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Grabb and Smith’s

Plastic Surgery
Seventh Edition

(c) 2015 Wolters Kluwer. All Rights Reserved.


Grabb and Smith’s
Plastic Surgery
Seventh Edition
Editor-in-Chief
Charles H. Thorne, MD
Associate Professor of Plastic Surgery
NYU Medical Center
New York, New York

Editors
Kevin C. Chung, MD, MS Babak J. Mehrara, MD
Charles B. G. de Nancrede Professor of Surgery Associate Attending, Department of Surgery
Section of Plastic Surgery, Department of Surgery Memorial Sloan-Kettering Cancer Center
Professor of Orthopaedic Surgery Associate Professor of Surgery
Assistant Dean for Faculty Affairs Weill Cornell University Medical Center
Associate Director of Global REACH New York, New York
University of Michigan Medical School
Ann Arbor, Michigan J. Peter Rubin, MD
UPMC Endowed Professor and Chair, Department of
Arun K. Gosain, MD Plastic Surgery
Division Head, Plastic Surgery Professor of Bioengineering
Ann & Robert H. Lurie Children’s Hospital of Chicago Director, Life After Weight Loss Body Contouring
Professor of Plastic Surgery Program
Northwestern University Feinberg School of Medicine University of Pittsburgh and UPMC
Chicago, Illinois Pittsburgh, Pennsylvania

Geoffrey C. Gurtner, md Scott L. Spear, md


Professor, Department of Surgery Professor, Department of Plastic Surgery
Stanford University School of Medicine Georgetown University Medical Center
Stanford, California Washington, District of Columbia

(c) 2015 Wolters Kluwer. All Rights Reserved.


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10 9 8 7 6 5 4 3 2 1

Library of Congress Cataloging-in-Publication Data


Grabb and Smith’s plastic surgery. — Seventh edition / editor-in-chief, Charles H. Thorne ; editors,
Kevin C. Chung, Arun Gosain, Geoffrey C. Gurtner, Babak Joseph Mehrara, J. Peter Rubin, Scott
L. Spear.
p. ; cm.
Plastic surgery
Preceded by Grabb and Smith’s plastic surgery / editor-in-chief, Charles H. Thorne ... [et al.] ;
­editors Robert W. Beasley ... [et al.]. 6th ed. 2007.
Includes bibliographical references and index.
ISBN 978-1-4511-0955-9
I. Thorne, Charles, 1952- editor of compilation.  II. Chung, Kevin C., editor of compilation.  III.
Gosain, Arun, editor of compilation.  IV. Guntner, Geoffrey C., editor of compilation.  V. Mehrara,
Babak Joseph, editor of compilation.  VI. Title: Plastic surgery.
[DNLM:  1. Reconstructive Surgical Procedures.  2. Cosmetic Techniques.  3. Surgery, Plastic.
WO 600]
RD118
617.9’5—dc23
2013017779

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To our patients who have inspired, humbled, frustrated,
and taught us, and without whom this book
would have no reason to exist.
——Charles H. Thorne, MD

(c) 2015 Wolters Kluwer. All Rights Reserved.


Contributing Authors

David M. Adelman, MD, PhD Scott P. Bartlett, MD


Assistant Professor Professor, Department of Surgery
Department of Plastic Surgery Perelman School of Medicine at the University of Pennsylvania
The University of Texas MD Anderson Cancer Center Chief, Division of Plastic Surgery
Houston, Texas Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
Jamil Ahmad, MD
Staff Plastic Surgeon Fritz E. Barton, Jr., MD
The Plastic Surgery Clinic Professor, Plastic Surgery
Mississauga, Ontario University of Texas Southwestern Medical Center
Dallas, Texas
Al S. Aly, MD
Professor Nicholas Bastidas, MD
Aesthetic & Plastic Surgery Institute Attending Physician
University of California Irvine North Shore-LIJ Health System
Orange, California New York, New York

Katerina Anesti, MD, MRCS Bruce S. Bauer, MD


Clinical Fellow Clinical Professor of Surgery, Plastic Surgery
Department of Plastic and Reconstructive Surgery University of Chicago, Pritzker School of Medicine
Guy’s and St Thomas’ NHS Trust Chicago, Illinois
London, United Kingdom Chief, Division of Plastic and Reconstructive Surgery
North Shore University Health System
Mark W. Ashton, MD Highland Park, Illinois
Head, Reconstructive Plastic Surgery
Royal Melbourne Hospital Michael S. Beckenstein, MD
Victoria, Australia Alabama Breast Surgery Center
Birmingham, Alabama
Christopher E. Attinger, MD
Professor, Department of Plastic Surgery Keith M. Blechman, MD
Georgetown University Chief Resident
Washington, District of Columbia Institute for Reconstructive Plastic Surgery
New York University School of Medicine
Kodi Azari, MD New York, New York
Associate Professor
Department of Orthopaedic Surgery and Division of George C. Bohle III, DDS
Plastic Surgery Implant & Prosthodontic Associates
David Geffen School of Medicine at UCLA Oklahoma City, Oklahoma
Los Angeles, California
James P. Bradley, MD
Stephen B. Baker, MD, DDS Professor, Sarnat Chair
Professor and Program Director Division of Plastic Surgery
Department of Plastic Surgery University of California, Los Angeles
Georgetown University Hospital Los Angeles, California
Washington, District of Columbia
Co-Director Gerald Brandacher, MD
Craniofacial Anomalies Program Associate Professor
INOVA Fairfax Hospital for Children Department of Plastic and Reconstructive Surgery
Falls Church, Virginia Johns Hopkins University School of Medicine
Baltimore, Maryland
Karim Bakri, MD
Chief Resident Donald W. Buck II, MD
Division of Plastic Surgery Division of Plastic & Reconstructive Surgery
Mayo Clinic Northwestern University
Rochester, Minnesota Chicago, Illinois

vi
(c) 2015 Wolters Kluwer. All Rights Reserved.
Contributing Authors vii
Louis P. Bucky, MD Daniel J. Ceradini, MD
Clinical Professor Assistant Professor
Department of Surgery Department of Plastic Surgery
University of Pennsylvania School of Medicine New York University School of Medicine
Chief of Plastic Surgery Chief of Plastic Surgery
Pennsylvania Hospital Manhattan Veterans Administration Hospital
Philadelphia, Pennsylvania New York, New York

Duc T. Bui, MD Benjamin Chang, MD


Associate Professor of Surgery Associate Professor of Clinical Surgery
Department of Surgery Division of Plastic Surgery
Director, Reconstructive Breast Surgery The Perelman School of Medicine at the University
Division of Plastic and Reconstructive Surgery of Pennsylvania
Stony Brook School of Medicine Attending Surgeon
Stony Brook, New York Division of Plastic Surgery
The Children’s Hospital of Philadelphia
Renee M. Burke, MD Philadelphia, Pennsylvania
Plastic Surgeon
Department of Surgery James Chang, MD
Good Shepherd Hospital Professor, Departments of Surgery (Plastic Surgery)
Barrington, Illinois & Orthopaedic Surgery
Plastic Surgeon Stanford University Medical Center
Chicago Aesthetic Surgery Institute Chief, Division of Plastic & Reconstructive Surgery
Rosemont, Illinois Stanford University Medical Center
Palo Alto, California
Mary C. Burns, OTR/L, CHT
Assistant Professor Johnny T. Chang, MD, MSME
Department of Surgery Division of Plastic Surgery
Southern Illinois University School of Medicine Brown Medical School
Certified Hand Therapist Providence, Rhode Island
Division of Plastic Surgery
Southern Illinois University School of Medicine Hand Therapy Center David W. Chang, MD
Springfield, Illinois Professor, Department of Plastic Surgery
M.D. Anderson Cancer Center
Charles E. Butler, MD
Houston, Texas
Professor with Tenure
Department of Plastic Surgery Harvey Chim, MBBS
The University of Texas MD Anderson Cancer Center Chief Resident, Plastic Surgery
Houston, Texas Case School of Medicine
Cleveland, Ohio
Dominick Cannavo, MD
New York, New York Matthew S.S. Choi, MD
Associate Professor of Plastic Surgery
Joseph N. Carey, MD
Department of Plastic and Reconstructive Surgery
Assistant Professor Hanyang University College of Medicine
Division of Plastic Surgery Seoul, South Korea
University of Southern California Chief, Department of Plastic and Reconstructive Surgery
Chief, Plastic Surgery Hanyang University Guri Hospital
LAC + USC Medical Center Guri, Gyunggi-do, South Korea
Los Angeles, California
J. Guilherme Christiano, MD
Brian T. Carlsen, MD Assistant Professor
Assistant Professor Division of Plastic Surgery
Division of Plastic Surgery, Division of Hand Surgery University of Rochester
Mayo Clinic Rochester, New York
Rochester, Minnesota
Kevin C. Chung, MD, MS
Grant W. Carlson, MD Charles B. G. de Nancrede Professor of Surgery
Professor of Surgery Section of Plastic Surgery, Department of Surgery
Emory University Professor of Orthopaedic Surgery
Wadley R. Glenn Professor of Surgery, Chief of the Division of Assistant Dean for Faculty Affairs
Plastic Surgery Associate Director of Global REACH
Emory University Hospital University of Michigan Medical School
Atlanta, Georgia Ann Arbor, Michigan

(c) 2015 Wolters Kluwer. All Rights Reserved.


viii Contributing Authors

Mark W. Clemens, MD Matthias B. Donelan, MD


Assistant Professor Chief, Plastic Surgery
Department of Plastic Surgery Department of Surgery
MD Anderson Cancer Center Shriners Hospitals for Children—Boston
Houston, Texas Associate Clinical Professor of Surgery
Harvard Combined Plastic Surgery Residency
Mark A. Codner, MD Training Program
Assistant Professor Harvard Medical School
Department of Plastic Surgery Boston, Massachusetts
Emory University
Atlanta, Georgia Susan E. Downey, MD
Associate Clinical Professor
Stephen H. Colbert, MD Department of Surgery (Plastic)
Assistant Professor Keck University of Southern California School of Medicine
Department of Surgery Los Angeles, California
University of Missouri
Head, Hand & Microsurgery Gregory A. Dumanian, MD
Division of Plastic Surgery Professor of Surgery
University of Missouri Health Care Division of Plastic Surgery
Columbia, Missouri Chief of Plastic Surgery
Northwestern Feinberg School of Medicine
Damon S. Cooney, MD, PhD
Chicago, Illinois
Assistant Professor of Plastic and Reconstructive Surgery
Johns Hopkins University School of Medicine Anthony Echo, MD
Baltimore, Maryland Clinical Instructor
Division of Plastic Surgery
Peter G. Cordeiro, MD
Stanford University Medical Center
Chief, Plastic & Reconstructive Surgery Palo Alto, California
Memorial Sloan-Kettering Cancer Center
New York, New York Cherry L. Estilo, DMD
Russell J. Corlett, MD Associate Attending
Department of Surgery
Jack Brockhoff Reconstructive Plastic Surgery Memorial Sloan-Kettering Cancer Center
Research Unit Assistant Attending
Department of Anatomy and Cell Biology Department of Surgery
University of Melbourne New York Presbyterian Hospital/Cornell
Melbourne, Australia New York, New York
Catherine M. Curtin, MD
Derek Fletcher, MD
Staff Physician
Resident, Plastic Surgery
Department of Surgery
University of Pittsburgh School of Medicine
Palo Alto Veterans Hospital
Pittsburgh, Pennsylvania
Assistant Professor
Division of Plastic Surgery Robert D. Galiano, MD
Stanford University
Assistant Professor
Palo Alto, California
Department of Surgery, Division of Plastic Surgery
Daniel Alexander Del Vecchio, MD, MBA Northwestern University Feinberg School of Medicine
Chicago, Illinois
Associate Clinical Staff
Department of Surgery Mary K. Gingrass, MD
Massachusetts General Hospital
Boston, Massachusetts Assistant Clinical Professor
Department of Plastic Surgery
Christopher A. Derderian, MD Vanderbilt University School of Medicine
Assistant Professor Nashville, Tennessee
Department of Plastic Surgery
Chad R. Gordon, DO
UT Southwestern Medical Center
Pediatric and Craniofacial Surgery Assistant Professor
Children’s Medical Center Johns Hopkins University School of Medicine
Dallas, Texas Clinical Director, Face Transplant Program
The Johns Hopkins Hospital
Joseph J. Disa, MD Baltimore, Maryland
Attending Physician
Department of Surgery Arun K. Gosain, MD
Memorial Sloan-Kettering Cancer Center Division Head, Plastic Surgery
Professor of Surgery Ann & Robert H. Lurie Children’s Hospital of Chicago
Department of Surgery Professor of Plastic Surgery
Wiell Cornell College of Medicine Northwestern University Feinberg School of Medicine
New York, New York Chicago, Illinois

(c) 2015 Wolters Kluwer. All Rights Reserved.


Contributing Authors ix
Nikolaus Gravenstein, MD Scott L. Hansen, MD
The Jerome H. Modell, MD Professor of Anesthesiology Assistant Professor
Professor of Neurosurgery Department of Surgery
Professor of Periodontology University of California, San Francisco
University of Florida College of Medicine San Francisco, California
Gainesville, Florida
Maximilian W.B. Hartmannsgruber, MD
Lorelei J. Grunwaldt, MD Attending Anesthesiologist
Assistant Professor of Surgery Anesthesia Associates of Park Avenue
Department of Plastic Surgery New York, New York
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania Robert J. Havlik, MD
J.J. Harbaugh Jr. Professor of Surgery and Chief
Geoffrey C. Gurtner, MD
Division of Plastic Surgery
Professor Indiana University
Department of Surgery Director, Cleft and Craniofacial Surgery
Stanford University School of Medicine Riley Hospital for Children
Stanford, California Indiana University School of Medicine
Indianapolis, Indiana
Nicholas T. Haddock, MD
Assistant Professor Larry H. Hollier, Jr. MD
Department of Plastic Surgery Professor, Division of Plastic Surgery
University of Texas Southwestern Medical Center Residency Program Director
Dallas, Texas Baylor College of Medicine
J. Joris Hage, MD, PhD Houston, Texas

Chief, Department of Plastic and Reconstructive Surgery Richard A. Hopper, MD, MS


Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital
Associate Professor
Amsterdam, The Netherlands
Department of Surgery
Elizabeth J. Hall-Findlay, MD University of Washington
Chief, Division of Plastic Surgery
Plastic Surgeon
Seattle Children’s Hospital
Mineral Springs Hospital
Seattle, Washington
Banff Alberta, Canada

Eric G. Halvorson, MD Erik A. Hoy, MD, MBA


Assistant Professor of Surgery Attending Physician, Plastic Surgery
Residency Program Director UHS
Director of Microsurgery Binghamton, New York
Division of Plastic & Reconstructive Surgery
Joseph P. Hunstad, MD
University of North Carolina
Chapel Hill, North Carolina Associate Consulting Professor
Division of Plastic Surgery
Warren C. Hammert, MD University of North Carolina
Associate Professor Section Head, Department of Plastic Surgery
Department of Orthopaedic Surgery Carolinas Medical Center University Hospital
Associate Professor Charlotte, North Carolina
Department of Surgery
Joseph M. Huryn, DDS
Division of Plastic Surgery
University of Rochester Medical Center Chief, Dental Service
Rochester, New York Department of Surgery
Memorial Sloan-Kettering Cancer Center
Dennis C. Hammond, MD Professor of Surgery (Oral and Maxillofacial Surgery)
Partners in Plastic Surgery of West Michigan Department of Surgery
Associate Program Director Weill Medical College of Cornell University
Plastic and Reconstructive Surgery New York, New York
Grand Rapids Medical Education Partners
Grand Rapids, Michigan Jeffrey E. Janis, MD
Associate Professor and Program Director
Matthew M. Hanasono, MD Department of Plastic Surgery
Associate Professor University of Texas Southwestern Medical Center
Department of Plastic Surgery Chief of Plastic Surgery
The University of Texas MD Anderson Cancer Center Parkland Health and Hospital System
Houston, Texas Dallas, Texas

(c) 2015 Wolters Kluwer. All Rights Reserved.


x Contributing Authors

Suhail K. Kanchwala, MD Emil J. Kohan, MD


Assistant Professor of Surgery Resident Physician
Department of Plastic Surgery Aesthetic and Plastic Surgery Institute
Hospital of the University of Pennsylvania University of California, Irvine
Philadelphia, Pennsylvania Orange, California

Michael A.C. Kane, MD John C. Koshy, MD


Associate Attending Physician Resident Physician
Department of Plastic Surgery Division of Plastic Surgery
Manhattan Eye, Ear & Throat Hospital Michael E. Debakey Department of Surgery
New York, New York Baylor College of Medicine
Houston, Texas
Nolan S. Karp, MD
Wee Leon Lam, MBChB, M Phil
Associate Professor
Department of Plastic Surgery Consultant Plastic Surgeon
New York University School of Medicine Department of Plastic, Reconstructive and Hand Surgery
Chief, Plastic Surgical Service Royal Hospital for Sick Children
Department of Plastic Surgery Edinburgh, United Kingdom
Tisch Hospital, NYU Langone Medical Center St John’s Hospital at Howden
New York, New York Livingston, United Kingdom

Armen K. Kasabian, MD Angela Song Landfair, MD


System Chief Chief Resident, Plastic Surgery
Department of Plastic Surgery Section of Plastic Surgery at Magee Women’s Hospital
North Shore-LIJ Health System Department of Plastic Surgery
New Hyde Park, New York University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania
Henry K. Kawamoto, MD, DDS
Patrick Lang, MD
Clinical Professor
Resident, Division of Plastic and Reconstructive Surgery
Division of Plastic Surgery
University of California, San Francisco
University of California at Los Angeles
San Francisco, California
Los Angeles, California
Howard N. Langstein, MD
Patrick Kelley, MD
Professor of Surgery
Medical Director, Craniofacial Center
Department of Surgery, Division of Plastic Surgery
Children’s Hospital of Austin
University of Rochester School of Medicine
Austin, Texas
Rochester, New York
Timothy W. King, MD, PhD W. P. Andrew Lee, MD
Assistant Professor Professor and Chairman
Departments of Surgery and Pediatrics Department of Plastic and Reconstructive Surgery
University of Wisconsin School of Medicine and Public Health Johns Hopkins University School of Medicine
Plastic Surgery Section Chief Baltimore, Maryland
Department of Surgery
William S. Middleton Memorial Veterans Hospital Gordon K. Lee, MD
Madison, Wisconsin Assistant Professor
Department of Surgery
Matthew B. Klein, MD
Residency Program Director
Assistant Professor Division of Plastic Surgery
Department of Plastic Surgery Stanford University School of Medicine
University of Washington Stanford, California
Associate Director
University of Washington Burn Center Valerie Lemaine, MD, MPH
Harborview Medical Center Assistant Professor of Plastic Surgery
Seattle, Washington Department of Surgery
Division of Plastic Surgery
James Knoetgen III, MD Senior Associate Consultant
Private Practice Department of Surgery
Fresno, California Division of Plastic Surgery
Mayo Clinic
Matthew E. Koepplinger, DO Rochester, Minnesota
Assistant Professor
Department of Orthopaedic Surgery Ashley K. Lentz, MD
University of Texas—Houston Health Science Center Assistant Professor of Surgery
Attending Physician, Division of Hand and Upper Extremity Surgery University of Florida
Houston, Texas Gainesville, Florida

(c) 2015 Wolters Kluwer. All Rights Reserved.


Contributing Authors xi
Salvatore C. Lettieri, MD Susan E. MacKinnon, MD
Assistant Professor of Plastic Surgery Professor and Chief
Rochester, Minnesota Division of Plastic and Reconstructive Surgery
Consultant, Department of Surgery Washington University School of Medicine
Division of Plastic Surgery Surgeon and Chief
Mayo Clinic Department of Surgery, Division of Plastic and
Rochester, Minnesota Reconstructive Surgery
Barnes-Jewish Hospital
Benjamin Levi, MD Saint Louis, Missouri
House Officer
Department of Surgery Evan Matros, MD, MMSC
Division of Plastic and Reconstructive Surgery Assistant Surgeon
University of Michigan Department of Surgery
Ann Arbor, Michigan Memorial Sloan-Kettering Cancer Center
Associate Professor
Steven M. Levine, MD Department of Surgery
Clinical Instructor Weill Cornell Medical School
Institute of Reconstructive Plastic Surgery New York, New York
New York University Langone Medical Center
New York, New York Joseph G. McCarthy, MD
Lawrence D. Bell Professor of Plastic Surgery & Helen Kimmel
Jamie P. Levine, MD
Professor of Reconstructive Plastic Surgery
Associate Professor, Plastic Surgery Department of Plastic Surgery
Chief of Microsurgery, Plastic Surgery New York University School of Medicine
NYU Langone Medical Center Chair, Department of Plastic Surgery
Chief of Plastic Surgery New York University Langone Medical Center
Bellevue Hospital New York, New York
New York, New York
Babak J. Mehrara, MD
Eric C. Liao, MD, PhD
Associate Attending, Surgery
Assistant Professor of Surgery Memorial Sloan-Kettering Cancer Center
Massachusetts General Hospital, Harvard Medical School Associate Professor, Surgery
Principal Investigator Weill Cornell University Medical Center
Center for Regenerative Medicine New York, New York
Harvard Stem Cell Institute
Boston, Massachusetts Frederick J. Menick, MD
Paul K. Lim, MD, FACS Private Practice
Tucson, Arizona
Assistant Professor
Department of Surgery Scott A. Mitchell, MD
University of Minnesota Medical School
Assistant Professor
Minneapolis, Minnesota
Department of Orthopaedic Surgery
Plastic Surgeon
University of California, Los Angeles
Center for Craniofacial Services
Santa Monica, California
Gillette Children’s Specialty Healthcare
St. Paul, Minnesota Steven L. Moran, MD
Michael A. Loffredo, MD Professor, Plastic Surgery and Orthopaedics
Private Practice Chair of Plastic Surgery
Cape and Islands Plastic Surgery Mayo Clinic
Hyannis, Massachusetts Rochester, Minnesota

Z. Paul Lorenc, MD Maurice Y. Nahabedian, MD


Attending Professor, Department of Plastic Surgery
Plastic Surgery Georgetown University
North Shore/LIJ Lenox Hill Hospital Washington, District of Columbia
Lorenc Aesthetic Plastic Surgery Center
New York, New York
James D. Namnoum, MD
Assistant Clinical Professor
David W. Low, MD Department of Plastic Surgery
Professor of Surgery Emory University
Division of Plastic Surgery Partner
Perelman School of Medicine at the University of Pennsylvania Atlanta Plastic Surgery
Philadelphia, Pennsylvania Atlanta, Georgia

(c) 2015 Wolters Kluwer. All Rights Reserved.


xii Contributing Authors

Kate W. Nellans, MD, MPH Ivona Percec, MD, PhD


Hand Fellow Assistant Professor
Department of Surgery Division of Plastic Surgery
Division of Plastic Surgery Perelman School of Medicine at the University of Pennsylvania
University of Michigan School of Medicine Philadelphia, Pennsylvania
Ann Arbor, Michigan
Linda G. Phillips, MD
David T. Netscher, MD Truman G. Blocker Distinguished Professor
Clinical Professor Chief, Division of Plastic Surgery
Department of Orthopaedic Surgery and UTMB Galveston
Division of Plastic Surgery Galveston, Texas
Baylor College of Medicine
Chief, Plastic Surgery Benjamin Z. Phillips, MD, MPH
VA Medical Center Chief Resident, Department of Plastic Surgery
Chief, Hand Surgery The Warren Alpert Medical School of Brown University
St. Luke’s Episcopal Hospital Providence, Rhode Island
Chief, Hand Surgery
Department of Orthopaedic Surgery and Karen L. Powers, MD
Division of Plastic Surgery Assistant Professor
Baylor College of Medicine Department of Surgery, Division of Plastic Surgery
Houston, Texas University of Texas Medical Branch
Galveston, Texas
Michael W. Neumeister, MD
Julian J. Pribaz, MD
Professor & Chairman
Division of Plastic Surgery Professor of Surgery, Department of Surgery
Southern Illinois University School of Medicine Harvard Medical School
The Elvin G. Zook Endowed Chair Boston, Massachusetts
Springfield, Illinois
Adrian M. Przybyla, MD
Bianca M. B. Ohana, MD Aesthetic Surgery Fellow
Marina Plastic Surgery Associates
Plastic Surgery Private Clinic
Marina del Rey, California
Salt Lake City, Utah

Leo R. Otake, MD, PhD Mark E. Puhaindran, MBBS, MRCS


Consultant, Department of Hand and Reconstructive Microsurgery
Clinical Instructor
National University Hospital
Department of Surgery, Division of Plastic Surgery
Singapore
Stanford University School of Medicine
Palo Alto, California Remus Repta, MD
Assistant Clinical Professor
Plastic and Reconstructive Surgery
Department of Surgery, Section of Plastic Surgery
Advanced Aesthetic Associates
Yale University School of Medicine
Scottsdale, Arizona
New Haven, Connecticut
Gary F. Rogers, MD
David M. Otterburn, MD
Division Chief, Plastic and Reconstructive Surgery
Assistant Professor of Surgery (Plastic Surgery) Children’s National Medical Center
Weill Cornell Medical College Washington, DC
Assistant Attending Surgeon
NewYork-Presbyterian Hospital Rod J. Rohrich, MD
New York, New York Professor and Chairman
Crystal Charity Ball Distinguished Chair in Plastic Surgery
Nima P. Patel, MD
Betty and Warren Woodward Chair in Plastic and Reconstructive Surgery
Private Practice Distinguished Teaching Professor
New York, New York Department of Plastic Surgery
Attending Surgeon and Chief of Microvascular Surgery UT Southwestern Medical Center
Department of Surgery Dallas, Texas
Maimonides Medical Center
Brooklyn, New York Harvey M. Rosen, MD, DMD
Associate Professor, Surgery
William C. Pederson, MD University of Pennsylvania School of Medicine
Adjunct Professor Philadelphia, Pennsylvania
Department of Surgery
University of Texas Health Science Center at San Antonio Stephen Alex Rottgers, MD
Fellowship Director Integrated Plastic Surgery Resident
Hand Surgery Fellowship Department of Plastic and Reconstructive Surgery
The Hand Center of San Antonio University of Pittsburgh School of Medicine
San Antonio, Texas Pittsburgh, Pennsylvania

(c) 2015 Wolters Kluwer. All Rights Reserved.


Contributing Authors xiii
J. Peter Rubin, MD W. Grant Stevens, MD
UPMC Endowed Professor and Chair, Department of Plastic Surgery Clinical Professor of Surgery
Professor of Bioengineering Department of Plastic Surgery
Director, Life After Weight Loss Body Contouring Program Keck School of Medicine of USC
University of Pittsburgh School of Medicine and UPMC Los Angeles, California
Pittsburgh, Pennsylvania Medical Director
USC – Marina del Rey Aesthetic Surgery Fellowship
Pierre B. Saadeh, MD University of Southern California
Residency Program Director Marina del Rey, California
Department of Plastic Surgery
New York University School of Medicine Patrick K. Sullivan, MD
New York, New York Associate Professor, Plastic Surgery
Brown University School of Medicine
Justin M. Sacks, MD Division Chief, Aesthetic Surgery
Assistant Professor Providence, Rhode Island
Department of Plastic and Reconstructive Surgery
Johns Hopkins School of Medicine Geoffrey Ian Taylor, AO, MD
Baltimore, Maryland Professor, Anatomy and Neuroscience
University of Melbourne
Jhonny A. Salomon, MD
Senior Consultant, Reconstructive Plastic Surgery
Private Practice Royal Melbourne Hospital
Coral Gables, Florida Victoria, Australia
Renato Saltz, MD Steven Alan Teitelbaum, MD
Saltz Plastic Surgery and Spa Vitoria Assistant Clinical Professor
Salt Lake City and Park City, Utah Plastic Surgery
Douglas M. Sammer, MD David Geffen School of Medicine at UCLA
Los Angeles, California
Associate Professor, Plastic Surgery
University of Texas Southwestern Medical School Julia K. Terzis, MD, PhD
Dallas, Texas
Adjunct Professor
Hani Sbitany, MD Department of Plastic Surgery
New York University Medical Center
Assistant Professor of Surgery
Clinical Professor
Division of Plastic and Reconstructive Surgery
Department of Surgery, Division of Plastic and
University of California, San Francisco
Reconstructive Surgery
Attending Physician
New York-Presbyterian Hospital, The University of
Department of Surgery
Columbia & Cornell
San Francisco General Hospital
New York, New York
San Francisco, California

Sandeep Jacob Sebastin, MCh (Plast) Alisa C. Thorne, MD


Consultant, Department of Hand & Reconstructive Microsurgery Professor of Clinical Anesthesia
National University Hospital Memorial Sloan-Kettering Cancer Center
Singapore New York, New York

Kenneth C. Shestak, MD Paul H. Tran, MD


Professor of Plastic Surgery Instructor in Plastic Surgery
Department of Plastic Surgery Division of Plastic Surgery, Department of Surgery
University of Pittsburgh School of Medicine Mayo Clinic
Chief of Plastic Surgery Magee Women’s Hospital Rochester, Minnesota
Pittsburgh, Pennsylvania
Robin H. Unger, MD
Jaimie T. Shores, MD Private Practice
Assistant Professor New York, New York
Department of Plastic and Reconstructive Surgery Assistant Clinical Professor
Johns Hopkins University School of Medicine Mount Sinai Hospital
Baltimore, Maryland New York, New York

Scott L. Spear, MD Walter P. Unger, MD., FRCP(C), FACP


Professor, Department of Plastic Surgery Clinical Professor (Dermatology)
Georgetown University Hospital Mount Sinai School of Medicine
Washington, District of Columbia New York

(c) 2015 Wolters Kluwer. All Rights Reserved.


xiv Contributing Authors

Allen L. Van Beek, MD Carlos K. Wesley, MD


Adjunct Professor Private Practice
Department of Surgery New York, New York
University Minnesota School of Medicine
Minneapolis, Minnesota Bradon J. Wilhelmi, MD
Professor and Chief
Andrea E. Van Pelt, MD Division of Plastic Surgery
Clinical Assistant Professor University of Louisville
Surgery/Plastic and Reconstructive Surgery Louisville, Kentucky
Michigan State University
Attending Physician Victor W. Wong, MD
Plastic and Reconstructive Surgery Chief Resident in Surgery
Grand Rapids Medical Education Partners Department of Surgery
Grand Rapids, Michigan Oregon Health Sciences University
Portland, Oregon
Stephen M. Warren, MD
Associate Professor of Plastic Surgery Michael J. Yaremchuk, MD
Department of Plastic Surgery Professor of Surgery
New York University Langone Medical Center Harvard Medical School
New York, New York Chief of Craniofacial Surgery
Surgery
Fu-Chan Wei, MD Massachusetts General Hospital
Professor, Department of Plastic Surgery Boston, Massachusetts
Chang Gung University and Medical College
Taoyuan, Taiwan

(c) 2015 Wolters Kluwer. All Rights Reserved.


Preface

Given the availability of information and images from the The book is intended for medical professionals and train-
Internet, is a hard-bound, single-volume, old-fashioned, com- ees at all levels: practicing plastic surgeons, surgeons in related
prehensive textbook of plastic surgery an anachronism? Having fields such as ophthalmology, otolaryngology, oral surgery,
spent three years on this book, I am afraid to confront the orthopaedics and general surgery, surgery residents in all sub-
answer to that question. What I do know is that there is noth- specialties, medical students, physician’s assistants, nurses,
ing like taking a real book to bed—well, almost nothing. I fell and nurse practitioners.
asleep reading Grabb and Smith when I was a medical student How is the seventh edition different from the sixth edition?
and a surgery resident and a craniofacial fellow and as a young First, the new edition is in color. Second, 55 of the 99 chapters
attending and I will be damned if current students, trainees, and are entirely new with new authors. The remaining chapters
young practitioners will not have that opportunity. I am kid- have been rewritten and are almost all substantively different
ding, of course. My motivation for editing this tome for the third from their predecessors. A new section on Body Contouring
and final time was less altruistic. I derive immense satisfaction has been added. The Transplantation chapter has been
from having a familiarity with the entire body of plastic surgical updated to reflect the extraordinary recent advances in that
knowledge and having read every word herein three times has field. The Hand section is entirely new with a new editor, new
hopefully provided that. I have been known to say to the resi- chapters, and new authors. Other changes such as consolida-
dents, only half in jest, that I will retire when one of them knows tion of chapters and changes in the sections are admittedly
more than I do. If there is anything more fun than learning, I more modest.
would appreciate someone telling me what it is…soon. I would like to thank the coeditors (who designed the sec-
A comprehensive, single-volume textbook of plastic surgery tions, chose the authors, and edited the text), the authors (who
will hopefully accomplish the following: (1) define the spec- put up with ruthless editing so that the book would remain a
trum that is plastic surgery; (2) provide a convenient source single volume), Lippincott Williams & Wilkins, Jenny Koleth,
of information for day-to-day studying; (3) deliver an attrac- and Sarah Granlund for their contributions.
tive introduction to the interested or uninitiated reader; and
(4) serve as the best single source for board exam preparation. Charles H. Thorne, MD

xv
(c) 2015 Wolters Kluwer. All Rights Reserved.
Contents

Preface  xv 18 Lasers In Plastic Surgery . . . . . . . . . . . . . . . . . . . . . 163


David W. Low and Ivona Percec

PART 1:
Principles, Techniques, and Basic Science part 3:
Congenital Anomalies and Pediatric
1 Techniques and Principles in Plastic Surgery . . . . . . . . 1 Plastic Surgery
Charles H. Thorne
19 Cleft Lip and Palate: Embryology, Principles,
2 Wound Healing: Normal and Abnormal . . . . . . . . . 13
and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
Geoffrey C. Gurtner and Victor W. Wong
Richard A. Hopper
3 Wound Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
20 Congenital Melanocytic Nevi . . . . . . . . . . . . . . . . . 200
Donald W. Buck and Robert D. Galiano
Harvey Chim and Arun K. Gosain
4 The Blood Supply of the Skin and Skin Flaps . . . . . . 29
21 Vascular Anomalies . . . . . . . . . . . . . . . . . . . . . . . . 206
Geoffrey Ian Taylor, Russell J. Corlett,
Harvey Chim and Arun K. Gosain
and Mark W. Ashton
22 Single-Suture Craniosynostosis and Deformational
5 Muscle Flaps and their Blood Supply . . . . . . . . . . . . 43
­Plagiocephaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Jamie P. Levine
Gary F. Rogers and Stephen M. Warren
6 Transplantation Biology and Applications to
23 Craniosynostosis Syndromes . . . . . . . . . . . . . . . . . . 232
Plastic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Scott P. Bartlett and Christopher A. Derderian
Damon S. Cooney, Justin M. Sacks, Gerald
Brandacher, and W. P. Andrew Lee 24 Craniofacial Microsomia and Principles
of Craniofacial Distraction . . . . . . . . . . . . . . . . . . . 241
7 Implant Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Joseph G. McCarthy
Timothy W. King
25 Orthognathic Surgery . . . . . . . . . . . . . . . . . . . . . . . 252
8 Principles of Microsurgery . . . . . . . . . . . . . . . . . . . . 70
Stephen B. Baker
Charles E. Butler and David M. Adelman
26 Craniofacial Clefts and Hypertelorbitism . . . . . . . . 266
9 Principles and Techniques of Peripheral Nerve
James P. Bradley and Henry K. Kawamoto
Repair, Grafts, and Transfers . . . . . . . . . . . . . . . . . . 77
Susan E. Mackinnon and Stephen H. Colbert 27 Ear Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . 283
Charles H. Thorne
10 Tissue Expansion . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Ashley K. Lentz and Bruce S. Bauer 28 Miscellaneous Craniofacial Conditions: Fibrous
Dysplasia, Moebius Syndrome, Romberg
11 Principles of Office Sedation for Cosmetic Surgery . . . 94 Syndrome, Treacher Collins Syndrome,
Maximilian W. B. Hartmannsgruber, Dermoid Cyst, and Neurofibromatosis . . . . . . . . . . 295
Dominick Cannavo, and Nikolaus Gravenstein Robert J. Havlik
12 Local Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Alisa C. Thorne
part 4:
Head and Neck
part 2:
29 Soft-Tissue and Skeletal Injuries of the Face . . . . . . 311
Skin and Soft Tissue
Larry H. Hollier Jr., Patrick Kelley, and John C. Koshy
13 Dermatology for Plastic Surgeons I—Skin care  30 Head and Neck Cancer and Salivary
and Benign Dermatologic Conditions . . . . . . . . . . . 105 Gland Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Renato Saltz and Bianca M. B. Ohana David M. Otterburn and Pierre B. Saadeh
14 Dermatology for Plastic Surgeons II—Cutaneous 31 Reconstruction of the Scalp, Calvarium,
Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 and Forehead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
Daniel J. Ceradini and Keith M. Blechman J.Guilherme Christiano, Nicholas Bastidas, and
15 Thermal, Chemical, and Electrical Injuries . . . . . . . 127 Howard N. Langstein
Matthew B. Klein 32 Reconstruction of the Eyelids, Correction
16 Principles of Burn Reconstruction . . . . . . . . . . . . . . 142 of Ptosis, and Canthoplasty . . . . . . . . . . . . . . . . . . 352
Matthias B. Donelan and Eric C. Liao Nicholas T. Haddock
17 Radiation and Radiation Injuries . . . . . . . . . . . . . . 155 33 Nasal Reconstruction . . . . . . . . . . . . . . . . . . . . . . . 361
James Knoetgen III and Salvatore C. Lettieri Frederick J. Menick
xvi
(c) 2015 Wolters Kluwer. All Rights Reserved.
Contents xvii
34 Reconstruction of Acquired Lip Deformities . . . . . . 372 55 Breast Reduction: Inverted-t Technique . . . . . . . . . 593
Evan Matros and Julian J. Pribaz Scott L. Spear
35 Reconstruction of the Cheeks . . . . . . . . . . . . . . . . . 384 56 Vertical Reduction Mammaplasty . . . . . . . . . . . . . 603
Babak J. Mehrara Elizabeth J. Hall-Findlay
36 Facial Paralysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399 57 Gynecomastia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
Julia K. Terzis and Katerina Anesti Nolan S. Karp
37 Mandible Reconstruction . . . . . . . . . . . . . . . . . . . . 410 58 Breast Cancer: Current Trends in Screening,
Joseph J. Disa and Evan Matros Patient ­Evaluation, and Treatment . . . . . . . . . . . . . 620
38 Craniofacial and Maxillofacial Prosthetics . . . . . . . 420
Grant W. Carlson
George C. Bohle III, Cherry L. Estilo, and 59 Breast Reconstruction: Prosthetic Techniques . . . . . 625
Joseph M. Huryn Joseph J. Disa and Nima P. Patel
39 Reconstruction of the Maxilla and Skull Base . . . . . 430 60 Latissimus Dorsi Flap Breast Reconstruction . . . . . 636
Eric G. Halvorson, Duc T. Bui, and Dennis C. Hammond and Michael A. Loffredo
Peter G. Cordeiro 61 Breast Reconstruction: Tram Flap Techniques . . . . 643
40 Reconstruction of the Oral Cavity, Pharynx, James D. Namnoum
and ­Esophagus . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443 62 Breast Reconstruction: Free Flap Techniques . . . . . 649
Matthew M. Hanasono Maurice Y. Nahabedian
63 Nipple Reconstruction . . . . . . . . . . . . . . . . . . . . . . 662
part 5: Michael S. Beckenstein
Aesthetic Surgery 64 Congenital Anomalies of the Breast: Tuberous
Breasts, Poland’s Syndrome, and Asymmetry . . . . . 668
41 Skin Resurfacing . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 Kenneth C. Shestak, Stephen Alex Rottgers,
Fritz E. Barton Lorelei J. Grunwaldt, Derek Fletcher,
42 Dermal and Soft-Tissue Fillers: Principles, and Angela Song Landfair
Materials, and Techniques . . . . . . . . . . . . . . . . . . . 458
Z. Paul Lorenc
part 7:
43 Botulinum Toxin . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Michael A.C. Kane Body Contouring
44 Fat Grafting in Plastic Surgery . . . . . . . . . . . . . . . . 473 65 
Liposuction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 679
Louis P. Bucky, Ivona Percec, and Mary K. Gingrass
Daniel Del Alexander Vecchio 66 Abdominoplasty and Belt Lipectomy . . . . . . . . . . . 688
45 Forehead and Brow ­Rejuvenation . . . . . . . . . . . . . . 480 Al S. Aly and Emil J. Kohan
Benjamin Z. Phillips, Erick A. Hoy, Johnny T. Chang, 67 Lower Body Lift and Thighplasty . . . . . . . . . . . . . . 696
Jhonny A. Salomon, and Patrick K. Sullivan Joseph P. Hunstad and Remus Repta
46 Blepharoplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 68 Brachioplasty and Upper Trunk Contouring . . . . . . 707
Mark A. Codner and Renee M. Burke Susan E. Downey
47 Facelift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501 69 Principles of Plastic Surgery After Massive
Charles H. Thorne Weight Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 713
48 Rhinoplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512 J. Peter Rubin
Jeffrey E. Janis, Jamil Ahmad, and Rod J. Rohrich
49 Otoplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530 part 8:
Charles H. Thorne
Hand
50 Facial Skeletal Augmentation with Implants . . . . . . 537
Michael J. Yaremchuk and Chad R. Gordon 70 Functional Anatomy and Principles
of Upper Extremity Surgery . . . . . . . . . . . . . . . . . . 721
51 Osseous Genioplasty . . . . . . . . . . . . . . . . . . . . . . . . 544
Kate W. Nellans and Kevin C. Chung
Harvey M. Rosen
71 Anesthesia Techniques . . . . . . . . . . . . . . . . . . . . . . 727
52 Hair Transplantation . . . . . . . . . . . . . . . . . . . . . . . 549
Warren C. Hammert
Carlos K. Wesley, Robin H. Unger,
and Walter P. Unger 72 Treatment of Hand Infections . . . . . . . . . . . . . . . . . 731
Benjamin Chang and Suhail K. Kanchwala
73 Soft Tissue Reconstruction of the Upper Extremity 737
part 6: Scott L. Hansen, Patrick Lang, and Hani Sbitany
Breast 74 Management of Nerve Injuries and Compressive
53 Augmentation Mammaplasty: Principles, Neuropathies of the Upper Extremity . . . . . . . . . . . 750
Techniques, Implant Choices, and Complications . . 565 Scott A. Mitchell and Kodi Azari
Steven Alan Teitelbaum 75 Management of Hand Fractures . . . . . . . . . . . . . . . 758
54 Mastopexy and Mastopexy/Augmentation . . . . . . . 582 Matthew S.S. Choi and James Chang
W. Grant Stevens, Andrea E. Van Pelt, 76 Management of Wrist Fractures . . . . . . . . . . . . . . . 767
and Adrian M. Przybyla Sandeep Jacob Sebastin and Kevin C. Chung

(c) 2015 Wolters Kluwer. All Rights Reserved.


xviii Contents
77 Flexor Tendon Repair . . . . . . . . . . . . . . . . . . . . . . . 784 90 Targeted Muscle Reinnervation and Upper
Bradon J. Wilhelmi Limb Amputation . . . . . . . . . . . . . . . . . . . . . . . . . . 900
78 Extensor Tendon Surgery . . . . . . . . . . . . . . . . . . . . 792 Gregory A. Dumanian
Mark E. Puhaindran 91 Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . 908
79 Tenosynovitis Disorders of the Upper Extremity . . . 799 David T. Netscher and Matthew E. Koepplinger
Mary C. Burns and Michael W. Neumeister
80 Principles of Tendon Transfers . . . . . . . . . . . . . . . . 807 part 9:
Douglas M. Sammer Trunk and Lower Extremity
81 Ligament Injuries of the Hand and Wrist . . . . . . . . 817
92 Chest Wall Reconstruction . . . . . . . . . . . . . . . . . . . 921
Karim Bakri, Brian T. Carlsen,
and Steven L. Moran Joseph N. Carey, Leo R. Otake, Anthony Echo,
and Gordon K. Lee
82 Management of Mutilating Injuries of the
Upper Extremity . . . . . . . . . . . . . . . . . . . . . . . . . . . 833 93 Abdominal Wall Reconstruction . . . . . . . . . . . . . . . 933
Jaimie T. Shores and W. P. Andrew Lee Gregory A. Dumanian
83 Replantation Strategies of the Hand 94 Lower Extremity Reconstruction . . . . . . . . . . . . . . 941
and Upper Extremity . . . . . . . . . . . . . . . . . . . . . . . 839 Armen K. Kasabian and Nolan S. Karp
Sandeep Jacob Sebastin and Kevin C. Chung 95 Foot and Ankle Reconstruction . . . . . . . . . . . . . . . 955
84 Thumb Reconstruction . . . . . . . . . . . . . . . . . . . . . . 854 Christopher E. Attinger
Wee Leon Lam and Fu-Chan Wei and Mark W. Clemens
85 Dupuytren’s Disease . . . . . . . . . . . . . . . . . . . . . . . . 863 96 Reconstruction of the Perineum . . . . . . . . . . . . . . . 971
Catherine M. Curtin Paul H. Tran and Valerie Lemaine
86 Hand Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 868 97 Lymphedema: Diagnosis and Treatment . . . . . . . . . 980
Benjamin Levi and Kevin C. Chung Steven M. Levine, David W. Chang,
and Babak J. Mehrara
87 Management of Vasoconstriction . . . . . . . . . . . . . . 878
Paul K. Lim and Allen L. Van Beek 98 Pressure Sores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 989
Karen L. Powers and Linda G. Phillips
88 Management of the Burned Hand . . . . . . . . . . . . . . 885
William C. Pederson 99 Reconstruction of the Penis . . . . . . . . . . . . . . . . . . 998
J. Joris Hage
89 Common Congenital Hand Anomalies . . . . . . . . . . 890
Robert J. Havlik Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1003

(c) 2015 Wolters Kluwer. All Rights Reserved.


PART I

Principles, Techniques, and


n  Principles, Techniques, and Basic Science

Basic Science
Chapter 1  n  Techniques and Principles
in Plastic Surgery
Charles H. Thorne

Plastic surgery is the single most diverse specialty in the This chapter outlines basic plastic surgery principles
medical field, dealing with problems from the top of the and techniques that deal with the skin. Cross-references
head to the tip of the toes and with patients ranging in to specific chapters providing additional information are
age from the newborn to nonagenarian. Plastic surgeons are provided. Subsequent chapters in the first section will dis-
the ultimate specialists but are also the modern day general cuss other concepts and tools that allow plastic surgeons to
practitioners, unrestricted by organ system, disease process, tackle complex problems. Almost all wounds and all pro-
or patient age. Without an organ system of its own plastic cedures involve the skin, even if it is only an incision, and
surgery is based on principles rather than specific proce- therefore the cutaneous techniques described in this chapter
dures in a defined anatomic location. Because of this free- are applicable to virtually every procedure performed by
dom, whole subspecialties can be added to the field when every specialty in surgery.
new ideas, procedures, and techniques are developed. Since
the previous edition less than a decade ago plastic surgery
has enlarged significantly, adding, for example, vascularized
Obtaining a Fine-Line Scar
composite allotransplantation (Chapter 06), fat grafting to “Will there be a scar?” Even the most intelligent patients
the breast (Chapter 44), and a variety of perforator flaps to ask this preposterous question. When a full-thickness injury
its armamentarium. occurs to the skin or an incision is made, there is always a
What is plastic surgery? No adequate definition exists. scar. The question should be, “Will I have a relatively incon-
What is the common denominator between craniofacial spicuous, fine-line scar?”
surgery and hand surgery and between pressure sore sur- The final appearance of a scar is dependent on many fac-
gery and cosmetic surgery? McCarthy from NYU defines tors, including the following: (a) Differences between indi-
it as the “problem-solving specialty.” A grandiose defi- vidual patients that we do not yet understand and cannot
nition from a plastic surgery states: “Plastic surgery is predict; (b) the type of skin and location on the body; (c) the
surgery of the skin and its contents.” The phrase, plastic tension on the closure; (d) the direction of the wound; (e)
surgery, is derived from the Greek “Plastikos,” meaning other local and systemic conditions; and, lastly, (f) surgical
to mold or to shape. While many plastic surgical pro- technique.
cedures deal with reshaping, the majority do not, mak- The same incision or wound in two different patients will
ing even the title of the specialty somewhat misleading. produce scars that differ in quality and aesthetics. Oily or pig-
No wonder the public has difficulty understanding what mented skin produces, as a general rule, more unsightly scars
plastic surgery is! (Chapter 2 discusses hypertrophic scars and keloids). Thin,
No specialty receives the attention from the lay press that wrinkled, pale, dry, “WASPy” skin of patients of English or
plastic surgery receives. At the same time, no specialty is less Scotch-Irish descent usually results in less conspicuous scars.
well understood. Although the public equates plastic surgery Rules are made to be broken, however, and an occasional
with cosmetic surgery, the roots of plastic surgery lie in its patient will develop a scar that is not characteristic of his or
reconstructive heritage. Cosmetic surgery, an important com- her skin type.
ponent of plastic surgery, is but one piece of the plastic surgi- Certain anatomic areas tend to produce unfavorable scars
cal puzzle. that remain hypertrophic or wide. The shoulder and sternal
Plastic surgery consists of reconstructive surgery and area are such examples. Conversely, eyelid incisions almost
cosmetic surgery but the boundary between the two, like always heal with a fine-line scar.
the boundary of plastic surgery itself, is difficult to draw. Skin loses elasticity with age. Stretched-out skin, combined
The more one studies the specialty, the more the distinction with changes in the subcutaneous tissue, produces wrinkling,
between cosmetic surgery and reconstructive surgery disap- which makes scars less obvious and less prone to widening in
pears. Even if one asks, as an insurance company does, about older individuals. Children, on the other hand, may heal faster
the functional importance of a particular procedure, the but do not heal “better,” in that their scars tend to be red
answer often hinges on the realization that the function of the and wide when compared with scars of their grandparents.
face is to look like a face (i.e., function = appearance). A cleft In addition, as body parts containing scars grow, the scars
lip is repaired so the child will look, and therefore hopefully become proportionately larger. Beware the scar on the scalp
function, like other children. A common procedure such as a of a small child!
breast reduction is enormously complex when one considers Just as the recoil of healthy, elastic skin in children may
the issues of appearance, self-image, sexuality, and woman- lead to widening of a scar, tension on a closure bodes poorly
hood, and defies categorization as simply cosmetic or neces- for the eventual appearance of the scar. The scar associated
sarily reconstructive. with a simple elliptical excision of a mole on the back will

1
(c) 2015 Wolters Kluwer. All Rights Reserved.
2 Part I: Principles, Techniques, and Basic Science

likely result in a much less appealing scar than an incisional Minimizing damage to the skin edges with atraumatic tech-
wound. The body knows when it is missing tissue. nique, debridement of necrotic or foreign material, and a ten-
The direction of a laceration or excision also determines the sion-free closure are the first steps in obtaining a fine-line scar.
eventual appearance of the scar. The lines of tension in the skin Ultimately, however, scar formation is unpredictable even
were first noted by Dupuytren. Langer also described the normal with meticulous technique.
tension lines, which became known as “Langer lines.” Borges Two technical factors are of definite importance in increas-
referred to skin lines as “relaxed skin tension lines” (Figure 1.1). ing the likelihood of a “good” scar. First is the placement
Elective incisions or the excision of lesions are planned of sutures that are not excessively tight and are removed
when possible so that the final scars will be parallel to the promptly so disfiguring “railroad tracks” do not occur. In
relaxed skin tension lines. Maximal contraction occurs when other words, removing the sutures may be more important
a scar crosses the lines of minimal tension at a right angle. than placing them! Plastic surgeons have been known to mock
Wrinkle lines are generally the same as the relaxed skin ten- other specialists for using heavy-gauge suture for skin clo-
sion lines and lie perpendicular to the long axis of the underly- sure, but the choice of sutures is irrelevant if the sutures are
ing muscles. removed soon enough and if they have not been tied so tightly
Other issues, which are not related to the scar itself but that they tear through the skin. Sutures on the face can usually
to perception, determine if a scar is noticeable. Incisions and be removed in 3 to 5 days and on the body in 7 days or less.
scars can be “hidden” by placing them at the junction of aes- Except for wounds over joints, sutures should rarely be left in
thetic units (e.g., at the junction of the lip and cheek and along for more than 1 week. A subcutaneous layer of closure and
the nasolabial fold), where the eye expects a change in contour Steri-Strips are usually sufficient to prevent dehiscence.
(Chapter xx). In contrast, an incision in the midcheek or mid- The second important technical factor that may affect the
chin or tip of the nose will always be more conspicuous. appearance of scars is wound-edge eversion. While there is no
The shape of the wound also affects ultimate appearance. evidence to support this statement, it is the author’s clinical
The “trapdoor” scar results from a curvilinear incision or experience that everted wound closures never look worse and
laceration that, after healing and contracture, appears as a often result in a less conspicuous scar than their non-everted
depressed groove with bulging skin on the inside of the curve. counterparts. In wounds where the skin is brought precisely
Attempts at “defatting” the bulging area are never as satisfac- together, there is a tendency for the scar to widen. In wounds
tory as either the patient or surgeon would like. where the edges are everted, or even hyper-everted in an exag-
Local conditions, such as crush injury of the skin adja- gerated fashion, this tendency may be reduced, possibly by
cent to the wound, also affect the scar. So, too, will systemic reducing the tension on the closure. In other words, the ideal
conditions such as vascular disease or congenital conditions wound closure is not perfectly flat, but rather bulges with an
affecting elastin and/or wound healing. Nutritional status obvious ridge, to allow for eventual spreading of that wound.
can affect wound healing, but usually only in the extreme Wound-edge eversion always goes away. The surgeon need not
of malnutrition or vitamin deficiency. Nutritional status is ever worry that a hyper-everted wound will remain that way.
overemphasized as a factor in scar formation.
Technique is also overemphasized (by self-serving plas-
tic surgeons) as a factor in determining whether a scar will Closure of Skin Wounds
be inconspicuous, but it is certainly of some importance. While the most common method of closing a wound is with
sutures, there is nothing necessarily magic or superior about
sutures. Staples, skin tapes, or wound adhesives are also useful
in certain situations. Regardless of the method used, precise
approximation of the skin edges without tension is essential to
ensure primary healing with minimal scarring.
Wounds that are deeper than skin are closed in layers. The
key is to eliminate dead space, to provide a strong enough clo-
sure to prevent dehiscence while wound healing is occurring,
and to precisely approximate the skin edges without tension.
Not all layers necessarily require separate closure. A closure
over the calf, however, is subject to motion, dependence, and
stretching with walking, requiring a stronger closure than the
scalp, which does not move, is less dependent, and not subject
to tension in daily activities. Placing deep absorbable sutures
is not always desirable. The author tends to use only Nylon
skin sutures without any deeper sutures when approximating
pediatric facial lacerations because of an impression that there
is less inflammation and erythema and certainly less chance of
suture abscess.
Except for dermal sutures, which are placed with the knot
buried to prevent it from emerging from the skin during the
healing process, sutures should be placed with the knot super-
ficial to the loop of the suture (not buried), so that the tissue
layers can be everted (Figure 1.2A).
Buried dermal sutures provide strength so the external
sutures can be removed early, but do not prevent the scar from
spreading over time. There is no technique, even the technique
of eversion described above, that reliably prevents a wound
that has an inclination to widen from doing so.

Figure 1.1.  Relaxed skin tension lines. (Reproduced with permis- Suturing Techniques
sion from Ruberg R. L. In: Smith DJ, ed. Plastic Surgery, A Core
Curriculum. St. Louis, MO: Mosby, 1994.) Techniques for suturing are illustrated in Figure 1.2 and are
listed below.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 1: Techniques and Principles in Plastic Surgery 3

Principles, Techniques, and


Basic Science
A B C

D E F

G H
Figure 1.2.  Types of skin closure. A. Simple interrupted. B. Vertical mattress. C. Horizontal mattress. D. Subcuticular continuous. E. Half-
buried horizontal mattress. F. Continuous over-and-over. G. Staples. H. Skin tapes (skin adhesive performs a similar function).

Simple Interrupted Suture.  The simple interrupted suture sutures tend to leave the most obvious and unsightly cross-
is the gold standard and the most commonly employed suture. hatching if not removed early.
The needle is introduced into the skin at an angle that allows
it to pass into the deep dermis at a point further removed from Horizontal Mattress Suture.  Horizontal mattress sutures
the wound edge. This allows the width of suture at its base in have been much maligned but are the author’s favorite suture
the dermis to be wider than the epidermal entrance and exit for reliable skin edge approximation and eversion. They are
points, giving the suture a triangular appearance when viewed particularly advantageous in thick glabrous skin (feet and
in cross section. It also everts the skin edges. Care must be hand). In the author’s opinion, horizontal mattress sutures are
taken to ensure that the suture is placed at the same depth on far superior to their vertical counterparts.
each side of the incision or wound, otherwise the edges will
overlap. Sutures are usually placed approximately 5 to 7 mm Subcuticular Suture.  Subcuticular (or intradermal) sutures
apart and 1 to 2 mm from the skin edge, although the location can be interrupted or placed in a running fashion. In a run-
and size of the needle and caliber of the suture material make ning subcutaneous closure, the needle is passed horizontally
this somewhat variable. through the superficial dermis, parallel to the skin surface,
to provide close approximation of the skin edges. Care is
Vertical Mattress Suture.  Vertical mattress sutures may taken to ensure that the sutures are placed at the same level.
be used when eversion of the skin edges is desired and cannot Such a technique obviates the need for external skin sutures
be accomplished with simple sutures alone. Vertical mattress and circumvents the possibility of suture marks in the skin.

(c) 2015 Wolters Kluwer. All Rights Reserved.


4 Part I: Principles, Techniques, and Basic Science

Absorbable or nonabsorbable suture can be used, with the lat-


ter to be removed at 1 to 2 weeks after suturing.

Half-Buried Horizontal Mattress Suture.  Half-buried


horizontal mattress sutures are used when it is desirable to
have the knots on one side of the suture line with no suture
marks on the other side. For example, when insetting the are-
ola in breast reduction, this method leaves the suture marks
on the dark, pebbly areola instead of on the breast skin.

Continuous Over-and-Over Suture.  Continuous over-


and-over sutures, otherwise known as running simple sutures,
can be placed rapidly but depend on the wound edges being
more or less approximated beforehand. A continuous suture
is not nearly as precise as interrupted sutures and the author
almost never uses them on the face. Continuous sutures can
also be placed in a locking fashion to provide hemostasis by
compression of wound edges. They are especially useful in
scalp closures.

Skin Staples.  Skin staples are particularly useful as a time-


saver for long incisions or to position a skin closure or flap
temporarily before suturing. Grasping the wound edges with
forceps to evert the tissue is helpful when placing the staples
to prevent inverted skin edges. Staples must be removed early
to prevent skin marks and are ideal for the hair-bearing scalp.

Skin Tapes.  Skin tapes can effectively approximate the


wound edges, although buried sutures are often required in
addition to skin tape to approximate deeper layers, relieve
tension, and prevent inversion of the wound edges. Skin tapes
can also be used after skin sutures are removed to provide Figure 1.3.  Elliptical excision. A. If the ellipse is too short, dog-ears
added strength to the closure. (arrows) form at the ends of the closed wound. B. Correct method
with length of ellipse at least three times the width.
Skin Adhesives.  Skin adhesives have been developed and
may have a role in wound closure, especially in areas where
there is no tension on the closure, or where strength of clo-
sure has been provided by a layer of buried dermal sutures. shown in Figure 1.4. Dog-ears are the bane of plastic surgical
Adhesives, by themselves, however, do not evert the wound existence and one must be facile with their elimination. Dog-
edges. Eversion must be provided by deeper sutures. ears do not disappear on their own.

Wedge Excision.  Lesions located at or adjacent to free


Methods of Excision margins can be excised by wedge excision. In some elderly
Lesions of the skin can be excised with elliptical, wedge, circu- patients, one third of the lower lip and one fourth of the upper
lar, or serial excision. lip can be excised with primary closure (Figure 1.5).

Elliptical Excision.  Simple elliptical excision is the most Circular Excision.  When preservation of skin is desired
commonly used technique (Figure 1.3). Elliptical excision (such as the tip of the nose) or the length of the scar must be
of inadequate length may yield “dog-ears,” which consist kept to a minimum (children), circular excision might be desir-
of excess skin and subcutaneous fat at the ends of a closure. able. Figure 1.6 shows some closure techniques. Figure 1.6 is
There are several ways to correct a dog-ear, some of which are included because these techniques may be of value, as well

Figure 1.4.  Three methods of removing a dog-ear caused by making the elliptical excision too short. A. Dog-ear excised, making the incision
longer, or converted to a “Y.” B. One method of removing a dog-ear caused by designing an elliptical excision with one side longer than the
other. Conversion to an “L” effectively lengthens the shorter side.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 1: Techniques and Principles in Plastic Surgery 5

Principles, Techniques, and


Basic Science
Figure 1.5.  Wedge excisions of the ear, lower eyelid, and lip.

as for historical purposes. Circular defects can also be closed


with a purse-string suture that causes significant bunching of
the skin. This is allowed to mature for many months and may
result in a shorter scar on, for example, the face of a child.

Serial Excision.  Serial excision is the excision of a lesion


in more than one stage. Serial excision and tissue expansion
(Chapter xx) are frequently employed for large lesions such
as congenital nevi. The inherent viscoelastic properties of skin
are used, allowing the skin to “stretch” over time. Serial exci-
sion enables wound closure to be accomplished with a shorter
scar than if the original lesion was elliptically excised in a
single stage.

Skin Grafting
Skin grafts are a standard option for closing defects that can-
not be closed primarily. A skin graft consists of epidermis and
some or all of the dermis. By definition, a graft is something
that is removed from the body, is completely devascularized, Figure 1.6. Closure of wounds following circular excision.
and is replaced in another location. Grafts of any kind require A. Skin graft. B. Sliding triangular subcutaneous pedicle flaps can be
vascularization from the bed into which they are placed for advanced to close the circular defect; the triangular defect is closed in a
survival. Any tissue that is not completely removed prior to V–Y fashion. C. Transposition flaps based on a skin pedicle and rotated
placement is not a graft. toward each other can also be used. Circular defects can also be closed
by other local flaps (Figures 1.10–1.15) or by purse-string suture.
Skin Graft Types
Skin grafts are classified as either split-thickness or full-thick-
ness, depending on the amount of dermis included. Split- heal secondarily, without any skin grafting, demonstrate the
thickness skin grafts contain varying amounts of dermis, greatest degree of contracture and are most prone to hyper-
whereas a full-thickness skin graft contains the entire dermis trophic scarring.
(Figure 1.7). The number of epithelial appendages transferred with a
All skin grafts contract immediately after removal from the skin graft depends on the thickness of the dermis present.
donor site and again after revascularization in their final loca- The ability of grafted skin to sweat depends on the num-
tion. Primary contraction is the immediate recoil of freshly ber of glands transferred and the sympathetic reinnerva-
harvested grafts as a result of the elastin in the dermis. The tion of these glands from the recipient site. Skin grafts are
more dermis the graft has, the more primary the contraction reinnervated by ingrowth of nerve fibers from the recipient
that will be experienced. Secondary contracture, the real nem- bed and from the periphery. Full-thickness skin grafts have
esis, involves contraction of a healed graft and is probably the greatest sensory return because of a greater availability
a result of myofibroblast activity. A full-thickness skin graft of neurilemmal sheaths. Hair follicles are also transferred
contracts more on initial harvest (primary contraction) but with a full-thickness skin graft. In general, full-thickness skin
less on healing (secondary contracture) than a split-­thickness grafts demonstrate the hair growth of the donor site whereas
skin graft. The thinner the split-thickness skin graft, the split-thickness skin grafts, especially thin split-thickness skin
greater the secondary contracture. Granulating wounds left to grafts, are generally hairless.

(c) 2015 Wolters Kluwer. All Rights Reserved.


6 Part I: Principles, Techniques, and Basic Science

Figure 1.7.  Skin graft thickness.

of the dermis, the original donor site may be used again for a
Requirements for Survival of a Skin Graft subsequent split-thickness skin graft harvest. Thus, the num-
The success of skin grafting, or “take,” depends on the ability ber of split-thickness skin grafts harvested from a donor site is
of the graft to receive nutrients and, subsequently, vascular directly dependent on the donor dermis thickness. Full-thickness
ingrowth from the recipient bed. Skin graft revascularization skin graft donor sites must be closed primarily because there are
or “take” occurs in three phases. The first phase involves a pro- no remaining epithelial structures to provide re-epithelialization.
cess of serum imbibition and lasts for 24 to 48 hours. Initially, Skin grafts can be taken from anywhere on the body,
a fibrin layer forms when the graft is placed on the recipient although the color, texture, thickness of the dermis, vascularity,
bed, binding the graft to the bed. Absorption of nutrients into and donor site morbidity of body locations vary considerably.
the graft occurs by capillary action from the recipient bed. The Skin grafts taken from above the clavicles provide a superior
second phase is an inosculatory phase in which recipient and color match for defects of the face. The upper eyelid skin can
donor end capillaries are aligned. In the third phase, the graft also be used, as it provides a small amount of very thin skin.
is revascularized through these “kissing” capillaries. Because Full-thickness skin graft harvest sites are closed primarily and are
the full-thickness skin graft is thicker, survival of the graft is therefore of smaller size. The scalp, abdominal wall, buttocks,
more precarious, demanding a well-vascularized bed. and thigh are common donor sites for split-thickness skin grafts.
To optimize take of a skin graft, the recipient site must be Surgeons should avoid the mistake of harvesting split-thickness
prepared. Skin grafts require a vascular bed and will seldom skin grafts from the most accessible locations such as the anterior
take in exposed bone, cartilage, or tendon devoid of their perios- thigh. Although donor sites heal by re-epithelialization, there is
teum, perichondrium, or paratenon. There are exceptions, how- always visible evidence that an area was used as a donor site.
ever, as skin grafts are frequently successful inside the orbit or This can vary from keloids to simple hyper- or hypopigmenta-
on the temporal bone, despite removal of the periosteum. Close tion. Less conspicuous donor sites are the buttocks or scalp.
contact between the skin graft and its recipient bed is essential. Split-thickness skin grafts harvested from the scalp will have hair
Hematomas and seromas under the skin graft will compromise in them initially but no hair follicles and therefore will ultimately
its survival, and immobilization of the graft is essential. be hairless. The hair in the scalp donor site will return after re-
epithelialization because the hair follicles were left undisturbed.
Skin Graft Adherence
For the skin graft to take, it must adhere to the bed. There Postoperative Care of Skin Grafts
are two phases of graft adherence. The first begins with place-
ment of the graft on the recipient bed, to which the graft and Donor Sites
adheres because of fibrin deposition. This lasts approximately Causes of graft failure include collection of blood or serum
72 hours. The second phase involves ingrowth of fibrous tis- beneath the graft (raising the graft from the bed and prevent-
sue and vessels into the graft. ing revascularization), movement of the graft on the bed inter-
rupting revascularization (immobilization techniques include
Meshed versus Sheet Skin Grafts the use of bolster dressings as shown in Figure 1.8), and
infection. The risk of infection can be minimized by careful
Multiple mechanical incisions result in a meshed skin graft,
preparation of the recipient site and early inspection of grafts
allowing immediate expansion of the graft. A meshed skin
applied to contaminated beds. Wounds that contain more than
graft covers a larger area per square centimeter of graft har-
105 organisms per gram of tissue will not support a skin graft.
vest and allows drainage through the numerous holes. Meshed
In addition, an infection at the graft donor site can convert
skin grafts result in a “pebbled” appearance that, at times, is
a partial-thickness dermal loss into a full-thickness skin loss.
aesthetically unacceptable. In contrast, a sheet skin graft has
The donor site of a split-thickness skin graft heals by re-
the advantage of a continuous, uninterrupted surface, often
epithelialization. A thin split-thickness harvest site (less than
leading to a superior aesthetic result, but has the disadvan-
10/1,000 of an inch) generally heals within 7 days. The donor
tages of not allowing serum and blood to drain through it and
site can be cared for in a number of ways. The site must be
the need for a larger skin graft.
protected from mechanical trauma and desiccation. Xeroform,
OpSite, or Adaptic can be used. Because moist, occluded
Skin Graft Donor Sites wounds (donor sites) heal faster than dry wounds, the older
The donor site epidermis regenerates from the immigration of method of placing Xeroform and drying it with a hairdryer
epidermal cells originating in the hair follicle shafts and adnexal is not optimal. An occlusive dressing, such as semipermeable
structures left in the dermis. In contrast, the dermis never regen- polyurethane dressing (e.g., OpSite), will also significantly
erates. Because split-thickness skin grafts remove only a portion decrease pain at the site.
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 1: Techniques and Principles in Plastic Surgery 7

Skin Flaps

Principles, Techniques, and


Unlike a skin graft, a skin flap has its own blood supply. Flaps
are usually required for covering recipient beds that have poor
vascularity; covering vital structures; reconstructing the full

Basic Science
thickness of the eyelids, lips, ears, nose, and cheeks; and pad-
ding body prominences. Flaps are also preferable when it may
be necessary to operate through the wound at a later date to
repair underlying structures. In addition, muscle flaps may
provide a functional motor unit or a means of controlling
infection in the recipient area. Muscle flaps and microvascular
free flaps are discussed in Chapters xx and xx.
In an experimental study, Mathes et al. compared muscu-
locutaneous flaps with “random” skin flaps to determine the
bacterial clearance and oxygen tension of each (Figure 1.9).
Placement of 107 Staphylococcus aureus underneath random
skin flaps in dogs resulted in 100% necrosis of the skin flaps
within 48 hours; the musculocutaneous flaps, however, dem-
onstrated long-term survival. The quantity of viable bacteria
placed in wound cylinders under these flaps demonstrated an
immediate reduction when placed deep to musculocutaneous
Figure 1.8.  Tie-over bolster dressing for skin grafts. flap. Oxygen tension was measured at the distal end of the
random flap and compared with that underneath the muscle
of the distal portion of musculocutaneous flap as well as in its
subcutaneous area. It was found that the oxygen tension in
the distal random flap was significantly less than in the distal
Biologic Dressings muscular and cutaneous portions of the musculocutaneous flap.
Skin grafts can also be used as temporary coverage of wounds This study has been used to justify transfer of muscle flaps in
as biologic dressings. This protects the recipient bed from infected wounds. It may be that well-vascularized skin flaps
desiccation and further trauma until definitive closure can would be equally efficacious as muscle flaps.
occur. In large burns where there is insufficient skin to be har- Finally, a flap may be chosen because the aesthetic result
vested for coverage, skin substitutes can be used (Chapter 18). will be superior. For example, a nasal defect from a skin can-
Biologic skin substitutes include human allografts (cadaver cer could be closed with a skin graft, leaving a visible patch.
skin), amnion, or xenografts (such as pig skin). Allografts A local skin flap may require incisions in the adjacent nasal
become vascularized (or “take”) but are rejected at approxi- tissue, but may be aesthetically preferable in the long term.
mately 10 days unless the recipient is immunosuppressed There is no better tissue to replace nasal tissue than nasal tis-
(e.g., has a large burn), in which case rejection takes longer. sue. Replace like with like.
Conversely, xenografts are rejected before becoming vascular- A skin flap consists of skin and subcutaneous tissue that
ized. Synthetic skin substitutes such as silicone polymers and are transferred from one part of the body to another with a
composite membranes can also be applied, and new skin sub- vascular pedicle or attachment to the body being maintained
stitutes are constantly being developed. Human epidermis can for nourishment. Proper planning of a flap is essential to the
be cultured in vitro to yield sheets of cultured epithelium that success of the operation. All possible sites and orientations for
will provide coverage for large wounds. The coverage is frag- the flap must be considered so that the most suitable option
ile as a result of the lack of a supporting dermis. is selected.

Figure 1.9.  “Old-fashioned” classification of skin flaps. A. Random pattern. B. Axial pattern.

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8 Part I: Principles, Techniques, and Basic Science

Planning the flap in reverse is an important principle. A


pattern of the defect is transferred onto a piece of cloth towel-
ing. The steps in the operative procedure are carried out in
reverse order, using this pattern until the donor site is reached.
The flap is designed slightly longer than needed, as some
length will be lost in the rotation process and slight redun-
dancy may avoid kinking of the flap blood supply. The pro-
cess is repeated, being certain each time the base is held in a
fixed position and not allowed to shift with the flap. Measure
twice, cut once. It is easier to trim a flap that is slightly long
than to add to one that is too small.
Planning a transposition or rotation flap requires atten-
tion to ensure that the line of greatest tension from the pivot
point to the most distal part of the flap is of sufficient length
(Figures 1.10, 1.11, and 1.12).
Local skin flaps are of two types: flaps that rotate about a
pivot point (rotation, transposition, and interpolation flaps)
(Figures 1.10 and 1.11) and advancement flaps (single-­pedicle
advancement, V–Y advancement, Y–V advancement, and
bipedicle advancement flaps) (Figures 1.17 and 1.18).

Flaps Rotating about a Pivot Point


Rotation, transposition, and interpolation flaps have in
common a pivot point and an arc through which the flap is
rotated. The radius of this arc is the line of greatest tension of

Figure 1.11.  Transposition flap. (A) The secondary defect is often


closed by a skin graft. (B) A back-cut can be used if the flap is under
excessive tension.

Figure 1.10.  Rotation flap. The edge of the flap is four to five times Figure 1.12.  Importance of the pivot point. A skin flap rotated
the length of the base of the defect triangle. A back-cut or a Bürow tri- about a pivot point becomes shorter in effective length the farther
angle can be used if the flap is under excessive tension. A. Pivot point it is rotated. Planning with a cloth pattern is helpful when designing
and line of greatest tension. B. Back-cut. C. Bürow’s triangle. such a flap.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 1: Techniques and Principles in Plastic Surgery 9
the flap. The realization that these flaps can be rotated only

Principles, Techniques, and


about the pivot point is important in preoperative planning.
The rotation flap is a semicircular flap of skin and subcuta-
neous tissue that rotates about a pivot point into the defect to
be closed (Figure 1.10). The donor site can be closed by a skin

Basic Science
graft or by direct suture of the wound.
A flap that is too tight along its radius can be released by
making a short back-cut from the pivot point along the base of
the flap. Because this back-cut decreases the blood supply to the
flap, its use requires some degree of caution. With some flaps
it is possible to back-cut only the tissue responsible for the ten-
sion, without reducing the blood supply to the flap. Examples
of this selective cutting are found in the galea aponeurotica of
the scalp and in areas over the trunk where the fascia within
the thick subcutaneous layer can be divided. The necessity for a
back-cut may be an indication of poor planning. A triangle of
skin (Bürow triangle) can be removed from the area adjacent
to the pivot point of the flap to aid its advancement and rota-
tion (Figure 1.10C). This method is of only modest benefit in
decreasing tension along the radius of the flap.
The transposition flap is a rectangle or square of skin and
subcutaneous tissue that also is rotated about a pivot point
into an immediately adjacent defect (Figure 1.11). This neces-
sitates that the end of the flap adjacent to the defect be des-
ignated to extend beyond it (Figures 1.12 and 1.13). As the
flap is rotated, with the line of greatest tension as the radius
of the rotation arc, the advancing tip of the flap will be suf-
ficiently long. The flap donor site is closed by skin grafting,
direct suture of the wound, or a secondary flap from the most
lax skin at right angles to the primary flap. An example of this
latter technique is the ingenious bilobed flap (Figure 1.14).
The key to a successful bilobed flap is an area of loose skin to Figure 1.13.  Transposition flap that can be used to close defects on
permit direct closure of the secondary flap defect. Pinching the the anterior cheek. A. Small defects can be closed by a single transpo-
skin between the examiner’s fingers helps find the loosest skin, sition cheek flap that follows the skin lines. B. Large defects can be
closed by a double transposition flap that uses a flap of postauricular
for example, in the glabellar area and lateral to the eyelids.
skin to close the secondary defect left by the cheek flap.
The Limberg flap is a type of transposition flap. This
flap, like the bilobed flap and the Z-plasty (discussed below),
depends on the looseness of adjacent skin, which can be
located by pinching various areas of skin between the thumb
and the forefinger. Fortunately, most patients who require that are the same length as the short axis of the rhomboid
local skin flaps are in the older age group and therefore have defect (Figures 1.15 and 1.16).
loose skin. A Limberg flap is designed for rhomboid defects
with angles of 60° and 120°, but most wounds can be made Advancement Flaps
rhomboid, or imagined as rhomboid, so the principle is appli- All advancement flaps are moved directly forward into
cable to most facial wounds. The flap is designed with sides a defect without any rotation or lateral movement.

Figure 1.14.  Bilobed flap. After the lesion is excised, the primary flap (P) is transposed into the initial defect. The secondary flap (S) is then
transposed into the defect left after the primary flap has been moved. The primary flap is slightly narrower than the defect caused by excision of
the initial lesion, and the secondary flap is half the diameter of the primary flap. For the bilobed flap to be successful, the secondary flap must
come from an area of loose skin so that the defect remaining after moving the secondary flap can be closed by approximation of the wound edges.
Three possible choices for the secondary flap (S1, S2, and S3) are depicted. The surgeon chooses the location of the secondary flap based on the
skin laxity and the location of the eventual scar.

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10 Part I: Principles, Techniques, and Basic Science

Figure 1.15.  Planning a rhomboid (Limberg) flap. The rhomboid defect must have 60° and 120° angles. The flap is planned in an area of loose
skin so that direct closure of the wound edges is possible. The short diagonal BD (which is the same length as each side) is extended by its own
length to point E. The line EF is drawn parallel to CD and is of the same length. After the flap margins have been incised, the flap is transposed
into the rhomboid defect.

Modifications are the single-pedicle advancement, the The V–Y advancement technique has numerous applica-
V–Y advancement, and the bipedicle advancement flaps. tions. It is not an advancement in the same sense as the forward
Advancement flaps are also used in the movement of movement of a skin flap just described. Rather, a V-shaped
expanded skin (Chapter 10). incision is made in the skin, after which the skin on each side of
The single-pedicle advancement flap is a rectangular or the V is advanced and the incision is closed as a Y (Figure 1.18).
square flap of skin and subcutaneous tissue that is stretched This V–Y technique can be used to lengthen such structures as
forward. Advancement is accomplished by taking advantage the nasal columella, eliminate minor notches of the lip, and, in
of the elasticity of the skin (Figure 1.17A) and by excising certain instances, close the donor site of a skin flap.
Bürow triangles lateral to the flap (Figure 1.17B). These trian-
gular excisions help to equalize the length between the sides of
the flap and adjacent wound margins. Z-Plasty
Geometric Principle of the Z-Plasty
The Z-plasty is an ingenious principle that has numerous
applications in plastic surgery (Chapter 18). Z-plasties can be
applied to revise and redirect existing scars or to provide addi-
tional length in the setting of scar contracture. The principle
involves the transposition of two triangular flaps (Figure 1.19).
The limbs of the Z must be equal in length to the central limb,
but can extend at varying angles (from 30° to 90°) depend-
ing on the desired gain in length. The classic Z-plasty has an
angle of 60° (Table 1.1) and provides a 75% theoretical gain
in length of the central limb by recruiting lateral tissue.
Gain in length is in the direction of the central limb of the
Z and depends on the angle used and the length of the central
limb. Although the theoretical gain can be determined math-
ematically, the actual gain is based on the mechanical proper-
ties of the skin and is always less.

Planning and Uses of the Z-Plasty


The resulting central limb, after flap transposition, will
be perpendicular to the original central limb. In scar revi-
sion, the final central limb should lie in the direction of the
skin lines and should be selected first. The Z-plasty is then
designed.
The Z-plasty principle can be used to increase the length
of skin in a desired direction. For example, it is useful for
release of scar contractures, especially in cases in which the
scar crosses a flexion crease. Any number of Z-plasties can
be designed in series, especially in cosmetically sensitive areas
Figure 1.16.  Four Limberg flaps are available for any rhomboid (such as the face) to break up the appearance of a straight
defect with 60° and 120° angles. The choice is made based on the line or to release a contracture. Large Z-plasties, however, do
location of the eventual scar, skin laxity, and blood supply of the flap. not look good on the face and it is better to use many tiny
Z-plasties. Congenital skin webs can also be corrected with

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Chapter 1: Techniques and Principles in Plastic Surgery 11

Principles, Techniques, and


Basic Science
Figure 1.19.  Classic 60° angle Z-plasty. Inset shows the method of
finding the 60° angle by first drawing a 90° angle, then dividing it in
thirds by sighting. The limbs of the Z must be equal in length to the
central member. A. Design. B. Transposition of flaps. C. Final result.
Note that the central limb has changed the direction by 90°.

and universality that Z-plasty has. This technique simply


involves excising the scar in multiple small triangles that are
so situated that they interdigitate (Figure 1.20). Although the
W-plasty changes the direction of the linear scar, it would only
be by chance that one of the limbs of the W would lie in the
same direction as the skin lines. Because a W-plasty does not
lengthen a contracted scar line, it is best to use the Z-plasty for
this purpose.
Both the Z-plasty and the W-plasty have the additional
attribute of breaking up a linear scar into an accordion-like
Figure 1.17.  Single-pedicle advancement flaps. A. Advancement by scar that has some degree of elasticity to it. This change per-
taking advantage of the skin elasticity. B. Advancement by excising mits the skin to be more mobile in its contribution to facial
Bürow triangles of skin laterally to equalize the length of the flap and expressions. To their detriment, both techniques more than
the adjacent wound edge. C. Pantographic expansion. This method is double the length of the scar. If the W-plasty is employed,
frequently used after the skin expansion but is risky as the back-cuts the triangles must be made very small to avoid worsening the
decrease the blood supply. appearance of the scar.

Reconstructive Ladder
Z-plasties. U-shaped or “trapdoor” scars may be improved The techniques described above are applicable to cutaneous
by breaking up the contracting line. Circumferential scars are defects. Plastic surgeons often are consulted regarding clos-
amenable to lengthening using Z-plasties, especially in con- ing more complex defects. When analyzing a wound, whether
stricting bands of the extremities. These deformities are best
released one-half at a time because of concern over interrup-
tion of blood supply to the extremity.
Borges described the W-plasty as another method of revis- Table 1.1
ing a scar. It is useful occasionally, but lacks the applicability
Z-Plasty, Angles, and Theoretical Gain

n Angels of z-plasty n theoretical gain


(degrees) in length (%)
30–30 25
45–45 50
60–60 75
Figure 1.18.  V–Y advancement. It is the skin on each side of the V 75–75 100
that is actually advanced. 90–90 120

(c) 2015 Wolters Kluwer. All Rights Reserved.


12 Part I: Principles, Techniques, and Basic Science

cutaneous or more complex, the options for closure are eval-


uated beginning with the simplest and progressing up the
“reconstructive ladder” to the more complex (Figure 1.21).
This progression from primary closure to skin graft, to local
flap, to regional flap, and to microvascular free flap pro-
vides a framework that can be applied to any reconstructive
situation. Application of the simplest option that meets the
reconstructive requirements ensures a “lifeboat” should the
procedure fail. In many situations, however, a higher “rung”
on the ladder is intentionally chosen. For example, a local
flap may be selected over a skin graft for a defect on the nose
because it may provide a superior result, or a free flap may be
chosen for a breast reconstruction when an attached, pedicled
flap would suffice because the blood supply of the former is
superior.
Figure 1.20.  The W-plasty can also be used to break up a long scar
that does not lie in the direction of the skin lines.
Conclusion
The application of fundamental principles in the practice of
plastic surgery allows the surgeon to approach even the most
FREE TISSUE complex problem in an organized, systematic fashion. This
TRANSFER chapter presents fundamental principles that can be applied to
any wound closure situation.

REGIONAL TISSUE Suggested Readings


TRANSFER Birch J, Branemark PI. The vascularization of a free full thickness skin graft: a
vital microscopic study. Scand Plast J Surg. 1969;3:1.
Borges AF. Elective Incisions and Scar Revision. Boston, MA: Little, Brown;
1973.
Capla J, Ceradini D, Tepper O, et al. Skin graft vascularization involves pre-
LOCAL TISSUE cisely regulated regression and replacement of endothelial cells through
TRANSFER both angiogenesis and vasculogenesis. Plast Reconstr Surg. 2005.
In press.
Converse JM, Rapaport FT. The vascularization of skin autografts and homo-
grafts: an experimental study in man. Ann Surg. 1956;143:306.
Edgerton MT. The Art of Surgical Technique. Baltimore, MD: Williams &
SKIN GRAFT Wilkins; 1988.
Edgerton MT, Hansen FC. Matching facial color with split thickness skin grafts
from adjacent areas. Plast Reconstr Surg. 1960;25:455.
Furnas DW, Fischer GW. The Z-plasty: biomechanics and mathematics. Br J
Plast Surg. 1971;24:144.
Krizek TJ, Robson MC. Evolution of quantitative bacteriology in wound man-
agement. Am J Surg. 1975;130:579.
DIRECT TISSUE CLOSURE Mathes S, Alpert B, Chang N. Use of the muscle flap in chronic osteomy-
elitis: experimental and clinical correlation. Plast Reconstr Surg. 1982;
69:815.
Robson MC, Krizek TJ, Heaggars JP. Biology of surgical infections. In:
Ravitch MM, ed. Current Problems in Surgery. Chicago; 1973.
ALLOW WOUND TO HEAL BY SECONDARY Rudolph R. Inhibition of myofibroblasts by sham skin grafts. Plast Reconstr
Surg. 1979;63:473.
INTENTION
Tanner JC, Vandeput J, Olley JF. The mesh skin graft. Plast Reconstr Surg.
1964;34:287.
Figure 1.21.  Reconstructive ladder demonstrating the fundamental Vogt PM, Andree C, et al. Dry, moist and wet skin wound repair. Ann Plast
principle in planning closure of a defect from simple to more complex. Surg. 1995;34:493.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 2  n  Wound Healing: Normal

Principles, Techniques, and


and Abnormal

Basic Science
Geoffrey C. Gurtner and Victor W. Wong

the myriad events occurring in wound healing, the reader is


The Response to Injury referred to a number of excellent recent reviews.3-5 However,
What is wound healing? Definitions might include the repair given the inherent lag in book publication and the rapid pace
or reconstitution of a defect in an organ or tissue, commonly of the field, the reader should refer to Medline (http://www
the skin. However, it is clear that the process of wounding acti- .ncbi.nlm.nih.gov/entrez/query.fcgi) and search for the
vates systemic processes that alter the physiology far beyond latest reviews in the field of wound healing to obtain the most
the confines of the defect itself. Inflammatory cascades that up-to-the-minute information.
impact nearly every organ system and have potentially dire
consequences for survival are initiated, as illustrated by multi-
system organ failure. Furthermore, recent research implicating Scar Formation Versus Tissue
the participation of stem and progenitor cells in the wound
healing process requires a broader perspective than one that
Regeneration
focuses solely on the defect itself.1,2 Wound healing may be As discussed, wound healing is an extremely broad and com-
best understood as an organism’s global response to injury, plex topic covering a variety of responses to injury in a variety
regardless of whether the location is in the skin, liver, or heart. of different organ systems. However, some common features
Seen from this perspective, it is certainly not an exaggeration exist. Generally, wound healing represents the response of an
to regard the response to injury as one of the most complex organism to a physical disruption of a tissue/organ to re-estab-
physiologic processes occurring during adult life. lish homeostasis of that tissue/organ and stabilize the entire
The complexity of this process is easily demonstrated in organism’s physiology. There are essentially two processes by
cutaneous wound healing. During the progression from a which this re-establishment of homeostasis occurs. The first
traumatic injury to a stable scar, the intrinsic and extrinsic is the substitution of a different cellular matrix as a patch to
clotting system are activated; acute and chronic inflamma- immediately re-establish both a physical and physiologic conti-
tory responses occur; neovascularization proceeds through nuity to the injured organ. This is the process of scar formation.
angiogenesis and vasculogenesis; cells proliferate, divide, and The second process is a recapitulation of the developmental
undergo apoptosis; and extracellular matrix (ECM) is depos- processes that initially created the injured organ. By reactivat-
ited and remodeled. These (as well as other events) occur ing developmental pathways, the architecture of the original
simultaneously and also interact and influence each other at organ is re-created. This is the process of regeneration.6
the level of gene transcription and protein translation in a The dynamic balance between scarring and tissue regenera-
dynamic and continuous fashion. Further, normally sterile tis- tion is unique to different tissues and organs (Figure 2.1). For
sues encounter and interact with bacteria and other elements example, neural injury is characterized by little regeneration
of the external environment in a way that never occurs except and much scarring, whereas hepatic and bone injury usually
following injury. Thus, it is not surprising that wound heal- heals primarily through regeneration. It is important to note,
ing and the response to injury are still poorly understood by however, that the liver can respond to injury with scarring as
scientists and clinicians alike, except at a purely descriptive it does in response to repetitive insults during the progression
or empiric level. The sheer number of commercially avail- of alcoholic cirrhosis. Moreover, the same injury in phyloge-
able products of unproven efficacy is a testament to the lack netically related species can result in very different responses.
of mechanistic understanding regarding this most common Thus, limb amputation in newts results in limb regeneration,
­surgical problem. whereas in humans, only scarring can occur.
Most textbook chapters on wound healing are an ency- It is important to realize that the balance between scar
clopedic catalog of the phenomenology of wound healing. and regeneration is likely subject to evolutionary pressures
They list the multitude of cytokines and growth factors that and may, in fact, be functional. Thus, a cutaneous injury in
are observed during wound healing, usually based on experi- our prehistoric predecessors disrupted their homeostasis with
mental models or in vitro systems that may be prone to arti- respect to thermoregulation, blood loss, and, most impor-
fact. With the increasing sensitivity of new technologies such tantly, prevention of invasive infection. In an era before anti-
as quantitative polymerase chain reaction and microarray, the biotics and sterility, invasive infection was clearly a threat to
list of cytokines, growth factors, chemokines, etc. that appear life. As such, a very rapid and dramatic recruitment of inflam-
during wound healing continues to grow at an alarming rate. matory cells and a proliferative/contractile burst of activity
How will we ever make sense of this mountain of data so that to close the wound as quickly as possible were adaptive. The
we can intervene and alter the outcome of wound healing/ more leisurely pace of tissue regeneration was a luxury that
response to injury? In this chapter, a theoretical framework could not be afforded. However, in the modern world, these
with which to classify wound healing will be proposed. The adaptive responses often lead to the disfigurement and func-
broad biologic transitions that occur during cutaneous wound tional disability characteristic of burn scars. What was once
healing (i.e., inflammatory phase, proliferative phase, and functional has become unwanted, in part because of our abil-
remodeling phase) will be described within this context. An ity to close wounds with sutures, circumventing the need for a
abbreviated list of major “factors” will be provided but not vigorous contractile response following injury.
discussed in detail since it remains unclear which of these fac- In the same way that scar formation is not always bad,
tors are of primary or incidental importance in either func- tissue regeneration is not always good. Peripheral nerve neu-
tional or abnormal wound healing. Finally, an attempt will romas are dysfunctional and harmful attempts at regeneration
be made to understand abnormal human healing within the of organ systems that have been damaged. They often result in
proposed theoretical context. For a more detailed list of disabling conditions that threaten the livelihood of an entire

13
(c) 2015 Wolters Kluwer. All Rights Reserved.
14 Part I: Principles, Techniques, and Basic Science

Semantics of Wound Healing


The nomenclature of both scientific and clinical wound
healing research is at times imprecise and confusing. For
example, what is the difference between a chronic wound
and a non-healing wound? For purposes of this chapter, sev-
eral terms should be defined. The vast majority of surgical
wounds are incisional wounds that are re-approximated by
sutures or adhesives and in the absence of complications will
heal “­primarily” or by “primary intention.” Generally such
wounds heal with a scar and do not require special wound care
or the involvement of a specialist in wound healing. This is in
contrast to wounds that are not re-approximated (for any rea-
son) and left “open.” The subsequent defect is “filled in” with
granulation tissue and then re-epithelialized. This is referred
to as healing by secondary intention and generally results in a
Figure 2.1. The different ways organisms and organ systems delay in the appearance of a healed or “closed” wound. Often
respond to injuries. Scar formation refers to the patching of a defect these wounds require special dressings and treatments (to
with a different or modified tissue (i.e., scar). Tissue regeneration be discussed in detail in Chapter 3) and have a higher likeli-
refers to the complete re-creation of the original tissue architecture. hood of progressing to a chronic wound. In the discussion of
Obviously, most processes involve both, but usually one predominates normal wound healing that follows, we will be discussing
and may be the source of undesirable side effects that we would like healing by secondary intention, although the same phases
to prevent or modify. For cutaneous wounds, scar formation usually occur in all wounds.
predominates (except in the unique situation of fetal wound healing)
An acute wound is a wound for which the injury has
and is the source of many of the problems plastic surgeons address.
occurred within the past 3 to 4 weeks. If the wound persists
beyond 4 to 6 weeks, it is considered a chronic wound, a term
that also includes wounds that have been present for months
organism. In these cases, scar formation would be preferable. or years. “Non-healing, recalcitrant,” and “delayed healing”
Indeed, the ablative measures used to treat these neuromas are are terms used interchangeably to describe chronic wounds.
attempts to prevent further regeneration. Wounds that are “granulating” represent the formation of
Thus, when analyzing an undesirable or dysfunctional highly vascular granulation tissue during the proliferative
response to injury in a tissue or organ system, it is useful phase of healing (see below).
to consider a) what the undesirable portion of the response
to injury is and b) whether substitution of a new tissue (scar)
or re-creation of the pre-existing tissue (regeneration) is Phases of Normal Wound
responsible for this undesirable effect. It is important to con- Healing
sider the possible adaptive role the dysfunctional process
The normal mammalian response to a break in cutaneous
might have. In the event of a neuroma, the case can be made
integrity occurs in three overlapping but biologically distinct
that the occasional return of protective or functional sensibil-
phases (Figure 2.2). Following the initial injury, there is an ini-
ity following a partial nerve injury is more adaptive and has
tial inflammatory phase, the purpose of which is to remove
a survival advantage over the occurrence of complete anes-
devitalized tissue and prevent invasive infection. Next, there
thesia in a peripheral nerve territory. Similarly with respect
is a proliferative phase during which the balance between
to fetal wound healing, in the sterile intrauterine environment
scar formation and tissue regenerations occurs. Usually, scar
the predominance of regenerative pathways may be adaptive,
formation predominates, although in fetal wound healing an
whereas for the adult organism existing in a microbe-filled
impressive amount of regeneration is possible. Finally, the lon-
environment, it may not be.
gest and least understood phase of wound healing occurs in
Such an analysis immediately suggests strategies to correct
the remodeling phase, whose main purpose is to maximize the
the undesirable end result in a given tissue or organ. If the
strength and structural integrity of the wound.
problem is overexuberant scar formation, then it is likely that
measures to decrease scarring would be helpful. However,
since this balance is dynamic, efforts at accelerating regen- Inflammatory Phase
eration might also be effective. And perhaps even better still The inflammatory phase (Figure 2.3) of wound healing begins
would be the simultaneous decrease in scar formation and immediately following tissue injury. The functional priori-
increase in tissue regeneration. ties during this phase of wound healing are attainment of
It is clear that the response to injury in different tissues hemostasis, removal of devitalized tissues, and prevention of
involves different proportions of scar formation and tis- colonization and invasive infection by microbial pathogens,
sue regeneration. By understanding the differences using the principally bacteria.
approach described above, we may be able to begin to under- Initially, components of the injured tissue, including
stand why different organs and tissues respond to injuries fibrillar collagen and tissue factor, act to activate the clot-
in very different ways. Just as a corneal ulcer, a myocardial ting cascade and prevent ongoing hemorrhage. Disrupted
infarction, and a stage IV decubitus ulcer have different func- blood vessels allow circulating elements into the wound
tional implications for the organism, the dynamic balance of while platelets clump and form an aggregate to plug the disrupted
scarring and regeneration will be different in the attempt to vessels. During this process, platelets degranulate to release
re-establish homeostasis. The failure of either scar formation growth factors such as platelet-derived growth factor (PDGF)
or regeneration may lead to similar appearing clinical prob- and transforming growth factor β (TGF-β). The end result of the
lems that have a completely different underlying etiology. coagulation cascade is the conversion of fibrinogen to fibrin and
Hopefully, this type of analysis will lead to a more organized subsequent polymerization into a mesh. This provisional matrix
approach to the classification and treatment of injuries in a provides the scaffolding for cell recruitment and attachment
variety of different organ systems. Most importantly, it may required during the subsequent phases of wound healing.
suggest strategies for intervention to optimize the response to Almost immediately, inflammatory cells are recruited to
injury and prevent the undesirable sequelae of wound healing. the wound site. During the initial stages of wound healing,

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 2: Wound Healing: Normal and Abnormal 15
and later stages of wound repair.10 Circulating monocytes

Principles, Techniques, and


traffic to wounds and egress into the tissue to become macro-
phages. By 3 days post-wounding, they are the predominant
cell type in the healing wound. Macrophages phagocytose
debris and bacteria, but are especially critical for the orches-

Basic Science
trated production of the growth factors necessary for the
production of the ECM by fibroblasts and the production of new
blood vessels in the healing wound. A partial listing of chemo-
kines, cytokines, and growth factors present in the healing wound
is provided in Table 2.1, but the list grows daily. The exact func-
tion of each of these factors is incompletely understood, and the
literature is filled with contradictory data. However, it is clear
that unlike the neutrophil, the absence of monocyte/macro-
phages has severe consequences for healing wounds.11
The lymphocyte is the last cell to enter the wound and
enters between days 5 and 7 post-wounding. Its role in wound
healing is not well defined, although it has been suggested that
populations of stimulatory CD4 and inhibitory CD8 cells may
usher in and out the subsequent proliferative phase of wound
Figure 2.2.  The three phases of wound healing (inflammatory, pro- healing.12 Similarly, the mast cell appears during the later part
liferative, and remodeling), the timing of these phases in adult cutane- of the inflammatory phase, but again its function remains
ous wound healing, and the characteristic cells that are seen in the unclear. Recently, it has become an area of intense research
healing wound at these time points. inquiry because of a correlation between mast cells and some
forms of aberrant scarring.
Given the consistent and precise appearance of different
inflammatory cells are attracted by numerous biophysical subsets of inflammatory cells into the wound, it is likely that
cues, including activation of the complement cascade, TGF-β soluble factors released in a stereotypic pattern underlie this
released by degranulating platelets, and bacterial degradation phenomenon. The source of these factors, the upstream regu-
products such as lipopolysaccharide.7 For the first 2 days fol- lators for their production, and the downstream consequences
lowing wounding, there is an impressive infiltration of neu- of their activity are extraordinarily complex topics and the
trophils into the fibrin matrix that fills the wound cavity. The subject of intense ongoing research. Again in Table 2.1, a
primary role of these cells is to remove dead tissue by phagocy- partial list of growth factors thought to be important during
tosis and prevent infection by oxygen-dependent and oxygen- wound healing is provided. All are targets for the development
independent killing mechanisms. They also release a variety of of therapeutics to either accelerate wound healing or decrease
proteases to degrade remaining ECM to prepare the wound for scar formation.5 However, the biologic relevance of any one
healing. It is important to realize that although neutrophils play factor in isolation remains unclear.
a role in decreasing infection during cutaneous wound healing,
their absence does not appear to prevent the overall progress of Proliferative Phase
wound healing.8 However, their prolonged persistence in the
wound has been proposed to be a primary factor in the conver- The proliferative phase of wound healing is generally accepted
sion of acute wounds into non-healing chronic wounds.9 to occur from days 4 to 21 following injury. However, the
Monocyte/macrophages follow neutrophils into the wound phases of wound healing are not exclusive and have features
and appear 48 to 72 hours post-injury. They are recruited to that overlap. Certain facets of the proliferative phase such as
healing wounds primarily by expression of monocyte che- re-epithelialization probably begin almost immediately fol-
moattractant protein 1. Monocyte/macrophages are a hetero- lowing injury. Keratinocytes adjacent to the wound alter their
geneous population of cells that critically regulate both early phenotype in the hours following injury. Regression of the
desmosomal connections between keratinocytes and to the
underlying basement membrane frees cells and allows them
to migrate laterally. Concurrent with this is the formation
of actin filaments in the cytoplasm of keratinocytes, which
provides them with the locomotion to actively migrate into
the wound. Keratinocytes then move via interactions with
ECM proteins (such as fibronectin, vitronectin, and type I
collagen) via specific integrin mediators as they proceed
between the desiccated eschar and the provisional fibrin
matrix beneath (Figure 2.4).
The provisional fibrin matrix is gradually replaced by a new
platform for migration: granulation tissue. Granulation tissue
is largely composed of three cell types that play critical and
independent roles in granulation tissue formation: fibroblasts,
macrophages, and endothelial cells. These cells form ECM
and new blood vessels, which histologically are the ingredients
for granulation tissue. Granulation tissue begins to appear in
human wounds by about day 4 post-injury. Fibroblasts are
the workhorses during this time and produce the ECM that
fills the healing scar and provides a scaffold for keratinocyte
Figure 2.3. The inflammatory phase of wound healing begins migration. Eventually this matrix will be the most visible
immediately following tissue injury and serves to achieve hemostasis, component of cutaneous scars. Macrophages continue to pro-
remove devitalized tissues, and prevent invasive infection by microbial duce growth factors such as PDGF and TGF-β1 that induce
pathogens. fibroblasts to proliferate, migrate, and deposit ECM, as well
as stimulate endothelial cells to form new vessels. During the

(c) 2015 Wolters Kluwer. All Rights Reserved.


16 Part I: Principles, Techniques, and Basic Science

Table 2.1
GROWTH FACTORS, CYTOKINES, AND OTHER BIOLOGICALLY ACTIVE MOLECULES IN WOUND HEALING

n  Name n  Abbreviation n  Source n  Description


Vascular endothelial VEGF Endothelial cells Promotes angiogenesis
growth factor
Fibroblast growth FGF-2 Macrophages, mast cells, Promotes angiogenesis. Stimulates
factor 2 endothelial cells, endothelial cell migration and growth
T lymphocytes Promotes epithelialization via
keratinocyte and fibroblast migration
and proliferation
Platelet-derived PDGF Platelets, macrophages, Enhances proteoglycan and collagen
growth factor endothelial cells synthesis
Recruits macrophages and fibroblasts
Keratinocyte growth KGF Fibroblasts Controls keratinocyte growth and
factor maturation
Induces epithelial secretion of other
growth factors
Epidermal growth EGF Platelets, macrophages Stimulates collagenase secretion by
factor fibroblasts to remodel matrix
Transforming growth TGF-β Platelets, macrophages, Promotes angiogenesis
factor beta T and B cells, hepatocytes, Establishes chemoattractant gradients,
thymocytes, placenta induces adhesion molecule expression,
and promotes proinflammatory
molecules that stimulate leukocyte
and fibroblast migration
Induces extracellular matrix synthesis
by inhibiting protease activity and
upregulating collagen and proteoglycan
synthesis
Tumor necrosis TNF-α Macrophages, T and B cells, Induces collagen synthesis in wounds
factor alpha NK cells Regulates polymorphonuclear neutro-
phil leukocyte (PMN) margination and
cytotoxicity
Granulocyte G-CSF Stromal cells, fibroblasts, Stimulates granulocyte proliferation,
colony-stimulating endothelial cells, survival, maturation, and activation
factor lymphocytes Induces granulopoiesis
Granulocyte- GM-CSF Macrophages, stromal cells, Stimulates granulocyte and macrophage
macrophage colony- fibroblasts, endothelial cells, proliferation, survival, maturation, and
stimulating factor lymphocytes activation
Induces granulopoiesis
Interferon alpha IFN-α Macrophages, B and Activates macrophages. Inhibits
T cells, fibroblasts, fibroblast proliferation
epithelial cells
Interleukin 1 IL-1 Macrophages, keratinocytes, Proinflammatory peptide
endothelial cells, lympho- Induces chemotaxis of PMNs,
cytes, fibroblasts, osteoblasts fibroblasts, and keratinocytes
Activates PMNs
Interleukin 4 IL-4 T cells, basophils, mast cells, Activates fibroblast proliferation
bone marrow stromal cells Induces collagen and proteoglycan
synthesis
Interleukin 8 IL-8 Monocytes, neutrophils, Activates PMNs and macrophages to
fibroblasts, endothelial cells, begin chemotaxis
keratinocytes, T cells Induces margination and maturation
of keratinocytes
Endothelial nitric eNOS Endothelial cells, neurons Synthesizes NO in endothelial cells with
oxide synthase multiple downstream effects
Inducible nitric iNOS Neutrophils, endothelial Synthesizes NO by macrophages
oxide synthase cells and basal keratinocytes, multiple
downstream effects

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 2: Wound Healing: Normal and Abnormal 17
In humans, remodeling is characterized by the processes of

Principles, Techniques, and


wound contraction and collagen remodeling (Figure 2.5). The
process of wound contraction is produced by wound myofi-
broblasts, which are fibroblasts with intracellular actin micro-
filaments capable of force generation and matrix contraction.14

Basic Science
It remains unclear whether the myofibroblast is a separate cell
from the fibroblast or whether all fibroblasts retain the capac-
ity to “trans-differentiate” to myofibroblasts under the right
environmental conditions. Myofibroblasts contact the wound
through specific integrin-mediated cell–matrix interactions
with the dermal environment.
Collagen remodeling is also characteristic of this phase. Type
III collagen is initially laid down by fibroblasts during the prolif-
erative phase, but over the next few weeks to months this will be
replaced by type I collagen. This slow remodeling phase is largely
mediated by a class of enzymes known as matrix metalloprotein-
ases that are secreted in large part by macrophages, fibroblasts,
and endothelial cells.15 The breaking strength of the healing wound
improves slowly during this process, reflecting the turnover in col-
Figure 2.4.  The proliferative phase of wound healing occurs from
lagen subtypes and increased collagen cross-linking. At 3 weeks,
days 4 to 21 post-wounding. During this phase, granulation tissue fills
the wound and keratinocytes migrate to restore epithelial continuity. the beginning of the remodeling phase, wounds have only about
20% of the strength of unwounded skin and will ultimately only
possess 70% to 80% of the breaking strength of unwounded skin
at 1 year.
proliferative phase, the provisional matrix of fibrin is replaced
with thinner type III collagen, which will in turn be replaced Abnormal Response to Injury
by thicker type I collagen during the remodeling phase.
Endothelial cells are a critical component of granulation tis-
and Abnormal Wound Healing
sue and form new blood vessels through angiogenesis and the Just as it is overly simplistic to consider all the different
newly described process of vasculogenesis, which involves the responses to injury seen in different tissues as simply “wound
recruitment and assembly of bone marrow–derived progenitor healing,” it is naïve to try to classify all the manifestations
cells.13 Proangiogenic factors that are released by macrophages of abnormalities in this process as simply “abnormal wound
include vascular endothelial growth factor, fibroblast growth healing.” To more accurately classify all the different types of
factor 2, angiopoietin 1, and thrombospondin. The upstream abnormal wound healing, it is useful to consider the balance
activator of gene transcription of these growth factors may be between attempts to replace tissue defects with new, substitute
hypoxia via hypoxia-inducible factor 1α protein stabilization. tissues (scar formation) against the re-creation of the original
The relative importance of these different vascular growth tissue in situ (regeneration), as illustrated in Figure 2.1. It is
factors and the precise timing of their arrival and disappear- also helpful to determine where within the normal phases of
ance are areas of active investigation. However, it is clear that wound healing the problem occurs. The goal is to understand
the formation of new blood vessels and subsequent granula- each abnormal process in terms of dynamic balance and to
tion tissue survival is important for wound healing during the propose therapeutic strategies to restore homeostasis on a cel-
proliferative phase of wound healing. lular, tissue, and organ level.
One interesting element of the proliferative phase of wound Such a process is not merely a semantic exercise but has
healing is that at a certain point all of these processes need to be potential therapeutic implications. Thus, although a corneal
turned off and the formation of granulation tissue/ECM halted. ulcer, a peripheral neuroma, and stage IV sacral decubitus
It is clear that this is a regulated event because once collagen
matrix has filled in the wound cavity, fibroblasts rapidly dis-
appear and newly formed blood vessels regress, resulting in a
relatively acellular scar under normal conditions. So how do
these processes turn off? It seems likely that these events are
programmed and occur through the gradual self-destruction
of cellular apoptosis. The signals that activate this program
are unknown but must involve environmental factors as well
as molecular signals. Since dysregulation of this process is
believed to underlie the pathophysiology of fibrotic disorders
such as hypertrophic scarring, understanding the signals for
halting the proliferative phase is of obvious importance for
developing new therapeutics for these disabling conditions.

Remodeling Phase
The remodeling phase is the longest component of wound
healing and in humans is thought to last from 21 days up to
1 year. Once the wound has been “filled in” with granulation
tissue and after keratinocyte migration has re-epithelialized
it, the process of wound remodeling occurs. Again, these pro-
cesses overlap and the remodeling phase likely begins with Figure 2.5.  The remodeling phase of wound healing is the longest
the programmed regression of blood vessels and granulation phase and lasts from 21 days to 1 year. Remodeling, though poorly
tissue described above. Despite the long duration of the remod- understood, is characterized by the processes of wound contraction
eling phase and the obvious relevance to ultimate appearance, it and collagen remodeling.
is by far the least understood phase of wound healing.

(c) 2015 Wolters Kluwer. All Rights Reserved.


18 Part I: Principles, Techniques, and Basic Science

ulcer are all examples of abnormal healing, the treatment as


guided by an understanding of the underlying mechanism
Excessive Regeneration Underlying
will be completely different. Thus, for a corneal ulcer, which an Abnormal Response to Injury
represents a defect in epithelial regeneration, growth factor These situations are relatively rare. In these cases, pathways of
therapy would make sense to augment the potential for regen- tissue regeneration lead to the re-creation of the absent tissue,
eration, whereas it would make less sense for a defect such but there are functional problems reintegrating the tissue into
as a peripheral neuroma. For a neuroma, treatments aimed the systemic physiology. They often occur in peripheral nerve–
at preventing nerve regeneration would seem to make more like tissue, such as peripheral nerve regeneration leading to
sense. In the following paragraphs, we will attempt to clas- neuroma. Other examples might include the hyperkeratosis
sify the various types of abnormal wound healing using the that occurs in cutaneous psoriasis or granuloma formation
dynamic balance between scar formation and regeneration. in healing wounds. It seems plausible that many conditions
It is hoped that such an analysis might elucidate and clarify we consider “precancerous” are the result of overexuberant
new therapeutic opportunities targeting one component or the attempts at tissue regeneration following minor traumatic
other, as illustrated in Figure 2.1. insults. This then leads to disordered and uncontrolled
growth. Clearly, in these situations, scar formation would be
Inadequate Regeneration Underlying preferable to regeneration because of the risk of loss of growth
an Abnormal Response to Injury control and possible transformation to overt cancer.
In these disease states, therapeutic measures are targeted
The classic example of this is found in central nervous system toward decreasing cellular proliferation and blocking or
injuries that occur following traumatic injury or following tumor impeding the aberrant regenerative pathways. Irritant strate-
ablation. The response to injury in these cases is usually char- gies to maximize scar formation may also play a role, as when
acterized by virtually no restoration or recovery of functional alcohol is injected into a neuroma. The goal is to limit the
neural tissue. The absence of neural regeneration is compensated ability of the tissue to activate pathways leading to regenera-
by a normal physiologic process of replacement with scar tis- tion. It is sobering to realize that although much current effort
sue, but in most cases this process does not appear excessive or is focused on maximizing tissue regeneration, there are cir-
overexuberant. Although efforts to decrease scar formation have cumstances where this already occurs and has proven to be
been attempted, it is currently thought that these will be ineffec- dysfunctional. It also illustrates the need to strictly control the
tive unless neural regeneration can also be achieved. Thus, cur- growth and development of tissue generation using emerging
rently efforts are focused on strategies to increase regeneration of stem and progenitor cell technologies.
neural tissue to treat this abnormal response to injury.16 Current
modalities under investigation include the use of implanted neu-
ral stem/progenitor cells or the use of developmental morphogens Excessive Scar Formation Underlying
to recapitulate the processes of neural development. Techniques
to decrease neural scar formation might also be useful to provide an Abnormal Response to Injury
a window of opportunity for regeneration to occur, but they are When these conditions affect the skin, they are very commonly
unlikely to be successful in and of themselves. Other examples treated by plastic surgeons, but they can occur elsewhere as in
of inadequate regeneration would include bone nonunions and pulmonary fibrosis or cirrhosis. “Excessive” cutaneous scar
corneal ulcers. formation remains a poorly understood and ubiquitous dis-
ease for which there are few treatment options. Abnormal
Inadequate Scar Formation Underlying scarring is classified as either hypertrophic scarring or keloid
formation. Both are manifestations of overexuberant scarring,
an Abnormal Response to Injury although the upstream etiology is probably different.18 Keloids
Many examples of impaired wound healing seen by plastic are less common and have a genetic component that limits
surgeons belong in this category. In most cases, these diseases them to <6% of the population, primarily the black and Asian
result from a failure to replace a tissue defect with a substitute populations. Histologically, keloids are differentiated by the
patch of scar (i.e., inadequate scar formation). In these condi- overgrowth of dense fibrous tissue beyond the borders of the
tions, stable scar tissue would be sufficient to restore cutane- original wound, with large thick collagen fibers composed of
ous integrity and eliminate the pathology. Regeneration of the numerous fibrils closely packed together. Hypertrophic scars
skin, although perhaps ideal, is not required for an adequate are also characterized by the formation of dense collagen fibers
functional outcome. Examples of these types of conditions following injury but, in contrast to keloids, do not extend
include diabetic foot ulcers, sacral decubiti, and venous sta- beyond the original wound margins. They are more prone to
sis ulcers. In all these cases, restoration of cutaneous integ- forming disabling contractures and are a near-­universal out-
rity would be sufficient, and as such, efforts must be made come following extensive deep burn injury.
to understand and correct the defects in scar formation that The etiology and pathophysiology of both hypertrophic
occur in these disease states. scarring and keloid formation remain unknown. Many theo-
Once the defect in scar formation is understood, therapeu- ries have been proposed to account for the fibroproliferation
tics can be rationally designed to correct these defects. At times, observed in hypertrophic scar and keloid formation, includ-
it is useful to subdivide the scar formation defects further and ing mechanical strain, inflammation, bacterial colonization,
examine whether the primary defect occurs in the inflamma- and foreign body reaction. Unfortunately, investigation of the
tory, proliferate, or remodeling phases of wound healing. For mechanisms underlying these diseases has been hindered by the
instance, in humans and experimental models, diabetic ulcers absence of animal models that reproduce the characteristics of
occur because of defects in the inflammatory and prolifera- human overscarring. Decreasing the process of scar formation
tive phases of wound healing. Accordingly, therapeutics are is the prime goal of therapy for both disease states. Modalities
targeted toward these phases.17 In contrast, wounds occurring employed include steroid injections, pressure therapy with sili-
because of vitamin C depletion (i.e., scurvy) are due to abnor- cone sheeting, and external beam irradiation. However, with
mal collagen cross-linking, which occurs during the remodel- current treatment modalities, recurrence rates approach 75%.19
ing phase of wound healing. Therapeutics should be directed The prolonged secretion of inflammatory cytokines has been
at this later phase. While in both cases therapeutic efforts are shown to induce fibrosis in numerous in vitro and animal mod-
focused on correcting defects in scar formation (as opposed els. Thus, researchers have long sought to manipulate the cyto-
to augmenting tissue regeneration), the therapeutic targets kine environment to prevent scar formation. Most recently, a
will be different. phase III clinical trial based on the use of recombinant human

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 2: Wound Healing: Normal and Abnormal 19
TGF-β3 (an antagonist of profibrotic TGF-β1) to improve scar These responses can be conceptualized as favoring replace-

Principles, Techniques, and


revision outcomes was terminated after failing to reach primary ment of injured tissue with a patch, otherwise known as
endpoints. Given the known complexity of wound healing, it scar formation, or recapitulating developmental processes to
should not be surprising that targeting a single cytokine would duplicate the original architecture, otherwise referred to as
be inadequate to reduce organ-level fibrosis. regeneration. The dynamic balance between these two pro-

Basic Science
Recent research has also implicated a key role for mechani- cesses may underlie the myriad abnormal responses to injury
cal force in promoting both hypertrophic scarring and keloid that occur in human disease states. It is hoped that such a
formation.20,21 Plastic surgeons have long recognized the framework will suggest new therapeutic strategies to correct
importance of tension during wound healing, and several imbalances, by either augmenting or suppressing one component
current treatments for scarring (e.g., silicone sheeting and or the other. This may provide a basis for accelerated prog-
compression garments) may have a “mechanomodulatory” ress in the care of patients with abnormal or dysfunctional
mechanism of action. Mechanical cues are known to activate responses to injury that result in human disease.
fibroproliferative pathways in skin cells, and the underlying
molecular pathways are only beginning to be uncovered in
vivo.22 Further, the ability of physical forces to control clini-
References
cal outcomes is demonstrated by the incorporation of nega- 1. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and
regeneration. Nature. 2008;453:314-321.
tive pressure wound therapies in modern wound treatment 2. Cha J, Falanga V. Stem cells in cutaneous wound healing. Clin Dermatol.
algorithms.23 Future strategies to prevent scar formation may 2007;25:73-78.
in fact be aimed at manipulating the mechanical and physical 3. Grose R, Werner S. Wound-healing studies in transgenic and knockout
cues controlling wound repair and fibrosis. mice. Mol Biotechnol. 2004;28:147-166.
4. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med.
1999;341:738-746.
Emerging Concepts in 5. Werner S, Grose R. Regulation of wound healing by growth factors and
cytokines. Physiol Rev. 2003;83:835-870.
Wound Healing 6. Woolley K, Martin P. Conserved mechanisms of repair: from damaged single
cells to wounds in multicellular tissues. Bioessays. 2000;22:911-919.
Human skin must continually adapt and renew during devel- 7. Martin P, Leibovich SJ. Inflammatory cells during wound repair: the good,
the bad and the ugly. Trends Cell Biol. 2005;15:599-607.
opment and in response to injury and disease. This suggests the 8. Simpson DM, Ross R. The neutrophilic leukocyte in wound repair: a study
intrinsic ability of the skin to “regenerate.” Several stem cell with antineutrophil serum. J Clin Invest. 1972;51:2009-2023.
populations have been identified in the skin and are increas- 9. Yager DR, Nwomeh BC. The proteolytic environment of chronic wounds.
ingly studied as potential therapies for wound repair. These Wound Repair Regen. 1999;7:433-441.
10. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev
progenitor populations include epidermal stem cells, hair fol- Immunol. 2005;5:953-964.
licle stem cells, and adipose-derived stem cells that have the 11. Leibovich SJ, Ross R. The role of the macrophage in wound repair.
capacity to restore almost all skin compartments.2,24,25 Further, A study with hydrocortisone and antimacrophage serum. Am J Pathol.
studies in mammalian digit tip regeneration suggest that the 1975;78:71-100.
12. Park JE, Barbul A. Understanding the role of immune regulation in wound
biologic machinery necessary to regrow damaged soft tissues healing. Am J Surg. 2004;187:11S-16S.
may already be present in adults in the form of tissue-specific 13. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor
adult stem cells.26 Thus, it is clear that stem cells play a key endothelial cells for angiogenesis. Science. 1997;275:964-967.
role in normal wound healing; the question for researchers 14. Desmouliere A, Chaponnier C, Gabbiani G. Tissue repair, contraction, and
the myofibroblast. Wound Repair Regen. 2005;13:7-12.
is how to exploit these powerful cell populations to promote 15. Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and
cutaneous repair in disease states. the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007;8:
Another component of the wound environment that has 221-233.
been largely overlooked is the ECM. As stated earlier, wound 16. Harel NY, Strittmatter SM. Can regenerating axons recapitulate devel-
opmental guidance during recovery from spinal cord injury? Nat Rev
remodeling is the least well understood phase of wound heal- Neurosci. 2006;7:603-616.
ing but appears to involve regulation of extracellular enzymes 17. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in
that control the structural architecture of the ECM. It has diabetes. J Clin Invest. 2007;117:1219-1222.
been shown that the ECM is a dynamic and active component 18. Kose O, Waseem A. Keloids and hypertrophic scars: are they two different
sides of the same coin? Dermatol Surg. 2008;34:336-346.
of the wound that can directly control cell activity,27 resulting 19. Mustoe TA, Cooter RD, Gold MH, et al. International clinical rec-
in a “dynamic reciprocity” between cells and their immediate ommendations on scar management. Plast Reconstr Surg. 2002;110:
environment that maintains skin homeostasis.28 This concept 560-571.
underlies the development of tissue engineering strategies to 20. Gurtner GC, Dauskardt RH, Wong VW, et al. Improving cutaneous scar by
controlling the mechanical environment: large animal and phase I studies.
deliver and re-create the precise biophysical cues that promote Ann Surg. 2011;254:217.
biologic programs conducive to healing.29,30 21. Ogawa R. Keloid and hypertrophic scarring may result from a mecha-
The three traditional phases of wound healing were estab- noreceptor or mechanosensitive nociceptor disorder. Med Hypotheses.
lished decades ago, and since then, research in wound repair has 2008;71:493-500.
22. Wong VW, Rustad KC, Akaishi S, et al. Focal adhesion kinase links
continued to build upon these fundamental concepts. However, mechanical force to skin fibrosis via inflammatory signaling. Nat Med.
as modern research continues to elucidate the complexity of 2011;18:148-152.
tissue repair processes, we will undoubtedly need to redefine 23. Orgill DP, Manders EK, Sumpio BE, et al. The mechanisms of action of
what normal wound healing is in terms beyond just inflam- vacuum assisted closure: more to learn. Surgery. 2009;146:40-51.
24. Blanpain C, Fuchs E. Epidermal stem cells of the skin. Annu Rev Cell Dev
matory cell trafficking and a handful of cytokines. Traditional Biol. 2006;22:339-373.
approaches to wound healing will also need to be integrated 25. Yang L, Peng R. Unveiling hair follicle stem cells. Stem Cell Rev.
with our improved understanding of the molecular pathophysi- 2010;6:658-664.
ology of aberrant cutaneous repair. Plastic and reconstructive 26. Rinkevich Y, Lindau P, Ueno H, Longaker MT, Weissman IL. Germ-layer
and lineage-restricted stem/progenitors regenerate the mouse digit tip.
surgeons need to be intimately familiar with these evolving con- Nature. 2011;476:409-413.
cepts to ensure the optimal care of our patients. 27. Hynes RO. The extracellular matrix: not just pretty fibrils. Science.
2009;326:1216-1219.
28. Schultz GS, Davidson JM, Kirsner RS, Bornstein P, Herman IM. Dynamic
Conclusions reciprocity in the wound microenvironment. Wound Repair Regen.
2011;19:134-148.
29. Glotzbach JP, Wong VW, Gurtner GC, Longaker MT. Regenerative medi-
In this chapter, a theoretical framework has been proposed cine. Curr Probl Surg. 2011;48:148-212.
with which to understand and classify the normal responses 30. Metcalfe AD, Ferguson MWJ. Bioengineering skin using mechanisms of
to injury that occur in different tissues and different species. regeneration and repair. Biomaterials. 2007;28:5100-5113.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 3  n  Wound Care
Donald W. Buck and Robert D. Galiano

addressing these factors, the surgeon will be able to manage


Introduction most wounds.
The wound is a microcosm of the patient. While most wounds
heal without intervention in healthy individuals, patients with Age and Wound Healing
systemic diseases or acute illnesses can develop non-healing Although most wounds heal without incident in aged
wounds that require evaluation by a plastic surgeon. In gen- patients, there is a slight, but consistent, decline in wound
eral, the plastic surgeon is consulted to evaluate three types of healing rates in the elderly. This decline is exacerbated when
wounds: (1) the acute wound where the final appearance may ischemia and infection are superimposed. Laboratory studies
be the principal concern, (2) the wound in a patient whose reveal a functional decline in aged fibroblasts and endothelial
medical status and/or mode of injury predisposes him or her to cells that leads to accelerated senescence, diminished growth
wound healing difficulties and the threat of a problem wound, factor production, decreased stress response to hypoxia and
or (3) the chronic wound refractory to past interventions. toxins, and a reduction in collagen and matrix production.
In recent years, significant strides have been made in our Interestingly, aged cells share many of the same molecular
overall understanding of problem wound physiology. This has derangements as those seen in diabetic patients and irradiated
led directly to clinical advances that have resulted in better wound beds. Obviously age cannot be reversed; however,
treatments and overall wound care. With the staggering prev- it should be considered an important component of wound
alence of chronic wounds and an ever-increasing armamen- pathology and prompt the surgeon to aggressively optimize
tarium of wound care tools, it is imperative that the plastic appropriate systemic parameters in these patients (nutri-
surgeon maintain an updated understanding of wound healing tion, infection, ischemia, etc.). The use of growth factors or
biology and the principles of wound care. In this chapter we advanced wound protocols should be considered earlier in
will focus on the basics of wound care and highlight some of the elderly patient.
the recent advances in this dynamic and expanding field.
Ischemia and Wound Healing
Fundamentals The role of hypoxia in wound healing is well established.
In fact, local tissue hypoxia is a common characteristic of
All wounds, whether acute or chronic, should be evaluated most chronic wounds. The diffusion of oxygen and nutri-
by a physician to determine their mechanism and to outline ents from capillaries to cells is limited to a distance of 60
an approach to treatment. Tetanus prophylaxis is adminis- to 70 µm in a person breathing room air. Therefore, any-
tered when prior immunity is unknown or the most recent thing that increases tissue diffusion requirements or limits
booster vaccine is over 5 years old. A thorough history and
physical examination should be performed, with particular
emphasis on any aspect that relates to the wound cause and/
or persistence (e.g., comorbidities, systemic diseases, and Table 3.1
medications). The term wound encompasses a broad range of
lesions without consideration to etiology, and the list of pos- Factors That Contribute to Wound
sible etiologies is vast. Table 3.1 lists some of the major fac- Healing Impairments
tors, both systemic and local, that can have profound effects
Age
on wound healing.
Adjunctive diagnostic tests are guided by history and phys- Ischemia
ical examination of the wound. Some useful studies include Reperfusion injury
laboratory tests that reflect nutritional status (albumin,
prealbumin, and transferrin levels), the level of physiologic Infection or bacterial bioburden
inflammation (C-reactive protein and erythrocyte sedimen- Malnutrition
tation rate), and the degree of diabetes control (plasma glu-
Foreign bodies
cose and hemoglobin A1c). In addition, patients should have
a recent complete blood count and basic chemistry panel to Diabetes
assess for leukocytosis, anemia, and renal disease. Other use- Steroids
ful laboratory tools include transcutaneous oxygen pressure
(tcPo2) measurements, toe pressures, neurofilament testing, Uremia
and ankle-brachial index (ABI) (Chapter 95). Results of these Jaundice
tests may direct the need for procedures such as surgical
Cancer
revascularization. Wound parameter documentation is also
useful to monitor the progression of wound healing in an Genetic causes (e.g., Ehlers-Danlos, Werner syndromes)
objective manner. Irradiation
The main fundamentals of wound care are summarized in
Table 3.2. To attain these goals, it is useful to emphasize the Chemotherapy
common causative factors that are shared by problem wounds, Tobacco use
as opposed to isolating the differences between diverse types of
Alcohol use
wounds. With this more simplistic view, it is possible to link the
majority of problem wounds to a combination of three factors: Edema
age, ischemia (including repeated episodes of ischemia–reper- Pressure
fusion injury), and bacterial infection. By understanding and
20
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 3: Wound Care 21
Table 3.2 Bacteria and Wound Healing

Principles, Techniques, and


Basic Fundamentals of Wound Care All wounds are contaminated, but excessive numbers of bacte-
ria will interfere with wound healing. A quantitative culture of
n  Optimize systemic parameters 105 bacteria per gram of tissue is usually diagnostic of infection.

Basic Science
 Nutrition However, this tool is rarely used because few microbiology lab-
oratories perform the test reliably. Furthermore, the value of
  Glucose control
105 is relative and not universally applicable. In fact, more viru-
  Smoking cessation lent strains of bacteria can establish systemic infections at much
n  Debride nonviable tissue lower densities. The presence of diabetes, ischemia, or other
comorbidities will also lower the threshold needed to estab-
n  Reduce wound bioburden lish a true infection to an unknown extent. Likewise, as more
n  Optimize blood flow research on the physiology of bacterial biofilms is introduced, it
is likely that only a fraction of the 105 bacterial count is actually
 Warmth necessary to establish a biofilm and create a significant barrier
 Hydration to wound healing.
  Surgical revascularization An important mechanism by which tissue hypoxia pre-
disposes wounds to infection is by impairing the “oxidative
n  Reduce edema burst” essential to microorganismal killing by leukocytes. This
 Elevation enormously elevated production of oxygen-derived radicals
is a self-regulated process that is important in clearing the
 Compression wound off bacteria. Notably, this process of radical produc-
n  Use appropriate dressings tion, which is normally limited to the early stages of wound
  Moist wound healing repair, can be aberrantly prolonged in the setting of persis-
tent infection or inflammation (Figure 3.1). This can result
  Exudate removal in bystander damage to the body’s normal cells and in many
  Avoidance of trauma to wound or patient
n  Use pharmacologic therapy when necessary Break in skin integrity,
bacterial inoculation
n  Close wounds surgically with grafts or flaps as indicated
Wound
INJURY hypoxia

available capillary delivery systems will establish a hypoxic Bacterial


colonization
environment. For example, oxygen tension in wound tissues Inflammatory
mediators
is reduced an average of 15 to 20 mm Hg (25 vs. 40 mm Resolution
Hg) as a result of the damage to small vessels in periwound (healed wound)

areas. Likewise, the tissue fibrosis commonly encountered in Neutrophils,


macrophages
chronic wounds can create a significant barrier to oxygen dif-
fusion that subsequently produces persistent tissue hypoxia Progression of
wound to later Oxidative burst
and further fibrosis. stages of healing ROS
Clearance
While hypoxia alone is an important component of of bacteria
chronic wounds, most problem wounds are characterized by
repeated episodes of ischemia followed by reperfusion. The Angiogenesis,
ROS
reversal of
detrimental effects of ischemia–reperfusion injury have been ischemia Resolution of
inflammation
Proteases

well established in cardiac pathology and organ transplanta- A


tion, but are underappreciated in cutaneous wound healing.
Reperfusion injury is particularly important in lower extrem-
INJURY
ity wounds, where walking and standing can lead to local-
ized ischemia in pressure-bearing areas, or through increased Insufficient oxidative
edema in patients with venous stasis. Pressure relief, through Wound hypoxia
burst due to regional ischemia
and immune dysfunction
+
sitting, rest, and foot elevation, leads to resumption of ade- Regional ischemia
(PVD, diabetes, radiation) Inflammation Persistent hypoxia
quate tissue perfusion and a vicious cycle ensues. Repeated due to regional
ischemia
episodes, sometimes multiple per day, result in gradual cel- Bacteria

lular damage and a chronic milieu of persistent inflamma-


Bacteria
tion. Similar cycles of ischemia–reperfusion may also occur (critical colonization)
in patients with pressure sores as they shift about in bed or Perpetuation and Elaboration
amplification of of biofilm,
wheelchairs. proinflammatory state pseudoeschar

Surgical and nonsurgical interventions can be undertaken Hypoxia


Inflammation,
to maximize oxygen delivery to tissues. Examples include ele- Proteases
persistence of
neutrophils
vation of edematous extremities, off-loading pressure points, ROS
Growth factors
debridement of necrotic tissue or foreign bodies that act as a Proangiogenic
milieu
physical barrier to diffusion, pain control that reduces sympa- Edema Wound
thetic constriction of peripheral vasculature associated with Exudate stasis
Cellular
the “fight-or-flight” response, heating that will result in vaso- damage Proteases
in wound Acidity
dilatation of cutaneous vasculature, and smoking cessation Zone of Free radicals
injury B
and hydration that increase oxygen delivery at the cellular
level. Recent research indicates that the benefits of ensuring Figure 3.1.  The normal healing milieu. A. Normal response to
adequate oxygen delivery to a wound not only are restricted injury. B. Response to injury in the problem wound. ROS, reactive
to established wounds but may also be useful in preventing oxygen species; PVD, peripheral vascular disease.
wound complications.

(c) 2015 Wolters Kluwer. All Rights Reserved.


22 Part I: Principles, Techniques, and Basic Science

cases characterizes the microenvironment of the indolent appetizing nutrients for most bacteria. Therefore, any pseu-
wound. This explains the benefit of dressings and the avoid- doeschar or eschar should be debrided as it accumulates. An
ance of foreign debris (and highlights the importance of deli- effective way to do this is through the proper use of dressing
cate tissue handling and the proper choice of suture material) and debriding agents, as detailed below and in Table 3.3.
in expediting healing. Debridement is typically considered a surgical tool, but
Bacteria exert adverse effects on wound healing in several it may also be accomplished through the use of enzymatic,
ways. As mentioned above, through a persistent inflamma- mechanical, or autolytic (through host leukocyte action)
tory response, they establish an environment of free radicals, means. Wound care manufacturers have produced numer-
secreted toxins, and proteases that act to degrade growth fac- ous enzymatic and pro-autolytic agents. While they have been
tors, prevent ordered assembly of matrix proteins, and result proven effective in mildly debriding wounds, their use should
in the creation of proteinaceous debris that constitutes a pseu- not supplant sharp surgical debridement as the method of
doeschar. In addition, they place a significant metabolic strain choice for more heavily contaminated wounds or wounds with
(bioburden) on the wound that the host may not be able to thicker levels of slough or eschar. Enzymatic and pro-autolytic
overcome. Importantly, wound bioburden is often stratified as agents work through preventing the cross-linking of exudated
a prognostic indicator and to assist in management decisions. components and impede the bacteria-sequestering pseudoe-
Wounds may be considered contaminated (bacteria present schar and biofilms from forming. Mechanical debridement
without proliferation), colonized (bacteria present and mul- can be achieved through dressings, or newer pressurized water
tiplying without overt host reaction), critically colonized (the devices, such as the VersaJet (Smith & Nephew, Largo, FL),
tipping point where host response is overcome by bacterial Waterpik (Waterpik Technologies, Fort Collins, CO), pulse-
proliferation), or infected (expanding bacterial quantity with lavage, or shower spray devices. Mechanical debridement is
ongoing host reaction). Critical colonization of a wound or effective at reducing bacterial counts and should be consid-
infection is often heralded by stasis in the progression of a ered adjuncts to surgical debridement. Similarly, a syringe
wound that was previously healing. In fact, if the rate of heal- with a 20-gauge needle will generate the 15 psi necessary to
ing decreases in any wound, it should be considered infected lower bacterial counts in tissue.
until proven otherwise. Other signs of bioburden progres- For historical purposes, another effective means of achiev-
sion and/or overt wound infection include increasing pain in ing wound debridement is through the use of maggot therapy.
the periwound area, increased wound edema, malodorous Maggots preferentially feed on devitalized tissue and spare via-
­discharge, increased drainage, or purulence. ble, well-perfused tissue; their secretions also target bacterial bio-
Systemic antibiotics are unnecessary for most wounds. By films. Although they are used sparingly throughout most parts
definition, most wounds are open and thus adequately man- of the country, some centers utilize maggot therapy extensively.
aged through “drainage” and proper debridements. In addi-
tion, systemic antibiotics are only delivered to adequately
perfused tissues; therefore, in the setting of most problem Negative-Pressure Wound Therapy
wounds, they are ineffective. However, there are settings where
Negative-pressure wound therapy (NPWT) has been a signifi-
systemic antibiotics are important. In general, any wound that
cant advance for the wound care practitioner. It consists of
is complicated by surrounding cellulitis should be treated with
the use of a porous sponge within the wound, covered by an
adjunctive antibiotics. As mentioned, any wound where the
airtight occlusive dressing, to which a vacuum is applied. This
rate of healing decreases is considered infected. Increased
modality has many uses and has found its way into the arma-
pain is another indication of a worsening infection. Another
mentarium of a wide array of surgical and nonsurgical spe-
sign of infection is the appearance of straw-colored “oozing”
cialties. It should best be thought of as an adjunct to assist in
from the skin; this is actually likely evidence of an underlying
surgical closure of a problem wound. It can and has been used
Staphylococcus cellulitis or lymphangitis. Antibiotics should
to completely heal a wound, but use in this manner is time-
also be considered in wounds contaminated by oral flora or
consuming, expensive, labor-intensive, and not always effec-
animal bites, as well as in patients with mechanical implants.
tive. A more practical indication is to expeditiously prepare a
In general, surface irrigation and lavage with saline may be
wound bed for surgical closure by tertiary intent.
all that is necessary for truly contaminated wounds, whereas
NPWT works through multiple important mechanisms
topical antibiotics and surgical debridement are often essential
including reduction of edema and removal of wound fluid rich
management tools for overtly infected wounds.
in deleterious enzymes, both patient and bacteria derived. In
addition, the cyclic compression and relaxation of the wound
Adjuncts to Wound Care tissue likely stimulates mechanotransduction pathways that
result in increased growth factor release, matrix production,
Debridement and cellular proliferation.
Debridement is the single most important wound care tool Common clinical scenarios amenable to NPWT include
to reduce bioburden and promote healing. Without adequate lymphatic leaks, venous stasis wounds, diabetic wounds,
debridement, a wound is persistently exposed to cytotoxic wounds with fistulae, sternal wounds, orthopedic wounds, and
stressors and competes with bacteria for scarce resources such abdominal wounds. Likewise, NPWT is used frequently as an
as oxygen and nutrients. Many surgeons underappreciate the alternative to bolster dressings for split thickness skin grafts.
importance of adequate debridement in the management of Notably, by reliably encouraging granulation tissue formation
both acute and chronic wounds. While most surgeons rec- and reducing wound edema, NPWT has permitted normally
ognize the importance of debridement of grossly necrotic or emergent wounds to be managed in a nonemergent fashion,
foreign material, many still allow wounds to “heal” under a allowing for medical stabilization and optimization prior to
“biologic dressing” or eschar. advanced reconstructive procedures. In some instances, it has
An eschar begins as a pseudoeschar, which is a provisional even enabled avoidance of free tissue transfer.
matrix of exudated serum components at the wound–air inter- There are several contraindications to the use of NPWT,
face. If allowed to dry, the gelatinous pseudoeschar will harden and these include the presence of a malignancy, use on wounds
to form a true eschar, or scab. Pseudoeschars and eschars may characterized by ischemia, as well as inadequately debrided or
play a role in prolonging the inflammatory stage of wound badly infected wounds. There have been reports of extension
healing, and hence establish an environment ripe for bacterial of the zone of necrosis when used on ischemic wounds; for
colonization in the compromised patient or susceptible wound this reason, these patients should be revascularized prior to
bed. Likewise, the proteinaceous components of the eschar are application of NPWT.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 3: Wound Care 23

Table 3.3

Principles, Techniques, and


Common Dressings in Wound Care

n D
 ressing n D
 ressing  onformability n Clinical
n C n C
 ommonly Used

Basic Science
Material Characteristics (Surface Application Products
Anatomy versus.
Cavity)

Gauze Moderate absorption Surface Superficial wounds Many, can be


Nonadhesive Light exuding wounds impregnated with
Light hydration As a secondary antimicrobials and gels
(if moistened with dressing
saline) Optimal for skin graft
donor sites and
surgical incisions
Films Nonabsorbing Surface Superficial wounds Tegaderm (3M, St.
Fully adhesive Light exuding wounds Paul, MN)
Slow hydration As a secondary Op-Site (Smith &
dressing Nephew, Largo, FL)
Optimal for skin graft
donor sites and
surgical incisions
Hydrogel Low absorption Surface Superficial wounds NU-GEL (Johnson &
sheets Nonadhesive or Light exuding Johnson, Somerville, NJ)
adhesive borders wounds Curafil (Kendall/Covidien,
Moderate hydration Painful wounds Mansfield, MA)
(once a day Flexigel (Smith &
application) Nephew)
Amorphous Low to moderate Cavities Clean, superficial to Curasol (Healthpoint,
hydrogels absorption deep wounds Fort Worth, TX)
Nonadhesive Light to moderately Tegagel (3M)
Quick hydration exuding wounds
Hydrocolloids Low to moderate Surface Superficial wounds DuoDERM (ConvaTec,
absorption Light to moderately Skillman, NJ)
Fully adhesive exuding wounds Replicare (Smith &
Moderate hydration May exacerbate Nephew)
wound odor Tegasorb (3M)
Ultec (Kendall/Covidien)
Foams High absorption Both depending on Superficial to deep Allevyn (Smith &
Full to nonadhesive dressing type wounds Nephew)
Not hydrating Moderately to Copa (Kendall/Covidien)
heavily exuding Lyofoam (ConvaTec)
wounds Optifoam (Medline,
Mundelein, IL)
Restore (Hollister,
Libertyville, IL)
Alginates High absorption Cavities Superficial or deep Algisite (Smith & Nephew)
Nonadhesive wounds Curasorb (Kendall/
Not hydrating Moderately to Covidien)
heavily exuding Kaltostat (ConvaTec)
wounds Maxorb (Medline)
Restore Alginate
(Hollister)
Collagens Moderate to high Cavities Superficial or Fibracol (Johnson &
absorption deep wounds Johnson)
Nonadhesive Light to moderately Colactive (Smith &
Not hydrating exuding wounds Nephew)
Puracol (Medline)
Negative- Moderate absorption Both Lymphatic leaks, V.A.C. (Kinetic Concepts
pressure wound Adhesive venous stasis wounds, Inc., San Antonio, TX)
therapy Not hydrating diabetic wounds, Renasys (Smith &
wounds with fistulae, Nephew)
sternal wounds, ortho-
pedic wounds, and
abdominal wounds

(c) 2015 Wolters Kluwer. All Rights Reserved.


24 Part I: Principles, Techniques, and Basic Science

rapidly degrade the protein. In addition, its use in patients


Hyperbaric Oxygen with malignancy has been cautioned.
Hyperbaric oxygen (HBO) has been shown to raise the dis- Although not growth factors per se, there has been an
solved oxygen saturation in plasma from 0.3% to nearly increase in the use of neonatal fibroblasts as a “carrier” for
7%, resulting in a four- to fivefold increase in the interstitial essential growth factors to the wound environment. Commonly
diffusion distance of oxygen. Historically, the initial enthu- used products include Apligraf (Organogenesis Inc., Canton,
siasm to HBO led to indiscriminate and unscientific use, MA) and Dermagraft (Advanced BioHealing, Westport, CT).
which created significant controversy with regard to safety These products are commonly used in patients with a sub-
and efficacy. Despite early disappointment, the use of HBO optimal wound environment, including venous stasis ulcers,
has gained increasing traction. In order to optimize results, diabetic wounds, and wounds in aged patients.
it is important to recognize which patients benefit the most
from such therapy. The use of transcutaneous oximetry Enzymes
has permitted evaluation of wound microcirculation, such
The rationale for using enzymatic debriding agents is that
that surgeons can accurately predict responders and non-
they offer a noninvasive means to selectively digest necrotic,
responders. In general, patients who demonstrate a rise in
devitalized tissue and prevent slough and eschar from accumu-
the wound tcPo2 when inspiring supplemental oxygen will
lating (Table 3.4). Papain-based products are no longer avail-
benefit from HBO. Patients that will not benefit from HBO
able in the United States since they were determined by the
include those with normal environmental perfusion and
FDA to be unapproved drugs with significant side effects. The
those with ischemic limbs who require a revascularization
sole enzymatic agent available for use is collagenase (Santyl,
procedure to restore adequate blood flow to the limb. It is
Healthpoint Ltd., Fort Worth, TX), which works by digest-
important to note that HBO use remains largely empiric as
ing necrotic collagen within wounds. Santyl is currently mar-
there is a paucity of prospective randomized trials support-
keted for patients with chronic dermal ulcers and burns and is
ing its use.
used frequently by wound care practitioners. It is important to
recognize that enzymatic debridement products are not sub-
Growth Factors stitutes for adequate mechanical debridement; however, when
properly used, they are often less traumatic to healthy sur-
The first growth factor approved by the Food and Drug rounding tissue. In general, these products should be used in
Administration (FDA) in the United States is platelet-derived wounds with small areas of eschar or necrotic debris.
growth factor (PDGF) or becaplermin (Regranex, Johnson &
Johnson, Somerville, NJ) (Table 3.4). Although it is only FDA
approved for use in the treatment of diabetic foot ulcers, is has Dressings
been widely used “off-label” for the treatment of a variety of Wound care dressings (Table 3.3) can be broadly divided
other wound types including irradiated wounds and wounds into seven classes: films, composites, hydrogels, hydrocol-
in elderly patients. Importantly, PDGF is only effective in the loids, alginates, foams, and absorptive dressings including
context of a well-prepared wound bed. Contaminated and/ NPWT. Unfortunately, within each class, there are a dizzying
or infected wound beds are filled with proteases, which will number of options and a paucity of prospective, randomized

Table 3.4
Common Growth Factors and Enzymes in Wound Care

n Name n G
 rowth n Uses n Comments
Factor/Enzyme

Regranex (Johnson & Platelet-derived Diabetic foot ulcers Degraded in contaminated or


Johnson, Somerville, NJ) growth factor (FDA approved, “off-label” infected wound beds
for irradiated wounds,
elderly patients)
Accuzyme Papain-urea Superficial wounds with Expensive; not useful in
Panafil presence of necrotic debris wounds with large amounts
(Healthpoint Ltd, or eschar of necrotic tissue
Fort Worth, TX)
Santyl Collagenase Superficial wounds with Expensive; not useful in
(Healthpoint Ltd) presence of necrotic debris wounds with large amounts
of necrotic tissue
Skin substitutes Neonatal fibroblasts, Poor wound environment Expensive; often used as a
 Apligraf (Organogenesis, hyaluronic acid (e.g., elderly, venous stasis “growth factor” carrier
Canton, MA) wounds)
 Dermagraft (Advanced
Biohealing, Westport, CT)
Integra (Integra Life Sciences, Collagen-GAG bilayer Coverage of partial and Useful in burns and to cover
Plainsboro, NJ) full-thickness wounds exposed tendon and bone
Biobrane (Mylan Laboratories, Silicone-nylon Coverage of partial thickness Useful as barrier to
Canonsburg, PA) bilayer with wounds, burns, skin grafts contamination for skin
imbedded collagen graft coverage, burn wound
coverage

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 3: Wound Care 25
clinical trials that definitively prove superiority of one type come in various physical forms including gels, sheets, and

Principles, Techniques, and


versus the other. With the seemingly endless options avail- impregnated into gauze. They are nonadhesive and therefore
able, it can often become overwhelming. To assist with this cause minimal pain with dressing changes. However, because
decision, it is best to consider the overall wound characteris- of this, they usually require a secondary dressing (e.g., gauze).
tics and treatment goals and match them to the appropriate

Basic Science
dressing class. Hydrocolloids.  Hydrocolloids typically come in pastes,
The goal in clean wounds that are to be closed primarily, powders, or sheets that are placed within the wound and cov-
or in wounds that are granulating well, is to provide a moist ered with a dressing to form an occlusive barrier that gels as
healing environment to facilitate cell migration and prevent it absorbs mild amounts of exudates. Hydrocolloids consist of
desiccation. Consequently, films can be used for incisions, and gel-forming agents (typically gelatin, carboxymethyl cellulose,
hydrogels or hydrocolloids can be used for open wounds. The or pectin) that are impermeable to gases and liquids. They
amount and type of exudate that is present in the wound will may be left on the wound for 3 to 5 days; during this time,
determine the dressing used in wounds that have some degree they provide a moist environment that promotes cell migra-
of bacterial colonization. In general, hydrogels, films, and tion and wound debridement by autolysis. However, because
composite dressings are best for wounds with lighter amounts of their occlusive nature, they should not be used in wounds
of exudates; hydrocolloids are used for wounds with moderate heavily colonized by bacteria, especially those with anaerobic
quantities; and alginates, foams, and NPWT are best used for strains. They are not highly absorbent and hence should not
wounds with heavier volumes of exudates. As mentioned pre- be used in highly exudative wounds.
viously, NPWT is also useful for wounds with heavy amounts
of lymph drainage as a consequence of a lymphatic leak, as Foam Dressings.  Foam dressings are made of nonadhering
well as for fistulae. Wounds with large amounts of necrotic polyurethane, which is hydrophobic, and an occlusive cover.
material should not be treated with dressings until a surgical The polyurethane is highly absorptive and acts as a wick
debridement has been performed. for wound fluids, making them useful for highly exudative
wounds. However, because of their high wicking ability, they
Gauze.  Gauze dressings are the traditional first choice for are not to be used on nonexudating or minimally exudating
generic wound care. The realization that the practice of moist wounds.
to dry dressings for wound care is actually traumatic and pro-
inflammatory has led to a decline in the use of these dressings Alginates.  Alginate dressings are derived from brown sea-
in the arena of wound care. In addition, the costs associated weed and are particularly useful in wound characterized by
with these dressings, particularly in personnel expenses, are significant amounts of exudate. Their use permits the desired
high compared with modern dressings that require less fre- removal of exudated fluids from the wound environment and
quent dressing changes. Gauze dressings are often painful to yet frees the practitioner from the burden of daily dressing
remove and are nonselective debriders that cause significant changes or multiple dressing changes per day. These products
collateral damage to healthy surrounding tissue. Furthermore, should also not be used in nonexudative wounds, as they can
many gauze dressings leave behind fine microfibers that can dry out the wound bed. They come in several forms, includ-
act as an irritant or a source of infection. ing a rope/ribbon form that is useful for packing wounds
Advantages of gauze dressings include a low material with deep pockets. These dressings can absorb approximately
expense and a readily available supply. Likewise, they may 20 times their dry weight in fluid. They should be covered
be purchased impregnated with petrolatum, iodinated com- with a semiocclusive or gauze dressing. If the surgeon desires
pounds, or other material useful in keeping the wound bed to use these alginate dressings on dry wounds, they should
moist. They make excellent surgical bandages and can be used be hydrated with sterile saline prior to being placed on the
in small, noncomplicated wounds or as secondary dressings. wound to maintain wound moisture and permit epithelializa-
Gauze dressings remain the “gold standard” to which the tion and autolysis. Some alginates are impregnated with silver.
FDA compares most dressings. There is no definitive evidence
that other dressings will heal a wound faster than moist gauze, Antimicrobials.  Antimicrobial dressings are a generic
although they may offer other advantages. term for a dressing that contains an antimicrobial agent.
The most beneficial agent appears to be silver. Silver is ion-
Semiocclusive Dressings.  These are sheets that are ized in the moist environment of the wound, and it is the
impermeable to fluids but permit the passage of small gas silver ion that has biologic activity. This agent has a broad
molecules. They are typically used in combination with spectrum of bactericidal activity with low toxicity to human
gauze or other dressings and act to maintain the moisture cells. Because of silver’s tri-pronged mechanism of action
content of clean wounds. Semiocclusive dressings are com- (cell membrane permeabilizer, inhibitor of cellular respira-
monly used to cover and protect freshly closed incisions and tion, and nucleic acid denaturer), it is active against a broad
skin graft donor sites and will enhance epithelialization when range of microorganisms in vitro, including highly resistant
used this way. They should not be used in wounds known to organisms such as VRE (vancomycin-resistant enterococcus)
be contaminated and wounds with moderate or higher exu- and MRSA (methicillin-resistant Staphylococcus aureus).
date levels and should be used cautiously in patients with There are a number of silver-impregnated dressings on the
fragile skin prone to tearing. market today, including Acticoat (Smith & Nephew, Largo,
FL), Aquacel Ag (ConvaTec, Skillman, NJ), and Silvasorb
Hydrogel Dressings.  Hydrogel dressings are useful in (Medline, Mundeleine, IL). Despite the expanding incorpo-
maintaining a moist wound bed and rehydrating wounds to ration of silver into many types of dressings, reliable indica-
facilitate healing through autolytic debridement. Thus, they tions for their use remain to be determined, and much of
are often useful in wounds with small amounts of eschar the use of silver-containing dressings is based on anecdotal
or that are predisposed to desiccation. Their usefulness is experience.
achieved by their intrinsic moisture content and hydrophilic Cadexomer iodine is another antimicrobial agent and is a
nature. They are usually composed of complex polysaccha- slow-release form of iodine formulated to achieve consistent
rides (e.g., starch). Unlike alginates and hydrocolloids, they are bactericidal levels within the wound bed without the wound
not dependent on the wound bed to maintain moist wound cell damaging effects seen with the use of povidone-iodine
microenvironments. Yet, like the other dressings, they can products. Other antimicrobials include silver sulfadiazine,
absorb moderate amounts of fluid from the wound. An addi- mafenide acetate, and preparations of sodium hypochlorite
tional benefit is that they can be used in infected wounds. They solution (Dakin’s solution).

(c) 2015 Wolters Kluwer. All Rights Reserved.


26 Part I: Principles, Techniques, and Basic Science
Intact skin
Skin Substitutes or Human Tissue Equivalents =100% Curve of ideal healing

These were among the first tissue-engineered products applied Curve of normal healing
to clinical use. As mentioned previously, besides providing
wound coverage, some of these products contain living cells Problem
that are cellular factories, secreting a panoply of growth fac- wound curve
tors and other bioactive molecules that assist the wound heal-
50% Augmented
ing cascade. One major disadvantage to their use is cost. They

Skin tensile strength


healing Delayed

(Degree of healing)
must be applied to meticulously clean wounds with adequate (hypothetical) healing
vascularity, and for certain products the site needs to be immo-
bilized to prevent shearing and graft loss. Representative prod-
ucts include cultured autologous keratinocyte sheets (Epicel,
Genzyme Corp, Cambridge, MA); dermal constructs such as
0%
Biobrane (Mylan Laboratories, Canonsburg, PA), Oasis (Cook 0 20 40 60 80
Biotech, West Lafayette, IN), Integra (Integra LifeSciences Time following injury (days)
Corp, Plainsboro, NJ), TransCyte (Smith & Nephew, Largo,
FL), and Dermagraft (Advanced Biohealing, Westport, CT); Figure 3.2.  The healing trajectories of a normal wound, a problem
and bilayered tissue-engineered constructs consisting of kera- wound, and a hypothetical ideal wound are depicted. Most normal
wounds heal with a slight lag phase, an exponential phase of active
tinocytes and fibroblasts such as OrCel (Ortec International,
gain in tensile strength with active matrix deposition, and a protracted
New York, NY), and Apligraf (Organogenesis, Canton, MA). resolution phase. Note that the normal wound heals with a scar that
The indications for their use are highly patient and center spe- does not achieve the tensile strength of unwounded skin (hypothetical
cific. Integra has proven especially useful for sites prone to wound curve). The curve on the right represents a problem wound
contracture (neck and axilla) and to replenish contour in burn curve. The exact shape of the curve is dependent on the patient
wounds and donor sites. In addition, it can enable coverage of and clinical scenario; however, prolongation of the lag phase, a more
tendons, bone, and surgical hardware and in select situation shallow exponential phase, and a reduction in final tensile strength
can obviate the need for more complex wound closures, such are to be expected.
as flaps.

Scar Modulating Therapies.  The use of silicone sheets wounds that will not heal is of tremendous importance and is an
improves the appearance of scars. This is likely the result of area of promising research. This also has practical importance, as
the increased moisture and slightly increased warmth pro- many third-party reimbursement agents will not cover specialized
vided by the continuous application of the silicone sheet, as care of wounds unless they have been present for a defined period
this increases slightly the rate of collagenolysis. Other useful of time. The standard definition of a chronic wound is one that
tools include steroids and pressure garments. Calcium channel has been present for 3 months but such a definition may be seized
blockers are used, but they are unproven, as are topical formu- upon by insurance carriers to deny specialized care to impaired
lations of salicylic acid, an anti-inflammatory agent, although wounds. Unfortunately, this condemns the patient to months of
the theoretical basis underlying the use of this agent appears unnecessary waiting, morbidity, and time away from work and
sound. Drugs targeting growth factors thought to be impor- may even worsen the outcomes in cases of threatened limb
tant in fibrosis are currently in clinical trials. loss, for example, by allowing the progression of osteomyelitis.
It is, therefore, perhaps time to redirect the conceptualization of
Common Clinical Wound Care Scenarios a problem wound to de-emphasize chronicity and re-emphasize
its fall off the trajectory of expected healing. The majority of
The Uncomplicated Wound.  Much is known about the problem wounds seem to share the traits of advanced age, infec-
healing rates of clean surgical incisions. The rate of healing tion, and ischemia with reperfusion injury, as described above. In
is a direct reflection of the kinetics of collagen deposition addition, many problem wounds suffer from one or more unique
and remodeling within the wound. When the healing cascade traits that retard the healing process further, including radiation
progresses normally, approximately 30% to 50% of the final exposure and systemic comorbidities such as diabetes.
strength of the wound is achieved in 42 days. It is for this
reason that elective surgery patients are told to refrain from Wounds in Patients on Steroids.  Wounds in patients
strenuous activity or heavy lifting for at least 6 weeks. This receiving steroids are prone to infection and show decreased
progression represents the expected course of healing. In rates of angiogenesis, collagen deposition, and cellular prolifer-
patients with underlying comorbidities, including renal failure, ation. It is important to remember that steroids may exert their
ischemia, and steroid use, this curve is delayed and shifted to impairments to healing even longer after their use is discon-
the right (see Figure 3.2). In these particular patients, postoper- tinued. Maintenance of a clean wound with minimal bacterial
ative instructions should be adjusted to reflect the anticipated colonization should be the main goal of care for these patients.
delay in healing. Note that in healthy patients, no pharmaco- In addition, experimental models of steroid-impaired healing
logic agent has been demonstrated to shift the curve to the left; have shown vitamin A to be a useful adjunct. The typical dose
that is, healing rates are for the most part maximized in healthy of vitamin A in patients receiving steroids is 25,000 IU daily
people. However, it may be possible to modify the quality by mouth or 200,000 IU topically three times a day.
of healing, and research on scar modulation and manipula-
tion is currently an area of significant future promise. Below Wounds in Patients with Irradiated Skin (Chapter
we will discuss common complicated wounds encountered by 17).  Patients with irradiated wounds represent a chal-
the plastic surgeon. General management plans can be found lenging problem. The progressive endarteritis obliterans
in Figure 3.3. and microvascular damage, along with fibrotic interstitial
changes, result in a wound marked by ischemia and cellu-
The Problem Wound.  Problem wounds are important enti- lar senescence and prone to infection. In addition, aggres-
ties that are frequently seen by plastic surgeons. In an ideal world, sive surgical debridement of these wounds often results in
these wounds would be seen by a wound care specialist as soon larger non-healing wounds. Thus, any surgical debridement
as possible. Unfortunately, in practice it is difficult to identify the should be conservative. Antimicrobial dressings capable of
incipient problem wound. Furthermore, not all problem wounds maintaining moist wound healing while promoting autolysis
are actually chronic wounds. The development of biomarkers for are also useful, as is the use of growth factors and even HBO

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 3: Wound Care 27

Patient has possible problem wound

Principles, Techniques, and


Thorough history and

Basic Science
physical examination, and
appropriate diagnostic
adjuncts:
- Labs
- Vascular studies
- Imaging

Optimize systemic Debridement Control of bioburden Care of wound


parameters

- Smoking cessation - Remove slough, eschar, - Remove nonviable, - Choose appropriate


- Treat or minimize obesity, debris, and biofilm via colonized tissue dressings to ensure moist
edema, and medical surgical or autolytic/ - Establish presence and healing and control exudation
comorbidities enzymatic debridement type of infection with cultures (see Table 3.4)
- Educate patient regarding - Give topical antimicrobials - If wound healing is stalled
wound when warranted or slow, consider growth
factors or biologic dressings
- Initiate preventative - Give systemic antibiotics if
measures as appropriate there is surrounding cellulitis - Administer NPWT as
or worsening infection appropriate

Figure 3.3.  A general algorithm for approaching the patient with a problem wound. After a thorough history and physical examination,
appropriate adjunctive diagnostic studies are obtained. Although each wound will vary, the approach should focus on four general themes:
optimization of systemic parameters, debridement, control of wound bioburden, and creation of a moist healing environment through appropriate
dressings. NPWT, negative-pressure wound therapy.

therapy. In general, these wounds will often need a microvas- stage II), a moist, clean environment is ideal. Films or hydrogels
cular free flap to attain stable wound coverage. are often useful in this situation. In deeper, more exudative pres-
sure sores (stage II to stage IV), more absorptive dressings can
The Pressure Sore Wound (Chapter 98).  Pressure be used, including hydrocolloids, alginates, or foams. Likewise,
sores represent a common problem affecting nearly 20% of in dirty or contaminated wounds, antimicrobial dressings or
all hospitalized patients. Patients who are prone to develop Dakin’s solution can be used to help reduce bioburden.
pressure sores are often debilitated and elderly or suffer from A tremendous advance in the care of pressure sore patients
some neurologic injury. Although successful healing can occur has been the evolution of support surface therapies. These
in the motivated patient, recurrence is more often the rule. therapies are both pressure reducing (reduction of pressure at
The underlying etiology of these wounds is, by definition, the ulcer site to a level that is less than that exerted by a regular
pressure over a bony prominence. Although pressure relief is surface) and pressure relieving (relief of pressure to a level less
paramount in promoting healing, aggressive management of than the capillary closing pressure). These devices include air-
comorbidities is critical to establish an adequate healing envi- fluidized beds, air mattresses, air flotation and water flotation
ronment. Most patients with pressure sores are malnourished devices, and low air-loss beds. The variables they control, in
and cachectic, which makes them more susceptible to wound addition to pressure, include moisture retention, shear force,
healing deficits. As a result, they should be aggressively nour- and temperature. A major drawback is their expense, which
ished (to an ideal albumin level > 3) and receive vitamin can be significant.
supplementation. Consideration should also be given to the
administration of growth hormone or anabolic steroids, such Wounds in Patients with Diabetes (Chapter 95).  The
as oxandrolene, as this steroid counteracts the catabolic state foundation of care in the patient with diabetes is recogni-
of these patients. tion that most of the ulcers seen are physiologically similar
Thorough surgical debridement of nonviable tissue is to pressure sores that have occurred in the setting of neu-
important to alter the biology of the wound from its chronic ropathy. The neuropathic ulcer is a multietiologic lesion,
state, creating a more acute wound. Given that many of these with components of pressure necrosis, functional micro-
patients are debilitated or insensate, debridement at the bedside angiopathy, and true neuropathic derangements. The term
is possible. Once a thorough debridement has been performed, “functional microangiopathy” is preferred because, although
adjunctive wound care tools can be used to promote healing. diabetics do not have anatomic abnormalities in their arte-
Many of these patients may ultimately require flap reconstruc- rioles and capillaries, they nevertheless do have a dysfunc-
tion to obtain a closed wound. A frustrating aspect of the tional microvasculature, with impairments in vasodilatation
care to these patients is the high rate of recurrence despite the and compensatory angiogenesis in response to ischemia.
best efforts of the surgeon, which often is a reflection of the The treatment of the diabetic foot is tailored to address
patient’s social situation and support system. these varied components. Management considerations in
Muscle spasms in these patients should be controlled either these patients include selective debridement, tight glucose
medically or, in extreme cases, surgically. Dressings should be control, pressure off-loading (either through noncontact
used strategically. In more superficial pressure sores (stage I or orthotics or surgically through Achilles tendon lengthening),

(c) 2015 Wolters Kluwer. All Rights Reserved.


28 Part I: Principles, Techniques, and Basic Science

revascularization when there is a significant arterial lesion, use perforating system. All patients with venous stasis ulcers resis-
of growth factors such as Regranex, and, in certain circum- tant to compression therapy merit vascular studies to deter-
stances, tibial nerve decompression. Given the complexity of mine suitability for these interventions. The use of subfascial
the derangements found in the so-called diabetic foot, and the endoscopic perforator surgery is under intensive study in asso-
plethora of treatment options, these patients are best served ciation with more traditional vascular approaches such as vein
by dedicated multidisciplinary wound/limb salvage centers. stripping.

Venous Stasis Wounds.  Venous stasis wounds develop


in the extremities of patients with incompetent veins, which The Future of Wound Care
leads to a complex physiologic environment consisting of Significant research is underway in the biology and tissue-
venous hypertension and relative ischemia from reduced capil- engineering potential of autologous stem cells. In the future,
lary flow gradients. Compression therapy is essential for these it may be possible to augment the wound healing deficits
wounds. This is true for patients who have undergone vas- seen in problem wound patients with the use of topical stem
cular surgery as for those who have not. More sophisticated cells. In addition, scar modulation and manipulation therapies
and individualized compression garments have been devel- will likely become available to assist in minimizing the cutaneous
oped. One caveat to the use of compression therapy is that this stigmata of surgery.
modality is contraindicated in patients with an ABI < 0.7 and
should be used under close medical supervision in extremities
with an ABI between 0.7 and 0.9.
Conclusion
Rigid compression products include the Unna boot-paste Wound care is an important component of plastic surgery. As
dressings and low-stretch bandages. Elastic compression students of soft-tissue anatomy, tissue healing, and surgical
dressings are more applicable for non-ambulatory patients, as reconstruction, plastic surgeons are equipped with the tools
they have a higher resting pressure than rigid products. Types necessary to treat most wounds. Understanding the fundamen-
of compression products include stockings, elastic wraps, and tal aspects behind the chronic and problem wound, strategies
multilayer wraps. Use of combination dressings incorporating can be employed to alter the wound environment and tip the
an elastic component and an absorptive minimally stretching balance toward healing. Plastic surgeons can also judiciously
component has achieved widespread acceptance as superior intervene surgically to promptly close appropriate wounds. Basic
to the traditional Unna boot, which does not achieve optimal science research and translational findings continue to advance
pressure by itself. However, when combined with elastic com- our knowledge of wounds and assist in the development of
pression wraps, the Unna boot can be quite useful. novel treatment approaches. Unfortunately, many of the wound
Compression garments should be individualized to the care products in use today are market and industry driven, with
patient. Although ideally the pressures exerted should be little prospective, randomized comparative studies evaluating
between 30 and 40 mm Hg, there are situations where more or efficacy. In addition, the concept of wound care centers has been
less pressure can be used. The rationale for 30 to 40 mm Hg aggressively marketed. While this concept can benefit patients,
therapy is experimental evidence showing that venous stasis many centers are company organized and are biased in treat-
ulceration is greatly increased when the ambulatory venous ments delivered. In addition, these centers are often staffed by
pressure rises above 30 mm Hg. Care should be taken not to personnel with limited backgrounds in surgery and/or wound
exceed the pressure recommended for the clinical indication, healing. The ideal wound care center is multidisciplinary, with
as secondary ulcerations can develop. A key to the use of com- participation of committed plastic surgeons who work closely
pression therapy is patient compliance and commitment. As with other team members for the benefit of the patient.
treatment progresses, the extremity becomes less edematous
and thus limb girth decreases. Patients must recognize when Suggested Readings
garments are not fitting appropriately and return to the clinic 1. Falanga V, ed. Cutaneous Wound Healing. London: Martin Dunitz; 2001.
to be resized. Therapy should be continued for several weeks 2. Galiano RD. Lower extremity ulcers. In: Souba W, et al., eds. ACS Surgery:
following successful closure of the wound to permit remodeling Principles and Practice. Hamilton: Decker Publishing; 2008.
3. Hess CT, ed. Clinical Guide: Wound Care. Philadelphia, PA: Lippincott
and strengthening of the neomatrix, and maintenance hosiery Williams & Wilkins; 2005.
needs to be instituted, often for the lifetime of the patient. 4. Hunt TK, Hopf HW. Wound healing and wound infection. What surgeons
Dressings are frequent adjuncts to compression therapy. and anesthesiologists can do. Surg Clin North Am. 1997;77:587.
The choice of dressing is dictated by the amount of drainage 5. Mustoe T. Understanding chronic wounds: a unifying hypothesis on their
pathogenesis and implications for therapy. Am J Surg. 2004;187:655.
present. Because many compression products are worn for 6. Park H, Copeland C, Henry S, Barbul A. Complex wounds and their man-
days at a time, the dressing chosen must be capable of absorb- agement. Surg Clin North Am. 2010;90:1181.
ing high levels of exudates and transudate. When edema and 7. Ramasastry SS. Acute wounds. Clin Plast Surg. 2005;32:195.
bioburden are controlled, closure is often expedited by the use 8. Ramasastry SS. Chronic problem wounds. Clin Plast Surg. 1998;25:367.
9. Robson MC, Steed DL, Franz MG. Wound healing: biologic features and
of tissue-engineered skin substitutes. approaches to maximize healing trajectories. Curr Probl Surg. 2001;38:72.
The indication for vascular surgical intervention remains 10. Wu SC, Marston W, Armstrong DG. Wound care: the role of advanced
superficial venous insufficiency with insufficiency of the wound healing technologies. J Vasc Surg. 2010;52:59S.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 4  n  The Blood Supply of the Skin

Principles, Techniques, and


and Skin Flaps

Basic Science
Geoffrey Ian Taylor, Russell J. Corlett, and Mark W. Ashton

Knowledge of the anatomy of the cutaneous arteries and way between the lobules of the subcutaneous fat, ultimately
veins is fundamental to the design of skin flaps and incisions. reaching the subdermal plexus, where they again travel for
Although detailed studies of these vessels were performed by variable distances to supply the overlying skin, being longest
Manchot,1,2 Spalteholz,3 Pieri,4 Esser,5 and Salmon,6,7 they where the skin is mobile.26 During their subcutaneous course,
were published in either German, Italian, or French. In the the cutaneous arteries (and veins) often travel with the cutane-
English-speaking world, little attention was paid to the precise ous nerves, either as long channels or as a chain-linked system
anatomy of the cutaneous vessels so that surgeons designed of vessels.28,29
skin flaps randomly on whatever vessels happened to be in the The density, size, and direction of the cutaneous perfora-
area, assigning rigid length-to-breath ratios to the flaps. It was tors vary from region to region, being modified by growth,
not until the last four decades, with the introduction of the differentiation, and the functional demands of the body part,
microsurgical free skin flap,8,9 the revival of the musculocu- factors that provide the basis for the various anatomic con-
taneous flap,10 the description of the fasciocutaneous flap,11,12 cepts that follow. In general, the vessels of the head, neck,
and the use of tissue expansion13 and flap prefabrication,14 torso, and proximal limbs are larger and more widely spaced
that surgeons and anatomists have returned to the anatomic than their counterparts in the forearms, legs, hands, and feet
dissecting room to search and research the intricacies of the (see Figure 4.1). Although the size and length of the cuta-
vascular pathways to and from the skin. This has been and neous perforators may vary, they all interconnect to form
still is an exciting period of anatomic renaissance, especially a three-dimensional “body carpet” that has a particularly
with the emergence of “perforator flaps.”15-22 well-developed horizontal strata of vessels in the dermis, in
Although much original data have been provided, there has the subdermis, on the undersurface of the subcutaneous fat,
been a concurrent bewildering explosion of new terms and and on the outer surface of the deep fascia (Figure 4.2).
attempts to classify the cutaneous circulation, often based on The connections between adjacent cutaneous arteries are
flap design rather than vascular anatomy. It is worth stating, either by true anastomoses, without change in caliber, or by
however, that many of the “new” flaps, whether island, fascial, reduced-caliber choke anastomotic vessels (Figure 4.3). The
neurocutaneous, direct, indirect, axial, random, super, septal, latter are plentiful in the integument (skin and subcutaneous
arterial, musculocutaneous, perforator, or otherwise, are each tissues) and may be important in regulating the blood flow
simply the product of a surgical insult inflicted on the same to the intact skin (Figure 4.1C). These choke vessels play an
basic vascular pattern that exists throughout the body, though important role in skin flap survival, where, like resistors in
viewed through different eyes. Converse23 stated that “there is an electrical circuit, they provide an initial resistance to blood
no simple and all encompassing system which is suitable for flow between the base and the tip of the flap. When a skin flap
classifying skin flaps.” He went on to state that “it is now is delayed by the strategic division of cutaneous perforators
generally agreed that the anatomical vascular basis of the flap along its length, these choke vessels dilate to the dimensions
provides the most accurate approach for classification.” Time of true anastomoses (see later), thus enhancing the circulation
has supported the veracity of this statement, emphasized by the to the distal flap. Although some dilatation of the choke ves-
recent refocus of attention on the anatomy of the cutaneous sels occurs because of the relaxation of sympathetic tone, the
perforators as the basis for skin flap design.15,17,18,20-22,24-27 major effect is seen between 48 and 72 hours after surgery.30,31
This is due to an active process resulting in hypertrophy and
hyperplasia of the elements of the vessel wall and a permanent
Overview increase in diameter of its lumen.30
The skin is the largest organ of the body. Temperature regu- The cutaneous veins also form a three-dimensional plexus
lation to maintain homeostasis is one of its major roles. This of interconnecting channels with dominant strata in the sub-
important function is provided by a rich network of cutaneous dermis (Figures 4.4–4.7). Although many of these veins have
arteries and veins, especially in the dermal and subdermal plexi, valves that direct the blood in a particular direction, they are
which supply the sweat glands and allow for heat exchange by often connected by avalvular veins.32 These avalvular (oscillat-
convection, conduction, and radiation. Although the cutaneous ing) vessels allow bidirectional flow between adjacent venous
circulation is rich and vast, the metabolic demands of the skin territories whose valves may be oriented in opposite direc-
elements are low so that only a small fraction of the potential tions, thus providing for the equilibration of flow and pressure
cutaneous circulation is necessary for skin viability—a fact that (Figure 4.6). Indeed, there are many veins whose valves direct
is pertinent to the design and survival of various skin flaps. flow initially in a distal direction, away from the heart, before
The cutaneous arteries arise directly from the underly- joining veins whose flow is proximal. The superficial inferior
ing source (segmental or distributing) arteries or indirectly epigastric veins (SIEVs) that drain the lower abdominal integ-
from branches of those source arteries to the deep tissues, ument toward the groin are good examples. In some regions,
especially the muscles (Figures 4.1 and 4.2). From here the valved channels direct flow radially away from a plexus of
cutaneous arteries follow the connective tissue framework of avalvular veins as, for example, in the venous drainage from
the deep tissues, either between or within the muscles, and the vertex of the scalp or the nipple-areolar summit of the
course for a variable distance beneath the outer layer of the breast. In other areas, valved channels direct flow toward a
enveloping “body suit” of deep fascia. They then pierce that central focus, seen in the groin or in the stellate limbs of the
structure, usually at fixed skin sites as cutaneous perforators. cutaneous perforating veins (Figures 4.4 and 4.6).
After emerging from the deep fascia, the arteries course on its In general, the cutaneous veins partner the arteries.
superficial surface for a variable distance, supplying branches However, the venous drainage of the skin is established in
to it and the deep surface of the fat. They then worm their the embryo in two stages, which interconnect but which are

29
(c) 2015 Wolters Kluwer. All Rights Reserved.
Figure 4.1.  A. Montage of the cutaneous arteries of the body. The skin has been incised along the ulnar border in the upper extremities, and
the integument has been removed with the deep fascia on the left side and without it on the right. B. A closer view of the vessels of the head and
neck from the side. C. The angiosome territory of a single cutaneous perforator (perforator angiosome) defined by a perimeter of reduced-caliber
“choke” anastomotic vessel. Note (1) the direction, size, and density of the perforators, which are large on the torso and head and get progressively
smaller and more numerous toward the periphery of the limbs; (2) the reduced-caliber (choke) anastomotic arteries, which link the perforators
into a continuous network, with an area highlighted (arrow) and enlarged in (C). (Reproduced with permission from Taylor GI, Palmer JH. The
vascular territories (angiosomes) of the body: experimental study and clinical applications. Br J Plast Surg. 1987;40:113).

Figure 4.2.  A schematic diagram shows a single direct septocutaneous


perforator (B) and various indirect musculocutaneous perforators of
varying sizes that pierce the muscle (or other specialized deep tissues)
early (C) or late (A and D) to supply the overlying integument. In each
case, the perforator supplies all adjacent tissues between the source
artery and the skin.

Figure 4.4.  The venous network of the integument of a female


Figure 4.3.  Schematic representation of choke anastomoses (A) and subject. (Reproduced with permission from Taylor GI, Caddy CM,
true anastomoses (B) between adjacent arteries. (Reproduction with Watterson PA, Crock JG. The venous territories (venosomes) of the
permission from Taylor GI, Minabe T. The angiosomes of the mammals human body: experimental study and clinical implications. Plast
and other vertebrates. Plast Reconstr Surg. 1992;89:181). Reconstr Surg. 1990;86:185).

30
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 4: The Blood Supply of the Skin and Skin Flaps 31

Principles, Techniques, and


Basic Science
Figure 4.6.  Schematic diagrams of the basic venous module (A), its
modified arrangement in different areas (B), and how these modules
interconnect to form a continuous network (C). In the integument,
this network of venous perforators of the secondary venous system
Figure 4.5.  Diagram of developing arteries and veins in the forelimb is connected in the subdermal plexus with the longitudinal channels
of one of our quail embryos where approximately 1 day in the quail of the primary venous system (D). The valved segments in blue and
equates to 1 week in the human embryo. Note the primary venous sys- the avalvular oscillating veins in yellow are highlighted. (Reproduced
tem that develops first, drains the ectoderm (later the dermis) and with permission from Taylor GI, Caddy CM, Watterson PA,
the deep tissues along the surface of the embryo, whereas the sec- Crock JG. The venous territories (venosomes) of the human body:
ondary venous system develops centrally, connects with the primary experimental study and clinical implications. Plast Reconstr Surg.
system, and drains areas of the ectoderm (dermis) radially and then 1990;86:185).
axially along the limb in company with the arteries. (Reproduced
with permission from Taylor GI. The Angiosome Concept and Tissue
Transfer, Publisher Quality Medical Publications (QMP) Jul 2013).
(Figures 4.2 and 4.4–4.7). Thus, from the dermal and subder-
mal venous plexi, the veins collect into a horizontal “freeway”
of large-caliber veins, where they are often related to the cutane-
separated in time by approximately 1 week of development ous nerves and a longitudinal system of chain-linked arteries, or
(Figure 4.5).25,33-35 alternatively they collect in centripetal or stellate fashion into a
The primary system of veins develops first in the human common channel that passes vertically down in company with
embryo at about 5 weeks in the subectodermal region and the cutaneous arteries to pierce the deep fascia (Figures 4.6 and
is represented in the adult by large-caliber veins, such as the 4.7). Thereafter, these perforating veins remain in company with
cephalic, saphenous, and external jugular. These veins course the direct and indirect cutaneous arteries, draining ultimately
often at some distance from the cutaneous arteries, they into the venae comitantes of the source arteries in the deep tissue.
are accompanied frequently by cutaneous nerves, 28,33,34 and Importantly, these two systems interconnect, especially in
they travel for long distances before piercing the deep fascia the subdermal plexus. This explains why, for example, the
(Figures 4.4, 4.5, and 4.6). radial forearm free flap will survive on either the secondary
The secondary system of veins develops approximately system of venae comitantes of the radial artery or the primary
1 week later in the embryo. This network consists of central axial cephalic or basilic veins.
source veins that accompany the axial source arteries and receive Thus, the skin is fed and drained by a continuous network
perforating veins from the subectodermal region that accompany of arteries and of veins formed by vessels whose size, shape,
the developing cutaneous arteries (Figure 4.5D). In the adult, density, and direction vary from region to region in the body.
they are represented by the venae comitantes of the cutaneous The following observations provide for a better understanding
perforating arteries with which they travel in close proximity of this variation in vessel anatomy.

(c) 2015 Wolters Kluwer. All Rights Reserved.


32 Part I: Principles, Techniques, and Basic Science

Figure 4.7.  Composite diagram of the integument and underlying muscle (shaded) illustrating the primary superficial (S) and secondary deep
(D) venous systems with their interconnections in the superficial and the deep tissues. A large vena communicans (C) connects these systems, and
the alternative pathways of four venae comitantes of the perforating arteries are shown. Note the bidirectional system of veins (yellow) within the
superficial fascia and the muscle (small arrows) and the diverging direction of flow of the muscular veins as determined by the orientation of their
valves. (Reproduced with permission from Taylor GI, Caddy CM, Watterson PA, Crock JG. The venous territories (venosomes) of the human body:
experimental study and clinical implications. Plast Reconstr Surg. 1990;86:185).

and venosomes (venous territories). Initially we described 40


Anatomic Concepts angiosomes, but this was an intentional oversimplification as
many of these territories can and have been subdivided fur-
The Angiosome Concept ther into smaller composite units, for example, the intercostal
A review of the works of Manchot1,2 and Salmon6,7 combined and lumbar angiosomes, and we took this concept down to
with our own studies of the blood supply to the skin and the final branches in the vascular tree, which in the skin is
the underlying deep tissues enabled us to segregate the body the cutaneous perforator (Figure 4.1C).26,29 In the same way,
­anatomically into three-dimensional vascular territories that we subdivided the deep tissues, for example, the muscles, into
we named “angiosomes.”26 These three-dimensional anatomic their component anatomical territories.
territories are supplied by a source (segmental or distributing) These composite blocks of skin, bone, muscle, and other
artery and its accompanying vein(s) that span between the soft tissue fit together like the pieces of an intricate jigsaw
skin and the bone (Figures 4.8–4.11). Each angiosome v can ­puzzle. In some angiosomes, there is a large, overlying cutane-
be subdivided into matching arteriosomes (arterial territories) ous “crust” and a relatively small deep tissue region; in others

Figure 4.8.  The sites of emergence of an average of 376 direct and indirect cutaneous arterial perforators of 0.5 mm or greater averaged from all studies.
Note their concentration near the dorsal and ventral midlines, around the base of the skull, and over or near the intermuscular septa. Direct perforators are
more common in the limbs, whereas indirect perforators predominate in the torso. The vessels were color coded to match their underlying source arteries
and to correlate with the angiosomes of the body. Compare with Figure 4.10.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 4: The Blood Supply of the Skin and Skin Flaps 33
tissue in the adjacent angiosome can usually be captured with

Principles, Techniques, and


safety when combined in the flap design.22,30,31,37,38
In the skin, the anatomical territory of each cutaneous
perforator forms a basic angiosome module, defined by a
perimeter of anastomotic vessels that connects it with its neigh-

Basic Science
bor in all directions (Figures 4.1C and 4.11), and we charted an
average of 376 such vessels of 0.5 mm or greater.26 In the skin
and subcutaneous tissues, these connections were usually, but
not always, by reduced-caliber vessels that we named “choke”
because of their narrowed lumen. Alternatively, these con-
nections were “true” anastomoses without change in caliber,
especially where vessels accompanied cutaneous nerves, but
seen more commonly in other tissues, especially the muscles
and the nerve trunks, or after a flap has been delayed.30,31,37,38
These basic skin modules (cutaneous perforator angiosomes)
link together like a patchwork quilt to form a continuous net-
work of vessels that surfaces the entire body (Figure 4.11). In
our original article where we charted 376 of these skin mod-
ules supplied anatomically by 40 bilateral (total 80) source
arteries, there was an average of 4.7 cutaneous angiosomes
per source artery.26 However, the size and number of these
skin modules vary within and between source arteries. In
some angiosomes, the cutaneous portion of the source artery
was represented by multiple skin perforators (defined as ves-
sels that pierce and emerge from the outer layer of the deep
fascia), for example, the perforators of the internal thoracic
and the deep inferior epigastric artery, whereas in other source
artery angiosomes just one, usually large, cutaneous vessel was
represented, for example, the superficial inferior epigastric
artery (SIEA), superficial circumflex iliac artery (SCIA), and
the lateral thoracic perforator (Figure 4.12). It should be
noted that in each case the cutaneous perforator supplied not
only the skin but also a block of tissue between the outer layer
of the deep fascia and the epidermis. In the chest, it includes
the breast tissue and in the neck the platysma muscle, for
example, as well as the subcutaneous fat.
This brings us to the next point—the clinical territory of
a cutaneous perforator. In a number of experiments, and in a
range of animals that included the pig,39 dog,37 guinea pig,31
and rabbit,30 as well as observations in patients undergo-
ing various surgical procedures,19,38,40 especially those that
Figure 4.9.  Schematic diagram of the cutaneous perforators (left) involved flap delay, we have observed and concluded on many
and their interconnections. The underlying source arteries, their inter-
occasions that one adjacent anatomical cutaneous perforator
connections, and the sites of origin of the cutaneous vessels (dots)
are shown on the right of the diagram. Only the major perforators territory (skin module) can be captured with safety radially
are illustrated. The vascular territories of the source arteries have in any direction on the perforator at the flap base. We have
then been defined in the integument (left) and in the deep tissues noted that necrosis, when it occurs, does so usually in the
(right) by lines drawn around their perimeter, across the choke, choke zone between this captured territory and the one
or true connecting arteries and arterioles. Note how the territories beyond, but sometimes an additional territory in the series will
correspond in each layer. When taken together they constitute the survive (Figure 4.13).
angiosomes. The safe length of such a flap depends, therefore, on the
size, direction, and span of the anatomical territory of each
perforator—the perforator on which the flap is based and the
next in the series. This is, therefore, the reliable clinical ter-
the reverse pattern exists. In some regions, the territory does ritory of the cutaneous perforator at the flap base where the
not reach the skin and is confined to the deep tissues as seen, anastomotic connections are by usually reduced-caliber choke
for example, in more recent studies of the head and neck.36 arteries (Figures 4.13–4.15). However, if the connections are by
Each angiosome is linked to its neighbor, in each tissue, by “true” anastomoses without change in caliber, then the survival
a fringe of either true (simple) anastomotic arteries without length of the flap will be longer with function similar to a flap
change in caliber or by reduced-caliber choke (retiform) anas- that has been delayed,38,40 seen especially in the skin where
tomotic vessels (Figure 4.1C). On the venous side, avalvular vessels accompany the cutaneous nerves.28
(bidirectional or oscillating) veins often match the anasto- (2) Because the junctional zone between adjacent angio-
motic arteries and define the boundaries of the angiosome, somes in deep tissues occurs usually within the muscles, rather
especially in the deep tissues. than between them, these muscles provide a vital anastomotic
detour if a main source artery or vein is obstructed.
Clinical Applications.  The angiosome concept has many (3) Similarly, because most muscles span two or more
implications. For example: angiosomes and are supplied from each territory, one is able to
(1) Each angiosome defines the safe anatomic boundary of capture the skin island from one angiosome via the muscle
tissue in each layer that can be transferred separately or com- supply in the adjacent territory.
bined together on the underlying source artery and vein as a This anatomic fact provides the basis for the design of many
composite flap. Furthermore, the anatomic territory of each musculocutaneous flaps.

(c) 2015 Wolters Kluwer. All Rights Reserved.


34 Part I: Principles, Techniques, and Basic Science

6
4 39
7
9 3 38
9 8
10 2 16
11 1
11 12 15
13
14 12 14
15 37 11 13
16 17 36
35
18
34
19 33

20 32
31
21
28
40
21 22
22 27
23 23 22A

24
30
26

25

29

Figure 4.10. The three-dimensional vascular territories—angiosomes—encompassing all tissues between skin and bone from (1) thyroid, (2) facial,
(3) buccal (internal maxillary), (4) ophthalmic, (5) superficial temporal, (6) occipital, (7) deep cervical, (8) transverse cervical, (9) acromiothoracic,
(10) suprascapular, (11) posterior circumflex humeral, (12) circumflex scapular, (13) profunda brachii, (14) brachial, (15) ulnar, (16) radial,
(17) posterior intercostals, (18) lumbar, (19) superior gluteal, (20) inferior gluteal, (21) profunda femoris, (22) popliteal, (22A) descending geniculate
(saphenous), (23) sural, (24) peroneal, (25) lateral plantar, (26) anterior tibial, (27) lateral femoral circumflex, (28) adductor (profunda), (29) medial
plantar, (30) posterior tibial, (31) superficial femoral, (32) common femoral, (33) deep circumflex iliac, (34) deep inferior epigastric, (35) internal tho-
racic, (36) lateral thoracic, (37) thoraco-dorsal, (38) posterior interosseous, (39) anterior interosseous and (40) internal pudendal source territories.

The deep fascia is also a honeycomb of connective tissue


Vessels Follow the Connective Tissue that is usually more rigid that its superficial counterpart. It has
Framework of the Body a tough outer layer that surrounds and sometimes provides
The fact that vessels follow the connective tissue framework is origin to the muscles as a sheath on the torso and a stocking
fundamental to the design of all flaps, especially the “fasciocu-
taneous” and “septocutaneous” perforator flaps.
Developmentally, the vascular system appears in the meso-
derm of the embryo as a continuous network of vessels. The
specialized tissues develop within the interstices of that vascu-
lar network. As growth and differentiation progress, vessels
become encased within the various tissues and are continuous
with vessels coursing between the tissues by way of vascular
pedicles at various sites. These sites, in turn, are determined
by the relative mobility of those tissues. The connective tissue
can be regarded as what is “left over” after the specialized
tissues have developed.41 Like a honeycomb, the connective
tissues house and support the specialized tissues and in so
doing support the vascular system of the body, with which
they have developed an intimate relationship.
It is important to differentiate between the superficial and
the deep fascia as these terms are often confused (Figure 4.16).
The superficial fascia is a loose connective tissue honeycomb
that connects the dermis to the outer layer of the deep fascia.
It houses the subcutaneous fat, the breast, and remnants of
the panniculus carnosus where it still exists (for example, the Figure 4.11.  Schematic representation of the cutaneous perforator
muscles of facial expression in the head, the platysma in the angiosomes showing the basic skin module (left) and several modules of
neck, the palmaris brevis in the hand, and the dartos muscle in different sizes combined to represent the cutaneous territory of a source
the scrotum). In the lower abdomen, it is separated into two artery (right).
layers by the fascia of Scarpa.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 4: The Blood Supply of the Skin and Skin Flaps 35
Transverse cervical artery

Principles, Techniques, and


Thoracoacromial
axis

Basic Science
Internal thoracic
artery
Lateral thoracic artery

Thoracodorsal artery
Superior
epigastric
artery

Posterior and lateral intercostal


perforators
Deep inferior
epigastric artery

Superficial inferior epigastric artery

Deep circumflex
iliac artery
Superficial circumflex iliac artery

Superficial external
pudendal artery

Deep external pudendal artery Perineal branches of internal pudendal artery


Figure 4.12.  The angiosome territories of the anterior chest and abdominal regions of the torso—each territory mapped to match the under-
lying source arteries with lines drawn through the perimeter of usually choke anastomotic arteries. Note that the SIEA and the lateral thoracic
angiosomes are supplied by a single large cutaneous perforator compared, for example, with the internal thoracic, lateral intercostal, and DIEA
angiosomes that have multiple cutaneous perforators, each of which could be subdivided further into individual cutaneous (angiosome) territo-
ries. This has been done on one side of the internal thoracic–superior epigastric territory to illustrate this point. SIEA, superficial inferior epigas-
tric artery; DIEA, deep inferior epigastric artery.

in the limbs. Often referred to as the deep fascia, this is only superficial fascia to reach another connective tissue structure,
the outer layer. Radiating intermuscular septa of the deep the dermis of the skin.
fascia, dense in some areas and looser in other, anchor the In some regions, the connective tissue is loose areolar, in
outer layer to the skeleton where the deep fascia becomes con- which case the vessels travel within the connective tissue to
tinuous with the periosteum. From these septa and from the allow the arteries to pulsate and the veins to dilate, for example,
periosteum, the deep fascia is continued into the muscles as within the carotid sheath. In other regions, the connective
intramuscular septa. tissue forms dense fibrous sheets, such as the outer layer of
In the adult, the major arteries are closely related to the the deep fascia, some intermuscular septa, and the periosteum
bones of the axial skeleton. Their branches follow the inter- of the bone. In these cases, the vessels course beside or on the
muscular connective tissues, where they divide to supply the dense fasciae, not within them.
muscles, bones, tendons, nerves, and deep fat deposits, in each
instance following the connective tissue framework of that Clinical Applications.  This vessel relationship to the dif-
structure down to the cellular level. ferent types of connective tissue achieves special significance
The cutaneous perforators exhibit the same pattern. They when the surgeon raises a cutaneous flap that includes the
usually arise from the source artery or from one of its muscle outer layer of the deep fascia (termed fasciocutaneous flap) or
branches, either before or after entering the muscle, and follow when the design is extended to include the intermuscular or
the intermuscular or intramuscular connective tissues of the intramuscular septa (the septocutaneous flaps).
deep fascia as direct or indirect cutaneous perforating vessels, In the former case, the deep fascia should be included in
respectively, as they pierce the outer layer of the deep fascia the design of the fasciocutaneous flap in those sites where the
(Figures 4.2, 4.16, and 4.17). Some cutaneous perforators, skin is relatively fixed to the deep fascia, for example, in the
however, are derived from branches to other deep structures, limbs or the scalp (Figures 4.16 and 4.17B). In these instances,
such as the nerves, the periosteum of bones, the joints, and the dominant cutaneous vessels course on, or lie adjacent to,
some glands. After emerging from the deep fascia, the cuta- the deep fascia. Although they can be dissected free in some
neous vessels follow the connective tissue framework of the cases, it is safer or more expedient to include the deep fascia

(c) 2015 Wolters Kluwer. All Rights Reserved.


36 Part I: Principles, Techniques, and Basic Science

Figure 4.13.  Skin from the torso of the dog that was removed by midline dorsal incision after the raising of a large island flap on one side (outlined)
1 week previously on a single arteriovenous pedicle (arrow). Comparable vessels are identified with dots and arrows on each side of the ventral
midline. Note the anatomical territory of this perforator (shaded yellow) and that (1) the choke vessels have enlarged to the size of true anasto-
moses within the flap, (2) the scalloped necrosis border is evident inside the flap margins (dotted), and (3) at least one adjacent vascular territory
has been captured radially on the artery in the flap pedicle to define the clinical territory of this perforator. (Reproduced with permission from
Callegari PR, Taylor GI, Caddy CM, Minabe T. An anatomical review of the delay phenomenon: 1. Experimental studies. Plast Reconstr Surg.
1992;89:397).

with the flap. However, where the skin and subcutaneous tis- than a true anatomic structure. This may occur, for exam-
sues are mobile over the deep fascia, for example, in the iliac ple, when the cutaneous perforators of a radial or an ulnar
fossa or the breast, it is unnecessary to include this fascial flap are dissected within an envelope of loose areolar tissue
layer as the major cutaneous vessels have already left its sur- between the flexor tendons. Furthermore, the septocutane-
face (Figure 4.17A). ous flap may provide traps for the unwary surgeon. In some
The term septocutaneous is sometimes misleading, espe- cases, the cutaneous artery and its accompanying vein leave
cially when used to describe a surgically created entity rather the underlying source vessels and course toward the surface
in a surgically favorable position, adjacent to a true white
fibrous intermuscular septum. This is typical of the blood
supply to the skin of the lateral arm flap, where cutaneous
perforators arise from descending branches of the profunda
brachii vessels and follow the lateral intermuscular septum
toward the skin. This pattern of supply usually exists where
the muscles glide on either side of the intermuscular septum.
However, if the muscles attach to either side of the intermus-
cular septum, then the course of the cutaneous perforator
may be quite variable.

a b c
A

a b c
B

Figure 4.15. Diagrammatic representation of the same flap raised


Figure 4.14.  Schematic representation of the safe clinical territory with and without a surgical delay to illustrate the necrosis line and the
of a cutaneous perforator (arrow) where anatomical territories of changes in the choke vessels—in the choke-vessel interface with vessel
adjacent perforators are captured radially. Note beyond the captured “b” or the one beyond. In B, vessel “a” has been delayed by a previous
perforators the irregular circumference of the necrosis line. (Compare operation before raising the flap. Note the effect on the choke vessels
with Figure 4.17). and the site of the necrosis line.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 4: The Blood Supply of the Skin and Skin Flaps 37

Principles, Techniques, and


Basic Science
A

Superficial
fascia

Deep
B fascia C

Femoral artery
Femoral artery

Lateral
Profunda circumflex
D artery artery E

Figure 4.16. Cross-sectional studies to illustrate the origin and the course of the cutaneous perforators from their source arteries in the deep tis-
sues. A. Oblique section of the anterior abdominal wall showing the supply to the integument and the underlying muscle, derived laterally
from a posterior intercostal artery (i) and medially from vessels arising in the groin. The latter vessels are the superficial inferior epigastric
artery (e) and the ascending branch of the deep circumflex iliac artery (D). Note the choke vessels that connect these angiosomes and that they
correspond in position in the superficial and the deep layers. B–E. Schematic diagrams and radiographic study at mid-thigh level of (B). The connective
tissue network of the superficial and deep fascia (C). The same as (B) but the vessels have been added that follow this connective tissue framework,
(D) the angiosomes supplied by each of the source vessels and (E) the lead oxide cadaver injection study that corresponds with (C). Note the
large direct cutaneous perforators that follow the intermuscular septa (s) and the large and small indirect musculocutaneous perforators (m).
(Reproduced with permission from Taylor GI, Palmer JH. The vascular territories (angiosomes) of the body: experimental study and clinical
applications. Br J Plast Surg. 1987;40:113).

This variability of anatomy is evident, for example, in Vessels Radiate from Fixed to Mobile Areas
the lateral aspect of the upper calf. If a compound skin and Vessels cross tissue planes at or near their fixed margins and
bone flap is designed over the lateral intermuscular sep- radiate to mobile areas. This concept is well illustrated in
tum, based on the cutaneous perforators of the peroneal the blood supply to the skin since vessels emerge from the
vessels, these skin vessels may course directly to the sur- deep fascia where the skin is fixed or tethered. From here, they
face, traveling in a favorable position, adjacent to the sep- travel for variable distances depending on the mobility of the
tum. Alternatively, they may arise indirectly from branches skin. The more mobile the integument, the longer the vessels.
to the soleus muscle as terminal twigs of muscle branches These fixed skin sites are seen in a well-muscled ­individual
that have arisen from the peroneal vessels at considerable at skin crease lines, over intermuscular septa, or near the
distance from the lateral intermuscular septum. In these fixed attachments of muscles to bone (see Figures 4.8, 4.9,
instances, a painful and laborious intramuscular dissection and 4.17).
of the cutaneous supply awaits the unfortunate surgeon.
These two pathways provide the basis for classifying the Clinical Applications.  It follows that long robust flaps
various “perforator flaps.” should be based where the skin is fixed, with their axes oriented

(c) 2015 Wolters Kluwer. All Rights Reserved.


38 Part I: Principles, Techniques, and Basic Science

Figure 4.17.  Sectional strip radiographic studies from above down, of the breast (A), thigh (B), sole of the foot (C), and buttock (D). D includes
the underlying gluteus maximus muscle. The schematic diagram illustrates the dominant horizontal axis of the vessels, which provides the
primary supply to the skin in each case and its relationship to the deep fascia (arrow). In type A, they predominate in the subdermal plexus.
Note from left to right the internal thoracic perforator and lateral thoracic artery converging on the nipple (arrow) in the radiograph of the loose
skin region of the torso. In type B, they are seen coursing on the surface of the deep fascia in this relatively fixed skin area. In type C, the source
artery itself is the dominant horizontal vessel supplying the skin, coursing beneath the deep fascia in this rigidly fixed skin region. In type D,
the horizontal vessel is again the source artery (inferior gluteal), but this time its branches have to pierce muscle indirectly to reach this fixed skin
region. Small arrows define the deep fascia, and the large arrow indicates the large fasciocutaneous branch of the gluteal artery, which descends
with the posterior cutaneous nerve of the thigh. (Reproduced with permission from Taylor GI, Palmer JH. The vascular territories (angiosomes)
of the body: experimental study and clinical applications. Br J Plast Surg. 1987;40:113).

along the lines of maximal skin mobility. The further the distance Whether the nerves pierce the deep fascia together with the
between fixed points, the longer the safe dimensions of the flap. vessels, emerge separately and cross the vessels at an angle, or
There are many instances in which this applies in practice. For approach the vessels from opposite directions, in each case, as
example, long flaps can be based at the groin, the paraumbilical if drawn by a magnet, the main trunk of the vessel or some of its
region of the abdomen, or the parasternal region of the chest branches “peel off” to course parallel to the nerve. These vessels
(Figures 4.12 and 4.18). Additional precision to flap design can either course in close proximity to the nerve or they travel
be obtained before surgery by the use of Doppler ultrasonic probe nearby (Figure 4.18).
to locate these perforators19 in thin individuals as they emerge
from the deep fascia or more recently with CT angiography.42 In Clinical Applications.  This neurovascular relationship
this way, a viable flap can be designed by basing it on a signifi- presents the basis for designing long flaps with the added
cant perforator that is located with the probe, by finding the next potential for sensation at the repair site. Many of the current
dominant perforator along the desired flap axis and then simply “axial” or “fasciocutaneous” flaps are in fact neurovascular
joining these two points, since we have found experimentally that flaps. The original long and short saphenous flaps in the calf
one adjacent vascular territory can be captured with safety described by Ponten12 are cases in point.
(Figure 4.13).22,30,31,37,38
Vessel Size and Orientation Are a Product
Vessels Hitchhike with Nerves of Tissue Growth and Differentiation
Our research has confirmed that the intimate relationship More than two centuries ago, John Hunter43 suggested that
between nerves and blood vessels that is known to exist in at some stage of fetal development, and certainly at birth, an
the deep tissues and in some areas of the integument is in fact individual has a fixed number of arteries in the body, the size,
present in all regions of the skin and subcutaneous tissues length, and direction of which are modified by subsequent
of the body.28 The cutaneous nerves are accompanied by a growth and differentiation of the parts. This helps explain
longitudinal system of arteries and veins that are often the why long vessels radiate from the skull base toward its vertex
dominant blood supply to the region. The veins in company as the brain and skull expand, why long vessels course on the
with the nerves are frequently large “primary” venous free- torso as the lungs expand and the fetus extends from the flexed
ways, such as the cephalic, basilic, long saphenous, and short position, and why long vessels converge on the nipple from the
saphenous systems. The arteries are either long vessels—for periphery as the breast develops in the female (Figure 4.19).
example, the supraorbital, lateral intercostal, or saphenous
arteries—or they exist as a chain-linked system of cutaneous Clinical Applications.  This information provides the basis
perforators, often joined in series by true anastomoses without for the logical planning of the various breast reduction opera-
change in caliber (Figure 4.18). tions. Each technique revolves around the design of a flap of skin

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 4: The Blood Supply of the Skin and Skin Flaps 39

Principles, Techniques, and


Basic Science
B

A
Figure 4.18. Arterial injection studies of the (A) right upper limb and (B) torso. Note the chain-linked systems of arteries (arrows) that course
with the cutaneous nerves in the upper limb. On the torso, the nerves are marked green on the arterial study. They either course with the cutaneous
arteries, cross them at angles, and collect arterial branches or approach the arteries from opposite directions (arrows). (Reproduced with permis-
sion from Taylor GI, Gianoutsos MP, Morris SF. The neurovascular territories of the skin and muscles: anatomic study and clinical implications.
Plast Reconstr Surg. 1994;94:1).

and subcutaneous tissue (including breast) that is based on one territories of adjacent arteries bear an inverse relationship
or more vessels as they pierce the deep fascia around the perim- to each other yet combine to supply the same region.” If one
eter of the pectoralis major muscle. Tissue expansion is another vessel is small, its partner is large to compensate and vice
example. Here existing vessels in the skin and subcutaneous tis- versa. This is well illustrated in the variability in size between
sues, like the vessels in the abdominal wall during pregnancy, each of the parasternal perforators of the internal mammary
hypertrophy and elongate as the fluid is introduced into the artery and between the internal mammary perforators and
expander. Therefore, if possible, the expander should be placed the cutaneous perforator of the adjacent angiosome: the
beneath mobile skin and between fixed skin sites to take maxi- thoracoacromial (see Figure 4.1). It is likely that the same
mal advantage of the inherent vascular anatomy of the region. relationship occurs between the cutaneous veins, for exam-
ple, between the venous perforators of the deep inferior epi-
gastric venae comitantes (DIEV) and the usually large SIEV.
Vessels Obey “The Law of Equilibrium” This may be critical in the design of a deep inferior epigastric
This concept was described by Debreuil-Chambardel and is perforator flap where the DIEV perforating vein is unexpect-
referred to constantly by Michel Salmon6,7 in his description of edly small. Hence the reason for preserving the SIEV, espe-
the cutaneous arteries. Basically, this states that “the anatomical cially on the contralateral side, as a potential “lifeboat.”

(c) 2015 Wolters Kluwer. All Rights Reserved.


40 Part I: Principles, Techniques, and Basic Science

vessel, or from one of its branches.28 Whichever is the case,


A their destination is constant to supply the integument of the
lower abdomen and the hip (see Figures 4.1 and 4.12).
X Y
Clinical Application.  Although this variability in vessel
origin may not be important when designing a pedicled flap at
the groin, it certainly becomes so if the flap is to be isolated on
its feeding vessels for microvascular transfer.8,9,44

B The Vessels Form a Continuous


Unbroken Network
X Y
This fact has been referred to already but is highlighted
because it is fundamental to the understanding of the vari-
ous skin flap designs where, for example, the same area of
skin and subcutaneous tissue can be raised as a “cutaneous”
C flap, a “fasciocutaneous” flap, a “septocutaneous” flap, a
“musculocutaneous” flap, or a “perforator flap.” In each
X Y case, regardless of the flap design, the vessels that enter the
flap at its base connect into the same vascular network. What
may vary between flap designs, however, are the size and site
of entry of the cutaneous perforators, thus influencing flap
D ­survival (see Figure 4.2).

X Y Clinical Applications. There are numerous instances


whereby the surgeon knowingly or unwittingly takes advantage
of this anatomic fact. For example, the skin and subcutaneous
E fat over the pectoralis major muscle can be designed (1) as a
musculocutaneous flap on small perforators emerging from the
X Y underlying muscle, (2) as a fasciocutaneous flap based either
medially on the large internal thoracic (internal mammary) per-
Figure 4.19.  Schematic diagram to illustrate John Hunter’s hypothesis forators or laterally on the dominant perforator(s) of the thora-
of a fixed number of cutaneous arteries in the fetus and how growth coacromial axis, or (3) as a neurovascular fasciocutaneous flap
and differentiation of the tissues could modify the definitive size and when based superiorly on the supraclavicular neurovascular
relationship of the arteries x and y in different regions of the body pedicles that flow down over the clavicle from the neck.
after they pierce the deep fascia. A. The “resting state.” B. The vessels
are stretched by expansion of structures beneath the deep fascia, for
Other important considerations are the anastomotic vas-
example, the skull and brain. C. The vessels are stretched and com- cular “keystones” usually formed by reduced-caliber choke
pressed toward the dermis by the developing breast above the deep arteries that link adjacent perforating cutaneous perforators
fascia. D. The vessels are stretched apart by the developing long bones to form the arterial network. When a flap is elevated, these
but still retain a dominant relationship to the deep fascia. E. Growth choke vessels, which initially impede flow from one arterial
again stretches the vessels apart, but this time a gliding plane develops territory to the next along the flap, enlarge to the caliber
between the deep fascia and the subcutaneous fat in this loose skin of the cutaneous arteries they connect (Figure 4.13).30,31,37,38
area, for example, the iliac fossa. However, this process of vessel enlargement is an active
event and takes time. It involves multiplication and elon-
gation of the cells in each layer of the vessel wall, with its
Clinical Applications.  The deltopectoral flap of Bakamjian maximal effect occurring between 48 and 72 hours after
is an excellent example. It is based medially over the second to operation.30
fourth intercostal spaces so as to embrace the variable size of Experimentally and clinically, it has been noted that one
the internal thoracic (internal mammary) perforators. Designed adjacent anatomic vascular territory can be safely captured
below and parallel to the clavicle, it is usually dissected in a in any direction on the cutaneous artery at the flap base that
medial direction from its tip at the shoulder. If small perfora- defines its reliable clinical territory (Figures 4.13–4.15).30,31,37
tors are noted over the deltoid muscle, and in particular from If necrosis occurs, it usually does so at the level of the next
the deltopectoral groove, the dissection is continued to the choke anastomosis in the arterial network or the one beyond.
flap base on the assumption that the internal thoracic perfora- Surgically, flap survival can be extended by the strategic division
tors will be large. If, however, a large cutaneous perforator is of vascular pedicles at various time intervals along the length of
seen emerging from the deltopectoral groove, then this pedicle the proposed flap—the “flap delay” procedure (Figure 4.15).
is usually ligated and further dissection of the flap is delayed
for 1 week because of the possibility that the adjacent inter-
nal thoracic perforators will be small. This delay procedure is
employed because of the risk of flap necrosis, especially if the
Classification of the
flap tip spans beyond the point of the shoulder. Cutaneous Blood Supply
We have left the contentious subject of classification of the
Vessels Have a Relatively Constant cutaneous blood supply until the end, as we believe it is more
Destination but May Have important to understand the pure and the applied (functional)
anatomy of the cutaneous arteries than to be concerned about
a Variable Origin which classification is the best. It is essential, however, to
This is typical of the vessels that emanate from the groin to differentiate between classifications based correctly on the
supply the skin of the lower abdomen and upper thigh. The anatomy and physiology of the cutaneous supply rather than
SIEA and the SCIAs, for example, may arise separately from those that focus on flap design, such as axial, random, cutane-
the common femoral artery, as a combined trunk from that ous, fasciocutaneous, septocutaneous, and musculocutaneous,

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 4: The Blood Supply of the Skin and Skin Flaps 41
each of which describes the method by which the flap is
Conclusions

Principles, Techniques, and


planned and dissected.
One of the oldest, simplest, and best classifications was Knowledge of the basic anatomy of the cutaneous vessels
offered by Spalteholz3 in 1893. He subdivided the cutane- coupled with an appreciation of the factors that influence
ous vessels into two groups, depending on whether they its structure in different regions of the body provides for the

Basic Science
were the main (dominant) supply to the area or whether they logical planning of flaps and incisions. In the sage words
had a relatively minor (supplementary) role (see Figure 4.2). of Michel Salmon, “Entre l’anatomie et la physiologie, il y
Recently this classification has been modified, stimulated by a place pour une anatomie de fonction, pour une anatomie
the resurgence of interest on the anatomically based “perfo- physologique”—“Between anatomy and physiology there is
rator flaps.”22,24,27,42 room for a functional anatomy, for a physiologic anatomy.”

Direct Cutaneous Perforator Vessels


References
These vessels contribute to the primary (dominant) cutaneous
supply to the area and are particularly well developed in the 1. Manchot C. Die Hautarterien des Menschlichen Korpers. Leipzig: F.C.W.
Vogel; 1889.
limbs. They arise from the underlying source artery or from 2. Manchot C. The Cutaneous Arteries of the Human Body. New York, NY:
one of its muscle branches before they enter the muscle. They Springer-Verlag; 1983.
pass between the muscles and other deep structures in the 3. Spalteholz W. Die Vertheilung der Blutgefasse in der Haut. Arch Anat; 1893.
intermuscular septa and rapidly reach and perforate the outer 4. Pieri G. La Circolazione Cutanea Degli Arti e del Tronco in Rapporto
alla Tecnica della Chirurgia e Plastica Cinematica. Chir Organi Mov.
layer of the deep fascia where their main destination is the 1918;2:37.
skin (Figures 4.2, 4.7, and 4.16). They are usually large and 5. Esser JFS. Artery Flaps. Antwerp: De Vos-van Kleef; 1929.
spaced well apart in the torso, head, neck, arms, and thighs, 6. Salmon M. Arteres de la Peau. Paris: Masson; 1936.
especially where the skin is mobile. They are smaller and more 7. Salmon M. Arteries of the Skin. In: Taylor GI, Tempest M, eds. London:
Churchill-Livingstone; 1988.
numerous in the forearms and legs except where they accom- 8. Daniel RK, Taylor GI. Distant transfer of an island flap by microvascular
pany cutaneous nerves. In the palms of the hands and the soles anastomoses. Plast Reconstr Surg. 1973;52:111.
of the feet, they are evident as a dense network of small vessels 9. Taylor GI, Daniel RK. The free flap: composite tissue transfer by vascular
(Figures 4.1 and 4.18). anastomosis. Aust N Z J Surg. 1973;43:1.
10. McCraw JB, Dibbell DG, Carraway JH. Clinical definition of independent
In each case, these direct cutaneous vessels follow the myocutaneous vascular territories. Plast Reconstr Surg. 1977;60:341.
connective tissue framework of the deep tissue to the skin. 11. Cormack GC, Lamberty BGH. The Arterial Anatomy of Skin Flaps.
They pass between the muscles and tendons supplying Edinburgh: Church-Livingstone; 1986.
branches to them as they pass, sometimes closely related 12. Ponten B. The fasciocutaneous flap: its use in soft tissue defects of the lower
leg. Br J Plast Surg. 1982;34:215.
to true intermuscular septa, as “septocutaneous vessels.” 13. Radovan C. Breast reconstruction after mastectomy using the temporary
If the source artery is close to the surface, for example, expander. Plast Reconstr Surg. 1982;69:195.
the radial, ulnar, or common femoral arteries, then their 14. Baudet J, Rivet D, Martin D, Boileau R. Prefabricated free flap transfers.
course to the outer layer of the deep fascia may be short. Presented at the 3rd Annual Meeting of the American Society for
Reconstructive Microsurgery, San Antonio, Texas, September 12-13, 1987.
Conversely, if the source artery is deeply situated then their 15. Allen RJ, Treece P. Deep inferior epigastric flap for breast reconstruction.
length is longer, for example, the direct cutaneous perfo- Ann Plast Surg. 1994;32(1):32-38.
rators of the profunda brachii, lateral femoral circumflex, 16. Blondeel PN, Boeckx WD. Refinements in free flap breast reconstruction:
and peroneal arteries. the free bilateral deep inferior epigastric perforator flap anastomosed to the
internal mammary artery. Br J Plast Surg. 1994;47(7):495-501.
When the cutaneous perforators are traced to the under- 17. Blondeel PN, Van Landuyt KHI, Monstrey SJM, et al. The “Gent” consensus
lying source vessels to provide “septocutaneous” perforator on perforator flap terminology: preliminary definitions. Plast Reconstr Surg.
flaps, the septum may be well formed, as seen in the lateral 2003;112(5):1378.
arm and thigh, or consist of loose areolar tissue as occurs in 18. Hallock GG. Direct and indirect perforator flaps: the history and the con-
troversy. Plast Reconstr Surg. 2003;111:855.
the forearm over the radial or ulnar vessels. 19. Taylor GI, McCarten G, Doyle M. The use of the Doppler probe for
planning flaps: anatomical study and clinical applications. Br J Plast Surg.
Indirect Cutaneous Perforator Vessels 1990;43:1.
20. Taylor GI. The angiosomes of the body and their supply to perforator flaps.
These vessels arise from the source arteries and penetrate the Clin Plastic Surg. 2003;30:331-342.
21. Taylor GI. Discussion on the “Gent” consensus on perforator flap terminology:
deep tissues, usually muscle, vertically or obliquely before preliminary definitions. Plast Reconstr Surg. 2003;112:5.
piercing the outer layer of the deep fascia (Figures 4.2, 4.7, 22. Taylor GI, Corlett RJ, Dhar SC, Ashton MW. The anatomical (angio-
and 4.16). They may be quite large and contribute to the some) and clinical territories of the cutaneous perforating arteries: what
primary (dominant) blood supply to the skin and are particu- goes around comes around. Plast Reconstr Surg. Apr 2011;127(4):
1447-1459.
larly well developed on the torso (for example, the internal 23. Converse JM, ed. Reconstructive Plastic Surgery. 2nd ed. Philadelphia, PA:
­thoracic, intercostal, and deep inferior epigastric musculo- Saunders; 1977:193.
cutaneous perforators). Alternatively, they may emerge as 24. Blondeel PN, Morris SF, Hallock GG, Neligan PC. Perforator Flaps:
small “spent” terminal branches to provide the secondary Anatomy, Technique and Clinical Applications. St Louis, MO: Quality
Medical Publications; 2006.
(supplementary) supply to the skin. These are small vessels, 25. Rozen WM, Ashton MW, Le Roux CM, Pan WR, Corlett RJ. The perfo-
often quite numerous, which emerge as terminal twigs of ves- rator angiosome: a new concept in the design of deep inferior e­ pigastric
sels whose predominant supply is to the various deep tissues, artery perforator flaps for breast reconstruction. Microsurgery 2010;
especially the muscles. 30(1):1-7.
26. Taylor GI, Palmer JH. The vascular territories (angiosomes) of the
Whatever their origin and size, these indirect cutaneous body: experimental study and clinical applications. Br Plast Surg. 1987;
perforators provide the basis for the musculocutaneous per- 40:113.
forator flaps that require a more tedious dissection with the 27. Saint-Cyr M, Wong C, Schaverien M, Mojallal A, Rohrich RJ. The perfo-
potential to preserve muscle function. Large or small, they rasome theory: vascular anatomy and clinical implications. Plast Reconstr
Surg. 2009;124(5):1529-1544.
enter, and become continuous with, the same vascular net- 28. Taylor GI, Gianoutsos MP, Morris SF. The neurovascular territories of the
work that is formed by the direct cutaneous arteries. Often skin and muscles: anatomic study and clinical implications. Plast Reconstr
the smaller indirect cutaneous vessels are the main blood sup- Surg. 1994;94:1.
ply to some musculocutaneous flaps, especially where the skin 29. Taylor GI, Palmer JH, McManammy D. The vascular territories of the body
(angiosomes) and their clinical applications. In: McCarthy J, ed. Plast Surg
island is sited over muscle to which it is loosely attached. For Vol. 1. Philadelphia, PA: Saunders; 1990.
example, the gracilis and the gastrocnemius musculocutane- 30. Dhar SC, Taylor GI. The delay phenomenon: the story unfolds. Plast
ous flaps. Reconstr Surg. 1999;104(7):2079-2091.

(c) 2015 Wolters Kluwer. All Rights Reserved.


42 Part I: Principles, Techniques, and Basic Science
31. Morris SF, Taylor GI. The time sequence of the delay phenomenon: when 37. Callegari PR, Taylor GI, Caddy CM, Minabe T. An anatomical review
is a surgical delay effective? An experimental study. Plast Reconstr Surg. of the delay phenomenon: 1. Experimental studies. Plast Reconstr Surg.
1995;95:526. 1992;89:397.
32. Taylor GI, Caddy CM, Watterson PA, Crock JG. The venous territories 38. Taylor GI, Corlett RJ, Caddy C, Zelt RG. An anatomical review of the delay
(venosomes) of the human body: experimental study and clinical implications. phenomenon: II. Clinical applications. Plast Reconstr Surg. 1992;89:408.
Plast Reconstr Surg. 1990;86:85. 39. Taylor GI, Corlett RJ. The cutaneous vascular territories in pig and man.
33. Bates D, Taylor GI, Newgreen D. The pattern of neurovascular development Surgical Forum #67 of ASPRS Meeting, New York; 1981.
in the forelimb of the quail embryo. Dev Biol. 2002;249:300-320. 40. Taylor GI. The delayed TRAM flap for breast reconstruction: why, when
34. Bates D, Taylor GI, Minichiello J, et al. Neurovascular congruence and how. Oper Tech Plast Surg. 1999;6:74-82.
results from a shared patterning mechanism that utilises semaphorin 3A 41. Johnson TB, Davies IES, Davies F, eds. Gray’s Anatomy. 32nd ed. London:
and neuropilin-1. Dev Biol. 2003;255:77-98. Longmans; 1958.
35. Taylor GI, Bates D, Newgreen DF. The developing neurovascular anatomy 42. Rozen WM, Palmer KP, Suami H, et al. The DIEA branching pattern and its
of the embryo: a technique of simultaneous evaluation using fluorescent relationship to perforators: the importance of preoperative CT angiography
labelling, confocal microscopy and 3D reconstruction. Plast Reconstr Surg. for DIEA perforator flaps. Plast Reconstr Surg. 2008;121(2):367-373.
2001;108:597-604. 43. Hunter JA. Treatise on the Blood, Inflammation and Gunshot Wounds.
36. Houseman ND, Taylor GI, Pan W-R. The angiosomes of the head and London: John Richardson; 1974.
neck; anatomic study and clinical applications. Plast Reconstr Surg. June 44. Taylor GI, Daniel RK. The anatomy of several free flap donor sites. Plast
2000;105(7):2287-2313. Reconstr Surg. 1975;56:243.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5  n  Muscle Flaps and Their

Principles, Techniques, and


Blood Supply

Basic Science
Jamie P. Levine

vascular connections to the skin, it became possible to include


Flaps a segment of skin with the muscle flap.3 Prior to identification
A flap is a unit of tissue that is transferred from a donor to a of the muscle skin territory, which allows its design as a mus-
recipient site with its blood supply. Numerous classification culocutaneous flap, the muscle flap was inset into the wound
schemes exist. Flaps may be characterized by their component and exposed portions were skin grafted for coverage. With a
parts (e.g., cutaneous, musculocutaneous, and osteocutane- composite of muscle and its overlying skin, defect closure can
ous), their special relationship to the defect (local, regional, be accomplished with muscle, subcutaneous tissue, and skin.
distant, or free), the nature of the blood supply (random vs. The ability to take an island of skin can also increase the cov-
axial), and finally by the movement that is required for the erage area of a single flap if it is designed appropriately and
flap to fill the desired defect (e.g., advancement, pivot, trans- also allows for improved postoperative monitoring as either a
position, and interpolation). This chapter will focus on the free or pedicled flap (Figure 5.1).
blood supply and classification systems for muscle flaps and As understanding of cutaneous blood supply increased, fas-
their associated uses. The blood supply to the muscle is inti- ciocutaneous flaps were also described.4 Finally, Ian Taylor
mately involved with the overlying fascia and skin. In general, was able, through ink injection analysis, to put the various
muscle flaps are “axial” pattern flaps, with a known blood concepts of skin circulation together in its most coherent form
vessel oriented longitudinally within the flap. These vessels and defined the concept of the angiosome (Chapter 4). These
will have perforating branches that then supply contiguous studies helped to define the vascular territories of the body
territories including the overlying skin. With the advancement (with an average of over 300 cutaneous perforators)5 and pro-
of and enthusiasm for perforator flaps, the knowledge of the vide a reliable guide to composite flap design based on cutane-
muscle blood supply has expanded into blood supply for ter- ous vascular anatomy. These concepts of vascular anatomy
ritories of tissues (Chapter 4). These territories can be har- have opened a new era of flap transfer by defining perforator
vested as composite flaps incorporating all of the tissue layers anatomy. The separation between pure fasciocutaneous and
or individual components can be taken separately based on muscle flaps has also been erased. It was believed that the ped-
the perforator blood supply. icle to fasciocutaneous flaps was always along the intermuscu-
lar septae. With the knowledge of perforator vessel dissection,
fasciocutaneous flaps can be dissected from muscle-based
History ­vessels and perforators.
Skin and subcutaneous tissue was initially elevated as “random” The next step in utilizing this knowledge of muscular vas-
pattern flaps either from a site adjacent to the wound or from a cular anatomy has been the creation of specially designed,
distant site. Due to unpredictable circulation, these flaps often chimeric flaps that can include segments of as much muscle,
went on to partial or complete necrosis. This era of flap sur- skin, and other tissues as needed for the reconstruction. This
gery required adherence to length and width ratios in hopes knowledge of vascular anatomy has also developed the con-
of maintaining adequate vascularity for flap survival. “Delay” cept of the free form perforator flap.6 These flaps can contain
techniques (Chapter 1) were also utilized to augment the vascu- any tissue zone supplied by a regional vascular perforator and
lar supply. The great advance in this area was the identification allows individualization of tissue thickness and texture to the
of specific vascular pedicles in consistent and reliable locations specific needs of the defect.
(dorsalis pedis, groin flap, etc.). Since these flaps could be ele-
vated with a defined vascular pedicle, it became possible to trans-
fer larger flaps.1 These early axial flaps were a vast improvement
with regard to size and reliability, but because they remained
pedicled, they were limited to specific topographic locations.
Next, the identification of muscle flaps as a source of tissue
offered tremendous flexibility and more options for wound
coverage and defect reconstruction.2 Muscles are available in
almost all topographical areas. As the vascular anatomy to
these muscles was elucidated, it became possible to detach the
muscle origin, insertion, or both and to transfer the muscle to
a new site while maintaining vascular perfusion. The decision
of which muscle to utilize for a given defect takes into account
multiple factors: the size and location of the defect, damage to
regional tissues, and the presence of exposed vital structures.
The ability to transfer muscles changed the way we are able to
manage complex wounds of any variety.
With increasing interest in muscle circulation, the contri-
bution of muscle flap circulation to the overlying skin was
then recognized. This further advanced our ability to close Figure 5.1.  Myocutaneous latissimus free flap for scalp coverage.
complex, composite defects with improved function, cosmetic Although skin grafting of the muscle is still required, the skin island
appearance, and donor site variety. Each superficial muscle provides extra coverage and an area for improved monitoring
provides vascular connections via musculocutaneous perfo- postoperatively.
rating vessels to the overlying skin. With the identification of
43
(c) 2015 Wolters Kluwer. All Rights Reserved.
44 Part I: Principles, Techniques, and Basic Science

Vascular delay can also be utilized to extend the size of


Blood Supply axial flaps. By pre-incising the skin and subcutaneous tissue in
a musculocutaneous or fasciocutaneous flap, or dividing the
Blood Supply: Random Flaps nondominant or codominant vascular pedicles, the tissue in a
Any flap requires an adequate blood supply after transfer to pedicled axial flap is maximized. An example is the delay of a
survive. “Random” cutaneous flaps are based on unnamed pedicled transverse rectus abdominis myocutaneous (TRAM)
smaller vessels. It was observed historically that the ratio of flap. Since the inferior epigastric vessels are the primary vascu-
flap length to width was a critical variable for flap survival. lar supply to the TRAM, division of this pedicle and attempts
These restrictions limit their reliability for use with large to transfer the flap based on the superior pedicle often lead to
defects. When utilized appropriately, however, random flaps areas of ischemia in the skin beyond the primary skin terri-
can be reliable first choices for coverage of smaller defects tory (zone one). By ligating the deep inferior epigastric vessels
throughout the body. The term “random” really means that with or without incising the skin paddle 1 to 2 weeks prior to
the surgeon does not know for sure if there is enough longitu- breast reconstruction surgery, a much larger and more reliable
dinally oriented (axial) vessels to keep the flap alive. skin paddle can be transferred.

Blood Supply: Axial Flaps Patterns of Muscle


In contrast to random pattern flaps, axial pattern flaps are Circulation
based on a reliable, anatomically defined vascular territory
that is oriented longitudinally within the flap and that extends The most universally accepted system of muscle flap blood
beyond the base of the flap. Since the description of the first supply was developed by Mathes and Nahai. Every muscle, in
axial flap (the deltopectoral flap) nearly four decades ago, part or as a whole, has the potential for use as a muscle flap.
the knowledge of the body’s various cutaneous angiosomes Muscle circulation is based on specific pedicles that enter the
and subsequent exploitation of axially based flaps has grown muscle between its origin and insertion and consist of an artery
significantly.7 The advances in anatomic vascular knowledge and single or paired venae comitantes.10 The position, number,
have increased the type and the reliability of axial pattern and size of the vascular pedicles influence both the likelihood of
flaps and have fostered the development of microsurgical free flap survival and the flap design. The relative importance of each
flap transfer. Because of their significantly greater reliability, vascular pedicle to muscle circulation has been determined in
axial flaps (flaps with known blood supply) are preferred for cadavers by colored latex and barium injections, allowing evalu-
coverage of moderate to large defects. ation of each vascular pedicle with regard to its length, diameter,
The reliability and volume of tissue that can be placed into location, and regional source. Subsequent use of the muscles as
a defect is markedly greater than with any type of random pat- flaps has confirmed the relative importance of each pedicle to
tern flap. Due to the axially oriented circulation, delay proce- muscle survival and the potential for various flap modifications.
dures are often not necessary even when mobilizing large tissue If a pedicle to a muscle is critical to muscle survival based on its
volumes in one procedure based on this direct circulation. The size and distribution to the internal vascular architecture of the
only limitation, when pedicled, is the limited topographic arc of muscle, it is specified as a dominant (where multiple pedicles are
rotation. These limitations have been essentially overcome by present) or major (where more than one pedicle is dominant)
microvascular free tissue transfer techniques (Chapter 8) that pedicle. Nondominant pedicles are labeled as minor pedicle(s).
are limited only by the availability of recipient blood vessels. When a series of segmental smaller vessels are identified that
may support muscle flap survival despite ligation of dominant
or major pedicles, these minor pedicles are considered second-
Blood Supply: Delay Phenomenon ary pedicles. Variations in major and dominant pedicle anatomy
In order to extend the somewhat restricted size of random are uncommon, although the location and number of minor
flaps, surgeons rely on the delay phenomenon. This is most pedicles is quite variable.
commonly achieved by interrupting a portion of the normal Five patterns of circulation to the muscle have been identi-
blood supply to the flap without transferring the flap from fied and are the basis of the classification system (Figure 5.2):
its native position. The associated sublethal ischemia results Types I to V.
in (1) opening of “choke” vessels that are normally closed As noted above, Taylor et al. performed injection studies
allowing blood flow into the ischemic region of the flap, leading to the angiosome concept of the body. They noted that
(2) reorientation of the vessels within the flap to a more lon- vessels frequently accompany nerves and described a classi-
gitudinal pattern, and (3) sprouting of new vessels within the fication system based on these observations.11 These studies
flap through angiogenesis, and perhaps via vasculogenesis.8 revealed that many of the currently used flaps can be consid-
Vessels within the flap also respond to the stress of delay by ered neurovascular flaps. Muscles were classified into four
increasing in caliber. Most surgeons find it prudent to delay a types according to their extrinsic and intrinsic neurovascular
flap for at least 7 days to 3 weeks prior to final transfer, thereby supplies. Type I muscles are supplied by a single unbranched
permitting a maturation of the process of neovascularization. nerve. In Type II muscles, the nerve branches before entering
Incorporating a planned delay can significantly improve the the muscle. Type III muscles receive multiple motor nerves
chances of complete survival of a large random pattern cuta- from the same nerve trunk, and Type IV muscles are supplied
neous flap,9 as in patients with an impaired microcirculation from multiple nerve trunks. This system provides the clinical
(e.g., smokers and diabetics). Furthermore, delay is always information necessary to divide muscles into functional neuro-
considered if a flap demonstrates signs of ischemia or venous vascular units for local and distant transfer.
congestion after elevation. In such cases the procedure is best
performed in a staged manner, following a period of delay.
Obviously, a planned surgical delay requires appropriate stag-
Mathes and Nahai
ing. In these cases intermediate coverage of critical structures Classification
may be required to bridge the gap between surgeries. If at all
possible, the resection or exposure of any critical structures Type I: Single Vascular Pedicle
such as bone, tendon, nerve, or vessels should be delayed till A single vascular pedicle enters the muscle and the muscle may
the final coverage is ready. This is not always possible, espe- be safely elevated on this pedicle.
cially in traumatic wounds. In these cases a delay procedure Muscles identified with this pattern of circulation include
may not be possible and another flap is chosen. the abductor digiti minimi (hand), abductor pollicis brevis,

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5: Muscle Flaps and Their Blood Supply 45

Principles, Techniques, and


Basic Science
Figure 5.2.  Patterns of vascular anatomy: Type I, one vascular pedicle; Type II, dominant pedicle(s) and minor pedicle(s); Type III, two dominant
pedicles; Type IV, segmental vascular pedicle; Type V, one dominant pedicle and secondary segmental pedicle. (From Mathes SJ, Nahai F.
Classification of the vascular anatomy of muscles: experimental and clinical correlation. Plast Reconstr Surg. 1981;67:177, with permission.)

anconeus, first dorsal interosseous, gastrocnemius, genioglossus, which generally enter the muscle at its opposite end from the
hyoglossus, longitudinalis linguae, styloglossus, tensor fascia site of entry of the dominant vascular pedicle. These second-
lata, transversus and verticalis linguae, and vastus lateralis. ary pedicles will also support the muscle if the dominant vas-
cular pedicle is divided. Thus, the muscle may be utilized as a
Type II: Dominant Vascular Pedicle(s) and flap based on either of the two sources of circulation. Muscles
with a Type V pattern include the following: internal oblique,
Minor Vascular Pedicle(s) latissimus dorsi, pectoralis major.
Use of a Type II flap generally requires division of part or
all of the minor pedicles with preservation of the dominant
pedicle. The muscle survives when elevated based on the Arc of Rotation
dominant vascular pedicle. Muscles with a Type II vascular Each muscle and myocutaneous flap has a limited arc of rota-
pattern include the following: the abductor digiti minimi tion when transferred as a pedicle flap. The distance from
(foot), abductor hallucis, brachioradialis, coracobrachiora- the point where the pedicle enters the flap to the distal end
dialis, flexor carpi ulnaris, flexor digitorum brevis, gracilis, of the flap defines the capability of that flap. A muscle flap
hamstring (biceps femoris), peroneus brevis, peroneus longus, that can be based on a dominant vascular pedicle can reach
platysma, rectus femoris, soleus, sternocleidomastoid, trape- adjacent areas that fall within the radius created by the ped-
zius, triceps, and vastus medialis. icle and the most distal portion of muscle that is supplied by
that circulation. Generally, the muscle is released from either
Type III: Dominant Pedicles its origin or its insertion. The muscle is then mobilized on
the major or dominant pedicle being utilized. In pedicle flap
Type III muscles contain two large vascular pedicles, each of
elevation, the pedicle is not usually skeletonized in order
which may support the entire muscle. Muscles with a Type III
to avoid vascular injury and kinking. These rotational limi-
vascular pattern include the following: gluteus maximus,
tations should be incorporated into the surgical plan so that
intercostal, orbicularis oris, pectoralis minor, rectus abdomi-
defect coverage will be maximized. With progressive mobi-
nis, serratus, and temporalis.
lization of the pedicle, the arc of rotation of the flap can
be increased. Release of the bony attachments overlying the
Type IV: Segmental Vascular Pedicles point of entry of the vascular pedicle will also allow the
This group of muscles contains a series of segmental pedicles— muscle to be elevated as an island flap based only on its vas-
generally of equal size—that enter the muscle along its course. cular pedicle with subsequent increase in its arc of rotation
Each segmental pedicle provides circulation to a portion (seg- (Figure 5.3A–C).
ment) of the muscle. Generally, division of two or more ped- Specific knowledge of anatomic landmarks including
icles is feasible for transposition of a portion of the muscle as muscle insertion and origin and where the vascular pedicle
a flap. However, the muscle generally will not survive if an enters the muscle will allow for better planning. A template
excessive number of the segmental pedicles are divided dur- can be made of the defect and then the arc of rotation of
ing flap elevation. Muscles with a Type IV vascular pattern potential regional muscles can be plotted. Certain defects
include the following: the extensor digitorum longus, exten- require two or more regional flaps, but knowledge of the
sor hallucis longus, external oblique, flexor digitorum longus, muscular anatomy will allow reliable planning Muscle flap
flexor hallucis longus, sartorius, and tibialis anterior. elevation based on the dominant pedicle is designated as the
standard flap. If a muscle flap is elevated on its secondary
Type V: Dominant Vascular Pedicle and pedicle, which requires division of the dominant pedicle,
the flap is classified as a “reverse” flap. An example of this
Secondary Segmental Vascular Pedicles is a pectoralis muscle flap that is normally elevated on its
In this pattern of circulation, the muscle receives a large vascu- dominant axial pedicle, the thoracoacromial vessels. The flap
lar pedicle that will reliably provide circulation to the muscle can also be raised as a turnover flap based on the secondary
when it is elevated solely based on this particular vascular vessels from the internal mammary circulation, to cover a
pedicle. However, the muscle has secondary vascular pedicles, midline sternal defect.

(c) 2015 Wolters Kluwer. All Rights Reserved.


46 Part I: Principles, Techniques, and Basic Science

A B C

Figure 5.3.  Arc of rotation. A. Arc of rotation with flap elevation to point of entrance of vascular pedicle to flap. B. Extended arc of rotation
based on flap elevation with dissection of pedicle to regional source. C. Extended arc of rotation based on flap elevation with pedicle dissection
and release of proximal fascia and/or muscle origin or insertion. (From Mathes SJ, Nahai F. Reconstructive Surgery Principles, Anatomy and
Technique. Vol 1. New York, NY: Churchill Livingstone; 1997:115, with permission.)

In a rotation advancement flap such as a gluteal flap for trade-off. Knowledge of the vascular territory of the donor
sacral wound coverage, the arc of rotation is based more on muscle based on either dominant or segmental supply helps
the pivot point of the cutaneous incision and any associated define which portion of the muscle can successfully be trans-
backcut rather than on the vascular pedicle. Clearly, these ferred or survive regional mobilization. Limiting the amount
flaps are limited by distance since a large cutaneous compo- of fascial harvest and muscle dissection can offer a functional
nent remains attached. benefit in certain donor regions. A classic example of this is
muscle and fascial harvest in TRAM flaps and the associated
Skin Territory risks of abdominal wall laxity and weakness. Although the
standard design of the muscle flap often represents the most
Musculocutaneous flaps are composite axial flaps that consist appropriate method to reach these goals, alterations in flap
of muscle and overlying subcutaneous tissue and skin. In most design may avoid problems at the donor site. Muscle spar-
cases, the muscle at the base of the flaps is supplied by a sin- ing and perforator approaches help to decrease the abdomi-
gle dominant vessel, which gives off one or more perforating nal wall morbidity associated with this type of flap harvest
vessels to supply the overlying subcutaneous tissue and skin. and minimize the need for alloplastic (mesh) reconstruction of
Examples of musculocutaneous flaps include the TRAM flap the donor site. Certainly, when harvesting bilateral flaps for
and the latissimus dorsi flap. Topographically, nearly any mus- breast reconstruction, a perforator dissection will minimize
cle in the direct subcutaneous location provides perforators to the overall tissue loss on the donor site and allow for an easier
the skin either directly through or adjacent to the muscle. This primary closure of the abdominal wall.
subcutaneous tissue and overlying skin can be incorporated
into a multilayered type of reconstruction. The skin territory of Segmental Flap
each superficial muscle is defined anatomically as that segment
of skin extending between the origin and insertion of the mus- As noted above, transferring a portion of a muscle has poten-
cle and located between its edges along the course of the muscle tial advantages, including functional preservation, decreased
and can even be extended beyond this territory. The pedicled bulk at the recipient site, and potential use of the remain-
musculocutaneous flap may be designed with the skin left intact ing muscle as a secondary flap.12 Type III muscles, especially
(rotation flap) at the flap base or a skin island (island flap) may the gluteus maximus, are ideally suited for segmental design
be designed over the flap. Generally, the more narrow muscles because these muscles have a dual blood supply. Thus, it is pos-
(i.e., gracilis) have a greater limitation in skin territory because sible to split the muscle, leaving half of it attached to its origin,
of the decreased number of perforating vessels to the overlying insertion, and motor nerve. The other half of the muscle can
skin and the increased importance of septocutaneous vessels to then be elevated as a transposition flap. This type of muscle
the skin territory in proximity to the muscle. flap modification may be used for both Type I and Type II
muscles because the muscle is divided based on branches of the
dominant vascular pedicle. Type V muscles, because of their
Flap Modifications blood supply, have the ability to be split and taken as smaller
The goals of reconstructive surgery include safety along with flaps based on the main or secondary circulations (Figure 5.4).
restoration of form and function. The donor site must also A Type IV muscle, in particular, requires elevation as a seg-
be considered. Repair of a defect in one region by creating an mental flap, because the entire flap generally does not survive
equally problematic defect in the donor site is not a satisfactory based on a single segmental vascular pedicle. Only a portion

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5: Muscle Flaps and Their Blood Supply 47
adjacent to the dominant or major vascular pedicle, the nerve

Principles, Techniques, and


may require division during pedicled or free flap elevation. If
divided, a neurorrhaphy may be performed to another sensory
nerve at the recipient site. Examples of this exist with breast
reconstruction. Neurorrhaphies can be performed between

Basic Science
the 11th intercostal nerve, which is involved in sensation to
the rectus flap, or the cutaneous branches of the 7th thoracic
nerve, which provides sensibility to the cutaneous component
of the latissimus flap, and the lateral cutaneous branch of the
4th intercostal nerve, which provides the major contribution
to sensation of the breast. Clinical and research studies have
shown more consistent sensory return to the recipient site when
a sensory neurorrhaphy is performed.16 The difficulty with this
approach is that sensory return is not a functional requirement
in all territories of the body. Even in areas such as the plantar
aspect of the foot where sensation is important for protection
and proprioception, function can be preserved without direct
Figure 5.4.  Split latissimus, along with other muscular flaps being
used to obliterate a bronchopleural fistula and empyema cavity.
sensory reconstruction. Many patients regain deep sensation
Latissimus was split and used superiorly and inferiorly to help fill the from local neural growth into the transplanted tissue. Also,
space in this reconstruction. sensory nerves supplying a given cutaneous territory may not
be clearly visible or consistent on dissection. The indications
for sensory reconstruction in these flaps must be individualized
and should be planned to help guide the flap dissection and the
of the muscle can be divided and used as a transposition flap. patient’s expectations. Division of sensory nerves must be per-
Use of the superior part of the sartorius muscle for groin ves- formed appropriately to avoid neuroma formation. Regional
sel coverage is an example of segmental muscle flap design. dysesthesia is a potential consequence with injury to, or harvest
The sartorius is elevated by ligating one or two (as many as of, sensory nerves supplying a cutaneous area.
needed) perforators and rotating the proximal muscle medi-
ally to cover the femoral vessels. More ligation of distal perfo- Vascularized Bone
rators may compromise the blood supply to the proximal flap,
which is required for the vessel coverage. Vascular connections between the muscle and bone are gener-
ally observed at the muscle–bone interface. If these vascular
connections are preserved, it is possible to elevate a segment of
Distally Based Flaps vascularized bone with the flap. A segment of the 6th rib with
Design of a flap on minor pedicles located opposite to the the pectoralis major muscle and a segment of the iliac bone
base of the standard flap is classified as a distally based flap.13 with the internal oblique muscle (deep circumflex iliac artery
Generally, the entire muscle will not survive division of the flap) are examples of muscle flaps that may include bone. In
dominant pedicle and, therefore, only a small part of the muscle a free fibula flap, the flexor hallucis longus is supplied by the
is elevated on a specific identified minor pedicle. Delay by liga- peroneal vessels and interconnected through this vasculature
tion of the dominant pedicle prior to flap elevation helps in suc- with the fibula bone (Figure 5.6A–C). Although the muscle
cessful elevation of distally based flaps, including the proximal dissection can be limited during the flap harvest, it is often
muscle. The main problem for these distally based flaps can be incorporated to supply extra internal or cutaneous coverage,
venous drainage, especially in the lower extremity. Elevation of bulk, and vascular supply.
the extremity to allow for postural drainage and surgical delay,
as mentioned above, helps the distally based flap to adapt the Tissue Expansion
venous circulation to its new circuitous pathway. An example
Although rarely used because of surgical staging difficulties and
of this is the use of the medial hemisoleus as a reversed flap
risk of complications, insertion of a tissue expander beneath
based on the distal posterior tibial perforators for coverage of
a musculocutaneous flap allows for an increase in skin island
ankle and distal third defects of the lower extremity.14
dimensions and assists in donor site closure (Chapter 10).17
In flap coverage surgery, tissue expansion is more commonly
Neurotized-Functional Muscle Flap utilized in preparation of fasciocutaneous advancement flaps.
A muscle flap may be used to provide motor function at the Tissue expansion can be utilized to increase the useable skin
site of reconstruction.15 Flap design requires preservation island in a latissimus musculocutaneous flap and also allow for
of both the dominant vascular pedicle and the motor nerve primary closure of the defect. When used for breast reconstruc-
(examples include the latissimus and the gracilis). In order to tion, the tissue expander increases the dimensions of both the
maintain effective muscle function, the muscle must be inset remaining skin envelope and the associated overlying pectora-
so that its resting length and tension is the same as it was in lis major muscle.
the donor site. A muscle may be designed both to provide cov-
erage of a defect and to restore function. An example of this Free Flaps
is the use of the latissimus dorsi muscle in the biceps region.
Free flaps are the natural extension of axially based muscle
It may be used as a pedicled flap on its motor nerve (thora-
and musculocutaneous flaps and have further advanced our
codorsal nerve) or a neurorrhaphy can be performed to the
­ability to provide reconstructive options. Pedicled flaps are
musculocutaneous nerve. In the forearm region it can be used
limited by their arc of rotation. Microvascular free tissue
as a free flap (Figure 5.5A–E).
transfer broadens the flaps’ usefulness to all areas of the body.
Free ­tissue transfer should, like all reconstructive techniques,
Sensory Flap be performed in a well-planned fashion and should not be per-
Sensory reinnervation of cutaneous islands after transfer is formed in lieu of appropriate regional options. The reasons for
unpredictable. A musculocutaneous flap may be designed to using muscles as free flaps are essentially fourfold. First, to over-
include a sensory nerve to the cutaneous portion of the flap. If come limited regional options such as in distal tibial and foot
the sensory nerve does not enter the skin territory of the flap defects. Second, the volume of the defect is larger than regional

(c) 2015 Wolters Kluwer. All Rights Reserved.


48 Part I: Principles, Techniques, and Basic Science

A B

C D

Figure 5.5.  Chimeric flap for thigh reconstruction. A. Massive thigh


sarcoma during resection, removing most of the anterior thigh muscu-
lature and skin. B. Contralateral thigh chimeric flap including vastus
lateralis, tensor fascia lata, and anterolateral thigh tissue along with the
accompanying motor and sensory nerves. C. The pedicle and associated
nerves are seen. D. Placement of the flap into the defect and neuror-
rhaphy between the muscular nerve branches and the recipient site
nerve branches for eventual neurotization. E. Six months postoperatively
with return of nerve function and improving knee extension.
E

tissues can reconstruct. Microvascular transplantation is fre- Flap design is essentially the same for both regional trans-
quently utilized in the head and neck region where there is a position and microvascular transplantation of muscle and
lack of suitable regional muscles to satisfy the reconstructive musculocutaneous flaps. The reconstructive needs are ana-
need for combined facial, oral, and nasal cavity defects. Third, lyzed and treated in a composite fashion. Like tissues are
when functional deficits from utilizing the regional muscle chosen to reconstruct the defect for both functional and aes-
supply may limit the outcome, nonessential distant muscle can thetic purposes. The consistent, long vascular pedicle to most
be utilized to provide a functional outcome. Fourth, for infec- Type I, II, and V muscles allows rapid elevation of the muscle
tions or prosthetic coverage when flap re-elevation is likely, with its vascular pedicle for microvascular transplantation
even when local, fasciocutaneous coverage can be performed. (Figure 5.7A–E).

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5: Muscle Flaps and Their Blood Supply 49

Principles, Techniques, and


Basic Science
A

Figure 5.6.  A. Fibula harvest for mandible reconstruction including


a portion of the flexor hallucis longus muscle, which is supplied by
the peroneal vasculature. B. Fibula osteotomized and plated while
remaining attached to its pedicle in situ. C. Fibula transferred and
revascularized. Bone inset has been performed and soft tissue inset
is next. Included is a skin island (osteomyocutaneous) for intraoral
reconstruction.
C

to all parts of the body. Defects in the head and neck can be
Perforator Flaps complex involving mucosal loss from the oral, nasal, and pha-
A muscle’s axial blood vessel provides perforators, which first ryngeal cavities; structural loss of either the bony or cartilagi-
supply the muscle and then proceed superficially to supply the nous skeleton; and cutaneous loss. In larger defects there is
overlying skin and subcutaneous tissue. These vessels can be no one flap that can provide all of these missing layers. By
meticulously dissected from the surrounding muscle to produce either incorporating multiple flaps (e.g., free osteocutaneous
a direct cutaneous perforator flap (Figure 5.8). These perfo- fibula free flap with a pedicled pectoralis myocutaneous flap
rator flaps are cutaneous flaps, which are based on the ves- for a composite mandibular defect) or by precise, planned flap
sels known to traverse various muscle flaps such as the deep prefabrication, these defects can be reconstructed. The use of
inferior epigastric, thoracodorsal, and superior gluteal vessels. thinned flaps with the pre-grafting of autologous or bioengi-
These flaps demonstrate that the unnamed cutaneous/perforat- neered structural elements such as bone and cartilage and the
ing vessels arise from larger, named vessels and travel through creation of new vascular bundles in desired donor sites are
the muscle or muscular septum to supply a large cutaneous well established in the literature. The advancement of in vivo
region. The reliability of these flaps is clearly more robust and ex vivo tissue engineering, with, and ultimately without,
than previously thought. The problem of anatomic variability immune modulation, is one of the next frontiers for recon-
to these cutaneous perforators is greater when not following structive surgery.
known muscle territories. Perforator flaps, while technically
challenging, may decrease some of the functional morbidity Combined Flaps
associated with the harvest of muscles and overlying muscle
Combined flaps are used when either a large volume of tis-
fascia in myocutaneous flap harvest. These flaps have become
sue is required, more than a single flap can provide, or when
widely utilized for breast reconstruction but can be used for
multiple tissue types are required in a complex position or ori-
any location throughout the body.18
entation. Instead of taking multiple pedicled or free flaps to
perform a given reconstruction, conjoined or chimeric flaps
Prefabricated Flaps can be used. Each of these groups has subcategories and indi-
Prefabrication represents the future of flap-based reconstruc- vidualized terminology within them but the basic principles
tion and is in essence in vivo tissue engineering. The goal of remain the same.21 The flaps in these groups are either attached
this type of reconstruction is to provide all missing compo- by a common vascular supply or are directly attached, each
nents of a given defect by positioning support, lining, and with its own vascular supply. Conjoined flaps are individual
coverage tissues in preplanned positions and allowing them flaps that have their own vascular territory but are attached
to vascularize prior to transfer, and minimize donor site mor- by a soft tissue bridge to form a larger flap with multiple vas-
bidity.19,20 Descriptions of prefabrication have been mostly cular territories being incorporated. An example of this is the
focused on the head and neck region but can be translated bridging of an extended myocutaneous latissimus flap with a

(c) 2015 Wolters Kluwer. All Rights Reserved.


50 Part I: Principles, Techniques, and Basic Science

A B

C D

Figure 5.7. A. Open ankle defect after orthopedic trauma. Bone


and hardware were exposed after debridement. B. Design of a same-leg
gracilis flap that approximated the defect size well and with lim-
ited donor site morbidity. C. Harvest of the gracilis (Type II) flap.
D. Intraoperative coverage of this small defect with well-vascularized
muscle. E. Several months postoperative picture showing excellent
healing and recontouring.
E

superficial inferior epigastric flap, which was first described since islands of tissue can be created on each perforator branch
by Harii et al., back in 1981.22 These flaps could be rotated on that emanates from the source supply of the lateral circumflex
either pedicle, with the other pedicle being attached microsur- femoral vessels. A final subtype of the chimeric flaps is the fab-
gically to enhance the blood supply and create a tremendously ricated chimeric flap. These are flaps that are attached to each
large flap for cutaneous coverage. These massive flaps can also other by microanastomosis either at branch points or at the dis-
be taken further as a pure free flap with double microvascular tal (flow-through) end to create a hybrid flap.
anastomoses. The use of these flaps obviously depends on the
defect. A flap can be considered conjoined between individual
perforators because each of these territories can be separated
Complex Wound Management
and can act as an individual flap unit. Muscle and musculocutaneous flaps are ideal for treating dif-
Chimeric flaps are individual flaps that are fully separated ficult soft tissue and bony or prosthetic infections. Although
from each other but linked together by a common source vessel. treatment to decrease the bacterial concentration below 105
The classic examples come from the subscapular system and per gram of tissue is necessary, subsequent coverage with
from the lateral circumflex femoral system. The subscapular well-vascularized muscle appears to further decrease the
system has a variety of tissue types from bone to skin that can all bacterial load, protect against recurrence of infection, and
be taken as separate flaps or in multiple combinations (Figure maintain wound closure. Planned treatment of complex
5.9A–E). The vascular supply for these flaps is from large inde- wounds with staged debridements followed by coverage with
pendent subfascial vessels that connect to the same source ves- well-vascularized tissue and appropriate antibiotic therapy has
sel. The anterolateral thigh chimeric flaps are perforator based revolutionized wound management and is the standard of care

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5: Muscle Flaps and Their Blood Supply 51
common and problematic example of osteomyelitis (Figure 5.11A

Principles, Techniques, and


and B). Treatment with serial debridement and antibiotics and
coverage with a muscle flap such as the pectoralis major and/or
the rectus abdominis are necessary for ultimate wound closure,
chest wall stabilization, and patient survival.

Basic Science
Vascular Insufficiency
Nonhealing wounds associated with vascular insufficiency
frequently require extremity amputation. Revascularization
of the leg may salvage the extremity, but the wound will still
necessitate flap coverage. Although revascularization provides
macroscopic blood flow to an extremity, the area of a specific
wound may still have insufficient microvascular perfusion or
be too large to heal on its own. Muscle flap placement pro-
vides transplanted microcirculation and tissue bulk to allow
these wounds to heal and ultimately provide for limb salvage.
Either simultaneous or delayed muscle flap transplantation
will allow preservation of a functional extremity despite
wound complexity.28 In certain circumstances, a flap can be
chosen that has a flow-through ability. With this type of flap
design, the vascular supply, more often, from a traumatic
injury or atherosclerotic disease can be augmented and flap
tissue placed to cover the defect. This type of reconstruction
requires precise planning and execution.

Radiation Wounds
Wounds associated with radiation injury do not respond
to local wound care and can be some of the most difficult
wounds to treat (Chapters 3 and 17). Tissue that has under-
gone high-dose ionizing radiation therapy has limited resis-
Figure 5.8.  Perforator TRAM (transverse rectus abdominis myocu- tance to injury and ability to regenerate. The effects of this
taneous) flap anastomosed to the internal mammary vessels. type of radiation are longstanding. Radiated tissue can remain
intact for decades but any form of tissue stress or injury can
form a chronic wound with critical structures ultimately being
exposed. Treatment of these wounds usually requires wide
in most situations. Historically, experimental studies compar- debridement of necrotic skin, affected soft tissue, and scle-
ing bacterial resistance in musculocutaneous as compared with rotic or infected bone and results in a complex wound usually
cutaneous and fasciocutaneous flaps have demonstrated superior associated with exposure of vital structures. If adjacent muscle
resistance to bacterial invasion and subsequent flap necrosis in units have vascular pedicles located distant to the radiation
the muscle and musculocutaneous flaps.23,24 Since muscle flaps port, regional muscle flaps may be useful for vascularized
appear to provide protection from progressing bacterial injury coverage (Figure 5.12A–C).29 In areas with poor local muscle
to the soft tissues and improved tissue vascularity, it has allowed availability such as the head and neck region, particularly in
for the management of complex wounds that traditionally did the skull, microvascular transfer of a muscle flap is generally
not respond well to local wound care. There have also been required for coverage.
studies showing no difference between muscle and fasciocuta-
neous flaps in infected wounds.25 It remains widely accepted,
however, that muscle flaps provide an excellent option for
coverage. Also, when comparing the use of muscle and fascio- Exposed or Infected Prosthesis
cutaneous free flaps in traumatic wounds, there does not appear When wound coverage overlying the site of a vascular or
to be an increased incidence of long-term postoperative infec- orthopedic prosthesis fails, early wound debridement, mus-
tion when appropriate debridement is performed.26 Muscle cle flap coverage, and culture-specific antibiotic therapy fre-
flaps are extremely useful in three-dimensional defects, which quently allow salvage of the prosthesis and simultaneously
require the flap to contour to irregular or complex topography. provide stable defect coverage.30 Once infection has been
established in the prosthesis, however, it is usually necessary
to remove the prosthesis. More common areas of exposure
Osteomyelitis for vascular grafts are in the groin and lower extremity. Groin
Following debridement of the infected bone associated with coverage is usually accomplished reliably with a sartorius
chronic osteomyelitis, a muscle flap is transposed as a regional muscle flap, but larger flaps can also be mobilized if needed.
flap or transplanted by microvascular technique into the defect. Orthopedic hardware is more commonly exposed in the mid-
The flap fills the area of bone debridement with well-vascularized line from spine surgery or over joint with limited coverage
tissue and provides stable wound coverage (Figure 5.10A–D). such as the knee. Spine hardware can usually be well covered
As noted above, short-term culture-specific antibiotic therapy with myocutaneous advancement flaps, whereas joint cover-
is utilized simultaneously. With this approach, successful man- age usually requires rotation flaps such as the gastrocnemius
agement of chronic infection in the site of bone or cartilage muscle. Lastly, hardware exposure can occur in combination
injury has been observed.27 Debridements can be performed in with trauma such as in lower extremity injuries or after radia-
a staged fashion depending on the amount of infection and sta- tion injury leading to exposure of underlying bony or vascular
bility of the patient. Coverage with the muscle flap is planned prostheses. In any of these cases, reconstruction with either a
immediately after the final debridement. Sternal wounds are a local or free muscle flap is almost always indicated.

(c) 2015 Wolters Kluwer. All Rights Reserved.


52 Part I: Principles, Techniques, and Basic Science

Figure 5.9.  Chimeric flap reconstruction in the head and neck.


A. Exposed mandibular plate along with an underlying mandibular
defect. B. Chimeric flap design from the subscapular system including
bone, muscle, and fasciocutaneous tissue. C. Flap harvested with the
separate components visualized, all attached to the main subscapular
system. D. Flap being placed into the bony and soft tissue defect prior
to microvascular reanastomosis. E. Closure of the cutaneous defect at
the end of the procedure.
E

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5: Muscle Flaps and Their Blood Supply 53

Principles, Techniques, and


Basic Science
A B

C D
Figure 5.10.  Reconstruction of osteomyelitis of the heel. A. Chronic draining heel wound with refractory calcaneal osteomyelitis. Prior
debridement was performed. B. The heel was opened transversally along its lateral surface to expose the calcaneal wound fully and allow for
debridement and subsequent coverage. The incision was carried up to the posterior tibial vessels where a muscle flap was anastomosed and
then placed inside of the heel for complete coverage of the debrided osteomyelitic space. C. Muscle in place after inset and prior to skin graft
placement. D. Six months postoperatively with a well-healed and contracted wound reconstruction.

plastic surgery. Their use has allowed for bolder, more effec-
Conclusions tive oncologic resections, limb salvage in previously irreparable
Muscle and musculocutaneous flaps are available in all body situations, improved functional restoration with motor unit
regions. With the selection of muscles with a suitable vascular loss, contracture release in secondarily healed or scarred joint
pedicle, the muscle may be safely elevated to provide cover- and soft tissue contractures, and improved aesthetic outcome
age and simultaneously restore form and function. Thorough for contour defects including breast reconstruction. Nearly
knowledge of the muscular anatomy, vascular circulation, and any defect can be closed with a careful analysis and a planned
the arc of rotation is required in order to select the optimal mus- approach for reconstruction. Use of muscle and musculocutane-
cle unit for specific defects throughout the body. When regional ous flaps broadens the options for defect closure in every area
muscle flaps are unavailable or undesirable, the surgeon may of the body. The future of flap reconstruction is also advancing
elect to transfer distant muscle or musculocutaneous flaps and becoming more refined with the use of perforator flaps,
microsurgically. Muscle and musculocutaneous flaps also pro- flap prefabrication, and chimeric flaps to more precisely recon-
vide a method to treat complex wounds—such as osteomyelitis, struct the most complex defects. All of these modifications and
radiation necrosis, traumatic defects, and exposed hardware— advancements in flap surgery have positioned the reconstruc-
that in the past were recalcitrant to wound care. Use of muscle tive surgeon at the forefront of clinical tissue engineering and
and musculocutaneous flaps has revolutionized reconstructive vascularized composite allotransplantation.

(c) 2015 Wolters Kluwer. All Rights Reserved.


54 Part I: Principles, Techniques, and Basic Science

A B
Figure 5.11.  Reconstruction of sternal osteomyelitis. A. Sternal osteomyelitis after wire removal and an initial debridement. Significant
debridement of the pectoralis muscle was also performed. B. Pedicled rectus abdominis flap placement into the defect.

A B
Figure 5.12.  (Continued)

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 5: Muscle Flaps and Their Blood Supply 55

Principles, Techniques, and


Basic Science
Figure 5.12.  Reconstruction of a radiated groin wound. A. Excision
of a radiated open tumor wound in the groin along with underlying
lymph node dissection and removal of surrounding radiated skin.
B. Elevation of a vertical rectus abdominis myocutaneous flap.
C. Placement of the flap through a subcutaneous tunnel with excellent
coverage of the defect including muscle over the entire wound bed and
complete cutaneous closure with the overlying skin paddle.
C

References 16. Yap LH, Whiten SC, Forster A, Stevenson HJ. Sensory recovery in the sensate
free transverse rectus abdominis myocutaneous flap. Plast Reconstr Surg.
1. McGregor IA, Morgan G. Axial and random pattern flaps. Br J Plast Surg. 2005;115(5):1280-1288.
1973;26(3):202-213. 17. Radovan C. Tissue expansion in soft-tissue reconstruction. Plast Reconstr
2. Mathes SJ, Nahai F. Clinical Applications for Muscle and Musculocutaneous Surg. 1984;74(4):482-492.
Flaps. St. Louis, MO: C.V. Mosby; 1982. 18. Geddes CR, Morris SF, Neligan PC. Perforator flaps: evolution, classification,
3. McCraw JB, Dibbell DG, Carraway JH. Clinical definition of indepen- and applications. Ann Plast Surg. 2003;50(1):90-99.
dent myocutaneous vascular territories. Plast Reconstr Surg. 1977;60(3): 19. Garfein ES, Orgill DP, Pribaz JJ. Clinical applications of tissue engineered
341-352. constructs. Clin Plast Surg. 2003;30(4):485-498.
4. Tolhurst DE. Surgical indications for fasciocutaneous flaps. Ann Plast Surg. 20. Pribaz JJ, Fine NA. Prefabricated and prelaminated flaps for head and neck
1984;13(6):495-503. reconstruction. Clin Plast Surg. 2001;28(2):261-272, vii.
5. Taylor GI, Palmer JH. The vascular territories (angiosomes) of the body: 21. Hallock GG. Further clarification of the nomenclature for compound flaps.
experimental study and clinical applications. Br J Plast Surg. 1987; Plast Reconstr Surg. 2006;117(7):151e-160e.
40(2):113-141. 22. Harii K, Iwaya T, Kawaguchi N. Combination myocutaneous flap and
6. Wei FC, Mardini S. Free-style free flaps. Plast Reconstr Surg. 2004; microvascular free flap. Plast Reconstr Surg. 1981;68(5):700-711.
114(4):910-916. 23. Calderon W, Chang N, Mathes SJ. Comparison of the effect of bacterial
7. Bakamjian VY, Long M, Rigg B. Experience with the medially based delto- inoculation in musculocutaneous and fasciocutaneous flaps. Plast Reconstr
pectoral flap in reconstructuve surgery of the head and neck. Br J Plast Surg. Surg. 1986;77(5):785-794.
1971;24(2):174-183. 24. Gosain A, Chang N, Mathes S, Hunt TK, Vasconez L. A study of the relationship
8. Ghali S, Butler PE, Tepper OM, Gurtner GC. Vascular delay revisited. Plast between blood flow and bacterial inoculation in musculocutaneous and fascio-
Reconstr Surg. 2007;119(6):1735-1744. cutaneous flaps. Plast Reconstr Surg. 1990;86(6):1152-1162; discussion 1163.
9. Atisha D, Alderman AK, Janiga T, Singal B, Wilkins EG. The efficacy of the 25. Salgado CJ, Mardini S, Jamali AA, Ortiz J, Gonzales R, Chen HC. Muscle
surgical delay procedure in pedicle TRAM breast reconstruction. Ann Plast versus nonmuscle flaps in the reconstruction of chronic osteomyelitis
Surg. 2009;63(4):383-388. defects. Plast Reconstr Surg. 2006;118(6):1401-1411.
10. Mathes SJ, Nahai F. Classification of the vascular anatomy of muscles: 26. Yazar S, Lin CH, Lin YT, Ulusal AE, Wei FC. Outcome comparison
experimental and clinical correlation. Plast Reconstr Surg. 1981;67(2):177-187. between free muscle and free fasciocutaneous flaps for reconstruction of
11. Taylor GI, Gianoutsos MP, Morris SF. The neurovascular territories of the distal third and ankle traumatic open tibial fractures. Plast Reconstr Surg.
skin and muscles: anatomic study and clinical implications. Plast Reconstr 2006;117(7):2468-2475; discussion 2476-2477.
Surg. 1994;94(1):1-36. 27. Mathes SJ, Alpert BS, Chang N. Use of the muscle flap in chronic osteo-
12. Mathes SJ, Vasconez LO. Myocutaneous free-flap transfer. Anatomical and myelitis: experimental and clinical correlation. Plast Reconstr Surg.
experimental considerations. Plast Reconstr Surg. 1978;62(2):162-166. 1982;69(5):815-829.
13. Mathes SJ, Nahai F. Reconstructive Surgery: Principles, Anatomy and 28. McCarthy WJ 3rd, Matsumura JS, Fine NA, Dumanian GA, Pearce WH.
Technique. New York, NY: Churchill Livingstone; 1997. Combined arterial reconstruction and free tissue transfer for limb salvage.
14. Pu LL. The reversed medial hemisoleus muscle flap and its role in reconstruc- J Vasc Surg. 1999;29(5):814-818; discussion 818-820.
tion of an open tibial wound in the lower third of the leg. Ann Plast Surg. 29. Mathes SJ, Alexander J. Radiation injury. Surg Oncol Clin N Am. 1996;
2006;56(1):59-63; discussion 63-64. 5(4):809-824.
15. Terzis JK, Sweet RC, Dykes RW, Williams HB. Recovery of function in 30. Greenberg B, LaRossa D, Lotke PA, Murphy JB, Noone RB. Salvage of
free muscle transplants using microneurovascular anastomoses. J Hand Surg jeopardized total-knee prosthesis: the role of the gastrocnemius muscle flap.
Am. 1978;3(1):37-59. Plast Reconstr Surg. 1989;83(1):85-89, 97-99.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 6  n  Transplantation Biology and
Applications to Plastic Surgery
Damon S. Cooney, Justin M. Sacks, Gerald Brandacher, and W. P. Andrew Lee

The transplantation of tissue from one location to another is a survived indefinitely. World War II accelerated progress in
fundamental concept in plastic surgery. It is not surprising that allotransplantation. Gibson, a plastic surgeon at the Glasgow
the first successful transplantation of tissue from one person Royal Infirmary, described the accelerated rejection of skin
to another in the form of a kidney transplant was performed grafts in pilots due to the presence of humoral antibodies
by a plastic surgeon, Dr. Joseph E. Murray. Other pioneer- after repeat exposure to the same donor, also known as the
ing plastic surgeons helped spawn the new field of allogeneic “second-set rejection.” Medawar joined Gibson to investigate
organ transplantation, and with the development of improved this phenomenon and, in combination with Billingham and
surgical techniques and modern immunosuppression, trans- Brent, laid the foundation for modern immunology. In 1954,
plantation has become the treatment of choice for end-stage Dr. Joseph E. Murray and colleagues performed the first
organ failure of the liver, heart, lung, pancreas, and kidney. successful kidney transplant between identical twins.
It is fitting that transplantation has returned to the field of Furthermore, the introduction of a novel immunosuppressive
plastic surgery more than 50 years later with the development drug, 6-mercaptopurine and its precursor azathioprine (AZT)
of reconstructive transplantation, the new era in transplant by Charles Zukosi and Roy Calne in 1960, was responsible
medicine. It is only within the last decade that transplantation for improvements in the field of organ transplantation.
of vascularized composite allografts (VCAs), such as hand and With the discovery of the first human leukocyte antigen
face transplants, has become a clinical reality. VCAs involve (HLA) in 1958, the matching of tissue beyond simply match-
transplantation of composite structures for reconstructive ing blood types became possible. Knowledge of these antigens
surgery and thereby fulfill a prime mandate of plastic sur- allowed the avoidance of graft-versus-host disease. The first
gery: to replace and restore devastating tissue defects using successful human bone marrow transplant was performed
“like-with-like.” The ability to transfer vascularized allografts in 1968. A 4-month-old boy who had Wiskott-Aldrich syn-
through microvascular surgical techniques, restoring form drome received a bone marrow transplant from his sibling that
and function for complex cutaneous and musculoskeletal effectively restored his immune system, duplicating Medawar’s
defects, is revolutionizing the field of reconstructive surgery animal findings that had previously resulted in immune tolerance
and has added another rung to the “reconstructive ladder.” in chimeric mice. Medawar’s chimeric mice contained genetically
Long-term allograft survival, however, can only be achieved, distinct cells originating from separate and unique zygotic cells.
as for any solid organ transplant, through the use of systemic Coinciding with these first successful human bone mar-
immunosuppression with its associated sequela of organ tox- row transplantations, all major components of human clinical
icity, opportunistic infections, and potential for malignancy. allotransplantation including immunosuppression, tissue pres-
Current research on immunomodulation and induction of ervation and matching, and complex microvascular techniques
tolerance holds promise for reducing the need for long-term were elucidated. Following the first kidney transplantation,
high-dose immunosuppression. Although reconstructive other solid organs such as the heart, liver, lung, and pancreas
allotransplantation in humans is a relatively new area with were transplanted and nonspecific immunosuppressive agents
small numbers of patients, there are reasons to think that such as cyclosporine A (CsA) and FK506 were developed.
new innovations in immunomodulation and tolerance may In the last two decades, over 150 different VCAs including
come from the field of VCAs. For example, reconstructive more than 80 upper extremities and 24 partial faces, as well as
transplant patients usually do not suffer from life-threatening abdominal walls, larynx, tongue, uterus, penis, vascularized bone
illness or comorbidities and therefore the impetus to minimize and joint, and individual tissue components like peripheral
side effects from immunosuppressive medications is stronger. nerve, flexor tendon, and skin have been successfully trans-
Also, the ability to directly and continuously observe trans- planted using conventional immunosuppressive protocols. Of
planted tissue that includes a skin component allows for the the upper extremity transplants performed to date, only one
use of novel experimental protocols as rejection is seen earlier graft was lost while patients were on high-dose immunosup-
and can potentially be reversed by topical agents. Finally, the pression. In the combined American and European experience,
presence of vascularized bone marrow in many VCA grafts the early to intermediate allograft survival is greater than 95%
raises the possibility of unique modulatory strategies, as will (Figure 6.1).
be discussed. Current immunosuppression protocols developed within
the last century have allowed these transplantation ideas to
become a surgical reality. The risk/benefit ratio that must be
Introduction optimized when transplanting a piece of tissue that optimizes
Human tissue transplantation is an ancient concept. According form and function but does not preserve or prolong life poses
to legend from the fourth century AD, Saints Cosmos and an ethical dilemma. Exposure to life-long immunosuppres-
Damian—twin brothers—replaced the gangrenous leg of a sion comes with risk that must be articulated to the patient.
parishioner with the leg of a deceased Ethiopian Moor. The Current immunologic research focuses on ways to obviate the
earliest reliable, documented outcomes of allogeneic and use of systemic immunosuppression for both solid organ and
xenogeneic skin grafts in human recipients were published reconstructive transplantation procedures. The field of recon-
by Schone in 1912 and Lexer in 1914. Schone and Lexer structive transplantation will become ubiquitous once toler-
demonstrated that these grafts did not survive more than ance can be achieved. Currently, great strides are being made
3 weeks after transplantation. Padgett provided further evi- in large animal studies and in the first clinical trials, moving
dence in 1932, when he reported rejection of all skin allografts ever closer to elucidating the immunologic processes that will
within 35 days in 40 patients. However, Padgett also dem- unlock these barriers and allow the next revolution in plastic
onstrated that skin grafts exchanged between identical twins surgery to begin.

56
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 6: Transplantation Biology and Applications to Plastic Surgery 57
25

Principles, Techniques, and


20

Basic Science
90
Hands Patients
80 78
15
Years

70

10 60
52
50

5
40 37

30
24 24
0
20 17

in

g
l
ce

ur

op int

ue

ve

n
al

15
ni

ru

Le
do
Sk
gu
m
lw

Fa

jo

er
ng
Pe

te

12
Fe

n
ha

N
ee
a

To

Te
in

Kn

10
m

es
do

/o
Ab

nx
ry

0
la
a/

ld

e
he

na

SA
or

ro
ac

hi

U
Eu
Tr

C
A B

10
Hands Face
9

7
Number of transplants

3 Figure 6.1. A–C. International experience with reconstructive


transplantation 1999 to 2012. A. The cumulative total for all types of
2
reconstructive transplant by type of transplant (except upper extrem-
ity) as of 2012. B. The cumulative total for upper extremity transplants
by region as of 2012. Upper extremity continues to be the most com-
1
monly performed vascularized composite allograft. C. The number of
hand and face transplants performed per year in the United States since
0 1999 broken down by year. Note the dramatic increase in reconstruc-
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 tive procedures in the last half-decade.
Hand and face transplants performed/year in the United States
C

A graft is tissue completely separated from its donor bed


Nomenclature and moved to a separate recipient bed, its survival relying
Proper nomenclature will help clarify subsequent discus- on ingrowth of new vessels from the surrounding recipient
sions. Certain terms such as transplant, flap, and graft are tissue (Chapter 1). A vascularized graft or flap either remains
often used to refer to a VCA. However, these terms should be attached to its native blood supply or becomes revascular-
used carefully with their true meaning in mind to ensure clear ized via microvascular anastomoses to recipient vessels (aka
communication. free flap). An autograft refers to tissue transplanted from one
Transplantation can be defined as the transfer of tissue or location to another within the same individual. An isograft is
an organ to another person or to a different location in the tissue transplanted between genetically identical individu-
same person. According to this definition, much of what recon- als, such as transplants between syngeneic mice or human
structive surgeons do can be classified as a type of transplant. monozygotic twins. An allograft or homograft is tissue trans-
However, in its usual medical usage, the term transplant is used planted between unrelated individuals of the same species. A
to describe an allotransplant or tissue transferred from a living xenograft or heterograft is tissue transplanted between differ-
or deceased human donor to another genetically not identical ent species.
human patient. Within this chapter, our discussion of transplan- Transplantation can also be described according to the site
tation will be focused mostly on the topic of allotransplantation, into which the tissue is transferred. An orthotopic transplant is
as the transfer of autologous tissue locally or distantly is covered transferred into an anatomically similar site, whereas a hetero-
elsewhere in the text. topic transplant is transferred into a different site from its donor

(c) 2015 Wolters Kluwer. All Rights Reserved.


58 Part I: Principles, Techniques, and Basic Science

origin. The term reconstructive transplantation is used to differ- Once T cells are activated, they become effector T cells and
entiate the transfer of composite tissues such as the hand or face migrate to the graft and mediate rejection. This is aptly named
from more traditional solid organ transplants. During the devel- the direct pathway of allorecognition. In contrast to the direct
opment of reconstructive transplantation, this novel field was pathway, host APCs play a significant role in the indirect path-
commonly referred to as composite tissue allotransplantation way of allorecognition where they present processed donor
(CTA). Unfortunately, the use of this term has caused some con- antigens to host T cells. Both pathways of allorecognition are
fusion and has largely fallen out of favor. In particular, the use important in mediating graft rejection; however, the indirect
of the word tissue raised the concern that reconstructive trans- pathway is thought to be of greater significance in the physiology
plantation could be confused by regulatory bodies (such as the of chronic graft rejection.
FDA) with non-vascular tissue transplantation, with potentially DCs are the most efficient APCs and have the capacity to
negative regulatory consequences. Therefore, vascularized com- take up, process, and present antigens to T cells in vivo. DCs
posite allograft (VCA) transplantation has supplanted the term rapidly respond to inflammatory stimuli, microbial products,
CTA to avoid this confusion. or alloantigens following transplantation and express high
levels of MHC class II and costimulatory molecules essential
Transplant Immunology for T-cell activation.

Transplantation Antigens Immunosuppression


Transplantation of organs or tissues between genetically All allotransplant recipients require some form of immuno-
disparate individuals of the same species (allogeneic indi- suppression. Without these immunosuppressive modalities,
viduals) leads to recognition and rejection of the allogeneic rejection would inevitably occur in individuals unless they
tissue by the recipient’s immune system. This “alloimmune were genetically identical (identical twins). The immunosup-
response” that discriminates between self- and non-self tis- pression used for transplantation of VCAs has for the most
sues remains the main barrier to successful transplantation. part mirrored the regimens for solid organ transplantation.
These immunologic responses are initiated by graft antigens Several pharmacological drugs are used to prevent and
that are genetically encoded polymorphic proteins. The result control graft rejection (Table 6.1). It is important to note that
of this interaction determines the acceptance or rejection of these drugs lack selectivity and cause generalized immuno-
allograft tissue. For this reason, learning how to suppress suppression rendering transplant patients highly susceptible
these responses is a major goal of transplant immunologists. to opportunistic infections and certain types of malignancies.
Transplant tolerance, as discussed, can be mediated by central Based on their mode of action, there are four main groups
or peripheral mechanisms and can be acquired with the assis- of immunosuppressive drugs: (1) steroids, (2) cytotoxic/anti-
tance of either immunosuppression or immunomodulation. proliferative drugs, (3) anti–T-cell agents (calcineurin inhibi-
Antigens are cell surface glycoproteins that are encoded tors), and (4) induction agents (polyclonal and monoclonal
in the major histocompatibility complex (MHC), a multigene antibodies). One of the first immunosuppressant used was
cluster located on chromosome 6 in humans. There are two steroids with broad anti-inflammatory actions (i.e., pred-
classes of MHC molecules, class I and II, that differ in their nisone and prednisolone). These medications inhibit acti-
structure, function, and tissue distribution. MHC class I anti- vation of several transcription factors, thus modifying
gens are expressed on all nucleated cells, whereas class II gene transcription and inhibiting cellular activation and
expression is restricted to antigen presenting cells (APCs), cytokine production. Prednisolone was one of the first
such as B lymphocytes, monocytes, macrophages, dendritic pharmacological agents used in allogeneic organ transplan-
cells (DCs), endothelial cells, and activated human and rat tation. Despite the well-known side effects of long-term
T cells. In humans, the MHC antigens are known as HLA. use, steroids are still widely used today in combination
Each individual has two MHC regions, one of paternal and with other immunosuppressive agents in most solid organ
one of maternal origin. Each MHC contains an inherited group and VCA protocols. Short courses of high-dose steroids
of HLA genes or haplotypes: HLA class I genes known as continue to be the frontline treatment for acute rejec-
HLA-A, -B, -C and HLA class II genes known as HLA-DR, -DP, tion episodes in all types of transplantation. Cytotoxic/
and -DQ. The HLA antigens determine the compatibility of all anti-proliferative drugs include cyclophosphamide, metho-
organ and tissue transplants. trexate, AZT, and mycophenolate mofetil (MMF). These
medications interfere with DNA replication and kill/arrest
Allogeneic Transplantation proliferating lymphocytes that are activated by alloantigens.
Billingham, Brent, and Medawar demonstrated in their semi- Earlier, nonspecific anti-proliferative agents such as AZT
nal 1953 Nature article that neonatal mice and irradiated had many side effects and increased the risk of transplant-
adult mice developed donor-specific tolerance to skin grafts associated malignancy. MMF has replaced the other agents in
subsequent to successful engraftment of splenic and bone mar- many protocols due to its ability to block purine synthesis selec-
row cells into the recipient. These animals were considered tively in T and B cells, which dramatically decrease side effects.
chimeras consisting of both donor and recipient T cells. This Agents that selectively inhibit the activation pathways of
built the foundation for the concept that cell-based therapies T cells are typically fungal or bacterial products (i.e., CsA,
in clinical transplantation could potentially modify the host tacrolimus [FK506], and rapamycin [RAPA; sirolimus]). CsA
immune system to allow minimization or even avoidance of and tacrolimus inhibit the signaling pathways of T-cell activa-
pharmacological immunosuppression. Since then, immune tol- tion by interfering with calcineurin activation and interleu-
erance has been the “Holy Grail” of transplantation research. kin (IL)-2 gene transcription (Figure 6.2). CsA is a metabolic
Rejection of transplanted tissue occurs through both extract from the fungus Tolypocladium inflatum gamus
cellular and humoral immune responses. These responses are described in 1976. Its discovery revolutionized the field of
generated when host APCs and T lymphocytes respond to solid organ transplantation by significantly increasing the sur-
the genetic differences in the MHC molecules expressed by vival of kidney, heart, and liver allografts. CsA was shown to
the donor cells. T cells have fundamental roles in graft rejection, prolong limb allograft survival in experimental animal mod-
and their responses are rapid and vigorous and ultimately will els and thereby encouraged clinicians to pursue VCA in the
lead to inflammation and tissue destruction. There are two main 1980s and 1990s. Tacrolimus is a macrolide lactone antibi-
pathways by which host T cells recognize donor alloantigens. otic isolated from soil fungus and also inhibits the calcineu-
Following transplantation, donor APCs migrate toward host rin/IL-2 pathway of T-cell activation, although at a different
lymphoid tissues and can directly activate recipient T cells. point in the pathway from cyclosporine. It has a favorable

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 6: Transplantation Biology and Applications to Plastic Surgery 59

Table 6.1

Principles, Techniques, and


IMMUNOSUPPRESSIVE AGENTS. MANY OF THE DRUGS CURRENTLY BEING USED FOR ORGAN AND
RECONSTRUCTIVE TRANSPLANTATION AND THEIR SIDE EFFECTS

Basic Science
n Type of Drug n Agents n Mechanism n Side Effect

Steroids Methylprednisolone, Multiple, Hip necrosis, dyslipidemia, weight gain,


prednisone anti-inflammatory DM, fluid retention
Calcineurin Cyclosporine, Blocks IL-2 production Nephrotoxicity, hypertension, hyperlipid-
inhibitors tacrolimus/FK506 emia, hirsutism, gingival hyperplasia
Anti-proliferative Azathioprine, Blocks DNA synthesis Myelosuppression, GI complaints, viral
drugs mycophenolate mofetil, and proliferation reactivation
cyclophosphamide
mTOR Rapamycin, Blocks cell receptor Wound healing problems,
inhibitors everolimus signaling cascade hyperlipidemia, thrombocytopenia
Depleting Antithymocyte Antibodies to lymphocytes Cytokine release syndrome, anemia,
antibodies globulin, OKT3, remove cells from bleeding, thromboembolism
alemtuzumab circulation

mTOR, mammalian target of rapamycin; IL, interleukin; DM, diabetes mellitus; GI, gastrointestinal.

side-effect profile as compared with CsA, with less transplant-


associated malignancy, although it has significant nephro-
toxicity when used for long periods of time. Tacrolimus
has replaced cyclosporine in many protocols for solid organ
Immunosuppressive Targets of T-Cell Activation transplantation and has been a mainstay in all the clinical
reconstructive transplantation treatment regimen. RAPA is
an inhibitor of the mammalian target of rapamycin (mTOR),
APC which in turn inhibits multiple biochemical pathways criti-
cal for cellular proliferation with the main target being
T cells. RAPA is an attractive alternative to CsA and FK506,
having a significantly different side-effect profile in particu-
lar with regard to its nephrotoxicity, promoting tolerance
B7 in some circumstances, and having anti-proliferative and anti-
neoplastic properties. It does, however, suffer from the draw-
MHC Rapamycin back of having profound negative effects on wound healing
Ag CD 28 that may preclude its use in the early postoperative period.
IL-2R
These immunosuppressive agents have been reported to allow
successful allogeneic transplantation in clinical solid organ
TCR transplantation and VCA such as extremity transplantation and
face transplants with both high graft and patient survival rates.
Cyclosporine mTOR In addition to the three classes of drugs used for maintenance
T-cell immunosuppression, many protocols include the addition of
Calcineurin an induction agent, which causes the depletion of T cells in the
FK506 Steroids perioperative period. The goal of this therapy is to decrease the
FKBP12 NF B chance of acute rejection immediately after the transplant,
but to allow the recovery of the immune system and repopu-
lation of the T-cell compartment in the presence of the new
graft and immunosuppressive medications. This may alter the
NF3 T-cell population toward a more tolerant phenotype allowing
MMF Cell cycle
NFAT less immunosuppression. Polyclonal anti-thymoglobulin and
Nucleotide AP-1 anti-lymphocyte sera have been used in several studies for the
systhesis depletion of recipient T cells and prevention of graft rejection.
IL-2 gene Furthermore, studies using monoclonal antibodies against
AZT T-cell receptors (TCRs), anti-CD3 immunotoxin, an anti-CD3
T Cell activation
monoclonal antibody conjugated to a mutant form of the
Figure 6.2. Immunosuppressive targets of T-cell activation. diphtheria toxin protein, and Campath-1H (alemtuzumab),
Immunosuppressive medications interrupt T-cell activation at various an anti-CD52 monoclonal antibody, have been used to deplete
pathways. Cyclosporine A and FK506 interrupt the T-cell receptor lymphocytes yielding beneficial results for prolongation of
(TCR) signaling cascade by blocking calcineurin activation, the latter by graft survival. Total body, thymic, and graft irradiation have
interaction with FK binding proteins. Rapamycin blocks the mammalian all been used as induction treatments in the early days of solid
target of rapamycin signaling from both interleukin 2 receptor activation organ transplantation in both clinical and experimental studies,
and TCR coreceptors interrupting the “second signal” pathway. Steroids
alter gene transcription by modulating the effects of transcription factors
although they are not commonly used in current protocols.
including several necessary for T-cell activation. Azathioprine and myco- The ultimate success and further acceptance of the field
phenolate mofetil inhibit the production of nucleotides in lymphocytes of reconstructive transplantation will depend on develop-
blocking the cell cycle and proliferation. ments that reduce immunosuppressive sequela. Immunologic
tolerance and the abrogation of the need for chronic

(c) 2015 Wolters Kluwer. All Rights Reserved.


60 Part I: Principles, Techniques, and Basic Science

immunosuppression will be the ultimate refinement in this auto- and allografts in sheep laid the groundwork for research
ongoing process. in the fields of both skin grafting and transplant immunology.
Baronio’s contributions are considered fundamental to the
Immunologic Tolerance field of plastic surgery. Experimental use of skin allografts
helped to elucidate and define the process and mechanisms
The precise definition of transplantation tolerance, often dis-
of allograft rejection. At first, a skin allograft is accepted just
cussed and rarely agreed upon, can be regarded as the lack
as any skin autograft. However, once the skin allograft is
of a destructive immune response toward the allograft in the
revascularized, the recipient immune system mounts a cellular
absence of ongoing immunosuppressive therapy. However,
immune response. Two to three weeks following placement,
implicit in this definition is that such a state must coexist
the allograft is rejected through an antigen-specific T cell–
with general immune competence, including normal immune
mediated response resulting in loss of the skin allograft, neces-
responses to pathogens and cancer risks no different than the
sitating alternative wound coverage most typically with skin
general population.
autograft.
Acceptance or tolerance of one’s own tissues first develops
The most frequent clinical use for skin allografts is in the
in utero, along with an immunologic ability to recognize for-
treatment of extensive burns. The ability to place temporary
eign tissue. The ability of the immune system to distinguish
skin grafts without jeopardizing limited autogenous donor
between self and foreign antigens is controlled by two mecha-
sites in these patients has resulted in dramatic improvements
nisms called central and peripheral tolerance. The thymus
in the survival of high total body surface area burn wounds
plays a major role in the maintenance of tolerance to self and
(Chapter 16). In some patients who are immunosuppressed
also the induction of tolerance to alloantigens. The mechanism
either through medications or through severe illness, skin
of T-cell tolerance in the thymus is based on the deletion of self
allografts have been shown to be tolerated with continued
or alloreactive T cells upon interaction with bone marrow–
immunosuppression. Anecdotal reports of patients who have
derived APCs. Since such clonal deletion causes the elimina-
undergone slow withdrawal of immunosuppression have not
tion of donor reactive T cells, it is considered one of the most
required re-grafting either through permanent tolerance of the
robust mechanisms for tolerance induction. In experimental
graft or more likely through slow substitution of the allograft
models, deletion of antigen-specific T cells can be induced by
with recipient cells.
direct injection of donor antigens into the thymus. Following
Skin allografts will continue to be one of the most com-
intrathymic injection, donor antigens will be presented by
mon forms of human allotransplantation. These grafts are
APCs to thymocytes, and this will allow for activation of allo-
vital to the treatment of wounds and burns. However, the
reactive T cells in the thymus and their deletion. Although
health status of patients presenting with these types of wounds
intrathymic injection has been successful in rodent models, it
precludes the use of long-term immunosuppression to achieve
has been of limited efficacy in larger animals. Another widely
graft maintenance due to the additional risk of opportunistic
researched approach for the induction of tolerance is the use of
infection. Future research developments that enable prolonged
hematopoietic bone marrow transplantations to induce mixed
skin graft survival in the absence of immunosuppression
chimerism. The term chimera is derived from the Greek myth-
would precipitate a significant paradigm shift in the treatment
ological figure comprised of the parts of different animals. The
of severe wounds and burns.
chimeric animals develop an immune system that is tolerant of
both donor and recipient antigens.
Immunologic tolerance is also controlled in the periphery. Skin Xenograft
The mechanisms of peripheral tolerance include T-cell anergy Porcine xenograft has been used as a temporary dressing
(non-responsiveness), induction of T regulatory/suppressor for large burns. It is applied with a technique similar to that
cells, or T-cell deletion. The induction of T-cell anergy has been used for human allograft, with seeding of autologous grafts
demonstrated by the blockade of costimulatory signals using beneath it. The application of xenogeneic dermis has also been
monoclonal antibodies during T-cell activation. The induc- found valuable in preparing a wound for subsequent grafting
tion of T regulatory/suppressor cells is another mechanism to by stimulation of granulation tissue formation. Xenogeneic
induce T-cell tolerance specific to donor antigens. T regulatory tissue has limited uses in skin grafting at present and its cellu-
cells play a key role in the maintenance of tolerance to both lar components are susceptible to hyperacute rejection typical
self and foreign antigens. Furthermore, studies in recent years of all xenograft materials.
have demonstrated the potential role for particular subtypes of
DCs such as plasmacytoid to promote and maintain peripheral
tolerance to transplantation antigens. Bone Allograft
As discussed previously, immunologic tolerance is defined Reconstruction of large bony defects in the axial and periph-
as specific unresponsiveness of the immune system to donor eral skeleton with non-vascularized allogeneic bone has been
antigens. However, this definition does not allow for the widely practiced. Well-organized tissue banks and improved
differentiation of systemic tolerance from the clinical situ- methods of bone sterilization and preservation have made
ation of immunosuppression-free long-term graft acceptance. this possible. Very few of the donor cells, if any, in the non-
Mononuclear cell infiltration and the induction of alloantibodies vascularized bone allograft survive. These donor cells express
have been observed in long-term renal allograft rhesus monkey antigens similar to other allogeneic tissues and are rejected.
recipients that were weaned off immunosuppression. Based The remaining bone acts as a scaffold for ingrowth of recipient
on this and similar observations, it is critical to define immu- mesenchymal stem cells (osteocyte precursors), which repopu-
nologic tolerance using stringent criteria as well as to develop lates the donor by “creeping substitution.” Although technically
assays and tools to monitor for donor-specific nonreactivity in an allogeneic tissue transplant, non-vascularized allografts are
operationally tolerant transplant recipients in the future. totally replaced by recipient cells once the healing process is
complete and no immunosuppression is given. Due to slow
Current Transplantation union, long-term fixation is required of bone allograft, which
is prone to stress fracture and loosening of fixation hardware.
in Plastic Surgery In studies of retrieved human allografts, however, union was
seen at the graft–host interface.
Skin Allograft Vascularized bone allograft on the other hand contains
Skin allografts are the most commonly performed human living donor cells and is susceptible to immunologic rejec-
allotransplant and were the basis of the first transplantation tion. The humoral and cellular responses generated by the
research. Pioneering experiments by Guiseppe Baronio on transplanted bone was found to be similar in intensity and
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 6: Transplantation Biology and Applications to Plastic Surgery 61
timing as that generated by other vascularized allogeneic tis- neurorrhaphy without tension. The nerve graft undergoes the

Principles, Techniques, and


sues such as the skin and muscle. Although individual bone same degenerative process as in the distal nerve after division.
cells express antigens, the predominant antigenic stimulus in The myelin sheath remains with Schwann cells that act as a bio-
a bone allograft is thought to be derived from the marrow. logical conduit for the regenerating axons. Vascularized nerve
Removal of bone marrow by irradiation or replacement with grafts are theoretically advantageous, particularly in scarred

Basic Science
recipient marrow has been shown experimentally to prolong beds. Other “conduits” used as nerve grafts have included
allograft survival. Like any other allogeneic tissue, this rejec- autologous vein, silicone tubes seeded with Schwann cells,
tion process can be ameliorated with immunosuppression, and and freeze-fractured autologous muscle. Autologous nerve
long-term survival of orthotopic vascularized skeletal allograft grafts with acceptable donor site morbidity are limited, and
has been achieved in animal models. However, the adverse extensive nerve reconstruction may require other sources such
effects of prolonged immunosuppression required for survival as nerve allografts. Immunologic rejection of nerve allograft
of a vascularized bone allograft preclude its clinical applica- can be ameliorated experimentally with immunosuppressive
tion currently as autologous sources of vascularized bone and drugs, and axons were found to traverse the allogeneic nerve
non-vascularized allograft are usually sufficient to reconstruct graft in rodents. A similar result has also been demonstrated
most simple bone defects. A series of knee vascularized com- in primates. Immunosuppression was necessary during axonal
posite allotransplants have been performed with poor results. regeneration but could be terminated afterward in some studies
Allografts failed in five of the six patients, presumably due with satisfactory nerve functions. In the only clinical experience,
to rejection and the lack of the ability to adequately monitor Mackinnon reported return of motor and sensory functions in
the immunologic status of the graft without an externalized the upper or lower limbs of six out of seven patients following
skin component. nerve allograft reconstruction.

Cartilage Allograft
Clinical Reconstructive Transplantation
Cartilage is composed of chondrocytes within lacunae dispersed
throughout a water-laden matrix. The matrix is composed Upper Limb Transplantation.  The field of reconstructive
predominantly of proteoglycans and type II collagen. Water is transplantation has been led by hand transplantation
important as cartilage has no intrinsic blood supply and relies (Figure 6.3). The first attempted hand transplantation
on diffusion of nutrients and oxygen through this matrix. occurred in 1964 in Ecuador by Dr. Robert Gilbert. Although the
The combination of water and proteoglycans imparts the surgery was successful, the immunosuppressive regime available at
characteristic of viscoelasticity depending on the relative that time was insufficient to prevent acute rejection and the trans-
concentrations of both elements. The variable water content planted hand was lost after only 3 weeks. This led to the conclu-
in the matrix causes a balanced tension within it and helps sion that hand transplantation or any transplant containing skin
maintain its three-dimensional shape. The viscoelastic property was not immunologically feasible. This attitude prevailed until
of the matrix confers “memory” such that cartilage returns to the late 1990s. The rapid growth of immunosuppressive medica-
its original shape after deformation. Surgical manipulation tions and the remarkable success of solid organ transplantation
or scoring disrupts this equilibrium. In contrast to osteocytes, in the 1980s and 1990s led to renewed interest in VCA.
chondrocytes have little reparative ability and heal by form- Through the pioneering work of Dr. Jean-Michel Dubernard
ing fibrous scar tissue. There are histologically three types of in France (1998) and Dr. Warren Breidenbach in the United
cartilage: hyaline, elastic, and fibrocartilage. States (1999), hand transplantation was shown to be possible
Chondrocytes express HLA antigens on their surface and with highly encouraging immunologic and functional results.
are thus immunogenic in isolation. Cartilage, however, is Furthermore, hand transplants could be maintained on conven-
immunologically privileged due to the shielding of chondro- tional triple-drug immunosuppression at levels similar to that
cytes by its matrix, which is only weakly antigenic. Surgical used in solid organ transplantation and patients had functional
scoring or dicing of cartilage allograft with the resultant expo- recovery similar to that seen with replantation. Although the
sure of allogeneic cells has been shown to hasten cartilage French patient became noncompliant with medication therapy
resorption. and ­subsequently required the removal of his transplant, the
Cartilage allografts have been used successfully for similar American patient has had almost a decade and a half of use
applications as autologous cartilage. Allogeneic cartilage can be from his transplanted hand and remains a vocal advocate of
either preserved or fresh. Preserved cartilage has the advantage of hand transplantation.
a more abundant supply and decreased risk of infection in com- In the intervening decades since the beginning of the mod-
parison to fresh cartilage. Although immunologically privileged, ern era of hand transplantation, there have been over 70
cartilage allografts are still susceptible to loss of volume through transplants performed worldwide in centers across the United
resorption. Whether this is due to immunologic rejection or States, Europe, and Asia. In general, the results have been
lack of viable cells following preservation is a matter of debate. excellent with very few grafts lost, good hand function,
It has also been noted that small allografts are less prone to and relatively few side effects. Of the centers participat-
volume loss than larger grafts. ing in the International Registry on Hand and Composite
Tissue Transplantation, results from 1998 to 2010 included
Cartilage Xenograft 49 transplanted hands in 33 patients. Of these patients, one
patient died due to sepsis following combined hand and face
Some authors have advocated the use of bovine-derived carti-
transplantation and three additional grafts were lost: one
lage xenografts. However, both chondrocytes and matrix are
from infection, one from patient noncompliance, and one
subject to xenogeneic mechanisms of rejection with a gener-
from intimal hyperplasia possibly representing a form of
ally poorer outcome in comparison to autologous or allogeneic
chronic rejection. All patients who have maintained their
cartilage grafts. Attempts to modify these xenogeneic responses
grafts developed protective sensation, 82.3% had discrimi-
by altering the graft’s immunologic stereotactic structure have
native sensation, and 75% reported significant improvement
been reported as being beneficial.
in quality of life. Immunosuppressive side effects included
opportunistic infection (i.e., cytomegalovirus reactivation),
Nerve Allograft diabetes, avascular necrosis of the hip, and post-transplant
The best clinical outcome following nerve transection is malignancy including one case of post-transplant lymphop-
achieved with primary repair. More extensive injuries or a delay roliferative disease.
in repair may result in a nerve gap following debridement of Although the risk/benefit ratio of placing a patient on
damaged nerves, and a nerve graft may be necessary to achieve long-term immunosuppressive medications must always
(c) 2015 Wolters Kluwer. All Rights Reserved.
62 Part I: Principles, Techniques, and Basic Science

Recipient arm

Volar skin flap

Brachioradialis muscle
Cephalic vein
Radial artery
Radius Flexor carpi radialis muscle
Flexor digitorum
superficialis muscle
Bone plate
Palmaris longus muscle
Flexor pollicis longus tendon Basilic vein
Flexor carpi radialis tendon Flexor carpi ulnaris muscle
Median nerve Flexor digitorum profundus tendon

Ulna
Ulnar artery

Ulnar nerve

Dorsal skin flap

Flexor carpi ulnaris tendon

Skin flap

Donor hand

Flexor digitorum profundus tendon

Flexor Policis tendon

Flexor digitorum superficialis tendon

Figure 6.3.  Hand transplantation. Schematic diagram showing the technique of mid-forearm hand transplantation. All structures are prepared
and labeled prior to transplantation and osseous fixation. Note the opposing, interdigitating skin flap design. Inset: photograph of allograft pre-
pared for transplant.

be considered, advances such as minimization protocols With an ever-increasing number of centers performing
using donor bone marrow infusion and monotherapy main- hand transplantation worldwide and more than a decade
tenance are currently being studied in humans and are of experience with the techniques, hand transplantation has
anticipated to favorably alter this balance in the future. become less novel. It is increasingly being seen as another
The senior author and his team have performed eight limb alternative in the reconstructive armamentarium used to
transplants in five patients using alemtuzumab induction treat patients with upper extremity amputation (Chapter 90).
therapy at the time of transplantation followed by an infu- Upper limb transplantation restores the structure and func-
sion of bone marrow cells collected from the vertebral tion of the hand in a way not possible with any other recon-
bodies of the limb donor. In four of the five patients, the structive technique with a reasonable level of safety. It appears
immunomodulation caused by the donor bone marrow that reconstructive transplantation will continue to play an
infusion has reduced the need for systemic immunosup- increasing role in the treatment of patients with upper limb
pression and allowed the use of single-agent therapy with amputations. However, as always the risk/benefit ratio for the
tacrolimus. use of systemic immunosuppression, regardless of whether it

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 6: Transplantation Biology and Applications to Plastic Surgery 63
is single drug or multidrug, must be considered when deciding
Other Areas of Reconstructive

Principles, Techniques, and


whether to operate on patients with complex injuries of the
upper extremity. Transplantation
Developments in reconstructive transplantation have
Facial Transplantation.  No other area of reconstructive clearly been led by upper extremity and facial transplan-

Basic Science
transplantation captures the imagination of patients, clinicians,
tation. However, there have been much smaller series
and the public like face transplantation. Human beings’ per-
of patients treated with transplantation of several other
ception of “self” is tied to one’s facial appearance; transferring
composite structures including vascularized knee joints,
these tissues from one person to another raises major questions.
lower extremities, trachea, larynx, abdominal wall, and
However, for some patients with severe and devastating injuries
reproductive organs. With the exception of vascularized
to the craniofacial skeleton and soft tissues of the face, there
knee joints (which have failed in five of the six patients
is no other acceptable, effective option using standard recon-
attempted), reconstruction with these varied types of
structive techniques. For these patients, transplantation of
transplants has met with some qualified success. In gen-
allogeneic cadaveric facial structures may be the only way of
eral, patients are maintained on standard types of immu-
regaining normal facial appearance and being able to reintegrate
nosuppression (i.e., triple-drug therapy) with no more or
into society in a meaningful way.
less complications from these regimens than those of solid
Dr. Dubernard and Dr. Devauchelle in France performed
organ transplant patients. While these less common types of
the first transplantation of facial tissue in 2005. Between 2005
transplants continue to be highly experimental, they dem-
and 2012, eighteen partial or full-face transplantations have
onstrate the possibilities that reconstructive transplantation
been performed worldwide. These were done by centers in
offers. Traditional plastic surgery techniques are unable to
the United States, France, Spain, and China. Transplanted
restore complex tissues and anatomical structures with
grafts have consisted of soft tissue (the nose and lips) up to
the fidelity equal to that of reconstructive transplantation,
and including all facial soft tissue and portions of facial bones
as evidenced by recipients’ functional and aesthetic out-
and the tongue (entire face, maxilla, anterior portion of the
comes. As clinical experience with these techniques is accu-
mandible, and tongue). Indications for these procedures have
mulated and immunosuppressive and immunomodulatory
included ballistic trauma sustained by military personnel and
protocols are optimized, the risk–benefit ratio of reconstruc-
civilians, animal bites, tumor resection, neurofibromatosis,
tive transplantation will continue to shift in favor of these
and burns. All of the patients’ transplants have included either
procedures, making these techniques an increasingly avail-
portions of the orbicularis oris or oculi; loss of the sphincter
able and important part of plastic surgeons’ reconstructive
function of the mimetic muscles of the face is generally con-
options for treating these crippling defects.
sidered to be one of the indications for facial transplantation.
In general, face patients have been maintained on immuno- Suggested Readings
suppression similar to that used in solid organ transplanta-
1. Brandacher G, Gorantla VS, Andrew Lee WP. Hand allotransplantation.
tion, with all patients receiving induction therapy followed by Semin Plast Surg. 2010;24(1):11-17.
triple-drug immunosuppression. 2. Chang J, Davis CL, Mathes DW. The impact of current immunosuppression
Overall, patient outcomes have been excellent. All strategies in renal transplantation on the field of reconstructive transplantation.
patients receiving facial transplantation have dramatically J Reconstr Microsurg. January 2012;28(1):7-19.
3. Devauchelle B, Badet L, Lengele B, et al. First human face allograft: early
improved their aesthetic appearance, allowing easier inte- report. Lancet. July 2006;368(9531):203-209.
gration back into society. All patients for whom outcomes 4. Hettiaratchy S, Melendy E, Randolph MA, et al. Tolerance to composite
have been reported in the literature report nearly normal sen- tissue allografts across a major histocompatibility barrier in miniature swine.
sory recovery, with return of normal two-point discrimina- Transplantation. 2004;77(4):514-521.
5. Lee WP, Yaremchuk MJ, Pan YC, Randolph MA, Tan CM, Weiland AJ.
tion between 3 and 8 months after transplantation. Motor Relative antigenicity of components of a vascularized limb allograft. Plast
recovery has been slower, but all patients have recovered Reconstr Surg. 1991;87(3):401-411.
some degree of motor function allowing for oral compe- 6. Levi DM, Tzakis AG, Kato T, et al. Transplantation of the abdominal wall.
tence. Typical motor recovery begins at 3 months, with Lancet. 2003;361(9376):2173-2176.
7. Mackinnon SE, Doolabh VB, Novak CB, Trulock EP. Clinical outcome
maximum recovery around 18 months after transplant. following nerve allograft transplantation. Plast Reconstr Surg. 2001;
Unfortunately, there have been 2 deaths (a 15% mortality 107(6):1419-1429.
rate) associated with facial transplantation among these 13 8. Madani H, Hettiaratchy S, Clarke A, Butler PE. Immunosuppression in an
patients. The first death was in a Chinese patient; however, emerging field of plastic reconstructive surgery: composite tissue allotrans-
plantation. J Plast Reconstr Aesthetic Surg. 2008;61(3):245-249.
this death has not been reported in the literature and so the 9. Petruzzo P, Lanzetta M, Dubernard J-M, et al. The International Registry
etiology remains unclear. The second death occurred in a on Hand and Composite Tissue Transplantation. Transplantation. 2010;
patient who received a combined bilateral hand and face 90(12):1590-1594.
transplant for the treatment of extensive burns. This patient 10. Pomahac B, Pribaz J, Eriksson E, et al. Three patients with full facial
transplantation. N Engl J Med. February 2012;366(8):715-722.
reportedly succumbed to overwhelming infection following 11. Sacks JM, Keith JD, Fisher C, Lee WP. The surgeon’s role and responsibility
immunosuppression. No surviving patients have lost their in facial tissue allograft transplantation. Ann Plast Surg. 2007;58(6):595-601.
grafts due to rejection to date. 12. Sacks JM, Horibe EK, Lee WP. Cellular therapies for composite tissue
Facial transplantation is following hand transplanta- allograft transplantation. Clin Plast Surg. 2007;34(2):291-301.
13. Shores JT, Brandacher G, Schneeberger S, Gorantla VS, Andrew Lee WP.
tion as the next success story of reconstructive transplan- Composite tissue allotransplantation: hand transplantation and beyond.
tation. Although technically demanding and potentially J Am Acad Orthop Surg. 2010;18(3):127-131.
dangerous, facial transplantation has the potential to 14. Shores JT, Imbriglia JE, Andrew Lee WP. The current state of hand trans-
reintegrate patients into society who have been injured plantation. J Hand Surg. 2011;36(11):1862-1867.
15. Siemionow M, Agaoglu G. Tissue transplantation in plastic surgery. Clin
so severely that they are simply unable to function in Plast Surg. 2007;34(2):251-269, ix.
or contribute to society in their current state. As more 16. Siemionow M, Ozturk C. An update on facial transplantation cases performed
and more centers perform this groundbreaking tech- between 2005 and 2010. Plast Reconstr Surg. 2011;128(6):707e-720e.
nique, the number of patients treated per year has steadily 17. Strome M, Stein J, Esclamado R, et al. Laryngeal transplantation and
40-month follow-up. N Engl J Med. 2001;344(22):1676-1679.
increased. There is a clear indication that for carefully 18. Wendt JR, Ulich TR, Ruzics EP, Hostetler JR. Long-term survival of
selected patients, facial transplantation offers a procedure human skin allografts in patients with immunosuppression. Ann Plast Surg.
that, while not life saving, is potentially life restoring. 2004;113(5):411-417.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 7  n  Implant Materials
Timothy W. King

be inert and withstand the corrosive environment within the


Introduction human body. Since metals cannot repair themselves after
While autogenous tissues are often the first choice, implant deformation or fatigue, they must have mechanical properties
materials have wide application in plastic surgery including that exceed the properties of the natural tissue they are sup-
reconstruction or augmentation of soft-tissue defects, bony porting or replacing (i.e., the metal must be both stronger and
deformities, or the fixation of fractures. Selecting the implant stiffer than the natural tissue).
material depends on the specific requirement for its applica-
tion. For example, tissue ingrowth into a polypropylene mesh Stainless Steel
or the rigid incorporation of a bone substitute is often desir- Stainless steel has been used as a biological implant since the
able, while the encapsulation (or lack of tissue ingrowth) of 1920s. Medical-grade stainless steel, alloys of iron–chromium–
a silicone Hunter rod allows for free gliding of a subsequent nickel, have a relatively high tensile strength but are easily
tendon graft. deformed (bent). While this is useful in some applications, such
Autologous tissue may be more appropriate in many clini- as the application of arch bars for maxillomandibular fixa-
cal scenarios including patients with a history of radiotherapy, tion, overall these mechanical properties are less desirable than
marginal blood supply of the surrounding tissue, or tenuous other currently available materials such as cobalt–chromium
soft-tissue coverage over the implant. In these cases, the risk and titanium. In addition, stainless steel leaches metallic ions
of implant-related complications, including infection and into the surrounding tissues, causing an inflammatory reac-
implant extrusion, is significant, and the use of an alloplastic tion and pain. Stainless steel is currently used in surgical wire
implant should be avoided if possible. and in arch bars. In the past, bone fixation systems utilized
Implant materials, however, can be used as alternatives to stainless steel, but other alloys have replaced stainless steel in
autogenous tissue in selected cases and in specific situations this application.
are superior to autogenous tissue. Implant materials can be
created to undergo no resorption and are preferable to autolo- Cobalt–Chromium
gous grafts that will resorb when used as onlay grafts. For
example, implants have been successfully used as bone graft Historically, cobalt–chromium alloys have been one of the
substitutes in orbital floor reconstruction, cranioplasty, and most significant biomaterials used in humans. Vitallium, a
maxillofacial reconstruction. They have the advantage of cobalt–chromium–molybdenum (Co-Cr-Mo) alloy, was first
avoiding operative time for graft harvesting and the absence described in 1932 to address some of the problems experi-
of donor site morbidity. enced with stainless steel. Co-Cr-Mo alloy was used in early
craniofacial miniplates and screws and revolutionized the field.
The major disadvantage of Co-Cr-Mo alloys is the scatter
History artifact on computed tomography (CT) imaging. Because
The first recorded use of an artificial material can be traced to of this, and other benefits, titanium has essentially replaced
30,000 B.C. where these materials were used as sutures. The Co-Cr-Mo alloys in most biomedical applications.
first recorded implant was thought to date back to 3,000 B.C.
where pre-Incan Peruvians used materials such as gold, silver, Titanium
or nut shells to repair trephination defects. However, recent Commercial-grade medical titanium implants were intro-
investigations have brought these reports into question. duced in the early 1980s and have almost entirely replaced the
Regardless, over the next 5,000 years, implant use was spo- other alloys in medical applications because they are stronger,
radic and limited by infection and foreign body reaction. The are lighter, have higher resistance to corrosion, and cause
modern era of medical implants is often attributed to British
ophthalmologist Harold Ridley who noted that Spitfire canopy
plastic unintentionally implanted in the eyes of pilots healed
without adverse reaction. Based on this finding he developed Table 7.1
and implanted the first artificial lens into a human in 1949. Properties of an Ideal Implant
As surgeons, engineers, and scientists continued to create
new implant materials, it became clear that there were certain Minimal foreign body reaction
properties that an ideal implant would impart. Cumberland1 Elastic or supple
and Scales2 described the properties of an ideal implant, which
are shown in Table 7.1. Remarkably, although these criteria Easily tailored
were published almost 60 years ago, they are still the funda- Good tissue incorporation
mental properties that manufacturers of modern biomaterials
Allow collagen ingrowth
attempt to achieve.
For the purpose of this chapter, implant materials will be Promote permanent tissue repair
divided into the following general categories: metals, poly- Good tensile strength
mers, ceramics, glues, skin substitutes, and bioprosthetic
meshes (Table 7.2). Tolerate infected environments
Minimal wound complications
Metals Data from Cumberland VH. A preliminary report on the use of
In order to achieve the mechanical and biophysical properties prefabricated nylon weave in the repair of ventral hernia. Med J Aust.
1952;1:143-144 and Scales JT. Materials for hernia repair. Proc R
desired for applications in medicine, combinations of metals Soc Med. 1953;46:647-652.
(alloys) have been developed. These alloys are designed to
64
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 7: Implant Materials 65
Table 7.2

Principles, Techniques, and


Implant Materials
Metals

Basic Science
  Stainless steel
 Cobalt–chromium
 Titanium
 Gold
 Platinum
Polymers
 Silicone
 Polytetrafluoroethylene
 Polyester
  Polypropylene (Prolene, Marlex)
Figure 7.1.  Titanium plates for midface reconstruction. L-shaped
  Polyethylene (Medpor) and curvilinear 2.0 mm plates with a 7, 5, and 3 mm length 2.0 mm
 Polymethylmethacrylate screw (left to right).
  Biodegradable polyesters
  Polyamides (Supramid, Nylamid)
Ceramics Gold
 Hydroxyapatite Although gold is chemically inert, it has poor mechanical
  Tricalcium phosphate properties in its pure form. When strength is required (for
example, in dental fillings), a gold alloy is used. For applica-
Adhesives and glues
tions such as eyelid weights in patients with lagophthalmos,
  Fibrin tissue adhesives where strength is not an issue, 24-carat gold alloy (99.9% w/w
 Cyanoacrylates purity) is used to ensure chemical inertness.
Biologic materials Platinum
 Skin substitutes Platinum is an inert metal and is the material of choice for
  Integra patients with gold sensitivity in need of eyelid implants
for lagophthalmos. Platinum has a higher density than gold,
  Epicel
thus the eyelid implants have a lower profile and are less
  Dermagraft noticeable than gold implants. Some formulations containing
  Apligraf platinum, however, have been shown to be immunogenic and
have raised concerns about long-term exposure. Platinum is
  Bioprosthetic mesh also used as a catalyst in the formation of some polymers,
   Small intestinal submucosa including the production of medical-grade silicone used in gel
breast implants.
   Human acellular dermal matrix
   Porcine acellular dermal matrix
Polymers
  Bovine pericardium
Polymers are molecules composed of repeating monomer sub-
   Bovine fetal dermis units. The physical characteristics of a polymer are defined
by the structure of the monomer, the number of monomer
units in the polymer chain, and the degree of cross-linking. As
polymer chains are cross-linked, the ability for them to move
less inflammation. Titanium also has less stiffness, which
independently is decreased. Thus, a polymer with little cross-
results in less stress shielding (localized osteopenia second-
linking might exist as a liquid while the same polymer with
ary to the implant protecting the bone from normal loading).
abundant cross-linking becomes a “gel” or “solid.”
More recently, some companies have also introduced titanium
alloy implants. The alloys are stronger than the pure titanium,
allowing for thinner plates without compromising their overall Silicone
strength. Pure titanium or titanium alloys (which have less Silicone is likely the most maligned and misunderstood
than 0.5% iron) have two additional beneficial properties: implant material today secondary to its use in breast implants.
they do not set off metal detectors, and they do not create Silicone gel–filled breast implants were first introduced in the
a significant artifact on CT or magnetic resonance imaging United States in 1962. Multiple variations and modifications
studies. Finally, titanium can form chemical bonds with the to the shell and gel were made over the years in an attempt to
surrounding mineralized bone without fibrous tissue form- improve the outcomes of breast augmentation and reduce the
ing between the implant and the bone. This unique charac- associated complications. In 1992, the U.S. Food and Drug
teristic allows titanium to be used to create osseointegrated Administration (FDA) stated that there was “inadequate
implants. Plastic surgery applications of these alloys include information to demonstrate that breast implants were safe
plates and screws for fixation of bone and titanium mesh for and effective” and placed a moratorium on silicone gel breast
use in applications such as orbital wall reconstruction (see implants for cosmetic purposes but allowed their continued use
Figure 7.1). for reconstruction after mastectomy, correction of congenital

(c) 2015 Wolters Kluwer. All Rights Reserved.


66 Part I: Principles, Techniques, and Basic Science

deformities, or replacement of ruptured silicone gel–filled


implants due to medical or surgical reasons.3 The Department Polytetrafluoroethylene
of Health and Human Services (HHS) subsequently appointed Polytetrafluoroethylene (PTFE) also known as Teflon was acci-
the Institute of Medicine (IOM) of the National Academy of dentally invented by Roy Plunkett in 1938 while he was trying
Science to begin one of the most extensive research studies to develop a refrigerant. It consists of a carbon backbone with
in medical history. In 1999, the IOM released a comprehen- fluorine side chains. Expanded PTFE (ePTFE or Gore-Tex) was
sive report on both saline-filled and silicone gel–filled breast created by Bob Gore in 1969. It is very chemically stable, cannot
implants finding that “evidence suggests diseases or condi- be cross-linked (which makes it flexible), and has a non-adher-
tions such as connective tissue diseases, cancer, neurological ent surface. It has been used for a wide variety of applications
diseases or other systemic complaints or conditions are no from hiking boots to coatings on frying pans. Within the medi-
more common in women with breast implants than in women cal field it is used for vascular grafts, as a mesh for abdominal
without implants.”3 wall reconstruction, and as implants for facial augmentation.
In 2006, the ban imposed by the FDA was lifted. As part
of the approval process, the FDA required the two approved Polyester
manufacturers to perform a 10-year study on the safety of the
Polyester contains an ester functional group in its main chain.
devices in 40,000 women.3 Extensive investigations by several
Mersilene is a knitted polyester mesh for use in hernior-
prestigious scientific bodies (e.g., the IOM4 and the British
rhaphy. Polyester mesh is softer and more hydrophilic than
Ministry of Health5) have failed to show that systemic illness
polypropylene and in animal studies has shown better tissue
is associated with silicones. For a discussion of the recently
ingrowth. Dacron is another form of polyester that has been
described anaplastic large cell lymphoma in breast implant
used for vascular grafts.
recipients, please see Chapter 53.
With all of this research into “silicone” one might ask
“what exactly is silicone?” Silicone is a family of polymers Polypropylene
consisting of alternating silicon (Si) and oxygen (O) molecules. Polypropylene has a carbon backbone and side chains of
Poly-dimethylsiloxane (PDMS), the polymer used in most hydrogen and methyl groups. It has been used in hernia and
medical applications, is made up of the silicone backbone with pelvic organ prolapse repair, but polypropylene mesh can
two methyl side chains. It is one of the most inert biomateri- erode through the soft tissues over time. Therefore, the FDA
als available for use in medical devices. Altering the length has issued warnings on the use of polypropylene mesh in pelvic
and molecular weight of PDMS can change the mechanical organ prolapse. It is also used as suture material because of its
properties and behavior of the silicone gel. Low-molecular- strength and low foreign body reaction within the body.
weight PDMS (<30 monomers) has a viscosity similar to
baby oil, while high-molecular-weight formulations ( >3,000 Polyethylene
monomers) are solids. Other methods of altering the mechani-
Polyethylene consists of a carbon backbone with hydrogen
cal properties include controlling the degree of cross-linking,
side chains (ethylene). A high-density porous form of polyeth-
changing the additives, and altering the curing process. For
ylene (Medpor) is used for facial implants (see Figure 7.2).
example, the silicone gel used in breast implants is cured in a
hydrosilation reaction where some of the methyl side chains
(CH3) are replaced with vinyl side chains (CH“CH2), which
then allows the silicone chains to cross-link with each other.
The silicone shell of a breast implant consists of fully polym-
erized silicone and an amorphous (noncrystalline) silica filler
added for strength.
Medical-grade silicone is ubiquitous, being found in more
than 1,000 medical products as a component or as a resid-
uum from the manufacturing process. For example, every
disposable needle, syringe, and intravenous tubing is lubri-
cated with silicone. Medications in stoppered vials contain
residual silicone from its use in the manufacturing process.
Silicone elastomers, in their solid form, are used for pace-
maker coatings, tubing, prosthetic joints, hydrocephalus
shunts, and penile implants. Like breast implants, some tes-
ticular and chin implants are made of a silicone gel in a sili-
cone envelope.
Silicones are also found in some medications. Ingredients
with the name “methicone” (e.g., simethicone) are silicones that
have been modified for human consumption. Silicones are
also used in household items such as lipstick, suntan/hand
lotion, hairspray, processed foods, and chewing gum. Medical-
grade silicones invoke a nonspecific foreign body response,
resulting in macrophage invasion, giant cell formation, and
eventual scarring.
Other plastic surgery applications of silicone include facial
implants for malar, nasal, and chin reconstruction or augmen-
tation and orbital floor reconstruction. Hand surgeons use
silicone implants for arthroplasty, flexor tendon replacement,
and bone block spacers. Silicone is beneficial in these appli-
cations because it is relatively inert, malleable, and deform-
able. Low-molecular-weight silicone was used in the past as
an injectable soft tissue filler but is not FDA approved for Figure 7.2.  High-density porous polyethylene (Medpor) implants for
medical use. This application should be avoided because it can facial augmentation.
cause tissue reactions or migrate.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 7: Implant Materials 67
The porosity allows for tissue and vascular ingrowth. It can also physical properties for biomedical use including decreased

Principles, Techniques, and


be carved to customize the implant for individual patients. The foreign body response, resisting bacterial colonization, a high
implants are more difficult to place than the ePTFE implants compressive strength, and tissue ingrowth into porous materi-
because they are firmer and stiffer. In addition, the soft-tissue als (100 µm pore size for bone and 30 µm pore size for soft
ingrowth makes the implant more difficult to remove. Porous tissue). However, their benefits are overshadowed by their

Basic Science
polyethylene alone or in combination with titanium mesh is weaknesses, namely they are brittle and easily fracture under
available for reconstruction of the orbital floor. One of the tensile, torsional, or bending loads. Their main uses in plastic
disadvantages of polyethylene alone for orbital floor recon- surgery are for bone augmentation and replacement. Calcium
struction is that the implant is not visualized on CT scans, phosphates are the most common ceramics used in plastic sur-
making it difficult to evaluate implant position. gery. In addition, calcium phosphates have been shown in the
laboratory to be both osteoinductive and osteoconductive, but
Polymethylmethacrylate this has not been demonstrated in the clinical setting.
Calcium phosphates come in two formulations for medical
Polymethylmethacrylate (PMMA) is a high-molecular-weight
use: hydroxyapatite (Ca10(PO4)6(OH)2) and tricalcium phos-
polymer commonly used as a replacement for bone. The
phate (Ca3(PO4)2). Tricalcium phosphate has a faster rate of
final product is created by adding liquid methylmethacrylate
resorption and replacement by bone when compared with
monomer to powdered methylmethacrylate polymer, which
hydroxyapatite. They are available as granules for injection
then forms a moldable putty. The monomer polymerizes, binds
and as blocks (both solid and porous), and hydroxyapatite
with the polymer particles, and hardens in about 10 minutes.
is also available as a cement paste. These implants are com-
The polymerization process is an exothermic reaction, which
monly used to reconstruct non–load-bearing bones of the face
generates high temperatures. Saline irrigation is used to cool
and cranium. The cement paste is beneficial in select cases,
the surrounding tissues during the curing process to avoid
such as a cranioplasty, because it is malleable and can be
local tissue damage such as bone necrosis or soft-tissue injury.
molded during the case. For a discussion on dermal and soft-
Applications in plastic surgery include cranial bone recon-
tissue fillers, please see Chapter 42.
struction. PMMA can be used alone or in combination with
wire or mesh reinforcement. The immobility and relatively
low stresses intrinsic to the calvarium contribute to the low Adhesives and Glues
morbidity of PMMA cranioplasty.
Fibrin Tissue Adhesives
Biodegradable Polymers The first fibrin tissue adhesive was described in 1944 and was
Biodegradable polymers were developed to overcome some of used to aid in the adherence of skin grafts to the recipient tissue
the disadvantages associated with permanent implants. Most bed. Fibrin sealants consist of two parts: fibrinogen and throm-
biodegradation occurs through a combination of chemical bin derived from screened donors. A small amount of factor XIII
reactions, such as hydrolysis or oxidation, and biological pro- and calcium is included to catalyze the reaction and form polym-
cesses (e.g., enzymatic or cellular). Both the biodegradable poly- erized fibrin. The strength of the fibrin glue is directly propor-
mer and all of its breakdown products must be biocompatible.6 tional to the concentration of fibrinogen in the mixture, while
Although there are a multitude of materials that will degrade in the rate of polymerization is regulated by the concentration
vivo, there are only a few that are clinically relevant as biodegrad- of the thrombin. Plastic surgery applications for fibrin sealants
able polymers. α-Hydroxy acids, specifically poly (lactic acid), include brow lift, facelift, abdominoplasty, the latissimus dorsi
poly (glycolic acid) (PGA) and combinations, or copolymers, donor site, DIEP/TRAM flap donor sites, and chronic seromas.
of these individual polymers known as poly (lactic-co-glycolic
acid) (PLGA) are the most common biodegradable polymers Cyanoacrylate
used in clinical applications. These polymers degrade through Cyanoacrylates were accidently discovered in 1942 by Dr. Harry
hydrolysis, ending in lactic or glycolic acid. Surgeons are familiar Coover and were marketed as “super glue.” During the Vietnam
with this polymer as it is used to make Vicryl (Polyglactin 910; War, surgeons saved many lives after they discovered that spray-
Ethicon, Somerville, NJ) sutures. These polymers have been used ing cyanoacrylates over open wounds would stop bleeding and
to create a biodegradable mesh for use in abdominal wall recon- allowed injured soldiers to be transported for treatment.
struction and plating systems for craniofacial or hand applica- The exothermic polymerization begins when the cyanoac-
tions as well as in the fabrication of resorbable scaffolds for rylate is exposed to moisture (there is enough moisture in the
tissue engineering and regenerative medicine applications. air to allow polymerization to occur). Applications in plastic
The rate of degradation can be modified by altering the surgery include skin closure. The superficial layer of the skin,
ratios of lactic to glycolic acid, adding carbon fibers or other where the product is applied, has no sutures to hold it together
polymers. In general, increasing the concentration of lactic so it is important to approximate the deep layers and provide
acid decreases the rate of degradation. Manufacturers modify a tension-free abutment of the two sides. Studies comparing
the ratio of lactic and glycolic acid, as well as the specific traditional suturing to octyl-2-cyanoacrylate showed that the
manufacturing protocol, to optimize the degradation rate and outcomes were equivalent.7
strength of the polymer. For example, LactoSorb (Biomet,
Warsaw, IN) consists of 82% poly-l-lactic acid and 18%
PGA, while Resorb-X (KLS Martin, Jacksonville, FL, used in Skin Substitutes
the SonicWeld system) is 100% poly-d, l-lactic acid. The
Over the past two decades, bioengineered skin substitutes
Endotine products (Coapt Systems, Inc., Palo Alto, CA) have
have become a mainstream therapy for wound management.
the same formulation as LactoSorb. At implantation, their
Originally designed to replace skin grafts for patients with
strength is equal to that of titanium plating and then decreases
severe burns, they are now also used in the treatment of chronic
with time. Typically their structural integrity is preserved for
venous and chronic diabetic ulcers. It is likely that applications
the first 8 weeks to allow for bony healing to occur.
for these products will broaden as they become more advanced.
The ideal skin substitute would8:
Ceramics • Adhere to the wound bed rapidly
Medical applications of ceramics were developed in the 1960s. • Recapitulate the physiologic and mechanical properties of
Ceramics have a crystalline structure and are made up of normal skin
inorganic, nonmetallic molecules. They have some appealing • Be inexpensive

(c) 2015 Wolters Kluwer. All Rights Reserved.


68 Part I: Principles, Techniques, and Basic Science

• Avoid immune rejection by the host Table 7.3


• Be highly effective in accelerating tissue regeneration and
wound repair Characteristics of the Ideal Bioprosthetic Mesh
A variety of cells, mediators, and polymers have been tested Resistant to bacterial colonization and infection
in various combinations to engineer cultured skin substitutes.9
Biocompatible
We review the most common of these below and in Chapter 3.
Noncarcinogenic
Integra Readily available
Integra (Integra LifeSciences Corporation, Plainsboro, NJ) Inexpensive
is a bilayer skin substitute consisting of a “dermal” (lower)
layer (bovine collagen base with the glycosaminoglycan Withstand physiological stresses for long periods of time
­chondroitin-6-sulfate) and a silicone sheet (upper) layer.10 As Promote strong tissue ingrowth
the wound heals, the dermal layer is replaced with the patient’s Maintain its original size
own cells. The silicone sheet, which acts as a temporary epi-
dermis, is removed and a thin split-thickness skin graft is Inhibit adhesions to visceral structures
applied to the neo-dermis. Integra is used in complex wounds Provide host cells with the framework and signals to grow and
such as partial or full thickness burns and multiple types of differentiate
ulcers. Studies evaluating the efficacy of Integra showed that it
has a higher infection rate compared with autograft, allograft, Remodel as the wound gains strength and new tissue is formed
or xenograft, but appeared to have a faster rate of wound Data from Bellows CF, Alder A, Helton WS. Abdominal wall reconstruc-
healing time.10 Integra can also be used in wounds where a tion using biological tissue grafts: present status and future opportunities.
skin graft would not adhere.10 The neo-dermis will attach to Expert Rev Med Devices. 2006;3:657-675.
the underlying bed, vascularize over 2 weeks, and then will
allow adherence of a split-thickness skin graft.

Epicel (Cultured Epidermal Autografts) Small Intestinal Submucosa


Epicel (Genzyme, Cambridge, MA) is a cultured epidermal Small intestinal submucosa (SIS or Surgisis; Cook Biotech,
autograft grown from the patient’s own keratinocytes derived West Lafayette, IN) is created from the small intestine of pigs.
from a small skin biopsy. The keratinocytes are grown in a co- The submucosa of the small intestine provides mechanical
culture with fibroblasts. Once the keratinocytes are 2 to 8 cell strength to the intestine and contains a biochemically rich
layers thick, the approximately 50 cm2 autograft is attached to and diverse extracellular matrix. First described as a vascular
a petrolatum gauze backing with stainless steel surgical clips graft in 1989, SIS has been applied to over 20 applications
and applied to the patient. in humans including multiple types of hernia repair, dural
Epicel is used in patients with deep dermal or full thickness repair, bladder reconstruction, and stress urinary incontinence
burns involving a total body surface area of ≥ 30%. It can be treatment.13
used with or without split-thickness skin grafts, depending on
the severity and extent of their burns. Human Acellular Dermal Matrix
There are several products classified as human acellu-
Dermagraft lar dermal matrix (HADM) including AlloDerm (LifeCell
Dermagraft (Advanced Biohealing, Westport, CT ) is a poly- Corp, Branchburg, NJ), Allomax (Bard Davol, Murray
glactin mesh seeded with neonatal fibroblasts. The mesh is Hill, NJ), and FlexHD (Ethicon360, Somerville, NJ). Each
resorbed and replaced with the patient’s own tissue. It is used manufacturer uses a proprietary technique to produce the
as both a temporary and permanent dressing to increase the HADM from donated allograft human dermis. In general,
successful take of meshed split-thickness skin grafts on excised after the epidermis and subcutaneous tissue are removed,
burn wounds and for venous and pressure ulcers. Dermagraft the dermis is processed, either with freeze-drying or chemi-
is equivalent to allograft with respect to infection, healing cal detergents, to eliminate everything but the collagen
time, time to closure, and graft take.11 structure of the dermal matrix. Applications of HADM
include implant-based breast, abdominal wall, chest wall,
Apligraf pelvis reconstruction, and lip augmentation.14,15 Micronized
HADM (Cymetra; LifeCell, Branchburg, NJ) is also avail-
Apligraf (Organogenesis, Canton, MA) is a bilayered skin
able and has been used for laryngoplasty and as soft-tissue
equivalent. The lower “dermal” layer consists of type I bovine
filler.
collagen and fibroblasts obtained from neonatal foreskin,
while the upper “epidermal” layer is derived from keratino-
cytes. It has a shelf life of 5 days at room temperature. It is used Porcine Acellular Dermal Matrix
for venous ulcers and diabetic foot ulcers as well as a tempo- Porcine acellular dermal matrix (PADM) has been developed
rary covering over meshed autografts in excised burn wounds. for applications similar to HADM. To inhibit immunogenicity
and reduce collagenase-dependent matrix degradation, first-
generation PADMs (CollaMend; Bard Davol, Cranston, RI
Bioprosthetic Mesh and Permacol; Covidien, Norwalk, CT) undergo chemical
Currently available bioprosthetic mesh materials are derived cross-linking of the collagen fibers during the manufactur-
from decellularized mammalian tissues, either human (allo- ing process, which changes the extracellular matrix structure
geneic) or animal (xenogeneic). Bioprosthetic mesh materials and inhibits cellular infiltration, revascularization, and matrix
are processed to remove cells and other potentially immuno- remodeling potential.
genic components while preserving the native extracellular A newer generation of PADMs (Strattice; LifeCell Corp,
matrix architecture. An ideal mesh possesses the characteris- Branchburg, NJ) is processed without chemical cross-linking.
tics shown in Table 7.3.12 Several bioprosthetic mesh materials The [galactose-α (1,3)-galactose] antigen, which is the major
are available. These materials are commonly used for complex cause of the immune response associated with acellular xeno-
torso reconstruction and breast reconstruction. grafts, is enzymatically removed.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 7: Implant Materials 69
It is not entirely clear which of these products has a better
References

Principles, Techniques, and


outcome. In a recent in vivo animal study comparing cross-
linked PADM with non–cross-linked PADM for abdominal 1. Cumberland VH. A preliminary report on the use of prefabricated nylon
weave in the repair of ventral hernia. Med J Aust. 1952;1:143-144.
wall reconstruction, non–cross-linked PADM appeared to have 2. Scales JT. Materials for Hernia Repair. Proc R Soc Med. 1953;46:647-652.
early clinical advantages.16 No comparative human studies, 3. Bondurant S, Ernster V, Herdman R, eds. Safety of Silicone Breast Implants.

Basic Science
however, have been preformed to date. Washington, DC: Institute of Medicine, National Academy Press; 1999.
4. Janowsky EC, Kupper LL, Hulka BS. Meta-analyses of the relation between
silicone breast implants and the risk of connective-tissue diseases. N Engl J Med.
Other Bioprosthetic Mesh Products 2000;342:781-790.
5. Nicolai JP. EQUAM Declaration on Breast Implants, July 4, 1998.
Bovine pericardium (Veritas; Synovis, St. Paul, MN) is a non– European Committee on Quality Assurance and Medical Devices in Plastic
cross-linked collagen matrix. Decellularization and reduction Surgery. Plast Reconstr Surg. 1999;103:1094.
of immunogenicity is achieved by capping free amine groups 6. Kohn J, Abramson S, Langer R. Bioresorbable and bioerodible materials.
In: Ratner BD, Hoffman AS, Schoen FJ, Lemons JE, eds. Biomaterials
using a proprietary chemical process. Science: An Introduction to Materials in Medicine. San Diego, CA: Elsevier
Bovine fetal dermis (SurgiMend; TEI, Boston, MA) is an Academic Press; 2004:115-125.
acellular matrix derived from fetal calves. It is not cross-linked 7. Toriumi DM, O’Grady K, Desai D, Bagal A. Use of octyl-2-cyanoacrylate for
and can facilitate cell penetration, revascularization, and inte- skin closure in facial plastic surgery. Plast Reconstr Surg. 1998;102: 2209-2219.
8. Eisenbud D, Huang NF, Luke S, Silberklang M. Skin substitutes and wound
gration with host tissues. healing: current status and challenges. Wounds. 2004;16:2-17.
9. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920-926.
10. Pham C, Greenwood J, Cleland H, Woodruff P, Maddern G. Bioengineered
Future Materials skin substitutes for the management of burns: a systematic review. Burns.
2007;33:946-957.
Biomaterials and implants have made huge impacts in medi- 11. Purdue GF, Hunt JL, Still JM Jr, et al. A multicenter clinical trial of a biosyn-
cine and surgery. Some implants are designed to have little thetic skin replacement, Dermagraft-TC, compared with cryopreserved
human cadaver skin for temporary coverage of excised burn wounds. J Burn
interaction with the body. Others are designed to interact Care Rehabil. 1997;18:52-57.
with the body in a passive way (e.g., biodegradable PLGA 12. Bellows CF, Alder A, Helton WS. Abdominal wall reconstruction using
polymers). Recent biomaterials are being designed to modu- biological tissue grafts: present status and future opportunities. Expert Rev
late their environment to create a tissue-specific response. Med Devices. 2006;3:657-675.
13. Ansaloni L, Catena F, D’Alessandro L. Prospective randomized, double-
Furthermore, hybrid biomaterials containing cells, poly- blind, controlled trial comparing Lichtenstein’s repair of inguinal hernia
mers, growth factors, etc. are currently being developed in with polypropylene mesh versus Surgisis gold soft tissue graft: preliminary
in vivo models. These biomaterials will eventually “sense” results. Acta Biomed. 2003;74(suppl 2):10-14.
their surroundings and change their biochemical/mechani- 14. Adetayo OA, Salcedo SE, Bahjri K, Gupta SC. A meta-analysis of outcomes
using acellular dermal matrix in breast and abdominal wall reconstructions:
cal properties in response to the needs of the environment. event rates and risk factors predictive of complications. Ann Plast Surg.
The ultimate goal is the creation of biomaterials with tis- 2011;[epub ahead of print].
sue-specific properties individualized to the exact biologic, 15. Kim JY, Davila AA, Persing S, et al. A meta-analysis of human acellular dermis
chemical, and functional needs of the reconstruction. The and submuscular tissue expander breast reconstruction. Plast Reconstr Surg.
2012;129:28-41.
continued evolution of the biomaterial field depends upon 16. Butler CE, Burns NK, Campbell KT, Mathur AB, Jaffari MV, Rios CN.
an interdisciplinary collaboration between engineers, scien- Comparison of cross-linked and non-cross-linked porcine acellular dermal
tists, clinicians, and industry. matrices for ventral hernia repair. J Am Coll Surg. 2010;211:368-376.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 8  n  Principles of Microsurgery
Charles E. Butler and David M. Adelman

These technical advances, along with increased interest in


Introduction and knowledge of fine vascular anatomy, have made avail-
Microsurgery refers to a set of surgical techniques performed able the wide variety of microsurgical reconstructive options
beyond the limits of human eyesight. These procedures included in the armamentarium of reconstructive surgeons
require magnification by either surgical loupes or an operating today.
microscope. Contemporary procedures that use microsur-
gical techniques include nerve and blood vessel repairs and
grafts, free tissue transfers, limb replantation, and composite Indications for Free
tissue allotransplantation. Technical expertise is essential for Tissue Transfers
success, but preoperative planning and postoperative moni-
The reconstructive “ladder” algorithm advocates repair-
toring are also critical in achieving a successful microsurgical
ing tissue defects with the least invasive option that will
reconstruction.
produce successful results. The simplest technique is direct
closure, and the most complex technique—with the great-
History est potential morbidity—is free tissue transfer. Free tissue
transfers, located at the “top” of the reconstructive ladder,
The first successful end-to-end arterial anastomosis was reported
are usually considered when local or regional tissues are
in 1889 by Jassinowski.1 He used fine, curved needles and
insufficient or suboptimal for reconstruction. The unavail-
silk sutures to join the cut ends of carotid arteries in sheep.
ability of local or regional tissues may be a result of infec-
In 1897, Murphy reported an invagination method in which
tion, inflammation, trauma, radiation, insufficient volume
two double-ended silk sutures were used to intussuscept one
or surface area, insufficient vascular pedicle length, and/
blood vessel end into another, following which interrupted
or the unacceptability of morbidity at that donor site.
sutures were used to oversew the overlapping ends. This
In these situations, free tissue transfer becomes the best
technique led to anastomotic narrowing and thrombosis in
option. Free tissue transfer is also the most suitable option
animal experiments but was used clinically for human femoral
when highly vascularized tissue is required, when special-
artery repair.
ized tissues (such as functional muscles) are not available
Prior to the standardization of vascular repair tech-
locally, or when specialized components (such as vascular-
niques, there was controversy regarding whether to include
ized bowel or bone) are required. Table 8.1 outlines com-
the tunica intima vasorum in vascular sutures. Carrel, Burci,
mon indications for free flap reconstruction.
and Jassinowski favored excluding the intima, whereas Briau,
A detailed discussion of the factors involved in choosing a
Dofler, Jensen, and Hopfer recommended including the intima
specific free flap for a particular reconstruction is beyond the
in anastomoses. Guthrie and Carrel examined various tech-
scope of this chapter but is covered elsewhere in this book.
niques for anastomoses and found that inclusion of the intima
Generally speaking, the operating surgeon should ensure that
promoted “uniformly successful results,” thus laying the foun-
the tissue chosen for free tissue transfer is of sufficient size to
dations for standardization of anastomotic techniques.1, 2
cover or fill the defect, is associated with acceptable donor
Carrel, who received the 1912 Nobel Prize in Medicine
and Physiology for his work in this field, first described the
technique of placing triangulating sutures to ensure equal
traction on the blood vessels being anastomosed. In 1966, Table 8.1
Buncke3 reported rabbit ear replantations with anastomosis of Common Indications for Free Tissue Transfer
vessels approximately 1 mm in diameter. This microsurgical in Reconstructive Surgery
procedure was made possible by the use of fine instruments
adapted from those used by watchmakers and jewelers and n  Indication n  Example
the development of thin sutures swaged on suitably small-
gauge needles. Obliteration or reduction Reconstruction after exten-
Advances in magnification technology often par- of dead space sive soft tissue resection
alleled those in surgical technique and were essential Coverage of exposed Reconstruction for
to the evolution of modern microsurgical techniques. bone and/or neurovascular calvarial, thoracic, or lower
Janssens invented the first compound microscope in the tissue extremity defects
1590s. However, it would be more than 300 years before
Nylen introduced the operating microscope for otolar- Volume and contour Reconstruction of the
yngologic surgery in 1921. The term microvascular sur- reconstruction breast
gery was coined by Jacobson, who wished to operate on Vascularized enteral Reconstruction for pharyn-
small blood vessels under microscopic magnification conduits geal or esophageal defects
and later demonstrated a 100% patency rate in vessels
from 1.6 to 3.2 mm in diameter.1 Further developments Composite reconstruction Combined mandibular and
included foot-operated microscope controls that freed the floor-of-mouth reconstruction
surgeons’ hands, a beam-splitting device to allow the use Functional muscle Facial reanimation for
of a second set of eyepieces for a surgical assistant during reconstruction paralysis
procedures, optical zoom and independent focus controls, Reconstruction and/or Digit, penile, and limb
and cooler fiberoptics with a reduced likelihood of tissue replacement of appendages reconstructions/replantation
desiccation and improved signal transmission.

70
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 8: Principles of Microsurgery 71
site morbidity (i.e., the benefits of the reconstruction outweigh
Preoperative Planning

Principles, Techniques, and


the disadvantages of the flap harvest), and replaces “like with
like,” as with any reconstruction. Additionally, factors such Careful preoperative planning is essential. This is particularly
as color, pedicle length, and vessel size similarity must be true in microsurgery, since the donor sites are limited and the
considered. consequences of flap failure are considerable. Often, the type

Basic Science
of reconstruction needed is known prior to surgery (e.g., breast
reconstruction). Other times, the extent of resection is altered
Patient Selection based on intraoperative findings and pathologic examina-
and Education tion (e.g., resection of head and neck tumors). In these latter
situations, having discussed multiple possible flap options
The reconstructive surgeon should establish that the patient
with the patient during consultation will allow for the most
is medically fit for the proposed procedure, which may be
appropriate reconstruction to be performed without the need
complex and lengthy. Microsurgical procedures are not
for delay or additional conversation. It is the responsibility of
specifically contraindicated by age, provided the patient
the microsurgeon to anticipate as many reconstructive variables
is in reasonable health. However, the surgeon should rule
as possible.
out the presence of significant cardiovascular, respiratory,
Multiple flap options are usually available and the micro-
hepatic, or renal dysfunction and abnormal bleeding or
surgeon must consider which to use. Donor site morbidity and
clotting states.
replacing “like with like” are critical. Patient positioning is
The proposed procedure should be discussed at a level of
also important. Certain flaps may be harvested simultaneously
detail suitable for the patient. This includes a discussion of
with the ablative resection or wound preparation; this may
the likely donor sites for the tissue transfer, anticipated mor-
decrease overall operative time and patient turning. Keeping
bidity at each site, expected intraoperative and postoperative
ischemia time to a minimum is equally important, and timing
course, possible donor and recipient site complications,
flap harvest with recipient site preparation is key. In cases in
expected level of discomfort and scarring, and expected post-
which the flap may be rendered ischemic by the ablative team
operative recovery times needed to regain preoperative function
(e.g., when using a filet of extremity plap for a proximal
and activity levels.
defect), dissection of the flap prior to disease resection may
maximize flap viability after reperfusion.
Equipment and Operative In the event of flap injury or flap failure, certain backup
flap options may become important. Planned vein grafts may
Preparation allow a short pedicle to reach the recipient vessels or bypass
The correct instrumentation should be available for the oper- an area of vessel injury or disease. Ensuring potential vein
ating team, along with additional sets in case of accidental graft harvest sites are appropriate for use and included in the
damage or contamination of the instruments during the pro- sterile surgical field will facilitate their use during surgery, if
cedure. A microsurgical instrument set minimally includes fine needed. Furthermore, in the case of recurrent disease or late
jeweler’s forceps, vessel-dilating forceps, straight and curved flap loss, backup options need to be considered for later use.
microsurgical scissors, and microsurgical needle holders. Communication with the ablative team preoperatively is
Heparinized saline solution is frequently used for irrigation of essential to understand the anticipated defect characteristics,
the vessel lumen. optimize flap choice, and, consequentially, maximize the out-
The choice of magnifying equipment depends on individual comes of the reconstruction.
surgeon preference. Surgical loupes, which typically range from
2.5 × to 5.5 × magnification, can be used for fine dissection
and the preparation of vessels. Some surgeons also prefer to
Operative Technique
use loupes rather than operating microscopes when performing Once the recipient site is available (e.g., after debridement or
the vascular anastomoses.4 The advantages of the operating tumor resection), the defect is evaluated, and the final deci-
microscope are that it provides wide-field adjustable magni- sion regarding the type of reconstruction is made. Surgical
fication and allows significant depth-of-field perception. The templates can be helpful in determining the exact dimensions
microscope should have two sets of eyepieces to allow the sur- and shape of the defect, particularly if it has a complex three-
geon and the assistant to operate simultaneously. The use of dimensional form.
a video output device allows viewing of the operative field on Prior to free flap harvest, the recipient vessels are evalu-
a separate monitor and is helpful for the scrub team in following ated. Factors to evaluate include the presence of vessels;
the anastomotic activity. their distance from the defect (i.e., pedicle length required);
The free tissue transfer procedure should be outlined pre- their size, patency, and flow; and their condition (including
operatively to the anesthetic and nursing teams, as well as the previous radiation damage, atherosclerotic change, previous
ablative surgical team. This ensures that all parties are aware trauma, and/or infection). If the initially chosen vessels are
of the donor and recipient sites and helps to streamline opera- inadequate, alternative recipient vessels are sought. Vein grafts
tive activity. The need for (or avoidance of) anticoagulation, may be required to bridge the distance between the donor
neuromuscular paralysis, vasopressors, and antibiotic prophy- and recipient vessels. Free tissue transfer requires a thorough
laxis should be discussed with the anesthesiologist. Patient understanding of the relevant donor and recipient site anat-
positioning and preparation, the expected length of the proce- omy, including the main arterial and venous supply, major
dure, and any resultant physiologic or anatomic risks should vessel variations, important associated structures, and associ-
also be discussed. Intravenous and intra-arterial access should ated nerve supply. The flap’s vascular pedicle is dissected under
be planned in conjunction with the anesthetic and nursing magnification, with care taken to avoid injury to the flap
teams to avoid interference with potential flap harvest and blood supply. The required pedicle length should be appar-
recipient sites. ent from operative planning and intraoperative measurement.
The patient should be positioned for easy access to the Ideally, the donor and recipient are vessels of similar diameter.
flap donor and recipient sites. Dependent and pressured The vessels are handled minimally and with care by holding
areas on the patient should be padded to avoid pressure the adventitial tissue on the outermost aspect of the vessel
damage, and the patient should be well secured on the oper- wall. It is equally important to avoid significant traction on
ating table to allow limited change of position without the the vessels. Manipulation of the lumen is avoided to minimize
risk of a fall. intimal injury.

(c) 2015 Wolters Kluwer. All Rights Reserved.


72 Part I: Principles, Techniques, and Basic Science

The microscope setup is one of the most important aspects


of an anastomosis. The operating table height is adjusted so
that the operative field is approximately level with the sur-
geons’ elbows. The height of the microscope is adjusted for
adequate focal length of the objective lens but in such a way
that the surgeons can avoid excessive flexion or extension of
their cervical spines or ligamentous and muscular strain. Both
eyepieces are set to neutral optical correction or adjusted for
each surgeon’s vision if corrective lenses are needed.
The recipient site is positioned for optimal exposure. This
includes retraction of the skin flaps or tissue using retrac-
tors, tension sutures, or skin hooks. The orientation of the
flap pedicle is checked to ensure that the anastomoses will
not be under excessive tension and the pedicle is checked for
acute bends or twists both before and after completion of
the anastomoses. The phrase “macro before micro” is a use-
ful reminder to check that the pedicle has an appropriate lie
within the recipient bed, prior to losing the wide perspective
under the microscope. To aid visualization during anastomo-
sis, a small sheet of plastic polymer “background material”
in a contrasting color can be placed under the vessels. If the Figure 8.1. Donor and recipient vessel preparation. The excess
operative field is deep, placing surgical sponges at the base of adventitial tissue near the cut edge of the vessel is removed with dissect-
the defect can elevate it. ing scissors to prevent intrusion into the lumen during the anastomosis.
The vessels to be anastomosed are positioned to allow Care is taken to avoid excessive thinning, which can result in vessel tears
during the placement of sutures. Visual Art © 2004 The University of
tension-free, surface-to-surface apposition. Once the pedicle Texas M. D. Anderson Cancer Center. Used with permission.
length and orientation of the donor and recipient vessels
are decided, low-pressure microvascular clamps are applied
for vascular control. Application of vessel clamps on the donor
vessels can help eliminate oozing from arterial inflow and distance apart to distribute the tension evenly around the cir-
venous backflow. The recipient artery and vein are checked cumference of the anastomosis.6
for open branches near the planned anastomoses; these are The method of suturing depends on surgeon preference.
then ligated. The cut edges of the donor and recipient vessels A popular method is to start with two orientation sutures
are checked for a clean, uniform edge and trimmed as neces- placed 180° apart (Figure 8.3A) or three orientation sutures
sary to avoid stray tissue ends encroaching into the lumen; placed 120° apart (Figure 8.3B). Some surgeons believe
these can be foci for thrombus formation. For an end-to-end that placing the correct number of sutures between the orien-
anastomosis, both the donor vessel and recipient vessel are tation sutures is easier when there are two; others believe that
most commonly cut perpendicular to the vascular axis. An using three orientation sutures reduces the risk of including the
oblique cut results in a larger circumference and can be used to
minimize vessel size mismatch when coapting vessels of different
diameters.
The quality of the luminal intima is then inspected for irreg-
ularities such as thrombi, atherosclerotic plaques, and friable,
calcified walls. Any detected debris is gently irrigated away.
If a satisfactory internal surface cannot be obtained by gentle
irrigation, the vessel should be cut back a suitable distance,
with care taken not to jeopardize the flap pedicle length or cali-
ber. It is also important to ensure that the recipient vessels are
outside any zone of injury or infection; using inflamed vessel
segments increases the risk of post-anastomotic thrombosis.5
If the recipient vessels do not appear suitable for microsurgical
anastomosis, then new recipient vessels are located. If they are
some distance from the original recipient vessels, vein grafts
may be needed to bridge the gap.
Once a satisfactory vessel segment is attained, adventitial
cleaning is carried out with sharp, curved microsurgical scissors
(Figure 8.1). It is important to avoid separation of the intima
from the media in arteries and to avoid excessive thinning of
the vessel walls. Excessive stripping of adventitia can result in
vessel tearing during suture placement. Judicious tangential
sharp excision is carried out for a distance of approximately
1 mm from the edge of each vessel. Some surgeons prefer to
maintain luminal apposition by careful vessel positioning
and/or the use of anastomotic retraction sutures; others prefer
to use double-approximating vascular clamps (Figure 8.2).6 Figure 8.2.  Use of double-approximating microvascular clamps.
After adequate preparation, the vessels are aligned for The donor and recipient vessels are placed within the clamps, and the
vessel ends are approximated along the direction of the arrows. This
suture placement. Fine, non-absorbable sutures appropriate to
technique maintains the correct orientation of the vessels and facili-
the size and thickness of the vessels are used (most commonly tates suture placement. After the anterior suture line is complete, the
8-0, 9-0, or 10-0 nylon). Ideally, suture entry is perpendicular clamps are turned over to allow access to the posterior suture line.
to the vessel wall surface. Each bite should be of a sufficient Visual Art © 2004 The University of Texas M. D. Anderson Cancer
distance away from the edge so that the suture will not cut Center. Used with permission.
through the wall. These sutures should be placed an equal

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 8: Principles of Microsurgery 73

Principles, Techniques, and


Basic Science
A B
Figure 8.3.  Orientation sutures. A. Bisecting interrupted sutures are placed 180° apart, dividing the vessel circumference in half. This technique is
particularly useful when there is a vessel size mismatch. B. Triangulating interrupted sutures are placed 120° apart, dividing the vessel circumference
into thirds. This technique helps prevent inadvertent inclusion of the opposite wall of the vessel in the remaining sutures; the surgeon applies gentle
downward traction on the posterior orientation suture while the other two sutures are gently retracted upward and laterally during placement of
the remaining anastomotic sutures. Visual Art © 2004 The University of Texas M. D. Anderson Cancer Center. Used with permission.

opposite wall in a suture (known as “backwalling”), as traction is carefully checked for active leaks, which are managed
on the third suture holds the opposite wall away from the by accurate placement of additional sutures. Small leaks
anterior suture line. from needle holes often stop on their own, and sometimes
The remaining sutures are then placed, usually beginning the anastomosis can be draped with a pledget of fat, which
on the posterior wall to facilitate visualization of the lumen provides tissue thromboplastin to further facilitate the process.
and continuing to the anterior wall. These sutures can be
interrupted or continuous (running). Interrupted sutures are
preferred when the size match of the two vessel ends is not
ideal. Continuous sutures require less knot tying, are faster,
and distribute the tension line evenly between the orientation
knots (Figures 8.4 and 8.5). In practice, arterial anastomoses
are often performed with interrupted sutures and venous anas-
tomoses with continuous sutures. Several studies have shown
no significant difference in thrombosis rates between the two A
suturing techniques.2,7,8
Accidental penetration into, or inclusion of, the opposite
(back) wall of a vessel in a suture is unacceptable and must
be avoided by careful visualization and meticulous technique.
Backwalling is prevented by a combination of luminal irri-
gation to distend the vessel (particularly thin-walled veins)
and ensuring the vessel edges are everted. The tips of jeweler’s
forceps can be placed just inside the vessel lumen to provide
counterpressure to facilitate external-to-intraluminal passage
of the needle (Figure 8.6A) and against the adventitial sur-
face of the vessel wall to facilitate intraluminal-to-external
passage of the needle (Figure 8.6B). B
Square knots are used whenever possible. For sutures under
some tension, such as the initial orientation sutures, a surgeon’s
knot is frequently preferred. Three square throws are usually
sufficient for interrupted suture knots. Ideally, sutures are tied
with a degree of tension sufficient to adequately coapt the vessel
edges but not to cause excessive bunching. However, sutures
that are tied too loosely may result in a thrombosis and/or
leakage at the anastomosis.
Nakayama introduced a vascular anastomotic coupling
device, which Ostrup and Berggren subsequently modified,
consisting of polyethylene rings secured with steel pins.9 The use
of such a device requires everted vessel walls and may not be C
possible with vessels that have a small diameter or athero-
sclerotic changes. Commercially available anastomotic cou-
pling systems are available for vessels 1 to 4 mm in diameter.
The patency rates achieved using anastomotic coupling Figure 8.4. End-to-end anastomosis using continuous (running)
devices are comparable to those using hand-sewn techniques. sutures. A. Donor and/or recipient vessel ends may be cut at an oblique
angle to increase their circumference and facilitate suturing, particu-
Figure 8.7 illustrates the technique for using an anastomotic larly for small vessels. B, C. Interrupted traction sutures are placed at
coupling device. 180° (shown) or 120° (not shown) to orient the vessels and facilitate
Antispasmodic agents, such as papaverine, can be used placement of the running sutures. Visual Art © 2004 The University of
throughout the dissection and anastomosis to reduce vaso- Texas M. D. Anderson Cancer Center. Used with permission.
spasm. After the vascular clamps are released, the anastomosis

(c) 2015 Wolters Kluwer. All Rights Reserved.


74 Part I: Principles, Techniques, and Basic Science

A B
Figure 8.7.  Use of an anastomotic coupling device. A. With the device’s lateral wings open, each vessel is passed through a plastic ring, and the
vessel walls are everted and impaled on pins mounted on the rings. B. After both vessels are mounted, the knob is turned to close the wings and
secure the rings with the vessels in opposition. The rings are securely attached to each other by the pins of one ring interlocking with the opposite
plastic ring. After the anastomosis, the coupled rings are released in the direction of the arrow by continuing to turn the knob. Visual Art © 2004
The University of Texas M. D. Anderson Cancer Center. Used with permission.

bleeding at the flap edges, hematoma formation, and even- is easily accessible (such as a buried flap), an implant-
tual concomitant loss of arterial inflow. These signs may be able Doppler ultrasonic probe can be used. This con-
easier to detect on a skin paddle than on a skin-grafted por- sists of a small probe attached to a polymer sleeve that
tion of muscle. Also, problems are detected more easily and is placed around a pedicle vein or artery adjacent to the
earlier when a large flap surface area is available for physical anastomosis; a thin probe lead wire exits through the inci-
examination. sion.12 The lead wire easily detaches from the probe and is
A Doppler ultrasonic probe is helpful for flap moni- removed through the incision with gentle traction on the
toring. The external pencil probe, which is applied on wire. Doppler signals have a characteristic pattern that
the skin paddle over a known cutaneous perforator can, with experience, be identified as arterial (pulsa-
location (often marked with a suture during surgery) tile) or venous (undulating). A change in the character
is one option. For flaps in which no perforator signal of the signals from strong to diminished or undetectable

A C

B D
Figure 8.8.  Use of the Acland test to confirm antegrade vascular flow through an anastomosis. A. The direction of blood flow is indicated by the
arrow. B. Two jeweler’s forceps are used to gently occlude the vessel distal to the venous anastomosis. C. Blood is milked out of the vessel between
the two forceps by gently sliding the distal forceps along the vessel without injuring it. This results in a segment of collapsed vessel between the
proximal and distal forceps. D. Releasing the proximal forceps allows the collapsed vessel segment to be filled by antegrade flow if the anastomosis
is patent. The distal forceps prevent retrograde filling of the collapsed segment. This test should be performed sparingly to minimize potential
trauma to the vessel intima. Visual Art © 2004 The University of Texas M. D. Anderson Cancer Center. Used with permission.

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 8: Principles of Microsurgery 75
During ischemia, the flap is often kept cold to minimize

Principles, Techniques, and


the metabolic demands of the tissue. However, once reperfu-
sion is established, the flap is warmed to decrease vasospasm
and thrombosis and to restore cellular activity to normother-
mic levels.

Basic Science
Postoperative Monitoring and
Troubleshooting
The anesthetic is reversed gently to avoid sudden changes in
blood pressure, which may cause unwanted bleeding. The
patient is kept warm, well hydrated, and pain free during
and after the procedure. The use of vasoconstrictive agents is
avoided. Blood pressure, oxygenation, ventilation, and fluid
balance are carefully monitored. The postoperative use of an
anticoagulant agent (such as dextran, heparin, or aspirin) is
dependent on surgeon preference. These anticoagulating agents
are usually used only if there is a higher-than-normal risk of
thrombosis, such as with procedures involving small-caliber
Figure 8.5. End-to-side anastomosis using continuous (running) vessels, poor quality vessels, friable vessel walls, previously
sutures. An elliptical opening is created on the recipient vessel wall, irradiated tissue, or patients who are heavy smokers.7,11
and the end of the donor vessel is anastomosed to this opening. The Experienced personnel are essential for monitoring the flap
end-to-side technique maintains distal flow in the recipient vessel and
is frequently performed when there is a donor and recipient vessel
postoperatively. The gold standard for assessing the viability
diameter mismatch. Visual Art © 2004 The University of Texas M. D. of transferred tissue is clinical examination.10 Identification
Anderson Cancer Center. Used with permission. of a failing or insufficiently perfused flap can occasionally
be challenging for even the most experienced microsurgeon.
Pattern recognition is essential to identify compromised flaps
within a “window of salvageability.” The threshold for opera-
The entire pedicle is examined to ensure there is no tension, tive re-exploration of a flap for suspected arterial or venous
torsion, or bleeding, particularly from vessel branches or the insufficiency should be extremely low, as salvage rates are
flap itself. The time at which flow resumes is then recorded significantly increased by early identification and treatment.
and the flap ischemia time totaled. One never regrets a “take back” but one may definitely regret
A gentle Acland (vessel strip) test can be carried out near postponing a “take back.”
an arterial or venous anastomosis to confirm anastomotic A number of clinical signs, when present either singly or
patency (Figure 8.8). Flap color, capillary refill, tissue bleeding, in combination, may suggest a perfusion problem. These
and flap temperature are all assessed to ensure adequate flap include pale flap color, reduction in flap temperature, loss of
perfusion.2,10 A Doppler probe can be used to assess vascu- capillary refill, and loss of flap turgor; all may indicate arte-
lar flow within the pedicle and/or specific areas of the flap. rial insufficiency. Venous insufficiency, on the other hand, can
These areas can be marked with a fine, non-absorbable suture result in a purple or blue hue in the flap, congestion, swell-
on the skin paddle for ease of location during postoperative ing, and rapid capillary refill in the early stages followed by
monitoring. eventual loss of capillary refill. There may be increased dark

A B
Figure 8.6.  Forceps counter-traction to facilitate needle placement and penetration. A. In select cases, partially open blunt jeweler’s forceps tips are
placed into the vessel lumen to evert the vessel wall, avoid inclusion of the back wall in sutures, and provide counter-traction for needle penetration.
Extreme care must be taken to avoid traumatizing the vessel intima; some microsurgeons avoid this technique for this reason. B. When the needle is
passed from inside the vessel lumen to outside the lumen, it is often useful to use the tips of the forceps to provide counter-traction on the adventitial
surface of the vessel to facilitate needle penetration. Visual Art © 2004 The University of Texas M. D. Anderson Cancer Center. Used with permission.

(c) 2015 Wolters Kluwer. All Rights Reserved.


76 Part I: Principles, Techniques, and Basic Science

may indicate vascular occlusion. Doppler monitoring is, flap salvage. Unfortunately, salvage rates decrease with cumu-
however, subject to error (both false-positive and false- lative injury to the flap. If the flap ultimately fails, it should
negative) and thus should never replace clinical assessments. be immediately debrided to prevent it from becoming a nidus
The time between the clinical diagnosis of a vascular prob- for infection. Concurrent with debridement, decisions must be
lem in the flap and the return to the operating room is criti- made regarding temporary versus definitive wound coverage.
cal for flap salvage. Beyond a certain period, depending on the Factors to consider include patient stability, presence of infec-
type of flap and clinical conditions, salvage of a compromised tion, availability of pedicled and free flap backup options, and
flap becomes impossible. It is therefore advisable to be overly quality of recipient vessels.
­cautious when assessing flap status, as the consequences of an
undiagnosed problem may result in partial or complete flap
loss.7 When in doubt, operative exploration can be both diag-
Conclusions
nostic and therapeutic. The use of microvascular techniques has revolutionized recon-
Once the patient is back in the operating room, the flap struction and expanded the range of options for repairing large
may be released from its inset if the pedicle is beneath it anatomic defects. Microsurgery is complex and technically
(e.g., breast reconstruction), or the pedicle may be exposed demanding, but with careful preparation, proper execution,
first through a separate incision (e.g., neck exploration for a and postoperative monitoring, it is beneficial to the patient and
compromised intraoral free flap). A tight flap inset can lead to rewarding to the surgeon.
decreased perfusion, and release alone may adequately restore
perfusion. If not, the position of the pedicle is examined, spe- References
cifically looking for a twist, kink, stretch, or compression that 1. Lee S, Frank DH, Choi SY. Historical review of small and microvascular
may have impeded flow. This can often happen postoperatively vessel surgery. Ann Plast Surg. 1983;11:53-62.
2. Weiss DD, Pribaz JJ. Microsurgery. In: Achauer BM, Eriksson E, Guyuron B,
secondary to swelling, patient activity, and/or infection. Flow et al., eds. Plastic Surgery: Indications, Operations and Outcomes. Vol 1.
across both the arterial and venous anastomoses is checked, St. Louis, MO: Mosby; 2000:163-183.
using any or all of the aforementioned techniques (Acland 3. Buncke HJ. Microsurgery—retrospective. Clin Plast Surg. 1986;13:315-318.
test, Doppler probe, palpation, etc.). If no flow is detected, 4. Shenaq SM, Klebuc MJ, Vargo D. Free-tissue transfer with the aid of
loupe magnification: experience with 251 procedures. Plast Reconstr Surg.
the anastomosis is opened and examined. Common findings 1995;95:261-269.
include thrombosis, suture occlusion of the lumen (by pre- 5. Johnson PC, Barker JH. Thrombosis and antithrombotic therapy in micro-
viously undiagnosed back wall placement), and dissection. vascular surgery. Clin Plast Surg. 1992;19:799-807.
Once the problem is determined, it can be repaired. Simple 6. Acland R. Microsurgery: A Practice Manual. St. Louis, MO: Mosby; 1980.
7. Chao JJ, Castello JR, English JM, et al. Microsurgery: free tissue transfer
revision of the anastomosis or thrombectomy via mechanical and replantations. Sel Read Plast Surg. 2000;9:1-32.
(e.g., Fogarty catheter) and/or chemical (e.g., thrombolytics) 8. Samaha FJ, Oliva A, Buncke GM, et al. A clinical study of end-to-end versus
means may be required. If inflow and/or outflow is diminished end-to-side techniques for microvascular anastomosis. Plast Reconstr Surg.
despite anastomotic patency, new recipient vessels may be 1997;99:1109-1111.
9. Ostrup LT, Berggren A. The UNILINK instrument system for fast and safe
required, along with new vein grafts to reach them. microvascular anastomosis. Ann Plast Surg. 1986;17:521-525.
Once the ischemia is eliminated and perfusion restored, 10. Neligan PC. Monitoring techniques for the detection of flow failure in the
additional monitoring of the flap is crucial. Increased post- postoperative period. Microsurgery. 1993;14:162-164.
reperfusion swelling of the flap tissue is common, and often 11. Reus WF 3rd, Colen LB, Straker DJ. Tobacco smoking and complications in
elective microsurgery. Plast Reconstr Surg. 1992;89:490-494.
the flap inset needs to be adjusted to avoid pressure-induced 12. Swartz WM, Izquierdo R, Miller MJ. Implantable venous Doppler microvas-
ischemia of the flap and surrounding tissues. In some situa- cular monitoring: laboratory investigation and clinical results. Plast Reconstr
tions, multiple trips to the operating room may be required for Surg. 1994;93:152-163.

(c) 2015 Wolters Kluwer. All Rights Reserved.


CHAPTER 9  n  Principles and Techniques

Principles, Techniques, and


of Peripheral Nerve Repair,
Grafts, and Transfers

Basic Science
Susan E. Mackinnon and Stephen H. Colbert

Injuries to peripheral nerves may be devastating due to the phagocytosed in a process termed Wallerian degeneration.
incomplete nature of nerve healing and the possibility of Neurotrophism, which literally means food for nerves, is
permanent functional impairment. Peripheral nerve injuries the ability of neurotrophins secreted in an autocrine or para-
require appropriate management to optimize motor and sen- crine fashion to enhance the elongation and maturation of
sory recovery and to minimize pain. The surgeon must accu- nerve fibers. Schwann cells assume a pro-regenerative pheno-
rately identify the injury, determine the primary therapeutic type instrumental in remyelinating and guiding regenerating
goal, and decide if and when to operate. The management of axons to their appropriate targets along residual endoneurial
peripheral nerve injuries has benefited from clinical experience tubes. The orderly arrangement of these Schwann cells along
gained in World War II, the evolution of microsurgical tech- the endoneurium forms the bands of Bungner. Functional
nique, improvements in surgical equipment, and the consis- recovery depends on the number of motor fibers correctly
tently advancing field of neuroscience. matched with motor endplates and the number of sensory
fibers correctly matched with sensory receptors.
Experimental studies show that regenerating fibers can
Nerve Anatomy and demonstrate both tissue and end-organ specificity.5 This pro-
Physiology cess is called neurotropism. The preference of a nerve fiber to
In the normal nerve (Figure 9.1), axons are either unmyelinated grow toward a nerve versus other tissue depends on a criti-
or myelinated. Unmyelinated axons are ensheathed by a single cal gap across which the fiber responds to the influences of
Schwann cell–derived double basement membrane, whereas the distal nerve. Current research suggests that the expression
myelinated axons are surrounded by a multilaminated, of various Schwann cell and myelin-associated glycoproteins
­laminin-rich, myelin sheath with stacks of individual Schwann may facilitate or impede the regeneration of damaged axons
cells along the length of the axon. Individual nerve fibers are to their correct targets.6
surrounded by the thin collagen of the endoneurium. Fibers
destined for a specific anatomic location are grouped together Classifying Nerve Injuries
in fascicles surrounded by the perineurium. The connective tis-
The classification of nerve injuries, originally proposed by
sue that surrounds the peripheral nerve is the epineurium. A
Seddon in 19437 and Sunderland in 1951,8 was subsequently
thin layer of loose areolar tissue, the mesoneurium, connects
expanded by Mackinnon9 to include a sixth category rep-
the epineurium to the surrounding structures and allows for
resenting a mixed injury pattern (Figure 9.2). The level and
the uninhibited excursion of nerves within the extremities.
degree of injury are important in determining treatment.
Regional arteries and veins supply the vasa nervorum, longi-
First-, second-, and third-degree injuries have the potential for
tudinal vessels running along the epineurium that communi-
recovery and for the most part do not require surgical inter-
cate with intraneural vessels running within the perineurium
vention. A first-degree injury recovers function quickly (within
and the endoneurium. Bidirectional axonal transport within
3 months). A second-degree injury recovers slowly (1 inch per
the nerve fiber is responsible for structural support of the
month) but completely, whereas recovery after third-degree
nerve and delivery of neurotransmitters and trophic factors. In
injuries is slow and incomplete. Fourth- and fifth-degree
the normal nerve, the intrinsic blood supply is substantial,
injuries will not recover without surgical intervention. A sixth-
allowing mobilization and elevation of nerves over a long dis-
degree injury shows a variable recovery.
tance (bipedicle width:length ratio of 64:1).
First-degree injury (neurapraxia). A localized conduc-
tion block is produced that may result in segmental
Nerve Injury demyelination. Because the axons are not injured,
Traumatized peripheral nerves are characterized by spe- regeneration is not required and remyelination and
cific changes both proximal and distal to the site of injury. complete recovery occur within 12 to 16 weeks.
Proximally, axons retract a variable distance depending on
Second-degree injury (axonotmesis). Axonal injury
the degree of injury and after a brief period of quiescence
occurs and the distal segment undergoes Wallerian
elongate as a hydra-like regenerating unit in which a single
degeneration. Proximal nerve fibers will regenerate at a
parent axon gives rise to multiple daughter axons. In myelin-
rate of 1 inch per month. By definition, the connective
ated nerves, axons sprout at unsheathed gaps known as the
tissue layers are uninjured. Recovery will be complete.
nodes of Ranvier and progress to their sensory or motor tar-
The progress of regeneration can be followed by the
gets. Observations and elegant studies by Cajal, Sunderland,
advancing Tinel sign.
Lundborg, Brushart, Mackinnon, and others have shown that
regenerating axons do not always take a direct course but do Third-degree injury. Wallerian degeneration is
preferentially target their appropriate end-organ receptors.1-5 combined with some fibrosis of the endoneurium.
Once a functional synapse is made, the remaining daughter Recovery will be incomplete because scar within the
axons degenerate, or are “pruned back.” In the distal nerve endoneurium may block or cause mismatching of
segment, Schwann cells, fibroblasts, myocytes, and injured regenerating fibers with the appropriate end organs.
axons express a host of neurotrophic factors, including glial Surgery is indicated if the lesion localizes to a known
and brain-derived neurotrophic factors at discrete concentra- area of entrapment where nerve regeneration is
tions and time points as the degrading neural elements are delayed. The recovery is uniformly better than that
77
(c) 2015 Wolters Kluwer. All Rights Reserved.
78 Part I: Principles, Techniques, and Basic Science

Endoneurium
Perineurium

Epineurium
Mesoneurium Nerve fiber

Microvessels
Fascicles Nuclei of
Schwann cells
Axon

Vasa nervorum

Myelin sheath

Node of Ranvier Basement membrane

Axon

Basement membrane

Schwann cell
Axon

um
uri
ne
do
En
Fibroblast

Nerve fiber
m Regeneration sprout
u riu
ne
do Growth cone
En
with filopodia
Wallerian degeneration
in distal nerve fiber
B C

Fibroblasts
Myelin sheath
Basement
membrane

Axon

Individually myelinated
sprouts

D E
Figure 9.1.  Nerve regeneration. A. The normal nerve consists of myelinated and unmyelinated axons. B. When a myelinated axon is injured,
degeneration occurs distally and for a variable distance proximally. C. Multiple regenerating fibers sprout from the proximal axon forming
a regenerating unit. A growth cone at the tip of each regenerating fiber samples the environment and advances the growth process distally.
D. Schwann cells eventually myelinate the regenerating fibers. E. From a single nerve fiber, therefore, a regenerating unit is formed that contains
several fibers, each capable of functional connections.

seen with a repair or graft unless it is associated with Sixth-degree injury. This represents a combination of
severe causalgia. any of the previous five levels of injury. Because of the
Fourth-degree injury. The nerve is in continuity but longitudinal nature of crushing injuries, different levels
with complete scar block resulting from injury to the of nerve injury can be seen at various locations along
endoneurium and perineurium. Regeneration will the nerve. This is the most challenging nerve injury for
not occur unless the block is excised and the nerve is the surgeon as some fascicles will need to be protected
repaired or grafted. and not “downgraded,” whereas others will require sur-
gical reconstruction.
Fifth-degree injury (neurotmesis). The nerve is com-
pletely divided and must be repaired before any regen- Proper clinical assessment is paramount to development
eration can occur. of a treatment plan. The extent of motor nerve injury is
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 9: Principles and Techniques of Peripheral Nerve Repair, Grafts, and Transfers 79

Principles, Techniques, and


Intact
Intact
endoneurium
Axon endoneurium Intact axons
Myelin sheath Cavities of injured axons
and myelin sheaths

Basic Science
Endoneurium Cavities of injured
Perineurium myelin sheaths

Normal fascicle First-degree injury Second-degree injury

Scarred
endoneurium

Intact
perineurium Intact ext.
Third-degree injury epineurium

A Fourth-degree injury Intact


mesoneurium

First
Second degree
degree

Intact nerve Fourth


degree Fourth
fibers Fifth degree degree

Third Third
degree degree

First
Second degree
degree

B Sixth degree

Figure 9.2.  Classification of nerve injuries. A. Uninjured nerve consists of myelinated axons, surrounded by the endoneurium, grouped into
fascicles surrounded by the perineum. The outer layer of the nerve is the epineurium. In a first-degree injury, the axons are only demyelinated,
whereas in a second-degree injury, the axons are injured and undergo degeneration. A third-degree injury includes damage to the axons, myelin,
and endoneurium. A fourth-degree injury is a complete scar block that prevents any regeneration, and a fifth-degree injury is a division of the
nerve. B. The pattern of injury may vary from fascicle to fascicle along the nerve. This mixed pattern of injury is considered a sixth-degree injury.

determined by an evaluation of weakness, loss of motion, “Ten Test.”10 Patients rank the quality of sensation in the
and atrophy. The extent of sensory nerve injury is deter- affected digit compared with that in the normal contralateral
mined by moving and static two-point discrimination, which digit using a scale from 0 to 10. Vibration instruments and
are measurements of innervation density and the number of Semmes-Weinstein monofilaments are also used as threshold
fibers innervating sensory end organs. Light moving touch, tests to evaluate the performance level of nerve fibers and
for example, evaluates the innervation of large A-β fibers are more useful in evaluating chronic compressive neuropa-
and can be quickly screened with the valid and reliable thies. Testing is also performed after nerve repair to assess
(c) 2015 Wolters Kluwer. All Rights Reserved.
80 Part I: Principles, Techniques, and Basic Science

the quality of nerve repair, determine the need for revision, fascicles. These fascicles are then visually traced back to the
and monitor recovery. level of injury.
Sharp nerve injuries are treated with repair or reconstruc- Knowledge of the usual internal topography of the periph-
tion in a timely fashion, generally with minimal delay unless eral nerves can direct proper alignment of fascicles at the
required to achieve a healthy wound bed. Closed injuries are time of nerve repair. For example, the fascicles of the ulnar
treated expectantly up to 12 weeks to allow for first-, second-, nerve in the mid- and distal forearm are divided into a dorsal
and third-degree injuries to show signs of recovery. Recovery sensory group, a volar sensory group, and a motor group.
is assessed with serial physical examinations and electrodi- In the ­mid-forearm, the motor group is positioned between
agnostic nerve studies at 6 and 12 weeks. This allows for the the ulnar dorsal sensory group and the radial volar sensory
accurate assessment of the degree of injury and appropriate group (Figure 9.3). The dorsal sensory group separates from
subsequent treatment plan. Fibrillations on electromyogra- the main ulnar nerve approximately 8 to 10 cm proximal to
phy (EMG) indicate axonal injury and will be present around the wrist. The motor group remains ulnar to the volar sen-
6 weeks postinjury (second-, third-, fourth-, and fifth-degree sory group until the Guyon canal, at which time it passes
injuries). By contrast, the presence of motor unit potentials dorsally and radially to become the deep motor branch to
(MUPs) does not occur until about 12 weeks postinjury. the intrinsic muscles. The motor group is two-thirds the size
MUPs are present in second- and third- but not fourth- and of the sensory group at this level. The median nerve topog-
fifth-degree injuries. The presence of MUPs on EMG is a raphy is more complex because it contains more fascicles. In
contraindication to surgery except for a simple decompres- the forearm, the anterior interosseous nerve is situated in the
sion at distal sites of compression. MUPs indicate collateral radial or posterior aspect of the median nerve as a distinct
sprouting of intact nerve fibers. Nascent units will occur later group. The distal internal topography of the median nerve
as actual injured axons regenerate to motor targets. MUPs approximates the distal anatomy; the motor fascicles to the
and nascent units are not present in fourth- and fifth-degree thenar muscles are on the radial side and the sensory fibers
injuries. to the third web space are on the ulnar side. Our web site,
nerveinjury.wustl.edu, details the internal topography of the
various nerves.
Principles of Nerve Repair
Basic principles of nerve repair include the use of meticu-
lous microsurgical techniques with adequate magnification,
microsurgical instruments, and sutures. When the clinical
and surgical conditions allow, a primary nerve repair is per-
formed in a tension-free manner. To facilitate the repair, the
injured segments of the nerve can be mobilized or, in the case
of the ulnar nerve at the elbow, transposed, to obtain length.
Intrinsically, peripheral nerves do afford a limited degree of
excursion. This property of intrinsic redundancy or elastic-
ity gives the peripheral nerves a horizontal or spiral banded
appearance called the bands of Fontana.11 The bands of
Fontana are created by laxity in nerve fibers. Thus, their pres-
ence in an injured nerve will let the surgeon know that nerve
fibers (first-, second-, or third-degree injury) are present. This
finding is helpful in evaluation of in-continuity nerve inju-
ries. These bands disappear when the nerve is compressed or
stretched. Extremes in the range of motion of joints in the
vicinity of the repair and facilitation of an end-to-end repair
with postural positioning of the extremity are discouraged.
If a tension-free repair cannot be achieved, an interposition
nerve graft is preferable with the limb in a neutral position.
In an effort to match sensory and motor modalities and to
optimize the specificity of nerve regeneration, a grouped
fascicular repair should be performed whenever the internal
topography of the nerve is segregated into motor, sensory, or
regional components. Otherwise an epineural repair is per-
formed. Postoperative motor and sensory reeducation maxi-
mizes the surgical result.

Fascicular Identification
Ulnar n.
The object of peripheral nerve repair is to restore the conti- Ulnar sensory Motor group
nuity of motor and sensory fascicles in the proximal segment group

with the corresponding fascicles in the distal segment. The


internal organization of nerves is distinct even in the proxi-
mal extremity, although nerves in the proximal extremity Radial volar
sensory group
are monofascicular. There is considerable plexus formation
between the fascicles, which decreases in the distal extremity. Figure 9.3. Ulnar nerve fascicular topography. A. At the mid-
As nerves progress distally, they become polyfascicular and forearm, the ulnar nerve is composed of three distinct fascicular
the fascicles are further differentiated into motor or sensory groups. The dorsal sensory branch separates from the motor branch
and the main sensory group. The motor branch remains ulnar to the
components.12,13 In the proximal segment of the nerve, motor sensory group until the Guyon canal, at which time it passes dorsally
fibers are distinguished from sensory fibers by knowledge of to the sensory branches of the little and ring fingers to innervate the
the internal topography, intraoperative stimulation, or “neu- intrinsic muscles. B. Knowledge of this topography can be used to
rolysis with the eyes.”14 Using this technique, the distal stump accurately reconstruct distal forearm nerve injuries.
of the injured nerve is dissected to discern motor from sensory

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Chapter 9: Principles and Techniques of Peripheral Nerve Repair, Grafts, and Transfers 81
When repairing the radial nerve at or above the elbow, the Fascicular identification can also be used to assist with

Principles, Techniques, and


priority is motor rather than sensory recovery (Figure 9.4). nerve reconstruction after tumor extirpation.16 If it appears
The distal sensory fascicles should be identified and can be likely that a functioning nerve will have to be sacrificed during
excluded from the repair or harvested and used as a graft tumor extirpation, the individual fascicles proximal and distal
to repair the motor fibers. In a similar fashion, the sensory to the resection site should be mapped. By performing direct

Basic Science
fibers of the peroneal nerve should be excluded from repair nerve-to-nerve stimulation and recording, the proximal and
and all efforts directed toward repairing the motor fibers to distal corresponding fascicles can be identified. After resection
the anterior tibialis muscle (Figure 9.4). The motor fibers of the involved nerve, the proximal fascicles are repaired to
to the anterior tibialis are located medially within the nerve their corresponding distal fascicles using nerve grafts.
as it crosses the knee and turns abruptly around the head
of the fibula. Several histochemical techniques have been
described that allow motor (acetylcholinesterase and choline
Timing of Nerve Repair
acetyltransferase) or sensory (carbonic anhydrase) discrimi- The best results are obtained after immediate repair of a
nation. However, these techniques require experienced histo- sharply transected nerve. The fascicular pattern and vas-
chemical personnel, are cumbersome, and are not universally cular landmarks guide the proper orientation of the nerve
available. ends. Retraction and neuroma formation, which may result
After the work of Sunderland, it was assumed that the in the need for grafting, are avoided, and within the first
motor and sensory fibers were diffusely scattered across 72 hours after injury, motor nerves in the distal nerve seg-
the different fascicles and followed a tortuous course of ment still respond to direct electrical stimulation because of
plexus formation until they finally organized themselves the presence of residual neurotransmitters within the nerve
into specific motor and sensory groups distally in the terminals. If the nerve was injured by a crush, avulsion,
extremity (Figure 9.5). Recent work contradicts this the- or blast injury, however, the surgeon must be cognizant
ory, showing that fibers destined for a specific territory of nerve injury proximal and distal to the site of transec-
organize themselves into distinct groups proximally within tion. In the acute setting, the extent of injury is difficult
the nerve.12,15 to determine even using the operating microscope. In this

Common
peroneal n.

Fibula

Motor branch to
Common ant. tibialis m.
peroneal n.
Radial n.

Sensory portion
as graft Motor branch to
Deep
Motor Sensory ant. tibialis m.
peroneal n.
fascicles fascicles
Superficial
peroneal n. Superficial
Deep
peroneal n.
peroneal n.

Common
peroneal n.
Motor branch to
ant. tibialis m.

Deep
peroneal n.

Superficial
peroneal n.

A B
Figure 9.4.  Radial and peroneal nerve fascicular anatomy. A. In the radial nerve, the motor and sensory components are separated into dis-
crete fascicles. Awake stimulation can be used to identify the motor and sensory components of the proximal nerve, whereas anatomic dissection
is used to identify them distally. The sensory portion should be excluded from the repair and can be used as a source of donor graft material. If
the sensory component cannot be separated from the distal stump because of plexus formation with the motor fascicles, it can be turned into the
extensor carpi radialis brevis to neurotize this muscle. This ensures that regenerating motor fibers will not be lost in the sensory territory of the
radial nerve. B. Foot dorsiflexion is the essential goal of peroneal nerve repair. Grafting may be limited to the motor branch of the anterior tibi-
alis, which lies on the medial side of the nerve as it rounds the head of the fibula and travels transversely to reach the anterior tibialis. Again, the
sensory portions of the nerve can be used as donor material.

(c) 2015 Wolters Kluwer. All Rights Reserved.


82 Part I: Principles, Techniques, and Basic Science

a nerve, healthy individual fascicles tend to herniate out from


the epineural sheath because of the normally high endoneu-
rial fluid pressure. At the time of epineural repair, the fascicles
may bend inward or ­outward, causing a misdirection of the
regenerating fibers (Figure 9.8). Appropriate trimming of the
fascicles will allow them to lie end-to-end within the epineural
sheath. The epineural sutures should be placed loosely so as
not to cause any additional bunching of the fascicles and so
that the nerve can be realigned appropriately.

Nerve Grafts
During the primary repair of a nerve, the two ends of the
nerve should lie in approximation without tension. If the
repair will not hold with 9-0 suture, or if postural position-
ing is required, a nerve graft is preferable. One challenge
with nerve grafting is to restore proper sensory/motor align-
ment. Often the internal topography of a nerve changes
across a gap. The proximal nerve may contain mixed motor
and sensory fascicles or a different number of fascicles com-
pared with the distal nerve, and thus the alignment of the
grafts cannot be specific. Proper orientation is aided by
knowledge of the internal anatomy, longitudinal epineural
vessel location, distal dissection, and “neurolysis with the
eyes.” A second challenge is to maximize the number of
axons that can traverse the nerve graft through both proxi-
mal and distal neurorrhaphy sites. To divert the maximal
number of axons distally, nerve grafts are reversed in ori-
entation. This maneuver is particularly important when a
long graft that possesses branches is utilized. If the graft is
placed anatomically, some regenerating axons travel along
these branches instead of to the distal neurorrhaphy site. If
the graft is reversed in orientation, it will funnel all regener-
ating axons distally.
When repairing long nerve defects, the surgeon may wish
to prioritize the functions of the nerve and consider exclud-
ing nonessential branches. In both the radial and peroneal
nerves, but not the median and tibial nerves, the sensory
components are expendable and the surgeon can concentrate
Figure 9.5.  Nerve topography. Early surgeons believed that the
fibers destined for a distinct fascicular group in the distal limb gradu- on restoring the motor function. If necessary, the sensory
ally came together as the plexus formation decreased. Recent work fascicles can be used as graft material. The distal end of the
shows that fibers of a distinct fascicular group are actually located excluded sensory component may be repaired in an epineu-
adjacent to each other, even in the proximal limb. ral, end-to-side fashion to a nearby donor sensory nerve,
not necessarily to restore excellent sensation, but to provide
some sensation and limit the potential for distally medi-
ated nerve pain by allowing reinnervation of some sensory
situation, the two nerve ends should be tacked together to receptors.17
prevent retraction and repair delayed for 3 weeks or until
the wound permits. At the time of re-exploration, the extent
of injury will be defined by neuroma and scar formation.
Neuroma in Continuity
The neuroma must be excised in a bread loaf fashion until A complete neuroma in continuity that has no transmis-
a healthy fascicular pattern is seen proximally and dis- sion of signals and no functioning component is treated
tally. The resultant defect usually requires nerve grafting. with resection and nerve grafting. However, an incomplete
Occasionally, when there are other associated significant neuroma in continuity or a mixed, sixth-degree injury may
injuries that require acute management that might be com- arise after a partial nerve injury or a previous nerve repair
promised with secondary surgery, we will do an acute nerve in which portions of the nerve are functioning while other
graft. In these cases, we will make sure that we bread loaf critical components are not. The surgeon must be careful not
proximally and distally enough to be well outside the zone to downgrade the patient’s function by sacrificing the func-
of injury. Our current algorithms for the timing of nerve tioning components in an attempt to repair the remainder
repair are shown in Figures 9.6 and 9.7. of the nerve. Careful preoperative assessment will determine
Clinical studies have not shown a clear superiority of fascic- which fascicular components are functioning and should be
ular repair over an epineural repair. If the internal topography preserved.
of the nerve is known to be segregated in discrete motor/sen- At the time of repair, the neuroma in continuity may
sory groups, however, a grouped fascicular repair should have involve the complete circumference of the nerve. Individual
benefit over an epineural repair; otherwise, the extra manipu- fascicles proximal and distal to the neuroma can be sepa-
lation and suture material may actually decrease the functional rated using a microneurolysis technique. A hand-held nerve
results. Unless the surgeon is specifically trying to direct motor stimulator or intraoperative nerve conduction testing is
and sensory alignment because of a favorable internal topog- used to help identify functioning motor fascicles. If sensory
raphy, an epineural repair is standard. Bleeding from epineural fascicles are to be protected, intraoperative nerve conduc-
vessels should be controlled with gentle pressure or fine bipolar tion testing proximal and distal to the neuroma may be
coagulation under microscopic guidance. After transection of required.18

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Chapter 9: Principles and Techniques of Peripheral Nerve Repair, Grafts, and Transfers 83

Principles, Techniques, and


Basic Science
Figure 9.6.  Algorithm for the management of closed nerve injuries. EMG, electromyography; MUPs, motor unit
­potentials; NAP, nerve action potential; NCS, nerve conduction studies.

Separating the functioning fascicles from within the neu- the lateral malleolus and is usually harvested in a retrograde
roma may cause additional injury to functioning components. direction. The resultant area of numbness on the lateral side
In this situation, the neuroma possessing functioning fascicles of the foot decreases in size over time. The disadvantages of
should be preserved, whereas the nonfunctioning proximal the sural nerve are the separate distal donor site and the less
and distal fascicles can be reconstructed with nerve grafts favorable neural-to-connective tissue ratio as compared with
“black boxing” around the neuroma (Figure 9.9). upper extremity donor nerves.
When a limited amount of graft material is required, the
medial or lateral antebrachial cutaneous nerve can be har-
Donor Nerve Grafts vested from the injured upper extremity. The lateral ante-
The sural nerve in the adult can provide 30 to 40 cm of nerve brachial cutaneous nerve is found adjacent to the cephalic
graft. In 80% of dissections, it is formed by a union of the vein along the ulnar border of the brachioradialis muscle.
medial sural cutaneous nerve and the lateral peroneal com- A maximum of 8 cm of nerve graft can be obtained and the
municating branch. When a large amount of graft material loss of sensation is negligible as a result of the overlap in
is needed, the communicating branch can contribute an addi- distribution by the radial sensory branch. The donor scar
tional 10 to 20 cm. It can also be neurolyzed from the tib- on the volar aspect of the forearm may be objectionable to
ial and peroneal nerves well proximal to the popliteal fossa. some patients. The medial antebrachial cutaneous (MABC)
The nerve is found adjacent to the lesser saphenous vein at nerve, found in the groove between the triceps and biceps

Figure 9.7.  Algorithm for the management of open nerve injuries. asurgeon uncertain as to proximal and
distal extent of injury; bas soon as soft tissue status permits.

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84 Part I: Principles, Techniques, and Basic Science
Sensory fascicles
of median n.

Motor group
of median n.

Figure 9.8.  Nerve repair. A. In an epineural repair, the fascicles


must be appropriately trimmed so that they do not buckle, which will
result in misdirection of the regenerating fibers. Excessive tighten-
ing of the epineural sutures can also cause buckling of the fascicles.
B. Well-performed nerve repairs will result in good alignment of
­fascicles without the need for fascicular sutures.

muscles adjacent to the basilic vein, has a posterior and


Neuroma
an anterior division. Harvesting of the anterior branch is
preferred because this results in loss of sensation over the
anterior aspect of the forearm, whereas loss of the posterior Median n.
branch causes numbness over the elbow and the resting por-
tion of the forearm. If necessary, up to 20 cm of nerve graft
can be obtained with the MABC, and the donor scar on the
medial side of the upper arm is more acceptable. Patients are
A C
instructed that an initial broad area of donor sensory loss
will gradually decrease in size over 2 to 3 years. We do an Figure 9.9.  Neuroma in continuity. A. When reconstructing a neu-
end-to-side transfer from the distal stump of the MABC to roma in continuity with intact motor function, the motor fascicles
the sensory side of the median nerve to rapidly decrease sen- through the neuroma must be preserved. B. Intraoperative nerve test-
sory donor deficit. ing can identify the motor fascicles proximal and distal to the neu-
roma. C. The remaining sensory fibers are divided proximally and
Patients with complete median nerve sensory loss have loss
distally, then reconstructed with grafts bypassing the neuroma. Any
of sensation in the first, second, and third web spaces. Because attempt to dissect the motor fascicles out of the neuroma will only
sensation is not critical in the third web space, the third web downgrade the function.
space nerve can be harvested to reconstruct the median nerve
defect, avoiding any additional morbidity caused by nerve
harvesting. The third web space nerve can be neurolyzed from
the main median nerve, providing up to 24 cm of nerve graft indicated in very proximal peripheral nerve injuries or root
(Figure 9.10). In a similar manner, the dorsal branch of the avulsions where a proximal stump is unavailable for pri-
ulnar nerve can be harvested to reconstruct the ulnar nerve. mary repair or grafting. Even when grafting is possible, the
When possible, the distal stump of the donor nerve is sewn injury may be so proximal that a nerve transfer facilitates
end-to-side to an adjacent normal nerve to restore improved better reinnervation of motor endplates than does a nerve
sensation to the donor territory. Vascularized nerve grafts graft. Nerve transfers are also indicated to avoid operating
have a limited role in peripheral nerve reconstruction, and in regions of severe scarring, when nerve injuries present in
their use is typically limited to lengthy, large caliber nerve a delayed fashion, when partial nerve injuries present with a
grafts such as the ulnar nerve. well-defined functional deficit, or when the level of injury is
Expendable motor nerves that can be used as motor nerve unclear such as in idiopathic neuritides or radiation-induced
grafts include the distal anterior interosseous nerve to the nerve injury.19
pronator quadratus, the obturator nerve branch to the graci- Motor nerve transfers require an expendable donor
lis, and the thoracodorsal nerve branches to the latissimus motor nerve with a large number of pure motor axons that
dorsi. In fact, any nerve innervating a free muscle transfer are located in close proximity to motor endplates, thus
could be used as a motor nerve graft. We use these motor minimizing the distance and time regenerating axons need
nerve grafts for reconstruction of critical motor function to travel to reinnervate their targets. It is also preferable
when nerve transfer does not provide a better option, such that the donor nerve innervates a muscle that is synergis-
as the intrinsic motor fascicle of the ulnar nerve at the hand tic with its target.13 The criteria for sensory nerve transfers
or wrist. include an expendable donor sensory nerve that innervates
a noncritical sensory distribution, contains a large number
of pure sensory axons, and is located near its sensory end
Nerve Transfers organs.
The use of nerve transfers has expanded over the last decade The most common applications of motor nerve transfers
based on a more detailed knowledge of the intraneural include the restoration of elbow flexion, shoulder abduc-
topography and branching patterns of peripheral nerves tion, ulnar-innervated intrinsic hand function, forearm
in the upper and lower extremities. Nerve transfers are pronation, and radial nerve function. 13 To restore elbow

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 9: Principles and Techniques of Peripheral Nerve Repair, Grafts, and Transfers 85
to the median nerve–innervated pronator teres can restore

Principles, Techniques, and


forearm pronation. Alternatively, the flexor digitorum
superficialis, or palmaris longus branches of the median
nerve, can be transferred to its pronator branch. The radial
nerve may be reconstructed by transferring median nerve

Basic Science
donors including redundant flexor digitorum superficialis
branches and flexor carpi radialis branches to the nerve to
extensor carpi radialis brevis and the posterior interosseous
nerve, respectively, perhaps in combination with a prona-
tor teres to extensor carpi radialis brevis tendon transfer.20
The site nervesurgery.wustl.edu has all our nerve transfers
available.

Nerve Conduits
Studies show that nerves will regenerate across a short
nerve gap through various conduits, such as veins, pseu-
dosheaths, and bioabsorbable tubes.21 The characteristics of
the ideal nerve conduit include low antigenicity, availability,
Figure 9.10.  Median nerve at the wrist. The nerve to the 3rd web-
space can be used as a nerve graft to assist in the reconstruction of
and biodegradability. Vein grafts have been used to recon-
the more critical nerves. The proximal portion is harvested as a graft struct distal sensory nerve defects of less than 3 cm. Sensory
(green). The distal end of the 3rd webspace nerve is repaired in an end- results with vein grafts have been acceptable but not as good
to-side epineural fashion to the nerve to the 2nd webspace (yellow). as conventional grafting. For this reason vein grafts are
recommended only for reconstruction of noncritical nerve
gaps of less than 3 cm.22
Nerve regeneration across a 3-cm gap through a biode-
flexion, the medial pectoral, thoracodorsal, or intercostal gradable polyglycolic nerve tube has been demonstrated in the
nerves can be transferred to the musculocutaneous nerve. primate model and in a clinical trial.13 Clinical recovery was
The flexor carpi ulnaris branch of the ulnar nerve and the comparable to that across a standard nerve graft. The inser-
flexor digitorum superficialis/flexor carpi radialis branch tion of a short piece of nerve graft material into the center
of the median nerve can also be transferred to the biceps of the conduit will enhance regeneration by providing a local
and brachialis branches of the musculocutaneous nerve source of trophic factors. The ready availability of biodegrad-
to more specifically restore elbow flexion and limit donor able synthetic grafts to span short nerve gaps would eliminate
nerve morbidity (Figure 9.11). To restore shoulder abduc- the morbidity associated with nerve graft harvest and would
tion, the distal accessory nerve can be transferred to the capitalize on the potential benefits of neurotropism in direct-
suprascapular nerve, or the medial head triceps branch of ing nerve regeneration. Synthetic nerve conduits are now
the radial nerve can be transferred to the axillary nerve. To available for reconstruction of small diameter nerves with a
restore intrinsic hand function, the distal anterior interosse- gap ≤3 cm, or with large diameter nerves with gaps ≤0.5 cm.
ous nerve can be transferred to the ulnar nerve. Transferring We recommend limiting the use of nerve conduits to bridging
redundant fascicles of the flexor carpi ulnaris branches of small sensory gaps and as nerve wraps and we would advise
the ulnar nerve or the extensor carpi radialis brevis nerve the addition of some proximal minced nerve to the center of

Ulnar n.
Ulnar n.

Musculocutaneous n.
Musculocutaneous n.
Median n. Median n.

Biceps brachii branch Redundant FCR fascicle


Biceps brachii branch Redundant FCU fascicle

Redundant FCU fascicle


Redundant FCR fascicle
Brachialis branch
Brachialis branch

A B

Figure 9.11.  A double fascicular transfer for elbow flexion. A. Transfer of a redundant fascicle of the ulnar nerve to the biceps
branch of the musculocutaneous nerve and a redundant fascicle of the median nerve to the brachialis branch of the musculocutaneous
nerve. B. Transfer of a redundant fascicle of the median nerve to the biceps branch of the musculocutaneous nerve and a redundant
fascicle of the ulnar nerve to the brachialis branch of the musculocutaneous nerve. FCR, flexor carpi radialis; FCU, flexor carpi ulnaris.

(c) 2015 Wolters Kluwer. All Rights Reserved.


86 Part I: Principles, Techniques, and Basic Science

the conduit to provide a source of Schwann cells and trophic


factors. Conclusion
Nerve repair and grafting have benefited from the development
Nerve Allografts of microsurgical techniques and advances in the neurosciences.
State-of-the-art nerve repair requires not only precision tech-
Nerve allografts have demonstrated clinical usefulness in the niques but also additional measures to direct nerve regenera-
setting of extensive peripheral nerve injuries where there is a tion to its original function. Although nerve grafting remains
paucity of donor nerve material. Because the nerve allograft the standard for reconstruction of the nerve gap, synthetic
serves as a scaffold that is repopulated by host axons and conduits, allografts, and nerve transfers now play a limited
Schwann cells over time, its challenge to the immune system role in the peripheral nerve surgeon’s armamentarium.
is of limited duration. The agent FK506 (tacrolimus) is most
ideally suited for treating patients with peripheral nerve References
allografts based on its dual role as an immunosuppressive
and a neuroregenerative agent. By accelerating the rate at 1. Cajal SRY. Degeneration and Regeneration in the Nervous System. Vol 1.
London: Oxford University Press; 1928.
which axons traverse the nerve allograft, FK506 shortens 2. Sunderland S. The capacity of regenerating axons to bridge long gaps in
the duration of immunosuppression and the period dur- nerves. J Comp Neurol. 1953;99:481-497.
ing which complications can develop. The optimal timing 3. Lundborg G, Hansson HA. Nerve lesions with interruption of continuity:
and dose of FK506 therapy has been identified in rodents, studies on the growth pattern of regenerating axons in the gap between
the proximal and distal nerve ends. In: Gorio A, Millesi H, Mingrino S,
and a synergistic effect with nerve allograft cold preserva- eds. Posttraumatic Nerve Regeneration: Experimental Basis and Clinical
tion, as well as an ability to rescue nerve allografts under- Implications. New York, NY: Raven Press; 1981:229-239.
going acute rejection, established. Based on these findings, 4. Mackinnon S, Dellon L, Lundborg G, Hudson A, Hunter D. A study of
FK506 is now the mainstay of clinical peripheral nerve neurotropism in the primate model. J Hand Surg [Am]. 1986;11:888-894.
5. Brushart TM, Seiler WD. Selective reinnervation of distal motor stumps by
allotransplantation. peripheral motor axons. Exp Neurol. 1987;97:289-300.
Potential candidates for peripheral nerve allotransplan- 6. Jabaley ME, Wallace WH, Heckler FR. Internal topography of major nerves
tation receive nerve allografts from donors that have been of the forearm and hand: a current view. J Hand Surg [Am]. 1980;5:1-18.
screened for ABO blood typing, HIV, and cytomegalovi- 7. Seddon HJ. Three types of nerve injury. Brain. 1943;66:237-288.
8. Sunderland S. A classification of peripheral nerve injuries producing loss of
rus. These grafts are stored in the University of Wisconsin function. Brain. 1951;74:491-516.
cold storage solution at 41°F (5°C) for at least 7 days. 9. Mackinnon SE, Dellon AL. Surgery of the Peripheral Nerve. New York,
This solution is supplemented with penicillin G, dexa- NY: Thieme; 1988.
methasone, and insulin. Immunosuppression of the nerve 10. Strauch B, Lang A, Ferder M, et al. The ten test. Plast Reconstr Surg.
1997;99:1074-1078.
allograft recipient begins 3 to 5 days prior to nerve trans- 11. Clarke E, Bearn JG. The spiral nerve bands of Fontana. Brain. 1972;95:1-20.
plantation and consists of FK506 whose dose is titrated 12. Williams HB, Jabaley ME. The importance of internal anatomy of the peripheral
to appropriate steady-state blood levels, azathioprine, and nerves to nerve repair in the forearm and hand. Hand Clin. 1986;2:689-707.
prednisone. The prednisone dose is tapered in the first 4 to 13. Dvali L, Mackinnon S. Nerve repair, grafting, and nerve transfers. Clin
Plast Surg. 2003;30:203-221.
8 weeks after surgery. Pneumocystis carinii prophylaxis is 14. Hallin RG. Microneurography in relation to intraneural topography:
performed at the time of immunosuppression to minimize somatotopic organization of median nerve fascicles in humans. J Neurol
opportunistic pulmonary infections. Immunosuppression Neurosurg Psychiatry. 1990;53:736-744.
continues for 6 months after a Tinel sign is noted to pass 15. Greenberg MM, Leitao C, Trogadis J, et al. Irregular geometries in normal
unmyelinated axons: a 3D serial EM analysis. J Neurocytol. 1990;19:978-988.
the last distal neurorrhaphy site and some functional 16. Lundborg G, Dahlin LB, Danielsen N, et al. Tissue specificity in nerve
recovery has occurred. Peripheral nerve allograft rejec- regeneration. Scand J Plast Reconstr Surg. 1986;20:279-283.
tion resembles a superficial phlebitis with inflammation 17. Dorsi[Q15] MJ, Chen L, Murinson BB, Pogatzki-Zahn EM, Meyer RA,
and tenderness, but is localized over the underlying nerve Belzberg AJ. Pain. 2008;134(3):320-334.
18. Lee GW, Mackinnon SE, Brandt K, et al. A technique for nerve recon-
allograft and not a vein. struction following resection of soft-tissue sarcoma. J Reconstr Microsurg.
Processed acellular cadaveric nerve allografts have 1993;9(2):139-144.
become available for clinical use recently (AxoGen, Inc., 19. Mackinnon SE, Novak CB, eds. Nerve transfers. Hand Clin. November
Alachua, FL). These grafts are available in different diam- 2008;24(4):319-488.
20. Ray WZ, Mackinnon SE. Clinical outcomes following median to radial
eters and lengths, are not immunogenic, and thus do not nerve transfers. J Hand Surg [Am]. 2011;36(2):201-208.
require immunosuppression. Some studies suggest that these 21. Weber RV, Mackinnon SE. Bridging the neural gap. Clin Plast Surg.
allografts allow regeneration over longer nerve gaps than 2005;32(4):605-616.
empty conduits, but they fail to be equivalent to nerve auto- 22. Moore AM, Kasukurthi R, Magill CK, Farhadi HF, Borschel GH, Mackinnon
SE. Limitations of conduits in peripheral nerve repairs. Hand. 2009;4(2):180-186.
graft.23 These acellularized allografts have largely replaced 23. Whitlock EL, Tuffaha SH, Luciano JP, et al. Processed allografts and type
nerve conduits, but we limit their use to noncritical sensory I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve.
nerve deficits ≤3 to 4 cm. 2009;39(6):787-799.

(c) 2015 Wolters Kluwer. All Rights Reserved.


CHAPTER 10  n  Tissue Expansion

Principles, Techniques, and


Ashley K. Lentz and Bruce S. Bauer

Basic Science
Tissue expansion provides additional cutaneous tissue, allow- tapering of tissue. In terms of shape, they follow three basic
ing the surgeon to optimize contour and color match in a given patterns: round, rectangular, and crescent. The more com-
reconstructive effort. Careful planning and follow-through monly used include the round and rectangular types. The cres-
are necessary to achieve the desired outcome and minimize cent-shaped prostheses were originally designed in an effort
complications. to minimize dog-ears at the donor site, but have fallen out of
favor. It has been recognized that the rectangular expanders
allow for additional expanded tissue, thereby increasing the
Background possible choices for flap design (Figure 10.1).
Although the genesis of modern-day tissue expansion is cred- Expander volumes have a wide range and the choice var-
ited to Radovan1 and Austad,2 the technique takes some of ies according to the anatomic site of expansion and need for
its roots from early lessons in distraction osteogenesis. Bone gained tissue. Round and rectangular expanders range in size
traction with either internal or external devices at the turn of from less than 100 cc to greater than 1,000 cc in volume.
the 20th century paved the way for the concept that mechan- Sterile technique is used to deliver saline to the valve port,
ical stress on tissue leads to lengthening. In the mid-1950s, which may be integrated into the expander device or attached
Neumann 3 became the first surgeon to use an expansile to the expander via silicone tubing of customized length.
implant when he used a latex balloon to enlarge periauricu- An integrated system is favorable if only one single pocket
lar skin for a traumatic ear deformity. Despite these early is undermined; however, the implant may be more prone to
efforts, it was not until 20 years after Neumann’s report that rupture during expansion. Remote ports avoid the danger of
tissue expansion was revisited. Charles Radovan, 1 a resi- inadvertent prosthesis rupture, but have their own set of com-
dent at Georgetown, reintroduced the concept of expansion plications including flipping or migration of the device in vivo,
when he inserted a contemporary device with an internally as well as tube obstruction. In an effort to avoid these compli-
placed port. Shortly thereafter, Eric Austad2 produced a self- cations, the port tunnel should be conservative in size and the
inflating device. In 1982, the first National Tissue Expansion port should be placed over firm supportive tissue and secured
Symposium was sponsored by the Plastic Surgery Educational with sutures if needed.
Foundation. This marked the recognition of a new advance
in reconstructive surgery. Since that time, expansion has
been applied to a multitude of reconstructive problems, with
Surgical Planning
applications demonstrated in both local expansion and dis- One aspect cannot be overemphasized: The design for flap
tant expansion for subsequent graft and flap transfer. Better expansion should be planned prior to surgery. Consideration
understanding of expansion has allowed modifications in for the incisions, expander placement, flap movement in rela-
flap design, increasing its value as a reconstructive option.4 tion to the defect, and postoperative scars require appreciable
preoperative planning. Thorough discussions with the patient
and family are critical for successful reconstruction. If home
Physiology tissue expansion is planned, then we suggest a separate clinic
When mechanical stress is applied to skin over time, two session devoted to education of the patient and family with
phenomena occur: mechanical creep and biologic creep. The regard to the goals of expansion, expansion technique, and the
former is based on morphologic changes that occur on a cel- need for keen observation of the skin throughout the process.
lular level in response to the applied stress. Mechanical creep
is essentially cellular stretch. However, biologic creep is a cel-
lular proliferation that results from the disruption of gap junc-
tions and increased tissue surface area. Growth of the tissue by
cellular proliferation restores resting tension of the stretched
tissue to baseline.5 The epidermis gets thicker with concurrent
thinning of the dermis and alignment of collagen fibrils. These
effects are maximized at 6 to 12 weeks post-expansion. On a
molecular level, various cytokines are induced in response to
expansion.6
The vascularity of an expanded flap is superior to its non-
expanded counterpart in both number and caliber of vessels.7
Moreover, angiogenic factors such as vascular endothelial
growth factor are expressed in expanded tissue at a signifi-
cantly higher level when compared with nonexpanded con-
trols. This augmentation in blood flow is attributable to the
capsule that forms around the prosthesis. Because of the simi-
larity between expanded and delayed flaps in vessel caliber,
tissue expansion is regarded as a form of the delay phenom-
enon. An expanded flap, therefore, is a delayed flap.

Expansion Devices
Figure 10.1.  Rectangular tissue expanders. Size 350 and 500 mL
Tissue expanders differ in size, shape, and type of filling tissue expanders with rectangular shape, thicker base plate, tubing,
valve. Expanders can be standard, customized to the donor and a small and large remote filling port.
site (breast), or can be designed to fill differentially to provide
87
(c) 2015 Wolters Kluwer. All Rights Reserved.
88 Part I: Principles, Techniques, and Basic Science

Donor site choice plays an important role in expansion as inserting the expanders, they should be placed in the subga-
the surgeon strives to provide a good match for color, texture, leal plane above the periosteum. Flaps should be designed with
and contour for an optimal aesthetic and functional outcome. careful attention to the dominant vessels of the scalp, includ-
Infection, unstable scars, and traumatized tissue of the donor ing the superficial temporal, postauricular, and occipital arter-
site may lead to implant failure or extrusion. When placing ies and contributions from the supraorbital arteries. Finally,
expanders, attention is paid to the location of the incision. port placement in the preauricular region produces the least
If the purpose is removal of a lesion, we recommend plac- migration.
ing the incision within the lesion borders. Gentle handling of
the skin flaps is mandatory, as rough or aggressive retraction Forehead
of the flaps can lead to skin edge necrosis. The port should
Expanded flap reconstruction of the forehead provides some
be placed in a region of firm skeletal support, such as rib,
of the most challenging cases because of the potential morbid-
iliac crest, or anterior thigh. Partial fill of the expander at the
ity and disfigurement of the brow and hairline. One must have
time of placement (approximately 10% to 20% of its listed
great respect for the aesthetic subunits to avoid late complica-
volume) assures that the expander is properly positioned
tions. We reported an aesthetic complication rate of 24% in
and without surface folds. Soft, flexible expanders should be
forehead tissue expansion, including brow asymmetry, brow
used and the redundant expander should be folded under-
ptosis, altered hair direction, and anterior hairline asymme-
neath the expander in order to avoid future interference with
try.10 Over the years, principles have been developed to mini-
the port during filling. Large expanders measuring greater
mize these complications: (a) bilateral expansion of normal
than 250 mL prove more effective and we routinely use
forehead tissue is often successful for midforehead lesions;
500 mL or larger expanders. We recommend the use of larger
(b) serial expansion of the forehead is often required for hemi-
ports for even the smaller expanders in order to avoid flip-
forehead nevi; (c) supraorbital and temporal nevi are man-
ping of the port and easier palpability. Small closed s­ uction
aged using a transposition of expanded normal skin medial
drains are used to close the potential dead space. In most
to the nevus; (d) with minimal involvement of the temporal
cases, the expander pocket incisions are closed in a watertight
region, expanded parietal skin can be advanced to reconstitute
fashion with 4-0 clear Nylon sutures and 4-0 Prolene running
the hairline; and (e) in cases of brow elevation, the abnormal
continuous sutures. Skin flaps are dressed with Bacitracin
brow can be returned to its preoperative position by interpos-
and Xeroform gauze followed by soft 4 × 4 fluffs. Patients
ing non–hair-bearing forehead skin.
may or may not require overnight admission for pain control
and monitoring of the skin flaps for potential compromise or
hematoma formation. Face and Neck
Serial expansion begins 7 to 10 days post-insertion, pro- Once again, strict adherence to the aesthetic subunit prin-
vided that the skin flaps are in excellent condition. Drains ciples is required to achieve optimal results. Careful plan-
are removed within 10 days of surgery. After detailed ning for expander placement and flap incision will ensure
training and education, pediatric patients participate in a that the final scars are “hidden” in natural creases such
home expansion protocol directed by the parent or guard- as the nasolabial fold. Undue tension on the middle and
ian. It has been demonstrated that home expansion is safe lower third of the face can result in lower lip droop, oral
and equivalent to office expansion with regard to success- incontinence, and an asymmetric smile. The advancement of
ful outcome.8 Expansion should render the skin tense, but cervical skin flaps has an exceptional tendency to result in
one should not expand until it is extremely painful to the these complications. Therefore, we prefer to expand trans-
patient or cause skin compromise. Both suggest overly position and rotation flaps from the lateral cheek or neck
aggressive expansion. The home expansion protocol typi- and postauricular region. The use of multiple prostheses
cally lasts 8 to 12 weeks in preparation for transfer of the and overexpansion is recommended in order to further min-
expanded tissue. imize these complications.
Although early dogma of tissue expansion emphasized Expansion may also be applied to donor sites in prepara-
expansion as a means of generating large advancement flaps, tion for full-thickness skin grafting.11 This technique elimi-
experience demonstrates that expanded transposition and nates the size of the graft as a limitation for reconstruction.
rotation flaps are frequently preferable. Clearly, the increased A portion of the expansion provides for the graft tissue, while
vascular supply of the expanded flap places little limitation the remainder serves to allow for primary closure of the donor
on the ingenuity of the surgeon in designing flaps unique to site. Expansion of the abdomen results in aesthetic wound clo-
the varied recipient defects. Although requiring more planning sure with the ability to hide the donor site scars. The supracla-
and forethought, transposition of the flap provides greater vicular skin is ideal for grafts on the face due to the excellent
versatility in flap design and range.4,9 color and texture match. Once expanded, these full-thickness
grafts have the same characteristics as their unexpanded
counterparts in terms of durability, texture, contraction, and
Head and Neck growth.
Scalp
Large areas of the scalp can be reconstructed using tissue expan- Trunk
sion to replace the defect with hair-bearing scalp. The scalp is Beyond the obvious indications for breast deformities, tissue
also the second most common site of reconstruction using tissue expansion has multiple applications on the trunk for treat-
expansion as well as the area with which surgeons have the most ment of giant congenital nevi, vascular malformations, and
familiarity. Scalp reconstruction is warranted in three scenarios: contour defects.
large congenital melanocytic nevi, scar and skin graft alopecia
(Figure 10.2), and traumatic or iatrogenically caused craniofacial
abnormalities. It has been thought that scalp tissue expansion Abdomen
may permanently affect cranial vault morphology; however, this The lower abdomen may be the most easily expanded ana-
is not the case. Temporary cranial molding occurs, but corrects tomic site. It can be used for full-thickness graft donor sites,
within 3 to 4 months. In the treatment of congenital melanocytic as mentioned above, or as donor tissue for transposition flaps
nevi, larger expanders are placed serially in order to distribute for coverage of the anterior thigh. Expansion may also be used
the expansile forces evenly over the hair follicles. The scalp to expand free tissue transfers. We have successfully used the
can double in size without causing obvious alopecia. When expanded free transverse rectus abdominis musculocutaneous

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 10: Tissue Expansion 89

Principles, Techniques, and


Basic Science
B

E
Figure 10.2.  Cranial defect after a train accident. A. Right cranial
defect. B. Multiple expanders were placed. C. Elevation of scalp flaps
after expansion. D. Placement of titanium mesh. E. Postoperative result.
C

(c) 2015 Wolters Kluwer. All Rights Reserved.


90 Part I: Principles, Techniques, and Basic Science

(TRAM) flap to treat shoulder defects as well as those of the time. Aesthetic surgeons also use this trick to adjust breast
upper extremity below the elbow.13 While the lower abdomen size over time. Use of either an expander or an expander-
can be successfully used as a donor site, the upper abdomen implant in these cases may constitute an off-label use for
and anterior trunk must be cautiously regarded, as there exists these devices. Expanders are not constructed for prolonged
the unwanted potential for breast distortion. use (i.e., over the 6 to 8 years of breast development).
Postoperatively adjustable permanent implants are designed
Back for longer term use but are supposed to have their ports
removed promptly after complete fill to prevent implant
Expansion of the posterior trunk is the preferred modality
deflation. As such, a discussion of these possibilities needs
for the treatment of congenital nevi of the back and buttock
to occur prior to placement. The postoperatively adjust-
(Figure 10.3). Whether advancing the skin caudally or ceph-
able implants come in sizes, shapes, and volumes particu-
alad, serial expansion is frequently required for excision of
larly suited to use in this situation. Depending on how much
extensive lesions. Expansion can begin as early as 6 months of
native breast exists, these expanders can be placed subglan-
age for treatment of pediatric nevi and proves easier in early
dularly or submuscularly.
childhood as compared with later age. The lower back may
Once the patient reaches maturity, the expander can be
be expanded to develop large transposition flaps for coverage
replaced with a permanent implant and balancing procedures
of the buttock. The use of large expanded transposition flaps
to match breast shape can be performed on the opposite
has allowed the excision and reconstruction of giant nevi with
breast for “out-of-a-bra” symmetry. In the case of a patient
fewer procedures and more aesthetic and functional position-
with Poland syndrome with significant infraclavicular soft-
ing of the final scars.13
tissue deficiency, a latissimus dorsi flap can be transferred or a
custom permanent implant manufactured at the time of defini-
Breast tive reconstruction.
Expanders and expandable implants are used in breast surgery
for postmastectomy reconstruction and treatment of congeni- Extremities
tal anomalies.
Classically, the extremity is viewed as an unfavorable donor
for an expanded flap. Complication rates in the limb are
Postmastectomy Reconstruction higher than those compared with other sites, and simple
Implant-based breast reconstruction remains the most common expansion does not provide a large amount of surface area
choice after mastectomy (Chapter 59). The relative ease and with which to work. These facts have led us to find alternative
rapidity of subpectoral expander placement make it a highly options and creative methods for successful reconstruction of
requested surgical option among women. Tissue expanders are the extremity. Additionally, extremity expansion should be
typically placed under the pectoralis muscle superiorly, while a avoided in unstable or infected wounds.
sling of acellular dermis or serratus anterior muscle covers the
expander inferiorly. Exchange of the expander for a perma- Upper Extremity
nent prosthesis may be performed after the patient has under-
gone serial outpatient expansion to a desired breast volume. A useful algorithm for complex defects has been devised
This topic is covered in detail in Chapter 59. for upper limb reconstruction.12,13 Based on our experience,
Expanders have been used as spacers during “delayed successful contour and color match of the upper extremity
primary” breast reconstruction. The expander placed at comes from approaching it in thirds (proximal to elbow;
the time of mastectomy preserves the skin envelope while midforearm; and the hands, web spaces, and fingers) and
awaiting final pathology results. If radiation is war- from whether or not the lesion is circumferential or non-
ranted, the expander holds the original skin envelope circumferential. For proximal noncircumferential defects,
until delayed reconstruction can be performed. If no post- expanded transposition flaps from the back or shoulder serve
mastectomy radiation is indicated, then the patient may the purpose well. If the lesion is large and circumferential,
proceed with either implant-based or autologous breast covering the majority of the proximal arm, expanded free
reconstruction. TRAM flaps are the method of choice. Distally, for large
circumferential mid- or lower forearm lesion, expansion of
Tissue Expansion in the Treatment of the flank creates a pedicled carrier “sling” through which
the forearm can be placed for 3 weeks prior to pedicle divi-
Congenital Breast Anomalies sion (Figure 10.4). As previously reported, expanded full-
Expanders can be helpful as “spacer” in the correction of thickness skin grafts from the abdomen or the groin remain
congenital breast anomalies. Requests for breast habilita- the treatment of choice for reconstruction of fingers, webs,
tion come from patients with breast agenesis associated with and hands.
Poland syndrome, idiopathic unilateral breast hypoplasia,
and iatrogenic breast asymmetry as a consequence of juve-
nile breast bud damage. Traditional wisdom has been to wait
Lower Extremity
for maturity prior to correcting breast asymmetries. This Skin of the lower extremity lacks flexibility and requires
strategy assures that the surgeon knows what needs to be complex solutions for wound closure. We have developed an
matched on the opposite side. Although this solution may algorithm for the treatment of congenital nevi of the lower
have been acceptable previously, today’s adolescent female extremity.14 This algorithm takes into consideration the size
has problems with changing in locker rooms, participat- and location of the defect, as well as the age of the patient.
ing in sports activities, and wearing fashionable clothing. Creative approaches for wound closure include expanded free
Questions of developing self-esteem, body image, and sexual flaps, expanded local transposition flaps (Figure 10.5), serial
identity further compound the issue of waiting. Expanders excision, and full-thickness skin grafts.
can function as an intermediate solution. This topic is cov-
ered in Chapter 64.
Many young women are happy with breast volume sym-
Complications
metry so that they appear normal in a bra. With this goal As mentioned above, site-specific complications may occur.
in mind, an expander can be placed as early as the oppo- Major complications include infection, implant exposure,
site breast begins to develop and can be expanded over and flap ischemia. Traditional dogma suggests that an

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 10: Tissue Expansion 91

Principles, Techniques, and


Basic Science
B

Figure 10.3. Giant congenital nevus of the back and buttock.


A. Preoperative appearance. B. Expander placement. C. Multiple
stages of expansion were required. D. Postoperative result.
C

(c) 2015 Wolters Kluwer. All Rights Reserved.


92 Part I: Principles, Techniques, and Basic Science

early postoperative infection requires expander removal. antibiotics may be administered until the wounds close
However, an infection occurring late in the expansion secondarily.
course can occasionally be salvaged with antibiotic ther- Minor complications with expansion include transient pain
apy. 15 Exposure of the implant may be treated the same during the expansion process, seroma formation, dog-ears at
way, especially if the expander is located in a dependent the donor site, and widening of the scars. The majority of these
portion of the open wound. Local wound care and oral complications resolve in time or with minor surgical revision.

A
D

E
Figure 10.4. Congenital giant nevus of the upper extremity.
A. Preoperative appearance. B. Expansion of the flank. C. Removal
of the upper extremity nevus. D. Pocket created to cover the upper
extremity defect. E. Postoperative result.
B

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 10: Tissue Expansion 93

Principles, Techniques, and


Basic Science
A

C
Figure 10.5. Lower extremity nevus. A. Posterior thigh tissue
expansion. B. The expander was removed, the nevus was excised, and
the posterior thigh flap was used to anchor the leg in a position of
flexion in order to cover the defect. C. After flap division and inset.
B

8. Mohmand MH, Sterne GD, Gower JP. Home inflation of tissue expanders:
References a safe and reliable alternative. Br J Plast Surg. 2001;54:610-614.
9. Bauer BS, Vicari FA, Richard ME. The role of tissue expansion in pediatric
1. Radovan C. Adjacent Flap Development Using Expandable Silastic
plastic surgery. Clin Plast Surg. 1990;17(1):101-113.
Implants. Paper presented at the Annual Meeting of the American Society of
10. Bauer BS, Few JW, Chavez CD, et al. The role of tissue expansion in the
Plastic and Reconstructive Surgeons, Boston, MA, September 1976. management of large congenital pigmented nevi of the forehead in the
2. Austad ED, Rose GL. A self-inflating tissue expander. Plast Reconstr Surg. pediatric patient. Plast Reconstr Surg. 2001;107(3):668-675.
1982;70:588. 11. Bauer BS, Vicari F, Richard ME, et al. Expanded full thickness skin grafts
3. Neumann CG. The expansion of an area of skin by progressive distention of in children: case selection, planning and management. Plast Reconstr Surg.
a subcutaneous balloon. Plast Reconstr Surg. 1957;19:124. 1993;92:59-69.
4. Bauer BS, Margulis A. The expanded transposition flap: shifting paradigms 12. Margulis A, Bauer B, Fine N. Large and giant congenital pigmented nevi of
based on experience gained from two decades of pediatric tissue expansion. the upper extremity: an algorithm to surgical management. Ann Plast Surg.
Plast Reconstr Surg. 2004;114:98-106. 2004;52:158-167.
5. DeFilippo RE, Atala A. Stretch and growth: the molecular and 13. Bauer BS. Commentary on Gosain AK et al. Giant congenital nevi: a 20 year
physiologic influences of tissue expansion. Plast Reconstr Surg. experience and an algorithm for their management. Plast Reconstr Surg.
2001;109(7):2450-2461. 2001;108:632-636.
6. Takei T, Mills I, Arai K, et al. Molecular basis for tissue expansion: 14. Kryger ZB, Bauer BS. Surgical management of large and giant con-
clinical implications for the surgeon. Plast Reconstr Surg . genital pigmented nevi of the lower extremity. Plast Reconstr Surg.
1998;102(1):247-258. 2008;121:1674-1684.
7. Cherry GW, Austad E, Pasyk K, et al. Increased survival and vascularity 15. Adler N, Dorafshar AH, Bauer B, et al. Tissue expander infections in
of random pattern skin flaps elevated in controlled, expanded skin. Plast pediatric patients: management and outcomes. Plast Reconstr Surg.
Reconstr Surg. 1983;72:680. 2009;124:484-489.

(c) 2015 Wolters Kluwer. All Rights Reserved.


CHAPTER 11  n  Principles of Office Sedation
for Cosmetic Surgery
Maximilian W. B. Hartmannsgruber, Dominick Cannavo, and Nikolaus Gravenstein

The integrity of defense: “A defense that is expecting many surgical procedures. These platelet-active drugs should
an attack has an advantage. If the element of surprise is not be modified without involving the patient’s cardiologist/
added, it is usually because the defenders ignored warn- internist as acute perioperative stent thrombosis has been
ings and did not take the attackers seriously” reported after discontinuation of antiplatelet therapy. 3 On
the other hand, if the patient has had coronary revascular-
–Samurai: “The Art of War” 2,500 years ization within 5 years and is asymptomatic, the risk of a
ago by the Chinese general Sun Tzu1 cardiac event is decreased and does not normally require
While the standard of care theoretically allows for compli- additional workup. If revascularization was performed more
cations related to sedation for cosmetic surgery, everyone’s than 5 years previously or the patient is symptomatic, car-
expectation is for perfect results. After all, cosmetic proce- diac risk is increased and a more extensive evaluation is
dures, especially office-based, are the most elective of all mandated.
procedures. Worse still, complications are not only debated Cardiac risk factor modification frequently includes beta
in grand rounds or journals but rather in newspapers and blockade and cholesterol statin therapy throughout the peri-
on television. Careful intra- and postoperative care in an operative period.4
accredited, properly equipped facility by adequately trained
practitioners is assumed. When complications do occur, they Pulmonary
are often the result of inadequate planning and/or improper With respect to pulmonary status, smoking, chronic obstruc-
patient selection. tive pulmonary disease (COPD), reactive airway disease, and
obesity are the major risk factors. As with cardiac evaluation,
Preoperative Evaluation patients should be screened based on symptoms and exer-
tional capacity. If they are asthmatic, the goal is to stabilize
and Optimization them and avoid an exacerbation. Pulmonary function tests are
The purpose of preoperative evaluation is not simply to pro- rarely indicated or useful for preoperative screening. Because
vide “medical clearance,” but rather to identify and modify cosmetic surgery is elective, there is an opportunity to imple-
any risk factors. A comprehensive discussion of every possible ment smoking cessation in order to reduce pulmonary and
risk factor is beyond the scope of this chapter; we limit the thromboembolic complications and improve wound healing
discussion to cardiovascular and pulmonary/smoking, obesity, and flap perfusion. Maximum benefit, however, is probably
and the risk of deep vein thrombosis (DVT). not achieved until at least a month after smoking cessation.
Shorter term smoking cessation actually causes some increase
Cardiac in pulmonary secretions.
The American Heart Association and the American College
of Cardiology guidelines advocate an approach that relates Obesity
major, intermediate, and minor cardiovascular risk fac- The comorbidities in obese patients include atherosclerotic
tors to the planned procedure. 2 For example, if a major heart disease, adult-onset diabetes, congestive heart fail-
cardiovascular predictor is present, nonemergency surgery ure, systemic hypertension, cardiac arrhythmias, pulmonary
should be delayed until risk factor modification has been hypertension, obstructive sleep apnea, gastroesophageal
accomplished. reflux (GERD), a predisposition to DVT, and sensitiv-
Clinical predictors for a major adverse cardiac event ity to narcotic analgesics. The excess adipose tissue on the
include recent (<1 month) myocardial infarction, unstable chest and abdominal wall compresses the lungs. The resul-
angina, decompensated congestive heart failure, severe valvu- tant increased intrathoracic pressure is magnified by exces-
lar heart disease, and significant arrhythmias. The presence of sive adipose tissues within the peritoneal cavity leading to
one of these major clinical predictors mandates postponement a further reduction in the functional residual capacity and
of any cosmetic surgical procedure. total lung capacity. Asthma, chronic cough, and pulmonary
Intermediate predictors include mild stable angina, previ- fibrosis may be manifestations of GERD, another common
ous myocardial infarction, compensated congestive heart fail- accompanying effect of the increased intra-abdominal pres-
ure, diabetes mellitus (especially type I), renal insufficiency, sure of obesity. It is important to appreciate that following
and poor exertional capacity. Adequate cardiovascular fit- an abdominoplasty, with plication of the rectus abdomi-
ness to undergo an elective procedure, especially office-based, nis muscles, intra-abdominal pressure is acutely increased,
can be estimated by the patient’s ability to climb one flight of which exacerbates any preexisting pulmonary compromise.
stairs or walk one block on level ground without shortness In addition, lower extremity venous flow is impeded by
of breath and/or angina. This equates to 4 METs (metabolic increased intra-abdominal pressure, creating venous stasis
equivalents) in a completed exercise test.2 and an environment conducive to venous thrombosis. The
With respect to ischemic heart disease, it is advisable to physiologic changes imposed by rectus plication are often
wait at least 6 months after a myocardial infarction and/ underappreciated and persist without concomitant weight
or revascularization, angioplasty, stent placement, or bypass loss. While the cosmetic result obtained with an abdomino-
before considering elective surgery.2 Patients with a coro- plasty might give the perception of actual weight loss, the
nary stent(s) are universally on at least one and often two intraperitoneal fat remains and is compressed into a smaller
platelet inhibitors (e.g., aspirin and clopidogrel). This ther- space, exacerbating all the underlying pulmonary and venous
apy is important for the stents but is a contraindication to stasis aberrations.5

94
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 11: Principles of Office Sedation for Cosmetic Surgery 95
4. preserved protective airway reflexes and
Deep Vein Thrombosis

Principles, Techniques, and


5. amnesia
As with cardiac risk factor stratification/modification, the risk
In contrast, unconscious or deep sedation is a state in
of DVT is considered and mechanical and/or pharmacologic
which the patient’s airway may require support and, although
prophylaxis implemented as indicated. Risk factors for DVT

Basic Science
the patient may be arousable, the stimulus required to gener-
include birth control pills or hormone replacement therapy,
ate a patient response is more vigorous or even noxious. Given
protein C or S deficiency, antithrombin III deficiency, lupus
the variability to patient response with respect to sedation,
anticoagulant, factor V Leiden along with acquired risk fac-
careful monitoring is essential.
tors that include smoking, diabetes, congestive heart failure,
obesity, and history of prior DVT. A history of DVT superim-
poses additional risk on the intrinsic thromboembolic risk of Monitoring
the procedure. Basic monitoring calls for compliance with the American
Surgery-specific risks can also be stratified as high, medium, Society of Anesthesiologists Monitoring Standards.7
and low. High risks for DVT are prolonged procedures and those
associated with significant blood loss or fluid shifts. Examples 1. Standard I
in plastic surgery include major flap procedures, abdomino-  Qualified anesthesia personnel present throughout the
plasties and/or lower body lifts, and large volume liposuction. procedure.
Intermediate-risk procedures include facelifts. Blepharoplasty 2. Standard II
and excision of small lesions present a low risk for DVT.  Patient’s oxygenation, ventilation, circulation, and tem-
The aggressiveness of DVT prophylaxis is dictated by perature shall be continually evaluated.
preexisting risk factors superimposed on the inherent risk   2.1 Oxygenation
of the procedure. Using Virchow’s triad (endothelial dam-   Inspired gas: When an anesthesia machine is used, the
age, stasis of blood flow, and hypercoagulability) as a model, concentration of oxygen in the breathing system shall
the latter two components of the triad can be addressed. be measured by an oxygen analyzer with a low oxy-
Sequential compression devices are utilized when possible to gen concentration limit alarm in use.
prevent stasis and ideally are applied prior to initiation of the   Blood oxygenation: During all anesthetics, a quantita-
sedation/anesthetic. Neuraxial anesthesia (spinal and/or epi- tive method of assessing oxygenation such as pulse
dural) should be considered for abdominoplasty. Neuraxial oximetry shall be employed. When the pulse oximeter
anesthesia provides a sympathetic block that promotes is utilized, the variable pitch pulse tone and the low
venous return and decreases the likelihood of stasis and an threshold alarm shall be audible.
environment conducive to thrombosis. In terms of hyperco- 3. Ventilation
agulability, pharmacologic prophylaxis is achieved with pre-  During regional anesthesia (with no sedation) or local
incision prophylactic administration of subcutaneous heparin anesthesia (with no sedation), the adequacy of ventila-
or factor Xa inhibitors such as enoxaparin (Lovenox) and tion shall be evaluated by continual observation of
fondaparinux (Arixtra). qualitative clinical signs. During moderate or deep seda-
tion, the adequacy of ventilation shall be evaluated by
Preoperative NPO Guidelines continual observation of qualitative clinical signs and
monitoring for the presence of exhaled carbon dioxide
Fasting from solid food should be at least 8 hours. Milk is unless precluded or invalidated by the nature of the
allowable up to 6 hours before initiation of sedation. Oral patient, procedure, or equipment. If invoking the preclu-
medications may be taken with a sip of water up to the time sion option, a statement in the record to explain why is
of surgery. To increase patient satisfaction, decrease gastric recommended.
liquid volume, and to decrease the risk of dehydration or 4. Circulation
hypoglycemia from fasting, we encourage clear liquids up to   4.1  Continuous display of the electrocardiogram
2 hours before the anticipated anesthesia start time in the first (ECG). A helpful intraoperative ECG montage is to
patient of the day and 3 hours for all following patients. Even use at least one precordial electrode (except in breast
though the minimum fast time for clear liquid is 2 hours, this surgery). If the ECG monitor has only three leads,
allows for timely induction of the subsequent patients should this is readily accomplished by placing the left leg
the earlier procedures be shorter than anticipated. Examples lead into the V5 position—anterior axillary line in
of clear liquids include water, fruit juices without pulp, car- the fifth intercostal space—and monitoring lead two
bonated beverages, clear tea, and black coffee. Gatorade (right shoulder-left leg). This configuration results in
or other clear liquid electrolyte sports drinks are attractive a modified V5 lead and is considerably more sensitive
because the stomach empties many times faster after these for identifying ischemia than any other single lead.
than after water alone because they contain sugar and salt that   4.2  Arterial blood pressure and heart rate determina-
accelerate absorption from the proximal gastrointestinal tract tion and evaluation at least every 5 minutes. Cautious
and the sugar also prevents hypoglycemia in patients who are interpretation of the patient’s blood pressure is
on a diabetes medication.6 essential, especially when the blood pressure cuff is
Pretreatment beginning the night before with H2 blockers placed lower than the heart (e.g., around the calf in a
such as ranitidine (150 mg po), especially in obese patients, patient who is in a semi-sitting position).8 Conversely,
should be considered. This class of drugs is inexpensive, avail- hypertension secondary to stimulation or inadvertent
able over the counter, and well tolerated. intravascular injection of local anesthetics with epi-
nephrine can lead to intra- and post-op bleeding and
Conscious and Deep Sedation wound hematoma as well as myocardial ischemia.
Perioperative treatment of blood pressure can help
The goal of both conscious and deep sedation is to provide
avoid ischemia as well as reduce intra- and post-op
safe, titrated sedation and analgesia to a patient undergoing a
bleeding as well as bruising. In general, it is desirable
surgical procedure.
to continue all cardiac and antihypertensive medi-
Conscious sedation is characterized by:
cations according to the patient’s normal regimen,
1. depressed consciousness as hypertension is much more likely to occur than
2. independent airway hypotension during procedures performed under local
3. responsiveness to verbal stimuli anesthesia with intravenous sedation.

(c) 2015 Wolters Kluwer. All Rights Reserved.


96 Part I: Principles, Techniques, and Basic Science

5. Body temperature 8
 To aid in the maintenance of appropriate body tem-
perature during all anesthetics, every patient receiving
anesthesia should have temperature monitored when
clinically significant changes in body temperature are
anticipated or suspected.

Sedation Principles

Fentanyl (µg/kg–1)
Clinical experience has shown that even small amounts of
benzodiazepines, narcotics, or propofol may result in uncon-
sciousness. As an example, the minimum effective plasma 4
concentration for midazolam (Versed) ranges from 30 to
1,000 ng/mL between individuals and generally decreases with

1
00
age (Figure 11.1). Paradoxically, at identical plasma concen-

0.
trations of midazolam, an oral dose induces more marked

<
P
effects than an intravenous administration, presumably
because of the active α-hydroxy metabolite.9 Given that there M+F
is such wide inter-patient response variability, the administra-
tion of sedatives is therefore titrated to effect.
An important cause of unintended, unconscious sedation is
drug interaction. When benzodiazepines, propofol, and nar-
cotics are used in combination, a potent drug synergy occurs, 0.10 0.20
i.e., the drug effect is many times greater than if the drugs’
Midazolam (mg/kg–1)
effects were simply additive. It is important to appreciate that
narcotics in conjunction with either propofol or midazolam Figure 11.2.  Drug synergy: by combining drugs, their effect is
disproportionately enhance the independent sedative effect of many times greater than if the drugs’ effects were simply additive.
either drug alone (Figure 11.2). From Ben-Shlomo I, Abd-El-Khalim H, Ezry J, et al. Midazolam acts
Conscious sedation may easily progress to unconscious synergistically with fentanyl for induction of anesthesia. Br J Anaesth.
1990;64(1):45-47.
sedation following incremental dosing of sedative or as pain-
ful stimulation diminishes or ends. The loss of the painful
stimulus that serves as an arousal mechanism results in deeper
sedation. Clinically, sedation should be considered a con-
recovery (10 to 20 minutes). It provides antegrade, dose-
tinuum from conscious to unconscious with both monitoring
dependent amnesia and is reversible with the specific ben-
and vigilance being employed to achieve the desired state.
zodiazepine antagonist flumazenil. When implemented, the
pharmacologic antagonism is effective quickly and only takes
Medications approximately one arm-brain circulation time (i.e., 30 to
The most commonly used sedatives are midazolam, fentanyl, 60 seconds). Midazolam causes less compromise of airway
ketamine, propofol, and recently dexmedetomidine. Local tone than propofol and less respiratory depression than nar-
anesthesia is used to provide the analgesia and occasionally cotics like fentanyl. Even though 1 mg of intravenous mid-
narcotic is added as a supplement. If the sedatives are used azolam in the elderly patient may cause severe respiratory
to anesthetize (i.e., provide the analgesia), then it is no longer depression and prolonged hypnosis, younger patients typically
“sedation.” Each of the sedative drugs listed with the excep- receive 5 mg intravenous (IV) midazolam once intravenous
tion of dexmedetomidine is also capable of inducing general access has been established. The clinical response ranges from
anesthesia when given in larger doses. no apparent effect to sleep. The response to this initial bolus
Midazolam (Versed) is a water-soluble benzodiazepine gives important clues to the anticipated drug requirement dur-
agonist characterized by rapid onset (30 to 60 seconds), with ing the remainder of the procedure.
peak effect (2 to 3 minutes) and, after small doses, also rapid Fentanyl is a synthetic opioid agonist also characterized by
rapid onset (30 to 60 seconds) and recovery (15 to 20 minutes).
Its peak effect is reached at approximately 10 minutes. Other
100 synthetic opioids include, from short to longer acting, remifent-
90 Age
anil (3 to 5 minutes), alfentanil and sufentanil (5 to 10 minutes).
Percent of patients demonstrating

Fentanyl when given as an infusion via an electronic pump at


no response to verbal command

80 80
70
2 µg/kg/h decreases the requirement for other sedative agents
70 60
50
by approximately 50% but increases the likelihood of postop-
60
erative nausea and vomiting. To decrease the incidence of nau-
40
50 sea, the complete avoidance of narcotics should be given serious
40 consideration because a large percentage of patients will be
30 substantially free of pain due to residual local anesthetic
effects at the end of the procedure and during their recovery
20
room period. This strategy markedly decreases motion-induced
10
nausea during the patient’s trip home or to the hotel.
0 While propofol was developed as an induction agent for
0 200 400 600 800 1,000 1,200
general anesthesia, it has become the mainstay for most mod-
Steady-state plasma midazolam concentration (ng/mL)
erate and deep sedation protocols where it is given as a titrated
infusion. Commonly, a level of sedation is initially achieved
Figure 11.1.  Inter-patient variability of minimum effective plasma
concentration in individual subjects and decrease with age. From with midazolam and then titrated small incremental bolus or
Jacobs JR, Reves JG, Marty J, et al. Aging increases pharmacody- continuous infusion propofol is added to facilitate the pro-
namic sensitivity to the hypnotic effects of midazolam. Anesth Analg. gression from mild sedation to deeper sleep. Propofol has a
1995;80:143-148. very rapid onset of effect <1 minute. When titrating to the
desired effect, about 2 minutes should be allowed after bolus

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 11: Principles of Office Sedation for Cosmetic Surgery 97
administration for peak drug effect to occur. Propofol is a Pulse oximetry is the method by which oxygenation is

Principles, Techniques, and


profound depressant of central respiratory drive and decreases objectively, continuously, and noninvasively assessed, and
airway tone and as a result further interferes with respiration. its use, as previously noted, is the standard of care during
In terms of pharmacokinetics, the elimination half-life of pro- sedation. The pulse oximeter is best utilized in the fastest
pofol is 30 to 60 minutes, while its duration of action is much response (usually not the factory default setting) and applied

Basic Science
shorter, <10 minutes, as a result of redistribution to muscle to a finger rather than a toe.
and fat. This short duration of action makes propofol given Ventilation is the other component of respiration. A coher-
as a continuous infusion an ideal drug for providing moder- ently talking patient is adequately ventilating. With rare excep-
ate to deep sedation. It is important to appreciate that with a tions, therefore, provided the presence of an adequate surgical
continuous infusion, as the volume of redistribution becomes block, reducing sedation and thereby getting the patient to fol-
saturated over time, a progressively greater portion of infused low complex commands (i.e., hold still) may be a safer choice
drug becomes bioavailable and the level of anesthesia deepens. than deepening a squirming/restless patient. If lightening the
A steady-state propofol infusion will continue to progressively patient is not an option, a pre-tracheal stethoscope is helpful
increase the plasma and effect site concentration of the drug to identify airway obstruction, wheezing, as well as the pres-
for over 25 minutes before a relative steady state tends to be ence or absence and frequency of ventilatory efforts.
reached.10 This requires constant assessment of the patient Ventilation can be simply monitored by chest wall imped-
and then tapering of the rate of infusion. The concept of titra- ance in which the ECG transduces a respiratory waveform,
tion to effect does not simply apply to achieving an appropri- allowing assessment of both rate and quality of respiration.
ate level of sedation but maintenance of that level as well. Specifically, chest wall impedance utilizes an electrical current
It is also important to appreciate the resultant synergy transmitted between the ECG electrodes through the thorax.
when propofol, benzodiazepines, and narcotics are used in Gas is a poor conductor of electrical current and with inspira-
combination. tion, the volume of gas increases in the chest and conduction
Benzodiazapines do not compromises airway tone to falls. This change in conduction or increasing impedance with
nearly the same extent as propofol but clinically the combi- inspiration is transduced into a waveform and rate so that res-
nation of the two facilitates deep sedation with relative pres- piration can be qualitatively and semiquantitatively assessed
ervation of airway tone. The combination of the two drugs simply and noninvasively. Impedance monitoring does not
is not fixed in terms of dose. Obese patients or patients with work in all patients and may fail to differentiate a patient who
a history of sleep apnea should generally receive relatively has chest movement but an obstructed airway from one who
more benzodiazepine and less proprofol. The addition of is not obstructed.
dexmedetomidine (Precedex) is useful to consider in these Capnography, end tidal carbon dioxide sampling with a
patients as well. It is a highly specific α2-adrenoceptor ago- carbon dioxide waveform display, is a more definitive form
nist with centrally mediated sympatholytic effects.11 Onset of of monitoring ventilation and can be accomplished with cap-
effect can be expected at 5 to 8 minutes, with a peak effect at nograph attached to a specially designed CO2 sampling nasal
10 to 20 minutes, and a duration of effect of 2 to 4 hours. It cannula or one that has been modified with a sampling cath-
has sedative and analgesic effects without respiratory depres- eter inserted through one of the nasal prongs. Capnography
sion and when titrated at rates between 0.4 and 0.1 µg/kg/h allows the most accurate monitoring of both rate and qual-
allows an approximately 30% to 40% reduction in anes- ity of ventilation. This technique will often underestimate but
thetic requirements. never overestimate arterial CO2. Capnography has recently
Ketamine is also an attractive medication in that it is both also become a formally stated standard of care during moder-
an analgesic and a sedative and is essentially devoid of respira- ate or deep sedation.7
tory depressant effects. It is important to be aware that ket- Contrary to the knowledge of many anesthesiologists,
amine can cause dysphoria and increases salivation. These side pulse oximetry (the monitor of oxygenation) can function as
effects are mitigated if a benzodiazepine such as midazolam a monitor of ventilation as well. During normal ventilation,
and an antisialagogue such as glycopyrrolate (0.2 mg) are while breathing room air, a person typically has a PaO2 ≈
used in combination. Intramuscular effects peak at 10 min- 75 mmHg, which translates to a saturation (SpO2) of ≈ 98%
utes, intravenous effects at 2 to 3 minutes. Intravenous ket- as displayed by the pulse oximeter. This places the PaO2 and
amine in doses of 10 to 20 mg has a short duration of action SpO2 at the point on the oxyhemoglobin saturation curve
(5 to 10 minutes) and is a potent integumental analgesic, so its where there is a nearly linear relationship between PaO2
administration should be timed to anticipate any particularly decrease and O2 saturation (Figure 11.3). At normal and
painful stimuli such as the infiltration of local anesthetic. low PaO2 values, there is great resolution for PaO2 changes
via the accompanying SpO2 changes. This has considerable
Monitoring impact in relation to PaCO2. Consider the simplified alveolar
Monitoring the level of sedation includes both subjective and gas equation:
objective assessments. With respect to subjective assessment, PaO2 ≈ PIO2 − PaCO2/R
does the patient appear comfortable, anxious, or drowsy?
Thus, a critical first element of monitoring conscious seda- (PIO2 = partial pressure of inspired oxygen; R = respiratory
tion is inspection and conversation to allow titration. A quotient calculated from the ratio of CO 2 eliminated/O2
common sedation endpoint is when the patient feels a drug consumed—typically 0.8)
­

effect, manifests a change in speech, or the appearance of In the patient breathing room air, a 10 torr increase in
lateral nystagmus. The same monitoring technique (i.e., con- PaCO2, as commonly occurs with narcotic administration,
versation) is also used to establish the second goal, namely therefore results in an approximately 12 mmHg decrease
verifying that the sedation is still of a conscious nature. It is in PaO2. In the patient who is significantly hypercarbic,
prudent to document conversation on the case record in the the increase in PaCO2 will, therefore, result in a significant
list of monitors used. decrease in SpO2, but only if the patient is breathing room air.
Respiration consists of two components, oxygenation and Thus, when applied in this context (without administration
ventilation. It is important to understand that with overseda- of supplemental O2 oxygen), ventilation can be monitored
tion, desaturation occurs secondary to decreased ventilation with a single device—the pulse oximeter. The pulse oxime-
and shallow breathing. In the conscious patient, ventilation is ter’s ability to detect changes in ventilation disappears when
somewhat more difficult to monitor continuously than in the PaO2 is increased to >75 mmHg and the patient is on the flat
unconscious, intubated patient. part of the oxyhemoglobin curve (Figure 11.3). It is therefore

(c) 2015 Wolters Kluwer. All Rights Reserved.


98 Part I: Principles, Techniques, and Basic Science

Oxyhemoglobin dissociation “curve” 2. Provided the SpO2 is normal and the patient is on room
SpO2 air, the PaCO2 must be essentially normal.
120 3. When even a small amount of oxygen is administered, the
pulse oximeter no longer functions as a monitor of ventilation.
100 75 600 4. With the titration of benzodiazepines and/or opioids in the
60 context of a saturation of >90% on room air, the patient
80 cannot be in CO2 narcosis.
50
40
5. Should desaturation occur, the airway is optimized and
60 supplemental oxygen is utilized while the level of sedation
is titrated downward.
40 With respect to respiratory physiology and its relation-
ship with sedation, narcotics and sedatives individually as
20 well as together depress the CO2 response curve. Under nor-
0 mal circumstances, ventilation increases as PaCO2 increases.
0 Sedatives, especially narcotics, desensitize the central respira-
0 100 200 300 400 500 700
600 tory centers to CO2, thereby shifting the CO2 response (thresh-
PaO2 old) to the right. The practical implication is less increase in
Figure 11.3.  Oxyhemoglobin dissociation curve. Y-axis = percent ventilation per unit increase in CO2. In addition, the slope
of arterial blood saturated with oxygen, X-axis = partial pressure of (sensitivity) of the CO2 response curve is shallower following
oxygen in arterial blood. sedative or narcotic administration.
All narcotics have similar efficacy, although within the
class there are marked differences in potency and duration
of action. Specifically with respect to duration of action:
advisable in our opinion to avoid routine use of supplemen- morphine > fentanyl > sufentanil > alfentanil > remifentanil.
tal oxygen in patients receiving conscious sedation so that the Alexander14 has shown that decreased awareness (sedation)
pulse oximeter is a more sensitive monitor of ventilation— also markedly decreases the slope of ventilation in response to
not just oxygenation. In overview, it is preferable to think hypoxia following midazolam. Furthermore, the ventilatory
of supplemental oxygen as a method to treat desaturation. response to CO2 in a patient receiving midazolam is dimin-
One needs to be cognizant that supplemental oxygen masks ished to a greater extent and for longer duration in patients
oversedation with hypoventilation and makes desaturation a with COPD.15 Thus, individual titration to effect with careful
late and precipitous sequel of oversedation. Besides the clini- monitoring is again the mainstay of sedative dosing.
cal advantage of converting the pulse oximeter from a pure Amnesia, an additional component of sedation, is pre-
oxygenation monitor into both a ventilation and oxygenation dominantly achieved through the use of benzodiazepines. It
monitor, the withholding of oxygen (when it is not necessary) must be appreciated though that actually achieving amnesia is
has additional advantages: 1) improved individual titration by inconsistent. Specifically, in the absence of pain, little sedation
early feedback via minor desaturations; 2) less likelihood of is required to achieve amnesia. Pretreatment with a benzodi-
combustion with the use of electrocautery and laser as is com- azepine, for example, 5 to 10 mg Valium, orally prior to OR
mon during head and neck cosmetic procedures.12 To reduce entry should be considered. If benzodiazepines are adminis-
the incidence of airway fire, provided a patient has a normal tered after the patient feels pain, amnesia is not predictable.
saturation on room air, it is acceptable practice to abandon Lastly, it is important to appreciate that while propofol and
CO2 monitoring with head and neck procedures, because the narcotics are not amnestic agents, they do synergize with ben-
required plastic components would increase the chance for zodiazepines to help achieve this goal.
combustion in the field. If supplemental oxygen is used during In terms of monitoring the depth of anesthesia and there-
procedures on the head or thorax done with sedation, then fore awareness and amnesia, bifrontal referential EEG (BIS)
either the airway should be protected (e.g., laryngeal mask or has been used with variable success.16 The inconsistent results
endotracheal tube) or the oxygen concentration coming out of are likely a consequence of the muscle movement electromyo-
the nasal cannula should not exceed 30%. The latter approach gram artifact.
requires an air oxygen blender or separate flow meters.
If a patient manifests decreased oxygen saturation and can- Oversedation
not be encouraged to ventilate, the initial intervention is that
A final consideration with respect to sedation is that of excess
of airway optimization followed by adding supplemental oxy-
drug effect from a drug administration error, drug synergy, or
gen and alerting the surgeon. This can include jaw lift, neck
a loss of offsetting noxious stimulus. In such a circumstance,
extension, and insertion of an oral or nasal airway. After the
the treatment approach is:
airway has been optimized, supplemental O2 can be phased
out while sedation is titrated downward. During the use of 1. stimulate the patient and support the airway;
supplemental O2, the drop in oxygenation is delayed in rela- 2. administer supplemental oxygen;
tion to the hypoventilation, but once it occurs, the speed of 3. discontinue sedative drug administration; and lastly
deterioration is independent of the presence or absence of sup- 4. consider an intravenous drug antagonist if the excess effect
plemental oxygen. Quite simply, supplemental oxygen masks is not attenuated or resolved by 1 to 3.
oversedation until it is late and intervention then must be
Toward that end, it is ideal to preferentially use sedative
faster and more definitive, which often involves violating the
drugs with a short half-life or for which a specific antagonist
surgical field. Because CO2 has an anesthetic potency about
is available. Narcotics can be antagonized with naloxone typi-
four times that of N2O,13 by the time desaturation occurs in
cally only requiring 20 to 40 µg (0.5 to 1 cc of 0.4 mg nalox-
the presence of oxygen, the patient may already be in CO2
one drawn up to a total volume of 10 cc). Benzodiazepines
narcosis and therefore less likely to respond to complex com-
are antagonized with flumazenil typically requiring 0.1 to
mands or to stimulation. Severe consequences may ensue if
0.3 mg (1 to 3 cc of standard concentration of 0.1 mg/cc).17 No
the patient subsequently is difficult to mask or intubate. It is
facility where sedation is performed should be without these
useful to stress several observations:
antagonists readily available. If only benzodiazepine has been
1. Above a PaO2 of 75 mmHg supplemental oxygen creates a administered, flumazenil should be utilized as naloxone would
false sense of security. be of no benefit. If a patient has received both benzodiazepine

(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 11: Principles of Office Sedation for Cosmetic Surgery 99
and narcotic sedation, it is common to use naloxone first as
Conclusion

Principles, Techniques, and


the narcotic component is the more likely cause of the respi-
ratory depression. Two other considerations are important. A safe outcome from an office procedure performed under
First, when possible, titrate the antagonist to avoid a sympa- IV sedation is predicated on patient preparation, planning,
thetic surge from acute withdrawal. Second, if several rounds and technique. Further, in the same way that understanding

Basic Science
of antagonist do not have the desired effect, consider other the operation helps the anesthesiologist optimize outcome,
diagnoses, for example, metabolic derangement or stroke. understanding the sedation can afford the same benefit to the
surgeon. While what we have written may seem unnecessarily
Postoperative Nausea and Vomiting detailed in some regards and superficial in others, our goal is
An important consideration with respect to any surgery is to provide a conceptual understanding of procedural sedation
postoperative nausea and vomiting (PONV). This is particu- beyond a simple knowledge of drug dosage and effect.
larly important in cosmetic surgery as PONV can detract from
the perception of the overall experience, no matter how ideal References
the outcome. Beyond the subjective implications, nausea and 1. Sun Tzu S. In: Griffith SB, ed. The Art of War. Oxford: Oxford University
vomiting can also undermine the outcome, especially in proce- Press; 1971.
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ing, as the intra-abdominal pressure is increased with a closed perioperative cardiovascular evaluation and care for noncardiac surgery: a
report of the American College of Cardiology/American Heart Association
glottis, the intrathoracic pressure increases, thus impeding Task Force on Practice Guidelines. Circulation. 2007;116(17):e418-e500.
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nificantly the development of a wound hematoma. Vomiting stents and anesthesia. Can J Anaesth. 2006;53:1230-1243.
is often accompanied by an increase in the blood pressure as 4. Le Manach Y, Ibanez E, Cristina M, et al. Impact of perioperative statin
therapy on adverse postoperative outcomes in patients undergoing vascular
well, which can further predispose to these complications. surgery. Anesthesiology. 2011;114:98-104.
Prophylactic pretreatment is essential as preventing nausea is 5. Kral JG. Surgical treatment of obesity. In: Bjorntorp P, ed. International
more easily accomplished and reliable than treating it. The use Textbook of Obesity. Hoboken, NJ: John Wiley & Sons Ltd; 2001.
of low-dose intraoperative corticosteroids has become routine 6. Practice guidelines for preoperative fasting and the use of pharmacologic
agents to reduce the risk of pulmonary aspiration: application to healthy
in plastic surgery and dexamethasone 10 mg has been shown patients undergoing elective procedures. A report by the American Society
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thought that dexamethasone may antagonize prostaglandin 7. Basic Anesthetic Monitoring, Standards for (Effective July 1, 2011). www.
asahq.org. Accessed December 11, 2012.
or release endorphins that elevate mood, improve one’s sense 8. Papadonilolatis A, Wiesler ER, Olympio MA, et al. Avoiding catastrophic
of well-being, and stimulate appetite. A useful multimodal complications of stroke and death related to shoulder surgery in the sitting
algorithm also includes intraoperative administration of position. Arthroscopy. 2008;24(4):481-482.
Ondansetron 4 to 8 mg IV along with the Decadron. Diabetes 9. Crevoisier C, Ziegler WH, Eckert M, et al. Relationship between plasma
concentration and effect of midazolam after oral and intravenous adminis-
is a relative contraindication to Decadron as even this small tration. Br J Clin Pharmacol. 1983;16:51S-61S.
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for awake craniotomy. Anesth Analg. 2001;92:1251-1253.
dimenhydrinate ½ tablet po or a scopolamine patch applied 12. Joint Commission on Accreditation of healthcare organizations: Sentinel Event
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sion after thiopental and midazolam in normal subjects and in patients with
as constipation and more importantly nausea and vomiting. chronic obstructive pulmonary disease. Anesthesiology. 1983;58:540-544.
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(c) 2015 Wolters Kluwer. All Rights Reserved.


Chapter 12  n  Local Anesthetics
Alisa C. Thorne

The clinically useful local anesthetics are either amino amides local anesthetic. In clinical settings, however, other fac-
or amino esters. These agents are effective when applied topi- tors, such as vasodilatory activity and the tissue redistribu-
cally, injected subcutaneously, or injected in the area of major tion properties of the different local anesthetics, influence
peripheral nerves. potency to some extent.

Onset of Action.  The onset of action is primarily a result


Mechanism of Action of the pKa, but the dose and the concentration are also fac-
Local anesthetics cause a blockade in nerve condition. The tors. In vitro studies confirm the relationship between pKa
local anesthetic diffuses passively through the neuronal cell of a local anesthetic compound and the onset of anesthesia.
membrane in the nonionic state, becomes charged, and blocks Lidocaine has a pKa of 7.4 and a more rapid onset of action
the sodium channel within the neuron. With sodium con- than tetracaine, which has a pKa of 8.6.
ductance inhibited, threshold potential is not reached and an
action potential is not generated.
Duration of Action.  In the clinical arena, the duration of
local anesthesia is principally influenced by the vasodilator
effects of the individual drugs. With the exception of cocaine,
Pharmacology all local anesthetics cause some degree of vasodilation. The
greater the degree of vasodilation, the greater the amount of
The molecular structure of local anesthetic agents consists of the drug that is absorbed by the vascular system, leaving less
an aromatic moiety at one end, an amine moiety at the other drug to act on the nerve cell. Therefore, the degree of vasodila-
end, and an intermediate chain between. The latter contains tion is inversely related to the duration of action. See the sec-
either an amide or an ester linkage, allowing local anesthet- tion “Addition of Epinephrine.”
ics to be classified as either amides or esters. Commonly used
esters are procaine (Novocain), chloroprocaine, tetracaine, Duration and Potency Summary.  In summary, agents
and cocaine. Commonly used amides are lidocaine, mepiva- with low potency and short duration are procaine (Novocain)
caine, prilocaine, bupivacaine (Marcaine), and etidocaine. and chloroprocaine; agents with ­moderate potency and dura-
Differences in the metabolism of local anesthetics, their stabil- tion are lidocaine (Xylocaine), mepivacaine, and prilocaine;
ity in solution, and differences in allergenicity are all related to agents with a high potency and a long duration are tetracaine,
the presence of an ester or amide linkage. bupivacaine (Marcaine), and etidocaine.

Metabolism Effect of Total Dose


Esters undergo hydrolysis in the plasma by pseudocholinester- Other factors determine a local anesthetic agent’s activity in
ase, whereas the amides are metabolized in the liver. The rate the clinical setting. Total dose is probably the single most
of metabolism of local anesthetics is related to the number of important factor in determining satisfactory local anesthesia.
additional carbon atoms on the aromatic or amine side of the Also, as mentioned earlier in the section “Onset of Action,” the
molecule. greater the dose, other factors being equal, the faster the onset
of action.
Stability in Solution
Esters are unstable in solution. Amides are stable in solution. Addition of Epinephrine
The addition of vasoconstrictors is another factor deter-
Allergenicity mining the performance of the local anesthetic. Epinephrine
Esters are also more likely to cause allergenic reactions than markedly prolongs the duration of action of all local anes-
amides. A true allergic reaction to lidocaine is extremely rare, thetics when used for local infiltration or peripheral nerve
although many patients will state, incorrectly, that they have blocks. By decreasing the rate of vascular absorption, vaso-
such an allergy. constrictors cause a higher concentration of local anes-
thetic molecules to be available to act on the nerve cell
membrane.
Potency and Toxicity Epinephrine is frequently used in combination with local
Potency and toxicity are determined by the structure of the anesthetics at concentrations of 1:100,000 or 1:200,000. In
aromatic and the amine group. fact, epinephrine is probably equally effective at much lower
doses (1:1,000,000) and might decrease the danger of an
intravascular injection.
Anesthetic Profile
The profile of a particular local anesthetic agent is related to Location of Injection
its lipid solubility, protein binding, acid strength (pKa), and
vasodilator activity. The anatomy of the site of injection also has a role in deter-
mining the activity of a local anesthetic. Intradermal injec-
tion allows for the most rapid onset of action but the shortest
Potency duration of these agents, whereas brachial plexus block injec-
Anesthetic potency is determined primarily by the degree tions yield some of the longest durations and slowest onsets
of lipid solubility. The local anesthetic molecule must pen- of action seen with local anesthetics. Although intradermal
etrate the nerve cell membrane to have an effect. In vitro, injection provides the most rapid onset, it is more painful than
hydrophobicity alone determines the potency of a given subcutaneous injection.

100
(c) 2015 Wolters Kluwer. All Rights Reserved.
Chapter 12: Local Anes