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 increased risk of stroke, particularly in older adult patients [73]. Blood pressure in acute hemorrhagic stroke In both intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), the approach to blood pressure management must take into account the potential benefits (eg, reducing further bleeding) and risks (eg, reducing cerebral perfusion) of blood pressure lowering. Recommendations for blood pressure management in acute ICH and SAH are discussed in detail separately. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Blood pressure management' and https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 14/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Blood pressure control'.) ACUTE THERAPY Ischemic stroke management For eligible patients ( table 2) with acute ischemic stroke, intravenous thrombolysis is first-line therapy, provided that treatment is initiated within 4.5 hours of symptom onset or the time last known to be well (ie, at neurologic baseline). Because the benefit of intravenous thrombolysis is time dependent, it is critical to treat patients as quickly as possible. Mechanical thrombectomy ( algorithm 1) is indicated for patients with acute ischemic stroke due to a large artery occlusion in the anterior circulation who can be treated within 24 hours of symptom onset or the time last known to be well at stroke centers with appropriate expertise, regardless of whether they receive intravenous thrombolytic therapy for the same ischemic stroke event. The eligibility criteria and utility of thrombolytic therapy, endovascular thrombectomy, and the treatment of patients not eligible for thrombolysis are discussed separately. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) In addition to intravenous thrombolysis and endovascular thrombectomy, a number of interventions for ischemic stroke are associated with either reduced disability, complications, or stroke recurrence, including: Antithrombotic therapy with aspirin initiated within 48 hours of stroke onset (see "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Efficacy of aspirin') Prophylaxis for deep venous thrombosis and pulmonary embolism (see "Prevention and treatment of venous thromboembolism in patients with acute stroke", section on 'Approach to VTE prevention') Antithrombotic therapy at discharge (see "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke" and "Atrial fibrillation in adults: Use of oral anticoagulants") Lipid lowering with high intensity statin therapy (see "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy') https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 15/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Blood pressure reduction after the acute phase of ischemic stroke has passed (see "Antihypertensive therapy for secondary stroke prevention" and "Overview of secondary prevention of ischemic stroke"); management of blood pressure in the acute phase of ischemic stroke is discussed above (see 'Blood pressure management' above) Behavioral and lifestyle changes including smoking cessation, exercise, weight reduction for patients with obesity, and a Mediterranean style diet (see "Overview of secondary prevention of ischemic stroke" and "Overview of smoking cessation management in adults") Appropriate and timely use of these therapies should be considered as soon as ischemic stroke is recognized. Utilization of these interventions may be improved by the use of standardized stroke care orders or critical pathways beginning with hospital admission through discharge [1,74]. Full-dose anticoagulation is rarely indicated in the hyperacute phase of ischemic stroke, although low-dose heparin anticoagulation is often used for prevention of venous thromboembolism in patients with restricted mobility. (See "Prevention and treatment of venous thromboembolism in patients with acute stroke".) The main indication for oral anticoagulation after ischemic stroke is atrial fibrillation. When indicated, oral anticoagulation can be started immediately for patients with a transient ischemic attack, and soon after ischemic stroke onset for medically stable patients with a small- or moderate-sized infarct and no bleeding complications or uncontrolled hypertension. For patients with atrial fibrillation who have a large infarct, symptomatic hemorrhagic transformation, or poorly controlled hypertension, withholding oral anticoagulation for one to two weeks is generally recommended. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Cardioembolic source'.) Statin therapy For patients with acute ischemic stroke, we suggest starting or continuing statin treatment as soon as oral medications can be used safely. There is clear evidence that long-term intensive statin therapy is associated with a reduced risk of recurrent ischemic stroke and cardiovascular events, as discussed separately (see "Overview of secondary prevention of ischemic stroke", section on 'LDL-C lowering therapy'). The utility of statin therapy during the acute phase of ischemic stroke is less well studied, but is supported by the following observations: A single-center randomized controlled trial of 89 patients who were already treated with a statin and were assigned to continuation or cessation of statin therapy in the acute https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 16/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate phase of ischemic stroke [75]. The rate of death or dependency at three months was significantly lower with continuation of statin treatment (39 versus 60 percent). An observational study, which evaluated over 12,000 subjects hospitalized with ischemic stroke, found that statin use before and during hospitalization was associated with improved outcome at hospital discharge and with improved survival at one year [76,77]. Furthermore, initiation of statin treatment early in hospitalization was associated with improved survival, while statin discontinuation early in hospitalization, even for a short period, was associated with decreased survival. An uncontrolled study of 448 patients reported that new or continued statin treatment in the first 72 hours after acute ischemic stroke was associated with improved early and late (one-year) survival [78]. An observational study of 2072 patients who received intravenous thrombolysis for acute ischemic stroke found that statin treatment started within 72 hours of thrombolysis was associated with a favorable functional outcome and a reduced risk of death at three months [79]. Of the 839 patients treated with statins, 65 percent were statin na ve. SSRIs For patients with hemiparesis but without depression after ischemic stroke, evidence from a few small randomized controlled trials (including the FLAME trial) suggested that early initiation of selective serotonin-reuptake inhibitors (SSRIs) enhanced motor recovery and reduced dependency [80-82]. However, subsequent randomized controlled trials, including the FOCUS, AFFINITY, and EFFECTS trials, which together enrolled over 5900 adult patients with acute ischemic stroke or intracerebral hemorrhage, found no benefit in functional outcome at six months for treatment with fluoxetine compared with placebo [83-85]. Treatment with fluoxetine reduced the risk of developing depression in FOCUS and EFFECTS but increased the risk of bone fractures in all three trials, increased the risks of falls and epileptic seizures in AFFINITY, and increased the risk of hyponatremia in EFFECTS. Intracranial hemorrhage management The treatment of patients with intracerebral hemorrhage or subarachnoid hemorrhage is reviewed in detail elsewhere. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis" and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use", section on 'Management of symptomatic intracerebral hemorrhage'.) https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 17/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Neuroprotective treatment Numerous neuroprotective agents have shown promising results in animal experiments. However, clinical trials have thus far failed to confirm consistent benefit [86]. This failure may be due, at least in part, to limitations of animal models of acute stroke and to shortcomings of clinical trials. The search for effective neuroprotective treatment continues [86-91]. As examples, nerinetide and remote ischemic conditioning have shown signals suggesting benefit in clinical trials [91- 94]. More study is needed to determine if these treatments are safe and effective for acute ischemic stroke. PREVENTION OF COMPLICATIONS The prevention of medical complications of stroke is an important goal of stroke management, and this aspect of care begins with initial evaluation of the patient. Common acute and subacute medical problems associated with stroke include: Myocardial infarction Heart failure Dysphagia Aspiration pneumonia Urinary tract infection Deep vein thrombosis Pulmonary embolism Dehydration Malnutrition Pressure sores Orthopedic complications and contractures The prevention, impact, and management of these complications are discussed separately. (See "Complications of stroke: An overview" and "Prevention and treatment of venous thromboembolism in patients with acute stroke".) Delirium, characterized by a disturbance of consciousness with decreased attention and disorganized thinking, is another potential complication of stroke [95]. Findings from systematic reviews and meta-analyses suggest that the rate of post-stroke delirium is approximately 25 percent [96,97]. Patients with delirium have longer hospital stays and higher inpatient and 12- month mortality rates [96]. Risk factors for developing post-stroke delirium include preexisting cognitive decline, infection, and greater stroke severity [98]. (See "Diagnosis of delirium and https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 18/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate confusional states" and "Delirium and acute confusional states: Prevention, treatment, and prognosis".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Stroke (The Basics)" and "Patient education: Hemorrhagic stroke (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)" and "Patient education: Ischemic stroke treatment (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Main goals of initial evaluation The main goals in the initial phase of acute stroke management are to ensure medical stability, to quickly reverse conditions that are contributing to the patient's problem, to determine if patients with acute ischemic stroke are candidates for reperfusion therapy, and to begin to uncover the pathophysiologic basis of the neurologic symptoms. (See 'Initial assessment' above.) https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 19/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Important aspects of immediate assessment Important aspects of acute stroke evaluation and management include the following: Vital signs Assess vital signs and stabilize airway, breathing, and circulation. (See 'Airway, breathing and circulation' above.) Rapid history and examination Obtain a rapid but accurate history and examination to help distinguish stroke mimics and other disorders in the differential diagnosis ( table 1) of acute stroke. (See 'History and physical' above and 'Neurologic evaluation' above.) Urgent brain imaging Obtain urgent brain imaging (with CT or MRI), neurovascular imaging (with CT angiography or magnetic resonance angiography [MRA]) and other important laboratory studies, including cardiac monitoring during the first 24 hours after the onset of ischemic stroke. (See 'Immediate laboratory studies' above and 'Neuroimaging' above and 'Cardiac studies' above.) Fluid management Manage volume depletion and electrolyte disturbances. (See 'Fluids' above.) Check serum glucose Low serum glucose (<60 mg/dL [3.3 mmol/L]) should be corrected rapidly. It is reasonable to treat hyperglycemia if the glucose level is >180 mg/dL (>10 mmol/L) with a goal of keeping serum glucose levels within a range of 140 to 180 mg/dL (7.8 to 10 mmol/L). Check swallowing All patients with acute stroke should be assessed for ability to swallow in order to prevent aspiration. (See 'Swallowing assessment' above and "Complications of stroke: An overview", section on 'Dysphagia'.) Optimize head of bed position For patients with intracerebral hemorrhage, subarachnoid hemorrhage, or ischemic stroke who are at risk for elevated intracranial pressure, aspiration, cardiopulmonary decompensation, or oxygen desaturation, we recommend keeping the head in neutral alignment with the body and elevating the head of the bed to 30 degrees (Grade 1C). For patients with stroke who are not at high risk for these complications, we suggest keeping the head of the bed in the position that is most comfortable. (See 'Head and body position' above.) Check for fever Evaluate and treat the source of fever, if present; for patients with acute stroke, we suggest maintaining normothermia for at least the first several days after an acute stroke (Grade 2C). (See 'Fever' above.) https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 20/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Blood pressure management The management of blood pressure in acute stroke depends on the type of stroke and anticipated treatment. (See 'Blood pressure management' above.) Thrombolytic therapy For patients with acute ischemic stroke who will receive intravenous thrombolytic therapy, antihypertensive treatment is recommended so that systolic blood pressure is 185 mmHg and diastolic blood pressure is 110 mmHg prior to treatment and <180/105 mmHg for the first 24 hours after treatment ( table 6). This issue is discussed in detail separately. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use", section on 'Management of blood pressure'.) No thrombolytic therapy For patients with acute ischemic stroke who are not treated with thrombolytic therapy, we suggest treating high blood pressure only if the hypertension is extreme (systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg), or if the patient has another clear indication (active ischemic coronary disease, heart failure, aortic dissection, hypertensive encephalopathy, or pre- eclampsia/eclampsia) (Grade 2C). When treatment is indicated, we suggest cautious lowering of blood pressure by approximately 15 percent during the first 24 hours after stroke onset (Grade 2C). (See 'Blood pressure goals in ischemic stroke' above.) Hemorrhagic stroke In both intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), the approach to blood pressure lowering must account for the potential benefits (eg, reducing further bleeding) and risks (eg, reducing cerebral perfusion). Recommendations for blood pressure management in acute ICH and SAH are discussed in detail separately. (See 'Blood pressure in acute hemorrhagic stroke' above and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Blood pressure management' and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Blood pressure control'.) Eligibility for reperfusion therapy For eligible patients ( table 2) with acute ischemic stroke, intravenous thrombolytic therapy is first-line therapy, provided that treatment is initiated within 4.5 hours of clearly defined symptom onset. Patients with acute ischemic stroke due to a proximal large artery occlusion who can be treated within 24 hours of time last known to be at neurologic baseline should be evaluated for treatment with mechanical thrombectomy ( algorithm 1). The eligibility criteria and utility of thrombolytic therapy, mechanical thrombectomy, and the treatment of patients not eligible for thrombolysis are discussed separately. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) https://www.uptodate.com/contents/initial-assessment-and-management-of-acute-stroke/print 21/47 7/5/23, 12:11 PM Initial assessment and management of acute stroke - UpToDate Other early interventions that improve outcome In addition to reperfusion therapy, a number of interventions for ischemic stroke are associated with either reduced disability, complications, or stroke recurrence, including (see 'Acute therapy' above): Antiplatelet therapy Antiplatelet agents should be started as soon as possible after the diagnosis of ischemic stroke is confirmed, even before the evaluation for ischemic mechanism is complete. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Treatment on presentation'.) Prophylaxis for venous thromboembolism Prophylaxis for deep venous thrombosis and pulmonary embolism is indicated for all patients with acute stroke and restricted mobility. (See "Prevention and treatment of venous thromboembolism in patients with acute stroke", section on 'Approach to VTE prevention'.) Statin therapy For patients with acute ischemic stroke, we suggest starting or continuing statin treatment as soon as oral medications can be used safely (Grade 2C). (See 'Ischemic stroke management' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Walter J Koroshetz, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Powers WJ, Rabinstein AA, Ackerson T, et al. 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