Manejo AVC I

ICSI
I NSTITUTE FOR C LINICAL

S YSTEMS I MPROVEMENT
Health Care Guideline
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ICS I
Health Care Guideline:
Diagnosis and Initial Treatment of Ischemic Stroke
I NSTITUTE FOR C LINICAL
S Y S T E M S I M P ROV E M E N T Screening (Ambulatory) Algorithm A = Annotation
Fifth Edition 1
February 2006
1
Initial contact with patient
with complaint of Initial contact with patient with
neurological symptoms complaint of neurological symptoms
Work Group Leader A
David Anderson, MD Primary care physician
Emergency Medical Service
Neurology, Hennepin Faculty 2 RN - phone referral
Associates Immediate screening for Non-medical evaluation (triage, etc.)
ischemic stroke
Work Group Members
Emergency Medicine A
Kathleen Neacy, MD
HealthPartners Medical Group 3
Latha Stead, MD 4
Mayo Clinic Symptoms consistent Refer to Emergency Department

with new ischemic no (ED) or physician's office as
Family Medicine stroke, appropriate for other conditions
Robert Koshnick, MD TIA or unsure? A
Dakota Clinic
James Lee, MD, MPH yes
RiverWay Clinics
5
Internal Medicine
Joseph McRaith, MD no Symptoms present yes
Aspen Medical Group now?
Neurology
A
Bret Haake, MD
MeritCare
6
Alejandro Robinstein, MD 9
8
Mayo Clinic Possible ischemic
Possible TIA -
Kamakshi Lakshminarayan, MD yes Call 911 and transport to ED yes stroke - symptoms
symptoms within
University of Minnesota 2 hrs? See ED (Treatment) algorithm onset within 24 hours?
Physicians
A
Nursing no A
Gail Wallace, RN, BSN, CCRN no
St. Marys/Duluth Clinic Health
10
System 11 7
Pharmacy TIA symptoms Transport to ED by 911 or

Ischemic stroke symptoms
> 2 hrs ago, but
yes other means
Jeff Larson, PharmD See ED (Treatment)
present for > 24 hrs
Allina Medical Clinic within last 48 hours? Symptoms mild and stable
algorithm
A A
Measurement/ A
Implementation Advisor no
Teresa Hunteman, RRT, CPHQ yes
ICSI 12 14
Evidence Analyst 15
Brent Metfessel, MD, MPH TIA symptoms
> 48 hrs ago, but
yes High risk for no Clinic appointment
ICSI within last 2 weeks? immediate future within 72 hrs
events? A
Facilitator
Sherri Huber, MT (ASCP) A A
ICSI no
These clinical guidelines are 13
designed to assist clinicians Clinic appointment within 1

by providing an analytical week of symptoms occurring
framework for the evaluation > 2 weeks ago
and treatment of patients, A
and are not intended either to
replace a clinician's judgment
or to establish a protocol for
all patients with a particular
condition. A guideline will
rarely establish the only www.icsi.org
approach to a problem.
Copyright 2006 by Institute for Clinical Systems Improvement 1
Fifth Edition/February 2006
ED Treatment Algorithm
17
Enters ED via:
Primary care physician referral
Triage
Walk-in
EMS
18
19
Neurological deficit no ED evaluation (per usual ED

present at time of triage), out of guideline
evaluation?
yes
20 21
22
Intra-arterial See Ischemic Stroke ED
Symptom onset allows for thrombolytic
evaluation and treatment no no Management (not a
candidate? thrombolysis candidate)
within 180 minutes (with (option available?)
thrombolysis IV)? algorithm, box 35
A A
yes yes
23 24
See Stroke Code
algorithm Out of guideline
A
23
The goal of the stroke code is to rapidly evaluate and
administer tPA in appropriately screened candidates.
The onset of symptoms to treatment can be up to 180
minutes, but the National Institutes of Health (NIH)
recommendation of "door to drug" is within 60
minutes.
A = Annotation
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Institute for Clinical Systems Improvement 2
Stroke Code Algorithm

25
Hospitals should consider developing
and implementing critical pathways,
25
standing orders and a stroke code
Stroke code process to accomplish this rapid
A evaluation and treatment.
26 27
Evaluation
(should occur concurrently with intervention) Intervention
Review history and review history and tPA (should occur concurrently with evaluation)
treatment indications and contraindications Educate patient/family
and baseline NIHSS Treat blood pressure (BP) if greater than
Perform exam with neuro checks and vital 185 systolic or 110 diastolic
signs every 15 minutes Initiate two IV lines
Record weight (estimate if needed) Start IV fluids
Draw blood for lab tests Treat hyperthermia
Perform EKG Treat hypo or hyperglycemia
Perform CT head without contrast Treat hypoxia
Other cardiac assessment as appropriate Treat hypotension
(telemetry)
A A
28
Patient meets criteria for

yes tPA, has no no
contraindications and
symptom onset still less
than 3 hours? 30
Document reason
A
29
31
Initiate tPA Initiate aspirin unless
A contraindicated (see
Annotation discussion)
A
32
Post-ED medical management 33
(post-thrombolysis) Post-ED medical management
Admit to ICU or acute stroke (not a thrombolysis candidate)
care unit/cardiac monitoring Admit to ICU or acute stroke
Perform vital signs with neuro care unit/cardiac monitoring
checks Perform vital signs with neuro
Treat BP if greater than 180 systolic checks
or 105 diastolic Treat BP if greater than 220 systolic
Initiate bleeding precautions or 120 diastolic or mean arterial
Monitor for CNS hemorrhage pressure (MAP) greater than 130
Initiate anti-thrombotic therapy Continue anti-thrombotic
24 hours after tPA therapy
A A
34
Other post-ED medical management (first 24-48 hours)

Continue to treat hyperthermia or hyperglycemia
Continue IV fluids
Inititate deep vein thrombosis (DVT) prophylaxis
Perform swallow evaluation
Initiate early rehabilitation therapy post-ED medical
management (first 24-48 hours)
Perform nutritional status assessment A = Annotation
A
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Ischemic Stroke ED Management (not a thrombolysis candidate)

Algorithm
35
A = Annotation
Ischemic stroke ED (Emergency
Department) management (not a
thrombolysis candidate)
36 37
Evaluation (should occur concurrently Intervention (should occur concurrently
with intervention) with evaluation)
Review history Educate patient/family
Perform neurologic examination Treat high BP only if ischemic stroke and
(baseline NIHSS) BP greater than 220 systolic or 120 diastolic
Perform cardiac monitoring/oximetry or MAP greater than 130 or concurrent
Perform neuro checks (not NIHSS), illness requiring treatment
every 15 minutes x 1 hour, re-evaluate (see Annotation #33)
acuity for future neurologic check Start IV fluids
frequency Treat hyperthermia
Draw blood for lab tests Treat hypo or hyperglycemia
Perform EKG Treat hypotension
Perform CT head without contrast Administer aspirin 160-325 mg (or other
Other cardiac assessment as anti-thrombotic) following CT evidence
appropriate (telemetry) of no hemorrhage
A A
38
yes Does the patient no

require hospital
admission?
A
39 40
Return to box 33, Post-ED Initiate appropriate

medical management (not a evaluation and treatment as
thrombolysis candidate) outpatient, out of guideline
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Table of Contents
Algorithms and Annotations ................................................................................................................1-36
Algorithm (Screening [Ambulatory]) ...................................................................................................1
Algorithm (ED Treatment)....................................................................................................................2
Algorithm (Stroke Code) ......................................................................................................................3
Algorithm (Ischemic Stroke ED Management [not a thrombolysis candidate]) ..................................4
Foreword
Scope and Target Population ..........................................................................................................6
Clinical Highlights and Recommendations ....................................................................................6
Priority Aims .. 6-7
Related ICSI Scientic Documents ................................................................................................7
Brief Description of Evidence Grading ..........................................................................................8
Disclosure of Potential Conict of Interest ....................................................................................8
Annotations ........... 9-35
Annotations (Screening [Ambulatory]) ..........................................................................................9-14
Annotations (ED Treatment) ..........................................................................................................14-18
Annotations (Stroke Code) .............................................................................................................19-33
Annotations (Ischemic Stroke ED Management [not a Thrombolysis Candidate]) .......................34-35
Appendices............ 36
Appendix A Glossary of Abbreviations .......................................................................................36
Supporting Evidence ..............................................................................................................................37-59
Evidence Grading System .....................................................................................................................38-39
References ............. 40-46
Conclusion Grading Worksheets ...........................................................................................................47-59
Conclusion Grading Worksheet A Annotation #27 (Hyperthermia)............................................47-50
Conclusion Grading Worksheet B Annotation #27 (Hyperglycemia) .........................................51-55
Conclusion Grading Worksheet C Annotation #31 (Heparin) .....................................................56-59
Support for Implementation ................................................................................................................60-65
Priority Aims and Suggested Measures ................................................................................................61-62
Key Implementation Recommendations ...............................................................................................63-64
Knowledge Products and Resources .....................................................................................................64
Other Resources Available ....................................................................................................................65
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Foreword
Scope and Target Population
Patients age 18 years or older who present with symptoms of recent neurologic dysfunction suggestive of
brain ischemia. The guideline focuses on management issues in the rst 48 hours.
Clinical Highlights and Recommendations

Patients who present in time to be candidates for treatment with tPA should be evaluated by a physician
within 10 minutes, undergo a CT scan within 25 minutes of arrival in the ED, and have CT interpreted
within 20 minutes of test completion. (Annotations #20, 25)
Intravenous tissue plasminogen activator, (tPA) if given, should be administered within 3 hours of stroke
onset and less than 60 minutes of arrival at the ED. (Annotations #20, 21, 23, 25, 26)
Patients presenting with stroke onset who are not candidates for intravenous tPA should promptly be
given aspirin, after exclusion of hemorrhage on CT scan. (Annotation #31)
Education regarding early stroke symptoms, risk factors, diagnostic procedures, and treatment options
should be offered to the patient and family. This should be documented in the patient chart. (Annota-
tion #27)
Medical management for prevention of complications within the initial 24-48 hours of diagnosis and
initial treatment of ischemic stroke include: (Annotation #34)
- continue appropriate blood pressure management
- continue to treat hyperthermia;
- continue to treat hypo or hyperglycemia;
- continue IV uids;
- initiate deep vein thrombosis prophylaxis;
- perform swallow evaluation;
- initiate early rehabilitation;
- perform nutritional status assessment.
Priority Aims and Suggested Measures

1. Increase the percentage of patients presenting within 3 hours of stroke onset who are evaluated within
10 minutes of arriving in the ED.
2. Increase the percentage of patients receiving appropriate thrombolytic and antithrombotic therapy for
ischemic stroke (use of tPA and aspirin).
3. Increase the percentage of non-tPA recipients who have hypertension appropriately managed in the rst
48 hours of hospitalization or until neurologically stable.
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Foreword Fifth Edition/February 2006
4. Increase the percentage of patients who receive appropriate medical management for prevention of
complications within the initial 24-48 hours of diagnosis:
continue to treat hypoglycemia and hyperglycemia
continue to treat hyperthermia
continue IV uids
continue to treat hypoxia
initiate deep vein thrombosis prophylaxis
perform swallow evaluation
initiate early rehabilitation (early mobilization)
perform nutritional status assessment
5. Improve patient and family education of patients with ischemic stroke in both the ED and the admitting
hospital unit.
Related ICSI Scientic Documents

Related Guidelines
Anticoagulation Therapy Supplement
Atrial Fibrillation
Diagnosis and Treatment of Chest Pain and Acute Coronary Syndrome (ACS)
Hypertension Diagnosis and Treatment
Venous Thromboembolism
Venous Thromboembolism Prophylaxis
Technology Assessment Reports
Tissue-type plasminogen activator for acute ischemic stroke (#28, 2005)
EEG Monitoring During Carotid Artery Surgery (#21, 1999)
Magnetic Resonance Angiography for Venous Sinus Thrombosis, Intracranial Atheroscherosis,
Intracranial Aneurysms, Carotid Artery Atherosclerosis, and Carotid or Vertebral Artery Dissection
(#29, 1996)
Order Sets
Admission for Ischemic Stroke, not tPA
Admission to CCU for Acute Coronary Syndrome
Patient and Family Guidelines
Hypertension Diagnosis and Treatment for Patients and Families
www.icsi.org
Foreword Fifth Edition/February 2006
Evidence Grading
Individual research reports are assigned a letter indicating the class of report based on design type: A, B,
C, D, M, R, X.
Key conclusions are assigned a conclusion grade: I, II, III, or Grade Not Assignable.
A full explanation of these designators is found in the Supporting Evidence section of the guideline.
Disclosure of Potential Conict of Interest

In the interest of full disclosure, ICSI has adopted the policy of revealing relationships work group members
have with companies that sell products or services that are relevant to this guideline topic. The reader should
not assume that these nancial interests will have an adverse impact on the content of the guideline, but they
are noted here to fully inform readers. Readers of the guideline may assume that only work group members
listed below have potential conicts of interest to disclose.
No work group members have potential conicts of interest to disclose.
ICSI's conflict of interest policy and procedures are available for review on ICSI's website at
http://www.icsi.org.
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Algorithm Annotations
Screening (Ambulatory) Algorithm Annotations
1. Initial Contact with Patient with Complaint of Neurological

Symptoms
This contact may occur with one of several medical system personnel, including primary care physicians,
other medical specialty physicians, emergency medical personnel, nursing staff in a clinic or urgent care
setting or even non-medical triage personnel. This does not refer to the ED evaluation. This contact may
be by phone or in person. Potential staff contacts should be educated in the importance of stroke symptom
recognition and the appropriate triage measures that should be taken.
2. Immediate Screening for Ischemic Stroke

This should include detail as to the location, severity, duration of symptoms and any aggravating or relieving
factors. Symptoms that are commonly associated with ischemic stroke or transient ischemic attack (TIA)
include:*
Sudden numbness or weakness of the face, arm or leg especially on one side of the body
Sudden mental confusion, trouble speaking or understanding
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden trouble seeing in one or both eyes
Sudden severe headache with no known cause
* List from American Stroke Association for public education.
Less common symptoms that may represent ischemic stroke or TIA include sudden onset vertigo, double
vision, nausea or vomiting, stupor or coma, difculty swallowing, a hoarse voice and/or shaking of a
limb.
Clinical diagnoses with neurologic symptoms that may imitate or supercially resemble ischemic stroke
or TIA include:
Migraine
Neurologic symptoms experienced with migraine tend to have a more gradual onset and slower
development. However, the two problems may be indistinguishable.
Seizures
Although seizures typically consist of a "positive" phenomenon (jerking of a limb) rather than loss
of neurologic function (weakness or paralysis of a limb), symptoms and signs during the ictus or
in the postictal state may be similar to ischemic stroke (e.g., confusion or speech arrest during the
ictus as in complex partial seizure, postictal confusion, postictal paralysis, and other sensory or
visual phenomenon.)
Syncope
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Algorithm Annotations Fifth Edition/February 2006
Transient global amnesia

This is characterized by a sudden onset antegrade and retrograde memory disturbance without other
focal neurologic symptoms. If the patient experiences symptoms of transient global amnesia it
would be inappropriate to assume the diagnosis without a complete neurologic exam.
Peripheral nerve disorders
Mononeuropathy and radiculopathy can be distinguished from ischemic stroke by the anatomic
distribution of the symptoms, and in the case of radiculopathy by the associated painful symptoms.
Bell's palsy, vestibular neuritis and extraocular muscle imbalance due to cranial neuropathy may
also imitate ischemic stroke and require a complete history and neurologic examination to accurately
differentiate from ischemic stroke.
Intracranial hemorrhage
Other intracranial masses, e.g., tumor, abscess (often differentiated by CT)
The mode of onset and early course tend to be more gradual in development.
Neuroses
Neuroses such as anxiety or panic disorder may need to be considered in some cases.
Metabolic disorders
Hypoglycemia is the most common metabolic disorder producing neurologic symptoms that imitate
stroke. A patient with known diabetes or liver disease should be screened for hypoglycemia.
This discussion is not meant to represent a detailed guide to discerning between ischemic stroke and other
diagnoses. If there is any uncertainty as to symptom causation, the evaluation should proceed as though
ischemic stroke or TIA are conrmed so as not to delay appropriate emergency treatment if needed.
4. Refer to Emergency Department (ED) or Physician's Ofce as

Appropriate for Other Conditions
Some of the diagnoses outlined in Annotation #2, "Immedidate Screening for Ischemic Stroke" may warrant
ED evaluation because of the urgency of the problem itself or the inability of the contact person to distinguish
the other condition from ischemic stroke. In these uncertain cases, the contact person should continue on
to box #5 in the Screening (Ambulatory) Algorithm.
5. Symptoms Present Now?

Refers to ongoing symptoms suggestive of cerebral ischemia. If symptoms have resolved and were present
for less than 24 hours, this is clinically dened as a TIA.
6. Possible Ischemic Stroke Symptoms Onset Within 24 Hours?

Key Point:
The onset of symptoms should be dened as the last time the patient was
known to be normal or at previous pre-stroke baseline.
If the symptoms resolve completely and then recur, for the purposes of determining whether thrombolysis
can be considered for stroke, the time of onset would be the last time the patient was normal (just prior to
the onset of the second set of symptoms.) Patients may be unable to give this information if they have an
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aphasia or mental confusion. Family members or other witnesses may need to give this information. If the
patient was sleeping and awoke with the problem, the time of onset would be the moment the patient was
last known to be normal just before falling asleep.
7. Ischemic Stroke Symptoms Present for > 24 Hours/Symptoms Mild

and Stable
Patients with stable mild decits present longer than 24 hours may be transported to the ED for evaluation
and treatment by means other than 911. As a rule, they should be admitted to the hospital to assure thorough
and expeditious evaluation and treatment. Outpatient evaluation and treatment is an acceptable alternative if
it can be done as quickly as it could be done inpatient and if all goals of inpatient assessment (diagnosis of
mechanism, initiation of appropriate secondary prevention, prevention of complications, early assessment
for and deployment of rehabilitative services) can be successfully addressed.
9. Possible TIA Symptoms Within 2 Hours?

Patients presenting with history suggestive of TIAs may have neurological decits they are unaware of. To
avoid missing the thrombolytic treatment window, patients with possible TIAs presenting within 2 hours of
symptom onset should be triaged like patients with stroke.
10. TIA Symptoms > 2 Hours Ago, but Within Last 48 Hours?
This work group recommends that the physician strongly consider hospitalization for TIA patients who
appear in the ED within 48 hours of the event to expedite work-up and possibly administer tPA if the decit
recurs.
11. Transport to ED by 911 or Other Means

Patients should be taken to the ED urgently.
12. TIA Symptoms > 48 Hours Ago, but Within Last 2 Weeks?
Patients with a single episode of transient ischemic symptoms greater than 48 hours from presentation but
within the last two weeks should be considered for an expedited outpatient evaluation within 72 hours. Those
with several TIAs (greater than 4) in that time frame require immediate evaluation and hospitalization.
13. Clinic Appointment Within One Week of Symptoms Occurring > 2

Weeks Ago
Risk of recurrence in this group may be lower than those with early presentation. Prompt outpatient evalu-
ation by a physician within one week is appropriate.
Refer to Annotation #14, "High Risk for Immediate Future Events?"
Refer to the Support for Implementation section, "Other Resources Available."
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14. High Risk for Immediate Future Events?

Key Points:
Risk of stroke is greatest in the immediate aftermath of TIA or minor
stroke.
Features of presentation dene those at highest risk.
Hospitalization should be strongly considered for those at highest risk.
Several studies have attempted to identify factors in patients presenting with transient ischemic attacks
(TIAs) which might predict progression to ischemic stroke so that these patients can be dealt with more
aggressively. Older studies measure factors predisposing to ischemic stroke within a time frame of years
or months after the initial TIA, but give us very little information as to acute risk. Several studies describe
factors that may increase risk including advanced age, presenting with more than 4 TIAs in the 2 weeks
prior to the index TIA, and the comorbidities of hypertension, myocardial infarction, cardiac arrhythmia,
and diabetes mellitus (Kernan, 1991; Friday, 1997; Hankey, 1992; Streier, 1995; Dennis, 1990). The
presentation of amaurosis fugax confers a more benign prognosis and may be appropriate for an expedited
outpatient evaluation (Wilterdink, 1992; Evans, 1994; Dennis, 1989). Brown, et al., proposed an algorithm
for triage and evaluation of patients with TIA and minor ischemic stroke citing these data to estimate specic
risk and make timing decisions (Brown, 1994; Flemming, 2004).
A recent cohort study described the early (one-week and 3-month) risk of recurrent ischemic stroke, cardio-
vascular events, and death in 1707 patients presenting with a diagnosis of TIA to Emergency Departments
(ED) within the Kaiser-Permanente system in northern California (Johnston, 2000). Fifteen percent of the
patients were admitted for further monitoring and the rest were discharged from the Emergency Department.
The risk of stroke or admission for other cardiovascular events (myocardial infarction, unstable angina,
cardiac arrhythmia, congestive heart failure) were reported as follows:
Event 3 months 7 days
Stroke 10.5% 6% (over half occurred within 2 days)
TIA 13%
CV events 2.7%
Death 2.6%
Taken in total, 26.2% of patients returned to the hospital within 3 months with some other cerebrovascular
or cardiovascular event.
In multivariate analysis, ve factors independently predicted higher risk:
Age greater than 60 years
Diabetes mellitus
TIA lasting longer than 10 minutes
TIA including weakness as a symptom
TIA including abnormal speech as a symptom
The same issue of early risk was examined in the population-based Oxford Vascular Study (Coull, 2004).
The short-term fate of 87 consecutive Oxfordshire residents with TIA or minor stroke was examined. Risk
of stroke was 8% at 1 week, 11.5% at 1 month, and 17.3% at 3 months. The risks were slightly higher after
minor stroke (11.5%, 15%, and 18.5%, respectively). Patients with carotid stenosis randomized to medical
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therapy after rst TIA in the North American Symptomatic Carotid Endarterectomy Trial had stroke risk of
5.5% at 2 days and 20.1% at 90 days (Eliasziw, 2004). Benet of carotid endarterectomy in such patients
drops signicantly as time to the procedure exceeds two weeks from the ischemic event (Rothwell, 2004).
Analysis of a population-based sample of TIA episodes (n=209) yielded the ABCD score identifying those
at high risk of stroke. The elements of the scale from this derivation sample are:
A - for age. Over the age of 60 years old =1 point;
B - for blood pressure. A systolic greater than 140 mm Hg or diastolic greater than 90 mm Hg = 1
point;
C - for clinical features. These include:
unilateral weakness = 2 points,
speech disturbance without weakness = 1 point, and
other = 0 points;
D - for duration of symptoms.
Symptoms lasting greater than 60 minutes = 2 points,
symptoms lasting 10-59 minutes = 1 point, and
symptoms lasting less than 10 minutes = 0 points.
The ABCD score was subsequently validated in a second population-based sample of TIA episodes (n=190).
The 7-day risks of stroke in the combined derivation and validation samples (n=299) were:
0-4 points: 0.4% (95% CI 0-1.1%) 73% of combined samples
5 points: 12.1% (4.2-20.0%) 18% of combined samples
6 points: 31.4% (16.0-46.8%) 9% of combined samples
Not settled is whether the assessment of those at low risk can be safely pursued at a more leisurely pace or
foregone altogether.
(Rothwell, 2005)
These recent reports highlight the frequent early recurrence of symptoms of stroke and other cardiovascular
events as well as the value of early intervention. Whether hospitalization would help to mitigate further
injury by ensuring appropriate surgical intervention when needed (carotid endarterectomy) or increasing
the percentage of patients receiving appropriate prophylaxis early in their course is not clear. However, it
would seem prudent to admit most patients to the hospital with transient ischemic attack that occurred within
48 hours of presentation in order to expedite their evaluation and address these issues promptly given the
immediate risk of recurrence described above. Furthermore, hospitalization would enable timely admin-
istration of lytic therapy in the interval of greatest risk, the initial 24-48 hours. The factors outlined above
which predict high risk of recurrence might inuence decision making in this patient group. Although the
data available cannot dene an appropriate triage decision for all patients, this information should serve as a
guide for appropriate and safe management of the patient with TIA. Certain diagnostic entities if suspected
may require hospitalization for specic management even with presentation later than 24 hours from TIA
occurrence (e.g., carotid or vertebral artery dissection, specic coagulopathy or arteriopathy, cerebral venous
thrombosis.)
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In summary, the Committee recommends consideration of hospitalization for patients with rst TIA within
the past 24-48 hours to facilitate early deployment of lytic therapy, if necessary, and to expedite institution of
denitive secondary prevention. For others, multiple and increasingly frequent symptoms ("crescendo TIAs")
and the clinical features described above might also justify hospitalization rather than expedited ambulatory
management. Whatever the strategy, speed is key. Patients managed in the outpatient setting should be fully
educated about the need to return immediately if symptoms recur to allow use of lytic therapy.
Supporting evidence is of classes: B, D, M, R
15. Clinic Appointment Within 72 Hours

Patients with fewer than ve TIAs, within a two-week time frame may be evaluated by a physician within
72 hours. A more emergent evaluation with hospitalization is indicated if there are features suggestive of
crescendo TIAs or factors predictive of a high risk of future events. (See Annotation #14, "High Risk for
Immediate Future Events?"
Refer to the Support for Implementation section, "Knowledge Products and Resources."
ED Treatment Algorithm Annotations
20. Symptom Onset Allows for Evaluation and Treatment Within 180
Minutes (with Thrombolysis IV)?
Key Points:
Treatment with IV tPA should begin within 3 hours (180 minutes) of symptom
onset.
Patients presenting to the ED within 150 minutes of symptom onset should
be evaluated rapidly for treatment with IV tPA.
Occasionally, patients may be able to receive tPA even if they present later
than 150 minutes if their work-up such as laboratory evaluation has been
completed and they have other aspects such as IV access in place.
Patients presenting to the ED soon after the onset of symptoms may be candidates for treatment with intra-
venous (IV) tissue plasminogen activator (tPA) and will therefore require a rapid evaluation and treatment
initiation (Albers, 2004). Although the time window from onset of symptoms to treatment can be up to 180
minutes, the evaluation in the ED will require at least 30 minutes in most cases (CT scan of head, labora-
tory tests performed and results have returned, IV access obtained, and neurological exam and history.) We
have therefore chosen 150 minutes as a practical cutoff time for this triage decision. Those who are not
candidates for thrombolytic therapy should be evaluated according to usual ED routine.
There are important exceptions to this time limitation guideline for triage of the patients into the "Stroke
Code" process. In certain instances, the time for evaluation may be shorter and this time limit of 150
minutes for triage to "Stroke Code" evaluation may be too conservative, and could be 165 or 170 minutes.
One example would be the patient who is already in the hospital and has received the appropriate labora-
tory evaluation, already has an IV access, and much of the history is already known. In that case, a brief
neurologic exam and rapid evaluation with CT may be the only items required prior to treatment and could
theoretically be performed in 10-15 minutes.
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Thrombolytic therapy for ischemic stroke using intravenous tissue plasminogen activator (tPA) has now been
tested in several large, randomized, placebo-controlled clinical trials. The National Institute of Neurological
Disorders and Stroke (NINDS) stroke trial compared placebo with tPA at a dose of 0.9 mg/kg given within 3
hours of symptom onset in 624 patients (NINDS Study Group, 1995). The time of stroke onset was strictly
dened, blood pressure was maintained within a specied range, and other anticoagulant and antiplatelet
drugs were avoided within the rst 24 hours of treatment. The predetermined threshold for a clinically
important difference at 24 hours was not seen. However, at 3 months and 1 year (Kwiatkowski, 1999) there
were signicantly increased numbers of patients with favorable outcomes (11-13%). Results were consistent
in all four measures of the clinical scales that were assessed. Treatment with tPA resulted in a signicantly
increased risk of symptomatic intracerebral hemorrhage (6.4% tPA treated vs. 0.6% in placebo group, p <
0.001). Mortality was lower at 3 months in those treated with tPA (17% vs. 21% in placebo treated), but
this did not reach statistical signicance. On the basis of the favorable results from these combined trials,
the FDA approved tPA for use in the United States.
The European Cooperative Acute Stroke Study (ECASS) performed concurrent with the NINDS trial also
compared intravenous tPA to placebo in a randomized, placebo-controlled trial in 620 patients. However,
the study design was different in a number of respects including longer time window to treatment (6 hours),
higher dose of tPA (1.1 mg/kg), and lack of strict blood pressure controls (Hacke, 1995). Over 80% of the
patients were treated between 3 and 6 hours after symptoms began. The intention-to-treat analysis did not
demonstrate signicant improvement in the primary outcome measure (combination of Barthel Index and
modied Rankin scale at 3 months), however, there was a high rate of major protocol violation in this study
(109 patients). In a secondary analysis including only the target population there was a signicant differ-
ence measured in favor of tPA treatment, but the ndings were not conclusive.
In 1998, a third large tPA study was completed. ECASS II had a nearly identical protocol to the original
ECASS study except that the tPA dose was lowered to 0.9 mg/kg (Hacke, 1998). A total of 800 patients
were enrolled, and approximately 80% were treated 3-6 hours after stroke onset. The results indicated that
there was no signicant difference in neurologic function between tPA and placebo patients. There was a
trend in favor of treatment that did not reach statistical signicance.
The Thrombolytic Therapy in Acute Ischemic Stroke Study sponsored by Genentech also used a 6-hour time
window, but was similar in other respects to the NINDS tPA trial (Clarke, 2000). Only 15% of patients were
enrolled within 3 hours. Although a signicantly higher percentage of tPA treated patients showed early
improvement at 24 hours measured with the National Institutes of Health Stroke Scale (NIHSS), these nd-
ings were reversed at one month with the placebo patients showing a statistically higher number of patients
showing improvement on this scale. Symptomatic intracerebral hemorrhage was signicantly increased
compared to placebo (11% vs. 0%) with the greatest risk of hemorrhage in patients treated between 5 and
6 hours.
Three similar large scale clinical trials utilizing intravenous streptokinase compared to placebo in random-
ized, placebo-controlled trial design were performed concurrent with the NINDS tPA and ECASS studies
(MAST, 1996; Donnan, 1996; MAST, 1995). All three studies were terminated before completion because
of safety concerns with excessive rates of intracerebral hemorrhagic complications and higher mortality in
the treated groups.
The tPA studies support a limited use of intravenous tPA at a dose of 0.9 mg/kg with appropriate precau-
tions and treatment beginning within 3 hours of symptom onset (Ingall, 2004). Following FDA approval of
tPA for stroke, several reports of community experience with this treatment have appeared in the literature
(Tanne, 1999; Buchan, 2000; Hanson, 2000; Chiu, 1998; Wang, 2000). Although clinical results for the
most part have been concordant with those in the NINDS study, two of these reports document an increase
in intracerebral hemorrhagic complications when patients are treated outside the NINDS protocol further
supporting the importance of following the NINDS tPA study protocol. The signicance of early time to
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treatment was further emphasized by a secondary analysis of the NINDS tPA study population showing
gradual decline in measured efcacy even within the 3-hour time window (Marler, 2000; ATLANTIS, ECASS,
and NINDS rt-PA Study Group Investigators, The, 2004). American Heart Association (AHA) consensus
guidelines for the use of tPA have been published and treating physicians are encouraged to evaluate patients
for this treatment and initiate treatment with urgency (Adams, 1996). Further detail from the clinical trials
outlined above is contained in an ICSI Technology Assessment Report specically addressing tPA treatment
for acute ischemic stroke (Institute for Clinical Systems Improvement, 2005).
Supporting evidence is of classes: A, C, D, R
21. Intra-Arterial Thrombolytic Candidate? (Option Available?)

Key Points:
Intra-arterial thrombolysis is an option for patients with middle cerebral artery
(MCA) or basilar artery (BA) occlusions presenting beyond the 3-hour time
window for intravenous tPA (i.e., 3-6 hours for MCA, 3-12 hours for BA).
There is no proof of superiority of the intra-arterial therapy over intravenous
therapy within 3 hours.
A combined intravenous/intra-arterial approach for the 3-hour window is
under study.
Intra-arterial thrombolytic therapy may be a treatment option for selected patients presenting in an early time
frame but beyond the 3-hour time window for intravenous tPA. Please note that the management during
and following intra-arterial treatment is outside the scope of this guideline.
This is not a routine treatment. The availability of this option will be institution dependent, and patients
must be highly selected. If considering this treatment option for a patient, a physician must explain to
the patient and family that this is an experimental treatment with substantial risk. Despite the limitations
of available study data, in cases of more severe presentation with basilar artery or middle cerebral artery
occlusion, intra-arterial thrombolytic treatment may be appropriate since the prognosis without treatment
is poor.
If the patient is an appropriate candidate for this treatment, consideration should be given to immediate
transfer to an institution offering this intervention. If an endovascular interventionist skilled in this technique
is available to the hospital, this person should be mobilized quickly.
Criteria for consideration of angiographic evaluation for intra-arterial treatment:
MCA occlusion dened by:
- Symptom complex consistent with this vascular distribution:
contralateral hemiplegia and face weakness
contralateral hemisensory loss
aphasia if ischemia is on left, "neglect" if on right
commonly, contralateral homonymous visual eld decit, reduced level of arousal, eye
deviation toward side of brain ischemia (away from side of weakness)
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- MCA "clot sign" on baseline pretreatment CT scan with appropriate clinical presentation
- CT angiogram, MRA or transcranial Doppler (TCD) demonstration of the occlusion with
appropriate clinical presentation
Treatment should begin greater than 3 hours but less than 6 hours from onset of symptoms
Basilar artery occlusion dened by:
- Symptom complex consistent with this vascular distribution:
quadriparesis, sometimes with posturing bulbar dysfunction (dysarthia, dysphagia,
dysphonia)
typically dysconjugate eye movement decits
commonly, depressed level of arousal, respiratory abnormalities
- Hyperdense "clot sign" in basilar artery on pretreatment CT scan with appropriate clinical
presentation
- CT angiogram, MRA or TCD demonstration of the occlusion with appropriate clinical presenta-
tion
Treatment should begin greater than 3 hours but less than 12 hours from onset of symptoms
Intra-arterial infusion of a thrombolytic agent directly into a clot would have theoretic advantages over
systemic (intravenous) treatment, offering a more focused approach with a purported higher recanalization
rate. However, with the exception of a few small randomized controlled studies, the available evidence for
intra-arterial thrombolysis primarily consists of reported case series as outlined below.
Basilar Artery Occlusion
The occurrence of acute basilar artery occlusion with bilateral brainstem symptoms is a catastrophic neuro-
logic event portending a poor prognosis if reperfusion does not occur, with estimations of over 75% mortality
and severe disability in survivors (Kubik, 1946; Archer, 1977; Caplan, 1983). Several investigators have
reported their results in series of treated patients with basilar thrombosis using intra-arterial urokinase or
tPA, showing recanalization rates between 40% and 78% and good outcome by various measures in 20% to
50% (Hacke, 1988; Zeumer, 1993; Becker, 1996; Brandt, 1996; Wijdicks, 1997; Gonner, 1998; Cross, 1997).
These are dramatic results when compared to the natural history of this disease reported in the literature.
There are no randomized, controlled trials of cases of basilar occlusion comparing intravenous tPA to
intra-arterial thrombolysis within 3 hours of symptom onset or intra-arterial therapy to placebo controls in
any time window, but the limited number of patients presenting with this specic entity would make this a
difcult undertaking.
Middle Cerebral Artery Occlusion

In the case of middle cerebral artery occlusion, the estimated degree of benet may seem to be less dramatic
than that with basilar occlusion, but the supporting studies offer a superior level of evidence. In the rst of
two PROACT studies (Prolyse in Acute Cerebral Thromboembolism Study), an improved rate of recanali-
zation was established when comparing use of intra-arterial recombinant pro-urokinase (r-proUK) plus IV
heparin to intra-arterial infusion of placebo plus IV heparin (57.7% versus 14.3%, 2p=0.017) (del Zoppo,
1998). This was a small phase II trial (n=40, 26 received r-proUK and 14 received placebo). Clinical
efcacy was not a primary endpoint and it was not established in this study. In PROACT II intra-arterial
r-proUK plus IV heparin (n=121) was compared to IV heparin alone (n=59) (Furlan, 1999). Signicant
clinical benet with treatment was established showing a 15% absolute increase in the number of patients
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with good outcome at 3 months (primary outcome measure was modied Rankin score of 2 or less). The
complication of symptomatic intracerebral hemorrhage was higher than that seen in the NINDS IV tPA
study (10.2% vs. 6.4% respectively). However, the pretreatment severity of stroke in PROACT II was also
higher than that in the NINDS study, probably accounting for this excess of hemorrhagic complications.
Despite these promising results, r-proUK was not approved by the FDA for the indication of ischemic stroke,
and r-proUK has never been available in the U.S. for any indication. The results of PROACT II, however,
served as a proof of principle for the efcacy of an intra-arterial lytic approach to proximal MCA (M1 or
M2 segment) occlusion in the 3-6 hour time frame. It should be recalled that the available lytic agent, tPA,
has not been examined in a randomized trial.
Other approaches to acute reperfusion are under study. One has been to combine the speed of the intravenous
therapy with the superior recanalization effect of intra-arterial administration. The Emergency Manage-
ment of Stroke (EMS) Bridging Trial was a small study (n=35) comparing combined use of intravenous and
intra-arterial tPA in patients presenting within the 3-hour time window (Lewandowski, 1999). This study
demonstrated the feasibility of the combined intravenous/intra-arterial approach showing better recanaliza-
tion rates when compared to intra-arterial treatment alone. The study was too small to adequately assess
efcacy and safety. A larger study (n=80) by the Interventional Management of Stroke (IMS) Investigators
compared efcacy and safety of the approach using matched historical controls from the NINDS IV tPA
trial (IMS Study Investigators, 2004). Efcacy was slightly greater and safety similar to the historical IV
tPA treated patients. A randomized trial is planned. Another approach uses mechanical rather than chemical
clot removal. The Mechanical Embolus Removal in Cerebral Ischemia phase I study (MERCI I) showed
that recanalization using a corkscrew-shaped retrieval devise could be safely performed with promising
efcacy results in patients presenting up to 8 hours after occlusion of a proximal artery, e.g. internal carotid,
MCA, BA, vertebral artery (Gobin, 2004). The device has been approved by the FDA and a larger trial is
underway.
At this point in time, there are no studies comparing intravenous to intra-arterial therapy within the 3-hour
window. Intravenous treatment with tPA is proven effective in this time frame. Intra-arterial thrombolysis
with the agents currently available for use has theoretic advantages in certain stroke types (demonstrated large
vessel occlusion of the internal carotid, middle cerebral, or basilar arteries), but its superiority in producing
improved clinical outcomes remains unproved. Also, there are logistic difculties with intra-arterial cath-
eter technique that may delay the time to intervention thus limiting the benet for these patients. For these
reasons, treatment within the three-hour time window with intra-arterial instead of intravenous thrombolysis
cannot be recommended for these large vessel occlusion cases. Centers with expertise in use of this technique
should be encouraged to continue utilizing intra-arterial thrombolysis in appropriate candidates presenting
beyond the three-hour time window (presentation within a 3- to 6-hour time window for MCA occlusion
[M1 or M2 segment], and 3- to 12-hour time window for basilar occlusion) while collecting outcome data
and reporting their experience to the medical community. Even more desirable, these same centers should
be participating in randomized, controlled trials so that the efcacy of this therapy can be fully established
and its role in the acute ischemic stroke treatment armamentarium could be claried for all.
Supporting evidence is of classes: A, C, D
23. See Stroke Code Algorithm

The goal of the stroke code is to rapidly administer tPA in appropriately screened candidates. The onset of
symptoms to treatment can be up to 180 minutes, but the NIH recommendation of "door to drug" is within
60 minutes.
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Stroke Code Algorithm Annotations
25. Stroke Code

Key Points:
"Door to rst physician contact" for thrombolytic candidates within 10
minutes.
"Door to initiation of CT scan" for thrombolytic candidates within 25
minutes.
"Door to drug" for thrombolysis treatment within 60 minutes.
This committee uses the term "stroke code" to refer to a process in the ED for the rapid evaluation and
treatment of patients who have presented in a time frame qualifying them for thrombolytic therapy. This
process may take many forms. It might include a formal "stroke team" that is called whenever a possible
candidate for tPA has presented or it may include the ED staff who have been trained in the rapid evaluation
and treatment of stroke victims. The general concept is one which includes:
Rapid triage of patients as soon as they arrive in the ED.
Immediate initiation of phlebotomy for appropriate blood tests followed by CT scan.
First physician contact for history and exam occurring early in the ED visit. The NIH recom-
mendation for timing of "door to rst physician contact" for thrombolytic candidates is within 10
minutes.
Rapid access to the best neurologic and radiologic expertise available at the individual institution
for evaluation of the patient and the CT scan prior to treatment. This may include a neurologist and
neuroradiologist present at the time of treatment. Alternatively, it may be a primary care physician
with expertise in stroke diagnosis and administration of tPA and a general radiologist with expertise
in reviewing head CT scans for early infarct change. The NIH recommendation for the timing of
"door to initiation of CT scan" for thrombolytic candidates is within 25 minutes.
The goal of the stroke code should be to rapidly administer tPA in appropriately screened candidates.
The NIH recommendation for the timing of "door to drug" for thrombolytic treatment is within 60
minutes (Bock, 1999).
26. Evaluation (Should Occur Concurrently with Intervention)

Key Points:
Review tPA indications/contraindications and document whether patient is
eligible.
Perform National Institutes of Health Stroke Scale (NIHSS).
Draw blood for lab tests.
Perform EKG.
Perform noncontrast head CT to exclude hemorrhage.
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Review History and tPA Treatment Indications and Contraindications, and Baseline
NIHSS
Take a complete patient history including a review of indications and contraindications for treatment with
tPA. The contraindications for treatment should be considered relative contraindications.
The recommendations for treatment indications and contraindications were modied from the Institute for
Clinical Systems Improvement (ICSI) Technology Assessment Work Group for tPA for Acute Ischemic
Stroke. They are based upon the NINDS study recommendations with amendments to include recommen-
dations from clinical practice at Mayo Clinic and treatment guidelines from the Stroke Treatment in the
Community study (Hanson, 2000).
See "ICSI Tissue-type plasminogen activator for acute ischemic stroke." TA # 28, 2005.
Supporting evidence is of class: D
Indications for tPA

Acute onset of focal neurologic symptoms in a dened vascular territory, consistent with ischemic
stroke
Clearly dened onset of stroke less than 3 hours prior to planned start of treatment; if the patient
awakens with symptoms, onset is dened as the time of the last known baseline neurological
status
Eighteen years of age or older
CT scan does not show evidence of intracranial hemorrhage, nonvascular lesions (e.g., brain tumor,
abscess) or signs of advanced cerebral infarction such as sulcal edema, hemispheric swelling, or
large areas of low attenuation consistent with acute stroke
Contraindications for tPA

Clinical Contraindications
Clearly dened onset of stroke greater than 3 hours prior to planned start of treatment; if the patient
awakens with symptoms, onset is dened as the time of the last known baseline neurological status
Rapidly improving symptoms
Mild stroke symptoms/signs (NIHSS less than 4)
- Sensory symptoms only
- Ataxia without other decits
- Dysarthria without other decits
- Mild motor signs (non-disabling)
- Visual eld defect without other decits
In the setting of MCA stroke, an obtunded, or comatose state may be a relative contraindication.
Seizure at onset of stroke symptoms or within the 3 hours prior to tPA administration
Clinical presentation suggestive of subarachnoid hemorrhage regardless of CT result
Hypertension systolic blood pressure (SBP) greater than 185 mm Hg or diastolic blood pressure (DBP)
greater than 110 mm Hg
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Patients with this BP excluded only if it remains elevated on consecutive measurements. Also exclude
if aggressive treatment is required to lower BP into appropriate range.
Throughout this guideline, the work group frequently refers to blood pressure limits that are represented
as systolic/diastolic. These ranges are intended to show the blood pressure limits as exceeding as either
a given systolic level OR a given diastolic level.
History Contraindications
Minor ischemic stroke within the last month
Major ischemic stroke or head trauma within the last 3 months
History of intracerebral or subarachnoid hemorrhage if recurrence risk is substantial
Untreated cerebral aneurysm, arteriovenous malformation (AVM), or brain tumor
Gastrointestinal or genitourinary hemorrhage within the last 21 days
Arterial puncture at a noncompressible site within the last 7 days or lumbar puncture within the last 3
days
Major surgery or major trauma within the last 14 days
Clinical presentation suggestive of acute myocardial infarction (MI) or post-MI pericarditis
Patient taking oral anticoagulants and INR greater than 1.7
Patient receiving heparin within the last 48 hours and having an elevated aPTT
Patient receiving low-molecular-weight heparin within the last 24 hours
Pregnant, or anticipated pregnant, female
Known hereditary or acquired hemorrhagic diathesis or unsupported coagulation factor deciency
Received tPA less than 7 days previously
Laboratory Contraindications
Glucose should always be measured prior to giving tPA; other parameters should be checked before treat-
ment if there is reason to believe they may be abnormal (e.g., INR and aPTT should be checked if patient
has been exposed recently to warfarin or heparin or if there is history of liver disease).
Glucose less than 50 or greater than 400 mg/dL
Platelet count less than 100,000 mm3
INR greater than 1.7
Elevated aPTT
Positive pregnancy test
Radiology Contraindications
Intracranial hemorrhage
Large area of low attenuation consistent with an evolving stroke. Early changes of this type suggest
that onset of symptoms occurred earlier than the history rst indicated. Recheck patient history and
time of symptom onset.
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Intracranial tumor, aneurysm, arteriovenous malformation (AVM) or other space-occupying

lesion
Once indications and contraindications have been reviewed, documentation of why patient was included
or excluded must occur.
Perform Vital Signs Every 15 Minutes with Neuro Checks

A history and neurological examination must be performed to assess whether the presentation is consistent
with a stroke diagnosis and to estimate the severity of the decit. Use of the NIHSS by physicians and
nursing staff is encouraged as this would provide a uniform method of evaluation to facilitate comparison
between examiners during the early hours of the stroke evaluation. We encourage use of the NIHSS as an
initial evaluation tool and after resuscitation or treatment to assess for change.
The NIHSS is a quantitative measure of neurologic decit in stroke patients that covers the key aspects
of the neurological exam including: level of consciousness and orientation, eye movements, visual elds,
facial weakness, motor strength in limbs, coordination, sensation, language and comprehension of language,
articulation, and neglect. It can be performed in rapid fashion (5-8 minutes) which is an important feature
in this clinical setting (Brott, 1992; Adams, 2003).
It has been demonstrated in several evaluations to have both validity and reliability as follows:
Content validity
- The items contained in the NIHSS were selected on the basis of expert opinion
and literature review, thus satisfying the requirements for content validity (Boysen, 1992).
Concurrent criterion validity
- The NIHSS correlates with lesion volume on CT scan (Brott, 1989).
- The NIHSS correlates with other measures of neurological outcome (Duncan, 1992).
Construct validity
- Factor analysis reported by Lyden et al dened two constructs relating to right and left hemi-
sphere function conrming construct validity of this scale (i.e., it is measuring what it was
designed to measure.) This nal factor structure remained consistent in both tPA treated and
placebo patients over time after ischemic stroke treatment (Lyden, 1999).
Predictive validity
- The NIHSS predicts three-month outcome (Muir, 1996; Adams, 1999).
Interrater-and-intrarater reliability
- The NIHSS has been shown to be a reproducible measure both comparing different examiners
and comparing repeated evaluations by the same examiner. Reliability has been demonstrated
for neurologists, other physicians, and nursing caregivers (Goldstein, 1989; Dewey, 1999;
Goldstein, 1997). Although the NIHSS was originally designed as a research tool, it has proven
to be an excellent measure of neurologic status and can be an important tool for the standardiza-
tion and communication of clinical information between nurse caregivers and between nurse
caregivers and other health care professionals (Spilker, 1997).
Supporting evidence is of classes: B, C, D, R
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Record Weight (estimate if needed)

Draw Blood for Lab Tests
Necessary/Critical Laboratory Tests are:
glucose
PT/INR (if patient on warfarin)
Recommended laboratory tests include:
complete blood count (CBC) with platelet count
electrolytes, BUN, creatinine
PT/INR, aPTT
Others to consider:
Troponin
AST
These tests are used to evaluate for dehydration, metabolic disorders which might inuence neurologic
status (especially hypoglycemia and hyperglycemia), hematologic disorders such as polycythemia which
may affect cerebral perfusion, or coagulopathies which could affect the treatment decision. Prior to admin-
istration of tPA, the platelet count and glucose level should be reviewed. If the patient is known to be on
warfarin or has received heparin within the last 24 hours, the prothrombin time and partial thromboplastin
time should be reviewed prior to treatment. A urine or serum pregnancy test should be obtained in women
of child bearing potential if there is substantial reason to believe the patient may be pregnant.
Perform EKG
An EKG should be performed for the purpose of screening for concomitant cardiac disease, either acute or
chronic, which may impact on immediate treatment decisions.
Perform CT Head Without Contrast

A CT scan without contrast must be performed prior to treatment with tPA, primarily for the purpose of
excluding hemorrhage. Early signs of infarct should also be sought as this nding confers greater risk of
symptomatic intracerebral hemorrhage with tPA treatment. It is suggested that the greatest level of radio-
logic expertise possible be obtained for this reading with the caveat that this CT reading should not create
excessive delays in the evaluation and treatment process. A procedure for rapid teleradiography CT readings
should be organized and in place if needed.
Other Cardiac Assessment as Appropriate (Telemetry)
27. Intervention (Should Occur Concurrently with Evaluation)

Key Points:
Educate and document education of patient and caregiver.
BP management for non-tPA candidates.
BP management for tPA candidates.
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Maintain euvolemia with isotonic uids.

Correct hyperthermia, hypo- or hyperglycemia, and hypoxia.
Educate Patient and Family
A process should be in place for the patient and family that will rapidly orient them to the suspected diag-
nosis, ED process, tests to be performed, tPA treatment and its risks, and other treatment measures to be
considered. This could include both caregiver face-to-face interaction with the patient and family as well
as teaching tools in written form. Education should be documented in the medical record.
Treat Hypertension if greater than 185 systolic or 110 diastolic

Patients with this BP excluded only if it remains elevated on consecutive measurements. Also exclude if
aggressive treatment is required to lower BP into appropriate range (e.g., if more than a few doses of any
medication is required or if nitroprusside drip is required.)
Recommendations for management of blood pressure in the setting of acute stroke (Adams, 2003)
Ischemic stroke, tPA candidate:
No tPA if diastolic blood pressure (DBP) greater than 140 on 2 readings, 5 min apart or use of
nitroprusside is necessary to control blood pressure
Treat systolic blood pressure (SBP) greater than 185 or DBP greater than 110 using easily titrated
agents (labetolol, enalapril). Do not use tPA if BP is difcult to lower below these thresholds.
Guidelines for blood pressure management in this setting have been slowly evolving (Adams, 1994; Adams,
1996; Strandgaard, 1996; Powers, 1993; International Society of Hypertension Group, 2003; Stead, 2004).
Although empirically many have considered hypertension in the acute stroke setting to be potentially inju-
rious, it is clear now that this is not the case.
A full understanding of this issue requires some understanding of the physiology. Cerebral blood ow
(CBF) is regulated by the relationship between cerebral perfusion pressure (CPP) and cerebrovascular
resistance (CVR) (CBF=CPP/CVR). CPP represents the difference between arterial blood pressure (BP)
forcing the blood into the cerebral circulation and the venous back pressure. Under normal circumstances
the venous back pressure is negligible and CPP is equal to arterial BP. Normally, changes in blood pressure
(or CPP) over a wide range have little effect on CBF. This phenomenon, termed autoregulation, is mediated
via changes in the CVR. An increase in CPP (or BP) produces vasoconstriction and a decrease produces
vasodilatation. This autoregulation keeps the cerebral blood ow at a steady level over a range of 60-150
mmHg mean arterial pressure. In individuals with chronic hypertension the range for autoregulation is
shifted upwards so that they may be more tolerant of higher blood pressure and less tolerant of lower blood
pressure (decreased cerebral blood ow).
Acute ischemic stroke will cause a change in autoregulation in the ischemic zone by two mechanisms:
First, when an artery is occluded, a central core of severe ischemia is produced. This is surrounded by
a zone with less reduction in blood ow where perfusion is maintained by collateral circulation, termed
the penumbra. These blood vessels are maximally dilated and for that reason blood ow through them
may be completely dependent on blood pressure.
Second, during the acute period the phenomenon of autoregulation can be impaired in patients both
with and without persistent arterial occlusion changing the autoregulation curve so that maintenance of
blood ow in this region is completely dependent on the blood pressure.
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These abnormalities in autoregulation can persist for days or weeks. There is evidence to suggest that
there is slow improvement in this phenomenon in the acute period. But early on, lowering the blood
pressure can bring the blood ow down to critical levels in the infarct region, potentially extending the
area of infarct. This is supported by data from both animal and human studies (Powers, 1993; Chris-
tensen, 2002).
Although the potential dangers of lowering arterial blood pressure in patients with acute ischemic stroke
are accepted theory inuencing practice, documentation of actual risk is based on a few published case
reports (Britton, 1980; Lavin, 1986; Grossman, 1996). The theoretical concerns are substantial and would
preclude consideration of attempting to normalize the blood pressure when elevated in this setting. However,
whether mild treatment of hypertension in acute stroke might be benecial has not been adequately studied.
One limitation of any study design is the fact that severe and sustained elevation of blood pressure is not a
common occurrence.
A study was made of the use of three antihypertensive medications versus placebo in a small group of patients
who were studied with SPECT imaging to assess changes in blood ow. In general, it was found that blood
pressure decreased signicantly in all groups, including the placebo group, raising the question as to whether
there is any need for this treatment (Lisk, 1993). Of the three agents used, nicardipine seemed to have the
greatest effect on blood pressure, and cerebral blood ow was adversely affected in the nicardipine treated
patients. The obvious limitation of this study is its small size limiting any analysis of clinical outcome.
A Cochrane review (2003) consisting of 34 randomized controlled trials and 5368 patients examined the
effect of various drugs on blood pressure (BP) during the rst 72 hours of acute ischemic stroke (AIS).
Drugs shown to actually reduce BP included oral and IV calcium channel blockers, oral beta blockers,
Glyceryl Trinitrate, ACE inhibitors, Prostacyclin (PGI2), and Streptokinase. However, the effect of blood
pressure reduction was not clear, likely due to the signicant imbalances in baseline blood pressure between
treatment and control groups. Outcomes sought included early death and overall case fatality. The review
concluded that there is insufcient evidence to evaluate the effect of altering blood pressure on outcome
after acute ischemic stroke, but that treatment with beta blockers or streptokinase appears to be associated
with early case fatality. Another systematic review demonstrated increased mortality, early deterioration,
and dependency associated with higher blood pressure in the acute stroke setting (Willmot, 2003).
The above review includes the IST trial (Leonardi-Bee, 2002) which demonstrated a U shaped curve when
BP was plotted against survival. Other investigators have also conrmed this (Castillo, 2004), providing
ground for the current consensus based guidelines to treat BP (Adams, 2003).
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Taking the above studies into consideration, the AHA has issued a revised 2003 edition of "Guidelines for
the management of patients with acute ischemic stroke." These consensus-based guidelines recommend
the following measures for treatment of BP in patients with AIS:
Approach to Elevated Blood Pressure in Acute Ischemic Stroke
Blood Pressure Level (mm Hg) Treatment

A. Not eligible for thrombolytic therapy
Systolic < 220 OR diastolic < 120 Observe unless other end-organ involvement, e.g., aortic
dissection, acute myocardial infarction, pulmonary edema,
hypertensive encephalopathy
Treat other symptoms of stroke such as headache, pain,

agitation, nausea, and vomiting
Treat other acute complications of stroke, including hypoxia,

increased intracranial pressure, seizures, or hypoglycemia
Systolic > 220 OR diastolic < 121-140 Labetalol 10-20 mg IV over 1-2 min
May repeat or double every 10 min (maximum dose 300 mg)
or Nicardipine 5 mg/hr IV infusion as initial dose; titrate to
desired effect by increasing 2.5 mg/hr every 5 min to
maximum of 15 mg/hr
Aim for a 10% to 15% reduction of blood pressure
Diastolic > 140 Nitroprusside 0.5 g/kg/min IV infusion as initial dose with
continuous blood pressure monitoring. Aim for a 10% to 15%
reduction of blood pressure
B. Eligible for thrombolytic therapy

Pretreatment
Systolic >185 OR diastolic >110 Labetalol 10-20 mg IV over 1-2 min
May repeat x 1 OR Nitropaste 1-2 inches if blood pressure is
not reduced and maintained at desired levels (systolic < 185
and diastolic < 110), do not administer rtPA
During and after treatment

Monitor BP Check BP every 15 min for 2 hours, then every 30 min
Diastolic > 140 for 6 hours, and then every hour for 16
Systolic > 230 OR diastolic 121-140 titrate to desired Sodium nitroprusside 0.5 g/kg/min IV infusion as initial
dose and blood pressure
Labetalol 10 mg IV over 1-2 min
May repeat or double labetalol every 10 min to a maximum
dose of 300 mg or give the initial labetalol bolus and then
start a labetalol drip at 2 to 8 mg/min
or
Nicardipine 5 mg/hr IV infusion as initial dose; Titrate to
desired effect by increasing 2.5 mg/hr every 5 min to
maximum of 15 mg/hr. If BP is not controlled by labetalol,
consider sodium nitroprusside.
Systolic 180-230 OR Labetalol 10 mg IV over 1-2 min

Diastolic 105120 May repeat or double labetalol every 10 to 20 min to a
maximum dose of 300 mg or give the initial labetalol bolus
and then start a labetalol drip at 2 to 8 mg/min.
Adapted from the American Heart Association.

In general, discontinuation of a patient's usual daily antihypertensive regimen is not advised as this may
result in unwanted rebound hypertensive effects. Exceptions to this practice might include holding these
medications if the BP is low, and holding diuretic therapy regardless of the BP, to avoid any problems with
volume depletion that might contribute to hemoconcentration that could limit blood ow.
Supporting evidence is of classes: A, D, R
www.icsi.org
Initiate 2 IV lines
Two intravenous (IV) lines should be started so that tPA may have a dedicated line.
Start IV Fluids
Treatment with a 0.9% normal saline at a rate of 75-125 cc/hr or 2-3 L/day should be administered for the
avoidance of dehydration. The rate may be adjusted for febrile patients.
Hemorrheologic disturbances may be a factor in limiting cerebral blood ow in the setting of ischemic
stroke. Attempts to affect blood viscosity by lowering hematocrit to increase blood ow and oxygen
delivery suggested the possibility of a useful therapeutic intervention (Thomas, 1977; Wade, 1983). Results
of studies of hemodilution techniques that attempt to decrease blood viscosity utilizing phlebotomy and
volume expansion with dextran or pentastarch have been mixed. Although there were promising results in
small clinical trials, when subjected to more rigorous study with large controlled trials, this treatment was
unsuccessful (Italian Acute Stroke Study Group, 1988; Scandinavian Stroke Study Group, 1987). Although
proponents of this treatment have argued that results would be improved with earlier time-to-treatment, a
more individualized approach with treatment decisions, or a more aggressive hypervolemic hemodilution
approach, additional large scale trials have not been repeated. In fact, use of a hypervolemic approach in
order to further raise cardiac output by volume expansion was complicated in some cases by cerebral edema
and increased mortality raising questions regarding the safety of this treatment (The Hemodilution in Stroke
Study Group, 1989). Therefore, hemodilution therapy is not recommended since the clinical benet has not
been established and the possibility of risk due to the development of cerebral edema has not been excluded.
Also, there is a risk of CHF as mentioned elsewhere.
However, in the general medical management of patients with stroke, it is important to administer adequate
uids to avoid the development of dehydration or to treat it when present since dehydration with hemocon-
centration may impair cerebral blood ow (Thomas, 1977). Dehydration with hemoconcentration may also
increase the risk of thrombus formation and recurrent embolization in cardiogenic stroke (Yasaka, 1993;
Yasaka, 1990; Arboix, 1998). Therefore, it is suggested that isotonic intravenous uids be administered in
those admitted with dehydration or at risk for subsequent dehydration due to problems with swallowing, or
general mobility, limiting maintenance of hydration with orally administered uids.
Supporting evidence is of classes: A, C, D, R
Treat Hyperthermia
The acutely injured brain, whether due to trauma or ischemia, is inordinately susceptible to the damaging
effects of brain temperature elevation. This fact is well supported by both animal and human studies (Gins-
berg, 1998).
Interventions for patients with temperatures of greater than 37.5C (99.5 F) include appropriate dosing of
acetaminophen (1 gram orally or 650 mg rectally every 4-6 hours, not to exceed 4-6 grams in 24 hours) and
regular monitoring of temperature status (every 4 hours.) For those patients with extreme hyperthermia,
greater than 39.4C (103 F), aggressive interventions including cooling blankets and ice packs are encour-
aged. Secondary causes for temperature elevation should be sought.
In human studies, early hyperthermia in acute stroke is associated with increased risk of poor outcome,
higher mortality, and increased infarct volume (Sharma, 1998; Ternt, 1981; Jorgensen, 1996; Reith, 1996;
Azzimondi, 1995; Castillo, 1998; Wang, 2000; Hajat, 2000). The causality and the relationship of tempera-
ture elevation to these poor outcomes is not fully understood. Whether intervention with cooling methods
will result in improved outcomes is unknown. [Conclusion Grade III: See Conclusion Grading Worksheet
A Annotation #27 (Hyperthermia)]
Supporting evidence is of classes: B, D, M, R
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Treat Hyperglycemia
Hyperglycemia may adversely inuence clinical outcome.
Early identication of patients with hyperglycemia in the setting of acute ischemic stroke or in those
at risk for cerebral ischemia (ED evaluation of glucose level) is recommended.
Avoid any agents or factors which might induce hyperglycemia.
- Eliminate glucose from any IV solutions used. (Recommend use of normal saline.)
- Avoid use of corticosteroids, even in those patients with cerebral edema, as it is unlikely to be
helpful and may be harmful. Separate recommendations are needed for those on maintenance
corticosteroids for concurrent conditions, and treatment decisions are left to the discretion of
the physician.
Use appropriate measures to maintain euglycemia, carefully avoiding hypoglycemia.
Continue to monitor glucose with bedside testing in those receiving treatment in order to maintain
euglycemia.
Most observational studies document either increased mortality or decreased functional outcome or both
with higher glucose. Some have speculated that early hyperglycemia in the setting of acute stroke is simply
a marker of physiologic stress and an epiphenomenon in those who have suffered severe stroke (Melamed,
1976; Woo, 1990; Counsell, 1997; Kiers, 1992; Jorgensen, 1994; Weir, 1997; Bruno, 1999). Others have
documented that it is an independent predictor of poor outcome and propose that it has a causative role.
Despite the extensive body of literature describing this relationship, clinical trials aimed at intervention to
improve outcome are still lacking. However, there has been a randomized controlled trial demonstrating the
benets of early aggressive glucose management in patients with acute myocardial infarction and a similar
study utilizing a continuous infusion of insulin, glucose and potassium in the setting of acute ischemic
stroke is now underway (Malmberg, 1997; Scott, 1999). It is unclear whether early hyperglycemia in the
setting of acute stroke may be a marker of physiologic stress or an independent predictor of poor outcome.
Usual management of hyperglycemia with gentle dosing of subcutaneous insulin in a timely manner during
acute ischemia would seem prudent until ongoing clinical trials address the appropriateness of more aggres-
sive treatment measures. [Conclusion Grade III: See Conclusion Grading Worksheet B Annotation #27
(Hyperglycemia)]
Supporting evidence is of classes: A, B
28. Patient Meets Criteria for tPA, Has No Contraindications and

Symptom Onset Still Less Than 3 Hours?
Refer to Algorithm Annotation #26, "Evaluation (Should Occur Concurrently With Intervention)," for
criteria.
29. Initiate tPA

Treatment should consist of tPA 0.9 mg/kg intravenously to a maximum dose of 90 mg. Ten percent of this
dose should be given as a bolus over 1-2 minutes and the remainder infused over one hour. This dosing
may be based upon actual or estimated weight.
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31. Initiate Aspirin Unless Contraindicated (See Annotation

Discussion)
Key Points:
ASA should be given rectally or via NG tube promptly in patients who are
not rt-PA candidates unless contraindicated (ASA allergy, GI bleeding).
There is no evidence to support therapeutic anticoagulation with unfractionated
heparin, LMW heparin or heparinoids. There is, as yet, insufcient evidence
to decide whether specic subgroups of ischemic stroke (e.g., dissection,
cardio-embolism with intra-cardiac clot) will benet from therapeutic anti-
coagulation.
If a decision is made to use continuous heparin infusion, boluses should be
avoided and aPTT should be maintained in the 1.5-2 times baseline range.
No anticoagulation or antiplatelet should be given when CT/MRI shows a
hemorrhagic stroke. This recommendation applies to ischemic stroke due to
arterial occlusion; hemorrhagic transformation in the setting of sinovenous
infarction is not necessarily a contraindication to antithrombotic therapy
including heparin.
Low dose prophylactic anticoagulation (e.g., unfractionated heparin 5,000 units
SQ twice daily) is benecial for prevention of DVT or PE in stroke patients
with limited mobility.
Aspirin (ASA)
Patients who are not candidates for tPA should be promptly given ASA in a dose of 160-325 mg orally,
rectally or by nasogastric tube and should be continued on a similar daily dose (Albers, 2004). Exceptions
to this approach would include avoiding treatment in those with contraindications to ASA therapy (e.g.,
ASA allergy, gastrointestinal hemorrhage).
Although the benets of aspirin therapy for long term preventive therapy for stroke are well established, the
use of aspirin to improve outcome in the acute treatment setting has only recently received attention. Large
randomized controlled trials have demonstrated a small but measurable benet with use of aspirin in the
rst 48 hours following ischemic stroke onset (Sandercock, 1993; Chinese Acute Stroke Trial Collaborative
Group, 1997; International Stroke Trial Collaborative Group, 1997; Bath, 2001).
The studies together demonstrate benet of small magnitude, but with statistical signicance in the following
outcome measures:
Preventing early recurrent ischemic stroke 7 fewer per 1000 treated (p< 0.0001) (comparable to
the preventive effects of ASA for one year non acute treatment)
Decreasing death from any cause 5 fewer per 1000 treated (p=0.05)
Decreasing death or early recurrence of nonfatal stroke 9 fewer per 1000 treated (p=0.001)
Decreasing death or dependency at discharge or 6 months 13 fewer per 1000 treated (p=0.007)
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Also, the measured hazard appears to be small and statistically insignicant:

Hemorrhagic stroke or transformation 2 more per 1000 in ASA treated (p=0.06)
Supporting evidence is of classes: A, M
Considerations with Heparin Use

In contrast, results from the International Stroke Trial provide powerful evidence against the routine use in
patients with acute ischemic stroke, of any heparin regimen as intensive as the moderate dose subcutaneous
regimen utilized in this very large clinical trial (unfractionated heparin 12,500 units subcutaneous twice
daily) (IST, 1997).
This would include the adjusted dose continuous infusion of unfractionated heparin that is commonly
employed for the treatment of stroke in the United States. The commonly cited indications of vertebrobasilar
distribution ischemia or ischemic stroke in the setting of atrial brillation were analyzed separately and there
was no measurable benet in these specic subgroups. Similarly, the weight of available data regarding
use of full dose low-molecular-weight heparin for the acute treatment of stroke do not support their routine
use for limiting disability or decreasing mortality in this setting.
The routine use of acute anticoagulation treatment with unfractionated heparin, low-molecular-weight
heparin, or heparinoid in acute ischemic stroke is not supported by the available evidence. This treatment
does not appear to improve clinical outcome from the index stroke. There may be subgroups who benet,
but further studies of this problem are required for conrmation. [Conclusion Grade I: See Conclusion
Grading Worksheet C Annotation #31 (Heparin)]
(MAST-I, 1995; Kay, 1995; TOAST, 1998; Albers, 2004; Berge, 2000; Diener, 2001; Coull, 2002)
Despite these discouraging results, the use of continuous heparin infusion in acute stroke has continued
to be common in clinical practice. Given these data, if the decision is made to use full dose continuous
heparin infusion for a specic indication (e.g., large vessel atherothrombosis or dissection), physicians
are strongly recommended to discuss with their patients the lack of proof for this therapy and to detail the
potential hazards of therapy.
Heparin Use for VTE Prophylaxis
Lower doses of these agents, (e.g., enoxeparin 40 mg subcutaneously daily or unfractionated heparin 5,000
IU subcutaneously twice daily), are benecial for the prevention of deep vein thrombosis or pulmonary
embolus in those stroke victims with limited mobility and can be advocated for that purpose. Pharmacologic
prophylaxis should be considered for patients at high risk for venous thromboembolism (VTE) including
an estimated length of stay of 4 days or more.
For patients at high risk for VTE where pharmacologic prophylaxis is contraindicated, elastic stockings are
recommended and consider intermittant pneumatic compression (IPC) if conned to bed.
(Kamphnisen, 2005)
See the ICSI Venous Thromboembolism Prophylaxis guideline for more information.
Supporting evidence is of classes: A, R
32. Post-ED Medical Management (Post-Thrombolysis)

Admit to intensive care unit or acute stroke care unit/cardiac monitoring
Perform vital signs and neurologic checks every 15 minutes for 2 hours, then every 30 minutes for
6 hours, then every 60 minutes for 24 hours (recommend use of an abbreviated NIHSS for neurologic
checks)
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Treat BP if greater than 180/105

- First 24 hours: Treat if SBP greater than 180 or DBP greater than 105
- Greater than 24 hours: Treat if SBP greater than 220, mean arterial pressure (MAP) greater than
130
- Monitor BP and any corresponding neurologic changes in the ED and rst few days of hospitaliza-
tion.
Initiate bleeding precautions:
- Avoid placement of central venous access or arterial puncture for the rst 24 hours.
- Placement of an indwelling bladder catheter should be avoided during drug infusion and for at least
30 minutes after infusion ends.
- Insertion of a nasogastric tube should be avoided, if possible, during the rst 24 hours.
- Avoid use of anticoagulant, antiplatelet, or non-steroidal anti-inammatory agents for the rst 24
hours.
- Monitor for CNS hemorrhage.
If any signs of CNS hemorrhage (e.g., neurologic deterioration, development of severe headache,
sudden severe elevation of BP, or new nausea or vomiting) or signs of major systemic hemorrhage
institute the following measures:
- Discontinue infusion of thrombolytic drug.
- Obtain hemoglobin, hematocrit, partial thromboplastin time, prothrombin time/INR, platelet count,
brinogen (also type and cross match if transfusions will be needed).
- Obtain surgical consultation if necessary.
- Obtain emergent CT head without contrast if CNS hemorrhage suspected.
Initiate anti-thrombotic therapy 24 hours after tPA administration (antiplatelet agent or anticoagulant
as appropriate).
33. Post-ED Medical Management (Not a Thrombolysis Candidate)

Treat BP if greater than 220/120 or MAP greater than 130.
Recommendations ischemic stroke, not a tPA candidate:
Treat BP only if systolic blood pressure (SBP) greater than 220, mean arterial pressure (MAP)
greater than 130
Use easily titrated agents, choosing those with the least effect on cerebrovasculature (labetolol,
enalaprilat). American Heart Association (AHA) recommendations support oral dosing, but if
swallowing is affected intravenous agents should be used.
Dosing examples:
Labetalol oral 100-200 mg by mouth initially and every 2 hrs as needed, up to
800 mg total in 24 hrs,
or
Labetalol IV 10 mg IV over 1-2 min, repeat or double dose every 10-20 min
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Captopril 6.25-25 mg by mouth (or sublingual) and repeat as required

Enalapril 0.625-1.25 mg IV over 5 min, repeat every 6 hours or as needed
Nitroprusside 0.3 mcg/kg/min IV; titrate for BP control as needed up to 10 mcg/kg/min.
(Nipride)
Avoid agents which tend to cause precipitous drops in BP (e.g., sublingual calcium channel
blockers)
Treat hypotension (IV uids, treat congestive heart failure or arrhythmia and consider pressors)
Monitor BP and any corresponding neurologic changes in the ED and rst few days of hospitaliza-
tion. Avoid overtreating BP.
It is important to recognize that these recommendations must be tailored to the individual, dependent on the
patient's acute presentation and whether or not there is a previous history of hypertension. Young patients
without a previous history of hypertension may be less tolerant of the higher extremes of blood pressure in
this setting. Specic comorbidities which may require a more aggressive use of antihypertensive therapy
in this setting include:
Left ventricular failure
Aortic dissection
Acute myocardial ischemia
Renal insufciency induced by accelerated hypertension
Hypertensive encephalopathy
Hemorrhagic conversion of an ischemic infarct
Thrombolytic treatment
In general, discontinuation of a patient's usual daily antihypertensive regimen is not advised as this may
result in unwanted rebound hypertensive effects. Exceptions to this practice might include holding these
medications if the BP is low and holding diuretic therapy regardless of the BP, to avoid any problems with
volume depletion that might contribute to hemoconcentration that could limit blood ow.
34. Other Post-ED Medical Management (First 24-48 Hours)

Continue to treat hyperthermia, hyperglycemia, or hypoglycemia
Refer to Annotation #27, "Intervention (Should Occur Concurrently with Evaluation.")
Initiate deep vein thrombosis (DVT) prophylaxis

Consider DVT prophylaxis in any patient admitted to the hospital with weakness related to an ischemic
stroke. The risk of DVT is high (25-50%), and prophylaxis with subcutaneous heparin decreases the inci-
dence (10 to 20%). The risk of pulmonary embolism appears to be decreased as well, although numbers
have been small and statistical signicance not achieved (Counsell, 2001).
All patients should receive patient education that includes signs and symptoms of VTE and therapy options
and encouraged to ambulate early and perform exion/extension exercises (Geerts, 2004). Elastic stockings
should be used for patients at high risk for VTE. IPC should be considered for patients at high risk for VTE
who have contraindications to pharmacologic prophylaxis (Bath, 2001).
www.icsi.org
Unfractionated heparin at 5,000 units every 12 hours is the standard dose; 5,000 units every 8 hours has been
used in larger individuals. Low-molecular-weight heparin and heparinoids may be slightly more effective
for DVT prophylaxis (decreased incidence from 22% with heparin to 13% with enoxaparin or danaparoid),
and theoretically potentially safer (less risk of bleeding), but it has not been conclusively demonstrated in
studies (Vanek, 1998).
Low-molecular-weight heparin is renally cleared. For patients with a CrCl less than 30 mL/min, use
unfractionated heparin. The patient should be monitored for the possible development of heparin-induced
thrombocytopenia (HIT) and bleeding. Obtain a platelet count and hemoglobin every other day beginning
on the second day of heparin therapy.
See the ICSI Anticoagulation Therapy Supplement and the Venous Thromboembolism Prophylaxis guide-
lines.
Supporting evidence is of class: M
Perform swallow evaluation

Early evaluation of swallow should be performed in patients at risk of aspiration so that an appropriate diet
adjustment may be instituted. Patients at risk include those with facial weakness, signicant dysarthria,
excessive drooling, sputtering, choking, gurgling, wet voice, or pocketing food in mouth. Clear liquids by
mouth and in some cases any food or uid should be avoided in this setting until a swallow evaluation has
established the patient's level of risk for aspiration with the various consistencies.
Swallow evaluation and dietary adjustments based on this information and early mobilization as effective
treatments for prevention of medical complications have not been adequately evaluated in randomized
clinical trials. However, in the absence of this level of proof, since these interventions are safe and have a
reasonable probability of improving care by decreasing complications, it is reasonable to advocate their use
in this setting. Several previously published guidelines advocate these practices.
Initiate rehabilitation early

Early mobilization within 48 hours of admission is advocated by means of early initiation of appropriate
rehabilitation swivels or other nursing intervention for the purpose of preventing complications related to
immobility, including deep vein thrombosis, contractures, joint disorders, and pressure sores/decubitus
ulcers (Adams, 1994; Helgason, 1997).
Perform Nutritional Status Assessment

Assessment of the patient's baseline nutritional status and the implementation of treatments to correct any
major nutritional problems are recommended (Adams, 2005). Poor nutritional status in patients admitted
for stroke are associated with increased morbidity and mortality (FOOD Trial Collaboration, 2003). Trials
are currently underway to assess whether more intensive nutritional interventions improve outcomes for
patients after stroke.
Supporting evidence is of class: R
www.icsi.org
Ischemic Stroke ED Management (not a thrombolysis candidate)

Algorithm Annotations
36. Evaluation (Should Occur Concurrently with Intervention)

Review history
Refer to Annotation #26, "Review History and tPA Treatment Indications and Contraindications and
Baseline NIHSS."
Perform neurologic examination
Refer to Annotation #26, "Perform Exam with Neuro Checks and Vital Signs Every 15 Minutes."
Draw blood for lab tests
Refer to Annotation #26, "Draw Blood for Lab Tests."
Perform EKG
Refer to Annotation #26, "Perform EKG."
Perform CT head without contrast
Refer to Annotation #26, "Perform CT Head Without Contrast."
37. Intervention (Should Occur Concurrently with Evaluation)

Educate patient/family
Refer to Annotation #27, "Educate Patient and Family."
Treat hypertension only if:
- Ischemic stroke and BP greater than 220 systolic, 120 diastolic, or mean arterial pressure (MAP)
greater than 130 or concurrent illness requiring treatment.
Refer to Annotation #33, "Treat BP if Greater Than 220/120 or MAP Greater Than 130."
Treat hyperthermia, hypo or hyperglycemia, and hypotension.
Refer to Annotation #27, "Treat Hyperthermia, Treat Hypo- or Hyperglycemia, and Treat Hyperten-
sion."
Administer ASA 160-325 mg (or other antithrombotic) following CT evidence of no hemorrhage
Refer to Annotation #31, "Initiate Aspirin Unless Contraindicated (see Annotation Discussion)."
38. Does the Patient Require Hospital Admission?

Key Points:
Hospitalization should be considered even in patients with subacute minor
stroke to arrange secondary prevention and address potential complications.
Patients with acute ischemic stroke or TIA (occurring less than 24 to 48 hours before presentation) should
generally be admitted to the hospital unless it is clearly based on expert opinion that outpatient evaluation
and treatment is appropriate. The purpose would be to determine whether thrombolysis should be consid-
ered. This also allows for a thorough and rapid evaluation and treatment, especially to evaluate whether
the patient is at high-risk for immediate future events.
www.icsi.org
Please refer to Annotation #14, "High Risk for Immediate Future Events?"
In patients with ischemic stroke occurring days to weeks prior to initial clinical evaluation with stable
neurologic decits, admission to the hospital is not always required. However, the following comorbidities
or complications should be considered as possible reasons for admission to the hospital.
Signicant impairment of activities of daily living that render return to home unsafe
Suspected medical complications of stroke such as aspiration pneumonia, deep vein thrombosis,
cardiac dysrhythmia, urinary tract infection, dehydration, rhabdomyolysis or other problems requiring
medical intervention
Other medical comorbidities such as uncontrolled diabetes, uncontrolled hypertension or unstable
ischemic cardiac disease or dysrhythmia
Cause for stroke unclear and hospital admission necessary to expedite evaluation for causation
Inadequate anticoagulation in patients with atrial brillation
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Appendix A Glossary of Abbreviations

ACCESS Acute Candesartan Cilexetil MRA magnetic resonance angiogram
Evaluation in Stroke Survivors
MRI magnetic resonance imaging
AHA American Heart Association
NIH National Institutes of Health
aPTT activated partial thromboplastin
NIHSS National Institutes of Health
time
Stroke Scale
ASA aspirin
NINDS National Institute of Neurological Disorders
AVM arteriovenous malformation and Stroke
BID twice daily PROACT Prolyse in Acute Cerebral
Thromboembolism
BP blood pressure
PT prothrombin time
BUN blood urea nitrogen
r-pro UK recombinant prourokinase
CBF cerebral blood ow
tPA tissue plasminogen activator
CNS central nervous system
SBP systolic blood pressure
CPP cerebral perfusion pressure
SPECT single proton emission tomography
CT computed tomography
TCD transcranial Doppler
CV cardiovascular
TIA transient ischemic attack
CVR cerebrovascular resistance
TOAST Trial of ORG 10172 in Acute Ischemic
DBP diastolic blood pressure
Stroke Trial
ECASS European Cooperative Acute
Stroke Study
ED Emergency department
EKG electrocardiogram
EMS Emergency medical system
FDA Food and Drug Administration
ICSI Institute for Clinical Systems
Improvement
ICU Intensive care unit
INR international normalized ratio
IV intravenous
MAP mean arterial pressure
MCA middle cerebral artery
MI myocardial infarction
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ICS I
Supporting Evidence:

I N S T I TU TE F OR C LIN ICA L
S Y S T E M S I M P ROV E M E N T
Availability of references
Document Drafted
Jan Jun 2000 References cited are available to ICSI participating member groups
First Edition on request from the ICSI ofce. Please ll out the reference request
Oct 2001
sheet included with your guideline and send it to ICSI.
Second Edition
Nov 2002
Third Edition
Nov 2003
Fourth Edition
Feb 2005
Fifth Edition Released in February 2006 for Sixth Edition.
Begins Mar 2006
The next scheduled revision will occur within 12 months.
Original Work Group Members

Ansar Ahmed, MD Diane Jacobsen, MPH Kathleen Neacy, MD
Neurology Measurement Advisor Emergency Medicine
HealthPartners Medical ICSI HealthPartners Medical
Group James Lee, MD Group
David Anderson, MD Family Practice Manuel Ramirez-Lassepas, MD
Neurology RiverWay Clinics Neurology
Hennepin County Medical Joseph McRaith, MD HealthPartners Medical
Center Internal Medicine Group
Diane Davies, MD Aspen Medical Group Kathryn Schultz, PharmD
BHCAG Representative Barbara Mullikin, MS Pharmacy
Pzer Facilitator Allina Medical Clinic
Spring Davis, RN, BSN ICSI Eelco Wijdicks, MD
Health Education Neurology
HealthPartners Health Plan Mayo Clinic
Sandra Hanson, MD
Neurology, Work Group Leader
Park Nicollet Health Services
Contact ICSI at:

8009 34th Avenue South, Suite 1200; Bloomington, MN 55425; (952) 814-7060; (952) 858-9675 (fax)
Online at http://www.ICSI.org
Evidence Grading System

I. CLASSES OF RESEARCH REPORTS
A. Primary Reports of New Data Collection:
Class A: Randomized, controlled trial
Class B: Cohort study
Class C: Non-randomized trial with concurrent or historical controls
Case-control study
Study of sensitivity and specicity of a diagnostic test
Population-based descriptive study
Class D: Cross-sectional study
Case series
Case report
B. Reports that Synthesize or Reect upon Collections of Primary Reports:
Class M: Meta-analysis
Systematic review
Decision analysis
Cost-effectiveness analysis
Class R: Consensus statement
Consensus report
Narrative review
Class X: Medical opinion
II. CONCLUSION GRADES
Key conclusions (as determined by the work group) are supported by a conclusion grading worksheet that
summarizes the important studies pertaining to the conclusion. Individual studies are classed according
to the system dened in Section I, above, and are assigned a designator of +, -, or to reect the study
quality. Conclusion grades are determined by the work group based on the following denitions:
Grade I: The evidence consists of results from studies of strong design for answering the question
addressed. The results are both clinically important and consistent with minor exceptions at most. The
results are free of any signicant doubts about generalizability, bias, and aws in research design. Studies
with negative results have sufciently large samples to have adequate statistical power.
Grade II: The evidence consists of results from studies of strong design for answering the question
addressed, but there is some uncertainty attached to the conclusion because of inconsistencies among the
results from the studies or because of minor doubts about generalizability, bias, research design aws,
or adequacy of sample size. Alternatively, the evidence consists solely of results from weaker designs
for the question addressed, but the results have been conrmed in separate studies and are consistent
with minor exceptions at most.
Grade III: The evidence consists of results from studies of strong design for answering the question
addressed, but there is substantial uncertainty attached to the conclusion because of inconsistencies
among the results from different studies or because of serious doubts about generalizability, bias, research
design aws, or adequacy of sample size. Alternatively, the evidence consists solely of results from a
limited number of studies of weak design for answering the question addressed.
www.icsi.org
Evidence Grading System Fifth Edition/February 2006
Grade Not Assignable: There is no evidence available that directly supports or refutes the
conclusion.
The symbols +, , , and N/A found on the conclusion grading worksheets are used to designate the quality
of the primary research reports and systematic reviews:
+ indicates that the report or review has clearly addressed issues of inclusion/exclusion, bias, generaliz-
ability, and data collection and analysis;
indicates that these issues have not been adequately addressed;
indicates that the report or review is neither exceptionally strong or exceptionally weak;
N/A indicates that the report is not a primary reference or a systematic review and therefore the quality has
not been assessed.
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References
Adams H, Adams R, Del Zoppo G, Goldstein LB. Guidelines for the early management of patients
with ischemic stroke: a scientic statement from the Stroke Council of the American Heart Associa-
tion/American Stroke Association. Stroke 2005; 36:916-21. (Class R)
Adams HP, Brott TG, Crowell RM, et al. 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. Circulation 1994;90:1588-1601. (Class R)
Adams HP, Brott TG, Furlan AJ, et al. Guidelines for thrombolytic therapy for acute stroke: a supple-
ment to the 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 Associa-
tion. Circulation 1996;94:1167-74. (Class R)
Adams HP Jr, Davis PH, Leira EC, et al. Baseline NIH Stroke Scale score strongly predicts outcome
after stroke; A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology
1999;53:126-31. (Class B)
Albers GW, Amarenco P, Easton DJ, et al. Antithrombotic and thrombolytic therapy for ischemic stroke:
the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:483S-
512S. (Class R)
Alberts MJ, Hademenos G, Latchaw RE, et al. Recommendations for the establishment of primary
stroke centers. JAMA 2000;283:3102-09. (Class R)
Arboix A, Garcia-Eroles L, Oliveres M, et al. Clinical predictors of early embolic recurrence in presumed
cardioembolic stroke. Cerebrovasc Dis 1998;8:345-53. (Class B)
Archer CT, Horenstein S. Basilar artery occlusion. Clinical and radiological correlation. Stroke
1977;8:383-87. (Class D)
ATLANTIS, ECASS, and NINDS rt-PA Study Group Investigators, The. Association of outcome with
early stroke treatment: pooled analysis of ATLANTIS, ECASS and NINDS rt-PA stroke trials. Lancet
2004;363:768-74. (Class M)
Azzimondi G, Bassein L, Nonino F, et al. Fever in acute stroke worsens prognosis: a prospective study.
Stroke 1995;26:2040-43. (Class B)
Bath PMW, Bath FJ, Smithard DG. Interventions for dysphagia in acute stroke. (Cochrane Review).
In The Cochrane Library, Issue 2, 2001. Oxford: Update Software. (Class M)
Bath PMW, Lindstrom E, Boysen G, et al. Tinzaparin in acute ischaemic stroke (TAIST): a randomized
aspirin-controlled trial. Lancet 2001;702-10. (Class A)
Becker KJ, Monsein LH, Ulatowski J, et al. Intra-arterial thrombolysis in vertebrobasilar occlusion.
AJNR 1996;17:255-62. (Class D)
Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in
patients with acute ischaemic stroke and atrial brillation: a double-blind randomised study. Lancet
2000;35:1205-10. (Class A)
Blood pressure in Acute Stroke Collaboration (BASC). Interventions for deliberately altering blood
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Work Group's Conclusion: In human studies, early hyperthermia in acute stroke is associated with increased risk
of poor outcome, higher mortality, and increased infarct volume. The causality and the relationship of temperature elevation to these
poor outcomes is not fully understood. Whether intervention with cooling methods will result in improved outcomes is unknown.
Conclusion Grade: III

Author/Year Design Class Quality Population Studied/ Sam- Primary Outcome Measure(s)/Results (e.g., p-value, Authors' Conclusions/
Type + , , ple Size confidence interval, relative risk, odds ratio, likelihood Work Group's Comments (italicized)
ratio, number needed to treat)
Azzimondi et Pro- B -183 patients admitted to -75% were fully alert; 43% had fever during the first 7 -Fever in the first 7 days was an independ-
al. (1995) spective hospital with stroke days, 42% of the 67 with complete paresis developed ent predictor of poor outcome during the
Cohort (ischemic or hemorrhagic) fever of 37.9C compared with 12% of the 116 first month after a stroke.
(Hyperthermia)
Study and examined within 48 without complete paresis

hrs; randomized into the -Mean max temp in 1st 7 days for 78 febrile patients
study from consecutive pa- was 38.3C (median 37.9C); onset of fever: 15% of NOTE: did not separate ischemic from
tients admitted; diagnosis febrile patients during 1st day, 49% on 2nd day hemorrhagic stroke because only 60% had
based on WHO criteria -Overall 30 day mortality was 29% CT scans; no data available on underlying
-Axillary temperature on -Multivariate logistic regression: age >75 yrs causes of fever
unaffected side of body (OR=3.8), impaired consciousness (OR=11.4), and
Institute for Clinical Systems Improvement

taken at least twice daily glycemia <6.7 mmol/L (OR=4.1) were predictive of
during first 7 days of hos- worse prognosis (all p0.003)
pitalization; recorded -With addition of fever (max temp 37.9C): age
maximum temperature and (OR=3.7), consciousness (OR=9.7), glycemia
day of onset of fever (OR=3.0), and fever (OR=3.4) were predictive of
worse prognosis (all p0.009)
-OR of death within 10 days vs. between 11-30 days
was 4.9 (95%CI: 1.2-25.2) with fever 37.9C
Reith et al., Pro- B -390 patients admitted 6 -24% of patients died during hospital stay; 5% were -Acute lowering of temperature after stroke
(1996) spective hours or less after stroke; discharged with Scandinavian Stroke Scale (SSS) could reduce mortality and improve out-
Cohort diagnosis based on WHO score <15, 7% with score 15-29, 9% with score 30- come in survivors; particularly with hyper-
Study criteria; excluded subarach- 44, 55% with score 45-58 thermic patients.
noid hemorrhage -Body temperature was independently and significantly
-CT done at median of 8 related to initial stroke severity, lesion size, mortality,
days (based on scanner and outcome in survivors NOTES: limited study to those admitted
availability) -Multivariate logistic regression: for mortality tem- within 6 hrs of onset based on work in
-Tympanic membrane perature OR=1.8 (95%CI 1.1-2.8); for poor outcome animals showing main benefit of hypo-
temperature recorded on (death or SSS score<30) temperature OR=2.2 (95%CI thermia in ischemia occurs in first few
admission 1.4-3.5); relations between temperature and poor out- hours; at baseline, 11% had temp. of
come was independent of stroke severity on admission 36.5C, 64% had temp of >36.5C to
-No association between season and body temp. 37.5C, 25% had temp >37.5C; mean
-Infection not related to mortality or poor outcome admission temp. was 37.2C
Conclusion Grading Worksheet A Annotation #27
www.icsi.org
47
Author/Year Design Class Quality Population Studied/ Sample Primary Outcome Measure(s)/Results (e.g., p-value, Authors' Conclusions/
Type + , , Size confidence interval, relative risk, odds ratio, likelihood Work Group's Comments (italicized)
Castillo, Pro- B -297 patients with cerebral -26 patients died between day 3 and last evaluation (3 -High body temperature within the first 24
Dvalos, Mar- spective infarction confirmed by CT; months); 7 patients not present at final visit; worse hours was independently related to larger in-
rugat, & Noya Cohort admitted within first 24 possible outcome scores assigned for those who died; farct volume, higher neurological deficit,
(1998) Study hours after onset of symp- last score carried forward for those lost and dependency at 3 months.
toms (or sleep) -In first 72 hours 158 (60.8%) developed hyperthermia
-37 patients died during 1st (91 in first 24 hrs, 49 in 24-48 hrs, 18 in 48-72 hrs)
3 days of data collection -Body temp. on admission was higher in the 37 who NOTES: use of antibiotics and antipyretics
leaving 260 for final analy- died in 1st 3 days (p=0.03); among survivors at 3rd day was not registered in the database
sis mortality rate at 3 months was 1% in normothermic
-Axillary temperature on and 16% those who developed hyperthermia within 1st
admission and every 2 hrs 72 hrs (p<0.001)
for 3 days; used highest -Canadian Stroke Scale (CSS) score on admission was
Annotation #27 (Hyperthermia)
temp. recorded in each 6 hr lower in hyperthermic patients (p<0.001); at 3

period from onset of stroke; months poor outcome in neurological deficit
Conclusion Grading Worksheet A
hyperthermia defined as (p<0.001) and functional capacity (p<0.001) was more

temp. >37.5C in 1 de- frequent in patients with hyperthermia; large cerebral

termination; tested for infec- infarct was more common in hyperthermic patients
tion in all patients with hy- (p<0.001)
perthermia; recorded time -Relationship between brain damage and hyperthermia
interval (from onset) at was greater the earlier the increase in temp.
which hyperthermia was -An infectious cause was found in 58% of patients
initially recorded with hyperthermia within 1st 72 hrs; mortality was
greater in those with infectious hyperthermia than
non-infectious (p<0.013)
-Multivariate logistic regressions: for patients with
hyperthermia initiated at 0-24 hrs OR for infarct vol-
ume was 3.23 (95%CI 1.63-6.43); OR for greater
deficit at 3 mos was 3.06 (95%CI 1.70-5.53); OR for
poor functional capacity at 3 most was 3.41 (95%CI
1.69-6.88); co-existent infections within the 1st 3 days
were not independently associated with poor prognosis
www.icsi.org
48
Sharma & Ross Pro- B Insuffi- -294 patients admitted with -Most significant predictors of mortality in 90 days: -Pyrexia may be related to stroke severity
(1998) (letter) spective cient in- acute stroke a. Dysphagia: RR=4.10 (95%CI: 2.39-7.05) in some patients, but is more likely to be
Cohort formation b. Pre-existing cardiovascular disease: RR=2.19 related to aspiration in the 54% of patients
Study (95%CI 1.45-3.30) who have unsafe swallowing.
c. Glasgow comma score <11: RR=2.22 (95%CI
1.48-3.33)
d. Rankin score>1: RR=1.78 (95%CI 1.20-2.64)
-Pyrexia not significant (RR=0.91, 95%CI 0.60-1.40)
Wang, Lim, Retro- B -509 patients admitted with -10.8% of ischemic patients died in hospital; of those -Among ischemic stroke patients, hypo-
Levi, Heller, & spective diagnosis of acute stroke discharged 17% died within 1 yr thermia was associated with a significant
Fisher (2000) Cohort -Excluded: no admission 54% of hemorrhagic patients died in hospital; of those reduction of in-hospital mortality; hyper-
body temperature in medical discharged 21% died within 1 yr thermia was associated with an increased
record; final diagnosis un- -ISCHEMIC STROKE: hypothermia at admission as- risk of 1 yr mortality.
clear or recorded only as sociated with reduced hospital mortality (OR=0.1;

acute cerebrovascular acci- 95%CI 0.02-0.5); swallowing difficulty, subcon-
dent sciousness, and unconsciousness associated (p<0.001) NOTES: initial screening identified 544
-86% ischemic stroke, 14% with increased hospital mortality; hyperthermia at ad- (excluded: 12 for subarachnoid hemorrhage,
hemorrhagic stroke mission associated with increased 1 yr mortality 7 for TIA, 1 for immediate death, 3 for in-
(RR=3.4; 95%CI 1.6-7.3); age, swallowing difficulty, complete records, 12 for diagnoses not
hypertension, ischemic heart disease, peripheral vascu- clearly classified as ischemic or hemor-
lar disease, and atrial fibrillation also significant pre- rhagic); no assessment of infarct or hemor-
dictors of 1 yr mortality rhage size; could not accurately determine
-HEMORRHAGIC STROKE: body temperature was presence of infection on admission but ele-
not a significant predictor of either hospital or 1 yr vated WBC count was not predictive of
mortality stroke outcome
www.icsi.org
49
Hajat, Hajat, & Meta- M N/A -9 studies included; 3790 -3 of 9 studies showed higher morbidity and mortality -The results suggest a detrimental effect of
Sharma (2000) Analy- patients in patients with hyperthermia hyperthermia on stroke outcome.
sis -2 studies showed higher mortality associated with
hyperthermia (morbidity not measured)
-2 studies showed mortality but not morbidity associ- NOTES: combined OR for mortality may
ated with hyperthermia be non-significant because majority of pa-
-2 studies showed mortality (the sole outcome meas- tients were from 2 negative studies (1924
ure) not associated with hyperthermia vs. 738); combined probability value was
-Combined OR for mortality (based on 5 studies 3 considered more representative; studies dif-
positive, 2 negative) was 1.19 (95%CI 0.99-1.43); fered in inclusion/exclusion of hemorrhagic
heterogeneity test p>0.05 stroke, assessment of/exclusion based on
-Combined probability value (based on 8 studies) was infection, statistical methods, duration at
significant (p<0.000001) which mortality and morbidity were meas-

ured; temperature measurement; definition
of hyperthermia

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50
Work Group's Conclusion: It is unclear whether early hyperglycemia in the setting of acute stroke may be a marker of physiologic stress or an
independent predictor of poor outcome. Usual management of hyperglycemia with gentle dosing of subcutaneous insulin in a timely manner during
acute ischemia would seem prudent until ongoing clinical trials address the appropriateness of more aggressive treatment measures.
Conclusion Grade: III

Author/Year Design Class Qual- Population Studied/Sample Size Primary Outcome Measure(s)/Results (e.g., p-value, Authors' Conclusions/
Type ity confidence interval, relative risk, odds ratio, likeli- Work Group's Comments (italicized)
+ , , hood ratio, number needed to treat)
Melamed Retro- B -Patients with acute complete -392 patients were included: 205 in Group A, 108 -A large number of stroke patients without a
(1976) spective stroke in Group B, 79 in Group C previous history of diabetes mellitus may
Cohort -3 stroke subtypes: cerebral in- -More brain-stem infarction and hemorrhagic stroke develop transitory reactive hyperglycemia
farction, brain-stem infarction, and less cerebral infarction in Group A vs. B soon after an acute cerebrovascular event.
and hemorrhagic stroke (includ- (p0.005); initial fasting glucose lowest in patients The reactive hyperglycemia is not an isolated
(Hyperglycemia)
ing subarachnoid) with cerebral infarction and highest in those with phenomenon but represents one aspect of the
-Excluded: transient attacks, hemorrhagic stroke (p0.05); there were more coma- multiple biochemical abnormalities associ-
admission >24 hrs after onset, tose and obtunded patients on admission in Group B ated with acute stroke. Regardless of the
undetermined stroke type, asso- (49%) than in Group A (18%) mechanism, there is a graver prognosis for
ciated acute major illness at time -In all Group B patients the initial hyperglycemia acute stroke patients with reactive hypergly-

of admission was reactive fasting serum glucose levels decreased cemia.
-Fasting serum glucose meas- by >20mg/100ml on follow-up measures
ured daily -Hospital mortality was 54% in Group B, 35% in
-3 groups: (A) non-diabetic, ini- Group C, 17% in Group A (p0.005 B vs. A); dif- NOTES: patients were classified as overt
tial glucose <120mg/100ml; (B) ference between B and A was not significant for diabetics if reliable history of diabetes was
not known to have diabetes, ini- those with brain-stem infarction (perhaps due to available; initial fasting glucose was taken
tial glucose >120mg/100ml; (C) small number of patients) the first morning after admission
known history of diabetes -79% of Group C had reactive increase in glucose
levels following stroke
Conclusion Grading Worksheet B Annotation #27
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51
Woo, Lam, Pro- B -Consecutive patients with acute -304 patients with strokes; 242 in 4 glucose toler- -The association between glucose concentra-
Kay, et al. spective stroke; examined within 48 ance categories tion and outcome is likely a reflection of
(1990) Cohort hours of ictus; excluded suba- -8% with cerebral infarct; 20% with intracerebral stress related to stroke severity and not a re-
rachnoid hemorrhage and TIAs hemorrhage, and 0% with lacunar infarct had stress sult of harmful effects of glucose on damaged
-3 stroke subtypes (based on hyperglycemia; if subjects with stress hyperglycemia neurons. Glucose concentration was related
clinical exam, CT, or autopsy): were excluded there was no difference in distribution to immediate outcome only in the intracere-
cerebral infarct, lacunar infarct, of diabetic and non-diabetic patients in 3 stroke sub- bral hemorrhage group and diabetic subjects
and intracerebral hemorrhage groups did not have a higher incidence of intracere-
-Fasting venous blood specimen -Mean plasma glucose concentration in diabetics was bral hemorrhage.
obtained within 24 hrs of admis- similar to that in patients with stress hyperglycemia
sion for estimation of glucose, -Highest mean glucose concentrations observed in NOTES: upper limits for normal HbA 1 and
glycosylated hemoglobin those who died; lowest concentrations in those who fructosamine were established for local Chi-
(HbA1), & fructosamine levels recovered completely (p<0.0001 for all strokes, nese population; blood samples not available
Annotation #27 (Hyperglycemia)
-4 glucose tolerance categories: p<0.02 for intracerebral hemorrhage) from all patients and not all patients fell into
Conclusion Grading Worksheet B
known diabetics, newly diag- -No association between glucose concentration and the 4 glucose tolerance categories

nosed diabetics, stress hypergly- degree of disability at 3 months
cemia, non-diabetics -Patients with stress hyperglycemia (n=23) had the Work Groups Comments: intracerebral
-Outcome at end of hospitaliza- highest mortality; if this group was excluded higher hemorrhage accounted for 28% of all strokes
tion was either full recovery, numbers of patients with diabetes had disability on which is higher than observed in white popu-
disability, or death discharge but by 3 months there was no difference in lations; study was financially supported by
-Assessed ADL, Barthel scale, disability or mental test score between diabetics and Merck, Sharp, & Dohme Ltd.
and cognitive function at 3 mos non-diabetics
Counsell, Pro- B Insuf- -530 patients seen within 30 -Diabetes mellitus was an adverse and independent -Hyperglycemia does not appear to be an in-
McDowall, & spective ficient days of stroke predictor of death (relative hazard 2.01; 95%CI 1.36- dependent prognostic factor in acute stroke.
Dennis (1997) Cohort Infor- -Developed model to predict 2.99)
(letter) mation probability of survival and dis- -Hyperglycemia was not a predictor of death (relative
ability; included history of dia- hazard 1.66; 95%CI 0.93-2.97) NOTES: a large randomized trial of glucose
betes, presence of acute hyper- -Neither diabetes mellitus nor hyperglycemia was an control in the acute phase of stroke is needed
glycemia and other variables in independent predictor of death or disability (modified to clarify the clinical management of patients
addition to several measures of Rankin score) at 6 months with hyperglycemia
stroke severity
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52
Kiers, Davis, Pro- B -176 consecutive patients admit- -10 patients with stress hyperglycemia (116 eugly- -Hyperglycemia or pre-existing diabetes (ei-
Larkins, et al. spective ted with acute stroke (excluding cemic with no history of diabetes, 20 new diabetics, ther known or newly diagnosed) are associ-
(1992) Cohort subarachnoid hemorrhage) and 30 known diabetics); 7 of the 10 had CT scans ated with a worse prognosis after stroke.
-Fasting glucose, HbA1c, cho- -Admission glucose concentration not significantly The difference appears to be related to bio-
lesterol, triglycerides, packed different between patients with stress hyperglycemia, chemical factors rather than stroke type or
cell volume, urea, creatinine, newly diagnosed diabetes, or known diabetes; each site. There is no proof of a causal relation
and fibrinogen assessed within group higher than euglycemic, non-diabetic group between hyperglycemia and adverse stroke
24 hrs after admission (p<0.001) prognosis.
-4 groups: euglycemic with or -No differences in type of stroke between 4 groups
without marginally elevated except greater proportion of cortical infarction in
HbA1c; stress hyperglycemic; newly diagnosed diabetics (vs. euglycemic, non- NOTES: patients with stress hyperglycemia
newly diagnosed diabetics; diabetics; p<0.05); combined hyperglycemic and dia- and known diabetics had CT scans signifi-
known diabetics betic groups not different from euglycemic, non- cantly earlier than euglycemic, non-diabetic
-5 stroke types (for 152 with CT diabetic group in stroke type patients (p<0.01); a randomized controlled
scans) -No difference between 4 groups in site of lesions trial is needed to study glucose management

-Ischemic lesions and cerebral -More large lesions in patients with stress hypergly- in acute stroke
hemorrhages were classified as cemia (vs. euglycemic, non-diabetics; p<0.05);
small, medium or large combined hyperglycemic and diabetic groups not
-Neurological deficits assessed different from euglycemic, non-diabetic group Work Groups Comments: small number of
on admission; in hospital mor- -Stroke severity worse in patients with stress hyper- patients with stress hyperglycemia
tality documented glycemia (p<0.001) and diabetics (p<0.05) (vs.
euglycemic, non-diabetics)
-Mortality significantly higher in patients with
stress hyperglycemia and newly diagnosed diabetes
(both p<0.001) (vs. euglycemic, non-diabetics)
-Mean admission glucose (entire group) significantly
higher in patients who died vs. survivors (p<0.05);
for hyperglycemic and diabetic patients no relation-
ship between glucose concentration and mortality;
combined hyperglycemic and diabetic groups had
higher proportion of patients who died (OR=4.5;
95%CI 2.1-10.0); survival for newly diagnosed dia-
betics intermediate between hyperglycemic and
euglycemic or known diabetic groups
-Significantly greater mortality in patients with
stress hyperglycemia was due to increase in early
deaths (all within 1 week after stroke; all neurologi-
cal causes)
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53
Jrgensen, Na- Pro- B -Patients admitted with acute -1135 included in study (176 with diabetes before -Admission glucose in diabetic patients does
kayama, spective stroke during a 2-yr period stroke, 57 with diagnosis after stroke) not affect initial stroke severity or mortal-
Raaschou, & Cohort -Excluded patients without reli- -Patients with diabetes before stroke were older ity. Admission glucose in patients without
Olsen (1994) able data about diabetes (2.9%) (p<0.001), fewer men (p=0.01), more likely to have diabetes is independently related to initial
and subarachnoid bleeding hypertension (p=0.00001), more likely to have in- stroke severity and increased glucose levels
-3 groups: without diabetes, tracerebral hemorrhage (p=0.002), more likely to die independently increase mortality from stroke.
known diabetes before stroke, during hospital stay (p=0.03), and more likely to Reducing high admission glucose levels in
diabetes diagnosed after stroke have a slower neurological recovery (p=0.01 at 1 nondiabetic stroke patients could have a
-Assessed neurological deficits week) but to be comparable at discharge beneficial effect on stroke outcome.
and functional ability -Blood glucose levels on admission (AGL) were as-
-CT scan done (median of 8 days sessed for patients admitted within 48 hours from NOTES: excluded patients with diabetes di-
after stroke onset) in 83% stroke onset (133 with diabetes, 623 without) agnosed after stroke from comparisons of pa-
-Assessed comorbidities and risk a. Patients with diabetes: no relation between AGL tients with and without diabetes because of
factors for stroke and initial stroke severity or mortality uncertainty over whether stroke preceded or
-5 categories of cause of death b. Non-diabetic patients: AGL related to initial provoked diabetes; also WHO stroke diagno-

(from directly due to stroke to stroke severity (p<0.0001) and mortality (p<0.0001) sis criteria applies to non-stressed situations
unrelated to stroke) with higher AGL associated with lower SSS score
and greater mortality Work Groups Comments: it is not clear
whether mortality data is in-hospital mor-
tality only
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54
Weir, Murray, Pro- B -All patients who present within -811 patients included; analysis focused on 750 non- -Plasma glucose concentrations above 8
Dyker, Lees spective 72 hrs of onset of acute neuro- diabetic patients mmol/l after acute stroke predicts a poor
(1997) Cohort logical deficit; diagnosis of -At 12 months, 60% were alive at home, 9% were prognosis after correcting for age, stroke se-
hemorrhagic or ischemic stroke alive in care, and 30% had died verity, and stroke subtype. The results sug-
is made with CT -Hyperglycemia led to higher mortality even after ad- gest that hyperglycemia is not solely a stress
-4 stroke subtypes justing for other prognostic variables (such as stroke response to neurological insult and therefore
-Glucose concentration from type, time to resolution of symptoms, blood pres- should be treated actively.
blood sample on day of admis- sure, smoking status)
sion (77%) or early the next -At 3 months, 15% of the hyperglycemic group were NOTES: 15 patients were lost to follow-up
morning (fasting, 23%) alive at home, 21% were alive in care, and 40% were for placement (in home or in care) but not
-Follow-up to 12 months after dead (p<0.0001 between groups) survival; a randomized trial is needed
admission via deaths register or -Estimated relative hazards of 1.87 (95%CI 1.43-
hospital discharge records 2.45; p<0.0001) for hyperglycemia; 1.36 (95%CI Work Groups Comments: this study was
1.21-1.53; p<0.0001) for increasing age (per decade), criticized by Counsell et al. (1997) for as-
2.15 (95%CI 1.15-2.05; p=0.015) for symptoms sessing stroke severity in a limited way (Ox-
remaining after 72 hours, and 1.67 for hemorrhagic fordshire Community Stroke Project classifi-

stroke (95%CI 1.22-2.28; p=0.001) cation and time to resolution of symptoms)
Bruno, Biller, Pro- B -Patients enrolled in a multi- -Very favorable outcome: score of 1 on Glasgow -Acute hyperglycemia is associated with
Adams, et al. spective center, randomized, double-blind, Outcome Scale and score of 19 on modified Barthel worse outcome from nonlacunar stroke.
(for TOAST Cohort acute ischemic stroke treatment Index Lowering elevated blood glucose levels dur-
Investigators) trial -Neurologic improvement: decrease of 4 points or a ing acute nonlacunar ischemic stroke might
(1999) -Study drug could be started final score of 0 on NIH Stroke Scale (at 3 months) be beneficial. For lacunar stroke, the out-
within 24 hrs of symptom onset -Hemorrhagic transformation assessed by CT at 7-10 come depended on treatment. In placebo
-Screening blood test days after drug infusion group, acute hyperglycemia was associated
-No standard protocol for treat- -Analyzed data from 1,259 of 1,281 randomized (6 with a better outcome. In active drug group,
ment of hyperglycemia lost to follow-up and 16 excluded for missing data) odds of good outcome decreased sharply as
-Neurologic exam, functional -Odds ratios for very favorable outcome associated the glucose levels rises to 150 mg/dL. After
assessment, determination of with every 100mg/dL increase in blood glucose 150 mg/dL there is little change in response
hemorrhagic transformation, (note: for all strokes and nonlacunar strokes higher to further increases in blood glucose level.
stroke subtype classified blood glucose associated with worse outcome):
-Logistic regression included a. All strokes OR=0.82 (p=0.03) NOTES: this study was part of a larger trial
possible confounding factors of b. Nonlacunar strokes OR=0.74 (p=0.02) testing the efficacy of low-molecular-weight
experimental drug treatment, c. Lacunar strokes no OR due to nonlinear re- heparinoid vs. placebo
diabetes mellitus, hypertension, sponse (p=0.002)
age, tobacco use, alcohol use, -Odds ratios for neurologic improvement were not
aspirin use in last 7 days, stroke significant for all strokes or either subtype
subtype -Hemorrhagic transformation odds ratio was not sig-
nificant for all strokes
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55
Work Group's Conclusion: The routine use of acute anticoagulation treatment with unfractionated heparin low-molecular-weight heparin,
or heparinoid, in acute ischemic stroke is not supported by the available evidence. This treatment does not appear to improve clinical outcome from
the index stroke. There may be subgroups who benefit, but further studies of this problem are required for confirmation.
Conclusion Grade: I
Author/Year Design Class Qual- Population Studied/ Sample Primary Outcome Measure(s)/Results (e.g., p-value, Authors' Conclusions/
Type ity Size confidence interval, relative risk, odds ratio, likeli- Work Group's Comments (italicized)
+ ,, hood ratio, number needed to treat)
Sandercock, van Meta- M N/A -15 completed, truly random- -11 trials of anticoagulant (6 heparin, 4 LMWH, 1 -For patients with acute ischemic stroke,
den Belt, Analy- ized trials of early treatment oral anticoagulants) vs. control in ischemic stroke; 1 there is uncertainty about the balance of risks
Lindley, & sis with antithrombotic agents in trial of heparin vs. control in hemorrhagic stroke and potential benefits from early antithrom-
Slattery (1993) patients with acute stroke; ran- a. 9 trials reported DVT data: overall, treatment was botic therapy with either heparin or aspirin.
domization took place 7 days associated with 79% reduction in odds of confirmed A policy of routine antithrombotic therapy
after onset of stroke; excluded DVT in scheduled treatment period (p<0.00001) in the acute phase of stroke cannot be justi-
trials in patients with only b. 3 trials reported PE data: overall, treatment was fied until the results of large trials are avail-
TIAs associated with 58% reduction in odds of PE (NS) able.

c. 12 trials reported death from all causes by end of
scheduled follow-up: overall, treatment was associ-
ated with 14% reduction in odds of death (NS); for
10 heparin trials in ischemic stroke reduction was
18% (NS); for 1 trial of hemorrhagic stroke treat-
ment was associated with 31% increase in odds of
death (NS)
d. 5 trials reported data on hemorrhagic transforma-
tion (HTI) detected by CT scan (performed for clini-
cal deterioration): treatment was associated with a
198% excess of HTI (NS); if analysis was restricted
to HTI on routine scans at end of scheduled treatment
period or fatal hemorrhagic stroke, treatment was as-
sociated with a 13% increase in HTI (NS)
-6 trials of antiplatelet therapy: 3 not completed at
time of publication; 2 did not systematically record
data on clinical events; 1 too small
Conclusion Grading Worksheet C Annotation #31 (Heparin)
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56
Kay, Wong, RCT A -Patients admitted to hospital; -312 patients randomized (11% of 2750 screened); -LMWH given as nadroparin at a dosage of
Yu, et al. clinical diagnosis of acute 308 included in analysis 4100 anti-factor Xa IU twice daily for 10
(1995) stroke; motor deficit present -No differences between groups at baseline days was effective in reducing the risk of
-Included: symptoms started -At 10 days: 23 deaths (7.5%) and 28 complications death or dependency 6 months after a stroke.
during previous 48 hrs leading to early discontinuation of study drug (no dif- The treatment was safe; there was no signifi-
-Excluded: age >80 yrs, intra- ferences among groups for either parameter) cant difference between the treated patients
cranial hemorrhage (by CT), -Of 245 who had second CT 22 (9%) had evidence of and those given placebo in rates of hemor-
transient neurological deficits, hemorrhagic transformation of infarcts (no differ- rhagic transformation of the infarct or other
sustained hypertension (SBP> ences among groups) complications.
Annotation #31 (Heparin)
180mmHg or DBP> 120 -At 3 months: 42 deaths (13.6%); 2 in high-dose

mmHg), major confounding ill- group couldnt be located; risk ratio for poor out-
ness, recent major operation, come in high-dose group vs. placebo was 0.83 NOTES: Nonstudy medications were al-
known tendency toward bleed- (95%CI: 0.66-1.05); risk ratio for low-dose group lowed; use of other antithrombotic agents
ing, current anticoagulation vs. placebo was 0.95 (95%CI: 0.76-1.17); no differ- was discouraged; CT scan at end of treatment
Conclusion Grading Worksheet C
therapy or valvular disease ne- ence in percent with poor outcomes among groups was added after 49th patient; 4 patients were
cessitating such therapy, known -At 6 months: 50 deaths (16.2%); 1 high-dose pa- found to be ineligible before randomization

hypersensitivity or adverse reac- tient located but another lost; risk ratio for poor out- code was broken; the measure of dependency
tion to heparin come in high-dose group vs. placebo was 0.69 used in this study had a sensitivity of 94%
-Randomly assigned to high- (95%CI: 0.54-0.90); risk ratio for low-dose group and a specificity of 80% relative to the
dose LMWH, low-dose LMWH, vs. placebo was 0.81 (95%CI: 0.64-1.02); favorable Barthel index
or placebo (subcutaneous, dose-dependent effect of LMWH (p=0.005)
2x/day for 10 days) -Between 3 and 6 months functional status of 26 pa-
-After 10 days all patients were tient improved (11 high-dose, 9 low-dose, 6 placebo)
given oral aspirin (100 mg/day) and 10 worsened (2 high-dose, 1 low-dose, 7 pla-
-Defined subtypes: total or par- cebo)
tial infarct of anterior circula- -Compliance: 10 in high-dose, 7 in low-dose, and 11
tion, lacunar infarct, infarct of in placebo group did not complete full 10 days of
posterior circulation treatment; at 3 months 87% were taking aspirin; at 6
-Initial assessment at 10 days af- months 81% were taking aspirin; no carotid endarter-
ter randomization (cause of any ectomies
death, complications, use of
nonstudy medications, CT scan)
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57
International RCT A + -Included: evidence of acute -19,435 patients were randomized (467 hospitals/36 -Heparin (low and medium dose combined)
Stroke Trial stroke (irrespective of severity) countries); outcome follow-up 99.99% complete at did not significantly affect deaths at 14 days
Collaborative with onset <48 hrs previously; 14 days and 99.2% complete at 6 months or death or dependency at 6 months.
Group (1997) no indications for or contraindi- -Heparin vs. avoid heparin:
cations to heparin or aspirin; a. no difference in deaths within 14 days; by causes
physician uncertain whether to of death more deaths attributed to hemorrhagic stroke NOTES: CT scan was done before randomi-
administer either or both of aspi- (p=0.04) and extracranial bleeding (p=0.02) in hepa- zation unless there was likely to be a long
rin or heparin rin group delay (in which case the initial doses could
-Excluded: small likelihood of b. heparin patients had fewer recurrent ischemic be given before CT with treatment stopped if
worthwhile benefit or high risk strokes in 14 days (p=0.005) but more hemorrhagic hemorrhage was found); intention-to-treat
of adverse effects stroke (p<0.00001); no difference in combined out- analysis (clinicians could depart from treat-
-CT before randomization where come of death or any non-fatal recurrent stroke; ex- ment but not withdraw a patient from fol-
possible, mandatory for coma- cess of 9 transfused or fatal extracranial bleeds per low-up); patients could continue any pre-
tose patients 1000 patients allocated heparin (p<0.00001); heparin scribed nonsteroidal anti-inflammatory drugs
-Defined infarcts as total or par- patients had fewer pulmonary emboli (p=0.02) but no aspirin groups were to avoid anal-

tial anterior; posterior, lacunar, c. at 6 months no difference in number of deaths or gesics containing aspirin unless necessary;
or other number alive but dependent compliance was good low dose heparin re-
-Prognosis predicted by model d. subgroup analyses no clear evidence of any ceived as scheduled by 90% and medium dose
-Randomized to 6 groups: beneficial effect from heparin heparin by 88%, no heparin was received by
a. 300 mg aspirin/12,500 IU -Medium vs. low dose heparin: 94% allocated to avoid heparin, aspirin was
heparin a. medium dose caused higher risk of death or non- taken as scheduled by 92% and avoided as al-
b. 300 mg aspirin/5000 IU fatal stroke within 14 days (p=0.007) located by 93%; chief reason for stopping
heparin b. no net effect on death or dependency at 6 months treatment before 14 days was early discharge
c. 300 mg aspirin/no heparin c. compared to avoid heparin low dose heparin (but
d. no aspirin/12,500 IU heparin not medium dose) was associated with reduced early
e. no aspirin/5000 IU heparin death or stroke (p=0.03)
f. no aspirin/no heparin
-Treatment for 14 days or until
prior discharge; clinicians con-
sidered aspirin at discharge
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58
Publications RCT A + -Included: 18-85 yrs old; evi- -1281 were enrolled (of 25,624 screened) -Despite an apparent positive response to
Committee for dence of acute or progressing -No differences between groups at baseline treatment at 7 days, emergent administration
the Trial of ischemic stroke with symptoms -No difference in rate of favorable outcome at 3 of the antithrombotic agent ORG 10172 is
ORG 10172 in present >1 hr but <24 hrs; esti- months, favorable outcome at 7 days, or very favor- not associated with an improvement in fa-
Acute Stroke mated prestroke modified Barthel able outcome at 3 months; 33.9% of ORG 10172 vorable outcome at 3 months. Emergent
Treatment index of 12 group and 27.8% of placebo group had a very favor- administration of antithrombotic drugs is as-
(TOAST) In- -Excluded: resolution of symp- able outcome at 7 days (p=0.01) sociated with major bleeding and an increased
vestigators toms; mild deficit; coma; mass -No difference in percentages with treatment stopped risk of intracranial hemorrhage especially
(1998) effect or intracranial blood on prematurely because of neurological deterioration, among persons with major stroke.
CT; active bleeding; major sur- percentages with worsening of 4 points (NIHSS
gery in previous 24 hrs; already score) at 1 wk, or improvement of 4 points (or
receiving anticoagulation; reached score of 0) NOTES: For patient safety two amendments
thrombolytic therapy in previ- -For patients with strokes due to large-artery athero- to the protocol were made during the study
ous 24 hrs; mean BP>130 sclerosis the rates of favorable (p=0.04) and very fa- patients with an NIHSS score of >15 or a
mmHg; complex or terminal vorable (p=0.02) outcomes at 3 months were higher body weight <125 lb were excluded; heparin,
medical illness; allergy to hepa- for those receiving ORG 10172; no differences for warfarin, ticlopidine, and NSAIDs were pro-

rin; pregnant or lactating other stroke subtypes hibited during the 7-day treatment period;
-Defined subtypes as large-artery -8.5% of ORG 10172 and 5.4% of placebo groups study did not enroll patients with severe defi-
atherosclerosis, cardioembolism, (p<0.05) had adverse experiences prompting prema- cits
small-artery occlusion, other, or ture termination of therapy
undetermined cause -Greater incidence of both serious bleeding and minor -Work Groups Comments: Subgroup
-Randomized to ORG 10172 or bleeding in the ORG 10172 group during treatment analyses showed important outcomes with
placebo; IV bolus dose then con- and within 10 days of enrollment (all p<0.05) strokes due to large vessel atherosclerosis;
tinuous infusion for 7 days -No difference between treatment groups in hemor- further studies are needed to confirm those
rhagic transformation of ischemic stroke within 10 findings
days of enrollment
-No difference between treatment groups in mortality
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59
ICS I
I NS TI TU T E F OR C L I N I C A L
S YS TE M S I M PROV E ME NT
Support for Implementation:
This section provides resources, strategies and measurement specications

for use in closing the gap between current clinical practice and the
recommendations set forth in the guideline.
The subdivisions of this section are:
- Measurement Specications
Key Implementation Recommendations
Knowledge Products and Resources
Other Resources Available


1. Increase the percentage of patients presenting within 3 hours of stroke onset who are evaluated within
10 minutes of arriving in the ED.
Possible measure for accomplishing this aim:
a. Percentage of patients presenting within 3 hours of stroke onset who are evaluated by a physician
within 10 minutes of arriving in the ED.
2. Increase the percentage of patients receiving appropriate thrombolytic and antithrombotic therapy for
ischemic stroke (use of tPA and aspirin).
Possible measures for accomplishing this aim:
a. Percentage of eligible patients presenting with ischemic stroke treated with tPA.
b. Percentage of patients who are not candidates for tPA treatment who receive aspirin within 24 hours
of hospitalization, after a negative head CT, unless contraindicated.
c. Percentage of patients receiving tPA according to guideline (Refer to Annotations #29 and 32).
d. Percentage of patients who are candidates for tPA with a "door to drug" time (time of arrival to time
of drug administration) of less than 60 minutes.
e. Percentage of patients who undergo a CT scan within 25 minutes of arrival in the ED.
3. Increase the percentage of non-tPA recipients who have hypertension appropriately managed in the rst
48 hours of hospitalization or until neurologically stable.
Possible measure for accomplishing this aim:
a. Percentage of non-tPA recipients who have hypertension appropriately managed according to the
guideline. (Refer to Annotation #33).
www.icsi.org
Priority Aims and Suggested Measures Fifth Edition/February 2006
4. Increase the percentage of patients who receive appropriate medical management for prevention of
complications within the initial 24-48 hours of diagnosis:
continue to treat hypoglycemia and hyperglycemia
continue to treat hyperthermia
continue IV uids
continue to treat hypoxia
initiate deep vein thrombosis prophylaxis
perform swallow evaluation
initiate early rehabilitation (early mobilization)
perform nutritional status assessment
a. Percentage of patients who receive appropriate intervention for hypoglycemia and hypergly-
cemia.
b. Percentage of patients who receive appropriate intervention for hyperthermia.
c. Percentage of patients who receive IV uids.
d. Percentage of patients who receive appropriate treatment for hypoxia.
e. Percentage of patients with ischemic stroke with paralysis or other reason for immobility receiving
appropriate prevention for venous thromboembolism (subcutaneous heparin or pneumatic compres-
sion device.)
f. Percentage of patients who are at risk for aspiration who receive an early swallow evaluation.
g. Percentage of patients mobilized from bed within 48 hours of admission.
5. Improve patient and family education of patients with ischemic stroke in both the ED and the admitting
hospital unit.
a. Percentage of patients presenting in the ED with ischemic stroke for whom patient/family education
is documented in the medical record.
b. Percentage of patients admitted to a hospital unit with ischemic stroke for whom patient/family
education is documented in the medical record.
At this point in development for this guideline, there are no specications written for possible measures listed
above. ICSI will seek input from the medical groups on what measures are of most use as they implement
the guideline. In a future revision of the guideline, measurement specications may be included.
www.icsi.org
Key Implementation Recommendations

The following system changes were identied by the guideline work group as key strategies for health care
systems to incorporate in support of the implementation of this guideline.
1. Hospitals should consider developing and implementing critical pathways, standing orders and a stroke
process to accomplish rapid evaluation and treatment.
a. Established process for expediting the evaluation and treatment of patients who are candidates
for intravenous tPA.
b. Presence of standing orders for acute stroke to include:
ongoing antithrombotic therapy
management of blood pressure
early mobilization
use of appropriate anti-embolism treatment in the paralyzed patient
2. A process should be in place for the patient and family that will rapidly orient them to the suspected
diagnosis, ED process, tests to be preformed, tPA treatment and its risks, and other treatment measures
to be considered. This could include both caregiver face-to-face interactions with the patient and family
as well as teaching tools in written form.
Joint Commission for Accreditation of Healthcare Organizations (JCAHO) Primary Stroke Center Certi-
cation
JCAHO offers certication as Primary Stroke Centers to hospitals that meet specic qualications. The
emphasis of the process is on the early recognition and management of stroke and the scope of accreditation
includes integrated efforts in public awareness, emergency medical services, emergency room and hospitaliza-
tion (Alberts, 2000). The link is: http://www.jcaho.org/dscc/dsc/performance+measures/stroke+measure+set.
htm
Among the requirements for certication is ongoing process improvement guided by data and benchmarking.
The quality indicators chosen by JCAHO overlap with those developed by the ICSI Diagnosis and Treatment
of Ischemic Stroke guideline work group. The JCAHO quality indicators have are:
1. Deep Vein thrombosis (DVT) Prophylaxis*
2. Discharge on Antithrombotics*
3. Patients with Atrial Fibrillation Receiving Anticoagulation Therapy*
4. Tissue Plasminogen Activator (t-PA) considered*
5. Antithrombotic Medication within 48 Hours of Hospitalization
6. Lipid Prole during Hospitalization
7. Screen for Dysphagia
8. Stroke Education
9. Smoking Cessation
10. Plan for Rehabilitation was Considered
www.icsi.org
Knowledge Products Fifth Edition/February 2006
* Initial standard stroke measure set. All ten measures comprise set for pilot testing.
Measures 1, 4, 5, 7, and 8 are similar to or identical to those measures listed in this document and within
the scope of the guideline.
Knowledge Products and Resources

Criteria for Selecting Resources
The preceding resources were selected by the Diagnosis and Initial Treatment of Ischemic Stroke guideline
work group as additional resources for providers and/or patients. The following criteria were considered
in selecting these sites.
The site contains information specic to the topic of the guideline.
The content is supported by evidence-based research.
The content includes the source/author, and contact information.
The content clearly states revision dates or the date the information was published.
The content is clear about potential biases, noting conict of interest and/or disclaimers as
appropriate.
Resources Available to ICSI Members Only

The following materials are available to ICSI members only. Also available is a wide variety of other
knowledge products including took kits on CQI processes and Rapid Cycling that can be helpful. To
obtain copies of these or other Knowledge Products, go to http://www.icsi.org/knowledge.
To access these materials on the Website you must be logged in as an ICSI member.
Educational Resources
Guideline pilot reports
Guideline Pilot Report from Park Nicollet Health Services
Process Improvement Reports (PIRs)
Example of a Systematic Approach to Process Change at Methodist Hospital
www.icsi.org
Other Resources Available

Title/Description Audience Author/Organization Websites/Order Information
comprehensive website Providers, patients ASA (American Stroke http://www.strokeassociation.
patient education resources and other users Association) org
across the
continuum
links to clinical trials Providers, patients NINDS http://www.ninds.nih.gov/
contains entire discussion and and other users (National Institute of
guidelines for system change to across the disease Neurological
address stroke treatment continuum Disorders and Stroke)
comprehensive website Users across the NSA (National Stroke http://www.stroke.org
patient education resources disease continuum Association)
links to survivor/caregiver
products and services and
additional related websites
contains tools for health care Providers, patients The Brain Attack http://www.stroke-site.org/
professionals developing and other users Coalition
systems to enable the rapid across the disease
diagnosis and treatment of continuum
acute stroke
patient education resources
www.icsi.org

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ICSI

I NSTITUTE FOR C LINICAL

Mayo Clinic Symptoms consistent Refer to Emergency Department

Pharmacy TIA symptoms Transport to ED by 911 or

These clinical guidelines are 13

designed to assist clinicians Clinic appointment within 1

Neurological deficit no ED evaluation (per usual ED

Stroke Code Algorithm

Patient meets criteria for

Other post-ED medical management (first 24-48 hours)

Ischemic Stroke ED Management (not a thrombolysis candidate)

yes Does the patient no

Return to box 33, Post-ED Initiate appropriate

Clinical Highlights and Recommendations

Priority Aims and Suggested Measures

Related ICSI Scientic Documents

Disclosure of Potential Conict of Interest

1. Initial Contact with Patient with Complaint of Neurological

2. Immediate Screening for Ischemic Stroke

Transient global amnesia

4. Refer to Emergency Department (ED) or Physician's Ofce as

5. Symptoms Present Now?

6. Possible Ischemic Stroke Symptoms Onset Within 24 Hours?

7. Ischemic Stroke Symptoms Present for > 24 Hours/Symptoms Mild

9. Possible TIA Symptoms Within 2 Hours?

11. Transport to ED by 911 or Other Means

13. Clinic Appointment Within One Week of Symptoms Occurring > 2

14. High Risk for Immediate Future Events?

15. Clinic Appointment Within 72 Hours

ED Treatment Algorithm Annotations

21. Intra-Arterial Thrombolytic Candidate? (Option Available?)

Middle Cerebral Artery Occlusion

23. See Stroke Code Algorithm

Stroke Code Algorithm Annotations

25. Stroke Code

26. Evaluation (Should Occur Concurrently with Intervention)

Indications for tPA

Contraindications for tPA

Intracranial tumor, aneurysm, arteriovenous malformation (AVM) or other space-occupying

Perform Vital Signs Every 15 Minutes with Neuro Checks

Record Weight (estimate if needed)

Perform CT Head Without Contrast

Other Cardiac Assessment as Appropriate (Telemetry)

27. Intervention (Should Occur Concurrently with Evaluation)

Maintain euvolemia with isotonic uids.

Treat Hypertension if greater than 185 systolic or 110 diastolic

Blood Pressure Level (mm Hg) Treatment

Treat other symptoms of stroke such as headache, pain,

Treat other acute complications of stroke, including hypoxia,

B. Eligible for thrombolytic therapy

During and after treatment

Systolic 180-230 OR Labetalol 10 mg IV over 1-2 min

Adapted from the American Heart Association.

28. Patient Meets Criteria for tPA, Has No Contraindications and

29. Initiate tPA

31. Initiate Aspirin Unless Contraindicated (See Annotation

Also, the measured hazard appears to be small and statistically insignicant:

Considerations with Heparin Use

32. Post-ED Medical Management (Post-Thrombolysis)

Treat BP if greater than 180/105

33. Post-ED Medical Management (Not a Thrombolysis Candidate)

Captopril 6.25-25 mg by mouth (or sublingual) and repeat as required

34. Other Post-ED Medical Management (First 24-48 Hours)

Initiate deep vein thrombosis (DVT) prophylaxis