Pain Management for Veterinary Technicians and ...

Pain Management for Veterinary Technicians and Nurses

Pain Management for Veterinary Technicians and Nurses Editor

Mary Ellen Goldberg Instructor VetMedTeam, LLC Executive Secretary International Veterinary Academy of Pain Management

Consulting Editor

Nancy Shaffran President-Elect International Veterinary Academy of Pain Management

This edition first published 2015 © 2015 by John Wiley & Sons, Inc. Editorial Offices 1606 Golden Aspen Drive, Suites 103 and 104, Ames, Iowa 50014-8300, USA The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 9600 Garsington Road, Oxford, OX4 2DQ, UK For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee codes for users of the Transactional Reporting Service are ISBN-13: 978-1-1185-5552-1/2015. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by health science practitioners for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data applied for. A catalogue record for this book is available from the British Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Set in 10/12pt Sabon by SPi Publisher Services, Pondicherry, India

1 2015

To Dr. Stephen J. Goldberg who has been my physical, mental, and financial support through this entire journey. Thank you for all you have given me professionally and personally. You have allowed me to expand in areas I never dreamed possible. For that you have my undying gratitude and love. MEG

Dedicated with unending gratitude to Rachel Malinowitzer who provides a constant rate infusion of analgesia for all the aches and pains of my life. NS

Contents

contributors Preface Acknowledgements About the Companion Website

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Chapter 4 Physiology of Pain Kristen Cooley

Chapter 1 Advancing Veterinary Pain Management into a New Era Patricia R. Zehna

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Chapter 2 Pain Management Careers for Veterinary Technicians and Nurses Mary Ellen Goldberg, Kristen Hagler, and Janel Holden

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Chapter 3 Pain Recognition in Companion Species, Horses, and Livestock Cheryl Irzyk Kata, Samantha Rowland, and Mary Ellen Goldberg

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30

Chapter 5 Analgesic Pharmacology Michelle Albino

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Chapter 6 Locoregional Analgesic Blocking Techniques 67 Mary Ellen Goldberg, Nancy Shaffran, Kim Spelts, David Liss, Tasha McNerney, Trish Farry, Samantha Rowland, and Jennifer L. Dupre

Chapter 7 Surgical Pain Management Tasha McNerney and Trish Farry

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viiiContents

Chapter 8 Analgesia for Emergency and Critical Care Patients Kim Spelts and David Liss

115

Chapter 15 Nutritional Considerations for Pain Management in Dogs and Cats Kara M. Burns

Chapter 9 Chronic Pain Management for the Companion Animal Christopher L. Norkus

125

Chapter 10 Analgesia for Shelter Medicine and Trap-Neuter-Return Programs Mary Ellen Goldberg

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Chapter 11 Analgesia in Equine Practice Samantha Rowland and Jennifer L. Dupre

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Chapter 17 The Veterinary Technician in Alternative Therapies 309 Stephanie Ortel, Mary Ellen Goldberg, Lis Conarton, Kari Koudelka, and Robin Downing

Pain Management for End-of-Life Care Amir Shanan

331

185

216

Chapter 14 Analgesia for Zoo Animal and Wildlife Practice Lindsay Wesselmann, Stephen J. Cital, and Mary Ellen Goldberg

Physical Rehabilitation and the Veterinary Technician Stephanie Ortel

Chapter 18

Chapter 13 Analgesia in Exotic Animals Kate Lafferty, Stephen J. Cital, and Mary Ellen Goldberg

Chapter 16

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Chapter 12 Analgesia for Livestock and Camelids Mary Ellen Goldberg

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Appendices Appendix A: Formulary Appendix B: Constant Rate Infusions Example Calculations Appendix C: Critical Care Case Studies Appendix D: Routine Case Protocols Appendix E: Key Signs of Pain According to Chapters of Text Appendix F: Further Reading

340 384 393 396 399 401

Index403

contributors

Michelle Albino, LVT, VTS (Anesthesia) Supervisor The Animal Medical Center Anesthesia Department New York, NY, USA Kara M. Burns, MS, MEd, LVT, VTS (Nutrition) President Academy of Veterinary Nutrition Technicians Wamego, KS, USA Stephen J. Cital, RVT, SRA, RLAT Surpass Inc. Interventionalist/Anesthesia Technician Lis Conarton, BS, LVT, CCRP, CVPP Physical Rehabilitation Director Veterinary Medical Center of CNY East Syracuse, NY, USA Kristen Cooley, BA, CVT, VTS (Anesthesia) Instructional Specialist Clinical Skills Training Center School of Veterinary Medicine University of Wisconsin Madison, WI, USA Robin Downing, DVM, CVPP, CCRP, DAAPM The Downing Center for Animal Pain Management, LLC Windsor, CO, USA

Jennifer L. Dupre, CVT, VTS (Anesthesia), CVPP Senior Anesthesia Technician Anesthesia Lab Coordinator School of Veterinary Medicine Ross University St. Kitts, West Indies Trish Farry, CVN VTS (ECC & Anes) Cert IV (TAA) Clinical Instructor & Anaesthesia Technician Veterinary Medical Centre The University of Queensland Gatton, Australia Mary Ellen Goldberg, BS, LVT, CVT, SRA, CCRA Instructor VetMedteam, LLC Executive Secretary International Veterinary Academy of Pain Management Nashville, TN, USA Kristen Hagler, BS (An. Phys.), RVT, CCRP, CVPP, COCM, CBW Penn HIP-Associate Member Veterinary Department Guide Dogs for the Blind, Inc San Rafael, CA, USA and

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Animal Wellness Center of Marin—Rehabilitation and Pain Management Director of Rehabilitation and Pain Management Services Janel Holden, LVT, VTS (Anesthesia) Veterinary Teaching Hospital Washington State University Pullman, WA, USA Cheryl Irzyk Kata, RVT, VTS (Anesthesia), CVPP Veterinary Teaching Hospital North Carolina State University Raleigh, NC, USA Kari Koudelka, RVT, CCRP, CVPP (pending) Director of Veterinary Rehabilitation and Pain Management Services Center for Veterinary Pain Management and Rehabilitation and Animal Clinics of The Woodlands The Woodlands, TX, USA Kate Lafferty, BFA, CVT, VTS (Anesthesia) Senior Technician Anesthesia and Pain Management Department Director Veterinary Technician Student Internship Program Veterinary Medical Teaching Hospital University of Wisconsin–Madison Madison, WI, USA David Liss, BA, RVT, VTS (ECC, SAIM), CVPM Consulting Veterinary Training and Consulting LLC Los Angeles, CA, USA Tasha McNerney, BS, CVT O.R. Technician Supervisor/Anesthesia Technician Rau Animal Hospital Glenside, PA, USA Christopher L. Norkus, DVM Department of Anesthesiology College of Veterinary Medicine Kansas State University Manhattan, KS, USA

contributors

Stephanie Ortel, BS, LVT, CCRP, CVPP Certified Canine Rehab Practitioner Certified Veterinary Pain Practitioner Clinical Associate American Academy of Pain Management Animal Pain Management Center Buffalo, NY, USA Samantha Rowland, LVT, VTS (Anesthesia) Supervisor Anesthesia Department Marion duPont Scott Equine Medical Center Leesburg, VA, USA Nancy Shaffran, CVT, VTS (ECC) Lecturer/Consultant President-Elect International Veterinary Academy of Pain Management Erwinna, PA, USA Amir Shanan, DVM Founder IAAHPC International Association for Animal Hospice and Palliative Care Chicago, IL, USA Kim Spelts, BS, CVT, VTS (Anesthesia), CCRP PEAK Veterinary Anesthesia Services Colorado Springs, CO, USA Lindsay Wesselmann, BS, RVT, LVT Lion Country Safari Loxahatchee, FL, USA and Point Defiance Zoo and Aquarium Tacoma, WA, USA Patricia R. Zehna, RVT California Registered Veterinary Technician Association Board Member (CaRVTA) Mentor Committee Veterinary Support Personnel Network (VSPN) Instructor/Board Moderator SPCA of Monterey County Wildlife Rehabilitation Volunteer

Preface

As recently as the 1990s, we did not manage animal pain as a rule. We did not even recognize animal pain, nor try to quantify or qualify it, much less treat it. We were taught that pain was a “good thing” and that it would prevent further postoperative injury by inhibiting an animal’s movement. The truth is we DID know or at least sense that animals were suffering more than necessary, and technicians and nurses all over the world were asking, sometimes begging, to be able to do something, anything for their patients. The reality was no one really knew what to do or how to safely and effectively treat animal pain. Fast forward to the 21st century when animal pain began to move to the forefront of everyone’s mind. Certainly we have spent the first decade of the 2000s trying to establish guidelines for measuring and treating animal pain. The recommendations have changed many times as we have understood more and more about the ways animals manifest and express painfulness as well as the unique ways that different species respond to analgesic drugs and alternative therapies. As a result, gone are the days where we believe that “a little pain postoperatively is a good thing” and gone too are the days of veterinary staff watching animals waking up crying, thrashing, and refusing to eat or sleep

for days. Today, whether treating companion, exotic, livestock, wild, or laboratory animals, pain management is a choice we can all make. Unfortunately, there are still those who do not choose optimum pain management holding to some of the old myths or beliefs that pain management is too costly or simply unimportant. As patient advocates, veterinary nurses and technicians bear the responsibility of beating the drum loudly and persistently until optimum pain management is provided for all animals in our care. The knowledge compiled into this book is the key to getting there. In the past few years, pain management has become recognized as a specialty area in its own right. We have seen the full emergence of the International Veterinary Academy of Pain Management (IVAPM)—thousands of individual veterinarians, technicians, acupuncturists, rehabilitation, and other specialists coming together for the common purpose of relieving animal pain and suffering. We now have professional Certified Veterinary Pain Practitioners (CVPPs) in the field. Veterinarians and technicians alike are certifying side by side to elevate the art of pain management even higher. How appropriate that this certification be offered equally to all licensed individuals in veterinary medicine, the

xiiPreface

most sincere acknowledgment that pain and its management is everyone’s issue! This book has been authored and edited by a group of extremely dedicated individuals who take the business of relieving animal pain and providing education for other members of the veterinary community very seriously. It is probably the most comprehensive guide to animal pain that has thus far been compiled, covering everything from routine dog and cat surgeries to laboratory animals, large animals, zoo, and exotics. In it you will find traditional western analgesic medicine as well as eastern medicine and alternative and adjunctive modalities. This

text is meant to be useful in your everyday practice regardless of your target species or area of special interest. It will help you deliver more and better pain management to all of the animals who are fortunate enough to be in your care. It has been my privilege to have spent the bulk of my career concentrating on the field of animal pain management. I am especially honored to have acted as a consulting editor for this book, and I have done so with great admiration for both its authors and its readers. Respectfully yours, Nancy Shaffran

Acknowledgements

The completion of this text has been a labor of love that would not have been possible without the talents of many people that need to be thanked. Erica Judisch, our editor at John Wiley & Sons, Inc., has provided guidance and encouragement for a novice like myself in the world of publishing. Nancy Shaffran, my consulting editor, whose knowledge, career, and gift of teaching has been and continues to be an inspiration for me to strive for the best in quality care of my patients. Besides that she is a “really good friend.” Kristen Cooley, my official illustrator. Without her skill and efforts, we would not have the majority of our figures for the text. All of my contributing authors have provided their time and knowledge beyond the “call of duty.” This text is truly a joint effort that would not have been possible without each of my colleagues’ efforts. They all continue to inspire me. Thank you for sharing your knowledge and experience. The International Veterinary Academy of Pain Management (IVAPM) Board of Directors and membership. Drs. Tamara Grubb, Sheilah Robertson, Robin Downing, Jamie Gaynor, Mark Epstein, Mike Petty, Douglas Stramel, Bonnie Wright, and countless others who have shared

their time and knowledge to assist me with this book. Dr. Janet Van Dyke opened the doors of veterinary rehabilitation to me and has provided the catalyst for me to continue to grow in knowledge and understand of pain management. Dr. Elizabeth Hammond who has allowed me to enter the world of Zoo Animal Medicine and all the staff at Lion Country Safari for teaching an old dog new tricks. All the Staff at VetMedTeam, LLC for providing me with the ability to share my passions of pain management and anesthesia in a teaching platform of continuing education for the veterinary professional. Dr. Rick Wall has shared his passion for learning about myofascial trigger points in veterinary patients. Dr. Bob Stein brought me into the world of IVAPM and continues to be an inspiration to me. Drs. Pablo Morales, Kristna Rivas Wagner, and Joseph Wagner of the Mannheimer Foundation, Inc. continue to provide me with education and experience of working with primates. Your knowledge and support have been invaluable. Drs. Bobby Collins, Mary Shall, Alex Meredith, Ms. Patricia Gerber, and all my “family” at Virginia Commonwealth University (VCU). You

xivAcknowledgements

elevated my knowledge and experience level exponentially. My 15 years at VCU continue to be the best job I ever had. Dr. Joel Ehrenzweig for providing me with educational opportunities to grow in pain management. Dr. R. B. Chenault who took a “retired housewife” and brought her back into veterinary practice 25 years ago. Mr. Robert J. White, Farrier. The best horseman I have ever met. He knows a horse’s mind.

His skill as a farrier and rider is superb. In 37 years, he has taught me more than I can imagine. Finally, I must thank all my patients over the past 40 years who have educated me. I can literally say I have worked with “All Creatures Great and Small.” This text is a combination of the efforts of all those named and many more unnamed. Mary Ellen Goldberg

About the Companion Website

This book is accompanied by a companion website: www.wiley.com/go/goldbergpainmanagement The website includes: • Videos • Review questions • Website links to videos • Supplementary materials • Powerpoints of all figures from the book for downloading

Advancing Veterinary Pain Management into a New Era

c h a p t e r

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Patricia R. Zehna

The July 15, 2002, issue of the Journal of the American Veterinary Medical Association published an article authored by Benjamin Howard, MD, MPH, regarding the course of a human neonate pain management case. It was a call for pain management for those who have no voice and pointed out not only the medical but also the ethical reasons that we must ensure appropriate pain management for our patients. A landmark case that established greater pain management practices took place in 1985. Jeffery Lawson, a 1-lb, 11-oz neonate, was operated on to correct patent ductus arteriosus and did not receive anesthesia for his operation (Lawson 1986). When he died a month later, his mother reviewed his medical record and discovered this fact. Jeffrey’s neonatologist had reassured her at the time of the operation that he would receive anesthesia. She was moved to confront this practice and wrote of his account, Jeffrey had holes cut in both sides of his neck, another cut in his right chest, an incision from his breastbone around to his backbone,

his ribs pried apart, and an extra artery near his heart tied off. This was topped off with another hole cut in his left side for a chest tube. This operation lasted hours. Jeffrey was awake through it all. The anesthesiologist paralyzed him with a curate drug (pancuronium bromide) that left him unable to move, but totally conscious. When I questioned the anesthesiologist later about the use of this drug, she said that Jeffrey was too sick to tolerate powerful anesthetics. Anyway, she said, it has never been demonstrated that babies feel pain. Her neonatologist described the lack of anesthesia for surgery as based on “ignorance, hubris and barbarism”. When her account was published in The Washington Post in August 1987, there was a public outcry and other p arents spoke of their experiences. The routine practice of administering little to no analgesia for surgery in premature and critically ill infants caught the attention of the public and became a social issue. (Lee 2002, p. 234)

Pain Management for Veterinary Technicians and Nurses, First Edition. Edited by Mary Ellen Goldberg and Nancy Shaffran. © 2015 John Wiley & Sons, Inc. Published 2015 by John Wiley & Sons, Inc. Companion Website: www.wiley.com/go/goldbergpainmanagement

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While this is difficult to read, it is a very good illustration of our responsibility to provide appropriate pain management not only because it is the right thing to do for our patients, both medically and ethically, but also because their owners, our clients, trust us to protect their pets. They expect that we will follow the first axiom of medicine “first do no harm,” and they assume that we are making their pets as comfortable as possible. Each of our perspectives about the current status of pain management will differ due to a number of factors. We are influenced by the branch of medicine in which we chose to practice, the level of medical advancement where we work, the amount of time that we have practiced medicine, and even our own personal experiences with pain and pain management. We are entering a new era of pain management in veterinary medicine and face the obstacles that go along with introducing new concepts. Many of the obstacles that we face are common to the human side of medicine; therefore, our research often overlaps. The International Association for the Study of Pain defines pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. The inability to communicate v erbally does not negate the possibility that an individual is experiencing pain and is in need of appropriate pain-relieving treatment” (IASP 1994). In 1999, the Veteran’s Administration declared “war” on pain by making it their fifth vital sign (Flaherty 2001). Since this time, veterinary organizations have tried to adopt pain as the fourth vital sign. Several organizations have published “guidelines” for pain management in veterinary patients: • The American College of Veterinary Anes thesiologists’ position paper on the treatment of pain in animals (http://www.acva.org/docs/ Pain_Treatment). • AAHA/AAFP Pain Management Guidelines for Dogs & Cats (https://www.aahanet.org/ Library/PainMgmt.aspx). • International Veterinary Academy of Pain Management (IVAPM) has several position


statement papers that are being prepared for peer review (www.ivapm.org). We need to be aware of what is contained in each document so we can share ideas with our colleagues about how to implement this advice. Although there have been many advances in human medicine, this excerpt from a 10-year-old medical journal is revealing about the pace at which medical professionals feel change is actually taking place. “The evidence that physicians and nurses do not treat pain adequately began to appear in the medical literature nearly 30 years ago. In the following decades, the accumulated data showed that many types of pain- acute pain, cancer pain, and chronic nonmalignant pain- were being undertreated. The reasons offered for under-treatment usually characterized as ‘barriers’ to effective pain relief, were remarkably consistent across the literature. Despite numerous calls to educate health care professionals about pain manage ment, only the rhetoric has expanded (Rich 2001, pp. 151–152)”.

Overcoming the Obstacles to Pain Management There are many obstacles to effective pain assessment and administration. Some of these exist with good reason, and some are outdated ideas, habits, or lack of education. Veterinary technicians must have a good working know ledge of these obstacles so they can overcome them and advocate for their patients. We carry the responsibility to impart this knowledge to other hospital team members and provide accurate client education. As an educator and patient advocate, the technician is the solution to breaking down the barriers to effective pain management and raising awareness on behalf of their patients. Veterinary technicians/nurses play an integral role in overcoming obstacles to pain management.

Chapter 1 Advancing Veterinary Pain Management into a New Era

An often referenced 1998 Canadian study revealed that veterinary practices that have trained veterinary technicians on staff practice better pain management. The quality of pain management in fact increased proportionately with the number of licensed technicians on staff and relative to the amount of continuing education (CE) the technicians received (Dohoo and Dohoo 1998). Examining common obstacles is a good start in developing programs with which to educate our colleagues and clients.

Common Obstacles • Inadequate knowledge of pain mechanisms and pain management options • Difficulty with pain assessment ○○ Pets mask pain ○○ Wide variation between breeds and species ○○ Objective tools are not available • Fears about analgesic side effects and how to manage them • Failure to make pain assessment and manage ment a priority for every patient ○○ Poor communication between staff members ○○ Lack of a systematic and collabor ative approach to pain assessment and management ○○ Lack of consistent pain management protocols ○○ Absence of accountability for pain management • Client-related issues ○○ Failure to recognize pain signs ○○ Difficulty administering medications ○○ Cost of pain medications and/or other treatment modalities

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team should have not only a clearly defined role within the pain management team but also be given the knowledge with which to effectively carry out their role. Pain mechanisms and pain management options can be better understood through required study of materials provided by the hospital. This can begin as part of an orientation and continue with on-the-job training and CE. Each practice should have at least one technician who is assigned to oversee pain management education and ensure the hospital remains current with new research and recommendations. The functions of the pain management technician/nurse should include:

Knowledge

• Providing CE opportunities on a regular basis either in house or utilizing other resources such as online CE, veterinary conferences, and local professional meetings. • Hands-on training in pain recognition/ differentiation including the use of pain scales and scoring systems. • Leading the team in the research of pain management topics and techniques in order to keep the practice current and have scientific data available to support requests for pain management to the veterinarian(s). • Acting as a liaison, meeting regularly with the veterinarian(s) in order to form a collaborative effort between the veterinarian(s) who carries the ultimate responsibility for pain management decisions and the support staff who provide frontline nursing care and therefore are usually the first to note changes in patient status. This will help the veterinarian(s) to make decisions regarding staff and their specific roles in regard to pain management decisions. • Developing pain management protocols with the veterinarian(s) approval and systems of accountability for pain management and record keeping.

The technician/nurse can help identify specific ways in which to help facilitate the practice in overcoming these obstacles. Each member of the

Larger hospitals may benefit from a pain team with several individuals (veterinarians and technicians)

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who partner to bring pain manage ment to all patients in the practice. (See last section on forming a pain team.)


Pain can be difficult to assess and differentiate from dysphoria or behavioral problems. Species and breeds within the same species also express pain differently. This is easily demonstrated by differences between the reactions to pain of northern breeds such as Siberian Huskies, who are very vocal, compared to sporting breeds such as Labradors, who are generally more stoic. Much of this knowledge is learned with experience but can be passed to less experienced team members as well. Pain scales as an assessment tool will be addressed in Chapter 3. Each physical examination should include a pain assessment and possible pain manage ment recommendations as part of each patient’s treatment plan. A system of accountability whereby this can be tracked should also be in place to ensure that this is not “falling through the cracks.”

microdose of dexmedetomidine IV at our usual dosage or do you have a dosage preference?” The veterinarian is much more likely to be responsive to a request when given a history and the reasons behind it. Another way of gaining trust through communication is to share observations about what protocols worked well or were not effective, with detailed reasons why, in a nonthreatening manner and at an appropriate time. This is a way not only of partnering with colleagues but also learning with them. For example, “I have noticed that when we add a microdose of a narcotic to our dental nerve blocks, they seem to be more effective.” “I wonder if we should consider using only bupivacaine instead of half bupivacaine and half lidocaine since a dental extraction and prophylaxis will almost always take longer than a half an hour.” This promotes discussion and shows interest beyond a basic job description. Those who attend CE events, belong to profess ional groups or simply read journals regularly will often hear about new techniques that might be beneficial to incorporate into the h ospital’s protocols.

Communication

Clients

A commonly heard complaint from technicians is that they feel their requests for pain manage ment are not taken seriously by veterinarians. Technicians/nurses need to learn how to request updated analgesia effectively. Instead of “That spay needs more pain management!!!,” which doesn’t convey any real information about the patient in question, a better approach is to present the request in a logical detailed manner. For example, “Paulina Smith, the yellow Labrador on which you performed an ovariohysterectomy on was extubated 10 minutes ago, is vocalizing and looking back at her incision site. She received the usual amount of postoperative morphine as you were closing, her heart rate is currently 126 beats per minute (bpm), and she seems agitated or a nxious. May I administer a

Clients’ obstacles must be handled with care. Time must be taken to teach clients how to administer medications so that the pet is receiving analgesia at the appropriate dose and recommended duration. Client education includes demonstration of at-home rehabilitation techniques. It might sometimes be necessary to find lower-cost options to medication protocols. Increased understanding of the human/ animal bond has drastically changed attitudes toward veterinary medical treatment. Not only are people willing to spend more on their pets, but they have an increased willingness to comply with treatment recommendations in order to keep their pets healthy and comfortable. When clients are asked, “What role does your pet play in your life,” nearly 100% of

Assessment


clients responded, “They are my child” or “They are part of the family.” While this is considered an improvement over old attitudes and in many ways this makes our jobs easier, the emotional attachment that goes along with this bond places added importance on not only how well we do our jobs but also our client’s interpretation of whether we are treating their “family” well enough. “Pet owners don’t want their pets to suffer, so we rarely encounter resistance to our pain management recommendations,” says Robin Downing, DVM, Dipl. AAPM, owner of Windsor Veterinary Clinic and The Downing Center for Animal Pain Management in Windsor, Colorado (Downing 2008). Dr. Downing’s practice has a script that technicians use to present the points of each case and also to guide the clients through the next steps of their pets’ treatment. The communication feels nonthreatening to the client; therefore, they are more receptive to the infor mation they are receiving. The Downing Center for Animal Pain Management has built a very high practice/client trust level not only through the quality of medicine that is practiced but also the care that is taken with clients. Start by having honest conversations with clients regarding their lifestyle, expectations, and abilities. This information should become part of the pet’s permanent medical record and should include the following: • Lifestyle—Activity level, work status, layout of home such as stairs or size of yard, small children, other pets, etc. • Expectations—Particular types of treatment, level of participation, level of improvement anticipated, etc. • Abilities—Physical, time, financial, etc. Pain management programs are tailored specifically for each client. While there are virtually no clients who want to see their pets suffer, there are still practical considerations. All clients deserve to know what treatment options are

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available. Specific client information creates the opportunity to offer assistance programs available through the practice or that exist in the community. For example, if the obstacle is financial, CareCredit or a charitable trust might be discussed. If the obstacle is physical and a pet is going to be immobilized or requires home physical rehabilitation, arrangements can be discussed and made in advance of the surgery/ procedure. Unless pain is traumatic, it’s not uncommon for a pet’s pain to go unrecognized. Animals have a “pain” language, but they often mask pain and seem to be capable of enduring large amounts of pain with the most subtle signs. It is important for us to share our pain assessment, in a positive way with our clients. Many clients will feel guilty because they didn’t notice or thought it was normal behavior or “slowing down.” In order to get them on board for treating pain, offering reassurance and support will be the correct way to overcome those obstacles. Pet owners can be taught to recognize obvious and subtle pain signs in their pets. There is a myriad of information, and mis information, which is readily available on the Internet, but it is important for the veterinary staff to be the client’s trusted resource. Quality client handouts whether generated commercially or from hospital staff are absolutely necessary. Clients don’t remember most of what’s said in the exam room, especially if they are worried about their pet. It is much better to discuss issues with the client prior to returning their pet. Once the beloved pet arrives, they will “hear” nothing that is said. Specific, detailed instructions will help to keep clients connected to the hospital when treating pets at home. Along with continuing education, wellthought-out organization and written materials, communication between staff, especially the technician and veterinarian, and the prac tice and the client is of major importance to providing optimal pain management for veterinary patients.

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Forming an In-Hospital Pain Team Large veterinary facilities and specialty hospitals often have great difficulty designing and enforcing consistent pain management plans. Veterinarians are often divided in their approach, resulting in great variation in pain management and exposing technicians to a wide variety of protocols and patient responses. When this vital information is captured, technicians can play a significant role in designing optimal protocols that are hospital based rather than clinician specific. Formation of an in-hospital pain team can be extremely b eneficial in designing effective hospital protocols and providing con tinuity of care for all patients (N. Shaffran, pers. comm.). Getting Started How to create the team 1. Get endorsement hospital wide establishing the pain team’s authority to make recommendations and offer treatment options for all painful animals. 2. Decide who should be on the team, how many members, and who the leader will be. The team should include technicians/nurses and veterinarians from various hospital sections and shifts. 3. Plan regular organized meetings for the pain team. Regularly have the pain team address the hospital staff with new information.


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Are there any underlying factors such as stress, anxiety, fear, or preexisting chronic pain conditions that could be causing an increased pain response? What is the normal behavior/disposition of the particular breed/species and for this animal in particular? Are there any contraindications to particular drugs or drug classes for this patient’s condition? Does this animal have a history of drug sensitivities? Consider interviewing the owner regarding the animal’s previous response to analgesia at home. Are there nonpharmacologic approaches that can be taken (i.e., massage, passive range of motion, physical therapy, hydrotherapy, acupuncture)?

Protocol changes may include adjustments in analgesic regimes (e.g., PRN injections to a constant rate infusion), changes or additions to drug protocols (e.g., adding an NSAID), or the possible addition of sedatives if needed. 3. Order new drugs or equipment as needed. 4. Set a regular cage-side rounds protocol/ frequency to ensure exchange of information between shifts and establish continuity of care. 5. Solicit feedback from and communicate goals regularly to all hospital members. 6. Provide careful documentation of analgesic type, dose, frequency, and, most importantly, response throughout the treatment period. 7. Stay current (monitoring the IVAPM, CE, journal clubs, etc.).

Specific Pain Team Tasks 1. Review existing protocols, including preemptive, perioperative, and take-home analgesia. 2. Set new protocols for assessment and treatment. The initial approach should be based on the following questions: ○○ How painful is the condition, procedure, or surgery expected to be?

Conclusion Effective pain management requires ongoing diligence on the part of the veterinary hospital. Reaching the goal of consistent pain management is best achieved when the entire healthcare team including veterinarians, veterinary technicians/


nurses, assistants, and pet owners communi cate in an effective manner. Owners need to be educated about how to assess their pet’s pain status. Dialogue continues concerning obstacles to pain management. The technician/veterinarian relationship continues to progress; it is trust based and built over time, through positive experiences and open communication. The best-case scenario is one where the veterinarian grows to consider the technician an integral player in the pain management team. The recognition and treatment of pain in veterinary medicine has advanced exponentially in a relatively short amount of time. The “new era” has begun, pain standards have been adopted by important veterinary organizations, pain is considered a vital sign, pain scales are a well- known tool, and pain management lectures are overflowing at meetings. Albert Einstein said, “We can’t solve problems by using the same thinking we used when we created them,” and thinking/attitudes have drastically changed in the area of pain management. “Pain is a message asking for our help” (Epstein 2008).

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The veterinary technician/nurse should make it their mission to provide that help.

References Dohoo, S.E. & Dohoo, I.R. (1998) Attitudes and concerns of Canadian animal health technologists toward positive perioperative pain management in dogs and cats. Canadian Veterinary Journal, 39 (8), 491–496. Downing, R. (2008) Sample script: How to discuss chronic pain management. Firstline, 4 (4), 1. Epstein, G. (2008) Kabbalah for Inner Peace, Acmi Press, New York, p. 72. Flaherty, J.H. (2001) Who’s taking your 5th vital sign? Journal of Gerontology: Medical Sciences, 56A (7), M397–M399. IASP (1994) IASP Task Force on Taxonomy, H. Merskey and N. Bogduk (eds), IASP Press, Seattle. Lawson, J. (1986) Letter, vol. 9. Perinatal Press, pp. 141–142. Lee, B.H. (2002) Managing pain in human neonates applications for animals. Journal of the American Veterinary Medical Association, 221 (2), 234. Rich, B.A. (2001) Physicians legal duty to relieve suffer ing. Western Journal of Medicine, 175 (3), 151–152.

Pain Management Careers for Veterinary Technicians and Nurses

c h a p t e r

1 2

Mary Ellen Goldberg, Kristen Hagler, and Janel Holden

The American Society for Pain Management Nursing has as its Mission Statement, “To advance and promote optimal nursing care for people affected by pain by promoting best nursing practices” (http://www.aspmn.org/). The Advanced Practice Pain Management Nurse opening description states, “This Advanced Practice nurse cares for patients experiencing acute or chronic pain. After Pain Management Nurses assess the source of pain, they work with other nurses and doctors to coordinate treatment and care. Pain Management Nurses are also teachers, showing patients how to help manage their own pain, their medications and alternative ways to relieve their pain” (http://www.discovernursing. com/specialty/pain-management-nurse#.UmK71 BAnWRM). It is the intent of this chapter to indicate where the veterinary technician/nurse can go to receive additional certification for specialization in veterinary pain management. The purpose of indicating the two human pain manage ment websites is to illustrate that the pain

management veterinary technician/nurse’s role highly resembles that of its human counterpart.

Pain Management Certifications Available for Veterinary Technicians/Nurses Certified Veterinary Pain Practitioner (CVPP) through the International Veterinary Academy of Pain Management (IVAPM) The International Veterinary Academy of Pain Management (IVAPM) certification program is designed to represent a minimum level of competence as an interdisciplinary pain practi tioner while providing the platform and incentive for continued and expanded learning in the field of veterinary pain management (http://www. ivapm.org/index.php?option=com_content &view=article&id=103&Itemid=99). The current


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Chapter 2 Pain Management Careers for Veterinary Technicians and Nurses

9

program will lead to the title of certified veterinary pain practitioner (CVPP) for veterinarians and licensed technicians with certification in canine rehabilitation. The IVAPM certification program is intended to emphasize the value of the many disciplines capable of enhancing patient comfort and quality of life and to facilitate an understanding of the modalities not necessarily in the member’s current area of familiarity. IVAPM hopes to facilitate the networking of professionals engaged in allopathic modalities, physical rehabilitation, and complimentary alternative therapies. IVAPM in general, and the CVPP in particular, provides the stage upon which all professionals committed to promoting, enhancing, and advancing pain management in animals may interface. It is the foundation upon which the veterinary profession can build the most effective multidisciplinary pain manage ment team. The aforementioned information is taken from the certification page of the IVAPM website. Full details about the process for this certification are available on the webpage.

Certification as a VTS (anesthesia) promotes patient safety, consumer protection, professionalism, and excellence in anesthesia care. The veterinary anesthesia arena is constantly evolving; thus, the attainment of competence is a continual activity. Details about the entire process for certification can be found at AVTA’s webpage.

Veterinary Technician Specialist (Anesthesia) through the Academy of Veterinary Technician Anesthetists

The surgical research anesthetist (SRA) certification is intended for the veterinarian, veterinary technician/nurse, physician, dentist, graduate student, or research assistant who works as an anesthetist who also has responsibilities as part of the surgical team that include aseptic preparation and perioperative care of surgical patients. The SRA candidate must have documented experience with at least two species as reflected in an anesthetic case log. Details relating to the certification process can be found at ASR’s webpage.

The Academy of Veterinary Technician Anesthetists (AVTA) exists to promote interest in the discipline of veterinary anesthesia. The Academy provides a process by which a veterinary technician may become certified as a veterinary technician specialist (VTS) (anesthesia). Mission (http://www.avta-vts.org/site/view/ 92019_MissionStatement.pml) The Academy provides the opportunity for members to enhance their knowledge and skills in the field of veterinary anesthesia. The veterinary technician who becomes certi fied as a VTS (anesthesia) demonstrates superior knowledge in the care and management of anesthesia cases.

Surgical Research Anesthetist through the Academy of Surgical Research Founded in 1982, the Academy of Surgical Research (ASR) promotes the advancement of professional and academic standards, education, and research in the arts and sciences of experimental surgery. The Academy interfaces with medical and scientific organizations and governmental agencies in establishing and reviewing ethics, theories, practices, and research pertaining to surgery and promotion of the results for clinical application (http://www.surgicalresearch.org/). Surgical Research Anesthetist (SRA)

University of Tennessee Companion Animal Pain Management Certificate Program The program is a 28 h online, on-demand course for veterinarians and veterinary technicians. This course is designed to help veterinarians and vet techs identify the pathologies that will

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benefit from effective pain management practices. It provides an in-depth discussion of the neurobiology of acute and chronic pain (http://www.canineequinerehab.com/pain- management.asp). Details can be found at the above website.

Clinical Associate, American Academy of Pain Management Clinical associate: bachelor or associate degree in a related healthcare field (e.g., BS, BSN, RPh, RPT, veterinary technician/nurse) This credential indicates the following: • You have demonstrated commitment to the field and understanding of integrative pain management. • You have gained important recognition with colleagues and patients. • You have a professional edge that helps lead to the success of your practice/career. • You have passed a rigorous credential exam. • You have committed to ongoing education in the field of pain management. • You have committed to the promotion of continuous quality improvement for the relief of pain. (http://www.aapainmanage.org/members/ Credentialing.php) Details about the process can be found at the above website.

Rehabilitation Veterinary Technician There are three schools where the veterinary technician can become certified in rehabilitation: 1. Canine Rehabilitation Institute—The Canine Rehabilitation Assistant (CCRA) program is for veterinary technicians and physical therapist assistants and is an American Association of Veterinary State Boards (AAVSB)- and Registry of Approved Continuing Education


(RACE)-approved program (http://www. caninerehabinstitute.com/CCRA.html). Details of the courses can be found at the above website. 2. The University of Tennessee—Certified Canine Rehabilitation Practitioner (CCRP) program. Aimed at professionals in the fields of veterinary medicine and physical therapy, we seek to provide information that will assist those exploring the field of canine rehabilitation to those already pursuing it through practice and/or research (http://www.utcaninerehab. com/). Certified Equine Rehabilitation Practitioner (CERP) program. Our mission is to promote the art and science of equine rehabilitation (http://www.utvetce.com/EquineRehabilitation. asp). Both courses are AAVSB and RACEapproved programs. Details of each course can be found at the above websites. 3. Animal Rehab Institute—The Certified Equine Rehabilitation Assistant (CERA) program is offered to veterinary technicians and physical therapist assistants. Veterinary CEUs are currently being applied for through the AVMA (http://www.animalrehabinstitute.com/ Rehab%20Cert/Overview.html). Details of this course can be found at the above website.

Certification in Massage Therapy Equine Massage Therapy Certification (CEMT) instruction provides students the skills necessary to perform a full body assessment and massage treatment incorporating effleurage, petrissage, tapotement, friction, vibration, trigger point, stress point, and myofascial release techniques on the horse. No indication of veterinary CEU has been specified (http://www.animalrehabinstitute. com/Pages/EQM1_EQMasscert.html). Details of this course can be found at the above website.


Medical Massage for Animals: Canine Course—offered through the Colorado Veterinary Medical Association (http://www.colovma.org/ displaycommon.cfm?an=1&subarticlenbr=152). Registrants must be licensed veterinarians, veterinary students, or certified veterinary technicians. Veterinarians and veterinary technicians will need to include a copy of their license/ certification with their registration form. Veterinary students must include a letter that they are in good standing from the dean’s office of their college. Pending approval from the Colorado Board of Veterinary Medicine, 15.5 h of CE is available. The Colorado Association of Certified Veterinary Technicians has approved 15.5 h of CE. Certificate of Completion is awarded at end of course. Participants must attend all lectures and laboratories to receive their certificate.

TCVM Veterinary Technician Program Offered by the Chi Institute TCVM for Veterinary Technicians is a program designed to teach the veterinary technician to support and promote TCVM services in practice. Through the program, techs are given the tools to speak knowledgeably about the purpose and value of TCVM and to teach clients how to care for their animals with food therapy and Tui na techniques. There is no certification available through this course. The purpose is to teach the technician/nurse about the five areas of TCVM: acupuncture, Tui na, herbal medicine, food therapy, and Qigong (http://www.tcvm.com/ Programs/TCVMforVetTechs.aspx).

Osteoarthritis Case Manager Offered through the University of Tennessee

Kristen Halger An osteoarthritis case manager (OACM) is a highly skilled veterinary technician who has obtained a specialized certification by becoming knowledgeable in pathophysiology, conditions, common

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pharmaceuticals, and complementary therapies used for osteoarthritis (OA) (http://www.utk9oa. com/). The OACM assists veterinarians with client education, advanced outcome assessments, and observations. Veterinary practices with specialized case managers such as the OACM benefit through specific attention dedicated to one area of patient care, improving outcomes and client expectations and compliance. For specifics about the disease mechanism of OA, please refer to Chapters 9 and 15.

The Veterinary Technician’s Role The veterinary technician’s role as the OACM is to recognize early side effects and improve overall safety from NSAID administration. The OACM can provide educational information to pet owners and become the point person for reporting improvement or decline in tolerance. The OACM can assist the veterinarian by tracking trends in blood work, providing feedback on physical improvement, reminding owners of upcoming rechecks, providing written dosing instructions, educating owners of contraindicated herbals and medications, providing hydration recommendations, and ensuring appropriate dispensing packaging. Medication safety and dosing information improves client compliance and patient care. The veterinary technician trained in OA management should understand the various surgical options available for altering disease progression and severity of long-term pain associated with various conditions. When possible, minimally invasive techniques are best, especially when postoperative recovery incorporates appropriate rehabilitative techniques. Regardless of surgical intervention chosen for OA management, pet owners should also be educated on possible alterations in functional capabilities and make appropriate lifestyle changes. Veterinary technicians possessing advanced skills and knowledge in specialty fields such as OA case management can improve care for patients and veterinary team effectiveness.

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Text Box 2.1 OACM training enables the veterinary technician to: • Have extensive knowledge regarding OA pathophysiology • Understand factors contributing to the development of OA • Recognize early risk assessment factors • Understand diagnostic tools • Possess adequate palpation and examination skills • Utilize subjective and objective outcome assessment tools • Provide individualized client education with appropriate environmental modification or assistive device counseling • Utilize pain scoring systems • Effectively collaborate with nutritional and rehabilitative specialists • Understand medications, herbals, nutraceuticals, and supplements used in OA management • Be able to communicate the role of acupuncture in chronic pain management • Improve pet owner compliance with progress evaluations • Develop incentive programs • Assess functional and disability capabilities • Maintain an OA participation list

Recognizing which patients are at risk for OA through risk factor assessment and early intervention are two keys for the OACM to maintain effectiveness and confidence by colleagues and pet owners.

Analgesia Careers in University Teaching Hospitals

Janel Holden The mission of a university teaching program is to educate, conduct research, and provide state-of-the-art care to veterinary patients. The


diverse university setting provides the opportunity to educate the entire veterinary team, which includes the client. Veterinary nurses and technician with a keen interest in pain management who enjoy teaching may find this environment extremely satisfying. When it comes to analgesia, the goal is to teach the “gold standard” of pain management to a variety of veterinary professionals and students. Veterinary pain management is a growing field, and the university strives to stay current with optimum analgesic techniques. The university setting provides the opportunity to trial new medications while assessing or researching their pros and cons. Veterinary and technician nursing students learn how to use and interpret monitoring equipment parameters useful in determining a patient’s pain response. For example, changes in heart rate and rhythm, respiratory rate, and blood pressure can indicate response to painful stimulus. These parameters can also be useful in determining adverse reactions to high doses of analgesics. Tachyarrhythmias have a number of underlying causes including painfulness. Other causes include light plane of anesthesia, hyperthermia, hypotension, hypercapnia, anemia, etc. (Egger 2007). Students are taught to determine the cause of the tachycardia by taking all parameters into account. A common misunderstanding is the student’s difficulty determining if the patient is in pain or in a light plane of anesthesia or if the tachycardia is due to hypotension or hypovolemia. Students are taught sensible approaches to resolving issues logically often by veterinary technicians. The university teaching hospital has the ability to offer services for nonpharmacologic therapy such as rehabilitation and acupuncture. For details about physical rehabilitation and acupuncture (refer to Chapters 16 and 17). Client education is an important part of the veterinary teaching hospital. Clients are educated on how to best manage and assess their animal’s pain at home before leaving the hospital. Clients


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Text Box 2.2 Veterinary technicians employed at a university have a variety of responsibilities: • Supervising and grading veterinary technician students at the university. • Guiding interns and residents on day-to-day procedures. • Assist in teaching veterinary students about local blocking techniques and medications involved. • Assist in teaching continuous rate infusions (CRIs) and medications utilized for this technique. CRIs are often calculated and maintained by veterinary technicians. Regional anesthesia and CRIs used in combination are effective in managing acute and chronic pain and when used in combination with inhalant anesthesia will greatly decrease the concentration of inhalant needed. Using this balanced anesthesia technique will lessen the negative cardiovascular effects caused by inhalant anesthesia (Kästner 2007). For more detailed information on CRIs, see the Appendix B. • Assist in teaching visiting veterinarians and veterinary technician, whether foreign or domestic, to improve their understanding and practice of pain management, perfect analgesic techniques, and improve knowledge of pain medications. • Veterinary and technician nursing students learn how to use and interpret monitoring equipment parameters useful in determining a patient’s pain response. For example, changes in heart rate and rhythm, respiratory rate, and blood pressure can indicate response to painful stimulus. These parameters can also be useful in determining adverse reactions to high doses of analgesics. Tachyarrhythmias have a number of underlying causes including painfulness. Other causes include light plane of anesthesia, hyperthermia, hypotension, hypercapnia, anemia, etc. (Egger 2007). Students are taught to determine the cause of the tachycardia by taking all parameters into account. A common misunderstanding is the student’s difficulty determining if the patient is in pain or in a light plane of anesthesia or if the tachycardia is due to hypotension or hypovolemia. Students are taught sensible approaches to resolving issues logically often by veterinary technicians.

learn how to administer prescriptions and perform physical therapy and how much exercise their animal needs for recovery. Students learn how to communicate these and other instructions to the clients for optimal recovery and pain management.

Pitfalls of University Programs Disadvantages of being at a university program include: • Delay of medications or services because of need to extensively explain even minor details to students. • Departmentalization: Anesthesia, soft tissue surgery, orthopedic surgery, internal medicine, oncology, radiology, neurology, cardi-

ology, critical care, etc. have distinct clinicians and technicians specialized in their fields. This construct can lead to a great deal of discrepancy in how to best manage a patient’s pain. Patient’s pain management can get lost in the shuffle from department to department. To combat this, it is imperative to keep complete records for each patient and communicate from one service to the other. It is also important that everyone involved with each patient use a consistent pain score record that stays in the medical file. • Turnover of new students, interns, residents, and doctors. New people coming into the environment take time to learn procedures and protocols. The number of people involved on each case can lead to human error without diligent communication and record keeping.

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At the core of maintaining communication is the veterinary technician/nurse. Keeping the lines of communication open between these highly trained and specialized individuals is what keeps the university running smoothly and optimal for patient care and safety. In conclusion, the university teaching hospital can offer “state-of-the-art” knowledge, research, techniques, and medications. The veterinary technician plays an integral role in all aspects of this practice.

Websites Academy of Surgical Research—http://www. surgicalresearch.org/ Academy of Veterinary Technician Anesthetists— http://www.avta-vts.org/site/view/92019_Mission Statement.pml American Academy of Pain Management— http://www.aapainmanage.org/members/Creden tialing.php American Society of Pain Management Nurses— http://www.aspmn.org/—Mission Statement Animal Rehab Institute—http://www.animal rehabinstitute.com/Rehab%20Cert/Overview. html http://www.animalrehabinstitute.com/Pages/ EQM1_EQMasscert.html

Canine Rehabilitation Institute—http://www. caninerehabinstitute.com/CCRA.html International Veterinary Academy of Pain Management—http://www.ivapm.org/index. php?option=com_content&view=article&id= 103&Itemid=99 The Advanced Practice Pain Management Nurse—http://www.discovernursing.com/ specialty/pain-management-nurse#.UmK71BAn WRM The Chi Institute—http://www.tcvm.com/ Programs/TCVMforVetTechs.aspx University of Tennessee—http://www.canine equinerehab.com/pain-management.asp http://www.utcaninerehab.com/ http://www.utvetce.com/EquineRehabilitation. asp http://www.utk9oa.com/

References Egger, C. (2007) Anaesthetic complications, accidents and emergencies. BSAVA Manual of Canine and Feline Anaesthesia and Analgesia, 2nd edn, British Small Animal Veterinary Association, Gloucester, UK; pp. 310–332. Kästner, S. (2007) Intravenous anaesthetics; C. Seymour & T. Duke-Novakovski (eds), BSAVA Manual of Canine and Feline Anaesthesia and Analgesia, 2nd edn, British Small Animal Veterinary Association, Gloucester, UK; pp. 147–148.

Pain Recognition in Companion Species, Horses, and Livestock

c h a p t e r

3

Cheryl Irzyk Kata, Samantha Rowland, and Mary Ellen Goldberg

Companion Animals Pain assessment is a vital and essential part of patient evaluation whether the patient presents with a problem or comes for a routine annual visit. The American Animal Hospital Association’s standards require that pain be included in every veterinary patient assessment regardless of a presenting complaint (Shaffran 2008). Making repeat regular assessments throughout hospitalization and recording of those assessments in the medical record is vital. The pain experience is different for each individual animal; however, there may be similarities in physiologic and behavioral characteristics within specific species. Regardless of individual experience, pain is always potentially detrimental to the patient.

The Negative Effects of Pain (Thomas and Lerche 2011) • Pain produces a catabolic state (energy release), which may lead to wasting.

• Pain suppresses the immune response, predisposing to infection or sepsis and increasing hospitalization time and cost. • Pain promotes inflammation, which delays wound healing. • Anesthetic risk is increased because higher doses of anesthetic drugs are required to maintain a stable plane of anesthesia. • Pain causes patient suffering, which is also stressful for owners and caregivers. Stress, fear, anxiety, hypotension, hypothermia, fever, etc. can influence the extent of damage that the body incurs. At the onset of pain, sympathetic tone increases—causing vasoconstriction, increased myocardial work (Lamont 2000), and increases in oxygen consumption. Catecholamines are released from the pituitary (ACTH) and adrenal glands (norepinephrine and dopamine). Glucagon is released into the blood causing hyperglycemia and insulin resistance. Protein catabolism, decreased gastrointestinal (GI) motility (ileus), decreased urinary tone, retention of water and


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Text Box 3.1 Pain-Related Physiological Changes Cardiovascular Hypertension Tachycardia, tachyarrhythmia Peripheral vasoconstriction (pale mucosa) Respiratory Tachypnea Hypoxemia Shallow breathing (abdominal or thoracic guarding) Exaggerated abdominal component Panting (dogs) Open-mouth breathing (cats) Pulmonary edema Respiratory acid–base imbalance Gastrointestinal Ulcers Ileus Nausea and vomiting Ophthalmic Mydriasis (dilation of pupil) Metabolic Cachexia Increased oxygen demand Negative nitrogen balance Immune function Hemorrhage Sleep pattern Behavior changes


Pain Charts and Scales Assessing pain requires skill and knowledge of what normal behavior looks like. Neonates have intact neural pathways for pain transmission, but both neonates and senior animals may not express their pain as plainly as other animals. There are many examples of pain scales. Each scale has its advantages and its limitations. Regardless of the scale utilized, it is important to choose one system to be used by the entire veterinary team. Pain signs may be obvious such as increased heart rate and blood pressure, increased respiratory rate, and vocalization. More subtle behavioral changes that occur such as general restlessness, decreased appetite, not sleeping, resenting handling, and not assuming a normal position may be even more significant. There are many pain scoring systems available, from simple to complex. The most important system to choose is one that is relatively straightforward to use, one that is fairly consistent between multiple users, and one that is not overly cumbersome. If there is a question or controversy regarding an animal’s pain status, then a more involved pain scale can be used in those situations. There are three main categories of pain scoring systems: preemptive, subjective, and objective. Predicting Pain Scores: Preemptive

sodium, and an increased excretion of potassium (Thurmon et al. 1996) place the body in a critical state increasing the risk for infections, slow healing, and morbidity (Gaynor and Muir 2009). Central nervous system (CNS) changes occur during a painful event releasing prostaglandins, bradykinin (Fleetwood-Walker 2012), and cytokines. Pain can cause atelectasis and hypercarbia by not allowing the chest to expand fully. The respiratory system will not work efficiently, and long-term pain can cause accelerated aging, weight loss, and poor coat condition (Gaynor and Muir 2009).

“Predicting” the pain a particular procedure may induce based upon the perceived degree of pain of the procedure is a method of categorizing usual responses to that procedure. For example, minor procedures such as radiography are thought to cause minimal pain. Minor surgeries, such as abscess repair, are considered to be minimally painful. Moderate surgeries, such as ovariohysterectomies or castrations, are considered to have moderate pain, and major surgeries, such as thoracotomies or exploratory laparotomies, are considered to have severe pain. Predicting scores is a very simple means of trying to address pain control prior to a surgery or procedure.

Chapter 3 Pain Recognition in Companion Species, Horses, and Livestock

Subjective Scoring The observer’s subjective opinion as well as physiological signs can be described utilizing a pain scale such as a visual analog scale (VAS). VAS designed for use in nonverbal human patients uses pictorial rather than numerical rating systems. The most common scale has a series of faces with varied expressions. The main difference between human and animal VAS is that in human medicine, the patient is the reporter of his or her pain level, whereas in veterinary medicine, VAS readings are most often provided by a veterinary technician/nurse who is always a second-party reporter. The observer makes a mark on the scale to indicate how much pain the animal appears to be exhibiting. The veterinary VAS utilizes subjective 0–10 or 0–100 numerical ratings where 0 correlates with no pain and 10 or 100 is the worst pain imaginable (Figure 3.1 and Table 3.1). Another type of subjective pain scale is a simple descriptive scale. This consists of a ranking system from 1 to 4. Number 1 indicates no pain, number 2 indicates mild pain, number 3 indicates moderate pain, and number 4 indicates severe pain. Although this scale is subjective, it is an easy way to record pain assessment in the medical record and watch trends over time (Figure 3.2). Objective pain scales frequently include numerical pain scales, which assign a rank number to various categories, and then the category numbers are added up for a final pain score. There are simple numeric pain scales that only include categories such as vocalization, movement, and agitation (Figure 3.3). The Colorado State Canine and Feline Pain Scales fall under the subjective pain scale 100 mm: the most pain ever

0 mm: no pain

Total line is 100 mm

Figure 3.1 Visual analog scale. Source: Drawn by Cheryl Kata.

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category. The scales use an observational period and hands-on evaluation of the patient in an easy-to-use format. The disadvantage of this scale is a lack of validation by clinical studies comparing it to other scales (Mich and Hellyer 2009) (http://www.csuanimalcancercenter.org/ assets/files/csu_acute_pain_scale_canine.pdf; http://csuanimalcancercenter.org/assets/files/csu_ acute_pain_scale_feline.pdf). Objective Scoring There are more advanced pain scales that include categories such as comfort, movement, appearance, unprovoked behavior, interactive behavior, vocalization, heart rate, and respiratory rate. The Glasgow Pain Scoring System is one of the more frequently utilized advanced pain scales and is considered possibly “state of the art.” “A pain scale that takes into account the various dimensions of pain is thought to be more useful in indicating how much the pain “meant” to the animal, but VAS, NRS and SDS scales are unidimensional. A pain scale should ideally be multidimensional, with several aspects of pain intensity and pain related disability included; and question especially the dynamic aspects. The Glasgow CPS is thought to be Multidimensional” (Karas 2011) (Figure 3.4). Pain assessments should be made at 4–6 hour intervals throughout hospitalization in the general patient population and much more frequently in the critical care setting where patient status is more dynamic. During the immediate postoperative period and throughout the critical phase, patients should be monitored as often as every 30 min. For consistency, assessments should be performed by the same person whenever possible. Repeat recorded assessments allow evaluation of the efficacy of analgesic protocols and make response to specific drugs more obvious. A complete patient description including physiological signs (temperature, pulse, respiration) as well as behavioral signs (vocalization, posturing, eating and sleeping habits) should be documented in the medical record. A simple chart

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Table 3.1 Pain behaviors in companion animals

Symptom

Dog

Cat

Vocalizing

Yes

Yes

Social behavior

Decreased

Will become solitary, reclusive

Restlessness

Yes

Possibly but more often its reduced activity, seclusion

Abnormal posturing

Yes; also reluctance to lie down or get up

Yes; reluctance to get up

Increased temp

Possibly

Possibly

Inappetence

Yes

Yes

Increased BP

Possibly

Possibly

Aggression

Yes

Yes

Frequent movement (weight shifting)

Yes especially for OA

No

Facial expression

Yes, fixed stares, depressed

Yes, depressed facial expressions, Squinted eyes, furrowed brows

Trembling

Yes

Yes

Depression

Yes—dull

Yes

Anxiety

Yes

Yes

Self-grooming

Self-mutilation

Unkempt

Papillary enlargement

Yes

Yes

Licking/chewing/staring at site

Yes

Yes

Respiration

Tachypnea

Tachypnea/open mouth panting

Tail carriage

Tucked down

Tail flicking but could also be anger

Inappropriate urination

Yes

Yes

Eyes

May be dilated and may move instead of head or neck

May be dilated, also squinting

Heart rate/rhythm

May have tachycardia but can be from other events; also pain can cause VPCs

May have tachycardia but can be from other events; also pain can cause VPCs

Facial expressions

Fixed stare or head down depressed

Furrowed brows

Hair coat

Hair loss/thin coat

Unkempt


No pain

Mild

Moderate

Severe

Very severe

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Worst

Figure 3.2 Simple descriptive scale. Source: Drawn by Mary Ellen Goldberg.

0__1__2__3__4__5__6__7__8__9__10 No pain

↑

↑

Worst pain

Figure 3.3 Numerical rating scale. Source: Drawn by Mary Ellen Goldberg.

system allows evaluation of the efficacy of the analgesic protocol. Chronic Pain Scales Several chronic pain scales have been developed for companion animals (see Chapter 9).

The Client Encouraging clients to continue record keeping after the patient leaves the hospital may be difficult but is imperative in helping steer the therapy. The weekend warrior patient may be more active on the weekend when the family is home versus during the week when the day is structured. On these days where activity is increased, a modification of medications may be needed, whereas on the less active days, the normal regiment is adequate. The record may help the client more accurately assess their pet’s quality of life when end of life is immanent.

Creating Your Own Pain Scales Most practices can create a simple pain scale and train the staff to use them during every patient visit. Commitment must be made to use the scale daily with every appointment, whether it is a routine puppy visit or a geriatric visit. The owner’s input should be solicited and included. Pain scales can be created by a number of methods. For example, the Colorado Pain Scale has pictures to help guide the viewer to the extent of the pain. Training the entire staff with the same guidelines can help reduce confusions and ensure the patient receives proper therapy.

Record Keeping The Hospital Record keeping in the veterinary hospital is mandatory. Every time the pain score is assessed, a copy should be given to the client. These assessments will help guide the treatments and keep a permanent record of results. This allows the entire team to understand current therapy in case the patient returns and is seen by a different team member.

Text Box 3.2 Using Pain Scoring Effectively • If possible, have same person evaluate the patient. • Request VAS readings as treatments. • Assess behavior. • Assess body posture, activity, and position in cage • Evaluate response to approach. • Interact with patient. • Palpation of surgical site using gentle pressure (acquired skill). • Ask patient to ambulate, if appropriate. • Ask patient to eat, if appropriate.

Key Signs 3.1 Dogs Inappetence, bites at pain regions, and abnormally apprehensive. Cats Stiff posture, demented behavior, lack of grooming, hunched head and neck, and inappetence.

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Figure 3.4 Glasgow composite pain scale. Source: Mich, P., Hellyer, P. Handbook of Veterinary Pain Management. 2009. © Elsevier.


A simple weekly chart can be constructed and modified to compliment the patient. The daily chart should include: • • • • •

Pain score Medications given, dose, and frequency Adverse events Whether the patient is eating Activity level

At week’s end or at next appointment, an assessment can be made for the effectiveness of the treatment. The assessment may benefit the practitioner in evaluation and modification of the patient’s therapy.

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• Normal rectal temperature • Ambulates normally, weight bearing on all four limbs • Performs work normally • Interacts with people and other horses normally The equine species has an intricate and expressive language; they are herd-based, social creatures with a specific hierarchy, which makes effective communication necessary. In addition to facial expressions and posture/position, the horse has many vocalizations used to express themselves. Equine vocalizations can be classified as neigh, whinny, nicker, squeals, snorts, and even roars (Figure 3.5).

Equine Pain Recognition The scientific theory that neurologic pathways of humans and animals are comparable in the way that they experience pain is now well defined. With that awareness, it can be reasonably assumed that if something were to cause a person pain, it will cause the animal to have pain as well (AAHA 2007). It is imperative that the equine technician be able to recognize both normal and abnormal behaviors in the horse in order to care for the animal appropriately and implement pain management when needed.

Appearance of the Normal Horse The normal, healthy equine should demonstrate these traits (Houpt 1998): • Alert mental state • Appropriate response to stimulus (not dull or unresponsive) • Good appetite • Able to chew and swallow normally and does not “drop feed” • Urinates normally, with normal color • Defecates normally, with formed manure • Normal respiratory rate and pattern • Normal heart rate and rhythm

Figure 3.5 Normal alert horse. Source: Courtesy of Robert White.

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Appearance of the Painful Horse The pain state in the horse is a multidimensional experience. Pain can be exhibited through changes in behavior, emotion, or physiologic parameters (DeGouff 2010). These changes can be difficult to assess, and therefore, the recognition of equine pain remains subjective. Recognition and treatment of pain is essential in providing the individual with a good quality of life. Horses experience physiologic/adaptive pain as well as clinical/maladaptive pain and idiopathic pain. Physiologic pain is a protective response by the CNS to warn the individual after a noxious stimulus occurs to prevent tissue damage (DeGouff 2010). Clinical or maladaptive pain is in response to damage already done to peripheral tissue or the nervous system and is classified as inflammatory or neuropathic pain. Inflammatory pain is further broken down to visceral or somatic pain; visceral pain involves the thorax and abdomen, while somatic pain involves muscles, joints, skin, and periosteum of the bones. Neuropathic pain is usually due to chronic pain of peripheral nerves or the spinal cord. Idiopathic pain is persistent pain without a specific source; it can be extreme and exacerbated by excitement, fear, and stress (Van Loon 2012). Horses are considered prey animals, and it is therefore part of their natural instinct to hide pain as much as possible in order to protect themselves (Lockhead 2010). Signs of pain in the horse can initially be subtle but can become obvious when they can no longer hide it due to its severity. Signs of pain can also vary based on the horse’s age, breed, temperament, and specific disease (Lerche 2009). Some horses such as draft horses are much more stoic than other breeds even in the face of severe pain. “Hot-blooded” breeds like Arabians and Thoroughbreds are more likely to show signs of pain, as are young horses and foals. When horses are in unfamiliar environments, such as the hospital, pain can be masked (stress-induced analgesia) (Lerche and Muir 2009). Some basic physiologic responses should be assessed when trying to gauge the level of pain in an


individual. These include behavior/attitude, activity level, overall appearance, appetite, posture, facial expressions, interaction with people and/or other horses, willingness to work, and response to being handled (Lerche and Muir 2009). Sometimes, the behaviors associated with pain can be nonspecific or correlate with a specific location such as the abdomen, limb, foot, head, mouth, or castration site (Lerche 2009). The most common types of pain in the horse include orthopedic pain and abdominal/colic pain. Orthopedic pain typically presents as a lameness and can include pain of the joints, tendon/ligaments, long bones, and back pain. Lameness is a result of the horse trying to avoid the painful area (Hubbell 2007) by compensating on the other limbs. Overload of the compensating limb can cause “support limb laminitis” secondary to the original lameness (Eades et al. 2002). Somatic pain indicators can include but are not limited to (Lerche and Muir 2009): • • • • • • • • • • •

Abnormal weight distribution Mild to severe lameness Guarding of a limb Weight shifting between limbs Pointing, hanging, or rotating of the limbs Reluctance to move Sensitivity response to palpation of painful area Pain after limb flexion testing Sensitivity to hoof tester application Recumbency Change in appetite

A specific syndrome of the horse that causes debilitating lameness and severe pain is laminitis, or founder. It is a disease of the sensitive and insensitive laminae, or soft tissue structures of the hoof (Eades et al. 2002). The inflammation and degeneration of the laminar structures can cause rotation or separation of the pedal bone (P3) from the hoof wall (Yaksh 2010). While rotation in itself is extremely painful, separation of P3 usually involves sinking, in which P3 can protrude through the sole of the hoof. This disease can end the riding career of the horse and be potentially fatal depending on the severity and how soon it is detected.


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Figure 3.6 Colic horse. Source: Courtesy of Samantha Rowland.

Signs of laminitis pain vary with the progression of the disease but can include (Eades et al. 2002; Driessen et al. 2010): • • • • • • • • • • • • •

Rocking or shifting weight to rear feet Anxiety Muscle fasciculation Sweating Lameness at the walk Reluctant to lift a forelimb Reluctant to walk at later stage Decreased appetite Stands at back of stall Increased digital pulses Camped-out stance Increased heart and/or respiratory rate Refusal to move or recumbency

Abdominal pain, or colic, in the horse can be caused by inflammation of the GI tract, gas distension of one or more loops of intestine, the root

of the mesentery being pulled on, or ischemia of the GI tract. Colic is one of the most common medical problems of the horse and should be treated readily (Porter 2009). Visceral pain indicators can include but are not limited to (Lerche and Muir 2009) (Figure 3.6): • • • • • • • • • • • • •

Depressed/dull appearance (chronic pain) Restlessness, anxiety, or agitation (acute pain) Flank watching Fixed stare and dilated nostrils Lowered head carriage Aggression (toward handlers, horses, or its own foal) Limited to no interaction with people Standing at back of stall Stretching/“parking out” Decreased appetite and food pocketing Groaning/grunting Rigid/reluctance to move Kicking at abdomen

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Key Signs 3.2 Equines (Wagner 2010) Lameness, restlessness, head lowering, teeth grinding, flaring of nostrils, sweating, rigid posture, head turning, kicking at the abdomen, reluctance to be handled, rolling, flight behaviors, and aggression.

• • • • • • •

Recumbency Rolling Increased heart rate Increased respiratory rate, typically shallow Violently throwing itself down (severe colic) Abdominal distension Little to no gut sounds on auscultation

Pain Scoring in the Horse Pain can manifest itself by producing changes in individuals’ physiology, behavior, and emotional state. Some of these changes can be subtle, and discussing the horse’s behavior with its owner or trainer can be beneficial, since they are most familiar with the animal. Pain recognition and the degree of pain management instituted by the veterinarian have been shown to be generational; newer graduates appear to assign higher pain scores than their predecessors (Wagner 2010). Developing a consistent pain scale or scoring system helps keep the assessment unbiased, as long as those observing the animals are trained appropriately on the particular system. Due to the fact that there is no single parameter that determines the animal’s pain experience, developing a pain scale is complicated for any species. The pain experience can also be affected by the horse’s psychological state when nociception occurred. Studies have shown that during periods of extreme stress or fear, pain can be suppressed by the animal’s body—“stress-induced analgesia.” This phenomenon is part of the “fight-or-flight response,” in which the sympathetic nervous system is engaged and endogenous catecholamines are released; the state of fear takes over, and pain is inhibited during that time. On the opposite end of this spectrum is the phenomenon of

“stress-induced hyperalgesia,” in which animals experiencing extreme anxiety can have increased perception of pain (Van Loon 2012). There are indications that horses and humans experience pain in a similar manner and that horses do exhibit emotional responses to pain as well. All vertebrates can experience emotional states; this is not an occurrence limited to human beings, as once was thought (Van Loon et al. 2010). In development is a “Horse Grimace Scale” that uses facial expressions to recognize painful behavior in horses. Six facial actions were defined in the scale: stiffly backward ears, orbital tightening, tension above the eyes, strained chewing muscles, mouth strain, and a pronounced chin and strained nostrils. The greatest pain was seen 8 h after the operation when in most cases analgesics have worn off (Minero 2013). It was noted that darker-colored horses were harder to score than lighter-colored ones. Many factors must be taken into account when using a pain scoring system in the horse, and there is no one particular standardized pain scale for the horse. In most cases, pain is assessed in a basic format such as mild, moderate, and severe. A horse exhibiting mild pain may be prescribed an NSAID, whereas a horse suffering from extreme pain needs significant analgesia that may require hospitalization (Lerche 2009). A few composite pain scales (CPS) have been used for horses in clinical practices. In 2008, a CPS was developed for orthopedic pain in horses by Bussières et al., which incorporated a numerical system that took into account many different factors including the horse’s response to stimuli, physiologic parameters, and spontaneous behavior. The score range for this scale is from 0, which is no sign of pain, all the way through 39 for the maximum pain. Some of the data recorded included behavioral changes such as overall appearance, posture, head or ear movement, pawing, kicking at abdomen, sweating, appetite, how the horse responds to people/interaction, and how the horse responds to stimulation of the painful area. The physiologic parameters included heart rate, respiratory rate, GI sounds, and temperature (Wagner 2010). These variables can be used to assess horses experiencing visceral pain as well (DeGouff 2010).


Table 3.2 AAEVT lameness grading system

Table 3.3 Pain Scoring System for Laminitis

Lameness Definition Grade

Modified Composite Pain Score

0

No lameness under any circumstances

Grade descriptor

1

Lameness difficult to observe, inconsistent regardless of circumstance

1 Frequent shifting of weight between the feet with no discernible lameness at the walk

2

Difficult to observe at walk and trot in straight line but apparent while carrying weight, on a circle, inclines, or hard surfaces

2 Does not resist having a foreleg lifted, is not reluctant to walk, but does show lameness at the walk

3

Consistently observable at the trot under all circumstances

4

Obvious lameness at the walk

5

Lameness produces minimal weight bearing in motion, at rest or has complete inability to move

Source: From Wagner (2010).

Dynamic Score: Modified Obel Grading System

3 Resists having a foreleg lifted and is reluctant to walk 4 Walks only if forced Static Score: Modified from Glasgow Composite Scale Score descriptor 1 No pain or distress: normal behavior 2 Mild pain: irritable, restless, decreased appetite

With regard to assessing lameness in the horse, the American Association of Equine Practitioners (AAEP) developed a grade system that is widely used among equine practitioners; this scale ranges from 0 to 5 (Table 3.2). There is a verbal rating scale, using A–F, which is fairly similar to the AAEP’s system. Lameness can also be assessed using force plate gait analysis, though there are variations in results based on breeds, and the force plate itself is not available to most practices (Van Loon 2012). Laminitis is one of the most agonizingly painful lameness syndromes in the horse. In order to attempt to provide appropriate analgesia to these patients, Niles Obel developed the Obel Laminitis Pain Scale (Menzies-Gow et al. 2010). There was also a modified composite pain scoring system developed that included the Obel pain scale and a numeric rating scale describing multifactorial behavioral and physiological components to better assess these patients (Van Loon 2012) (Table 3.3).

3 Mild pain: 2 plus resists handling 4 Mild–moderate pain: 3 plus standing in back of stall or with back to stall door 5 Moderate pain: 4 plus camped-out legs, increased digital pulses 6 Moderate–severe pain: 5 plus frequent recumbency, HR > 44 beats/min, and/or RR > 24 breaths/min 7 Moderate–severe pain: 6 plus sweating, muscle fasciculation, head tossing 8 Severe pain: 7 plus unwilling to move 9 Severe–extreme pain: 8 plus not weight bearing when standing 10 Extreme pain: 9 or entirely recumbent, bordering on agonal Maximum possible score: 14 Source: From Driessen et al. (2010).

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There are other types of pain scoring systems devoted to assessing abdominal/colic pain, wound sensitivity, and others. The desire and effort in attempting to gain further knowledge about equine pain response is continuing to increase. Over time, this will help improve pain recognition and overall pain management in this species.

Recognition of Pain in Livestock (Cattle, Sheep and Goats, and Pigs) The following animal species are included in this group: cattle, sheep and goats, and pigs.

Indications of Pain in Cattle (Hudson et al. 2008; Shaffran and Grubb 2010) • Decreased movement/locomotion • Decreased interaction with other animals in the group • Decreased feed intake (e.g., “hollow” left flank caused by an empty rumen) • Changes relevant to the source of the pain being experienced (e.g., altered locomotion, flank watching or kicking, or ear twitching) • Level of mental activity/responsiveness (animals in severe pain often show reduced responsiveness to stimuli) • Changes in normal postures associated with pain (e.g., lateral recumbency, standing motionless, or drooping of the ears) • Easily measurable indicators of physiological stress (e.g., increased heart rate, increased pupil size, altered rate and depth of respiration, or trembling) • Bruxism (tooth grinding) • Poor coat condition (e.g., rough, dusty, or unkempt) caused by decreased grooming Cattle in pain often appear dull and depressed, with the head held low and showing little interest in their surroundings. There are inappetence, weight loss, and, in milking cows, a sudden drop in milk yield. Severe pain often results in rapid

Figure 3.7 Bovine pain stance. Source: Courtesy of Kristen Cooley.

shallow respirations. On being handled, cows may react violently or adopt a rigid posture designed to immobilize the painful region. Grunting and grinding of the teeth may be heard. Acute pain may be associated with bellowing. Generally, signs of abdominal pain are similar to those seen in the horse but are less marked. Rigid posture may lead to a lack of grooming due to unwillingness to turn the neck. In acute abdominal conditions, such as intestinal strangulation, the animal adopts a characteristic stance with one hindfoot placed directly in front of the other (Figure 3.7). Localized pain may be indicated by persistent licking of an area of skin or kicking at the offending area. Bovine orbital tightening or ear position may be an indication of pain and should be pursued (Millman 2013). Cows with moderate

Key Signs 3.3 Cows: Dull, depressed, inappetence, grunting, grinding of the teeth, and rigid posture.


clinical mastitis can exhibit an increased heart rate, temperature, and respiratory rate (Leslie and Petersson-Wolfe 2012). Cortisol levels were increased as well as increased “hock-to-hock” distances indicating an altered stance (Milne et al. 2003). Mastitis cows also have an increased mechanical pressure sensitivity on the leg that is closest to the infected mammary quarter, suggesting a change in pain information processing as a result of inflammation (Leslie and PeterssonWolfe 2012). A gait locomotion scoring system has been published and found to be sensitive to identify cows with severe hoof lesions (Flowers and Weary 2006; Millman 2013) as well as lame cows that were provided with a local anesthetic (Rushen et al. 2007).

Sheep and Goats Sheep often only show subtle signs of pain, while goats are intolerant of painful procedures (Galatos 2011). Goats will often bleat, while sheep may only exhibit tachypnea, inappetence, grinding of teeth, immobility, or abnormal gait (Hall et al. 2001). Following procedures such as castration and tail docking, lambs may show signs of discomfort such as standing up and lying down repeatedly, tail wagging, occasional bleating, neck extension, dorsal lip curling (Flehman), kicking, rolling and hyperventilation. Key Signs 3.4 Sheep and goats: Rigid posture and reluctance to move.

Normal Behavioral Observations in Swine (Carr and Wilbers 2008) • • • • • • •

Interest in the surroundings, including staff Willingness to move around Explorative behavior Tail wagging Reaction to handling Vocalization when presented with feed Willingness to eat

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Key Signs 3.5 Pigs Vocalization and the lack of normal social behavior may be helpful indicators of a pig in pain.

When swine react differently from this pattern, pain and distress might be the cause (Bollen et al. 2000). Pigs in pain may show changes in gait and posture. They normally squeal and attempt to escape when handled; however, these reactions may be accentuated when the animal is in pain. Adult pigs may become aggressive. Squealing is also characteristic when painful areas are palpated. Handling of chronic lesions may not elicit signs of pain. Pigs will often be unwilling to move and may hide in bedding if possible. Animal welfare has increased the importance of pain management in livestock. Multimodal analgesia is the preferred method of pain relief for even minor surgical procedures. Animal suffering is no longer tolerated nor is the unwillingness by owners to pay for medications (George 2003).

References American Animal Hospital Association; American Association of Feline Practitioners; AAHA/AAFP Pain Management Guidelines Task Force Members et al. (2007) AAHA/AAFP Pain Management Guidelines for Dogs and Cats. Journal of the American Animal Hospital Association, 43, 235–248. Bollen, P.J.A., Hansen, A.K. & Rasmussen, H.J. (2000) The Laboratory Swine, Laboratory Animal Pocket Reference Series. CRC Press, Boca Raton, FL. Carr, J. & Wilbers, A. (2008) Pet pig medicine: the normal pig. In Practice, 30, 160–166. DeGouff, L. (2010) Basic physiology of pain. S. Bryant (ed), Anesthesia for Veterinary Technicians, Blackwell Publishing, Ames, IA, pp. 325–332. Driessen, B., Bauquier, S.H. & Zarucco, L. (2010) Neuropathic pain management in chronic laminitis. Veterinary Clinics of North America: Equine Practice, 26 (3), 315–337.

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Eades, S.C., Holm, A.M.S., Moore, R.M. (2002) A Review of the Pathophysiology and Treatment of Acute Laminitis: Pathophysiologic and Therapeutic Implications of Endothelin-1. AAEP Proceedings, Vol. 48, Orlando, FL, December 4–8, pp. 353–361. Fleetwood-Walker, S. (2012) Assessment of animal pain and mechanism-based strategies for its reversal. The Veterinary Journal, 193, 305–306. Flowers, F.C. & Weary, D.M. (2006) Effects of hoof pathologies on subjective assessments of dairy cow gait. Journal of Dairy Science, 89, 139–146. Galatos, A.D. (2011) Anesthesia and analgesia in sheep and goats. Veterinary Clinics of North America: Food Animal Clinics, 27, 47–59. Gaynor, J.S. & Muir, W. (2009) Handbook of Veterinary Pain management, 2nd edn. Mosby, St. Louis, MO. George, L.W. (2003) Pain control in food animals. E.P. Steffey (ed.), Recent Advances in Anesthetic Management of Large Domestic Animals. International Veterinary Information Service, Ithaca, NY. www.ivis.org [accessed on May 4, 2014]. Hall, L.W., Clarke, K.W. & Trim, C.M. (2001) Anaesthesia of sheep, goats and other herbivores. L.W. Hall, K.W. Clarke & M. Cynthia (eds), Veterinary Anaesthesia, 10th edn, WB Saunders, London, pp. 341–366. Houpt, K. (1998) Domestic Animal Behavior for Veterinarians and Animal Scientists, Iowa State University Press, Ames, IA, pp. 7–12. Hubbell, J. (2007) Horses. In: W.J. Tranquilli, J.C. Thurmon & K.A. Grimm (eds), Lumb & Jones’ Veterinary Anesthesia and Analgesia, Blackwell Publishing, Ames, IA, pp. 717–731. Hudson, C., Whay, H. & Huxley, J. (2008) Recognition and management of pain in cattle. In Practice, 30, 126–134. Karas, A. (2011) Pain, Anxiety, or Dysphoria—How to Tell? A Video Assessment Lab. In: Proceedings from the American College of Veterinary Surgeons, Chicago, IL, November 3–5, pp. 509–512. Lamont, L.A. (2000) Physiology of pain. Veterinary Clinics of North America Small Animal, 30 (4), 703–728. Lerche, P. (2009) Clinical commentary: assessment and treatment of pain in horses. Equine Veterinary Education, 21 (1), 44–45. Lerche, P. & Muir, W. (2009) Perioperative pain management. In: W. Muir & J. Hubbell (eds), Equine Anesthesia, Elsevier, St. Louis, MO, pp. 369–380.


Leslie, K.E. & Petersson-Wolfe, C.S. (2012) Assessment and management of pain in dairy cows with clinical mastitis. Veterinary Clinics of North America: Food Animal Clinics, 28, 289–305. Lockhead, K. (2010) Pain assessment. In: S. Bryant (ed), Anesthesia for Veterinary Technicians, Blackwell Publishing, Ames, IA, pp. 333–344. Menzies-Gow, N.J., Stevens, K.B., Sepulveda, M.F., Jarvis, N. & Marr, C.M. (2010) Repeatability and reproducibility of the Obel grading system for equine laminitis. Veterinary Record, 167, 52–55. Mich, P.M. & Hellyer, P.W. (2009) Objective, categoric methods for assessing pain and analgesia. In: J.S. Gaynor & W.W. Muir (eds), Handbook of Veterinary Pain Management, Mosby/Elsevier, St. Louis, MO, pp. 98–99. Millman, S.T. (2013) Behavioral responses of cattle to pain and implications for diagnosis, management, and animal welfare. Veterinary Clinics of North America: Food Animal Practice, 29, 47–58. Milne, M.H., Nolan, A.M., Cripps, P.J., et al. (2003) Preliminary Results of a Study on Pain Assessment in Clinical Mastitis in Dairy Cows. Proceedings of the British Mastitis Conference, Stoneleigh, Lancashire, North West England. The Dairy Group, New Agriculture House, Somerset, pp. 117–119. Minero, M. (2013) Development of facial expression pain scale in horses. The International Society for Equitation Science (ISES). http://www.equitationscience. com/documents/Conferences/2013/ISES%202013%20 Development%20of%20facial%20expression%20 pain%20scale%20in%20horses%20undergoing %20routine%20castration.pdf [accessed on May 4, 2014]. Porter, M. (2009) Common equine medical emergencies. D. Reeder, S. Miller, D. Wilfong, M. Leitch & D. Zimmel (eds), AAEVT’s Equine Manual for Veterinary Technicians, Wiley Blackwell, Ames, IA, pp. 341–354. Rushen, J., Pombourcq, E. & de Passille, A.M. (2007) Validation of two measures of lameness in dairy cows. Applied Animal Behavioral Science, 106, 173–177. Shaffran, N. (2008) Pain management: the veterinary technician’s perspective. Veterinary Clinics of North America: Small Animal Practice, 38 (6), 1419. Shaffran, N. & Grubb, T. (2010) Pain management. In: J.M. Bassert & D.M. McCurnin (eds), McCurnin’s Clinical Textbook for Veterinary Technicians, 7th edn, Elsevier, St. Louis, MO, p. 864.


Thomas, J.A. & Lerche, P. (2011) Analgesia. In: J. Thomas & P. Lerche (eds), Anesthesia and Analgesia for Veterinary Technicians, 4th edn, Mosby/Elsevier, St. Louis, MO, p. 208. Thurmon, J.C., Tranguilli, W.J. & Benson, G.J. (1996) Lumb & Jones Veterinary Anesthesia, 3rd edn. Lippincott Williams &Wilkins, Philadelphia, PA. Van Loon, J., Back, W., Hellebrekers, L.J. et al (2010) Application of a composite pain scale to objectively monitor horse with somatic and visceral pain under hospital conditions. Journal of Equine Veterinary Science, 30 (11), 641–649.

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Van Loon, T. Analgesia in the horse: assessing and treating pain in Equines. Veterinary Sciences Tomorrow, July 2012. Wagner, A. (2010) Effects of stress on pain in horses and incorporating pain scales for equine practice. Veterinary Clinics of North America: Equine Practice, 26, 481–492. Yaksh, T.L. (2010) The pain state arising from the laminitic horse: insights into future analgesic therapies. Journal of Equine Veterinary Science, 30, 79–82.

Physiology of Pain

c h a p t e r

Kristen Cooley

Introduction All living organisms require the ability to respond to potentially harmful situations. This ability to sense noxious stimuli in the immediate environ ment and respond accordingly is essential to survival. The term noxious refers to stimuli, or sensory feedback, capable of causing excitement within the nervous system that can be perceived as pain. Avoiding this type of input is critical to survival. Humans born without the ability to sense pain (congenital analgesia) may succumb to their injuries prior to reaching adulthood (Woolf 1995). Multicellular organisms have evolved specialized nerve endings called nociceptors that have the extraordinary ability to differentiate noxious from innocuous stimuli. This allows for the detection of temperature extremes, excessive pressure, tissue damage, and chemical exposure as damaging and general touch or vibration as nonthreatening. Noxious stimuli are translated and transmitted to the dorsal horn of the spinal cord where it is mod ulated or changed and sent up to the brain to be perceived as pain. This nervous system activity is

1 4

termed nociception and allows the body to initiate protective reflexes in response to discomfort (Woolf and Salter 2000; Julius and Basebaum 2001). The protective function of the pain pathway is based on a handful of fundamental principles that include the capacity to detect a variety of physical, chemical, and thermal inputs. These principles con sist of the ability to differentiate between noxious and innocuous stimuli by setting specific response thresholds and the capacity to reset these thresholds and sensitize the system to guard against further injury (Julius and McClesky 2006). The pathway consists of four events: transduction of noxious input, transmission of the signal, modulation of sensory information, and the perception of pain.

The Pain Pathway Transduction Nociceptors detect sensory input when tissues are damaged either by injury or surgery. Nociceptors are a specialized class of sensory


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Chapter 4 Physiology of Pain

31

on

pti

rce Pe

n

tio

ula

d Mo

ion

ss mi

s

n Tra

on

cti

du

ns Tra

Inflammatory soup Transmission Nociception

Leukotrienes

Bradykinin

uli

tim

ss

iou

x No

Glutamate

Transduction

Prostaglandin Histamine

Serotonin

Arachidonic acid Substance P Mast cell

Tissu

e dam

age

Cytokines

Figure 4.1 The pain pathway. The pain pathway begins when tissue damage releases inflammatory mediators, which are transduced or translated into the language of the nervous system. These action potentials are transmitted up to the dorsal horn of the spinal cord for modulation and then transmitted or projected up to the brain to be perceived. Source: Drawn by Kristen Cooley.

nerve fibers that are also referred to as primary afferents, primary meaning the first to receive the information and afferent meaning to carry toward the central nervous system (CNS). These primary afferent nerves are located throughout the body and initiate the nociceptive, or pain detecting process. The nociceptive process involves the encoding and processing of noxious or potentially painful stimuli (Loeser and Treede 2008). Stimulation of the primary afferent noci ceptors occurs when the pain threshold is reached. The pain threshold is the minimum stimulus required to elicit nervous system activity (Muir 2009). Primary afferent terminals act as transducers, which convert the chemical, mechanical, or thermal energy at the site of

injury into electrical activity that the nervous system can understand. This results in the spread of impulses along the afferent nerve fibers to the dorsal horn of the spinal cord and onto the brain (Figure 4.1). Stimulation that may result in the percep tion of pain can originate from a variety of sources. Specialized receptors detect stimuli from thermal, chemical, or mechanical data according to the type of injury to which they are sensitive. Thermoreceptors are sensitive to both high and low temperatures. Chemical nocicep tors respond to the release of endogenous chem icals from damaged cells (see “inflammatory soup”) as well as to external chemicals (capsa icin, menthol). Mechanoreceptors are sensitive

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Table 4.1 Inflammatory Mediators of Pain

Mediator

Origin

Action

Bradykinin

Damaged tissue

Inflammatory chemical implicated in the production of other chemicals like histamines and prostaglandins. Bradykinin has been shown to produce pain by attaching to nociceptors and initiating CNS impulses

Serotonin

Degranulated mast cells in the peripheral tissues

Excitatory neurotransmitter that can potentiate the pain caused by bradykinin. Serotonin has the potential to modulate pain in the dorsal horn

Histamine

Mast cells

Inflammatory mediator that causes vasodilation and edema, enhances the response to bradykinin and heat, and excites polymodal visceral nociceptors. Also plays a role in the response to allergens and causes itching

Cytokines

Released from cells during inflammation

Cytokines may excite nociceptors by stimulating the release of other mediators like prostaglandins. May play a role in hyperalgesia

Interleukins

Generated during acute inflammation

A type of cytokine that can cause fever and initiate prostaglandin production and stimulated the secretion of ACTH and cortisol

Arachidonic acid

Damaged tissue

Mediators and regulators of inflammation as well as the actions of prostaglandins (platelet aggregation, blood clotting, smooth muscle contraction, immune function, etc.)

Prostaglandins

Derived from arachidonic acid and released from damaged cells

Both homeostatic and pathogenic functions including generation of the inflammatory response, which contributes to the signs associated with inflammation, pain, redness, swelling, and heat

Leukotrienes

Derived from arachidonic acid

Arachidonic acid metabolite that mediates inflammation and promotes GI mucosa damage and pain

Substance P

Damaged tissue

Neurotransmitter that transmits pain impulses from PNS to CNS

Glutamate

Damaged tissue

Excitatory neurotransmitter used by all primary afferent nerves to elicit fast, excitatory responses to noxious stimuli

Sources: From McMahon et al. (2006); Woolf et al. (1997); Muir (2009).

to pressure, swelling, and cutting-type injury and include tissue damage such as trauma, injury, surgery, inflammation, infection, or ischemia. When tissue damage is significant, several chemicals are released into the area surrounding the injury. This acidic mixture of “inflammatory soup” stimulates and sensitizes the nociceptors and creates a hyperalgesic or hypersensitive state to guard against further damage. The major

ingredients in “inflammatory soup” include bradykinin, serotonin, histamine, cytokines, interleukins, arachidonic acid, prostaglandins, leukotrienes, hydrogen ions, substance P, and glutamate. Each constituent is briefly outlined in Table 4.1. In addition to the single-mode nociceptor described, polymodal nociceptors can be excited by strong pressure, heat or cold, and chemical insults.


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Transmission Once the information detected is translated (by transduction) into electrical signals called action potentials, specialized nerve endings pick up the noxious information and transmit it to the CNS via nerve fibers. The nerve endings vary in sensi tivity and have unique minimum requirements to prompt an electrical signal, or stimulus threshold (Muir 2009). The nerve fibers may be A-delta, A-beta, or C fibers. A-delta and C fibers are necessary for the detection of all pain sensations (nociceptors), whereas A-beta fibers are respon sible for conducting harmless information. Low-threshold A-beta receptors can be found in the skin, muscles, and joints and respond to inputs like touch, vibration, movement, proprioception, and pressure (Muir 2009; Todd 2010). The highthreshold nociceptor, A-delta, is a small nerve fiber covered in a fatty, electrically insulating substance called myelin that helps to transmit impulses more quickly. The A-delta receptors are activated by thermal or mechanical stimulation and produce short-lived, discriminative, sharp pain. Pain asso ciated with this type of nociceptor activation is often referred to as “first pain” because it is the sharp pain felt first following injury. “Second pain” is conducted through smaller unmyelinated

C fibers. These fibers are polymodal, which means they respond to mechanical, thermal, and chemical input. Their conduction velocity is slower than that of the A-delta fibers, and the sensation associ ated with their activation is a poorly localized burning type of pain accompanying tissue damage and inflammation (Lamont et al. 2000; Muir 2009; Patel 2010). C fibers are also implicated in chronic pain (Figure 4.2). Transmission takes place from the site of injury to the dorsal horn of the spinal cord, from the spinal cord to the brainstem (projection) then along sensory tracts to the brain. The A-delta and C fibers end in the dorsal horn of the spinal cord. There is a synaptic cleft at their terminal end. In order for the signal to jump this cleft and resume the signal’s journey to the brain, excitatory neu rotransmitters like norepinephrine and serotonin are utilized (Muir 2009).

Modulation The modulation of pain involves the changing, inhibiting, or amplifying of the transmission impulses within the spinal cord. The spinal cord can be divided up into the nerve cells that consti tute the gray matter and the axons of nerve fibers Dorsal root ganglion

Peripheral nerve

Aβ Spinal cord Aδ C-fibers

Sympathetic ganglion

Figure 4.2 Low-threshold A-beta nerve fibers; high-threshold, myelinated A-delta fibers; and small, unmyelinated C fibers lie within the peripheral nerve sheath and synapse in the dorsal horn of the spinal cord. Source: Drawn by Kristen Cooley.

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that make up the white matter. Gray matter is separated into three zones: the dorsal horn, the ventral horn, and the intermediate zone. Dorsal Horn The dorsal horn receives and manages sensory information and relays that information to the brain for further processing. It consists of inter connecting nerves called interneurons and ascending pathways, which shuttle information to the brain. The interneurons are either excit atory or inhibitory in nature and serve to transmit information and participate in local signal management. The sensory information that is received in the dorsal horn is transmitted across the synaptic cleft, or the space between two neu rons, and then projected to the brain for processing. This initiates descending control sys tems that influence the sensitivity of the dorsal horn to excitatory and inhibitory impulses (Muir 2009; Lamont et al. 2000). An assortment of neurotransmitters is responsible for communi cating information from the periphery to the spinal cord neurons. These constituents include substance P, glutamate (excitatory neurotrans mitter), gamma-aminobutyric acid (GABA—the chief inhibitory neurotransmitter in the mamma lian nervous system), endogenous opioids, and monoamines like serotonin and norepinephrine (Muir 2009). These elements act on excitatory or inhibitory receptors to modulate or modify incoming signals. For example, the excitatory neurotransmitter glutamate can amplify the pain signal, whereas GABA can inhibit it. Serotonin and norepinephrine can inhibit excitatory neuro transmitters like glutamate and facilitate inhibi tory neurotransmitters like GABA, helping to augment and decrease the pain signal before it reaches the brain (Stamford 1995; Todd 2010). The dorsal horn is organized into families of nerve cells that have related functions. It is then divided into 10 layers called Rexed laminae. Incoming information from sensory nerve fibers is conveyed to the assorted laminae where amino acids like glutamate and peptides like substance


P work to activate a variety of postsynaptic receptors (Todd and Robitaille 2006). Laminae I and II are chiefly responsible for nociceptive input and are collectively referred to as the superficial dorsal horn. Lamina I is also called the marginal layer and lamina II the substantia gelatinosa (Figure 4.3). Ventral Horn and Intermediate Zone The ventral horn of the spinal cord consists of interneurons and is involved with motor activity and skeletal muscle function rather than sensory information. The intermediate zone in the spinal cord exists in the space between the dorsal por tion of the butterfly-shaped gray matter and the ventral portion. This area is responsible for impulses that facilitate control of the viscera and transmit information to higher centers (Muir 2009). White Matter White matter contains three areas of interest: dorsal column, ventral column, and lateral column, which consist of axons that dispatch information to and from the brain. The dorsal column is involved in somatic sensory information transmission to the medulla. The ventral column encompasses transmissions that descend from the brain to the skeletal muscle. The lateral column is implicated in somatic sensory information to the brain and contains nerve fibers from both sensory and motor as well as autonomic regions (Muir 2009). Descending Pathways Pain sensations are modulated during their way up to the brain via ascending pathways in the dorsal horn. In addition, descending pathways exist to control pain by sending signals from higher centers in the brain (Stamford 1995). This control is established through pathways that originate at the level of the cortex, thalamus, and brainstem. Descending inhibition is mediated by


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C-fiber • Primary afferent nociceptor • High threshold C • Small, thin, unmeylinated • Slow, dull, and chronic pain

A-delta

A-delta fiber • Primary afferent nociceptor • High threshold • Small and myelinated • Fast, sharp acute pain

I Mar gina l

IIo

laye r

Sub stan tia g elatin osa

A-beta A-beta • Sensory nerve �ber • Low threshold • Large diameter, myelinated • Innocuous sensations

IIi

III/IV

Nuc leus prop r

Super cial dorsal horn

ius

Figure 4.3 A-delta, A-beta and C fiber synapse within the superficial laminae of the dorsal horn of the spinal cord. Source: Drawn by Kristen Cooley.

relay stations in the brainstem and utilizes the neurotransmitters serotonin and norepinephrine as well as the endogenous opioids (among others) to aid in pain inhibition (Stamford 1995).

and not allowing them to relay information to the brain (Melzack and Wall 1965).

The Gate Control Theory

Perception of pain is a dynamic conscious experience characterized by the recognition of sensory input. An area of the cerebrum called the somatosensory cortex is responsible for the higher processing and awareness of pain.

The gate control theory of pain modulation was first proposed in 1965 and helped to explain why people often rub or put pressure on an injury in an attempt to dull the pain of it. The theory assumes that by activating larger, low-threshold A-beta receptors through rubbing, shaking, or pressing on injured tissue, the inhibitory effects of interneurons are increased, thereby reducing the transmission of pain. A-beta inhibitory inter neurons reduce the output of the active A-delta and C nociceptive neurons by closing a “gate”

Perception

Spinothalamic Tract From the dorsal horn, spinal neurons send the signals up through the white matter of the spinal cord via the spinothalamic tract. The spinotha lamic tract is an ascending nociceptive pathway, sending information about tissue damage or

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Pain

Ascending pathway

Primary somatosensory cortex

Thalamus

Medulla oblongata (brain stem)

Spinalthalamic tract

A-delta and C- ber primary afferent nociceptors

Dorsal horn Intermediate zone Ventral horn

Re ex pathway

Figure 4.4 A-delta and C fibers enter the dorsal horn of the spinal cord. Here, the impulse can generate a reflexive response by following the reflexive pathway or be sent up to the brain for further processing. The spinothalamic tract travels through the medulla, to the thalamus, and then on to the somatosensory cortex where it can be perceived as pain. Source: Drawn by Kristen Cooley.

potential tissue damage upward toward the brain. It originates in the dorsal horn of the spinal cord and works to transmit superficial pain and tactile sensations like touch. The spi nothalamic tract is thought to be the primary conscious pain pathway in carnivores (Hellyer et al. 2007). Projections from this tract go through the brainstem to the thalamus and then on to the somatosensory cortex in the brain (Figure 4.4).

Spinoreticular Tract Sensations originating from the visceral organs or deeper tissues travel via the spinoreticular tract. Most of these projections bypass the thalamus and end in the reticular formation, a region in the brainstem responsible for filtering incoming stimuli. The reticular formation regulates heart rate and respiratory rate and plays a role in cortical alertness and maintenance


of consciousness (Hellyer et al. 2007; Lamont et al. 2000). In the reticular formation, an emotional response to pain is elicited through activation of the limbic system, a collection of structures that supports a variety of functions including emotions, behavior, olfaction, and memory. This pathway is rather diffuse, making the pain perceived here poorly localized.

Pain and Stress The negative effects that pain has on health are similar to the negative effects that stress has on health. Pain in and of itself is stressful. The nega tive effect stems from the activity that pain initiates within the hypothalamus in the brain. The hypothalamus is the brain’s coordinator of autonomic responses and primary integrator of physiologic and emotional reactions. Input trig gers activity in the sympathetic nervous system (fight or flight) and pituitary gland, increasing circulating adrenaline (epinephrine and norepi nephrine) as well as glucocorticoids (i.e., the stress response). Like a dog chasing his tail, stress can increase the perceived intensity of pain, and pain can compound stressful situations.

Types of Pain Pain can be classified based on the site of origin. Nociception stemming from injury to the skin, muscles, joints, and deep tissues is somatic pain. Noxious stimulus originating in the internal organs of the thorax or abdomen is visceral pain, and damage to the peripheral nervous system (PNS) or CNS is termed neuropathic pain. Pain can also be classified based on its duration of action: acute or chronic, adaptive or maladap tive, and physiologic or pathologic.

Somatic and Visceral Pain Somatic pain arising from the skin and muscles is conducted via A-delta and C fibers and is often

37

discrete and easy to localize. This is due to the high degree of somatotopy or point-to-point cor relation of a body area with a specific location in the CNS (Woolf 1995; Lemke 2004). When you receive a paper cut, it is very easy to pinpoint exactly where the injury is located. Most pain research has been done on superficial-type stimu lation, and until recently, this information was erroneously extrapolated to include visceral pain as well. We now know that these two types of pain are very different. Visceral pain arises from internal organs and is conducted via C fibers only. Visceral pain is often dull, aching, or burning pain that is difficult to localize due to the low degree of somatotopy. Skin is a protective covering that has evolved to respond and shield mammals from external insults. Nociceptive information is detected and processed, and avoidance strategies are insti tuted. This is characteristic of somatic pain. Visceral pain is different because the viscera are not exposed to comparable insults but instead are the target area for many disease processes (Lamont et al. 2000). The protective function of visceral pain is not as obvious as it is for somatic pain; therefore, visceral pain poses a challenge to healthcare professionals in the human as well as in the veterinary field. It is interesting to note that many life-threatening forms of tissue destruction like intestinal perforation and vis ceral neoplasia are not painful by themselves, but a nonlife-threatening event like intestinal disten sion (gas) is. Visceral organs are sensitive to distension (e.g., intestines, gallbladder, and urinary bladder), ischemia (e.g., heart attack in humans), and inflammation as is seen with nephritis or pancre atitis. Visceral pain may manifest as diffuse pain, general malaise, or nausea, and it may be referred to somatic structures. Referred pain is often associated with visceral pain whereby the sensa tion of pain is felt elsewhere besides the area of injury. For example, liver pain or diaphragm pain may be referred to the shoulder and myo cardial ischemia to the left arm (Lamont et al. 2000). Visceral organs do not have A-delta fibers but

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utilize C fibers to carry nociceptive information. These fibers both converge on the same area of the spinal cord where A-delta fibers carry somatic information and C fibers carry visceral and somatic information. The brain may then localize the visceral pain to a somatic structure due to the high somatotopy of the somatic neurons.

Physiologic and Pathologic Pain Physiological pain typically results from inflam mation or injury and has an adaptive and biolog ically useful function, defending an individual against harmful external stimuli, which may induce tissue injury and become life threatening. As a response to this input, a number of different withdrawal reflexes and avoidance responses are activated designed to protect the individual from more extensive injuries (Muir 2009). Physiological pain is acute in nature but differs from visceral pain in the sense that its protective function is not to prevent damage altogether, but to prevent further damage and to enable healing and repair to occur undisturbed. Acute physiological pain has a reparative function. It hypersensitizes sur rounding tissues, increasing sensitivity and encouraging the individual to leave the tissue alone and allow it to heal. Even though acute pain serves an initial purpose, it should be managed to avoid development into pathologic or chronic pain syndromes (Muir 2009; Lamont et al. 2000). Pathologic pain may arise from massive tissue damage and inflammation where a certain degree of peripheral and central sensitization accom panies extensive injury. This pain can be diffuse, disproportionate to the degree of injury, and debilitative and often continues beyond the reso lution of the inflammatory process (Melzack et al. 2001; Patel 2010). Pathologic pain is often classified into inflammatory pain (somatic or vis ceral) of either an acute or chronic nature or neu ropathic pain (damage to PNS or CNS) (Lamont et al. 2000).


Chronic pain persists beyond tissue healing and offers no useful biologic function or survival advantage (Lamont et al. 2000). Chronic pain is more than just pain of a prolonged duration (anywhere from days to weeks or even months); it is a result of peripheral and central sensitiza tion, neuroplasticity, and memory. Chronic pain significantly affects a patient’s quality of life and tends to be debilitating and poorly responsive to traditional analgesic therapy. Neuropathic pain arises from damage to or dysfunction in the nervous system as a result of trauma, infection, ischemia, cancer, or chemically induced (chemotherapy). Some types of neuro pathic pain may develop when the PNS becomes damaged. This can cause the nociceptors to transmit pain signals repeatedly leading to hyper sensitivity. Prolonged central sensitization as a result of ongoing ectopic C fiber stimulation either at the site of injury or in the dorsal horn of the spinal cord can result in neuropathic pain (Woolf 1995). Neuropathic pain can also be a result of significant, prolonged acute pain that leads to peripheral sensitization. This abnormal peripheral input then leads to abnormal central processing and the persistence of hypersensitivity associated with neuropathic pain. Dorsal horn structural reorganization where innocuous A-beta fibers terminate in the areas of the dorsal horn normally occupied by A-delta and C fibers may provide an explanation for neuropathic pain (Melzack et al. 2001).

Peripheral Sensitization Peripheral sensitization is a reduction in threshold and an increase in responsiveness of peripheral nociceptors. Normally, high-threshold nocicep tors A-delta and C fibers are activated in response to noxious stimuli. Damaged cells release chemical mediators in response to tissue injury and inflammation. These substances have direct effects on the excitability and sensitizing of sensory nerve fibers. They promote vasodilation and recruit inflammatory cells, macrophages,


lymphocytes, platelets, as well as the substances implicated in “inflammatory soup.” This effec tively lowers the response threshold for A-delta and C fiber activation. Silent nociceptors are exquisitely sensitive to the effects of “inflammatory soup” and go from benign unmy elinated polymodal C fibers to vigorously firing C fibers (Muir 2009).

Central Sensitization Central sensitization is contingent on the development of peripheral sensitization and is the indirect consequence of tissue trauma and inflammation. Sensations of pain spread beyond the site of insult to nearby undamaged tissue. Central sensitization can result from unre lenting stimulation to the peripheral nocicep tors, which lead to sustained release of glutamate and other neurotransmitters from primary afferent nerves. The liberation of these substances activates dorsal horn receptors like 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) and N-methyl-Daspartic acid (NMDA), which will then lead to an increase in the excitability of the dorsal horn neurons projecting up to the brain (Lamont et al. 2000; Muir 2009). This “windup” of the CNS is the inciting cause of central sensitiza tion, exaggerating subsequent nociceptive and nonnociceptive input. The AMPA and the NMDA receptors are both activated by glutamate, but each has its own dis tinct properties. Noxious stimulation causes a release of glutamate, which binds to both AMPA and NMDA receptors. Weak stimulation acti vates only the AMPA receptor, resulting in slight cell depolarization by making the postsynaptic neuron permeable to Na+ and K+ (to generate action potentials). The NMDA receptor is nor mally blocked by Mg2+ so it doesn’t allow ions to freely pass through to generate an impulse. During weak stimulation, excitatory signals are mediated entirely by the AMPA receptors. When greater stimulation occurs, AMPA receptors can

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depolarize the membrane with the strength to dislodge the Mg2+ from the NMDA receptor, allowing it to now actively respond to glutamate (Figure 4.5). When activated, the NMDA receptor allows large amounts of Ca2+ to pass through, activating several intracellular signaling cascades and ulti mately leading to increased nerve transmission and heightened nerve excitability (Woolf and Salter 2006).

Neuroplasticity and the Memory of Pain Neuroplasticity refers to the ability of neurons to change their structure and function in response to different environmental stimuli. This type of flexibility allows us to navigate our environment and respond to its evolution. In response to trauma, unrelenting pain, or peripheral and central sensitization, the nervous system can reorganize itself and develop new stimulus–response relationships (Muir 2009). The CNS forms memories and relationships that may be beneficial but are more often detri mental. Pain can alter gene expression, and those patients who have a history of injury may be more sensitive to future nociceptive input. How memory affects pain and how pain effects memory depends on the individual’s environ ment, expectations, and behaviors as well as the intensity of the painful event. The response to subsequent pain is likely to be more severe and disproportionate to the stimulus encountered. Patients with a history of significant pain or central sensitization from prolonged pain are harder to treat and are less responsive to anal gesic therapy likely due to the formation of these memories and alterations of the nervous system (Song and Carr 1999; Muir 2009). Preemptive analgesia is thought to decrease the emergence of central sensitization and all of the negative sequelae associated with it including nervous system reorganization and the memory of pain.

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Presynaptic neuron

Presynaptic neuron

Glutamate Magnesium (Mg2+) Glutamate

Sodium (Na+) 2+

Na+

Ca + Na

Mg2+ NMDA receptor

AMPA receptor

Mg

2+

Glutamate

+

Na

NMDA receptor

Na+

Postsynaptic neuron

Calcium (Ca2+)

AMPA receptor

Na+

Ca2+

Na+

Postsynaptic neuron

Figure 4.5 Noxious stimulation causes a release of glutamate, which binds to both AMPA and NMDA receptors. Weak stimulation only activates the AMPA receptor to generate action potentials. The NMDA receptor is normally blocked by Mg2+, not allowing ions to freely pass through to generate an impulse. During significant stimulation, the AMPA receptor can depolarize the membrane with the strength to dislodge the Mg2+ from the NMDA receptor, allowing it to respond to glutamate. Once activated, the NMDA receptor allows large amounts of Ca2+ to pass through, activating several intracellular cascades leading to heightened nerve excitability (Woolf and Salter 2006). Source: Drawn by Kristen Cooley.

Conclusion The ability of an organism to traverse its envi ronment and adequately respond to sensory input is essential for survival. Nociceptive input and pain can shape the nervous system so that it inappropriately responds to subsequent stimula tion. This negatively affects health, healing, and quality of life and should be prevented or mini mized. A thorough understanding of the physi ology of pain allows the veterinary nurse or technician to help reduce pain and suffering in veterinary patients.

References Hellyer, P.W., Robertson, S.A. & Fails, A.D. (2007) Pain and its management. W.J. Tranquilli, J.C. Thurmon & K.A. Grimm (eds), Lumb and Jones’

Veterinary Anesthesia and Analgesia, 4th edn, Blackwell, Ames, IA, pp. 31–57. Julius, D. & Basebaum, A.I. (2001) Molecular mechanisms of nociception. Nature, 13 (6852), 203–210. Julius, D. & McClesky, E.W. (2006) Cellular and molecular properties of primary afferent neurons. S.B. McMahon & M. Koltzenburg (eds), Wall and Melzack’s Textbook of Pain, 5th edn, Elsevier, Philadelphia, PA, p. 35. Lamont, L.A., Tranquilli, W.J. & Grimm, K.A. (2000) Physiology of Pain. Veterinary Clinics of North America, 30 (4), 703–723. Lemke, K.A. (2004) Understanding the pathophysi ology of perioperative pain. Canadian Veterinary Journal, 45, 405–413. Loeser, J.D. & Treede, R.D. (2008) The Kyoto protocol of IASP basic pain terminology. Pain, 137 (3), 473–477. Melzack, R. & Wall, P.D. (1965) Pain mechanisms: a new theory. Science, 150 (3699), 971–979.


Melzack, R., Coderre, T.J., Katz, J. & Vaccarino, A.L. (2001) Central neuroplasticity and pathological pain. Annals of the New York Academy of Sciences, 933, 157–174. McMahon, S.B., Bennett, D.L.H. & Bevan, S. (2006) Inflammatory mediators and modulators of pain. S.B. McMahon & M. Koltzenburg (eds), Wall and Melzack’s Textbook of Pain, 5th edn, Elsevier, Philadelphia, PA, pp. 51–55. Muir, W.W. (2009) Physiology and pathophysiology of pain. J.S. Gaynor & W.W. Muir (eds), Handbook of Veterinary Pain Management, 2nd edn, Elsevier, St. Louis, MO, pp. 13–41. Patel, N. (2010) Physiology of pain. A. Kopf & N.B. Patel (eds), Guide to Pain Management in LowResource Settings, International Association for the Study of Pain, Washington, DC, pp. 31–35. Stamford, J.A. (1995) Descending control of pain. British Journal of Anaesthesia, 75, 217–227. Song, S.O. & Carr, D.B. (1999) Pain and memory. Pain, 7 (1), ISSN 1083-0707.

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Todd, A.J. (2010) Neuronal circuitry for pain processing in the dorsal horn. Nature Reviews Neuroscience, 11 (12), 823–836. Todd, K.J. & Robitaille, R. (2006) Neuron–glia inter action at the neuromuscular synapse. Novartis Foundation Symposium, 276, 222–229. Woolf, C.J. (1995) Somatic pain-pathogenesis and prevention. British Journal of Anaesthesia, 75, 169–176. Woolf, C.J. & Salter, M.W. (2000) Neuronal plasticity: increasing the gain of pain. Science, 288 (5472), 1765–1769. Woolf, C.J. & Salter, M.W. (2006) Plasticity and pain: role of the dorsal horn. S.B. McMahon & M. Koltzenburg (eds), Wall and Melzack’s Textbook of Pain, 5th edn, Elsevier, Philadelphia, PA, pp. 94–97. Woolf, C.J., Allchorne, A., Safieh-Garabedian, B. & Poole, S. (1997) Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. British Journal of Pharmacology, 121 (3), 417–424.

Analgesic Pharmacology

c h a p t e r

Michelle Albino

Introduction There are a large variety of analgesic medications available in veterinary medicine. The success of analgesic therapy is dependent on many factors. These factors can be patient or drug related and include the route of drug administration; the patient’s age, body condition score, temperature, and perfusion status; and the pharmacokinetics (PK) and pharmaco dynamics (PD) of the particular drug. While opioids remain the cornerstone of pain management, a vast array of other analgesics can be added to a pain management protocol, including nonsteroidal anti-inflammatory drugs (NSAIDs), NMDA antagonists, local anesthetics, alpha-2 agonists, and others. The use of a multi modal analgesic protocol is effective because it targets the nociceptive (pain) pathway at more than one phase providing more complete analgesia.

1 5

Pharmacokinetics and Pharmacodynamics PK refers to the series of events that occur after a drug is administered to a patient. Once a drug has been administered, it is absorbed and then distributed to various tissues and fluids in the body. The degree to which a drug is absorbed and reaches general circulation is referred to as bioavailability. There are many reasons why a drug’s rate of absorption is variable including the route of administration, solubility of the drug, condition of the GI tract (if given orally), firstpass effect, perfusion status of the animal, dosage, and interaction with other medications. The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption,


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Chapter 5 Analgesic Pharmacology

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which is generally related to the liver and gut wall. Distribution of the drug is how the drug then travels to its site of action where it is then metab olized, or biotransformed, by the body into a form that can be eliminated. This most often occurs in the liver. The drug is then typically eliminated from the body (urine excretion) via the kidneys. PD refers to the way particular drugs affect the body, with the dose–response relationship and drug–receptor relationship for each drug being of particular importance. A “lock-and-key” model is often used to illustrate the way in which drugs combine with receptors (see Figure 5.1). The tendency of a drug to combine with a receptor is called affinity, and the degree to which the drug binds with its receptor helps to deter mine drug efficacy (Wanamaker and Massey 2004). Efficacy (Emax) refers to the maximum response achievable from a drug.

Drug molecule

The therapeutic index refers to the relationship between a drug’s ability to achieve the desired effect and its tendency to produce a toxic effect (Figure 5.2). This relationship becomes important when referring to dosing and constant rate infusions (CRIs) of drugs versus bolus dosing. The mecha nism of action of a drug, or MOA, refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A MOA usually includes the specific molecular targets to which the drug binds, such as an enzyme or a receptor. An elimination half-life is the time it takes for a drug to lose onehalf of its pharmacologic or physiologic activity. The half-life may also describe the time it takes for the concentration in blood plasma of a sub stance to reach one-half of its steady-state value (the “plasma half-life”).

Receptor

Action by agonist. Affinity + efficacy (“fit”) present

Drug molecule

Receptor

Little or no actionpartial agonist. Affinity but poor efficacy (“fit”) present

Drug molecule

Receptor

Figure 5.1 Drug/receptor. Source: Heather Sherman.

No action-blockage. Agonist is blocked from receptor

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Side effects Peak effect

Plasma drug concentration

Adverse response Onset of effect Therapeutic window

Desired response Duration of action Subtherapeutic

Time Figure 5.2 Drug curve response. Source: Heather Sherman.

Classes of Analgesics

Opioids

Opioids, NSAIDs, and local anesthetics are three of the major classes of analgesics in veteri nary medicine. NMDA antagonists have also been incorporated into pain management regi mens because of their ability to eliminate or prevent “windup” pain and treat neuropathic pain conditions. Alpha-2 agonists are used in premedication combinations and micro-rescue doses and as CRIs, because while they are prin cipally used for their sedative effects, they also possess some analgesic activity and can enhance the efficacy of opioid analgesics. In addition, there are adjunct analgesics. These include drugs such as amitriptyline, gabapentin, and trama dol. Throughout this chapter, for each class of analgesics, there will be a review of the current drugs available, their PK, PD, MOA, absorption, metabolism, elimination, and side effects. CRI calculations and multimodal pain plans will be detailed.

Opioids remain the cornerstone of pain management in human and veterinary medicine. All opioid analgesics are chemically related to a group of compounds that have been purified from the juice of a particular species of poppy: Papaver somniferum (Lamont and Mathews 2007). The extract is called opium, which contains active compounds such as morphine and codeine. Morphine is a naturally acting narcotic to which all other opioids are compared to in terms of potency and efficacy. In addition to morphine, multiple semisyn thetic and synthetic analogs of morphine have been created for clinical use. They are further classified by the receptors they activate. There are three well-defined types of opioid receptors: mu, delta, and kappa. Receptor subtypes have also been identified, including three subtypes for mu, two delta subtypes, and as many as four receptor subtypes for kappa receptors.


Text Box 5.1 Potency versus Efficacy Potency refers to the amount of drug (usually expressed in milligrams) needed to produce an effect, such as relief of pain. For instance, if 5 mg of drug A relieves pain as effectively as 10 mg of drug B, drug A is twice as potent as drug B. Efficacy refers to the potential maximum therapeutic response that a drug can produce. For example, the opioid morphine actives the mu receptor producing more analgesia than buprenorphine, which only partially binds there. Thus, morphine has greater efficacy than buprenorphine. Greater potency or efficacy does not necessarily translate into one drug being preferable to another. When judging the relative merits of drugs for a specific patient, many factors may be considered, such as side effects, potential toxicity, duration of effect (which determines the number of doses needed each day), and cost.

This is important as researchers continue to create more subtype-specific drugs in an effort to eliminate adverse side effects, but is not clinically applicable to the veterinary community as yet. Mechanism of Action Opioids work by binding to specific receptors in the brain and spinal cord, producing a variety of effects including analgesia, euphoria, dysphoria, sedation, and excitement. Opioid receptors are G-protein-coupled receptors that induce intracel lular signaling that ultimately inhibits adenylyl cyclase activity and suppress calcium ion currents. At the presynaptic level, decreased calcium influx reduces the release of transmitter substances, such as substance P, from primary afferent fibers in the spinal cord dorsal horn, thereby inhibiting syn aptic transmission of nociceptive input (Inturrisi 2002). Opioid receptor activity has also been shown to inhibit GABA release into the synaptic cleft, leading to analgesia.

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Absorption Opioid administration given via intravenous (IV), intramuscular (IM), or subcutaneous (SC) injection will produce a rapid onset of action through interaction with CNS receptors. Depending on the agent, opioids given via oral, transdermal, buccal, or rectal administration will have variable systemic absorption. There is significant first-pass effect for the opioid morphine, which is why it is typically not administered orally. In addition to IM or IV injection, neur axial administration into the subarachnoid or epidural space can also be an efficacious route for opioid analgesia. Small doses of opioids intro duced via these routes readily penetrate the spinal cord and interact with spinal and/or supraspinal opioid receptors to produce profound and poten tially long-lasting analgesia, the characteristics of which will depend on the particular drug used (Lamont and Mathews 2007). Opioids can also potentiate analgesia peripherally even though it is well known that these are centrally acting drugs. Because of this finding, opioids can poten tially be injected into local sites, reducing the side effects of systemic administration. Research on this phenomenon is still being conducted. Side Effects There are many potential adverse side effects associated with administration of opioid analge sics. One common side effect is nausea and vom iting caused by direct stimulation of the chemoreceptor trigger zone for emesis. This can be both species and agent specific. Nausea and vomiting are less often seen when opioids are administered to an animal that is already experi encing some degree of pain as compared to when used preemptively as premedication for surgery. In these circumstances, an antiemetic can be given to relieve the animal’s discomfort and reduce risks of regurgitation and aspiration. Arousal can be another unwanted side effect that is species and agent specific. There are numerous factors that determine whether or not

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a patient will experience excitation. Should exci tation occur, the opioid could be reversed, the dose lowered, or another agent used to try to achieve the desired analgesic effect. Hypothermia is a common side effect due to CNS depression (Posner 2007). Some animals, specifically cats, can exhibit hyperthermia after administration of pure opioid agonists, so tem perature must be monitored closely in this species (Niedfeldt and Robertson 2006). In human medicine, respiratory depression is a major side effect of opioid administration, but this is less frequently observed in animals. However, some opioids may cause dose-dependent depres sion of ventilation leading to hypercarbia, whereas others can cause hyperventilation (particularly in dogs). This is of concern when treating pain in a breed or patient predisposed to respiratory distress, such as a brachycephalic dog or patient with collapsing trachea, and should be considered when designing a patient-specific pain regime. Opioids have minimal effect on the cardiovas cular system. They can potentially decrease cardiac output by causing bradycardia, but this is more likely in critically ill patients who are unable to appropriately compensate for heart rate depression. However, most patients readily respond to an anticholinergic for opioid-induced medullary vagal stimulation. Upon administration, most opioids will cause some animals to defecate and may then later cause constipation. Gastrointestinal (GI) side effects (constipation) are more commonly seen with multiple doses or chronic opioid administration but can be treated with dietary changes or stool softeners (Plumb 2011). Full (Pure) Agonists Almost all clinically useful opioids exert their analgesic effects by acting as agonists at mu receptors. Pure or full opioid agonists can elicit maximal activation of the receptor when they bind to it, and the subsequent downstream processes produce a maximal analgesic effect (Lamont and Mathews 2007).


Morphine Morphine is a naturally acting narcotic and acts as a full opioid agonist at mu, delta, and kappa receptors. Currently, no other opioid has been proven to be a more efficacious analgesic than morphine. Following one dose of morphine, clinical effects are usually seen for 3–4 h. Histamine release from stimulation of mast cell degranula tion is a concern. Most often, preservative-free morphine is used for epidural administration. Given this route, morphine provides minimum alveolar concentration (MAC) reduction and long-lasting analgesia for orthopedic and soft tissue surgical procedures. There has been recent research recommending morphine use for postop pain relief in hemilaminectomies when used in Gelfoam® (Pfizer, New York, NY) placed on the spinal cord. The study states that topical epidural of preservative-free morphine administered via Gelfoam is not a sufficient analgesia alone post hemilaminectomy but in conjunction with other opioid administration may lead to superior pain relief (Barker et al. 2013). Fentanyl (Fentanyl Citrate) Fentanyl is a pure mu opioid agonist, with 100× potency compared to morphine. It is shortacting with peak analgesic effects occurring approximately 5 min postinjection and lasting approximately 30 min. It is highly lipid soluble, making it suitable for transdermal uptake. In high doses, it can cause apnea and bradycardia, but this is mainly at intraoperative analgesic doses where positive pressure ventilation can be admin istered and ventilation closely monitored. Because of its short duration of action, it is often used in CRI form or as adjunct analgesia for animals under anesthesia for significant MAC reduction with minimal CV side effects. Fentanyl can be given in combination with a benzodiazepine for cardiovascularly unstable patients. More recently, Recuvyra™ (Elanco, Greenfield, IN), transdermal sustained-release fentanyl (4 days), was Food and Drug Administration (FDA) approved for post surgical pain. It is placed between the shoulder blades like similar topical transdermal products.


Remifentanil Remifentanil is a pure mu opioid agonist, with 50× potency compared to morphine. It has a very short duration of action with a half-life of 6 min in dogs and 17 min in cats. It is a unique drug among opioids in that it is metabolized by non specific plasma esterases to inactive metabolites, independent of hepatic metabolism. This makes the drug specifically efficacious for patients with hepatic or renal compromise, that is, a patient undergoing anesthesia for liver tumor removal or liver shunt repair. Oxymorphone (Oxymorphone Hydrochloride) Oxymorphone is a synthetic pure mu opioid agonist, with 10× potency compared to morphine. When compared with morphine, oxymorphone is less likely to cause nausea and vomiting in dogs and cats and also provides more sedation. It is also less likely to cause dogs to pant, making it an ideal choice for respiratory-compromised animals or brachycephalic breeds (Lamont and Mathews 2007). It provides analgesia within 3–5 min when given IV and 15 min when given IM and has a duration of action of 4–6 h. Hydromorphone (Hydromorphone Hydrochloride) Hydromorphone is a synthetic pure mu opioid ago nist, with 5–10× potency compared to morphine. Clinically, hydromorphone and oxymorphone have similar efficacy, potency, and duration of analgesic action. Hydromorphone is less expensive and more likely to cause vomiting and panting. It has been shown to cause hyperthermia in cats. Methadone (Methadone Hydrochloride) Methadone is a synthetic pure mu opioid agonist, with 1.5–4× potency to morphine. It provides analgesia for 2–4 h after IV administration in dogs. Methadone is unique in that it possesses addi tional affinity for NMDA receptors and alpha-2 adrenergic receptors (Codd et al. 1995) and also may decrease norepinephrine and serotonin reuptake to augment analgesia, making it poten tially useful for neuropathic or windup pain. It is

47

less likely to make animal patients vomit when compared to hydromorphone. Methadone may be administered as an oral transmucosal medication (OTM) in cats. In one study, sedation was greater and lasted longer after OTM administration at a dosage of 0.6 mg/kg (Ferreira et al. 2011). Meperidine (Meperidine Hydrochloride) Meperidine is a synthetic pure mu opioid agonist, with 1/8 the potency of morphine. It is irritating when administered SQ and must be given slowly IV to prevent histamine release. After IM administration, peak effects occur between 30 and 60 min, with analgesic activity only being present for 1–2 h in dogs and cats. It can potentially cause tachycardia because of its modest atropine-like effects, as opposed to bradycardia with most other opioids (Lamont and Mathews 2007). Codeine (Codeine Phosphate) Codeine is an orally available weak mu opioid agonist. It has mild analgesic qualities but very effective antitussive effects. It is effective 30 min after PO administration. It has been used orally in combination with acetaminophen in dogs for outpatient pain control. Partial Opioid Agonists Partial opioid agonists are drugs that bind to mu opioid receptors but produce only a limited clinical effect. These agents have what is called a ceiling effect, where increasing doses does not produce additional effects, either adverse or analgesic. They are used when mild to moderate analgesia is desired. Buprenorphine/Buprenorphine SR™ Buprenorphine is a semisynthetic partial opioid agonist with 20–30× potency compared to mor phine. It has a very high affinity for mu receptors, but cannot elicit a maximal clinical response, making it better suited to treating mild to moderate pain in dogs. Because of this ceiling effect, it also does not reduce MAC as effectively as pure mu opioids. It has a dose-dependent

48

duration of analgesia and can range from 4 to 24 h depending on dosage given. Due to their unique oral pH, buprenorphine can also be administered buccal mucousally in cats for pain relief. The medication should be placed in the cheek pouch at 40–120 µg/kg (Ko 2013). Buprenorphine SR (sustained release) (SR Veterinary Technologies LLC, Windsor, CO) is used as a single SQ injection for prolonged release for outpatient procedures in cats. It has been shown to have comparable efficacy and adverse effect profile as that of twice daily OTM administration of buprenorphine before and after surgery (Catbagan et al. 2011). Opioid Agonist–Antagonists Opioid agonists–antagonists are competitive mu receptor antagonists but exert analgesic activity by stimulating kappa receptors. Since these agents have limited analgesic efficacy, they do not reduce MAC significantly and should not be used when moderate to severe pain is present or expected. Butorphanol/Nalbuphine Butorphanol is a synthetic mu antagonist and kappa agonist, with 5× potency compared to morphine at kappa receptors where it exerts its sedative effects. Butorphanol is an antagonist at the mu receptor making it a poor choice for pain relief. It has a short duration of action of about 1–3 h. Butorphanol is a good sedative and an effective antitussive agent, making it ideal for animals in respiratory distress, such as dyspnea from collapsing trachea. Nalbuphine is also an agonist/antagonist opioid and is clinically similar to butorphanol. Both these drugs are enhanced when combined with sedatives such as acepromazine or benzodiazepines. Pure Opioid Antagonists Naloxone (Naloxone Hydrochloride) Naloxone is a pure mu opioid antagonist that reverses all opioid agonist effects at all recep tors. IV doses last between 30 and 60 min, so


subsequent doses may be required (Lamont and Mathews 2007). Excitation and aggravation can occur following naloxone administration; therefore, the dose is titrated slowly and given to effect (Table 5.1).

Nonsteroidal Anti-inflammatory Agents NSAIDs are commonly used in veterinary medi cine for the relief of both acute and chronic inflammatory pain. An appealing quality of this class of drugs is excellent therapeutic analgesic activity and an extended duration of action. NSAIDs are frequently used perioperatively for their anti-inflammatory properties and as part of a multimodal pain management plan. They are used to treat a myriad of inflammatory condi tions including postoperative pain, tissue trauma, osteoarthritis, and cancer pain among others. NSAIDs appear behave synergistically when used in combination with opioids and may have opioid-sparing effects (Lamont and Mathews 2007). NSAIDs are available in injectable, pill, chewable, oral liquid, paste, and granule forms. Patients must be carefully selected prior to NSAID administration, as numerous adverse effects can occur. Mechanism of Action NSAIDs exert their analgesic effect by inhibition of the enzyme cyclooxygenase (COX). The COX enzymes facilitate the breakdown of arachidonic acid to produce several biological mediators including prostaglandins, prostacyclins, and thromboxane. The prostaglandins are of parti cular importance in pain management, as they induce swelling, pain, and fever, all of which function to enhance nociception. Historically, two COX isoenzymes were known (COX-1 and COX2), and more recently, a newly identified COX-3 has been identified (Botting 2003). COX-1 is ubiquitous in the body and is involved in many biological functions including gastric mucosal health, platelet aggregation, and modulation of


49

Table 5.1 Opioid doses

Opioid agonists Agent

Dog

Cat

Horse

Cow

Goat

Pig

Morphine

0.4–1.0

0.1–0.2

0.04–0.1

0.04

0.04

0.05–0.1

Meperidine

1–5

0.5–1.0

2–4

2–4

—

0.4–1.0

Hydromorphone

0.1–0.2

0.1

0.02–0.1

—

—

—

Oxymorphone

0.1–0.2

0.1

0.02–0.1

—

—

—

Methadone

0.5–1.0

0.1–0.2

0.05–0.10

—

—

0.1–0.2

Fentanyl

2–6 µg/kg

1–3 µg/kg

0.07–0.15

—

—

—

Buprenorphine

0.02

0.01–0.02

0.01

—

—

—

Buprenorphine SR

0.12–0.27

0.12

—

—

—

Nalbuphine

0.05–0.2

—

—

—

—

Butorphanol

0.2–0.4

0.2–0.4

0.01

Naloxone

0.2–0.4

0.2–0.4

0.1–0.2

Codeine

0.5–2 (PO)

0.5–2 (PO)

—

—

—

—

—

All analgesic doses are taken from Muir et al. (2013). All doses are IV mg/kg unless otherwise noted. IM dose is one to two times the IV dose.

renal blood flow. COX-2 is an inducible isoenzyme that is upregulated at sites of tissue inflammation. Newer NSAIDs that selectively inhibit COX-2 are thought to produce fewer GI side effects (Wanamaker and Massey 2004). The COX-3 isoenzyme possesses COX activity that differs pharmacologically from both COX-1 and COX-2 but is more similar to COX-1. COX also plays a role in fever production. Certain anti-inflammatory agents such as acet aminophen and aspirin have been shown to have antipyretic effects and have been used clin ically in dogs. In feline patients, ketoprofen and meloxicam have been shown to reduce fever with fewer adverse side effects (Lamont and Mathews 2007).

Side Effects Adverse Drug Events and NSAIDs Adverse drug effects (ADEs) related to NSAID use most commonly affect the GI system, kidneys, liver, and platelet function. Lessons learned from the long-term use of NSAIDs in dogs suggest that this class of drug is often used inappropriately and without screening and monitoring (Lascelles et al. 2005). Adverse drug event reports at the US FDA Center for Veterinary Medicine provide some insights as to why ADEs from NSAID use might be so high: • Twenty-three percent of pet owners state that veterinarians never discuss adverse effects of the medication.

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Text Box 5.2 Recommendations of the ISFM and AAFP on the use of NSAIDs in cats (Sparkes et al. 2010) • Perform a detailed physical examination, including assessment of blood pressure and ideally hematology, blood biochemistry, and urine analysis, prior to commencement of the NSAID therapy. • Conduct routine monitoring of the patient (e.g., every 3–6 months depending on clinical status). • Ensure accurate dosing. • If the animal is overweight or obese, base the dose on ideal or lean body weight. • Give the drug with or shortly after food. • Feed moist food and ensure a good fluid intake. • Make sure owners are aware of any side effects that may develop. • Stop the drug if the animal stops feeding. • Titrate the dose to the lowest effective level. • Reduce the dose if other therapeutic drugs are being used. • Never use with glucocorticoids.

• Twenty-two percent of pet owners state they are not given client information sheets about the prescribed drugs, which are provided by pharmaceutical companies for the purpose of pet owner education. • Fourteen percent of prescribed NSAIDs are dispensed in other than original packaging, thereby denying pet owners drug information provided on the label. • Only four percent of pet patients’ prescribed drugs are given preadministration blood analyses. As a class of drug, NSAIDs are most commonly associated with adverse reactions to the GI tract (64%), renal system (21%), and liver (14%), respectively (Hampshire et al. 2004). GI prob lems associated with NSAIDs can be as benign as regurgitation or as serious as gastric ulceration and perforation. Vomiting has been identified as


the most frequent clinical sign associated with gastric perforation. Pet owners should be informed that if their pet vomits while taking an NSAID, the drug should be discontinued and the patient promptly examined. Of the reports involving unauthorized use in cats, nine were associated with the oral administration of meloxicam after its parenteral administration. This dosage regimen is not autho rized for use in cats. Of these nine cases, eight cats developed renal insufficiency and one cat developed dyspnea and died within 48 h after the start of oral meloxicam administration. A warning that oral follow-up therapy using meloxicam or other NSAIDs should not be administered in cats is included in the SPCs for all injectable products containing meloxicam authorized for use in this species (Dyer et al. 2010). In a month-long study, 18% of cats showed intermittent signs of GI upset (vomiting and/or diarrhea), but signs were not severe enough to terminate treatment in any cat (Clarke and Bennett 2006). In addition, more serious complications have been observed including gastric ulceration and bleeding, acute kidney injury, and thrombocyto pathias. Accurate dosing is imperative, as many NSAIDs have a very narrow margin of safety. Patients selected to receive NSAIDs should have no evidence or concern for gastric ulceration and have normal renal and hepatic function and normal hemostatic function. In addition, patients should be euvolemic and normotensive. Age and weight restrictions vary between NSAIDs and should be observed. In the largest clinical study to date (Gunew et al. 2008), 4 out of 46 cats vomited during meloxi cam treatment, and 2 of these cats were with drawn from the study. The most common adverse effect associated with piroxicam in cats with neo plasia was vomiting (Bulman-Fleming et al. 2010). Differences in hepatic biotransformation can lead to prolonged half-lives and the potential for tox icity in cats, so caution should be exercised when administering NSAIDs more than once in feline patients. “Many of the concerns about the use of


51

NSAIDs relate to the unique metabolism of cats; the relative deficiency of glucuronyl transferase enzymes in this species, for example, may lead to a prolonged half-life for some drugs. However, some NSAIDs, including meloxicam, piroxicam, and robenacoxib, are cleared by oxidative enzymes and do not appear to have prolonged half-lives in cats” (Robertson 2013). Concurrent administration of NSAIDs with corticosteroids or other NSAIDs greatly increases the likelihood of an adverse event and should be avoided. When switching from one NSAID to another or from a corticosteroid to an NSAID (or vice versa), a “washout” period of 3–5 days should be observed to minimize this risk (Fox 2013; Mealey 2013). In dogs, most ADEs related to NSAID use occurs between 14 and 30 (range 3–90) days after the start of treatment (Hampshire et al. 2004). Therefore, it is recommended to screen blood profiles and chemistry values before use, and then at 2–4 weeks follow-up. Chronic drug therapy can induce liver enzymes. A three- to fourfold increase in hepatic enzyme values from baseline may indicate hepatotoxicity. Two courses of action could be taken:

2. More specific liver function tests, such as bile acid assays, can be performed.

1. The drug could be discontinued, and if values return to baseline, a link between treatment and hepatic impairment is likely.

Carprofen Carprofen is a COX-2 preferential NSAID approved for perioperative and chronic pain con ditions in dogs in the USA and dogs and in cats in the UK and other countries. Carprofen is available in injectable, chewable, and caplet formulations.

Text Box 5.3 Absolute contraindications for the use of NSAIDs 1. In combination with another NSAID or corticosteroid 2. Protein-bound medications (warfarin, digoxin, anticonvulsants phenobarbital) and chemotherapeutic agents 3. Angiotensin-converting enzyme inhibitors and diuretics 4. In a dehydrated or hypovolemic patient 5. In a patient with preexisting gastrointestinal ulceration

A decrease in hematocrit and an increase in BUN suggest GI bleeding, but any change in BUN warrants measurement of creatinine and urine-specific gravity to assess renal function. Educating owners to recognize early signs of problems is vital. Clients should be advised to stop administering the NSAID and to call their veterinarian if they notice any changes in their pet, such as inappetence, vomiting, diarrhea, lethargy, or bloody feces. The decision to stop or continue NSAID treatment would depend on further consultation and diagnostic tests. All adverse drug events should be reported to the relevant pharmaceutical company and or regula tory board as soon as possible. Animals with preexisting renal or liver disease may not be candidates for NSAID administration for acute or chronic pain management; however, in some cases, NSAIDs may be used with caution to manage chronic inflammation if quality-of-life issues outweigh the risks (Sparkes et al. 2010). Examples of NSAIDs

Meloxicam Meloxicam is a COX-2 preferential NSAID. The oral formulation approved for use in dogs, and parenteral formulation approved for one time use in cats. In the USA, Metacam carries an FDA block box warning regarding the likelihood of renal failure as a result of repeat dosing in cats. The European label states that meloxicam is contraindicated in dogs with active GI ulcera tion or bleeding; impaired hepatic, cardiac, or renal function; and hemorrhagic disorders (Plumb 2011).

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OroCAM® (Abbott, Abbott Park, IL) OroCAM provides transmucosal oral delivery of the NSAID meloxicam for the control of pain and inflammation in dogs. It is administered as a mist into the cheek or gums of the patient. It was found to be safe and effective in dogs for the con trol of pain and inflammation associated with osteoarthritis (Cozzi and Spensley 2013). Robenacoxib (Onsior®; Novartis Animal Health, NAH Communications, Switzerland) Robenacoxib is a new NSAID with a fast onset of action that comes in both injection and oral for mulations. It has high selectivity for the COX-2 isoform of COX. In one study, robenacoxib by SQ injection followed by oral tablets had good tolera bility and noninferior efficacy compared to meloxi cam for the management of perioperative pain and inflammation associated with soft tissue surgery in dogs (Gruet et al. 2013). In cats, the oral form is approved for 3-day postoperative use in the USA. Ketoprofen Ketoprofen is a propionic acid derivative with antipyretic, anti-inflammatory, and analgesic qual ities. It is an inhibitor of both COX-1 and COX-2, so patient selection is imperative. It is approved for use in horses (IV) and in dogs and cats (IV, IM, SQ) for the treatment of postoperative and chronic pain. It should not be administered to a patient where hemorrhage is a concern (post-op laparo scopic liver biopsy) but can be safely administered for post-op orthopedic procedures. Flunixin Meglumine Flunixin is an NSAID, non-COX-2 selective, labeled for use in horses and cattle but has extralabel uses in other species. Its clinical uses in horses include alle viation from pain associated with musculoskeletal disorders and colic, as it has great ability to inhibit visceral pain. It can be toxic in dogs and cats. Ketorolac A COX-1 and COX-2 inhibitor, ketorolac is not approved for use in veterinary patients, but used in research settings when it is more readily available


than other NSAIDs. It is comparable to ketoprofen in duration and efficacy in managing postlaparotomy and orthopedic pain in dogs (Matthews et al. 1996). Firocoxib Firocoxib is of the coxib class and is currently available in chewable tablet form providing analgesia from osteoarthritis in dogs. It is COX-1 sparing in effect (Plumb 2011). Standard NSAID side effects may occur. Deracoxib Deracoxib is an NSAID and analgesic of the coxib class. It is available in oral form and labeled for the control of pain and inflammation in orthopedic surgery or osteoarthritis in dogs. Piroxicam Piroxicam has been proven to be effective in dogs as an analgesic on the lower urinary tract associ ated with transitional cell carcinoma or cystitis and urethritis. The administration of concurrent gastroprotectants is advisable (Plumb 2011). Acetaminophen Acetaminophen is a COX-3 inhibitor with little effects on COX-1 and COX-2, making it of limited use in veterinary patients. It possesses mild analgesic qualities and is an effective antipy retic. Its use is contraindicated in cats because of deficient glucuronidation of acetaminophen in this species, leading to the buildup of toxic metabolites and resultant toxicity. It has been given to dogs, most effectively in conjunction with an opioid (tylenol with codeine). Aspirin Aspirin is most commonly used in low doses as a platelet inhibitor for the treatment of cardiomy opathy in cats and numerous hypercoagulable disorders in both dogs and cats. Cats are very susceptible to overdose because of their inability to metabolize it rapidly. Aspirin is contraindi cated in dogs for osteoarthritis due to permanent platelet inhibition and is not recommended for pain control in dogs or cats (Table 5.2).


53

Table 5.2 NSAIDs and doses

Drug

Dogs

Cats

Horses

Ruminants

Routes

10–35

10–15

—

100

PO

Salicylates Aspirin Propionic acids Carprofen

2.2–4.4

PO, SQ SQ IV

2 0.05–1.10 Ketoprofen

0.5–2.2

0.5–2.2 1.1–2.2

2

IM (dogs), SQ, PO IV

0.2–1.1

1

IV, IM IV

Fenamates Flunixin

0.25–1

Not used

Oxicams Piroxicam

0.2–0.4

Not used

PO

Meloxicam

Loading: 0.2 Maintenance: 0.1 Loading: 0.2 Maintenance: 0.1

Preoperative: 0.3 Loading: 0.2 Maintenance: 0.1

Loading: IV or SQ Maintenance: PO SQ, PO

Deracoxib

1–4

Not used

PO

Firocoxib

2–5

Not used

PO

Robenacoxib

1

(1 mg/kg) orally once daily, for a maximum of 3 days PO (cats)

Coxibs

Phenacetin derivatives Acetaminophen

10–15

PO

All drugs in mg/kg dose.

Local Anesthetics Local anesthetics reversibly bind sodium channels and block impulse conduction in nerve fibers. They produce desensitization and analgesia of skin surfaces (topical anesthesia), tissues (infiltra tion and field blocks), and regional structures (conduction anesthesia, IV regional anesthesia)

(Muir et al. 2013). Local anesthetics provide preemptive analgesia and reduce the potential for the development of central sensitization. The local anesthetics used most often in veterinary medicine are lidocaine, bupivacaine, and mepiva caine. They can and should be used whenever possible as a part of a multimodal pain mana gement plan. A 2011 International Veterinary

54

Academy of Pain Management (IVAPM) Position/ Consensus statement advises that “Locoregional anesthesia should be used, insofar as possible, with every surgical procedure.”


drug therapy is indicated, diazepam being the drug of choice.

Applications Mechanism of Action Local anesthetics are membrane-stabilizing agents that enter and occupy sodium ions channels. By blocking sodium channels, nerve cell depolariza tion is prevented, thus slowing or stopping the conduction of nerve impulses. The potency of local anesthetics is directly correlated with the lipid solubility of the drug. The smaller the molecule and larger the lipophilic property of the local anesthetic, the more readily the anesthetic permeates the axonal nerve mem branes. These nerve membranes are highly lipid in composition and bind sodium channels with greater affinity (Skarda and Tranquilli 2007). The speed of onset is also most likely associated with the lipid solubility of the anesthetic. Local anesthetics are absorbed from the mucous membranes, serosal surfaces, respiratory epithelium, IM deposition, SC deposition, and injured skin but very poorly absorbed through intact skin. Recovery time for return of normal sensation is determined by the gradual dissipa tion of the drug from the nerve membrane. Side Effects The major concern with local anesthetic drugs are CNS and cardiovascular toxicity. Because of this, doses for dogs and cats should always be carefully calculated and reduced in sick patients. As the plasma concentration of the drug increases, humans experience a sequence of signs and symptoms, such as numbness of tongue, light headedness, visual disturbance, muscle twitching, unconsciousness, and convulsions, which may progress to coma, respiratory arrest, cardiovascular depression, and death (Skarda and Tranquilli 2007). The first signs of toxicity typically observed in dogs and cats are muscle twitching and convulsing. If this occurs, anticonvulsant

Topical Anesthesia Topical local anesthetics can be applied to mul tiple surfaces of mucous membranes including the mouth, esophagus, genitourinary tract, and tracheobronchial tree. They can also be used on the eye for ocular procedures or the larynx to help facilitate tracheal intubation. EMLA® cream can be used on the skin to facilitate IV catheter placement. Lidoderm® patches are 5% lidocaine patches used for topical anesthesia. The proposed mecha nism of the lidocaine patch is that it allows the topically applied lidocaine to bind to neuronal membrane receptors and stabilize neuronal mem branes by inhibiting sodium ion influxes, thereby inhibiting initiation of the action potential and conduction of nerve impulses (Gammaitoni et al. 2003). Animals that undergo abdominal surgery, including ovariohysterectomy or laparotomy, can benefit from lidocaine patch application at the ventral abdominal midline. The patch can also be applied after thoracotomy, sternotomy, dorsal hemilaminectomy, cruciate repair, total ear canal ablation, and amputations. An in-depth discussion of local anesthetic nerve blocks and regional blocks can be found in Chapters 5 and 7. Infiltrative/Continuous-Infiltration Anesthesia Local anesthetics can be deposited around a specific nerve to facilitate minor procedures or as part of a multimodal pain management plan for surgical procedures. Local infiltration is pri marily used in veterinary medicine before surgery for the removal of tumors or masses, superficial biopsies, or laceration repairs. Recently, the development of diffusion or wound catheters has allowed for the delivery of local anesthetics. A diffusion or wound catheter is simple fenestrated tubing that is sterilely placed at a painful site


55

for continuous or intermittent administration of local anesthetics. This is especially useful in cases eliciting moderate to severe post-op pain such as limb amputations, total ear canal ablations, and radical mastectomies.

Intercostal nerve blocks can be performed before or after surgery of the thoracic cavity, such as a lateral thoracotomy or median sternotomy, as these procedures usually elicit the most severe postoperative pain.

Regional or Nerve Block Regional anesthesia is the injection of a local anesthetic into the area around a peripheral nerve to block sensory and/or motor function.

Neuraxial Anesthesia An epidural is a form of regional analgesia involving the administration of drugs through an injection or catheter into the epidural space. Spinal (subarachnoid) anesthesia is a technique whereby a local anesthetic drug is injected into the cerebrospinal fluid. When administered spi nally, local anesthetics produce motor and sympathetic blockade as well as sensory inter ruption. They reduce the MAC of volatile inhal ants and provide long-lasting analgesia.

Peripheral Nerve Blocks Onychectomy is a common procedure for cats in the USA and parts of Canada. A circumferential nerve block technique can add substantially to analgesia concurrently with injectable opioids and NSAIDs (Figure 5.3).

Radial nerve Median nerve

Ulnar nerve Carpal pad

Dorsal + Palmar digital nerves

Dorsal branch of the ulnar nerve

Metacarpal pad Palmar proper digital nerves

Dorsal proper digital nerves

Dorsal view Figure 5.3 Cat onychectomy block. Source: Heather Sherman.

Digital pad

Palmar view

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Contraindications to neuraxial administration include clotting disorders, sepsis, infection at the site of needle placement, severe hypovolemia, fracture near the site of administration, or increased ICP (Skarda and Tranquilli 2007).

Local Anesthetic Agents Lidocaine Lidocaine is an amide local anesthetic that pro duces reversible depression of nerve conduction by blocking sodium channels. It has a rapid onset of action (2–5 min) and a very short duration of action (20 min to 2 h). It is metabolized in the liver and excreted by the kidneys. It is available for use in injectable form, spray, or lubricant gel. It is also available in combination with epineph rine to prolong duration of action via vasocon striction—but this form should never be used when treating ventricular arrhythmias or when ever vasoconstriction is contraindicated. The addition of lidocaine to an analgesic plan has several benefits. It is reported to have some cytoprotective effects, such as weak calcium channel inhibition, which may be helpful in pre venting reperfusion injury (Schmid et al. 1996), and reduced neutrophil chemotaxis and platelet aggregation (which could help significantly in cases with the potential for DIC or SIRS, including GDVs and splenectomies). Also, lidocaine has some activity in preventing ileus, which is poten tially useful for enterotomies.


Mepivacaine Mepivacaine is also an amide local anesthetic that is approved for use in dogs and horses, but not as commonly used in veterinary medicine as lidocaine and bupivacaine. It has a moderate onset of action (5–10 min) and moderate duration of action (2–4 h). It is metabolized by the liver and excreted by the kidneys. It does not sting upon injection, which makes it advantageous for use in companion animals (Table 5.3).

Alpha-2 Agonists Alpha-2 agonists have been used in veterinary medicine for years for their sedative effects, but only more recently have the analgesic effects of these drugs been appreciated as a part of multi modal pain management plans. Medetomidine, dexmedetomidine, and xylazine are the most commonly used alpha-2 agonists in veterinary medicine. Xylazine use has now been largely replaced by medetomidine and dexmedetomi dine in companion animals because of their higher specificity for the alpha-2 receptor and decreased side effects. Alpha-2’s can be used for short procedure sedation and in premedication combinations, small bolus rescue doses, epidu rals, or constant infusions as adjunct analgesia. One of the benefits of using alpha-2 agonists is that they can be reversed by the antagonist atipamezole if unwanted side effects occur, or the sedation in the patient is no longer wanted or needed.

Bupivacaine

Mechanism of Action

Bupivacaine is also an amide local anesthetic that works similarly to lidocaine by blocking sodium channels and preventing nerve conduction. It has a slower onset of action (10–15 min) and a longer duration of action (4–6 h). It is also metabolized by the liver and excreted by the kidneys. It can be combined with an opioid to extend the length of duration (Candido et al. 2002).

Alpha-2 agonists produce CNS depression by stimulating both pre- and postsynaptic alpha-2 adrenoceptors in the periphery and CNS, decreasing norepinephrine release centrally and peripherally and reducing ascending nociceptive transmission (Muir et al. 2013). They produce profound sedation, analgesia, muscle relaxation, and anxiolysis.


Table 5.3 Local anesthetics Epidural analgesia Lidocaine (preservative-free, use ampules) 2–3 mg/kg, dilute to 0.3 ml/kg with sterile saline, maximum volume 6 ml Bupivacaine (preservative-free, use ampules) 0.25–0.5 mg/kg dilute to 0.3 ml/kg with sterile saline, maximum volume 6 ml Combinations of morphine/lidocaine or morphine/bupivacaine can be used Maximum total infiltrative dose: Lidocaine: 8 mg/kg Bupivacaine: 2 mg/kg Another epidural combination (not to exceed 6 ml total): Ketamine: 0.1–0.3 mg/kg Dexmedetomidine: 0.1 µg/kg Morphine: 0.05–0.1 mg/kg Bupivacaine: 0.3–0.4 mg/kg Regional anesthesia Local block Lidocaine: 0.2–2 mg/kg Bupivacaine: 0.2–2 mg/kg Mepivacaine: 0.5–2 ml per site Intercostal nerve block Bupivacaine: 2 mg/kg Interpleural Bupivacaine: 2 mg/kg diluted to 1 ml/kg and placed in thoracic cavity Intra-abdominal Bupivacaine: 2 mg/kg in 0.8 ml/kg 0.9% NaCl dripped into the abdominal cavity before surgical closure

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Table 5.3 (Continued) Intra-articular Bupivacaine and/or morphine Morphine alone: 1.0 mg of preservative-free morphine diluted to 5–6 ml with saline Bupivacaine alone: 5–10 ml 0.5% bupivacaine (max 2 mg/kg) Morphine 0.1 mg/kg with 4–5 ml bupivacaine (max 2 mg/kg) Wound diffusion catheter Lidocaine CRI: 15 µg/kg/min (dog, cat) Bupivacaine CRI: 2 mg/kg/day (cat) 2–4 mg/kg/day (dog) Lidocaine patches (10 × 14 cm): Dosing guideline for dogs and cats Body weight (lb; kg)

Patch(es)

3–5; 1.4–2.3

One-sixth to one-quarter

6–10; 2.7–4.5

One-half

11–20; 5–9.1

One

21–40; 9.5–18.2

Two

41–60; 18.6–27.3

Two and one-half to three

61–100; 27.7–45.5

Three to four

The syringe must be aspirated first before each injection to ensure it is not administered intravenously. It is best to err on the low side of lidocaine when administering in cats because of the potential for CNS side effects including drowsiness, ataxia, muscle tremors, and seizures.

In contrast to the physiological effects medi ated by alpha-2 receptors, activation of alpha-1 receptors produces arousal, excitement, and increased locomotor activity in animals (Lemke 2007). Xylazine possesses a high affinity for alpha-1 receptors; therefore, these unwanted side effects are more common. This is one of the

reasons medetomidine and dexmedetomidine have widely replaced xylazine for companion animals and some exotics. Alpha-2’s are rapidly absorbed after IV, IM, SQ, or transmucosal administration and metab olized rapidly in the liver and excreted in the urine.


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Side Effects

Examples of Alpha-2 Agonists

Alpha-2 agonists can cause cardiovascular changes that are well tolerated in patients with healthy hearts but not appropriate for patients with cardiovascular disease. Initial peripheral vasoconstriction causes pale mucous membranes, cold extremities, and hypertension with reflexive bradycardia. This dramatic increase in systemic vascular resistance can cause cardiac output to decrease by 30–50% and significantly increases myocardial oxygen consumption. First- and second-degree AV block can occur, but complete AV block is uncommon. Ventricular bradycardia or tachycardia may occur following pronounced sinus bradycardia or sinus arrest (Muir et al. 2013). Conversely, continuous infusion is associ ated with hypotension secondary to vasodilation caused by central sympatholysis. The initial vaso constriction can cause pale mucous membranes and cold extremities. Alpha-2 agonists also decrease the respiratory center’s sensitivity to hypercarbia and depress respiratory centers centrally. Patients given large doses for sedation should be kept on flowby oxygen for this decrease in tidal volume and respiratory rate. The oxygen is also beneficial for the increase in myocardial oxygen consumption. Alpha-2’s can initiate vomiting in dogs and cats; in fact, xylazine is often used as an emetic in cats. Repeated or prolonged use decreases GI motility and delays gastric emptying and predis poses to bloat in large-breed dogs and horses (Muir et al. 2013). Instances where vomiting is contraindicated include brachycephalic patients, enucleations, neonates, and bronchoscopy. Transient hypoinsulinemia and hyperglycemia have been reported in several species sedated with xylazine and other alpha-2 agonists. They suppress insulin release by stimulating receptors in the pancreas, which results in an increase in plasma glucose concentration and glucosuria. Because of this, alpha-2 agonists should be used with caution or not at all in patients with renal disease or diabetes (Plumb 2011).

Xylazine Xylazine is an alpha-2 agonist with some alpha-1 affinity. It is used in veterinary medicine as a sedative, analgesic, and muscle relaxant and for emesis in cats. In dogs, xylazine may transiently increase cardiac sensitivity to catecholamineinduced arrhythmias, which is not seen with other alpha-2 agonists. This should be used with caution in ruminants that are extremely sensitive to the adverse side effects of xylazine. It can cause pronounced sali vation, pulmonary edema in some sheep, and decreased PCV in cattle (Blaze and Glowaski 2004). In horses, it is often used to treat colic (visceral pain). However, it can predispose horses to bloat by delaying gastric emptying (Blaze and Glowaski 2004). Xylazine can be reversed with the antagonists yohimbine or atipamezole. Medetomidine Medetomidine is a highly selective alpha-2 ago nist that is supplied as a racemic mixture of two optical enantiomers. Dexmedetomidine is the active enantiomer, and levomedetomidine has no apparent pharmacological effect (Lemke 2007). It is used in veterinary medicine for sedation and restraint for physical exams, diagnostic imaging, and minor procedures; as a premedication to decrease MAC; for additive analgesia; and as an anxiolytic. It is more potent than xylazine and doses based on a microgram-per-M2 basis. Medetomidine has been shown to be synergistic with opioids, and concurrent use results in pro longed opioid activity (Grimm et al. 2000). It can be used preoperatively to help relieve stress in anxious or fractious patients to better facilitate IV catheter placement. Medetomidine is also used in epidural form to reduce MAC and work synergistically with opioids and local anesthetics. Postoperatively, it can be administered in small doses or by CRIs to augment analgesia or reduce dysphoria or anxiety.

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As with all other alpha-2 agonists, patient selection is essential. ECG monitoring and sup plemental oxygen should be kept on all animals receiving a moderate to large sedative dose to monitor for arrhythmias and increase the patient’s inspired oxygen content. Caution should be used in excited dogs, as they may exhibit a paradoxical excitatory response. Finally, it should not be used in hemodynamically unstable animals; animals with respiratory, renal, or hepatic disease; preg nant animals; or animals with GI obstruction. Medetomidine is reversed with atipamezole. Dexmedetomidine Dexmedetomidine is a synthetic alpha-2 agonist. It contains only the active enantiomer of the racemic mixture medetomidine, because levome detomidine has no sedative, analgesic, or cardio respiratory effect. Dexmedetomidine is twice as potent as medetomidine. All other PK and PD remain the same as medetomidine. Detomidine Detomidine is an alpha-2 agonist that is primarily used in horses. It produces analgesia, sedation, and muscle relaxation, which is rapidly seen after IV or IM administration. Detomidine is a very effective visceral anal gesic and can be used alone or in combination with butorphanol to produce standing sedation for diagnostic and surgical procedures and as an analgesic for horses with abdominal pain (Lemke 2007). Like other alpha-2 agonists, it produces marked cardiovascular side effects so patients should be carefully selected.

Alpha-2 Antagonists Yohimbine Yohimbine is an alpha-2 antagonist that reverses all effects of alpha-2 agonists, including sedation and analgesia. It is used in veterinary medicine to


reverse the agonist xylazine. It is usually adminis tered IV but can also be given SC or IM for slower reversal. CNS excitement and muscle tremor may occur when administering yohimbine (Blaze and Glowaski 2004). When given IV, the agent should be administered slowly and titrated to effect to help counteract these effects.

Atipamezole Atipamezole is an alpha-2 antagonist used for the reversal of medetomidine, dexmedetomidine, and xylazine. It reverses all effects of these drugs, including sedation and analgesia. It can occasion ally cause vomiting, diarrhea, and salivation. The drug is formulated such that the volume of atipamezole required for IM injection equals the volume of medetomidine or dexmedetomidine administered. It is preferable to use the IM route. The drug can be given IV; however, it can cause excite ment or aggression, so it should be titrated slowly to effect (Blaze and Glowaski 2004) (Table 5.4).

Adjunct Analgesics While NSAIDs, opiates, and local anesthetics are known as the traditional analgesics, “adjunct analgesics” augment analgesic activity in certain conditions, although their primary use is for con ditions other than pain. In the chronic pain setting, the adjunctive analgesics are administered (i) to manage pain that is refractory to t raditional analgesics, (ii) to enable the dose of traditional analgesics to be reduced in order to lessen side effects, and (iii) concurrently to treat a symptom other than pain (Lamont and Mathews 2007). There are multiple drugs that can be considered adjunct analgesics, including antidepressants, oral local anesthetics, NMDA receptor antagonists, and anticonvulsants (gabapentin). Some of the agents most commonly used in veterinary medi cine include tramadol and amitriptyline. Maropitant is an antiemetic and neurokinin-1


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Table 5.4 Alpha-2 agonists and antagonist doses

Agent

Dog

Cat

Horse

Cow

Goat

Pig

Xylazine

0.4–1.0

0.4–1.0

0.4–1.0

0.02–0.1

0.02–0.07

1–2

Medetomidine

0.005–0.02

0.01–0.04

0.005–0.02

—

—

—

Dexmedetomidine

0.005–0.02

0.01–0.04

0.005–0.02

—

—

0.005–0.2

Detomidine

—

—

5–20 µg/kg

Doses are given in mg/kg, IV. Agent

Dose/route

Yohimbine

0.1–0.3 IV 0.3–0.5 IM

Atipamezole

Amount of medetomidine or dexmedetomidine given IM 0.05 IV slow

Doses are in mg/kg. All effects are reversed with alpha-2 antagonists including analgesia.

(NK-1) receptor antagonist and has been shown to reduce MAC and augment analgesia.

NMDA Antagonists NMDA receptor antagonists are used in neuro pathic pain conditions as a part of multimodal pain therapy, to eliminate windup and to “reset” the spinal cord once traditional analgesics are no longer effective. They include the drugs ketamine, amantadine, and memantine.

Mechanism of Analgesia The NMDA receptor is located on postsynaptic neurons in the dorsal horn. Nerve injury causes an increase in spinal glutamate, which opens the NMDA channel resulting in a cascade effect that leads to spinal windup. NMDA antagonist agents block the NMDA channel to prevent and elimi nate allodynic and hyperalgesic states that this spinal windup can produce.

Examples of NMDA Antagonist Ketamine Ketamine is an NMDA antagonist and dissocia tive anesthetic that produces a cataleptic state and provides analgesia at subanesthetic doses. A CRI can be used as an adjunct for pain management. Because of its NMDA antagonism at low doses, ketamine can contribute substan tially to analgesia by minimizing CNS sensitiza tion, potentially preventing or eliminating windup pain. It reduces MAC (up to 45% when administered in CRI form at 0.6 mg/kg/h) during general anesthesia and can be used as a part of a multimodal pain management regimen when applicable. Ketamine can provide NMDA antag onism when administered epidurally. When given this route, ketamine has a MAC-sparing effect and postoperative analgesia with minimal respiratory depression and changes in heart rate. Salivation, pupillary dilation, and mild respiratory depression can be seen following

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ketamine administration. Seizures have been reported in up to 20% of cats that receive ket amine at therapeutic doses (Plumb 2011). In addition, ketamine can increase heart rate and increase blood pressure and myocardial oxygen consumption; therefore, it should be avoided in cats with hypertrophic cardiomyopathy or in other patients with unstable shock or congestive heart failure (Plumb 2011). Long-term clinical use is difficult due to the route of administration (CRI) and the psychedelic side effects it can pro duce, including hallucinations. Amantadine Amantadine had been used primarily as an anti viral agent in human patients but recently was discovered to be an effective treatment for severe neuropathic pain conditions. It exerts its anal gesic qualities through antagonism of NMDA receptors similar to ketamine. In one study, amantadine was shown to be a useful adjunct therapy for the clinical management of canine osteoarthritic pain by improving physical activity in these dogs (Lascelles et al. 2008). It also appears to be efficacious in the management of neuropathic types of pain in animals suffering from hyperalgesia and allodynia. The suggested course of treatment in dogs and cats is 3 mg/kg SID for 21 days. Memantine Memantine is a noncompetitive NMDA receptor antagonist, traditionally used in human medicine for the treatment of Alzheimer’s disease. In animal studies, intrathecal memantine was shown to have the greatest potency among the NMDA antagonists (Suzuki 2009). Phantom limb pain is a neuropathic condition that is produced in a number of human patients undergoing limb amputations, but it may also occur in veterinary patients. There have been two case reports that have demonstrated the reduction of phantom limb pain by early administration of memantine (Hackworth et al. 2008). It exhibited multiple advantages over ketamine including


slower elimination half-life, high potency, and reduced risk of side effects (Suzuki 2009). Possible adverse effects may include ataxia, tremors, a prone position, and bradypnea as seen in human patients, but more studies are needed in veterinary patients. Perioperative infusions of ketamine followed by long-term administration of memantine could potentially be employed in the future of neuro pathic pain treatment.

Tramadol Tramadol is a synthetic, weak mu opioid analog that is used for mild to moderate pain. It is used in veterinary medicine to treat conditions such as canine osteoarthritis, diabetic neuropathy, and other neuropathic pain conditions. It is not a true opioid, but does bind weakly to mu opioid receptors causing some opioid-like analgesic activity in cats. In addition to this activity, it also inhibits neuronal reuptake of norepinephrine and serotonin, which is thought to contribute to analgesic activity (Lamont and Mathews 2007). Tramadol’s activity has been attributed to a metabolite of tramadol, O-desmethyltramadol, known as M1. The specific CYP associated with tramadol metabo lism to M1 has not been identified in dogs; so analgesia is likely not related to opioid activity in this species, but rather to its norepinephrine and serotonin reuptake and potential alpha-2 receptor affinity (KuKanich and Papich 2011). Serotonin syndrome is a potentially life-threat ening drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, or overdose of particular drugs. There have been some case reports of animals exhibiting signs of serotonin syndrome when administered tramadol, and it has been docu mented in human medicine when tramadol was administered to patients on antidepressants (SSRIs) or monoamine oxidase inhibitors (MAOIs) (Nelson and Philbrick 2012). Because of this, tramadol should be avoided in veterinary patients already receiving either of these agents.


Gabapentin Gabapentin is a human anticonvulsant drug that was discovered to also possess analgesic qualities several years after it was approved by the FDA. Its MOA is unknown, but it appears to increase central inhibition or reduce synthesis of glutamate. In human medicine, it has been advocated for various neuropathic pain syndromes, incisional pain, and arthritis. In veterinary medicine, it has been adopted for treatment of pain related to osteoarthritis and cancer and also in neuro pathic pain conditions, such as cervical disc disease. Applications for controlling neuro pathic sensations such as burning, itching, pins and needles, and tingling have also been described. Side effects of gabapentin may include drowsi ness, loss of balance, swelling of the limbs, and rarely vomiting or diarrhea.

Amitriptyline Amitriptyline is a tricyclic antidepressant that is used for neuropathic pain in small animals. It can also be used as a behavior modifier for such con ditions as separation anxiety or general anxiety in dogs and cats (Plumb 2011) and for some pru ritus in small animals. When other traditional analgesics have failed to achieve complete anal gesia, the addition of amitriptyline may prove successful in managing refractory chronic pain. Tricyclic antidepressants are contraindicated in patients with seizure disorders, as these agents may lower the seizure threshold.

Maropitant (Cerenia®) Maropitant is a central-acting antiemetic that antagonizes NK-1 receptors in the vomiting center, preventing the binding of substance P. It is used in veterinary medicine as an antinausea and antiemetic agent. However, recent research has shown it to have MAC-sparing qualities, as the role of NK-1 receptor antagonists on visceral

63

nociception has been reported (Laird et al. 2000). This makes maropitant useful perioperatively, not only to reduce opioid-associated nausea and vomiting, but also to reduce MAC when given preoperatively. In one study, maropitant decreased the anesthetic requirements d uring visceral stimulation of the ovary and ovarian ligament in dogs. These results suggest the poten tial role for NK-1 receptor antagonists to manage ovarian and visceral pain (Boscan et al. 2011). Maropitant is thought to provide anti-inflammatory effects through substance P inhibition (Table 5.5).

Constant Rate Infusions Many of the drugs in this chapter can be used in CRI form as a part of a multimodal pain management plan. When drug concentrations are kept more steadily in the therapeutic window, periods of subtherapeutic doses are less likely. The following examples demonstrate the basic steps involved in calculating continuous infusion dosing and dilutions. The most common error in drug administration in veterinary medicine is using the wrong agent or administering at the wrong dose. It is essential that veterinary technicians are able to perform drug calculations, including CRI calculations swiftly and accurately. All syringes containing mixtures of more than one agent should be appropriately labeled with the date, time, initials of person making the combination, and all agents added and placed on the syringe. Typically, any agent in a plastic syringe should be discarded after 24 h and kept out of direct light. When calculating for smaller patients, the dose should be diluted to be deliv ered at a minimum of 1 ml/h to ensure accuracy of delivery and ease of further dosing. For example, a patient is on a lidocaine CRI; the dose can easily be increased by increasing the rate per hour (Table 5.6). Constant rate infusion calculations are covered in Appendix B. Please refer Appendix B to have a better knowledge on these calculations.

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Table 5.5 NMDA antagonists and adjunct analgesic drugs and doses

Agent

Dog

Cat

Gabapentin

2–10 PO q 8–12 h

2–10 PO q 8–12 h

Tramadol

2–10 PO q 12–24 h

?

Maropitant

1 IV, SQ q 24 h

1 IV, SQ q 24 h

Amitriptyline

1–2 PO q 12–24 h

0.5–2 PO q 24 h

Ketamine

0.5 mg/kg IV loading bolus, followed by an infusion of 2–10 µg/kg/min

0.5 mg/kg IV loading bolus, followed by an infusion of 2–10 µg/kg/min

Amantadine

3–5 PO q 24 h

3–5 PO q 24 h

Memantine

0.4 PO q 12 h

?

NMDA antagonists

?

indicates that reliable doses have not been established for this species; all drugs are expressed in mg/kg dose.

Table 5.6 Common analgesic CRIs for IV administration

Agent

Dose

Species

Fentanyl

3–5 µg/kg/h

Dog, cat

Hydromorphone

0.01–0.04 mg/kg/h

Dog, cat

Ketamine

2–10 µg/kg/min

Dog, cat

Lidocaine

10–50 µg/kg/min 10–30 µg/kg/min

Dog Cat

Morphine

0.05–0.1 mg/kg/h

Dog

Dexmedetomidine

0.2–1.0 µg/kg/h

Dog, cat

Butorphanol

0.1–0.2 mg/kg/h

Dog, cat

Methadone

1–2 µg/kg/min a

Dog, cat

Muir 2013, pers. comm.

a


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Management: A Color Handbook, Manson Publishing Ltd, London, UK, p. 78. KuKanich, B. & Papich, M.G. (2011) Pharma cokinetics and antinociceptive effects of oral tramadol hydrochloride administration in Grey- hounds. American Journal of Veterinary Research, 72, 256–262. Laird, J.M.A., Olivar, T., Roza, C., De Felipe, C., Hunt, S.P. & Cervero, F. (2000) Deficits in visceral pain and hyperalgesia of mice with a disruption of the tachykinin NK1 receptor gene. Neuroscience, 98, 345–352. Lamont, L.A. & Mathews, K.A. (2007) Opioids, non-steroidal anti-inflammatories and analgesic adjuvants. In: W.J. Tranquilli, J.C. Thurmon & K.A. Grimm (eds), Lumb & Jones’ Veterinary Anesthesia and Analgesia, 4th edn, Blackwell Publishing, Ames, IA, pp. 241–271. Lascelles, B.D., Blikslager, A.T., Fox, S.M. & Reece, D. (2005) Gastrointestinal tract perforation in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases (2002–2003). Journal of the American Veterinary Medical Association, 227 (7), 1112–1117. Lascelles, B.D., Gaynor, J.S., Smith, E.S., et al. (January– February 2008) Amantadine in a multimodal anal gesic regimen for alleviation of refractory osteoarthritis pain in dogs. Journal of Veterinary Internal Medicine, 22 (1), 53–59. Lemke, K.A. (2007) Anticholinergics and sedation. In: W.W. Tranquill, J.C. Thurmon & K.A. Grimm (eds), Lumb and Jones Veterinary Anesthesia and Analgesia, 4th edn, Wiley/Blackwell Publishing, Ames, IA, p. 210. Matthews, K.A., Paley, D.M., Foster, R.A., Valliant, A.E. & Young, S.S. (1996) A comparison of ketoro lac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs. The Canadian Veterinary Journal, 37, 557–567. Mealey, K. (2013) Common Adverse Drug Reactions in Veterinary Patients. Western Veterinary Conference Proceedings, Las Vegas, NV, February 16–20.


Muir, W.W., Hubbell, J.A., Bednarski, R.M. & Lerche, P. (2013) Handbook of Veterinary Anesthesia, 5th edn. Elsevier/Mosby, St. Louis, MO. Nelson, E.M. & Philbrick, A.M. (2012) Avoiding sero tonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors. The Annals of Pharmacotherapy, 46 (12), 1712–1716. Niedfeldt, R.L. & Robertson, S.A. (2006) Postanesthetic hyperthermia in cats: a retrospective comparison between hydromorphone and buprenorphine. Veterinary Anaesthesia and Analgesia, 33, 381–389. Plumb, D.C. (2011) Veterinary Drug Handbook, 7th edn. Wiley-Blackwell, Ames, IO. Posner, L.P. (2007) Perioperative Hypothermia in Veterinary Patients. NAVC Clinicians Brief, North American Veterinary Community, Gainesville, FL, pp. 19–21. Robertson, S.A. (2013) The Use of NSAIDS in Cats. Proceedings from American Animal Hospital Association, Phoenix, AZ, March 14–17. Schmid, R., Yamashita, M., Ando, K., Tanaka, Y., Cooper, J.D. & Patterson, G.A. (1996) Lidocaine reduces reperfusion injury and neutrophil migration in canine lung allografts. The Annals of Thoracic Surgery, 61 (3), 949–955. Skarda, R.T. & Tranquilli, W.W. (2007). In: W.W. Tranquill, J.C. Thurmon & K.A. Grimm (eds), Lumb and Jones Veterinary Anesthesia and Analgesia, 4th edn, Elsevier Publishing, Ames, IA, pp. 395–418. Sparkes, A.H., Helene, R., Lascelles, B.D. et al. (2010) ISFM and AAFP consensus guidelines: long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery, 12, 519–538. Suzuki, M. (2009) Role of N-methyl-d-aspartate receptor antagonists in postoperative pain management. Current Opinion in Anesthesiology, 22, 618–622. Wanamaker, B.P. & Massey, K.L. (2004) Applied Pharmacology for the Veterinary Technician, 3rd edn. Saunders Publishing, St. Louis, MO.

Locoregional Analgesic Blocking Techniques

c h a p t e r

6

Mary Ellen Goldberg, Nancy Shaffran, Kim Spelts, David Liss, Tasha McNerney, Trish Farry, Samantha Rowland, and Jennifer L. Dupre

Introduction Blocking the transmission of painful signals via nerve fibers is one of the most effective ways of managing pain. Local anesthetics are inexpensive yet quite effective in blocking the transmission of nociceptive signals (nerve impulses) at their source. Disrupting neural transmission of pain information results in diminished signaling to the spinal cord with a likely reduction in further neuropathic pain. Local anesthetics inhibit generation and transmission of nerve impulses by blocking sodium channels in the neuron’s cell membrane. This slows the rate of depolarization of the neuron cell membrane and prevents the threshold potential from being reached. Use of local anesthetics offers a number of benefits. First, local anesthetics produce true analgesia resulting in the complete absence of pain for the duration of the block. Second, long-term (chronic) pain states may be diminished or eliminated. Thirdly, these drugs are nonscheduled agents, so there’s no cumbersome paperwork or special license required. Finally, the techniques

used to administer these drugs are relatively easy to perform. When administered at an appropriate dose, local anesthetics have relatively few, if any, adverse side effects. The potential systemic side effects of local anesthetics involve the central nervous system and cardiovascular system (Skarda and Tranquilli 2007c). Other potential side effects include development of methemoglobinemia, nerve and skeletal muscle toxicities, and allergic reactions, including hypersensitivity or anaphylactic responses (Skarda and Tranquilli 2007c) (Table 6.1). Use of local anesthetics has become more common in small animal practice in recent years. Local anesthetics can be used very effectively in a number of procedures, including thoracotomy, elbow surgery, maxillomandibular procedures, local incisions, feline declawing, regional blockades, rear limb procedures, and stifle surgery. There are several blocking agents available. Choice of blocking agent is typically made based on onset of action, duration of action, and route of administration. (Specific information on blocking agents is available in Chapter 5.)


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Table 6.1 Short- and long-term local anesthetics

Drug

Onset (min)

Duration (h)

Lidocaine

10–15

1–2

Mepivacaine

5–10

2–2.5

Bupivacaine

15–20

2.5–6

Ropivacaine

5–15

2.5–4

3. Insert needle subcutaneously across paw to cover entire top surface. 4. After aspirating, slowly withdraw needle while injecting ¼ total volume to form a line. 5. Repeat on underside of forepaw just above the accessory carpal pad (Figures 6.1 and 6.2). 6. Change needle. 7. Repeat procedure on opposite side. 8. Massage forepaw gently to distribute local anesthetic.

The faster the absorption rate, the shorter the duration of action and the greater the risk of systemic toxicity.

Mandibular Nerve Block: Small Animal

Companion Animal Techniques

The mandibular nerve block is an extremely effective way to manage pain involving the mandible in both dogs and cats. Pain may be due to dental extractions, fracture repair, or other surgical procedures. Injections are made around the mandibular nerve just prior to its entry into the mandibular foramen on the inner surface of the mandible. This technique provides nerve block to the either lower quadrant of the jaw sufficient to eliminate pain for up to 8 h. In cats, the maximum dosage is 1 ml of 0.5% bupivacaine per 5 kgs of body weight; however, most cats will only require about 0.1–0.2 ml per injection site. In dogs, up to

Circumferential Block for Feline Onychectomy (Declaw) Circumferential ring block is an extremely easy, inexpensive, and effective way to manage postoperative pain for cats undergoing onychectomy. This block can also be utilized for dogs undergoing procedures to the paws including cauterizing nail trims. Injections are made just above the carpal bend on the top side of the paw and just above the accessory carpal pad on the underside. This 4-injection technique provides regional nerve block sufficient to eliminate pain for up to 8 h postsurgery. In cats, the dosage is 1 ml of 0.5% bupivacaine per 5 kgs of body weight divided equally among the injection sites. Sterile saline can be added to achieve sufficient coverage for smaller cats. In dogs, up to 2 ml per 5 kg of body weight can be used. Equipment • 1 ml syringe • 25 gauge 1″ needles × 2 • 0.5% bupivacaine Procedure (Tranquilli et al. 2000; Muir 2002) 1. Draw full volume of local block into syringe. 2. Tent skin horizontally across the top of the forepaw just above the carpal bend.

Figure 6.1 Needle placement on the forepaws for a circumferential block. Source: Courtesy of Nicole Valdez.

Chapter 6 Locoregional Analgesic Blocking Techniques

Figure 6.2 Needle placement on the forepaws for a circumferential block. Source: Courtesy of Nicole Valdez.

2 ml per 5 kg of body weight can be used, but this maximum volume is rarely required to achieve full effect. In practice, typically 0.1 ml per 5 kg per site is generally sufficient volume for mandibular blockade in both dogs and cats. An epinephrine wash is recommended to control bleeding from extractions. The syringe is simple rinsed with epinephrine prior to drawing up bupivacaine.

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3. Identify the mandibular notch on the external surface of the jaw with the same hand that will later hold the syringe. 4. Insert forefinger from the opposite hand into the mouth, and slide along the inner surface of the mandible until the two finger tips touch. 5. Using the internal finger, strum gently across the mandible feeling for the mandibular nerve, which is round and firm much like a guitar string. 6. Once the nerve is palpated, hold it firmly under the fingertip of the internal finger. 7. Take the external finger away and pick up syringe. 8. Insert syringe from the exterior surface just under the mandible into the gingival tissue where the mandibular nerve is located. Do not attempt to inject into the nerve, but rather bathe the area around it. The needle tip can be guided by the internal fingertip. 9. After aspirating, slowly inject anesthetic around the nerve until a bleb is formed. 10. Withdraw needle and keep pressure on bleb for several seconds. 11. Change needle and repeat procedure on opposite side if indicated (Figure 6.3).

Equipment • 1 ml syringe • 25 gauge 1″ needles × 2 • 0.5% bupivacaine Procedure (Tranquilli et al. 2000; Muir 2002) 1. Wash syringe with epinephrine if desired. 2. Draw full volume of local block into syringe.

Figure 6.3 Needle placement on a skull and on an anesthetized dog. Source: Courtesy of Kristen Cooley.

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Infraorbital Nerve Block The infraorbital nerve block provides analgesia (intra- and postoperative) for maxillary canine, molar, and premolar extractions. It also provides analgesia to the area around the upper lips and nares. Infraorbital blocks anesthetize the upper lip, nose, roof of the nasal cavity, and skin as far caudal as the infraorbital foramen. The maxillary incisors are inconsistently blocked with this technique, particularly in dogs. This block should be performed cautiously in brachycephalic dogs and cats (e.g., Himalayans, Persians) because of the proximity of the ocular orbit to the foramen and the potential for penetrating the globe (Egger and Love 2009b). The infraorbital artery and vein travel with the nerve within the canal. These should be avoided when injecting local anesthetic (Tranquilli et al. 2004a).


increased chance of lacerating the nerve. In small animals or brachycephalic breeds, placement can be just at the entrance to the infraorbital foramen. 4. Elevate the head, and aspirate before injection. 5. Apply digital pressure over the foramen as local anesthetic is injected slowly to facilitate its movement caudally into the foramen. 6. Remove needle and maintain pressure over the foramen for several seconds (Figures 6.4 and 6.5).

Equipment (Ko and Inoue 2013) A combination of 0.5 ml 2% lidocaine and 0.5 ml 0.5% bupivacaine dosed at 0.15/4.5 kg. This combination takes advantage of the fast onset of action of lidocaine (3–5 min) and the longer duration of action (6–8 h) of bupivacaine. • 1 ml syringe. • A 25–29 gauge, 1–1.5 in. needle should be used. • Lidocaine with epinephrine (1:100,000) may be used to prolong the duration of the effect.

Figure 6.4 Needle placement on a skull and on an anesthetized dog. Source: Photo courtesy of Kristen Cooley.

Procedure (Beckman 2013; Gracis 2013) 1. The upper lip is raised to expose the teeth and soft tissue. 2. The infraorbital foramen is palpated through the buccal mucosa dorsal to the upper third molar. 3. The needle is inserted, either percutaneously or directly through the buccal mucosa, into the foramen and advanced 1–2 mm. Advancing the needle farther into the foramen is not recommended because of

Figure 6.5 Needle placement on a skull and on an anesthetized dog. Source: Photo courtesy of Vickie Byard.

Chapter 6 Locoregional Analgesic Blocking Techniques

Mental Nerve Block Blocking the mental branch of the mandibular nerve as it exits the largest and most rostral of the mental foramina anesthetizes the lower incisors and skin and tissues rostral to the foramen (Egger and Love 2009b). Indications are to provide intra- and postoperative analgesia for mandibular canine, molar, and premolar tooth extractions. Analgesia also extends to the lower lip (Ko and Inoue 2013). The foramina are located on the lateral aspect of the mandible, ventral to the third premolar tooth, ventral to the mesial root of the second premolar tooth, and ventral to the first incisor tooth. In cats, the middle mental foramen is located equidistant between the third premolar tooth (the first tooth after the canine tooth in cats) and the canine tooth, under the lip frenulum, at midheight of the mandible (Gracis 2013).

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nose, and upper lip. These blocks can be a valuable component of the analgesia plan for surgery of the nose and maxilla. To block the maxillary nerve, the needle is placed transcutaneously along the ventral border of the zygomatic arch and directed toward the maxillary foramen. To block the infraorbital nerve, which is the nerve supplying sensory innervation to the rostral portion of the maxilla, local anesthetic is (a)

Equipment (Gracis 2013) • • • •

Disposable or sterile gloves as needed Local anesthetic solution 1.0–2.5 ml aspirating syringes 25–27 gauge extrashort or short needle

Note that if the needle is inserted into the foramen, it may be advisable to use a 27–30 gauge needle. Procedure (Beckman 2013) 1. Palpate the mental foramen on the lateral aspect of the mandible just caudal to the canine tooth. 2. Insert the needle into the mental foramen. 3. Aspirate for blood. 4. Inject a small amount of local anesthetic (usually 4 h

Butorphanol

Nalorphine Lidocaine 1–2%

Local infiltration or mixed in gel for superficial use

Local anesthetic; use with caution


340

341

Appendix A: Formulary

Drug

Dose (mg/kg)

Route

Dose Interval

Comment

Ketorolac

26

Dorsal lymph sac

Dexmedetomidine

*40–120

Dorsal lymph sac

*> 4 h

*ED50 in leopard frog (R. pipiens)

Xylazine

10

Intracoelomic

q12–24 h

Codeine

53

Unspecified

>4 h

References Carpenter, J.W. & Marion, C.J. (2013a) Exotic Animal Formulary, 4th edn. Elsevier/Saunders, St. Louis, MO. Goldberg, M. (2010a) The “fourth vital sign” in all creatures great and small. The NAVTA Journal, 31–54. Stevens, C. (2004) Opioid research in amphibians: an alternative pain model yielding insights on the

*ED50 in leopard frog (R. pipiens)

evolution of opioid receptors. Brain Research. Brain Research Reviews, 46 (2), 204–215. Stevens, C. (2011) Analgesia in Amphibians, Elsevier Inc., Tulsa, OK, pp. 33–44. West, G., Heard, D. & Caulkett, N. (2007a) Zoo Animal and Wildlife Immobilization and Anesthesia, 1st edn. Wiley-Blackwell, Ames, IA.

Appendix A.II Analgesia for Birds (Longley 2008; Carpenter 2013) Drug

Species

Dose (mg/kg)

Route

Dosing Interval

Comment

Bupivacaine

Ducks and chickens

2

SC, IA; topical, IM, SC

Not known 4–6 h in mammals

Dilute 1:10 or more

Lidocaine

All

1.0–3.0

90–200 min in mammals

Small birds dilute 1:10

Dexamethasone

Most species

0.2–4.0

IM, IV

12–24

Anti-inflammatory, shock, trauma, may affect immune competency

Carprofen

All

2.0–4.0

PO, IM, IV, SC

8–12

Doses 90 days; self-mutilation; no adverse effects

Bald Eagles Peafowl Red–tailed Hawk Amazon parrot

5 7.5 8-11 30

PO, IV PO PO PO

12 12 6

Sedation evident after multiple dosing

Gabapentin

Tramadol

Key: IM, intramuscular; IV, intravenous; PO, oral; SC, subcutaneous; IA, intra-articular.

Longley, L.A. (2008a) Avian anaesthesia. Anaesthesia of Exotic Pets, Saunders/Elsevier, London, p. 162.

References Carpenter, J.W. (2013) Birds. Exotic Animal Formulary, 4th edn, Elsevier, St. Louis, MO, pp. 256–281.

Appendix A.III Analgesia for Camelids Continuous rate infusions for camelids (Plummer and Schleining 2013a) CRI Trifusion

Dose

Route

Frequency

Butorphanol

0.05–0.1 mg/kg

IV, IM

Loading dose

0.022 mg/kg/h

IV

CRI

1.0 mg/kg

IV

Loading dose

Lidocaine

Comments

Administer slowly

343


CRI Trifusion

Dose

Route

Frequency

3.0 mg/kg/h

IV

CRI

0.6 mg/kg/h

IV

CRI

No loading dose needed

Morphine

0.025 mg/kg/h

IV

CRI


Lidocaine

1.0 mg/kg

IV

Loading dose

Administer slowly

3.0 mg/kg/h

IV

CRI

0.6 mg/kg/h

IV

CRI

Ketamine

Comments

Or

Ketamine


References Plummer, P.J. & Schleining, J.A. (2013a) Assessment and management of pain in small ruminants and camelids. Veterinary Clinics of North America: Food Animal Clinics, 29 (1), 185–208.

Analgesia for camelids (Plummer and Schleining 2013; Shaffran and Grubb 2010) Drug Class/Drug

Dosage (mg/kg)

Route

Dosing Interval

Comments

Morphine

0.05–0.1

IV, IM

q4 h

Inject slowly if IV

Butorphanol

0.01–0.02

IM, IV

q2–3 h

Shaffran and Grubb (2010)

0.05–0.1

IV, IM

q4–6 h

Plummer and Schleining (2013)

Fentanyl

150–225 µg/kg/h

Transdermal

Place new patch q48 h


Buprenorphine

0.01 mg/kg

IV, IM

4–6 mg/kg

PO

2–4 mg/kg

IV

Opioid


NSAIDS Phenylbutazone

q24–48 h


(Continued)

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Drug Class/Drug

Dosage (mg/kg)

Route

Dosing Interval

Comments

Flunixin meglumine

1.0 mg/kg

PO, IV, IM

q12–24 h


1.1 mg/kg

IV

q8 h


Ketaprofen

2–3 mg/kg

PO, IV, IM, SQ

q24 h


Carprofen

0.7 mg/kg

IV

q24–48 h


Meloxicam

1.0 mg/kg

PO

q3d


0.5 mg/kg

IV

0.2–0.4 mg/kg

IV, IM

Alpacas are more resistant than llamas and should be dosed at 0.3–0.6 mg/kg IV, IM

0.1 mg/kg

Epidural


0.01–0.03 mg/kg

IV, IM

q2–4 h


Lidocaine 2%

As needed for tissue infiltration; total dose ≤ 5 mg/kg 0.2–0.4 mg/kg 0.1 mg/kg 1 ml/22.67 kg

Tissue Epidural IA Epidural

q1–3 h q1–3 h q1–3 h

Shaffran and Grubb (2010) Plummer and Schleining (2013)

Bupivicaine

As needed for tissue infiltration; total dose ≤ 2 mg/kg

Tissue

q4–6 h


Tramadol

2.0 mg/kg

IV, IM

q2–3 h


Gabapentin

8000–11,000 mg total

PO

q12 h

Personal communication with AZVT

Alpha-2-agonists Xylazine

Medetomidine Local anesthetics

Other

References Plummer, P.J. & Schleining, J.A. (2013b) Assessment and management of pain in small ruminants and camelids. Veterinary Clinics of North America: Food Animal Clinics, 29 (1), 185–208.

Shaffran, S. & Grubb, T. (2010) Pain management. J.M. Bassert & D.M. McCurnin (eds), McCurnin’s Clinical Textbook for Veterinary Technicians, 7th edn, Elsevier, St. Louis, MO, pp. 858–886.

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Appendix A.IV Analgesics for cattle Drug

Dose (mg/kg)

Route

Dose Interval (h)

Species

Morphine

0.05–0.5 0.1 Loading dose: 0.1 mg/kg 0.025 mg/kg/h

IM,IV Epidural IV CRI IV

q6 h q6–12 h q1 h

Cattle Cattle (diluted with 0.02–0.05 ml/kg of saline CRI

Meperidine

3.3–4.4

IM, SC

q0.25–0.5 h

Cattle

Butorphanol

0.05–0.2 Loading dose: 0.02–0.05 0.022 mg/kg/h

IM, IV IM, IV IV

q1–3 h

Cattle

q1 h

CRI

Buprenorphine

0.0015–0.006

IM, IV

q4–6 h

Cattle

Oxymorphone

0.005

IM

q4 h

Cattle

Xylazine

0.05–0.2 0.05

IM, IV Epidural

q2–4 h q2 h

Cattle cattle (diluted to 5 ml with sterile saline)

Detomidine

0.003-0.01 0.04

IM, IV Epidural

q2-4h q3h

Cattle cattle (diluted with 5 ml sterile saline)

Medetomidine

0.005–0.01 0.015

IM, IV Epidural

q2–4 h q7 h

Cattle cattle (diluted to 5 ml with sterile saline)

Romifidine

0.003–0.02 0.05

IM, IV Epidural

q2–4 h up to 12

Cattle Combine with morphine 0.1 mg/kg

Lidocaine

0.2–0.4 0.2–0.4 Loading dose 1 mg/kg 50 µg/kg/min

Infiltration Epidural CRI IV

q1–2 h q1–2 h q1 h

Cattle Cattle CRI

Bupivacaine

0.05

Epidural

q2–3 h

Cattle

Meloxicam

0.5

IV, SC

q27 h

Not approved in cattle

Flunixin meglumine

1.0

IV

q3–8 h

Cattle

Carprofen

1.4

IV, SC

30

Detomidine

10–40 µg

5–10

60

Gel 1 ml per 125–200 kg

35–45 (transmucosal)

Romifidine

0.1

5–10

>120

Dexmedetomidine

3.5 µg

5

60

Medetomidine

5 µg

5

60

Drug

Dosage per kg of body weight

Onset (min)

Duration (min)

Epidural Lidocaine

0.35 mg

5–10

Up to 120

Bupivacaine

0.06–0.08 mg

30–45

80–240

Xylazine

0.1–0.3 mg

5–10

Up to 226

Morphine

0.1 mg

20–30

18–24

Tramadol

0.5 mg

35–45

60

Ketamine

0.5–1 mg

Drug


Drug


Opioids Butorphanol

10–50 µg

NSAIDs Phenylbutazone

4.4 mg (IV & PO BID-TID)

351


Drug


Drug


Buprenorphine

6 µg

Flunixin meglumine

1.1 mg (SQ? IV TID)

Morphine

0.1–0.3

Meloxicam

0.6 mg (IV)

Carprofen

0.7 mg (IV & PO SID) 2 mg, then 1 mg (IV & PO BID)

Other Ketamine

0.4–0.6 mg

Vedoprofen

Tramadol

2.5 IV (7.5 PO)

Firocoxib

CRI Combinations for Donkeys Butorphanol: 0.02–0.04 mg/kg/h + Lidocaine: 1.5 mg/ kg/h + Ketamine: 0.4–0.6 mg/kg/h Propofol: 12 mg/kg/h + Dexmedetomidine TIVA 2 µg/kg/h Detomidine: 8–10 µg/kg/h + Lidocaine 1.5 mg/kg/h + Ketamine 0.4–0.6 mg/kg/h Medetomidine: 3 µg/kg/h

References Alkattan, L.M. (2012) Analgesia and anesthesia with epidural xylazine/ketamine in donkeys. Diagnostic and Therapeutic Study, 1 (2), 37–44. Amin, A.A., Ali, A.F. & Mutheffer, E.A. (2012) Biochemical changes induced by general anesthesia with romifidine as a premedication, midazolam and ketamine induction and maintenance by infusion in donkeys. Iraqi Journal of Veterinary Sciences, 26 (Suppl II), 19–22. Coakley, M., Peck, K.E., Taylor, T.S., Matthews, N.S. & Mealy, K.L. (1999) Pharmacokinetics of flunixin meglumine in donkeys, mules and horses. American Journal of Veterinary Research, 60, 1441–1444. Faleiros, R., Alves, G., Andrade, V. et al. (2004) Epidural analgesia with tramadol and morphine in a donkey with oncologic pain. Journal of Veterinary Emergency and Critical Care Society, 14, S1–S17. Giorgi, M., Del Carlo, S., Sgorbini, M. & Saccomanni, G. (2009) Pharmacokinetics of tramadol and its metabo-

lites M1, M2 and M5 in donkeys after intravenous and oral immediate release single-dose administration. Journal of Equine Veterinary Science, 29, 569–574. Grosenbaugh, D.A., Reinemeyer, C.R. & Figueiredo, M.D. (2011) Pharmacology and therapeutics in donkeys. Equine Veterinary Education, 23, 523–530. Joubert, K.E., Briggs, P., Gerber, D. et al. (1999) The sedative and analgesic effects of detomidine-butorphanol and detomidine alone in donkeys. Journal of the South African Veterinary Association, 70 (3), 112–118. Lizarraga, I. & Beths, T. (2012) A comparative study of xylazine-induced mechanical hypoalgesia in donkeys and horses. Veterinary Anaesthesia and Analgesia, 39, 533–538. Lizarraga, I. & Janovyak, E. (2013) Comparison of the mechanical hypoalgesic effects of five alpha2-adrenoceptor agonists in donkeys. Veterinary Record, 173 (12), 294. Lizarraga, I., Sumano, H. & Brumbaugh, G.W. (2004) Pharmacological and pharmacokinetic differences between donkeys and horses. Equine Veterinary Education, 6, 130–144. Makady, F.M., Seleim, S.M., Seleim, M.A. & AbdelAll, T.S. (1991) Comparison of lidocaine and xylazine as epidural analgesics in donkeys. Assiut Veterinary Medical Journal, 25, 189–195. Matthews, N.S. (2010) Donkey anesthesia and analgesia—not just small horses. In: NAVC Conference, January, Orlando, FL, pp. 208–210. Matthews, N.S. & Van Dijk, P. (2004) Anesthesia and analgesia for donkeys. In: N.S. Matthews & T.S. Taylor (eds), Veterinary Care of Donkeys. International Veterinary Information Service, Ithaca, NY.

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Matthews, N.S., Grosenbaugh, D., Kvaternick, T. et al. (2009) Pharmacokinetics and oral bioavailability of firocoxib in donkeys. Abstracts presented at the 10th World Congress of Veterinary Anaesthesia, 31st August–4th September 2009, Glasgow, UK. Veterinary Anaesthesia and Analgesia, 37, 13. Mealey, K.L., Matthews, N.S., Peck, K.E. et al. (1997) Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys. American Journal of Veterinary Research, 58 (1), 53–55. Mealey, K.L., Matthews, N.S., Peck, K.E., Burchfield, M.L., Bennett, B.S. & Taylor, T.S. (2004) Pharmacokinetics of R(–) and S(+) carprofen after administration of racemic carprofen in donkeys and

horses. American Journal of Veterinary Research, 65, 1479–1482. Mostafa, M.B., Farag, K.A., Zomor, E. & Bashandy, M.M. (1995) The sedative and analgesic effects of detomidine (domosedan) in donkeys. Journal of Veterinary Medicine Series A, 42, 351–356. Portier, K., Jaillardon, L., Leece, E. et al. (2009) Castration of horses under total intravenous anaesthesia: analgesic effects of lidocaine. Veterinary Anaesthesia and Analgesia, 36, 173–179. Sarrafzadeh-Rezaei, F., Rezazadeh, F. & Behfar, M. (2007) Comparison of caudal epidural administration of lidocaine and xylazine to xylazine/ketamine combination in donkey (Equus asinus). Iranian Journal of Veterinary Surgery, 2 (5), 7–15.

Appendix A.VII Analgesics for Elephants Drug

Dose

Determining method

Ketoprofen

1–2 mg/kg q24–48 h PO or IV

Pharmacokinetics

Butorphanol

0.015 mg/kg IV or IM q24 h

Pharmacokinetics

Phenylbutazone

1–2 mg/kg q 24 h 4 mg/kg q12 h

Empirical Metabolic

Flunixin

1 mg/kg q24 h 0.7 mg/kg q40 h

Empirical Metabolic

Ibuprofen

0.5–4.0 mg/kg q24 h

Empirical

References Fowler, M. (2007) Zoo and Wild Animal Medicine Current Therapy, 6th edn. Saunders, St. Louis, MO. Fowler, M. & Mikota, S. (2006) Biology, Medicine and Surgery of Elephants. Blackwell Publishing, Ames, IA.

West, G., Heard, D. & Caulkett, N. (2007b) Zoo Animal and Wildlife Immobilization and Anesthesia, 1st edn. Wiley-Blackwell, Ames, IA.

353


Appendix A.VIII Ferret Analgesia Drug

Dose

Route

Dose Interval

Butorphanol

0.2–0.8

SC, IM, IV

q2–4 h

0.1–0.2 mg/kg/h

CRI

0.2–2.0

IM

Single dose

0.25–1

IM, SC, IV

q3–4 h

0.1

Epidurally

Hydromorphone

0.025–0.1

SC, IM, IV

q6–8 h

Occasional vomit; bradycardia and respiratory depression may occur

Fentanyl

4–10 µg/kg

IM, IV

q30 min

Bradycardia and respiratory depression may occur

20–30 µg/kg/h IV

CRI

During anesthesia to reduce volatile inhalant concentrations

1–4 µg/kg/h IV

CRI

For analgesia

Oxymorphone

0.05–0.2

SC, IM, IV

q6–8 h

Meperidine

5–10

IM, SC

q2–4 h

Buprenorphine

0.01–0.02

SC, IM, IV

q6–8 h

0.01–0.03

IV, IM, SC, transmucosal (TM)

q6–10 h

Tramadol

5

PO

q12 h

Medetomidine

0.02–0.04

IM, SC, IV

30–60 min

Dexmedetomidine

0.01–0.03

SC, IM, IV

30–60 min

Xylazine

1–2

IM

30–50 min

Ketamine

0.5

IV before surgery

Morphine

Comments

May vomit; bradycardia may occur with doses higher than 0.5 mg/kg

(Continued)

354

Drug


Dose

Route

Dose Interval

10 µg/kg/min

IV CRI during surgery

For 24 h

2 µg/kg/min

IV CRI

Postoperatively

Ketoprofen

1–2

SC, IM, IV, PO

q24 h

Carprofen

2–4

SC, IM, IV, PO

q24 h

Meloxicam

0.2

SC, IM, IV, PO

q24 h

Lidocaine

2

Locally

60 min

4.4

Epidurally

1

Local infiltration

1.1

Epidurally

2

Local infiltration

Bupivacaine

Mepivacaine

Comments

q4–6 h

q2–3 h

Reference Goldberg, M.E. (2010c) The fourth vital sign in all creatures great and small. The NAVTA Journal, 31–54.

Injectable drugs administered as constant-rate-infusions used for perioperative and postoperative analgesia in ferrets (Hawkins and Pascoe, 2012) Drug

Dosage

Comments

Butorphanol

Loading dose: 0.05–0.2 mg/kg

Less respiratory depression than with fentanyl

Maintenance: 0.1–0.4 mg/kg/h Fentanyl citrate

Loading dose: 5–10 µg/kg IV

Perioperative CRI

Maintenance: 10–30 µg/kg/h IV

Postoperative analgesia

1.25–5.0 µg/kg/h

Combine with ketamine CRI to reduce overall doses

355


Drug

Dosage

Comments

Ketamine

Loading dose: 2–5 mg/kg IV

More useful when intubation is not possible because there is less respiratory depression than with opioids

Perioperative CRI

Maintenance: 0.3–1.2 mg/kg/h IV

Postoperative analgesia

0.1–0.4 mg/kg/h

Can be combined with fentanyl to reduce overall doses of both drugs

If using for postoperative analgesia only, a loading dose should be used. Gradually wean from postoperative CRI over 12–24 h. Species and individual variation in response to a drug or combination of drugs can be uncertain, so the dosage should be adjusted depending on the clinical response of the animal.

Reference Hawkins, MG and Pascoe, PJ. 2012a. Anesthesia, analgesia and sedation of small mammals.

Quesenberry KE and Carpenter JW (eds). Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery, 3rd edn. Elsevier/Saunders. St. Louis, MO, pp. 429–451.

Appendix A.IX Analgesia for Fish Drug

Dose (mg/kg)

Route

Comments

Butorphanol

0.1–0.4

IM

q24 h

Carprofen

2–4

IM

q3–5 days

Flunixin meglumine

0.25–0.5

IM

q3–5 days

Ketoprofen

2

IM

Meloxicam

0.1–0.2

IM

Morphine

0.3

IM

Tramadol

5–10

PO

q48–72 h

Lidocaine

Do not exceed 1–2 mg/kg total dose

Infiltrate

Local anesthesia

q24–48 h

356


Reference Goldberg, M.E. (2010d) The fourth vital sign in all creatures great and small. The NAVTA Journal, 31–54.

Appendix A.X Analgesia for Horses Dosages of NSAIDS Drug

Dose

Duration

Flunixin meglumine

0.25–1.1 mg/kg IV or PO

6–12 h

Phenylbutazone

2.2–4.4 (up to 6) mg/kg IV or PO

Up to 14 h

Ketoprofen

2.2–3.6 mg/kg IV or IM

6–24 h

Diclofenac (1%)

5″ strip of cream applied over affected joints

Firocoxib

0.3 mg/kg PO loading dose then 0.1 mg/kg PO

24 h for PO

0.09 mg/kg IV

24 h for IV

Meloxicam

0.6 mg/kg IV or PO

12–24 h

Carprofen

0.7 mg/kg IV or 1.4 mg/kg PO

24 h for PO/IV

Vedaprofen

2 mg/kg PO then 1 mg/kg PO

12 h

References Davis, J. (2009) Equine pharmacology. In: D. Reeder, S. Miller, D. Wilfong, M. Leitch, D. Zimmel (eds), AAEVT’S Equine Manual for Veterinary Technicians, Wiley-Blackwell, Ames, IA, pp. 165–187. Driessen, B., Bauquier, S.H. & Zarucco, L. (2010) Neuropathic pain management in chronic laminitis. Veterinary Clinics of North America: Equine Practice, 26, 315–337.

Michou, J. & Leece, E. (2012a) Sedation and analgesia in the standing horse 1. Drugs used for sedation and analgesia. Practice/Equine Practice, 34, 524–531. van Weeren, P.R. & de Grauw, J. (2010) Pain in osteoarthritis. In: W. Muir (ed), Pain in Horses: Physiology, Pathophysiology and Therapeutic Implications. Veterinary Clinics of North America: Equine Practice, W.B. Saunders, Philadelphia, PA, pp. 619–642.

357


Common non-NSAID analgesics in the horse Drug

Dose Range

Butorphanol

0.01–0.02 mg/kg IV 0.01–0.02 mg/kg/h CRI

Morphine

0.05–0.3 mg/kg IV or IM 0.03–0.1 mg/kg/h CRI

Meperidine

1–2 mg/kg IM 0.5–1 mg/kg IV

Fentanyl

0.002–0.005 mg/kg IV 0.005–0.01 mg/kg/h CRI

Methadone

0.05–0.2 mg/kg IV or IM

Buprenorphine

10–20 µg/kg IV

Ketamine

2–2.5 mg/kg IV loading dose 0.5–3 mg/kg/h CRI anesthesia adjunct 0.5–1.5 mg/kg/h CRI standing analgesia

Lidocaine

1.3–2 mg/kg IV loading dose 3 mg/kg/h

Xylazine

0.5–1.1 mg/kg IV 0.65 mg/kg/h

Detomidine

0.01–0.04 mg/kg IV or IM 0.01–0.02 µg/kg/min CRI 0.04 mg/kg PO (gel)

Romifidine

0.04–0.12 mg/kg IV

Medetomidine

5–20 µg/kg IV or IM 3.5 µg/kg/min CRI

References Clutton, E. (2010) Opioid analgesia in horses. In: W. Muir (ed), Physiology, Pathophysiology and Therapeutic Implications. Veterinary Clinics of North America: Equine Practice: Pain in Horses, W.B. Saunders, Philadelphia, PA, pp. 493–514.

Lerche, P. & Muir, W. (2009) Perioperative pain management. In: W. Muir & J. Hubbell (eds), Equine Anesthesia Monitoring and Emergency Therapy, 2nd edn, Saunders Elsevier, St. Louis, MO, pp. 369–378. Michou, J. & Leece, E. (2012b) Sedation and analgesia in the standing horse 1. Drugs used for sedation and analgesia. In Practice, 34, 578–587.

358


Muir, W. (2010) NMDA receptor antagonists and pain: ketamine. In: W. Muir (ed), Physiology, Pathophysiology and Therapeutic Implications. Veterinary Clinics of North America: Equine Practice: Pain in Horses, W.B. Saunders, Philadelphia, PA, pp. 565–578. Nann, L. (2010) Equine anesthesia. In: S. Bryant (ed), Anesthesia for Veterinary Technicians, WileyBlackwell, Ames, IA, pp. 357–371. Robertson, S. & Sanchez, L. (2010) Treatment of visceral pain in horses. In: W. Muir (ed), Physiology,

Pathophysiology and Therapeutic Implications. Veterinary Clinics of North America: Equine Practice: Pain in Horses, W.B. Saunders, Philadelphia, PA, pp. 603–618. Yamashita, K. & Muir, W. (2009a) Intravenous anesthetic and analgesic adjuncts to inhalation anesthesia. In: W. Muir & J. Hubbell (eds), Equine Anesthesia Monitoring and Emergency Therapy, 2nd edn, Saunders Elsevier, St. Louis, MO, pp. 260–276.

Triple drip maintenance combinations Drugs

Respective Dose Ranges

Ketamine + Guaifenesin + Xylazine

1–2 mg/ml + 50 mg/ml + 0.5 mg/ml at 1–1.5 ml/kg/h PRN

Ketamine + Xylazine

35–70 µg/kg/min + 90–150 µg/kg/min

Xylazine + Ketamine + Diazepam then Ketamine + Xylazine

1.1 mg/kg + 2.2 mg/kg + 0.06 mg/kg then 0.25 mg/ kg + 0.25 mg/kg PRN

2nd edn, Saunders Elsevier, St. Louis, MO, pp. 260–276.

Reference Yamashita, K. & Muir, W. (2009b) Intravenous anesthetic and analgesic adjuncts to inhalation anesthesia. In: W. Muir & J. Hubbell (eds), Equine Anesthesia Monitoring and Emergency Therapy,

Appendix A.XI Analgesia for Invertebrates Agent

Dose

Comment

Ketamine

0.025–0.1 mg/kg

Anesthesia within 15–45 s

90 µg/g IM

Duration ≤ 1 h

Lidocaine

30 µg/g IM

Injected intrathoracically; duration 25 mins

Procaine

25 mg/kg

Anesthesia within 20–30 s, duration 2–3 h

Xylazine HCl

70 mg/kg

Anesthesia within 5–6 min, duration 45 min

359


Agent

Dose

Comment

16–22 mg/kg

Anesthesia within 2–3 min

3% (30.0 ml/l)

Induction

1.5% (15 ml/l) ethanol in seawater

Anesthetic maintenance

Isoflurane

5–10%

Anesthesia of terrestrial invertebrates

Sevoflurane

5–10%


CO2

10–20%


MS-222

100 mg/1 l of water

Buffering MS-222 with the addition of sodium bicarbonate is recommended for use in invertebrates with sensitive skin, such as snails and slugs

MS-222 and benzocaine

0.4 g/l

In seawater for both chemicals

Gramine

0.01 mg/ml

Serotonin antagonist inhibits pumping

Imipramine

20 µg/ml

Stimulates pumping; high concentration act as anesthetic

Ivermectin

0.05 ng/ml

Inhibits pumping

Muscimol

2 µg/ml

This GABA agonist inhibits pumping

Serotonin

1 mg/ml

Stimulates pumping

Ethanol

Reference Goldberg, M.E. (2010e) The fourth vital sign in all creatures great and small. The NAVTA Journal, 31–54.

Appendix A.XII Analgesia for Miscellaneous Small Mammals Species

Drug

Dose (mg/kg)

Route

Dose Interval

Hamsters

Morphine

2–5

SC, IM

q2–4 h

Aspirin

100

PO

q4–8 h (Continued)

360

Species

Gerbil

Chinchilla


Drug

Dose (mg/kg)

Route

Dose Interval

Buprenorphine

0.05–0.1

SC

q6–12 h

Butorphanol

1–5

SC

q4 h

Carprofen

5

SC

q24 h

Flunixin

2.5

SC

q12–24 h

Ketoprofen

5

SC

q12–24 h

Nalbuphine

4–8

IM

q3 h

Oxymorphone

0.2–0.5

SC, IM

q6–12 h

Meperidine

20

SC, IM

q2–4 h

Aspirin

100

PO

q4–8 h

Butorphanol

1–5

SC

q4 h

Carprofen

5

SC

q24 h

Flunixin

2.5

SC

q12–24 h

Ketoprofen

5

SC

Morphine

2–5

SC, IM

q2–4 h

Nalbuphine

4–8

IM

q3 h

Oxymorphone

0.2–0.5

SC, IM

q6–12 h

Meperidine

20

SC, IM

q2–4 h

Buprenorphine

0.05–0.1

SC

q6–12 h

Aspirin

100

PO

q4–8 h

Buprenorphine

0.05–0.1

SC

q6–12 h

Butorphanol

0.2–2.0

SC, IM, IP

q2–4 h

Carprofen

4

SC

Q24 h

Flunixin

1–3

SC

q12–24 h

Ketoprofen

1

SC, IM

q12–24 h

Oxymorphone

0.2–0.5

SC, IM

q6–12 h

Meperidine

1–2

SC, IM

q2–4 h

361


Species

Drug

Dose (mg/kg)

Route

Dose Interval

Prairie dog

Butorphanol

0.1–0.4

SC, IM

q8 h

Carprofen

1

PO

q12–24 h

Ketoprofen

1–3

SC, IM

Buprenorphine

0.01–0.05

SC, IP

q6–12 h

Meperidine

10–20

SC

q2–3 h

Morphine

2–5

SC

q4 h

Oxymorphone

0.2–0.5

SC, IM

q6–12 h

Meloxicam

0.1–0.2

PO

q24 h

Aspirin

50–100

PO

q4 h

Butorphanol

0.2

IM

q4 h

Flunixin

2.5

SC

q12–24 h

Meperidine

10–20

IM, SC

q3–4 h

Aspirin

150

PO

q4–6 h

Buprenorphine

0.1–0.2

SC

q8 h

Butorphanol

1–5

SC

q2–4 h

Flunixin

2.5

SC

q12–24 h

Meperidine

20

SC, IM

q3–4 h

Buprenorphine

0.01

SC, IM, slow IV

q8–12 h

Butorphanol

0.1–0.5

SC, IM

q4–6 h

Flunixin

1

SC, IM

q12–24 h

Woodchuck

Use same dosages

As prairie dogs

Ground squirrels

Use same dosages

As prairie dogs

Degus

Duprasi (fat-tailed Gerbil)

Herbivorous marsupials

Reference Goldberg, M.E. (2010f) The fourth vital sign in all creatures great and small. The NAVTA Journal, 31–54.

362


Adapted analgesia for Hedgehogs and Sugar Gliders Drug

Hedgehog

Sugar Glider

Comment

0.01 SC, IM q6–8 h

0.01 SC, IM q 6–8 h

Johnson-Delaney (2006)

0.01–0.03 mg/kg IM

0.01–0.03 mg/kg IM

Lennox (2007)

0.01–0.5 mg/kg SC, IM q8–12 h

0.005–0.01 mg/kg SC, IM q8 h

Brust and Pye (2013), Carpenter and Marion (2013)

0.05–0.4 SC, IM q6–8 h

0.05 SC, IM q6–8 h


0.2–0.4 mg/kg SC q8 h

0.5 mg/kg IM q8 h

Lennox (2007)

0.05–0.1 mg/kg SC, IM q8–12 h

0.1–0.5 mg/kg SC, IM q6–8 h


Morphine

0.1 IM

0.1 SC, IM q6–8 h


Naloxone

0.1 SC, IM q6-8h

0.1-0.16 mg/kg SC, IM q6-8h


Opioid Buprenorphine

Butorphanol

Brust and Pye (2013), Carpenter and Marion (2013) NSAID Carprofen

1.0 PO, SC q12–24 h

1.0 PO, SC q24 h

1 mg/kg PO, SC q12–24 h

Meloxicam

Flunixin meglumine

0.2 PO, SC q24 h

0.3 mg/kg SC q24 h

Johnson-Delaney (2006) Brust and Pye (2013), Carpenter and Marion (2013)

0.2 PO, SC q24 h


0.1–0.2 mg/kg PO, IM q12 h; 0.1–0.2 mg/kg PO, SC q24 h


0.1–1 mg/kg IM q12–24 h


Corticosteroids Dexamethasone

0.1–1.5 mg/kg IM; 1–4 mg/ kg SC, IM, IV

Carpenter and Marion (2013)

Methylprednisolone

1–2 mg/kg SC


Prednisolone

2.5 mg/kg PO, SC, IM q12 h


Triamcinolone

0.2 mg/kg SC, IM


363


References Brust, D.M. & Pye, G.W. (2013) Sugar gliders. In: J.W. Carpenter (ed), Exotic Animal Formulary, 4th edn, Elsevier/Saunders, St. Louis, MO, p. 443. Carpenter, J.W. & Marion, C.J. (2013b) Hedgehogs. In: J.W. Carpenter (ed), Exotic Animal Formulary, 4th edn, Elsevier/Saunders, St. Louis, MO, p. 463.

Johnson-Delany, C.A. (2006) Common procedures in hedgehogs, prairie dogs, exotic rodents and companion marsupials. Veterinary Clinics Exotic Animal, 9, 415–435. Lennox, A. (2007) Emergency and critical care procedures in sugar gliders, African hedgehogs and prairie dogs. Veterinary Clinics Exotic Animal, 10, 533–555.

Appendix A.XIII Analgesics for Non-Human Primates Drug

Dose (mg/kg)

Route

Dose Interval

Morphine

1–2

IM, SC

q4h

Fentanyl

1–2 µg/kg 2–10 µg/kg 10–25 µg/kg/h 50–70 µg/kg/h to 70–100 µg/kg/h

IV IV IV-CRI IV-CRI

q30 min

Fentanyl transdermal patch

4 µg/kg/h or 25 µg/kg/h times 2 patches

Transdermal drug delivery-topical

q72 h

Alfentanil

3–32 µg/kg

IV

q15 min

Remifentanil

3.2–5.6 µg/kg

IV

Ultra short acting