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Surgical Endovascular Neuroradiology

Theory and Clinical Practice

Charles J. Prestigiacomo, MD, FAANS, FACS

Professor and Chairman
Department of Neurological Surgery
Professor of Radiology and Neurology and Neurosciences
Director of Cerebrovascular and Endovascular Surgery
Rutgers New Jersey Medical School
Newark, New Jersey
Contributing Editors

E. Jess Duffis, MD
Neurointerventional Surgery
Department of Neurology
Baystate Medical Center
Springfield, Massachusetts
Chirag D. Gandhi, MD, FACS, FAANS
Associate Professor of Neurological Surgery, Neurology, and Neuroscience
Department of Neurosurgery
Rutgers New Jersey Medical School
Newark, New Jersey

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Library of Congress Cataloging-in-Publication Data
Surgical endovascular neuroradiology : theory and clinical
practice / [edited by] Charles J. Prestigiacomo, E. Jesus Duffis,
Chirag D. Gandhi.
p. ; cm.
Includes bibliographical references.
ISBN 978-1-60406-057-7 (hardback : alk. paper)
ISBN 978-1-60406-778-1 (e-book)
I. Prestigiacomo, Charles, editor. II. Duffis, E. Jesus, editor.
III. Gandhi, Chirag D., editor.
[DNLM: 1. Cerebrovascular Disorderssurgery.
2. Endovascular Proceduresmethods. 3. Radiography,
Interventionalmethods. WL 355]
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Alejandro Berenstein, MD


General Endovascular Tenets

Vascular Biology of the Endothelium
Gaurav Gupta and Charles J. Prestigiacomo

Hemostasis 9
Ravi Shah, Tareq Kass-Hout, and Charles J. Prestigiacomo
Medicolegal Aspects of Complications and Adverse Outcomes
Celina Crisman, Christine Villegas, Charles J. Prestigiacomo, and Chirag D. Gandhi


Training Standards and Quality Assurance
E. Jess Duffis


The Endovascular Suite
Vivek H. Tank, E. Jess Duffis, and Charles J. Prestigiacomo



Perioperative Care

Perioperative Planning
Robert Alex Hirschl and Louis P. Caragine Jr.


Guilherme Dabus and Raul G. Nogueira


Intensive Care Management
Nazli Janjua and Elia Haddad


Nursing Considerations
Maria G. Farrow


Physiological Considerations
Lana Christiano, Chirag D. Gandhi, and Charles J. Prestigiacomo


vi Contents

Angiographic Fundamentals

Angioanatomy of the Head and Neck
Jacqueline A. Bello and David W. Minsky


Cerebral Angiography
Kevin M. Cockroft


Spinal Angiography and the Angiographic Anatomy of the Spine
Jeffrey A. Stone



Intracranial Aneurysms and Vasospasm

The Biophysics of Aneurysm Formation and Rupture
Charles J. Prestigiacomo


Endosaccular Treatment of Anuerysms
Charles E. Romero and In Sup Choi


Deconstructive Methods for Endovascular Aneurysm Treatment
Raqeeb Haque, Christopher Paul Kellner, Sean D. Lavine, and Philip M. Meyers


Primary Endoluminal Approaches to Cerebral Aneurysm Therapy
Maksim Shapiro, Tibor Becske, Kathleen McConnell, Martin M. Ollenschleger,
and Peter K. Nelson


Balloon-Remodeling Techniques in Aneurysm Treatment
Pascal Jabbour, Erol Veznedaroglu, and Badih Daou


Complex Aneurysms: Stent versus Balloon versus Deconstructive Techniques
A Review of the Evidence
Min S. Park, Michael F. Stiefel, Cameron G. McDougall, and Felipe C. Albuquerque


Postoperative Management Strategies
Michael J. Alexander and Abhineet Chowdhary


Diagnosis and Management of Residual and Recurrent Cerebral Aneurysms
Aditya Pandey, B. Gregory Thompson, Cormac O. Maher, Neeraj Chaudhary,
Augusto Elias, and Joseph J. Gemmete


Intra-arterial Pharmacotherapy of Cerebral Vasospasm
Reza J. Karimi, Osamah Choudhry , and Charles J. Prestigiacomo


Transluminal Balloon Angioplasty for Cerebral Vasospasm
Muhammad M. Abd-El-Barr, Brian L. Hoh, and J Mocco


The Treatment of Vasospasm: What Does the Evidence Demonstrate?
David S. Lee, Aclan Dogan, and Stanley L. Barnwell


Arteriovenous Malformations

Arteriovenous Malformation Hemodynamics and Vascular Remodeling
William L. Young and Tomoki Hashimoto


Embolic Agents
W. Christopher Fox and Brian L. Hoh


Brain Arteriovenous Malformations: Treatment with Liquid Embolic Agents
Scott E. Olson and Charles Kerber




Dural Arteriovenous Malformations

Pathophysiology of Dural Arteriovenous Malformations
Ziad A. Hage, Bernard R. Bendok, Daniel L. Surdell, Ali Shaibani, Michael Hurley,
Christopher C. Getch, Issam A. Awad, and H. Hunt Batjer


Treatment of Intracranial Dural Arteriovenous Fistulas
Y. Jonathan Zhang, Ferdinand K Hui, C. Michael Cawley, Frank C. Tong, and Jacques E. Dion


Transarterial Approach to Dural Arteriovenous Fistulas
Andrew Kelly Johnson, Michael Chen, and Demetrius K. Lopes


Transvenous Approaches
Paula Klurfan and Karel terBrugge


VII Lesions of the Head and Neck

Intracranial Tumor Embolization
Beverly Aagaard Kienitz and Lei Feng


Embolization of Extracranial Tumors of the Head and Neck
Theodore C. Larson III


Epistaxis 352
Joan C. Wojak
Endovascular Chemotherapy for Tumors of the Head, Neck, and Central Nervous System 360
Justin F. Fraser, Muhammad Shazam Hussain, and Y. Pierre Gobin
Sclerotherapy 373
Wayne Yakes

VIII Atherosclerotic Disease

Pathobiology of Atherosclerosis
Dimitrios Giannakidis, Daniel A. Nguyen, Yazan J. Alderazi, and Chirag D. Gandhi


Angiographic Modifications for the High-Risk Patient
Babak S. Jahromi, Charles A. Guidot, J Mocco, Elad I. Levy, and L. Nelson Hopkins


Extracranial Carotid Artery Angioplasty and Stenting
Anu Bansal, Avi Mazumdar, and Colin P. Derdeyn


Angioplasty and Stenting of the Vertebral Arteries and Great Vessels
Vikas Gupta, Nakul Sheth, and Chirag D. Gandhi


Intracranial Atheromatous Disease: When and How to Treat
Athos Patsalides, Y. Pierre Gobin



Acute Stroke Interventions

The Cerebrovascular Accident: A Primer
Mahmoud Rayes, Paritosh Pandey, Sunil Manjila, and Andrew R. Xavier


Intra-arterial Thrombolysis
Kristine Blackham, Daniel P. Hsu, Jason Wilson, and Robert W. Tarr


Intracranial Mechanical Thrombectomy
Yince Loh and Gary R. Duckwiler



viii Contents
Angioplasty and Stent Placement in Acute Ischemic Stroke Therapy
Sha-Naz Khan and Andrew J. Ringer


Central Retinal Artery Occlusion
Roger E. Turbin and Charles J. Prestigiacomo


Lesions of the Spine

Spinal Anatomy and Radiographic Interpretation for Trans- and Extra-pedicular
Approaches to the Vertebral Body
Ira M. Goldstein


Spinal Tumor
David Altschul, Gaurav Jain, and Allan L. Brook


Spinal Vascular Diseases
Neil V. Patel, Gabriela Spilberg, and Ajay K. Wakhloo


Principles of Vertebroplasty 563
Albert J. Yoo, Ruchira M. Jha, and Joshua A. Hirsch
Principles of Kyphoplasty
Ira M. Goldstein


Sacroplasty 585
Keith E. Kortman

XI Additional Endovascular Applications

Intraoperative Angiography
Michelle J. Smith, Athos Patsalides, Y. Pierre Gobin, Philip Stieg, and Howard A. Riina


Inferior Petrosal Sinus Sampling
Scott A. Meyer, Chirag D. Gandhi, David M. Johnson, and Aman B. Patel


Balloon Test Occlusion
Koji Ebersole, Charles J. Prestigiacomo, Chirag D. Gandhi


Cerebral Venous Thrombosis: Diagnosis and Management
Robert W. Hurst and John B. Weigele


Vein of Galen Aneurysmal Malformations: Diagnosis and Management
Robert W. Hurst, Gregory G. Heuer, Rebecca Ichord, and Phillip B. Storm


Endovascular Management of Trauma
Randy S. Bell, Ryan L. Roberts, Robert D. Ecker, and Rocco Anthony Armonda


Diagnosis and Endovascular Treatment of Direct Carotid Cavernous Sinus Fistulas
Mary E. Jensen





Dr. Charles Charlie Prestigiacomo, whom I had the

great pleasure and honor of working with during his
formative years, is a one-of-a-kind individual. He has
the uniqueness of a well-rounded intellect, bringing
a scientific, analytical approach to any problem and
an organized, methodical structure to any concept, as
well as bringing sensitivity to his humane treatment
of others, whether they are patients, colleagues,
trainees, or coworkers. He is a true intellectual and
one of the people Im most proud to have trained.
The global integration of his mind is reflected in
this incredible book on our dynamic specialty of surgical neuroangiography, where he has integrated the
more basic and fundamental aspects of what we do
and has given us comprehensive, but practical and
easy to understand, knowledge on subjects like the
vascular biology of the endothelium and hemostasis.
We are constantly trying to close or open a vascular
structure, but none of our specialty training teaches
us the basics of endothelium and hemostasis, the
fundamental knowledge we need for day-to-day
practice, as well as for shaping future developments
in our field.

The book addresses many aspects of real practice that influence our resource management and
workflow organization, and provides insight into the
socioeconomic aspects of our field. The bibliography
is very useful for those who would like to further
research a particular topic.
One of the tremendous values of the book is that
many of the organizational aspects will outlast the
rapid introduction of newer techniques, which is a
tremendous challenge in a book of such dynamic
I want to thank Charlie and the impressive list of
contributors for dealing with such a dynamic specialty, which will help doctors at various stages of
their careers to take better care of their patients.
Alejandro Berenstein, MD
Hyman-Newman Institute for
Neurology and Neurosurgery
Mount Sinai St. LukesRoosevelt
and Mount Sinai Beth Israel
New York, New York



Few medical fields have enjoyed the explosive growth

and continued maturation as the subspecialty of
endovascular surgical neuroradiology. Unique in
many respects, this specialty carries the histories
and traditions of many other specialties in medicine
and surgery. Though some might refer to the first
endovascular embolization of a fistula in Washington DC by Luessenhop and Velasquez as the birth
of endovascular in the 1960s, in fact, the concepts
of an endovascular approach to treating vascular disease of the nervous system has its roots in the first
days of Monizs successes in cerebral angiography,
which took place in the late 1920s.
Since that time, there has been an explosive
growth of the field through the advancement of
technology and the original and bold thinking of pioneering interventionalists. With this has come our
ability to help many whom we were unable to help
before. Previously inoperable conditions are now
treatable with a lower morbidity and a lower mortality. Patients are benefiting from this growth.
In pouring through the literature on all things
associated with neurointerventional, I recognized
the need to develop a resource that brought into
focus the many devices, techniques, and procedures
we use. This book does just that: it brings into sharp
focus the most current and up-to-date methods of
an ever-changing specialty. It brings this information
to you through the lens of experts in their respective fields, focusing their research into the textbook
that sits before you. This is the Theory part of the
As neurointerventionalists, we all believe that
theory is best served when applied to practice. The
Clinical Practice section of this textbook integrates
and translates this theory into a working paradigm
that brings benefit to our patients. By focusing on
technique and emphasizing complication avoidance
andin those unfortunate times when the complication occurscomplication management, your

patient benefits. These benefits stem not only from

authors providing their benefit of years of experience by describing some of the nuances of their techniques, but also by firmly planting the conclusions
and recommendations on literature-based data.
Though this book is comprehensive and exhaustive, it is useable and practical. It successfully blends
the knowledge one can glean from an exhaustive
search through the literature with the practical solutions involved in the management of these oftentimes very sick patients. It provides the reader with
a synopsis of key points for each chapter that can be
easily referenced, as well as key information that can
be easily gleaned. These key summary elements and
elements of complication avoidance and management help focus the reader on the take home message for each chapter.
Most importantly, this book serves as a reference
for all members of the neurointerventional community. From the early learning resident to the fellow
who is achieving proficiency, to the neurointerventionalist who has achieved expert status, this text
serves as the principle reference source for any neurointerventional topic. The self-contained chapters
allow the reader to turn to a specific topic without
reading the text from the initial chapters (though
there is a logical flow to the material presented).
As an example, residents and fellows will learn
insights beyond the basic principles of, what I
describe as, the deliver, deploy, detach philosophy
of aneurysm therapy. The young, as well as experienced practitioners, will discover subtle nuances in
the complication avoidance and complication management sections that will enhance their respective
In providing chapters on nursing considerations,
critical-care management, training, and the medicolegal aspects of patient care in this field, this textbook
has an appeal to members of the medical community
beyond the neurointerventional surgeon.

Growth in a field is welcomed. It ensures survivability and creates a legacy. The field of endovascular surgical neuroradiology continues to enjoy this
explosive growth by developing new techniques and
technologies that will improve patient outcomes. This
textbook provides the most current state-of-the-art
snapshot for endovascular surgical neuroradiology
as written by many current and emerging leaders
of the field. As you immerse yourself in the pages of
this text, identify how you serve as an integral part

of this fields growth and success. Seek out the next

frontiers in neurointerventional as delineated in the
pages of this text. Finally, contribute to the field with
improved patient outcomes through the self-learning and self-improvement that this brings to you. For
it is through the interactions and contributions of all
members of this small community whence future
success shall emerge.
Charles J. Prestigiacomo, MD, FAANS, FACS



Beverly Aagaard Kienitz, MD

Associate Professor of Radiology and Neurosurgery
Department of Radiology
University of WisconsinMadison
Madison, Wisconsin
Muhammad M. Abd-El-Barr, MD, PhD
Brigham and Womens Hospital
Boston Childrens Hospital
Harvard Medical School
Boston, Massachusetts
Felipe C. Albuquerque, MD
Assistant Director of Endovascular Neurosurgery
Department of Neurosurgery
The Barrow Neurological Institute
Phoenix, Arizona
Yazan J. Alderazi MB, BCh
Department of Neurological Surgery
Rutgers University
New Jersey Medical School
Newark, New Jersey
Michael J. Alexander, MD, FACS, FANNS
Professor and Vice-Chairman
Clinical Chief, Department of Neurosurgery
Director, Neurovascular Center
Cedars-Sinai Medical Center
Los Angeles, California
David Altschul, MD
Assistant Professor of Neurosurgery and
Interventional Neuroradiology
Department of Neurosurgery
Montefiore Medical Center
Albert Einstein College of Medicine
Bronx, New York


Col. Rocco Anthony Armonda (Ret.), MD

United States Marine Corps
Director, Neuroendovascular Surgery
Co-Director, Neuro-ICU and Neurotrauma
Department of Neurosurgery
Georgetown University Hospital and Washington
Hospital Center
Washington, DC
Issam A. Awad, MD, MSc, FACS, MA (Hon)
The John Harper Seeley Professor
Department of Surgery (Neurosurgery)
Neurology and the Cancer Center
Director of Neurovascular Surgery
University of Chicago Medicine and Biological
Chicago, Illinois
Anu Bansal, MD
Director of Neuroradiology
Jefferson Radiology
East Hartford, Connecticut
Stanley L. Barnwell, MD, PhD
Dotter Interventional Institute
Department of Neurological Surgery
Oregon Health and Science University
Portland, Oregon
H. Hunt Batjer, MD
Lois C. A. and Darwin E. Smith Distinguished Chair
in Neurological Surgery
Department of Neurological Surgery
University of Texas Southwestern Medical Center
Dallas, Texas
Tibor Becske, MD
Clinical Assistant Professor
Departments of Radiology and Neurology
New York University Langone Medical Center
New York, New York

Randy S. Bell, MD
Director, Cerebrovascular Surgery and
Interventional Neuroradiology
Walter Reed National Military Medical Center
Uniformed Services University of Health Sciences
Bethesda, Maryland
Jacqueline A. Bello, MD, FACR
Professor of Clinical Radiology and Neurosurgery
Director of Neuroradiology
Albert Einstein College of Medicine
Montefiore Medical Center
Bronx, New York
Bernard R. Bendok, MD, FACS
Professor of Neurological Surgery
Northwestern University Feinberg School of Medicine
Chicago, Illinois
Kristine Blackham, MD
Program Director, Neuroradiology
University Hospitals Case Medical Center
Assistant Professor
Department of Radiology
Case Western Reserve University School of Medicine
Cleveland, Ohio
Allan L. Brook, MD
Professor of Clinical Radiology and Neurosurgery
Department of Radiology
Albert Einstein College of Medicine
Bronx, New York
Louis P. Caragine Jr., MD, PhD, FAANS
Vascular, Endovascular and General Neurosurgery
Director, Cerebrovascular and Endovascular
Saint Francis Medical Center
Cape Girardeau, Missouri
C. Michael Cawley, MD, FACS
Associate Professor
Departments of Neurosurgery and Radiology
Emory University School of Medicine
Atlanta, Georgia
Neeraj Chaudhary, MD, MRCS, FRCR
Assistant Professor, Neurointerventional Radiology
Departments of Radiology and Neurosurgery
University of Michigan Health System
Ann Arbor, Michigan
Michael Chen, MD
Associate Professor
Departments of Neurological Sciences and
Rush University Medical Center
Chicago, Illinois


In Sup Choi, MD, FACR

Director, Interventional Neuroradiology
Lahey Hospital Medical Center
Burlington, Massachusetts
Professor of Radiology
Tufts University, School of Medicine
Boston, Massachusetts
Osamah Choudhry, MD
Department of Neurosurgery
New York University Langone Medical Center
New York, New York
Abhineet Chowdhary, MD
Director of Neurosurgery
Director of Neuro-Interventional Surgery
Overlake Hospital
Bellevue, Washington
Lana Christiano, MD
Neurological Associates, Inc
Charleston, West Virginia
Kevin M. Cockroft, MD, MSc, FAANS, FACS, FAHA
Department of Neurosurgery, Radiology, and Public
Health Sciences
Penn State Hershey Medical Center
Hershey, Pennsylvania
Celina Crisman, MD
Rutgers New Jersey Medical School
Newark, New Jersey
Guilherme Dabus, MD
NeuroInterventional Surgery Fellowship Program
Baptist Cardiac and Vascular Institute
Baptist Neuroscience Center
Associate Professor
Herbert Wertheim College of Medicine
Florida International University
Miami, Florida
Badih Daou, MD
Department of Neurosurgery
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania
Colin P. Derdeyn, MD, FAHA, FACR
Professor of Radiology, Neurology, and Neurological
Mallinckrodt Institute of Radiology
Director, Stroke and Cerebrovascular Center
Washington University School of Medicine/Barnes
Jewish Hospital
St. Louis, Missouri


xiv Contributors
Jacques E. Dion, MD, FRCP
Professor of Radiology and Neurosurgery
Departments of Radiology and Neurosurgery
Emory University Hospital
Atlanta, George
Aclan Dogan, MD
Assistant Professor
Head of the Skull Base and Cerebrovascular Surgery
Department of Neurological Surgery
Oregon Health and Science University
Portland, Oregon
Gary R. Duckwiler, MD
Diagnostic Radiology, Neuroradiology, Vascular and
Interventional Radiology
Ronald Reagan UCLA Medical Center
Los Angeles, California
E. Jess Duffis, MD
Neurointerventional Surgery
Department of Neurology
Baystate Medical Center
Springfield, Massachusetts
Koji Ebersole, MD
Assistant Professor
Departments of Neurosurgery and Radiology
Director of Endovascular Neurosurgery
Kansas University Medical Center
Kansas City, Kansas
Robert D. Ecker, MD
Director of Cerebrovascular/Endovascular Neurosurgery
Neuroscience Medical Director
Maine Medical Center
Portland, Maine
Associate Professor of Neurosurgery
Tufts University School of Medicine
Boston, Massachusetts
Augusto Elias, MD
Medical Director of Neurointerventional Surgery
Clinical Assistant Professor of Radiology and
Southern Illinois University School of Medicine
Memorial Medical Center
Springfield, Illinois
Maria G. Farrow, MSN, ACNP-BC
Nurse Practitioner
Department of Neurological Surgery
New YorkPresbyterian, Columbia University
Medical Center
New York, New York

Lei Feng, MS
Principal Statistical Analyst
MD Anderson Cancer Center
Houston, Texas
W. Christopher Fox, MD
Assistant Professor of Clinical Neurological Surgery
Columbia University College of Physicians and
New York, New York
Justin F. Fraser, MD
Assistant Professor of Cerebrovascular,
Endovascular, and Skull Base Surgery
Director, Cerebrovascular Surgery
Department of Neurological Surgery
University of Kentucky
Lexington, Kentucky
Chirag D. Gandhi, MD, FACS, FAANS
Associate Professor of Neurological Surgery,
Neurology, and Neuroscience
Department of Neurosurgery
Rutgers New Jersey Medical School
Newark, New Jersey
Christopher C. Getch, MD (Deceased)
Department of Neurological Surgery
Northwestern University Feinberg School of
Chicago, Illinois
Joseph J. Gemmete, MD, FSIR, FACR
Associate Professor
Department of Radiology and Neurosurgery
University of Michigan Hospitals
Ann Arbor, Michigan
DimitriosGiannakidis, MD
Department of Neurology and Neurosciences
Rutgers New Jersey Medical School
Newark, New Jersey
Y. Pierre Gobin, MD
Professor of Radiology in Neurosurgery and
Director of Interventional Neuroradiology
Department of Neurosurgery
Weill Cornell Medical College
New York, New York
Ira M. Goldstein, MD
Associate Professor of Neurological Surgery
Rutgers New Jersey Medical School
Director of Neurotrauma
The University Hospital
Newark, New Jersey

Charles A. Guidot, MD
Chief, Interventional Neuroradiology
MidMichigan Medical Center
Midland, Michigan
Gaurav Gupta, MD
Cerebrovascular and Endovascular Neurosurgery
Rutgers University
Robert Wood Johnson Medical School and Hospital
New Brunswick, New Jersey
Vikas Gupta, MD
Associate Professor, Vascular and Interventional
Department of Neurology
University of Missouri
Columbia, Missouri
Elia Haddad, MD
Stroke Director
Assistant Professor
Department of Neurology
Loma Linda University School of Medicine
Loma Linda, California
Raqeeb M. Haque, MD
Associate Neurosurgeon
Cleveland Clinic Foundation
Cleveland, Ohio
Ziad A. Hage, MD
Department of Neurosurgery
University of Illinois at Chicago
Chicago, Illinois
Tomoki Hashimoto, MD
Department of Anesthesia and Perioperative Care
University of California, San Francisco
San Francisco, California
Gregory G. Heuer, MD, PhD
Assistant Professor of Neurosurgery
Division of Neurosurgery
Childrens Hospital of Philadelphia
Philadelphia, Pennsylvania
Joshua A. Hirsch, MD, FACR, FSIR
Vice Chair and Service Line Chief, Interventional
Division Chief, NeuroInterventional Services
Chief, Minimally Invasive Spine Surgery
Department of Radiology
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts


Robert Alex Hirschl, MD

Chairman and Medical Director
Department of Neurosurgery
Mercy Medical Center
Des Moines, Iowa
James and Newton Eblen Professor
Department of Neurosurgery
University of Florida
Gainesville, Florida
L. Nelson Hopkins, MD FACS
Distinguished Professor of Neurosurgery
Professor of Radiology
School of Medicine and Biomedical Sciences
University at Buffalo, SUNY
Gates Vascular Institute
Kaleida Health
Chief Executive Officer
Jacobs Institute
Buffalo, New York
Daniel P. Hsu, MD
Goodman Campbell Brain and Spine
Indianapolis, Indiana
Ferdinand K. Hui, MD
Cerebrovascular Center
Neurological Institute
Cleveland Clinic
Cleveland, Ohio
Michael Hurley, MD
Assistant Professor
Radiology and Neurological Surgery
Northwestern University Feinberg School of
Chicago, Illinois
Robert W. Hurst, MD
Professor of Radiology
Professor of Neurosurgery
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Muhammad Shazam Hussain, MD, FRCP (C)
Cleveland Clinic Stroke Program
Associate Professor
Cleveland Clinic Lerner College of Medicine
Neurological Institute
Cleveland Clinic
Cleveland, Ohio


xvi Contributors
Rebecca Ichord, MD
Associate Professor
Departments of Neurology and Pediatrics
Childrens Hospital of Philadelphia
Perelman School of Medicine at the University of
Philadelphia, Pennsylvania
Pascal Jabbour, MD
Associate Professor
Department of Neurological Surgery
Chief, Division of Neurovascular Surgery and
Endovascular Neurosurgery
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania
Babak S. Jahromi, MD, PhD, FRCSC
Surgical Director
URMC Comprehensive Stroke Center
Departments of Neurosurgery, Neurology, and
Imaging Sciences
University of Rochester
Rochester New York
Gaurav Jain, MD
Assistant Professor of Neurological Surgery
Thomas Jefferson University
Philadelphia, Pennsylvania
Nazli Janjua, MD
Asia Pacific Comprehensive Stroke Network
Department of Interventional Neurology
Pomona Valley Hospital Medical Center
Pomona, California
Mary E. Jensen, MD
Director, Interventional Neuroradiology
Professor of Radiology, Neurology, and Neurological
Department of Radiology and Medical Imaging
University of Virginia Health System
Charlottesville, Virginia
Ruchira M. Jha, MD
University of Pittsburgh Medical Center
Department of Critical Care Medicine
Pittsburgh, Pennsylvania
Andrew Kelly Johnson, MD, MS
Department of Neurosurgery
Rush University Medical Center
Chicago, Illinois

David M. Johnson, MD
Associate Professor of Radiology and Neurosurgery
University of Vermont Medical Center
Burlington, Vermont
Reza J. Karimi, MD
Senior Endovascular Fellow
Department of Neurological Surgery
Rutgers New Jersey Medical School
Newark, New Jersey
Tareq Kass-Hout, MD
Department of Neurosurgery
Rutgers University
Newark, New Jersey
Christopher Paul Kellner, MD
Department of Neurological Surgery
Columbia University
New York, New York
Charles Kerber, MD
Professor Emeritus
Radiology and Neurosurgery
University of CaliforniaSan Diego Medical Center
San Diego, California
Shah-Naz Hayat Khan, MD, FRCS(C), FAANS
Director, Endovascular Neurosurgery
Insight Institute of Neurosurgery and Neuroscience
Flint, Michigan
Paula Klurfan, MD
Associate Professor
Division of Neurosurgery
Department of Surgery
McMaster University
Hamilton, Ontario
Keith E. Kortman, MD
Department of Neuroradiology and Interventional
San Diego Imaging
San Diego, California
Theodore C. Larson III, MD
Director of Neurointervention
Centura Health Physician Group
Neuroscience and Spine
Lakewood, Colorado
Sean D. Lavine, MD
Associate Professor of Neurological Surgery and
Columbia University College of Physicians and
New York, New York

David S. Lee, MD
Assistant Professor
Interventional Neuroradiology
Dotter Interventional Institute
Interventional Cardiology
Division of Cardiovascular Medicine
Oregon Health and Science University
Center for Health and Healing
Portland, Oregon
Elad I. Levy, MD, MBA, FACS, FAHA
Professor and Chair of Neurosurgery
Professor of Radiology
School of Medicine and Biomedical Sciences
University at Buffalo, SUNY
Medical Director of Neuroendovascular Services
Gates Vascular Institute
Kaleida Health
Toshiba Stroke and Vascular Research Center
University at Buffalo, SUNY
Buffalo, New York
Yince Loh, MD
Associate Professor
Uniformed Services University
Bethesda, Maryland
Radiology and Neurosurgery
University of California, Los Angeles
Los Angeles, California
Demetrius Lopes, MD
Section Chief, Cerebrovascular Surgery
Surgical Director, Rush Stroke Program
Surgical Director, Rush Interventional Surgery
Department of Neurosurgery
Rush University Medical Center
Chicago, Illinois
Cormac O. Maher, MD
Associate Professor
Department of Neurosurgery
University of Michigan
Ann Arbor, Michigan


Kathleen McConnell, MD
Winchester, Virginia
Cameron G. McDougall, MD
Director of Endovascular Neurosurgery
Department of Neurosurgery
The Barrow Neurological Institute
Phoenix, Arizona
Scott A. Meyer, MD
Atlantic Neurosurgical Specialists
Morristown, New Jersey
Philip M. Meyers, MD
Department of Radiology and Neurological Surgery
Columbia University, College of Physicians &
New York Presbyterian Hospitals and the
Neurological Institute of New York
New York, New York
David M. Mirsky, MD
Pediatric Neuroradiologist
Childrens Hospital Colorado
Assistant Professor of Radiology
University of Colorado
Aurora, Colorado
J Mocco, MD, MS
Associate Professor
Department of Neurological Surgery
Vanderbilt University
Nashville, Tennessee
Peter K. Nelson, MD
Chief, Neurointerventional Service
Department of Radiology
New York University Langone Medical Center
New York, New York
Daniel A. Nguyen, BS
Rutgers New Jersey Medical School
Newark, New Jersey

Sunil Manjila, MD
Department of Neurological Surgery
Neurological Institute
University Hospitals Case Medical Center
Cleveland, Ohio

Raul G. Nogueira, MD
Director, Neuroendovascular Division
Department of Neurology
Marcus Stroke and Neuroscience Center
Grady Memorial Hospital
Emory University School of Medicine
Atlanta, Georgia

Avi Mazumdar, MD
Diagnostic Neuroradiology and Interventional
Central DuPage Hospital
Winfield, Illinois

Martin D. Ollenschleger, MD
Attending Interventional Neuroradiologist
Department of Radiology
Hartford Hospital
Hartford, Connecticut


xviii Contributors
Scott E. Olson, MD
Assistant Clinical Professor
University of CaliforniaSan Diego
San Diego, California
Aditya S. Pandey, MD
Assistant Professor of Neurosurgery and Radiology
Director of the Comprehensive Stroke Center
Department of Neurosurgery and Radiology
University of Michigan
Ann Arbor, Michigan
Paritosh Pandey, MCh
Additional Professor
Department of Neurosurgery
Bangalore, India
Min S. Park, MD
Assistant Professor
Department of Neurosurgery
University of Utah Medical Center
Salt Lake City, Utah
Athos Patsalides, MD, MPH
Assistant Professor of Radiology and Neurological
Interventional Neuroradiology
Department of Neurological Surgery
Weill Cornell Medical College
New York, New York
Aman B. Patel, MD
Robert G. and Jean A. Ojemann Associate Professor
of Neurosurgery
Department of Neurosurgery
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Neil V. Patel, MD
Interventional Neuroradiologist
Department of Radiology
Lehigh Valley Health Network
Allentown, Pennsylvania
Charles J. Prestigiacomo, MD, FAANS, FACS
Professor and Chairman
Department of Neurological Surgery
Professor of Radiology and Neurology and
Director of Cerebrovascular and Endovascular
Rutgers New Jersey Medical School
Newark, New Jersey

Mahmoud Rayes, MD
Department of Neurology
Wayne State University
Detroit, Michigan
Howard A. Riina, MD
Professor and Vice Chairman
Department of Neurosurgery
New York University School of Medicine
New York University Langone Medical Center
New York, New York
Andrew J. Ringer, MD
University of Cincinnati College of Medicine
Director of Cerebrovascular Surgery
University of Cincinnati Medical Center
Mayfield Clinic
Cincinnati, Ohio
Ryan L. Roberts, MD
Department of Ophthalmology
Madigan Army Medical Center
Tacoma, Washington
Charles E. Romero, MD
Medical Director
Neuro Intensive Care
Department ofNeurointerventional Radiology
University of Pittsburgh Medical CenterHamot
Erie, Pennsylvania
Ravi Shah, BS, BA
Department of Neurosurgery
Rutgers New Jersey Medical School
Newark, New Jersey
Ali Shaibani, MD
Associate Professor
Departments of Radiology and Neurosurgery
Co-director, Neurointervention
Director, Pediatric Neurointervention
Northwestern University Feinberg School of
Chicago, Illinois
Maksim Shapiro, MD
Department of Radiology and Neurology
New York University School of Medicine
Bernard and Irene Schwartz Interventional
Neuroradiology Center
New York, New York
Nakul Sheth, BA
Department of Neurological Surgery
Rutgers New Jersey Medical School
Newark, New Jersey

Michelle J. Smith, MD
Assistant Professor of Neurosurgery
Department of Neurosurgery
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania
Gabriela Spilberg, MD
University of Massachusetts
Worcester, Massachusetts
Michael F. Stiefel, MD, PhD
NeuroVascular Institute
Westchester Medical Center
Maria Fareri Childrens Hospital
New York Medical College
Westchester, New York
Philip Stieg, MD, PhD
Professor, Chairman
Department of Neurological Surgery
New York Presbyterian Hospital
Weill Cornell Medical Center
New York, New York


Karel terBrugge, MD, FRCPC

The David Braley and Nancy Gordon Chair in
Interventional Neuroradiology
Professor of Radiology and Surgery
Division of Neuroradiology
University of Toronto
Toronto Western Hospital
Toronto, Ontario
B. Gregory Thompson, MD
Professor and Program Director
Department of Neurosurgery
University of Michigan
Ann Arbor, Michigan
Frank C. Tong, MD
Assistant Professor of Radiology and Neurosurgery
Emory University School of Medicine
Atlanta, Georgia

Jeffrey A. Stone, MD, FACR

Associate Professor
Department of Radiology
Mayo Clinic
Jacksonville, Florida

Roger E. Turbin, MD, FACS

Assistant Professor
Associate Director, Neuro-ophthalmology
Institute of Ophthalmology and Visual Science
Rutgers New Jersey Medical School
Newark, New Jersey
Chief of Neuro-opthalmology Service
Department of Veterans Affairs Medical Center
East Orange, New Jersey

Phillip B. Storm, MD
Chief, Division of Neurosurgery
Leslie N. Sutton Chair of Neurosurgery
Perelman School of Medicine
University of Pennsylvania and Childrens Hospital
of Philadelphia
Philadelphia, Pennsylvania

Erol Veznedaroglu, MD, FAANS, FACS, FAHA

Capital Institute for Neurosciences
Department of Neurosurgery
Stroke and Cerebrovascular Center of New Jersey
Pennington, New Jersey

Daniel L. Surdell, MD
Associate Professor
Department of Surgery, Neurological Surgery
University of Nebraska Medical Center
Omaha, Nebraska

Christine Villegas, MBS

Rutgers New Jersey Medical School
Newark, New Jersey

Vivek H. Tank, MD
Rutgers New Jersey Medical School
Newark, New Jersey
Robert W. Tarr, MD
Section Head of Neuroradiology
Professor of Radiology, Neurology, and
University Hospitals Case Medical Center
Case Western Reserve University
Cleveland, Ohio

Ajay K. Wakhloo, MD, PhD, FAHA

Professor of Radiology, Neurology, and
Division Chief
Neurointervention and Imaging
University of Massachusetts
Amherst, Massachusetts
John B. Weigele, MD, PhD (deceased)
Assistant Professor of Clinical Radiology
Department of Radiology
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania


xx Contributors
Jason Wilson, MD, MS
Assistant Professor
Department of Neurosurgery
Louisiana State University Health Science Center
New Orleans
New Orleans, Louisiana
Joan C. Wojak, MD
Womens and Childrens Hospital
Regional Medical Center of Acadiana
Lafayette, Louisiana
Andrew R. Xavier, MD
Director, Vascular and Interventional Neurology
Department of Neurology
Wayne State University School of Medicine
Detroit, Michigan
Wayne Yakes, MD
Vascular Malformation Center
Interventional Neuroradiology and Interventional
Swedish Medical Center
Colorado Neurological Institute
Englewood, Colorado

Albert J. Yoo, MD
Assistant Professor in Radiology
Department of Interventional Neuroradiology
Massachusetts General Hospital
Boston, Massachusetts
William L. Young, MD (deceased)
James P. Livingston Professor and Vice Chair for
Department of Anesthesia and Perioperative Care
Professor of Neurological Surgery and Neurology
University of CaliforniaSan Francisco
San Francisco, California
Y. Jonathan Zhang, MD, FAANS
Assistant Professor of Neurological Surgery
Department of Neurosurgery
Houston Methodist Neurological Institute
Weill Medical College of Cornell University
Houston, Texas

Part I

General Endovascular Tenets

Vascular Biology of the Endothelium

Gaurav Gupta and Charles J. Prestigiacomo

The word endothelium is derived from the Greek
endon (i.e., within) and thele (i.e., nipple). The endothelium is the largest endocrine organ of the human
body and approximately 110 grams in physical mass1
with only about 1 mL in volume for a 1,200 g human
brain.2 The term bloodbrain barrier was coined in
1900 by Max Lewandowsky (18761916), who called
it bluthirnschranke. Paul Ehrlich in (18541915) was
the first to observe the special barrier function of
the cerebral endothelial cells. In 1885, Ehrlich observed that water-soluble dyes injected into the peripheral circulation did not stain the brain or color
the cerebrospinal fluid (CSF); however, the choroid
plexus showed heavy staining. Additional experiments showed that the same dyes injected into the
subarachnoid space colored the brain and CSF but
not the peripheral tissues. German neuropathologist
Hugo Spatz (18881969) demonstrated the contribution of the endothelial cells of what was then termed
the hematoencephalic barrier function.3 However, in
1941, Tore Broman demonstrated the contribution of
the basement membrane to the bloodbrain barrier.4
He observed that there were two barrier systems in
the brain, the bloodCSF barrier at the choroid plexus and the bloodbrain barrier (BBB) at the cerebral
microvasculature. In 1952, Niessing and Rollhuser5
demonstrated the role of the basement membrane,
and Tschirgi in 1952 showed the role of the glia limitans (formed by the foot processes of the astrocytes).
In 1959, Rollhuser showed the contribution of the
pericytes separately in forming an effective BBB. The
debate as to whether the astrocytic end feet or the
capillary endothelium comprises the BBB was laid to
rest by electron microscopy and the landmark paper
on diffusion of horseradish peroxidase and lanthanum salt, which stopped at the level of tight junctions after intracerebral injections performed in the
late 1960s by Reese and Karnovsky6 and by Brightman and colleagues.7

The endothelium is critical for maintaining a constant ion balance for highly selective neurons, astrocytes, and oligodendrocytes. It acts both as a target
and as a source of autocoids, growth factors, apoptosis,8 cytokines/chemokines,9 oxygen radicals, and
hemostatic factors.10 The key concept that the endothelium acts not only as a physical permeability
barrier but also in an autocrine/paracrine manner
emerged after the discovery of the endotheliumderived relaxing factor (EDRF) in 1980. EDRF was
later characterized as nitric oxide (NO) in 1987.11,12 In
1992, nitric oxide was named Molecule of the Year
by the journal Science, the Nitric Oxide Society was
founded, and a scientific journal devoted entirely to
nitric oxide was established. In 1998, the Nobel Prize
in Physiology or Medicine was awarded to Ferid Murad, Robert F. Furchgott, and Louis Ignarro for the
discovery of the signaling properties of NO. Before
the discovery of the EDRF, prostacyclin (PGI2) was
regarded as the best-known endothelial vasodilator
in addition to its activity as a platelet aggregation inhibitor. These two relaxing factors are released from
endothelial cells in response to a variety of vasoactive
substances and are thought to regulate vascular tone.

In mice and rats, the BBB does not develop fully until
7 to 8 weeks postpartum, but the BBB of pigs, sheep,
and primates is fully developed at birth and is indistinguishable from that of an adult. In general, the
mammalian BBB is present at birth or no later than
2 months postpartum.13 Developmentally, central
nervous system (CNS) capillaries originate from solid
cords of endothelial cells,14 which develop a slitlike
lumen that progressively increases in caliber. The
cords are separated from the adjacent neurons by the
basement membrane, and with time they become
surrounded by resident astrocytes. The rapid proliferation of the capillary endothelial cells has to keep up
with the metabolic demands of rapid CNS growth and

4 Part I General Endovascular Tenets

is directly proportional to the metabolic activity and
oxygen consumption inherent to each brain region.

Endothelium and the

Subendothelial Matrix
The distance between capillaries in the brain is approximately 40 m, indicating that virtually every
single neuron is supplied by its own independent
blood vessel catering to the extensive metabolic
needs of the neuron2 (Fig. 1.1).
Dysfunction of the human brain microvascular
endothelial cells (HBMECs) is a key risk factor for the
development of macro- and microvascular disease.15
Under physiological conditions, endothelial cells are
crucial in maintaining a nonthrombogenic interface
between vessels and circulating blood. The luminal
surface of the endothelium is covered with a 500 nm
gel-like layer of endothelial glycocalyx, which helps
in the interaction with red blood cells and plasma as
well as the penetration of leucocyte microvilli.16 On
the abluminal side, they are directly in communication with the subendothelial matrix and with smooth
muscle cells or glial cells.17 The brain arteries, in contrast to the arteries in the systemic circulation, have a
single internal elastic lamella instead of the internal
and outer elastic lamellae found in the general circulation. This is one of the mechanisms postulated for
the development of brain aneurysms, which classically occur at the point where intracerebral arteries
branch. Approximately 30% of aneurysms occur at the
branch point between the internal carotid and posterior cerebral arteries. The rest occur at more distal
branch points, including the level of the anterior communicating artery, the first branch points of the middle cerebral artery, and the tip of the basilar artery.
The basement membrane is composed of collagens; laminin; fibronectin III, IV, and VII; entactin; heparan sulfate proteoglycans; and chondroitin
sulfate proteoglycans. The endothelial cells and the
pericytes share a common capillary basement mem-

Fig. 1.1 Brain capillary. A network of capillaries supplies

brain cells with nutrients. Tight seals in their walls keep blood
toxinsand many potentially beneficial drugsout of the
brain. (Image courtesy of D. Ferber [Ferber 2007].)

brane. Pericytes are perivascular cells associated

with capillaries and postcapillary venules and are
embedded in the basement membranes of vessels.
They extend long cytoplasmic processes around the
capillary tubes, forming the so-called peg and socket
contacts. There is approximately one pericyte for every two to four endothelial cells. They play a major
role in endothelial cell contractility, activity, and inflammation. Endothelial cell cytoplasmic structures
include the Golgi apparatus adjacent to the nucleus,
mitochondria, and a granular matrix. The cytoplasm
contains enzymes, such as adenosine triphosphatase
(ATPase), dehydrogenases (succinate, lactate, glutamate, and glucose), nicotinamide adenine dinucleotide (NAD), monoamine oxidase, acid and alkaline
phosphatases, DOPA decarboxylases, and gammaglutamyl transpeptidases.13
Endothelial cells in the brain differ from those of
other vascular beds because of the tight cellcell contacts that are key for the BBB. Further distinguishing features include the paucity of pinocytic activity
(clathrin or calveolae mediated), the high number of
mitochondria, and the absence of fenestrations that
maintain the high transendothelial electrical resistance (TEER) secondary to reduced paracellular flux
of ions and charged particles.
The walls of capillaries in peripheral tissues
are like Swiss cheese, whereas the walls of capillaries in the brain are like cheddar cheese
William Pardridge18
CNS endothelium can be continuous due to the occluding tight junctions seen in the brain, retina, and
spinal cord, allowing only a little paracellular diffusion and highly selective transendothelial transport19
(Table 1.1). Alternatively, they may be fenestrated endothelium, as seen in the choroid plexus of the brain,
or discontinuous, as seen in the liver, spleen, and bone
marrow. Circumventricular organs (i.e., pineal, choroid
plexus, area postrema, pituitary gland, median eminence, subfornical organ, organum vasculosum laminae terminalis), however, lack the tight junctions. Here
the endothelium is fenestrated, allowing free passage
of molecules and hormones. The endothelialtight
junction complex is made up of the tight junctions, the
zonula occludens, the zonula adherens, and the desmosomes. The bloodretinal barrier of the vascularized inner retina of the eye has many properties similar
to those of the BBB, but the permeability is higher.
The power of the endothelium to locally control
vasoconstriction is maximal in small-caliber vessels,
which contain the majority of the endothelial cells
within the vascular tree, rather than in the larger vessels, such as the coronary arteries or the carotid arteries.8 The fenestrae, which lack a lipid bilayer, allow
more permeability to water, ions, and smaller solutes
but do not allow any greater permeability to plasma
proteins than do continuous capillaries. However,

1 Vascular Biology of the Endothelium

Table 1.1 Functions of tight junctions of the
bloodbrain barrier

Blood vessel with intact endothelium


1. Regulation of transmembrane tight junction proteins via
G proteins, tyrosine kinases



2. Regulation of intracellular and extracellular calcium and

cyclic adenosine monophosphate (cAMP) levels

3. Regulation of intracellular metabolism via proteases and

tumor necrosis factor alpha (TNF-)

they do have a heparan sulfate proteoglycan that imparts a highly negative charge to the cells.20 Water and
small lipid-soluble substances like oxygen, nitrogen,
and carbon dioxide directly penetrate the cell surface.
Larger, water-insoluble lipid molecules diffuse laterally within the lipid bilayer, and cations (Na+, K+), anions (Cl, HCO3), and small solutes like amino acids
and glucose permeate the intercellular junctions.2123 It
has been shown that the endothelial fenestrae are dynamic, rather than fixed, structures, whose diameter
and surface properties can be altered by hypoxia,2426
epilepsy,27 luminal pressure,28 shock,29 vasoactive substances, drugs, radiation,30,31 toxins,32,33 and ultrasound
waves.34 Endothelial cells in culture change their morphology under flow conditions as well as under static
or pulsatile conditions.3537 In disease states, the vascular characteristics of large arteries contribute to the
development of atherosclerotic plaques by imbibing
circulating lipids and incorporating them into plaques.
This results in thrombus deposition secondary to the
denudation of endothelium, which in turn causes expression of powerful procoagulant tissue factors.38
The BBB is a dynamic or a modular system
with continuous interactions between the endothelium, astrocytes, neurons, pericytes, and microglia
(Fig.1.2). Endothelial cells from arteries produce
different physiological responses than do endothelial cells from veins and capillaries. The endothelium
synthesizes both pro- and anticoagulants. The main
endothelium-derived procoagulants are plasminogen activator inhibitor (PAI)-1, von Willebrand factor
(vWF), protease-activated factors, and tissue factors.
The main anticoagulants are tissue factor pathway inhibitor (TFPI), heparin, endothelial protein C receptor
(EPCR), tissue type plasminogen activator, ecto-ADPase, prostacyclin, and NO. Arterial endothelial cells
express tissue plasminogen activator (t-PA), arterial
endothelial NO synthase (eNOS), and EPCR.3941 Venous endothelial cells express EPCRs and vWFs. Capillary endothelial cells express TFPIs. In addition to
the presence of tight junctions6,7 and the lack of vesicles, a number of enzymes, including alkaline phosphatase, gamma-glutamyl transpeptidase, and Na+,
K+-ATPase are present in higher concentrations in
the cerebral endothelium than in other tissues.42



Perivascular feet








Blood vessel with damaged endothelium







Perivascular feet




muscle cells




Fig. 1.2 (a, b) The bloodbrain barriera dynamic modular


Certain genes are preferentially expressed exclusively by the brain as compared with the peripheral
endothelial cells, for example, vascular endothelial
growth factor (VEGF), fibroblast growth factor (FGF-2),
insulin-like growth factor (IGF) binding protein, follistatin (an angiogenic protein), integrin-beta 5 and alpha-1, and transforming growth factor (TGF) beta-2.28
Other important genes expressed by the peripheral endothelial cells but not expressed in the brain
are platelet endothelial cell adhesion molecule (PECAM-1), adhesion molecule ICAM-2, and some matrix
metalloproteinases, among others.43 In addition, brain
cells have a much higher expression of growth factors
such as brain-derived neurotrophic factor (BDNF),
stem cell factor (SCF), TGF beta-2, interleukin (IL)-6,

6 Part I General Endovascular Tenets

Table 1.2 Chemical influences on the endothelial cells

Nitrous oxide (NO), endothelium-derived hyperpolarization factors (EDHFs), prostacyclin (PGI-2), PGE-2


Endothelium-derived constriction factors (EDCFs), superoxide radical, endothelins,3941

thromboxane A2, angiotensin II


Endothelin 1, angiotensin II

Growth factors

Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming
growth factor beta (TGF-)

Other bioactive proteins

Fibrinogen, von Willebrand factor (vWF), tissue factor, platelet activating factor (PAF), tissue plasminogen activator (tPA), -urokinase, natriuretic peptide (B and C)

and monocyte chemoattractant protein (MCP-1),

which are thought to be neuroprotective44 (Table 1.2).
For transendothelial transport of molecules such
as sugars, amino acids, and other organic acids, the
rate is determined by molecular size, lipid solubility, and the presence of a specific carrier-mediated
transport system.13 In tissues other than the CNS,
concentrations of various metabolites (amino acids,
K+) can undergo frequent fluctuations. The CNS must
keep rigorous control over the extracellular cerebral
fluid composition, preventing the mirroring of transient fluctuations in blood, because abrupt changes
in these metabolites can translate to aberrant CNS
function.45 The main mechanisms for transendothelial transport are carrier-mediated transport for small
polar substances (e.g., glucose, amino acids, thyroid
hormones, and water-soluble vitamins), receptormediated transcytosis (e.g., insulin, transferrin, leptin,
low-/high-density lipoprotein), active-efflux transporter (e.g., for low molecular weight end-products
and xenobiotics), and absorptive-endocytotic pathway (e.g., for cationic albumin).46,47
Loss of BBB function may contribute to postischemic cerebral injury by as yet unknown mechanisms.
What is known is that it occurs early and is modulated over time, contributing to loss of neuronal function due to metabolic and ionic imbalance. There is
leakage of diagnostic contrast agents in computed
tomographic and magnetic resonance imaging scans.
BBB disruption after ischemia causes the tight junctions to become leaky and is associated with degradation of basal lamina matrix proteins, alterations
of glia limitans, increased pinocytic activity, and vesicular transport in cerebral endothelial cells.48 Ischemia is associated with anoxia, aglycemia, and loss
of flow (i.e., shearing forces).49 Recent studies have
shown that ischemic preconditioning may protect
the HBMECs from ischemia-reperfusion injury,50 and
several therapeutic targets may be available to protect cerebrovascular endothelium from apoptotic
injury following cerebral ischemia.51 At a cerebral endothelial level, BBB leakage can be seen as early as 3
hours after an ischemia-reperfusion injury. There is
upregulation of the Na+/K+ cotransporter leading to
sodium influx into the brain interstitial fluid, which
leads to edema. In addition, there is upregulation of
enzymes of the glycolytic pathways, proteins of the

endoplasmic reticulum, and the cytoskeleton.52 Endothelial BBB dysfunction is the leading cause of both
ionic and vasogenic edema.8 The integral concept of
the neurovascular unit/bloodbrain barrier shifts the
former neurocentric view of stroke to an integrative brain response to ischemia in which the outcome
is determined by the interaction between affected
cells and matrix.8,53,54
The endothelial cell transport of tumor necrosis factor (TNF) is upregulated early with increased expression
of its receptors TNFR-1 and TNFR-2.55 It is also thought
that impaired function of the brain vasculature/
endothelium might contribute to the development of
HIV-associated dementia because injury or dysfunction
of brain microvascular endothelial cells (BMECs) can
lead to the breakdown of the BBB and thus allow accelerated entry of the HIV-1 virus into the CNS.56
Organ-specific differences in the endothelial cells
and the epinephrine/Eph system establish the arterial endothelial and venous endothelial identity
separately. Even in the same organ (brain), there are
significant vascular-bed-specific differences in the
endothelial cells.57 This is more important in conditions like arteriovenous malformations, which are
thought to be induced by loss of this very structural
segregation and specificity.58

Endothelial cells are responsible for the maintenance of the nonadhesive and antithrombogenic properties of the inner lumen or the
endothelial side of the blood vessels and form
an integral part of the bloodbrain and blood
cerebrospinal fluid barrier.
Cytokines, secreted by the perivascular astrocytes, help to maintain the function or selective permeability of the bloodbrain barrier
and also maintain its modularity.
During times of stress, ischemia, or injury, there
is selective endothelial ischemia and/or damage, leading to an activation of vasogenic and
cytotoxic cascades, ultimately leading to failure
of the integrity of normal vascular biology and
loss of integrity of the bloodbrain barrier.

1 Vascular Biology of the Endothelium

The authors thank Peter Pytel, MD, Associate Professor of Pathology/Neuropathology, the University of
Chicago, for his editorial assistance.

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11 PubMed
26. Witt KA, Mark KS, Huber J, Davis TP. Hypoxia-inducible factor
and nuclear factor kappa-B activation in blood-brain barrier
endothelium under hypoxic/reoxygenation stress. J Neurochem 2005;92(1):203214 PubMed
27. Librizzi L, Regondi MC, Pastori C, Frigerio S, Frassoni C, de Curtis M. Expression of adhesion factors induced by epileptiform
activity in the endothelium of the isolated guinea pig brain in
vitro. Epilepsia 2007;48(4):743751 PubMed
28. Fraser R, Bowler LM, Day WA, Dobbs B, Johnson HD, Lee D. High
perfusion pressure damages the sieving ability of sinusoidal
endothelium in rat livers. Br J Exp Pathol 1980;61(2):222228
29. Frenzel H, Lenz W, Kremer B. The fine structure of sinusoidal
lining cells in rat liver in the early stage of endotoxic shock.
A TEM and SEM study [in German]. Verh Dtsch Ges Pathol
1978;62:269274 PubMed
30. Frenzel H, Hcker H, Richter IE, Kremer B. Ultrastructure of
the liver sinus following lethal and therapeutic Roentgen irradiation [in German]. Verh Dtsch Ges Pathol 1975;59:565
31. Frenzel H, Hcker H, Kremer B. The liver sinusoids in rats
following fractionated local telecobalt-irradiation: a transmission and scanning electron microscopic study [in German]. Virchows Arch A Pathol Anat Histol 1977;375(1):3751
32. Doran KS, Liu GY, Nizet V. Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain
endothelium and contributes to development of meningitis. J
Clin Invest 2003;112(5):736744 PubMed
33. van Sorge NM, Ebrahimi CM, McGillivray SM, et al. Anthrax
toxins inhibit neutrophil signaling pathways in brain endothelium and contribute to the pathogenesis of meningitis.
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34. Sheikov N, McDannold N, Sharma S, Hynynen K. Effect of focused ultrasound applied with an ultrasound contrast agent
on the tight junctional integrity of the brain microvascular
endothelium. Ultrasound Med Biol 2008;34(7):10931104
35. Dewey CF Jr, Bussolari SR, Gimbrone MA Jr, Davies PF. The
dynamic response of vascular endothelial cells to fluid shear
stress. J Biomech Eng 1981;103(3):177185 PubMed
36. Remuzzi A, Dewey CF Jr, Davies PF, Gimbrone MA Jr. Orientation of endothelial cells in shear fields in vitro. Biorheology
1984;21(4):617630 PubMed

8 Part I General Endovascular Tenets

37. Davies PF, Remuzzi A, Gordon EJ, Dewey CF Jr, Gimbrone MA Jr.

Turbulent fluid shear stress induces vascular endothelial cell

turnover in vitro. Proc Natl Acad Sci U S A 1986;83(7):2114
2117 PubMed
38. Caplan LR, Fisher M. The endothelium, platelets, and brain
ischemia. Rev Neurol Dis 2007;4(3):113121 PubMed
39. Aird WC. Endothelium as a therapeutic target in sepsis. Curr
Drug Targets 2007;8(4):501507 PubMed
40. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res
2007;100(2):158173 PubMed
41. Aird WC. Phenotypic heterogeneity of the endothelium: II.
Representative vascular beds. Circ Res 2007;100(2):174190
42. Bradbury MW. The structure and function of the blood-brain
barrier. Fed Proc 1984;43(2):186190 PubMed
43. Kallmann BA, Wagner S, Hummel V, et al. Characteristic gene
expression profile of primary human cerebral endothelial
cells. FASEB J 2002;16(6):589591 PubMed
44. Jttler E, Tarabin V, Schwaninger M. Interleukin-6 (IL-6): a
possible neuromodulator induced by neuronal activity. Neuroscientist 2002;8(3):268275 PubMed
45. Yang J, Aschner M. Developmental aspects of blood-brain barrier (BBB) and rat brain endothelial (RBE4) cells as in vitro
model for studies on chlorpyrifos transport. Neurotoxicology
2003;24(4-5):741745 PubMed
46. Pardridge WM. Blood-brain barrier biology and methodology.
J Neurovirol 1999;5(6):556569 PubMed
47. Pardridge WM. Drug and gene targeting to the brain with molecular Trojan horses. Nat Rev Drug Discov 2002;1(2):131139
48. Sasaki S, Ferszt R, Cervs-Navarro J. Transendothelial vesicular
transport of protein in brain edema induced by ultraviolet irradiation. Acta Neuropathol 1977;40(3):207212 PubMed

49. Krizanac-Bengez L, Kapural M, Parkinson F, et al. Effects of

transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6. Brain Res 2003;977(2):239
246 PubMed
50. Vlasov TD, Korzhevski DE, Poliakova EA. Ischemic adaptation
of the rat brain as a method for protection of endothelium
from ischemic reperfusion injury [in Russian]. Ross Fiziol Zh
Im I M Sechenova 2004;90(1):4048 PubMed
51. Zhang Y, Park TS, Gidday JM. Hypoxic preconditioning protects
human brain endothelium from ischemic apoptosis by Aktdependent survivin activation. Am J Physiol Heart Circ Physiol
2007;292(6):H2573H2581 PubMed
52. Haseloff RF, Krause E, Bigl M, Mikoteit K, Stanimirovic D, Blasig
IE. Differential protein expression in brain capillary endothelial cells induced by hypoxia and posthypoxic reoxygenation.
Proteomics 2006;6(6):18031809 PubMed
53. Lo EH, Moskowitz MA, Jacobs TP. Exciting, radical, suicidal:
how brain cells die after stroke. Stroke 2005;36(2):189192
54. Nagaraja TN, Knight RA, Croxen RL, Konda KP, Fenstermacher JD. Acute neurovascular unit protection by simvastatin in
transient cerebral ischemia. Neurol Res 2006;28(8):826830
55. Pan W, Ding Y, Yu Y, Ohtaki H, Nakamachi T, Kastin AJ. Stroke
upregulates TNFalpha transport across the blood-brain barrier. Exp Neurol 2006;198(1):222233 PubMed
56. Toborek M, Lee YW, Pu H, et al. HIV-Tat protein induces oxidative and inflammatory pathways in brain endothelium. J Neurochem 2003;84(1):169179 PubMed
57. Aird WC. Vascular bed-specific thrombosis. J Thromb Haemost
2007;5(Suppl 1):283291 PubMed
58. Hirashima M, Suda T. Differentiation of arterial and venous
endothelial cells and vascular morphogenesis. Endothelium
2006;13(2):137145 PubMed

Ravi Shah, Tareq Kass-Hout, and Charles J. Prestigiacomo

Hemostasis is the mechanism by which the body mitigates blood loss to maintain a stable internal environment upon blood vessel injury. Hemostasis can
be divided into two stages, primary and secondary.
Primary hemostasis describes the action of platelets
immediately following the insult, whereas secondary
hemostasis denotes the initiation and progression of
the coagulation cascade to the formation of a stable,
impermeable clot. Hemostasis and thrombosis are
innately linked, but the method of platelet aggregation preserves their uniqueness. The main glycoprotein-mediating platelet aggregation, von Willebrand
factor (vWF), is primarily active during conditions of
high shear stress and high-velocity flow, conditions
that typically occur upon vessel injury.1
The body must preserve a delicate balance
between procoagulatory and anticoagulatory mechanisms to prevent pathological activation of the coagulation cascade. This balance is maintained at the level
of platelet aggregation and fibrinogen polymerization.
Subtle disturbances in such balance can be deleterious, as is evidenced in the clinical setting by various
thrombophilias and hemophilias.

Disruption of cytokine


Rapid Response

It is important to remember that very few proteins serve only one function or interact with just
one enzyme. Hemostasis after vessel injury proceeds
from the initial vascular spasm/vasoconstriction to
platelet plug formation and finally to fibrin clot formation. Fibrinolysis and dissolution of the clot ultimately occur, completing the hemostatic response
(Fig. 2.1). This chapter presents a systematic approach
to hemostasis, isolating the individual components
and defining their distinct and integrative roles.

Formation of a Hemostatic Plug

Endothelial response to insult, under shear stress,
oxidative damage, infection, hypoxia, and other
irritants, can be divided into two phases. The first
rapid response is a shift in the balance of cytokines
and vasoactive factors, such as prostaglandins, nitric
oxide, endothelin, and vWF, among others. The second, slower response is a change in the properties
and remodeling of the endothelium, basement membrane, and extracellular matrix (ECM) in prepara-



Slower Response

of vessel

Fig. 2.1 Vessel response to injury.

Vessel response to injury

10 Part I General Endovascular Tenets

tion for architectural change to the vessel wall.2 The
rapid response results in vasoconstriction, which is
thought to occur primarily via the upregulation of
endothelin-1, and to a lesser extent endothelin-2
and -3.3 Endothelin-1 can bind to either endothelin
receptor type A (ETA) or type B (ETB), both of which
are G-protein coupled receptors. Endothelin-1 binding to ETB promotes a vasodilatory response, possibly
by a nitric oxidecyclic guanosine monophosphate
(GMP) pathway, prostaglandin production, and voltage-activated potassium channels.4 ETA serves endothelin-1s vasoconstrictive functions via activation of
a protein kinase G pathway.5

cium from the plasma that is also triggered by platelet activation. The increase in calcium concentration
serves as an important signaling mechanism that
activates various pathways for efficient hemostasis. These pathways include exposure of negatively
charged phospholipids on the platelet surface, a vital
step for coagulation factor activation, and induction
of actin filament polymerization and interaction
with contractile proteins.8,9 Platelet conformation
becomes irregular with protruding filopodia as a
consequence of these molecular changes.

Platelet Activation

Under homeostatic conditions, platelets are able to

flow through endothelial celllined vessels without
adhering to or aggregating at the vessel wall.10 Platelet adhesion and aggregation at the site of vascular
injury are mediated by ECM proteins and signaling
pathways. There are a vast number of extracellular
matrix proteins that can promote aggregation. These
proteins include collagen, fibrinogen, laminin, thrombospondin, fibronectin, and vWF, along with others
whose functions have not yet been fully elucidated.
Of these aforementioned proteins, vWF plays a vital
role when there is high sheer stress involved. Platelet
cohesion, or aggregation, is as important to plug formation as the initial platelet adhesion and involves
many of the same receptors and ligands, including vWF, fibrinogen, IIb3, and GPIb. The bridge
between platelets and collagen is formed primarily by
vWF present on vascular tissue and its platelet receptor, GPIb. vWF binds to the GPIb platelet receptor
that is a part of the larger GPIb-IX-V complex responsible for tethering platelets to collagen at high shear
rates.11 vWF is synthesized in both, endothelial cells

Platelet activation occurs simultaneously with vasoconstriction. Platelets are activated at the site of
vessel injury by interaction of the now exposed glycine-proline-hydroxyproline (GPO) domain of collagen to glycoprotein VI in platelet membranes.6 The
integrin 21, also in platelet membranes, binds to
newly exposed collagen fibers as well, further activating the platelets and initiating the release of and
dense granule contents. Immediate chemical mediators of platelet activation include adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin.
ADP is released from dense granules and endothelial
cells, whereas TXA2 synthesis is upregulated after
injury.7 Thrombin is formed via the concomitant progression of the coagulation cascade (Fig. 2.2).
Expression of collagen- and fibrinogen-binding
integrins, 21 and II3, respectively, is upregulated via positive feedback from the aforementioned
chemical mediators. There is concomitant release of
calcium from platelet organelles and an influx of cal-

Platelet Adhesion and Aggregation

Fig. 2.2 The platelet activation cascade. ADP, adenosine diphosphate; GPVI, glycin-hydroxyproline domain of glycoprotein VI in
platelet membrane; TXA2, thromboxane A2.

and stored in granules in megakaryocytes12,13 and is
usually deposited in the subendothelium or released
into the plasma.14 Although it can be generally stated
that collagen supports platelet adhesion, collagens
IIV support platelet adhesion at high shear rates,
whereas adhesion to types VIVIII is flow dependent.15 Type V collagen supports adhesion only under
static conditions. Although many platelet receptors have the ability to bind collagen, it seems that
21 and GPVI play major pathophysiological roles
in platelet adhesion defects, whereas GPIV, another
platelet adhesion protein, plays a lesser role.1619
Although platelets must adhere to the subendothelium to provide hemostatic functions, they must
bind to fibrin and fibrinogen to cross-link with each
other.20 The platelet receptor for both fibrin and
fibrinogen is GPIIb/IIIa (integrin IIb3). Alpha granules in platelets are covered by GPIIb/IIIa molecules,
which are externalized upon platelet activation.7
It primarily binds fibrinogen but also has affinities
for vWF, cluster of differentiation 40L (CD40L), and
fibronectin.2123 In Bernard-Soulier syndrome, where
GPIb is lacking, impaired platelet binding to fibrinogen is also observed.24 This may be consistent with
the theory that platelet adhesion to fibrinogen is
facilitated by platelet adhesion to vWF via GPIb at
high shear rates.25
Fibronectin is a plasma protein as well as an ECM
protein that mediates a wide variety of interactions,
ranging from cell adhesion and migration to cell differentiation.26 It also plays a role in platelet cohesion
and aggregation that is mainly mediated by integrins
IIb3 and 51.2729 In the absence of fibronectin,
delayed thrombus formation and shedding of platelets is observed.30 Thrombospondin and laminin also
play a role in platelet adhesion and aggregation, but
one that is less clearly defined. Their absence may
not be as noticed as would be the absence of collagen, fibrin, and fibronectin.31

Formation of Insoluble
Fibrin Clot

The coagulation cascade ultimately leads to the formation of an insoluble fibrin clot. The cascade serves
to amplify the initial activation of clotting zymogens
and to provide multiple levels of control to prevent
inadvertent activation. Extrinsic and intrinsic pathways exist that intersect at the activation of factor X.
The extrinsic pathway is initiated upon tissue factor,
also known as thromboplastin, release following vessel injury. The intrinsic pathway can be activated by
contact with subendothelial collagen, high-molecular weight kininogen, and kallikrein.
Subendothelial layers of the vessel wall, fibroblasts, smooth muscle cells, and endothelial cells
express tissue factor after perturbation. Endothelial

cells actively initiate and propagate procoagulant

reactions.32 Vessel wall injury allows complexion of
tissue factor with circulating factor VII in a one-toone complex that requires the presence of calcium
and a phospholipid membrane to activate factor
VII.33,34 The newly formed extrinsic factor Xase, tissue factor and factor VIIa complex that cleaves factor X, activates a minor amount of factor X. Factor
Xa rapidly and preferentially activates factor VII in
an amplification step.35,36 Extrinsic Xase also activates
factor IX from the intrinsic pathway in the presence
of a phospholipid membrane and calcium.3739
The intrinsic factor Xase complex is formed by
the association of factor VIIIa with factor IXa in the
presence of calcium ions and a phospholipid membrane.40 It is significantly faster at catalyzing the activation of factor X and is 50-fold more efficient than
extrinsic Xase.39
The prothrombinase complex, which cleaves
prothrombin, consists of factor Xa, factor Va, calcium, and a phospholipid membrane and is the primary activator of thrombin.36,41 Alpha-thrombin is
produced by the initial cleavage of prothrombin by
factor Xa on an anionic membrane surface in the
absence of factor Va. Factor V activation is catalyzed
by alpha-thrombin. Upon activation of factor V, prothrombinase is formed and the reaction is shifted to
producing meizothrombin, an intermediate that is
consequently cleaved to form thrombin.36,42 Thrombin activates factor VIII and is considered the only
true, effective activator of factors VIII and V.43,44 Prothrombin cleavage is also contingent upon the presence of calcium ion and a phospholipid membrane.45
Thrombin positively feeds back on itself by activating factor XI, which subsequently cleaves factor
IX to produce factor IXa.46 Factor IX can also be activated by factor XIIa, but thrombin is a more effective
activator of factor IX in the absence of cofactors.46
This positive feedback loop completes activation of
factor V and factor VIII.47,48 Factor VIII is carried in
plasma by vWF via noncovalent interactions as vWF
plays a number of roles in protecting factor VIII from
degradation.49 The following table enumerates these
Functions of vWF and the vWF-factor VIII complex5057
1. Stabilizes factor VIII in plasma, making it less labile
2. Protects factor VIII from cleavage by protein C or factor Xa
3. Prevents premature binding of factor VIII to phospholipid
4. Protects factor VIII from lipoprotein receptor-related
protein (LRP) binding and subsequent degradation
5. Prevents factor VIII endocytosis by dendritic cells and
successive presentation to immune effectors
6. Inhibits factor IXa binding to factor VIII and thus stops its
participation in the intrinsic Xase complex


12 Part I General Endovascular Tenets

The conversion of fibrinogen to fibrin is catalyzed
by thrombin to form an insoluble cross-linked clot.
Although it is generally portrayed as a single step,
the conversion requires three independent reversible steps. Thrombin catalyzes only the very first
step, the release of fibrinopeptides A and B, to form
the fibrin monomer.58 Thrombin also cleaves factor
XIII, fibrin-stabilizing factor, to complete construction of the insoluble fibrin clot.59

Fibrin Structure
Fibrinogen is a dimeric molecule composed of two
sets of three unique polypeptide chains (A, B, ).60
Upon cleavage by thrombin, fibrinopeptide A (FpA) is
released, followed by the cleavage of fibrinopeptide B
(FpB). It is important to note that the and portions
of the A and B chains remain attached to the fibrinogen molecule.61 Fibrinopeptide A is cleaved before
fibrinopeptide B due to greater thrombin specificity
for the A peptide.62 The remainder of the fibrin monomers polymerize to staggered, double-stranded protofibrils in the presence of calcium.63,64 The protofibrils
polymerize spontaneously in a longitudinal fashion,
but factor XIIIa is needed to form lateral bonds. Factor
XIII, a zymogen transamidase of the transglutaminase
family, increases the mechanical rigidity of the fibrin
clot.65,66 In its inactivated form, factor XIII is a heterodimer of two unique polypeptide chains designated
A2B2.67 The two A subunits serve the catalytic transglutaminase role, whereas the two B subunits serve as
inhibitory/carrier proteins. Although its activation is
mediated by thrombin, the presence of fibrin sharply
increases factor XIIIs rate of activation.59,68 The crosslinking function factor XIIIa plays is absolutely vital
to fibrin clot integrity because fibrin clots formed in
the absence of factor XIIIa lead to bleeding disorders.69
Factor XIIIa catalyzes the formation of both and
chain bonds. The -chain cross-link occurs between a
multitude of glutamine and lysine residues present in
the peptide chain, which may allow the fibrin clot to
become highly complex and intricate. -Chain crosslinking occurs specifically between the Lys406 and
Gln 398 or 399 residues. -Chain cross-linking confers
more rigidity and stability than -chain cross-linking
and is thought to provide the most overall stability to
fibrin clot structure.70

Vitamin K
-Carboxyglutamate was initially discovered on
prothrombin because the peptide containing the
glutamate-like residue had an electrophoretic mobility too high to be explained by only the properties
of glutamate. The modified amino acid was found
to be essential to the ability of prothrombin to bind
calcium, a mechanism vital to its activation.71,72 The

same landmark study found that in the presence

of a vitamin K antagonist, prothrombin lacked the
-carboxyglutamate residues and lost the ability
to bind Ca2+. Vitamin K serves as a reducing agent
and is oxidized by carboxylase reductase during
-carboxylation of glutamate residues. Factor II, factor VII, factor IX, factor X, protein C, and protein S are
also vitamin K dependent.73,74 Vitamin K is recycled
back to its reduced form via epoxide reductase and
vitamin K reductase. Coumarins (e.g., warfarin) function to reduce blood coagulation by inhibiting the
action of vitamin K epoxide reductase. There is lag
time between administration of the drug and its anticoagulation due to preexisting -carboxylated coagulation factors. There is also a theoretical transient
paradoxical increase in blood coagulability in the initial stages of coagulation due to decreased protein C
levels. Protein C has a shorter half-life than the other
coagulation factors, leading to a relative increase in
the concentrations of the coagulation factors. This
imbalance could be addressed by bridging with heparin until coagulation factor levels decrease.75,76

Clot fibrinolysis is mediated primarily by plasmin. Plasmin activation from plasminogen is tightly controlled
and can be achieved by either tissue plasminogen activator (tPA) or urokinase plasminogen activator (uPA).
Fibrinolysis mediated by tPA is thought to function
more in the vasculature, whereas fibrinolysis mediated by uPA is thought to function in cancer cells.77
Plasmin formation is mediated by a positive feedback mechanism that takes two forms. The first is
fibrin cleavage by plasmin, which generates more
C-terminal lysine residues on fibrin that promote plasminogen and tPA binding. This ultimately increases the
efficiency and rate of plasmin formation. The second
method is via the N-terminal cleavage of Glu-plasminogen to Lys-plasminogen by plasmin. Lys-plasminogen
does not require lysine residues on partially cleaved
fibrin molecules to bind to tPA and is ultimately a better substrate for tPA than Glu-plasminogen.78
tPA and its recombinant form, reteplase, are used
clinically for thrombolysis and acute recanalization
of vessels in patients suffering from acute thromboocclusive episodes. These diseases include acute
ischemic stroke, ST segment elevation myocardial
infarction (STEMI), and pulmonary embolism.7981


The balance between coagulation and fibrinolysis is

paramount to preventing thrombosis while maintaining hemostatic function. This balance is achieved

by the interactions of anticoagulatory mechanisms
and mechanisms of fibrinolysis inhibitors. Anticoagulation works at the level of the fibrin clot, initiation
of coagulation, and modulation of individual factors
involved in the coagulation cascade. The inhibitors
of fibrinolysis generally modulate plasmin activity
given plasmins major role in fibrinolysis.

The functionality of the coagulation cascade and
hemostatic plug formation would be compromised
without the ability to modify clotting behaviors
(Figs. 2.3 and 2.4). The difference between hemostasis and thrombosis is maintained partially by anticoagulatory mechanisms. Unlike fibrinolysis, there are
many enzymes that reserve the ability to disengage
the coagulation cascade and platelet plug formation
(Tables 2.1 and 2.2).
Platelet activation is constitutively suppressed
by prostacyclin (prostaglandin I2 [PGI2]), nitric oxide
(NO), prostaglandin E2 (PGE2), and ectonucleotidases
at the unperturbed endothelial surface. PGI2, NO,
PGE2, and adenosine also cause vasodilation.82 Platelet aggregation is prevented by the cleavage of vWF
by a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13). The coagulation
cascade can be modulated at the very beginning of


the cascade by tissue factor pathway inhibitor (TFPI)

or somewhere along the cascade by antithrombin III
and protein C.83

Prostacyclin, Nitric Oxide, Prostglandin E2

PGI2 and NO are antiplatelet factors that are secreted
by the endothelium. They serve to prevent platelet
aggregation by inhibiting platelet activation. PGI2
functions by binding to either surface PGI2 receptors on platelet membranes or intracellular PPAR/
receptors. PGI2 receptor binding signals the activation
of adenylate cyclase, subsequent elevation of plasma
cyclic adenosine monophosphate (cAMP) levels, and
protein kinase (A) activation. This leads to a decrease
in the intracellular calcium level and downregulation
of platelet activation pathways.84 PGE2 functions in a
similar manner with similar potency. It is expressed
predominantly in the endothelium of small vessels,
whereas PGI2 is predominant in the endothelium of
large vessels.82,85
NO modulates platelet adhesion to collagen by
elevating platelet plasma cyclic guanosine monophosphate (cGMP) levels. Heightened cGMP levels
activate a protein kinase G pathway that ultimately
leads to the downregulation of platelet activatory
response.86 NO production is enhanced by increased
shear forces. Although nitric oxide synthase (NOS)





Tissue Factor






Prothrombin (II)

Thrombin (IIa)


Cross-linked clot

Fig. 2.3 The coagulation cascade. Roman numerals are used to refer to the numbering of the anticoagulation factors. a, activated
state of the anticoagulation factors.

Coagulation Cascade


14 Part I General Endovascular Tenets






Tissue Factor







Antithrombin III

Prothrombin (II)

Thrombin (IIa)


Cross-linked clot

Fig. 2.4 The coagulation cascade showing the role of the principal anticoagulants. Roman numerals are used to refer to the numbering of the anticoagulation factors. Tissue factor pathway inhibitor (TFPI) is the main inhibitor of the extrinsic initiation complex
(VIIa and Xa). Activated protein C (APC), with
the help of protein
S, inhibits
Va and
VIIIa. a, activated state of the anticoagulaCoagulation
tion factors.

Table 2.1 Endogenous anticoagulant factors and their functions




Inhibits platelet activation and promotes vasodilation

Nitric oxide

Inhibits platelet activation and promotes vasodilation


Stops platelet activation amplification

Tissue factor pathway inhibitor (TFPI)

Inhibits tissue factor

Antithrombin III

Inhibits factor Xa and thrombin

Activated protein C (APC)

Cleaves factors Va and VIIIa

ADAMTS13 (a disintegrin and metalloproteinase with

thrombospondin motifs 13)

Cleaves von Willebrand factor

Table 2.2 Endogenous coagulation modulators

Endogenous anticoagulants

Endogenous fibrinolysis inhibitors

Prostacyclin/prostaglandin E2

Thrombin-activatable fibrinolysis inhibitor (TAFI)

Nitric oxide

Plasminogen activator inhibitor (PAI-1)



Antithrombin III
Tissue factor pathway inhibitor (TFPO)
Activated protein C (APC)
ADAMTS13 (a disintegrin and metalloproteinase with
thrombospondin motifs 13)

is constitutively expressed in endothelium it is not
activated until the cell is stimulated. Physiological
stimulation leads to an increase in intracellular calcium, which eventually leads to the activation of NOS
and synthesis of NO. An increase in intracellular calcium also enhances PGI2 production, resulting in the
simultaneous release of both antiplatelet, vasodilatory factors.83 The final blow to platelet activation is
dealt by ectonucleotidase (CD39) on endothelial cells.
CD39 cleaves ADP released by platelets, which would
otherwise amplify platelet activation, to adenosine.

ADAMTS13 is a metalloprotease whose properties
were elucidated relatively recently. ADAMTS13 functions by cleaving vWF multimers and effectively
precluding platelet binding to collagen. This prevents inadvertent platelet adhesion under homeostatic conditions. Its importance is demonstrated
in patients who have thrombotic thrombocytopenic purpura (TTP) due to ADAMTS13 deficiency.87
These patients present with pervasive formation of
thrombi and intravascular hemolysis.

Antithrombin III
Antithrombin III is an 2-globulin serine protease
inhibitor.88,89 It binds to its main targets, thrombin and factor Xa, thereby inhibiting their protease
function. It also has the ability to bind factors IXa,
XIa, XIIa, tPA, urokinase, trypsin, plasmin, and kallikrein.9093 Antithrombin circulates in essentially
latent form and is activated to almost one thousand
times its basal level of activity by heparin and heparin-like glycosaminoglycans.94 Antithrombin forms
an enzyme-inhibitor complex with thrombin, which
is then bound by heparin, stabilizing the complex.95
In contrast, antithrombin binds heparin before inhibiting factor Xa.

Tissue Factor Pathway Inhibitor

TFPI is the main inhibitor of TF-VIIa-Xa, the extrinsic
initiation complex.96 It does not prevent the release
of tissue factor but rather prevents downstream activation of the pathway by inactivating both factors Xa
and VIIa. TFPI is dependent on calcium as well as factor Xa to inhibit the TF-VIIa complex. It must initially
bind to factor Xa before it can bind and effectively
inhibit TF-VIIa.97 Once all four proteins have bound
each other, the complex is endocytosed, leading to

degradation and effective downregulation of TF

expression. TFPI has a full-length and truncated form,
but the highest level of inhibition is achieved by the
full-length protein. Although TFPI can function in its
truncated forms, it must have an intact C-terminal
to facilitate binding to cell surface proteins, such as
heparan sulfate proteoglycans and low density lipoprotein receptor-related protein.98 TFPI in circulation
is generally bound to and inactivated by low density
lipoproteins.99,100 Active TFPI is found mainly at the
endothelial surface but can be released from platelets upon activation by thrombin and collagen.101,102
TFPI is also expressed on the surface of platelets but
is not found in -granules.103

Thrombomodulin, Protein C, Protein S

Thrombomodulin, an endothelial transmembrane
protein, binds to thrombin once it is activated from
its precursor.104 Thrombomodulin has six epidermal
growth factor (EGF)-like domains that function to initiate and stabilize interactions with its ligands. EGF46, the central portion of the molecule, primarily binds
thrombin and serves as a cofactor in protein C activation.105 The EGF5-6 domain interacts with exosite
I of thrombin, essential to thrombins ability to bind
other coagulant molecules, and thus prevents further procoagulant activity of thrombin.106 The exosite
I-EGF5-6 interaction also allosterically activates the
ability of thrombomodulin to cleave protein C.105
Protein C is a vitamin Kdependent anticoagulant. It has a -carboxyglutamic acid residue that
interacts with calcium ions.107 Protein C specifically
binds to the endothelial protein C receptor (EPCR) via
its Gla domain, although it can also bind negatively
charged phospholipids on the endothelium. EPCR
aligns protein C to the cleavage domain of thrombinthrombomodulin, catalyzing protein C activation.108
Cleavage of protein C yields the serine protease, activated protein C (APC). APC requires the presence of
protein S to effectively inactivate factor Va. The complex can cleave factor Va at three sites, depending on
the complement of cofactors and the presence of an
appropriate membrane. APC requires the synergistic
function of cofactors protein S and factor V in order
to effectively inactivate factor VIIIa.
Although protein S serves as a cofactor to APC
for the cleavage of factor Va and factor VIIIa, there is
evidence that it can perform anticoagulatory functions independent of APC. Protein S has also been
implicated in serving as a cofactor for TFPI.109 Protein
S holds much clinical significance in renal nephrotic
syndromes, where it is lost in the urine, leading to a
hypercoagulable state.


16 Part I General Endovascular Tenets

Fibrinolysis Inhibition
Thrombin-Activatable Fibrinolysis
Thrombin-activatable fibrinolysis inhibitor (TAFI)
acts at the interface of plasmin degradation of the
fibrin clot (Table 2.2). It interrupts the positive feedback loop of plasminogen activation and thwarts
fibrin clot degradation.110 TAFI cleaves the C-terminal lysine residue on fibrin, essential for catalysis
of plasmin activation, from the partially degraded
fibrin clot. Its activation is mediated mainly by the
thrombinthrombomodulin complex, but it can
also be activated by trypsin, plasmin, thrombin, and

XIIIa catalyzes 2-AP binding to fibrinogen in plasma

as well.119 2-AP also effectively reduces the available
catalytic surface for plasminogen activation by binding to fibrinogen.

Hemophilic and Thrombophilic

Given the intricacies and interdependencies of coagulation, anticoagulation, and platelet aggregation, there
are bound to be quite a few disorders associated with
hypercoagulable and hypocoagulable syndromes.
Thrombophilic and hemophilic states can be results
of genetic defects, adverse drug effects, and sequelae
from disease. This section gives brief overviews of
selected pathological states affecting hemostasis.

Plasminogen Activator Inhibitor

Thrombophilic States

Plasminogen activator inhibitor-1 (PAI-1) does exactly

what its name suggests. By forming an inert, nonreactive covalent complex with either tPA or uPA, PAI
inhibits the activation of plasminogen and the subsequent fibrinolysis. Four types of PAI have been identified, PAI-1, PAI-2, PAI-3, and protease nexin.112 PAI-1
and PAI-2 play the largest roles in fibrinolysis inhibition. PAI-1 binds both tPA and uPA, whereas PAI-2
binds only uPA.113 PAI-1 is a serine protease inhibitor
that has a domain that mirrors that of the serine protease substrate. PAI-1 in plasma needs to be stabilized
by vitronectin to maintain its active form.114 Vitronectin has been shown to restore inhibitive function
to tPA mutants, solidifying the view that vitronectin
bound to PAI-1 is the active form of PAI-1.115 Due to the
direct role PAI plays in tPA and uPA inactivation, the
fibrinolytic ability of human blood is dictated largely
by the relationship between PAI and PA.

Primary hypercoagulable states generally result from

either a deficiency in antithrombotic protein or an
increase in prothrombotic factors.120 Common genetic
defects of antithrombotic proteins include antithrombin, protein C, and protein S deficiencies. Mutations
leading to decreased coagulation factor degradation
and a hypercoagulable state include factor V Leiden,
prothrombin gene mutation G20210A and increased
levels of factors VII, XI, IX, VIII, and vWF.
Factor V Leiden, also known as activated protein
C resistance, is most often caused by a mutation that
changes arginine506 to glutamine.121 This mutation
prevents activated protein C from cleaving and inactivating factor Va, increasing the risk of thrombus formation.122 Prothrombin gene mutation G20210A results
from a guanine to adenine nucleotide substitution in
the prothrombin gene, leading to greater expression
and constitutively high levels of prothrombin.120
Secondary thrombophilic conditions include
nephrotic syndrome, pregnancy, and heparin-induced
thromobocytopenia, among others. Nephrotic syndrome is defined as urinary protein loss of greater than
3.5 g per 1.73 m2 of body-surface area per day.123 The
protein loss is often accompanied by sodium retention, edema, and hyperlipidemia as well as thrombophilia. The thrombophilia has not been attributed to
one singular factor but is accepted as a multifactorial
process resulting from loss of antithrombotic proteins, namely antithrombin III and protein S, due to
the proteinuria.124
Pregnancy has been shown to be a hypercoagulable
state, and, although the mechanism is complex, involving both the fibrinolytic and anticoagulation systems,
there are distinct physiological changes that predispose gravid women to thrombus formation.125 Effective coagulation is paramount in preventing maternal
mortality, evidenced by the fact that postpartum hemorrhage remains a leading cause of maternal death

2-Antiplasmin (2-AP) is the third and most vital
inhibitor of fibrinolysis after TAFI and PAI-1. 2-AP
acts at the level of the fibrin clot and at the interface
of plasminogen activation. It acts in three ways: by
forming an inert complex with plasmin, by binding
with fibrin itself to limit plasminogen binding, and
by integrating into the fibrin structure by binding to
factor VIIIa.116 2-AP has unique N- and C-terminal
extensions that allow it to dampen fibrinolysis on
more than one level. The C-terminal peptide chain
contains many lysine residues, of which the Lys464
is the most crucial for 2-AP to plasmin binding and
inhibition of fibrinolysis.117 The Gln2 residue of the
N-terminus is the site at which the transglutaminase factor XIIIa acts to covalently integrate 2-AP into
the fibrin clot.118 Recent evidence suggests that factor

in developing nations. There are downsides to the
hypercoagulable state, as rates of stroke, acute myocardial infarction, and venous thromboembolism are
increased in pregnant women.126,127 There is a measurable increase in the level of clotting factors I, II, VII, VIII,
IX, and X as well as PAI-1 and PAI-2. There is simultaneous decrease in the level of protein S, activated protein C, and TPA, causing the balance to be shifted in
favor of coagulation.128,129 Although many have blamed
increased estrogen levels, citing increased liver production of clotting factors, the claim is still controversial because antithrombotic factor production may
also thus be upregulated by the same mechanism.
Heparin-induced thrombocytopenia (HIT) often
manifests as thromboembolic events despite what
its name would lead us to believe. In HIT, an immunoglobulin G (IgG) antibody, directed against heparin bound to platelet factor 4, also binds to platelets
via an Fc receptor and thereby activates them. The
coagulation cascade may also be simultaneously
triggered via endothelium perturbation.130 Type I
HIT is largely asymptomatic, whereas type II HIT can
lead to a severe clinical picture that includes fever,
tachycardia, flushing, and headache.131 The frequency
of thromboembolic events has not been determined
definitively because studies have shown the risk to
range from 17 to > 50%, depending on the time frame
and experimental conditions used.132
Autoimmune diseases also complicate the hemostasis picture; systemic lupus erythematosus (SLE),
antiphospholipid syndrome, dermatomyositis, ulcerative colitis, immune thrombocytopenic purpura,
and other autoimmune diseases have been shown to
increase the risk of thrombosis.133 The pathophysiology seems to be related to the ongoing inflammation
and release of inflammatory factors that lead to an
ongoing hypercoagulable state. The two processes,
inflammation and coagulation, share many of the same
pathways, including tissue factor expression, inhibition of fibrinolysis, and protein C inhibition.134 The
link between cancer, cancer treatment, and thrombosis has long been established and is also dependent
on the same principle. Damage to the endothelial cell
wall and release of inflammatory cytokines via cell
rupture result in thrombophilia.135 Patients presenting
with malignant neoplasms with and without chemotherapy treatment have been found to have a four- to
sixfold increased risk of venous thromboembolism.136

Hemophilic States
Hemophilic or hypocoagulable states can be inherited as well as acquired. Congenital hemophilias
occur due to deficiencies in active coagulation factors,
platelet disorders, and vWF deficiencies. Hemophilia
A, hemophilia B, von Willebrand disease, BernardSoulier syndrome, and Glanzmann thrombasthenia
are the more commonly known bleeding disorders.

Deficiencies in any one of the coagulation factors will

cause hemophilic complications. Hemophilia A and B
occur as a result of deficiencies of factors VIII and IX, respectively, both encoded by genes on the X chromosome,
and are the two most common types of hemophilias.137
Acquired hemophilias involve patients developing antibodies directed against clotting factors. Of these autoimmune conditions, acquired hemophilia typically refers to
antibodies formed against factor VIII.138 von Willebrand
disease is characterized by deficient or dysfunctional
vWF. It impacts not only platelet aggregation and adhesion but also factor VIII levels, because vWF plays a role
in supporting platelet adhesion to the subendothelium
and in the stabilization of factor VIII in plasma.139
The inherited platelet disorders include BernardSoulier syndrome and Glanzmann thrombasthenia.
Bernard-Soulier syndrome results from a lack of, or
dysfunctional, GPIb-IX-V receptor complex on platelets. Recall that the GPIb-IX-V complex is responsible
for recognition of vWF, without which platelet adhesion and aggregation cannot occur.140,141 Glanzmann
thrombasthenia results from ineffective platelet aggregation due to deficient or dysfunctional GPIIb-IIIa
complex.142 The GPIIb-IIIa complex is responsible for
platelet cohesion. Dysfunctional GPIIb-IIIa precludes
vWF and fibrinogen from adequately binding platelets
together and forming a sufficient hemostatic plug.143

The blood coagulation cascade is essential in
controlling blood loss and in repairing vascular
injuries. On the other hand, overactivation of
the procoagulant and proinflammatory systems
in specific pathological processes (e.g., diabetes
mellitus, atrial fibrillation, atherosclerotic disease, etc.) will lead to a thrombotic vascular disease, which has necessitated the development
of antithrombotic and antiplatelet medications.
Intra- and perioperative hemostatic management is critical, particularly in procedures
using an endovascular approach. This is due to
the need for eliminating both hemorrhagic and
thrombotic complications.
Technical improvements, along with better
understanding of the coagulation systems, have
led to improved and more accessible coagulation assays that might play a key role intraoperatively. These tests include thromboelastometry,
thrombin generation assay, and point-of-care
platelet function aggregation assays.
As more hemostatic interventions are becoming available, such as concentrates of recombinant factors, cryoprecipitate, and fresh frozen
plasma, a validated and accessible coagulation
monitor assay becomes a necessity in managing patients with hemostatic disorders.


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Medicolegal Aspects of Complications

and Adverse Outcomes
Celina Crisman, Christine Villegas, Charles J. Prestigiacomo, and Chirag D. Gandhi

Malpractice claims represent a significant concern

among physicians of all backgrounds. In no group
is this concern more justified than among doctors
using specialized technical skills in emergent situations. Neurointerventionalists are among these
physicians, who typically experience the greatest
exposure to malpractice suits given the nature of
their work. Potential allegations are numerous and
most commonly include generalized failure of the
procedure with regard to the desired outcome, vascular or nerve injury, postoperative infection, and
inappropriate indication for operative intervention.1 Neurointerventional surgery also represents
a rapidly developing specialty with ever-evolving
devices, requiring awareness of the legal implications of off-label use of medical devices. This chapter
explores the legal issues admixed with endovascular practice, because it is often not possible to direct
a successful medical career in complete isolation
from legal concerns.

General Medicolegal

A recently published study saw 7.4% of physicians,

regardless of specialty, facing a malpractice claim
each year.2 The proportion of physicians exposed
to a malpractice claim ultimately ranged from 2.6%
among psychiatrists to 19.1% in neurosurgery. Specialties deemed at low risk of litigation included dermatology, family practice, pediatrics, and psychiatry.
Meanwhile, neurosurgery, thoracic-cardiovascular
surgery, orthopedic surgery, and plastic surgery
encompassed the highest-risk specialties. Strikingly,
projections based on these data see 88% of physicians
in high-risk fields facing a malpractice claim by age
45 and 99% of such physicians being named in claims
by age 65. Lower-risk specialties fare slightly better,
with 36% facing a first claim by age 45 and 75% doing
so by age 65.


The multitude of malpractice suits filed each

year, as well as the medical communitys growing
concern with litigation, contrasts with the rather
specific focus of the legal system regarding medical
malpractice. Medical malpractice claims are pursued
under the tort system; this system exists to compensate plaintiffs injured by negligence, to discourage
negligence, and to exact corrective justice in cases
of negligence. Negligence, legally, denotes a failure
to provide the standard level of care and does not
encompass all adverse events or system errors.3 By
extension, medical malpractice requires that a physician stray from acceptable standards of medical
practice and that such departure directly results in
patient harm. Theoretically then, medical malpractice cases are decided in favor of the plaintiff, typically the injured patient or the patients estate, only
when the patient sustains an injury directly attributable to negligence.
Numerous studies and reviews indicate that
actual negligence occurs quite rarely and is often
not demonstrated in alleged cases of medical malpractice.4 In one study, only 15% of malpractice cases
presented evidence of negligence.5 Additionally,
a recent congressional report found that 80% of all
malpractice cases reviewed involved no negligence.6
Over 60% of medical malpractice lawsuits filed are
summarily dismissed as having no grounds to justify
filing, and ultimately less than 1% of all filed claims
result in a verdict for the plaintiff.3,4
Although such statistics are encouraging, they do
not mitigate the real, prevalent, and generally justifiable concern for being named in a malpractice claim
often experienced by physicians. A review of New
York neurosurgeons covered by the Medical Liability Mutual Insurance Company (MLMIC) of New York
found that 58% of malpractice cases were either discontinued or dismissed. Thirty-two percent were
settled, and ultimately only seven cases resulted
in jury verdicts for the plaintiff. Nonetheless, the
company disbursed approximately 60 million dollars in indemnity, accounting for the high insurance

3 Medicolegal Aspects of Complications and Adverse Outcomes

premiums paid by covered neurosurgeons. When a
survey was sent to all U.S. members of the American Association of Neurosurgeons with valid e-mail
addresses, 71.3% of respondents either strongly
agreed or agreed with the statement medical liability affects my decision on where, geographically, to
practice neurosurgery. Similarly, 71.2% agreed that
medical liability affects [the] decision on how long
to continue to practice neurosurgery.

The DoctorPatient

Todays neurointerventionalists not only must master anatomy and various procedures, but must
also develop a strategy for thriving within the current medicolegal environment. Clearly, it is of foremost importance to adopt the principles of the
oft-repeated Hippocratic Oath and endeavor to do no
harm and certainly avoid negligent practice. Defensive medicine is a recent and widely recognized phenomenon adopted, intentionally or unintentionally,
by many physicians out of concern for litigation.
However, the practice of viewing every patient as a
possible lawsuit and ordering excessive tests, studies, and consults in anticipation of a lawsuit, leads
directly to increased health care costs. It may also
result in the deterioration of the physicianpatient
As a response to the legal concerns physicians face,
medical schools across the country have started to
provide education in techniques that may reduce the
risk of being named in a malpractice suit or losing a
case. These methods are also designed to strengthen
interactions between doctors and their patients.
Studies have demonstrated the effectiveness of a
patient-centered approach to evidence-based medicine not only in terms of patient satisfaction but also
as it relates to patient compliance and a decreased
number of lawsuits.7 It is important to maintain a
suitable level of professionalism and build proper
rapport with the patient. Complaints from patients
leveled at physicians of indifference, arrogance, lack
of sympathy, unavailability, and failure to communicate have been found to increase the possibility of
a suit.1 It is important that the soft skills of professionalism and humanism (i.e., admitting mistakes,
delivering bad news, patient communication, teamwork, cultural competence, and self-awareness) are
developed not only to facilitate better care but also
to build a better relationship with each patient. In
particular, prompt and proper disclosure of medical
error may mean the difference between an understanding patient and a patient with an impetus for

There are inherent risks in all neurointerventional

procedures. Although outcomes cannot be predicted
and complications are unforeseeable, it is imperative
that physicians remain available and forthcoming to
the patient and the patients family.9 In particular,
patients want to know if there was indeed a mistake, what went wrong, and why. It is important to
provide information about the specific implications
of the error for the patients medical care and hospital course. A mistake disclosure plan can be created
and implemented to ensure transmission, as well as
proper and compassionate disclosure, of all necessary
information.10 Patients frequently seek out an apology from their health care providers, especially interventionalists, when a mistake occurs. A survey of
plaintiffs in medical malpractice cases suggests that
monetary gain ranked secondary to other concerns in
motivating litigation. Concerns having primacy over
monetary gain included disclosure of information or
the desire for an apology or explanation.3 It is thus
conceivable that a well-thought-out apology may satisfy a patient considering litigation. Finally, patients
often greatly value communication regarding how
the physician and institution will learn from the mistake in order to avoid a repeat error.1,3,11 Such efforts
may appease injured patients and leave them with
the impression that they have been treated justly
without the need to pursue legal recourse.

Documentation and
Informed Consent

Proper documentation is of paramount importance

in practice, but especially once a lawsuit has been
filed. Records of consultations and other important
patient interactions should be maintained, and all
documents, such as radiology reports and written
correspondence from other physicians regarding the
patient, should be reviewed promptly. Maintaining an
up-to-date medical record is required, and it is especially important to obtain informed consent when
performing procedures associated with high risks of
complications or unfavorable outcomes. Interventions must be fully discussed with and understood
by patients, and physicians do well to document
a patients assent to the proposed treatment plan
and their understanding of associated risks, potential benefits, and complications. The operative note
should be completed immediately. Notes completed
after some delay have been described as self-serving and tailored by plaintiffs attorneys.3 Especially
applicable to neurointerventional procedures, the
neurological status pre-and postoperatively should
be indicated in the patients records, and any deficit
should be noted immediately.1


24 Part I General Endovascular Tenets

Interestingly, many of the malpractice cases
brought against neurointerventionalists to date
involve purported issues with the informed consent
obtained for the case in question. In finding consent
invalid, it is theoretically possible to obtain judgment
against a physician and bypass issues of adherence to
the standard of care.12 Traditionally, informed consent denotes a documented conversation between
physician and patient (or patients representative, in
the case of a minor or patient unable to provide consent) that addresses the following issues: diagnosis,
proposed treatment, risks and benefits associated
with the proposed treatment, alternative treatment
options, and the natural course of the disease without treatment.13 The physician is obligated to disclose
material risks in lay language such that a reasonable
person in the plaintiffs position would understand.14
Risks qualify as material when they would influence a reasonable persons decision of whether to
undergo a procedure. It is generally better to err by
including more details and possible mechanisms
through which a complication may occur; however,
it is virtually impossible to envision every possible
scenario and fortunately is not legally necessary.
Legally, it is important to emphasize ultimate complications and harms. For instance, in Little vs. Boston
Scientific Corporation, the plaintiff suffered a stroke
after a coil migrated during an elective aneurysm
coiling. Because the consent form did not specifically
mention coil migration, the plaintiffs alleged malpractice and pursued a lawsuit. The court found the
informed consent adequate because it mentioned
stroke, the actual harm experienced by the patient.
Coil migration represented a likely immaterial
mechanism too rare to quantify as a percentage, that
is, furthermore, not always associated with complications.14 Additional items suitable for mention within
a consent form include the practitioners personal
experience with the procedure in question. Notably,
the mere presence of a signed consent form within a
patients chart has historically not been sufficient to
prevent claims of inadequate consent from surfacing
in court; however, detailed signed forms have often
proven instrumental to a successful defense.

The Use of Off-label Devices

An issue especially pertinent to neurointerventionalists is the use of devices off-label. Any use
not specifically approved by the Food and Drug
Administration (FDA) qualifies as off-label use. FDA
approval, however, is intended as a restriction on
marketing and promotion rather than on medical
use.13 An amendment to the Food, Drug, and Cosmetic Act of 1997 states that nothing in the act will
limit or interfere with the authority of a health care

professional to prescribe or administer any legally

marketed device to a patient for any condition or
disease.13,15 The argument that off-label use of a
device constitutes negligence per se and violates the
standard of care has been advanced in court.16 The
notion of negligence per se essentially holds that any
use aside from that specifically approved constitutes
negligence in and of itself. However, such arguments
are not typically successful provided that defendants
exercise reason and incorporate off-label use into a
sound clinical plan. The idea that physicians may use
devices for a reasonable clinical indication, whether
on- or off-label, has generally been upheld by the
Although physicians are free to use devices offlabel on a case-by-case basis, they are legally prohibited from promoting such off-label uses. Off-label
use may be discussed in peer-reviewed professional
publications and conferences, but it must be clearly
designated as off-label. Such publications may not
be used by manufacturers to promote the off-label
use or to seek FDA approval for it.13 Physicians should
clearly and frankly discuss off-label use of devices
with patients while obtaining consent, and in some
institutions a separate/additional consent form may
be needed if an off-label use is to be pursued.16

Peer Review of Complications

A rapidly developing field, such as neurointerventional surgery, advances through review of both successes and complications. Morbidity and mortality
rounds allow for formal discussion of cases proceeding less than ideally and are conducted in virtually
every field and institution. Although the material of
such rounds may be of interest to plaintiffs in a malpractice case, there exists a legal concept of a peerreview privilege. This privilege protects information
generated in peer-review committees from discovery
in litigation. Although there is no explicit assurance
of a peer-review privilege in federal law, the Health
Care Quality Improvement Act, passed in 1986, states
that there is a national need to provide incentive
and protection for physicians engaging in effective
peer review.18 The act was created due to a concern
for patient safety and largely to mitigate the legal
concerns of physicians reporting unsafe practices
by their peers. It is based, at least in part, in the idea
that effective professional peer review is a means
of restrict[ing] the ability of incompetent physicians to move from state to state without disclosure
or discovery of the physicians previous damaging or
incompetent performance.18 However, this federal
act protects participants rather than the documents
generated by peer review. State laws granting peerreview-related documents privilege from discovery

3 Medicolegal Aspects of Complications and Adverse Outcomes

are widespread and espouse the public policy goal of
improving health care through candid peer review.
All states, with the exception of New Jersey, have
enacted laws granting some form of peer-review
privilege. However, the extent of protection and the
circumstances under which protection is ensured
vary from state to state.19 Although New Jersey has no
specific law related to medical peer-review privilege,
its courts have recognized a public interest in improving quality of care by protecting as confidential the
proceedings of peer-review committees. Its courts
have thus protected certain peer-review documents
from disclosure in malpractice cases.20 Although confidentiality of peer-review proceedings is generally
touted as a public policyrelated ideal, courts dealing with the issue must reconcile it with a plaintiffs
right to due process. In general, courts construe medical peer-review privilege narrowly; protection may
be afforded to documents and discussions existing
solely within the peer-review proceedings, but not to
facts obtainable elsewhere.21
Neurointerventionalists practice medicine in
the midst of unique legal concerns. These challenges relate to the inherently delicate procedural
work, the treatment of emergency cases, as well as
the technological developments that rapidly and
constantly advance the field. There are strategies,
however, that the neurointerventional surgeon can
employ to reduce medicolegal risks while improving patient satisfaction and outcomes. Exercising
caution in using devices for off-label purposes and
properly educating and informing the patient during
the consent process are some of the considerations.
The most important of these strategies is to maintain
the highest standards of professionalism, availability, and honesty. This will result in a better doctor
patient relationship and has been shown in various
studies to be one of the best methods by which to
reduce the legal risk.

1. Rovit RL, Simon AS, Drew J, Murali R, Robb J. Neurosurgical

experience with malpractice litigation: an analysis of closed

claims against neurosurgeons in New York State, 1999 through
2003. J Neurosurg 2007;106(6):11081114 PubMed
2. Jena AB, Seabury S, Lakdawalla D, Chandra A. Malpractice
risk according to physician specialty. N Engl J Med 2011;
365(7):629636 PubMed
3. Sohn DH. Negligence, genuine error, and litigation. Int J Gen
Med 2013;6:4956 PubMed
4. Weinstein SL. Medical liability reform crisis 2008. Clin Orthop
Relat Res 2009;467(2):392401 PubMed
5. Weiler PC. A Measure of Malpractice: Medical Injury, Malpractice Litigation, and Patient Compensation. Cambridge,
MA: Harvard University Press; 1993
6. The perverse nature of the medical liability system. In: Committee JE, ed. 2005. http://www.house.gove/jec/publication/

Neurointerventional surgeons face a unique
medicolegal environment because of the
inherently complex, high-stakes, procedural
service that they provide combined with the
rapid technological evolution within the field.
Establishing an honest, professional doctor
patient relationship prior to the procedure as
well as during any treatment complications is
critical to limiting legal risk.
An incomplete consent process has been the
cause of many legal actions. The physician
should be thorough when obtaining consent,
concentrating on the common and ultimate
complications, as well as the planned use of any
devices in an off-label manner.
Physicians are legally protected in the off-label
use of devices as long as their use can be clinically justified and appropriately consented to.
The Health Care Quality Improvement Act of
1986 and regulations in most states are designed to protect physicians during the peer
review of complications with the aim of improving patient outcomes.

7. Smith RC, Marshall-Dorsey AA, Osborn GG, et al. Evidence-

based guidelines for teaching patient-centered interviewing.

Patient Educ Couns 2000;39(1):2736 PubMed
8. Gallagher TH, Waterman AD, Ebers AG, Fraser VJ, Levinson W.
Patients and physicians attitudes regarding the disclosure of
medical errors. JAMA 2003;289(8):10011007 PubMed
9. Irving AV. Twenty strategies to reduce the risk of a malpractice
claim. J Med Pract Manage 1998;14(3):130133 PubMed
10. Petronio S, Torke A, Bosslet G, Isenberg S, Wocial L, Helft PR.
Disclosing medical mistakes: a communication management
plan for physicians. Perm J 2013;17(2):7379 PubMed
11. Gallagher TH, Waterman AD, Ebers AG, Fraser VJ, Levinson W.
Patients and physicians attitudes regarding the disclosure of
medical errors. JAMA 2003;289(8):10011007 PubMed
12. Rebecca Marie Waldt v University of Maryland Medical System
Corporation, 2006 (MD Ct Spec App)
13. Brown OW. Legal implications of pushing the endovascular
envelope. J Vasc Surg 2012;56(1):273274 PubMed
14. Little v Boston Scientific Corporation, 2009 (LA Ct App 5th Cir
15. SEC. 906 [21 USC sec396] practice of medicine
16. Iacangelo v Georgetown University, 2006 (United States District Court, District of Columbia)
17. Femrite v Abbott Northwestern Hospital, 1997 (MNCt App)
18. Health Care Quality Improvement Act. 42 USC 11101 1986: U.S
19. Modak-Truran A. A fifty-state survey of the medical peer review privilege. In Case Law
20. Christy and Bates v. Helene Fuld Medical Center and Capital
Health Systems, 2004 (NJ Super Ct)
21. American Jurisprudence, Second Edition in American Jurisprudence 2013, Westlaw: Westlaw. p. 16


Training Standards and Quality Assurance

E. Jess Duffis

The field of endovascular surgical neuroradiology

(ESNR) has rapidly expanded in the last 2 decades,
driven primarily by improvements in microcatheter
and device technology, intense clinical investigation,
and a perceived need to meet a growing demand for
neuroendovascular expertise. To this end, it is estimated that the workforce of neurointerventionalists
practicing in the United States has nearly quadrupled within the last 10 years and is on pace to more
than double within the next few years.1,2 Multiple
training pathways exist, and the field comprises
practitioners with backgrounds in several specialties, including neurology, neurosurgery, and neuroradiology. In this context, standardizing the training
experience across programs represents a unique
challenge. However, as a community we must confront this challenge, for ultimately it is patients who
will suffer the most from an overcrowded field populated with potentially undertrained practitioners.
This chapter reviews the current state of ESNR training and standards and discusses future challenges in
quality assurance in ESNR.

Current State of Training

in Endovascular Surgical

As of this writing there are currently only seven

ESNR training programs in the United States that are
approved by the Accreditation Council for Graduate Medical Education (ACGME).3 There are no data
as to the total number of ESNR training programs
currently in existence; however, estimates place the
number of graduating fellows at anywhere from 40
to 100 per year, with each program typically graduating 1 to 2 fellows per year.2,4 This would yield a
rough estimate of 40 to 50 active ESNR training programs in the country; however, some have estimated
the number to be closer to 80.2 As a result, the vast


majority of training programs are not accredited, and

some authors have even described the current state
of training as an apprenticeship in which all that is
required is at least 1 teacher and 1 fellow regardless
of the ability of a training program to provide an adequate educational experience.5
Several explanations have been proposed for the
rapid proliferation of ESNR training programs, including a perceived demand and undersupply of neurointerventionalists. Roughly 10 years ago the field was
propelled into prominence due to the overwhelmingly positive results of the International Subarachnoid Aneurysm Trial (ISAT) comparing coiling versus
clipping in patients with aneurysmal subarachnoid
hemorrhage (SAH). The result was an increase in the
number of endovascular procedures performed for
the treatment of aneurysmal SAH.6 This undoubtedly
contributed in large part to the early proliferation of
ESNR trainees, as evidenced by the enormous rise
in the number of practicing neurointerventionalists
in the last 10 years. Specifically, in 2002 it was estimated that the number of practicing ESNR specialists was fewer than 300, whereas currently there are
over 800 practitioners in the field.1,2
More recently, intense enthusiasm for the application of neuroendovascular techniques to the
treatment of acute ischemic stroke (AIS) has led to
continued growth in the field. Given the large public health burden posed by ischemic stroke and the
successful model of catheter-based reperfusion in
cardiovascular disease, it is almost natural to assume
that neuroendovascular treatment of AIS would result
in a large demand for neurointerventionalists. However, the estimated potential volume of endovascular AIS procedures is often overinflated and is based
primarily on the overall incidence of stroke, which
does not account for the fact that the large majority
of patients presenting with AIS are not candidates for
endovascular treatment. Thus it is unlikely that the
current workforce of ESNR-trained specialists will be
unable to meet current or future needs for the care
of patients with AIS from a personnel perspective.4,7

4 Training Standards and Quality Assurance

A separate but related question to personnel is
the quality of training received by new practitioners as well as the varying level of expertise and
interests among practicing neurointerventionalists.
ESNR is not unlike any other specialty of medicine
in that each practitioner brings to the field a variety
of interests and areas of expertise. Not every ESNR
practitioner is necessarily interested in, proficient in,
or even willing to attempt treating stroke patients or
SAH patients. Thus the sheer number of ESNR practitioners may not reflect the true number of experts
in a particular procedure. The problem is further
compounded by the dilution of case volumes across
centers as well as the variability in training received
even at so-called high volume centers. From a training perspective it makes a limited difference to have
observed 100 aneurysm embolizations but to never
have performed a single one.
It is evident to most in the field that the current
state of affairs cannot and should not continue for
the sake of the field and the quality of patient care.
Less apparent is a viable solution and a method for
its implementation. Some have called for suspending
all ESNR training indefinitely.2 This is not a realistic
solution; most if not all programs in existence would
not be willing to give up the considerable resource
that fellows represent. Undoubtedly, the solution
is more complex than getting rid of all fellows and
likely entails ensuring that those trainees entering
fellowship programs receive an adequate, and ideally
standardized, experience.

Current Standards of Training

for the Performance of ESNR

There are sufficient data to support the notion that

operator experience and training in the performance
of ESNR procedures is a vital determinant of patient
outcome. To ensure quality of care, the ACGME has
published training requirements for ESNR.8 Several
societies with practicing ESNR members have also
published similar and complementary standards
for a variety of specific procedures.9,10 The following reviews the cognitive, technical, and program
requirements for general training in ESNR as outlined by the ACGME.

Cognitive Requirements and

Eligibility Criteria
As mentioned earlier, there are currently three major
pathways toward ESNR training in the United States.
Most fellowship candidates will have first completed
an ACGME-approved program in neurology, neuro-

surgery, or radiology. For trainees with a neurology

background an additional 1 to 2 years of training in
vascular neurology and/or neurological critical care
is typically required. Candidates who have completed
a radiology training program are required to complete a minimum 1 year neuroradiology fellowship
prior to ESNR training, including at least 6 months
of clinical training in neurological critical care, vascular neurology, and neurosurgery. Thus, regardless
of the pathway chosen, the typical fellowship candidate has completed 5 to 7 years of training prior to
commencing ESNR training. These eligibility criteria
are designed to ensure that all candidates possess
the necessary knowledge in vascular anatomy and
pathophysiology as well as the clinical skills necessary to deliver adequate patient care.

Diagnostic Radiology Requirements

Both the ACGME and various neuroscience societies have recognized a minimum diagnostic technical
component for training in ESNR.811 All candidates
must have received training in diagnostic cerebral
angiography with a minimum performance of 100
cervicocerebral angiograms under the supervision
of a qualified physician. The minimum requirement
reflects the linear decrease in complications and
decrease in fluoroscopy time observed after the first
100 cases.12 Typically, the requisite diagnostic experience is acquired in a preliminary year prior to the
initiation of ESNR interventional training so that
the total training time is a minimum of 2 years. This
preliminary year allows for the development of the
skill set necessary to learn interventional techniques.
These skill sets are summarized in the following list
and include familiarity with the use of needles, catheters, and guidewires as well as basic knowledge of
radiation safety and patient evaluation and management procedures. The preliminary skills required for
ESNR training include:
1. Familiarity with the use of needles, wires, and
2. Basic radiation safety, including radiation
physics, protection, and pharmacological characteristics of radiographic contrast materials
3. Basic neuroangiographic image interpretation
4. Familiarity with and proper use of relative laboratory testing as well as adjunctive noninvasive imaging and monitoring
5. Clinical aspects of patient management and
treatment planning
6. Clinical indications and risks of endovascular
7. Familiarity with the use of pharmacological
agents relevant to ESNR, including antithrombotics, analgesics, and neuroanesthetic agents.


28 Part I General Endovascular Tenets

Program Requirements
Requiring the availability of specific institutional and
program resources ensures that trainees receive an
organized and comprehensive educational experience. The fellows primary purpose thus should be to
learn how to be competent ESNR practitioners and
not solely to provide additional human resources to
the service. Unfortunately, due to the lack of oversight
at most programs, the latter often takes precedence.
The first general requirement outlined by ACGME
standards is that training in ESNR be conducted in
an environment conducive to investigative clinical
or basic science studies.13 In addition, the program
should be jointly administered by ACGME-accredited
programs in neurology, neurosurgery, and neuroradiology within the same institution. The program
should appoint a program director whose primary
responsibility is to ensure that the program fulfills
its educational mission and adheres to the curriculum guidelines outlined by the ACGME.
These curriculum guidelines are summarized
in the following list.8 The training program must
provide knowledge and experience in nine general
1. Anatomical and physiological basic knowledge, including basic knowledge in arterial and
venous angiographic anatomy of the brain, spinal cord, and head and neck
2. Collateral circulation and anastomosis, cerebral
blood flow and autoregulation, as well as pharmacological mechanisms of the vasculature
3. Catheter and delivery systems and embolic
agents, as well as complications of cerebral,
spinal, and head and neck embolizations
4. Electrophysiological processes as well as provocative testing and noninvasive imaging
5. Properties of pharmacological agents, including contrast materials, provocative testing
agents, anticoagulants, and thrombolytics
6. Coagulation cascade
7. Classification, clinical presentation, epidemiology, natural history, and management alternatives for cerebral aneurysms, arteriovenous
malformations, ischemic stroke, and arteriovenous fistulas
8. Tumors of the head, neck, and spine
9. Revascularization for occlusive disease, including balloon angioplasty, thrombolytics, and
10. Embolization for epistaxis and other
11. Functional testing
Briefly, the duration of the training period in
ESNR should be 12 continuous months, during which

the fellow should receive training and experience in

recognition of conditions amenable to endovascular
treatment, limitations of treatment including alternatives, and technical aspects of ESNR interventional
procedures. Of note, the ACGME makes no mention of
minimum numbers of specific procedures performed
at an institution in order to be considered eligible
for accreditation. As part of the required competencies, however, the fellow must perform a minimum
of 100 therapeutic endovascular procedures. This
lack of minimum case numbers for specific procedures poses a special challenge because patient outcomes have been shown to be determined by case
volume.14,15 If specific procedural case volume alone
were used as a surrogate for suitability of a particular institution to provide adequate ESNR training,
then few U.S. hospitals would likely qualify.16
Availability of institutional resources is also
used to determine eligibility for accreditation by the
ACGME. Needless to say, the equipment and facilities must be adequate to perform ESNR procedures.
Ancillary facilities capable of advanced neuroimaging and emergency evaluation and treatment of
patients should also be available. For additional specific program requirements, such as fellow evaluation, participation in scholarly activities, and duty
hours, the reader is referred to the ACGME website.13

Quality Assurance in ESNR

In addition to ensuring proper training standards for
those engaged in the practice of ESNR, institutional
quality improvement and assurance (QI/QA) initiatives are essential for continued delivery of highquality patient care. Neurological multispecialty
societies have recognized the importance of QI/QA in
ESNR and have published various standards of practice and guidelines.10,1719 These standards should be
adhered to in order to ensure that patients are being
selected appropriately for treatment and procedural
outcomes fall within acceptable ranges for success
and complications.

Future Challenges
As mentioned earlier, the field of ESNR is at a crossroads. At the current rate of proliferation of ESNR
trainees, and without proper oversight, the field cannot ensure that all physicians currently performing
these procedures are adequately trained and are qualified to do so. The current state of affairs is undoubtedly due to a combination of the relative novelty of
the field combined with overexuberance. The salient
question moving forward is what we as a community
should do to ensure quality of care. It seems the first

4 Training Standards and Quality Assurance

step is to examine the quality of training and education that ESNR trainees currently receive, rather than
just citing the total number of programs in existence.
A move toward increasing the number of ACGMEaccredited programs would provide a mechanism to
regulate and oversee the existing educational programs. Ultimately, however, only the development of
a subspecialty examination and accreditation board
similar to other medical and surgical subspecialties would ensure the regulation of both the quality
and the number of practitioners. The multispecialty
nature of the field undoubtedly has discouraged
attempts to achieve a subspecialty board; however;
several examples currently exist of successful boarded
specialties with practicing members having different
training backgrounds. As a community we must see
this challenge as an opportunity to actively direct the
future path of our specialty, for if we fail to act, others
may make that determination for us.

The current state of ESNR training is dominated by unregulated training programs with
variable educational experiences.
In order to ensure quality patient care, training programs should adhere to standards and
guidelines set forth by various neuroscience
societies as well as the ACGME.
Current standards of training consist of cognitive and technical prerequisites necessary to
competently practice ESNR.
Future challenges include increasing the
number of accredited training programs and
developing a subspecialty board examination to ensure that the number and quality of
practitioners are regulated and meet current
quality standards.

1. Cloft HJ, Tomsick TA, Kallmes DF, Goldstein JH, Connors JJ. As-

sessment of the interventional neuroradiology workforce in

the United States: a review of the existing data. AJNR Am J
Neuroradiol 2002;23(10):17001705 PubMed
2. Fiorella D, Hirsch JA, Woo HH, et al. Should neurointerventional fellowship training be suspended indefinitely? J Neurointerv Surg 2012;4(5):315318 PubMed
3. [10/23/2013]; https://www.acgme.org/ads/public
4. Zaidat OO, Lazzaro M, McGinley E, et al. Demand-supply of
neurointerventionalists for endovascular ischemic stroke
therapy. Neurology 2012;79(13, Suppl 1):S35S41 PubMed
5. Cloft HJ. The neurointerventional bubble. AJNR Am J Neuroradiol 2010;31(7):11621164 PubMed
6. Qureshi AI, Vazquez G, Tariq N, Suri MF, Lakshminarayan K,
Lanzino G. Impact of International Subarachnoid Aneurysm
Trial results on treatment of ruptured intracranial aneurysms in the United States. Clinical article. J Neurosurg 2011;
114(3):834841 PubMed

7. Cloft HJ, Rabinstein A, Lanzino G, Kallmes DF. Intra-arterial

stroke therapy: an assessment of demand and available work

force. AJNR Am J Neuroradiol 2009;30(3):453458 PubMed
8. Higashida RT, Hopkins LN, Berenstein A, Halbach VV, Kerber C.
Program requirements for residency/fellowship education in
neuroendovascular surgery/interventional neuroradiology: a
special report on graduate medical education. AJNR Am J Neuroradiol 2000;21(6):11531159 PubMed
9. Connors JJ III, Sacks D, Furlan AJ, et al; Neuro Vascular Coalition
Writing Group; American Academy of Neurology; American Association of Neurological Surgeons; American Society of Interventional and Therapeutic Neuroradiology; American Society of
Neuroradiology; Congress of Neurological Surgeons; AANS/CNS
Cerebrovascular Section; Society of Interventional Radiology.
Training, competency, and credentialing standards for diagnostic cervicocerebral angiography, carotid stenting, and cerebrovascular intervention: a joint statement from the American
Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology,
the Congress of Neurological Surgeons, the AANS/CNS Cerebrovascular Section, and the Society of Interventional Radiology. J
Vasc Interv Radiol 2004;15(12):13471356 PubMed
10. Meyers PM, Schumacher HC, Alexander MJ, et al. Performance
and training standards for endovascular acute ischemic stroke
treatment. Neurology 2012;79(13, Suppl 1):S234S238 PubMed
11. Connors JJ III, Sacks D, Furlan AJ, et al; American Academy of
Neurology; American Association of Neurological Surgeons;
American Society of Interventional and Therapeutic Neuroradiology; American Society of Neuroradiology; Congress of Neurological Surgeons; AANS/CNS Cerebrovascular Section; Society
of Interventional Radiology; NeuroVascular Coalition Writing Group. Training, competency, and credentialing standards
for diagnostic cervicocerebral angiography, carotid stenting,
and cerebrovascular intervention: a joint statement from the
American Academy of Neurology, the American Association of
Neurological Surgeons, the American Society of Interventional
and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, the AANS/
CNS Cerebrovascular Section, and the Society of Interventional
Radiology. Neurology 2005;64(2):190198 PubMed
12. Dion JE, Gates PC, Fox AJ, Barnett HJ, Blom RJ. Clinical events
following neuroangiography: a prospective study. Stroke 1987;
18(6):9971004 PubMed
13. www.acgme.org/acgmeweb
14. Gupta R, Horev A, Nguyen T, et al. Higher volume endovascular
stroke centers have faster times to treatment, higher reperfusion rates and higher rates of good clinical outcomes. J Neurointerv Surg 2013;5(4):294297 PubMed
15. Hoh BL, Rabinov JD, Pryor JC, Carter BS, Barker FG II. In-hospital morbidity and mortality after endovascular treatment
of unruptured intracranial aneurysms in the United States,
1996-2000: effect of hospital and physician volume. AJNR Am
J Neuroradiol 2003;24(7):14091420 PubMed
16. Grigoryan M, Chaudhry SA, Hassan AE, Suri FK, Qureshi AI.
Neurointerventional procedural volume per hospital in United States: implications for comprehensive stroke center designation. Stroke 2012;43(5):13091314 PubMed
17. Duffis EJ, Gandhi CD, Prestigiacomo CJ, et al; Society for Neurointerventional Surgery. Head, neck, and brain tumor embolization guidelines. J Neurointerv Surg 2012;4(4):251255 PubMed
18. Hussain MS, Fraser JF, Abruzzo T, et al; Society for Neurointerventional Surgery. Standard of practice: endovascular treatment of intracranial atherosclerosis. J Neurointerv Surg 2012;
4(6):397406 PubMed
19. Patsalides A, Bulsara KR, Hsu DP, et al. Standard of practice:
embolization of ruptured and unruptured intracranial aneurysms. J Neurointerv Surg 2013;5(4):283288 PubMed


The Endovascular Suite

Vivek H. Tank, E. Jess Duffis, Charles J. Prestigiacomo

The field of interventional neuroradiology was pioneered by Dr. Egas Moniz, who performed the first
cerebral angiogram at the University of Lisbon in Portugal in 1927. Dr. Moniz was likely unaware that this
step in the advancement of medical science would, 85
years later, blossom into one of the most promising
fields of modern health care. The future of medicine
undoubtedly lies in the development of minimally
invasive therapies, such as interventional neuroradiology, which afford the advantages of decreased
infections, blood loss, and recovery time compared
with open surgical techniques for diagnosis and treatment of a variety of neurological conditions.
Cerebral angiography has come a long way since
the time of Dr. Moniz. Today, an angiography suite is
a high-tech theater incorporating the latest technology in fluoroscopy with powerful computers capable of converting raw data into beautifully rendered
three-dimensional (3D) images. Along with the technology, there is a requirement for highly skilled physicians, nurses, and technicians to orchestrate the
delicate dance that is cerebral angiography.
Fluoroscopy systems come in a variety of configurations from a number of manufacturers. Although
cerebral angiography could be performed using a
single-plane fluoroscopic imaging system, a biplane
fluoroscopic system is preferred to perform these
procedures efficiently and with minimum risk to the
patient. The basic room layout of each of the major
competitors supplying biplane fluoroscopy equipment consists of a multidirectional patient table, a
bank of monitors for viewing the live fluoroscopy
and other information, and the two C-shaped arms
of the biplanar configuration. This chapter focuses on
this general setup, rather than the specifications of
any particular equipment manufacturer.

Radiation Safety

Safety is of paramount importance during all angiographic procedures. All members of the endovascular
team should wear wraparound lead protective gear,

including thyroid shields and protective eyewear.

Furthermore, additional shields should be available
to afford added protection for those members of
the team closest to the fluoroscopic equipment. The
patients exposure to radiation should also be kept in
mind. Wherever possible, steps should be made to
minimize radiation exposure by using various techniques. These include positioning the fluoroscopy
machine by visual cues rather than using constant
fluoroscopy. Also, newer machines can create virtual
roadmaps from previous runs, which eliminates the
need for redundant imaging. Another key step is to
use the machines user-defined presets to store a
position for a particular patient, such as the standard anteroposterior (AP) and lateral view for an ICA
injection. Because this position will be used on both
sides, it can easily be reproduced with the touch of
a button without exposing the patient to unnecessary radiation. Other steps to decrease the radiation
dosage include manipulating the machines settings
to decrease the frame rate and pulse rate. Manufacturers and vendors can create low-dose protocols to
limit radiation exposure. The use of collimators can
not only decrease the area of exposure to radiation
but also improve image quality by decreasing artifact.

Patient Preparation
Any interventional procedure begins with a basic
medical workup that includes a history and a physical exam, a thorough neurological exam, bloodwork, electrocardiography (EKG), and imaging. Prior
imaging, including computed tomography (CT) and
magnetic resonance imaging (MRI), along with noninvasive angiograms, should be carefully reviewed
to ascertain vascular anatomy and any underlying
anomalies that can impact the performance of the
angiogram. Many patients who present for angiography have comorbid conditions for which they
see a variety of specialists. These patients should
obtain medical clearance from their primary physician and/or cardiologist prior to the procedure. Once

5 The Endovascular Suite

the patient is cleared for the study, a detailed and
thorough explanation of the procedure, indications,
risks, benefits, and alternatives should be given to
the patient and/or the patients family members.
Although risks are rare, the most common or serious
complications should be explained to the patient,
including allergic reactions, kidney injury, infection,
stroke, loss of neurological function, groin hematoma, femoral nerve or arterial injury, and death. A
study of 2,899 patients found a 1.3% risk of neurological injury overall, with a total of 39 complications,
14 (0.5%) of which were permanent deficits.1 A comparable study including 1,517 patients performed 20
years earlier reported similar results, with 2.6% neurological complications, 0.33% of which were permanent.2 Dawkins et al in 2007 reported an even lower
incidence of neurological complications (0.34%) with
no permanent deficits among 2,924 patients undergoing diagnostic cerebral angiography.3 As previously
mentioned, kidney injury is a possible side effect
from the administration of contrast during angiography. Therefore, the patients kidney function should
be ascertained with regular lab tests, including blood
urea nitrogen (BUN) and creatinine (Cr), prior to
proceeding. Patients with mild renal insufficiency
(Cr 1.31.5) may still undergo cerebral angiography; however, the procedure should be performed
with judicious use of contrast, and pretreatment
of the patient with N-acetylcysteine may be advisable for possible renal protection. Another potential
pitfall to contrast administration is an allergic reaction to the iodine in the contrast medium. Patients
at higher risk for an anaphylactic reaction to iodinated contrast include those with a previous reaction
to contrast, asthma, renal insufficiency, and cardiac
disease.4 Patients should be premedicated with steroids and diphenhydramine prior to the introduction of contrast, and medications should be readily
available to rapidly treat any signs or symptoms of
an acute allergic reaction. Diabetic patients who are
taking metformin and metformin-containing antihyperglycemic medications should withhold this medication prior to and for 48 hours after the procedure
to decrease the risk of metformin-associated lactic

Equipment and Setup

Table 5.1 describes the necessary tools for performing diagnostic angiography. The suite consists of a
procedure room (see Fig. 5.1) and a control room.
All necessary catheters, sheaths, coils, guidewires,
and medications should be present and easily accessible along the walls of the angiography suite. Additionally, the anesthesiologist should have access to
all equipment, supplies, and medications necessary
for safe and effective administration of sedation and
anesthesia necessary for any given procedure.

Table 5.1 Sample equipment setup for a diagnostic

cerebral angiogram
1% lidocaine
No. 11 blade
2Transparent bio-occlusive dressings, such as Tegaderm
(3M, St. Paul, MN)
18-gauge single-walled needle for femoral artery access
0.035 J wire
15 French sheath
21 L bags normal saline (with air previously removed and
4,0006,000 U/L of heparin added)
1Package of sterile towels
1Diagnostic catheter (i.e., 5 French Vert or Terumo
1Hydrophilic coated guide wire
1Wire torque device
2Three-way stopcock
1Intravenous extension tubing for contrast injector
1Short extension tubing
1250 mL container of Omnipaque contrast solution
1Automated contrast injection machine
2Intravenous color-coded extension lines
1Large basin containing sterile saline
1Needle holder to secure used sharps
220 mL syringes
218-gauge angiocath tips
Multiple 10 mL syringes (color coded to differentiate saline
from contrast)
1Mosquito clamp

Preparation for a procedure begins even before the
patient enters the room. Each day, prior to use, the
equipment must be tested and calibrated to ensure
patient and operator safety. Furthermore, the necessary equipment should be stocked and easily accessible (Fig. 5.2). This can be achieved by maintaining
an accurate inventory record of items used and in
low supply.
After careful preprocedure preparation, the
patient can be brought into the room and placed on
the angiography table. The first step in any procedure is positioning the patient appropriately; with
angiography there are some special considerations
depending on the angiography equipment used. The
head should be comfortably placed within a radiolu-


32 Part I General Endovascular Tenets

Fig. 5.1 Room setup

Fig. 5.2 Setup for a diagnostic angiography table.

cent head holder to help ensure minimal movement

and proper alignment with the fluoroscopy tubes.
Next, the arms should be placed within arm guards
to prevent them from falling off the table edge and
interfering with the movement of the tubes. A pillow may also be placed under the patients knees

for comfort and to prevent knee hyperextension and

possible peroneal nerve injury.
Once the patient is positioned comfortably, the
puncture site must be prepped and draped in a
sterile fashion. Bilateral groin sites are shaved and
then prepped using a Betadine scrub followed by

5 The Endovascular Suite

chlorhexidine scrubs. Next, sterile towels are placed
along the borders of the sterile field to prevent further
contamination. A sterile drape is then applied with
two openings overlying the prepped groin sites. With
the patient prepped and draped, the heparinized
saline flush lines are then prepared. Two flush lines
are needed for a diagnostic procedure: one to connect
directly to the femoral sheath and the second to connect to the catheter system. Thus two 1 L bags devoid
of all air are placed in individual pressure bags, and
intravenous tubing is connected. Extreme care must
be taken to run the saline through these lines slowly,
ensuring all air is removed from each.5 The pressure
lines are run continuously at a very slow rate to prevent the formation of blood clots within the catheter
system as well as to prevent the introduction of air
bubbles within the system. The stopcock is turned
off to the pressure bag only during contrast injection,
either manually or during automated injections used
for image acquisition. Catheters can also be flushed
manually in lieu of the continuous irrigation already
described as long as the entire length of the catheter
is routinely double flushed, approximately every 90
seconds.5 The continuous irrigation system described
allows the operator to focus on the acquired images
and on the performance of the procedure, with only
a glance at the pressure bags and tubing necessary to
ensure proper irrigation of the entire system is maintained. The syringes are filled and labeled appropriately with saline, 50-50 contrastsaline solution, and
full-strength contrast solutions. Great care must be
taken to appropriately label all syringes in order to
prevent inadvertent injection of dangerous medications into the central circulation, including lidocaine
and tissue plasminogen activator (tPA).

Caveats for Interventional Procedures

Patient positioning is identical for diagnostic and
therapeutic procedures within the angiography
suite. Patient preparation, however, differs slightly
(Table 5.2). The need for sedation should also be
determined prior to the procedure. Procedures like
diagnostic cerebral angiography can be performed
easily and safely in a cooperative patient simply
with mild sedation with fentanyl and/or midazolam
without the need for intubation. However, if the
patient is anxious, nervous, or has altered mental
status precluding cooperation, or if intervention is
expected, it may be easier and safer to attain sedation with intubation and general anesthesia. Because
both approaches have significant pros and cons, the
decision as to whether to sedate or intubate is largely
guided by physician preference for one method versus the other.
An arterial line is obtained and a baseline activated
coagulation time (ACT) is determined in the angiography suite using a Hemochron Response Whole

Table 5.2 Additional equipment that may be needed

for interventions
Embolization materials: coils, particles, cyanoacrylate, or Nbutyl-2-cyanoacrylate (NBCA) glue, alcohol, Onyx or others
1Tuohy-Borst Y-adapter
Various microcatheter and microwire systems
Extra heparinized saline flush bag with pressure line setup
as in a diagnostic procedure
Proprietary coil detachment systems
1 mL syringes

Blood Coagulation System (International Technidyne

Corp. [ITC], Edison, NJ) in the event heparin needs to
be given later during the procedure. A target value for
the ACT is 1.5 to 2 times the baseline value or 300 to
350 s.6,7 These values are recommended empirically
or based on relatively small cardiac catheterization
trials.8,9 The use of heparinization during interventional procedures is also an area of debate. Although
there are few data to support one approach versus
another, heparin is typically used to prevent adverse
events related to thromboembolic complications,
especially with the use of microcatheters in small
vessels, embolic materials, or extended angiographic
procedures. Protocols for heparinization vary by
institution and operator preference.
With the patient intubated or sedated, paralyzed,
prepped, and draped, the lines are run as described
for a diagnostic procedure except there are now three
pressure lines. All lines are checked twice for the
absence of air to prevent air emboli to the brain prior
to continuing with the procedure. One pressure bag is
connected directly to the sheath as already described
in the diagnostic angiography section. The catheter
pressure bag system is also identical except for the
addition of a Tuohy-Borst Y-adapter between the catheter and the three-way stopcock, as shown in Fig. 5.3.

Fig. 5.3 Catheter, Tuohy-Borst Y-adapter, three-way stopcock, extension tubing, second three-way stopcock.


34 Part I General Endovascular Tenets

A second table should be set up on which to prepare all embolization materials. This table is separate from the main table housing all the equipment
for the diagnostic portions of the procedure. Any
preparation of the embolization materials must take
place on the second table, and when personnel have
finished using the embolization materials, either
between runs or after complete obliteration of the
lesion, the embolization materials must be returned
to this table. Taking such a regimented approach to
embolization materials helps to ensure no aberrant
particles, glue, or free materials are unintentionally
injected into the cerebral vasculature causing an
embolic stroke. Also, keeping the embolic materials
separate prevents their exposure to ionic material,
such as blood, which can cause premature polymerization, thus rendering the material unusable. Specific techniques for embolization of aneurysms and
arteriovenous malformations (AVMs) are addressed
in later chapters.
Other equipment and materials needed for embolization procedures include a steamer to allow for
customized microcatheter shaping, a vortex shaker
to agitate Onyx liquid embolic material prior to use,
dimethyl sulfoxide (DMSO)-compliant microcatheters (Echelon, Marathon, and Ultraflow line of microcatheters from ev3 Endovascular, Inc., Plymouth,
MN) to use in conjunction with Onyx sterile D5W
to irrigate the catheter prior to N-butyl-2-cyanoacrylate (NBCA) injection, and proprietary detachment
devices to deploy coils.

Be meticulous in all preparations of lines and
when using embolization materials.
Air is your enemy; keep it out of the lines.
Check stopcocks and lines frequently to maintain a steady flow of heparinized saline flush
through the lines or flush the lines manually.
Flush vigorously and often to prevent clot formation within the system.
Maintain sterility at all times.

1. Willinsky RA, Taylor SM, TerBrugge K, Farb RI, Tomlinson G,

Montanera W. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of
the literature. Radiology 2003;227(2):522528 PubMed
2. Earnest F IV, Forbes G, Sandok BA, et al. Complications of cerebral angiography: prospective assessment of risk. AJR Am J
Roentgenol 1984;142(2):247253 PubMed
3. Dawkins AA, Evans AL, Wattam J, et al. Complications of cerebral angiography: a prospective analysis of 2,924 consecutive
procedures. Neuroradiology 2007;49(9):753759 PubMed
4. Harrigan MR. Handbook of Cerebrovascular Disease and Neurointerventional Technique. 2nd ed. New York, NY: Humana
Press; 2013:121123
5. Morris P. Practical Neuroangiography. 2nd ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 1997:716
6. Chew DP, Bhatt DL, Lincoff AM, et al. Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials.
Circulation 2001;103(7):961966 PubMed
7. Cipolle RJ, Seifert RD, Neilan BA, Zaske DE, Haus E. Heparin kinetics: variables related to disposition and dosage. Clin Pharmacol Ther 1981;29(3):387393 PubMed
8. Narins CR, Hillegass WB Jr, Nelson CL, et al. Relation between
activated clotting time during angioplasty and abrupt closure.
Circulation 1996;93(4):667671 PubMed
9. Ferguson JJ, Barasch E, Wilson JM, et al; Heparin Registry Investigators. The relation of clinical outcome to dissection and
thrombus formation during coronary angioplasty. J Invasive
Cardiol 1995;7(1):210 PubMed

Part II

Perioperative Care

Perioperative Planning
Robert Alex Hirschl and Louis P. Caragine Jr.

All interventions require proper preparation, which

is critical for success. Anticipating the numerous
steps and the associated pitfalls with their possible
solutions helps the interventionalist minimize the
potential complications of any procedure. This chapter covers perioperative planning, which includes
preoperative, operative, and postoperative strategies
for the most common disorders seen and treated by
neuroendovascular physicians. Intracranial aneurysms (both ruptured and unruptured), arteriovenous malformations, dural fistulas, carotid sacrifice,
and carotid and intracranial stenosis are discussed in
further detail.

Intracranial Aneurysm

Preoperative Planning
Unruptured aneurysms are usually incidental findings resulting from workups for unrelated symptoms, such as headaches and vertigo. Unruptured
aneurysms may also present with cranial nerve
palsy, secondary to mass effect. Often the noninvasive imaging clearly demonstrates the anatomy of
the aneurysm and allows for planning the optimal
treatment.1 However, for smaller aneurysms, a formal angiogram is often indicated to better delineate
the pathology. Once the anatomy and location of the
aneurysm are known, the treatment options can be
discussed with the patient. These options include
observation, endovascular treatment like coiling or
stent-assisted coiling, or open surgery.
Many factors determine the most appropriate
treatment. The size, geometry, and location of the
aneurysm, the tortuosity of the proximal vessels,
as well as the overall health and age of the patient
will dictate the best course of action. According to
the literature, aneurysms less than 7 mm in size
have a very low rupture rate, and one may feel more

comfortable just observing these small aneurysms,

as compared with larger aneurysms that have a statistically greater chance of rupture.2 Aneurysms that
have a favorable geometry, location, and proximal
vessels that allow catheters or stents to reach their
destination should at least have the option of endovascular treatment. Older patients or those in poor
health who have aneurysms of favorable geometry
and location, as well as navigable proximal vessels,
should undergo endovascular treatment.
Once the decision is made to proceed with endovascular treatment, the patient may require medication prior to the procedure. Patients with unsecured
aneurysms must have their blood pressure well controlled and, if necessary, be placed on hypertensive
medication to achieve normotensive blood pressure.
There is no literature to support that pharmacotherapy is required prior to the procedure for aneurysms
that have good dome to neck ratios and can be coiled
without stent assistance. However, our practice is to
premedicate for 3 to 5 days prior to the procedure
with one aspirin (81 mg) a day for enhanced antiplatelet effect. If the aneurysm has a poor dome to
neck ratio, then stent placement or balloon assistance should be considered. Placing a stent requires a
minimum of 3 days3,4 of Plavix (75 mg a day) (BristolMyers Squibb, New York, NY) and aspirin (81 mg a
day) prior to the procedure.

Operative Planning
For endovascular embolization of an aneurysm, it is
recommended that the patient be placed under general anesthesia and the patients head be secured to
the table. This helps eliminate excess radiation by
preventing movement of the patients head, which
can alter your road map and make the procedure
more time consuming and difficult. A baseline activated clotting time (ACT) or other means of calculating coagulation should also be obtained at the
beginning of the procedure, before any heparinized


38 Part II Perioperative Care

drips are started. We routinely use continuous electroencephalographic (EEG) monitoring throughout
the case. Although this is not performed by everyone, it is recommended for its sensitivity to embolic
events in the cerebral cortex, which is the most common complication of this procedure. Needle electrodes cause very minimal artifact, and they do not
interfere with the imaging. Heparinized saline is recommended for all drips used during the procedure
(2,000 U of heparin in 1L of saline). Before the guide
for the microcatheter is inserted, full anticoagulation
of the patient to two times the baseline ACT is performed. The anesthesiologist should have protamine
readily available in case of aneurysmal rupture during treatment. The heparin is then stopped once the
aneurysm is fully embolized. Low-magnification
anteroposterior and lateral views should be obtained
to visualize the distal vasculature and assess for
emboli prior to the removal of the guide catheter.
If one is considering using a closure device, heparin
can be reversed at this time using protamine. Once
the heparinization is reversed, a final angiogram will
often demonstrate the aneurysm to be completely
embolized, if small residual filling was noted while
the patient was fully anticoagulated.

Postoperative Planning
Postoperative management depends upon the size
of the coil mass exposed and whether a stent was
placed. If there is a large amount of coil mass exposed
to the parent artery, consider keeping the patient on
an 81 mg aspirin regimen for 6 weeks, unless this is
contraindicated for other medical reasons. This is to
help prevent platelet aggregate formation until the
coils are endothelialized.
If a stent is placed, it is recommended to give 75 mg
of Plavix for a minimum of 6 weeks and 81 mg aspirin
for 6 months to life. For young patients, it is reasonable to stop the aspirin regimen after 6 months, but for
patients over the age of 40, it is reasonable to continue
this regimen lifelong.
The postoperative management of an embolized
aneurysm with a small amount of coil mass opposing the parent vessel and no stent placement is to
avoid all anti-inflammatory medication. It is recommended that these patients do not take aspirin,
ibuprofen, or any other anti-inflammatory for a minimum of 6 months until follow-up studies are completed, to allow for endothelialization.
Obtaining a follow-up angiogram in 6 months, as
well as a magnetic resonance angiographic (MRA)
scan at the same time for comparison is recommended. If the studies match up well, future followup imaging may consist of only noninvasive studies.
We recommend follow-up with imaging at 1 year
and then every 4 years thereafter.

Ruptured Intracranial

Preoperative Planning
Patients who present with confirmed subarachnoid
hemorrhage (SAH) from a ruptured aneurysm should
obtain a neurological examination, which includes a
Hunt and Hess grading score and a computed tomography angiographic (CTA) scan. Multislice CTA is very
reliable for the detection of aneurysms, both ruptured
and unruptured, especially if the aneurysm is > 4 mm in
size.1,5,6 If the CTA is determined to be nondiagnostic, a
formal angiogram is recommended. The SAH grade will
often dictate the course of action and the time frame in
which it is achieved. Because the rehemorrhage rate is
approximately 4% in the first 24 hours, most clinicians
will attempt to treat within this window.
Blood pressure should be kept within normal limits while the aneurysm remains unsecured. For highgrade SAH patients or those with signs of elevated
intracranial pressure, a ventriculostomy should be
placed prior to any endovascular treatment. Some
clinicians will argue that treatment is necessary in
all SAH cases, regardless of grade. Others will argue
that simply watching patients with very high grade
SAHs to see if they will survive the next few days is
the proper treatment. These decisions are left to the
treating physicians discretion.

Operative Planning
The patient should be placed under general anesthesia
and monitored with continuous EEG. The head should
be secured into position to prevent movement during
the procedure. Patients should be kept normotensive
until the aneurysm is secured. From this point, the
operative management is the same as for unruptured
aneurysms, with the exception of anticoagulation. A
half loading dose of heparin is recommended prior to
placing the guide catheter and microcatheter to a goal
of approximately 1.5 times the baseline ACT. The predetermined coil should be readily available, as well as
one size larger and one size smaller. Once a few coils
are in position and the operator feels that the dome or
area of rupture is protected, then the patient should
be fully heparinized to 2 times the ACT baseline. From
this point on, the operative management is the same
as for unruptured aneurysms.

Postoperative Planning
Patients should be treated and observed in an intensive care unit. Nimodipine should be given for 21 days,
which has been shown to improve outcome.7 Some

6 Perioperative Planning
literature suggests that simvastatin may be beneficial
in reducing vasospasm,8 but this is still under investigation and not the standard of care. If the aneurysm
is well secured and the patient has no other aneurysms, the blood pressure is maintained between
140 and 180 mm Hg. Some have allowed the systolic
blood pressure to elevate up to 220 mm Hg before
starting treatment, with good results.9 However, we
recommend keeping the systolic blood pressure less
than 180 mm Hg following the intracranial hemorrhage guidelines, unless the patient is in vasospasm.
Patients must be monitored for vasospasm,
which can occur between days 3 and 21, but is most
common around days 4 to 7. Physical examination,
transcranial Dopplers, and EEG are all very helpful in
diagnosing vasospasm. If the patient deteriorates due
to vasospasm, then intravascular volume should be
increased (hypervolemia) as well as induced hypertension, and hemodilution to a hematocrit around
30 to 35%. These measures are known as triple H
therapy. Endovascular treatment, such as balloon
angioplasty or intra-arterial pharmacotherapy, may
be implemented if the patient does not respond to
triple H therapy.
A follow-up angiogram is obtained in 6 months
and correlated with an MRA scan. If these studies
match up well, future follow-up imaging may consist of only noninvasive techniques. Follow-up imaging is recommended at 1 year and then every 4 years

Arteriovenous Malformations
Preoperative Planning
Arteriovenous malformations (AVMs) present as
intracranial hemorrhages, seizures, or incidental
findings. Patients presenting with seizures should
begin antiepileptic medications and management
per neurology recommendations. Patients presenting with an intracranial hemorrhage must have their
coagulopathies corrected, if present. Decompression
or other neurosurgical management may be necessary if there is a large hematoma causing elevated
intracranial pressure. Most clinicians would recommend waiting at least 6 weeks after a hemorrhage
before attempting any therapy to allow resolution of
edema. MRA or CTA may be useful; however, a formal
angiogram is usually required to appreciate all of the
arterial supply and venous drainage. MRI is also useful for grading the AVM and for operative planning.
Treatment options include embolization for angiographic cure or preoperative embolization followed
by surgery or stereotactic radiation. We consider the
Spetzler-Martin grading scale as well as the modified grade III scale in our decision-making process.

Operative Planning
Patients should be placed under general anesthesia and monitored with continuous EEG and the head
secured into position for the reasons explained above.
The patients blood pressure should be kept under good
control before, during, and after surgery. A baseline ACT
should be obtained prior to the start of the procedure.
Patients should be fully anticoagulated prior to the
insertion of the guide catheter and microcatheter. Some,
though not all, institutions suggest performing provocative testing of the territory to be embolized with Amytal
and lidocaine in order to determine whether embolization of the pedicle will result in a neurological deficit.
Once the AVM is embolized and the catheters are withdrawn, the heparin should be discontinued or reversed.

Postoperative Planning
It is important to maintain blood pressure control
to prevent reperfusion hemorrhage or hemorrhage
from the AVM itself in cases of preoperative embolization. Appropriate therapy should be determined
by the Spetzler-Martin grade, percentage of embolization, and size and location of the AVM. If the AVM
is completely embolized and radiographically cured,
then it is reasonable to just observe the patient with
serial imaging. AVMs that are not surgically accessible, but small enough in size, should be considered
for stereotactic radiation. If the AVM is not completely obliterated and is accessible, then we perform
surgery within 48 hours of embolization.

Dural Arteriovenous Fistula

Dural arteriovenous fistulae (DAVFs) are abnormal
arterial and venous connections located within the
dura mater involving a dural sinus or cortical veins.10
DAVFs represent 10 to 15% of intracranial arteriovenous shunts. The transverse sigmoid sinus represents the most common location of DAVFs.

Preoperative Planning
The most important aspects of DAVFs are the patients
symptoms and the grade of the fistula. There are many
different grading systems for DAVFs, all of which are
based on the venous drainage. For the most part, lowgrade fistulas have normal antegrade venous drainage
without drainage into cortical veins, and high-grade
fistulas have cortical venous drainage. This is important because high-grade DAVFs have a high rupture rate
and require treatment. It is strongly recommended that
high-grade DAVFs be treated during the same hospital


40 Part II Perioperative Care

stay as that for diagnosis. Also, patients presenting with
infarction, hemorrhage, or visual loss require emergent
The several different treatment options for DAVFs
include compression therapy, transarterial embolization, transvenous embolization, radiosurgery, and surgical excision. We discuss the endovascular treatment
options, transarterial and transvenous embolization.
There are many embolic agents available for both
transarterial and transvenous embolization of DAVFs.
These include liquid adhesives, such as N-butylcyanoacrylate (NBCA), and Onyx, alcohol, Embospheres, polyvinyl alcohol (PVA), and even silk suture.
The fistula must be obliterated in order to cure the
DAVF, otherwise recurrence is imminent. This can
rarely, if ever, be accomplished using the transarterial
approach alone. Hence the transvenous approach,
when applicable, is the technique of choice.
Transarterial embolization is usually used as an
adjunct with other treatment options.11 The most
important preoperative planning for this type of
treatment is learning the anatomy and having a thorough understanding of extracranial to intracranial
anastomoses.11,12 Occluding the arterial supply proximally will only result in revascularization from collaterals and should be avoided.12 Also, occluding the
arterial supply proximally interferes with access to
the lesion for future therapies.11
It is essential to evaluate the venous phase of
the angiogram prior to the consideration of using
transvenous embolization. If the sinus is patent and
functioning, then transvenous embolization is not a
good option and may result in venous infarction. If
the venous sinus is fully arterialized, and not used
physiologically, then the transvenous approach to
the fistula is the option of choice.
Patients with low-grade, low-risk fistulas may be
observed without treatment or treated transarterially for a palliative effect. These patients should avoid
antiplatelet medications, such as aspirin, which may
interfere with spontaneous closure of the fistula.12

Operative Planning
The patient is usually placed under general anesthesia
and is monitored with continuous EEG while the head
is secured into position. The patients blood pressure
should be kept under good control before, during, and
after the case. A baseline ACT should be obtained prior
to the start of the procedure. For unruptured DAVFs,
the patient is fully anticoagulated for transarterial
approaches, with an ACT 2 times normal, but only
partially anticoagulated for transvenous approaches,
with a goal ACT of 1.5 times baseline.
Selective provocative testing with lidocaine prior
to transarterial embolization is recommended to
reduce the risk of cranial nerve injury.11,12 Lidocaine
should also be given if ethanol is going to be used in
a dural artery and the patient is not under general

anesthesia. Injecting ethanol into a dural artery is

extremely uncomfortable for the patient.

Postoperative Planning
Patients should be observed in an intensive care unit
(ICU) postembolization. The patient should remain
normotensive, and frequent neurological checks are
recommended. After a day of observation in the ICU,
the patient may be transferred to the floor and subsequently home. A follow-up angiogram is recommended in 6 months for all high-grade fistulas and
for those who have hemorrhaged previously.

Carotid Sacrifice
Preoperative Planning
Balloon test occlusion (BTO) is warranted in any case
where carotid sacrifice is a consideration, such as in
cases of giant cavernous aneurysms, trauma, or skull
base tumors. All patients who are clinically stable
should undergo a balloon occlusion test prior to
carotid sacrifice.

Operative Planning
Patients are awake and have continuous EEG monitoring during the procedure. A baseline ACT should be
obtained prior to any heparinized drips being started.
The patient undergoes anticoagulation to 2 times the
baseline ACT before either a guide catheter or standard
balloon catheter is inserted. During a 30 minute occlusion test, if the patient has no new neurological deficits,
hypotension is induced to two thirds the mean arterial pressure for the last 10 minutes. BTO with a hypotensive challenge is a safe and sensitive way to screen
patients to determine who will tolerate a carotid sacrifice.13 However, if the patient fails, then other options
should be explored, such as EC-IC bypass.

Postoperative Planning
Following a successful BTO and carotid sacrifice,
the patient is kept very well hydrated, the volume
is expanded, and heparin is continued overnight to
prevent stump emboli formation. The patient is kept
flat for 24 hours to allow for slow acclimation. The
head of the bed is gradually elevated over the next
48 hours. Orthostatic blood pressure is checked prior
to sitting the patient upright. If any new neurological signs are encountered, the patient is placed back
in the recumbent position, and the process is started
again. The patient is placed on an 81 mg aspirin a day
for 6 weeks, if no operative procedure is planned.

6 Perioperative Planning

Carotid and Intracranial


Preoperative Planning
Patients with high-grade stenosis of 70 to 99%, or
symptomatic patients with stenosis of 50 to 69%,
may benefit from intervention.14 Patients with intracranial stenosis and medically intractable transient
ischemic attacks (TIAs) or strokes may benefit from
intracranial balloon angioplasty and stenting of a
severely stenosed vessel.
All patients who are candidates for carotid or
intracranial stents should be placed on 75 mg Plavix
and 81 mg of aspirin for a minimum of 3 days prior
to the procedure.

Operative Planning
These procedures may be performed under conscious sedation; however, general anesthesia is preferred for patient comfort and better intracranial
visualization. Continuous EEG monitoring should
be performed by a neurophysiologist and overseen
by the department of neurology during the procedure. A baseline ACT should be obtained prior to any
heparinized drips being started. The patient then
undergoes anticoagulation to no less than 2 times
the baseline ACT before the guide catheter and stent
system are inserted.

Postoperative Planning
The patients blood pressure should be very well controlled to prevent reperfusion injury immediately
following reestablishment of normal blood flow and
during the entire period of extubation and transport
to the ICU. The patient should also be placed on Plavix
for a minimum of 6 weeks and an aspirin (81 mg) a day
for a minimum of 6 months. A follow-up scan using
noninvasive imaging is obtained in 6 months time.

Preoperative assessment of the images to determine the potential pitfalls of the procedure
is critical in mitigating the complications.
Have specific treatment goals in mind prior to
the initiation of the procedure but be flexible enough to modify the plan in the event of
adverse or unexpected events.
Anticipate complications and strive to avoid them.

1. Yoon DY, Lim KJ, Choi CS, Cho BM, Oh SM, Chang SK. Detection

and characterization of intracranial aneurysms with 16-channel

multidetector row CT angiography: a prospective comparison
of volume-rendered images and digital subtraction angiography. AJNR Am J Neuroradiol 2007;28(1):6067 PubMed
2. Wiebers DO, Whisnant JP, Huston J III, et al; International
Study of Unruptured Intracranial Aneurysms Investigators.
Unruptured intracranial aneurysms: natural history, clinical
outcome, and risks of surgical and endovascular treatment.
Lancet 2003;362(9378):103110 PubMed
3. Lee TH, Kim DH, Lee B-H, et al. Preliminary results of endovascular stent-assisted angioplasty for symptomatic middle cerebral artery stenosis. AJNR Am J Neuroradiol 2005;
26(1):166174 PubMed
4. Alfke K, Straube T, Drner L, Mehdorn HM, Jansen O. Treatment of intracranial broad-neck aneurysms with a new selfexpanding stent and coil embolization. AJNR Am J Neuroradiol
2004;25(4):584591 PubMed
5. Colen TW, Wang LC, Ghodke BB, Cohen WA, Hollingworth
W, Anzai Y. Effectiveness of MDCT angiography for the detection of intracranial aneurysms in patients with nontraumatic subarachnoid hemorrhage. AJR Am J Roentgenol 2007;
6. Westerlaan HE, Gravendeel J, Fiore D, et al. Multislice CT angiography in the selection of patients with ruptured intracranial
aneurysms suitable for clipping or coiling. Neuroradiology
2007;49(12):9971007 PubMed
7. Barker FG II, Ogilvy CS. Efficacy of prophylactic nimodipine
for delayed ischemic deficit after subarachnoid hemorrhage:
a metaanalysis. J Neurosurg 1996;84(3):405414 PubMed
8. Lynch JR, Wang H, McGirt MJ, et al. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke 2005;36(9):
20242026 PubMed
9. Lanzino G, Fraser K, Kanaan Y, Wagenbach A. Treatment of
ruptured intracranial aneurysms since the International Subarachnoid Aneurysm Trial: practice utilizing clip ligation and
coil embolization as individual or complementary therapies. J
Neurosurg 2006;104(3):344349 PubMed
10. Caragine LP, Halbach VV, Dowd CF, Ng PP, Higashida RT. Parallel
venous channel as the recipient pouch in transverse/sigmoid
sinus dural fistulae. Neurosurgery 2003;53(6):12611266,
discussion 12661267 PubMed
11. Malek AM, Halbach VV, Higashida RT, Phatouros CC, Meyers PM,
Dowd CF. Treatment of dural arteriovenous malformations and
fistulas. Neurosurg Clin N Am 2000;11(1):147166 PubMed
12. McDougall CG, Halbach VV, Higashida RT, et al. Treatment of
dural arteriovenous fistulas. Neurosurg Q 1997;7(2):110134
13. Standard SC, Ahuja A, Guterman LR, et al. Balloon test occlusion of the internal carotid artery with hypotensive challenge.
AJNR Am J Neuroradiol 1995;16(7):14531458 PubMed
14. Ferguson GG, Eliasziw M, Barr HW, et al. The North American
Symptomatic Carotid Endarterectomy Trial: surgical results in
1415 patients. Stroke 1999;30(9):17511758 PubMed


Guilherme Dabus and Raul G. Nogueira

The field of neuroendovascular surgery is constantly

evolving. Other chapters in this book address the recent
advances in imaging and device technology. This chapter reviews the various pharmacological strategies
currently employed in conjunction with neuroendovascular procedures, including medications for anesthesia or conscious sedation, intra- and periprocedural
anticoagulation and/or platelet inhibition, as well as
thrombolysis. Futuristic but potentially viable therapies are briefly reviewed. It is crucial for neuroendovascular specialists to have an overall understanding

of the mechanism of action, pharmacodynamics, pharmacokinetics, and safety profile of the aforementioned
agents. Some topics, including coagulation and platelet
activation systems, intra-arterial pharmacotherapy for
vasospasm, embolic agents, intra-arterial chemotherapy, sclerotherapy, and intra-arterial chemical thrombolysis, are covered in other chapters in this book and
thus receive only brief coverage here.
This chapter is divided into sections according to
drug function, a brief summary of which is included
in Table 7.1.

Table 7.1 Pharmacotherapy in neuroendovascular surgery

Class of agent of action

Mechanism of
action (if known)



12 min

Potentiation of GABA CNS depression,

paradoxical stimulation,
coughing, bronchospasm,
tachycardia, arrhythmia,
hypotension, nausea/

Most commonly



Very rapid
(1 min)

Alpha-2 adrenergic
receptor agonist


Usage limited


hypnotic agent

Very rapid
(< 1 min)

Involves GABA

depression and

Usage is generally
limited to anesthesia or critical care



25 min

Binds to mu-1 and

mu-2 receptors and
causes supraspinal

Respiratory depression

Typically the
analgesic of choice
for conscious



5 min

GP IIb/IIIa inhibitor





5 min (with Irreversibly

inactivates COX-1
3060 min)

Neutropenia, nausea/
vomiting, GI bleed,
rash, tinnitus/hearing
loss, hyponatremia,
thrombocytopenia and

240% of individuals
respond poorly to

Agent name

Major side effects



Antiplatelet agents



Agent name

Class of agent of action





Mechanism of
action (if known)

Major side effects


2 h after a
Binds to the ADP
75 mg dose platelet receptor
and inhibits the
activation of the
GP IIb/IIIa complex

Bleeding, neutropenia/
GI symptoms, rash,

2852% of
individuals are poor
responders; studies
show prasugrel,
a novel thirdgeneration oral
thienopyridine, is
more effective than


10 min

Inhibits the GP IIb/

IIIa complex (but
long dissociation


Overall favorable
response by patients


state in
46 h

Inhibits platelet
Bleeding, rare allergic
aggregation by
reversibly binding the
GP IIb/IIIa receptor



Anticoagulation Immediate,
activity of
30 min

Inactivating factors
Xa and IIa by
activation of the
plasma serine
protease inhibitor
antithrombin (AT)

diarrhea, hypersensitivity, rash, urticaria,
hemorrhage, thrombocytopenia, anaphylaxis
(hypotension reported)

One of the most

important drugs
in the neuroendovascular specialist


Anticoagulation 3060 min

Direct thrombin


Monitor with PTT


Anticoagulation Steady
state is
after bolus
and a 4 h

Binds to thrombin at
two different sites

Bleeding, back pain,

nausea, vomiting,
hypotension, headache



Anticoagulation Steady
within 13
h of initiating infusion

Binds reversibly to
the catalytic site
of thrombin;
metabolized and
excreted by hepatobiliary mechanisms


FDA-approved for
the treatment of
HIT; no antidote


effect is mediated
through inhibition of
the vitamin K
dependent gammacarboxylation of
coagulation factors
II, VII, IX and X


INR critical in
confirming proper

tissue plasminogen


half-life of
3.5 min

Initiates local

Hemorrhage, edema,



half-life of
18 min

Initiates local

Hemorrhage, edema

Oral anticoagulants

Thrombolytic agents

Lower binding
affinity to fibrin,
thus may better
penetrate clot


44 Part II Perioperative Care

Sedation and Analgesia

Conscious sedation is a moderate sedation/analgesia that results in a drug-induced depression of
consciousness during which patients respond purposefully to verbal commands or light tactile stimulation. No interventions are required to maintain
a patent airway, and cardiovascular function and
spontaneous ventilation are adequate.1
Benzodiazepines (BZPs) are commonly used as
sedatives for conscious sedation. They increase the
responsiveness of central nervous system (CNS)
receptors potentiating endogenous -aminobutyric
acid (GABA), the main inhibitory neurotransmitter,
providing anxiolytic effect, sedation, and anterograde amnesia with only minimal cardiovascular or
respiratory depression.2,3 However, because they are
not analgesics, they are usually administered with
opioids, producing a synergistic response in sedation
but at the cost of respiratory depressive effects.2
Midazolam is the most commonly used BZP.2 It is
a short-acting agent that is three to four times more
potent than diazepam. Its popularity comes from
its fast onset of action (12 minutes after administration) along with a relatively short duration
(approximately 30 minutes). The plasma half-life of
1 to 4 hours is shorter than that of lorazepam (10
20 hours) or diazepam (2137 hours).2,3 Midazolam
has predominant renal excretion, and its elimination
half-life is increased by chronic renal failure or congestive heart failure. The typical initial dosage is 1 to
2 mg intravenously over 2 to 3 minutes (0.51.5 mg
in older patients). Maintenance dose is approximately 25% of initial dose. Total dose in healthy adults
is up to 0.15 mg/kg.3 Midazolam is contraindicated in
cases of sensitivity to the medication and narrowangle glaucoma. Side effects include CNS depression,
paradoxical stimulation, coughing, bronchospasm,
tachycardia, arrhythmia, hypotension, and nausea/
vomiting.4 In cases of BZP oversedation, flumazenil,
a BZP-competitive antagonist, can be given intravenously (IV) at a dosage of 0.2 mg every minute up to
1 mg until reversal is observed. Of note, the half-life
of flumazenil is only 1 hour; therefore resedation
could happen with long-acting BZPs.2
Opioids are usually the analgesics of choice for
conscious sedation. They bind to mu receptors in the
CNS, causing supraspinal analgesia (mu-1). This typically occurs at the cost of some degree of respiratory
depression and bradycardia (mu-2). Fentanyl is a synthetic opioid and is commonly used for analgesia in
conscious sedation. It binds to mu-1 and mu-2 receptors.2 Its onset of action is 2 to 5 minutes, and its duration is 30 to 60 minutes. Fentanyl has a half-life of
approximately 3 to 4 hours. The typical loading dose
is 25 to 100 g over 1 to 2 minutes. Analgesia can then
be maintained with 25 to 50 g every 30 minutes. Its
most important side effect is respiratory depression.

For reversal, naloxone 0.1 to 0.4 mg over 2 to 3 minutes should be used.3,4 Remifentanyl is a synthetic
opioid with a very short half-life (614 minutes) and
a very predictable rapid offset. It can be used as an
infusion and titrated to the length of the procedure.2
Other analgesics, such as morphine and meperidine,
can be used but have disadvantages compared with
fentanyl for procedural conscious sedation.2
Propofol is a sedative and hypnotic agent with a
very rapid onset and offset. It has no analgesic properties. Its mechanism of action has not been well
defined but appears to involve GABA channels. The
main side effects include cardiorespiratory depression and hypotension, but hypertriglyceridemia,
pancreatitis, and propofol infusion syndrome (rhabdomyolysis, lactic acidosis, arrhythmias) may be seen
with prolonged, high-dose infusions. Dexmedetomidine (Precedex, Hospira, Inc., Lake Forest, IL) is a
selective 2-adrenergic receptor agonist with anxiolytic, analgesic, and sedative properties. Side effects
include hypotension, bradycardia, and asystole with
rapid administration. In general, use of propofol and
dexmedetomidine is limited to anesthesiologists or
critical-care personnel.

Antiplatelet Agents
Antiplatelet medications constitute an important
and evolving subject in the field of neuroendovascular procedures. Their use has become particularly
important due to the development and increasing use of implanted endovascular devices, such as
stents and coils, as well as treatment modalities that
may injure the endothelial surface (angioplasty).
Basic knowledge of the mechanisms underlying platelet adhesion, activation, and aggregation is
essential to the understanding of how the antiplatelet
agents work. The intact endothelium releases prostacyclin (prostaglandin I2 [PGI2]) and nitric oxide (NO),
which inhibit platelet activation.5 When the endothelial surface is injured (e.g., shear stress or angioplasty), it exposes the subendothelial matrix and
adhesive glycoproteins, which are usually covered by
normal endothelial lining. Platelets have receptors
for these glycoproteins. When these receptors are
activated, they will bind immediately to the exposed
glycoproteins, covering the area of injured endothelium. This process is called adhesion and is mediated
by receptors like GP Ib/IX complex. After adhesion,
platelets are activated and secrete additional agonistic substances, such as adenosine diphosphate
(ADP), calcium, serotonin, and thromboxane A2. They
also undergo a conformational change at the GP IIb/
IIIa site. This conformational change activates this
receptor, making it a high-affinity binding site for
fibrinogen and von Willebrand factor (vWF). Both
fibrinogen and vWF have multiple binding sites and

can bind to multiple platelets, causing cross-linking
with platelet to platelet and platelet to matrix adhesive interactions that result in platelet aggregation
at the site of the injury.5,6 It is believed that platelet
aggregation as a response to a foreign body is a result
of a combination of turbulent flow, shear stress, and
chemical composition induced by the device, altering the hemodynamic endovascular environment.5

The antiplatelet effects of aspirin have been well
known since the 1960s.7 Aspirin irreversibly inactivates cyclooxygenase-1 (COX-1), inhibiting the conversion of arachidonic acid to prostaglandin G2 and
H2 and, ultimately, the production of thromboxane
A2. It also inhibits the vascular synthesis of PGI2.5,6,8,9
It has a fast onset of action (approximately 5 minutes after oral dose), with maximum effect at 30 to
60 minutes. It is metabolized by sterases in the liver
and has a half-life of 15 to 20 minutes, but its effect
is stable for 24 hours. The dose is a subject of controversy. Small doses (up to 325 mg) have similar levels
of platelet inhibition with a better risk profile than
larger doses.5,912 A major issue is that approximately 2
to 40% of individuals are resistant or poor responders
to aspirin.5,1315 Side effects include thrombocytopenia, neutropenia, nausea/vomiting, gastrointestinal
(GI) bleeding, rash, tinnitus/hearing loss, hypoglycemia, and hyponatremia.4

Clopidogrel is a thienopyridine that binds to the ADP
platelet receptor and inhibits the activation of the
GP IIb/IIIa complex, ultimately inhibiting platelet
aggregation. It requires hepatic conversion to active
metabolites.3,5 After a single 75 mg dose, some platelet inhibition can be seen in 2 hours. With continued
administration, steady state is seen in 3 to 7 days. Platelet activity usually returns to baseline within 5 days
after treatment is stopped. With a loading dose of 300
to 600 mg, maximum levels of inhibition of 40 to 50%
are observed in 2 to 5 hours.3,16 Resistance to clopidogrel has been seen in up to 31% of patients.17 Adverse
events include bleeding, neutropenia/agranulocytosis,
GI symptoms, rash, and thrombotic thrombocytopenic purpura.18 Three recent studies demonstrated that
the number of patients who have a poor response or
are resistant to clopidogrel varies from 28 to 52%.13,14,19
Mller-Schunk et al described a series of 50 patients
who underwent supra-aortic stenting. Five patients
had adverse events, and all of them were considered
nonresponders to clopidogrel tested by impedance
aggregometry. This association was statistically significant.19 Prabhakaran et al found that age (> 55 years)
and diabetes were inversely related to platelet inhibi-

tion.14 Another study found an association between

higher body weight and poor therapeutic response.13
Prasugrel is a novel third-generation oral thienopyridine that is a specific and irreversible antagonist to
the ADP platelet receptor. Preclinical and early-phase
clinical studies have shown prasugrel to have more
potent antiplatelet effects, lower interindividual variability in platelet response, and faster onset of activity
than clopidogrel.
Despite being commonly used along with aspirin as dual antiplatelet regimen for neuroendovascular procedures, a substantial number of patients
demonstrate non-, low- or hyper-reponse to clopidogrel.2022 Also, a wide and dynamic variability to
clopidogrel response has been demonstrated.22 Due
to the increase in the number of procedures consisting in the implantation of stents and flow diverters
in the intracranial vessels the use of methods trying to quantify the degree of platelet inhibition has
gained wider popularity. VerifyNow (Accumetrics,
San Diego, California) is a point-of-care platelet function test that measures the degree of P2Y12 receptor inhibition.2022 Its results are reported in PRUs
(P2Y12 reaction units) with a PRU values inversely
corresponding to the inhibition (low PRUs greater
inhibition; hi PRUs lower inhibition). The use of preprocedure antiplatelet testing in a clinical setting is
controvertial and still a matter of debate. Despite
that, PRU results have been shown to correlate with
thromboembolic or hemorrhagic complications
in patients treated with flow diverters. In a study
of 44 patients with 48 flow diverter procedures,
PRU < 60 or > 240 were independent predictors of
hemorrhagic (PRU < 60) or thromboembolic (PRU >
240) perioperative complications.20 Another study
reported that a PRU > 208 had an OR of 11.32 (95%
CI 0.06 to 212.57) for symptomatic thromboembolic
complications, although the results were not statistically significant.21
Since approximately 30% of patients are low
responders to clopidogrel, which may increase the
risks of platelet aggregation leading to thromboembolic complications, some neurointerventionalist
advocate using newer oral antiplatelet drugs such as
prasugrel or ticagrelor.2326,33

Prasugrel and Ticagrelor

Prasugrel is a newer third-generation oral thienopyridine with a specific and irreversibly inhibiting effect
on the P2Y12 platelet receptor.23,27 Prasugrel is rapidly metabolized to active form with plasma half life
of 4h.24,28 Compare to clopidogrel, prasugrel has more
potent antiplatelet effects, lower interindividual variability in platelet response, and faster onset of activity.23 A large series comparing prasugrel to clopidogrel
in cardiac patients demonstrated that prasugrel therapy was associated with less ischemic events and


46 Part II Perioperative Care

stent thrombosis but also had higher major bleeding
rates (2.4%).29 Prasugrel has been used in neuroendovascular patients, however its safety profile is not fully
known. Leslie-Mazwi et al reported a case where of
a patient with intracranial stent-assisted coil embolization with clopidogrel resistance that was loaded
urgently with 60 mg of prasugrel followed by 10 mg
daily maintenance dose; this patient course was complicated retroperitoneal hemorrhage requiring blood
transfusion.23 Akbari et al compared their hemorrhagic complications in patients taking aspirin and
clopidogrel versus patients taking aspirin and prasugrel.24 Fifty-five procedures were done on aspirin and
clopidogrel and 31 procedures were done on aspirin
and prasugrel (60 mg loading dose followed by 10
mg daily). Hemorrhagic complications were noted in
3.6% of the aspirin and clopidogrel group compared
to 19.4% in the aspirin and prasugrel group (p = 0.02).
The authors concluded that the combination of aspirin
and prasugrel may increase the risk of hemorrhagic
complications during neuroendovascular procedures
compared to aspirin and prasugrel.24 In another study
where 16 patients underwent neurointerventional
procedures on aspirin and prasugrel the authors
reported no hemorrhagic complication.25 Although
unclear why these differences are seen between these
two studies, on potential explanation may be the
smaller doses used in the latter study (40 mg loading
dose followed by 10 or 5 mg daily maintenance dose).
Ticagrelor is a potent P2Y12 receptor antagonist
from the class of the cyclopentyltriazolopyrimidines.
It does not require metabolic activation to an active
form and binds rapidly and reversibly to the P2Y12
receptor. It is rapidly absorbed, with a median time
to maximum concentration of 1.32.0 hours. The
pharmacokinetic profile of ticagrelor is not significantly affected by age, gender, or administration with
food, nor by prior treatment with, or responsiveness
to, clopidogrel. Ticagrelor is primarily metabolized
via the cytochrome P450 CYP3A4 enzyme. Also, the
pharmacodynamic characteristics of ticagrelor are
not influenced by CYP2C19 and ABCB1 genotypes.30
Ticagrelor has faster and greater platelet inhibition rate than clopidogrel with comparable efficacy
with no significant side effects.26,31,32 Compared to
clopidogrel and prasugrel, the need of twice a day
administration and faster platelet activation after
discontinuation of the drug are potential drawbacks (which may increase risk of thromboembolic
events); in the other hand, faster platelet activation
after discontinuation of the drug may also lead to
decrease morbid-mortality associated with current
antiplatelet regimens.26 In the PLATelet inhibition
and patient Outcomes (PLATO) trial, ticagrelor significantly reduced rates of vascular and total death
compared with clopidogrel and the bleeding causing or contributing to death did not differ between
treatments.33 There is few data on the efficacy and

safety of ticagrelor in the neuroendovascular procedures. Hanel et al described their experience with
ticagrelor in 18 patients who were non-responders
to clopidogrel and underwent neuroendovascular
procedures.26 All patients received a loading dose of
180 mg of ticagrelor followed by a 90 mg twice a day
maintenance dose. There were no adverse events
during or following the postoperative period that
could be correlated to the medication.26

Ticlopidine is another thienopyridine that was used as
an antiplatelet medication. Its use practically stopped
due to its severe side effects (bone marrow depression
and neutropenia) and the emergence of clopidogrel
with its accelerated effect in platelet inhibition.34,35

Dipyridamole is a pyrido-pyrimidine derivative that
vasodilates coronary microvessels and inhibits platelet activation by increasing levels of cyclic adenosine
monophosphate and cyclic guanosine monophosphate.36 It also has vasodilator effects, which could
lead to coronary steal phenomenon. It is typically
used twice a day as an extended-release formulation
(200 mg) combined with low-dose (25 mg) aspirin
(Aggrenox, Boehringer Ingelheim Pharmaceuticals,
Inc., Ridgefield, CT).5,36

Abciximab is a monoclonal antibody (c7E3) that
has high affinity for platelet GP IIb/IIIa receptors.5,6
Its plasma half-life is 10 minutes because it binds
immediately to circulating platelets. The dissociation time, however, is long, with the activity lasting
for 12 to 14 hours.5 Therefore, it has a short onset
of action and slow reversal in activity after discontinuation. Its use in the coronary vasculature
usually consists of a loading dose of 0.25 mg/kg
IV followed by an IV infusion of 0.125 g/kg/min
for 12 hours,5 but lower dosages are typically recommended with neurointerventional procedures.
Adverse reactions include hemorrhagic complications, thrombocytopenia, and hypersensitivity.3 Offlabel intra-arterial (IA) use of abciximab has also been
reported.37,38 Mounayer et al administered abciximab
through a microcatheter as a bolus of 4 to 10 mg
over a period of 10 to 20 minutes for treatment of
thromboembolic complications during endovascular
treatment of cerebral aneurysms in 13 patients, with
good results.23 Similarly favorable responses have
been described by other authors.24


Eptifibatide is a synthetic cyclic heptapeptide,
structurally analogous to barbourin, that reversibly inhibits platelet aggregation by blocking
the binding of adhesive ligands to the GP IIb/IIIa
receptor. 3,5 Its plasma half-life is 1.5 to 2.5 hours,
and its primary excretion is renal.3,5,6 A steadystate level is usually reached in 4 to 6 hours at the
recommended coronary doses (IV boluses of 180
g/kg followed by IV infusion of 1 to 2 g/kg/min
for up to 24 hours). 3 Platelet inhibition and bleeding time decrease rapidly in 4 to 6 hours after discontinuing the infusion. Complications include
bleeding and rare allergic reactions.3 In our service we have used up to 9 mg of IA eptifibatide for
the treatment of thromboembolic complications
during endovascular procedures. If necessary, we
have combined this IA bolus with an IV bolus to a
maximum combined IA/IV bolus of 90 g/kg, followed by a 0.5 to 2 g/kg/min IV infusion (http://

Tirofiban is a nonpeptide tyrosine derivative with
low molecular weight that competes for the GP IIb/
IIIa receptors by mimicking the binding sequence
of the natural ligand.5,6 Tirofiban is administered as
a 10 g/kg bolus followed by IV infusion of 0.15 g/
kg/min for 12 hours, resulting in 96% and 100% of
platelet inhibition at 5 minutes and 2 hours, respectively.5,39 It has a half-life of 1.6 hours and is excreted
by both renal and nonrenal mechanisms.6,40

Antiplatelet Protocol
At our institution, all elective aneurysm coiling
cases with or without adjunct therapy (stent placement or balloon remodeling) and all angioplasty
and stent placement cases receive dual antiplatelet therapy. The patients are usually premedicated
for 10 days before the procedure with 75 mg of
clopidogrel and 325 mg of aspirin. In urgent cases,
patients receive a loading dose of 300 to 600 mg of
Plavix and the usual 325 mg of aspirin before the
procedure. The dual antiplatelet therapy is usually
maintained for at least 6 to 8 weeks after the procedure. On the rare occasions where the patient
could not be premedicated or loaded before the
procedure, eptifibatide IV bolus followed by IV
infusion is used. For thromboembolic complications we have used eptifibatide in doses that range
from 3 to 9 mg IA followed or not by an IV infusion
as already described.

Anticoagulation Agents
Heparin and Its Derivatives
Heparin is one of the most important drugs in the
neuroendovascular specialist armamentarium. It
was introduced into clinical use in 1935, and it is
estimated that 30% of all patients admitted to a hospital receive heparin.41 Heparin is used both intravenously (as a bolus or continuous infusion) and
intra-arterially (mixed with saline in the continuous
flushing system for catheters and microcatheters).
Despite its unpredictable pharmacokinetics and its
heterogeneous molecular structure, heparin is still
largely used.42 Heparin acts by inactivating factors Xa
and IIa (thrombin) by activation of the plasma serine protease inhibitor antithrombin (AT). Thrombin
and factor Xa are most responsive to inhibition, and
human thrombin is about 10-fold more sensitive to
inhibition by the heparin-AT complex than factor Xa.
Heparin also inhibits factors IXa, XIa, and XIIa, interacts with platelets to inhibit clot formation, and has
a direct effect in the microvasculature preventing
At the molecular level, heparin binds to the lysine
site on AT, producing a conformational change at
the arginine-reactive site that converts AT from a
slow, progressive thrombin inhibitor to a very rapid
inhibitor of thrombin and factor Xa. By inactivating
thrombin, heparin not only prevents fibrin formation but also inhibits thrombin-induced activation of
factors V and VIII as well as platelets. It also induces
secretion of tissue factor pathway inhibitor by vascular endothelial cells that reduces procoagulant activity of the tissue factor VIIa complex, and this could
contribute to its antithrombotic action.43
Heparin is cleared by the reticuloendothelial cells
of the liver with a half-life of 60 to 90 minutes. Its
onset of action is immediate, with maximum activity in 30 minutes. Heparin side effects include nausea and vomiting, diarrhea, hypersensitivity, rash,
urticaria, hemorrhage (38%), thrombocytopenia,
and anaphylaxis.3,4 Significant hypotension has also
been reported, requiring management with vasoactive medications.44 Heparin-induced osteoporosis happens as a result of suppression of osteoblast
formation and activation of osteoclasts promoting bone loss. Decrease in bone density resulting
in symptomatic fractures might happen in patients
requiring long-term use of heparin.43 A very important consideration is the entity of heparin-induced
thrombocytopenia (HIT). Two types of HIT have been
identified. HIT type I is nonimmune and tends to
occur during the first few days after heparin exposure. This syndrome typically has a benign course
and is not associated with thrombotic events (white
clot syndrome). HIT type II is an immune-mediated


48 Part II Perioperative Care

disorder characterized by the formation of antibodies against the heparinplatelet factor 4 complex,
resulting in thrombocytopenia, platelet aggregation,
and the potential for arterial and venous thrombosis (e.g., white clot formation). The possibility of
HIT type II should be raised in patients who demonstrate a platelet count drop to less than 100,000,
or by greater than 50% from baseline, in the setting
of heparin therapy (usually 512 days after initial
exposure). Unexplained thrombotic events should
also evoke this diagnosis, even in the setting of a
normal platelet count. Its incidence is approximately
17% of patients exposed to unfractionated heparin
and 8% of patients exposed to low-molecular-weight
heparin (LMWH); however, only 20% of patients
with antibodies will develop thrombocytopenia, and
only 0.03 to 0.09% will have clinical manifestations of
HIT.41,45 Currently, direct thrombin inhibitors (lepirudin and argatroban) are the main treatment for HIT.45
Unfractionated heparin is reversible with administration of IV protamine sulfate (10 mg of protamine
per 1,000 units of heparin at a rate 20 mg/min and no
more than 50 mg over any 10 minute period). The use of
protamine is associated with a small risk of anaphylaxis,
in particular in patients who have had previous exposure to protamine (e.g., diabetic patients receiving protamine-containing insulin) and those with fish allergy.
LMWHs (e.g., enoxaparin, dalteparin, tinzaparin)
and fondaparinux are newer anticoagulants derived
from heparin. These drugs are available only as subcutaneous (SQ) injections, require more complex assays if
close monitoring is needed, and are not fully reversible
by protamine. Therefore, they are not typically used in
association with neurointerventional procedures. Similarly to unfractionated heparin, LMWHs inactivate
factor Xa, but they have a lesser effect on thrombin
and thus do not prolong the aPTT. LMWHs are thought
to be at least as effective as unfractionated heparin and
have some potential advantages over it, including a
much lower likelihood of inducing immune-mediated
thrombocytopenia and a much easier administration
scheme that allows for safe administration in the outpatient setting. Of note, protamine sulfate (1 mg/100
anti-Xa units of LMWH) does not completely eliminate
the anti-Xa activity of LMWH.
Fondaparinux (Arixtra, GlaxoSmithKline, Philadelphia, PA) is a synthetic pentasaccharide derived
from the minimal AT binding region of heparin.
This drug binds to AT with greater affinity than the
native pentasaccharide of unfractionated or lowmolecular-weight heparin. It does not interact with
other plasma proteins or cellular elements, including platelets or platelet factor 4, and therefore does
not induce thrombocytopenia or HIT. Fondaparinux
is 100% bioavailable after SQ injection, with a mean
half-life of 17 hours, and thus can be given once daily.
Full anticoagulation can be achieved with a weightbased scale (5, 7.5, or 10 mg SQ once daily for patients
weighing < 50, 50 to 100, or > 100 kg, respectively).

The drug is cleared by the kidney, and its use is contraindicated in the presence of renal insufficiency.
No antidote is known. Specifically, fondaparinux is
not inactivated by protamine. Even at therapeutic
doses, fondaparinux results in only slight prolongation of the aPTT and, if required, monitoring should
be performed via an anti-factor Xa assay.

Direct Thrombin Inhibitors

Lepirudin was approved by the Food and Drug Administration (FDA) for treatment of HIT in 1998. It was the
first direct thrombin inhibitor to be approved by the
FDA. It is a recombinant form of hirudin (r-hirudin), an
anticoagulant produced by the parapharyngeal glands
of the leech (Hirudo medicinalis).35,46 It has bivalent
properties, binding to the fibrinogen-binding site and
to the catalytic site of thrombin.41 Lepirudin reaches
therapeutic levels after 30 to 60 minutes, has a mean
half-life of 80 minutes, and has renal clearance. The
recommended dose is a 0.4 mg/kg bolus followed by
0.15 mg/kg/h continuous infusion. Its anticoagulant
effect should be monitored with aPTT.35,46 Recombinant factor VIIa has been used to treat life-threatening
refractory bleeding from lepirudin anticoagulation.47

Bivalirudin has been increasingly used for anticoagulation during interventional cardiology procedures.
Bivalirudin is an oligopeptide analogue of hirudin with
bivalent properties. It binds transiently to thrombin at
two different sites without the need for a cofactor.48 It
inhibits thrombin in free solution or bound to fibrin.
It has minimal antigenic potential. Bivalirudin has a
half-life of 25 minutes and is excreted by proteolysis
(80%) with minor renal excretion.48 The activated clotting time (ACT) as well as the aPTT can be used to control its anticoagulant effect. The FDA-approved dose is
a 0.75 mg/kg bolus followed by 1.75 mg/kg/h continuous infusion given for the duration of the procedure.41
Bivalirudin side effects include bleeding, back pain,
nausea, vomiting, hypotension, and headache.48

Argatroban is an FDA-approved medication for treatment of HIT. It is a univalent synthetic direct thrombin inhibitor derived from the l-arginine that binds
reversibly to the catalytic site of thrombin. It inhibits
free as well as clot-bound thrombin.41,49 Argatroban is
a reversible inhibitor with a half-life of 40 to 50 minutes. It is metabolized and excreted by hepatobiliary
mechanisms. The recommended dose is 2 g/kg/min
IV continuous infusion. The ACT as well as the aPTT

can be used to control its anticoagulant effect. There
is no antidote to argatroban.41,46,48
At our institution, for diagnostic angiograms or
neuroendovascular procedures, all patients who
have been diagnosed with HIT or if there is clinical
suspicion for HIT are treated with 1 to 2 g/kg/min
of IV argatroban infusion. No heparin is used intravenously or in the arterial pressurized infusion systems
in these cases (pressurized flush only with saline
infusion). The argatroban infusion is usually stopped
at the end of the procedure, and the arterial sheath
is removed immediately. We have not experienced
major hemorrhagic complications using this protocol.

Oral Anticoagulants
This class of drugs includes warfarin and other
vitamin K antagonists (e.g., acenocoumarol, phenprocoumon, fluindione). Their anticoagulant effect is
mediated through inhibition of the vitamin Kdependent gamma-carboxylation of coagulation factors II,
VII, IX, and X. However, they also have potentially
thrombogenic effects because they also inhibit the
vitamin Kdependent gamma-carboxylation of proteins C and S, which have anticoagulant properties
via their inhibition of activated factors VIII and V. The
anticoagulant effect of warfarin is delayed until the
normal clotting factors, especially prothrombin, are
cleared from the circulation. Thus heparin and warfarin treatment should overlap by 4 to 5 days when
warfarin is initiated in patients with thrombotic disease. Warfarin has a biological half-life of 36 to 42
hours. Oral anticoagulants require close monitoring
via prothrombin time (PT) and its international normalized ratio (INR) because they interact with a wide
range of medications and dietary factors and have
a narrow therapeutic window. The anticoagulation
effects of warfarin can be reversed within 12 to 24
hours after the administration of vitamin K. However,
cases of active hemorrhage or urgent reversal also
require aggressive use of fresh frozen plasma (1020
mL/kg) or inactivated prothrombin-complex concentrate (which contains factors II, VII, IX, and X) along
with close monitoring of coagulation parameters.

Thrombolytic Agents
Plasminogen Activators
These drugs act by converting the inactive proenzyme, plasminogen, into the active enzyme, plasmin. Plasmin digests fibrinogen, fibrin monomers,
and cross-linked fibrin (as found in a thrombus) into
fibrin degradation products. The plasminogen activators vary in stability, half-life, and fibrin selectivity.
The thrombolytics that have been reported for use

in stroke IAT include urokinase, alteplase, reteplase,

prourokinase (pro-UK), and streptokinase (SK).50,51
In general, the non-fibrin-selective drugs (e.g., UK
and SK) can result in systemic hypofibrinogenemia,
whereas the fibrin selective agents (e.g. rtPA and
r-pro-UK) are mostly active at the site of thrombosis.

First-Generation Agents
SK, a protein derived from group C -hemolytic
streptococci, has a half-life of 16 to 90 minutes and
low fibrin specificity. This drug proved to have a very
narrow therapeutic window and significant rates of
ICH and systemic hemorrhage52; thus it is no longer
used for stroke IAT. UK is a serine protease with a
plasma half-life of 14 minutes and low fibrin specificity. The UK dose used in cerebral IAT has ranged
from 0.02 to 2 106 units.50

Second-Generation Agents
Alteplase (rtPA) is a serine protease with a plasma halflife of 3.5 minutes and a high degree of fibrin affinity
and specificity. The rtPA dose used in cerebral IAT has
ranged between 20 and 60 mg.50 The theoretical disadvantages of alteplase include its relatively short half-life
and limited penetration into the clot matrix because
of strong binding with surface fibrin, which could
delay recanalization and increase the risk of recurrent
occlusion. Additionally, rt-PA appears to have some
neurotoxic properties, including activation of metalloproteinases, which may result in increased bloodbrain
barrier permeability, leading to cerebral hemorrhage
and edema, as well as amplification of calcium currents
through the NMDA receptor, leading to excitotoxicity
and neuronal death.39 Prourokinase (r-pro-UK) is the
proenzyme precursor of UK. It has a plasma half-life of
7 minutes and high fibrin specificity. Despite the favorable results of r-pro-UK in the PROACT I and II trials,54,55
the FDA did not approve its use in stroke IAT.

Third-Generation Agents
Reteplase is a structurally modified form of alteplase,
with a longer half-life (1518 min). In addition, it does
not bind as highly to fibrin; unbound reteplase can
theoretically thus better penetrate the clot and potentially improve in vivo fibrinolytic activity. Qureshi et al
have reported the use of low-dose IA reteplase (up to 4
units) in conjunction with mechanical thrombolysis.51
TIMI 2-3 recanalization was achieved in 16/19 patients,
with no sICHs. Tenecteplase is another modified form
of rt-PA with a longer half-life (17 min), greater fibrin
specificity, and greater resistance to PAI-1. Pilot clinical
trial data of IV tenecteplase in acute ischemic stroke
suggest the drug is safe and promising.56


50 Part II Perioperative Care

New-Generation Agents
Desmoteplase is a genetically engineered version of
the clot-dissolving factor found in the saliva of the
vampire bat (Desmodus rotundus). This drug is more
potent and more selective for fibrin-bound plasminogen than any other known plasminogen activator.
Unlike tPA, desmoteplase is not activated by fibrinogen or -amyloid proteins, factors that may exacerbate the risk for ICH. Moreover, desmoteplase inhibits
tPA-induced potentiation of excitotoxic injury. The
effect of IV administration of desmoteplase 3 to 9
hours after symptom onset in stroke patients who
present with mismatch on magnetic resonance imaging (MRI) or computed tomographic (CT) perfusion
was systematically investigated in the DIAS, DEDAS,
and DIAS-2 trials and has demonstrated a good safety
profile.5759 These studies were notable for their reliance on newer, advanced imaging algorithms to plan
IA therapy. A new trial (DIAS-3) is planned.
No direct comparison trials have been reported
between the different thrombolytic agents in acute
ischemic stroke. In a retrospective review of the
results for acute stroke IAT performed at our center,
we have found significantly higher rates of recanalization and good clinical outcome in the era in which
IA UK was used versus the era in which UK was not
available and IAT with rtPA was the primary treatment.60 Conversely, in another retrospective study,
Eckert et al found no major difference between the
recanalization rates of UK and rtPA.61

Alternatives to Plasminogen Activation:

Other Thrombolytics
Thrombolytics that are currently on the market are
plasminogen activators, making their successful use
reliant, at least in part, on the amount of plasminogen in the thrombus. New drugs that do not depend
on the availability of plasminogen are being evaluated for stroke therapy.

Direct Fibrinolytics
V10153 (Vernalis, Winnersh, UK) is a recombinant
variant of human plasminogen that has been genetically modified to be activated to plasmin by thrombin rather than by endogenous plasminogen activator
enzymes, such as tPA. Because thrombin activity is
primarily localized at the site of new thrombus formation, administration of V10153 results in selective production of plasmin at the site of a newly formed clot.
Consequently, thrombus dissolution may be achieved
without systemic plasmin generation, which should
result in a reduced risk of hemorrhage. The relatively
long plasma half-life (34 hours) of V10153 allows for
bolus administration, and persistence in the circula-

tion may help prevent early vascular reocclusion. The

V10153 Acute Stroke Thrombolysis Trial (VASTT) was
a phase 2, dose-escalation, multicenter study of IV
V10153 in stroke patients (NIHSS > 5 20; ASPECTS
5) within 3 to 9 hours after stroke onset. Preliminary
analysis has shown that out of the 40 patients enrolled
in the first three dose groups (1, 2.5, and 5 mg/kg) 16
(40%) achieved a mRS 2 at 90 days. The trial has been
halted because three of the nine patients in the 7.5
mg/kg group developed significant hemorrhagic complications. Further studies with a dose of 5 mg/kg are
Microplasmin (ThromboGenics NV, Heverlee, Belgium) is a truncated form of plasmin that is more
resistant to the effects of antiplasmin. In a rabbit
stroke model, IV microplasmin infusion resulted in
a high rate of clot lysis without increasing the rate of
ICH. In addition, there was significant improvement
in the behavioral rating scores, suggesting a neuroprotective effect.62 The Microplasmin In Treatment of
Ischemic strokeIntraVenous (MITI IV) trial, a phase
2, multicenter, randomized, double-blinded, placebocontrolled, ascending-dose clinical trial, evaluated
the safety and preliminary efficacy of IV microplasmin in 40 patients treated 4 to 12 hours after stroke
onset. There was no evidence of increased bleeding
risk with microplasmin. Reperfusion occurred in 25%
of patients treated with microplasmin versus 10% of
placebo-treated patients.
Alfimeprase (Nuvelo, Inc., San Carlos, CA) is a recombinant truncated form of fibrolase, a fibrinolytic zinc
metalloproteinase isolated from the venom of the southern copperhead snake. It degrades fibrin directly and
achieves thrombolysis independent of plasmin formation. Alfimeprase is rapidly inactivated by alpha-2 macroglobulin as it moves away from the site of delivery into
blood circulation. Thus its thrombolytic activity appears
to be localized to the site of delivery. These properties
should theoretically result in faster recanalization and
lower hemorrhagic conversion risk. The initial data on
the safety and efficacy of alfimeprase appeared promising,49 but subsequent phase 3 trials of the drug in peripheral arterial disease and catheter obstruction failed to
meet their primary and key secondary end points of
revascularization. A phase 2 multicenter, open-label,
dose-escalation study (CARNEROS-1) of alfimeprase
in the treatment of acute ischemic stroke within 3 to 9
hours of stroke onset is planned.

Defibrinogenating/Fibrinogenolytic Agents
Ancrod (Viprinex, Neurobiological Technologies,
Inc., Emeryville, CA) is the purified fraction of the
Malayan pit viper venom. It acts by directly cleaving
and inactivating fibrinogen and thus indirectly promoting anticoagulation. The reduction in the blood
levels of fibrinogen also leads to reduced blood viscosity, which may improve blood flow to the affected

areas of the brain. In addition, ancrod promotes an
indirect activation of the plasminogen-plasmin
pathway. In the Stroke Treatment with Ancrod Trial,
500 stroke patients presenting within 3 hours of
symptom onset were randomized to receive ancrod
(n = 248) or placebo (n = 252). Good outcome (Barthel Index 95100 at 3 months) was achieved in
42.21% and 34.4% of the patients, respectively (p =
0.04). There was no significant difference in mortality, but a trend toward more sICH with ancrod (5.2%
vs. 2%; p = 0.06).64 The ASP-II Trial is currently enrolling patients with an NIHSS score between 5 and 25
who present within 6 hours of stroke onset for treatment with ancrod or placebo.

Contrast Agents
Several different iodinated contrast agents have been
developed and are distributed by different manufacturers.65 They can be used almost anywhere in the
body, including the IV, IA, intrathecal, and intraabdominal routes of administration.66 All currently
available contrast agents consist of benzene ring
derivatives (benzene is the parent molecule) with
chemical modifications in the 2,4,6-tri-iodinated
benzene ring.65,66 The element used in contrast media
is the iodine. Because of the high atomic number of
iodine, photoelectric interactions dominate at all
diagnostic x-ray energies, providing high contrast
density compared with the adjacent soft tissues. It
also firmly binds to the benzene molecule and has low
toxicity.66 Contrast agents can be divided into ionic
and nonionic groups. Ionicity refers to the property
of a molecule to break up into positively and negatively charged particles, which increases the osmolality (number of molecules per kilogram of water).
Nonionic agents do not have this property and do
not require an accompanying cation. Therefore, the
nonionic agents are low osmolality.65,66 Nowadays,
most, if not all, of the contrast agents used for neuroangiography and neurointerventional procedures
are nonionic. Examples of nonionic low-osmolarity
agents include iopamidol (Isovue, Bracco Diagnostics, Princeton, NJ), iohexol (Omnipaque, GE Healthcare, Princeton, NJ), ioversol (Optiray, Mallinckrodt,
Hazelwood, MO), and iopromide (Ultravist, Bayer
Vital, Leverkusen, Germany). The content of iodine
in the contrast media formulation is written in the
label for nonionic agents (p.ex. Isovue-370 has 370
mgI/mL of solution; Ominipaque-300 has 300 mgI/
mL of solution). For most nonionic agents, the osmolality depends on the concentration. It varies from
670 mOsm/kg H2O with Omnipaque-300 to 884
mOsm/kg H2O with Omnipaque-350).65,66 Recently,
a new nonionic contrast agent has been introduced.
Iodixanol (Visipaque, GE Healthcare, Princeton,
NJ) is a nonionic dimeric contrast agent that is iso-

osmolar to blood (Visipaque-320 has 320 mgI/mL of

solution with osmolality of 290 mOsm/kg H2O).65,66
After administration, the contrast agent is distributed through rapid exchange between plasma and
extracellular space; contrast agents do not cross an
intact bloodbrain barrier. They are excreted by glomerular filtration with no significant tubular excretion or reabsorption in the tubules; hepatic excretion
increases in renal failure.65,67
Adverse reactions can happen during or after
the administration of any pharmaceutical, including contrast agents. It is very important that anyone
performing contrast studies (p.ex. neuroangiography and neurointerventional procedures) be familiar
with the possible adverse reactions, which include
anaphylactoid and physiochemotoxic reactions,
and their management. It is beyond the intent of
this chapter to provide a detailed discussion of the
reactions and their management. Anaphylactoid
reactions could be mild (hives, itching, nausea),
moderate (facial/laryngeal edema, bronchospasm,
dyspnea, tachy- or bradycardia), or severe (severe
bronchospasm, severe laryngeal edema, arrhythmias, hypotension, pulmonary edema, death) and
usually require urgent/emergent treatment.66 It is
worth mentioning contrast-induced nephropathy
(CIN). With the increased number of procedures
performed that require administration of contrast
media, CIN has become one of the leading causes
of hospital-acquired acute renal failure.68 CIN is an
exclusion diagnosis defined as an acute decline of
renal function (relative rise in serum creatinine > 25%
or an absolute increase of 0.5 mg/dL from baseline)
after administration of iodinated contrast.69 Direct
toxicity to tubular cells and renal medullary ischemia seem to be the main mechanisms of renal toxicity, with a generally accepted idea that osmolality
of the agent is directly related to its potential nephrotoxicity.69 Risk factors for CIN include advanced
age, diabetes, preexisting renal dysfunction, studies/
procedures that require a large volume of contrast,
and concomitant use of other medications that could
potentialize renal problems.68 Several studies have
been performed comparing ionic or nonionic lowosmolality agents to iodixanol, which is iso-osmolar.
A recent prospective, controlled, randomized, double-blind study compared the cardiorenal safety of
iodixanol (nonionic iso-osmolar) to iopromide (nonionic low-osmolality) in patients with chronic kidney disease. The results showed that iodixanol was
associated with lower CIN compared with iopromide
in this population.70 In January 2009, Heinrich and
colleagues published a meta-analysis of randomized
controlled trials that compared nephrotoxicity of
iso-osmolar iodixanol to nonionic low-osmolar contrast agents.71 The authors concluded that, in patients
with intra-arterial administration of contrast and
renal insufficiency, iodixanol was associated with
reduced risk of CIN compared with iohexol (nonionic


52 Part II Perioperative Care

low-osmolar agent).71 At our institution, we reserve
the use of iodixanol for patients with chronic renal
disease, patients at risk for CIN, or cases that may
require a large volume of contrast. Renal protective
measures are also employed in these patients (acetylcysteine, intravenous sodium bicarbonate pre- and

Protamine sulfate should be available whenever
heparin is being administered (1 mg/100 units
heparin) accounting for time interval between
administration of heparin and the use of protamine sulfate.
1-Deamino-8-d-arginine vasopressin (20 g/kg)
and platelet transfusion may be useful in reversing the actions of antiplatelet agents.

Careful monitoring of the patients airway with
appropriate airway assessment is mandatory
when administering conscious sedation.
Monitor ACT relative to the preprocedural
baseline to avoid dangerous levels of anticoagulation during the procedure.
Monitor antiplatelet assays to ascertain adequate platelet inhibition prior to beginning procedures requiring the use of antiplatelet agents.

It is important to include analgesic agents when
using sedation during procedures because this
results in a synergistic effect to the patient.
Midazolam and fentanyl are a common sedative/
analgesic combination that achieves this goal.
Appropriate training and credentialing are
necessary to perform conscious sedation.
As antiplatelet agents and antithrombotic
agents come into more common use during
neurointerventional procedures, it is important
to understand their respective mechanisms of
action and anticipate potential complications.
Though routinely used, heparin must be administered with care and careful attention to
its potential complications.
Contrast-induced nephropathy is one of the leading causes of hospital-acquired acute renal failure.

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54 Part II Perioperative Care

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Intensive Care Management

Nazli Janjua and Elia Haddad

The periprocedural management of patients undergoing neurointerventional procedures in the intensive care unit (ICU) is a key component of their
outcome, particularly in acute, emergent cases. The
field of neurocritical care (NCC) has also been developing in parallel with advances in endovascular
surgical neuroradiology (ESNR), and the interplay
between these two specialties has had an enormous
impact on cerebrovascular disease. Care of patients
in the ICU can be approached from a general sense,
encompassing aspects of critical care management
that are uniform across many disease subtypes, as
well as those strategies that are focused on specific
disease states.

World Federation of Neurological Surgeons grading scale,4 commonly used to describe the condition
of patients with subarachnoid hemorrhage (SAH),
should be recorded at initial presentation in these
patients; subsequent scores may serve as objective
comparisons to detect neurological worsening (or
improvement). Should it prove infeasible for a busy
NCCU to perform a detailed neurological scale on a
frequent basis, documentation of level of consciousness, motor function, and pupillary size should be
noted on a frequent basis. The last, being less affected
by sedation,5 is of particular importance in indicating
the development of mass lesions and herniation syndromes that may occur with malignant hemispheric
infarction or intracranial hemorrhage (ICH).

General Considerations

Sedation Management

of Neurocritical Care

Bedside Clinical Neurological Evaluation

Ongoing, bedside clinical neurological examination,
along with recording and management of intracranial pressure (ICP) and its alterations, are the two
defining features of a neurocritical care unit (NCCU).
Abnormality discovered in the neurological
examination may be the first indicator of neurological dysfunction, leading to further diagnostic testing
and specific remedy. Several bedside tests can be
quickly mastered by ancillary staff and recorded in
nursing flow records (Table 8.1). The Glasgow Coma
Scale (GCS)1 ranges in score from 3 to 15, with 1 to
4, 1 to 5, or 1 to 6 points allotted for eye opening,
verbal response, and motor response. The National
Institutes of Health Stroke Scale2 ranges from 0 to 42
points (higher scores indicating greater abnormality)
based on scores for level of consciousness, language,
motor, sensory, and other signs. These scales have
high interrater reliability and are easily quantifiable
measures of changes in the neurological examination. The grading system of Hunt and Hess3 or the

Continuous, intravenous (IV) sedation, commonly

used in the ICU to eliminate ventilator-associated
discomfort and agitation, has the detrimental effect
of depressing consciousness, thereby masking the
neurological examination. To enable clinical assessments, sedation should be lifted at a minimum daily,
unless the clinical situation precludes it (e.g., ventilatory distress). Apart from the obvious benefit of
permitting evaluation of neurological function, daily
interruption of sedation has been shown to reduce
the length of stay in ICUs and decrease the time of
endotracheal intubation for patients on mechanical
ventilator support.6
Agents commonly used for sedation in the NCCU
include propofol (Diprivan, AstraZeneca Pharmaceuticals LP, Wilmington, DE), a lipid-soluble agent with
unknown mechanism of action, possibly dependent
on -aminobutyric acid (GABA) receptor potentiation;
fentanyl, a potent opioid analgesic; and midazolam
(Versed, Roche Pharmaceuticals, Hertfordshire, UK),
a benzodiazepine, all of which are primarily metabolized in the liver. Among these agents, fentanyl may
have less effect on blood pressure.7 These agents, particularly propofol, are attractive options in the intensive care setting because of their rapid onsets and short


56 Part II Perioperative Care

Table 8.1 Clinical scales used in the NCCU

3 Visual fields

0 No visual loss
1 Partial hemianopsia

Coma Scale

Range 115; 15 best


1 No movement
2 Decerebrate (extensor) posturing

2 Complete hemianopsia
3 Bilateral hemianopsia
4 Facial paresis

0 Normal movement

3 Decorticate (flexor) posturing

1 Minor paresis

4 Withdrawal to pain

2 Partial paresis

5 Localizing to pain
6 Spontaneous movement/following commands

3 Complete palsy
58 Right/left arm/
leg motor

1 No response

3 No effort versus gravity

3 Nonsensical speech

4 No movement

4 Disoriented speech

1 No eye opening

X Untestable
9 Limb ataxia

0 Absent
1 Present in 1 limb

2 Eye opening to pain

2 Present in 2 or more limbs

3 Eye opening to voice

4 Eye opening spontaneously

1 Drift
2 Some effort versus gravity

2 Unintelligible speech

5 Oriented, normal speech

0 No drift

X Untestable
10 Sensory

0 Normal

Hunt-Hess Scale
for SAH

Range 05; 0 best, 1 best in


Grade 0

Incidental (unruptured aneurysm)

Grade I

Mild headache

Grade II

Severe headache or cranial nerve


Grade III

Alteration of consciousness,

Grade IV


1 Mild-to-moderate dysarthria

Grade V


2 Unintelligible or rose


Range 042; 0 best

1a Level of
consciousness (LOC)

0 Alert

3 Comatose
0 Answers both correctly
1 Answers one question correctly
2 Answers neither question correctly
1c LOC commands

0 Obeys both correctly

1 Obeys one correctly
2 Both incorrect

2 Best gaze

2 Dense loss
11 Best language

0 Normal
1 Partial gaze palsy
2 Forced deviation

0 No aphasia
1 Mild-to-moderate aphasia
2 Severe aphasia
3 Mute

12 Dysarthria

0 Normal articulation

X Untestable
13 Neglect/

0 No neglect
1 Partial neglect

1 Drowsy
2 Stuporous

1b LOC questions

1 Partial loss

2 Complete neglect

World Federation of Neurological Surgeons Grading

Scale for SAH; 1 best
GCS score

Motor symptoms









Present or absent


Present or absent

Abbreviations: NIHSSS, National Institutes of Health Stroke

Scale score (see text); SAH, subarachnoid hemorrhage.

8 Intensive Care Management

durations of action, but in the practical setting, against
the backdrop of an injured brain, they may impair
neurological performance for hours.8 Impairment of
consciousness may be of additional concern when
patients are being weaned from ventilatory support.
A new central 2-agonist, dexmedetomidine (Precedex, Hospira, Inc., Lake Forest, IL) has indication for the
weaning period where liberation from the ventilator is anticipated within 24 hours, and it has shown
promise in the NCCU setting as a sedative that may
potentially decrease medication-related neurological dysfunction and shorten ventilator periods.9 It has
shown promise in many NCCUs in combating agitation
associated with intoxication or withdrawal states (e.g.,
alcohol) and other neurological diseases, which may
cause sympathetic surges. The major adverse reaction
to dexmedetomidine is profound hypotension, often
undesirable in NCCU patients. Furthermore, because it
has no analgesic properties, it cannot be used solely in
patients in whom postoperative discomfort is a major
concern. However, concomitant use may result in
lower doses of analgesics, which can potentially allow
more accurate neurological testing.

Ventilatory Support
Though major expositions on ventilator management may be found in other textbooks and are outside the scope of this chapter, certain points relevant
to the NCCU are discussed here.
The typical NCCU patient will not be suffering
from extensive pulmonary pathology, and as such,
the general indication for mechanical ventilation is
maintenance of ventilatory effort and prevention
of aspiration when consciousness is impaired. This
fact may be less obvious to physicians outside the
scope of neurosciences, who may focus primarily on
oxygenation. Oxygenation is an important parameter and should be attended to, with an oxygen
saturation goal of 95%. In addition, exhaled carbon
dioxide (CO2) should be monitored in patients with
alterations of consciousness, who are at greater risk
for CO2 narcosis than hypoxia. In intubated patients,
continuous CO2 monitoring can be a useful adjunct to
address patient readiness for extubation. Additionally, because hyperventilation can be a life-saving
measure to treat abrupt elevations in intracranial
pressure (ICP) and reverse acute herniation, online
CO2 readings can prove essential. Care should be
given to avoid overhyperventilation and respiratory
alkalosis on a long-term basis because this induces
vasoconstriction and may cause ischemia and seizures. A goal for partial pressure of arterial CO2
(Paco2) in the NCCU typically ranges from 30 to 40
mm Hg, and the goal for partial pressure of arterial
oxygen (Pao2) is 90 to 100 mm Hg.
Many medical intensivists may attempt to minimize positive end-expiratory pressure (PEEP) in
order to avoid increases in ICP (which may result

with increased intrathoracic pressure impairing

venous return). However, in most circumstances,
physiological PEEP of 5 to 8 mm Hg does not affect
ICP and may actually be beneficial.10 Increasing PEEP
may be necessary in patients with superimposed
lung pathology and should be individualized in the
context of other physiological parameters. Although
all patients in the NCCU with depressed cardiac function are at risk for the development of pulmonary
edema (particularly with the hypervolemic strategies often used to augment cerebral perfusion), certain disease conditions induce additional pulmonary
pathology, such as SAH, which can lead to neurogenic pulmonary edema, in the absence of cardiac
dysfunction.11,12 Diagnosis is established by chest
X-ray showing pulmonary edema with lower than
expected central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) readings than
would be found with cardiac causes of pulmonary
edema. Treatment includes diuresis and supplemental oxygenation and ventilatory support.
Liberation from the ventilator should be attempted
only when gas exchange is deemed to be adequate
for physiological homeostasis and there is no evidence of excess mechanical respiratory effort, which
can be easily estimated by the rapid shallow breathing index. The ratio13 of respiratory rate (RR) to tidal
volume (TV) in liters can be easily noted, and if
> 100 it should preclude extubation, whereas if < 40,
it predicts a reasonable chance of successful extubation. Apart from this, an adequate level of consciousness prior to extubation is paramount in the NCCU
patient.14 This must be assessed while taking into
consideration all other focal neurological injury that
may be present. For instance, a patient with dominant
hemispheric pathology may be awake, though aphasic,
and in this circumstance may be unable to follow commands but may be capable of generating a spontaneous respiratory drive. Therefore, the benchmark used
to assess the patients neurological readiness for extubation should be appropriate to the disease condition.
Examination of the gag reflex and cough response is
also important because these are key mechanisms for
preventing microaspiration postextubation.
Other useful bedside adjuncts for maintaining pulmonary toilet are bedside chest physiotherapy, deep
orotracheal suctioning, and incentive spirometry,
which can prevent atelectasis. Early efforts to mobilize
patients out of bed to a chair also helps to improve spontaneous lung recruitment and minimize atelectasis.

Blood Pressure Control

The tight regulation of blood pressure (BP) within
a desired range is part and parcel of NCCU care and
closely correlated with monitoring of the ICP. Perhaps
this area of critical care management, more than any
other, generates much controversy between the medical intensivist and the neurointensivist. Whereas it is


58 Part II Perioperative Care

not uncommon in the NCCU to see systolic BP of 200
mm Hg as acceptable and in fact intended in a postcoiling SAH patient, the goal BP is diametrically opposed
in managing this same condition, with an unsecured
ruptured aneurysm.
The ideal agent for BP reduction and control is
one that is rapidly titratable in the event that sudden change in neurological status warrants sudden
hemodynamic intervention. Beta-blockers like labetolol offer cardiac protection, which is an added benefit in a patient soon to undergo general anesthesia
for endovascular treatment, but care should be taken
in those with increased ICP who may demonstrate
Cushing phenomena and bradycardia. Similarly, calcium channel blockers, such as nicardipine, which
are also well titrated, may adversely affect heart rate.
These agents are of further concern in SAH patients
receiving nimodipine because the combination of
agents may compound depression of nodal conduction. Hydralazine and angiotensin-converting
enzyme inhibitors like enalapril may be administered IV and do not exert these effects on heart rate,
though hydralazine is not available as a continuous
infusion. Nitroglycerin and nitroprusside, both powerful antihypertensives commonly used in coronary
care unit settings where dramatic BP reductions are
desirable, are nonspecific vasodilators, causing venodilation as well, which may potentially increase ICP.
Induced hypertension may be needed in any case
of shock or pathological hypotension and in other
circumstances where increasing cerebral perfusion
pressure (CPP) is needed, such as during vasospasm
following SAH (see later discussion). Phenylephrine,
a direct arterial constrictor, is generally used as firstline therapy for this purpose in the NCCU, though it
may cause reflex bradycardia, which again may be
of concern in a patient exhibiting Cushing-related
bradycardia. Norepinephrine (levophed), a beta- and
alpha-agonist, and dopamine, a dopamine receptor
agonist, are also commonly used to raise blood pressure. At least daily assays of cardiac enzymes and
electrocardiograms should be obtained in patients
undergoing therapeutic, induced hypertension.

Fluid-Electrolyte Management
and Alimentation
Management of fluid balance and electrolyte homeostasis largely follow parameters that would be seen
in any other ICU setting, with the caveat that in certain disease conditions hypermagnesemia may be
therapeutic (see discussion of SAH later in the chapter). Alimentation should be started as early as possible and may require nasogastric tube placement in
patients for whom an oral diet is unsafe. Swallowing
of 30 mL of thin liquid without subsequent coughing
or abnormal phonation of vowels is a reliable indicator of patients abilities to swallow orally.15,16 In all
patients, aspiration precautions should be consid-

ered when appropriate, with additional maneuvers

as needed to prevent aspiration, such as elevation of
the head of bed to 30 degrees or more during feeding, the use of dietary thickening agents, and assistance and observation during feeding. Proton-pump
inhibitors and H2 receptor blockers are important in
the NCCU patient population to prevent the development of Cushing ulcers.17
For patients deemed unsafe for long-term oral
feeding, in whom gastrostomy tube placement is
needed, and who also may require ventriculoperitoneal shunting (VPS), the optimal timing of each
procedure should be discussed with all involved

Prevention of Deep Venous Thrombosis

Another subject of debate in the NCCU is appropriate timing for therapy to prevent venous thromboembolism in immobile patients with ICH. Many
patients, who present acutely with ruptured aneurysms to be urgently secured within the next 24 to
48 hours, can be safely managed with lower-extremity pneumatic compression devices until such time
as aneurysm repair is achieved.18 For patients status
postaneurysm coil embolization, or in whom delay
in embolization may be necessary for other reasons,
subcutaneous (SQ) heparin should be considered by
48 hours. Even in patients with ICH, institution of SQ
heparin 48 hours after the ictus has not been associated with hematoma enlargement or rebleeding.18

Hemoglobin, Hematocrit, and Anemia

Whereas hemodilution had previously been considered a mainstay of management of SAH-induced
vasospasm, it now has been abandoned. However,
decreasing blood hemoglobin levels and hematocrit
are byproducts of prolonged hospitalization, particularly in the ICU setting, where frequent phlebotomy
and aggressive IV hydration are common. As in the
case of cardiac disease, for the vast majority of NCCU
patients, maintenance of circulating hemoglobin over
10 to 11 gm/dL may improve outcome in certain conditions.19 Further management of erythrocyte count
according to disease-specific therapies is discussed
later in the chapter.

Management of Access
Site Complications and
Retroperitoneal Hemorrhage
Vigilance against the development of groin hematoma
and retroperitoneal hemorrhage (RPH) is of utmost
importance in the care of any patient who has undergone endovascular treatment. This becomes of potentially greater consequence in patients on multiple

8 Intensive Care Management

anticoagulants or antiplatelet agents such as aspirin
and clopidogrel, who may also receive large doses of
intraprocedural heparin or systemic local intra-arterial (IA) thrombolytics.20 Careful marking of any access
site swelling immediately after compression should be
done immediately so that any subsequent enlargement
can be readily detected and managed. Femoral compression devices, such as the Femo Stop (Radi Medical Systems AB, Uppsala, Sweden), may be of some use
to limit hematoma expansion, but they should not be
used at the expense of more definitive interventions,
which may be needed to secure hemostasis. In very
thin patients or older patients with loosely adherent
dermal and SQ adipose and muscular layers, dangerously deceptive amounts of bleeding into the medial
compartment of the thigh, posterior flank, and inguinal area can occur before being visibly noted.20 Access
sites should be monitored every 15 to 30 minutes for
the first 1 to 4 hours following the procedure, then at
least hourly for the next few hours and then per nursing shift until stability is ensured. Refractory and severe
hypotension with or without groin hematoma should
prompt consideration of RPH, which should immediately be supported with vasopressors like phenylephrine, urgently investigated with noncontrast computed
tomography (CT) of the abdomen/pelvis, and treated
with manual compression until (surgical) vascular
hemostasis is achieved. In emergency/unstable situations, unfractionated heparin (UH) should be reversed
with protamine sulfate (1 mg for every 100 U heparin administered, with decreasing dose requirements
with prolonged intervals from the last UH dose),21 and
cryoprecipitate may be given to overcome the fibrinolytic effects of thrombolytics.22 Alternate agents that
may have some utility as antidotes to thrombolytics
include epsilon aminocaproic acid (Amicar, Hospira,
Inc., Lake Forest, IL) and activated factor VIIa.23
Apart from access site bleeding, inadvertent vascular injury causing arterial occlusion should also
be monitored. Pedal pulse check for femoral artery
access either manually or with handheld Doppler,
and bilateral comparative continuous pulse oximetry and radial pulse check for radiobrachial access
should be assessed along with the access site. Should
pulse discrepancy, decreased digital capillary refill,
or cold extremity develop, urgent vascular surgery
consult should be obtained. Repeat angiography may
also be necessary to demonstrate the exact site of
injury prior to surgical correction.

Fever Control
Fever is known to impact outcome in NCCU patients
and should be prevented and investigated when it
occurs. Pan-culture to rule out infection and inspection for truncal rashes to indicate drug-related allergy
should be performed in febrile patients. Empirical
antibiotics to cover skin contaminants in patients
with external ventricular drains (EVDs) and central

lines should be considered, and broad-spectrum antibiotics for patients at risk for ventilator-associated
pneumonia should be offered until microbial-specific
therapy can be instituted based on culture results.
Often, no source of fever can be found, and fever may
be assumed to be secondary to a central cause or a
systemic inflammatory response. Acetaminophen 650
mg every 4 hours should be administered as needed,
or even on a standing basis in persistently febrile
patients. Surface cooling blankets can be used for
refractory fevers. Commercial cooling blankets, such
as the Arctic Sun (Medivance, Inc., Louisville, CO), with
internal feedback mechanisms for tighter temperature
regulation have been studied in the NCCU.24 If cooling
blankets are used, care should be taken to avoid distal
ischemia in patients also receiving vasoconstrictors.
Skin should be carefully inspected every 1 to 4 hours
for the presence of breakdown or ulceration.

Contrast Allergy
Allergic reaction to contrast media may develop
postprocedurally in the ICU. Diffuse truncal rash,
urticaria, and in severe cases anaphylaxis may
develop in such instances. Methylprednisolone
(MP) 32 to 125 mg IV and diphenhydramine 25 to
100 mg IV, to be repeated every 6 hours for at least
24 hours, should be acutely administered to halt
inflammatory phenomena. If anaphylaxis results
in respiratory compromise, emergent endotracheal
intubation should be performed. Preoperatively, the
risk of contrast-related allergic reaction and complications can be minimized by querying patients about
prior history of contrast-related allergy (and history
of any prior contrast exposure), allergy to iodine or
shellfish, or severe allergic asthma. A positive history may be managed with preprocedural steroid
administration (if the procedure is not emergent) 24
hours in advance. If advance dosing is not possible,
MP as dosed for acute documentation of allergy can
be given at the time of contrast administration.25 H2
blockers given prior to procedure commencement
may also inhibit the allergic response.

Contrast-Induced Nephropathy
Iodinated contrast media carry the potential risk of
contrast-induced nephropathy (CIN).26 The use of isoosmolar contrast medium27 (rather than low osmolar
contrast) and preprocedural IV hydration28 may limit
the occurrence of CIN, particularly in patients with
diabetes. IV sodium bicarbonate administration29
and N-acetylcysteine30 (NAA, 600 mg by mouth twice
daily) at least 24 hours in advance of contrast administration may be of additional value, though the
data provide mixed support for these therapies.31 IV
hydration with isotonic fluids may also confer equal
benefit to sodium bicarbonate.


60 Part II Perioperative Care

Disease-Specific Therapy
Intracranial Hypertension
Management of elevated ICP focuses on reduction
of expendable cranial contents (e.g., cerebrospinal
fluid, interstitial fluid, and venous volume), suppression of neural activity, and direct therapy for the
cause of intracranial hypertension. Osmotic diuretics like mannitol and hypertonic saline cause water
to shift from the intracellular to the interstitial compartment and across the bloodbrain barrier.32,33
Hyperventilation leads to vasoconstriction, thereby
reducing vascular volume. This is mainly a temporizing solution for acute ICP crisis. Long-term effectiveness of this therapy is limited by subsequent
refractoriness and potential ischemic complications
with excess vasoconstriction. Many patients, particularly those with SAH, may have EVDs in place. Lowering passive drainage levels of EVD collection bags
may quickly and effectively lower plateau pressures.
However, caution is needed in patients awaiting
aneurysm repair because sudden changes in transmural pressure may promote aneurysm rerupture.
If no other surgical option exists, such as hematoma evacuation, or ICP elevation is global rather
than focal, sedation with propofol or barbiturates
can suppress neural and brain metabolic activity,
thereby reducing ICP.33,34 The effects of these agents,
particularly barbiturates, are typically titrated to
electrophysiological (EEG) activity, but even without
this, ICP can rapidly decrease in most circumstances.
Mild induced hypothermia (MIH), which is gaining some attention for its possible neuroprotective
effects, also acts by the same mechanism.3537 Complications of barbiturate therapy and MIH include
hypotension, shock, coagulopathy, and promotion of

sepsis. Patients receiving these therapies should be

monitored with invasive arterial pressure and central venous pressure monitoring and in some cases
even pulmonary artery pressure monitoring. A stepwise approach to the treatment of elevated ICP is
shown in Table 8.2.

Ruptured Aneurysms/Subarachnoid
Aneurysmal SAH is one of the prototypical NCCU
diseases, for which therapeutic protocols are legion.
Knowledge of the consequences of SAH and protocols of care should be mastered by anyone taking
care of these patients in an ICU setting. They are
discussed here as they pertain to the immediate
periprocedural care of patients undergoing endovascular treatment.
As stated earlier, control of blood pressure is
initially very strict prior to aneurysm embolization in the acute setting. Continuous invasive arterial pressure monitoring is a must. Sudden blood
pressure spikes may indicate rerupture and should
be urgently investigated. In these circumstances,
the goal, as always, is early aneurysm repair and
other supportive care. This may include control of
increased ICP with cerebrospinal fluid (CSF) diversionary techniques (e.g., EVD placement). Care
should be taken to avoid aggressive CSF removal
prior to aneurysm repair because sudden changes
in transmural pressure may precipitate rerupture.
The presence of hydrocephalus and/or alteration of
consciousness, as may be seen in Hunt-Hess grade III
SAH patients, may necessitate emergent EVD placement. Otherwise, placement may be avoided unless
specifically clinically indicated. Some interventionalists advocate prophylactically placing EVDs prior to

Table 8.2 Stepwise approach to elevated ICP


Dose/titration effect


Goal reversal of syndrome (e.g., reversal of pupillary dilatation), or titrate directly to ICP < 20
mm Hg, or titrate to CO2 3035 mm Hg

Osmolar therapy
Hypertonic saline

Initial dose 1 g/kg followed by 0.251 g/kg every 6 hours. Titrate to serum osmolality of
310320 mOsm.
Initial dose of 23.4%, 30 mL volume followed by infusions of 3% sodium chloride or sodium
acetate at rates of 50150 mL/h. Titrate to serum sodium of 150160 mEq/mL


Propofol or pentobarbital, titrate to ICP < 20 mm Hg or to electrical burst suppression

pattern of 2 bursts per minute

CSF diversion

Ventriculostomy passive drainage acutely below tragus to facilitate rapid removal of 510 mL
CSF. Subsequent drainage level 010 cm H2O as needed depending on initial response and
other therapies


Goal target temperature 3234 C

Surgical decompression

Definitive reversal/removal of cause of increased ICP

Abbreviations: CO2, carbon dioxide; CSF, cerebrospinal fluid; ICP, intracranial pressure.

8 Intensive Care Management

aneurysm coil embolization in the event that intraprocedural rupture ensues. However, given the relatively low rate of intraprocedural rupture in all cases
of aneurysms treated via the endovascular approach,
we cannot routinely recommend this for all patients.
Should an EVD be noted to be in suboptimal position requiring retraction or readvancement, if at all
possible, manipulation should be withheld until the
postprocedural period when any intraprocedural
heparin is likely to have been metabolized.
After aneurysm repair, liberalization of previously
restrictive blood pressure parameters is advised. Blood
pressure may often normalize in this time period, particularly in patients who have EVDs in place and have
decreasing ICP. Sudden BP spikes should prompt consideration of aneurysm rerupture or the development
of vasospasm or other neurological catastrophe. Head
CT should be obtained in cases of suspected vasospasm to assess for the presence of cerebral infarction,
which may impact intraprocedural anticoagulation
that may otherwise be used. Management of vasospasm is discussed further in the chapters on aneurysm and SAH. Other concerns about the SAH patient
in the ICU setting include the development of neurogenic cardiac dysfunction and hyponatremia.

Unruptured Aneurysms
The treatment of unruptured aneurysms is far less
complicated than the management of an acutely ruptured aneurysm. Nonetheless, overnight monitoring
in a critical care or stepdown level nursing environment is essential for the detection of any subsequent
neurological impairment. For the most part, thromboembolic complications or aneurysm rupture will be
recognized and dealt with intraprocedurally. Should
either event occur, then expectant postoperative management in the ICU setting will be required. Antiplatelet medications may be administered for patients with
recognized coil extrusion in the parent vessel or other
pericoil thrombotic phenomena. For patients in whom
intraprocedural rupture occurs, management should
follow that of a spontaneously ruptured aneurysm.

Ischemic Stroke/Postthrombolysis or
Postthrombectomy Patients
Just as with SAH, the literature abounds on the care
of acute ischemic stroke (AIS) patients. Management
centers on the prevention of reperfusion hemorrhage, maintenance of cerebral perfusion, management of cerebral edema and herniation, and other
supportive care.
Though no clear guidelines exist for the postthrombolysis management of patients solely receiving
intra-arterial (IA) thrombolytics, in the major trials
evaluating thrombolytics for middle cerebral artery
strokes as well as those for thrombectomy devices,

guidelines for therapy generally followed those used

for management of patients having received IV tissue
plasminogen activator (tPA).3840 According to the clinical guidelines studied, BP maintained at 180/105
mm Hg and normoglycemia are important factors in
preventing postthrombolytic ICH.41 Once again, extra
attention should be paid to the access site because
these patients, in addition to receiving blood thinners, may also have had arterial access with very large
sheaths, up to 8 or 9 French, to allow the use of various
thrombectomy device guiding catheters.
Neurological monitoring cannot be overemphasized in the postoperative period, and any change
in status warrants urgent cranial imaging to assess
for bleeding or herniation from completed infarction
and infarct-related edema.

Arteriovenous Malformations
Ruptured arteriovenous malformations (AVMs) may
present with ICH or SAH. If the latter, then care
should be followed as for aneurysmal SAH. Parenchymal hemorrhage may result in intracranial hypertension, which should be dealt with as already outlined.
All AVMs, postembolization, both ruptured and
unruptured, are at risk for perfusion pressure breakthrough hemorrhage, which may occur when a previously underperfused brain is suddenly faced with
rerouted blood flow after significant nidal flow has
been reduced.42,43 In this case, the onset is far more
insidious than that seen with thrombolytic-related
hemorrhage in AIS, and in some instances may occur
more than 24 to 48 hours after embolization. As such,
periods of postoperative ICU monitoring may be longer
than that for unruptured aneurysms, depending on the
size of the AVM and the degree of embolization performed. BP is often more tightly controlled following
AVM embolization than with aneurysm embolization.
Seizures may occur with AVMs prior to or following
embolization. Patients who have known seizure disorders should be maintained on their anticonvulsants at
doses adequate to achieve therapeutic levels. In those
not known to have seizures, intraprocedural and periprocedural anticonvulsants may be considered.

Extracranial Carotid Disease/

PostCarotid Stent Placement
Patients undergoing internal carotid artery (ICA) origin stent placement are at high risk for intra- and postprocedural hypotension and bradycardia. Because of
the stimulation of the carotid sinus and its effect on
lowering heart rate, dopamine, which stimulates beta
receptors to increase heart rate, as well as dopamine
receptors, may be the preferred vasopressor in this
case. A low threshold for blood transfusion should
be applied in these patients because, once again, the
large sheath sizes used may engender greater blood


62 Part II Perioperative Care

loss with catheter and device exchange during the
angiographic procedure. Often (as with all endovascular cases), a combination of fluid resuscitation
and hemodilution secondary to contrast may falsely
lower circulating hematocrit levels. However, the
suspicion and treatment should be for a truly anemic
state, and maintenance of adequate hemoglobin levels is important. Early mobilization of patients out of
bed to a chair, including in cases where the femoral
sheath is to be removed when coagulation parameters normalize, will further stimulate increases in BP.
These patients are usually on at least two antiplatelet agents; therefore, as with the care of AIS
patients in the postangiography ICU suite, attention
to the access site is crucial.

Epistaxis/Head and Neck

Tumoral Hemorrhage
Acute hemorrhage prior to the endovascular procedure in patients suffering from epistaxis or head
and neck cancer is likely to have already led to blood
transfusion and BP support with crystalloids and
blood transfusion. Continued assay of hemoglobin
and hematocrit is required after the procedure for at
least the first 24 hours. If the hemostatic packing is
not removed after the initial embolization procedure,
this should be done as soon as possible thereafter, ideally while the patient is still in the ICU. In some cases,
ear, nose, and throat doctors will seek to remove the
packing while the patient is still intubated, so that
if rehemorrhage occurs and repacking is required,
sedation can be used to alleviate discomfort.
As with the subtle development of hemorrhage that
may occur with AVM embolizations, ischemic changes
may also subtly manifest themselves in the postprocedural period. Because this complication develops
from disruption of collateral and accessory rather than
direct cerebral pathways, they may not be so readily
recognized during the procedure. Crystalloids to augment cerebral flow through indirect routes should
be liberally given if ischemia is suspected. The role
of antiplatelet agents is minimal in this circumstance
because the ischemia is due to permanent or nonpermanent embolic agents (e.g., polyvinyl alcohol) rather
than an intrinsic platelet plug. However, there may be
some putative benefit of aspirin and similar agents to
circumvent superimposed spontaneous thrombosis,
which may be accelerated after iatrogenic thrombosis.
Visual acuity and pupillary reactivity should be
included in bedside clinical assessments because,
with extracranial head and neck embolization, the
orbit is more at risk for ischemic complications than
the brain.
Antibiotics may be needed in selected patients
with posterior nasal packing, to prevent sinus colonization. Penicillins or first-generation cephalosporins
with anaerobic coverage are the drugs of choice.44

Neuroendovascular patients require frequent
neurological evaluations. Therefore, patients
requiring ventilator support should have sedation held periodically through the day to allow
for appropriate neurological assessment.
Respiratory rate to tidal volume ratio < 40 in the
presence of an adequate level of consciousness
predicts a high likelihood of successful extubation.
Patients undergoing therapeutic induced hypertension should have daily cardiac enzyme
Intracranial pressure control and control of cerebral perfusion pressure are critical in caring
for the neurocritical care patient.

Adequate prehydration and the use of iso-osmolar contrast media as opposed to low-osmolar
contrast media for angiography will reduce the
rate of contrast-induced nephropathy.
The use of sodium bicarbonate and N-acetylcysteine given 24 hours prior to angiography
may significantly reduce the incidence of
contrast-induced nephropathy.
Maintaining hemoglobin at 10 to 11 gm/dL has
been shown to correlate with better outcomes
under certain conditions.

In the case of a contrast allergy, methylprednisolone (MP) 32125 mg IV and diphenhydramine
25100 mg IV are to be repeated every 6 hours
for at least 24 hours. In the setting of anaphylaxis, respiratory support should be instituted.
Aggressive treatment of pyrexia should
include acetaminophen every 4 hours and, if
necessary, the use of surface cooling or more
invasive cooling methods.

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exhausted response to mannitol and barbiturates. Neurol Res
1999;21(8):758764 PubMed
33. Levin AB, Duff TA, Javid MJ. Treatment of increased intracranial pressure: a comparison of different hyperosmotic
agents and the use of thiopental. Neurosurgery 1979;5(5):
570575 PubMed
34. Eisenberg HM, Frankowski RF, Contant CF, Marshall LF, Walker
MD. High-dose barbiturate control of elevated intracranial
pressure in patients with severe head injury. J Neurosurg
1988;69(1):1523 PubMed
35. Himmelseher S, Werner C. [Therapeutic hypothermia after
traumatic brain injury or subarachnoid hemorrhage. Current
practices of German anaesthesia departments in intensive
care]. Anaesthesist 2004;53(12):11681176 PubMed
36. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after
cardiac arrest. N Engl J Med 2002;346(8):549556 PubMed
37. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose
survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346(8):557563 PubMed
38. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke
Study Group. N Engl J Med 1995;333(24):15811587 PubMed
39. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a
randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 1999;282(21):20032011 PubMed
40. Smith WS, Sung G, Saver J, et al; Multi MERCI Investigators. Mechanical thrombectomy for acute ischemic stroke:
final results of the Multi MERCI trial. Stroke 2008;39(4):
12051212 PubMed
41. Kase CS, Furlan AJ, Wechsler LR, et al. Cerebral hemorrhage
after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial. Neurology 2001;57(9):16031610 PubMed
42. Sekhon LH, Morgan MK, Spence I. Normal perfusion pressure breakthrough: the role of capillaries. J Neurosurg 1997;
86(3):519524 PubMed
43. Morgan MK, Johnston IH, Hallinan JM, Weber NC. Complications of surgery for arteriovenous malformations of the brain.
J Neurosurg 1993;78(2):176182 PubMed
44. Kucik CJ, Clenney T. Management of epistaxis. Am Fam Physician 2005;71(2):305311 PubMed


Nursing Considerations
Maria G. Farrow

Since the inception of neuroendovascular therapy

as a formalized discipline in the 1980s, nursing has
maintained an integral role in the care of patients
undergoing neuroendovascular therapy. As this
treatment modality continues to expand technologically, so too evolves the complexity of nursing care of
the neuroendovascular patient.
Today, professional registered nurses (RNs) use
multiple skills to directly care for adult and pediatric
patients. In interventional neuroradiology, RNs have
developed subspecialized skills to complement the
advancing technology used in the treatment of cerebrovascular disorders. Nursing functions include patient
care, teaching about disease states and procedures, and
education of staff members, including other nurses
and radiation technologists. Also, as patient advocates,
nurses keep patients and their families informed while
ensuring their safety and comfort during the process of
pre-, intra- and postendovascular treatment. Therefore,
nurses contribute significantly to the care and successful outcomes for neuroendovascular patients.
In addition to care provided by RNs, there are
multiple levels of nursing provided by advanced
practice registered nurses (APRNs) involved in this
specialty. APRNs are RNs who hold a masters or
doctorate degree and are trained in specialized clinical knowledge and skills.1 This group includes nurse
practitioners (NPs), clinical nurse specialists, and
certified registered nurse anesthetists.
Registered professional nurses are licensed and
authorized by each state, commonwealth, or territory
to practice nursing.1 Their undergraduate education
prepares them to meet the complex care needs of
patients. Specialty roles in nursing can be obtained
through training on the job, continuing education, or competence demonstrated and acknowledged through credentialing in various specialties.
The American Association of Neuroscience Nurses
(AANN) provides certification in neuroscience nursing for nurses caring for neuroendovascular patients.


Advanced Practice Registered


Nurse Practitioners
NPs are independent practitioners who have indepth training and a knowledge base allowing them
to manage the care of patients undergoing endovascular procedures and to monitor for complications.
NPs develop differential diagnoses and order,
conduct, supervise, and interpret pertinent diagnostic and laboratory tests. They also prescribe pharmacological and nonpharmacological interventions in
the management of patients with acute and chronic
illness and disease.1 They incorporate nursing experience with clinical competence in this unique field
to promote health and the prevention of illness and
injury of the neuroendovascular patient. NPs have
autonomy through the scope of practice of the profession, which contributes tremendous assistance
to the team in various aspects of the care of these
patients. Through collaboration between the neurointerventionalist, critical care nurse or floor nurse,
and other members of the health care team, the NP
is a crucial link between holistic nursing and medical
management of these patients.
NPs may receive certification after successful
completion of a credentialing process that includes
meeting educational requirements, fulfilling a
requirement of clinical hours, and passing a national
board certification exam in their specialty. The specialties include acute care, adult, family, geriatrics,
oncology, and pediatrics. The two largest bodies for
NP certification in the United States are the American
Nurses Credentialing Center (ANCC) and the American Academy for Nurse Practitioners (AANP).
NPs are trained to perform history and physical
examinations, which can be obtained on initial visits
and as part of preprocedure workups.1 Their ability

9 Nursing Considerations
to extract detailed patient information with understanding of selection criteria assists the neuroendovascular surgeon in the decision-making process
of a treatment plan for the patient. Concurrently,
NPs help patients (and perhaps patients families)
to understand their disease and the particular techniques used for treatment in their case. For example,
the NP can preconsent and describe in detail the
process of endovascular coiling to a patient with a
cerebral aneurysm who may potentially undergo
this treatment procedure. The discussion may further explain how the aneurysm patient is evaluated
for treatment by coiling based on age, medical condition, and aneurysm characteristics (size, shape,
location, and neck width). The NPs repetition of
information provided earlier by the neurointerventionalist helps the patient to understand the condition and the plan of care. The NPs thorough, detailed
explanation of endovascular procedures can alleviate patients concerns while ensuring that they have
given informed consent. NPs reduce potential late
cancellations by verifying that patients are suitable
candidates for neuroendovascular procedures, which
includes obtaining required clearances. Patients are
seen by NPs in office visits or as inpatients.
In an acute hospital setting, NPs assess patients,
coordinate the plan of care, including requesting
consultations from other medical services, writing
orders, prescriptions, admissions and discharges, if
authorized by the hospital. Interactions between the
NPs and care coordinators and other interdisciplinary team members in physical therapy, occupational
therapy, speech pathology, respiratory therapy,
social work, nutrition, and pastoral care leads to a
cohesive discharge plan and ultimately a reduction
in the inpatient length of stay.
In some institutions NPs can be credentialed to
assist in neurointerventional radiology procedures,
including cerebral and spinal angiograms, coiling
of intracranial aneurysms, percutaneous vertebroplasty, carotid artery stenting, intra-arterial thrombolysis, embolization (including intracranial and
spinal arteriovenous malformations [AVMs] as well
as head, neck, and intracranial trauma), care for
head and neck trauma, and percutaneous ablation of
venous vascular malformations.2
Continuity of care is maintained by interactions
between patients, their families, and the NP while
the neurointerventionalist is occupied with procedures or other responsibilities. Pre- and postoperative education in particular can be reinforced from
first-time visits through hospitalization and followup visits. The NP role is not limited to clinical duties
but also encompasses coordinating patient transfer from other facilities, facilitating direct inpatient
admission, and scheduling of procedures. NPs also
lead, organize, and assist with cerebrovascular dis-

ease support groups, such as those for brain aneurysms, AVMs, and stroke.

Clinical Nurse Specialists

Clinical nurse specialists (CNSs), as described by the
ANA, are clinical experts in evidence-based nursing
practice within their specialty, managing the health
concerns of patients. They provide leadership in
advancing the practice of nursing to achieve quality
and cost-effective patient outcomes as well as leadership in multidisciplinary groups in designing and
implementing innovative alternative solutions that
address system problems and patient care issues.1
This is often demonstrated in CNS-driven ongoing staff education, which promotes advancing the
skill set of nurses caring for the neuroendovascular

Certified Registered Nurse Anesthetists

Certified registered nurse anesthetists (CRNAs) are
graduates of nurse anesthesia educational programs
accredited by the Council on Accreditation of Nurse
Anesthesia Educational Programs or its predecessor
and have passed the certification examination.1 They
provide anesthesia and anesthesia-related care to the
neuroendovascular patient from preanesthetic preparation and evaluation through induction, maintenance, emergence, and postanesthesia care. The
extent and frequency of CRNA management of these
patients is dependent on the institution.
RNs provide care for the neuroendovascular
patient in an array of areas, including the neuroendovascular suite, preadmission areas, the floors of
acute inpatient units, intensive care units, and postanesthesia recovery units.
When caring for patients who require endovascular therapy for aneurysms, AVMs, carotid stenosis,
intracranial stenosis, stroke, and cerebral vasospasm
postsubarachnoid hemorrhage, nurses must remain
current on the specific treatment modalities for each
individual disease state. In-service training may be
available in certain institutions.
A strong knowledge base of the indications and
multiple treatment modalities currently available
to this patient population prepares the nurse to
provide the patient and family optimal education.
Because patients often develop a level of comfort
with the nurse providing their daily care, they may
also frequently ask questions and voice concerns.
The nurses ability to provide answers keeps the
patient informed, helps alleviate fears, and prevents
frustration, thereby promoting improved patient


66 Part II Perioperative Care

A detailed description and review of the neuroendovascular procedure with the patient and family
is commonly expected of nurses at all levels. Therefore, familiarity with the following fundamentals of
an angiogram enhances the ability to be informative
to patients. The minimally invasive procedure is performed by a specially trained physician (a neurointerventionalist) in a neuroangiography suite under
fluoroscopy, usually employing biplanar technology.
All procedures take place using sterile technique.
Via percutaneous access, a catheter over a guidewire
is navigated through a femoral artery to the arteries leading to the identified area of treatment. The
guidewire is removed, then contrast is injected into
the bloodstream so visualization of blood vessels
is achieved. A smaller microcatheter is then placed
within the initial catheter and guided to smaller vessels of the brain or spine. The preparation of patients
and their families for these procedures aids in limiting the fear of the unknown.
Critical care skill competency is usually a requirement for nursing care during the procedure and
immediately postoperative for patients undergoing
interventions. As more technologically complex,
minimally invasive procedures like neuroendovascular therapy advance health care, the standards of
nursing practice raise expectations for high-quality
care of these patients. Many institutions require
multiple certifications, including Basic Cardiopulmonary Life Support (BCLS), Advanced Cardiovascular Life Support (ACLS), and Pediatric Advanced Life
Support (PALS) for employment in the neuroangiography suite and in the various intensive care unit and
postanesthesia care units.

Orders unique to this specialty, including assessments, mobility, and medication administration,
are important considerations for the nurse caring
for neuroendovascular patients. Nursing care and
management of the patient undergoing endovascular therapy encompasses various duties performed
by RNs pre-, intra- and postprocedure. Each phase is
detailed here (see Table 9.1).

Preendovascular Procedure
Nursing Care

Preparing the patient for the endovascular procedure

involves completing clinical duties and following
institutional protocols.
Identification of the patient upon arrival in the
neuroangiography suite is primary to ensure patient
safety. Individual institutional policies generally
include comparison of medical record number with
wrist name band and the patient chart, preceding
any intervention with the patient.
Baseline neurological assessment, vital signs, and
neurovascular assessment of bilateral peripheral
pulses are pertinent before the start of the procedure
to provide a comparison with potential changes both
during and postprocedure.
Nursing practice includes maintaining policies
and procedures during all stages of the endovascular
surgical treatment.3 Institutions may vary in requirements prior to the procedure. These policies generally
include the documentation of height, weight, allergies, and medications, and reviewing medical history.

Table 9.1 Nursing care of the neuroendovascular patient




Assessment: neurological assessment,

vital signs, distal peripheral pulses

Assessment: neurological assessment,

vital signs, distal peripheral pulses

Assessment: neurological assessment,

vital signs, distal peripheral pulses, groin
puncture site

Drug therapy:
Drug therapy:
Contrast allergy premedication = meth- Conscious sedation
ylprednisolone and diphenhydramine
Heparin in normal saline bags
Prophylaxis for contrast-induced nephropathy = N-acetylcysteine and sodium bicarbonate
Prestent placement - Acetylsalicylic
acid and clopidogrel bisulfate
Hold metformin
Patient support:
Explain procedure to patient, ensure
informed consent, emotional support

Patient safety/support:
Physical support on the angiography table with adequate positioning
and padding to maintain safety and

Drug therapy:
Acetylsalicylic acid and/or clopidogrel
bisulfate poststent
 -acetylcysteine for continued
Hold metformin

Assess for bleeding:

Check groin puncture site
Check peripheral pulses of affected leg
Assess for contrast-induced nephropathy:
Maintain intravenous fluids as ordered
Monitor urine output
Monitor renal function tests

9 Nursing Considerations
It is a preprocedure requirement for the patient to be
assessed by a physician, NP, or physician assistant.
The patient record should include a recent history
and physical (usually within 30 days), laboratory and
diagnostic results (complete blood cell count, basic
metabolic panel, coagulation studies: prothrombin
time/partial thromboplastin time/international normalized ratio, type and screen, pregnancy test, chest
X-ray, and electrocardiogram), and signed informed
consent from the patient or guardian (for the procedure, moderate sedation, anesthesia, and blood
products if indicated). These may be considered a
responsibility of the nurse sending the patient to the
procedure from the inpatient unit and/or the nurse
admitting the patient to the neuroangiography suite.
Although obtaining informed consent is the
responsibility of the physician, it is important for
the RN to be aware of the patients, familys, and/
or guardians verbalized understanding of what
was discussed to ensure that they are informed and
to provide any further clarification. Many patients
undergoing these procedures may have a decreased
level of consciousness, cognitive deficits, or aphasia,
limiting their ability to provide consent. It is then
imperative that appropriate policy be followed to
determine the guardian who can sign for consent
and to ensure that the guardian understands the
purpose, potential risks, and benefits of the procedure. This form of patient and caregiver education
is aimed at reducing postponement of a procedure
due to a patient or guardians perception of a lack of
information. In situations where there is a language
barrier, the nurse can advocate for the patient to be
provided with the appropriate translation for sufficient understanding and responses to questions.
Encouraging the patient to verbalize any recent
changes in health, such as a cold or fever, provides
information that might potentially result in the delay
or cancellation of the procedure.
Preprocedure orders must be obtained from a
physician, NP, or physician assistant. These orders
may include prehydration, nothing by mouth, premedication, or intravenous (IV) access.
IV hydration is commonly ordered to prevent
dehydration in the patient during nonoral feeding
and will assist the clearance of the intra-arterial contrast that is used during the procedure. Initiation of
an IV is necessary or the nurse may need to verify
patency of an existing IV.
Verifying that the patient has not eaten after midnight the night before the procedure is imperative
because either conscious sedation or general anesthesia may be administered depending on the treatment plan.
It is also essential to check that the patient has
not taken medications in accordance with prior
instructions from the neurointerventionalist, NP, or
physician assistant. Such medications may include

nonsteroidal anti-inflammatory drugs, metformin,

and glucophage, and a decreased dose of the patients
long-acting insulin on the eve of the procedure if the
patient is diabetic, given that food is withheld after
midnight the day before the procedure.

Administration of Preprocedure
Drug Therapy
Patients with a known allergy to IV contrast or shellfish require premedication prior to treatment. If the
patient is admitted on the day of the procedure, verify
that pretreatment steroids and antihistamines were
taken as ordered to prevent contrast reaction due to
noncompliance regarding medications. Methylprednisolone (Medrol) and diphenhydramine (Benadryl)
are often ordered to be taken 12 hours and again 2
hours prior to the procedure. If the patient is admitted to the hospital, it is the responsibility of the nurse
caring for the patient to administer the ordered medications or to inquire for such orders if there are none
and the patient has a documented contrast allergy.
A medication prescribed for prevention of contrast-induced nephropathy (CIN) is off-label use of
N-acetylcysteine (Mucomyst). Studies show this
drug reduces the risk of acute renal failure by minimizing oxygen free radical generation and promoting renal vasodilation after a radiocontrast dye load.4
The commonly used dose is 600 mg orally twice a
day, on the day before, the day of, and 2 days after
the procedure.5 However, other studies have shown
slightly better outcomes when the dose is doubled to
1,200 mg orally twice daily, and this is thus the preferred dose for some neurointerventialists.6,7 CIN is
the development of acute renal impairment secondary to contrast infusion in the absence of other identifiable causes of the renal failure. Recognizing those
at high risk for developing this untoward complication allows the RN to determine if the patient meets
the criteria for receiving this medication. Patientrelated risk factors for CIN include preexisting renal
dysfunction, diabetes mellitus, hypovolemia, heart
failure, advanced age (71 or older), concurrent use of
nephrotoxic drugs like aminoglycosides, and concurrent use of drugs thought to increase renal perfusion,
such as angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blockers (ARBs), or nonsteroidal anti-inflammatory drugs (NSAIDS).8,9 NPs
can instruct outpatients on when and why to take
N-acetylcysteine the day prior to their procedure as
well as prescribe this medication in both the in- and
outpatient setting.
Sodium bicarbonate is another medication that
can be prescribed to prevent CIN. An average dose
of sodium bicarbonate is a 3 mL/kg bolus per hour
for 1 hour before contrast is given, then 1 mL/kg per
hour for 6 hours after the procedure. Hydration with


68 Part II Perioperative Care

sodium bicarbonate is more effective than sodium
chloride hydration alone for reducing potential
Acetylsalicylic acid (aspirin) and clopidogrel
bisulfate are premedications ordered for patients
who may undergo stent placement (carotid or intracranial) or other implant procedures, such as coiling
of an aneurysm.12 Although these are normally held
in most invasive procedures, the RNs understanding
that they should actually be given under this circumstance can prevent inadvertent medication error.
Metformin and drugs combined with it have been
recommended to be withheld 24 hours prior to the
procedure and 72 hours after to prevent lactic acidosis.13 The RN should note if the patient is taking
this medication on the day of the procedure or just
prior to the procedure, and inform the health care
provider (physician/NP/physician assistant) to make
appropriate changes.
End-stage renal patients may need special
arrangements for timing of their dialysis pre- and
postangiography.14 Nurses should be aware of special
coordination to avoid the effect of IV contrast dye on
severely renal compromised individuals.

Patient and Caregiver Support

Families may be directed to waiting areas during the
procedure for updates on the progress and the report
of results upon completion. If the patient is scheduled for same-day discharge, identify who will be
responsible for taking the patient home and inform
the person as to when the patient may be ready.
Nurses can anticipate patient problems, such as
a knowledge deficit about a new diagnosis, anxiety,
and fear of the unknown, potential risks, and even
death. Assessment of the level of these issues with
the patients and families and being a supportive and
reassuring resource can allay further manifestation.
The NP should also provide clearly understandable
information. Patient and family education preprocedure on activity limitations can help with postprocedure compliance.

Intraendovascular Procedure
Nursing Care

Preparation requirements for neurointerventional

procedures include a neuroangiography suite appropriately stocked and containing functional equipment. Stock includes oxygen equipment, suction
equipment, catheters, guidewires, microcatheters,
embolic materials, such as glue, and coils.15 It may be
a nursing responsibility to have the room adequately
prepared to accept a patient.

Procedure table setup under aseptic technique

may also be a responsibility of the RN. Standard equipment that is part of the setup follows hospital policy
standards and generally includes but is not limited
to an interventional angiopack, a sterile drape, normal saline bags, pressure bags, a sterile basin, power
injector tubing and syringe, syringes, tubing, and
lidocaine. In addition, setup requires 1,000 mL normal saline bags to have 2,000 units of heparin added
per the neurointerventionalists order. This must subsequently be labeled with the medication, date, time,
and preparer. This is followed by placing the normal
saline bags in pressure bags, spiking the bag with
tubing, and then inflating the bags to 300 mm Hg. The
lines are then flushed and carefully inspected for any
bubbles, which must be cleared from the line.
A code cart and resuscitation equipment should
be immediately available in the angiography suite.
Nurses follow institutional protocols for checking the
monitor/defibrillator and code cart to ensure function and availability of equipment and medications
during an emergency or code situation. Emergency
medications should include antiarrhythmics, atropine, and those that treat hypertension and hypotension. Situations may arise for the nurse to use BCLS
and ACLS and to lead other personnel during patient
Patient assessment should begin with a documented baseline neurological examination, vital
signs, and peripheral pulse distal to the access site.
Continuous assessment of cardiac monitoring is
maintained, and vital signs including heart rate,
respiratory rate, and blood pressure (arterial and
noninvasive) and oxygen saturation are recorded at a
frequency indicated per institutional protocols. During the procedure the neurointerventionalist should
be notified of any adverse changes in the baseline,
such as tachypnea (respiratory rate > 12 a minute),
bradycardia (heart rate < 40 a minute), significant
hypotension or hypertension (systolic 90 mmHg
or 160 mm Hg) or a significant decrease in oxygen
saturation (< 92%).
During crucial moments of the procedure, careful attention to continuous cardiac monitoring and
neurological assessment is essential preparation for
unexpected outcomes. Vital signs should be noted
after catheter placement, contrast injections, injection of embolic materials, stents, embolic protection
devices, and balloon inflations.
In certain circumstances the neurointerventionalist might request a particular variant in the vital
signs. For example, when treating an AVM, the neurointerventionalist may request that the patients
blood pressure be lowered to a mean arterial pressure of 50 to 60 mm Hg before injecting a liquid
embolic agent.
General anesthesia or conscious sedation is used
in most therapeutic interventions.15 Anesthesiologists

9 Nursing Considerations
or CRNAs provide general anesthesia during cases and
maintain the patients on ventilators. RNs should, however, maintain awareness of airway patency whether
it is via endotracheal tube or laryngeal mask airway
device. Conscious sedation may be administered by
an anesthesiologist, a CRNA, or an RN, depending on
institutional guidelines. Patients receiving this form of
anesthesia receive a continuous supply of oxygen and
respiratory status monitoring by the nurse. Nurses
must ensure that the sedation and analgesia protocols
of the neurointerventionalist remain aligned with
institutional protocols.
Physical support of the patient must be maintained for safety and comfort. Protection of skin
integrity is carefully monitored because some procedures may require the patient to be immobile for
several hours. The nurse should secure the patient
once the patient is placed supine on the procedure
table and is attached to the hemodynamic monitoring. The joints and lumbar area should be supported,
pressure points, such as heels and elbows, should be
provided with extra padding, and extremities should
be maintained in a nondependent position. The angiography suite can be a cold environment, therefore
layering the patient with blankets and using a warming device will protect the patient from exposure and
prevent discomfort.
Insertion of a Foley catheter for urinary drainage
is generally required and initiated by the RN prior to
draping the patient. During long procedures under
anesthesia, careful attention must be paid to assessing catheter patency and recording urine output. If a
catheter is not placed, as in shorter cases, assessment
of elimination needs can be continued by offering the
use of a bedpan or urinal after hydration and contrast. It is crucial to monitor and record strict intake
and output throughout the procedure to obtain an
accurate record of fluid balance.
Implementation of the sterile prep and drape
of the groin following protocols is often a nursing
responsibility but can be completed by other members of the team, such as radiology technicians,
depending on institutional practices. Attention
should be placed on providing the endovascular surgeon access to the puncture site while keeping the
patient free of potential infection.
Another responsibility of the nurse is to administer and monitor anticoagulation. An activated clotting time (ACT) baseline is obtained generally at the
start of some cases (e.g., endovascular coiling). The
nurse, competent in the use of ACT machines used to
obtain this measurement, takes the patients blood
sample from the neurointerventionalist and processes it through the machine to receive the result.
This is also done serially through the procedure to
maintain anticoagulation 2 to 2 1/2 times the baseline ACT. During the case, the nurse may be the person responsible for verifying an adequate supply

of heparinized normal saline administration to the

patient intra-arterially as well as its preparation.
Orders to start a continuous heparin infusion may be
given by certain interventionalists. Aspirin administration may also be requested upon completion of
the procedure.
For those patients allergic to, or who have developed antibodies against, heparin, other medications
have been substituted.16 For example, bivalirudin is
an alternative IV anticoagulant that can be mixed
in normal saline and used during angiography
On admission, the nurse must assess the patient
for a latex allergy and identify the allergic patient
with a latex allergy band and documentation in
the medical record.18 Latex allergic patients require
identification prior to the procedure as a safety measure, and nurses must follow the hospitals policy
for latex allergy patient care. This generally includes
use of only nonlatex gloves by all staff providing care
to the patient. Also, prior to the patients entry, the
procedure room must be stocked with only latexfree materials for use during the procedure. Careful
attention must be paid to the use of only latex-free
equipment and care products. Immediately inform
the physician/NP/physician assistant if a latex-free
alternative is not available for the procedure. Scheduling the latex-allergic patient for the first case of
the day will lower the ambient latex levels in areas
where sterile latex gloves are frequently used.
The nurse should inform all health care personnel
involved in the patients care of the patients latex
sensitivity and should again provide the information
during report when handing over the patients care
or transferring the patient to another unit.
Psychosocial support should be rendered throughout the procedure. When under conscious sedation,
patients have fears alleviated through explanation
of various parts of the procedures. Frequent assessment of the patients comfort level minimizes postprocedure pressure sores and pain. Attention should
be paid to the noise level in the angiography suite to
optimize the patients experience. If it is an alternative during the procedure, the patients inclusion in
the choice of music played may lead to a more positive outlook. Although catheter access is obtained
through a femoral artery after sterile groin preparation, keeping all other areas covered assures the
patient of privacy.
Radiation safety is a concern for both the patient
and all staff working in the neuroangiography suite.
Once the patient is physically supported on the table,
it is imperative to cover the genitalia with lead draping for protection from radiation during the procedure, especially in the setting of spinal angiography.
All staff, including nurses, are required to wear protective lead garments during neurointerventional


70 Part II Perioperative Care

At the completion of the procedure, the nurse
should contact the receiving unit to give a full report
of what treatment was done during the neuroendovascular procedure and the patients current condition and should document the interaction. Special
detail should be given to the description of the neurological status, appearance of the groin site, and
neurovascular status of the limb of puncture.

Postendovascular Procedure
Nursing Care

Immediately following the completion of endovascular treatment, the patient will continue to have
intensive care monitoring primarily, when possible,
in a neurological intensive care unit, another intensive care unit, or a postanesthesia care unit (PACU),
depending on the institution. After approximately
12 to 24 hours, patients may be moved to a regular
neurological floor to complete recovery once it has
been determined that less intensive monitoring is
required. This judgment is determined by the neurointerventionalist and is based on the patients needs.
If the patient is undergoing an outpatient or inpatient diagnostic angiogram, the patient may recover
in a PACU environment prior to discharge home or
return to the inpatient unit.
Following the patients arrival in the unit, nursing
care continues to include the comprehensive assessment initiated preprocedure with additional considerations specific to the potential complications of this
specialty. If this is a same-day outpatient procedure,
such as a cerebral angiogram, the patient would go to
a designated recovery area for postprocedure monitoring until ready for release home.
Nursing assessment and documentation of vital
signs includes blood pressure (invasive via arterial
line or noninvasive via cuff measurement), heart
rate, respiratory rate, and oxygen saturation via pulse
oximetry. In the NICU, ICU, or PACU setting, this is
done initially every 15 minutes for 1 hour, then every
30 minutes for 1 hour, then hourly for an additional
2 to 4 hours.

Neurological Assessment
Continuous neurological assessment is essential
to rapidly evaluate acute change, such as ischemic
events from clot formation of emboli or thrombus
within the vessels after catheter manipulation. This
assessment, done hourly (on average) in an ICU,
includes level of consciousness; pupillary size, shape,
and reaction to light; motor function (hand grasps,
pronator drift, motor strength of extremities); cranial
nerve deficits (blurred vision/diplopia, extraocular

movement deficits, ptosis, facial weakness, tongue

deviation); and aphasia.19,20 The Glasgow Coma Scale
(GCS) is often used to limit observer variability in
patients with a decreased level of consciousness. It
relies on three tests of best eye opening, best verbal
response, and best motor response. Scores can range
from 15 for a patient who is awake and alert to 3
for a patient who is moribund.21 In the setting of an
acute neurological deterioration, rapid preparation
for necessary imaging, such as computed tomography (CT) or return to the angiography suite, can save
time and lead to better patient outcomes. Nursing
preparation for unexpected acute neurological deterioration leads to an expedited transfer to emergent
imaging and better potential patient outcomes.
Neurological status continues to be assessed once
the patient is transferred to less intensive monitoring with a decrease in frequency following individual
floor protocols.

The activity order expected immediately postprocedure will include strict bed rest with the leg of the
femoral artery puncture site maintained straight to
prevent bleeding for an average of 4 to 6 hours, depending on the request of the neurointerventionalist.
Patients received with the femoral intra-arterial
sheath used for arterial access remaining in the groin
must maintain the leg with the sheath extended at
all times. Patients may be allowed to log roll toward
the side of the sheath in a way that the leg remains
in the extended position while the contralateral leg
can be flexed for comfort. A pillow along the patients
back will assist in providing the patient additional
comfort in this position. While in place, the sheath is
connected to a heparinized pressure bag and transduced to the monitor. Attention to the waveform
of the intra-arterial groin sheath is necessary and
the physician/NP/physician assistant must be notified immediately if the waveform dampens. Once
the sheath is removed, the lower extremity should
remain extended for the remaining amount of hours
as ordered before liberalizing movement. Care must
be taken when transferring the patient with the
groin sheath in place. Use of a sliding board and two
members of the health care team can ensure safe
transfer. After moving a patient, immediately check
the sheath site for bleeding, hematoma, and the
presence of distal pulses on that leg.
It may be necessary to provide continual reminders for the patient to maintain the leg with the groin
sheath or leg of the puncture site extended for the
ordered period of time. Discomfort due to limited
mobilization may lead to a tendency to flex the leg,
but optimal teaching emphasizing the risks of bleeding from the site may ensure compliance.

9 Nursing Considerations
These patients are at risk for deep vein thrombosis (DVT) and pulmonary embolism due to limited
mobilization. Studies have indicated that pneumatic
compression devices with or without elastic stockings and unfractionated and low-molecular-weight
heparin are effective forms of DVT prophylaxis22 and
are often prescribed for these patients. However,
they should not be placed on the leg with the puncture site immediately postprocedure.

Assess for Bleeding

Visual and manual inspection of the groin puncture
site provides assessment of potential complications,
including rebleeding of the site, hematoma formation, retroperitoneal bleeding, arterial dissection,
and pseudoaneurysm. Generally, the groin site is
ordered to be checked at 15 minute intervals initially
for an hour, then every 30 minutes for the second
hour, then hourly. Any bleeding should be reported
immediately to the physician/NP/physician assistant
for rapid assessment. If a small area of bleeding or
hematoma is noted, the area should be marked with
a circle to evaluate if there is an increase in size outside the area of measurement. If the bleeding is copious, apply direct pressure to the femoral artery until
arrival of the physician/NP/physician assistant.
Currently, percutaneous vascular closure devices
achieve hemostasis in less time than manual compression. Their use in groin closure has increased
secondary to promoting patient comfort, earlier
return to ambulation, and less need for personnel to
manually compress the groin. A Mayo Clinic study
found that infection with such devices, although
uncommon, may lead to serious complications leading to surgical debridement, prolonged hospitalization, and the need for antibiotic therapy.23 Therefore,
familiarity with direct observation of various groin
closure devices prevents delayed diagnosis and treatment. Some consist of collagen plugs, sutures, or clips
to maintain integrity of the site so they may appear
different during inspection. The choice of device is
operator specific and varies in use per institution.
If a new device is introduced, the manufacturer
should be contacted for information on risk factors
for the common complications and their preventive
strategies and be sure nursing protocols reflect the
Careful monitoring must also be placed in the
setting of a decrease or change in circulation of the
affected leg. Initial comparison of both lower extremities will assist in identifying variation. Noting the
presence or absence of pedal pulses, particularly the
dorsalis pedis and posterior tibialis, as well as the
warmth, color, and capillary refill of that extremity
can provide early detection of a serious complication. Notify the physician/NP/physician assistant of

any signs of neurovascular compromise, in particular

pain, pallor, pulselessnesss, coolness to touch, and
Patient complaints of flank or back pain may
not be due to positioning, but, rather, secondary to
a retroperitoneal hematoma and must be reported
as quickly as the previously described symptoms. In
addition to the physical findings, it is important to
monitor the patients vital signs, which may be the
first indication of this complication (hypotension
and tachycardia). Hemoglobin and hematocrit blood
lab values should be monitored for an unexpected
drop in values, which may be secondary to a loss of
blood not readily visible.

Assess for Contrast-Induced

Nephropathy and Allergy
CIN is renal failure after intravascular administration
of contrast media with no other apparent cause.25
Patients at the highest risks for CIN are diabetics and
those with chronic kidney disease. The focus of nursing management both pre- and postprocedure is on
those patients at highest risk and those with other
patient-related risk factors, including hypovolemia
and nephrotoxic drugs.
Postprocedure care includes a strict record of fluid
intake primarily consisting of maintenance of the IV
fluids as ordered. The nurse or NP should encourage
oral fluids for alert patients who can tolerate intake
by mouth to ensure adequate flushing of contrast dye
through the kidneys. The health care provider should
be notified if the patient returns from a procedure
that has used a contrast medium but has no order for
IV hydration, unless contraindicated. Those patients
started on IV sodium bicarbonate as prophylaxis for
CIN will continue the infusion of 1 mL/kg per hour
for 6 hours after the procedure.10
The majority of patients recovering from endovascular treatment are received in the inpatient unit
with a Foley catheter to gravity drainage. Strict measurement of urine output is essential and is often
recorded hourly in the ICU. If the output decreases,
check for patency of the catheter to clarify a structural flow issue from kinking or clotting of the
catheter versus decreased urine output from renal
compromise, because both can be detrimental to
kidney function and must have immediate treatment. Patients who have received intravenous contrast are at increased risk for renal complications. As
a result, it is crucial to notify the physician/NP/physician assistant if urine output decreases to below 30
mL/h. Additionally, any signs of a possible fluid overload as a consequence of overhydration, including
weight gain, oliguria, hypertension, new or worsening edema, or cardiopulmonary congestion, must be
noted and reported.


72 Part II Perioperative Care

Renal function tests, blood urea nitrogen, and
creatinine should be monitored for early detection of
any kidney compromise for at least 48 to 72 hours
in patients having undergone prolonged procedures.
Seek prompt intervention if values continue to elevate; most studies have used 25% elevation in serum
creatinine 2 to 7 days following contrast administration as an indicator of CIN.2
Patients should also be assessed for potential allergic reaction to the contrast media. Erythema, hives,
itching, periorbital edema, angioedema, laryngeal
edema, and shortness of breath should be reported

Assess for Vasospasm

Patients who have survived a subarachnoid hemorrhage after an aneurysmal rupture are at risk for
the complication of cerebral vasospasm from days 4
to 14 posthemorrhage. Careful assessment of these
patients for early recognition of vasospasm leads
to rapid treatment. Delayed ischemic neurological
deficit, such as a decrease in level of consciousness,
with or without focal symptoms, such as hemiplegia,
hemiparesis, or aphasia should be reported immediately. In the setting of vasospasm, intensive medical
management should be administered to reperfuse
the brain, including the use of therapy consisting of hypertension, hypervolemia, and hemodilution (HHH), which are used to reperfuse the brain.
Recently, the use of hypervolemia and hemodilution
has been minimized, whereas hypertensive therapy continues to serve as a first-line treatment for
patients with clinical vasospasm. The calcium channel blocker nimodipine may be prescribed for oral
administration to the patient as a prophylactic treatment of vasospasm until day 21 postsubarachnoid
hemorrhage.26 In the setting of severe spasm, expect
to prepare the patient emergently for endovascular
treatment of either intra-arterial papaverine, verapamil, nicardipine, and/or transluminal balloon
angioplasty. Consistent nursing assessment for subtle or dramatic neurological changes of the patient is
ongoing during this tenuous time, both before and
after these treatments.

Administration of Postprocedure
Drug Therapy
Antithrombotic agents like acetylsalicylic acid (aspirin) and/or clopidogrel bisulfate can be expected as
part of poststent placement orders. Nurses should
explain to the patient that the aspirin will be prescribed indefinitely and the clopidogrel bisulfate
for approximately a few months, depending on the
physicians determination, in order to prevent poten-

tial clot breakage resulting in clotting smaller distal

arteries of the brain. A brief description of the medications effects on platelet function with a reduction
of the platelets ability to stick together and form
clots, promotes further understanding, comfort, and
compliance in patients. Patients should be instructed
to use care and a soft toothbrush when brushing their
teeth. Avoidance of activity that may cause bleeding
can be advised. Prepare the patient for the possibility of bruising, and instruct the patient to notify the
health care provider of the formation of petechiae or
a hematoma.
Metformin and all combination drugs containing metformin should be withheld the day of, and up
to 48 hours after, the procedure to prevent acidosis
after administration of contrast dye. Inform the physician/NP/physician assistant if it has been ordered
postop and anticipate changes to alternative oral
medication or insulin for administration. Frequent
blood glucose monitoring will be necessary to assess
and treat hyperglycemia.
As discussed in preprocedure care, nurses should
expect to give N-acetylcysteine (Mucomyst) orally
600 to 1,200 mg twice a day to renal-impaired
patients on the day of the procedure and for 2 days
postprocedure. Some evidence suggests that better
outcomes are noted with the higher dosing.7,28

Patient Education on Discharge

Reinforcement of the preprocedure teaching for
routine care improves patient compliance. Thus a
review of activity levels, diet, medications, and signs
and symptoms to observe and report to health care
providers is important as the patient is prepared for
discharge. Patients should be instructed to call the
doctors office or the hospital same-day unit if redness, swelling, bleeding, or drainage is noted at the
groin site. Patients should be provided with written
instructions to take home.
Patients who have undergone outpatient angiography should be instructed to rest at home for 24
hours prior to resuming normal activities, including
showering the next day.
Patient education on incision care after discharge
will continue the process of complication prevention. Teach the patient how to inspect the groin site,
including hand washing prior to palpation. Patients
who have difficulty viewing the site due limitations
in mobility can be assisted with a mirror, or a family
member or friend may need to be instructed on how
to inspect the area. If the patient is discharged with
a groin dressing, instruction should be received on
when and how to remove it. Reinforce with the patient
which complications can occur after discharge and
the importance of reporting these changes immediately. In particular, patients should be advised against

9 Nursing Considerations
lifting heavy objects (in some institutions, a limit of
10 lb is suggested) for 2 weeks in order to mitigate
the risk of hematoma or pseudoaneurysm formation.
Return to work can be addressed on an individual
basis as determined by the patients health status,
the procedure, and the preference of the neurointerventionalist. Patients should also be instructed to follow-up with their neurointerventionalist and should
be provided the necessary contact numbers for the
physicians office as well as the emergency room and
same-day surgery unit.
Home medication instruction is as crucial as inpatient medication administration. Patients need to be
aware of which home medications should be resumed
and which should be held until advised by the physician/NP/physician assistant. Patients who have
undergone only angiography or angiography with
embolization are often instructed to avoid aspirin and
other nonsteroidal anti-inflammatory agents. However, patients who are postangioplasty and stenting
or aneurysm stent/coiling are advised to take aspirin
and clopidogrel bisulfate for specified periods of time.
Patient teaching should cover the goal of mobilizing contrast dye through the kidneys by promoting
adequate hydration upon discharge. Encourage the
patient to continue to maintain oral hydration unless
contraindicated by a preexisting condition. The
patient should be directed to contact the health care
provider if edema or significant weight gain occurs
within the first few days postprocedure.
Rehabilitation may be necessary for patients with
motor or cognitive deficits and those with extensive
stays in an acute inpatient hospital. Nursing identification of these individuals as early as admission
and during assessment of initial mobilization can
assist with timely disposition from the hospital to
the appropriate facilities, such as acute and subacute
rehabilitation. This is also achieved by consistent
interaction with other interdisciplinary staff, such as
physical, occupational, and speech therapists.

Nursing management of the patient by APRNs
assists the neurointerventionalist in managing and coordinating the care of the patient
and leads to increased patient knowledge and
ultimately a reduction in the length of stay.
Nursing care responsibilities for patients at all
levels of the neuroendovascular spectrum are
an integral component in the multidisciplinary
team management of these individuals.
Continuous nursing assessment is vital in order to obtain the patients baseline status and
detect early signs of any potentially deleterious

Frequent neurological assessment to detect
early signs of ischemia occurring from formation of emboli or thrombus within the vessels
after catheter manipulation
Continuous assessment of the groin puncture
site for hematoma formation or bleeding, including complaints of flank pain
Avoidance of contrast-induced nephropathy
with rigorous monitoring and recording of
patient intake and output of fluids and administration of prophylactic medication for those
patients at risk

Notify physician/NP/physician assistant of any
neurological changes and prepare for resulting
treatment, including imaging, such as CT scan,
medical therapy, or return to the angiography
Notify physician/NP/physician assistant of
groin puncture site bleeding and apply direct
pressure to femoral artery until arrival.
Notify physician/NP/physician assistant and
obtain hematocrit for any groin puncture site
swelling or complaint of flank pain to recognize a drop in value.
Notify physician/NP/physician assistant of
the first signs of decreased urine output and
elevated creatinine when monitoring the patients renal function tests while maintaining
rigorous IV hydration.

1. American Nurses Association. Nursing: Scope and Standards

of Practice. Washington, DC: American Nurses Association;

2. Stowe HO. Development of an NP role in interventional radiology. Nurse Pract 2003;28(8):5758 PubMed
3. Tarolli KA. Percutaneous interventions. Crit Care Nurs Q 2007;
30(1):1219 PubMed
4. Bettmann MA. Contrast medium-induced nephropathy:
critical review of the existing clinical evidence. Nephrol Dial
Transplant 2005;20(Suppl 1):i12i17 PubMed
5. Nallamothu BK, Shojania KG, Saint S, et al. Is acetylcysteine effective in preventing contrast-related nephropathy? A metaanalysis. Am J Med 2004;117(12):938947 PubMed
6. Castanares-Zapatero D, Hantson P. Pharmacological treatment
of delayed cerebral ischemia and vasospasm in subarachnoid
hemorrhage. Ann Intensive Care 2011;1(1):12 PubMed
7. Marenzi G, Assanelli E, Marana I, et al. N-Acetylcysteine and
contrast-induced nephropathy in primary angioplasty. N Engl
J Med 2006;354(26):27732782 PubMed


74 Part II Perioperative Care

8. Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy.

AJR Am J Roentgenol 2004;183(6):16731689 PubMed

9. Kohtz C, Thompson M. Preventing contrast medium-induced nephropathy. Am J Nurs 2007;107(9):4049, quiz 4950 PubMed
10. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrastinduced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291(19):23282334 PubMed
11. Morelli P, Davis KL. Stenting fights carotid disease. Nurse Pract
2007;32(6):4951, 5152 PubMed
12. Bashore TM, Bates ER, Berger PB, et al; American College of
Cardiology. Task Force on Clinical Expert Consensus Documents. American College of Cardiology/Society for Cardiac
Angiography and Interventions Clinical Expert Consensus
Document on cardiac catheterization laboratory standards.
A report of the American College of Cardiology Task Force
on Clinical Expert Consensus Documents. J Am Coll Cardiol
2001;37(8):21702214 PubMed
13. Needham E. Management of acute renal failure. Am Fam Physician 2005;72(9):17391746 PubMed
14. Pope WL. Cerebral vessel repair with coils and glue. Nursing
2002;32(7):4649 PubMed
15. Brettler S. Endovascular coiling for cerebral aneurysms. AACN
Clin Issues 2005;16(4):515525 PubMed
16. DiGiovanni CW. Current concepts review: heparin-induced thrombocytopenia. Foot Ankle Int 2008;29(11):11581167 PubMed
17. Alaraj A, Wallace A, Tesoro E, et al. Heparin induced thrombocytopenia: diagnosis and management. J Neurointerv Surg
2010;2(4):371378 PubMed

18. Dakin MJ, Yentis SM. Latex allergy: a strategy for manage-

ment. Anaesthesia 1998;53(8):774781 PubMed

19. Hickey J. The Clinical Practice of Neurological and Neurosurgi-

cal Nursing. 6th ed. Philadelphia, PA: Wolters Kluwer Health/

Lippincott Williams & Wilkins; 2009
20. Ropper AH. Neurological and Neurosurgical Intensive Care.
4th ed. Arch Neurol 2004; 61(10):1623-1624
21. Layon AJ, Gabrielli A, Friedman WA, et al. The Textbook of
Neurointensive Care. Philadelphia, PA: Saunders; 2004
22. Browd SR, Ragel BT, Davis GE, Scott AM, Skalabrin EJ, Couldwell
WT. Prophylaxis for deep venous thrombosis in neurosurgery: a
review of the literature. Neurosurg Focus 2004;17(4):E1 PubMed
23. Sohail MR, Khan AH, Holmes DR Jr, Wilson WR, Steckelberg JM,
Baddour LM. Infectious complications of percutaneous vascular
closure devices. Mayo Clin Proc 2005;80(8):10111015 PubMed
24. Gibson D. Vascular closure devices: What you know can
prevent serious complications. American Nurse Today
25. Sharma J, Nanda A, Jung RS, Mehta S, Pooria J, Hsu DP. Risk
of contrast-induced nephropathy in patients undergoing endovascular treatment of acute ischemic stroke. J Neurointerv
Surg 2013 PubMed
26. Barker FG II, Ogilvy CS. Efficacy of prophylactic nimodipine
for delayed ischemic deficit after subarachnoid hemorrhage:
a metaanalysis. J Neurosurg 1996;84(3):405414 PubMed
27. Briguori C, Colombo A, Violante A, et al. Standard vs double
dose of N-acetylcysteine to prevent contrast agent associated
nephrotoxicity. Eur Heart J 2004;25(3):206211 PubMed


Physiological Considerations
Lana Christiano, Chirag D. Gandhi, and Charles J. Prestigiacomo

The physiological state of each patient must be considered prior to any angiographic procedure. Particular
physiological/pathophysiological states require additional planning and preangiography counseling. Such
conditions as diabetes mellitus, hypertension, contrast
allergy, and chronic renal insufficiency require specific preangiography screening and potentially premedication to prevent contrast-media complications.
In particular, specific patient populations, including
pregnant patients and pediatric patients, require additional counseling regarding the risks of angiography.
This chapter discusses these physiological states and
provides a review of the recent literature.

Preadmission Evaluation
Preadmission evaluation consists of a comprehensive patient history, physical examination, and laboratory review. A thorough history is of paramount
importance in preparing a patient for angiography.
Specifically, past medical history, medication usage,
previous surgeries, and previous angiograms should
be documented. Regarding the past medical history,
patients should be asked specifically about a history
of hypertension, diabetes mellitus (DM), renal failure
or impaired renal function, congestive heart failure
(CHF), or any bleeding diatheses. Each of these medical
conditions requires special consideration in the angiography suite, which is covered in more detail later.
Each medication the patient is taking should also be
documented. Specifically, the use of blood thinners or
antiplatelet agents, metformin, antihypertensives, or
antiepileptics should be noted in addition to the last
dose taken of each medication. Lastly, any prior surgeries or angiograms should be noted. If the patient
has previously undergone angiography, the date of
all previous angiograms should be noted in addition
to the method of closure. Multiple angiograms may
result in subcutaneous scarring and therefore difficulty in accessing the artery. Also, if the patient has
had a percutaneous closure device within the previ-

ous 3 months, the puncture site should be 1 cm proximal on the femoral artery, or the contralateral femoral
artery should be used for access. Surgery of the vascular system or abdomen is also of significance in the
preprocedural planning for a cerebral angiogram. For
instance, prior surgery for a femoral artery graft or
femoral artery-to-venous fistula might be a relative
contraindication for accessing that femoral artery.
There are numerous aspects of the physical exam
that are particularly important. Because most diagnostic angiograms are done under conscious sedation, it is important to examine the patients airway
and nares. The lungs, heart, and neck should be auscultated to evaluate respiratory status, cardiac murmur or arrhythmia, and carotid bruit, respectively.
The abdomen should be evaluated for prior surgeries, groin hernia, or previous angiography puncture
sites. A baseline neurological exam should also be
documented. The dorsalis pedis pulse should be palpated; if it cannot be palpated, a Doppler ultrasound
may be required at the time of angiography.
Preadmission testing is routinely done on patients
scheduled for cerebral angiography. The basic studies all patients undergo include SMA, complete
blood count (CBC), and PT/PTT. Specific attention
should be paid to the sodium, blood urea nitrogen
(BUN), creatinine, glomerular filtration rate (GFR),
glucose, hemoglobin, hematocrit, platelet count,
PT, international normalized ratio (INR), and PTT.
Patient-specific issues must also be considered. For
example, in patients with DM, the GFR and possibly a creatinine clearance are assessed. For patients
with cardiovascular disease, consider checking an
electrocardiogram (EKG), a chest X-ray (CXR), an
echocardiogram, brain natriuretic peptide (BNP),
and a dobutamine stress test, and obtaining cardiac
clearance. For those patients taking aspirin or Plavix
(Bristol-Myers Squibb, New York, NY) we routinely
check platelet function studies to evaluate treatment, such as VerifyNow Aspirin and VerifyNow IIb/
IIIa (Accumetrics, San Diego, CA). Finally, all women
of child-bearing age undergo a pregnancy test on the
day of the angiogram.


76 Part II Perioperative Care


Contrast Allergy

Anesthesiologists are instrumental in ensuring

patient safety and cooperation, allowing the interventionalist to focus on the procedure. The method
of anesthesia employed should be based on the
patients ability to cooperate, the duration of the
procedure, and the need to serially test the patients
neurological exam.1 Conscious sedation (intravenous
sedation) is ideal for diagnostic angiograms and
interventions requiring serial neurological exams.
The patient should have noninvasive monitoring,
including blood pressure cuff, heart rate and rhythm,
and pulse oximetry. A nasal cannula should be placed
on the patient prior to the procedure to provide supplemental oxygen. Arterial cannulation is the most
uncomfortable part of the procedure; therefore, local
anesthesia should be administered at the site of the
puncture prior to cannulation. Risks of conscious
sedation include an unprotected airway, aspiration,
hypoxemia, and hypercapnea.1
General patient considerations that may make one
more inclined to employ general anesthesia include
body habitus,2 obstructive sleep apnea,1,2 arthritis
or other ailments prohibiting lying supine for long
periods,1,2 mental retardation,2 or gastroesophageal
reflux.2 General anesthesia should also be considered for procedures on children because there is an
increased risk of vessel injury in an uncooperative
child.3 In general, at our institution we tend to use
general anesthesia for all interventional procedures
except those requiring serial neurological exams,
such as carotid stenting, balloon temporary occlusion, provocative testing of arteriovenous malformations (AVMs), and some thrombolysis procedures.

Contrast allergies can be categorized into mild,

moderate, and severe reactions. Mild reactions
include symptoms of nausea, vomiting, mild urticaria, or mild pallor. These reactions occur in 15%
of patients receiving ionic contrast media and 3%
in nonionic media.6 Moderate reactions occur in 1
to 2% of patients receiving ionic contrast media and
0.04% receiving nonionic contrast. These symptoms
include severe vomiting, extensive urticaria, laryngeal edema, dyspnea, and rigors.6 Severe reactions
include anaphylaxis, pulmonary edema, cardiac
arrhythmias, cardiac arrest, circulatory collapse, and
unconsciousness. These occur in only 0.2% and 0.04%
of patients receiving ionic and nonionic contrast
media, respectively.6 Despite the low incidence, these
reactions happen suddenly and are associated with
significant morbidity and mortality.
The pathogenesis of the adverse reaction is still
unclear. The release of histamine and triggering of
mast cells are postulated as the sources of severe
reactions, including anaphylaxis.7 Antibodies to
contrast media have not been found consistently
to prove these are true allergies.6 However, up to
35% of patients with a history of contrast-mediated
adverse reaction will develop another adverse reaction with contrast injection.6 Predisposing factors
for contrast media allergy include previous adverse
reaction, history of asthma, history of allergy, heart
disease, dehydration, sickle cell anemia, polycythemia, myeloma, preexisting renal disease, infants and
elderly patients, anxiety, beta-blockers, and nonsteroidal anti-inflammatory drugs.6
Many different premedication regimens have
been described to prevent contrast-mediated allergies. H1 antihistamines (hydroxyzine, diphenhydramine, clemastine, chlorpheniramine, and
dimenhydrinate), corticosteroids (betamethasone,
dexamethasone, methylprednisolone, and prednisolone), and H1H2 antihistamine combinations (clemastinecimetidine) have been evaluated.6,7 A study
recently published by Tramr et al7 concluded that
the incidence of severe anaphylactic reaction is such
a rare phenomenon that the number needed to treat
in order to prevent one anaphylactic reaction was
too low to warrant pretreatment. At our institution,
however, we feel that the risk of severe morbidity or
mortality from an anaphylactic reaction outweighs
the risk of premedication. We prescribe oral prednisone 50 mg at 24, 12, and 1 hour prior to the procedure in addition to oral diphenhydramine 50 mg 1
hour prior to the procedure, as described by Greenberger and Patterson.8
Preparation is the best defense against a severe
adverse reaction. All angiography suites should be
supplied with Advanced Cardiovascular Life Support
(ACLS) medications and equipment. Additionally, an

The contrast medium is a hydrophilic, iodine-based
liquid that may be injected intravenously or intraarterially. Contrast media are classified as ionic or
nonionic, monomer or dimer, and by the osmolarity (osmolar contrast media [OCM] categorized as
high [HOCM], low [LOCM], iso-osmolar [IOCM]).4
The osmolarity is determined by the ratio of iodine
atoms to the dissolved, active particles. The HOCM
has a ratio of 0.5 iodine atoms to 1 active particle and
an osmolarity of 2,000 mOsm/kg.4,5 The LOCM is 3:1
iodine to active particles and 600 to 800 mOsm/kg.4,5
Finally, the IOCM is 6 iodine atoms to 1 active particle
with an osmolarity of 290 mOsm/kg.4,5 A higher content of iodine yields better attenuation of the radiographic image; however, the HOCM has demonstrated
increased risk of contrast-induced nephropathy (CIN),
allergic reactions including anaphylaxis, and cardiovascular adverse events compared with LOCM.4

10 Physiological Considerations
oxygen tank and masks should be easily accessible.
Other medications for treatment of anaphylactic
reactions should also be available, including: racemic epinephrine, corticosteroids, and intravenous

Renal Insufficiency/

Contrast-Induced Nephropathy

CIN is the third leading cause of acute renal failure in

hospitalized patients.9 There are two leading hypotheses regarding the pathogenesis of CIN. Some postulate that the contrast media may cause direct toxicity
to the tubular cells of the kidney. The viscosity and
osmolarity of the contrast media are thought to be
the primary contributors to the toxicity.9 Another
theory includes an increase in adenosine, endothelin, and free radicals, associated with a reduction in
nitric oxide and prostaglandins, resulting in vasoconstriction and reduced renal blood flow, which
may lead to ischemia of the medulla.9
In the general population, the risk of developing CIN
is 2%. If, however, a patient has DM and a serum creatinine of 1.5, the risk increases to 38%; and if a patient
has DM and serum creatinine of 4 to 5 the risk rises to
50%. Additional risk factors include preexisting renal
dysfunction, DM (especially with underlying nephropathy), age > 70, volume depletion, anemia, heart failure, intra-aortic balloon pump, hypotension, and use
of nephrotoxic drugs (nonsteroidal anti-inflammatory
drugs, diuretics, aminoglycosides, amphotericin B,
angiotensin-converting enzyme inhibitors, cyclosporine, and chemotherapy medications).9,10
Contrast-related risk factors include using highvolume, high-osmolar, and high-viscosity contrast
media.9,10 Injecting > 140 mL, 5 mL/kg divided by
serum creatinine in milligram per deciliter, or additional contrast injections within 72 hours are associated with increased risk of nephrotoxicity.4,9,10
Additionally, intra-arterial contrast injection has
an increased risk of nephrotoxicity compared to
intravenous (IV), likely due to the higher intrarenal
concentration of contrast from an arterial injection
compared with IV.4 As previously discussed, HOCM
is also associated with a higher risk of nephrotoxicity compared with LOCM.4 When LOCM has been
compared with IOCM, no statistical difference has
been found.5 IOCM has a higher viscosity than LOCM,
which may negate the benefits of the lower osmolarity in IOCM. When nonionic and ionic contrast
agents were compared, no definitive conclusions
could be drawn because the investigators could not
control for osmolarity.5
There is significant debate in the literature
regarding the definition of renal insufficiency. Most
agree that a GFR less than 30 and serum creatinine

of 4 to 5 defines the patient as high risk for developing CIN.9,10 What is less clear is the risk stratification
if the patient falls somewhere below this threshold
but above normal values. Multiple studies have been
conducted regarding the appropriate measures to
prevent CIN. Most agree that patients with a GFR less
than 60, creatinine clearance less than 60, and/or
serum creatinine more than 1.5 should receive prophylaxis prior to angiography.9,10
One of the simplest means of preventing CIN is
stopping nephrotoxic medications prior to angiography.9 Such nephrotoxic medications include nonsteroidal anti-inflammatory drugs, aminoglycosides,
amphotericin B, diuretics, and angiotensin-converting enzyme inhibitors. Metformin should not be
taken for 48 hours following angiography to prevent
lactic acidosis.9 Another simplistic solution is to use
low osmolar, nonionic contrast media and to limit
the quantity of contrast administered.
Intravenous hydration is another means for prevention of CIN. Renal effects of contrast media were
initially studied in dogs, which demonstrated a
correlative decrease in renal perfusion.11 Based on
the hypothesis that CIN occurs by vasoconstriction
resulting in medullary ischemia and the documented
decrease in renal perfusion in dogs, IV hydration has
been implemented as a means of preventing the
hemodynamic shifts that can lead to CIN.10
Much debate, however, still revolves around the
formulation of the fluid, the rate of fluid infusion, and
the duration of fluid infusion. In a randomized study
of 1,620 patients undergoing coronary angioplasty,
the use of normal saline (0.9%) was compared with
half-normal saline (0.45%). The study concluded that
normal saline significantly decreased the incidence
of CIN compared with half-normal saline.12 The success of isotonic saline as compared with hypotonic
saline is likely due to the capacity of the isotonic fluid
to expand the intravascular space, thus preventing
vasoconstriction and renal medullary ischemia.10
The debate between normal saline and sodium
bicarbonate is not as clearly resolved. Sodium bicarbonate is proposed as a prophylactic agent due to
its antioxidant and free-radical scavenging characteristics.13,14 The initial study evaluating preprocedural sodium bicarbonate versus sodium chloride
demonstrated profound results. At interim analysis, only one patient receiving sodium bicarbonate
developed CIN compared to eight patients receiving
normal saline.15 Due to these astounding results, the
study was terminated early. Since then, six additional studies have evaluated the benefits of sodium
bicarbonate versus sodium chloride, with conflicting results. A meta-analysis of these six studies was
published by Hogan et al14 in 2008; they concluded
that sodium bicarbonate significantly reduced the
incidence of CIN compared with normal saline. They
also found, however, that there was publication bias


78 Part II Perioperative Care

due to the large treatment effect seen in smaller
N-Acetylcysteine is another agent used in the prevention of CIN. The exact mechanism of action is not
clear; however, it has been suggested that the associated increase in production of nitric oxide causes
vasodilation and increased renal perfusion.9,10 It has
also been suggested that N-acetylcysteine may act
as a scavenger of free radicals, decreasing the oxidative tissue damage caused by the contrast media.9,10
Twenty-four studies and 11 meta-analyses have
evaluated the use of N-acetylcysteine as a prophylactic agent.9 The majority of the studies demonstrated benefit in preventing CIN. However, there was
significant variation in the studies regarding dosing
regimen, route of administration, the definition of
nephropathy, types of contrast media used, quantity
of contrast media used, and adjunct intravenous therapy. Additionally, not all of the studies reached statistical significance. At our institution, we prescribe 600
mg of N-acetylcysteine twice a day starting the day
prior to angiography, for a total of four doses in those
patients at risk for developing CIN.
The final measure in prevention of CIN is prophylactic hemodialysis. Lee et al16 reviewed 82 patients
with chronic renal failure (creatinine more than 3.5
mg/dL) undergoing coronary angiography. They were
randomized into an IV fluid hydration group or prophylactic dialysis within hours after the angiography
procedure. The authors found a statistically significant higher creatinine clearance on day 4 and less of
a change in creatinine clearance in the hemodialysis
patients. Also statistically significant were the number of patients requiring subsequent hemodialysis in the hydration-only group compared with the
prophylactic hemodialysis group. We suggest that,
in preparation for an angiography procedure in a
patient with chronic renal failure, a nephrologist be
involved in the patients care and that the possibility of dialysis, temporary or permanent, be discussed
with the patient.

Cardiovascular Disease
Cardiovascular disease affects one in every three
adults.17 Preoperative cardiac clearance should be a
consideration in preparing patients for the angiography suite. Preparation can be as minimal as starting
a beta-blocker or it can include multiple noninvasive
studies, including stress tests. Regardless of the plan,
it is always a good idea to have a primary care doctor
or cardiologist involved preprocedure.
During the procedure, it is ideal to maintain a
relatively stable blood pressure. In an awake patient,
the time of puncture is usually the most noxious part
of the case and a common place for elevated blood
pressure. Although an elevated blood pressure may

assist in palpation and catheterization of the femoral

artery, it is not good for the patients cardiac tolerance. Additionally, manipulation of the blood pressure may be warranted during the procedure; the
assistance of an anesthesiologist in this case is very
helpful. We often use neosynephrine or phenylephrine when an elevated blood pressure is warranted
(e.g., in the setting of subarachnoid hemorrhage and
vasospasm). When a lower blood pressure is ideal,
as in AVM embolization or balloon test occlusion, we
use labetalol or nicardipine boluses or drips.
In a patient with CHF, we try to limit the amount
of IV fluids administered during the procedure. A
central line may be helpful in assisting with fluid
balance, and in very ill patients a Swan-Ganz catheter may be required. We routinely monitor cardiac
enzymes, EKG, BNP, and CXR postprocedure.
For a stenting procedure, we premedicate 1 week
prior to the procedure with aspirin and/or clopidogrel. On the day of the procedure, we check platelet
function studies prior to the procedure to confirm a
therapeutic level. At our institution we use the VerifyNow Aspirin and VerifyNow IIb/IIIa tests (Accumetrics). If the level is not adequate, then a loading dose
is given or a GPIIb-IIIa inhibitor medication, such as
abciximab (Reopro, Janssen Biotech, Inc., Horsham,
PA) or eptifibatide (Integrilin, Millennium Pharmaceuticals, Inc., Cambridge, MA), is given to bridge the
patient until the oral medications are therapeutic.

Diabetes Mellitus
There are a few specific measures that should be
addressed in a patient with DM. Metformin, a diabetic
medication, has a well-documented association with
lactic acidosis and worsening of renal function secondary to iodinated contrast media. Metformin may be
taken the morning of angiography; however, it should
be held for 48 hours after angiography.9 Secondly,
patients are often asked not to eat 8 hours prior to
angiography so that conscious sedation may be administered safely. Patients with DM should have a blood
glucose finger stick prior to angiography. If necessary,
the patient may require subcutaneous or intravenous
insulin to maintain glucose control during and after the
procedure. If there is any concern of decreased renal
function in a patient with DM, we suggest following
the precautions discussed in the CIN section.

Pregnancy presents an increased risk of neurological events, including stroke,18 subarachnoid hemorrhage,18,19 aneurysm rupture,18,19 AVM rupture,18 and
venous sinus thrombosis.18 All of these conditions

10 Physiological Considerations
potentially require cerebral angiography. Expectant families, however, will likely have trepidation
regarding radiation exposure to the fetus. Radiation
exposure is inversely related to the distance from the
radiation source by a power of 2.20 Although a lead
shield will help to prevent external radiation scatter,
internal scatter within the mother cannot be prevented. Therefore, fetal exposure can be determined
by the quantity of radiation, distance of the radiation
source from the fetus, and internal scatter of radiation within the mother.20
Fetal effects of radiation can include growth retardation, microcephaly, mental retardation, and childhood tumors. During the first 14 days of gestation
there is a risk of prenatal death. It is, however, not
increased from the risk of spontaneous prenatal death
during the first trimester.20 During gestational weeks 1
through 8, growth retardation may be seen with fetal
doses of 20 to 25 rads.20 The most vulnerable time
for a fetus to receive radiation is between gestational
weeks 8 and 15,20 due to the effects on neurodevelopment. If a fetus receives more than 10 rad during
this period, the fetus may suffer from microcephaly
or mental retardation.20 It is approximated that there
will be a decrease in intelligence quotient of 25 points
for every 100 rads20 the fetus receives. Another concern of fetal radiation is the increased risk of childhood tumors. The general consensus is that a fetal
dose of less than 5 rads does not increase the risk of
childhood tumors.2022 A phantom study conducted by
Marshman et al19 found that the fetal dose of radiation
from a relatively prolonged embolization procedure
is 4.9 millisieverts (mSv), which is equal to 0.49 rads.
This study indicates that cerebral angiography can
be done with minimal harm to the fetus. We do not,
however, advocate radiation in pregnancy, except in
extreme, life-threatening circumstances.
Another concern of cerebral angiography during
pregnancy is the risk of iodinated contrast material to
the fetus. Iodinated, nonionic contrast material does
cross the placenta to the fetus, which can potentially
result in decreased fetal thyroid function.23 It is now
standard of care to perform serological thyroid function tests on all infants in whom maternal iodinated
contrast was given.23

Children are susceptible to strokes; however, the
cause varies from the typical atherosclerotic plaque
that affects adults.24 Children often present with
stroke due to sickle cell disease, moyamoya disease,
acquired or genetic cardiac abnormalities, cerebral
vasculopathy, cerebral vasculitis, metabolic disorders, or hypercoagulable disorders.3,24

Specific considerations relating to the pediatric

population must be taken into account. First, volume status varies based on the weight and age of
the child. The pediatric critical team or neonatology
team should be consulted regarding the quantity of
fluid the child may receive during the angiogram. For
instance, the treatment of sickle cell disease involves
aggressive hydration, and treatment of hypotension
and hypoxia, with or without an exchange transfusion.24 Patients with vein of Galen malformations
(VOGM) can present with CHF, in which case fluid
balance is key in management. Monitoring plasma
BNP has been reported as an effective method of
monitoring and documenting progress in the treatment of VOGM-associated CHF.25 It is important to
monitor the quantity of both IV and intra-arterial
fluids infused. Second, general anesthesia is often
required. The risk of arterial injury is greater in an
uncooperative child, and the use of general anesthesia allows a more rapid and thorough examination to
be performed.3
An additional consideration is the small caliber of
the arterial vessels. This is particularly true during
the first year of life.3 Smaller sheaths and catheters
should be used. Complications associated with catheter angiography in the pediatric population include
damage to the blood vessel catheterized (usually the
femoral artery), catheter-induced dissection of the
cervicocranial vessels, thromboembolic events, and
allergic reactions to the contrast media.3

Planning is key in preventing angiography-related
complications, such as contrast allergies, CIN, chronic
renal insufficiency, DM, hypertension, and CHF. Pregnant and pediatric patients and their specific considerations must be taken into account.

A thorough preadmission evaluation, including
history, physical exam, and appropriate tests,
is the cornerstone of morbidity prevention.
CIN is the third leading cause of acute renal
Pediatric patients require general anesthesia
during cerebral angiography to prevent motion, arterial injury, and appropriate management of fluid administration.


80 Part II Perioperative Care

Premedicate patients with a known contrast
allergy with oral prednisone 50 mg 24, 12, and
1 hour prior to the procedure and oral diphenhydramine 50 mg 1 hour prior to the procedure.
Stop nephrotoxic medications prior to the angiogram: NSAIDs, metformin, aminoglycosides,
angiotensin-converting enzyme inhibitors,
diuretics, and amphotericin B.
Check platelet inhibition prior to stenting
procedures, even if the patient was placed on
an antiplatelet medication as an outpatient. If
the level is low, give either a loading dose of
clopidogrel or an IV GPIIb-IIIa inhibitor.

If a patient develops CIN, aggressively hydrate
the patient with either normal saline or sodium
bicarbonate, serially monitor renal function, and
consult a nephrologist for possible hemodialysis.
If you are planning on placing a stent but the
patient is not on antiplatelet therapy, then give
a loading dose of clopidogrel or an IV GPIIb-IIIa
If a patient develops CHF, serially monitor cardiac enzymes, BNP, and chest X-ray. Additionally,
intravascular monitoring via triple-lumen catheter or Swan-Ganz catheter may be required.
Treat with gentle diuresis and fluid restriction.

1. Varma MK, Price K, Jayakrishnan V, Manickam B, Kessell G. An-

aesthetic considerations for interventional neuroradiology. Br

J Anaesth 2007;99(1):7585 PubMed
2. Armonda RA, Vo AH, Dunford J, Bell RS. Anesthesia for endovascular neurosurgery. Neurosurgery 2006;59(5, Suppl
3):S66S76, discussion S3S13 PubMed
3. Roach ES, Golomb MR, Adams R, et al; American Heart Association Stroke Council; Council on Cardiovascular Disease in the
Young. Management of stroke in infants and children: a scientific
statement from a Special Writing Group of the American Heart
Association Stroke Council and the Council on Cardiovascular
Disease in the Young. Stroke 2008;39(9):26442691 PubMed
4. Gleeson TG, Bulugahapitiya S. Contrast-induced nephropathy.
AJR Am J Roentgenol 2004;183(6):16731689 PubMed
5. ten Dam MA, Wetzels JF. Toxicity of contrast media: an update.
Neth J Med 2008;66(10):416422 PubMed
6. Namasivayam S, Kalra MK, Torres WE, Small WC. Adverse reactions to intravenous iodinated contrast media: a primer for
radiologists. Emerg Radiol 2006;12(5):210215 PubMed
7. Tramr MR, von Elm E, Loubeyre P, Hauser C. Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systematic review. BMJ 2006;333(7570):
675681 PubMed
8. Greenberger PA, Patterson R. The prevention of immediate
generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol 1991;87(4):867872 PubMed

9. Massicotte

A. Contrast medium-induced nephropathy:

strategies for prevention. Pharmacotherapy 2008;28(9):
11401150 PubMed
10. Pannu N, Wiebe N, Tonelli M; Alberta Kidney Disease Network. Prophylaxis strategies for contrast-induced nephropathy. JAMA 2006;295(23):27652779 PubMed
11. Katzberg RW, Morris TW, Schulman G, et al. Reactions to
intravenous contrast media. Part II: Acute renal response in
euvolemic and dehydrated dogs. Radiology 1983;147(2):
331334 PubMed
12. Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast
media-associated nephropathy: randomized comparison of 2
hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162(3):329336 PubMed
13. Brar SS, Shen AY, Jorgensen MB, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced
nephropathy in patients undergoing coronary angiography: a
randomized trial. JAMA 2008;300(9):10381046 PubMed
14. Hogan SE, LAllier P, Chetcuti S, et al. Current role of sodium
bicarbonate-based preprocedural hydration for the prevention of contrast-induced acute kidney injury: a meta-analysis.
Am Heart J 2008;156(3):414421 PubMed
15. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrastinduced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291(19):23282334 PubMed
16. Lee PT, Chou KJ, Liu CP, et al. Renal protection for coronary angiography in advanced renal failure patients by prophylactic
hemodialysis. A randomized controlled trial. J Am Coll Cardiol
2007;50(11):10151020 PubMed
17. Rosamond W, Flegal K, Friday G, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics2007 update: a report
from the American Heart Association Statistics Committee and
Stroke Statistics Subcommittee [published correction appears
in Circulation. 2010 Jul 6;122(1):e9 : Kissela, Bret corrected to
Kissela, Brett]. Circulation 2007;115(5):e69e171 PubMed
18. Witlin AG, Friedman SA, Egerman RS, Frangieh AY, Sibai BM.
Cerebrovascular disorders complicating pregnancybeyond
eclampsia. Am J Obstet Gynecol 1997;176(6):11391145, discussion 11451148 PubMed
19. Marshman LA, Aspoas AR, Rai MS, Chawda SJ. The implications of ISAT and ISUIA for the management of cerebral aneurysms during pregnancy. Neurosurg Rev 2007;30(3):177180,
discussion 180 PubMed
20. Ratnapalan S, Bentur Y, Koren G. Doctor, will that x-ray harm
my unborn child? [published correction appears in CMAJ.
2009 Apr 28;180(9):952: Dosage error in article text]. CMAJ
2008;179(12):12931296 PubMed
21. Marshman L, Aspoas R, Rai M, Chawda S. The implications of
ISAT and ISUIA for the management of cerebral aneurysms
during pregnancy. Neurosurg Rev 2008;31:353354 PubMed
22. McCollough CH, Schueler BA, Atwell TD, et al. Radiation exposure and pregnancy: when should we be concerned? Radiographics 2007;27(4):909917, discussion 917918 PubMed
23. Webb JA, Thomsen HS, Morcos SK; Members of Contrast
Media Safety Committee of European Society of Urogenital
Radiology (ESUR). The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol 2005;
15(6):12341240 PubMed
24. DeVeber G, Kirkham F. Guidelines for the treatment and
prevention of stroke in children. Lancet Neurol 2008;7(11):
983985 PubMed
25. Tan LH, Johnson BA, Mawad ME, Chang AC. Neonate with
vein of Galen malformation and heart failure: serial changes
in plasma B-type natriuretic peptide following endovascular
embolization. Pediatr Cardiol 2006;27(2):276278 PubMed

Part III

Angiographic Fundamentals


Angioanatomy of the Head and Neck

Jacqueline Bello and David W. Minsky

ies (SCA and CCA). The second vessel off the aortic
arch, the left CCA, arises distal to the brachiocephalic
trunk. It ascends anterolateral to the trachea and
anteromedial to the internal jugular vein. At the level
of the upper thyroid cartilage, the left CCA branches
into the left internal and external carotid arteries.
The left subclavian artery, typically the final arch
vessel, arises just distal to the left CCA. It ascends
into the neck, passing lateral to the medial border of
the anterior scalene muscle, before turning laterally
to supply the left upper extremity. The left and right
subclavian arteries give rise to the left and right vertebral arteries (VAs), respectively1,2 (Fig. 11.1).

The Arterial System

The aortic arch, the second major segment of the
thoracic aorta, gives rise to the great vessels, the
three major arteries that supply the upper extremities, head, and neck. The first branch off the arch is
the brachiocephalic artery, also called the innominate artery. It is the largest branch, arising from the
superior convexity of the arch, ascending anterior to
the trachea. At the level of the right sternoclavicular
joint, the brachiocephalic artery bifurcates into the
right subclavian and right common carotid arter-

Fig. 11.1 Normal arch branching pattern. (a) Catheter angiography and (b) computed tomographic angiography, reconstructed
image demonstrate the normal branching pattern of the aortic arch in two different patients.


84 Part III Angiographic Fundamentals

The classic arch configuration described is the
most common branching pattern, seen in up to
80% of cases. The second most common variant of
aortic arch branching occurs in 13% of cases, when
the left CCA shares a common origin with the brachiocephalic trunk, also known as a bovine arch
(Fig. 11.2). The term bovine arch is actually a misnomer; the branching pattern it describes is rarely
found in cattle.3 It has been suggested that this term
may have originated because of the gross similarity
between the appearance of this branching pattern
and cattle horns.4 Current classification schemes
make use of more anatomical descriptions of the different branching patterns to avoid use of such misnomers. As a less common variant, the left CCA may
arise from the brachiocephalic trunk (9%) distal to
its origin. Even more rare is the left brachiocephalic
trunk, when the left CCA and the left subclavian
artery share a common origin (12%).2,4 Occasionally, the left VA arises directly from the aortic arch
(0.51%)5 (Fig. 11.2).

Arch anomalies are rare and result from aberrant

development of the embryonic pharyngeal arch system. The most common congenital arch anomaly is a
left aortic arch with aberrant right subclavian artery
(12%) (Fig. 11.3). In this setting, the right subclavian
artery arises distal to the left subclavian artery as the
last aortic branch. It courses cephalad, usually behind
the trachea and esophagus.6 A diverticulum of Kommerell, focal dilatation of the proximal aberrant subclavian artery, is seen in 60% of cases.7 The right aortic
arch is a less common anomaly seen in 0.1 to 0.2% of the
population. When it is associated with mirror image
great vessel branching, there is a 98% incidence of congenital heart disease. In the setting of a right aortic arch
without mirror image branching and with an aberrant
left subclavian artery, the incidence of congenital heart
disease is significantly lower (10%). This variant is most
notable for forming a true vascular ring.8 The least
common of the arch anomalies is the double aortic
arch, highly associated with a complete vascular ring
and rarely associated with congenital heart disease.

Fig. 11.2 Bovine arch and left vertebral artery origin from arch. (a) Two-dimensional time-of-flight magnetic resonance angiogra-

phy of the aortic arch and (b) catheter angiography demonstrate the left vertebral artery (solid arrow) arising directly from the aortic
arch in two different patients. Incidentally noted is a common origin (asterisk) of the brachiocephalic trunk and the left common
carotid artery, a bovine arch, in both patients.

11 Angioanatomy of the Head and Neck

Fig. 11.3 Aberrant right subcavian artery. (a) Catheter

angiography, (b) axial contrast-enhanced computed tomography, and (c) three-dimensional reconstruction from computed tomography angiography in three different patients
demonstrate anomalous origin of the right subclavian artery
(asterisk) from the aortic arch, distal to the left subclavian artery origin, passing posterior to the esophagus.

The extracranial circulation consists of the CCAs

and their branches, the internal and external carotid
arteries, and the VA. The CCAs are paired vessels
located anteriorly within the neck. In the majority of cases, the right CCA arises at the bifurcation
of the brachiocephalic artery, whereas the left CCA
arises directly off of the aortic arch just distal to the
brachiocephalic trunk. Each CCA courses superiorly
within the carotid sheath, accompanied posterolaterally by the internal jugular vein and the vagus
nerve. The CCAs generally bifurcate at the C3C4
level; however, the bifurcation may occur anywhere
from C1 to T21 (Fig. 11.4).

Each internal carotid artery (ICA), a terminal
branch of the CCA, supplies the anterior circulation
of the brain. Classically, the ICA is divided into four
segments: cervical, petrous, cavernous, and supraclinoid. However, a more recent classification system9
based on anatomical compartments divides it into
seven segments: cervical (C1), petrous (C2), lacerum
(C3), cavernous (C4), clinoid (C5), ophthalmic (C6),
and communicating (C7). The cervical segment, the
only extracranial portion of the ICA, extends from
the common carotid bifurcation to the carotid canal
in the skull anterior to the jugular foramen. It has
no named branches. The remaining six segments


86 Part III Angiographic Fundamentals

has extensive anastomotic potential with the ECA.
In addition, it gives rise to the superior hypophyseal
artery. The ophthalmic segment extends distally to
just below the origin of the posterior communicating
artery. Finally, the communicating segment extends
from below the posterior communicating artery to
the bifurcation of the ICA into the anterior and middle cerebral arteries. Both the posterior communicating and the anterior choroidal arteries arise from
this segment (Fig. 11.5).
Anomalies of the ICA include an aberrant petrous
segment that courses more posterolaterally than

Fig. 11.4 Common carotid bifurcation. Reconstructed image from computed tomography angiography demonstrates
normal common carotid bifurcations bilaterally (solid arrows)
at the C3C4 level.

are defined by location. The petrous segment is contained within the carotid canal of the temporal bone.
It gives off the vidian artery, the artery of the pterygoid canal, which anastomoses with the external
carotid artery (ECA), as well as the caroticotympanic
artery, which supplies the middle ear. The lacerum
segment extends from the petrous apex above the
foramen lacerum, toward the cavernous sinus. The
cavernous segment is surrounded by the venous
cavernous sinus and has two named branches: the
meningohypophyseal artery and the inferolateral
trunk. This latter branch anastomoses with the ECA
through the foramina rotundum, spinosum, and
ovale. The clinoid segment is a short segment of the
ICA with no named branches. It is the last extradural
segment before the carotid enters the subarachnoid
space near the anterior clinoid process. The ophthalmic segment gives off the ophthalmic artery, which

Fig. 11.5 Ophthalmic, posterior communicating artery
(PCoA), anterior choroidal arteries. Lateral projections from a
catheter angiogram. (a) Early and (b) later-phase images demonstrate the normal supraclinoid internal carotid artery branches: (1) ophthalmic artery, (2) PCoA, (3) anterior choroidal artery.

11 Angioanatomy of the Head and Neck

usual, presenting as a retrotympanic pulsatile mass,
which should not be mistaken for a cholesterol granuloma or a glomus tympanicum tumor.10 Recognition
of this anomaly avoids disastrous consequences due
to inappropriate intervention. Persistent embryonic
anastomoses between the internal carotid and basilar arteries are rare anatomical variants that provide
additional routes of collateralization between the
anterior and posterior circulations. The most common of these anastomoses is the persistent trigeminal artery, an anastomosis between the cavernous
ICA and the basilar artery. Less common carotid
basilar connections include the persistent hypo-

glossal artery, persistent otic artery, and proatlantal

intersegmental artery11,12 (Fig. 11.6).
The ECA, the smaller of the two terminal branches
of the CCA, supplies most of the extracranial soft tissues of the head and neck. At its origin, it is usually
anteromedial to the ICA. The branches of the ECA
are the superior thyroid, ascending pharyngeal, lingual, facial, occipital, and posterior auricular, and
two terminal branches, the superficial temporal and
internal maxillary arteries13 (Fig. 11.7). An impor-

Fig. 11.7 External carotid artery circulation. Lateral pro-

Fig. 11.6 Persistent embryonic anastomoses. (a) Diagram illustrating various persistent embryonic anastomoses between
the anterior and posterior circulations. (b) Lateral view from an
internal carotid artery injection demonstrates the most common of these, a persistent trigeminal artery (solid arrow) between the internal carotid and basilar arteries.

jection from a common carotid catheter angiogram demonstrates the normal branching pattern of the external
carotid artery. Occlusion of the internal carotid artery is
noted, secondary to chronic dissection (solid arrow). External branches illustrated include S, superior thyroid; L,
lingual; F, facial; A, ascending pharyngeal; O, occipital;
M, internal maxillary; T, superficial temporal. The middle
meningeal artery (mm) is noted arising from the internal
maxillary artery coursing through the foramen spinosum
(open arrow).


88 Part III Angiographic Fundamentals

Fig. 11.8 Anomalous origin of the ophthalmic artery from the middle meningeal artery. (a) Common carotid artery injection,
lateral projection, fails to opacify the ophthalmic artery from the internal carotid artery. (b, c) External carotid artery injections, with
and without subtraction, demonstrate the ophthalmic artery (solid arrows) arising from the middle meningeal artery (open arrows).

11 Angioanatomy of the Head and Neck

tant branch of the internal maxillary artery is
the middle meningeal artery, which enters the
skull base through the foramen spinosum before
it branches into anterior and posterior divisions.
Rarely, the ophthalmic artery may arise from the
middle meningeal artery.
The ECA has numerous anastomoses with the
ICA, as well as the VA, which in the setting of ICA
and VA stenosis or occlusion may serve as important sources of collateral blood flow. For the anterior circulation, these include collateral flow to
the ophthalmic segment of the ICA from the facial
artery and the distal, sphenopalatine, segment of
the internal maxillary arteries through the ophthalmic artery (Figs. 11.8 and 11.9). The internal
maxillary has the ability to further collateralize
with the cavernous ICA via the inferolateral trunk
through the middle meningeal artery. Less commonly, the cavernous ICA can receive collateral
blood flow through the anterior division of the
ascending pharyngeal artery.14,15 The occipital
artery and the posterior division of the ascending
pharyngeal artery are important collateral routes
from the external circulation to the VA (Fig.
11.10). Knowledge of these potential pathways is
important for understanding disease processes as
well as for endovascular treatment planning.
The VAs are the first and largest branches
of the subclavian arteries, supplying the spinal
cord, muscles of the neck, and posterior circulation of the brain. They may be divided into four
anatomical segments. The first segment (V1)
arises from the subclavian artery and courses
posterosuperiorly to enter the C6 transverse
foramen. It gives off cervical muscular and spinal branches. The second segment (V2) ascends
through the C6 to C1 transverse foramina and

Fig. 11.9 External carotid artery (ECA) to internal carotid artery

(ICA) collaterals. (a, b) Catheter angiography, lateral projections,

demonstrates retrograde filling of the intracranial ICA (asterisk) via
sphenopalatine segment collaterals (solid arrows) from the internal
maxillary artery to the ophthalmic artery (open arrows) in two different patients with proximal ICA occlusion.


90 Part III Angiographic Fundamentals

Fig. 11.10 Extracranial collaterals: vertebral artery to the

external carotid artery. Lateral projection, vertebral injection,
reveals muscular branch anastomoses (open arrow) between
the vertebral (solid arrow) and occipital (asterisk) arteries.

gives rise to the anterior meningeal artery, as well

as muscular and spinal branches (Fig. 11.11). After
exiting the C1 foramen, the third segment (V3) turns
sharply laterally to course around the lateral mass
of C1 before traveling anterosuperiorly to pierce the
dura at the foramen magnum. The posterior meningeal artery arises from this third segment. The
fourth segment (V4) ascends through the foramen
magnum, coursing superomedially behind the clivus, and unites with the contralateral VA to form the
basilar artery at or near the pontomedullary junction. In addition to providing anterior and posterior
spinal arteries, as well as perforating branches to the
medulla, this fourth segment gives rise to the posterior inferior cerebellar artery (PICA). The basilar
artery courses superiorly within the prepontine cistern. It gives rise to the anterior inferior cerebellar
arteries (AICAs), superior cerebellar arteries (SCAs),
as well as numerous pontine and midbrain perforating branches. It bifurcates into its terminal branches,
the posterior cerebral arteries (PCAs), within the
region of the dorsum sellae.16
Variants of the vertebrobasilar system are not
uncommon. The VAs vary in size; dominance of one
side, predominantly left, is the norm. As previously
described, an aortic arch origin of the left VA may
occur. Posterior circulation variations in course and
branching patterns are common, including AICA/
PICA common trunk (Fig. 11.12), fenestrated or
duplicated vessels (most commonly SCA) (Figs. 11.13

Fig. 11.11 Vertebral artery. Reconstructed image from

computed tomography angiography demonstrates the normal course of the vertebral arteries entering the C6 transverse
foramina bilaterally.

and 11.14), and embryonic carotidbasilar anastomoses already described17 (Fig. 11.6). Rarely, the vertebral artery may terminate in a PICA (Fig. 11.15).
The circle of Willis (COW), originally described
by Dr. Thomas Willis in 1664, comprises the central
anastomotic pathway of the brain. It is a vascular
ring, more appropriately described as a polygon, and
is the major source of collateral blood flow within
the brain (Fig. 11.16). It is composed of paired ICAs,
the horizontal segments (A1) of the anterior cerebral
arteries (ACAs), the anterior communicating artery
(ACoA), paired posterior communicating arteries
(PCoAs), the basilar artery, and the horizontal segments (P1) of the PCAs. The COW lies above the
sella in the suprasellar cistern just below the diencephalon. The hypothalamus, infundibular stalk, and
optic chiasm are bordered by the COW. Important
anatomical relationships include the horizontal ACA

11 Angioanatomy of the Head and Neck

Fig. 11.12 Anterior inferior cerebellar arteryposterior inferior cerebellar artery (AICAPICA) common trunk. Left vertebral angiogram, anteroposterior projection, demonstrates a
common trunk (solid arrow) of the left AICA and PICA arising
from the basilar artery. Independent origins of the right AICA
(white open arrow) and PICA (black open arrow) are noted.

segments coursing above cranial nerve (CN) II (the

optic nerves), the PCoAs coursing below the optic
tracts and above CN III (the oculomotor nerves), and
the oculomotor nerves coursing between the PCAs
and SCAs18 (Fig. 11.17).
Many important perforating branches arising from COW supply the central base of the brain,
including the hypothalamus, internal capsule, optic
tracts, thalamus, and midbrain. The anterior circulation perforators, or lenticulostriate arteries, arise
from the horizontal segments of the ACA and MCA.
The medial lenticulostriate arteries and recurrent
artery of Huebner arise from the A1 segments. The
lateral lenticulostriate arteries arise from the M1
segments. The posterior circulation perforators are
known as the thalamostriate or thalamoperforators. The anterior thalamoperforators arise from the
PCoAs, whereas the posterior thalamoperforators
and thalamogeniculate arteries arise from the basilar artery and P1 segment of the PCAs (Fig. 11.18).
Additional perforating arteries supplying the optic
chiasm, hypothalamus, corpus callosum, and fornix
arise from the ACoA.18
Rarely is the COW seen in its entirety, and anatomical variations are the rule. Absence, or hypopla-

sia, of one or more of the segments (PCoA, ACoA, or

horizontal ACA or PCA segment) is fairly common,
often limiting collateral flow in cases of large vessel
occlusion. An isolated MCA occurs in the setting of
an absent A1 segment and absent PCoA (Fig. 11.19).
A not uncommon variant is the fetal origin of the
PCA from the ICA. In this scenario, there is an absent
P1 segment of the PCA, and the PCoA appears similar in caliber to the ipsilateral PCA19 (Fig. 11.20). True
anomalies are rare and are often associated with an
increased risk of aneurysm formation due to altered
flow dynamics (Fig. 11.21). A single (azygous) ACA
can be seen in association with holoprosencephaly.
Although exceedingly rare, infraoptic origin of the
ACA has been described, and recognition of this
anomaly is vital for presurgical planning.
The ACA, a midline landmark, is divided into three
segments. As previously described, the horizontal,
or precommunicating segment (A1), courses above
the optic nerve and connects to the contralateral A1
segment via the ACoA. The vertical, or postcommunicating segment (A2), courses superiorly within the
interhemispheric fissure, around the genu of the corpus callosum. It gives rise to two cortical branches:
the orbitofrontal and frontopolar arteries. Lastly, the
distal segment (A3) courses posteriorly under the
free margin of the falx cerebri before dividing into
the pericallosal and callosomarginal arteries.20 As
discussed earlier, variants and anomalies of the anterior circulation are not uncommon, and as a result of
these variants, the ACoA is a common site for aneurysm formation (Fig. 11.21).
The MCA, the larger of the two terminal branches
of the ICA, is composed of four segments. The horizontal segment (M1) lies lateral to the optic chiasm
and bifurcates just before the sylvian fissure, distal
to the origin of the anterior temporal artery. There is
high variability within the branching pattern of the
MCA. Early M1 bifurcation may occur, or, not uncommonly, a distal origin of the anterior temporal artery
may result in a trifurcation (Fig. 11.22). Multiple
insular branches (M2) arise from the postbifurcation trunks, course superiorly, and subdivide over
the surface of the insular cortex. The opercular segments (M3) exit the sylvian fissure and give rise to
the cortical segments (M4), which ramify over the
surface of the brain. The cortical branches are named
according to their vascular distribution (angular a.,
temporo-occipital a., posterior temporal a.).21
The PCAs, terminal branches of the basilar artery,
also consist of four segments. Extending laterally from
the basilar bifurcation, the precommunicating segment (P1) courses above the oculomotor nerve to unite
with the PCoA. The ambient segment (P2) lies above
the tentorium, paralleling the basal vein of Rosenthal,
curving around the midbrain within the ambient cistern. It gives rise to both the medial and the lateral
posterior choroidal arteries. In addition, the poste-


92 Part III Angiographic Fundamentals

Fig. 11.13 Fenestrated vessels. Fenestrated arteries are seen in

three different patients. (a) Three-dimensional time-of-flight magnetic resonance angiography of the circle of Willis (COW) demonstrates
fenestration (solid arrow) of the A1 segment of the left anterior cerebral artery (ACA). (b) Catheter angiography, internal carotid artery
(ICA) injection in an anteroposterior (AP) projection, demonstrates
fenestration (solid arrow) of the right carotid terminus. (c) Catheter
angiography, left vertebral artery injection in an AP projection, demonstrates fenestration (solid arrow) of the basilar artery below the superior cerebellar artery origins.

rior temporal artery is fed by the ambient segment,

which serves as a potential collateral pathway with
the anterior temporal arterya branch of the MCA.
As the name implies, the quadrigeminal segment (P3)
is a short segment within the quadrigeminal cistern.
Finally, the calcarine segment (P4) terminates within
the calcarine fissure.19 The distal segment of the PCA
also gives rise to the splenial artery. Variants, such as

fetal origin of the PCA and persistent carotidbasilar

anastomoses, have already been described.
Although the COW serves as the main route of
collateral circulation to the brain, many additional
pathways exist to provide cerebral blood flow when
primary channels fail. The ophthalmic artery provides
a route for extracranial to intracranial blood supply
in the setting of ipsilateral ICA occlusion. Secondary

11 Angioanatomy of the Head and Neck

Fig. 11.14 Duplicated superior cerebellar artery (SCA). (a) Anteroposterior projection of a LV catheter angiogram and (b) coronal
T2-weighted magnetic resonance imaging scan demonstrate duplication of the SCAs (solid arrows).

Fig. 11.15 Vertebral artery (VA) terminating as the posterior inferior cerebellar artery (PICA). Three-dimensional time-of-flight
magnetic resonance angiography demonstrates the right VA terminating as the PICA (solid arrow).


94 Part III Angiographic Fundamentals

Fig. 11.17 Important anatomical relations of the circle of

Willis. Coronal T2-weighted magnetic resonance imaging
demonstrates the oculomotor nerves (solid arrows) coursing
between the posterior cerebral arteries and superior cerebellar

transdural and transosseous communications

(Fig. 11.26). Moyamoya (puff of smoke) describes a
perforator collateral pathway in patients with supraclinoid carotid occlusion (Fig. 11.27). The friability of
these vessels predisposes them to bleed.23
Fig. 11.16 Circle of Willis. (a) Three-dimensional time-of-

flight magnetic resonance angiography and (b) computed

tomography angiography, reconstructed images demonstrate
complete circle of Willis in two different patients.

collateral pathways such as leptomeningeal anastomoses provide communication between the distal
cortical segments of the major cerebral vessels (ACA,
MCA, PCA) (Fig. 11.23) over the cerebral hemispheres
and between the cerebellar vessels (SCA and PICA)
(Fig. 11.24). Additional secondary collaterals occur
in deeper locations, including the splenial artery
(branch of PCA) to pericallosal artery (branch of ACA)
(Fig. 11.25), and anterior temporal artery (branch of
MCA) to posterior temporal artery (branch of PCA).22
Less commonly encountered collateral routes include

The Venous System

The dural sinuses are large, endothelial-lined venous
channels that are contained within the outer (periosteal) and inner (meningeal) dural layers. The sinuses
receive blood from both the internal and external
cerebral veins, thin-walled, valveless structures that
cross the subarachnoid space to enter the sinuses.
The sinuses contain the arachnoid granulations, an
extension of the subarachnoid space, which serve
to transmit cerebrospinal fluid back to the venous
The superior sagittal sinus (SSS) courses posteriorly in the midline along the inner calvarial vault
at the superior margin of the falx cerebri. It receives
blood from superficial cortical veins, the largest of
which is known as the vein of Trolard. The SSS terminates at the torcular herophili, the venous sinus

11 Angioanatomy of the Head and Neck

Fig. 11.18 Anterior and posterior perforators. Catheter angiography (a) anteroposterior projection, anterior circulation, demonstrates lenticulostriate perforators from the carotid terminus, A1 and M1 segments (solid arrows). (b) Lateral projection, posterior
circulation, demonstrates thalamostriate perforators (solid arrows) from the Pcomm, basilar tip, and P1 segment of the posterior
cerebral artery. Also demonstrated in (a) is the anterior choroidal artery (open arrow) and in (b) the medial and lateral posterior
choroidal arteries (open arrow).

Fig. 11.19 Isolated middle cerebral artery (MCA). (a) Three-dimensional time-of-flight magnetic resonance angiography of the circle of Willis demonstrates absence of the left A1 and P1 arterial segments (asterisks) resulting in an isolated left MCA (solid arrow). (b)
Anteroposterior projection, right internal carotid artery angiogram, reveals an isolated right MCA (solid arrow) in a different patient.


96 Part III Angiographic Fundamentals

confluence. The inferior sagittal sinus (ISS) courses
along the inferior free margin of the falx cerebri. It
lies above the corpus callosum and terminates at the
falcotentorial apex, joining the vein of Galen (VOG)
to form the straight sinus. The VOG is formed by the
union of the paired internal cerebral veins (ICVs) and
basal veins of Rosenthal (BVRs). The ICVs are parallel
vessels that course below the splenium of the corpus
callosum and above the third ventricle. Each ICV is
formed by the union of the septal and thalamostriate

veins, the latter a marker for the foramen of Monro.

The sinus confluence, also known as the torcular
Herophili, is formed from the union of the SSS, the
straight sinus, and the paired transverse sinuses. The
transverse, or lateral, sinuses are contained between
the attachments of the tentorium to the calvarium.
They extend laterally from the torcular to the posterior aspect of the petrous bone. They are often asymmetric in size, the right transverse sinus usually being
larger than the left. The transverse sinuses receive

Fig. 11.20 Persistent fetal posterior cerebral arteries (PCAs). Anteroposterior (AP) projections of the (a) right and (b) left internal
carotid arteries (ICAs) demonstrate direct origins of the PCAs (solid arrows) from the ICAs bilaterally. This is confirmed by (c) AP and
(d) lateral posterior circulation injections, which demonstrate only infratentorial vascular opacification.

11 Angioanatomy of the Head and Neck

Fig. 11.21 Hypoplastic A1 with anterior communicating artery (ACoA) aneurysm. Catheter angiography of the (a) right internal
carotid artery (ICA) and (b) left ICA demonstrates an ACoA aneurysm (solid arrow) in the setting of a hypoplastic A1 segment (open
arrow) of the right anterior cerebral artery.

Fig. 11.22 Middle cerebral artery (MCA) variants. (a) Catheter angiography demonstrates trifurcation of the MCA (solid arrow).
(b) Three-dimensional time-of-flight magnetic resonance angiography shows the origin of the anterior temporal artery (open arrow)
prior to the right MCA bifurcation.


98 Part III Angiographic Fundamentals

Fig. 11.23 Cerebral leptomeningeal collaterals. Catheter angiography, anteroposterior projections, demonstrates anastomoses

(solid arrows) between the distal segments of (a) the left anterior cerebral artery to the middle cerebral artery (MCA) and (b) the
left posterior cerebral artery to the MCA in a patient with proximal left MCA occlusion.

Fig. 11.24 Cerebellar leptomeningeal collaterals. Vertebral artery injection, lateral projection, in (a) early and (b) later arterial
phases demonstrates collateralization between the distal segments of the superior cerebellar artery and posterior inferior cerebellar
artery (solid arrows).

11 Angioanatomy of the Head and Neck

Fig. 11.25 Secondary collaterals. Lateral projection, vertebral artery injection, in a patient with a frontal arteriovenous
malformation (asterisk) reveals collateral flow (solid arrow)
from the splenial branch of the posterior cerebral artery to the
pericallosal branch of the anterior cerebral artery.

the important vein of Labb, which constitutes the

major cortical venous drainage for the temporal lobe.
The sigmoid sinuses are the S-shaped continuation
of the transverse sinuses anteroinferiorly, which terminate as the internal jugular veins2426 (Fig. 11.28).
The cavernous sinuses, irregularly shaped venous
compartments immediately lateral to the sella turcica, are contained laterally by a thin dural wall.
They are bordered anteriorly by the superior orbital
fissures and posteriorly by the clivus. They contain
the cavernous segment of the ICA, CN VI (medially),
and CNs III, IV, V1, and V2 (laterally). They receive the
superior and inferior ophthalmic veins, a pathway
for extra- to intracranial communication, as well
as the sphenoparietal sinus; posteriorly, they connect with the petrosal sinuses and the clival venous
plexus. The right and left cavernous sinuses communicate via the anterior and posterior intercavernous
Anatomical variants and anomalies of the intracranial venous system are common. Absence of the
anterior portion of the superior sagittal sinus or an
off-midline course terminating in one of the transverse sinuses can occur. Absence or hypoplasia of
part or all of a transverse sinus frequently occurs.
Giant arachnoid granulations, seen on imaging as
ovoid cerebrospinal fluid filling defects within the
dural sinuses, must not be mistaken for pathology.
The classic anomaly of lambdoid-torcular inversion

is seen with the Dandy-Walker malformation. The

VOG malformation, a misnomer, is an arteriovenous
fistula between the deep choroidal arteries and the
median prosencephalic vein of Markowski. Sinus
pericranii is an abnormal connection between the
dural venous sinus and the extracranial veins.2528
Extracranial veins include the scalp, skull (diploic),
face, and neck veins. Scalp veins connect via emissary veins to the cranial dural sinuses. Diploic veins
are endothelial-lined channels within the diploic
spaces of the calvarium that communicate with
dural sinuses and meningeal veins. They may form
large venous lakes. Facial veins consist of the superficial and deep facial veins, the pterygoid plexus,
and the retromandibular vein. The superficial facial
vein receives tributaries from the orbit, lips, jaw, and
facial muscles. It begins at the angle between the eye
and the nose and courses across the masseter muscle, around the mandible, to join the internal jugular vein (IJV) at the level of the hyoid bone. The deep
facial vein receives blood from the deep face and
connects the facial vein with the pterygoid plexus.
The pterygoid plexus exists within the masticator
space and serves as a connection between the cavernous sinus, the clival venous plexus, and the face/
orbit tributaries. Lastly, the retromandibular vein is
formed from a union of the maxillary and superficial temporal veins. It lies within the parotid space,
superficial to the ECA but beneath the facial nerve,
and empties into the external jugular vein (EJV).
The EJV, formed by the junction of the retromandibular vein with the posterior auricular vein,
receives the greater part of the blood from the exterior of the cranium and the deep parts of the face. Its
size and extent are highly variable, coursing inferiorly
on the surface of the sternocleidomastoid muscle
and draining into the subclavian vein. The IJV, a
continuation of the sigmoid sinus, originates at the
jugular foramen at the skull base and courses inferiorly within the carotid space, deep to the sternocleidomastoid muscle. At its somewhat dilated origin
it is called the jugular bulb. The IJV unites with the
subclavian vein to form the brachiocephalic vein.
There is significant size variability between the IJVs,
the right usually being larger than the left. The IJV is
a common site of thrombosis because it is a major
access route for central venous catheter placement.
In summary, knowledge of the major extracranial and intracranial arterial and venous circulations
contributes to the interpretation of multimodality
angiography as well as cross-sectional imaging. Recognition of normal variants and anomalies is important in both diagnosis and treatment. Understanding
the intracranial collateral pathways and extracranial
to intracranial collateral pathways is critical to the
workup and treatment planning for acute stroke and
for both embolization and revascularization procedures. Accurate anatomical vascular definition is the
key to successful intervention.


100 Part III Angiographic Fundamentals

Fig. 11.26 Transdural and transosseous collaterals. In a patient with moyamoya disease, (a) vertebral artery injection, lateral projection, and (b) anteroposterior projection of the left external carotid artery demonstrate transdural (solid arrows) and transosseous
(open arrow) collaterals to the cerebral circulation.

Fig. 11.27 Moyamoya disease. (a) Cerebral angiography and (b) three-dimensional time-of-flight magnetic resonance angiography demonstrate a moyamoya pattern of striate collaterals (asterisks) secondary to internal carotid artery occlusion.

11 Angioanatomy of the Head and Neck

Fig. 11.28 Venous anatomy. (a, b) Anteroposterior and (c)

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torcular herophili (white asterisks), transverse sinus (black asterisk), vein of Trolard (black solid arrow), vein of Labb (white solid
arrow), straight sinus (double white solid arrows), vein of Galen
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embryology of anomalous arteries of the head and neck. AJR
Am J Roentgenol 1998;170(1):197203 PubMed
12. Woodcock RJ, Cloft HJ, Dion JE. Bilateral type 1 proatlantal arteries with absence of vertebral arteries. AJNR Am J Neuroradiol 2001;22(2):418420 PubMed
13. Osborn AG. The external carotid artery. In: Diagnostic Cerebral Angiography. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:329
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HG. Anomalies and variations of the middle cerebral artery:
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Cerebral Angiography
Kevin M. Cockroft

Unlike most other diagnostic radiological tests

requested or performed by physicians, cerebral angiography carries with it a small but significant risk of
debilitating neurological injury. As a result, the performance of diagnostic cerebral angiography must
be held to the highest standard in order to maintain the safety of the patient. This chapter reviews
the basic equipment and techniques for diagnostic
cerebral angiography, with particular emphasis on
complication avoidance and management. The postprocedural care of the access site and arterial closure
devices are also discussed.


The amount of heparin is optional and in many

instances may be eliminated entirely. Various diagnostic catheters exist, and the choice of catheter is
largely dependent on the users preference as determined by training and experience. Berenstein (BER),
Headhunter (H1H) and Bentson-Hanafee-Wilson
(JB1 or JB2) are all reasonable choices. However,
catheters that require shaping or forming within
the vasculature and excessive manipulation without
a guidewire, such as the Simmons catheters (SIM1,
SIM2), should be avoided for routine procedures.
For most adults, a 4 or 5 French catheter is adequate
for diagnostic procedures. Catheters should be navigated by means of a hydrophilic guidewire; 0.035
and 0.038 inches are common sizes.

Consumable Supplies


At most institutions, consumable supplies for cerebral angiography are packaged in a customized sterile
pouch. The degree of customization varies by institution, but several companies are available to create a
predetermined collection of supplies. The basic contents should include a large sterile drape with precut access areas for both femoral arteries, a typical
access needle, a closed (push-pull) flush system for
refilling syringes and disposing of liquid waste, standard polypropylene syringes for heparinized saline
flush, color-coded polycarbonate (clear) syringes for
contrast injection, a sharps collection device, gauze,
sterile prep solution and applicators, and additional
drapes and towels as necessary (Fig. 12.1ad).
Typically we perform our diagnostic and interventional procedures through a short (10 cm) sheath
(Fig. 12.1d). A long sheath (25 cm) may be useful in
obese patients or those with iliofemoral tortuosity.
We recommend the use of a continuous flush system
via microdrip-enabled pressure tubing (Boston Scientific, Natick, MA) for both the groin sheath and the
diagnostic catheter (Fig. 12.1b). At our institution we
add heparin to the saline flush solution (3,000 U/L).

This topic is covered in detail elsewhere. However,

the main prerequisites for optimal diagnostic studies include an angiography suite capable of obtaining biplanar digital subtraction images. The ability to
perform rotational angiography with three-dimensional reconstructions is an additional benefit, as
is the ability to create computed tomographic (CT)
scanlike images from rotationally acquired data.
Consumable supplies should be stored within the
room if possible so they are easily accessible.

The majority of diagnostic cerebral angiography procedures are performed via a transfemoral approach.
Typically, the common femoral artery is accessed
in the inguinal region. The right groin is used most
commonly because the majority of practitioners are
right handed. However, both inguinal regions should


104 Part III Angiographic Fundamentals

Fig. 12.1 Typical table setup for diagnostic cerebral angiogram. (a) Includes (1) two pressurized lines with microdrip chambers,
(2) closed saline flush/waste system (in this case attached to a small bowl, which may be used to keep small guidewires), (3) foam
container for sharps, (4) disposable sterile gowns, (5) large basin for guidewire (in this case on a ring stand with wheels to allow
convenient positioning), (6) sterile drape with prep solution and towels, (7) arterial access supplies (includes single-wall needle,
guidewire, sheath, and straight clamp). (b) Close-up photograph of pressurized lines shows (1) 1 L bag of heparin-saline (3,000
U/L) with air removed and (2) microdrip chamber. Note red tag on line to designate purpose of this particular line (in this case the
diagnostic catheter flush). Bag is pressurized to the redline300 mm Hg. (c) Close-up photograph of pressurized line to be connected to the diagnostic catheter shows (1) rotating hemostatic valve (RHV) (aka Tuohy connector); (2) soft, flexible, clear tubing
with flow-switch (Cook Medical, Bloomington, IN) for connection to injector tubing; and (3) roller clamp for control of flush rate.
Note three-way stopcock, which allows for easy switching between continuous flush and power injector as well as red tag on roller
clamp, again marking this as the line to the diagnostic catheter. (d) Close-up photograph of arterial access supplies. Items include
(from left to right), small guidewire for sheath insertion, 5F sheath with detachable hub, single-wall needle, no. 11 blade knife, 30
silk suture, adhesive dressing strips, and a straight clamp.

12 Cerebral Angiography
be prepped in the event that the right side is not
accessible. We recommend placing a pulse oximetry
probe on the great toe ipsilateral to the puncture site
to provide an early warning of potential limb hypoperfusion. If an intervention is contemplated, some
practitioners recommend puncturing the groin ipsilateral to the side of the cranial pathology, so that in
the unlikely event of both a femoral artery complication and an adverse intracranial event, the patient is
not left with two debilitated lower extremities. A single fluoroscopic image should be obtained to localize the femoral head. A straight clamp may be used
as a reference to mark the relationship between the
femoral head and the pulsation of the common femoral artery. Typically, this area is located approximately
two thirds of the way from the anterior superior iliac
crest to the pubic symphysis. We recommend a singlewall puncture using an 18-gauge needle placed via a
45-degree angle such that the arterial entry point is
directly over the femoral head. These steps will minimize the risks of retroperitoneal hemorrhage and
maximize the effectiveness of manual compression
for hemostasis at the conclusion of the procedure.
For angiography being performed while the patient
is anticoagulated or taking antiplatelet medication,
we recommend the use of a micropuncture kit (e.g.,
Transitionless Micropuncture Introducer Set, Cook
Medical, Bloomington, IN) for arterial access.
We use a groin sheath for all of our neuroendovascular procedures and highly recommend this
practice. A groin sheath is particularly useful in
elderly patients, those on anticoagulation, those with
scarring from previous angiograms, and patients in
whom a catheter exchange may be needed. Because
these conditions occur in a significant subset of neuroangiographic patients, we feel that the benefits of
consistently using a sheath outweigh the slight cost
and time savings of the bare catheter technique.
For patients undergoing a routine diagnostic procedure after which the sheath will be removed, we
secure the sheath with Steri-Strips (3M, St. Paul,
MN). In patients who are anticoagulated or particularly difficult to access, suturing the sheath in place
may be a wise choice. Once secure, the sheath should
be connected to a continuous pressurized flush of
heparin-saline. If continuous invasive blood pressure
monitoring is desired, the groin sheath may be transduced in the same manner as a radial arterial line.
For an ideal waveform and to allow for withdrawal
of blood specimens, a sheath one size larger than the
anticipated diagnostic catheter size should be used.

Arch Injection
At this point, the actual angiogram may begin, and
a decision must be made whether to perform an
aortic arch injection. Although it may be relatively

easy to place a pigtail catheter in the ascending

aorta, the extra effort, time, and contrast load, not
to mention the added risk of an embolic shower,
makes it inadvisable to perform this study as a routine. The two most common arch anomalies, origin
of the left common carotid artery (CCA) from the
brachiocephalic trunk (bovine arch) and origin of
the left vertebral artery directly from the arch, are
usually easily recognized. If occlusive disease of the
great vessel ostia is suspected or if vessel selection
proves to be particularly difficult, an arch injection can be performed. Most information is usually
gained from an oblique projection with the anteroposterior (AP) tube angled approximately 15 to 30
degrees to the left.

Vessel Selection
For the most part, we recommend proceeding initially with the operators diagnostic catheter of
choice. Some operators advocate the use of a J-wire
in the aortoiliac system to prevent the catheter from
entering unwanted branches on the way to the arch.
However, with experience it is usually possible to feel
the resistance of a small branch and adjust accordingly. Routine use of fluoroscopy from groin to chest
is not recommended given the cumulative exposure
to the left hand. Once in the aortic arch, there is no
definitive order to the catheterization of the vessels.
Some practitioners recommend starting the procedure with the vascular territory that harbors the suspected pathology in case the procedure needs to be
prematurely terminated; others prefer to leave this
area for last in anticipation of proceeding directly to
intervention, and still others will simply move from
right to left across the aortic arch.
The appropriate vessel origin is selected with the
catheter tip. Once the ostium of the vessel is engaged,
the hydrophilic wire can then be passed into the vessel. When entering the desired vessel it is important
to lead with the hydrophilic wire rather than with
the catheter itself. With current wire technology, the
technique of puffinginjecting small amounts of
contrast through the catheter via a handheld syringe
while steering and advancing the cathetershould
probably be avoided. When catheterizing the CCA for
the first time it is good practice to maintain the wire
and catheter below the CCA bifurcation until imaging
is obtained that confirms no significant atherosclerotic disease or stenosis at the carotid bulb. However, in some patients this is not possible, and given
the number of noninvasive tests usually performed
prior to angiography such precautions may not be
necessary. Once the CCA is catheterized, the cervical
carotid artery can be imaged either by biplane digital
subtraction angiography (DSA) or by using road mapping functionality. In either case, live fluoroscopy can


106 Part III Angiographic Fundamentals

be superimposed on the image and used for navigation into the internal or external carotid artery (ICA
or ECA). In cases where the selective catheterization
of both vessels is planned, it is usually preferable to
catheterize the ECA first with the aid of the saved
image because this vessel tends to be the harder one
to select. Later, the typically straighter pathway into
the ICA will facilitate selection of this vessel without
the need for the creation of an additional road map
or image overlay. In the ICA, catheter position at the
base of the C2 vertebral body on the lateral projection
or midmandible on the AP projection is usually high
enough to obtain adequate opacification of the intracranial vessels without undue reflux into the external
carotid system. When a catheter with an angled tip
is used, the catheter should be positioned such that
the tip follows the natural curve of the vessel. In the
ECA it may be difficult to achieve an adequate catheter position that allows for the opacification of all the
important branches. In many instances the ascending
pharyngeal artery or even the occipital artery may be
missed if the catheter is too high (or simply just high
enough to avoid popping out into the ICA during
injection). As a result, if ECA pathology is suspected,
additional cerebral DSA images should be obtained
with the catheter in the CCA. For the posterior circulation, some practitioners recommend routinely
obtaining a road map of the subclavian artery in
order to exclude stenosis or atherosclerotic disease at

the vertebral artery origin. We generally reserve road

mapping for instances where the vertebral artery is
not easily accessed or where the patients history or
preprocedural imaging studies suggest a high risk for
occlusive disease.

Standard Views
Standard views in an anterior projection vary according to the position of the petrous ridges relative to
the orbital rims, whereas in the lateral projection
variation is based on rotation about the long axis of
the patient. The anterior plane is often referred to
as AP (anteroposterior), although strictly speaking,
because the X-ray beam is generally coming from
behind the patient (i.e., posterior), the term PA (posteroanterior) is more correct. An initial image with
the petrous ridges positioned just below the orbital
rims affords a decent view of most of the intracranial
circulation (Fig. 12.2a). In a Townes view, the X-ray
tube is angled cranially, leaving the orbital rims low
relative to the petrous bone and thus enhancing the
view of the posterior circulation (Fig. 12.2b). In a
Waters view, on the other hand, the tube is angled
caudally and the petrous ridges are much lower than
the orbits. This view may be useful for straightening
loops of the ICA, clearing the anterior communicating region, and demonstrating the neck of an anterior

Fig. 12.2 Standard posteroanterior (PA) and Townes views during diagnostic cerebral angiography. (a) Initial PA view. Note superior orbital rims are positioned just above the petrous ridges. The image intensifier or flat panel detector is brought close to the
patient, and the X-ray beam is collimated so that the skull fills the field, scatter is reduced, and the image is as sharp as possible.
(b) PA Townes view. Note superior orbital rims are positioned below the petrous ridges, thus giving a good view of the posterior
circulation vasculature.

12 Cerebral Angiography

Fig. 12.3 The Waters projection demonstrates the neck of an anterior pointing basilar artery apex aneurysm. (a) Lateral digital

subtraction angiography image of a left vertebral artery injection demonstrating an anteriorly pointing basilar artery apex aneurysm. (b) Unsubtracted Waters view (note petrous ridges well below inferior orbital rims) showing the neck of the basilar artery apex
aneurysm seen in Fig. 11.3a (white arrow).

pointing basilar apex aneurysm (Fig. 12.3a, b).

In another commonly used eponymous view, the
Caldwell projection, the petrous ridges are superimposed on the orbital floor. Rotation about the long
axis of the patient leads to various oblique projections (Fig. 12.4).
Most modern biplane neuroangiography suites
now have the capability to perform rotational angiograms and create subsequent three-dimensional
reconstructions (Fig. 12.5a, b). Although these reconstructed images can be invaluable during treatment
planning, they should not be used as a substitute
for adequate vessel visualization during traditional
biplanar DSA. Unfortunately, the volume averaging
that occurs during reconstruction can either create
the appearance of abnormalities when none is in fact
present or, alternatively, can suggest that a vessel is
normal when a lesion is present.
When performing a diagnostic cerebral angiogram, the key is to obtain the number of views necessary to answer the question at hand. Proving a
patient has vasculitis of the central nervous system
may simply require the selection of a subset of vessels with only basic views. However, proving that a
patient with a subarachnoid hemorrhage does not
have an angiographically visible structural cause
for the hemorrhage may entail the injection of both

Fig. 12.4 Ipsilateral left anterior, transorbital oblique. Image

intensifier or flat panel detector is rotated off midline and positioned over the orbit ipsilateral to the artery to be injected,
in this case the left internal carotid artery (ICA) is injected, and
the gantry is rotated to the left. Note the ICA terminus appears
within the orbit.


108 Part III Angiographic Fundamentals

Fig. 12.5 Three-dimensional reconstructions created after rotational digital subtraction angiography. (a, b) Images show a saccular aneurysm arising from the dorsal internal carotid artery (ICA), just distal to the origin of the ophthalmic artery. Note the
gantry orientation is displayed in the upper right hand corner of the images. These images were created by a Siemens AXIOM Artis
(Siemens AG, Munich, Germany), using a 5 second spin at 1.5 frames per second with two-thirds strength Omnipaque-300 (GE
Healthcare) injected at a rate of 2.5 mL/s for 7 seconds.

internal carotid arteries, both common carotid arteries, both external carotid arteries, and both vertebral
arteries, with each injection frequently requiring
multiple projections.

Alternative Access
Various sites of arterial access have been used as
alternatives to the common femoral artery approach.
The most common alternatives are the radial artery
and the brachial artery. These access sites tend to be
reserved for patients with tortuous cervicothoracic
and/or iliofemoral vasculature, or when femoral access
is not possible secondary to local injury or disease.
Arm access may also be useful for intraoperative angiography when the patient is prone or almost prone.1
Spasm is a common complication of radial access.2
In contrast, the lack of major collateral vessels at the
level of the brachial artery makes a potentially limbthreatening complication much more of a concern
at this access site. Both techniques have the advantage of early ambulation and discharge without the
need for a closure device.24 From the arm, the vertebral arteries are usually relatively straightforward
to access. For other supra-aortic vessels, a reverse
angle catheter (Simmons or the like) may be helpful.4 Although not frequently necessary, for cerebral
angiography the ability to use alternative access sites
outside of the common femoral artery is an important skill for the neuroendovascular specialist.

Power Injector
The power injector is a useful tool for cerebral arteriography. Image acquisition is based on the principle
that the injected contrast is traveling faster than the
native blood flow. Although a typical hand injection generates a rate of approximately 5 mL per second, much higher flow rates can be achieved with
the power injector, thus leading to improved vessel
opacification (Table 12.1). Although no large series
has demonstrated a correlation between power
injector use and vascular/neurological complications,
there are practitioners who will not use the power
injector because of such concerns. In order to minimize the chances of such complications when using
a power injector, the catheter position and orientation, as well as vessel flow, should always be checked
prior to injection. This can be done by simply having
an assistant give a hand twist of the injector knob.
Employing a rate-rise (time required for the injection
to reach its full rate) setting of 0.2 to 0.4 seconds may
also be helpful.
The combination of the power injector and todays
high-resolution equipment allows the operator to
acquire excellent quality images with two-thirds or
even half-strength contrast. We routinely use twothirds strength contrast with a power injector for
the majority of our diagnostic and therapeutic neuroendovascular procedures. The risk of air emboli is
reduced because the integrity of the catheter system
does not have to be continually breached prior to DSA

12 Cerebral Angiography
Table 12.1 Typical injector settings for a cervically
placed catheter during diagnostic cerebral angiography
in nonstenotic normal vessels


Common carotid artery

(cervical imaging)

Common carotid artery

(cranial imaging)



Internal carotid artery

External carotid artery

Vertebral artery






Subclavian artery

Common femoral arteryb


For visualization of the ipsilateral vertebral artery, typically

performed with a blood pressure cuff inflated on the ipsilateral arm.
For purposes of closure device placement.

acquisition. Finally, using the injector has the added

benefit of allowing the operator to leave the room
during the acquisition and thus avoid the period of
greatest radiation exposure. We recommend using
a rate rise of 0.2 seconds routinely and increasing it
to 0.3 or 0.4 seconds in instances where the catheter
position may be tenuous or the catheter and vessel
size are closely matched.

good evidence to support shorter bed rest intervals.

In a 2003 study in the United Kingdom, Pollard et al5
randomized 750 nonanticoagulated patients undergoing elective 6 French cardiac catheterization via the
femoral artery to either 4.5 hours of bed rest with sit
up (raising head of bed to 60 degrees) after 4 hours
or 2.5 hours of bed rest with sit up after 1 hour. The
study found no significant difference in the incidence
of groin site bleeding, and there was only one pseudoaneurysm occurrence in each group. There was a
trend toward more frequent hematoma formation
in the 2.5 hour group (44 patients vs. 34 patients),
but this was not statistically significant (p = 0.146).
There were, however, significantly fewer complaints
of pain or discomfort in the 2.5 hour group.

Mechanical Compression
Proponents of mechanical compression devices cite
their noninvasive nature and the potential for reducing the operator time required to obtain hemostasis.
Examples of these devices include the CompressAR
(Instromedix, Inc., Rosemont, IL), a reusable mechanical clamp that compresses the artery via a disposable disc applied to the patient, and the FemoStop
(RADI Medical Systems, Inc., Reading, MA), a disposable inflatable device mounted to a plastic cradle and
secured to the patient with a belt. However, in spite
of the theoretical advantages, the literature is decidedly mixed as to the benefits of these mechanical
devices versus manual compression.

Access Site Management

Closure Devices

Traditionally, manual compression has been the gold

standard for the management of the arterial access
site after diagnostic or therapeutic endovascular procedures. However, the range of compression times
varies significantly, as do the times to ambulation. In
addition, although over the years catheter sizes have
decreased, the increasing use of anticoagulants and
antiplatelet agents in both diagnostic and therapeutic procedures continues to make vascular access site
management a potential challenge.

Most patients dissatisfaction after angiography stems

from the prolonged bed rest and subsequent backache
after the procedure. Mechanical compression does
little to change this problem. Closure devices, on the
other hand, not only provide rapid closure of the arterial puncture site but also facilitate early ambulation
and improve patient satisfaction.613 These devices
come in several types, but fall into two general categories, those that use a plug of hemostatic material and those that use a suture or clip (Table 12.2).
Commonly used devices that employ a hemostatic
plug include the VasoSeal (Datascope, Montvale, NJ),
Angio-Seal (St. Jude Medical, St. Paul, MN) and Duett
Pro (Vascular Solutions, Minneapolis, MN). The most
commonly used suture deployment device is the Perclose (Abbott Laboratories, Abbott Park, IL).
The VasoSeal device delivers an extraluminal collagen plug and can be used with a sheath diameter
of up to 8 French. The manufacturer has announced
plans to seek a buyer for the VasoSeal product but
will continue to produce and support the product
until the end of the 2007 fiscal year. Angio-Seal uses
an external collagen plug combined with an absorb-

Manual Compression
For most patients with normal coagulation profiles
and normal platelet function undergoing a diagnostic procedure with a 4 or 5 French catheter, 10 to 20
minutes of direct manual compression should be sufficient to achieve hemostasis. Once hemostasis has
been achieved, various periods of bed rest have been
prescribed, ranging from 1 to 24 hours. Although we
generally use a protocol of 6 hours of bed rest with
head elevation to 30 degrees after 3 hours, there is


110 Part III Angiographic Fundamentals

Table 12.2 Comparison of five commonly used arterial puncture closure devices
Time to
ambulationa body








St. Jude Medical

External collagen plug

with intravascular anchor


10 s

20 min


3 mon


Access Closure

Polyethylene glycol-based 57F


3 min






Nonabsorbable suture







Cardiva Medical

External collagen plug


45 min






External collagen plug


58 min



6 wk

Compression and ambulation times are based on product literature for diagnostic cases without anticoagulation.
Perclose may be used to close even larger arteriotomies if placed beforehand in conjunction with a smaller sheath using the pre-close
method described in the text.


able intravascular anchor. The plug and anchor are

connected by an absorbable suture, which enables
the two components to be sandwiched together during deployment. The implanted components are all
absorbed within 30 days. The Angio-Seal comes in
two platforms, one for sheaths up to 6 French and
another for up to 8 French. During Duett placement,
a temporary 3 7 mm balloon mounted on a 3 French
catheter is introduced through the sheath and used
to temporarily occlude the puncture site while the
sheath is partially withdrawn. Once the sheath has
been withdrawn beyond the vessel lumen, a slurrylike mixture of collagen and thrombin is injected
through the sidearm of the sheath into the soft tissue surrounding the puncture site. The balloon is
then deflated and removed. Manual compression is
held for 2 to 5 minutes depending on the size of the
puncture and the patients anticoagulation status. A
temporary pressure dressing is recommended after
compression, and the Duett may be used in conjunction with sheaths up to 9 French.
Perclose placement begins with the exchange of
the sheath over a guidewire for the device. Once in
position, the Perclose device deploys two needles
bearing nonabsorbable suture into the walls of the
arteriotomy site. A knot is then slid down to close the
puncture site. The device is approved for the closure
of arterial punctures from 5 to 8 French and is available in a variety of suture configurations.
Various studies have shown that all of these
devices can be deployed with a high rate of success,
with satisfactory hemostasis and little or no increased
risk of complications compared with manual compression alone.8,11,12,1427 Angio-Seal is approved for
ambulation after 20 minutes, whereas the earliest
recommended ambulation after the Duett is 2 hours.
Arteries closed with the Duett and Perclose may be
reaccessed immediately, whereas a delay of 4 to 6
weeks is recommended for both the Angio-Seal and

the VasoSeal. Perclose has the advantage of being able

to close much larger arteriotomies if it is placed, but
not tied in conjunction with a smaller size sheath at
the beginning of the procedurea so-called pre-close
maneuver.28 However, the Perclose is the only one of
these devices that leaves a permanent foreign body.
At our institution, we use Angio-Seal devices in
most anticoagulated patients and elective patients
in whom we do not anticipate a need to reaccess
in the near future. We have found the device to be
particularly easy to use, with an extremely low failure rate. In patients whom we plan to reaccess in
the near future or suspect a reasonable likelihood of
re-treatment, we use a Duett. Although reasonably
effective, the Duett requires very careful attention to
every step in the deployment process, lest the device
fail. Thin patients, in particular, may be difficult to
successfully close because the lack of subcutaneous
tissue around the artery often results in much of the
thrombotic material being expressed through the
skin incision.

Device Placement
Prior to placement of a closure device, the femoral
artery should be imaged, preferably with DSA, to
confirm that the puncture is in the common femoral artery and to exclude stenosis, spasm, dissection, or other pathology that might preclude closure
device placement. The usual projection to image the
common femoral artery and its bifurcation into the
superficial femoral artery (SFA) and profunda branch
is an ipsilateral oblique of approximately 30 degrees.
However, although it nicely separates the branches,
this projection tends to leave the sheath overlying the
femoral artery. As a result, we recommend isocentering on the femoral head and using a contralateral
oblique to throw the catheter/sheath off the artery.

12 Cerebral Angiography
All of the closure devices discussed are designed
to be placed in the common femoral artery. Placement at branch points should be avoided. For the
Angio-Seal, arterial diameter should be at least 5
mm. Excess scarring is a potential disadvantage to
the use of devices and, along with the added expense,
accounts for the most commonly cited reason for not
using these products.

Complications: Avoidance and


Fortunately, major life-altering or life-ending complications are rare in diagnostic cerebral angiography. Pryor et al, in a 1996 review of complications
in cerebral angiography, divided complications into
three categories: local, systemic, and neurological.29

Local Complications
Local complications, those involving the access site,
typically the common femoral artery, were estimated
to occur at a 5% incidence.29 Local complications may be
minor, such as a small hematoma or a local infection;
moderate, such as pseudoaneurysm or asymptomatic dissection; or even severe, such as limb-endangering ischemia or life-threatening retroperitoneal
hemorrhage. Attention to accurate common femoral artery access, management of coagulopathy, and
careful postprocedure hemostasis can help reduce
the chances of a catastrophic retroperitoneal hemorrhage. Initial arterial entry with a soft-tipped or J wire
can minimize the risk of dissection. Multiple catheter
changes have also been linked to an increased risk
of arterial wall injury, making the use of an arterial
sheath of particular importance in such situations.
Depending on their severity, arterial dissections may
be treated with antiplatelet drugs, anticoagulation
therapy, or nothing. Most pseudoaneurysms can now
be treated with local thrombin injection.

Systemic Complications
Systemic complications are most commonly related
to the medications used in association with the
angiographic procedure, the classes of which include
anxiolytics, analgesics, local anesthetics, and contrast media. Oversedation may lead to pulmonary
or cardiovascular suppression. Fortunately, reversal
agents are available for most commonly used medications. Oxygen and resuscitation equipment should
be kept available at all times. Contrast media yield
two potential areas of concerncontrast-induced
nephropathy (CIN) and allergic reaction. The non-

ionic contrast agents in common use today are

certainly less nephrotoxic than older ionic agents.
Nevertheless, CIN remains an issue. A serum creatinine should be obtained in all patients prior to the
administration of contrast dye. For older patients, an
estimate of the glomerular filtration rate (GFR) and
stratification of CIN risk is important. A web-based
calculator may be found at http://www.kidney.org/
professionals/KDOQI/gfr_calculator.cfm. A GFR of
< 60 mL/min/1.73 m3 represents significant renal
dysfunction and defines a patient as high risk for
CIN.30 Based on a review of available evidence and
physician consensus, the Society for Cardiovascular
Angiography and Interventions (SCAI) has developed
guidelines for patients at high risk for CIN.31 Preprocedural intravenous hydration with either isotonic
(normal) saline or an isotonic sodium bicarbonate
solution should be performed. The sodium bicarbonate solution, which demonstrated efficacy in a single
study,32 uses 154 mEq (3 ampules) NaHCO3 in 1 L
of 5% dextrose in water (D5W) or sterile water and
is started at a rate of 3 mL/kg/h, beginning 1 hour
before contrast administration and then continued
at 1 mL/kg/h for 6 hours following contrast exposure. Potential nephrotoxic medications should be
withheld if possible, including aminoglycosides and
nonsteroidal anti-inflammatories. N-acetylcysteine
given as 600 mg orally every 12 hours for four doses
prior to the procedure has been shown to decrease
the incidence of CIN in some clinical trials; however,
the most comprehensive metanalysis performed to
date did not support its use in the prevention of CIN.
Contrast volume should be kept to a minimum and a
low- or iso-osmolal agent should be used. Finally, a
serum creatinine level should be obtained 48 hours
after the procedure, and nephrotoxic medication
should be held until renal function returns to normal. At our institution, we use the aforementioned
sodium bicarbonate solution protocol in all patients,
along with a two-thirds dilution of low osmolality
contrast (iohexolOmnipaque, GE Healthcare, Princeton, NJ). For those considered to be at high risk for
CIN, we use a 50% dilution of iso-osmolal contrast
(iodixanolVisipaque, GE Healthcare, Princeton, NJ)
and consider adding preprocedural N-acetylcysteine
(Mucomyst, Bristol-Myers Squibb, Princeton, NJ).
We withhold metformin in all patients until at least
48 hours after the procedure and/or confirmation
that renal function has not deteriorated.
Allergic reactions can present with a wide variation in severity, from a simple rash to life-threatening anaphylaxis. As part of the patients preoperative
evaluation, a complete medical history, as well as
a listing of all medications and allergies, should be
obtained. A previous history of an allergic or anaphylactic reaction to contrast media, renal insufficiency,
asthma, multiple food/medication allergies, multiple medical problems, and advanced age have all


112 Part III Angiographic Fundamentals

been associated with adverse reactions to contrast
material.33 There is, however, no proven association
between a seafood allergy specifically and a reaction
to contrast media. The presence of these risk factors
should prompt the use of a nonionic, iso- or lowosmolality contrast agent. In addition, the presence
of a previous allergic reaction, in particular, should
prompt premedication prior to contrast administration. Corticosteroids are the most important component of any premedication regimen, and their use is
well supported.34,35 Typically, methylprednisolone (32
mg, 12 and 2 hours before the study) or prednisone
(50 mg, 12 and 1 hour before the study) are used.
The incidence of adverse reaction may be further
reduced by the addition of an H1 receptor blocker,
diphenhydramine (usually 50 mg, 1 hour before the
study) and an H2 blocker, such as cimetidine or ranitidine (1 hour before the study).

Neurological Complications
Fortunately, neurological complications are relatively
rare. Reported rates of all neurological complications
range from 1 to 4%, with permanent deficits reported
at 0.4 to 1%.3639 The risk factors for neurological
injury during cerebral angiography remain controversial. Although increasing age and the presence of
atherosclerotic cardiovascular disease are generally
agreed upon risk factors, others, such as total fluoroscopy time, type of operator (attending, fellow or
resident), number of catheters used, and volume of
contrast administered are controversial and may be
more related to the degree of difficulty of the case
In these days of advanced noninvasive imaging,
perhaps the best way to prevent an angiographically
induced infarction is not to perform the procedure
in the first place. Therefore, it is especially important to be certain of the reason and benefits for the
procedure and to confine the study to the vessels
relevant to the question at hand. Once the procedure
is decided upon, a brief neurological examination
should be performed prior to the start of the procedure and again at the procedures conclusion, in order
to accurately recognize problems in a timely manner.
During the procedure, care must be taken to
avoid the entry of air into the catheter system and
to prevent other forms of emboli. Both intravenous
heparin administration and the use of in-line air
filters have been shown to reduce the rate of silent
ischemic events, as demonstrated by lesions on
diffusion-weighted sequences from postprocedural
magnetic resonance imaging.40 Other technique variations, such as the type of catheter flush employed
(continuous vs. intermittent) and the method of

catheter navigation (through contrast flushing or

guidewire manipulation), have not demonstrated a
consistent impact on outcome. Nevertheless, we prefer a continuous flush of heparinized saline to help
reduce clot formation within the catheter system.
The addition of a double-flush technique, performing a manual aspiration and flush of the catheter system after wire removal, may provide added security.
Furthermore, the use of a power injector reduces the
need to breach the continuity of the system for contrast injection and may reduce the frequency of air
emboli. Although not necessarily confirmed in the
literature, minimizing wire manipulation and always
leading the catheter with a soft hydrophilic guidewire may help reduce the incidence of dissection and
emboli from intra-arterial plaque/thrombus.
In the event a new neurological deficit is detected
at the conclusion of the procedure, thought should
be given to immediate angiographic reexamination.
This is especially true if intra-arterial therapies are
available for the treatment of a new vessel occlusion.
Intravenous recombinant tissue plasminogen activator (rtPA) may also be a consideration. The presence
of a femoral artery puncture (a compressible site) is
not an absolute contraindication to intravenous rtPA.
Anticoagulation may be appropriate in cases of dissection, to prevent further emboli.

In general, with careful attention to detail and
appropriate patient selection, diagnostic cerebral
angiography can be a safe and valuable tool in the
investigation of neurological disease, especially disorders of a vascular nature. Many techniques and
devices are available to allow for the successful
completion of a cerebral angiogram, and practitio-

Successful angiographic technique depends
upon meticulous care in the preparation of
all equipment. Preprocedural understanding
of the goals of the angiogram is important
in determining which vessels will need to be
Though many catheters can be used to perform
successful angiography, complex-shaped catheters or catheters requiring reforming, such as
Simmons catheters, should not be used as the
initial catheter.

12 Cerebral Angiography

Ensure all catheters are flushed and all syringes are bubble-free.
Careful subtraction-based fluoroscopic guidance during each vessel catheterization reduces the risk of complications.
To reduce the chances of vessel injury, use 4 or
5 French catheters for diagnostic angiography.
Image the inguinal region to minimize the risk
of a high puncture and possible retroperitoneal

Most pseudoaneurysms are now treated with
thrombin injections.
Neurological deficits postangiography should
be evaluated with magnetic resonance imaging.
In the case of iatrogenic dissection, heparin
should be initiated in order to prevent embolic

ners should maintain a thorough understanding of

these in order to remain proficient. It is essential to
the patient that the risks of cerebral angiography
be kept as low as possible and that the information
gained from the study be of utmost relevance to the
patients management.

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335340, discussion 340342 PubMed
3. Nohara AM, Kallmes DF. Transradial cerebral angiography:
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7. Zhang Z, Mahoney EM, Gershony G, et al. Impact of the Duett

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the safe and effective vascular hemostasis (SEAL) trial. Am
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9. Kussmaul WG III, Buchbinder M, Whitlow PL, et al. Rapid
arterial hemostasis and decreased access site complications
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16. Michalis LK, Rees MR, Patsouras D, et al. A prospective randomized trial comparing the safety and efficacy of three commercially available closure devices (Angioseal, Vasoseal and Duett).
Cardiovasc Intervent Radiol 2002;25(5):423429 PubMed
17. Silber S, Bjrvik A, Mhling H, Rsch A. Usefulness of collagen
plugging with VasoSeal after PTCA as compared to manual
compression with identical sheath dwell times. Cathet Cardiovasc Diagn 1998;43(4):421427 PubMed
18. Brachmann J, Ansah M, Kosinski EJ, Schuler GC. Improved
clinical effectiveness with a collagen vascular hemostasis device for shortened immobilization time following diagnostic
angiography and percutaneous transluminal coronary angioplasty. Am J Cardiol 1998;81(12):15021505 PubMed
19. Silber S, Tofte AJ, Kjellevand TO, Grube E, Gershony G. Final
report of the European multi-center registry using the Duett
vascular sealing device. Herz 1999;24(8):620623 PubMed
20. Mooney MR, Ellis SG, Gershony G, Yehyawi KJ, Kummer B,
Lowrie M. Immediate sealing of arterial puncture sites after
cardiac catheterization and coronary interventions: initial
U.S. feasibility trial using the Duett vascular closure device.
Catheter Cardiovasc Interv 2000;50(1):96102 PubMed
21. Heyer G, Atzenhofer K, Meixl H, Lampersberger C, Gershony G.
Arterial access site closure with a novel sealing device: Duett.
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22. Cremonesi A, Castriota F, Tarantino F, et al; El Jamal B. Femoral
arterial hemostasis using the Angio-Seal system after coro-


114 Part III Angiographic Fundamentals

nary and vascular percutaneous angioplasty and stenting. J
Invasive Cardiol 1998;10(8):464469 PubMed
23. Kapadia SR, Raymond R, Knopf W, et al. The 6Fr Angio-Seal arterial closure device: results from a multimember prospective
registry. Am J Cardiol 2001;87(6):789791, A8 PubMed
24. Gerckens U, Cattelaens N, Lampe EG, Grube E. Management
of arterial puncture site after catheterization procedures:
evaluating a suture-mediated closure device. Am J Cardiol
1999;83(12):16581663 PubMed
25. Baim DS, Knopf WD, Hinohara T, et al. Suture-mediated closure of the femoral access site after cardiac catheterization:
results of the Suture To Ambulate aNd Discharge (STAND I and
STAND II) trials. Am J Cardiol 2000;85(7):864869 PubMed
26. Kahn ZM, Kumar M, Hollander G, Frankel R. Safety and efficacy
of the Perclose suture-mediated closure device after diagnostic
and interventional catheterizations in a large consecutive population. Catheter Cardiovasc Interv 2002;55(1):813 PubMed
27. Fram DB, Giri S, Jamil G, et al. Suture closure of the femoral
arteriotomy following invasive cardiac procedures: a detailed
analysis of efficacy, complications, and the impact of early
ambulation in 1,200 consecutive, unselected cases. Catheter
Cardiovasc Interv 2001;53(2):163173 PubMed
28. Katz SG, Abando A. The use of closure devices. Surg Clin North
Am 2004;84(5):12671280, vi PubMed
29. Pryor JC, Setton A, Nelson PK, Berenstein A. Complications of
diagnostic cerebral angiography and tips on avoidance. Neuroimaging Clin N Am 1996;6(3):751758 PubMed
30. National Kidney Foundation. K/DOQI clinical practice guidelines
for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2, Suppl 1):S1S266 PubMed
31. Schweiger MJ, Chambers CE, Davidson CJ, et al. Prevention of
contrast induced nephropathy: recommendations for the high

risk patient undergoing cardiovascular procedures [published

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1;69(6):931. Zang, Shaoheng removed] . Catheter Cardiovasc
Interv 2007;69(1):135140 PubMed
32. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrastinduced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291(19):23282334 PubMed
33. Maddox TG. Adverse reactions to contrast material: recognition, prevention, and treatment. Am Fam Physician
2002;66(7):12291234 PubMed
34. Lasser EC, Berry CC, Talner LB, et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. N Engl J Med 1987;317(14):845849 PubMed
35. Greenberger P, Patterson R, Kelly J, Stevenson DD, Simon D, Lieberman P. Administration of radiographic contrast media in high-risk
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cerebrovascular disease. Stroke 1990;21(2):209222 PubMed
37. Willinsky RA, Taylor SM, TerBrugge K, Farb RI, Tomlinson G,
Montanera W. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of
the literature. Radiology 2003;227(2):522528 PubMed
38. Leffers AM, Wagner A. Neurologic complications of cerebral
angiography. A retrospective study of complication rate and
patient risk factors. Acta Radiol 2000;41(3):204210 PubMed
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1994;15(8):14011407, discussion 14081411 PubMed
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2004;110(15):22102215 PubMed


Spinal Angiography and the

Angiographic Anatomy of the Spine
Jeffrey A. Stone

Spinal angiography is often used for the evaluation of

suspected vascular malformations and hypervascular
tumors of the spinal column. It frequently precedes
endovascular intervention and is used to assess the
lesion of interest as well as the normal blood supply to the spinal cord and vertebral body. The vascular supply and drainage of the spinal column are
complex, and thorough understanding of the normal
spinal vascular anatomy is essential to proper and
complete evaluation. Many of the smaller nerve and
spinal cord blood vessels are not normally seen on
angiography. They are, however, important to understand because they frequently enlarge in pathological states. This chapter illustrates the normal arterial
supply and venous drainage of the spinal column and
reviews the technique of spinal angiography.

Spinal Angiographic Anatomy

The nomenclature for the arterial supply to the spinal axis is complex, varied, and often inconsistent
between authors. It is most useful to understand
the fundamental vascular structures and territories
that supply the bony vertebrae, spinal nerves, dura,
and spinal cord. The arterial supply to the spinal axis
develops early in embryogenesis as paired segmental branches supplying each metamere. A paired
segmental arrangement persists in the thoracic and
lumbar regions in adulthood as the intercostals and
lumbar arteries, respectively. These arteries arise at
each spinal level and typically supply the same level
vertebral bony structures, dura, and paraspinal
musculature. The cervical region consists of many
anastomotic channels, and spinal arterial supply is
more variable. The principal cervical branches that
supply the spine arise from the vertebral artery,
ascending cervical artery, and deep cervical artery.
The cervical vertebrae receive blood from a com-

bination of these three arteries due to the extensive longitudinal intersegmental anastomoses that
exist in this region. Additional blood supply to the
C1C2 region comes from segmental arteries that
arise from the ascending pharyngeal and occipital
The spinal arterial supply can generally be divided
into four territories. The first are small branches
arising from the segmental artery (i.e., intercostal,
lumbar) in the thoracic and lumbar regions or the
vertebral or ascending cervical arteries in the cervical region. This anterolateral supply provides blood
flow to the anterior and lateral portions of the vertebral body.1 The second territory is the anterior
spinal canal supply entering the spinal canal along
the ventral portion of the spinal nerve root.1 These
radicular branches typically arise from a branch
(dorsospinal artery) of the segmental, vertebral, or
iliolumbar artery and include the vascular arcade
underneath the posterior longitudinal ligament supplying the posterior vertebral body as well as vessels
that supply the anterior dura and spinal cord. If the
radicular branch supplies the anterior spinal artery,
it is referred to as a radiculomedullary branch.
Radicular branches that course posterior to supply
the paired posterior spinal arteries or posterior pial
network (vasa corona) are referred to as radiculopial
branches. The third territory is the posterior spinal
canal supply and enters along the dorsal surface of
the spinal nerve root and courses through the posterior epidural space, supplying the ventral surface
of the lamina and base of the spinous process.1 The
fourth territory is the posterior supply arising from
branches of the distal dorsospinal artery as it courses
posterior and supplies the transverse process, dorsal
surface of the lamina, and spinous process.1 Lateral
and dorsal muscular branches also arise from the
distal dorsospinal artery in this region.
The thoracic and lumbar region receives blood
from paired segmental branches (intercostal and
lumbar arteries) from the aorta. Embryological variation may occasionally result in two adjacent levels


116 Part III Angiographic Fundamentals

arising from a common trunk off the aorta, and collateral communications also exist between adjacent
levels. The longitudinal distance between origins of
consecutive adjacent level segmental arteries in the
upper thoracic region is shorter than in the lower
thoracic and lumbar region, and the origin of the
left segmental artery is slightly superior to the same
level on the right in the upper thoracic region due to
the effect of aortic arch curvature.2 The longitudinal
distance lengthens and the paired segmental arteries tend to arise at the same level as one reaches the
midthoracic branches. The ostea of the intercostal
and lumbar arteries are typically located immediately below the level of the pedicle on frontal view
fluoroscopy. The proximal segmental arteries of the
upper thoracic region course nearly parallel to the
coronal plane along the rib and gradually assume a
posterolateral course along the surface of the vertebral body as one moves caudal.2 This change in the
origin and course of the segmental arteries is dependent on the aorta as it shifts anteriorly and medially
from a left lateral position along the spinal column
in the thoracic region to an anterior position in relation to the spinal column in the lumbar region. These
anatomical relationships of the segmental artery
origins are important to recognize when attempting
catheterization of the segmental arteries.
The intercostal arteries supply the thoracic spinal structures and arise from the posterior thoracic
aorta. These paired arteries are typically found at
the level of, and caudal to, the fifth thoracic vertebra,
due to the level of the descending aorta. The superior
intercostal levels (T1T4) often arise from branches
off the supreme intercostal artery, a branch with
variable location and bilaterality, located immediately below the aortic arch. These are the most
cephalic intercostal arteries and supply multiple
intercostal branches. The third and fourth intercostal
arteries may occasionally arise as a distinct branch,
particularly on the left side of the aorta, where there
is a longer convex curvature of the aortic arch. The
lumbar arteries are also paired and arise from the
posterolateral abdominal aorta.
Small perforating arteries arise from the segmental arteries (anterolateral supply) and supply the
anterolateral vertebral body. The paired segmental
arrangement results in each artery (left and right)
supplying approximately 50% of the vertebral body
and paraspinal musculature at that level, although
variations exist due to the absence of a midline
raphe. The relative midline location of the abdominal
aorta results in a hemivertebral blush during selective angiography. The anterolateral location of the
upper thoracic aorta, however, results in the right
intercostal artery supplying the right hemivertebra
as well as the anterior left lateral portion of the vertebra. This can result in the angiographic appearance
of the entire vertebra during right intercostal artery

injection, and care must be taken to evaluate the left

posterior vertebral body blood supply that arises
from the left intercostal artery.
The sacral region is supplied by a terminal branch
of the descending aorta called the middle sacral
artery. Additional sacral blood supply is derived from
pretransverse anastomoses from the internal iliac
arteries called the lateral sacral arteries. The fifth
lumbar segment or transitional segments may derive
blood supply from either lumbar or sacral branches
or both.
A branch called the dorsospinal artery arises
as the intercostal or lumbar artery courses laterally from the vertebral body. The dorsospinal artery
has numerous small branches that supply the spinal nerve and dura. These are often referred to as
radicular branches, and they supply the ipsilateral
nerve root but are rarely seen at angiography due to
their very small caliber. The dorsospinal artery also
divides into ventral and dorsal radicular branches at
the level of the neural foramen, termed the radiculomedullary artery if supplying the anterior spinal
artery and the radiculopial artery if supplying the
posterior spinal arteries or vasa corona (Fig. 13.1).
These ventral and dorsal radicular arteries follow the
ventral and dorsal nerve roots through the dura and
to the spinal cord. Their size and visibility on angiography vary depending on the contribution of flow to
the spinal cord, and they may be enlarged in pathological conditions that result in high-flow states.
The small radiculopial arteries frequently course
along the ventral surface of the dorsal nerve root to
reach the lateral and dorsal surface of the spinal cord.
These branches normally remain monosegmental
and arise at every level. They contribute supply to the
pial network (vasa corona) but do not typically contribute supply to the anterior spinal axis other than
occasionally through vasa corona anastamoses.3 Very
small radial perforators (2550 m) called the rami
perforantes arise from the radiculopial branches
and course into the posterior and lateral spinal cord
The radiculomedullary branches represent the
dominant supply to the spinal cord, contributing both
segmental and longitudinal vascular supply. These
arteries arise from a ventral radicular artery and typically course along the ventral surface of the ventral
nerve root to enter the spinal canal. Small branches
(rami perforantes) may arise in this region to supply
the anterior spinal cord pial network. The number of
radiculomedullary arteries varies between individuals, and their level of origin is highly variable. The
size of the radiculomedullary artery is dependent
on the total number of arteries contributing to the
longitudinal vascular supply of the spinal cord by
way of the anterior spinal artery. The anterior spinal
artery gives off perforator branches called sulcocommissural arteries that supply the anterior spinal cord

13 Spinal Angiography and the Angiographic Anatomy of the Spine

Fig. 13.1 The normal segmental branches that arise from the aorta to supply the spinal cord. The T10 and T12 intercostal arteries
demonstrate radicular branches to the spinal nerve. There is further division into anterior and posterior radicular arteries that follow
the anterior and posterior nerve roots, respectively. The left T10 intercostal artery in this illustration also contributes blood supply
to the left posterior spinal artery by way of a radiculopial artery. The left T12 intercostal artery has a dominant radiculomedullary
branch that supplies the anterior spinal artery. This is the artery of Adamkiewicz, also known as the great radicular artery (as labeled
in figure).

substance. These branches course posterior through

the ventral sulcus of the spinal cord, are 50 to 75 m
in size, and represent end arteries that terminate
deep in the spinal cord gray and white matter.
The cephalic portion of the anterior spinal artery
is principally formed from a small branch of the distal
vertebral artery at the level of the medulla oblongata
(Fig. 13.2). The cephalic anterior spinal artery may
arise from one or both distal vertebral arteries, and
the contribution is variable, with frequent contribution from smaller radiculomedullary branches and
the artery of cervical enlargement (discussed later).
The anterior spinal artery courses longitudinally
along the anterior surface of the spinal cord within
the anterior median (ventral) sulcus and supplies
the anterior and lateral substance of the spinal cord.
The anterior spinal artery extends from the level
of the basilar artery to the filum terminale. It may
frequently remain unfused in the cervical region,
appearing as if duplicated and probably related to
the multiple, bilateral sources of blood supply to this
region.3 The anterior spinal artery may normally be
interrupted along its course at a level where a dominant radiculomedullary artery contributes flow. The

anterior spinal artery contributes over two thirds of

the blood supply to the spinal cord.1 The anterior spinal artery transit time is approximately 10 seconds.3
This is the average length of time between maximum
anterior spinal artery enhancement and maximum
median vein enhancement.3
A pair of posterior spinal arteries course longitudinally along the posterior paramedian surface of the
spinal cord. The posterior spinal arteries frequently
arise from the vertebral arteries, with additional
contribution from small branches from the radiculopial arteries. The posterior spinal arteries supply
up to a third of the posterior spinal cord, particularly the dorsal columns. The anterior spinal artery
forms a complex anastomosis with the pial network
of the posterior spinal arteries at the level of the
conus medullaris. This complex anastomosis has the
appearance of a basket of small vessels enveloping
the conus. The blood supply to the filum terminale
arises from this arterial basket and courses along its
ventral aspect, often considered the caudal continuation of the anterior spinal artery. There is no lumbar or sacral arterial supply to the filum below the
level of the conus because no nerve roots arise from


118 Part III Angiographic Fundamentals

Fig. 13.2 Right frontal vertebral artery injection in a patient with subarachnoid hemorrhage. The superior origin of the anterior
spinal artery (arrow) is seen to arise from the distal right vertebral artery immediately proximal to the vertebrobasilar junction. An
additional branch from the contralateral vertebral artery may also be present. A dissecting aneurysm of the right posterior inferior
cerebellar artery (PICA) is noted. It is important to note the origin of the anterior spinal artery distal to the PICA when planning
endovascular intervention.

the conus. Therefore, a lesion of the filum terminale

will be supplied by the ventral arterial supply arising
from the basket and not have contribution from the
low lumbar or sacral radicular arterial supply.
Six to 10 radiculomedullary branches typically
contribute blood flow to the anterior spinal artery
(Fig. 13.3).4 The location of these branches is highly
variable, but a few important dominant branches
typically exist. Two radiculomedullary arteries of
particular interest are the artery of lumbar enlargement, commonly known as the artery of Adamkiewicz, and the artery of cervical enlargement.
The artery of Adamkiewicz commonly arises from
an intercostal artery or, less often, a lumbar artery
and is a very important feeding vessel of the caudal
spinal cord (Fig. 13.4). It arises on the left side in 68
to 73% of cases.5 It originates between the T9 and T12
level in up to 75% of patients, although variability
exists.6 When it is the sole dominant radiculomedullary artery supplying the anterior spinal artery, its
diameter is 0.8 to 1.3 mm.5 A second dominant radiculomedullary artery typically exists if the origin of

the artery of Adamkiewicz is above T8 or below L2.6

The caliber of both these arteries is often reduced in
this situation and may be difficult to identify without great attention to angiographic technique.6 This
artery is not always identified during angiography,
particularly with advanced atherosclerosis of the
aorta, aortic aneurysm, and aortic dissection, where
it is reportedly identified in 60 to 65% of spinal angiograms specifically performed for its identification.7,8
The artery of Adamkiewicz is the major blood supply
to the thoracolumbar portion of the anterior spinal
artery. The radiculomedullary arteries, including the
artery of Adamkiewicz, have a characteristic hairpin
bend on angiography.
The artery of cervical enlargement arises at the
C5 or C6 level from the vertebral or ascending cervical artery (Fig. 13.5a, b).9 In combination with the
branches arising from one or both distal vertebral
arteries proximal to the vertebrobasilar junction,
this is the major blood supply to the cervical and
upper thoracic portion of the anterior spinal artery.
As a result of this thoracolumbar (artery of Adamkie-

13 Spinal Angiography and the Angiographic Anatomy of the Spine

Fig. 13.3 Illustration on the left shows multiple radiculomedullary branches arising from the aorta and contributing blood to the
anterior spinal artery. In this illustration, radiculomedullary arteries arise from the vertebral artery T1 level via a supreme intercostal
artery, T7 intercostal artery, L1 lumbar artery, and S1 lateral sacral artery. The lateral sacral arteries may contribute blood supply to
the nerve roots within the thecal sac. The figure on the right shows the intercommunication between the posterior spinal arteries
and anterior spinal artery via the vasa corona, a rich capillary plexus along the pia of the spinal cord. An anterior sulcal artery is seen
to arise from the anterior spinal artery and supplies the anterior two thirds of the spinal cord, including the spinothalamic tract. The
dorsal columns are typically supplied by branches arising from the posterior spinal arteries.

Fig. 13.4 Left T11 intercostal artery angiogram in the frontal plane
shows a large radiculomedullary branch (small arrow) coursing superiorly
to form a classic hairpin configuration. The anterior spinal artery (large
arrow) is seen to opacify in a cephalic to caudal direction from the radiculomedullary branch that represents the artery of Adamkiewicz (the great
radicular artery). The artery of Adamkiewicz most often arises from the
left side of the aorta and most often between T9 and T12. Variation to
the right or craniocaudal to these levels occurs in 25 to 30% of patients.


120 Part III Angiographic Fundamentals

Fig. 13.5 Left vertebral artery angiogram in the (a) frontal and (b) lateral projections. The artery of cervical enlargement (short
arrow) is seen arising from the vertebral artery (bold arrow) at the C6 level. It is seen to fill the anterior spinal artery (long arrow) in a
bidirectional fashion (cephalic and caudal flow). There is retrograde opacification of a right (contralateral) radiculomedullary branch
seen on the frontal angiogram.

wicz) and cervical blood supply to the anterior spinal

artery, a potential watershed region typically exists
at the T4 level.

The spinal cord has an intrinsic network of medullary veins that are arranged radially and have a rich
anastomotic network. These veins are not normally
visualized on angiography but drain into an extrinsic venous network along the surface of the spinal
cord consisting of distinct surface veins that may be
identified. The gray matter venous outflow drains
into dorsal and ventral sulcal veins (posterior and
anterior median spinal veins, respectively). These
veins, particularly the anterior median spinal vein,
help form the longitudinal connection of the venous
system. Short intersegmental bridges linking adja-

cent radial collecting veins are located laterally but,

as seen with the arteries, do not form a longitudinal
venous network. A single longitudinal vein is typically seen in the cervical and lumbar regions, but up
to three may be encountered in the thoracic region.
These drain through the dura by way of the radicular veins. The radicular veins may course through the
dura with the nerve root (60%) or through a separate
foramen (40%) in the dura between spinal nerves.6
Although the radicular veins are valveless, their
transdural course extending up to 1 cm in length is
believed to result in an antireflux arrangement protecting against increases in intrathoracic or intraabdominal pressure.6 The radicular veins drain into
the spinal nerve venous channels and the extradural
vertebral venous plexus within the epidural space.
The epidural plexus drains through the neural foramina through paravertebral veins. These drain into the
suboccipital venous system and jugular veins in the

13 Spinal Angiography and the Angiographic Anatomy of the Spine

cervical region; the azygos and hemiazygos veins in
the thoracic region; the ascending lumbar, azygos
vein, inferior vena cava, and left renal vein in the
lumbar region; and the iliac vein by way of the lateral
sacral vein in the sacral region.

Procedural Overview
Angiography of the spinal axis can be time consuming, and every effort should be made to reduce
radiation exposure to the lowest dose possible. The
procedure is preferentially performed on a biplanar
angiography unit, but single-plane units may suffice.
It is useful to screen vessels using frontal projection
angiography, reserving lateral plane angiography
for anatomical definition, vessel orientation, and
confirmation of a vascular abnormality. General
anesthesia is often used for patient comfort and to
reduce patient-induced motion. It is helpful to use
suspended respiration during injection to reduce
motion induced from the diaphragm. Glucagon may
also be administered prior to the procedure to reduce
bowel motion artifact.
The cervical contribution to the spinal blood supply is typically assessed using a standard cervicocerebral 5 French diagnostic catheter with a 30 to 45
degree curved tip, such as a Berenstein or DAV catheter. Assessment of the intercostal and lumbar arteries requires a reverse curvature catheter (modified
shepherds hook type of configuration), due to the
cephalic to caudal orientation at the origin of these
vessels. A 5 French catheter of 80 to 100 cm length
is typically used. The intercostal arteries most often
require a shorter and more acute curvature, such as
the Mikaelson, Debrun, Cobra, or Shetty catheters.
The lumbar arteries and middle sacral artery often
require a larger, less tightly curved catheter due to
the larger diameter of the abdominal aorta. A Simmons type catheter is often best in this region and
can be used to evaluate the internal iliac arteries
as well. These catheters are available in sizes small
enough to catheterize the segmental arteries yet
large enough to accommodate a microcatheter.
Nonionic contrast should be used for all injections, with careful attention to the amount of contrast injected during the procedure. Contrast may
be diluted by 33 to 50% using heparinized normal
saline. Patient size and the anatomical level of injection often dictate the amount of contrast dilution
used while preserving image quality. Contrast may
be injected using a power injector, typically at a
rate of 1 to 2 mL/s. Hand injection is also frequently
used and is preferred by the author. It enables rapid
injection with decreased catheterization time, easier

manual stabilization of the catheter within the vessel, and adjustments in injection rate based on both
visual and tactile feedback.
Imaging should include both the arterial and venous
phases of injection, particularly in the case of vascular
malformations. Additional angiography of anatomical
levels above and below the catheterized vessel is typically necessary to fully evaluate the arterial and venous
communications with the lesion being evaluated, as
well as relationships with normal structures.

It is critical to thoroughly evaluate the clinical history
and cross-sectional imaging prior to performing spinal angiography. This helps determine the region and
extent of angiography required. Adequate evaluation
of spinal tumors often requires a localized exam, with
inclusion of the adjacent normal vasculature. Spinal
vascular malformations may, however, require evaluation of the entire spinal axis, particularly when the
vascular malformation has complex blood supply and
spans multiple vertebral levels. Spinal angiography
should define the exact location and configuration of
the lesion; the vascularity of the lesion, including all
feeding arteries and draining veins; and the normal
regional vasculature of the spinal cord.9
It is important to meticulously position the
patient prior to commencement of angiography.
All pressure points should be properly padded. It is
useful to elevate the arms at the patients side using
radiolucent cushions to allow for adequate lateral
plane imaging. Anesthesia-related devices should be
outside the field of view at all levels, including cardiac leads. A Foley catheter is recommended given
the length of the procedure and the amount of contrast used. A vascular access sheath is also recommended at the site of arteriotomy and is placed to
a slow continuous heparinized saline infusion. The
sheath allows easy exchange of the diagnostic catheters needed to complete the exam.
It is essential to have a designated member of
the team available and ready to annotate or record
the level of each injection. A long radiopaque angiographic ruler may also be placed under the patient.
A systematic approach to catheterization should be
used to ensure that all necessary levels and sides are
evaluated. Catheterization of the intercostal, lumbar,
and sacral arteries should be performed near their
origin without occluding blood flow, given the small
caliber of the vessel, and the catheter tip should not
be so deep as to occlude flow in the dorsal or ventral
branches that supply the spinal axis. This may require
manual fixation of the catheter to ensure stability
during injection. It is also important to position the
tip of the catheter in the direction of the segmental
artery, keeping in mind the change from coronal to


122 Part III Angiographic Fundamentals

posterolateral orientation as one moves caudally from
the thoracic to the lumbar region. Low-pressure test
injection with contrast should be performed prior to
diagnostic injection to ensure adequate antegrade
flow without stasis. Once this has been confirmed,
diagnostic angiography is rapidly performed. Breathhold technique to reduce motion is often employed
and is easy when the patient is under general endotracheal anesthesia. The images should be reviewed
after each injection, and lateral imaging or larger field
of view imaging may be performed as indicated. The
catheter should then be removed from the vessel origin to allow adequate flow and decrease the risk of
thromboembolism. All vessels to be studied are then
catheterized and evaluated in a similar fashion.

Complications related to spinal angiography are
considered rare, but the frequency is difficult to
determine given the relative infrequency of the
examination and limited literature addressing this
issue. The most serious potential complication is a
neurological deficit, frequently caused by thromboembolism. Most reported neurological deficits
have been transient. A 1965 prospective study of
134 consecutive spinal angiograms in 96 patients
reported a 2.2% rate of neurological complication
over 24 hours postangiography and nonneurological local (i.e., vascular access complications) and
systemic (i.e., contrast related) complication rates of
8.2% and 3.7%, respectively.10 These rates have presumably decreased with advances in digital imaging
that limit the time of examination, improvement of
diagnostic catheter design, and use of low-osmolar
nonionic contrast. It is recommended that heparinized flush solutions be used whenever possible and
catheterization times within each vessel be held to
a minimum to reduce the risk of thromboembolism.
Over-the-wire technique for catheter placement
should be used, particularly in the cervical vessels, to
reduce the risk of injury to the vessel intima. The diagnostic catheter may be placed to a slow continuous
flush solution between injections or during review of
images. This may reduce the risk of catheter-induced
thromboembolism. Improper catheterization or miscues in injection technique may lead to blood vessel dissection. An initial graded rise in injection rate
should be used when using a power injector to reduce
the risk of intimal injury and catheter displacement.
Renal impairment is always a risk with administration of iodinated contrast and is particularly significant with spinal angiography, given the large contrast
volume used for complete examination. Renal function should be assessed prior to spinal angiography

and laboratory studies obtained in any patient with a

history of renal function impairment. Nonionic contrast should always be used. Contrast use should be
kept at the lowest volume that results in good quality diagnostic images. Adequate preprocedure hydration of the patient is also essential. Contrast may be
diluted appropriately as previously described, and an
estimated glomerular filtration rate (eGFR) should
be determined in high-risk patients. Two or more
separate sessions of angiography may be necessary
to complete the exam in certain cases. Patients with
a documented adverse reaction to iodinated contrast
should be premedicated with appropriate steroids
and H2 blockers prior to spinal angiography.

Spinal angiography is a complex procedure that evaluates the vascular supply and drainage of the spinal
axis. It requires patience and due diligence to ensure
that the evaluation is complete. Although there is
significant variation in nomenclature pertaining to
the spinal vascular structures, a basic understanding
of the segmental arrangement and major branches
discussed in this chapter will enable the neuroangiographer to comprehensively and safely perform
spinal angiography.


Complete angiographic evaluation of the
spinal axis arterial supply requires selective
angiography of the vertebral, external carotid,
ascending cervical, intercostal, lumbar, middle
sacral, and internal iliac arteries.
The radicular arteries branch at each level to
supply the ipsilateral nerve root. Radiculopial
branches of the radicular artery course posterior
to supply the pia and posterior spinal arteries. Radiculomedullary arteries arise from the
radicular artery and supply the anterior spinal
artery. Six to 10 radiculomedullary arteries are
typically present.
Two dominant radiculomedullary arteries
that are important to identify are the artery
of cervical enlargement and the artery of
Systematic catheterization of the segmental
arteries in the thoracic and lumbar region,
with assistance in documentation of each level
evaluated, is essential to ensure complete angiographic evaluation of the spinal axis.

13 Spinal Angiography and the Angiographic Anatomy of the Spine

Minimize the depth of catheterization into
each vessel to reduce the likelihood of stasis
and subsequent thrombosis/embolus in the
Use low-osmolar nonionic contrast.
Use continuous catheter flush whenever
possible, particularly during image intensifier positioning or image review, to minimize
thrombotic complications.

If postspinal angiography neurological deficits
occur, consider pressor management to a mean
arterial pressure of 85 mm Hg for several days.

1. Choi IS, Berenstein A. Surgical neuroangiography of the

spine and spinal cord. Radiol Clin North Am 1988;26(5):

11311141 PubMed
2. Shimizu S, Tanaka R, Kan S, Suzuki S, Kurata A, Fujii K. Origins
of the segmental arteries in the aorta: an anatomic study for
selective catheterization with spinal arteriography. AJNR Am J
Neuroradiol 2005;26(4):922928 PubMed
3. Pattany PM, Saraf-Lavi E, Bowen BC. MR angiography of
the spine and spinal cord. Top Magn Reson Imaging 2003;
14(6):444460 PubMed
4. Gillilan LA. The arterial blood supply of the human spinal
cord. J Comp Neurol 1958;110(1):75103 PubMed
5. Yoshioka K, Niinuma H, Ohira A, et al. MR angiography and CT
angiography of the artery of Adamkiewicz: noninvasive preoperative assessment of thoracoabdominal aortic aneurysm.
Radiographics 2003;23(5):12151225 PubMed
6. Lasjaunias P, Berenstein A. Spinal and spinal cord arteries and
veins. In: Lasjaunias P, Berenstein A. Surgical Neuroangiography. New York, NY: Springer Verlag; 1990:1587
7. Minatoya K, Karck M, Hagl C, et al. The impact of spinal angiography on the neurological outcome after surgery on the descending thoracic and thoracoabdominal aorta. Ann Thorac Surg
2002;74(5):S1870S1872, discussion S1892S1898 PubMed
8. Heinemann MK, Brassel F, Herzog T, Dresler C, Becker H, Borst
HG. The role of spinal angiography in operations on the thoracic aorta: myth or reality? Ann Thorac Surg 1998;65(2):
346351 PubMed
9. Nelson PK, Setton A, Berenstein A. Vertebrospinal angiography
in the evaluation of vertebral and spinal cord disease. Neuroimaging Clin N Am 1996;6(3):589605 PubMed
10. Forbes G, Nichols DA, Jack CR Jr, et al. Complications of spinal
cord arteriography: prospective assessment of risk for diagnostic procedures. Radiology 1988;169(2):479484 PubMed


Part IV

Intracranial Aneurysms and Vasospasm


The Biophysics of Aneurysm

Formation and Rupture
Charles J. Prestigiacomo

For every machine and structure, whether artificial or natural, there is set a necessary limit
beyond which neither art nor nature can pass.
Galileo Galilei, Two New Sciences, 16381
Why do aneurysms form? More importantly, why do
aneurysms rupture? Despite the numerous advances
in microsurgical and endovascular treatment since
the early days of Dott and Dandy,2 the mortality and
morbidity from aneurysmal rupture remain unacceptably high. In turn, though the microsurgical and
endovascular management of intracranial aneurysms has enjoyed a substantial improvement in
outcomes, these procedures nonetheless carry a significant complication rate. Several reports describe
an incidence of subarachnoid hemorrhage as ranging
from 8 to 10 per 100,000 population.3 A recent metaanalysis suggests that the prevalence of aneurysms is
2% in a population free of comorbidities, with a mean
age of 50 and 33% male.4,3 A recent meta-analysis suggests an annual rupture risk of 1.9%. This mismatch
clearly suggests that not all aneurysms rupture.
It is thus imperative that, to maximize the outcome for patients with aneurysms, one must identify
which aneurysm has a significant risk of rupture and
thus expose only those patients with that high rupture risk to the potential complications of treatment,
while avoiding this treatment risk in patients with
aneurysms that would not rupture. Identifying criteria that will provide the clinician this algorithm
in many ways remains the holy grail of aneurysm
treatment.57 The literature is replete with the analysis of the pathophysiology of aneurysm formation
and rupture as it relates to genetics, environmental
factors like smoking, physiological factors like physical stress and hypertension, and immune-mediated
or inflammatory factors.
In recent years, the literature has demonstrated
somewhat of a shift in the focus of the clinical and
research community in its emphasis on the analysis
and stratification of aneurysm rupture risk. Improvements in imaging, a shift to quantitative and not
just qualitative analysis, and a focus on flow and

flow dynamics as a force of influence in rupture

have changed the landscape of research for cerebral
aneurysms. No longer are the primary investigators
in this field limited to neurologists, neurosurgeons,
and neuroradiologists. Mathematicians, aeronautical
engineers, materials scientists, and biomedical engineers have provided much-needed insight into the
behavior of these potentially lethal lesions.
Truly understanding these lesions is thus critical to predicting aneurysm behavior and saving lives
before patients are harmed. This chapter briefly
reviews the compendium of literature dedicated to
understanding the biopathophysiology of aneurysm
formation. It then reviews the history and current
status of research in the biophysical nature of aneurysm growth, rupture, and regrowth in the setting
of treated lesions. In so doing, an understanding of
which criteria might be used to help clinicians determine a true rupture risk for each individual aneurysm is assessed.

Historical Perspectives
Studying mechanical properties in a systematic
way may have its origins with Galileos work, which
for the first time discussed the strength of materials and determined a way to measure the force and
motion of these materials.1 However, this fascination and interest in describing how things work
was a strong theme that was seen in Aristotles On
the Parts of Animals and in the anonymously written
Chinese text, Internal Classic.8,9 The transition from
the science to the use of technological concepts in
the description of biological structures took place in
the 17th century with Galileo, and with his contemporaries, such as William Harvey, who first described
circulation.10 Through the works of Galileo, Harvey,
Newton, and others, mathematics was emphasized
as a cornerstone in understanding the physical and
biological universe as it pertained to the mechanics
of function.


128 Part IV Intracranial Aneurysms and Vasospasm

Though Galen first palpated and described the
pulse in terms of rate, rhythm, and strength, it was
not until Hales that blood pressure was first measured in 1733.11 As mathematical theory continued
to develop, especially with Newtons development of
calculus, Leonhart Euler began to describe fluid flow
mathematically. Interestingly, the field continued
to advance through the contributions of individuals with expertise in more than one field. Poiseuille,
a physician and physicist, was able to describe the
relationship of flow to the radius of a tube, its length,
and the viscosity of the fluid. It is from these beginnings that the current field has matured. Though in
many ways the observations made by these pioneers
may be considered simple and obvious in todays
world, what is more critical is that these individuals
began the application of stringent scientific principles to biological systems that made the field what it
is today. It is this philosophy that continues to breed
success in the understanding of aneurysm behavior.

Pathophysiology of Intracranial
Aneurysm Formation:
A Brief Review

Certain risk factors have been associated with aneurysm incidence and with rupture. Taken together,
several reports suggest that the risk of rupture may
be 1 to 2.3%.12,13 Smoking, alcohol consumption, and
hypertension have been implicated in formation
and rupture. 14,15,16 In addition to some autosomal
hereditary disorders, such as polycystic kidney disease, Ehlers-Danlos syndrome, and fibromuscular
dysplasia, people of Finnish or Japanese descent
and women in general have a higher risk of aneurysm incidence, growth, and rupture.17,1821 A recent
review of genome-wide association in aneurysm
formation describes the significant progress in this
field and emphasizes the genetic mechanisms that
contribute to aneurysm formation (Fig. 14. 1).22 The

Fig. 14.1 The significant genes in aneurysm formation identified through genome-wide association studies.22

14 The Biophysics of Aneurysm Formation and Rupture

role of inflammatory mediators, such as the cytokines and locally acting metalloproteinases, and the
mechanical factors affecting inflammation within
the aneurysm wall have been strongly implicated in
the genesis of cerebral aneurysms.2326,27 Histological
studies have carefully evaluated the wall of the parent vessel and aneurysm in the setting of ruptured
and unruptured aneurysms.23 Recent studies have
suggested that perhaps another method of classifying aneurysms is by assessing the characteristics of
the vessel wall.23 In all cases, a better understanding
of the histological and cellular processes occurring
in aneurysm formation is critical in understanding
how they shape the physical properties of the vessels and the principal force of interaction, the flow
of blood.

Physical Properties

of Vessels and Blood

Vessels are elastic organs with hysteresis. In other

words, they are viscoelastic tubes (similar to springs)
that can deform under the pulsations of the heart and
propagate flow by those very same properties of the
elastic wall that returns them to their original state.28
From an energy perspective, they deform and tend
to return to a more natural and lower energy state.
Indeed, during asystole, intracranial arteries demonstrate a baseline tension that maintains a mean
arterial pressure (MAP) of approximately 20 mm
Hg.29 Unlike rigid tubes, vessels with these viscoelastic properties allow for a more steady flow of blood
(dampening) despite the extremes of the systolic and
diastolic pulse. In addition, the elasticity of the vasculature allows blood to continue to flow forward
during diastole because the vessel itself provides the
energy to propel blood forward. Intracranial arteries are histologically, and thus likely mechanically,
different from the extracranial vasculature. Lacking
an adventitia, the supraclinoid carotid artery mea-

sures approximately 4 mm in diameter, whereas

the basilar artery measures approximately 3 mm in
diameter. Thus the average wall thickness is approximately 0.5 to 0.8 mm, with wall tension of less than
60,000 dynes/cm. Internal pressures in vessels of this
size may be less than 75 to 90 mm Hg in an upright
standing position.30
Because the vessels are elastic, they exhibit some
mechanical properties of all elastic bodies. Stress
is the force per unit area applied to a structure,
whereas strain is the ratio of the deformation from
baseline for a given stress. Within certain boundaries, stress and strain are linearly related, as described
by Hookes law. For purposes of this discussion, vessels can be considered Hookean in their behavior, and
thus each vessel, secondary to its biological nature
and composition, has specific mechanical properties
that can be expressed as constants, such as the Young
modulus, which is essentially the spring constant
of a vessel along the longitudinal axis of the vessel
(Fig. 14.2). This longitudinal elastic modulus is especially important in vessels because it represents
the vessels ability to withstand the tangential and
shearing forces that have been implicated in aneurysm formation and rupture.
As mentioned, the physical characteristics of these
properties are derived from the molecular structure
of the vessel. All tissues (e.g., from bone to skin) or the
components that make up tissues have an inherent
elasticity that can be measured. Whereas bone has a
very high coefficient (the Young modulus), suggesting a rather low capacity to deform, vessel walls have
a much lower Young modulus (Table 14.1). Furthermore, those very components present within the vessel wall, namely collagen and elastin, have different
moduli. It can be assumed that, as one component
of the vessel wall is reduced or destroyed, the ability of the vessel wall to return to its original state is
compromised. Because vessels are alive and remodel
with varying stress, the additional collagen (not elastin) that is deposited alters the characteristics of the
vessel and thus its behavior. Current studies have not

Fig. 14.2 Schematic illustration of the Young modulus in relation to the stress and strain a vessel experiences along the flow of
blood. F, force on the wall; A, area; L, change in vessel segment length; L, original segment length.


130 Part IV Intracranial Aneurysms and Vasospasm

Table 14.1 Values of the Young modulus for various

Young modulus

Blood vessel components


1 108 1 109

Smooth muscle

5 106
1 105 1 107

Biological materials

1 1011

Tooth enamel

5 1011

Tooth dentin

1 1011


2 109


1 107


3 109

Vulcanized rubber

5 105


1 1011


2 1012


7 1010


11 1010


7 1010

clearly delineated this phase of aneurysm formation

because it is difficult to determine if the forces and
impulses result in degradation of the internal elastic lamina or if the lack of a complete internal elastic
lamina precipitates the formation of the aneurysm.
Blood is a two-component viscoelastic fluid,
which is composed of approximately 65% liquid (in
the form of 8095% water and many proteins) and
35% cells. Though blood is 90% water by weight, the
presence of the proteins (7% of the plasma by weight)
and cells gives blood unique properties.28 Additionally, blood is an active participant in the formation of
aneurysms, in that its flow provides the mechanical
triggers for reactions in the vessels at the level of the
endothelium, while is is also a biological participant
in the inflammatory cascade.31,32 This dual function of
blood contributes significantly to the degradation of
the arterial wall in the formation of aneurysms.

Methods of Analysis
The biophysical nature of aneurysms is inferred. No
current study or in vivo analysis has yet been developed to allow clinicians to accurately predict the

rupture status of aneurysms, let alone accurately

predict which aneurysms are at risk for future rupture. Consequently, several surrogate markers have
been studied and have served as the initial parameters in helping to understand aneurysmal behavior.
Each methodology provides insight and important
data on aneurysm growth, rupture, and potentially
Each method of analysis requires the development of models that can be categorized by the type of
information they provide. Biomorphometric studies
demonstrate relationships between various observable, physical characteristics of aneurysms and their
parent vessels and rupture status. Biomathematical models are based on established biomechanical
principles that can broadly demonstrate biological
behaviors. Computational models allow a more realistic approach to developing relationships because
they include a dynamic analysis of flow and its interactions with the aneurysm and vessel. In vitro models of glass and silicone provide excellent data on the
behavior of aneurysms, especially when modeled
after aneurysms obtained from patient-specific imaging studies. Finally, in vivo animal models, though not
critical to predicting aneurysmal rupture, have been
vital to the development of technology used to treat
aneurysms and to the efficacy of treatment.

Biomorphometric Analysis
of Aneurysms

The most fundamental approach to studying aneurysms and determining the potential for rupture is
the observational analysis of the imaging characteristics of aneurysms. The literature includes many
such studies that have assessed one or more characteristics as a means of determining which aneurysms
might be at risk for rupture. Several studies have certainly identified size as an important determinant of
rupture status, though some controversy exists as to
the actual range for rupture risk.33,34
The locations of aneurysms have been linked to
rupture status; most clinical series report the anterior communicating artery as the most frequent site
for ruptured aneurysms, whereas the middle cerebral artery is the most common location for unruptured aneurysms, as determined in autopsy series.33,35
Though difficult to quantitate, aneurysm shape
has been implicated in the rupture of aneurysms,
particularly, as first described by Murphy and colleagues, as the presence of a bleb (Fig. 14.3).36,37 Subsequently, shape has been qualified in other studies
that correlate aneurysm rupture with specific shape
characteristics (Fig. 14.4).38,39
The aforementioned characteristics, which can
be directly gleaned from any of a variety of imag-

14 The Biophysics of Aneurysm Formation and Rupture

Fig. 14.3 Aneurysm blebs. (a) Anteroposterior view of a basilar tip aneurysm with a large bleb pointing superiorly relative to the

aneurysms dome, demonstrating the relative size to which such blebs can grow. (b) Lateral view of a posterior communicating
aneurysm demonstrating multiple blebs of different sizes and projections suggesting the complexity with which some aneurysms
may grow.

Fig. 14.4 Schematic of aneurysm shapes and the correlation with rupture predictability.39


132 Part IV Intracranial Aneurysms and Vasospasm

ing studies without additional calculations, are
primary criteria. Secondary criteria are those criteria that require additional manipulations (calculations) that are used for aneurysm rupture status
The aspect ratio is defined as the ratio between
the height of the aneurysm and the diameter of the
ostium.43 A similar correlative relationship between
the volume of the aneurysm and the orifice has likewise demonstrated some correlation to rupture.44
Size ratio and growth rate of aneurysms that have
been followed longitudinally have been important
factors as well.45,46,47
Such analyses provide excellent insight and correlation to the rupture status of aneurysms as individual parameters. Recent correlations involving
binary logistic regression analysis have looked at
several different biomorphometric criteria and have
demonstrated 84% accuracy in predicting aneurysm
rupture status by including several primary and
secondary criteria in an independent prospective
cohort. Nonetheless, an accuracy of 84%, though significant, requires additional validation in order to be
clinically relevant.6,7
The geometric relationships of aneurysms and
the bifurcation configurations are of importance as
well. Recent studies on true and junctional posterior
communicating artery aneurysms demonstrate that
aneurysms with acute angulations from the main
velocity vector have a higher propensity to rupture.48

Biomathematical Modeling
Biomathematical models in general provide first
approximations to the behavior of aneurysms based
on the biophysics and the physiological characteristics of the aneurysm. By derivations of well-known
formulae as applied to a viscoelastic system, general trending can be delineated, which can serve as
a sometimes excellent approximation of predicted
behavior. Dynamic and static equations can be used
to help explain the behavior of aneurysms in specific
conditions, and subsequent predictions or trends
can be made. Although some quantitative data can
be generated, in general analysis with biomathematical models may be more qualitative. Though these
equations may not be able to directly address which
aneurysms are at highest risk of rupturing, they
demonstrate important trends in understanding the
principles of aneurysm behavior.
One of the more obvious approaches to studying aneurysms through a known biomathematical
entity is through the use of the law of Laplace and
Hookes law. Both laws relate the stress and strain on
any given elastic object, as was previously described.
Thus, as a rough approximation, one can analyze an
aneurysms stress and strain pattern with respect to

the criteria that would result in failure of the aneurysm wall. In this instance, the static properties of
the aneurysm (wall thickness and stress), as opposed
to dynamic properties (flow and shear), are assessed
for rupture potential. Recent studies have described
the use of Laplaces law to determine the relationship between wall thickness of the aneurysm and
the radius of the aneurysm.
In brief, Laplaces law states that there is a linear
relationship between the circumferential stress of a
sphere and its radius. In other words, as the sphere
increases in size, there is a directly proportional
increase in the stress placed on the wall, which for
the purposes of description is represented by a thin
shell. This can be represented by the equation:
Equation 1:
S = PR/2h
where S represents the circumferential stress on the
aneurysm wall, P is the blood pressure, R is the aneurysm radius and h is the aneurysms wall thickness.
Kyriacou and Humphrey looked at the aneurysm, by first approximation, as an elastic shell that
exhibited nonlinear behavior under a finite stress,
thus modifying the aforementioned equation.49 By
employing data obtained from prior investigations
that reported on pressurevolume relationships in
aneurysms,50 the investigators were able to determine that increases in stress and strain were most
correlated with increase in aneurysm size, aspect
ratio, and distending transmural pressure. These
changes and risks were most likely to occur at the
fundus, which correlates with clinical observations.
These results, however, were based on two-dimensional stress-strain energy functions. Though most
of the stress and strain in aneurysms may arguably
be in a two-dimensional orientation parallel to the
flow of blood, three-dimensional analysis was performed to generate a more robust model in understanding rupture.
Studies by Chaudhry et al accounted for threedimensional stress on the model and thus demonstrated that when the ratio of aneurysm radius to
wall thickness is 6.10 10-3, the stress of analyzing with suboptimal information51 n the wall of the
aneurysm will exceed limits, and thus the aneurysm
will theoretically rupture.
Another application of Laplaces law was
described by Meng et al in their analysis of aneurysm blebs and their effect on aneurysm rupture.52
In their intriguing study, they demonstrated that the
formation of a bleb (hemispheric in shape) would
actually reduce the circumferential stress of the
aneurysm, thus reducing the likelihood of rupture
(Fig. 14.5). As the bleb grows, in essence, it resets
the rupture limit of the now-modified shell such
that rupture is delayed. However, further analysis
revealed that as the bleb continues to grow, indeed,

14 The Biophysics of Aneurysm Formation and Rupture

Fig. 14.5 The relationship between parent and daughter aneurysm. h', daughter aneurysm height; r, daughter aneurysm
radius; a', daughter aneurysm orifice radius; R, parent aneurysm radius.52

rupture ensues. This strongly suggests that bleb formation may protect against, or rather delay, rupture
in the early phases of bleb formation. Indeed, applying
Chaudhrys derivation of Laplaces law to this model,
it was noted that rupture of the daughter bleb would
occur when the ratio of wall thickness to aneurysm
radius in the daughter aneurysm equals the same
ratio as the wall thickness to aneurysm radius of the
parent aneurysm, 6.10 10-3. Other studies confirm
this finding.53
As with all biomathematical models, some stringent assumptions must be made that may not be generalizable to the clinical scenario. For instance, the
aforementioned studies assume that all aneurysms
are hemispheric in shape; that is, they exhibit the
regular shape of a sphere transected along a certain
chord. It is interesting to note that few aneurysms,
especially ruptured aneurysms, exhibit this regular
shape. Additionally, it is assumed that all aneurysms
exhibit a constant wall thickness throughout the
shell, but direct observations suggest that this is not
the case. Nonetheless, such modeling continues to
be of great import in providing investigators with a
first pass54 understanding of the complex relationships between shape, stress, and some of the physical
characteristics of the tissues making up aneurysms
and their parent vessels. A more granular assessment of rupture status and risk can be achieved if
a dynamic assessment of the interplay between the
physical characteristics of the wall and the flow of
blood can be modeled.

Rheology and Computational


Blood and blood flow are fascinating in their complexity. Blood is characterized as a thixotropic
fluid; that is, its properties change with changes

in speed. In general, fluids are of two types based

on their flow characteristics. Newtonian fluids
exhibit a constant viscosity during increases in
velocity and demonstrate a proportional relationship with sheer stress. Non-Newtonian fluids demonstrate a change in viscosity as velocity changes,
and the resulting shear stress is not proportional.
The velocity of blood changes. Therefore, because
bloods viscosity changes as velocity changes at the
small arteriolar and capillary level while inducing
a variable shear stress, it can be considered nonNewtonian. However, in large arteries and medium
arterioles, the Newtonian properties of blood
greatly dominate its behavior. The benefit of this
observation means that, when addressing the flow
of blood in the arteries of the cerebral circulation,
one can assume that blood is behaving as a Newtonian fluid by first approximation. As such, one can
begin to model the flow of blood in a vessel using
several equations that have been derived for flow
in rigid tubes. Subsequent to that, modifications for
the flow of blood in a specific environment (flow
within the viscoelastic tube that is an artery) can
be made to determine behavior of blood flow and
its interactions on the vessel wall.
Flow is primarily defined through Poiseuilles
law, where flow (Q) is directly proportional to the
inflow pressure (P) and the radius of the vessel to
the fourth power (R), while inversely proportional
to the length of the tube (vessel, L) and the viscosity
of the fluid (blood, ):
Equation 2:

PR 4t

Blood, however, is driven through a pulsatile,

not constant, force and pressure. Thus, in order to
compensate for the inertial component of flow, the
Navier-Stokes equations were derived to explain flow
through tubes where the inertia as represented by
the variables to the right of the equation, is related to
the pressure gradient ( p ), the viscosity ( 2v ),
and the other physical forces ():

Equation 3:
( + v

v) = p + v +

These differential equations account for the

interactions of flow as it accelerates and decelerates during a cardiac cycle. In general, the equations demonstrate a proportional association of the
fluids viscous forces with the fluids viscosity and
the velocity gradient within the zone of interest (the
blood vessel). The equations allow investigators to
approximate analytical and numerical solutions only.


134 Part IV Intracranial Aneurysms and Vasospasm

Thus, solving these equations for a particular set
of parameters requires a series of repetitive calculations to allow a steady state. This is accomplished,
in brief, through computational fluid dynamics (CFD)

Computational Fluid Dynamics

CFD serves two purposes: (1) It helps to describe
and explain how various biomechanical forces act
on the vessel wall and in aneurysms in general, and
(2) it provides valuable data when patient-specific
aneurysms are constructed that may provide some
prediction of an aneurysms behavior. The rise of
the personal computer, with its near-exponential
growth in computing power, has made the ability
to understand aneurysms and aneurysm growth
possible through the use of CFD.55,56 Prior to the
introduction of CFD for aneurysms, the interest in
understanding how flow influences aneurysm formation grew with the development of endovascular
techniques. Through the many observations made
in the endovascular treatment of aneurysms, new
phrases have been introduced into the neuroendovascular therapists lexicon. No longer is there simply a discussion of an anatomical aneurysmal neck or
aneurysmal dome. There is extensive discussion of
physiological inflow zones and outflow zones within
the anatomical neck of aneurysms. Such phrases
developed because of the angiographic observations made during microcatheter manipulations to
engage the aneurysm for coiling. The incidence of
recurrence has also been related to the inflow and
outflow zones. The personal computer has brought
CFD analysis to the clinical realm and almost to the
patients bedside.
By employing proprietary or bundled software to
define and describe blood flow and the vessel within
which it flows, investigators can generate time-dependent models from which one can derive important
information regarding blood velocity and its effects on
the surrounding vessel by analyzing dynamic forces,
dynamic pressures, and shear stress along any portion
of the vessel. Such computer-generated models have
been independently validated by comparing the qualitative results from bench-top models with the CFD
profiles (Fig. 14.6).57 This allows several advantages in
studying very specific questions in aneurysm formation with a relatively lower cost. It also provides additional information on the changes in dynamic forces
exerted on aneurysms as morphological changes in
the parent vessel or aneurysm occur.
Though it is clear that dynamic forces have a direct
effect on the formation of aneurysms and aneurysmal rupture, there is much controversy over the role
of wall shear stress in aneurysm growth and rupture.

Fig. 14.6 Computational fluid dynamics (CFD) analysis demonstrating dynamic forces along the flow of blood in this simulated model that duplicated a bench silicone model by Byun et al.57

Kulcsr et al, in a preliminary study of three patients,

demonstrated that high wall shear stress is required
for the initiation and possible growth of cerebral
aneurysms.58 On the other hand, low wall shear stress
may induce an inflammatory response that subsequently results in excessive wall thinning and possibly rupture.59

In Vitro Phantom Models

Perhaps some of the earliest models to be constructed to help study aneurysms were made of glass
or elastic (Fig. 14.7).6062,63 Variable color dye introduced into a laminar flow fluid model demonstrated
the sometimes nonintuitive flow patterns generated
by flow in the carotid and vertebral arteries. Though
purely qualitative, initial studies demonstrated the
concepts of zones of impingement and turbulent
flow that have since been evaluated through the
use of CFD and other computer-based technologies.
Nonetheless, the newer, patient-specific siliconebased models and the inclusion of newer techniques,
such as particle velocimetry, provide an elegant
method to assess some of the dynamic aspects of
flow in aneurysms that might help predict regrowth.
Additionally, such models may ultimately be of help
in testing the various treatment options that exist for
these patients by specifically studying the dynamics

14 The Biophysics of Aneurysm Formation and Rupture

Fig. 14.7 A patient-specific glass model of a wide-necked midbasilar aneurysm (a) at peak systole with evidence of entry flow
via the distal neck and (b) during the subsequent cycle with documented vorticeal flow within the dome.62 (Reprinted with permission. Imbesi SG, Kerber CW. Analysis of slipstream flow in a wide-necked basilar artery aneurysm: evaluation of potential treatment
regimens. AJNR Am J Neuroradiol 2001;22:721724. By American Society of Neuroradiology.)

of flow after an aneurysm has been coiled. Such studies may help in predicting coil compaction or aneurysm recurrence.

In Vivo Models
Several methods have been reported for creating
aneurysms in animals.6469 Through the use of biochemical degradation of the media, induced hypertensive therapy to engage stress-based remodeling at
the tissue level, genetics, or the challenging surgical
creation of an aneurysm, in vivo models have been
important in advancing the science and technology
of aneurysm therapy. However, the technical nuances
of reproducing a consistent aneurysm in canine or
porcine models, along with the cost of boarding animals, can make this method of studying aneurysm
formation and growth costly and unpredictable.
Nonetheless, such models have been of great importance in helping to derive and understand the endovascular management of these lesions.

Aneurysm Formation
Cerebral aneurysms most often form at bifurcations.
The genesis of aneurysms, as noted, has numerous biological factors. The environmental stress
and strain imparted by flow past the bifurcation
have been implicated in several pathological entities. Computational analysis has demonstrated that
wall shear stresses are at a maximum just distal to
the bifurcation and correlate with the presence of
plaques in large arteries. As discussed, the geometry
of the various bifurcations around the circle of Willis
adds additional stress to the vessel walls, given the
significant shifts in flow velocity, dynamic forces,
and shear stress.70 Thus, high flow across a wall that
is not designed for the exposed pressures results
in tissue injury and remodeling. The biological result
may be plaque or may be an aneurysm, depending
on the presence (or absence) of an intact media.
As discussed, the role of shear stress is very controversial.7173 Several studies suggest that the direct
effect of shear stress on the vessel wall results in


136 Part IV Intracranial Aneurysms and Vasospasm

injury and thus degeneration of the walls media,
which leads to aneurysm formation. Others suggest
that, indeed, low shear stress in the aneurysm and
the vessel wall may result in small thrombus formation, endothelial reactivity, and inflammation at
the site, which, in turn, weakens the vessel. Various
models have been analyzed in vivo as well as in vitro,
with conflicting (or rather, seemingly conflicting)
results. Further analysis may demonstrate that each
is responsible for damage at specific phases of aneurysmal development and rupture.
Aneurysm rupture has been suggested to occur
as aneurysm expansion approaches and exceeds
the physical limits of the tissue. Hademenos et al
and others have generated various biomathematical
equations to suggest a size range or wall-thickness
range for which rupture would occur.74,75 Clinical
studies corroborate this only in part.
It has also been suggested that the vibrations
induced by pulsatile flow and the subsequent resonant frequency may promote aneurysmal rupture.7681
By measuring intra-aneurysmal frequencies, Ferguson noted documented vibrational tones ranging to
the 460 Hz in unruptured aneurysms.82 Therefore,
though this range exceeds normal acoustic ranges of
physiological processes of 20 to 200 Hz, it is unclear
if such observations correlate with future rupture.
The presumptive mechanism of action is the noted
degradation of vessel walls due to repetitive vibrations at high frequencies. Thus, although not directly
resulting in aneurysmal rupture, vibrational irregularities secondary to the presence of the aneurysm
may accelerate the degeneration of the aneurysmal
wall and subsequently lead to rupture.

Can Aneurysmal Rupture

Be Predicted?

Just as in the 17th and 18th centuries, advances in

the field of aneurysm biophysics rest on the involvement of many disciplines. Though in earlier centuries this was achieved by a few individuals who
were dual trained in various disciplines, such as
medicine and physics or medicine and mathematics,
today, the body of knowledge available within each
discipline outstrips the ability of any one individual
to embrace it. Teams of researchers from all fields
now share in the interest and desire to understand
and thus treat, or better yet prevent, aneurysms.
Patient-specific modeling, though not available for
real-time analysis, continues to shed new light
on the pathophysiology of aneurysms. The biology,
genetics, and subsequent pathobiology cannot be
overemphasized. However, as the disciplines continue to shed new insights into aneurysm formation,

it is not outside the realm of possibility to eventually

create a predictive model that will encompass all biological and biophysical aspects of a patients newly
discovered aneurysm into an admittedly complex
algorithm that will provide an accurate prediction
of rupture. With this knowledge, ideally only those
patients at high risk for rupture will be exposed to
the risks of treatment, thus maximizing benefit and
minimizing risk.

Future Directions
Understanding the biophysics of aneurysm formation is a stepping stone to understanding the efficacy
of aneurysm treatment. In conjunction with studies in the genetics, epidemiology, and pathobiology
of aneurysm formation, studying the biophysics
of aneurysm formation provides a more complete
picture of how these factors interact. The next step
in this endeavor is to develop a method by which
the seemingly disparate analyses can be integrated
into a comprehensive view of aneurysm formation.
What would follow is the development of an albeit
complex algorithm that would allow multiple input
parameters obtained from images, serological studies, and genetics testing that would provide a relative rupture risk for a patient-specific aneurysm.
Thus, the physician would be given an important
tool to help guide the patient toward the best option
for treatment or observation. Indeed, such software
and algorithms would likewise enable clinicians to
determine best treatment patterns or perhaps simulate the best therapy and assess long-term efficacy.
After all, exposing only those patients at a true risk
of rupture to treatment is what all clinicians strive
for. Further studies in biophysics will help us achieve
this goal.

Understanding the biophysics and mathematics of aneurysm formation, growth, and rupture can be important in predicting aneurysm
Current progress in biomorphometrics, biomathematics, fluid dynamics, and in vitro and
in vivo models provides distinct and complementary aspects to understanding aneurysm
With appropriate, highly accurate, and highly
predictive models, future clinicians may help
patients in deciding on the best management
for these potentially lethal lesions.

14 The Biophysics of Aneurysm Formation and Rupture

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Endosaccular Treatment of Aneurysms

Charles E. Romero and In Sup Choi

Intracranial aneurysms constitute a significant public health problem in the United States. Subarachnoid
hemorrhage as a consequence of spontaneous aneurysmal rupture affects approximately 10 patients per
100,000 yearly.1 Roughly 10% of these patients die
before reaching the hospital. The greatest morbidity and mortality affecting the survivors of the initial
event is the risk of rebleeding and cerebral vasospasm.2,3 As such, cerebral aneurysms deserve a thorough evaluation for potential treatment, given that as
many as 50% of subarachnoid hemorrhage patients
eventually die as a result of their hemorrhage.2

History of Endosaccular


Several endosaccular techniques to treat intracranial

aneurysms have been investigated and refined over
the last 25 years. Initial attempts used flow-directed
detachable balloons that were guided directly into the
aneurysm lumen. There were a few problems with
the balloon technique.46 Navigation of balloons into
the aneurysm lumen was often difficult and proper
fitting of the balloons in the lumen of the aneurysm
was not always possible. The technique required the
operator to exchange the existing contrast material
in the tubing and balloon with a permanent solidifying agent, 2-hydroxyethyl methylacrylate, to prevent balloon deflation.7 The procedure had a high
morbidity as a result of acute or delayed rupture of
the aneurysm after balloon placement and possible
thromboembolic events during the embolization.8
In 1991, Guglielmi developed a detachable coil
system to pack the aneurysm sac without significant
manipulation inside the lumen.9,10 This breakthrough
system using the principles of electrothrombosis and
electrolysis revolutionized the management of intracranial aneurysm. Electrothrombosis occurs when a

positively charged electrode that has been placed in

the bloodstream attracts negatively charged blood
elements: red and white blood cells, platelets, and
fibrinogen. Electrolysis occurs when the two electrodes positioned in a solution are connected to
direct current. The ferrous ion of the wire at the positive end dissolves into the solution, and the negative
end recruits the migrating ferrous ions.9
To create this coil system, Guglielmi exploited the
electrolytic property of stainless steel and the nonelectrolytic property of the noble metal platinum. The distal
coil, which is made of platinum, is attached to a detaching segment wire, which is made of stainless steel.
When the direct current is applied to this coil system,
the positively charged platinum coils promote electrothrombosis while at the same time electrolysis of the
junctional stainless steel wire occurs, detaching the
platinum coil in the aneurysm without any traction.10
In initial animal studies, the coil mesh in the
aneurysm lumen permits organized thrombus formation followed by the subsequent creation of a thin
membrane across the neck of the aneurysm. This is
believed to prevent flow of blood into the aneurysm.
However, further animal studies and clinical practice
have illustrated that the newly formed thrombus may
not be permanent. Furthermore, the aneurysm lumen
may recanalize despite these physiological changes.
Technological advances have improved outcomes
of endovascular treatment. The addition of complexshaped and softer coils of several sizes and lengths
has allowed for safer delivery and tighter coil packing densities. These improvements, coupled with
superior detachment systems, have dramatically
reduced current procedure times, translating to better clinical outcomes.

Advantages of Endosaccular

Endosaccular occlusion of aneurysm with platinum coils has become a proven method of treating

15 Endosaccular Treatment of Aneurysms

intracranial aneurysm. For aneurysms in certain
locations (vertebrobasilar system, paraclinoid
region of the internal carotid artery, or anterior
communicating artery territories), the endovascular approach is more favorable. Better clinical outcomes can also be seen after endovascular therapy
in patients with other medical problems apart
from the subarachnoid hemorrhage.1113
The procedure allows for the possible treatment
of multiple aneurysms during the initial procedure,
reducing the need for multiple interventions. It also
allows for early therapeutic intervention, often in the
same setting as the initial diagnostic angiographic
study. This is particularly appealing in patients with
high clinical grades, who may be medically or neurologically unstable.14,15 The possible treatment at
the time of the initial diagnostic cerebral angiogram
after an acute subarachnoid hemorrhage may also
reduce a chance of rerupture.16
Endosaccular treatment of aneurysms has also
been revolutionized by the remarkable technical
refinements in the area of microcatheters. Transfemoral access to intracranial aneurysms located at
practically any site can be obtained with the new
generation of microcatheters and guidewires. The
newer generations of microcatheters are constructed
of braided, hydrophilically coated polymers, allowing for improved maneuverability. These technological breakthroughs translate into increasing our
chances of obtaining aneurysm occlusion.

Patient Selection
Ruptured aneurysms are more often considered
for coiling, unless they are associated with a large
intraparenchymal hematoma or have unfavorable
geometric characteristics.17,18 The decision to treat
surgically or endovascularly is best made by a multidisciplinary team approach.1922
Intuitively, patients who have aneurysms with a
small neck are considered to have a favorable geometric configuration.23 This is also true for instances
where the dome to neck ratio is 2. In these cases,
the aneurysm configuration allows for better coil
mesh packing (Fig. 15.1ae). For each sequential
loop delivered into the lumen, it is more likely that
the loop will remain in the aneurysm sac. Alternatively, in wide-neck aneurysm cases, the possibility
of a coil loop protruding into the parent vessel lumen
remains high.
Aneurysms that have surgical necks > 4 mm or
a dome to neck ratio < 2 are considered to have an
unfavorable configuration. In addition, unfavorable
configurations include aneurysms with necks that
involve branch points and aneurysms with anatomy
that is difficult to define despite three-dimensional

(3D) angiography (e.g., ones that involve middle cerebral artery bifurcation or trifurcation segments).24 In
these instances, the incidental occlusion of the parent vessel or one of the branch vessels would yield an
unacceptable operative risk. The endosaccular treatment of aneurysms with unfavorable configurations
may warrant the use of additional instrumentation,
including vascular reconstruction devices, for successful embolization.25

Cerebral aneurysms are traditionally classified as
saccular or fusiform. A full overview of aneurysm
etiologies is beyond the scope of this chapter. It
should be stated, however, that the aneurysm shape
and size largely determine the mode of endovascular treatment. For example, the treatment of saccular
aneurysms with a well-circumscribed neck can be
achieved by packing the aneurysm lumen with coils.
The treatment of fusiform, irregularly shaped aneurysms may require vessel reconstruction or occlusion of the parent artery in certain cases for durable
That said, endovascular treatments can be
divided into two categories: reconstructive, those
that preserve the parent artery, and deconstructive,
those that involve its occlusion. Parent artery occlusion can be useful in situations where the neck of the
aneurysm is too wide to retain coils within the sac
or in fusiform-shaped aneurysms with no definable
neck. The safety of parent vessel occlusion is obviously dependent on adequate collateral supply to the
arterial territory of the vessel to be sacrificed.
Endovascular coil treatment of aneurysms is performed with the patient under general anesthesia
and with complete paralysis. In cases of unruptured
aneurysm, the procedure is performed under systemic heparinization. Activated clotting times (ACTs)
are checked at close intervals to maintain a level
between 250 and 300 seconds. Typically, a bolus of
3,000 to 5,000 units of heparin is injected as soon
as the guiding catheter is properly positioned in the
parent artery. Additional heparin boluses of 1,000
units per hour are given until the end of the procedure to maintain the ACT at the desired goal. In cases
of ruptured aneurysm, systemic heparinization is
started after the first coil is placed into the dome,
securing the ruptured point of the aneurysm.
The sheath, guiding catheter, and microcatheter
are also continuously flushed with heparinized saline
(4,000 units of heparin per liter of saline) to prevent
formation of clots in the catheter system. Heparin is
usually maintained for 24 hours after the end of the
procedure in our practice. In most cases, a 6F guiding catheter is used unless aneurysm configuration


142 Part IV Intracranial Aneurysms and Vasospasm

Fig. 15.1 Endovascular coil treatment of small-necked aneurysm. Unruptured large left posterior communicating artery
aneurysm of a 76-year-old female with diplopia and third nerve
palsy. (a) Magnetic resonance imaging (MRI) T2-weighted sequence, left-sided posterior communicating aneurysm, (b) lateral projection, preembolization angiogram, (c) lateral projection,
placement of first coil forming stable basket, (d) lateral projection, placement of 10th coil filling back toward aneurysm neck,
(e) lateral projection, final angiogram after placement of 17 coils.

15 Endosaccular Treatment of Aneurysms

is such that balloon remodeling is required or the
concomitant deployment of a vascular reconstruction device is expected. Typically, a 6F guiding catheter lumen allows the microcatheter to advance easily
and provides enough space for repeated injections of
iodine contrast for angiographic study.
In cases where the balloon remodeling technique
is to be implemented, both the balloon catheter and
the microcatheter are run simultaneously in a coaxial
system, inside the same 7F guiding catheter.25 Alternatively, bilateral groin punctures, two sheaths, and
two smaller guiding catheters can be used simultaneously to target the aneurysm.
There are numerous microcatheters available
on the market today. Microcatheter selection most
importantly depends on the size and configuration
of the aneurysm to be treated. The newer catheters
are constructed of proprietary braided shafts with
reinforced distal segments to help reduce kinking. Microcatheters come in several lengths, inner
diameter sizes, and distal tip shapes. Each variable is
important to ensure proper placement into the aneurysm sac. Most microcatheters can be shaped into
any number of subtle configurations using a metallic
mandrel and heating the distal end with steam for
several seconds. Microcatheter tip shape selection is
made according to the orientation of the neck of the
aneurysm and the curve of the parent vessel at the
aneurysm, if present.
For successful placement of the microcatheter into the aneurysm dome, the microcatheter is
advanced over a soft-tip guidewire. Once in proper
position, detachable coils are introduced into the
lumen. If the coil migrates or protrudes into the parent vessel, it can be repositioned until a satisfactory
position is reached. Subsequent coils of decreasing
size are then introduced, filling the aneurysm and
ultimately blocking blood flow.

Selecting the First Coil

One of the critical steps for a successful endosaccular treatment is proper selection of the first coil.
This coil sets the stage for determining the packing density. Ideally, the first coil is chosen 1 to 2
mm wider than the maximum diameter of the
aneurysm. The proper technique is to maintain the
distal tip of the microcatheter in the middle of the
dome. The use of 3D coils may help form a stable
basket. During coil placement, we always attempt
to cover the neck of the aneurysm with several
loops of the first coil.
Great care must be taken at all times to minimize
the risk of aneurysm rupture.27 The tip of the catheter must be accurately visualized when deploying
the first coil to avoid perforation of the dome wall
with either the coil itself or the microcatheter during

the procedure. The microcatheter tip might require

repositioning after the coil loops are advanced into
the sac of the aneurysm. The technique of slowly
deploying coil loops that are arranged in different
positions within the aneurysm sac can lead to the
formation of a stable basket. The first coil can be
safely detached once it is confirmed that the loops of
the coil are within the aneurysm lumen and are not
protruding through the neck (Fig. 15.2ae).
In cases involving bilobed aneurysms, the operator may decide to close each dome separately because
a simple spherically shaped initial basket may not
provide proper occlusion of the aneurysm lumen.
The coil size has to be selected according to the size
of the main dome to make a complex-shaped basket.
For unproportionally elongated aneurysms, especially with wide necks, it may not be feasible to form
a proper basket covering both the dome and the neck.
In such instances, it is necessary to place the first coil
in the distal part of the dome despite the fact that
the coil loops do not cover the neck of the aneurysm.
Once the distal portion is properly closed, the loops
of subsequent coils introduced can be drawn back
toward the neck. The process continues until the new
coil mesh ultimately covers the neck gradually. This
is the so-called piecemeal technique (Fig. 15.3ae).
As the first coil is advanced through the microcatheter, the catheter tip may shift inside the aneurysm dome, and the tip may progressively become
immobilized, or in some instances, be pushed out of
the aneurysm altogether. Maneuvering the catheter
back into the aneurysm over the partially deployed
coil as a guidewire can sometimes be accomplished.
Great care should be used whenever maneuvering
the microcatheter to reenter an aneurysm to avoid
dome perforation or thromboembolic complications.
At the end of the coiling procedure, the aneurysm
should ideally be densely packed across the neck
with no visible gaps between the coil loops on either
anteroposterior or lateral views. It is not uncommon to have an empty pocket in the middle of the
coil mesh or part of the aneurysm. Our technique is
always to attempt to reposition the tip of the microcatheter into such a pocket whenever possible. The
ability to achieve a tight packing density often relies
on subtle resistance and friction cues within the
microcatheter system that are felt by the operator as
each coil loop is advanced millimeter by millimeter
with great care.

Types of Coils
There are various types of coils available. It is generally understood that there is no clear evidence demonstrating benefit of one coil over another; however,
brief mention of the key features of coils available
today is warranted. All coils used today share a plati-


144 Part IV Intracranial Aneurysms and Vasospasm

Fig. 15.2ac Basket technique. Unruptured basilar tip aneurysm of a 53-year-old woman that was incidentally discovered. (a)

Anteroposterior (AP) projection, irregularly shaped top of the basilar aneurysm, (b) AP projection, placement of first coil forming
stable basket, (c) lateral projection, placement of first coil forming stable basket.

15 Endosaccular Treatment of Aneurysms

Fig. 15.2de (continued) Basket technique. (d) AP projection, angiographic view after stable basket is formed, (e) AP projection,
final angiogram after placement of 16 coils.


146 Part IV Intracranial Aneurysms and Vasospasm

Fig. 15.3ac Piecemeal technique. Ruptured distal anterior cerebral artery aneurysm of a rapidly deteriorating 38-year-old

woman who presented for evaluation of thunderclap headache (Hunt and Hess grade 4). (a) Lateral projection, irregularly shaped
elongated aneurysm, preembolization angiogram, (b) lateral projection, placement of first coil closing distal dome of elongated
aneurysm, neck remains unprotected, (c) lateral projection, placement of fourth coil, filling back toward aneurysm neck.

15 Endosaccular Treatment of Aneurysms

Fig. 15.3df (continued) Piecemeal technique. Ruptured distal anterior cerebral artery aneurysm of a rapidly deteriorating
38-year-old woman who presented for evaluation of thunderclap headache (Hunt and Hess grade 4). (d) Lateral projection, placement of fifth coil closing aneurysm neck, (e) lateral projection, final angiogram after placement of six coils, (f) lateral projection,
1-year follow-up angiogram.


148 Part IV Intracranial Aneurysms and Vasospasm

num filament core that undergoes an initial wind to
form a traditional helical shape, a 3D form, or a more
complex proprietary design. The key features targeted in the microcoil design are stretch resistance,
softness, conformability, uniformity of coil distribution once deployed, and the ability of the coil to cover
the aneurysm neck and thus reduce recurrence. Coil
composition and bioactivity may also improve packing density and reduce recurrence.
There are some coil design features that may provide a key benefit or disadvantages worth discussion.
In the case of the Trufill DCS Orbit system (Codman
Neurovascular, New Brunswick, NJ), the softer coil
profile and complex shape allow for increased volumetric filling. These coils form random loops and
breaks that seek out the true aneurysm periphery,
allowing for true concentric filling. Another soft
coil available on the market today is the Deltapaq
microcoil system (Micrus Endovascular Corp., San
Jose, CA). This microcoil, designed for the treatment of complex cerebral aneurysms, is a conformable, stretch-resistant microcoil designed to provide
stable framing or filling of aneurysms. This is often
needed in cases involving irregularly shaped aneurysms or in the treatment of ruptured aneurysms.
The initial profile of this microcoil system was firm
or stiff; however, this has improved through its proprietary infinity loop design, which also yields excellent conformability with increased packing volume.
Manufacturers have explored coil composition and bioactivity to improve packing density to
ultimately reduce recurrence. The first commercially available bioactive microcoil was the Matrix
Coil (Boston Scientific, Natick, MA). The company
has subsequently developed a newer Matrix2 360
Detachable Coil, which features a new 360-degree
complex shape that is claimed to allow greater conformability and more uniform distribution within
intracranial aneurysms. These microcoils employ
a well-characterized polyglycolic-polylactic acid
(PGLA) copolymer over an inner platinum main coil.
The copolymer runs the entire length of the main coil
and constitutes approximately 70% of the total coil
volume. It is typically absorbed by the body within
90 days. A lubricious coating on the surface of the
outer copolymer coil facilitates coil deployment and
retraction when wet. The coils in some cases may
actually yield less volumetric packing and thus result
in more recanalization.
Another coil with unique composition is the
HydroCoil (MicroVention, Inc., Tustin, CA). This
device uses an expandable polymer to generate up to
11 times the volumetric dimensions compared with
bare platinum coils. This potentially provides the
ability to more effectively fill a cerebral aneurysm.
This microcoil is a hydrogel-coated platinum coil
that swells when it contacts blood to provide higher
filling volumes than bare platinum coils by filling the

interstices of the coil mass.28 The combination of the

platinum coil platform coupled with the expandable
hydrogel material, which increases sevenfold in volume when placed into a physiological environment,
has a theoretical disadvantage of expansion while
positioning if the product working time is exceeded.
The expanded hydrogel can achieve high rates of
volumetric occlusion compared with bare platinum

In 1999, Vanninen et al30 conducted a small prospective randomized study (n = 109) to compare coil
occlusion with surgical ligation for the management
of acutely ruptured intracranial aneurysms. The
study design randomly assigned patients to either
coil embolization (n = 52) or surgical ligation (n =
57). Outcome measures included angiographically
confirmed obliteration of the aneurysm, techniquerelated mortality, and clinical outcome as measured
by the Glasgow Outcome Scale (GOS).
In this study, the primary angiographic results
were better after surgery in patients with anterior
cerebral artery aneurysms (n = 55) and after endovascular treatment in patients with posterior circulation aneurysms (n = 11). There was no significant
difference in angiographic results seen in patients
with middle cerebral artery or internal carotid artery
aneurysms. The technique-related mortality rate
was 4% in the surgical group and 2% in the endovascular group, with no significant difference between
the groups in clinical outcome at 3 months.
The 1-year outcomes of this study were later published by Koivisto et al in 2000.31 Of the 57 patients
assigned to surgical ligation, 43 had good or moderate recovery, 5 had severe disability or were in a vegetative state, and 9 had died. Of the 52 patients who
received coil embolization, 41 had good or moderate
recovery, 4 had severe disability or were in a vegetative state, and 7 had died. Patients with good clinical
outcome did not differ in their neuropsychological
test scores.
The authors reported that endovascular treatment of acutely ruptured intracranial aneurysms
results in early clinical and neuropsychological outcome equal to the outcome of acute surgical clipping and that the endovascular treatment group also
experienced significantly less magnetic resonance
imaging (MRI)-detectable brain injury. The authors
concluded endovascular treatment is suitable for a
selected group of patients, but its long-term efficacy
in preventing rebleeding remains unknown.
In 2003, a large multicenter randomized trial comparing endovascular coiling with neurosurgical clipping
in 2,143 patients with ruptured intracranial aneurysms
was published.32,33 The International Subarachnoid

15 Endosaccular Treatment of Aneurysms

Aneurysm Trial (ISAT) randomly assigned patients to
neurosurgical clipping (n = 1,070) or endovascular coil
embolization (n = 1,073). The proportion of patients
at 1 year with a modified Rankin scale score of 3 to 6
(indicating dependency or death) was evaluated, as was
the interim assessment of rebleeding and death at 2
months and at 1 year.
The study reported 23.7% of patients in the endovascular group were either dependent or had died
at 1 year, compared with 30.6% in the neurosurgical
group. The risk of rebleeding was slightly higher in
the endovascular group, at two per 1,276 patientyears versus zero per 1,081 patient-years for the surgical group. The authors concluded that, in patients
with a ruptured intracranial aneurysm for which
endovascular coiling and neurosurgical clipping are
options, the outcome in terms of disability-free survival at 1 year is significantly better with endovascular coiling, and that the long-term risk of further
bleeding is low with either therapy, although slightly
higher with endovascular treatment.
Wiebers et al,34 lead authors of the International
Study of Unruptured Intracranial Aneurysms (ISUIA),
assessed 4,060 patients with unruptured aneurysms.
The study evaluated the morbidity and mortality
associated with repair of unruptured aneurysms by
surgical clipping or endovascular repair. In addition,
the natural history of patients who had no surgery
was also recorded. Over a 5-year period, 18% of the
1,692 patients who did not receive endovascular or
surgical treatment died due to intracranial hemorrhage. Outcomes were much better for the 451
patients who received endovascular therapy and
the 1,917 who received surgical clipping, with death
rates of 1.8% and 1.5%, respectively.
We have reviewed our single-operator experience in a case series to evaluate clinical outcomes of
patients treated for basilar tip intracranial aneurysms.
We reviewed complications and successful aneurysm obliteration by coil embolization for 68 basilar
tip aneurysms treated between September 1992 and
December 2007. In our experience, at least 95% posttreatment (acute) occlusion was achieved in 89.7%
(61 aneurysms) of the coil-treated BA tip aneurysms
(87.5% for ruptured and 91.7% for unruptured). Posttreatment occlusion of 100% was achieved in 39.7%
(27 aneurysms), and near-complete occlusion was
obtained in 50.0% (34 aneurysms). Incomplete occlusion was seen in 10.3% (7 aneurysms) in our series.
Significantly lower rates of occlusion were achieved
during the first treatment session in aneurysms with
larger neck widths and larger aneurysmal size.
Data in the literature confirm a relationship
between aneurysm neck size and the degree of occlusion on follow-up, with a higher chance of recanalization occurring in wide-necked aneurysms.35 In our
study, there was a significant difference in aneurysmal size and neck width between the recanalized

and the nonrecanalized groups, and we confirmed

the higher chance of recanalization in aneurysms
larger than 10 mm.

Complications are typically categorized into two
groups: neurological and nonneurological. These
groups can be further subdivided into transient
or permanent subgroups. Reported complications
of endovascular coiling include bleeding, cerebral
embolus, cerebral vasospasm, coil stretching, herniation, migration, dissection, errant coil placement,
and thrombosis.3638 Incomplete obliteration and
aneurysm recurrence may also occur. All series in the
literature report low morbidity and mortality rates,
both of which decrease with operator experience.
Several mechanisms have been proposed to
explain the pathogenesis of cerebral ischemia. Early
ischemic complications may result from direct aneurysm perforation, vasospasm, or vessel occlusion.37
Late complications may result from thromboembolic events that can be precipitated by endothelium
injury during the procedure. Procedural morbidity
rates of 4 to 6% and mortality of 1 to 4% have been
Device failure (i.e., coil fracture, premature
deployment, or coil stretching) may lead to additional complications. The presence of coil segments
in the parent artery may result in thrombus formation and stroke. Another concern is delayed hemorrhage.39 One possible mechanism is bleeding within
a small infarct site that resulted from emboli forming
on the coil surface. Another presumed explanation
is delayed aneurysm rupture, whereby the coil mesh
itself compacts after treatment; the aneurysm dome
recanalizes and then ruptures.
In our series, we encountered complications
during the procedure in 4.3% (aneurysm rupture
in 2.9% and thromboembolic events in 1.5%), and
transient delayed events in 9.3% (increased mass
effect in 1.5% and delayed transient ischemic attack
or infarct in 7.4%). Similar to other published series,
77.9% of our patients were independent (GOS score
of 4 or 5), 5.9% were dependent (GOS score of 3),
and 8.8% had died.
Despite the aforementioned benefits of endosaccular treatment of aneurysms, complete aneurysm
obliteration may not always be possible. A small
portion of the neck may be left in some instances.
In these cases, a residual lumen may be visible on
the final postembolization angiogram. The results of
the treatment are dependent on many factors, the
most important being the geometry of the aneurysm
being treated. Follow-up studies may reveal a recanalized aneurysm lumen that may have been closed


150 Part IV Intracranial Aneurysms and Vasospasm

at the time of the final postembolization angiogram.
This is most often seen in cases where the lumen is
not packed tightly or when fresh thrombus was present, as is the case in giant aneurysms.
Aneurysm location is also an important factor
that may relate to the higher incidence of recanalization.27,36,38 This can be illustrated best in cases of
end-on bifurcation aneurysms, such as basilar tip
aneurysms, compared with sidewall aneurysms. A
possible reason that basilar tip aneurysm may recanalize more often is the constant water hammer
effect placed on the coil mesh.
In our series of basilar tip aneurysms, 55 lesions
were evaluated and 16 lesions (29.1%) recanalized.
Twelve of these lesions were re-treated (Fig. 15.4af).
The time interval between the treatment and detection
of the recanalization was 14.6 9 months (mean standard deviation [SD]). The mean time interval between
treatment and last follow-up angiographic examination was 24.5 months (range 0.1123 months).
Recanalization was not related to subarachnoid
hemorrhage history. We did, however, notice a statistically significant difference in aneurysmal size
and neck width between recanalized and nonrecanalized groups.40 The aneurysms larger than 10 mm

showed significantly higher incidence of recanalization. In our series, approximately half of all aneurysms that recanalized did so after 12 months and
up to 24 months. Rebleeding after coil embolization
occurred in one case.
Some authors claim that 6 months is sufficient to
reevaluate aneurysm percent occlusion and that the
yield of angiography after that time interval is low.41
We believe it is necessary to extend the follow-up
time period for at least 2 years.

Endosaccular treatment of intracranial aneurysms
was originally performed only to treat aneurysms
unsuitable for surgery. The technique has been used
with increasing frequency following convincing evidence demonstrating coil embolization as a safe and
effective alternative to traditional craniotomy and
surgical clipping in properly selected cases. Endovascular repair is a feasible alternative to surgical clipping for ruptured or unruptured aneurysms when
the aneurysm size, location, and characteristics make
surgical repair technically difficult or unfeasible.

Fig. 15.4ab Aneurysm recanalization. Unruptured basilar artery tip aneurysm of a 61-year-old woman was occluded 90% initially. Follow-up angiograms show recanalization of the aneurysm neck with compaction of coil mesh. The aneurysm was re-treated
twice. (a) Anteroposterior (AP) projection, preembolization angiogram, (b) AP projection, final angiogram after first embolization

15 Endosaccular Treatment of Aneurysms

Fig. 15.4cf (continued) Aneurysm recanalization. Unruptured basilar artery tip aneurysm of a 61-year-old woman was occluded
90% initially. Follow-up angiograms show recanalization of the aneurysm neck with compaction of coil mesh. The aneurysm was
re-treated twice. (c) AP projection, 6-month follow-up angiography after first embolization treatment, (d) AP projection, final angiogram after second embolization treatment, (e) AP projection, 10-month follow-up angiogram after second treatment, (f) AP
projection, final angiogram after third embolization treatment.


152 Part IV Intracranial Aneurysms and Vasospasm

Achieve the appropriate placement of the
microcatheter tip such that there is excellent
visualization of the coil as it is deployed into
the aneurysm dome.
Ensure that the patient is well anticoagulated
throughout the procedure to avoid thromboembolic events.
In repositioning the microcatheter when the
catheter prematurely comes out of the aneurysm (e.g., small aneurysms), attempt to reintroduce the microcatheter across the partially
deployed coil.

In the setting of intraprocedural rupture,
reverse heparinization or antiplatelet agents
with protamine or platelets and DDAVP, respectively, and continue to coil the aneurysm
until occluded.
Thromboembolic events might require additional heparinization or intra-arterial

Though the specifics of individuals techniques
differ, the endosaccular occlusion of an aneurysm is performed, in general, under either
systemic heparinization or with appropriate
antiplatelet therapy.
Preoperative planning should include a careful
assessment of the aneurysm and neck size in
order to choose the appropriate first coil. The
formation of the basket, with several loops
of coil at the neck of the aneurysm, may be
important in the successful, long-term stability
of the coil mass.
In all cases, maximizing the packing density
of the coil mass without compromising the
parent artery lumen is important in successful,
long-term stability of the coil mass.

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40. Choi IS. Basilar tip aneurysms: results of a single operator series during a 14 year period (19922005). (Unpublished data)
41. Sluzewski M, van Rooij WJ, Rinkel GJ, Wijnalda D. Endovascular treatment of ruptured intracranial aneurysms with
detachable coils: long-term clinical and serial angiographic
results. Radiology 2003;227(3):720724 PubMed
42. Chen PR, Frerichs K, Spetzler R. Current treatment options
for unruptured intracranial aneurysms. Neurosurg Focus
2004;17(5):E5 PubMed



Deconstructive Methods for

Endovascular Aneurysm Treatment
Raqeeb Haque, Christopher Paul Kellner, Sean D. Lavine, and Philip M. Meyers

Because of progressive refinements in clipping and

coiling techniques to treat cerebral aneurysms,
deconstructive strategies are more frequently held
in reserve as a last resort to treat the most difficult
vascular abnormalities. Deconstructive therapies
are treatments that permanently sacrifice the parent artery in order to prevent access of blood to the
aneurysm. These techniques contrast with reconstructive therapies, which involve the targeted
occlusion of the vascular abnormality in question
without impairment of blood flow in the parent
vessel. Lesions that merit deconstructive methods
with parent artery sacrifice are most often complex
aneurysms, but have also included such pathology as
vascular tumors, arteriovenous malformations and
fistulae, and arterial dissection, among others. This
chapter focuses on the indications, testing, and complications involved in deconstructive endovascular
methods used for the treatment of complex cerebral



The use of deconstructive methods for aneurysm

treatment long predated more finely targeted reconstructive therapies, beginning in 1785 with John
Hunters historical ligation of the femoral artery to
treat a popliteal aneurysm.1 The first successful ligation of the carotid artery was performed by Astley
Cooper in 1808.2 Hunterian ligation to treat a cerebral vascular aneurysm followed later that year, as
Victor Horsley successfully ligated the common
carotid artery for a giant internal carotid artery (ICA)
aneurysm. Further progress in the field would have
to wait approximately 100 years until Edgar Moniz
pioneered angiography in the 1920s.3 In 1937, Walter
Dandy performed his famous first direct clipping of a
cerebral aneurysm in his report of a patient presenting with an acute third nerve palsy found on exploration to have a right posterior communicating artery
aneurysm abutting the nerve as it entered the cav-

ernous sinus.4 Charles Drake developed techniques

for endovascular occlusion of complex aneurysms of
both the anterior and posterior circulations, which
were published in a large series of 723 patients in
1994.5 In the modern era of neurosurgery, throughout the last 15 to 20 years, endovascular techniques
have transformed the treatment of cerebral vascular
disease with balloon occlusion, angioplasty, stenting, and coiling. From this recent, rapid expansion of
new surgical possibilities, reconstructive therapies
have become the standard for aneurysm treatment,
whereas deconstructive strategies are now reserved
for the most challenging, complex aneurysms.

The evidence supporting endovascular balloon
occlusion is based predominantly on observational
data from case series and individual reports.6 This
technique is used primarily for giant and fusiform
aneurysms, as well as some posttraumatic pseudoaneurysms and infectious aneurysms that pose additional risks for endovascular treatment. Ideally, all
intracranial aneurysms would be treated by reconstructive surgical or endovascular methods, excluding the lesion alone from the cerebral circulation
while maintaining normal blood flow through the
parent artery. Unfortunately, as many as two thirds
of giant intracranial aneurysms may not be amenable
to clip reconstruction due to an inaccessible location
or an unfavorable neck configuration, although with
evolving endovascular technology and techniques,
this number may be shrinking.5 In these cases, alternative methods, such as parent artery sacrifice with
or without a cerebral artery bypass, is considered.
Preoperative methods to differentiate patients who
require vascular bypass rather than deconstructive
strategies alone are described here.
General contraindications to parent vessel sacrifice include circumstances in which cerebrovascular
reserve is likely to be compromised. For instance,

16 Deconstructive Methods for Endovascular Aneurysm Treatment

subarachnoid hemorrhage (SAH) is generally a major
contraindication to arterial ligation due to a significantly increased risk of ischemic deficits in the
setting of decreased blood flow should severe vasospasm occur. If possible, ruptured aneurysms that
require deconstructive therapy may therefore be
treated in a delayed fashion or temporized with partial endovascular occlusion following SAH to avoid
concurrent arterial ligation and reactive vasospasm.
Approaches vary among institutions, with some
surgeons advocating a universal reconstructive
approach while others practice selective reconstruction. Because extracranial to intracranial cerebral artery bypass is a complex procedure carrying
significant risk, parent artery occlusion alone may
be preferable if the patient can tolerate it. No data
exist evaluating the long-term morbidity of permanent occlusion (PO) or reconstructive methods like
bypass construction. If PO is considered, patients
should undergo cerebral reserve testing (CRT) to
evaluate whether or not adequate cerebral blood
flow to the involved area(s) of the brain would be
maintained following PO. If not, then construction
of a bypass may be necessary before PO to prevent
stroke. Although the approach to CRT varies substantially from institution to institution, most groups
describe a protocol including temporary balloon test
occlusion (BTO) in conjunction with clinical neurological evaluation, neurophysiological monitoring,
angiographic and cerebral hemodynamic perfusion
assessment, and, finally, provocative measures, often
including a hypotensive challenge (HC).

Approaches to the Occlusion

of Specific Cerebral Vessels

Internal Carotid Arteries

Permanent occlusion has been reported with success for various forms of vascular pathology in all of
the major cerebral vessels. Due to robust collateral
circulation often present through the circle of Willis
and surgical inaccessibility of various portions of its
course, the ICA is the vessel most commonly treated
with deconstructive therapy. PO of the ICA has been
successfully used primarily for lesions of the carotid
artery itself, but it may also be used for other lesions
involving the circle of Willis, the middle cerebral
artery (MCA), and the anterior cerebral artery (ACA).
In a series of 58 operations using PO of the ICA in a
15-year period, Larson et al described aneurysms in
the following locations: 40 intracavernous, 5 petrous
carotid, 3 cervical carotid, and 10 ophthalmic segment aneurysms. BTO was performed for all of these
patients, and treatment was accompanied by extracranialintracranial bypass when necessary.7 With a

mean follow-up of 76 months, these authors reported

that 3 patients died during treatment; 6 developed
transient ischemia; 2 developed delayed infarction;
and the aneurysm of one patient enlarged following
endovascular occlusion, requiring surgical clipping.7
Permanent occlusion has been demonstrated to
be the therapy of choice, particularly in blood blister aneurysms (BBAs) of the ICA. In 2007, Park et al
reported 12 patients presenting with ICA-BBA, of
whom 7 were treated with conventional endovascular coiling or stent-assisted coiling, and the other 5
were treated with BTO and endovascular trapping.8
All 7 patients treated with targeted endovascular
coiling demonstrated aneurysm regrowth, and 3
experienced rebleeding with devastating neurological results. All patients treated with PO exhibited
excellent neurological outcomes. With appropriate
testing, PO of the ICA can be an important treatment
modality that may even be the preferred intervention in selected cases.

Vertebral-Basilar Circulation
In 1975, Drake reported the use of vertebral artery
ligation, both unilateral and bilateral, for the treatment of large vertebral-basilar aneurysms in 14
patients, with only 3 patients making complete
recoveries.9 Despite the results of this early experience, multiple series were published in the 1990s
justifying the use of PO in the proximal posterior
circulation.10,11 Aymard et al performed unilateral or
bilateral endovascular PO of the vertebral artery in 21
patients: 13 patients enjoyed complete clinical recovery, whereas 6 patients had partial aneurysm thrombosis, 1 patient had no thrombosis, 1 patient died,
and 1 suffered a transient stroke. Due to a moderately
high rate of morbidity, these authors advocate rigorous BTO before PO. They also note that PO of the vertebral artery is most effective at the level of C1 because
antegrade collateral flow is possible through external
carotid artery muscular anastomoses, although it has
been reported that this collateral flow can prevent
aneurysmal thrombosis if too robust.9
More recently, simultaneous endovascular trapping has been demonstrated with success.12 Eleven
patients who suffered SAH from dissecting vertebral artery aneurysms were treated with the double
microcoil technique following BTO of the vertebral
artery proximal to the aneurysm. This technique
entails simultaneously occluding proximally and
distally to the aneurysm. One patient experienced
transient dysphagia, but otherwise there was no
morbidity or mortality associated with the operation. In modern practice, supple microcoils can be
used to occlude a dissecting vertebral artery aneurysm without occlusion of the vessel proximal or distal to the aneurysm sac (Fig. 16.1).


156 Part IV Intracranial Aneurysms and Vasospasm


Fig. 16.1 A 50-year-old woman presented with impaired consciousness. On arrival to the emergency room, the patient was

found to have a subarachnoid hemorrhage (SAH) on (a) computed tomographic (CT) scan. (b, c) Further workup with cerebral
angiography demonstrated a right vertebral artery dissecting aneurysm proximal to the posterior inferior cerebellar artery (PICA) .
(d) Deconstructive occlusion was performed at the level of the aneurysm and proximal to the origin of the PICA. (e, f) Retrograde
filling is not observed.

Vertebral aneurysms involving the origin of the

posterior inferior cerebellar artery (PICA) present
an additional challenge to the treatment of vertebral artery dissecting aneurysms. Iihara et al propose a decision analysis based on involvement of the
PICA origin in the aneurysm sac.13 If the aneurysm is
separate from the PICA origin, then the aneurysm is
treated with internal occlusion. However, if the aneurysm does involve the origin of PICA and presents
with SAH, proximal occlusion and internal trapping
are recommended. If the aneurysm incorporating the
PICA origin does not present with SAH, BTO should be
performed, followed by occipital arteryPICA bypass,
if possible. The authors employing this algorithm
treated 18 patients and showed a morbidity of 16.7%
with no PICA region infarction and no mortality.

The Distal Circulation

Although the ACA, MCA, and posterior cerebral
artery (PCA) lie distal to the circle of Willis, aneurysms involving these vessels have been successfully

treated with surgical or endovascular PO. For the vessels distal to the circle of Willis, leptomeningeal collaterals provide cross-territory blood supply in many
circumstances. In 1994, Drake et al described the
largest case series to date using PO as a treatment for
distal aneurysms specifically involving the ACA and
MCA.5 In 29 cases, Drake et al used surgical occlusion and bypass to treat MCA and ACA aneurysms. In
four cases of distal MCA aneurysms, the bypass failed
postoperatively, but none of these patients suffered
postoperative neurological morbidity due to robust
leptomeningeal collateral flow that filled the M2 segment. In one case, the collaterals were demonstrated
on angiography to be providing retrograde backflow
to the thrombosed aneurysm. Three ACA aneurysms
arose from the A1 segment near its origin; in two
of them, the anterior communicating artery was
not patent. The other four aneurysms were located
near the origin of the A2 segment. In two patients,
complete thrombosis of the ACA resulted in death or
severe neurological morbidity.
Few other groups have reported on endovascular PO of the ACA and MCA. In 1991, Hodes et al

16 Deconstructive Methods for Endovascular Aneurysm Treatment

described three M1 aneurysms, one M3 aneurysm,
and one A1 aneurysm treated with endovascular
PO.14 In each case, BTO was performed for 30 minutes
with extensive clinical testing, and cerebral blood
flow (CBF) was assessed using brain single-photon
emission computed tomography (SPECT) before PO.
The occlusion testing method used by Hodes et al to
evaluate an M3 segment aneurysm was to place the
microcatheter immediately proximal to the lesion and
inject 50 mg of amobarbital. All patients who underwent testing also underwent PO with no morbidity.
Series describing PO of the PCA at the P2 segment
have reported results comparable to reconstructive endovascular therapy or surgery.1518 Xavier et al
treated three patients with P2 fusiform aneurysms
with PO and reported no postoperative neurological
morbidity.18 Arat et al reported exclusively on PCA
aneurysms treated with PO, describing 8 patients
with 6- to 12-month follow-up resulting in no mortality but 12.5% morbidity.19 Three of the patients presented with SAH and were treated emergently. One of
the SAH patients who presented with Hunt and Hess
grade 3 suffered a left occipital infarct that resulted in
homonymous hemianopsia on the day of the operation. One other patient presenting with headache
developed contralateral hemiparesis that resolved
in 2 to 3 weeks and contralateral hyperesthesia that
resolved in 1 year. It has been suggested that the PCA
is commonly amenable to PO due to leptomeningeal
and choroidal collaterals. For instance, Vishteh et al
reported visual impairment in only 17% of patients
with PCA aneurysms treated with P2 sacrifice.20
Recent studies have demonstrated that PO can be
an effective treatment option for ruptured mycotic
aneurysms of the distal circulation. Dhomne et
al report 12 patients with cerebral mycotic aneurysms of the distal circulation that were all effectively treated with PO of the parent vessel.21 Ten of
12 patients exhibited normal neurological status following treatment, and 2 patients died after treatment
related to the initial stroke. Thus PO has shown efficacy in a variety of lesions in the distal circulation and
should be considered an effective treatment option
when endosaccular aneurysm occlusion alone is not
possible or is unlikely to produce a positive result.

Cerebral Reserve Testing

Balloon Test Occlusion
Idiosyncratic variations in cerebral artery collateral
circulation among individuals will lead some to tolerate parent artery occlusion, whereas others will
fail and suffer ischemia. Tolerance of parent artery
sacrifice depends primarily on collateral blood flow,
but also location (eloquent versus noneloquent

cortex) and neuronal status (undamaged tissue vs.

weakened tissue) may be determining factors in the
clinical outcome. The existence of sufficient collateral blood flow may be congenital or related to prior
episodes of cerebral ischemia due to decreased cerebral blood flow, such as transient ischemic attacks.
Morbidity and mortality for sudden vessel occlusion
have been studied.
In 1911, Allen and Matas first recognized and
evaluated the benefit of testing a patients tolerance
to occlusion preceding Hunterian ligation.22 This
practice makes up an essential part of deconstructive
strategies today; numerous studies have been performed to determine its dependability and practicality. BTO has been shown to be both safe and beneficial
before permanent cerebrovascular occlusion. In 1966,
Nishioka reported that, in 129 patients who underwent carotid occlusion in the Cooperative Study of
Intracranial Aneurysms, sudden permanent occlusion of the common carotid artery (CCA) led to stroke
26% of the time, whereas sudden occlusion of the ICA
resulted in stroke in 49% of cases.23 In 1995, Mathis et
al reviewed 500 cases of BTO, reporting that sudden
ICA occlusion leads to mortality in 12% of patients.24
A large body of research now shows that patients
who tolerate BTO have a significantly lower rate of
neurological injury following subsequent permanent
carotid occlusion. In 2000, van Rooij et al showed
that, of 17 patients who passed BTO, none had neurological deficits following permanent ICA occlusion.25
Inversely, patients who perform poorly during BTO, by
exhibiting neurological deficits during examination or
by showing signs of poor vascular perfusion on angiography, have a very high rate of neurological injury
if permanent occlusion is attempted without bypass.
Initially, the protocol for BTO involved expanding
an endovascular balloon (i.e., HyperForm, Covidien
Neurovascular, Irvine, CA) in the artery of choice, most
often the ICA, and examining the patient for neurological deficits. A subset of patients who passed this test
were found to be susceptible to ischemic injury following permanent occlusion, so additional testing at
the time of the BTO, including HC, is recommended. In
this procedure, BTO is performed for 20 minutes with
neurological testing every 5 minutes or if a deficit is
noted. After 20 minutes, the mean arterial blood pressure is reduced to two thirds of the patients baseline
and maintained at that level for 20 minutes, again with
neurological testing every 5 minutes. Using this protocol, Standard et al showed that this testing reduced
morbidity/mortality to 5% after PO.26

Adjunctive Testing
Numerous techniques have been developed in an
attempt to improve the sensitivity and specificity of
BTO, including electroencephalography, stump pres-


158 Part IV Intracranial Aneurysms and Vasospasm

sure, near-infrared spectroscopy, transcranial Doppler (TCD) ultrasonography, 99mTc-HMPAO, SPECT,
PET, stable xenon computed tomography (Xe-CT),
and patient-specific computer modeling.2730 Neurophysiological monitoring, including electroencephalography (EEG) and brainstem evoked potentials, in
26 patients undergoing BTO detected abnormalities
in 3 patients when neurophysiological monitoring
did not.31 TCD ultrasonography has also been shown
to be a useful, noninvasive predictor of poor tolerance to BTO. In one study evaluating manual compression of the carotid artery with TCD of the MCA in
22 patients, the authors correlated TCD flow < 65% of
baseline in the MCA with intolerance of BTO, with a
positive predictive value of 93% and a negative predictive value of 86%.32
Although data supporting adjunctive testing
methods are largely observational, studies have suggested that CBF studies during BTO, such as 99mTcHMPAO and Xe-133, may add to the ability of BTO
to predict poor outcome following PO. Marshall et al
conducted a prospective study on 33 patients undergoing BTO and CBF testing with Xe-133 scintigraphy.
Detection of a CBF < 30 mL/100 g/min during BTO
proved to be the most significant factor in determining intolerance to PO and was a stronger predictor
than conventional neurological testing.33 This study
and others have led to the adoption of CBF testing by
a variety of means as a commonly employed adjunctive test during BTO.
Although less commonly employed in practice,
various other techniques have shown efficacy in
aiding cerebral reserve testing. A recent study performed by van Rooij et al showed that angiographic
evaluation of synchronous venous filling (< 0.5 second delay) between the occluded and normal territories predicted a good outcome after permanent
occlusion in 98% of cases.34 Although angiographic
opacification is an indirect and inexact measure, the
authors showed that it is a useful observation. Synchronous venous filling evaluated by Xe-CT was also
shown to be a strong predictor of positive outcome
following PO.35 In addition, computer models have
been developed to evaluate hypotensive blood flow
patterns recorded using SPECT.36 With new methods, CRT will continue to improve, and in the future
patients will continue to be more appropriately
assigned to the various treatment options.

Because lesions requiring deconstructive endovascular intervention are by nature complex, complications may be encountered. The most common
complication following PO is ischemic stroke, followed by postocclusion thromboembolism. Great
effort, as described earlier, has been invested with

partial success into reduction of these complications through extensive preoperative hemodynamic
evaluation. Nishioka in 1966 reported a complication rate of 26% of 129 patients.23 Drake et als large
series of 160 patients who underwent Hunterian
ligation for anterior circulation giant intracranial
aneurysms showed a complication rate of 10% in
160 patients, noting ischemic infarction in only two
of the patients.5 With advances in preoperative testing and concurrent improvements in reconstructive therapies as an alternative to vessel sacrifice,
complication rates have continued to fall. Recently,
smaller case series have shown lower rates of morbidity. Van Rooij et al reported positive outcomes for
all 17 patients in their series, and in 2005 Abud et
al reported no neurological sequelae in 60 patients
who underwent PO of the ICA.25,37

Endovascular Occlusion
The patient should be intubated with general endotracheal anesthesia in order to prevent sudden movements, control respirations, and prepare for a surgical
emergency should a complication occur. Draping is
performed in the usual manner; bupivacaine without epinephrine is administered at the site of the
femoral artery. A 5 French sheath is placed in the
common femoral artery, sutured in place, and maintained with a constant heparinized saline infusion.
A 5 French catheter (e.g., Tempo, Cordis, and numerous other options) is passed over a guidewire (Bentson, Cook Medical, Bloomington, IN) and advanced
over the aortic arch under direct fluoroscopic guidance. The catheter and guidewire are then advanced
sequentially into the right subclavian, right vertebral,
left subclavian, left vertebral, right common carotid,
and left common carotid arteries to perform a full
diagnostic cerebral angiogram.
After completion of the diagnostic cerebral angiogram, a 5 French MPD guide catheter (Cordis Corp.,
Bridgewater, NJ) is passed over the Bentson guidewire into the origin of the diseased vessel. A Prowler
Plus microcatheter (DePuy Orthopaedics, Inc., Warsaw, IN) is then prepared with a microguidewire (we
often use a 0.014 inch Transcend platinum microguidewire), which is passed to the level of the aneurysm or chosen site of occlusion. The microguidewire
is then removed and the microcatheter is maintained
with constant heparinized saline infusion. Occlusion
of the aneurysm or parent vessel is then performed
by the deployment of multiple platinum coils under
direct fluoroscopic guidance until sufficient occlusion is noted. Biplanar arteriography is then performed to confirm vessel occlusion.

16 Deconstructive Methods for Endovascular Aneurysm Treatment

Case Examples
Occlusion of the Vertebral Artery
The patient was a 50-year-old woman with a past
medical history of hypertension and hypothyroidism
who presented to our institution from an outside
hospital with neurological impairment evaluated as a
Hunt and Hess grade 3, and a computed tomographic
(CT) scan showing SAH. A CT scan at our institution
confirmed the presence of an SAH, specifically in the
right cerebellopontine angle, prepontine cistern, and
fourth ventricle (Fig. 16.1a). Angiography was then
performed, which demonstrated a 7 5 4 mm ruptured fusiform aneurysm of the right vertebral artery
(Fig. 16.1bc). Deconstructive occlusion was performed using Guglielmi detachable coils below the
level of the PICA (Fig. 16.1d). Cerebral angiography
demonstrated deployed coils, complete occlusion of
the fusiform aneurysm, and adequate backflow from
the contralateral vertebral artery (Fig. 16.1ef).
The patient experienced no complications from
the endovascular occlusion and at examination on
SAH day 10, she had recovered to a Hunt and Hess
grade 1, showing no signs of significant vasospasm
or rebleeding.

Occlusion of the Posterior

Cerebral Artery
A 32-year-old woman developed left-sided numbness in her first trimester of pregnancy. To rule out
multiple sclerosis, she underwent magnetic resonance imaging/magnetic resonance angiography
(MRI/MRA) and was found to have a 6 mm aneurysm on the P2 segment of the PCA. After delivery
of the child at term by cesarean section, the patient
underwent angiography, which confirmed the
presence of a 6 mm right PCA aneurysm of the P2
P3 segment (Fig. 16.2a). The aneurysm was treated
endovascularly with multiple platinum detachable
coils (Fig. 16.2b). She was discharged home in good
neurological condition. At 6-month follow-up, she
underwent surveillance angiography that demonstrated an interval regrowth and recanalization
of a dissecting aneurysm at the parieto-occipital
artery junction of the right PCA as well as interval
development of a second 5 3 mm aneurysm of
the occipital artery bifurcation involving the right
PCA (Fig. 16.2c). Due to the fusiform nature of the
dissecting aneurysm and the presence of a tandem
aneurysm, deconstructive occlusion of the PCA was
performed (Fig. 16.2d).

Under direct fluoroscopic guidance using a digital

road map technique, the microcatheter system was
passed beyond the previously treated aneurysm at
the right P3 segment of the PCA, across the stenotic
segment of the occipital branch of the right PCA, and
into the fusiform aneurysm of the occipital branch
of the PCA.
At 3-month follow-up, the patient was neurologically at her baseline. Angiography at that time
demonstrated continued complete endovascular
occlusion of the tandem, dissecting aneurysms.
Interestingly, distal leptomeningeal reconstitution of
the occipital and parietal branches of the right PCA
was noted. Now, 3 years following her initial evaluation, the patient remains at her neurological baseline
without any symptoms.

Occlusion of the Carotid Artery

The patient was a 63-year-old woman presenting with
double vision who was found on examination to have
a right sixth nerve palsy. A CT scan showed a 2.5 to 3
cm left carotid aneurysm, and the patient was transferred to our institution. MRI confirmed the presence of a left internal carotid aneurysm (Fig. 16.3a).
ICA arteriography demonstrated a 22 mm supraclinoid fusiform aneurysm (Fig. 16.3bc). Due to the
complicated nature of the aneurysm, deconstructive
occlusion was considered and BTO was performed.
Arteriography during cross clamping showed hypoplastic communicating arteries in the circle of Willis
(Fig. 16.3de). After 21 minutes of manual left carotid
compression, the patient developed dysphasia and
confusion and showed left hemispheric hypoperfusion on brain SPECT (Fig. 16.3f). Due to the failed BTO,
reconstruction of the left ICA was performed. The
operation was successfully completed, and the patient
was discharged from the hospital with no new neurological deficits.

Deconstructive endovascular methods continue to
be an important method to treat giant and complex
intracranial aneurysms when clipping is not feasible.
Although some authors advocate a universal reconstructive approach, the majority of centers practice
patient-specific therapy in which each patients
tolerance to PO is comprehensively evaluated with
CRT that consists of BTO, HC, and adjunctive testing.
With appropriate evaluation, risks can be minimized,
making parent vessel occlusion a favorable option for
complex intracranial lesions.


160 Part IV Intracranial Aneurysms and Vasospasm

Fig. 16.2 A 32-year-old pregnant woman presented with left-sided numbness. (a) Cerebral angiography demonstrated a right

posterior cerebral artery (PCA) aneurysm that was (b) treated with endovascular coiling. (c) At 3-month follow-up, cerebral angiography showed interval aneurysmal regrowth and development of a tandem dissecting aneurysm. (d) Both lesions were treated with
permanent occlusion of the right PCA.

16 Deconstructive Methods for Endovascular Aneurysm Treatment

Fig. 16.3 A 63-year-old woman presented with visual abnormalities. (a) A T2-weighted coronal magnetic resonance imaging
brain scan showed a 22 mm supraclinoid left internal carotid artery aneurysm (arrow) deforming the left optic tract and chiasm. (b)
Left internal carotid arteriography with planar and (c) three-dimensional reconstructions demonstrated the 22 mm fusiform left
internal carotid aneurysm with the left anterior choroidal artery draped over its dorsal surface (arrows). (d) Right internal carotid
and (e) left vertebral arteriography with manual cross compression of the left carotid artery showed hypoplastic communication
through the circle of Willis. (f) Technetium 99-m axial brain single-photon emission computed tomography performed during temporary left carotid occlusion showed profound hypoperfusion of the left cerebral hemisphere.


162 Part IV Intracranial Aneurysms and Vasospasm



Deconstructive strategies continue to play a

part in the management of complex intracranial vascular and tumor pathology.
BTO with neurophysiological monitoring
should be considered in all patients in whom
either a deconstructive or reconstructive strategy is being considered to more clearly assess
intracranial vascular reserve and collaterals.
Adjunctive testing, such as a hypotensive challenge, synchronous contralateral filling time,
and cerebral blood flow assessments (SPECT
CT), may further improve efficacy of BTO.
Endovascular vessel occlusion can be safely
performed with the use of detachable coils.

BTO has a procedural risk of embolic stroke

and vessel dissection.
Embolic risk can be greatly reduced with the
use of heparinization during the p