| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2001;32:12.)
© 2001 American Heart Association, Inc.
Original Contributions |
Protocol Violations in Community-Based rTPA Stroke Treatment Are Associated With Symptomatic Intracerebral Hemorrhage
From the Department of Neurology, Indiana University School of Medicine, Indianapolis, Ind (A.M.L.-Y., A.B., L.S.W., E.Y., J.B.); Roudebush Veterans Administration Medical Center, Indianapolis, Ind (L.S.W.); Regenstrief Institute for Health Care (L.S.W.), Indianapolis, Ind; and Sanatorio Mitre, Buenos Aires, Argentina (Z.C.).
Correspondence to Alfredo Lopez-Yunez, MD, Department of Neurology, Indiana University 1050 Walnut St, 6th Floor, Indianapolis, IN 46202. E-mail alopez1{at}iupui.edu
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background—Recombinant tissue plasminogen activator (rTPA) is an established treatment for acute ischemic stroke. The rate and type of protocol violations in rTPA use and their effect on patient outcomes in this setting are not well understood.
Objective—The objective of this study was to examine associations between protocol violations and outcomes in community-based rTPA use.
Methods—We reviewed medical records of stroke patients treated with rTPA in 10 acute-care hospitals in Indianapolis from July 1996 to February 1998 and assessed complications and outcome. Retrospective National Institute of Health Stroke Scale (on admission and discharge), Canadian Neurological Scale, and length of hospital stay were calculated. Appropriate use of rTPA was determined by the National Institute of Neurological Disorders and Stroke (NINDS) protocol.
Results—Fifty patients (mean age, 66 years; 76% white; 56% men) were treated by general neurologists (70%), stroke neurologists (24%), or emergency physicians (6%). Mean times to hospital arrival, brain CT, and start of rTPA infusion were 44, 86, and 141 minutes, respectively. In-hospital mortality rate was 10% (4 intracerebral hemorrhage [ICH], 1 cardiogenic shock). Complications were more frequent among patients with protocol violations (n=8) compared with those without all hemorrhages (75% versus 10%, P<0.001), symptomatic ICH (38% versus 5%, P<0.02), and ICH attributable to rTPA, occurring within 36 hours (38% versus 2.4%, P<0.01), respectively.
Conclusions—NINDS protocol violations are relatively common and are associated with symptomatic cerebral and systemic hemorrhages. When the NINDS protocol is strictly followed, hemorrhage rates in community-based rTPA use are similar to those in the NINDS trial.
Key Words: intracerebral hemorrhage • plasminogen activator, tissue-type • stroke, ischemic
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Intravenous recombinant tissue plasminogen activator (rTPA) is currently the only approved therapy for acute ischemic stroke within 3 hours of symptom onset. Its efficacy was demonstrated in the multicenter, randomized trial sponsored by the National Institute of Neurological Disorders and Stroke (NINDS).1 Post hoc analysis of patients treated within 3 hours of stroke in the ECASS I and ECASS II trials suggests a possible clinical benefit.2 3 Despite a proven 11% to 13% absolute benefit over placebo in reducing disability at 3 months and sustained benefit at 1 year,4 rTPA use in acute ischemic stroke remains a source of debate.5 6 7 There are still concerns and questions among physicians about adherence to protocol and intracerebral hemorrhage (ICH) rate in community-based rTPA administration. Physicians may be unaware of certain exclusion criteria.8 The purpose of our study was to evaluate outcomes in community-based rTPA use and to assess the relation between protocol violations and outcome.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We retrospectively reviewed paramedic and hospital records on all patients (n=50) who were treated with rTPA for acute ischemic stroke in 10 major hospitals in Indianapolis. Patients treated from July 1996 to February 1998 were identified by linking discharge ICD-9 codes for stroke and pharmacy records of rTPA administration. The pharmacy in each participating hospital keeps a computerized record of rTPA use in each instance. To the best of our knowledge, this sample represents all the patients with acute ischemic stroke treated with rTPA in these hospitals in Indianapolis during the study period. Two of the hospitals did not treat any acute stroke patients with rTPA in the specified period. Neurologists in private practice cared for most patients with acute stroke in these hospitals. We classified stroke neurologists as those who completed a stroke fellowship training program.
Using a standardized data extraction form, we recorded
patient demographics, stroke risk factors, time of symptom onset, time
of arrival to the emergency department, time to CT, time to rTPA
administration, ancillary test results, complications, length of
hospital stay, and discharge type. We calculated a retrospective score
for the Canadian Neurological Scale (CNS) and the National Institute of
Health Stroke Scale (NIHSS) at admission and discharge. Both scales
have been validated for retrospective
calculations.9 10
We defined improvement as a complete or almost complete resolution of
deficits (NIHSS of 0 or 1, CNS >11) or by a reduction of 
8 points in
the NIHSS from admission to discharge. Neurological deterioration was
defined as any neurological worsening during hospital stay. We
classified stroke subtype according to Trial of Org 10172 in Acute
Treatment (TOAST)
criteria.11 The use of
antiplatelet drugs or warfarin before and after treatment was
recorded.
We determined appropriateness of intravenous rTPA administration according to published guidelines12 and did not assess other relative contraindications proposed in the literature.3 13 The following were considered protocol violations: rTPA administration beyond 3 hours; rTPA dose >0.9 mg/kg or >90 mg; baseline international normalized ratio (INR) >1.7 or elevated activated partial thromboplastin time (aPTT); platelet count <100 000/mm3; previous stroke or severe head trauma in the past 3 months; major surgery in the past 14 days; baseline blood pressure >185/110 mm Hg; blood glucose <50 mg/dL or >400 mg/dL; seizure at stroke onset; gastrointestinal or urinary bleeding within the preceding 21 days; use of antiplatelet agents or anticoagulants within the 24 hours after rTPA administration.
All neuroimaging studies performed during hospitalization were reviewed for evidence of hemorrhage. Asymptomatic ICH was defined as any incidental ICH seen on CT or MRI not associated with clinical deterioration. Symptomatic ICH was defined as ICH seen on CT or MRI associated with deterioration in the patient’s neurological status. ICH attributable to rTPA was defined as ICH occurring within 36 hours of rTPA infusion. Brain CTs demonstrating ICH were reviewed with criteria from the NINDS Trial.14
2 tests or Fisher’s exact
tests were used to evaluate categorical data. Differences in continuous
variables between the two groups were compared by use of the
Student’s t
test.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Fifty patients received intravenous rTPA for acute ischemic stroke in Indianapolis between July 1996 and February 1998. General neurologists in private practice treated most patients (70%), followed by stroke neurologists (24%) and emergency physicians (6%). Two hospitals had a written rTPA protocol and 7 had rTPA available in the emergency room.
Patient demographics, risk factors, prestroke use of aspirin
or warfarin, baseline NIHSS, CNS, stroke subtype, mean times to
evaluation and treatment, and outcomes are summarized in
Table 1
. In-hospital mortality rate was 10%, as the result
of ICH (n=4) and cardiogenic shock (n=1). Thirty nine (78%)
records had documentation of discussing the risk-benefit of rTPA
administration in acute stroke.
|
Protocol violations occurred in 8 patients (16%), as
detailed in
Table 2. All hemorrhages, all ICH
(symptomatic plus asymptomatic),
symptomatic ICH, and ICH within 36 hours were significantly
increased in cases with protocol violations
(Table 3). Systolic blood pressure and mean
arterial blood pressure levels before infusion, median
NIHSS, CNS, stroke subtype, and glucose were not associated with ICH.
There were no significant differences in blood pressure and admission
blood glucose between protocol violation and non–protocol violation
groups.
|
|
Importantly, when patients were treated according to the NINDS protocol, hemorrhage rates were nearly identical to those published in the trial (symptomatic ICH attributable to rTPA in 2.5%, all symptomatic ICH in 5%, and all hemorrhagic complications in 10%).
Of the 11 hemorrhages, 4 were systemic and 7 were intracerebral. Two of the ICHs were asymptomatic (found incidentally on MRI follow-up scans) and 5 were symptomatic. Four of the symptomatic ICHs occurred within 36 hours of rTPA infusion. The fifth symptomatic ICH occurred 57 hours after infusion in a patient receiving intravenous heparin. Four of the 5 symptomatic ICHs were fatal. Of the 4 systemic hemorrhages, 1 was a large hematoma in the femoral puncture site, 1 was gingival, 1 was gastrointestinal, and 1 was a ruptured abdominal aneurysm in a patient without any history of peripheral vascular disease, occurring 50 hours after rTPA administration. This last patient required several transfusions but survived without neurological deficits.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Several studies have reported the experience with rTPA for acute ischemic stroke after the NINDS stroke trial. Most of these studies described patients treated predominantly by stroke neurologists with experience in acute stroke trials (including the NINDS)15 16 17 or used protocols different from the original one reported in 1995.13 18 Our study not only extends the generalizability of the NINDS trial to a community largely treated by non–stroke specialists but also highlights the importance of strict adherence to the original protocol.
Chiu et al15
prospectively studied 30 patients in the Houston area treated with
intravenous rTPA by an experienced stroke team. Rates of
symptomatic ICH, fatal and favorable outcomes, were
comparable with the NINDS trial. They concluded that rTPA
administration is feasible, safe, and efficacious when guidelines are
carefully followed in an urban setting. Similar results were reported
from the Oregon Stroke
Center.17 Patients were
treated following the NINDS protocol and 2 additional criteria: NIHSS
of 4 and absence of hypodensity in greater than one third of the
middle cerebral artery territory on initial cerebral CT. Among 33
patients with mean NIHSS of 14.7, a favorable outcome at 3 months was
achieved by 39% (Rankin 0 or 1). Rates of symptomatic and
fatal ICHs were 9% and 6%, respectively. No protocol violations were
reported.
Grond et al18 reported 100 patients with acute ischemic stroke treated with intravenous rTPA, followed by immediate use of intravenous heparin and mannitol or glycerol. Hemorrhagic infarctions and parenchymal hemorrhages occurred in 18%, a third of which were associated with neurological deterioration (6%). Outcomes were slightly better than in the NINDS trial, perhaps because of a younger patient population and lower mean NIHSS. Two deviations from their protocol occurred, both as the results of inaccuracies in the timing of symptom onset, and both were fatal as the result of cerebral edema. Interestingly, immediate use of heparin, a NINDS protocol violation, did not result in higher rates of symptomatic ICH.
Tanne et al16
described protocol violations in 30% (56 of 159) of patients and found
a trend but no significant association with ICH. Their ICH rate after
excluding these violations was also 4%. Buchan et
al19 reported 68 patients
treated with rTPA within 3 hours of stroke onset in a single hospital
in Calgary, Canada. Protocol violations were found in 16% of patients
who had a lower probability of independence and neurological recovery,
as well as a high probability of symptomatic
hemorrhage compared with patients treated according to the
NINDS protocol. Six of the 11 violations were CT violations and 5 were
clinical including prolonged window, thrombocytopenia, dementia, and
loss of consciousness. The Standard Treatment with Alteplase to Reverse
Stroke (STARS)20
investigators found protocol violations in 32.6% of 389 patients
treated with rTPA for ischemic stroke in academic and community
hospitals. Almost half of the violations were either rTPA
administration >3 hours after onset of symptoms or use of
anticoagulants within 24 hours of treatment. Symptomatic
ICH occurred in 3.2% of the patients, but no significant difference
was found between patients with and those without protocol
violations.18 This lack of
association between symptomatic ICH and protocol deviations
has also been reported by Katzan et
al.21 They described 70
patients treated with rTPA in 29 hospitals in the Cleveland
metropolitan area. Symptomatic ICH was found in 15.7% of
patients, the highest rate reported to date in the United States. The
authors found a trend toward symptomatic ICH in those
patients, with no documentation of stroke severity (60% in their
cohort) and in those whose blood pressure monitoring deviated from the
protocol. Differential effects on ICH risk according to the type of
protocol violation may explain the discrepancies between these reports
and our results
(Table 4). Protocol violations in our community were
somewhat different than in the STARS or Cleveland area studies. None of
ours were time violations, whereas a large number of violations in
STARS (41%) and Cleveland (26%) were of this type. If time violations
are not as dangerous as anticoagulation or elevated blood pressure
during the 24 hours after infusion, then this may explain in part the
lack of association between violations and ICH in these studies. In
addition, the reports from Buchan et al (Calgary), Tanne et al
(multicenter), and our data have a disproportionate large percentage of
"other" protocol violations including head trauma, recent stroke,
and abnormalities on CT, among others. These studies found a strong
association or a trend for association between violations and ICH,
which supports the notion that ICH risk depends on the type of protocol
violation rather than on the presence of any violation. Further studies
are needed to establish the type of violations with greatest ICH
risk.
|
Our study focused on adherence to published guidelines for intravenous rTPA treatment of acute ischemic stroke in a community-based setting. Previously, we found that only a minority of neurologists and emergency physicians have used rTPA to treat acute ischemic stroke.8 When asked about potential contraindications to its use, most of the survey respondents recognized the 3-hour time window but failed to recognize uncontrolled hypertension as a protocol violation. General neurologists or emergency physicians, not stroke specialists, treated 76% of patients in our study. Therefore, our results may be more generalizable to usual clinical settings. Patients’ age, sex, risk factors, and in-hospital mortality rates were comparable to the NINDS trial. The median admission NIHSS in our study is lower than in the NINDS trial (11 versus 14), but symptomatic and fatal ICH rates are higher in our study, probably because of the deviations from the protocol. When the NINDS protocol was followed, symptomatic and fatal ICH rates in our study were similar to those in the NINDS trial.
Our results support the need for strict adherence to the NINDS rTPA protocol for treatment of acute ischemic stroke. In our study, recent stroke (within the past 2 weeks of index stroke) and immediate heparin use after rTPA infusion accounted for half of the violations and 2 of the symptomatic ICHs. In the absence of a written protocol, physicians may remember the time window but may not remember the important, less obvious contraindications. Educational efforts should stress these clinical contraindications as well as the avoidance of antiplatelet or anticoagulant agents for 24 hours after infusion of rTPA in acute stroke, a relevant difference from the rTPA protocol for myocardial infarction.
In addition to improving adherence to the
thrombolysis protocol, some other aspects of rTPA
delivery may also be improved. Infusion of rTPA was started 
100
minutes after arrival to the emergency room and 70 minutes after CT.
Both time periods are beyond the recommended Advanced Cardiac Life
Support (ACLS) guidelines.22
These times may be shortened by prompt neurological consultation or
stroke team activation (where available), by implementation of a
thrombolysis protocol, and by ensuring rTPA
availability in emergency rooms.
This study has some limitations. It is relatively small and retrospective, and data extractors were not systematically blinded to patients’ outcome. However, we attempted to enhance the uniformity of data collected by using a standardized data collection sheet for documentation of adherence to protocol.
Our results show that protocol violations in community-based rTPA administration for acute stroke are associated with serious complications. Conversely, when the protocol is followed, rTPA may be administered as safely as in the NINDS trial. Periodic physician education efforts about appropriate rTPA administration for acute ischemic stroke may help avoid protocol violations.
|
Acknowledgments |
|---|
The authors wish to thank the Staff and Medical Records Departments of the following hospitals in Indianapolis: St Francis Community Hospital, Hendricks Community Hospital, Community Hospital East, Community Hospital South, St Vincent’s Hospital, Methodist Hospital, Winona Memorial Hospital, Wishard Hospital, Richard L. Roudebush Veterans Affairs Administration Hospital, and Indiana University Hospital.
|
Footnotes |
|---|
Reviews of this article were directed by Vladimir Hachinski, MD.
Received April 3, 2000; revision received September 29, 2000; accepted September 29, 2000.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. The National Institute of Neurological Disorders, and Stroke r-tPA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–1587.
2.
Hacke W, Bluhmki E,
Steiner T, Mahagne MH, Sachetti ML, Meier D. Dichotomized efficacy end
points and global end-point analysis applied to the ECASS
intention-to-treat data set: post hoc analysis of ECASS I.
Stroke. 1998;29:2073–2075.
3. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind-placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II): second European-Australasian acute stroke study investigators. Lancet. 1998;352:1245–1251.[Medline] [Order article via Infotrieve]
4.
Kwiatkowski TG,
Libman RB, Frankel M, Tilley BC, Morgenstern LB, Lu M, Broderick JP,
Lewandowski CA, Marler JR, Levine SR, Brott T, for the National
Institute of Neurological Disorders and Stroke Recombinant Tissue
Plasminogen Activator Stroke Study Group.
Effects of tissue plasminogen activator for
acute ischemic stroke at one year.
N Engl J Med. 1999;340:1781–1787.
5.
Caplan LR, Mohr JP,
Kistler JP, Koroshetz W. Should thrombolytic therapy be
the first-line treatment for acute ischemic stroke?
Thrombolysis: not a panacea for stroke.
N Engl J Med.. 1997;337:1309–1313.
6. Haley EC, Lewandowski C, Tilley BC. Myths regarding the NINDS rt-PA Stroke Trial: setting the record straight. Ann Emerg Med. 1997;30:676–682.[Medline] [Order article via Infotrieve]
7. Osborn TM, LaMonte MP, Gaasch WR. Intravenous thrombolytic therapy for stroke: a review of recent studies and controversies. Ann Emerg Med. 1999;34:244–255.[Medline] [Order article via Infotrieve]
8. Meschia JF, Williams LS, Fleck JD, Bruno A, Biller J. Views on the use of tissue plasminogen activator in acute ischemic stroke: a state-wide survey among neurologists and emergency physicians in Indiana. J Stroke Cerebrovasc Dis. 1999;8:207–210.
9.
Goldstein LB,
Chilukuri V. Retrospective assessment of initial stroke severity with
the Canadian Neurological Scale.
Stroke. 1997;28:1181–1184.
10.
Williams LS,
Yilmaz EY, Lopez-Yunez AM. Retrospective assessment of initial stroke
severity with the NIH stroke scale.
Stroke. 2000;31:858–862.
11.
Adams HP,
Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE, and
TOAST Investigators. Classification of subtype of acute
ischemic stroke: definitions for use in a multicenter clinical
trial. Stroke. 1993;24:35–41.
12.
Adams HP, Brott
TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM, Kwiatkowski T, Lyden
PD, Marler JR, Torner J, Feinberg W, Mayberg M, Thies W. Guidelines for
thrombolytic therapy for acute stroke: a supplement to
the guidelines for the management of patients with acute
ischemic stroke: a statement for health care professionals from
a special writing group of the Stroke Council, American Heart
Association. Circulation. 1996;94:1167–1174.
13. Wirkowski EJ, Gottesman MH, Mazer C, Brody GM, Manzella SM. Tissue plasminogen activator for acute stroke in everyday clinical practice. J Stroke Cerebrovasc Dis. 1999;8:291–294.
14.
NINDS rt-PA
Stroke Study Group. Intracerebral hemorrhage
after intravenous t-PA therapy for ischemic stroke.
Stroke. 1997;28:2109–2118.
15.
Chiu D, Krieger
D, Villar-Cordova C, Kasner SE, Morgenstern LB, Bratina PL, Yatsu FM,
Grotta JC. Intravenous tissue plasminogen
activator for acute ischemic stroke: feasibility,
safety, and efficacy in the first year of clinical practice.
Stroke. 1998;29:18–22.
16.
Tanne D, Bates
VE, Verro P, Kasner SE, Binder JR, Patel SC, Mansbach HH, Daley S,
Schultz LR, Karanjia PN, Scott P, Dayno JM, Vereczkey-Porter K, Benesch
C, Book D, Coplin WM, Dulli D, Levine SR, and the t-PA Stroke Survey
Group. Initial clinical experience with IV tissue
plasminogen activator for acute
ischemic stroke: a multicenter survey.
Neurology. 1999;53:424–427.
17. Egan R, Lutsep HL, Clark WM, Quinn J, Kearns K, Lockfeld A, Ireland S, Goins S, Buchholz G. Open label tissue plasminogen activator for stroke: the Oregon experience. J Stroke Cerebrovasc Dis. 1999;8:287–290.
18.
Grond M, Stenzel
C, Schmülling S, Rudolf J, Neveling M, Lechleuthner A, Schneweis S,
Heiss W-D. Early intravenous thrombolysis
for acute ischemic stroke in a community-based approach.
Stroke. 1998;29:1544–1549.
19.
Buchan AM, Barber
BA, New N, Karbalai HG, Demchuk AM, Hoyte KM, Klein GM, Feasby TE.
Effectiveness of t-PA in acute ischemic stroke: outcome relates
to appropriateness. Neurology. 2000;54:679–684.
20. Albers GW, Bates VA, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) Study. J AMA. 2000;283:1145–1150.
21. Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, Hammel JP, Qu A, Sila CA. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. J AMA. 2000;283:1151–1158.
22. Advanced Cardiac Life Support. Dallas, Tex: American Heart Association; 1997:10-17.
This article has been cited by other articles:
 |
|
 |
|
  D. Summers, A. Leonard, D. Wentworth, J. L. Saver, J. Simpson, J. A. Spilker, N. Hock, E. Miller, P. H. Mitchell, and on behalf of the American Heart Association Counci Comprehensive Overview of Nursing and Interdisciplinary Care of the Acute Ischemic Stroke Patient: A Scientific Statement From the American Heart Association Stroke, August 1, 2009; 40(8): 2911 - 2944. [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Leira, D. C. Hess, J. C. Torner, and H. P. Adams Jr Rural-Urban Differences in Acute Stroke Management Practices: A Modifiable Disparity Arch Neurol, July 1, 2008; 65(7): 887 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 630S - 669S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aleu, P. Mellado, C. Lichy, M. Kohrmann, and P. D. Schellinger Hemorrhagic Complications After Off-Label Thrombolysis for Ischemic Stroke Stroke, February 1, 2007; 38(2): 417 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. I. Gropen, P. J. Gagliano, C. A. Blake, R. L. Sacco, T. Kwiatkowski, N. J. Richmond, D. Leifer, R. Libman, S. Azhar, M. B. Daley, et al. Quality improvement in acute stroke: The New York State Stroke Center Designation Project. Neurology, July 11, 2006; 67(1): 88 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Audebert, C. Kukla, B. Vatankhah, B. Gotzler, J. Schenkel, S. Hofer, A. Furst, and R. L. Haberl Comparison of Tissue Plasminogen Activator Administration Management Between Telestroke Network Hospitals and Academic Stroke Centers: The Telemedical Pilot Project for Integrative Stroke Care in Bavaria/Germany Stroke, July 1, 2006; 37(7): 1822 - 1827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamaguchi, E. Mori, K. Minematsu, J. Nakagawara, K. Hashi, I. Saito, Y. Shinohara, and for the Japan Alteplase Clinical Trial (J-ACT) Gro Alteplase at 0.6 mg/kg for Acute Ischemic Stroke Within 3 Hours of Onset: Japan Alteplase Clinical Trial (J-ACT) * Supplemental Appendix 2 Stroke, July 1, 2006; 37(7): 1810 - 1815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.G. Gonzalez Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain". AJNR Am. J. Neuroradiol., April 1, 2006; 27(4): 728 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cocho, M. Borrell, J. Marti-Fabregas, J. Montaner, M. Castellanos, Y. Bravo, L. Molina-Porcel, R. Belvis, J.-A. Diaz-Manera, A. Martinez-Domeno, et al. Pretreatment Hemostatic Markers of Symptomatic Intracerebral Hemorrhage in Patients Treated With Tissue Plasminogen Activator Stroke, April 1, 2006; 37(4): 996 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. T. Bateman, H. C. Schumacher, B. Boden-Albala, M. F. Berman, J.P. Mohr, R. L. Sacco, and J. Pile-Spellman Factors Associated With In-Hospital Mortality After Administration of Thrombolysis in Acute Ischemic Stroke Patients: An Analysis of the Nationwide Inpatient Sample 1999 to 2002 Stroke, February 1, 2006; 37(2): 440 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Part 9: Adult Stroke Circulation, December 13, 2005; 112(24_suppl): IV-111 - IV-120. [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Hill, A. M. Buchan, and for The Canadian Alteplase for Stroke Effectivenes Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study Can. Med. Assoc. J., May 10, 2005; 172(10): 1307 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Aiyagari, A. Gujjar, A. R. Zazulia, and M. N. Diringer Hourly Blood Pressure Monitoring After Intravenous Tissue Plasminogen Activator for Ischemic Stroke: Does Everyone Need It? Stroke, October 1, 2004; 35(10): 2326 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Ingall, W. M. O'Fallon, K. Asplund, L. R. Goldfrank, V. S. Hertzberg, T. A. Louis, and T. J. H. Christianson Findings From the Reanalysis of the NINDS Tissue Plasminogen Activator for Acute Ischemic Stroke Treatment Trial Stroke, October 1, 2004; 35(10): 2418 - 2424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 483S - 512S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Trouillas, L. Derex, F. Philippeau, N. Nighoghossian, J. Honnorat, M. Hanss, P. Ffrench, P. Adeleine, and M. Dechavanne Early Fibrinogen Degradation Coagulopathy Is Predictive of Parenchymal Hematomas in Cerebral rt-PA Thrombolysis: A Study of 157 Cases Stroke, June 1, 2004; 35(6): 1323 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Graham Tissue Plasminogen Activator for Acute Ischemic Stroke in Clinical Practice: A Meta-Analysis of Safety Data Stroke, December 1, 2003; 34(12): 2847 - 2850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Camilo and L. B. Goldstein Statewide Assessment of Hospital-Based Stroke Prevention and Treatment Services in North Carolina: Changes Over the Last 5 Years Stroke, December 1, 2003; 34(12): 2945 - 2950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Higashida and A. J. Furlan Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke Stroke, August 1, 2003; 34 (8): e109 - e137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Bravata, N. Kim, J. Concato, H. M. Krumholz, and L. M. Brass Thrombolysis for Acute Stroke in Routine Clinical Practice Arch Intern Med, September 23, 2002; 162(17): 1994 - 2001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.K. Gilligan, R. Markus, S. Read, V. Srikanth, T. Hirano, G. Fitt, M. Arends, B.R. Chambers, S.M. Davis, and G.A. Donnan Baseline Blood Pressure but Not Early Computed Tomography Changes Predicts Major Hemorrhage After Streptokinase in Acute Ischemic Stroke Stroke, September 1, 2002; 33(9): 2236 - 2242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Meschia, D. A. Miller, and T. G. Brott Thrombolytic Treatment of Acute Ischemic Stroke Mayo Clin. Proc., June 1, 2002; 77(6): 542 - 551. [Abstract] [PDF]
|
|
|
|
|
|
L. B. Morgenstern, L. Staub, W. Chan, T. H. Wein, L. K. Bartholomew, M. King, R. A. Felberg, W. S. Burgin, J. Groff, S. L. Hickenbottom, et al. Improving Delivery of Acute Stroke Therapy: The TLL Temple Foundation Stroke Project Stroke, January 1, 2002; 33(1): 160 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Gladstone and S. E. Black Update on intravenous tissue plasminogen activator for acute stroke: from clinical trials to clinical practice Can. Med. Assoc. J., August 1, 2001; 165(3): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||