Table Of ContentTHROMBOLYTIC THERAPY FOR STROKE
Thrombolytic
Therapy
for Stroke
Edited by
D.
PATRICK LYDEN, MD
UCSD Stroke Center
San Diego, CA
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SPRINGER SCIENCE+BUSINESS MEDIA, LLC
© 2001 Springer Science+Business Media New York
Originally published by Humana Press Inc. in 200 I
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Library of Congress Cataloging-in-Publication Data
Thrombolytic therapy for stroke/edited by Patrick D. Lyden.
p. cm.
Includes bibliographical references and index.
ISBN 978-1-4757-6843-5 ISBN 978-1-59259-131-2 (eBook)
DOI 10.1007/978-1-59259-131-2
1. Cerebrovascular disease-Chemotherapy. 2. Thrombolytic therapy I. Lyden, Patrick D.
[DNLM: 1. Cerebrovascular Accident-drug therapy. 2. Thrombolytic therapy. WL
355 T5307 2001]
RC388.5.T4772001
616.8' l-dc2l
DNLMIDLC
for Library of Congress 00-044910
CIP
This book is dedicated to ourf amilies, who daily cope with the vagaries,
inconveniences, and turmoil surrounding our involvement in a Stroke Team.
It is also dedicated to the patients who volunteered to participate in the
placebo-controlled trials oft hrombolytic stroke therapy: a more courageous
and selfless group act, on such a scale, may not be seen again in medical
research
v
PREFACE
Thrombolytic Therapy for Stroke is intended for physicians who will be
treating patients in the first few hours after stroke: neurologists, neurosurgeons,
emergency medicine physicians, internists, and radiologists. In some areas, fam
ily medicine general practice physicians may provide the majority of acute stroke
care. We will provide the reader with all the data necessary to understand the
utility and limitations of thrombolytic therapy. By reading the protocols, and
working through the case tutorials, the reader will become sufficiently familiar
with the indications and contraindications of thrombolytic therapy to begin evalu
ating potential patients. Although nothing can replace direct instruction by more
experienced physicians, we hope that by imparting our accumulated knowledge
we may guide those physicians who cannot attend a "hands-on" workshop, or
who, having heard the appropriate lectures, feel the need for further guidance.
We will review the scientific rationale for thrombolysis: first, most ischemic
stroke is caused by thrombo-emboli; second, a portion of brain, the penumbra,
remains salvageable for a few hours after vascular occlusion; and third, promptly
delivered thrombolysis can remove the offending occlusion and restore cerebral
blood flow to the penumbra in time to salvage brain and neurologic function.
Then we will review the preclinical development of thrombolytics for stroke pa
tients and the early pilot trials. Next, we will present the pivotal clinical trials that
demonstrated the efficacy and safety of thrombolysis. Then we will describe the
treatment protocol for treating patients: field triage and management, Emergency
Department therapy, brain imaging, clinical decision making and patient selec
tion, drug administration, post thrombolysis management and treatment of com
plications. In the final section of the book, we will demonstrate the use of the
protocol using a series of real patient case histories.
Since most medical books are "out of date" when published, we do not
include extensive literature on topics that are controversial or in development.
Rather, we have assembled the essential papers and protocols that are well
accepted and will stand the test of time. We intend this guide to be useful as
a starting point, and as a ready reference for the clinician encountering a novel
or unusual case.
We recognize that thrombolytic therapy was viewed with some skepti
cism until recently. In 1999 and early 2000, however, the tide seemed to turn
in favor of thrombolysis, despite its risks. One of the prominent early critics,
Dr. Lou Caplan, graciously agreed to summarize his arguments against throm
bolytic stroke therapy as a chapter in this book (Chapter l3). Together with a
vii
viii Preface
rebuttal, this point-counterpoint leads off Section 3. We think the reader will
benefit from hearing both sides of the debate. Dr. Caplan points out, however,
he is no longer opposed to thrombolytic therapy, having personally treated
several patients. He does continue to suggest that patients undergo vascular
imaging prior to treatment. On this, and on all other issues raised in this book,
we have tried to present multiple viewpoints, supported by data, to allow the
reader to decide independently.
We are hopeful that you will find Thrombolytic Therapy for Stroke useful
and entertaining. It is brief, because time is precious, and our message is simple.
We look forward to a future in which more stroke victims enjoy the benefits of
thrombolytic stroke therapy, and are returned to a productive, independent life.
Patrick D. Lyden, MD
ACKNOWLEDGMENTS
Editing a multi authored book is a harrowing and gratifying experi
ence, one that would be impossible without the able and noble efforts of
others. I am grateful to the authors for diligently writing and revising their
work. Without the expert and tireless assistance of Alyssa Chardi and Tony
Di Lullo, I could never have begun, let alone finished this work. My special
thanks go to Dr. Steven Levine, for graciously contributing several case
tutorials, and to Dr. Justin Zivin, for years of mentoring. The nurses on staff
at the UCSD Stroke Center, phenomenally dedicated to stroke research and
patient care, include Nancy Kelly, Janet Werner, and Teri McClean, all of
whom helped collect cases for the tutorial section. I most especially recog
nize my colleague in managing our thrombolytic trials, Karen Rapp,
a nurse and clinical researcher of the highest caliber, motivation, and
compassion. Finally, my deepest gratitude goes to my colleague, partner, and
companion, Dr. Cristy Jackson, sine qua non at work and at home, and our
children Jessica, Hannah, and Hillary.
lX
CONTENTS
Dedication ......................................................................................................... v
Preface ............................................................................................................ vii
Acknowledgments .......................................................................................... ix
Contributors ................................................................................................... xiii
PART I BACKGROUND AND BASIC INVESTIGATIONS
1 Mechanisms of Thrombolysis .................................................................. 3
Gregory J. del Zoppo and Naohisa Hosomi
2 Pathogenesis of Cervico-cranial Artery Occlusion ............................... 29
Louis R. Caplan
3 The Ischemic Penumbra and Neuronal Salvage .................................... 43
Patrick D. Lyden
PART II SCIENTIFIC RATIONALE AND CLINICAL TRIALS
4 Pre-Clinical Testing of Thrombolytic Therapy
for Stroke ............................................................................................ 65
Anne M. Guyot and Steven R. Levine
5 Combination of Thrombolytic Therapy with
Neuroprotectants ................................................................................ 75
James C. Grotta
6 Early Studies of Thrombolytic Therapy for Stroke ............................... 91
Anne M. Guyot, Luchi Quinones, and Steven R. Levine
7 Phase 2 Experience with Intravenous Thrombolytic
Therapy for Acute Ischemic Stroke ................................................. 129
E. Clarke Haley, Jr.
8 Intravenous Thrombolytic Therapy for Acute
Ischemic Stroke: Results of Large, Randomized
Clinical Trials .................................................................................. 141
Rashmi U. Kothari and Joseph P. Broderick
9 Further Analysis ofNINDS Study: Long-Term Outcome,
Subgroups, and Cost Effectiveness .................................................. 153
Susan C. Fagan, Thomas Kwiatkowski, and Patrick D. Lyden
xi
xii Contents
10 Intra-Arterial Thrombolysis in Acute
Ischemic Stroke ................................................................................ 175
Anthony J. Furlan, Randall Higashida, Irene Katzan,
and Alex Abou-Chebl
11 Combinations of Intravenous and Intra-Arterial
Thrombolysis ................................................................................... 197
Joseph P. Broderick and Rashmi Kothari
III
PART USING THROMBOLYSIS FOR ACUTE STROKE
12 The Case for Thrombolytic Therapy in Stroke Patients ...................... 211
Patrick D. Lyden
13 The Case Against the Present Guidelines for Stroke Thrombolysis:
The Present Recommendations for Clinical Use Should
Be Modified ...................................................................................... 223
Louis R. Caplan
14 How to Run a Code Stroke .................................................................. 237
Christopher Lewandowski
15 Interpretation of CT Scans for Acute Stroke ....................................... 255
Rudiger von Kummer
16 Identifying and Overcoming Obstacles to Acute
Stroke Treatment with rt-PA:
Establishing Hospital and EMS Protocols ...................................... 283
Karen S. Rapp and Patti Bratina
17 The NINDS t-PA for Acute Stroke Protocol ....................................... 297
John R. Marler and Patrick D. Lyden
18 Research Directions and the Future of Stroke Therapy ...................... 309
Patrick D. Lyden
IV:
PART ILLUSTRATIVE CASES
Illustrative Cases .................................................................................. 313
Index .............................................................................................................. 399
