JOSEPH P. BRODERICK, M.D., university of Cincinnati clinical Center, Cincinnati, Ohio

Am Fam Physician. 1998 Jan 1;57(1):73-80.

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This short article exemplifies the juniorg8.com 1997–98 annual Clinical emphasis on prevention and also management that cardiovascular disease.


Successful treatment of patients with ischemic stroke relies on the ability to treat in ~ three hours of onset, because tissue plasminogen activator has actually not yet been proved effective beyond this time frame. The two significant causes of delay in treatment are failure, on the part of the patience or family, to identify stroke symptoms and also failure to access the medical device most efficiently—by phone call 911. Hospital hit teams can shorten the time in between patient come at the emergency department and also treatment. Guidelines because that the evaluation and also treatment of potential stroke patients space presented, together with goal times because that arrival-to-treatment intervals.


In June that 1996, the U.S. Food and Drug management approved the use of intravenous recombinant tissue plasminogen activator (t-PA) for usage in accordingly selected patients through ischemic stroke if administered within three hours from onset of symptoms. Approval was based on two researches funded by the national Institute that Neurological Diseases and Stroke (NINDS).1 this studies represent the first demonstrated reliable treatment because that ischemic stroke.

Animal models that thrombolytic treatment for acute ischemic stroke show that thrombolytic therapy need to be administered in ~ the first hour after ~ stroke onset to provide the biggest chance for success.2 evidence for efficiency of thrombolysis beyond three hours after beginning of ischemia in pets is minimal.2–5 with regard to human being studies, the 2 NINDS studies1 the t-PA space the just ones that suggest a convincing advantage with t-PA, yet only if t-PA is given within three hrs of start to appropriately selected patients. Time to treatment is the most vital determinant of success in treating ischemic stroke through t-PA.

The European participating Acute Stroke examine of t-PA (ECASS)6 showed no benefit and an enhanced risk of bleeding complications with t-PA. It has been said that the reason for this disappointing result rests in the choice of patients in this trial. Patients were treated in a six-hour quite than a three-hour window and may have had much more extensive ischemic damages on the baseline computed tomographic (CT) scan than is now thought to it is in acceptable.


Because therapy within three hrs of onset is crucial, effective treatment of stroke patients in the general population is dependence on educating stroke patient to come at a hospital in ~ this time frame. The significant components of the procedure of evaluation and also treatment of the stroke patience include: recognition of punch by patient or family, contact with and access to medical care, acknowledgment of a “possible stroke” by the 911 dispatcher, identification of stroke together the greatest level that emergency by the regional Emergency Medical system (EMS), fast transport that the stroke patient to the emergency department, testimonial of hit in the emergency department and initiation of suitable treatment.

Factors that have actually been presented to be linked with delay in treatment encompass calling the main physician rather of the emergency medical number, living alone, onset when asleep, start at house rather than at work and also a milder severity that stroke.7–9

In addition, stroke damage often impairs one of two people perception of a problem (parietal lobe) or the capability to communicate (temporal, frontal and parietal lobes).

However, the major delay in time to treatment is probably resulted in by the lack of acknowledgment of hit signs and also symptoms and also failure to make the ideal response. Just 58 percent of patients in a recent Gallup vote of persons at least 50 year of age recognized weak of an eight or leg together symptoms of stroke, and only 32 percent recognized difficulties with speaking as a warning authorize of hit (unpublished data). In a study conducted in better Cincinnati,10 only 37 percent of stroke patients and also their family members members knew the their symptoms were caused by a hit at the time of symptom onset. Of the 163 patient in the study, 62 (38 percent) go not recognize a single warning symptom that stroke, and another 45 (28 percent) might identify just one symptom.

The 2nd most important cause of delay in evaluation of stroke patient is the contact made to accessibility the clinical system.7 In 3 U.S. Communities, potential stroke patients who very first called their main physician landed on the emergency department in ~ a typical time the 379 minutes, compared with a median time that 155 minutes for patients who referred to as 911, the emergency access number.7 It need to be provided that in many communities, punch is not taken into consideration by the EMS to be a level-one emergency, equivalent to trauma and also myocardial infarction. Stroke, or “brain attack,” should be treated with the exact same urgency as trauma and also myocardial infarction. Family physicians should support efforts to label stroke “the highest possible level that emergency” because that their neighborhood EMS.

Family physicians need to educate your patients about the warning signs and symptoms of stroke and also instruct them to contact 911 if a hit is suspected. This advice is particularly important for patients at greater risk because that stroke, such together persons with a ahead transient ischemic assault or little stroke.


Only 3.6 percent of more than 17,000 potential punch patients were eligible for treatment in the two NINDS randomized researches on t-PA because that acute stroke.11 In contrast, about 33 percent of patients v an acute myocardial infarction in the national Registry the Myocardial Infarction II12 are right now treated v a thrombolytic agent (26 percent) or alternative reperfusion techniques (7 percent) such as recanalization by invasive cardiac catheterization or angioplasty.

It is most likely that enhancing public awareness and also expediting prehospital treatment will rise the variety of stroke patient eligible because that thrombolytic treatment. Current differences in the prehospital technique to stroke and myocardial infarction are contrasted in Table 1. The significant difference at present is the perception amongst physicians and also hospitals the myocardial infarction is an emergency, if stroke is not. For example, in the NINDS studies, the many ambitious stroke examine thus far in terms of time to treatment, the goal for time from come at the emergency room to treatment was 55 minutes. In contrast, existing guidelines for myocardial infarction talk around a time from come to therapy of 30 minutes.13


TABLE 1Logistic Differences in between Treatment the Stroke and Treatment that Myocardial InfarctionFactorStrokeMyocardial infarction

Public awareness

Poor public knowledge of warning signs

Excellent public awareness that warning signs

EMS designation

Inconsistent EMS designation as highest possible level the emergency

EMS designation as highest possible level of emergency

Presenting symptoms

Multiple possible presenting symptoms

A few presenting symptoms

Complicating clinical features

Impairment the communication and also perception

No impairment

Pain together a clinical clue

No pain

Often prominent pain and shortness that breath

Treatment window

Treatment window of three hours

Treatment home window of at the very least six hours

Treatment goal

Recommended time from emergency department come to treatment: 60 minutes (new goal—rarely reached at present)

Recommended time native emergency department come to treatment: 30 minute (goal frequently attained)


TABLE 1Logistic Differences in between Treatment of Stroke and also Treatment of Myocardial InfarctionFactorStrokeMyocardial infarction

Public awareness

Poor public knowledge of warning signs

Excellent public awareness that warning signs

EMS designation

Inconsistent EMS designation as greatest level that emergency

EMS designation as highest possible level that emergency

Presenting symptoms

Multiple feasible presenting symptoms

A few presenting symptoms

Complicating clinical features

Impairment that communication and perception

No impairment

Pain as a clinical clue

No pain

Often significant pain and shortness of breath

Treatment window

Treatment home window of three hours

Treatment window of at the very least six hours

Treatment goal

Recommended time indigenous emergency department arrival to treatment: 60 minute (new goal—rarely got to at present)

Recommended time from emergency department come to treatment: 30 minute (goal typically attained)


In Houston, the notification and presence of a designated “stroke team” shortened the moment to examination of a stroke patience by a doctor by 13 minutes and the time to CT scan by 63 minutes.14 This research illustrates the importance of stroke teams in the beforehand evaluation and also treatment of hit patients. The hatchet “stroke team” refers to an organized group of physicians, nurses and also allied health and wellness personnel committed to rapid treatment, with field of expertise in the evaluation and treatment of hit patients.

In December 1996, the NINDS-sponsored national Symposium on fast Identification and also Treatment of Acute Stroke15 recommended guidelines because that the evaluation and also treatment that potential stroke patients (Table 2). Two crucial times space a time from arrival to CT scan of 25 minutes and a time from arrival to therapy (with t-PA or as-yet potential agents) the 60 minutes, with a goal of 80 percent compliance. This times have to be viewed as ideal purposes for all hospitals treating patients with acute stroke.


TABLE 2Recommended Guidelines for Time between Arrival in the Emergency Department and also Evaluation and Treatment the Patients through Acute Ischemic StrokeTaskTime indigenous emergency department come to perfect of task

Evaluation by physician

10 minutes

“Stroke expertise” or “neurologic expertise” contacted (i.e., stroke team)

15 minutes

CT scan the the head

25 minutes

Interpretation that CT scan

45 minutes

Start the treatment

60 minutes

Monitored bed in unit

3 hours


Information from national Symposium on fast Identification and also Treatment the Acute Stroke, December 13, 1996. Washington, D.C.: nationwide Institute the Neurological Disorders and Stroke (NINDS), 1997.


TABLE 2Recommended Guidelines because that Time between Arrival in the Emergency Department and Evaluation and Treatment that Patients with Acute Ischemic StrokeTaskTime indigenous emergency department arrival to completion of task

Evaluation through physician

10 minutes

“Stroke expertise” or “neurologic expertise” contacted (i.e., punch team)

15 minutes

CT scan of the head

25 minutes

Interpretation of CT scan

45 minutes

Start the treatment

60 minutes

Monitored bed in unit

3 hours


Information from nationwide Symposium on quick Identification and Treatment that Acute Stroke, December 13, 1996. Washington, D.C.: national Institute that Neurological Disorders and Stroke (NINDS), 1997.


This conference also listed a encourage pathway for triage and evaluation of stroke patient in the emergency room (Figure 1). Triage is one means to emphasis resources. For example, stroke patients with a gentle or moderate and also stable neurologic deficit that appear more than six hours after symptom onset must be evaluate promptly however not with the very same urgency the is forced to treat a patient who arrives in ~ a an extremely early home window (e.g., less than three hrs after onset) v t-PA.


View/Print Figure

FIGURE 1.

Pathways for evaluation of stroke patients in the emergency department, consisting of decision making for thrombolysis. (CT = computed tomography; ED = emergency department)


FIGURE 1.

Pathways for evaluation of stroke patients in the emergency department, consisting of decision making because that thrombolysis. (CT = computed tomography; ED = emergency department)


Treatment of ischemic stroke patients with a thrombolytic agent calls for that a physician experienced in the care of stroke patient decide the a given patient has actually a far-ranging neurologic deficit as result of stroke and not to one more cause. This patient have to then satisfy all the inclusion and exclusion criteria for treatment with t-PA that were provided in the NINDS study or in the parcel insert because that t-PA in acute ischemic punch (Table 3). CT scan that the brain must not display acute hemorrhage or a large, already-developing cerebral infarction. Finally, treatment need to be administered in ~ three hrs of stroke onset.


TABLE 3Guidelines for usage of t-PA in Patients through Acute Ischemic Stroke*

Eligibility because that IV treatment v t-PA

Age 18 or older

Clinical diagnosis of ischemic stroke causing a measureable neurologic deficit

Time the symptom beginning well created to be much less than 180 minutes before treatment would begin

Patient selection: contraindications and also warnings

Evidence the intracranial hemorrhage on pretreatment CT†

Clinical presentation suggestive the subarachnoid hemorrhage, also with normal CT†

Active inner bleeding†

Known bleeding diathesis, including yet not minimal to:

• Platelet count much less than 100,000 per mm3 (100 × 109 every L)†

• Patient has actually received heparin within 48 hours and has an elevated aPTT (greater than top limit of regular for laboratory)†

• current use of dental anticoagulants (e.g., warfarin ) or recent use through an elevated prothrombin time higher than 15 seconds†‡

Within 3 months: any intracranial surgery, major head trauma or previous stroke†

On recurring measurements, systolic blood press is better than 185 mm Hg or diastolic blood pressure is greater than 110 mm Hg at the time treatment begins or patient needs aggressive treatment to reduce blood press to within these limits†

History that intracranial hemorrhage†

Known arteriovenous malformation or aneurysm†

Patient to be observed to have seizure at the very same time the beginning of hit symptoms to be observed§

History of gastrointestinal or urinary street hemorrhage within 21 days§

Recent arterial puncture at a noncompressible site§

Recent lumbar puncture§

Abnormal blood glucose level (400 mg per dL <22.2 mmol every L>)§

Only young or rapidly enhancing stroke symptoms§

Postmyocardial infarction pericarditis§


t-PA = organization plasminogen activator; IV = intravenous; CT = computed tomography; aPTT = set off partial thomboplastin time.


*—This protocol is based on research supported by the national Institute that Neurological Disorders and Stroke (NINDS): N01-NS-02382, N01-NS-02374, N01-NS-02377, N01-NS-02391, N01-NS-02379, N01-NS-02373, N01-NS-02378, N01-NS-02376, N01-NS-02380. Medical professionals should also refer come the manufacturer"s prescribing information for alteplase (Activase), Genentech Inc., south San Francisco, Calif.


‡—In patients without recent use of dental anticoagulants or heparin, treatment through t-PA have the right to be initiated before availability of coagulation research results yet should be stop if the prothrombin time is higher than 15 secs or the partial thromboplastin lasting time is elevated by neighborhood laboratory standards.


TABLE 3Guidelines for use of t-PA in Patients with Acute Ischemic Stroke*

Eligibility for IV treatment v t-PA

Age 18 or older

Clinical diagnosis of ischemic stroke bring about a measureable neurologic deficit

Time the symptom beginning well created to be less than 180 minutes prior to treatment would begin

Patient selection: contraindications and also warnings

Evidence that intracranial hemorrhage ~ above pretreatment CT†

Clinical presentation suggestive of subarachnoid hemorrhage, even with typical CT†

Active internal bleeding†

Known bleeding diathesis, including however not limited to:

• Platelet count much less than 100,000 per mm3 (100 × 109 per L)†

• Patient has actually received heparin in ~ 48 hours and also has an elevated aPTT (greater than upper limit of regular for laboratory)†

• existing use of oral anticoagulants (e.g., warfarin ) or recent use through an elevated prothrombin time greater than 15 seconds†‡

Within 3 months: any type of intracranial surgery, severe head trauma or vault stroke†

On repetitive measurements, systolic blood push is better than 185 mm Hg or diastolic blood press is higher than 110 mm Hg at the time treatment starts or patient requires aggressive therapy to mitigate blood press to within these limits†

History of intracranial hemorrhage†

Known arteriovenous malformation or aneurysm†

Patient to be observed to have seizure at the exact same time the beginning of hit symptoms was observed§

History of cradle or urinary tract hemorrhage within 21 days§

Recent arterial puncture at a noncompressible site§

Recent lumbar puncture§

Abnormal blood glucose level (400 mg per dL <22.2 mmol per L>)§

Only minor or rapidly enhancing stroke symptoms§

Postmyocardial infarction pericarditis§


t-PA = organization plasminogen activator; IV = intravenous; CT = computed tomography; aPTT = set off partial thomboplastin time.


*—This protocol is based upon research sustained by the national Institute the Neurological Disorders and Stroke (NINDS): N01-NS-02382, N01-NS-02374, N01-NS-02377, N01-NS-02391, N01-NS-02379, N01-NS-02373, N01-NS-02378, N01-NS-02376, N01-NS-02380. Medical professionals should also refer to the manufacturer"s prescribing information for alteplase (Activase), Genentech Inc., southern San Francisco, Calif.


‡—In patient without current use of oral anticoagulants or heparin, treatment with t-PA have the right to be initiated before access of coagulation research results yet should be stop if the prothrombin time is greater than 15 secs or the partial thromboplastin lasting time is elevated by neighborhood laboratory standards.


Patients who are treated through t-PA need to be cared because that in an experienced intensive treatment unit or a monitored unit and also should have access to neurosurgical expertise if a hemorrhagic complication occurs. No heparin or anti-platelet agents should be administered until 24 hours after initiation the t-PA therapy (because of the increased risk of bleeding) and a 24-hour safety CT has ruled out intracranial hemorrhage. Arterial blood pressure must be retained just below a systolic press of 185 mm Hg and a diastolic push of 105 mm Hg throughout the an initial 24 hours to minimization the danger of intracerebral hemorrhage. Ideal antihypertensive agents include small doses of intravenous medicines such as labetalol (Normodyne, Trandate). A said plan that baseline activities studies and physician orders for the an initial 24 hours of therapy after ischemic punch is displayed in Table 4.


TABLE 4Physician Orders because that the first 24 Hours complying with Treatment of Stroke through t-PA

Continue emergency room orders because that t-PA infusion and monitoring crucial signs and also neurologic checks till two hrs after begin of t-PA infusion.

Check vital signs (blood pressure, pulse, respiration) and also make neurologic checks (level of consciousness, arm/leg weakness) every 30 minutes because that 6 hours, then every 60 minutes for 16 hours after beginning t-PA.

Bleeding precautions: inspect puncture sites because that bleeding or hematomas. Apply digital push or push dressing to active compressible bleeding sites. Evaluate urine, stool, emesis or other secretions for blood. Perform occult blood trial and error (guaiac) if there is evidence of bleeding.

Call stroke-team medical professional (pager #_______) automatically to seek proof of bleeding, neurologic destruction or an important signs exterior the adhering to parameters:

Systolic blood pressure better than 185 mm Hg or systolic blood pressure much less than 110 mm Hg

Diastolic blood pressure greater than 105 mm Hg or diastolic blood pressure less than 60 mm Hg

Pulse much less than 50

Respirations greater than 24

Decline in neurologic condition or worsening of stroke signs

0.45 typical saline or common saline IV, to save vein open, in ~ 50 mL every hour because that 24 hours

Oxygen at 2 L per minute by sleep cannula

Continuous cardiac monitoring

Intake and output

Diet: nothing by mouth other than medications for 24 hours

Bed rest

Medications: acetaminophen, 650 mg orally because that pain every 4 to 6 hours, together needed

Patient"s formerly prescribed regular medications, if appropriate.

No heparin, warfarin or aspirin for 24 hours. ~ 24 hours: CT come exclude intracranial hemorrhage before any kind of anticoagulants room administered.


note: these orders represent only one potential method to the monitoring of patients v ischemic stroke. Physicians and institutions must identify treatment ideal for every patient.


Information from national Symposium on quick Identification and also Treatment that Acute Stroke, December 13, 1996. Washington, D.C.: national Institute of Neurological Disorders and also Stroke (NINDS), 1997.


TABLE 4Physician Orders because that the very first 24 Hours complying with Treatment the Stroke with t-PA

Continue emergency department orders because that t-PA infusion and monitoring vital signs and also neurologic checks until two hours after begin of t-PA infusion.

Check critical signs (blood pressure, pulse, respiration) and also make neurologic checks (level that consciousness, arm/leg weakness) every 30 minutes because that 6 hours, climate every 60 minutes because that 16 hours after beginning t-PA.

Bleeding precautions: examine puncture sites for bleeding or hematomas. Apply digital press or push dressing to energetic compressible bleeding sites. Advice urine, stool, emesis or other secretions because that blood. Execute occult blood testing (guaiac) if there is evidence of bleeding.

Call stroke-team medical professional (pager #_______) immediately to seek evidence of bleeding, neurologic degradation or vital signs outside the following parameters:

Systolic blood pressure better than 185 mm Hg or systolic blood pressure less than 110 mm Hg

Diastolic blood pressure greater than 105 mm Hg or diastolic blood pressure much less than 60 mm Hg

Pulse less than 50

Respirations higher than 24

Decline in neurologic standing or worsening of punch signs

0.45 typical saline or normal saline IV, to save vein open, in ~ 50 mL per hour for 24 hours

Oxygen in ~ 2 L per minute by nasal cannula

Continuous cardiac monitoring

Intake and output

Diet: nothing by mouth other than medications because that 24 hours

Bed rest

Medications: acetaminophen, 650 mg orally for pain every 4 come 6 hours, as needed

Patient"s formerly prescribed constant medications, if appropriate.

No heparin, warfarin or aspirin because that 24 hours. ~ 24 hours: CT come exclude intracranial hemorrhage before any anticoagulants are administered.


note: these orders represent just one potential method to the monitoring of patients through ischemic stroke. Physicians and also institutions must recognize treatment ideal for each patient.


Information from nationwide Symposium on fast Identification and Treatment the Acute Stroke, December 13, 1996. Washington, D.C.: nationwide Institute that Neurological Disorders and also Stroke (NINDS), 1997.


Each hospital should develop a treatment setup for acute hit that reflects its abilities and limitations. Hospitals without brain imaging capacity should never act patients v a thrombolytic agent. Hospitals v easy-access brain imaging, radiologic expertise and an experienced medical professional should have the ability to treat suitable patients with t-PA. However, if an active intensive treatment unit or neurosurgical field of expertise is lacking, patient who room treated v t-PA have to be moved urgently after treatment has begun to an additional hospital wherein these capabilities are present.

Teleradiography will probably play an progressively important function in the treatment of stroke patients at countryside and little outlying hospitals. In the future, treatment of ischemic punch patients through neuroprotective agents (currently in development) that are safe and do not need a CT scan before treatment can theoretically be done at any hospital, possibly also in the field by paramedics. However, this opportunity depends on outcomes of ongoing and also future randomized trials of together agents.


Patients through an ischemic stroke that are accordingly selected and also treated with t-PA in ~ three hours from onset are at the very least 33 percent much more likely to have actually a regular or near-normal neurologic examination score (the national Institutes of health punch scale) or common or near-normal Barthel index score (a measure up of the activities of daily living) at three months ~ treatment. In terms of absolute benefit, one patient, who otherwise would not, returns to regular or close to normal at three months for every six to nine patients who obtain t-PA fairly than placebo.16 However, t-PA is no a cure because that ischemic stroke: 50 percent that patients that were treated with t-PA in the 2 NINDS studies had actually mild or greater special needs as measure up by a Barthel index score of much less than 95 at 3 months (100 is normal and also 0 is the worst score).1

The significant risk that t-PA is symptomatic intracerebral hemorrhage, which emerged in 6.4 percent of patients who received t-PA, as contrasted with 0.6 percent of patient who obtained placebo.1 These numbers represent an absolute difference in the threat of symptomatic intracerebral hemorrhage the 6 percent. Seventy-five percent the the patients v a symptomatic intracerebral hemorrhage were dead at three months. Yet regardless of the threat of intracerebral hemorrhage, the mortality at three months to be insignificantly lower in patients treated with t-PA (17 percent) 보다 in placebo-treated patients (21 percent). 2 reasons might underlie the comparable mortality the t-PA–treated and also placebo-treated patients regardless of a greater risk the symptomatic intracerebral hemorrhage amongst patients treated v t-PA. First, most patients who had actually an intra-cerebral hemorrhage had large strokes and were likely to execute poorly regardless of the visibility of intracerebral hemorrhage in ~ the damaged brain. Secondly, t-PA most likely makes part “big” strokes lot smaller. The patient with small strokes are less likely to die.

Patients treated through t-PA who have very huge strokes (very severe neurologic deficits, definition an NIH stroke range score better than 20) and who already have evidence of a huge acute ischemic punch on baseline CT have actually an raised risk that symptomatic intra-cerebral hemorrhage.17 However, patients in these 2 subgroups who receive t-PA are much more likely to go back to normal 보다 patients who space treated with placebo. The decision to use t-PA in these patients must be made just after frank discussion of the potential risks and also benefits through both the patient and also the family.

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