Acute Management of Stroke

Initial Treatment

The goal for the acute management of patients with stroke is to stabilize the patient and to complete initial evaluation and assessment, including imaging and laboratory studies, within 60 minutes of patient arrival.^[1] (See Table 1, below.) Critical decisions focus on the need for intubation, blood pressure control, and determination of risk/benefit for thrombolytic intervention.

Table 1. NINDS* and ACLS** Recommended Stroke Evaluation Time Benchmarks for Potential Thrombolysis Candidate

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Hypoglycemia and hyperglycemia need to be identified and treated early in the evaluation. Not only can both produce symptoms that mimic ischemic stroke, but they can also aggravate ongoing neuronal ischemia. Administration of glucose in hypoglycemia produces profound and prompt improvement, while insulin should be started for patients with stroke and hyperglycemia. Ongoing studies will help to determine the optimal level of glycemic control.^[2]

Hyperthermia is infrequently associated with stroke but can increase morbidity. Administration of acetaminophen, by mouth or per rectum, is indicated in the presence of fever (temperature >100.4° F [38° C]).

Supplemental oxygen is recommended when the patient has a documented oxygen requirement. To date, there is conflicting evidence whether supernormal oxygenation improves outcome.

Optimal blood pressure targets remain to be determined. Many patients are hypertensive on arrival. American Stroke Association guidelines have reinforced the need for caution in lowering blood pressures acutely.

In the small proportion of patients with stroke who are relatively hypotensive, pharmacologically increasing blood pressure may improve flow through critical stenoses.

Serial monitoring and interventions when necessary early in the clinical course and eventual stroke rehabilitation and physical and occupational therapy are the ideals of management. (See Table 2, below.)

In patients with transient ischemic attacks (TIAs), failure to recognize the potential for near- term stroke, failure to perform a timely assessment for stroke risk factors, and failure to initiate primary and secondary stroke prevention exposes the patient to undue risk of stroke and exposes clinicians to potential litigation. TIAs confer a 10% risk of stroke within 30 days, and one half of the strokes occurring after a TIA, occurred within 48 hours.^[3]

Table 2. General Management of Patients With Acute Stroke^{[1, 4]}

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• References

Thrombolytic Therapy

Current treatments for acute ischemic stroke include IV thrombolytic therapy with tissue-type plasminogen activator (t-PA) and endovascular therapies using stent retriever devices.^[5] .  A 2015 update of the American Heart Association/American Stroke Association guidelines for the early management of patients with acute ischemic stroke recommends that patients eligible for intravenous t-PA should receive intravenous t-PA even if endovascular treatments are being considered and that patients should receive endovascular therapy with a stent retriever if they meet criteria.^[5]

Newer stroke trials have explored the benefit of using neuroimaging to select patients who are most likely to benefit from thrombolytic therapy and the potential benefits of extending the window for thrombolytic therapy beyond the guideline of 3 hours with t-PA and newer agents. CT angiography may demonstrate the location of vascular occlusion. CT perfusion studies are capable of producing perfusion images and together with CT angiography are becoming more available and utilized in the acute evaluation of stroke patients.^[6]

The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) trial suggested that there might be benefit of administering IV t-PA within 3-6 hours of stroke onset in patients with small ischemic cores on diffusion-weighted magnetic resonance imaging (MRI) and larger perfusion abnormalities (large ischemic penumbras).^[7]

The Desmoteplase In Acute Ischemic Stroke (DIAS) trial sought to show the benefit of administering desmoteplase in patients within 3-9 hours of onset of acute stroke with a significant mismatch (>20%) between perfusion abnormalities and ischemic core on diffusion-weighted MRI^[8] .  Larger randomized trials of desmoteplase were negative.^[9]

Muchada et al performed a study on 581 consecutive patients treated with alteplase to identify the impact of time-to-treatment according to stroke severity on functional outcome in patients with acute ischemic stroke. They found that the window for favorable outcome was 120 minutes or less for moderate strokes, but time-to-treatment seemed unrelated to functional outcome in mild and severe stroke.^[10]

In a study of 285 patients who received intravenous recombinant tissue-type plasminogen activator, revascularization (modified Thrombolysis In Cerebral Infarction scores, 2b and 3) occurred in 73.9%; 5.6% developed symptomatic intracerebral hemorrhages; 43.3% achieved good functional outcome; and 22.2% died within 90 days. According to the authors, adjusted comparisons by subgroups (age ≤ or >80 yr; onset-to-groin puncture ≤ or >6 hr; anterior or posterior strokes; previous IV recombinant tissue-type plasminogen activator or isolated endovascular treatment/therapy; revascularization or no revascularization) systematically favored revascularization (lower proportion of symptomatic intracerebral hemorrhages and death rates and higher proportion of good outcome), and multivariate analyses confirmed the independent protective effect of revascularization.^[11]

A study by Jovin et al showed successful endovascular therapy beyond 8 hours from time last seen well in patients selected for treatment based on MRI or CT perfusion imaging. Revascularization was successful in about 73% of patients.^[12]

Advanced neuroimaging with diffusion and perfusion imaging may then serve an important role in identifying potentially salvageable tissue at risk and guiding clinical decision making regarding therapy.^{[8, 13, 14, 15, 16]}

The iScore may also be used in patients with an acute ischemic stroke to predict clinical response and risk of hemorrhagic complications following IV thrombolytic therapy.^[17]

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Stabilization of Airway and Breathing

Patients presenting with Glasgow Coma Scale scores of 8 or less, rapidly decreasing Glasgow Coma Scale scores, or inadequate airway protection or ventilation require emergent airway control via rapid sequence intubation.

When increased intracranial pressure (ICP) is suspected, rapid sequence induction should be directed at minimizing the potentially adverse effects of intubation.

In unusual cases of potential imminent brain herniation, where the goal of mechanical ventilation is hyperventilation to decrease ICP by decreasing cerebral blood flow, the recommended endpoint is an arterial pCO₂ of 32-36 mm Hg. IV mannitol can be considered as well.

Supplemental oxygen use should be guided by pulse oximetry. Patients should receive supplemental oxygen if their pulse oximetry reading or arterial blood gas measurement reveals that they are hypoxic (SaO ₂ < 94%). The most common causes of hypoxia in the patient with acute stroke are partial airway obstruction, hypoventilation, atelectasis, or aspiration of stomach or oropharyngeal contents.^{[18, 19]}

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Intravenous Access and Cardiac Monitoring

Patients with acute stroke require IV access and cardiac monitoring in the emergency department (ED). Patients with acute stroke are at risk for cardiac arrhythmias. In addition, atrial fibrillation may be associated with acute stroke as either the cause (embolic disease) or as a complication.

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Blood Glucose Control

Severe hyperglycemia appears to be independently associated with poor outcome and reduced reperfusion in thrombolysis, as well as extension of the infarcted territory.^{[20, 21, 22]} Additionally, normoglycemic patients should not be given excessive glucose-containing IV fluids, as this may lead to hyperglycemia and may exacerbate ischemic cerebral injury.

Blood sugar control should be tightly maintained with insulin therapy, with the goal of establishing normoglycemia (90-140 mg/dL). Additionally, close monitoring of blood sugar level should continue throughout hospitalization to avoid hypoglycemia.^[1]

• References

Patient Positioning

Studies have previously shown that cerebral perfusion pressure is maximized when patients are maintained in a supine position. However, lying flat may serve to increase ICP.  A cluster-randomized crossover trial in patients with acute stroke (85% ischemic) showed that disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours.^[23]   Because prolonged immobilization may lead to its own complications, including deep venous thrombosis, pressure ulcer aspiration, and pneumonia, patients should not be kept flat for longer than 24 hours.^[24]

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Blood Pressure Control

In poor flow states―which occur with thrombotic and embolic ischemic stroke, as well as with increased ICP due to cerebral edema―the cerebral vasculature loses vasoregulatory capability and thus relies directly on mean arterial pressure (MAP) and cardiac output for maintenance of cerebral blood flow. Therefore, aggressive efforts to lower blood pressure may decrease perfusion pressure and may prolong or worsen ischemia. Rapid reduction of blood pressure, no matter the degree of hypertension, may in fact be harmful. Both elevated and low blood pressures are associated with poor outcomes in patients with acute stroke.^[25] (See Table 3, below.)

Studies have demonstrated that blood pressure typically drops in the first 24 hours after acute stroke, whether or not antihypertensives are administered. Furthermore, studies have revealed poorer outcomes in patients with lower blood pressures, with these outcomes correlating with the degree of pressure decline.^{[25, 26]}

In a 2012 analysis of data from The Scandinavian Candesartan Acute Stroke Trial, acute stroke patients with a large decrease or increase or no change in systolic blood pressure experienced an increased risk of early adverse events compared with patients with a small decrease, and patients with an increase or no change in systolic blood pressure had an increased risk of poor neurological outcome compared with other patients. Routine attempts to lower blood pressure in the acute phase of stroke should probably be avoided.^[27]

The consensus recommendation is to lower blood pressure only if systolic pressure is in excess of 220 mm Hg or if diastolic pressure is greater than 120 mm Hg.^[19] However, a systolic blood pressure greater than 185 mm Hg or a diastolic pressure greater than 110 mm Hg is a contraindication to the use of thrombolytics. Therefore, the management of elevated blood pressure in acute ischemic stroke may vary, depending on whether the patient is a candidate for thrombolytic therapy.

Hypertension control in non–rt-PA candidates

For patients who are not candidates for thrombolysis with recombinant t-PA (rt-PA) and who have a systolic blood pressure of less than 220 mm Hg and a diastolic blood pressure of less than 120 mm Hg in the absence of evidence of end-organ involvement (ie, pulmonary edema, aortic dissection, hypertensive encephalopathy), blood pressure should be monitored (without acute intervention) and stroke symptoms and complications (eg, increased ICP, seizures) should be treated.

For patients with a systolic blood pressure above 220 mm Hg or a diastolic blood pressure greater than 120 mm Hg, labetalol (10-20 mg IV for 1-2 min) should be the initial drug of choice, unless a contraindication to its use exists. Dosing may be repeated or doubled every 10 minutes to a maximum dose of 300 mg.

Alternatively, nicardipine may be used for blood pressure control. Nicardipine is given intravenously at an initial rate of 5 mg/h and titrated to effect by increasing the infusion rate 2.5 mg/h every 5 minutes, to a maximum of 15 mg/h. Lastly, nitroprusside at 0.5 mcg/kg/min IV infusion may be used in the setting of continuous blood pressure monitoring. The goal of intervention is a reduction in blood pressure of 10-15%.

Hypertension control in rt-PA candidates

For patients who will be receiving rt-PA, systolic blood pressure greater than 185 mm Hg and diastolic blood pressure greater than 110 mm Hg require intervention. Monitoring and control of blood pressure during and after thrombolytic administration are vital, because uncontrolled hypertension is associated with hemorrhagic complication.^[28]

The initial drug of choice, labetalol (10-20 mg IV for 1-2 min), may be repeated (maximum dose 300 mg). One to 2 inches of transdermal nitropaste (see nitroglycerin topical) may also be used. As an alternative to these choices, nicardipine infusion at 5 mg/h, titrated up to a maximum dose of 15 mg/h, can be used.^[19]

Monitoring of blood pressure is crucial; for the first 2 hours, blood pressure should be checked every 15 minutes, then every 30 minutes for 6 hours, and finally, every hour for 16 hours. The goal of therapy should be to reduce blood pressure by 15-25% in the first day, with continued blood pressure control during hospitalization.

For patients with systolic blood pressure of 185-230 mm Hg or diastolic blood pressure of 110-120 mm Hg, labetalol is given at a dose of 10-20 mg IV over 1-2 minutes; the dose may be repeated every 10-20 minutes, up to 300 mg total, or an infusion rate of up to 2-8 mg/min may be used.^[1]

For systolic blood pressure of greater than 230 mm Hg or diastolic blood pressure of 121-140 mm Hg, labetalol at the above doses can be considered. However, nicardipine infusion administered at a rate of 5 mg/h, to a maximum of 15 mg/h, might be a better first choice. For difficult-to-control blood pressure, sodium nitroprusside can be considered.^[1]

The use of sublingual nifedipine to lower blood pressure in the ED is discouraged, since extreme hypotension may result. Trials of nimodipine, initially thought to be beneficial given its vasodilatory effect as a calcium-channel blocker, have failed to demonstrate any beneficial outcome in comparison with placebo.^[18]

Consensus agreement is that these blood pressure guidelines should be maintained in the face of other interventions to restore perfusion, such as intra-arterial thrombolysis.^[1]

Table 3. Blood Pressure Management in Patients With Stroke*

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Control of hypotension

Given the need to maintain adequate cerebral blood flow, severe hypotension should be managed in standard fashion with aggressive fluid resuscitation, a search for the etiology of hypotension, and, if necessary, vasopressor support. Evidence suggests that baseline systolic blood pressure below 100 mg Hg and diastolic blood pressure below 70 mm Hg correlate with a worse outcome.^[25]

Further Outpatient Care

Poststroke outpatient care largely focuses on rehabilitation and prevention of recurrent stroke. Rehabilitation planning and initiation begins within the first day of the acute stroke. Recent research has demonstrated the benefits of early and aggressive mobilization.^[29]

• References

Additional Care

Referral to a physician with a special interest in stroke is ideal. Stroke care units with specially trained personnel exist and are said to show improved outcomes Comorbid medical problems need to be addressed. Assessments of swallow function prior to the reinstitution of oral feeding is recommended.^[1] Patients should receive deep venous thrombosis prophylaxis, although the timing of institution of this therapy is unknown.

Medical/Legal Pitfalls

In patients with transient ischemic attacks, failure to recognize the potential for near term stroke, failure to perform a timely assessment for stroke risk factors, and failure to initiate primary and secondary stroke prevention exposes the patient to undue risk of stroke and exposes clinicians to potential litigation.^[3]

• References

Author

Edward C Jauch, MD, MS, FAHA, FACEP, Chief of System Research, Mission Research Institute, Mission Health; Adjunct Professor, Department of Bioengineering, Clemson University

Disclosure: Received grant/research funds from Genentech for site pi.

Coauthor(s)

Brett Kissela, MD, MS, Professor and Chair, Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine

Disclosure: Received honoraria from Medscape Education for an educational activity; Received fees for adjudication of adverse events for clinical trial, payment per event reviewed from AbbVie and Janssen. Work performed as anindependent contractor.

Brian Stettler, MD, Assistant Professor, Program Director, Emergency Medicine Residency Program, Department of Emergency Medicine, and Faculty Greater Cincinnati/Northern Kentucky Stroke Team, University of Cincinnati

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Consultant, Abbott Vascular, Inc. .

Acknowledgements

Thomas A Kent, MD Professor and Director of Stroke Research and Education, Department of Neurology, Baylor College of Medicine; Chief of Neurology, Michael E DeBakey Veterans Affairs Medical Center

Thomas A Kent, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, New York Academy of Sciences, Royal Society of Medicine, Sigma Xi, and Stroke Council of the American Heart Association

Disclosure: Nothing to disclose.

Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center

Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acknowledgments

The authors would like to thank Dr. Jennifer Franklin for her assistance in the updating of this article.

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