What additional assessment and stabilization activities should be completed within the first 10 minutes after patient arrival?

Nearly 15 years of increased stroke education and organization has produced significant strides in public awareness and development of stroke systems of care. Despite these successes, though, each year 795 000 people suffer a new or repeat stroke, and stroke remains the third leading cause of death in the United States.1 Many advances have been made in stroke prevention, treatment, and rehabilitation, but arguably the greatest gains have been in the area of stroke systems of care. Integrating public education, 911 dispatch, prehospital detection and triage, hospital stroke system development, and stroke unit management have led to significant improvements in stroke care. Not only have the rates of appropriate fibrinolytic therapy increased over the past 5 years, but also overall stroke care has improved, in part through the creation of stroke centers.2 To achieve further improvement in reducing the burden of stroke, healthcare providers, hospitals, and communities must continue to develop systems to increase the efficiency and effectiveness of stroke care.3 The “D's of Stroke Care” remain the major steps in diagnosis and treatment of stroke and identify the key points at which delays can occur.4,5

  • Detection: Rapid recognition of stroke symptoms

  • Dispatch: Early activation and dispatch of emergency medical services (EMS) system by calling 911

  • Delivery: Rapid EMS identification, management, and transport

  • Door: Appropriate triage to stroke center

  • Data: Rapid triage, evaluation, and management within the emergency department (ED)

  • Decision: Stroke expertise and therapy selection

  • Drug: Fibrinolytic therapy, intra-arterial strategies

  • Disposition: Rapid admission to stroke unit, critical-care unit

This chapter summarizes the early management of acute ischemic stroke in adult patients. It describes care from out-of-hospital therapy through the first hours of in-hospital therapy. For additional information about the management of acute ischemic stroke, see the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for the management of acute ischemic stroke.3,6,7

Management Goals

The overall goal of stroke care is to minimize acute brain injury and maximize patient recovery. The time-sensitive nature of stroke care is central to the establishment of successful stroke systems, hence the commonly used refrain “Time is Brain.” The AHA and ASA have developed a community-oriented “Stroke Chain of Survival” that links specific actions to be taken by patients and family members with recommended actions by out-of-hospital healthcare responders, ED personnel, and in-hospital specialty services. These links, which are similar to those in the Adult Chain of Survival for victims of sudden cardiac arrest, include rapid recognition of stroke warning signs and activation of the emergency response system (call 911); rapid EMS dispatch, transport, and prehospital notification; triage to a stroke center; and rapid diagnosis, treatment, and disposition in the hospital.

The AHA ECC stroke guidelines focus on the initial out-of-hospital and ED assessment and management of the patient with acute stroke as depicted in the algorithm Goals for Management of Patients With Suspected Stroke (Figure). The time goals of the National Institute of Neurological Disorders and Stroke (NINDS)8 are illustrated on the left side of the algorithm as clocks. A sweep hand depicts the goal in minutes from ED arrival to task completion to remind the clinician of the time-sensitive nature of management of acute ischemic stroke.

What additional assessment and stabilization activities should be completed within the first 10 minutes after patient arrival?

Figure. Goals for management of patients with suspected stroke.

The sections below summarize the principles and goals of stroke system development and emergency assessment and management, as well as highlight new recommendations and training issues. The text refers to the numbered boxes in the algorithm.

Stroke Systems of Care

The regionalization of stroke care was not widely considered in the era before availability of effective acute therapies. With the NINDS recombinant tissue plasminogen activator (rtPA) trial, the crucial need for local partnerships between academic medical centers and community hospitals became a reality.9 The time-sensitive nature of stroke requires such an approach, even in densely populated metropolitan centers. The idea of a “stroke-prepared” hospital emerged after the United States Food and Drug Administration (FDA) approved rtPA for stroke. In 2000 the Brain Attack Coalition provided a description of “primary stroke centers,” which would ensure that best practices for stroke care (acute and beyond) would be offered in an organized fashion.7 The logic of having a multitiered system such as that provided for trauma was evident. Therefore, in 2005 the Brain Attack Coalition followed the statement on primary stroke centers with recommendations for comprehensive stroke centers.6 Following the establishment of primary stroke centers and comprehensive stroke centers, the new concept of a stroke-prepared hospital has recently emerged. This stroke-prepared hospital can access stroke expertise via telemedicine. The comparison with a trauma system with Level 1, 2, and 3 centers is rational and quite intuitive to emergency care providers familiar with such configurations.

Substantial progress has been made toward regionalization of stroke care. Several states have passed legislation requiring prehospital providers to triage patients with suspected stroke to designated stroke centers. This is contingent on the accuracy of dispatch, an area where further improvement is needed.10 The integration of EMS into regional stroke models is crucial for improvement of patient outcomes.11 Efforts have been strong in many regions, especially in regions with relatively high population density and large critical mass of stroke centers to effectively create a model for stroke regionalization.12 Although a large proportion of the US population is now within close proximity to a stroke center, it is not clear how many stroke patients arrive at stroke-prepared hospitals.

Additional work is needed to expand the reach of regional stroke networks. Healthcare professionals working in EMS, emergency medicine, or emergency nursing can also assist in this process by determining which hospitals in their community offer care concordant with the Brain Attack Coalition recommendations for primary stroke centers.7,11,13,14

Stroke Recognition and EMS Care (Box 1)

Stroke Warning Signs

Identifying clinical signs of possible stroke is important because recanalization strategies (intravenous [IV] fibrinolysis and intra-arterial/catheter-based approaches) must be provided within the first few hours from onset of symptoms.9,15,16 Most strokes occur at home, and just over half of all victims of acute stroke use EMS for transport to the hospital.17–21 Stroke knowledge among the lay public remains poor.22,23 These factors can delay EMS access and treatment, resulting in increased morbidity and mortality. Community and professional education is essential22,24 and has successfully increased the proportion of stroke patients treated with fibrinolytic therapy.25–27

Patient education efforts are most effective when the message is clear and succinct. The signs and symptoms of stroke include sudden weakness or numbness of the face, arm, or leg, especially on one side of the body; sudden confusion; trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; or sudden severe headache with no known cause. Educational efforts need to couple the knowledge of the signs and symptoms of stroke with action—call 911.

911 and EMS Dispatch

EMS systems of care include both 911 emergency medical dispatch centers and EMS response personnel. It is imperative that the stroke system of care provide education and training to 911 and EMS personnel to minimize delays in prehospital dispatch, assessment, and transport. Emergency medical telecommunicators must identify and provide high-priority dispatch to patients with stroke symptoms. Current literature suggests that 911 telecommunicators do not recognize stroke well and that the use of scripted stroke-specific screens during a 911 call may be helpful.10,28 Studies are ongoing to investigate the effectiveness of such a stroke assessment tool for 911 telecommunicators.29,30

In settings where ground transport to a stroke center is potentially long, air medical services may be used. Regional stroke resources work with EMS agencies to establish criteria for the use of air medical transport for patients with acute stroke and determine the most appropriate destination based on distance and the hospital's stroke capability. As with ground transportation, prehospital notification should be performed to ensure appropriate activation of stroke resources.

Stroke Assessment Tools

EMS providers can identify stroke patients with reasonable sensitivity and specificity, using abbreviated out-of-hospital tools such as the Cincinnati Prehospital Stroke Scale (CPSS)31–34 (Table 1) or the Los Angeles Prehospital Stroke Screen (LAPSS).35,36 The CPSS is based on physical examination only. The EMS provider checks for 3 physical findings: facial droop, arm weakness, and speech abnormalities. The presence of a single abnormality on the CPSS has a sensitivity of 59% and a specificity of 89% when scored by prehospital providers.33 Another assessment tool, the LAPSS, requires that the provider rule out other causes of altered level of consciousness (eg, history of seizures, hypoglycemia) and then identify asymmetry in any of 3 examination categories: facial smile or grimace, grip, and arm strength. The LAPSS has a sensitivity of 93% and a specificity of 97%.35,36

Table 1. The Cincinnati Prehospital Stroke Scale

Facial droop (have patient show teeth or smile)
  • Normal—both sides of face move equally

  • Abnormal—one side of face does not move as well as the other side

  • Arm drift (patient closes eyes and holds both arms straight out for 10 seconds)

  • Normal—both arms move the same or both arms do not move at all (other findings, such as pronator drift, may be helpful)

  • Abnormal—one arm does not move or one arm drifts down compared with the other

  • Abnormal speech (have the patient say “you can't teach an old dog new tricks”)

  • Normal—patient uses correct words with no slurring

  • Abnormal—patient slurs words, uses the wrong words, or is unable to speak

With standard training in stroke recognition, paramedics demonstrated a sensitivity of 61% to 66% for identifying patients with stroke.34,37,38 After receiving training in use of a stroke assessment tool, paramedic sensitivity for identifying patients with stroke increased to 86% to 97%.36,39,40 We recommend that all paramedics and emergency medical technicians-basic (EMT-basic) be trained in recognition of stroke using a validated, abbreviated out-of-hospital screening tool such as the CPSS or LAPSS (Class I, LOE B).

Prehospital Management and Triage (Box 2)

As with any other time-sensitive acute illness, prehospital providers must perform an initial assessment and intervene if necessary to provide cardiopulmonary support. In addition, for stroke, providers must clearly establish the time of onset of symptoms. This time represents time zero for the patient. If the patient wakes from sleep or is found with symptoms of a stroke, the time of onset of symptoms is defined as the last time the patient was observed to be normal. EMS providers must be able to support cardiopulmonary function, perform rapid stroke assessment, establish time of onset of symptoms (or the last time the patient was known to be normal), triage and transport the patient, and provide prearrival notification to the most appropriate receiving hospital.31,41–44

Patients with acute stroke are at risk for respiratory compromise from aspiration, upper airway obstruction, hypoventilation, and (rarely) neurogenic pulmonary edema. The combination of poor perfusion and hypoxemia will exacerbate and extend ischemic brain injury and has been associated with worse outcome from stroke.45 Both out-of-hospital and in-hospital medical personnel should administer supplemental oxygen to hypoxemic (ie, oxygen saturation <94%) stroke patients (Class I, LOE C) or those with unknown oxygen saturation.

Although blood pressure management is a component of the ED care of stroke patients, there are no data to support initiation of hypertension intervention in the prehospital environment. Unless the patient is hypotensive (systolic blood pressure <90 mm Hg), prehospital intervention for blood pressure is not recommended (Class III, LOE C).

Transport and Destination Hospital

EMS providers should consider transporting a witness, family member, or caregiver with the patient to verify the time of stroke symptom onset. En route to the facility, providers should continue to support cardiopulmonary function, monitor neurologic status, check blood glucose if possible, and provide prehospital notification.

Prearrival hospital notification by the transporting EMS unit has been found to significantly increase the percentage of patients with acute stroke who receive fibrinolytic therapy.46–48 Bypass of community hospitals in favor of transporting patients directly to a stroke center has undergone investigations that merit attention. Investigators in New York, Canada, Italy, and Australia have performed before-and-after studies examining the difference in rates of rtPA administration after implementation of a hospital bypass protocol for EMS. All have found significantly larger percentages of patients with ischemic stroke treated with rtPA when patients are transported directly to stroke centers.47,49,50 Recently investigators have begun to examine the impact of direct activation of stroke teams by EMS.50,51

EMS providers must rapidly deliver the patient to a medical facility capable of providing acute stroke care and provide prearrival notification to the receiving facility.41,46,48 Each receiving hospital should define its capability for treating patients with acute stroke using the definitions established for stroke-prepared hospitals, primary stroke centers, and comprehensive stroke centers3,6,7 and should communicate this information to the EMS system and the community. Although not every hospital is capable of organizing the necessary resources to safely administer fibrinolytic therapy, every hospital with an ED should have a written plan that is communicated to EMS systems describing how patients with acute stroke are to be managed in that institution. The plan should detail the roles of healthcare professionals in the care of patients with acute stroke and define which patients will be treated with fibrinolytic therapy at that facility and when transfer to another hospital with a dedicated stroke unit is appropriate.

The role of stroke centers and in particular stroke units continues to be defined, but a growing body of evidence47,49,50,52–58 indicates a favorable benefit from triage of stroke patients directly to designated stroke centers (Class I, LOE B). EMS systems should establish a stroke destination preplan to enable EMS providers to direct patients with acute stroke to appropriate facilities. When multiple stroke hospitals are within similar transport distances, EMS personnel should consider triage to the stroke center with the highest capability of stroke care.

Multiple randomized clinical trials and meta-analyses in adults50,59–62 document consistent improvement in 1-year survival rate, functional outcome, and quality of life when patients hospitalized with acute stroke are cared for in a dedicated stroke unit by a multidisciplinary team experienced in managing stroke. Although the studies reported were conducted outside the United States at in-hospital units that provided both acute care and rehabilitation, the improved outcomes were apparent very early in stroke care. These results should be relevant to the outcome of dedicated stroke units staffed with experienced multidisciplinary teams in the United States. When such a facility is available within a reasonable transport interval, stroke patients who require hospitalization should be admitted there (Class I, LOE B).

In-Hospital Care

Initial ED Assessment and Stabilization (Box 3)

Protocols should be used in the ED to minimize delay to definitive diagnosis and therapy: “Time is Brain.”43 As a goal, ED personnel should assess the patient with suspected stroke within 10 minutes of arrival in the ED. General care includes assessment, cardiopulmonary support (airway, breathing, circulation), and evaluation of baseline vital signs. Administration of oxygen to hypoxemic patients with stroke (oxygen saturation <94%) is recommended (Class I, LOE C).

On arrival ED personnel should establish or confirm IV access and obtain blood samples for baseline studies (eg, complete blood count, coagulation studies, blood glucose). If not already identified in the prehospital setting, ED staff should promptly identify and treat hypoglycemia. The ED physician should perform a neurologic screening assessment, order an emergent computed tomography (CT) scan of the brain, and activate the stroke team or arrange for consultation with a stroke expert.

A 12-lead electrocardiogram (ECG) does not take priority over the CT scan but may identify a recent acute myocardial infarction or arrhythmias (eg, atrial fibrillation) as the cause of an embolic stroke. If the patient is hemodynamically stable, treatment of other arrhythmias, including bradycardia, premature atrial or ventricular contractions, or asymptomatic atrioventricular conduction block, may not be necessary.63 There is general agreement to recommend cardiac monitoring during the first 24 hours of evaluation in patients with acute ischemic stroke to detect atrial fibrillation and potentially life-threatening arrhythmias.64

Assessment (Box 4)

The treating physician should review the patient's history and verify time of onset of symptoms.65–67 This may require interviewing out-of-hospital providers, witnesses, and family members to establish the time that the patient was last known to be normal. Neurologic assessment is performed, incorporating either the National Institutes of Health Stroke Scale (NIHSS) or the Canadian Neurological Scale (CNS) (see the ASA website: www.strokeassociation.org).

Management of hypertension in the stroke patient is dependent on fibrinolytic eligibility. For patients potentially eligible for fibrinolytic therapy, blood pressure must be ≤185 mm Hg systolic and ≤110 mm Hg diastolic to limit the risk of bleeding complications. Because the maximum interval from onset of stroke until effective treatment of stroke with rtPA is limited, most patients with sustained hypertension above these levels (ie, systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg) will not be eligible for IV rtPA (Tables 2 and 3).68

Table 2. Potential Approaches to Arterial Hypertension in Acute Ischemic Stroke Patients Who Are Potential Candidates for Acute Reperfusion Therapy

Patient otherwise eligible for acute reperfusion therapy except that blood pressure is >185/110 mm Hg
  • Labetalol 10–20 mg IV over 1–2 minutes, may repeat ×1, or

  • Nicardipine IV 5 mg/hr, titrate up by 2.5 mg/hr every 5–15 minutes, maximum 15 mg/hr; when desired blood pressure reached, lower to 3 mg/hr, or

  • Other agents (hydralazine, enalaprilat, etc) may be considered when appropriate

If blood pressure is not maintained at or below 185/110 mm Hg, do not administer rtPA
Management of blood pressure during and after rtPA or other acute reperfusion therapy:
  • Monitor blood pressure every 15 minutes for 2 hours from the start of rtPA therapy; then every 30 minutes for 6 hours; and then every hour for 16 hours

If systolic BP 180–230 mm Hg or diastolic BP 105–120 mm Hg
  • Labetalol 10 mg IV followed by continuous IV infusion 2–8 mg/min, or

  • Nicardipine IV 5 mg/h, titrate up to desired effect by 2.5 mg/hr every 5–15 minutes, maximum 15 mg/h

If blood pressure not controlled or diastolic BP >140 mm Hg, consider sodium nitroprusside

Table 3. Approach to Arterial Hypertension in Acute Ischemic Stroke Patients Who Are Not Potential Candidates for Acute Reperfusion Therapy

Consider lowering blood pressure in patients with acute ischemic stroke if systolic blood pressure >220 mm Hg or diastolic blood pressure >120 mm Hg
Consider blood pressure reduction as indicated for other concomitant organ system injury
  • Acute myocardial infarction

  • Congestive heart failure

  • Acute aortic dissection

A reasonable target is to lower blood pressure by 15% to 25% within the first day

Imaging (Box 5)

Ideally the CT scan should be completed within 25 minutes of the patient's arrival in the ED and should be interpreted within 45 minutes of ED arrival. Centers may perform more advanced neurologic imaging (multimodal magnetic resonance imaging [MRI], CT perfusion, and CT angiography), but obtaining these studies should not delay initiation of IV rtPA in eligible patients. Emergent CT or MRI scans of patients with suspected stroke should be promptly evaluated by a physician with expertise in interpretation of these studies.69 During the first few hours of an ischemic stroke the noncontrast CT scan may not indicate signs of brain ischemia. If the CT scan shows no evidence of intracerebral hemorrhage, the patient may be a candidate for fibrinolytic therapy (Boxes 6 and 8). If hemorrhage is noted on the CT scan, the patient is not a candidate for fibrinolytic therapy. Consult a neurologist or neurosurgeon and consider transfer as needed for appropriate care (Box 7).

If hemorrhage is not present on the initial CT scan and the patient is not a candidate for fibrinolytic therapy for other reasons, consider administration of aspirin (Box 9) either rectally or orally after the patient is screened for dysphagia (see below). Admit the patient to a stroke unit (if available) for careful monitoring (Box 11).

Fibrinolytic Therapy (Boxes 6, 8, and 10)

The treating physician should review the inclusion and exclusion criteria for IV fibrinolytic therapy (Tables 4 and 5) and perform a repeat neurologic examination incorporating the NIHSS or CNS. If the patient's neurologic signs are spontaneously clearing (ie, function is rapidly improving to normal and is near baseline), administration of fibrinolytics may not be required (Box 6).64

Table 4. Inclusion and Exclusion Characteristics of Patients With Ischemic Stroke Who Could Be Treated With rtPA Within 3 Hours From Symptom Onset

Inclusion criteria
  • Diagnosis of ischemic stroke causing measurable neurologic deficit

  • Onset of symptoms <3 hours before beginning treatment

  • Age ≥18 years

  • Exclusion criteria

  • Head trauma or prior stroke in previous 3 months

  • Symptoms suggest subarachnoid hemorrhage

  • Arterial puncture at noncompressible site in previous 7 days

  • History of previous intracranial hemorrhage

  • Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)

  • Evidence of active bleeding on examination

  • Acute bleeding diathesis, including but not limited to

    Platelet count <100 000/mm3

    Heparin received within 48 hours, resulting in aPTT >upper limit of normal

    Current use of anticoagulant with INR >1.7 or PT >15 seconds

  • Blood glucose concentration <50 mg/dL (2.7 mmol/L)

  • CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Relative exclusion criteria

Recent experience suggests that under some circumstances—with careful consideration and weighing of risk to benefit—patients may receive fibrinolytic therapy despite 1 or more relative contraindications. Consider risk to benefit of rtPA administration carefully if any of these relative contraindications is present

Only minor or rapidly improving stroke symptoms (clearing spontaneously)

Seizure at onset with postictal residual neurologic impairments

Major surgery or serious trauma within previous 14 days

Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days)

Recent acute myocardial infarction (within previous 3 months)

Table 5. Additional Inclusion and Exclusion Characteristics of Patients With Ischemic Stroke Who Could Be Treated With rtPA From 3 to 4.5 Hours From Symptom Onset

Inclusion criteria
  • Diagnosis of ischemic stroke causing measurable neurologic deficit

  • Onset of symptoms 3 to 4.5 hours before beginning treatment

Exclusion criteria
  • Age >80 years

  • Severe stroke (NIHSS >25)

  • Taking an oral anticoagulant regardless of INR

  • History of both diabetes and prior ischemic stroke

Notes
  • The checklist includes some FDA-approved indications and contraindications for administration of rtPA for acute ischemic stroke. Recent guideline revisions have modified the original FDA criteria. A physician with expertise in acute stroke care may modify this list

  • Onset time is either witnessed or last known normal

  • In patients without recent use of oral anticoagulants or heparin, treatment with rtPA can be initiated before availability of coagulation study results but should be discontinued if INR is >1.7 or PT is elevated by local laboratory standards

  • In patients without history of thrombocytopenia, treatment with rtPA can be initiated before availability of platelet count but should be discontinued if platelet count is <100 000/mm3

As with all medications, fibrinolytics have potential adverse effects. The physician must verify that there are no exclusion criteria, consider the risks and benefits to the patient, and be prepared to monitor and treat any potential complications. The major complication of IV rtPA for stroke is symptomatic intracranial hemorrhage. This complication occurred in 6.4% of the 312 patients treated in the NINDS trials9 and 4.6% of the 1135 patients treated in 60 Canadian centers.70 A meta-analysis of 15 published case series on the open-label use of rtPA for acute ischemic stroke in general clinical practice showed a symptomatic hemorrhage rate of 5.2% of 2639 patients treated.71 Other complications include orolingual angioedema (occurs in approximately 1.5% of patients), acute hypotension, and systemic bleeding. In one large prospective registry, major systemic bleeding was uncommon (0.4%) and usually occurred at the site of femoral puncture for acute angiography.70,72

If the patient remains a candidate for fibrinolytic therapy (Box 8), the physician should discuss the risks and potential benefits of the therapy with the patient or family if available (Box 10). After this discussion, if the patient/family elects to proceed with fibrinolytic therapy, begin the rtPA bolus and infusion as quickly as possible and begin the stroke pathway of care (see below). Careful dose calculation and removal of excess rtPA help prevent inadvertent administration of excess rtPA. Typically neither anticoagulant nor antiplatelet treatment may be administered for 24 hours after administration of rtPA until a repeat CT scan at 24 hours shows no hemorrhagic transformation.

Several studies9,15,70 have documented a higher likelihood of good to excellent functional outcome when rtPA is administered to adult patients with acute ischemic stroke within 3 hours of onset of symptoms. These results are obtained when rtPA is administered by physicians in hospitals with a stroke protocol that rigorously adheres to the eligibility criteria and therapeutic regimen of the NINDS protocol. These results have been supported by a subsequent 1-year follow-up study,73 reanalysis of the NINDS data,74 and a meta-analysis.75 Evidence from prospective randomized studies9,15,74,76 in adults also documents a greater likelihood of benefit the earlier treatment is begun. Additional analyses of the original NINDS data by an independent group of investigators confirmed the validity of the results,74 verifying that improved outcomes in the rtPA treatment arm persist even when imbalances in the baseline stroke severity among treatment groups is corrected.77

Treatment of carefully selected patients with acute ischemic stroke with IV rtPA between 3 and 4.5 hours after onset of symptoms has also been shown to improve clinical outcome, although the degree of clinical benefit is smaller than that achieved with treatment within 3 hours.16,78 Data supporting treatment in this time window come from a large, randomized trial (ECASS-3) that specifically enrolled patients between 3 and 4.5 hours after symptom onset, as well as a meta-analysis of prior trials. Criteria for inclusion in ECASS-3 were similar to the NINDS criteria, except that ECASS-3 excluded patients older than 80 years of age, with a baseline NIHSS >25, taking oral anticoagulants, or who had a combination of diabetes and prior stroke. At present, use of IV rtPA within the 3- to 4.5-hour window has not yet been FDA approved, although it is recommended by a current AHA/ASA science advisory.78 Administration of IV rtPA to patients with acute ischemic stroke who meet the NINDS or ECASS-3 eligibility criteria is recommended if rtPA is administered by physicians in the setting of a clearly defined protocol, a knowledgeable team, and institutional commitment (Class I, LOE B).

It is important to note that the superior outcomes reported in both community and tertiary care hospitals in clinical trials of rtPA may be difficult to replicate in hospitals with less experience in, and institutional commitment to, acute stroke care.79,80 Failure to adhere to protocol is associated with an increased rate of complications, particularly the risk of symptomatic intracranial hemorrhage.79,81 There is a relationship between violations of the NINDS treatment protocol and increased risk of symptomatic intracerebral hemorrhage and death.71 In Germany there was an increased risk of death after administration of rtPA for acute ischemic stroke in hospitals that treated ≤5 patients per year, suggesting that clinical experience is an important factor in ensuring adherence to protocol.72 Adding a dedicated stroke team to a community hospital can increase the number of patients with acute stroke treated with fibrinolytic therapy and produce excellent clinical outcomes.82 There is also strong evidence to avoid all delays and treat patients as soon as possible. These findings show that it is important to have an institutional commitment to ensure optimal patient outcomes.

Evidence from 3 prospective randomized studies in adults and a meta-analysis83–87 have demonstrated improved outcome from intra-arterial fibrinolysis. Thus, for patients with acute ischemic stroke who are not candidates for standard IV fibrinolysis, administration of intra-arterial fibrinolytics is reasonable (Class I, LOE B). To date, intra-arterial administration of fibrinolytics has not been FDA approved. In carefully selected patients, catheter-based thrombectomy is being performed at centers where resources and expertise are available. The pending ASA acute ischemic stroke guidelines will provide greater detail about intra-arterial strategies.

General Stroke Care

Recent studies establish that stroke unit care is superior to care in general medical wards, and the positive effects of stroke unit care can persist for years. The benefits from treatment in a stroke unit are comparable to the effects achieved with IV rtPA. Patients should be admitted to a stroke unit (if available) for careful observation (Box 11), including monitoring of blood pressure and neurologic status and physiologic optimization. General stroke care, centered on physiologic optimization, includes prevention of hypoxia, management of hypertension, optimal glucose control, maintenance of euthermia, and nutritional support. Additional efforts center on prevention of complications associated with stroke (eg, aspiration pneumonia, deep venous thrombosis, urinary tract infections) and initiation of secondary stroke prevention.

Given the requirements for frequent neurologic assessment and vital sign measurements, especially after administration of IV rtPA, patients should be admitted as quickly as possible, ideally within 3 hours from arrival.8 If the patient's neurologic status deteriorates, an emergent CT scan is required to determine if cerebral edema or hemorrhage is responsible for the deterioration. Treatment of hemorrhage or edema should be started immediately as indicated.

Blood Pressure Management

Blood pressure management varies depending on whether or not fibrinolytic or intra-arterial therapies were used. Current recommendations for control of blood pressure in patients who receive IV rtPA or intra-arterial recanalization therapies are shown in Table 2. In those patients for whom recanalization is not planned, more liberal acceptance of hypertension is recommended, provided no other comorbid conditions require intervention (Table 3). Normal saline, administered at a rate of approximately 75 to 100 mL/h, is used to maintain euvolemia as needed. In stroke patients who may be relatively hypovolemic, careful administration of IV normal saline boluses may be appropriate.

Glycemic Control

Hyperglycemia is associated with worse clinical outcome in patients with acute ischemic stroke,88–95 but there is no direct evidence that active glucose control improves clinical outcome.96,97 There is contradictory evidence for the benefit of insulin treatment of hyperglycemia in other critically ill patients.98,99 Current AHA/ASA recommendations call for the use of insulin when the serum glucose level is greater than 185 mg/dL in patients with acute stroke (Class IIa, LOE C); however, the utility of administration of IV or subcutaneous insulin to lower blood glucose in patients with acute ischemic stroke when serum glucose is ≤185 mg/dL remains uncertain.

Temperature Control

Hyperthermia in the setting of acute cerebral ischemia is associated with increased morbidity and mortality and should be managed aggressively (treat fever >37.5°C [99.5°F]).100–103 Hypothermia has been shown to improve survival and functional outcome in patients following resuscitation from ventricular fibrillation (VF) sudden cardiac arrest; however, there are limited data on the role of hypothermia specific to acute ischemic stroke. At this time there is insufficient scientific evidence to recommend for or against the use of hypothermia in the treatment of acute ischemic stroke (Class IIb, LOE C).

Dysphagia Screening

All patients with stroke should be screened for dysphagia before they are given anything by mouth. A simple bedside screening evaluation involves asking the patient to sip water from a cup. If the patient can sip and swallow without difficulty, the patient is asked to take a large gulp of water and swallow. If there are no signs of coughing or aspiration after 30 seconds, then it is safe for the patient to have a thickened diet until formally assessed by a speech pathologist. Medications may be given in applesauce or jam. Any patient who fails a swallow test may be given medications such as aspirin rectally or, if appropriate for the medication, intravenously, intramuscularly, or subcutaneously.

Other Stroke Management

Additional stroke care includes support of the airway, oxygenation and ventilation, and nutritional support. Seizure prophylaxis is not recommended, but for patients who experience a seizure, administration of anticonvulsants is recommended to prevent more seizures.104 In patients with severe stroke, posterior circulation stroke, and in younger patients, healthcare providers must observe for signs of increased intracranial pressure.

Summary

Advances in stroke care will have the greatest effect on stroke outcome if care is delivered within a regional stroke system designed to improve both efficiency and effectiveness. The ultimate goal of stroke care is to minimize ongoing injury, emergently recanalize acute vascular occlusions, and begin secondary measures to maximize functional recovery. These efforts will provide stroke patients with the greatest opportunity for a return to previous quality of life and decrease the overall societal burden of stroke.

Disclosures

Guidelines Part 11: Stroke: Writing Group Disclosures

Writing Group MemberEmploymentResearch GrantOther Research SupportSpeakers' Bureau/HonorariaOwnership InterestConsultant/Advisory BoardOther
Edward C. JauchMedical University of South Carolina-ProfessorNIH trials related to strokeNoneNoneNoneNoneNone
Brett CucchiaraUniversity of Pennsylvania–Assistant Professor of Neurology†NIH RO1-migraine imaging research-significantNone*Multiple CME talks at different institutionsNoneNone*Occasionally serves as expert witness for medicolegal cases
Opeolu AdeoyeUniversity of Cincinnati–Assistant Professor of Emergency Medicine and NeurosurgeryNoneNone*Genentech EKR TherapeuticsNoneNoneNone
William MeurerUniversity of Michigan–Assistant ProfessorNoneNoneNoneNoneNoneNone
Jane BriceUniversity of North Carolina: Associate professor in the department of emergency medicine. Perform clinical work in the emergency department. Perform research in the areas of EMS and stroke. Teach in the School of Medicine–Associate ProfessorNoneNoneNoneNoneNoneNone
Yvonne (Yu-Feng) ChanThe Mount Sinai School of Medicine–Assistant Professor of Emergency MedicineNoneNoneNoneNoneNoneNone
Nina GentileTemple University–Professor, Department of Emergency Medicine†Active Support: 5 NIH U01 NS044876–03. Insulin Resistance Intervention after Stroke (IRIS) Trial. Investigation of the effect of Pioglitazone on development of diabetes and stroke recurrence after ischemic stroke or TIA. Total Award to Temple, direct costs: $184,000 2005–2010 NIH NINDS U01 NS40406-04 Albumin in Acute Ischemic Stroke (ALIAS) Trial. Human Serum Albumin will be compared to placebo on improving the 3 month outcome of ischemic stroke patients when administered within 5 hours of symptom onset. Total Award to Temple, direct costs: $225,000 2008–2011NoneNoneNoneNoneNone
Mary Fran HazinskiVanderbilt University School of Nursing—Professor; AHA ECC Product Development–Senior Science Editor †Substantial consulting fees as a senior science editor for the AHA ECC Product Development.NoneNoneNoneNoneNoneNone

Footnotes

References

  • 1. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond. Circulation. 2010; 121:586–613.LinkGoogle Scholar
  • 2. Schwamm LH, Fonarow GC, Reeves MJ, Pan W, Frankel MR, Smith EE, Ellrodt G, Cannon CP, Liang L, Peterson E, Labresh KA. Get With the Guidelines–Stroke is associated with sustained improvement in care for patients hospitalized with acute stroke or transient ischemic attack. Circulation. 2009; 119:107–115.LinkGoogle Scholar
  • 3. Schwamm LH, Pancioli A, Acker JE, Goldstein LB, Zorowitz RD, Shephard TJ, Moyer P, Gorman M, Johnston SC, Duncan PW, Gorelick P, Frank J, Stranne SK, Smith R, Federspiel W, Horton KB, Magnis E, Adams RJ. Recommendations for the establishment of stroke systems of care: recommendations from the American Stroke Association's Task Force on the Development of Stroke Systems. Circulation. 2005; 111:1078–1091.LinkGoogle Scholar
  • 4. Hazinski M. D-mystifying recognition and management of stroke. Curr Emerg Cardiac Care. 1996; 7:8.Google Scholar
  • 5. Acute stroke: current treatment and paradigms. In: Cummins R, Field J, Hazinski M eds. ACLS: Principles and Practice. Dallas, Tex: American Heart Association;2003:437–482.Google Scholar
  • 6. Alberts MJ, Latchaw RE, Selman WR, Shephard T, Hadley MN, Brass LM, Koroshetz W, Marler JR, Booss J, Zorowitz RD, Croft JB, Magnis E, Mulligan D, Jagoda A, O'Connor R, Cawley CM, Connors JJ, Rose-DeRenzy JA, Emr M, Warren M, Walker MD. Recommendations for comprehensive stroke centers: a consensus statement from the Brain Attack Coalition. Stroke. 2005; 36:1597–1616.LinkGoogle Scholar
  • 7. Alberts MJ, Hademenos G, Latchaw RE, Jagoda A, Marler JR, Mayberg MR, Starke RD, Todd HW, Viste KM, Girgus M, Shephard T, Emr M, Shwayder P, Walker MD. Recommendations for the establishment of primary stroke centers. Brain Attack Coalition. JAMA. 2000; 283:3102–3109.CrossrefMedlineGoogle Scholar
  • 8. Marler J, Jones P, Emr M eds. Setting New Directions for Stroke Care: Proceedings of a National Symposium on Rapid Identification and Treatment of Acute Stroke. Bethesda, Md: National Institute of Neurological Disorders and Stroke; 1997.Google Scholar
  • 9. 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; 333:1581–1587.CrossrefMedlineGoogle Scholar
  • 10. Buck BH, Starkman S, Eckstein M, Kidwell CS, Haines J, Huang R, Colby D, Saver JL. Dispatcher recognition of stroke using the National Academy Medical Priority Dispatch System. Stroke. 2009; 40:2027–2030.LinkGoogle Scholar
  • 11. Acker JE, Pancioli AM, Crocco TJ, Eckstein MK, Jauch EC, Larrabee H, Meltzer NM, Mergendahl WC, Munn JW, Prentiss SM, Sand C, Saver JL, Eigel B, Gilpin BR, Schoeberl M, Solis P, Bailey JR, Horton KB, Stranne SK. Implementation strategies for emergency medical services within stroke systems of care: a policy statement from the American Heart Association/American Stroke Association Expert Panel on Emergency Medical Services Systems and the Stroke Council. Stroke. 2007; 38:3097–3115.LinkGoogle Scholar
  • 12. Gropen T, Magdon-Ismail Z, Day D, Melluzzo S, Schwamm LH. Regional implementation of the stroke systems of care model: recommendations of the northeast cerebrovascular consortium. Stroke. 2009; 40:1793–1802.LinkGoogle Scholar
  • 13. Park S, Schwamm LH. Organizing regional stroke systems of care. Curr Opin Neurol. 2008; 21:43–55.CrossrefMedlineGoogle Scholar
  • 14. Summers D, Leonard A, Wentworth D, Saver JL, Simpson J, Spilker JA, Hock N, Miller E, Mitchell PH. Comprehensive overview of nursing and interdisciplinary care of the acute ischemic stroke patient: a scientific statement from the American Heart Association. Stroke. 2009; 40:2911–2944.LinkGoogle Scholar
  • 15. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004; 363:768–774.CrossrefMedlineGoogle Scholar
  • 16. Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008; 359:1317–1329.CrossrefMedlineGoogle Scholar
  • 17. Barsan WG, Brott TG, Olinger CP, Adams HP, Haley EC, Levy DE. Identification and entry of the patient with acute cerebral infarction. Ann Emerg Med. 1988; 17:1192–1195.CrossrefMedlineGoogle Scholar
  • 18. Barsan WG, Brott TG, Broderick JP, Haley EC, Levy DE, Marler JR. Time of hospital presentation in patients with acute stroke. Arch Intern Med. 1993; 153:2558–2561.CrossrefMedlineGoogle Scholar
  • 19. Pepe PE, Zachariah BS, Sayre MR, Floccare D. Ensuring the chain of recovery for stroke in your community. Chain of Recovery Writing Group. Prehosp Emerg Care. 1998; 2:89–95.CrossrefMedlineGoogle Scholar
  • 20. Evenson KR, Foraker RE, Morris DL, Rosamond WD. A comprehensive review of prehospital and in-hospital delay times in acute stroke care. Int J Stroke. 2009; 4:187–199.CrossrefMedlineGoogle Scholar
  • 21. Adeoye O, Lindsell C, Broderick J, Alwell K, Jauch E, Moomaw CJ, Flaherty ML, Pancioli A, Kissela B, Kleindorfer D. Emergency medical services use by stroke patients: a population-based study. Am J Emerg Med. 2009; 27:141–145.CrossrefMedlineGoogle Scholar
  • 22. Kleindorfer D, Khoury J, Broderick JP, Rademacher E, Woo D, Flaherty ML, Alwell K, Moomaw CJ, Schneider A, Pancioli A, Miller R, Kissela BM. Temporal trends in public awareness of stroke: warning signs, risk factors, and treatment. Stroke. 2009; 40:2502–2506.LinkGoogle Scholar
  • 23. Jones SP, Jenkinson AJ, Leathley MJ, Watkins CL. Stroke knowledge and awareness: an integrative review of the evidence. Age Ageing. 2010; 39:11–22.CrossrefMedlineGoogle Scholar
  • 24. Lyden P, Rapp K, Babcock T, et al. Ultra-rapid identification, triage, and enrollment of stroke patients into clinical trials. J Stroke Cerebrovasc Dis. 1994; 2:106–113.CrossrefGoogle Scholar
  • 25. Morgenstern LB, Staub L, Chan W, Wein TH, Bartholomew LK, King M, Felberg RA, Burgin WS, Groff J, Hickenbottom SL, Saldin K, Demchuk AM, Kalra A, Dhingra A, Grotta JC. Improving delivery of acute stroke therapy: the TLL Temple Foundation Stroke Project. Stroke. 2002; 33:160–166.LinkGoogle Scholar
  • 26. Morgenstern LB, Bartholomew LK, Grotta JC, Staub L, King M, Chan W. Sustained benefit of a community and professional intervention to increase acute stroke therapy. Arch Intern Med. 2003; 163:2198–2202.CrossrefMedlineGoogle Scholar
  • 27. Scott PA. Enhancing community delivery of tissue plasminogen activator in stroke through community-academic collaborative clinical knowledge translation. Emerg Med Clin North Am. 2009; 27:115–136.CrossrefMedlineGoogle Scholar
  • 28. Rosamond WD, Evenson KR, Schroeder EB, Morris DL, Johnson AM, Brice JH. Calling emergency medical services for acute stroke: a study of 9-1-1 tapes. Prehosp Emerg Care. 2005; 9:19–23.CrossrefMedlineGoogle Scholar
  • 29. Liferidge AT, Brice JH, Overby BA, Evenson KR. Ability of laypersons to use the Cincinnati Prehospital Stroke Scale. Prehosp Emerg Care. 2004; 8:384–387.CrossrefMedlineGoogle Scholar
  • 30. Hurwitz AS, Brice JH, Overby BA, Evenson KR. Directed use of the Cincinnati Prehospital Stroke Scale by laypersons. Prehosp Emerg Care. 2005; 9:292–296.CrossrefMedlineGoogle Scholar
  • 31. Kothari R, Barsan W, Brott T, Broderick J, Ashbrock S. Frequency and accuracy of prehospital diagnosis of acute stroke. Stroke. 1995; 26:937–941.LinkGoogle Scholar
  • 32. Kothari R, Hall K, Brott T, Broderick J. Early stroke recognition: developing an out-of-hospital NIH Stroke Scale. Acad Emerg Med. 1997; 4:986–990.CrossrefMedlineGoogle Scholar
  • 33. Kothari RU, Pancioli A, Liu T, Brott T, Broderick J. Cincinnati Prehospital Stroke Scale: reproducibility and validity. Ann Emerg Med. 1999; 33:373–378.CrossrefMedlineGoogle Scholar
  • 34. Smith WS, Isaacs M, Corry MD. Accuracy of paramedic identification of stroke and transient ischemic attack in the field. Prehosp Emerg Care. 1998; 2:170–175.CrossrefMedlineGoogle Scholar
  • 35. Kidwell CS, Saver JL, Schubert GB, Eckstein M, Starkman S. Design and retrospective analysis of the Los Angeles Prehospital Stroke Screen (LAPSS). Prehosp Emerg Care. 1998; 2:267–273.CrossrefMedlineGoogle Scholar
  • 36. Kidwell CS, Starkman S, Eckstein M, Weems K, Saver JL. Identifying stroke in the field. Prospective validation of the Los Angeles prehospital stroke screen (LAPSS). Stroke. 2000; 31:71–76.LinkGoogle Scholar
  • 37. Ellison SR, Gratton MC, Schwab RA, Ma OJ. Prehospital dispatch assessment of stroke. Mo Med. 2004; 101:64–66.MedlineGoogle Scholar
  • 38. Wojner AW, Morgenstern L, Alexandrov AV, Rodriguez D, Persse D, Grotta JC. Paramedic and emergency department care of stroke: baseline data from a citywide performance improvement study. Am J Crit Care. 2003; 12:411–417.CrossrefMedlineGoogle Scholar
  • 39. Smith WS, Corry MD, Fazackerley J, Isaacs SM. Improved paramedic sensitivity in identifying stroke victims in the prehospital setting. Prehosp Emerg Care. 1999; 3:207–210.CrossrefMedlineGoogle Scholar
  • 40. Zweifler RM, York D, et al. Accuracy of paramedic diagnosis of stroke. J Stroke Cerebrovasc Dis. 1998; 7:446–448.CrossrefMedlineGoogle Scholar
  • 41. Sayre MR, Swor RA, Honeykutt LK. Prehospital identification and treatment. In: , Emr M ed. Setting New Directions for Stroke Care: Proceedings of a National Symposium on Rapid Identification and Treatment of Acute Stroke. Bethesda, Md: National Institute of Neurological Disorders and Stroke;1997:35–44.Google Scholar
  • 42. Zachariah B, Dunford J, Van Cott CC. Dispatch life support and the acute stroke patient: making the right call. In: Proceedings of the National Institute of Neurological Disorders and Stroke. Bethesda, Md: National Institute of Neurological Disorders and Stroke; 1991:29–33.Google Scholar
  • 43. A systems approach to immediate evaluation and management of hyperacute stroke. Experience at eight centers and implications for community practice and patient care. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group. Stroke. 1997; 28:1530–1540.CrossrefMedlineGoogle Scholar
  • 44. Crocco TJ, Grotta JC, Jauch EC, Kasner SE, Kothari RU, Larmon BR, Saver JL, Sayre MR, Davis SM. EMS management of acute stroke–prehospital triage (resource document to NAEMSP position statement). Prehosp Emerg Care. 2007; 11:313–317.CrossrefMedlineGoogle Scholar
  • 45. Langhorne P, Tong BL, Stott DJ. Association between physiological homeostasis and early recovery after stroke. Stroke. 2000; 31:2518–2519.LinkGoogle Scholar
  • 46. Kim SK, Lee SY, Bae HJ, Lee YS, Kim SY, Kang MJ, Cha JK. Pre-hospital notification reduced the door-to-needle time for IV t-PA in acute ischaemic stroke. Eur J Neurol. 2009; 16:1331–1335.CrossrefMedlineGoogle Scholar
  • 47. Quain DA, Parsons MW, Loudfoot AR, Spratt NJ, Evans MK, Russell ML, Royan AT, Moore AG, Miteff F, Hullick CJ, Attia J, McElduff P, Levi CR. Improving access to acute stroke therapies: a controlled trial of organised pre-hospital and emergency care. Med J Aust. 2008; 189:429–433.CrossrefMedlineGoogle Scholar
  • 48. Abdullah AR, Smith EE, Biddinger PD, Kalenderian D, Schwamm LH. Advance hospital notification by EMS in acute stroke is associated with shorter door-to-computed tomography time and increased likelihood of administration of tissue-plasminogen activator. Prehosp Emerg Care. 2008; 12:426–431.CrossrefMedlineGoogle Scholar
  • 49. Gropen TI, Gagliano PJ, Blake CA, Sacco RL, Kwiatkowski T, Richmond NJ, Leifer D, Libman R, Azhar S, Daley MB. Quality improvement in acute stroke: the New York State Stroke Center Designation Project. Neurology. 2006; 67:88–93.CrossrefMedlineGoogle Scholar
  • 50. Gladstone DJ, Rodan LH, Sahlas DJ, Lee L, Murray BJ, Ween JE, Perry JR, Chenkin J, Morrison LJ, Beck S, Black SE. A citywide prehospital protocol increases access to stroke thrombolysis in Toronto. Stroke. 2009; 40:3841–3844.LinkGoogle Scholar
  • 51. Douglas VC, Tong DC, Gillum LA, Zhao S, Brass LM, Dostal J, Johnston SC. Do the Brain Attack Coalition's criteria for stroke centers improve care for ischemic stroke?Neurology. 2005; 64:422–427.CrossrefMedlineGoogle Scholar
  • 52. Chapman KM, Woolfenden AR, Graeb D, Johnston DC, Beckman J, Schulzer M, Teal PA. Intravenous tissue plasminogen activator for acute ischemic stroke: a Canadian hospital's experience. Stroke. 2000; 31:2920–2924.LinkGoogle Scholar
  • 53. Merino JG, Silver B, Wong E, Foell B, Demaerschalk B, Tamayo A, Poncha F, Hachinski V. Extending tissue plasminogen activator use to community and rural stroke patients. Stroke. 2002; 33:141–146.LinkGoogle Scholar
  • 54. Riopelle RJ, Howse DC, Bolton C, Elson S, Groll DL, Holtom D, Brunet DG, Jackson AC, Melanson M, Weaver DF. Regional access to acute ischemic stroke intervention. Stroke. 2001; 32:652–655.LinkGoogle Scholar
  • 55. Cross DT, Tirschwell DL, Clark MA, Tuden D, Derdeyn CP, Moran CJ, Dacey RG. Mortality rates after subarachnoid hemorrhage: variations according to hospital case volume in 18 states. J Neurosurg. 2003; 99:810–817.CrossrefMedlineGoogle Scholar
  • 56. Domeier R, Scott P, Wagner C. From research to the road: the development of EMS specialty triage. Air Med J. 2004; 23:28–31.CrossrefMedlineGoogle Scholar
  • 57. Pepe PE, Zachariah BS, Sayre MR, Floccare D. Ensuring the chain of recovery for stroke in your community. Acad Emerg Med. 1998; 5:352–358.CrossrefMedlineGoogle Scholar
  • 58. Wojner-Alexandrov AW, Alexandrov AV, Rodriguez D, Persse D, Grotta JC. Houston paramedic and emergency stroke treatment and outcomes study (HoPSTO). Stroke. 2005; 36:1512–1518.LinkGoogle Scholar
  • 59. Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. Stroke Unit Trialists' Collaboration. BMJ. 1997; 314:1151–1159.CrossrefMedlineGoogle Scholar
  • 60. How do stroke units improve patient outcomes? A collaborative systematic review of the randomized trials. Stroke Unit Trialists Collaboration. Stroke. 1997; 28:2139–2144.CrossrefMedlineGoogle Scholar
  • 61. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev. 2002:CD000197.Google Scholar
  • 62. Ma RH, Wang YJ, Zhao XQ, Wang CX, Yang ZH, Qu H. [The impact of stroke unit on early outcome of cerebral infarction patients]. Zhonghua Nei Ke Za Zhi. 2004; 43:183–185.MedlineGoogle Scholar
  • 63. Oppenheimer SM, Cechetto DF, Hachinski VC. Cerebrogenic cardiac arrhythmias: cerebral electrocardiographic influences and their role in sudden death. Arch Neurol. 1990; 47:513–519.CrossrefMedlineGoogle Scholar
  • 64. Adams HP, Adams RJ, Brott T, del Zoppo GJ, Furlan A, Goldstein LB, Grubb RL, Higashida R, Kidwell C, Kwiatkowski TG, Marler JR, Hademenos GJ. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke. 2003; 34:1056–1083.LinkGoogle Scholar
  • 65. LaMonte MP, Bahouth MN, Hu P, Pathan MY, Yarbrough KL, Gunawardane R, Crarey P, Page W. Telemedicine for acute stroke: triumphs and pitfalls. Stroke. 2003; 34:725–728.LinkGoogle Scholar
  • 66. Rymer MM, Thurtchley D, Summers D. Expanded modes of tissue plasminogen activator delivery in a comprehensive stroke center increases regional acute stroke interventions. Stroke. 2003; 34:e58–e60.LinkGoogle Scholar
  • 67. Audebert HJ, Kukla C, Clarmann von Claranau S, Kuhn J, Vatankhah B, Schenkel J, Ickenstein GW, Haberl RL, Horn M. Telemedicine for safe and extended use of thrombolysis in stroke: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria. Stroke. 2005; 36:287–291.LinkGoogle Scholar
  • 68. Adams HP, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Stroke. 2007; 38:1655–1711.LinkGoogle Scholar
  • 69. Latchaw RE, Alberts MJ, Lev MH, Connors JJ, Harbaugh RE, Higashida RT, Hobson R, Kidwell CS, Koroshetz WJ, Mathews V, Villablanca P, Warach S, Walters B. Recommendations for imaging of acute ischemic stroke: a scientific statement from the American Heart Association. Stroke. 2009; 40:3646–3678.LinkGoogle Scholar
  • 70. Hill MD, Buchan AM. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. CMAJ. 2005; 172:1307.CrossrefMedlineGoogle Scholar
  • 71. Graham GD. Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data. Stroke. 2003; 34:2847–2850.LinkGoogle Scholar
  • 72. Heuschmann PU, Berger K, Misselwitz B, Hermanek P, Leffmann C, Adelmann M, Buecker-Nott HJ, Rother J, Neundoerfer B, Kolominsky-Rabas PL. Frequency of thrombolytic therapy in patients with acute ischemic stroke and the risk of in-hospital mortality: the German Stroke Registers Study Group. Stroke. 2003; 34:1106–1113.LinkGoogle Scholar
  • 73. Kwiatkowski TG, Libman RB, Frankel M, Tilley BC, Morgenstern LB, Lu M, Broderick JP, Lewandowski CA, Marler JR, Levine SR, Brott T. Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group. N Engl J Med. 1999; 340:1781–1787.CrossrefMedlineGoogle Scholar
  • 74. Ingall TJ, O'Fallon WM, Asplund K, Goldfrank LR, Hertzberg VS, Louis TA, Christianson TJ. Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial. Stroke. 2004; 35:2418–2424.LinkGoogle Scholar
  • 75. Wardlaw JM, Zoppo G, Yamaguchi T, Berge E. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2003:CD000213.Google Scholar
  • 76. Marler JR, Tilley BC, Lu M, Brott TG, Lyden PC, Grotta JC, Broderick JP, Levine SR, Frankel MP, Horowitz SH, Haley EC, Lewandowski CA, Kwiatkowski TP. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology. 2000; 55:1649–1655.CrossrefMedlineGoogle Scholar
  • 77. Kwiatkowski T, Libman R, Tilley BC, Lewandowski C, Grotta JC, Lyden P, Levine SR, Brott T. The impact of imbalances in baseline stroke severity on outcome in the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study. Ann Emerg Med. 2005; 45:377–384.CrossrefMedlineGoogle Scholar
  • 78. Del Zoppo GJ, Saver JL, Jauch EC, Adams HP. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009; 40:2945–2948.LinkGoogle Scholar
  • 79. Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, Sila CA. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA. 2000; 283:1151–1158.CrossrefMedlineGoogle Scholar
  • 80. Bravata DM, Kim N, Concato J, Krumholz HM, Brass LM. Thrombolysis for acute stroke in routine clinical practice. Arch Intern Med. 2002; 162:1994–2001.CrossrefMedlineGoogle Scholar
  • 81. Lopez-Yunez AM, Bruno A, Williams LS, Yilmaz E, Zurru C, Biller J. Protocol violations in community-based rTPA stroke treatment are associated with symptomatic intracerebral hemorrhage. Stroke. 2001; 32:12–16.LinkGoogle Scholar
  • 82. Lattimore SU, Chalela J, Davis L, DeGraba T, Ezzeddine M, Haymore J, Nyquist P, Baird AE, Hallenbeck J, Warach S. Impact of establishing a primary stroke center at a community hospital on the use of thrombolytic therapy: the NINDS Suburban Hospital Stroke Center experience. Stroke. 2003; 34:e55–e57.LinkGoogle Scholar
  • 83. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999; 282:2003–2011.CrossrefMedlineGoogle Scholar
  • 84. Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke. 2004; 35:904–911.LinkGoogle Scholar
  • 85. Ogawa A, Mori E, Minematsu K, Taki W, Takahashi A, Nemoto S, Miyamoto S, Sasaki M, Inoue T. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan. Stroke. 2007; 38:2633–2639.LinkGoogle Scholar
  • 86. del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. Stroke. 1998; 29:4–11.LinkGoogle Scholar
  • 87. Saver JL. Intra-arterial fibrinolysis for acute ischemic stroke: the message of melt. Stroke. 2007; 38:2627–2628.LinkGoogle Scholar
  • 88. Alvarez-Sabin J, Molina CA, Montaner J, Arenillas JF, Huertas R, Ribo M, Codina A, Quintana M. Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator–treated patients. Stroke. 2003; 34:1235–1241.LinkGoogle Scholar
  • 89. Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, Colman PG, Chambers BR, Davis SM. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003; 34:2208–2214.LinkGoogle Scholar
  • 90. Parsons MW, Barber PA, Desmond PM, Baird TA, Darby DG, Byrnes G, Tress BM, Davis SM. Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study. Ann Neurol. 2002; 52:20–28.CrossrefMedlineGoogle Scholar
  • 91. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001; 32:2426–2432.LinkGoogle Scholar
  • 92. Bhalla A, Sankaralingam S, Tilling K, Swaminathan R, Wolfe C, Rudd A. Effect of acute glycaemic index on clinical outcome after acute stroke. Cerebrovasc Dis. 2002; 13:95–101.CrossrefMedlineGoogle Scholar
  • 93. Bruno A, Biller J, Adams HP, Clarke WR, Woolson RF, Williams LS, Hansen MD. Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Neurology. 1999; 52:280–284.CrossrefMedlineGoogle Scholar
  • 94. Celik Y, Utku U, Asil T, Balci K. Factors affecting haemorrhagic transformation in middle cerebral artery infarctions. J Clin Neurosci. 2004; 11:656–658.CrossrefMedlineGoogle Scholar
  • 95. Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, Fineberg SE, Tierney WR. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology. 2002; 59:67–71.CrossrefMedlineGoogle Scholar
  • 96. Scott JF, Robinson GM, French JM, O'Connell JE, Alberti KG, Gray CS. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia: the Glucose Insulin in Stroke Trial (GIST). Stroke. 1999; 30:793–799.LinkGoogle Scholar
  • 97. Gray CS, Hildreth AJ, Alberti GK, O'Connell JE. Poststroke hyperglycemia: natural history and immediate management. Stroke. 2004; 35:122–126.LinkGoogle Scholar
  • 98. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001; 345:1359–1367.CrossrefMedlineGoogle Scholar
  • 99. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009; 360:1283–1297.CrossrefMedlineGoogle Scholar
  • 100. Hajat C, Hajat S, Sharma P. Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke. 2000; 31:410–414.LinkGoogle Scholar
  • 101. Azzimondi G, Bassein L, Nonino F, Fiorani L, Vignatelli L, Re G, D'Alessandro R. Fever in acute stroke worsens prognosis. A prospective study. Stroke. 1995; 26:2040–2043.LinkGoogle Scholar
  • 102. Reith J, Jorgensen HS, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, Olsen TS. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet. 1996; 347:422–425.CrossrefMedlineGoogle Scholar
  • 103. Boysen G, Christensen H. Stroke severity determines body temperature in acute stroke. Stroke. 2001; 32:413–417.LinkGoogle Scholar
  • 104. Adams HJ, Brott T, Crowell R, Furlan A, Gomez C, Grotta J, Helgason C, Marler J, Woolson R, Zivin J, Feinberg W, Mayberg M. Guidelines for the management of patients with acute ischemic stroke: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 1994; 25:1901–1914.LinkGoogle Scholar