizing expertise in vascular neurology and neurosurgery [47,48]. Additional components include prompt availability of neuroimaging (eg, CT, MRI, various types of angiography, ultrasound, transcranial Doppler) and cardiac imaging. Implementation of stroke protocols and disease- performance measures may contribute to improved outcomes and decreased risk of stroke- related complications, as shown in some reports [49,50]. Current national guidelines support stroke unit care, when available, for patients with suspected acute stroke [1,51]. BLOOD PRESSURE MANAGEMENT The approach to blood pressure management in acute ischemic stroke is inherently different from the approach in acute hemorrhagic stroke. For this reason, a neuroimaging study with CT or MRI is critical to help guide blood pressure therapy in patients with acute stroke. Likewise, there are important differences between the blood pressure management in the acute and chronic phases of stroke. The management of blood pressure in acute phase of stroke is reviewed in the sections that follow. The management of blood pressure after the acute phase of stroke is discussed separately. (See "Antihypertensive therapy for secondary stroke prevention".) Blood pressure in acute ischemic stroke The long-term benefit from antihypertensive therapy does not mean that a reduction in blood pressure will be beneficial during initial management of an acute ischemic stroke [52]. In patients with ischemic stroke, the perfusion pressure distal to the obstructed vessel is low, and the distal vessels are dilated. Because of impaired cerebral autoregulation ( figure 2), blood flow in these dilated vessels is thought to be dependent upon the systemic blood pressure. The arterial blood pressure is usually elevated in patients with an acute stroke. This may be due to chronic hypertension, an acute sympathetic response, or other stroke-mediated mechanisms https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 11/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate [53]. In many cases, however, the acutely elevated blood pressure is necessary to maintain brain perfusion in borderline ischemic areas [54]. The observation that the blood pressure frequently rises spontaneously following cerebral ischemia is consistent with this protective hypothesis, although a stress response to the acute event and to hospitalization may also contribute [55]. The hypertensive effect is transient, as blood pressure falls by as much as 20/10 mmHg within 10 days. An analysis from the International Stroke Trial of 17,398 patients with an ischemic stroke noted a U-shaped relationship between baseline systolic blood pressure and outcomes [56]. Elevated systolic blood pressure was associated with an increased risk of recurrent ischemic stroke (50 percent greater risk of recurrence with a systolic blood pressure of >200 mmHg versus 130 mmHg), while low blood pressure (particularly <120 mmHg) was associated with an excess number of deaths from coronary heart disease. A subsequent analysis of 1004 patients with acute ischemic stroke from Okinawa also found a U- shaped relationship between admission blood pressure and death within 30 days after stroke onset [57]. The U-shaped relationship was shifted toward higher pressure in patients who had previous hypertension compared with those who did not have previous hypertension. This finding mirrors the shift seen in cerebral autoregulation that occurs in longstanding hypertension ( figure 2) [58]. Effect of lowering blood pressure There are few data from randomized controlled trials specifically designed to guide blood pressure management in the acute phase of ischemic stroke (ie, the first 24 hours) when the ischemic penumbra may be at risk of irreversible damage if cerebral blood flow is reduced by lowering the blood pressure [59]. The MAPAS trial found no clear benefit for blood pressure lowering within 12 hours of acute ischemic stroke onset, but an adjusted analysis suggested that a goal systolic blood pressure of 161 to 180 mmHg increased the odds of a good outcome compared with higher or lower goal blood pressures [60]. The RIGHT-2 trial found that lowering blood pressure within four hours of onset of suspected stroke did not improve functional outcomes; the results are confounded by inclusion of patients with transient ischemic attack (TIA), intracerebral hemorrhage, and stroke mimics [61]. Lowering the systemic blood pressure in patients within 24 hours of acute ischemic stroke onset has been associated with clinical deterioration in several observational studies [62-64]. Other large trials (eg, CATIS [65], SCAST [66], COSSACS [67], and ENOS [68]) enrolled patients as long as 30 to 48 hours after stroke onset, and are therefore less informative regarding the impact of blood pressure treatment in the first hours of ischemic stroke. In addition, many of these trials, including the meta-analyses discussed below, enrolled patients with intracerebral https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 12/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate hemorrhage, a group that might be expected to benefit from early blood pressure lowering. Keeping these limitations in mind, some of the randomized trial data suggest that initiating blood pressure reduction in acute stroke or merely continuing prestroke blood pressure medications can be harmful: In a 2014 meta-analysis of 16 trials (including ENOS) of antihypertensive medications that included over 19,000 patients with acute stroke, early blood pressure reduction had no effect on functional outcome (OR 1.0, 95% CI 0.93-1.07) [68]. Similarly, a 2015 meta-analysis of 13 randomized trials (also including ENOS) and over 12,000 subjects found that blood pressure lowering started within three days of ischemic stroke onset did not alter the risk of death or dependency at three months or trial end point (relative risk, 1.04, 95% CI 0.96- 1.13) [69]. A meta-analysis of individual patient data from COSSACS and ENOS trials found that continuing versus stopping antihypertensive treatment had no effect on the risk of death or dependency at final follow-up [70]. However, in a subgroup analysis, patients who stopped antihypertensives within 12 hours of stroke onset showed a nonsignificant trend towards less death or dependency. In the ENOS trial itself, the group assigned to continuing blood pressure treatment had an increased likelihood of hospital death or discharge to an institution, an increased risk of death or disability (Barthel index <60) at 90 days, and significantly lower cognition scores at 90 days compared with the group that stopped treatment, even though there was no difference in functional outcome between the two groups [68]. These results are not definitive for the reasons noted above. Blood pressure goals in ischemic stroke Special considerations apply to blood pressure control in patients with acute ischemic stroke who are eligible for intravenous thrombolytic therapy. Before thrombolytic therapy is started, treatment is recommended so that systolic blood pressure is 185 mmHg and diastolic blood pressure is 110 mmHg ( table 6) [1]. The blood pressure should be stabilized and maintained at or below 180/105 mmHg for at least 24 hours after thrombolytic treatment. This issue is discussed in detail separately. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use", section on 'Management of blood pressure'.) For patients with ischemic stroke who are not treated with thrombolytic therapy, blood pressure should not be treated acutely unless the hypertension is extreme (systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg), or the patient has active ischemic coronary disease, heart failure, aortic dissection, hypertensive encephalopathy, or pre- https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 13/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate eclampsia/eclampsia [1,71]. When treatment is indicated, cautious lowering of blood pressure by approximately 15 percent during the first 24 hours after stroke onset is suggested. It is reasonable to start or restart antihypertensive medications during hospitalization for patients with blood pressure >140/90 mmHg who are neurologically stable, unless contraindicated [1]. This can be done as early as 24 to 48 hours after stroke onset for most hospitalized patients, with the goal of gradually controlling hypertension within a few days to a week [72]. Importantly, patients with extracranial or intracranial large artery stenoses may require a slower reduction in blood pressure (eg, over 7 to 14 days after ischemic stroke), as some degree of blood pressure elevation may be necessary to maintain cerebral blood flow to ischemic brain regions. For this reason, we suggest not restarting antihypertensive agents until after vascular imaging is completed and a symptomatic large artery stenosis is excluded. If acute antihypertensive therapy is needed, intravenous agents are generally used. (See 'Choice of antihypertensive agent' below.) Systemic hypotension and hypovolemia should be corrected to improve cerebral blood flow and systemic organ function [1]. However, drug-induced hypertension is unproven for the treatment of ischemic stroke. Choice of antihypertensive agent In the acute phase of stroke, there is no good evidence to support the use of any specific antihypertensive agent to achieve recommended blood pressure goals. Nevertheless, reversible and titratable intravenous agents are best suited for precise blood pressure lowering. Consensus guidelines suggest intravenous labetalol, nicardipine, and clevidipine as first-line antihypertensive agents if pharmacologic therapy is necessary in the acute phase, since they allow rapid and safe titration to the goal blood pressure ( table 6) [1]. Intravenous nitroprusside should be considered second-line therapy since it carries added theoretical risks of increasing intracranial pressure or affecting platelet function. Medications likely to cause a prolonged or precipitous decline in blood pressure (eg, rapid-acting formulations of nifedipine) should be avoided. In addition, their use is associated with an