V 71 no 2 2001 by Joanne Paterson

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LIPITOR • is an HMG - CoA reductase inhibitor (stalin). LIPITOR is indicated as an adjunct lo diet for the reduction of elevated total cholesterol, LDL -C, triglycerides, and apolipoprotein Bin hype!1ipidemic and dyslipidemic conditions Onduding primary hypercholesterolemia, combined [mixed] hyperlipidemia, dysbetalipoproteinemia, hypertriglyceridemia, and familial hypercholesterolemia) when response to diet and other non-pharmacological measures alone has been inadequate. See prescribing information for complete warnings, precautions, dosing and administration. LIPITOR is contraindicated during pregnancy and lactation. Upid levels should be monrtoned periodically and, necessary,lhe dose of UPITOR adjusted based on target lipid levels recommended by guidelines. Caution should be exercised in severely hypercholesiEro lemic patients wllo are also renally impaired, elderly, or are concomi1anl!y being administered digoxin or CYP 3A4 inhibitors. Liver function tests should be performed before the in~iation of treatment, and periodically lhereafter. Special attention should be paid to patients wl1o develop elevated serum transaminase levels, and in these patients measurements should be repeated promptly and lhen performed more frequently.The effects of atorvastatin induced changes in lipoprotein levels, induding reduction in serumcholesterol, on cardiovascular morbidrty, mortalrty,or total mortalrty have not been established.

Recent clinical data showed that LIPITOR actually gets patients to target with fewer titrations and fewer repeat visits than Przocofl (simvastatin), PrPravachol®(pravastatin) or p'Lescol®(fluvastatin).t¥ (Type II a and lib) over the full dose range 2

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Excepti on al LDL-C reduction s of

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Significantly better LDL-C and TC/HDL-C ratio reductions compared to Zocor or Pravachol at starting dosesM§t

• Th e add ed benefit of excellent TG reduction s of dose range 2

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Less than 2% of patients discontinued therapy due to adverse experiences. Most common adverse effects were myalgia, headache, constipation, diarrhea, dyspepsia, flatulence and nausea 2

¥ Results from a 54-week. randomiZed. open-label. treat-to-target study wrth 336 patients enrolled Patients were treated wrth UPrTOR 10 mg (n=140), Lescol20 mg (n=58), Pravachol20 mg (n=72) or Zocor 10 mg (n=66) and titrated until LDL-C target was achreved Cholestyramrne was added for patients not reachrng LDL-Ctarget at maxrmum dose pdJ 005 § Results at 16 weeks in a study of 177 hypercholesterolemic patients taking UPrTOR 10 mg or Zocor 10 mg in a one-year, randomized. double-blind study. The LIPrTORgroup had LDL-C and TCreductions of 37% and 29% and an HDL-C Increase of 7%, whrle the Zocor group had LDL-C andTC reductions of 30% and 24% respec~vely (p<0.05) and an HOL-CIncrease of 7%. t Results at 16 weeks rna study of 305 hyperchOlesterolemic patients taking LIPrTOR 10 mg or Pravachol20 mg In a one-year, randomized, double-blind study. The LIPITORgroup had LDL-C and TCreductions of 35% and 25% and an HDL -C Increase of 6%, while the Pravachol group had UOL-Cand TC reductions of 23% and 17% re~vely (p<O.OS) and an HDL -CIncrease of 8%. ; Based on acQuisition costs, excludrng drspensrng fees for a 30-day scnpt ot the stalin at the usual starting dose, UPITOR (1 0 mg) costs $48, and Zocor (1 0 mg) and Pravachol (20 mg) each cost $53 40. Adapted from reference 5. RegiStered trndemart<s ZCX1l'" - Merck FrossL Pravacoor - Br1stJj-Myers SQurbb, Lescol" - Novartls.

Muuhtr

OMJ

Volume 71 Number 2

Fall2001

Contents EDITORIAL

Surgery: The two moons Eric Wong, Editor-in-Chief

FEATU RE ARTI C LES

Surgery in the nineteenth century: The conquest of pain and sepsis Samir K. Sinha

Off-pump coronary artery bypass surgery: What are the pros and cons? Robin Vargh ese

Surgical options for the correction of craniofacial soft ti ssue defects Vic/a-am Chahal, Martin Lacey

Diagnosis of the acute abdomen: Back to basics Peter Kim

Guglielmi detac hable coi ls and the subarachniod hae morrhage: Radiology 's encroachment on neurosurgery Jason Ashley

A compari son of open surgery versus endovascul ar repair in the treatment of abdo minal ao rti c aneurysms Radu Bulan

Role of imaging in the di agnosi of acute appendicitis Eric Wong

DEPARTMENT ARTICLES

Ethics Refusal to care for HIV and AIDS patients is unethica l Nya n Narine

History of Medicine Ectopic pregnancy: The evolution of current day management Chetna Tailor

Medical Humour The Sturgeon vs. The Surgeon - A comparison Keir Peterson

Medicine and the Law Bloodless surgery: Questioning the standard of care in the treatment of Jehovah's Witnesses Birinder Singh, Azadeh Moaveni

Profiles Interview with Dr. Quan: A transplant surgeon Maryanne Rockx

Promotion and Prevention Psychic surgery: Opening the mind and heart to a new medicine A lan S. Kahn 17 Thinking on Your Feet A case of laryngeal cancer John Lee

21 M ISCE LLANEO US ARTI C LES

Vocabulary H eather Coc/qve/1, Joe Chan, Chris Chu

Zebra Files A review of Stevens-Johnson syndrome and toxic epidermal necrolysis Chinedu Onochie

Differences in prescribing practice between board certified prescribing psychologists and psychiatrists Larry C. Litman

The end of the shift Pat Marley-Forster

ÂŠ200 1 UWOMJ UWOMJ is published every 4 months.

Editorial Staff Next Issue: EDITORIAL BOARD

PSYCHIATRY

COVER ART The cover of this issue is designed by Felix Wong. He is a 4th year engineering student at the University ofToronto specializing in mecha ntroni cs at the Department of Mechanical and Industrial Engineering. Equipped with an interest and skills in photoediting, he served as newspaper editor for the Chinese Engineering Students' Association, and has designed numerous web-sites for other student organizations.

Editor-in-Chief (middle) Senior Associa te Editor (right) Junior Associate Editor ( left)

Eric Wong Jason Ashley Shas hie Sade

Meds 2002 Meds 2003 Meds 2004

DEPARTMENTAL EDITORS Ethics Sr.: Boris So, Meds 2004 Jr. : Adnan Pirbhai, Meds 2005

Medicine on the Internet Sr. : Gabri el Chang, Meds 2004 Jr.: Deric Morrison, Meds 2005

C linical Procedures Sr.: Eliza beth Au- Yeun g, Meds 2004 Jr.: Rya n Punambo, Meds 2005

Profiles Sr. : Marya nne Rockx, Meds 2004 Jr.: Magdalena Lipowski, Meds 2005

Di ag nostic Review Sr.: Jessica Hopkins, Meds !004 Jr.: N ina Ghosh, Meds 2005

Thinking on Your Feet Sr.: Chris Chu, Meds 2004 Jr. : Jay Bane1jee, Meds 2005

Health Promotion Sr.: Alan Kahn , Meds 2004 Jr.: Anna Labuda, Meds 2005

Zebra Files Sr: Chinedu Onochie, Meds 2004 Jr: Suza nne Ri chter, Meds 2005

History of Medicine Sr.: Chetna Tailor, Meds 2004 Jr.: Marll is Sabo, Meds 2005

Senior Editors Azadeh Moaveni , Meds 2003 Mark Baumga rtner, Meds 2003 John Lee, Meds 2003 Heather Cockwe ll , Meds 2002

Medicine and the Law Sr. : Birinder Singh, Meds 2004 Jr.: Leanne Tran, Meds 2005

UWOMJ ADVISORY COUNCIL

Poster Designer Eli za beth Au- Ye ung, Meds 2004

Dr. Co lby, Microbio logy Dr. Wex ler, Anesthesio logy Dr. Ri eder, Pediatrics

Dr. Silcox , Obstetrics I Gynecology Dr. N isker, Obstetri cs I Gynecology Dr. Gupta, Cardio logy

ADVERTISING Kenmara Inc.

PRINTER Willow Printing Group Ltd .

UWOMJ 7 1(2) 200 1

UWOMJ Room MS-175 Medical Sciences Building The University of Western Ontario London, Ontario N6A SC I Phone/Fax : (5 19) 661-4283 Email : journal@uwo.ca URL : www.med.uwo.ca/medjrnl For information about writing for UWOMJ, pl ease visit our web site. All editorial matter in UWOMJ represents the opinions of the authors and not necessari ly those of the editorial staff and advisory council. The editorial staff and advisory council assume no responsibility or liability for damages arising from any error or omission or from the use of any information or advice contained in UWOMJ. Canada Post - Publication Mail Agreement Number 1720 198 POSTMASTER: Undeliverable copies, please return to address above .

Editorial

Surgery: The two moons

Eric Wong

There is an old Chinese story about a young girl who, for the very first time, took notice of a bright yellow object in the clear blue sky one evening. She ran inside her home and demanded an explanation for this magnificent phenomenon from her grandfather. Her grandfather gently smiled, took hold of her hand and led her outside their home. He explained that the ball hanging up high in the heavens was the moon, and its light was the traveler 's best guide and companion at night. Being curious and na'ive, the little girl asked her grandfather to help her take the moon down from the sky. Upon hearing this, the grandfather's eyes twinkled with wisdom . After getting a big bowl from inside the house, both he and his granddaughter headed to a still dark pond where the moon 's reflection could be clearly seen. He dipped the bowl into the pond and filled it with water. The reflection of the moon was also now in the bowl. The girl saw the reflection and quickly snatched the bowl from her grandfather's hands. She ran back inside the house with the bowl only to find that her moon had disappeared. Like the moon in the evening sky, the surgical specialty is one of the brightest stars in medicine. To any cancer patient with resectable disease, it traditionally has been their hope and panacea. It also represents the only provider of self-confidence and dignity for those who suffered cosmetically damaging injuries. To any student of the medical sciences, it is the ultimate combination of the practice of pharmacological treatment and therapy via anatomic modifications. Surgery is also the moon in the water-filled bowl, as it provokes curiosity and the desire to possess its beauty and knowledge, which often captures the minds of many student physicians. But like the little girl , once its practitioner thinks that he or she has captured surgery's essence and secrets, surgery has already advanced to a different phase. The acceleration of surgical evolution is evident in the 20th Century through advancements in fiber optic and robotic technologies. Laparoscopy is now the standard procedure in many surgical disciplines for diagnosis and treatment of specific dis-

eases in the shoulder, abdomen , and pelvis. Similarly, endoscopic procedures are commonly used to diagnose and treat diseases of the head and neck region, and respiratory and gen itourinary systems. More recently, the combined usage of robotics and endoscopic techniques has revolutionized the way ischemic heart diseases can be treated. While still in its infancy, this type of surgery has attracted much deserved attention internationally due to its potential to significantly reduce morbidity and conva lescent time. The London Health Sciences Centre has played a worldwide leadership role in this arena. Surgery in the future will be similar, yet very di fferent from that of the present and the past. While still involved with work inside crevices and cavities of the human body, the means through which this art wi ll be accomplished will be less invasive and traumatic, but at the same time, more precise and technical. Steady hands , or rather, steady robotic extensions of the hands will be emphasized, and computer generated images of anatomy from one continent wi ll travel across skies and oceans to another where the operating surgeon is maneuvering his endoscopic and robotic instruments. Further, the operating theatre will have a markedly different atmosphere with the presence of robotic arms and computer systems. It is certa inly with excitement that the surgical field is developing. And it is also with excitement that I present to you this marvelous issue of the UWOMJ that features the surgical specialty.

Eric Wong Editor-in-Chief UWOMJ

UWOMJ 71 (2) 200 I

Ethics

Refusal to care for HIV and AIDS patients is unethical

Nyan Narin e, Meds 2002

Acquired immunodeficiency syndrome (AIDS) is the scourge of the new millennium. MiiJions of people around the world are infected with the human immunodeficiency virus (HIV). lllV and AIDS make no discrimination between race, gender, rich or poor. In addition to fear and anxiety about their future, HIV patients must also face stigma and persecution by their peers, friends and family. Unfortunately, many patients have been shunned by the very people who are trained to care for their health. Do health care workers not have a duty to care for their patients? Does the duty to care for their patients outweigh their duty to care for their own health and their loved ones? Health care workers must provide the highest standard of care for all of their patients, yet they must also respect and care for themselves. Kantian deontology provides a solid foundation which health care workers around the world may heed and treat all of their patients equally, while respecting their duty to themselves.

The global AIDS epidemic has presented today 's health care workers (HCWs) with many medical and moral chall enges. One of the major issues for HCW is the duty to care for patients who are infected with the human immunodeficiency virus (HIV) . The term ' duty to care ' refers to the professional obli gation of HCWs to provide all patients with the best quality treatments and health care possible5,21. However, some health care workers are either hesitant to treat HIVI AIDS patients, or refuse to treat these patients altogether. Many justify their deci sion with their fear of becoming infected with the incurable virus. Is thi s a violation of the duty to care, or do HCWs, like the general public, have a right to take measures to protect them se lves against what they perceive to be a significant threat to their own health and safety? Do HCWs have a duty to care for their patients that prevails over perce ived threats to their own personal safety? What is the extent of HCWs ' obligations? Di stributive justice demands that equals be treated as equal s and unequal s as unequals. Thus, HIV positive pati ents must be treated like any other patients with terminal infectious di seases suc h as tuberculosis, Hepatitis B and C, and AIDS . Kantian deontology is based on Kant's fundamental principle of categorical imperative. Kant's philosophy argues that HCWs have a professiona l and moral obli gation to provide all 4

UWOMJ 71(2) 2001

patients with the best possible health care. They may not ethically refu se to treat selected patient populations. It is equally unacceptable to compromise the quality of treatment to a specific patient population, in this case, those suffering from HIV/AIDS . A literature survey6.9,12,JS,J6,19,20 of the ethical obligations of HCWs indicates that they have an absolute duty to provide the highest standard of care to all patients. Refusal to treat a specific patient popul ation because of the nature of the disease with which they are afflicted is unjust. HCWs are obligated to respect their patients ' autonomy and to prevent harm . If they adhere to this duty to care, patients with AIDS would receive therapies and prophylactic treatments that would protect them from life-threatening secondary opportunistic infections. Providing prophylactic therapies against opportunistic infections is a simple, yet effective way for HCWs to protect their patients from harm , while also promoting their well being. Patients can be relieved from depressive symptoms associated with the knowledge of their bleak prognosis if they know that supportive care is avai lable. This would considerably improve the quality of their lives . Proper health care may also increase the likelihood that HIV/AIDS patients will continue working despite their diagnosis .

This is quite common since the advent of antiviral polypharmacy protocols. Protection from financial hardship and promotion of mental and social welfare qualify as requirements under the duty to care. Getting people back to work is an essential social objective achievable by HCWs via empowerment of HIVIAIDS patients. Through this strategy, the patients' dignity and autonomy are restored, which may allow them to care for themselves both financially and medically. Since the cost associated with the antiviral drug regimens is astronomical, an income is necessary to manage these expenses. Having an income also helps many of these patients qualify for assistance from various social services and government drug plans (e.g. Ontario's Trillium Plan) . Health care workers harm their patients by omission of help when essential treatments are withheld . Distributive justice demands that equals be treated as equals. As such, patients with HIVI AIDS should be treated just like any other patient with an infectious disease (e.g. hepatitis B & C and tuberculosis , both of which are more contagious than HIV). If proponents of the refusal to treat argument feel that they can refuse to treat patients with HIVI AIDS, then they must also refuse to treat patients suffering from any other infectious disease. One exception to this principle is where a surgeon may refuse a patient with AIDS on the basis associated surgical complications, morbidity and mortality. Thus, it is justified to refuse care on grounds of medical instability and risks, but not due to fear of contracting HIV Kant's categorical imperative, "I ought never to act except in such a way that I can also will my maxim should become a universal law"I4. This requires HCWs not to discriminate against a particular group of patients for any reason. They must treat all patients including patients with AIDS as they themselves would like to be treated as patients. Kantian deontology is an obligationbased moral theory, which holds that the moral value of an individual's actions is dependent on the moral acceptability of the motivation driving their decision2,3,I4. Thus, the individual 's action only possesses moral value when that individual selflessly performs the action out of obligation and out of good will , free from discrimination. Another common interpretation of Kant 's categorical imperative is as follows: never treat persons as a means to an end, but rather, always as ends in themselves2,3,I4. HCWs who refuse to treat patients with AIDS for fear of their personal safety or who give substandard or unequal treatment are treating these patients as means to their own ends. They have based the refusal to treat in their end to protect themselves. This decision is grounded in their personal fear and ignorance of the mechanism of disease transmission . They are not performing their duty selflessly or to the best of their ability because they are concerned primarily with their own interests. HCWs who minimize contact or omit services to patients with HIVI AIDS , and yet continue to treat them for fear of compromising their reputation as humanitarians are also using these patients as a means to an end. Their primary motivation to treat in this scenario is to protect their professional reputation. This behaviour is unethical according to Kantian philosophy. HCWs have a Kantian duty to promote their own autonomy by choosing to use the appropriate infection control measures to protect themselves against possible occupational infection. This duty does not require that caregivers perform acts of heroic self-

sacrifice (e.g. unprotected contact with infectious bodily fluids), as they must also promote their own health and welfare. Similarly, they also have a duty to improve themselves by continually acquiring new knowledge about the di sease and ways to further reduce risks of transmission. HCWs al so share a commitment to promote patient welfare. If they are unable to do this due to extenuating circumstances (e.g. futility or exorbitant cost of treatment), then they are required to remove harm from patients and maximize their comfort. The main argun1ent justifying the decision to refuse care for patients with HIVI AIDS is fear of accidental infection through occupational hazards such as needlestick injuries. In an effort to understand this fear many empirical studies around the world tried to identify the risk determinants perceived by HCWs6,9,I2,I5,I6, I9,20. The major factors identified are a lack of knowledge about the disease and its transmission, lack of experience in treating HIVI AIDS patients, and disapproving and prejudicial attitudes against the lifestyles of HIV I AIDS patients6,9,I2,I5,I6,I9,20. Although HCWs have the duty to care for patients with HIVIAIDS , they also have a right to protect themselves against the possibility of being infected. HCWs who choose to work in a setting where they come in contact with patients with HIVI AIDS may exercise their right to protect themselves from occupational infection by either withdrawing from this positionS, or by using appropriate precautionary measures to avoid contact with infectious body fluids . Competent autonomous individuals are free to choose their work setting, but they must accept the responsibilities and risks associated with their informed decision. As such, it is unethical for HCWs who knowingly work in an environment where they must care for HIVI AIDS patients to refuse care for these patients due to fear of disease transmission. Refusing care for patients with HIVIAIDS out offear and concern for oneself also conflicts with Kant 's philosophy since it is a self-serving decision. The basis of the appeal to the principle of autonomy is that HCWs have the right to refuse to treat HIVIAIDS patients to lessen the risk of being infected. However, this choice is made at the expense of the health of those patients to whom the HCWs have a duty to treat. HCWs are entitled to employ all measures necessary to protect themselves while caring for their patients. It is necessary to use universal body fluid precautions when dealing with patients who are suffering from any virulent, infectious disease. But it would be wrong to implement unnecessarily measures, such as restricted scheduling or wearing extra gloves' , masks or gowns, which serve only to alienate the patients5. One limitation to their appeal for autonomy, which champions our right to self-governance, is that autonomy does not excuse one from harming others. By refusing patients the care needed for the preservation of their health, HCWs bring harm to their patients. In this situation, one's ability to act freely and autonomously is in direct conflict with one's duty to prevent hatm. Two studies on the determinants of fear in HCWs concluded that the fear of infection is exaggerated5,''路 The risk of HIV transmission through occupational hazards is actually very low5,7, IO,ll ,I7,23. Even in cases ofneedlestick injuries, the number of seroconversions was very low (approximately between 0.1 %0.3 % of needlestick exposures seroconverted to HIV-positive sta-

UWOMJ 71(2) 2001

tus)5,7,10.11 .17,23. Non-percutaneous exposure to the virus carries an even lower risk of seroconversion II. The risk of seroconversion is also reduced by post-exposure prophylaxisi O. Many studies agree that improving access to information about HIVI AIDS for HCWs is critical 6,7,.9, 11 ,12. 15, 16. With recent advancement in knowledge about HIVIAIDS and the granting of civil rights to gays and lesbians, there has been more education and publicity about homosexuality. The public majority no longer tolerates homophobia. The Canadian Government has passed legislation making gay hate crimes and acts of hate-motivated violence illegal. It seems that the stigma against homosexuality is slowly beginning to fade among Canadians, especially in younger generations. Since the announcement of the ' HIV crisis ' in the early to mid 1980s, health care workers have also gained more experience in managing HIVI AIDS patients. These developments have weakened the arguments of HCW s who continue to refuse to treat patients with HIVIAIDS . However, many cling to the principle that they have a duty to themselves, their families and their other patients to maintain and promote their own health and welfare. They argue that they have a right to self-governance and can select patients for treatment in circumstances where their own health may be at risk. Physicians and nurses have an important role in patient advocacy. HCWs can become necessary public advocates for those living with the stigma of being infected with HIV The advocacy role extends to helping patients make decisions and plans for the future (e.g. decisions about life-support and referral to support staff such as chaplains, social workers and counselors). HCWs have a duty to provide patients with the necessary information so that their patients can make informed decisions about their own care, legal issues (e.g. durable power of attorney, living will), and updated information regarding available treatments and procedures . This is even more crucial in AIDS patients suffering from dementia. It is important that HCWs facilitate the clarification of patients ' wishes in advance of possible dementia. In the absence of dementia, they must allow competent patients to reconsider previous decisions even if thi s creates contradiction or causes conflict among family members. Failure to do so would constitute paternalism, where patients' wishes are disregarded or overridden. Some argue that HCWs should serve as public educators . Working closely with patients with AIDS, they send a message to the public that it is safe to continue in relationships with these patients, as there is no immediate danger of infection through normal everyday contact. Refusa l to treat those in need and the provision of substandard care to HIVIAIDS patients constitute violations of the Kantian categorical imperative. Such behaviours cannot be sanctioned as ethical. Health care workers must adhere to their duty to care if they are to ethically perform their Kant ian and professional duties to provide the best quality of health care. They must, however, respect their own autonomy by using universal precautions. Effective precautions can be taken to prevent a health care worker from becoming infected with the HIV virus. It is the duty of the health care worker not to rely on personal superstition when caring for their patients, but to seek out current information about the actual risks associated with their care. They must also be just and treat HIVI AIDS patients as they would any other patients 6

UWOMJ 71(2) 200 I

with infectious diseases as demanded by distributive justice. HCWs cannot be morally virtuous without considering their obligation to promote their patients ' well being in addition to their obligation to protect them from harm. REFERENCES 1.

2. 3. 4. 5. 6.

8. 9.

10. 1f . 12. /3.

14.

15.

16. I 7.

I 8. 19. 20. 21. 22. 23.

24.

Avery CM el al. Double gloving and a glove pe1joration indica/ion syslem during !he dental treatment of Hili-positive patients: Are they necessary ? Br Dent J 1999; 186(1):27-9. D1: Bany Brown, PHI 281 Y Lecture: 2519/97, University of Toronto, Toronto, Canada. Beauchamp TL, Childress JF Principles of biomedical ethics. 4th ed. New York: Oxford University Press Inc; 1994. Beauchamp TL, Wa llers L. Contempora1y issues in bioelhics. 4th ed. Belman/ (USA): 1nlernalional Thomson Publishing; 1994. Chiodo G, To lie SW Th e ethicalfoundalions of a duty lo treat HJV-positivepalients. General Dentisfly 1997; 45(1): 14-16. Da vidson G, Gillies P. Safe wor/.."ing practices and HJV infection : knowledge, attitudes, perception of risk, and policy in hospital. Qual Health Care 1993:2(1):21-6. de Graaf R et a/. Occupational risk of HIV infection among western health care professionals posted in AIDS endemic areas. AIDS Care 1998: 10(4):441-52. Dickens BM. Legal rights and duties in th e AIDS epidemic. Science 1988; 239(4840): 581-585. Gerberding JL. Does knowledge of human immunodeficiency virus infection decrease the frequency of occupalional exposure lo blood? Am J Med 1991 ,91(3B):308S-31JS. Goldberg D eta/. Risk of HIV transmissionfrom patients to surgeons in !he era of post-exposure prophy laxis. J Hosp Infecl 2000;44(2):99-105. Grady C. Elhica/ issues in providing nursing care to Hili-infected populations , Nursing Clinics of North America I 989; 24(2): 523-534. Hodgson, I. Attitudes toward people wilh HI VIAJDS: Entropy and health care ethics. Journal ofAdvanced Nursing, 1997; 26(2) : 283-288. Horsman JM. Sheeran P. Health care workers and HIVIAIDS: a critical review of th e literalure. Socia l Science and Medicine I 995; 41(1 1): 1535-1567. Kant I, Calm SM, editor. Grounding/or the melaphysics of morals. In : Classics of Western Philosophy. 3rd ed. Indianapolis (USA): Ha ckett Publishing Co: /990. Krasnik A et a/. Health care workers and AIDS: Knowledge, attitudes and experiences as determinants of anxiety. Scandinavian Jouma/ of Social Medicine /990:18: 103-113. McCann TV. Willingness to provide care and treatm ent fo r patients with HI VIA IDS. Journal ofAdvanced Nursing, 1997; 25(5): 1033-1039. 0 'Neill TM et a/. Risk ofneedlesticks and occupational exposures among residents and medical students. Arch Intern Med /992; 152(7): 1451-6. Patterson JM et a/. Surgeons ' concern and practices of protection against bloodborne pathogens. Ann Surg 1998;228(2):266-72. Sim J AIDS. nursing and occupalional risk: An ethical analysis. Journal ofAdvanced Nursing / 992; 17(5): 569-5 75. Schecter WP. Swgica/ care of the Hili-infected patient: a moral imperative. Cambridge Quarterly of Healthcare Ethics 1992; 1 (3): 223-228. Smol/.."in D. HI V infection. risk taldng, and the duty to /rear. J Med Philos 1997;22(1):55- 74. Wa lters L. Ethical Issues in the Prevention and Treatment of HIV Infection and NIDS. Science 1988;23 9(4840) : 597-603. Case-control study of HJV seroconversion in health-care workers after percutaneous exposure to HI V-il?{ecled blood-France, United Kingdom , and United Slates, January 1988-A ugust 1994. MMWR Morb Mortal Wkly Rep 1995;22;44(50):929-33. Protease inhibitors reduce virus in sperm. AIDS Alert 1997;12(6):69-70.

History of Medicine

Ectopic pregnancy: The evolution of current day management

Chetna

Ta ilo1~

Meds 2004

An ectopic pregnancy is characterized by the implantation of a fertilized ovum outside the uterus. Historically, this condition was rarely diagnosed and surgical intervention non-existent. As a result, ectopic gestation almost always proved fatal for both mother and fetus. Miraculous accounts of maternal survival due to the dead fetus becoming an encysted lithopedion or being extruded through a paraumbilical abscess in the abdominal wall or via a rectal fistula can be found in early medical publications. During the mid-nineteenth century, various methods to destroy the ectopic fetus began to appear in these medical publications. The late nineteenth century saw surgical intervention begin to be accepted as a possible treatment for ectopic gestation in Europe and the United States. The symptoms and signs of ectopic pregnancy were soon afterward characterized. The first diagnostic procedure developed was culdocentesis which was followed by laparotomy. These procedures were ultimately replaced by the current diagnostic procedures, transvaginal ultrasonography, serial hCG determinations and occasionally, MRis. Recent studies into ectopic pregnancies have found a 6 fold increase in incidence in the last 20 years in industrialized countries. Coupled with the disasterous consequences of the still frequent misdiagnosis, it becomes imperative that both physicians and society at large better recognize the warning signs of ectopic gestations. An ectopic pregnancy is characterized by implantation which has occurred outside the endometrium and endometrial cavity. Possible locations of ectopic implantation include: the cervix, fallopian tubes, ovaries, and abdominal or pelvic cavity. Ectopic pregnancies, currently recognized as potentially life-t hreatening, are usually diagnosed early and may require surgica l intervention. It is interesting to note that such an 'invasive' treatment option was not accepted until late in the nineteenth century.' As a result, ectopic pregnancy was historically almost always fa tal for both the mother and fetu s. Cases recorded in literature as early as the sixteenth century documented unusua l instances in which the mother survived the ectopic pregnancy. Survival was due to the dead fetus becoming an encysted lithopedion (a calcified fetus in the body of the mother), being extruded through a paraumbili ca l abscess in the abdomenal wall, or via a rectal fistula (fig . 1)3. 1.2 A lthough the most common site of ectopic implantation is the uterine tube, many of the cases where the mother survived involved implantation of the fertilized ovum in the abdominal cavity. This is understandable as tubal pregnancies would have inevitably, with the growth of the fetus, resulted in tubal rupture followed by hemorrhage, shock, and the eventual death of mother and fetus . One of the earliest documented cases of ectopic pregnancy was recorded by Albucasis, a tenth-century Arab surgeon living in Spain. He had been asked to treat a woman whose first fetus had

died in utero, had conceived again and whose second fetus had also died. Some time after the death of the second fetus she experienced a swelling in her umbilicus which grew until it opened and began to produce pus. Small bones soon began to extrude fro m the wo und. Albucasis deduced that the woman had had an abdominal pregnancy and that these were the remain of the dead fetus .' An interesting case of abdominal pregnancy was reported by Abraham Cyprian, a dutch surgeon. In 1694 he had been asked to treat a 32 year old woman who claimed to have been pregnant for 2 1 months. After nine months fetal movements had stopped, she had no milk in her breasts, and her mensus had started agai n. She felt pain in the area of the umbilicus, where a ' fungous ulcer' had appeared. Cyprian investigated the woman s condition by dilating the tract of the ulcer and exploring with his little finger. He was thus able to identify a cranial bone. Upon being convinced that she would die without an operation, the patient consented. Cyprian made an incision on her left side, exposing a lithopedion. Whi le exh路acting the fetus with one hand he used the other to prevent extrusion of the patient's intestines. The wound was closed and the mother recovered completely and subsequently gave birth to a singleton and a set of twins .' The case of Mrs. Ball , submitted to the Philosophical Transactions of the Royal Society of London, is also interesting. In the sixth month of her pregnancy, in April 1731 , Mr . Ball sensed a weakening of fetal movements for 6-7 days after which UWOMJ 71(2) 2001

Figure 1. A 32-week lithopedion resulting from an intra-abdominal pregnancy which had died and calcified three years prior to surgical removal fro m an 37-year old Zairian .female living in a village o.f Malanga.

all motion ceased. At thi s time Mrs. Ball started to experience ' labour pains'. A phys ical examination performed by a doctor confirmed fetal death . She was then given some 'forcing medicines' which prompted a discharge of what appeared to be part of the placenta and a small quanti ty of water. The pains ceased although the size of her abdomen remained the same. Her pains returned intermittently and she was examined again . At this point a child was felt through the integuments of the abdomen . She was then referred to Dr. Myddleton. Twenty-seven months after the death of the fetus , she co n~i ved again. Upon deli very of thi s child and removal of the placenta, Dr. Myddleton found the fetus lodged in the cavity of the abdomen and felt th at it 'was beyond the reach of human art to reli eve her'. Mrs. Ball deli vered 3 more children in the presence of Dr. Myddleton who took each opportuni ty to examine the state of her abdomen and found the initial fetus unchanged. Upon Mrs. Ball 's death in 1747 Dr. Myddleton performed her autopsy. He found a calcified fetus attached to the ilium and neighbouring membranes by a portion of the peritoneum which seemed to also contain the fimbria and part of the right fallopian tube. The fetus had been in this positi on for 16 years while it 's mother had subsequently delivered 4 children .4 The beli ef that no medical action co uld be taken in the eve nt of an ectopic pregnancy to prevent the ensuing complications continued until th e mid-nineteenth century, when papers describing various methods by which to destroy the fetus began to appear. In 1850 Paulin Cazeau, a professor in the Faculty of Medicine in Paris, recommended copious bleedings in the early stages of extrauterine gestation. His subsequent suggestion of destroying the fetus by electric shock was attempted by Odoardo

UWOMJ 71(2) 2001

Bacchetti of Paris in 1853 . A needle inserted into the cyst, through which an electric current was passed. The fetus gradually shrank and the mother began menstruation within two months. I Another method of terminating an ectopic pregnancy, proposed by J. D. Joulin of Paris in 1863, involved injecting chemica_ls into the fetal sac. Succeeding this proposal, N . F. Fnedretch of Heidelberg reported two cases in which repeated injections of morphine into the fetal prominence through the vagina or abdominal wall terminated fetal movement. I In the late nineteenth century surgical intervention in ectopic pregnancies become more plausible. One of the greatest contributions towards the acceptance of surgical mterventwn was made by Lawson Tait, a Birmingham gynecologist. In 1881 Tait refused to operate on a woman who had begun to hemorrhage int? ~he peritoneal cavity from a ruptured tubal gestation. After exarnmmg the postmortem results, Tait was convinced that surgery would have been fea sible and potentially life-saving. In 1883 he was presented with a similar case which he decided warranted surgery. Instead of tying off the source of the bleeding immediately, he chose to separate the adhesions first, which resulted in the death of the patient. He recognized his mistake and when presented yet again with a tubal rupture three months later, his surgery was successful. By 1888 Tait had performed forty-two such surgenes, with only two deaths. I Surgical intervention soon became an accepted treatment for ectopic pregnancy across Europe and the United States. Due to the inavailability of adequate blood storage for transfusion during this time, the major complication leadirig to death in these suraeries was excessive hemorrhage. These deaths were reduced however, with the recognition that the placenta should be left in situ and the abdomen closed without drainage when the placenta was likely to be attached to vital organs. Removal in these cases could lead to uncontrollable hemorrhage. The placenta could be removed however, in cases where its blood supply could be easily interrupted. I More modern studies examirlirlg ectopic pregnancies and their surgical treatment quickly elucidated the mystery behind ectopic pregnancies. By the 1950s the symptoms and signs had been recogni zed as well as diagnostic and treatment procedmes standardized. Characteristic symptoms include abnormal vaginal bl eeding followed by abdominal pain and physical signs of pain upon movement of the cervix, tenderness of the abdomen with rebound pain and guarding. s.6.7,8,9 The diagnosis of ectopic pregnancy has evolved since the time ofTait, when a careful history accompanied by an abdominal and vag inal exam were paramount.I OThe first diagnostic procedure to conclusively verify ectopic gestation was an culdocentesis (sampling of fluid from the cul-de-sac between the uterus and rectum- often including blood) . A positive diagnosis would be made if the sample did not clot.5,8,11 Although regarded as a fairly good diagnostic test, some studies showed it to have a false positive and false negative rate of up to 23%.8 Culdocentesis was soon accompanied by laparotomy (surgica l section of the abdominal wall) as a diagnostic tool. Widespread use of laparoscopy in the U.S . occurred by the late 1960s. By June 1970 there was a significant decrease in the rate of tubal ruptures, from 63% to 45%.8

Currently, transvaginal ultrasonography and serial hCG determinations are the cornerstones for diagnosis of ectopic gestation. In these cases, hCG is usually above normal but not at the level expected for gestationa l time and ultrasonography shows no intrauterine gestation.9,12 MRI with intravenous contrast is also used to specifically diagnose a tubal pregnancy. Laparoscopy is currently the surgical treatment of choice for ectopic pregnancies.1 2 If a tubal pregnancy has not ruptured and is less than 3.5 em in diameter and there is also no fetal heart activity, a single dose of methotrexate may be used as a medical treatrnent.9 In cases of combined intra- and extrauterine pregnancies, a single injection of potassium chloride into the abdominal pregnancy is sometimes given. l2 One of the greatest problems in medically treating ectopic pregnancy has resulted from the difficulty in diagnosing the condition. In spite of recent advancements in technology, ectopic pregnancy is sti ll frequently misdiagnosed at the initial visit. 8. 12 If the pregnancy is tubal and remains undetected, rupture will occur between 6-8 weeks with marked sudden lower abdominal pain and fainting, both of which are indicative of intra-abdomina l hemorrhage. If the pregnancy is interstitial, cramping and spotting will be followed by catastrophic rupture between 12-16 weeks, leading to life-threatening shock.9 Older studies regarding the incidence of ectopic pregnancies have found a higher occurrence rate in the African-American population and in those with previous pelvic infection or operationJ,IO,II More current studies have uncovered a rhythmic seasonal variation in ectopic gestations with peaks in June and

December.l2 More di sturbingly, these studies have also found a 6 fold increase in incidence of ectopic pregnancy in industrialized countries over the last twenty years- a rate not even closely matched by undeveloped countries.12 These findings emphasize the importance of recognizing the warning signs of ectopic gestations. REFERENCES 1. Wangensteen 0 , Wangensteen S. Ectopic Pregnancy. In : The Rise of Surgery. Ontario: Burns & Ma cEachern. 1978: 214-226. 2. Houstoun R. An account of an extra-uterine fo etus, taken out of a woman after death, that had continued five years and a half in the body. Phil. Trans. 1723; 32: 387-390. 3. www.obgyn.net/englishlpubs/articleslstone_baby.htm 4. Myddleton S. An account of a child being taken out of the abdomen, after ha ving lain there upwards of 16 years, during which time the woman had 4 children, all born alive. Phil. Trans. I 747; 44: 617-621 . 5. Armstrong J, Wills S, Moore J, Lauden A. Ectopic pregnancy. Am. J Obst. & Gynec. 1959; 77(2) : 364-370. 6. Bobrow M, Bell H. Ectopic pregnancy: a 16-year survey of 905 cases. Obstet. Gy nec. 1962; 20: 500-506. 7. Beacham W, Hernquist W, Beacham D, Webster H. Abdominal pregnancy at Charity Hospital in New Orleans. Am. J Obst. & Gy nec. 1962; 84: 1257- 1270. 8. Helvacioglu A, Long E, Yang S. Ectopic pregnancy: an eight-year review. J Reprod. Med. 1979; 22(2): 87-92. 9. www. merck.com/pubslmmanual/section1 8/chapter2521252b.htm 10. Ware H. Observations on thirteen cases of late extrauterine pregnancy. Am. JObst.& Gy nec. 1948; 55 (4) : 561-582. 11 . Webster H, Barclay D, Fischer C. Ectopic pregnancy: a seventeen-year review. Am. J Obst. & Gynec. 1965; 92(1) : 23-34. 12. Lemus J Ectopic pregnancy: an update. Cun: Opin. Obstet. Gy necol. 2000; 12(5) : 369-375.

London Hospitals ... . . . Committed to providing the best health care system possible ur journey toward fully restructuring the London hospitals continues. This year, we celebrate the recent integration of the former London and St. Thomas Psychiatric Hospitals into St. Joseph's Health Care, London; the integration of the Renal Dialysis

Program to new facilities at the Victoria Campus, London Health Sciences Centre, and the consolidation of Rheumatology at St. Joseph's. Through the dedicated efforts of our physicians, staff and leadership, we are able to sustain our excellence in patient care, research and teaching, while we work through this complex and ongoing transformation.

LONDON Health Sciences Centre Building solutions for a healthier tommorrow UWOMJ 71(2) 2001

Medical Humour

The Sturgeon vs. The Surgeon - A comparison

Keir Peterson, Meds 2003

Those of us in the medical fie ld are qu ite aware of what a "surgeon" is. There remains, however, much confusion about this topic among the general public. To help clarify things, I present the fo llowing ... Sturgeon

Surgeon

Winner

Classification:

Acipenseridae

Homo sapiens (Although there is some debate in the scientif ic community regarding this classification.)

Sturgeon

Historical Origins:

7 meter long, tooth less Jurass ic ancestors.

Barber-Surgeo ns, who would cut hair, perfo rm amputations, and remove teeth in the 13th and 14th centuries. (Their services were, however, shunned by the sturgeon community, who had been gloriously toothless for hundreds of millions of years.)

Sturgeon

Defenses:

Bony plates along the back and sides.

Hostili ty Sarcasm Scalpel

Surgeon

Sense of Humour:

One type of sturgeon is called the "shove !nose." Not like ly (This must be somewhat humourou , at least for the other sturgeons.)

Sturgeon

Contribution to Society:

Caviar

Cher Michael Jackson Pamela Anderson

Draw

Distinctive Odour:

Fishy

Stale coffee

Sturgeon

Varieties:

White sturgeon Green sturgeon Shovelnose sturgeon

Somewhat arrogant Arrogant Ex tremely arrogant

Surgeon

Rumoured To Consume:

Small animals and plants, which they suck into extendibl e, toothless mouths.

Medi cal students and residents. (Whil e orne surgeo ns may also possess extendible toothless mo uths like the sturgeo n, this is not a consistent fea ture of the surgeo n, typica lly found only in the older members of the profession.)

Sturgeon

Method of Locomotion:

Tastefully self-propelled, producing only environmentally frie ndly waste produ cts.

Contribute to global warming by using motorized vehicle , often adorned with somewhat tacky va nity plates that make less-than-obscure reference to the surgeon 's specialty of choice.

Sturgeon

Is Currently Threatened By:

Dams Ove r-harvesting Pollution

The increasing number of procedures being performed by radi olog ists.

Surgeon

Greatest Fear:

Extincti on

Journal articles comparing them to fish.

Sturgeon

And the winner is ... the fish over the physician, with a 7-3 victory by the sturgeon over the surgeon. 10

UWOMJ 7 1(2) 200 1

Medicine and the Law

Bloodless surgery: Questioning the standard of care in the treatment of Jehovah's Witnesses

Birinder Singh, Meds 2004

Azadeh Moaveni, Meds 2003

With the a~v.ent of new bloodies~ surgery techniques in the medical world, the standard of care for emergency room physicians may be changmg to mandate the use of such techniques when treating patients who are Jehovah's Witnesses. In light of the Malette v. Shulman case, it is clear that blood products cannot be administered to a patient when he or she has made an advance directive prohibiting the use of such agents. But with the current state of medical law, as it is described in the Ter Neuzen case, courts may begin to find that this stand~~d of care ~ay be inadequate; more may be required to manage Jehovah 's Witnesses than simply abstammg from usmg blood products. New bloodless techniques may find their way into the standard of care sooner than the practicing medical community uses them as a part of common practice. As a result, hospitals must be acutely aware of the changing standard of care, as liability due to inappropriate care may soon follow these common law changes.

INTRODUCTION One of the most controversial medical legal problems confronting hospitals and health care providers today is the treatment of the Jehovah's Witness who refuses a life-saving blood transfusion due to religious beliefs. In the past, physicians have acted contrary to these beliefs and administered a transfusion on the basis of medical principles, which emphasize the preservation of life. These violations constitute a breach of an individual 's physical integrity under the common law tort of battery as demonstrated by the findings in the court decision of Malette v. Shulmanl As medical technology advances, similar actions by physicians may come under the purview of medical negligence, constitutional and human rights law. As new and innovative techniques such as bloodless surgery have been adapted to better serve the needs of the Jehovah 's Witness community, cases comparable to Malette v. Shulman 2 will likely decrease in regularity. In the last five years, the practice of bloodless surgery has exploded in popularity. Currently, there are physicians in over 50 centres in the United States and 90,

000 doctors world-wide listed by the Hospital Liaison Comrnittees3 of the Jehovah's Witness community who provide bloodless medical care.4 Specific techniques within the bloodless care regin1en such as electrocautery have also been incorporated from mainstream practice to enhance these treatments. Although clinical disagreements on the efficacy and cost-effectiveness5 of these bloodless surgery techniques remain, the existence and implications of bloodless surgery for law and policy cannot be ignored. ~TIS

BLOODLESS SURGERY?

The term "bloodless surgery" can be misleading. In fact, the patient will be most likely to lose blood during the procedure, but the blood is not replaced with a transfusion from another individual. This term is used to refer to surgery that is done without blood, where a blood transfusion would traditionally have been required to be used to achieve a successful outcome. There are also varying degrees of bloodless surgery usage. Some physicians may simply offer the use of blood alternatives, whereas others may use aggressive techniques in times of life-threatening, emerUWOMJ 71(2) 2001 11

gency surgery. Bloodless techniques are commonly used in gynecological, orthopedic, vascular and prostate surgery.6 In emergency situations, they may be utilized for the patient who refuses blood donation. Although bloodless techniques vary between hospitals, there are some key common elements. Acceptance of certain bloodless techniques varies within the Jehovah 's Witness community and is a matter of personal conscience.? Pre-operatively, one or a combination of the following procedures may be used: • The patient's blood count is maximized with nutritional and pharmaceutical methods including iron supplements , vitamin Bl2 and synthetic erytluopoietin .s • Tolerance to low blood levels may be increased by training the patient in a hyperbaric chamber. • Routine blood testing is replaced by microsampling to reduce blood loss before surgery.9 Peri-operatively, one or a combination of the following procedures may be used: • Cryosurgery is used to freeze tissue before it is removed . • Electrosurgical Coagulator/Electrocautery is used to limit internal bleeding. • Isovolumic hemodilution is a technique in which blood taken pre-operatively is re-infused postoperatively. • Hypervolemic hemodilution is a technique in which large volumes of colloid or crystalloid are infused before or during surgery, or at both times, so that the blood lost in surgery is diluted and more hemoglobin is retained.IO • Cell Saver is a surgical suction device that permits collection of intraoperatively shed blood. The blood is then stored in a reservoir with anticoagulants. The filling stage consists of spinning the blood in a centrifuge bowl causing erythrocytes to be packed. The solution is then washed with saline, and plasma hemoglobin, cel lular stroma, anticoagulants and contaminants are removed . The washed solution and erythrocytes are then emptied into a bag that is re-infused by cardiopulmonary bypass. The process creates a product with average hematocrit of 50%, (increased from the 18% hematocrit level of shed blood) and minimal coagulation factors.'' • Albumin, a protein, may be given to maintain or increase blood pressure and blood vo lume. This is prepared by fractionation from plasma of donors and subsequent pasteurization. Post-operatively, the following procedure can be used : • Autotransfusion of shed blood from chest tubes or surgical drains enables additional blood conservation .

THE IMPLICATIONS FOR LAW AND CLINlCAL PRACTICE The stance of Jehovah 's Witnesses on the use of blood for transfu sions has been made clear to the medical community: To take in blood into the body, either by the mouth or through the veins, is a violation of God 's law.l2 These concerns stem from a religious mandate, as well as concerns about the safety of blood transfus ions. These fears should not be taken lightly, especia lly 12

UWOMJ 7 1(2) 200 1

considering the value Canadians place on promoting religious freedoms . Beyond religious interests, it is becoming apparent that individual liberty interests have received vast protection from the courts in Canada, and that a competent individual 's choice to refuse blood should be respected. In Malette v. Shulman1 3, the plaintiff was an unconscious woman injured in an automobi le accident. She was brought into the emergency room of a local hospital where the attending defendant physician determined that a blood transfusion was necessary. A nurse discovered a card in the plaintiff's wallet that stated: NO BLOOD TRANSFUSION! As one of Jehovah's Witnesses with firm religious convictions, I request that no blood or blood products be administered to me under any circumstances. I fully realize the implications of this position, but I have reso lutely decided to obey the Bible command: "Keep abstaining ... from blood." (Acts 15 :28, 29). However, I have no religious objection to use the non-blood alternatives, such as Dextran, Haemaccel, PVP, Ringer's Lactate or saline solution . The physician was made aware of this card. Upon consulting another physician, he felt that not administering blood would create a grave risk to his patient. He also felt that he could not verify whether this card was indicative of Mrs. Malette 's current state of mind as it was not dated. He would not take the risk of not transfusing her if there was a possibility that she had changed her mind about this issue, or even about her religion. As such, he commenced the transfusion. During the transfusion, the plaintiff's daughter arrived at the hospital and verified her mother 's beliefs and wishes. She demanded that the transfusions be stopped immediately. She signed a document stating this as her mother's wish, and releasing the doctor and hospital of any liability that could follow once transfusions were discontinued. The doctor refused to abide by the daughter's wishes, stating that he had a professional responsibility to continue to care for his patient in the best way possible. The tri al court found that he did not have a valid reason for ignoring the card and the daughter, and found him liable for battery, and awarded damages of $20,000. The Ontario Court of Appeal affirmed thi s decision. Although many issues were raised, the court resolved them all in favour of the plaintiff. Even though the physician may act without consent because of necessity in emergency situations, this principle does not allow a physician to ignore the advance directives of a patient. As well , a competent adult ha the right to refuse life-sustaining treatment. The interest of the state in preserving the life of its citizens does not override this right of the individual. Finally, the fact that the physician did not have the opportunity to counsel the patient did not affect the validity of her advance directive. At present, battery is the most prevalently used legal principle when issues surrounding blood and Jehovah 's Witnesses arise. However, wi~h advances in bloodless surgery techniques, plaintiffs may begm to use the principle of medical negligence to hold physicians responsible for the manner in which they treat patients who refuse transfusions . This may be true because of how courts

determine the appropriate standard of care to be used by a physician. The courts use expert testimony of what the conduct of a similarly situated physician would be. Once thi s normal conduct is determined, it is used as the appropriate standard of care. The Supreme Court of Canada laid out this principle quite clearly in

Ter Neuzen v. Korn 14: It is well settled that physicians have a duty to conduct their practice in accordance with the conduct of a prudent and diligent doctor in the same circumstances. In the case of a specialist, such as a gynaecologist and obstetrician, the doctor's behaviour must be assessed in light of the conduct of other ordinary specialists, who possess a reasonable level of knowledge, competence and skill expected of professionals in Canada, in the field. Therefore, as more physicians begin to utilize bloodless surgery in their practices (according to the Jehovah 's Witness community, in 1997 over 75,000 physicians practised bloodless surgery in U.S.)15, the standard of care in treating patients will evolve to require more universal knowledge of bloodless techniques, or referral to specialists who can perform such procedures. Doctors do not have to constantly try out new innovative techniques to meet the requisite standard of care, but once such procedures have become commonly used, it is incumbent on physicians to utilize them .16 Thus, the way the average physician treats her Jehovah's Witness patients will likely change quite rapidly over the next few years. Even though referral to a specialist to perform bloodless surgery may be feasible for physicians dealing with non-life threatening situations, this may not be the case for the emergency room (ER) physician. It may become necessary for ER doctors to be able to perform full-fledged bloodless procedures when faced with patients who do not want blood transfusions . If they do not, they could be held civilly liable for not meeting the appropriate standard of care for these patients. Beyond the point of the eventual progression of the standard of care, if an action were brought before the courts for the wrongful death of a Jehovah 's Witness today, the courts may find that the standard is even higher than that practised by the average emergency room physician . The reason for this derives from an exception that was reiterated by the Supreme Court in Ter Neuzen 17, which deals with whether a judge or jury can find the actual common practice of the profess ion itself to be negligent: I conclude from the foregoing that, as a general rule, where a procedure involves difficult or uncertain questions of medical treatment or complex, scientific or highly technical matters that are beyond the ordinary experience and understanding of a judge or jury, it will not be open to find a standard medical practice negligent. On the other hand, as an exception to the general rule, if a standard practice fails to adopt obvious and reasonable precautions which are readily apparent to the ordinary finder of fact, then it is no excuse for a practitioner to claim that he or she was merely conforming to such a negligent common practice.

Hence, it may be argued that any standard of not ro utine ly using bloodless surgery in any way when operating on a Jehovah 's Witness is negligent apart from whether or not that is the common practice of the physician 's peers. While it is quite technical to assess whether the use of bloodless techniques is beneficial overall in comparison to blood-utilizing techniques , it is not nearly as technical to determine whether using bloodless techniques are beneficial in comparison to no such technique at a ll , or to using blood when it is contrary to the patient 's wishes. In light of these options, it seems that using bloodless techniques may be mandated in today's soc iety when dea ling wi th someone who objects to usage of blood products. When there are options to doing nothing, and when doing nothing will likely result in the death of the patient, doing something will undoubtedly be better than doing nothing. Even providing a small chance of surv ival for the patient is beneficial to the overall outcome, and this seems to necessitate a change in the standard of care. The options of these procedures also provides a more acceptable option to many physici ans who have great qualms with doing nothing when a Jehovah's Witness comes through their doors who requires a blood transfusion . Courts and juries may see this as being quite clear and find that lack of knowledge and usage of these procedures on the part of the emergency room physici an as behav iour below the required standard expected of these physicians. Simply put, the court has the discretion to hold that a higher standard is required in light of available tools or techniques.18 Although the above argument seems plausible for the application of the above exception, the fact is that medical evidence is lacking to support this finding. As yet, there fails to be any comprehensive, conclusive study that supports the proposition that using bloodless surgery has inherently better outcomes than with using no blood at all. Nor is it reasonable to assume that such a study could ethically be done . As such, it is probable that the Ter Neuzen exception may not be invoked here, for we cannot expect physicians to adopt a standard that has yet to be proven beneficial. However, if such a study were completed to ultimately show the safety and efficacy of bloodless techniques, the argument using the Ter Neuzen exception would likely apply. As well, each of the various procedures would have to be assessed separately by the courts, for there are many different types of procedures available. Some of these procedures that are less invasive should already be considered to be currently part of the standards of care, for they are options with little to no risk that should be given to a patient refusing other treatn1ent. Legal issues may develop for hospitals if they do not offer bloodless surgery. Constitutional protection for Jehovah 's Witnesses under the Charter of Rights and Freedoms along with provinci al and federal protection of religious freedom under human rights legislation will possibly create a duty to accommodate on the part of the hospitals. Equality law dictates that if bloodless surgery is a beneficia l technique, hospitals must provide it so that Jehovah's Witnesses will have equal access to health care. This argument is comparable to that made in Eldridge v. British Columbia (Attorney Genera/)1 9, where the fact that sign interpreters were not available at a hospital for a deaf person violated their right to access to health care under the Charter. Providing interpreters was mandated, seeing that the cost to the

UWOMJ 71 (2) 2001 13

provincial health care budget would not have created an undue burden. A similar argument could be made in the situation with Jehovah's Witnesses. If the cost of the equipment for bloodless techniques is not prohibitive, then the courts may find it necessary to dictate thi s aspect of hospital administration to accommodate for the rights protected by the Charter. Even though this is not an identical situation to that in Eldridge, some of the same principles of law will apply. Thus, hospitals and other health care providers should be aware of possible liability in this situation.

REFERENCES 1. 2. 3. 4.

CONCLUSIONS

The advancement of bloodless surgery techniques and their reasonable acceptance as a part of mainstream practice has significant imp lications for legal po licy for hospital regu lations and clinical practice guidelines for physicians. As the legal principles of the Malette v. Sh ulman case has demonstrated, and the Ter Neuzen case emphasized, the progression of these techniques may shape a new standard of care for surgical patients in Canada.

7. 8. 9. I 0. 11 . 12.

ACKNOWLEDGEMENTS The authors would like to thank Professor Robert Solomon of the Faculty of Law at the University of Western Ontario for reviewing this paper.

13. 14. 15. 16.

17. 18. 19.

Humber River Regional Hospital is a 600 bed community hospital serving the citizens of northwest Toronto with world-class patient care and state-of-the-art technology. It provides a full range of acute medical/surgical services on two si tes, including two Emergency Departments with 120,000 vi its annuall y, Regional Dialy i and Pediatric programs, a Level [( Nursery and other exciting medical programs. More than 650 physicians en ompassing 28 specialties and a large Family Practice group hel p thi s growing community hospital serve a large and diver e community. Patient focused care is provided through 6 program management teams - Emergency, Ambulatory and Community Services; Medical Program; Mental Health Program; Surgical Program; Women 's and Children's Health; and Diagno tic and Clinical Services.

Lf you are interested in pursuing a career at a well established and caring hospital which is "committed to patient needs," please forward a letter and detailed curriculum vitae, indicating your area of interest to: Medical Affairs Humber River Regional Hospital 200 Church Street Weston, Ontario Canada M9N IN8 Fax: 416-243-4547 e-mail: ml atter@hrrh .on.ca

Humber River REG I ONAL HOSPITAL

The hospital of choic ... committed to patient needs

UWOMJ 71(2) 2001

72 OR (2d) 417 (Ont.C.A) . ibid. Carikas DA . Bloodless Surgery Developments Accommodate Patient's Choice ofTreatment. Medicine and Law. 18(4):505-13, 1999. DeCastro, RM. Bloodless Surgery: establishment of a program for the special medical needs of tlze Jehovah 's witness community-the gynecologic surge1y experience at a com munity hospital. American Journal of Obstetrics and Gynecology. 180: 1491-8, 1999 Jun . ConeJet a/. Blood products: optimal use, conservation and safety. Jnsh路uctional Course Lectures. 39:431-4,1990. http://www.bloodlessmed.com. NJ Institute for th e Advancement of Bloodless Medicine and Surge')' at Englewood Hospital and Medical Cente1: Supra note 4. http://www.brookdalehospital.com/htnlllbloodless_surgery.html Langone J Bloodless Surge1y . Time Special issue Fa/1199 7. P 74-6 Supra note 4. Ley, S.AACN Clinical Issues. 7(2): 238-48, 1996 May) Blood-Vita/ for Life. How Blood Can Save your Life. Watchtower Bible and Tract Society of Canada. Georgetown Canada. p.5. 1990. Supra note I. (1995), 127 D.L.R. (4th) 577 (S.C.C.) . Supra note 9. Legal Liability ofDoctors and Hospitals in Canada. 3rd edition. Picard, Ef and Robertson, GB. 1996. Carswell Thomson Professional Publishing. pp. 200. Supra note 14. Supra note 16 at pp. 201 . [1997} 3 S.C.R. 624

New Beginnings Bring PRHC is about ro embark on the single largest hospital construction project in the hisrory of the city. This new facility will improve health care delivery and allow PRHC to further fulfill its regional role with more than 500 beds. Until then, PRHC's role will continue to grow as more specialized services, such as dialysis, MRI (magnetic resonance imaging) and an expanded paediattic diabetes program are added. PRH C, working in co-operation with its regional health care partnen;, strives to be a place of excellence for healcl1 care and treatment. Cw-rendy a 360-bed regional referral centre, d1e Peterborough Regional Health Centre serves Halibw-ton, orthumberland, Victoria and Peterborough counties. W/e are a centre of excellence in the delivery of comprehensive and accessible care. Through a welcoming and healing environment, our caring staff partner in a health continuum d1at involves the community, patients and d1eir families. For further in formation, contact Jane Parr, Corporate Director, Human Resources, jparr@prhc.on.ca or visit www.prhc.on.ca.

Profiles

Interview with Dr. Quan: A Transplant Surgeon

Maryann e Rockx, Meds 2004

Dr. Doug Quan is a surgeon at the London Health Sciences Centre University Campus. During his general surgery residency at the University of Western Ontario, his interest was in hepatobiliary surgery. Since he also did research in transplant immunology as a resident, he was encouraged to become a transplant surgeon. Dr. Quan has since done part of a fellowship in London, spent a year in Toronto, and was in Cambridge, England for a year and a half where his research focused on xenotransplantation. Dr. Quan 's surgical practice now includes hepatobiliary surgery as well as both adult and pediatric liver transplants. The percentage of his practice which deals with transplants depends. on the timing because of donors . However, overall , transplantatiOn accounts for 40-50 % of his practice. An excellent website (http://www.lhsc.on.ca) describes the organs implicated in various transplants and has lists of dates in regards to transplantation from Canada and around the world. More than thirty years ago, the world's first liver transplant was performed in Colorado (in 1968). Canada's ~irst adult liver tran~足 plant occurred in 1977 and the first pedtatn~ ltver transplant m 1984 both or which occurred in London, Ontano. The Multt-Organ Tran~plant Unit opened a few years later, in 1987, at LHSC-UC.

What has been the impact of the Multi-Organ Transplant Unit on the transplant program and how does it compare to other centres? The whole multi-organ transplant program, not just the unit, I think irt general is more of a community feel an~ is more of _a cohesive group. It appears to me when workmg wtth _t~e coordtnators and the nurses in the unit, everyone knows thetr JOb really well and I can be confident in whatever they are telling me. And it is all for a common goal - and that is the best interest ?f the patient. I think that in this particular program, of the one s that

I've seen, people are more willing to go that extra mile to have things run properly.

LHSC-UC can be considered a leader in Canadian medicine for its transplant program. The original liver transplant program in Canada was at LHSC-UC, pioneered in part by Dr. Wa ll, the current program director. There have been many Canadian 'firsts ' performed at this centre. In 1988 surgeons at LHSC-UC performed the world's first small bowel and liver transplant. Although you were not on staff at the time, can you tell me about that procedure? Transplanting the small intestine has traditionally been very difficult to do because of primarily many immunological barriers. One of the surgeons, David Grant, who is now at another centre, was interested in trying to pioneer the field and succeeded in doing so by transplanting the liver in association with the small bowel. It appeared that the liver helped to protect the intestinal graft from rejection which has been shown in other organs as well.

In 1990 the world's first cluster transplant (liver, small bowel, pancreas, stomach) was performed at LHSC UC. This is a rare procedure carried out because of something such as desmoid tumours (benign tumours found in the retroperitoneum which are otherwise unremovable). Worldwide experience is still limited and is still considered borderline experimental. The results are not as good as some of the other organs transplanted. Canada's first living donor liver transplant was performed at LHSC-UC in 1993. Is this procedure becoming more common and will this be the the trend be in the future? It is becoming more common; we have done two and we are planning to do another one in the new year (January 2001). It is becoming more common but it is not without controversy because you are taking an otherwise completely normal person and subjecting them to a fairly big operation. But as long as you have people who are experienced with working around and through the liver, then it becomes much safer. But it is a very intense opera-

UWOMJ 7 1(2) 2001 15

tion because you don 't want anything to go wrong - it's j ust be lieving you can do it. Can you describe a typical procedure for a cad:1veric donor transplant, from the time a liver becomes available? The donor coordinator will call and say that they are in the process of working up a potential donor at another centre and they are talki ng with their coordinators. Then they get a brain-death declarati on and then arrange transportati on in terms of organ identif ication, th at is, which organs are being considered for retrieva l and fro m which centres are those people coming. You then have to coordinate when you can get there. Then you have to physically get there, on ground or by air. For us, it is usually the fe llows who go out to do the procurements then they do the operation and assess the liver. If everything goes we ll , they f ini sh the operati on and flu sh the liver and bring it back here on ice. Often we have our recipient operati on started before they get arrive back so that, if we can, shortly after they 're back we can put the liver in fa irly quickly. We try to stay within twe lve hours outside the body. The operati on can be f ive to fo urteen hours. I have been told that you are working on laproscopic surgery with the kidney. Could you explain to me your involvement in this area? A lot of the research that is currently go ing on in transplantati on has to do with the di screpancy between supply and demand of organs. If we had a more pl enti fu l supply, we would be able to help more peopl e. One of the new techniques that has been developed in the States is a procedure call ed laproscopic donor nephrectomy where we would do the di ssecti on of a relative of someone who needed a kidney transpl ant. We would do the di ssection of the kidney using a laproscope so it would be all inside the abdominal cavity through a scope and camera so the incisions made are very small. As a result, it is much better tolerated by the donor. However, you are taking an otherwise hea lthy person and subjecti ng them to an operati on. The operati on is not quite as bi g as the liver one, but still signi ficant. Thi s has been shown to improve donor stati stics in the U.S ., because peopl e have been more willing to donate if it i eas ier on them, and understandably so. It is someth ing our centre does not currently have ; a lot of centres do have it in the States and it is something we should have. What is your opinion on the numbers of cadaveric donors here in Canada compared to other countries?

have thi s program . Can you tell me about your future goals? Ri ght now I' m trying to get a lab started. We have a lab but we have not done that many experiments. There is a bi g transpl ant research group here and one of the main focuses is that of xenotransplati on. It would solve the problem if we could have an inexhaustible supply of organs. We would be abl e to help a lot more people. Ri ght now we do not accept people on our transpl ant waiting list if we don't fee l they would do well , even though there is no alternative. There is no liver dialysis. We turn many people away and there are peopl e who di e on our waiting list, about 15%. Thi s is not insignificant. If we had a supply of organs, such as fro m pigs, we would, theoretically, be abl e to transpl ant as many pig organs, if it works, into as many peopl e as we wanted. That's the next big th ing if it happens but there are so many challenges and questions that still need to be met. People here are working hard at it. We have world-class faci liti es and researchers in xenotranspl antati on and I' m just becoming a small part of that.

Post Script: I was invited to see a living-donor liver transp lant and would like to thank D1" Quan and Dr. Wall and the OR nurses for allowing me to see so much in the operating th eatre and for their explanations of the procedure.

SCHERING CANADA INC.

rnELOCOM

In Canada, our donation rate is 14 to 16 per milli on, whi ch if you compare it to the rest of the world is pretty poor, actuall y. The U.S. has 20 to 23 per million. The mode l that everyone looks up to is the Spanish model. They are about 35 per milli on, above everyone else. Why do you think that is ? Cultural, pro bably. Cul tura l barriers are signi f icant. In Japan, they j ust recently adopted bra in -death laws so now it is lega l to have brain-dead donors. In 1998 or 1999 they had a total of th ree in the who le coun try so it really vari es in each country. Lucki ly, in our region, the London region, our donor rate is 23 to 25 per milli on and I think that is an indicati on of how this particul ar community supports our program. It 's in the medi a a fa ir amount here compared to other ci ties and I th ink that peopl e are pro ud to 16

UWOMJ 7 1(2) 2001

Nasonex lllPrometrium

Promotion and Prevention

Psychic surgery: Opening the mind and heart to a new medicine

Alan S. Kahn, lvfeds 2004

The exciting field of mind-body medicine has rapidly emerged over the last decade. It continues to grow and ~omplements tremendous advances in the biochemical, physiological, and genetic understanding of the physIcal human body. A narrative exploration of three key medical doctors: Dr. Herbert Benson, Dr. Dean Ornish, and Dr. David Spiegel, and their landmark research in this diverse field will serve as an introduction to a refreshingly holistic and empowering approach to medicine.

INTRODUCTION Evidence continues to accumulate showing that psychic and emotional practices can have healing effects. For instance, an experiment testing the effects of verbal instructions on the ability of patients to shunt their own blood away from the site of spina l surgery found that this group lost nearly 500 cc less blood than the control group'路 In another study, patients who listened to a tape of "positive therapeutic suggestions" while under genera l anesthesia for a total abdominal hysterectomy required 24 percent less pain medication the day after surgery than patients who listened to a blank tape2. A Harvard study testing the effects of a preoperative, anesthetist-initiated discussion regarding the use of conscious relaxation to alleviate the expected pain after abdominal surgery found that the surgeons, blinded to the randomization, released these special-care patients 2. 7 days earlier than the control patients3. On a psychosocial level, a Dartmouth study found that for older patients undergoing open-heart surgery, those who neither had regular group participation nor drew strength or comfort from religion were more than seven times more likely to die six months after surgery4. These studies illustrate the significant role a patient's mind plays in surgical outcome, a process often mistakenly thought of as a purely physical act dependent entirely upon the surgical team and the patient's cooperative body. The movement within the field of medicine to recognize the patient as a whole person with unique feelings, background, and roots has been growing to counter the traditional mechanistic approach to disease. Over the past 30 years, a growing body of research has begun to show evidence for the healthier and, in some cases, lengthier life achieved through strong social, spiritual, and/or religious ties. This type of health promotion clearly extends beyond the realm of surgery. A

review of a number of these mind-body studies will il lustrate the potential transforming effect of this holistic movement on an individual's perception of self-health and the current practice of medICine .

THE RELAXATION RESPONSE In 1968, Harvard cardiologist Dr. Herbert Benson was testing the relation between a monkey 's behavior and blood pressure when some unusual characters walked in, proposing a novel study. They were practitioners of Transcendental Meditation a form of meditation that gained popularity in the 1960's, and tl~ey claimed to be able to control their blood pressure through their meditative practice. Although very reluctant at first, Benson 's curiosity prevailed, leading him to produce a significant body of research on a phenomenon he termed the "relaxation response" .5 When following the simp le steps of finding a comfortable, peaceful location to sit, relaxing one's muscles, allowing one 's self to breathe slowly and naturally, and then concentrating on a repeated syllable or word such as peace or amen for 20 minutes Benson observed that this meditation induced a hypometaboli~ state. The physiological changes that occurred included a decrease in respiratory rate, a drop in blood pressure, a decrease in oxygen consumption, and an increase in the slower alpha brain waves (normally present during pleasure experiences). Benson explained that these effects were due either to a mind-initiated dec~ease in sympathetic response or an increase in parasympathetic response6. These internal changes were also observed in other meditative techniques such as yoga, autogenic training, and hypnosis with suggested deep relaxation. The most fascinating component of this research was the clinical application of these relaxation techniques. For patients

UWOMJ 71(2) 2001 17

with hypertension , their systolic and diastolic blood pressures significantly dropped from a premeditation average value of 146/92 mrnHg to a normal average value of 135/87 mmHg through bidaily meditative practice spanning twenty minutes7 In another group of patients experiencing frequent premature ventricular contractions (PVC) , the average PVCs/hr dropped significantly fro m 151 to 131 after on ly four weeks of meditative practice. An even larger drop was experienced during sleepi ng hours as it decreased from 125 to 88 PVCs/hr8. Further studies have shown the effectiveness of the relaxation response in alleviating headaches, pain, insomni a, anxiety, mild or moderate depression, and even infertility. Benson has even suggested that if society placed a greater emphasis on mind/body health and somethi ng he call s our body's " remembered wellness", nearly 40% of physician visits cou ld be eliminated9. The healthcare savings could be enormous. To further illustrate the amazing power of the mind, Benson and team measured a 64 percent decrease in the metaboli sm of a Sikkim monk performing Tum-mo yoga during an investigative trip to a Tibetan monastery (Rwntek)I O. This is the lowest level ever documented in a hum an being! Such unexpected benefits are quite an accomplishment for an interventi on that is inexpensive and virtually harm free. The additional bonus of achi eving a greater awareness and appreciation for one 's body, self, and place within the external surroundings certainly paints these meditative practices as truly ideal healing interventions. However, Benson does stress that instead of worrying about how well one is performi ng the technique, one must maintain a passive attitude. It is a positiv , " let it happen" attitudell grounded in a strong personal belief system, be it philosophica l or religious, that relaxes the body and releases its healing power. This is expanded upon in hi s book "Beyond the Relaxation Response" where he introduces the concept of the Faith Factor as being a necessary component of a successful meditative practice1 2.

REVERSING HEART DISEASE Rated by Life magazine as one of the fifty most important influential members of hi s ge~e ration l 3, internist Dr. Dean Ornish first made quite a stir in the early 1980 's with the publi cat ion of a novel heart disease study. The study showed that when hi s patients w ith coronary atherosc lerosis underwent intensive lifesty le changes consisting of a I 0% fat, who le foods , vegetarian di et, aerobic exercise, stress management training, and psychosoc ial support groups, a signi fica nt reversa l of their bl ocked coronary arteries began to occur l4. Leadi ng up to the initial study, support and funding at this time were extreme ly difficult to find due to the w idely held medi ca l beli ef that coronary atiery di sease could only be fixed wi th surgery (coronary artery bypass graft) or cho lesterol-lowering drugs IS. Yet, repeated tria ls by Ornish showed similar positive results. In Ornish 's most recent study, when compa red to the control gro up, those patients who were randomly ass igned to the intervention group experi enced relative decreases in artery bl ockage of 4.5 % over I year and a 7.9% decrease over 5 years, compared to those people in the control group who experienced a 27.7% relative worsening of diameter stenosis over 5 yea rs1 6. For peopl e in the experimenta l arm , angina symptoms and cardiac events were 18

UWOMJ 7 1(2) 2001

significantly less (over 50%) over five years compared to the control group, and most experienced a revitalization of functional capacity. Ornish also found that the extent of decrease in blockage was proportional to the degree of adherence to this comprehensive lifestyle change program. This study is important to the evolution of mind-body medicine because Ornish firmly believes that while the diet and exercise played a large role in the reversal, participation in the support groups was the most important factor in the healing process 17. The sharing of hardships and advice between people in the group made the strugg le more bearable. Mutual feelings , stories, and in some cases love joined the participants in a bond of dedication to leading fuller and healthier lives. " It is a different kind of open heart surgery. We are asking people to open their heart in ways that go beyond just splitting open their chests," 18 Ornish says about the experience. This "emotional open heart surgery" may prove just as effective, if not more, than other much costlier interventions such as bypass surgery (~$35K U.S .), angioplasty (~$ 1 OK U.S.), and cholesterol-lowering drugs (~$1.5K U.S ./yr.)1 9. Although these studies are by no means suggesting that a do-it-yourself program (with encouragement and support) should replace all surgery and drugs, they do indicate that some illnesses may be more effectively treated by life tyle-changing interventions. Proper diet, adequate exercise, and stress-reduction techniques that optimize the relaxation response appear to be obvious methods to optimize a person's hea lth . But perhaps most importantly, the individual regains control of his or her own health both through the increase in fa ith in one's self and the positive interaction with others.

PSYCHOTHERAPY SUPPORT GROUPS, CANCER, AND PROLONGED LIFE Another ground-breaking study illustrating the importance of support groups and stress-relieving techniques is that perfonned by Stanford psych iatri sts David Spiegel and Irvin Yalom in the early 1980 's2o. They tested the effects of a weekly psychotherapy support group program for women with metastatic brea t cancer. By facilitating the di scussion of their illness, dying process, and how to live as fully as possible in the face of death, these groups acted a an " antidote to the isolation that so often accompanies the process of dying' 21. During these sessions, participants also learned the technique of self-hypnosis for pain control. At the end of this year-long randomized-control study, the women in the treatment support group had significantly lower mood disturbance such as anxiety, fatigue , confusion, as well as lowe r maladaptive coping responses. This illustrated the therapeuti c importance of open, trustin g social interaction and the various we llness habits they harboured. However, the truly remarkable results of this study were not discovered until ten years later when Dr. Spiegel decided to conduct a follow-up on these patients. One of the intentions was to disprove Yale surgeon Dr. Bernie Siegel's assertion that cancer patients with an exceptional fighting attitude live longer than other more passive patients22. (Another was to distant himself from Dr. Siegel 's name, one which people often confused with his own23 .) With an ex pected survival rate of two years after breast cancer metastasis , it was not surprising to find only 3 of the 86

women still alive. The shocking discovery was that compared to the controlled group's average survival rate of 18.9 months after study entry, the women participating in the 1-year support groups lived an average of 36.6 months after study entry24. When comparing the survival from time of first metastasis to death the ' women in the intervention grouped lived, on average, 14 months longer. This divergence in survival time did not begin to occur until 8 months after the first year was over. Evidence for this benefit of group therapy and self-hypnosis was further strengthened by indications that this increase in quality and quantity of survival time was propot1ional to adherence to the program, although thi s particular evidence is also strongly related to the health status of the patients before study entrance25 . For the first time, solid scientific evidence supported the claim that this type of intervention can not only enhance the quality of a patient's life, but in some circumstances also lengthen it. Recent studies of a similar nature are supporting this revolutionary conclusion26. Spiegel indicates that there are at least four different pathways explaining how psychosocial benefit to the mind can benefit the body27. The first relates to how interaction with others stimulates one to maintain a healthy diet, suitable exercise regime, and a routine sleeping habit. Ornish 's reversing heart disease program likely worked through this mechanism . Second, cancer patients in the support group may have built up the confidence and belief that they were receiving the best possible medical treatment as well as being able to refuse unwanted treatment. Spiegel is convinced that even the best combination of chemotherapy regimens is unable to account for the 18-month increase in survival time. The third suggested mechanism by which support groups can act is similar to that involved in Benson's relaxation response. By acting as a buffer against stress and depression, this intervention prevents a hyperstimulation of the autonomic system, thus reducing the production and secretion of stress hormones such as prolactin (a potential stimulator of tumour growth) and cortisol (a suppressor of immune function) . The latter effect is connected to the fourth proposed mechanism that is based upon the recently discovered neural and hormonal connections between the brain and the immune system, the basis of an emerging field called psychoneuroimmunology28. Thus, stress-relieving techniques and group-producing comfort are possible mechanisms to increase the levels of immune cells and suppress cancer growth. Despite these possible quantitative benefits, one must still remember that even if a prolongation oflife cannot be guaranteed, solid evidence recommends these mind-body interventions as effective means of assisting people to achieve a calmer, more peaceful closure to life. Despite these amazing and unexpected results, it should be noted that those from a somewhat comparable study were more disappointing. In 1993 , the above-mentioned Dr. Bernie Siegel found that psychosocial support therapy for 34 women with breast cancer enrolled in the Exceptional Cancer Patients (ECaP) program had no significant effect on length of survival after diagnosis29. However, unlike David Spiegel, who was initially cynical regarding the "often overstated claims made by those who teach cancer patients that the right mental attitude will help them to defeat cancer"30, Siegel's program was designed to not only enhance the quality of patients' lives, but to also prolong it. Both

Spiegel and Siegel both agree that Siegel's program 's lack of quantitative impact on survival was likely due to the emphasis placed on the use of menta l imagery and the dumping of negati ve emotions to fight and beat cancer, whereas Spiegel's Stanford program pl aced emphasis on interpersonal relationships, strategies to cope with pain, and se lf- hypnosis for pain controJ. 28 Paradoxically, what the above suggests is that, in some cases, one may actually be able to prolong life by going through a process of "death detoxification", where fears of dying and loss of control are shared and mind-body techniques are performed to alleviate stress and the disease symptoms. Putting one's mind towards appreciating life and its gifts is more likely to enhance the quality and length of one's life, whereas the direct attempt to live longer through the potentially sires iful mental process of fighting cancer and other disease may fail to do so. This possible mechanism relates back to Benson 's idea that the relaxation response is most effective when the meditation technique is supported by the individual 's philosophical , spiritual, or religious belief system. A passive accepting mind-state may better allow the body to naturally take care of itse lf than when the mind is actively interfering with it. Ornish 's revers ing heart disease program also requires the participants to have a similar type of belief in the body 's ability to heal , although not necessa ry cure, itself in conjunction with mind-willed healthy living. It is quite possible that studies showing the positive effect of prayer and religious belief on health and longevity31 work in a similar fashion .

CONCLUSION The above studies provide excellent scientific evidence for the mind 's ability to influence general health states and disease processes of the body. Doors are currently opening to a very exciting time in medicine. Instead of viewing the physical body as simply a machine, an increasingly popular view is beginning to incorporate the concept of a willful mind being at the center of our own individual systems. In light of this potential return to a unified conception of the mind and body, many exciting ideas have only begun to be investigated. Besides more obvious questions like the role oftouch32, pets33, and parents34 on health, some of the more mysterious areas that have begun to be investigated include the infant medical field of neurogastroenterology35 and the controversial claims regarding the healing effects of intercessory prayer36 and non-local effects37. There is no doubt that these and many other currently unfathomable questions will begin to be seriously answered in this new century of the mind .

ACKNOWLEDGEMENT The author would like to thank fellow medical students, Danielle Martin and Albina Veltman for providing helpful insights.

REFERENCES HL, Benson DR, Kuiken DA. Preoperative instructions for decreased I. bleeding during spine surgery. Anesthesiology 1986; 65: A245. 2. McLintock TTC, Aitken H, Downie CFA , Kenny GNC. Postoperative analgesic requirements in patients exposed to positive intraoperative suggestions. BMJ 1990; 301: 788-790.

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9. 10. I 1. 12. 13.

14.

15. 16.

17. 18. 19. 20.

21. 22.

23. 24.

25. 26.

27. 28. 29.

Egbert LD, Battit GE, Welch CE, Bartlett MK. Reduction ofpostoperative pain by encouragement and instruction of patients. NEJM 1964; 270: 825-827. Oxman TE, Freeman DH, Manheimer ED. Lack of social participation or religious streng th and comfort as risk factors fo r death after cardiac surge1y in the elderly. Psychosomatic Medicine 1995; 57: 5-15. Benson H. The Relaxation Response. New York: William Morrow, 1975. and Benson H, Beary JF, Carol MP Th e relax ation resp onse. Psychi atry 1974; 37: 37-46. Benson H. The Relaxation Response: Hist01y , physiologic basis and clinical usefuln ess. Acta Medica Scandinavica (supplementum) 1982; 660: 231-237. Benson H, Rosner BA, Mar::etta R, Klemchuk H. Decreased blood pressure in pharmacologically treated hypertensive patients who regularly elicited the relaxation response. Lancet 1974; i: 289-291. Benson H, Alexander S, Feldman CL. Decreased premature ventricular contractions through the use of the relaxation response in patients with stable ischemic heart disease. Lancet 1975; ii: 380- 382. Benson H with Mwg Stark. Timeless Healing. New York: Scribne1~ 1996. Pg. 226. Benson H. Timeless Healing. pg. 166. Benson H. The Relaxation Response. pg. 160 Benson H. Beyond the Relaxation Response. New York: Tim es Books, 1984. Ornish D. Love & Survival: The scienti fie basis for the healing power of intimacy. New York: Harper Collins, 1998. see inlay card [n.b.: chapter 2 provides an info rmative summa1 y of over 100 studies exhibiting th e healing effect of community involvement, emotional support, and love.] Ornish D, Brown SE, Scherwit:: LW, et at. Can lifesty le changes reverse corona1y heart disease ? Th e lifestyle heart trial. Lancet 1990: 336: 129-133. Ornish, D. Dr. Dean Ornish 's Program for Rever ing Heart Disease. New York: Random House, 1990. Ornish D, Scherwit:: LW, Billings JH, et al. Intensive lifestyle changes for reversal of corona1y heart disease. JAMA 1998; 280(23): 20012007. Ornish D. Love & Survival. pg. 118- 124. Moyers, Bill. "Changing Life Habits." In Healin g and the Mind. New York: Doubleday, 1993. pg. 109 Moyers, Bill. Healing and the Mind. pg. 112 Spiegel D, Bloom JR, Yalom !D. Group support for patients with metastatic cancer: A randomized prospective outcome s tudy. Arch Gen Psychiatry 198 1; 38: 527-533. Spiegel D. Group s upport fo r patients with metastatic cance1: pg 532 Siegel B. Love, Medicine, & Miracles. New York: Harp er and Row, 1986. and Siegel B. Peace, Love, & Healing. New York: Harper and Row, !989. Ornish D. Love & Survival. pg. 51-53 Spiegel D, Bloom JR, Kraemer HC, Gottheil E. Effect of psy chosocial h·eatm ent on survival of patients with metastatic breast cance1: Lancet 1989; ii: 888-89 1. Spiegel, D. Living Beyond Limits: New Hope and Help for Facing LifeThreatening Illness. New York: Tim es Books, /993. pg. 80-8 1. Fawzy FI, Fawzy NW, Hy un CS, et at. Malignant Melanoma: Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years late1: Arch Gen Psychiatry 1993 ; 50: 68 1-689. see also Richardson JL , Shelton DR, Krailo M, Levine AM. Th e effect of compliance with treatment on survival among patients with hematologic malignancies. J Clin One 1990; 8: 256-64. Spiegel, D. Living Beyond Limits: New Hope and He lp for Facing LifeThreatening Illness. pg. 91 Ader R, Felten DL, Cohen N, eels. Psychoneuroimmunology, 2nd edition. New York: Academic Press, 1991 . Gellert GA , Maxwell RM, Siegel BS. Survival of Brest cancer patients receiving adjunctive psy chosocial supp ort therapy : A 10-year follow-up study. J C lin One 1993; 1 I {I) : 66-69.

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30. Gellert GA . pg. 68. and Spiegel D. Living Beyond Limits. pg. 73-4, 85-6. 31. Koenig HG, Idler E, Kas/ S, et. at. Religion, spirituality, and medicine: A rebuttal to skeptics. Int J Psychiatry in Medicine /999; 29(2): 123131 . 32. Field T Massage th erapy for infants and children. Journal of Developmental & Behavioral Pediatrics 1995; 16(2): 105-111. 33. Friedmann E, Thomas SA. Pet ownership, social support, and one-year survival after acute myocardial infarction in the Cardiac Arrhythmia Suppression Trial (CAST). American Journal of Cardiology 1995; 76: 1213-1 217. 34. Russek LG, Schwart:: GE. Perceptions ofparental caring predict health s tatus in midlife : a 35-year fo llow-up of the Harvard maste1y of Stress Study. Psychosomatic Medicine 1997; 59(2): 144-149. 35. Gershon MD. The Second Brain. New York: Harpercollins, 1998. 36. Harris WS, Gowda M, Kolb JW, et a/. A randomized, conh-olled trial of the effects of remote, intercess01y prayer on outcomes in patients admitted to th e coronal)' care unit. Arch Intern Med 1999; 159{19): 227322 78. and By rd RC. Positive therapeutic effects of intercess01y prayer in a coronG/y care unit population. Southern Medical Journal 1988; 81 (7): 826-829. 37. Dossey L. Reinventing Medicine: Beyond mind-body to a new era of healing. New York: HG1percollins, 1999.

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Thinking on Your Feet

A case of laryngeal cancer

John Lee, Meds 2003

You are a 3rd year general surgery res ident, rotating through a 2~month elective in otolaryngology when you encounter the following situation.

It is Monday morning and you are scheduled to begin your first clinic with one of the E.N T specialists in the city. Th e first patient you see is a 53-year-old man by the name of "M1~ Johnson ". After taking a detailed hist01y, Mr. Johnson reveals that he has been referred by his fa mily physician because ofpersistent hoarseness during the last 5 weeks. 1. Define hoarseness and identify 6 common problems associated with this presenting symptom.

Th e rest of the clinical history is insignificant except fo r the fact that Mr. Johnson admits to being a 35 pack year smoker who drinks alcohol 7-8 times a week. Th ere is no evidence of a recent respiratory tract infection. You proceed to complete a full head and neck examination including an indirect visualization of the larynx using a large diam eter mirro1~ Although both vocal cords are mobile, you are particularly concerned about an area of reddening and thickening on the anterior two-thirds of the right vocal cord. Palpation of the neck do es not reveal any masses. 2. What are the signs and symptoms of laryngeal carcinoma and how is it diagnosed?

You and y our consultant proceed to biopsy the suspicious area under general anaesthesia and the pathology report comes back confirming a diagnosis of squamous cell carcinoma of the

right vocal cord. at this time.

M1~

Johnson wants to know what his options are

3. Describe the staging system for glottic carcinoma and the different modalities of treatment?

For the next 6 weeks, Mr. Johnson receives radiotherapy at the cancer centre and fo llows up at the clinic every 3 weeks to assess the progress of treatment. Five months later, Mr. Johnson s voice has gotten worse and is now more "breathy" than before. On examination, the right vocal cord is immobile and ulcerations are present on its mucosal swface. 4. Why did radiotherapy fail and what is your plan of treatment now? Briefly describe the total laryngectomy procedure?

Mt: Johnson s wife and daughter are very concerned about an invasive procedure such as a total laryngectomy. Before consenting to the surge1y, they want to make sure that this is the best decision for Mt: Johnson. 5. What are the risks and post-operative complications associated with a total laryngectomy? How successful is the procedure?

Mr. Johnson sfa mily is now feeling more comfortable about going ahead with the surgery. However, th ey are worried that because this surge1y involves removing the voice box, Mr. Johnson will never speak again. 6.

How do patients communicate after this surgery? UWOMJ 71(2) 2001 21

ANSWERS: 1. Hoarseness is defined as a change in the quali ty of a patient's voice. The voice abnormality can range from a weak, breathy vo ice to one which is harsh and scratchy. There are 6 common problems associated with hoarseness : (1) acute viral laryngitis; (2) vocal cord nodules; (3) voca l cord paralys is; (4) postnasal drip ; (5) gastroesophageal reflu x; (6) laryngea l cancer. 4.5 2. It is important to remember that laryngeal cancer can arise in each of the three anatomi ca l divi ions of the larynx: (40%) supraglottis, (59%) glottis, and (1 %) subglotti s. A supraglotti c tumour usually causes a muffled " hot-potato" voice with assoc iated symptoms of odynophagia, dysphagia, and a persistent sore throat.6 Glottic tumours tend to present ea rly wi th a change in vo ice qua lity that is usua lly described as being hoa rse .? Hoarseness lasting fo r more than 3 weeks should be referred to an ENT speciali st to eva luate the poss ibili ty of laryngea l cancer.8 And fin ally, subglotti c tumours may present with respiratory di stress, hemoptys is and a cough. If the cancer spreads beyond the level of the larynx , other symptoms such as referred ipsilateral otalgia may occur. The gold standard for the diagnosis of laryngeal cancer is the bi opsy of suspi cious ti ssue while performing a direct laryngoscopy under general anaesthes ia using an anterior commisure ri gid laryngoscope. Esophagoscopy, nasopharyngoscopy, and bronchoscopy can be done at the same time to eva luate the upper aerodigesti ve tract for other primary tumours. CT and MRl imaging is used to assess tumour extension and metastatic cervical disease while chest X-rays are done routinely to rul e out lung metastases. 6,7

3. Table l briefly describes the general tumour staging system for glotti c cancer as set forth by the American Joint Committee on Cancer (AJCC). It is important to note that there is a separate classification for supraglottic and subglottic carcinoma. The nodal and metastases staging system is identical to that for other form s of head and neck cancer and will not be discussed in thi s case study. The di fferent moda li ties o f treatment are based primarily on the various stages of laryngea l eancer. Earl y cancers (T l & T2) are usually treated by radi otherapy for cure, a modali ty that has the advantage of being orga n sparin g. A pati ent will typi ca ll y rece ive a dos ing reg imen for 4-6 consec utive weeks, 5 times a week.6 Endoscopic laser-ass isted surgery ca n also be used for small

Tumour Stage T1

tumours. On the other hand, late tumours (T3 & T4) usually do not respond very well to radiotherapy alone . Most centres ad~o足 cate radical surgery techniques such total laryngectomy With adjuvant radiotherapy. Any nodal or metastatic involvement classifies a patient as having a late tumour and will subseq~e~tly receive the corresponding therapy. Chemotherapy has a hmJted role in head and neck cancers and is usually reserved for palliative therapy or controlled trials. l,2,6,7 4. Various studies have reported high cure rates for early glottic cancer using radi otherapy alone. Five year survival rates range from 77-92%. 1 However, there is still the possibility that these tumours can progress to a more advanced stage. When a vocal cord becomes immobil e even after radiotherapy treatment, the only options left for a patient are mainly surgical. A total laryngectomy is a radical surgical technique used for advanced or recurrent laryngeal cancers. A basic description of thi s procedure is that it invo lves removing the connection between the upper aerodi gestive tract (nose and mouth) and lower respiratory tract (lungs). Intra-operative ly, thi s invol ves an incision just below the level of the cricoid cartil age in the neck, and separating the sternohyo id and sternothyroi d strap muscles in order to open a window to remove the larynx. A partial thyroidectomy is also performed to remove the side of the thyroid gland on the cancerinvolved side. Before the larynx is completely freed from its attachments, a tracheostomy is also performed in order to establi sh a direct connection between the lungs and the external environment. When the airway is stabilized, all the cartilages of the larynx are removed up to and including the hyoid bone. The pharynx is then directly connected to the esophagus by closing the pharyngeal mucosa. It is important to note that there are many variations of the laryngectomy procedure based on the extent and invas iveness of the cancer. I .3

5. Undoubtedly, there are inherent risks with every major surgery. This includes the risks from anaesthetics, intra-operative bl eeding, and dam age to related structures in the anatomical area being operated on. In a total lar yngectomy, critical structures include the thyroid gland, the superior lary ngea l artery and vein, the carotid artery and the internal jugular vein. However, operative mortali ty is usually less than 0.1%. Complications of this surgery include hematomas, fi stula formation, tracheal stomal strictures, wound infec tions, as we ll as pulmonary and cardiac prob-

Clinical Description

tum our limited to voca l cords with normal mobili ty

TlA

tumour limited to one vocal cord

TlB

tumour limited to both voca l cords

tumour extending to suprag lotti s or subglotti s with impaired vocal cord mobility

tumour confined to larynx with fixed voca l cord

tumour outside the larynx with thyroid cartilage destruction

Table 1. Staging System of the American Joint Committee on Cancer for Glotti c Carcinoma6 22

UWOMJ 7 I (2) 200 l

lems.3 However, these can be usually avo ided with adequate postoperative drainage, monitoring, and a short co urse of prophylactic antib iotics. Five year survival rates of T3 and T4 glottic cancers after receiving radiation and surgery have been reported to range from 50-66%. However, carci noma of the larynx can become quite invasive and the absence of treatment would result in a much poorer prognosis.6

Despite removing the larynx which conta ins the voca l cords, a total laryngectomy does not prevent speech production in the patient. This paradox is explained by the fact that speech can be generated by vibrating air in the pharynx . There are 3 alternatives fo r a patient to produce speech fo ll ow ing such a surgery: (1 ) a battery-powered device can be used to ca use vibrati on of air in the oral cavity and pharynx ; (2) esophageal speech can take place where patients regurgitate air into the pharynx and then use it as a source for arti culation ; (3) a one way channel can be created during surgery between the trachea l stoma and the pharynx so that during exhalation, the patient can produce vibrati ons of a ir in the pharynx (tracheo-esophageal speech). Thi s last technique involves the implantation of a special valve.4.8

REFERENCES 1. 2.

Ballenger JJ, SnoH; JB. Otorhinolal)'llgology: Head and Neck SwgeiJ'. Philadelphia : William s & Wilkens, 1996: 585-645. Cummings CW. Fredrickson JM, Harker LA , Krause CJ. Richardson MA , Schuller DE. Oto lary ngology Head and Neck Sw 路geiJ'. Missouri: Mosby-Year Book In c.. 1998: 2130-2 175. Declo !-IH. Sutgel)' of the LWJ'IlX and Trachea. Hong Kong: B. C. Decker Inc., 1990:310-34 7. Dhillon RS, East CA. Ew~ Nose and Throat and Head and Neck Surge!) '. New York: Churchill Livingstone. 1996: 54-61 , 96-99. Jafek BT楼, StarkAK. ENT Secrets. Philadelphia : Hanley & Belfus, 1996: 149-152, 208-213. Lee KJ Essential Otolary ngology, Head and Neck SLugery. Conneticut: Appleton & Lange, 1995: 555-568. Meyerhoff WL . Rice Df-1. Otolwyngo logy - Head and Neck Surgery. Philadelphia : W. B. Saunders Company, 1992: 739-769. 0 'Donoghue GM, Nanda AA. Bates GJ Clinical ENT. Canada : Singular Publishing Group, 2000: 2 11-2 18.

ACKNOWLEDG EMENT The author would like to thank Dr. Jason Atlas and Dr. John Yoo for reviewing thi s ca e. Dr. Atlas is a PGY2 res ident in Otolaryngology at the University of Western Ontario. Dr. Jolm Yoo is an Otolaryngologist, Head and Neck Surgeon at the London Health Sciences Centre, Westminster Campus.

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UWOMJ 71(2) 2001 23

Vocabulary

A century of radiation oncology

Heather Cockwell, Meds 2002

Joe Chan, Meds 2002

Chris Chu, Meds 2004

Thi s secti on is des igned to test and expand your knowledge of medical terminology. H 6w many items can yo u correctly define? Scoring:

13-1 4 = exce ll ent I 0-1 2 = above average 8-9 = good 5-7 = fair l- 5 = poor

1. Blepharectomy a) surg ical removal of a vein or part of a vei n b) surgical exc ision of all or part of an eye lid c) surgical removal of a pedunculated tumour d) incision of the nose for drainage purposes 2. Litholapexy a) washing of stomach to remove irritating contents or po isons b) surgical drainage of aqueous humour fro m eye, used to treat glaucoma 24

UWOMJ 7 1(2) 200 1

c) crushing a stone in the bladder foll owed by washing of the fragments through a catheter d) scraping of diseased ti ssue from a joint 3. Myotenotomy a) division of the tendon of a muscle b) removal of a portion of muscle or muscular ti ssue c) suture of a muscle wound d) excision of a tumour containing muscle ti ssue 4. A lexander-Adams operation a) surgical removal of the uterus, fa llopian tubes, ovaries, adj acent lymph nodes , and a part of the vagina b) shortening of the uterine round ligaments and suturing of the ligament ends to the external abdominal ring c) creation of an artificial opening in a fa llopian tube, to relieve an occ lusion arising from inflammation or scarring d) plastic surgery of the urethral-bladder jw1ction to relieve urinary stress incontinence

5. Paralytic ileus a) dilatation of a portion of the large bowel, due to amebic col its, ulcerative colitis or other bowel disease b) blockage and inflarrunation at the ileocecal valve due to a bil' iary calculus that cannot be passed c) protmsion of a loop of bowel through the omentum, which prevents normal bowel motility d) loss of bowel motility following surgery, accompanied by abdominal distension and vomitting 6. Swan-Ganz catheter a) catheter used for suction curettage of the uterus b) catheter recently shown to be useful in palliative drainage of pleural effusions c) balloon-tipped catheter used to estimate pressure in the left atrium of the heart d) balloon-tipped catheter used to drain the bladder 7. Glover's suture a) suture entering and exiting around the periphery of a circular opening, closing when drawn taut b) deep suture for joining the deep tissues of a wound c) suture formed by winding thread around pins placed opposite each other on the two sides of a wound d) continuous suture in which the needle is passed through the loop of the preceding stitch 8. Trendelenburg position a) patient standing, leaning forward, and supporting upper body with arms braced against a wall or chair b) patient lying supine on a bed tilted 45 degrees, with the head low c) patient lying with knees elevated, and with the head of the bed raised about 1.5 feet d) patient kneeling, with thighs upright, head and upper part of chest resting on table, and arms crossed above the head 9. Hartmann 's Procedure a) longitudinal opening of the main pancreatic duct, and anastomosis with the jejunum b) resection of all or part of the colon, with closure of the distal rectal stump c) anastamosis of an existing pancreatic pseudocyst to a blind loop of jejunum d) radical resection of pancreas, duodenum, and part of the stomach, followed by gastro-jejunal anasotomosis 10. Dehiscence a) collapse of alveoli in lungs; corrunon cause of early post-op fevers b) separation or rupture of a wound closure c) dismption of the abdominal wall such that abdominal contents are able to protrude d) sloughing of the epidermis, due to a staphylococcal infection ofthe skin

11 . Bistoury a) small, delicately pointed hemostat b) instrument used to explore the depth and direction of a wound Or SlllUS

c) spoon-shaped instrument for removing foreign matter from a cavity d) small surgical knife used in minor operations 12. Spigelian hernia a) herniation in which only one side of the intestinal wall is involved b) ventral herniation due to a defect in the linea semilunaris muscle c) herniation due to defect in superior posterior abdominal wall d) herniation due to defect in inferior posterior abdominal wall 13 . Intussusception a) failure of the bowel to form a complete, patent loop during development b) torsion of the bowel on itself, leading to intestinal obstruction c) prolapse of one segment of bowel into the lumen of another segment d) inflarrunation of a pouchlike hernia which lies in the muscular layer of the small bowel 14. Monteggia fracture a) fracture of the fifth metacarpal neck b) fracture of the ulnar head, associated with radial head dislocation c) fracture of the distal radius, often associated with shortening and dorsal angulation of the distal fragment d) incomplete fracture wherein a significant portion of the periosteum remains intact

ANSWERS 1. b) Surgical excision of all or part of an eyelid; a)Phlebectomy, c) Polypectomy, d) Rhinotomy

2. c) Crushing a stone in the bladder followed by washing of the fragments through a catheter; a) Gastric lavage, b) Goniapuncture, d) Arthroxesis 3. a) Division of the tendon of a muscle; b) Myomectomy, c) Myorrhaphy, d) Myomotomy 4. b) Shortening of the uterine round ligaments and suturing of the ligament ends to the external abdominal ring; a) Radical hysterectomy, c) Salpingostomatomy, d) Urethrocystopexy 5. d) loss of bowel motility following surgery, accompanied by abdominal distension and vomitting; a) toxic megacolon, b) gallstone ileus, c) omental hernia 6. c) Balloon-tipped catheter used to estimate pressure in the left atrium of the heart; a) Karman catheter, b) Tenckhoff catheter, d) Foley catheter

UWOMJ 71(2) 2001 25

7. d) Continuous suture in which the needle is passed through the loop of the preceding stitch; a) Purse-string suture, b) Approximation suture, c) Implanted suture 8. b) Patient lying supine on a bed tilted 45 degrees, with the head low a) Noble's position, c) Fow ler's position, d) Genupectoral position

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9. b) resection of all or part of the colon, with closure ofthe distal rectal stump; a) Puestow procedure, c) Roux-Y-Y cystojejunostomy, d) Whipple procedure 10. b) separation or rupture of a wound closure; a) atelectas is, c) evisceration, d) staphy lococcal sca lded skin syndrome 11 . d) Small surgical knife used in minor operations; a) Mosquito forceps , b) Probe, c) Curette 12. b) ventral herniation due to a defect in the linea semilunaris muscle; a) Richter 's hernia, c) Grynfeltt's hernia, d) Petit's hern ia 13 . c) prolapse of one segment of bowel into the I umen of another segment; a) developmenta l intestina l atresia , b) volvu lus, d) diverticulitis

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14. b) fracture of the ulnar head, associated with radial head dislocation; a) boxer's fracture , c) Colle's fracture , d) Greenstick fracture

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UWOMJ 71(2) 200 1

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Zebra Files

A review of Stevens-Johnson syndrome and toxic epidermal necrolysis

Chinedu Onochie, Meds 2004

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are varying degrees of a rare form of severe drug-induced cutaneous reaction. Characteristic skin lesions are small purpuric-centered macules accompanied by areas of confluent erythema. TEN and SJS differ primarily in the degree of skin and systemic involvement, with TEN being the more severe form of the cutaneous disorder and carrying a higher mortality rate. TEN and SJS are both rapidly progressive diseases that make early identification and treatment difficult. Once identified, however, management focuses on prevention of morbidity and mortality and skin re-growth. Techniques of epithelial tissue engineering and transplantation may one day revolutionize the treatment of TEN and SJS.

INTRODUCTION

TYPICAL SIGNS ANDS SYMPTOMS

Severe cutaneous reactions to medication are an extremely rare but potentially lethal risk of pharmaceutical use. Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are names used to describe what is believed to be varying degrees of a single form of drug induced reaction. 8. I2,I4 In 1922 the less severe form of this disorder, SJS, was characterized. Several decades later, in 1956, TEN was formally identified.9 Both of these disorders were initially identified by characteristic skin lesions. Skin lesions in SJS usually appear as small blister-like purpuric macules in conjunction with regions of skin in which the epidermal layer has detached from the dermal layer. 1 Skin lesions in TEN exhibit essentially the same characteristics but present with large areas of highly confluent erythema and larger sheets of detached epidermis.! TEN is among the most lethal form of druginduced cutaneous reaction, with a 30% fatality rate among affected individuals. Fortunately, both of these drug-induced reactions are quite rare. The incidence of SJS is approximately 1 to 6 cases per million individuals per year while the incidence ofTEN is 0.4 to 1.2 cases per million persons per year.IO

Most SJS patients present with rapidly spreading symmetrical lesions across the trunk and face.! These lesions appear as small purpuric centered macules accompanied by occasional areas of confluent erythema. Affected individuals also present with detachment of epidermis from dermis over l % to 10% of their body surface. I SJS and TEN are thought to be varying degrees of the same disorder, thus TEN patients present with all of the above symptoms. However, patients afflicted with TEN display a more confluent erythema, larger areas of necrotic epidermis, and total detachment of more than 30% of the body surface .1.8 Furthermore, more than 38% of TEN patients present with fever, a significantly higher proportion than is found in SJS.9 In addition to these cosmetic signs, TEN affected individuals present with acute skin failure, leukopenia, asthenia, skin pain, and severe anxiety.9 SJS and TEN patients often present with mucosal lesions (90% of cases) in addition to surface skin lesions.& These crustlike lesions may potentially appear anywhere on the body where a mucosal lining is present. Of particular concern are lesions of UWOMJ 71(2) 200 1 27

the respiratory and gastrointestinal tracts that are observed in I 0% to 30% of cases. Common patient symptoms associated with mucosal lesions are difficulty with alimentation, photophobia, and painful micturition _2.tl ,l6 Mucosal lesions of the conjunctiva (present in 85% of patients) may lead to hyperemia , pseudomembrane formation , synechiae between eyelids, and conjunctiva,7.9,20 A SJS or TEN diagnosis is based upon clinical ctiteria and a skin biopsy.

COMPLICATIONS The presence of SJS or TEN decrease an individual's immunity while simultaneously increasing that individual 's internal exposure to infectious organisms. This set of circumstances can potentially lead to sepsis, the most common cause of mortality in SJS and TEN.9 TEN is among the most letha l form of drug-induced cutaneous reaction, with a 30% fatality rate in the affected. In comparison, SJS has a morta lity rate of 5%.8,14 In individuals affected 'with TEN, mortality is most often an indirect result of acute skin failure or respiratory tract lesions. In individuals affected with SJS, complete skin failure is rare, and mortality is more likely an indirect result of respiratory tract lesions.9 In the presence of either disease, widespread interstitial pneumonitis may precede adult respiratory distress syndrome. Transepidermal fluid loss resulting in an electro lyte imbalance is another common problem associated with SJS and TEN. Genearlly, the extent of fluid loss is proportional to the area of affected tissue . In severe cases, as much as four liters of fluid per day is lost. 8 As a result of the various physiological pressures placed upon the body, biochemical disorders develop . It is not unusual for a patient with SJS or TEN to develop prerenal azotemia, hypercatabolism, or insulin resistance.9 Those who survive SJS or TEN are at risk of developing skin abnormalities such as extensive scarring, irregu lar pigmentation, eruptive nevi , persistent erosions of the mucous membranes, phimosis, vaginal synechiae, and abnorma l growth of nails .8 Approximately 35% of individuals that survive TEN and a slightly lower proportion of those who survive SJS also develop ocular problems such as Sjogren-like sicca syndrome, inturned eyelashes, squamous metaplasia, neovascularization of conjunctiva, neovascularization of the cornea, symblepharon, punctate kerati tis, corneal scarring, persistent photophobia, burning eyes, visual impairment, and blindnes. 9

EPIDEMIOLOGY SJS and TEN occur with approximately equal incidence between the sexes and among different races.9 The incidence of SJS is 1 to 6 cases per million individuals per year while the incidence ofTEN is 0.4 to 1.2 cases per million persons per year.IO However, SJS and TEN occur at a rate of one per one thousand AIDS patients per year.t 3,9

ETIOLOGY/PATHOGENESIS It has been demonstrated that the development of SJS and TEN is associated with the use of antibacterial sulfonamides, 28

UWOMJ 71(2) 2001

anticonvulsants, oxicam NSAIDS , allopurinol, chlormezanone, and corticosteroids. to SJS or TEN normally take two weeks to appear after initial exposure to the reacting drug. One to three days prior to the development of skin and mucosal lesions , the individual experiences feverish symptoms. The disease reaches its peak severity within four days of onset. 9 It has been theorized that SJS and TEN are caused by a direct toxic mechanism.9 However, more compelling evidence suggests that SJS and TEN are immunologically based.8 It is thought that the individual 's immune system, primarily CD8 lymphocytes, destroy the affected individual 's epidermal cells. Furthermore, symptoms of fever and muscular weakness are thought to be caused by cytokine activity. It is believed that this entire response is normally stimulated by an excess amount of drug-reactive metabolites.J,4,6,19 However, TEN can also be triggered by an inunune reaction to transplanted tissue- in such a case, the disorder is known as graft-versus-host-disease (GVHD) .5, t8

TREATMENT/CONCLUSION Treatment of SJS and TEN involves prompt identification and cessation of the use of the reacting drug. Acutely, the patient's pain, fluid loss, and any potential bacterial infection is treated. Administering corticosteroids to halt the spread of TEN has been attempted with poor results . Halting the progression of TEN is difficult and often ineffective because of its rapid onset. Treatment is aimed towards preventing acute mortality and aiding skin re-growth. Inactivity and rest in a hospital setting is normally required for approximately three weeks. 9 A potential surgical step is the application of skin grafts. Autologous skin grafts are not always possible because of extensive skin loss. Donor skin grafts pose a rejection and GVAD risk. Bioengineered skin grafts cultured from the patients ' own tissue is another option. This replacement tissue provides protection from infection while releasing cytokines/growth factors that stimu late growth of new tissue and replacement of the skin graft. IS As was mentioned earlier, partial loss of sight and blindness are major comp li cations of SJS and TEN. Recently, clinicians have developed methods to artificially reconstruct damaged corneas by transplanting cu ltured autologous limbal epithelial cells onto the damaged contralateral eye. A recent study has demonstrated successful application of this procedure in cases of unilateral vi ion impairment. Eyesight was improved from 20/ 112 to 20/45 in 83% of patients (n=6).17 However, the techniques of epithelia l tissue engineering and transplantation are far from being practically applicable . Difficulties in stem cell harvesting and reintegration have yet to be fully addressed. The time required to cu lture tissue is also problematic in light of the rapid development of this disease and its various complications. Also, the long term safety of engineered epithelial tissues has not been exhaustively studied.I S However, maturation of this technology should revolutionize the treatment ofTEN and SJS.

~ ~ ~

REFERENCES 1. Bastuji-Garin S. , Rzany B., Stern R.S., Sh ear N. H. , Naldi L. , Roujeau J C. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and eryth ema multiforme. Arch Dermatol. 1993; 129:92-6. 2. Chosidow 0. , Delchier J C., Chaumette M. T. intestinal involvement in drug -induced tox ic epidermal necrolysis. Lancet. 1991;337:928. 3. Correia 0. , Delgado L., Ramos JP , Resende C., Torrinha JA . Cutaneous T-cell recruitment in toxic epidermalnecrolysis: furth er evidence of CD8+ ly mphocyte involvement. Arch Dermatol. 1993;129:466-8. 4. Heng M.C. , Allen S.C. Efficacy of cyclophosphamide in toxic epidermal necrolysis: clinical and pathophysiolog ic aspects. J Am Acad Dermatol. 1991 ;25:778-86. 5. McDonald B.J , Singer J W, Bianco JA . Toxic epidermal necrolysis possibly linked to aztreonam in bone marrow transplant patients. Ann Pharmacother. 1992;26:34-5. 6. Merot Y, Gra vallese E., Guillen FJ , Murphy G.F Ly mphocyte subsets and Langer hans ' cells in toxic epidermal necrolysis: report of a case. Arch Dermatol. 1986; 122:455-8. 7. Prendiville JS., Hebert A.A., Greenwald M.J, Esterly N. B. Managem ent of Stevens-Johnson syndrome and toxic epidermal neo-olysis in children. J Pedian: 1989;115:881-7. 8. Revu:: J, Penso D., Roujeau J C., eta!. Toxic epidermalnecrolysis: clinical findings and prognosis factors in 87 patients. Arch Derma/of. 1987; 123:1160-5. 9. Roujeau J C. , Stern R.S. Severe adverse cutaneous reactions to drugs. Th e New England Journal of Medicine. 1994;331 (19):1272-1284. 10. Roujeau JC. , Kelly JP, Na ldi L. , R::any B., Stern R.S. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermaln ecrolysis. 333(24): 1600-1609. 11. Roupe G., Ahlmen M. , Fagerberg B. , Suurkula M. Toxic epidermal necrolysis with extensive mucosal erosions of the gastrointestinal and respiratory tracts. lnt Arch Allergy Appllmmunol. 1986;80: 145-51 . 12. Ruiz-Maldonado R. Acute disseminated epidermal necrosis types 1,2, and 3: study of sixty cases. JAm Acad Dermatol. 1985;13:623-35. 13. Rzany B. , Mockenhaupt M., Stocker U., Hamouda 0. , Schopf E. In cidence of Stevens-Johnson syndrome and toxic epidermalnecrolysis in patients with the acquired immunodeficiency syndrome in Germany. Arch Dermatol. 1993;129:1059. 14. Schopf E. , Stuhmer A., Rzany B., Victor N., Zentgraf R. , Kapp JF, Toxic epidermal necrolysis and Stevens-Johnson syndrome: an epidemiologic study from West Germany. Arch Dermatol. 1991 ;127: 839-42. 15. Schwab 1., Rivkah lsseroff R. Bioengineered corn eas- the promise and the challenge. New England Journal of Medicine. 2000;343(2) :136138. 16. Timsit JF, Mion G., Rouyer N., Le Gulluch e Y. , Carsin H. Bronchopulmonary disn'ess associated with toxic epidermal necrolysis. Intensive Care Med. 1992; 18:42-4. 17. Tsai R. J , Li L.M., Chen JK. Reconstruction of damaged corneas by h'ansplantation of autologous limbal epithelial cells. New England Journal of Medicine. 2000;343(2): 86-93. 18. Vii/ada G., Roujeau JC., Cordonnier C. Toxic epidermal necmlysis after bone transplantation: study of nine cases. JAm Aca Dermatol. 1990;23:870-5. 19. Viii ada G., Roujeau J C. , Clerici T. , Bourgault !. , Revu:: J immunopathology of toxic epidermal necrolysis: keratinocytes, HLADR expression, Langerhans cells, and mononuclear cells : an immunopathologic study offive cases. Arch Dermatol. 1992128:50-3. 20. Wilkins J , Morrison L., White CR. Oculocutaneous manifestations of the erythema multiforme/Stevens-Johnsonltoxic epidermal necrolysis spectrum. Dermatol Clin. 1992;10:5 71-82.

Sjogren-like sicca syndrome inturned eyelashes squamous metaplasia neovascularization of the cornea symblepharon punctate keratitis corneal scarring persistent photophobia burning eyes visual impairment blindness

Table 1. Ocular complications associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.

GREY BRUCE

Health SERVICES Grey Bruce Health Services is one organization operating on seven site in Grey and Bruce Counties. Our family physicians and specialist practice in the six hospitals and two clinics, ranging from Meaford, Markdale and Southampton in the south, Owen Sound in the middle and Wiarton, Lion 's Head and Tobermory in the north, with a total of 360 beds. The Owen Sound site is a Level C referral centre with 238 beds and a full complement of consultants. Located two hours from Toronto on beautifuJ Georgian Bay and Lake Huron; enjoy swimming, cliving, sailing, fi hing, skiing (both downhill and cross country), hiking, golf, cycling, snowmobiling, Jr."A" Hockey, theatre, and Folk Festival are just some of the activities available in these recreational communities. We are looking for: • Family Physicians • lnterni ts (General , plus Rheumatology, Cardiology, Neurology) • Obstetrician • Physiatrist • Psychiatrists • Pediatrician Interested parties are requested to contact: Sharon Winegarden, P.O. Box 1800, Owen Sound, Ont. N4K 6M9 (5 19)376-2121 Fax 519-376-9760 Email : swinegarden @owensound.healthserv.org

UWOMJ 71(2) 2001 29

Features Articles

Surgery in the nineteenth century: The conquest of pain and sepsis

Samir K. Sinha, Meds 2002

INTRODUCTION Surgery has pl ayed a central role in health and healing throughout the ages . Its name, which derives from the Latin word chirutg ia, f inds its roots in th e Greek words cheiros (hand) and ergon (work) . While some cultures looked on handwork as meni al and ranked it below that done by the mind, others, more like our own, have pri zed it above all other ski lls. However, it wasn't unti l the nineteenth century that two instrumental fac tors all owed th e profession to make tremendous progress to evo lve into its present fo rm . They were the discovery of anaesthes ia and th e proof that germs cause infec ti on. Prior to the nineteenth century, surgeons were necessarily re luctant to cut whi le the concept of humoralism held sway. In their view, it was absurd to remove a tumor; fo r examp le, beli eving th at it was only the ex pression of a dyscras ia and wou ld be bound to grow again on the same or another spot. These views wo uld finally change with the ri se of loca li sti c path ologica l anatomy around the advent of the nineteenth century. Surgica l activity as a res ult increased and a new type of surgeon arose, very di ffere nt from the traditi onal type, whose main occupati on had been the setting of fractures, treatment of wounds and amputati on in war. Despite their new know ledge and growing repertoire of techniques, the scope of a surgeon's work remained severely limited to minor surgeri es due to the lack of effecti ve pain control methods and by devastating postoperati ve infections. Abdominal operati ons including Caesari an secti ons were indeed performed at various times and pl aces, but the systemati c invas ion of body cavi-

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ties and internal systems, however, would not be feasible until the pati ent cou ld be put to sleep deeply and safely enough to permit unhurri ed operative maneuvers. Future developments in surgery, as a result, waited on the discovery of adequate pain-control methods.

THE ADVENT OF ANAESTHESIA A lthough effective anaesthesia was f irst discovered and put to surg ica l use in the United States, soporific potions, and analges ic agents such as opi ates and plants like mandragora had been put to use for thousands of years. There are many references in early medi ca l writings and general literature to pain-kil ling drugs g iven by mouth , although we have no real evidence about their efficacy or know ledge of the extent of their usage. Without kn ow ledge of their active ingredi ents, it is probable that the action o f the e crude concocti ons was very uncertain , sometimes ending tn death . Alcoho l had also been resorted to for centuries to make a pati ent oblivio us enough to pain to permit surg ical procedures whi le bleeding or reducti on of brain blood flow had also been emp loyed to decrease pain and sensibi lity. N evertheless the best reli ef for a person undergoing surgery was rapid los; of consc iousness, caused either by the analges ia or by the procedure itse lf. Surgeons, needless to say, strove for accuracy and speed. O~ e method of producing analges ia used intermittently from ea rly .ttmes w tth vari abl e success was compress ion, the concept of bluntt.ng the senstbtltty of nerves by compressing them with a tourntqu~t. The next step in the search for a sati sfactory method of mducmg surg ical anaesthes ia was connected with the earliest

work on hypnotism. A lthough branded as quackery, the pseudoscience of mesmerism, or animal magneti sm as an early form of hypnotism inspired some surgeons to investi gate its poss ibilities of making people insensitive to pain. In 1845 , James Esdail e, a Scottish surgeon in the East India Company, decided to try the method for the purpose of preventing pain during a surgical operation . Using the technique, he eventually had a record of 261 painless operations with a mortality of 5.5 per cent. Although hi s work was full y described in his book Mesmerism in India, the medical profess ion worldwide remained unconvinced fo r two reasons. In the first pl ace, not all pati ents were equally susceptibl e and induction of a hypnotic trance sufficiently deep to guarantee insensibility to pain took a very long time. Secondly, the work of these early pioneers coincided in time with that of the early pioneers of inhalation anaesthesia who were neither surgeons nor physicians but chemi sts and dentists with remarkabl e personalities. In 1772, Joseph Priestly di scovered nitrous oxide gas and within decades whiffs of ' laughing gas ' and ether were indulged in as sources of amusement at so-call ed ' froli cs ' where they produced rapid nonsensica l inebri ation. Later, European sc ienti sts, beginning with the English chemi st Sir Humphry Davy, suggested the possibility of using nitrous oxide as an anesthetic in 1800, but no one followed up his suggesti on. As anatomica l knowledge and surgical techniques improved, the search for safe methods to prevent pain became even more press ing. The advent of profess ional dentistry added a new urgency to this quest. The urge to see a denti st, however, was easily resisted, so it may be more than coincidence that denti sts seized the initiative in the quest for freedom from pain. The decisive step in thi s direction was taken in 1844 by the Connecticut dentist Dr. Horace Wells, who on learning of the properti es of nitrous oxide, tested them by having one of hi s own teeth removed by a colleague whil e under the influence of the gas. Delighted with the results, he successfull y started the practi ce of giving nitrous ox ide to several of his pati ents. Wells then traveled to Boston, where he met the fa mous Boston surgeon Dr. John Collins Warren who invited him to give a demonstration before his medical class at Harvard . The demonstrati on was duly given in January 1845 , but unfortun ate ly the boy whose tooth was being extracted groaned during the operation, alth ough he later stated he had felt no pain . The critical audi ence booed and hi ssed and Well s was mocked with cries of ' Humbug !' Following Wells ' failure, hi s friend and fellow dentist Dr. William Thomas Green Morton began experimenting with sulfuric ether as a poss ibl e anaestheti c agent at the suggestion of the Boston chemist Dr. Charles T. Jackson. Encouraged by its effectiveness in his dental practice, he, too, contacted Dr. Warren and requested the trial of the new method in a surgica l operati on. The famou s trial operation, the f irst publi c demonstrati on of surgery without pain, took pl ace in the Massachusetts General Hospital on October 16, 1846, and was a full success. Poss ibly alluding to the sad experiences of the past, Warren is said to have turned to the excited audi ence as the patient awoke and exclaimed, ' Gentlemen, thi s is no humbug !' After several more operations using ether, November 18, 1846 marked the day the great di scovery was announced to the world in a paper by Dr. Henry J. Bigelow, in the Boston Medical and Surgical Journal. N ews of

this momentous event spread rapidly, but until the physician and man of letters, Oliver Wendell Ho lmes, supplied the name 'anaesthes ia,' the Boston medica l communi ty had been at a loss for a term to descri be the condition brought on by thi s new miracu lous agent. On December 2 1, 1846, Dr. Robeti Li ston at the University College Hospital in London carried out the f irst major operation under anaesthes ia in Europe - an amputation of the thi gh. By February 184 7 the Lancet and other medi cal journa ls were reporting anaestheti c operati ons fro m all parts of Great Britain and the use of ether in most E uro pean countries. Sadly, the three earli est promoters of anaesthes ia became embroil ed in an ugly wrangle about priori ty and all di ed tragic deaths. In vexation over Morton 's success, Well s became addicted to chl oroform. Whil e intox icated, he threw vitrio l at a prostitute and was tossed into a New York City jail, where he commi tted sui cide. Jackson became insane, and Morton who tried unsuccessfully to conceal hi s sulfuric ether mixture's compos ition until he obtained a profitabl e patent di ed a pauper. The irony of fa te is that none of them was in fac t the f irst to practice gaseous anaesthes ia on a human patient. In 1842, Dr. Willi am E. Clarke of Rochester who had acquired some knowledge of sulfuri c ether from froli cs attended, administered it on a towel to a young woman who then had one of her teeth extracted pa inl essly. Not realizing the signif icance of what he had done, Clarke made no effoti to public ize hi s di scovery or to fo llow it up . After ether was widely accepted, Sir James Simpson, professor of obstetrics in Edinburgh, abandoned it for chl oroform in 184 7. He had introduced chloroform into surgica l practi ce because of the di sagreeabl e odor, irritating properti es, and long induction period of ether. In Britain, Simpson's advocacy of anaesthesia in childbirth was vehemently condemned by the Calvinist church fathers as contrary to the Biblical admonition that a woman must bring forth her child in pain . Simpson, however, reminded his opponents that the Lord caused a deep sleep to fall on Adam before the bitih of Eve and opposition virtually ceased when Queen Vi ctoria consented to the use of chloroform by her physician Dr. John Snow in her own case in 1853. According to her j ournal she said " Dr. Snow gave me the bl essed chloroform and the effect was mild, calming and beautiful beyond bounds." For about a century, chloroform continued to be the choice agent in Britain until its unmanageable toxicity and delayed damage to the liver was appreciated. Since that time, many other agents have been invented, and techniques have been refined and improved. These advances allowed anaesthes ia to become a spec ialty unto itself. The invention of general anaesthes ia was foll owed forty years later by the inventi on of various form s of loca l anaesthes ia. Once anaesthesia became accepted, longer and more complex operations were conce ivable, and surgeons began to contemplate opening the sanctuari es of the thorax and abdomen. Yet the potenti al benefi ts of surgery were overshadowed by the frequent, devastating infections whi ch often resulted in death. Indeed, images fro m this period are intri gu ing - distinguished surgeons dominate the scenes dressed in elegant frock coats, their hair, moustaches, and beards blowing in the breeze, their hands bare and only nominally clean.

UWOMJ 7 1(2)200 1 31

ANTISEPSIS AND ASEPSIS By the middl e of the nineteenth century, pain had been banished from surgica l operations, but one grave danger still faced every patient submitting himself or herself to the surgeon 's knife - the ever-prese nt ri sk of sepsis. Hospital di seases such as erysipelas, pyemi a, septicaemia and gangrene were rife and the growing number of operations had caused mortality rates to climb to levels never witnessed before. Sir James Simpson said "A man laid on an operating table in one of our surgical hospitals is exposed to more chances of death than was the English soldier on the field of Waterl oo." This was in fac t an understatement. In the 1850s, the death rate after amputations vari ed from 25 to 60 per cent in di ffe rent countries and in military practice it reached the appalling f igure of 75 to 90 per cent. The fact that all these di seases were consequences of some form of contagion had long been suspected, but the general view was that whatever was responsible was generated spontaneously in wounds. The early nineteenth century surgeons made some attempts at cleanliness. For example, a surgeon usually kept a special coat for operating or he wore an apron, but these garments were often stiff with congealed bl ood and matter. Those who washed their hands and cleaned their instruments traditi onally did so only after rather than before operating. Some had postul ated the ex istence of minute particles in the air, which carri ed ' contagion ' . The Italian Giro lamo Fracastoro in hi s treatise De Contagione described three modes of infection by contact, by clothing, utensils etc., and infec ti on at a di stance by the air. One di fficul ty that made the doctrine of contagion hard to accept was that no one could see the supposed agents. That changed in 1658 with Athanasius Kircher, the first man to employ the mi croscope in investigating the causes of diseases who demonstrated how maggots and other living creatures developed in decaying matter. An thony van Leewenhoek, the great pioneer of modern mi croscopy, made many furth er discoveries in thi s field. In spite of the propheti c utterings and observations of these men, medi ca l men were very slow to accept the theory of infection by mi croorgani sms. Even th ose who were di sposed to beli eve in the ex istence of di sease-causing organi sms were mi sled by the theory of' spontaneous generati on' stating that th e small fo rms of life appearing in decay ing matter arose by themse lves. The hi story of modern asepsis beg ins on a tragic note and with a trag ic fi gure. Alm ost a generati on before the triumph of modern surgery, an obscure obstetric ian named Ignaz Philipp Semmelweis di scovered the clue to puerperal infecti on. Whil e working at the first obstetri c clini c of the U ni versity of Vienna, Semmelwe is was struck by the marked di ffe rence between his f irst and second obstetri c clini c in the number of puerperal mortaliti es. The first clinic 's morta li ty rate was appallingly three times hi gher th an the other at ten per cent. Only the f irst clini c was open to medica l students, whil e the second served fo r the instruction of midwives. In investi gating these deaths from puerperal feve r through a judicious analys is of autopsy reports, Semme lweis came to the correct conclusion that all the deaths were caused by infec ti on from ' putrid materi al', carried on the hands of students who often went direct from the di ssecting room to labour wards. Semme lwe is instituted a routine of handwashing

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with chloride of lime before manual examinations and by this simple measure the mortality rate was reduced to 1.27 per cent. The ideas of Semmelweis, however, were ridiculed and met with fi erce opposition. His fate indeed was tragic: the neglect of his work so preyed on his sensitive mind that he became insane. In 1865, he died at the age of forty- seven of sepsis at an insane asylum in Vienna. Semmelweis' di scovery was by no means entirely original. Eighteenth-century British obstetricians Alexander Gordon of Aberdeen and Charles White of Manchester had suspected that doctors carried the source of puerperal infection and that cleanliness reduced puerperal mortali ty. Oliver Wendell Holmes also expressed simil ar ideas in 1843, but met the same kind of malicious resistance that Semmelweis had encountered. However, Holmes did not insist on his discovery; and limited himself to the teaching of anatomy and the fathering of poetry. The man who elucidated the true nature of infection, founded the science of bacteri ology, and paved the way for Li ster and the anti septic system in surgery was Louis Pasteur. Pasteur was led to his di scoveries regarding bacteria and other microorganisms by hi s investigation into the process of fermentation. Pasteur showed conclusively through painstaking experiments that fermentati on was caused by some agent that entered the wine and not by the spontaneous generati on of some noxious agents or purely by chemi cal means. He proved that the contaminating agents were living organi sms (bacteria) whi ch were everywhere, and that putrefaction was caused by their presence in foods and in wounds. Pasteur next showed that certain diseases were caused by mi croorganisms and he devised means of preventing those diseases by the use of vacc ines, prepared from attenuated cultures of the organi ms in questi on. Pasteur's greatest triumphs were in regard to the causati on and preventi on of anthrax and rabies, but the principles of hi s revolutionary di scoveri es were soon extended to many other di seases like diphtheria, typhoid, cholera and pl ague. The application of Pasteur 's di scoveries to surgical practice was the work of Joseph Li ster. As a medica l student, Li ster had been present at the f irst operati on under anaesthesia in Europe by Robert Li ton and was appo inted a professor of surgery at G lasgow in 1860. As a young surgeon, Li ster was appall ed by the fr ightful results of even the mo t simple of operations and devoted ~nu ch ti~e to the tudy of infl ammation and suppuration . While workmg on the probl em, his colleague, Thomas Anderson drew hi s attention to the work of Loui s Pasteur and it occurred to Lister that bacteri a from the air mi ght enter the wound to produce the deadly septicemia. Lister appli ed Pasteur 's principl es to the preventi on of suppurati on and determined to prevent access of organi sms by killing them in or on the surface of the wound. After try ing various chemica l agents he f inally selected carbolic acid ~ nd i~ s i sted that everything in contact with the wound, like dresst~gs , In struments and f ingers, should be treated with thi s anti septic. He even produced an anti septi c atmosphere by means of a carbolic spray. Li ster first used thi s antiseptic system in 1865 in a case of compound fracture of the leg. Lister's first results, published in 1.867, were astoni shing : eleven cases, nine recoveri es of life and limb, one amputation and one death. These res ults were main-

tained and Lister publ ished detai led descripti ons of his methods. He soon extended the use of carbolic aci d to all f ields of surgery, calling his new principl e the anti septic principl e. In spite of Lister's convi ncing resu lts, acceptance of his new methods was neither rapid nor widespread. It was only after the Germans had taken up his techniques in the early seventies that medical men in the United States, France, and England eventually foll owed suit. Lister's methods were eventually replaced in the 1880 's by the technique of ' asepsis ' chi efl y deve loped by Professor Ernst von Bergmann and hi s clini c in Berlin. Thi s new technique insured freedom fro m bacteria by di sinfecting instruments w ith steam, and hands and f ield of by means of va ri ous other agents. Rubber gloves were patented the foll owing year in 1878 . In the end, anti sepsis and asepsis rejuvenated surgery entirely and transformed surgical wards, after centuries of hospital gangrene, into places fro m which one could enter with the hope of leaving alive. Surgeons began to invade regions of the human body that they had never before dared to touch - the joints, the abdomen, the head, and the vertebral co lumn, and older operations were tremendously improved.

THE CENTURY OF THE SURGEON After opposition to anaesthes ia and anti sepsis faded away, a period of unbounded optimism ensued - the "Century of the Surgeon." New achi evements were described in military terms of "victory" and " conquest." Indeed, no medical heroes have enjoyed greater prestige than the surgeons of the late nineteenth and early twentieth centuri es who devised daring and prev iously inconceivable responses to internal pathology. The instruments and procedures that they invented still bear their names, and the list of their contribution fl ow like a litany of legendary expl oits. So many were the innovati ons and so far was the domai n of surgery extended that by World War I, most of the basic operati ve procedures performed today, with the principal exceptions of thoracic and cardi ac surgery, had already been deve loped. Indeed, the same fo rces that rejuvenated surgery had opened new horizons.

Sanofi-Synthe labo, a globa l healt hca re company bu ilt on the successes of an innovative worldwide R&D organ ization, congratulates the 2001 graduates for all the ir passion and co mm itmen t.

Sanofi- Synthelabo, une groupe pharmaceutique global, constru it grace aux succes d'une Recherche mondiale innovante, tient a feliciter les dipl6mes 2001 pou r leur passi on et leur engageme nt.

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REFERENCES 1.

2. 3. 4.

5. 6.

Ackerknecht EH. A short histOJ)' of medicin e. Baltimore: John Hopkins Press; 1982. Bishop W J Th e early histOIJI of surge1y. London: Olbourne Book Co.; 1961. Duffin J History of medicin e - A scandalously short introduction. Toronto : Uni versity ofToronto Press; 1999. Haeger K. Th e illustrated history of surge1y . New York: Bell; 1988. Lyons AS. Medicine: An illustrated hist01 y New York: H. N. Abrams; 1978. Packard FR. HistOJ )' of medicine in the United States. New York: Hafn er Pub. Co.; 1963. Pernick MS. A calculus of suffe ring: Pain, professionali::.ation, and anaesthesia in nineteenth century America. New York: Columbia Un iversity Press: 1985. Nuland SB. Doctors, the biography of medicine. New York: Alfred A. KnopfCo.; 1988.

UWOMJ 7 1(2) 2001 33

Off-pump coronary artery bypass surgery: What are the pros and cons?

•

•.'h~~ '·- .,

.·

·.

Robin Varghese, Meds 2002

Coronary artery bypass grafting (CABG) surgery has been traditionally performed using the cardiopulmonary bypass (CPB) machine. This allows the operation to be performed in a bloodless and controlled field. However, in the recent past there has been renewed interest in carrying out CABG surgery on the 'beating heart' without the heart-lung machine. This provides for a technically more difficult operation, but advocates point out the benefits to the patient as sufficient evidence to support this method. Nonetheless, there are those who feel that the benefits don ' t outweigh the risks in operating without CPB support. As off-pump CABG (OPCAB) surgery continues to establish itself as a more common procedure, we examine the pros, cons and indications for using or avoiding the CPB machine in light of a review of the current literature.

INTRODUCTION Today, an estimated 800 000 indi viduals undergo co ronary artery bypass surgery annually worldw ide. I For close to 50 yea rs now, us ing cardi opulmonary bypass (CPB) has been the go ld standard by which coronary artery bypass graftin g (CA BG) has been perfor med. Us ing th e bypass machin e provides a moti onless, bl oodless f ield. Thi s all ows the operation to be done under clear direct vision with less techn ica l di fficul ty. In cardi opul monary bypass the right atria is cannul ated and bl ood is drained into the bypass machine where it is oxygenated via a syntheti c membrane and then is pumped back to the prox imal aorta. In recent years there has been an interest in performing CAB G without the use ofCPB in a procedu re often referred to as "off-pump CABG" or OPCAB. OPCAB can be performed via a left anterior small thoracotomy, as minim ally invas ive direct coronary artery bypass (MIDCAB) grafting or by the more common median sternotomy which in this article will be referred to as OPCAB. The rati onale behind thi s phil osophy was initi ally based on the beli ef that CPB was th e cause of a vari ety of deleterious side effects experienced by patients duri ng surgery and post-operatively, including an infl ammatory response to the artif icial sur-

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faces of the c ircuit, increased neurological complications, and hemodiluti on. However today there exists some clear evidence of the benefits of OPCAB versus conventional CABG . If that is the case the questi on that ari ses is why are only less than 10% of patients today undergo ing CABG without the use of CPB ?2 The answer li es in the fac t that OPCAB has its opponents who are not co nvin ced of the benefits of avo iding CPB and believe there may actually be additi onal negative effects for pati ents undergoing bypass surgery w ithout the use of the CPB machine. In addition OPCAB brings new technical challenges to the cardiovascular surgeon as the hea11 continues to beat during the grafting of the vesse ls. Thi s article will examine the pros and cons of OPCAB in li ght of a review of the current literature on the issue.

NEUROCOGNITIVE BENEFITS One of the initi al reasons for considering OPCAB was the beli ef that CPB res ulted in microthrombi being released into the cerebral circul ati on eventually leading to cognitive impairments post-operatively. U nlike the two-phase pressure created by the heartbeat, CPB perfuses the organs at one relatively continuous pressure. Today a vari ety of studies have shown that the CPB

itself is not responsible for causing the release of cerebra l microemboli .3 However studies continue to report a lower incidence of neurocognitive impairment in off-pump cases. In their research comparing conventional CABG to OPCAB Murkin et al provided a variety of explanations for these outcomes. They showed that during the process of cannu lating and cross clamping the aorta for CPB, microemboli are released into the circu lation eventually fi nding their way to the cerebra l circul ation .4 In addition dislocation of the heart in the presence of a single, two-stage venous return cannu la during CPB may occlude the SVC resulting in poor cerebra l perfusion despite a measured normal mean arterial pressure. s Patients who underwent OPCAB/MIDCAB showed a significantly lower incidence of cognitive dysfunction at 5 days (66% vs 90% respectively) and 3 months postoperatively (5 % vs 50% respectively) compared with those who underwent conventi onal CABG.6 INFLAMMATORY RESPONSE Another benefit of avoiding CPB is the diminished inflammatory response experienced by patients. In CPB, the patient's blood travels through the CPB circuit and comes in contact with numerous artificial surfaces. This resu lts in an inflammatory response that affects multi-organ systems. Specific detrimental effects have been documented in the heart, lungs , kidneys, central nervous system and gastrointestinal tract.? Activated neutrophils, free oxygen radicals, and cytotoxins lead to myocardial edema and decreased contractility, thus directly contributing to card iac dysfunction .& This translates into a severe strai n applied to the body systems, requiring patients to remain in hospital for an average of five to seven days. OPCAB avo ids this iatrogenic insult as the blood does not leave the body and come in contact with synthetic materials. Moreover numerous studies have confidently established that patients undergoing OPCAB have a decreased requirement for transfusions (Table 1) and postoperative ventil atory support. 9,10,11 ,12,13 PATIENT POPULATION Some of the strongest opponents of OPCAB have contended that it can only be done on selected vessels - primarily the left Table 1. Perioperative blood loss and blood transfusion need28 Group 1 Hematological event Off-pump

anterior descending coronary artery (LAD). This is due to the technical difficulty in access ing vesse ls oth er than the LAD while the heart is beating. This was the case when OPCAB was in its infancy. Today complete revascu lari zation of the heart including the circumflex, obtuse marginal, intermedi ate diagonal, right coronary and LAD arteri es is poss ible and being performed in many centres. This is a result of new technical equipment such as the Cardiothoracic System (CTS) myocardial stabilizing system wh ich provide for a more stable field whil e operating on the beating heart.1 4 As well surgeons have climbed further up on the learning curve as more OPCAB procedures are performed each year. In spite of this, complete revasculari zation is not common in all centres since they lack the experience to perform such cases. As OPCAB continues to become a more common practice, new techniques and devices wi ll allow surgeons to access a greater number of vesse ls. There is still a concern of causing hemodynamic instability or ischemic myocardial dysfunction whi le displacing the heart in an attempt to graft the more posterior located marginal branches of the heart, especia ll y in those patients who have poor ventricular function. IS As the risks of CABG continue to improve, surgeons are beginning to operate on a more senior patient population - some of them octogenarians who intrinsically possess greater morbidity and mortality to the operation. The society of thoracic surgeons database reported a two-thi rds increase in the number of octogenarians undergoing CABG fro m 1987 to 1990.1 6 In order for OPCAB to gain recognition it must prove its safety and efficacy in this elderly group. This appears to be the case. OPCAB has proven to be no different with respect to postoperative myocardial infarction, atria l fibrillation, bleeding, neurologic complications or renal failure rates when compared with conventiona l CABG in a few studies. In fact , OPCAB patients demonstrated a shorter postoperative length of stay and lower transfusion requirements than the conventional CABG group.17 Moreover, it has also been shown by Boyd et al that OPCAB displayed substantial reductions in morbidity and mortality in high-risk patients compared to conventional CABG (Table 2).18 Today, re-intervention after CABG is not an uncommon

Group 2 CPB

P-value

Total blood loss (m l)

993 +/- 605

1139+/- 687

n.a.

Periop. blood loss (ml)

376+/- 241

470+/- 220

0.07

Transfusion Rate (%)

0. 11

OPCAB (n=36)

CABG (n= l99)

P-value

Hospital stay (d)

7.0 +/- 4.0

I 0.6+/- 10.2

.001

ICU stay (hr)

23.9+/- 10.0

65 .0+/- 128.4

.001

Major Complicationt

2 (6)

79 (40)

1 (3 )

21 (11)

Table 2. Postoperative Outcomes*29 Characteristic

Low output syndrome

*Presented as mean +/- SD or number (%) where applicable. Percentages are rounded to the nearest whole number. tRepresents postoperative complications that led to postoperative hospital stay > II days, ICU stay >60 hour , or death .

UWOMJ 71(2) 200 1 35

occurrence and is associated with higher morbidity and mortality than original CABG . Many techniques have been introduced to minimize this increased risk. One option was to attempt OPCAB on patients who required re-operation. In a recent study published Stamou et al. showed some startling resu lts. They demonstrated that re-do conventional CABG patients had a higher rate of postoperative transfusions (58% vs. 27% respectively), prolonged ventilatory support (17% vs . 4% respective ly) , and a higher rate of postoperative atrial fibri llation (29% vs . 14% respectively) when compared to OPCAB.19 They concluded that single-vessel off-pump redo CABG could be performed safely with a lower operative morbid ity and mortality than on-pump CABG.20 When opting for OPCAB, one concern is the risk of converting to cardiopulmonary bypass if a problem arises during the surgery. This has actually been proven to be a safe practice and does not increase morbidity or mortality when compared with conventional CABG or successfu l OPCAB procedures. 21

ECONOMIC/COST ANALYSIS With the ever-increasing pressure by governm ents to minimize the cost of health-care, hospitals are endeavouring to ascertain methods of curtailing the cost of proced ures. It is well known that the costs surrounding coronary artery bypass surgery are hi gh and funding fo r CABG is only set to increase as more procedures are required . An excell ent prospective study was carried out by Asci one et al looki ng at the costs of bed occupancy, operating materials , and transfusion requirements between OPCAB and conventional CABG at the Bristol Heart Institute in Bristol, United Kingdom. In the conventional CABG group operative costs were almost $300 more, bed occupancy was > $300 more expens ive and transfusion costs were >$ 160 more in comparison to the OPCAB group .22 C loser to home, a study was undertaken by Del Rizzo et al. where OPCAB cases were compared to conventi onal CABG patients in high-risk patients.23 The results were even more startling. The results showed an est imated cost-savi ngs of 50% when OPCAB was used in this patient population . ICU stay was dramatically reduced to 1. 1 +/- 0.5 days from an expected stay of 4. 1 +/- 1.2 day for these high-risk patients. These results only conti nue to encourage and support the use ofOPCAB procedures from an economic perspective as hea lth -care costs continue to spiral upwards.

INDUCED MYOCARDIAL ISCHEMIA In order to anastomose a coronary vesse l to a graft during an OPCAB procedure the coronary ves e l must be temporarily cross-clamped whi le the graft is being sutured in place. Criti cs of OPCAB state that coronary vesse l occ lusion may impair left ventricular function resulting in further damage to the myocardium.24 However using biochemical markers of myoca rdi al injury no increased muscle damage cou ld be shown during the OPCAB cases.25 In actual fact , Troponin I release was constantly lower in OPCAB patients as compared to conventional CABG . This was a consequence of a decreased incidence of arrhythmi as. Most studies publish an average time of 11-25 min for anastomosis of internal mammary artery to LAD. This is genera lly not sufficient enough time for permanent damage to occur.26 Some papers have discussed ischemic preconditioning of the heart by mechanical or 36

UWOMJ 7 1(2) 200 I

chemica l means as a method of preventing ischemic damage whil e performing the anastamoses of the vessels. In order to further minimize any risk of damage to the myocardium, it is advised that extra care be taken to ensure adequate venous return, and one should avoid over hydration or dehydration .27

SUMMARY With the aging baby boom generation there will be an increased demand for coronary artery bypass grafting. There has been strong debate over the issue of performing CABG without the use of extra corporeal circulation . At the recent Outcomes 2000 meeting in Key West Florida a structured debate took place between world-renowned cardiovascular surgeons Dr. Denton Coo ley and Dr. Michael Mack on the use and future of OPCAB. Both parties presented va lid arguments that mirrored the ongoing debate in the field of cardiovascular surgery. Supporters of OPCAB surgery point out the neurocognitive benefits and diminished inflammatory response. OPCAB cases have also consistently shown a decreased need for transfusion, patients are able to be extubated sooner, and have a lower rate of morbidity. Currently, at most centres, OPCAB is not commonly used for comp lete revascularization. Off-pump surgery is not recommended in certai n cases including: cardiomegaly, small intramyocardial or heavi ly calcified vessels and hemodynamic instability. It does however present as an interesting alternative for a variety of situations including elderly patients, re-do cases, patients at risk of stroke and patients with renal compromise. Proponents ofOPCAB point out that many of the studies that have "shown OPCAB to have more favourable results are not randomized. It is true that most studies are not randomized controlled trials, however thi s does not negate the results. Good studies have been done that compared patients with equal cardiac risk stratificatio n and measured outcomes between OPCAB and conventional CABG contro lling for all other factors. Moreover the results of these studies have been reproduced many times over by different researchers from a variety of institutions. It is definite that off-pump coronary artery bypass surgery is here to stay. Its advantages can be of great benefit in selected patient populations. As research continues, the indications and safety of OPCAB are becoming more evident. Despite certain technical limitations, the utilization of this procedure is increasing at institutions worldwide due to its low perioperative morbidity and mortality rates, satisfacto ry graft patency rates and symptomatic improvement that it achi eves . Moreover, a variety of institutions have proven its cost-effectiveness in an economi c climate where politicians are looki ng at methods of capping hea lth-care expenditure. And f inally, in li ght of the more recent advances in minimally invasive coronary artery bypass surgery, and robotassisted coronary artery bypass surgery the use of off-pump surgery wi ll be a safe and necessary requirement.

ACKNOWLEDGEMENT The author would like to thank Cardi ac Surgeon Dr. Douglas Boyd, Director of the Minimally Invas ive Cardiac Surgery Program at LHSC for hi s va luabl e advice and contribution to thi s article.

REFERENCES: 1.

2. 3.

10. 11.

I 2.

I3.

14.

15.

I 6.

17.

18.

19.

20.

Murkin JM, Boyd WD, Ganapathy S, Adams SJ, Peterson RC. Beating heart surge1y: why expect less central nervous system morbidity? Annals ofThoracic Surgery 1999; 68:1498-50 1. Svennevig JL. Off-pump vs on-pump surgery. Scandinavian Cardiovascular Journal 2000; 34:7-11 Taggart DP, Browne SM, Halligan PW, Wade DT i s cardiopulm onmy bypass still th e cause of cognitive dysfimction after cardiac operations? J Thora c Ca rdiovasc Surg 1999; 11 8:4 14-421 Murkin JM, Boyd WD, Ganapathy S, Adams SJ, Peterson RC. Beating heart surge1y: why expect less central nervous system morbidity? Annals ofThoracic Surgery 1999; 68:1498-501 . Murf..:in JM, Boyd WD, Ganapathy S, Adams SJ, Peterson RC. Beating heart surgery: why expect less central nervous system morbidity? Annals of Thoracic Surge1y 1999: 68: 1498-501 . Murl..'in JM, Boyd WD, Ganapathy S, et al. Postoperative cognitive dysfimction is significantly less after coronmy arte1y revascu/ari::ation without cardiopulm onwy bypass [Abstract]. Ann Thorac Surg 1999; 68: 1469. Kwon K, Jenkins D, Firpo R. T::eng T, Craig J. Complete myocardial revascularization on the beating heart. American J of SLag 1999; 178:502-3. Kwon K, Jenkins D, Filpo R, Tzeng T, Craig J. Complete myocardial revascularization on the beating heart. American J of Surg 1999; 178:502-3 . Rivetti LA, Gandra SM. Initial experience using an intraluminal shunt during revasculari::ation of the beating heart. Ann Thorac SL11~ 1997; 63: 1742-47. Cartier R. Systematic off-pump coronmy artery revasculari::ation: experience of275 cases. Ann Thorac SL11g 1999; 68: 1494-97. Bouchard D, Cartier R. Off-pump revascularization ofmultivessel coronQ/y artel)' disease has a decreased myocardial infarction rate. Eur J Cardiothoracic Swg 199; I4 Suppl I :20-24. Vura l KM, Tasdemir 0 , Karagoz H, Emir M, Tarcan 0 , Bayazit K. Comparison of early results of coronaty arte1y bypass grafting with and without extracoporeal circulation. Thora c Cardiovasc Surg I 995; 43:320-325. Benneti FJ, Naselli G, Wood M, Geffner 1. (1991) Direct myocardial revascularization without extrac01poreal circulation. Experience in 700 patients. Chest 100:3 12-3 I 6. Kwon K, Jenkins D, Filpo R, T::eng T, Craig J. Complete myocardial revascularization on th e beating heart. American J of Surg 1999; 178:502-3. Diegeler A, Falk MV, Binner Ch, Walther Th, Autschbach R, Mohr FW Indication and patient selection in minimally invasive and 'off-pump' coronCIIy arte1y bypass grafting. European Journal of Cardio-thoracic Surge1y 1999; 16 (Suppl. 1) S79-82. Edwards FH, Clark RE, Schwartz M. Coronmy arte1y bypass grafting: The Society of Th oracic Surgeons Natio nal Database Experience. Ann Th orac Surg 1994;57: 12-9. Koutlas TC, Elbee1y JR, Williams JM, Moran JF, Franca /ancia NA, Chitwood WR . Myocardial resvascularization in the elderly using beating heart coronary artery bypass surge1y. Ann Thora c Surg 2000; 69:1042- 7 Boyd WD, Desai ND, Novick RJ, McKen::ie FN, De/Ri::zo DF, Menkis AH. Use of cardiopu/monCIIy bypass in high-risk patients is a predictor of adverse outco me. Seminars in Cardiothoracic and Vascu lar Anesthesia 2000: 4:86-91. Stamou SC, Pfister AJ, Dangas G, Dullum MKC, Boyce SW, Bafi AS, Garcia JM, Corso Pl. Beating heart versus conventional single-vessel reoperative coronCify arte1y bypass. Ann Thora c Surg 2000; 69:1383-7. Stamou SC, Pfister AJ, Dangas G, Dullum MKC, Boyce Sf¥, Bafi AS. Garcia JM, Corso Pl. Beating heart versus conventional single-vessel reoperative coronary arte1y bypass. Ann Th orac Surg 2000; 69:1383- 7.

21. So/tos/..7 P, Salerno T Levins!..)• L, Schmid S, Hasnain S. Diesfeld T, Huang C, Akhter M, Alnoweiser 0, Bergs/and J. Conversion to cardiopulmonwy bypass in off-pump coronCIIJ' arte1y bypass grafting: its effect 011 outcome. J Card Swg 1998; I 3:328-34. 22. Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA. FETCS, Angelini GD. Economic outcome of off-pump coronal)' arte1y bypass surgery: a prospective randomi::ed study. Ann Th orac Surg 1999: 68:2237-42. 23. Del Ri::::o DF, Boyd WD, Novick RJ, McKenzie FN. Desai ND, Menkis AH. Safety and cost-effectiveness of MIDCABG in high-risk CABG patients. Ann Thorac Surg I 998; 66: I 002- 7. 24. Sven nevig JL. Off-pump vs on-pump surgery. Scandinavia n Cardiovascular Journal 2000: 34:7- I 1 25. Lotto AA, Cap uto M, Ascione R, Lloyd CT, Lucchetti V, Angelini GD. Evaluation of myocardia/ metabolism and fun ction during beating heart coronal )' sugel)'· Eur J Cardiothorac Surg I 999; 16 Suppl I :11 2-6. 26. Kondo K, Mino hara S, Sawada Y, Irie H. Okamoto K, Kinugasa S, Nakao M, Sasal..'i S. Indications and problems of coronal)' arte1y bypass grafting without cardiopulmonCIIy bypass. Surge1y Today I99 7; 27:2026. 27. Kondo K, Minohara S, Sawada Y, l rie H, Okamoto K. Kinugasa S, Nakao M, Sasaki S. Indications and problems of corona1y arte1y bypass grafting without cardiopu/monC/1 )' bypass. Surge1y Today I 997; 27:2026. 28. Bouchard D, Cartier R. Off-pump revasculari::ation ofmultivessel coronaly artery disease has a decreased myocardial infarction rate. European Journal ofCardio-thoracic Surg I 998; I 4 (Sup pl. I) S20-S24. 29. Boyd WD, Desai ND, Novick RJ, McKen::ie FN. De/Ri::zo DF, Menkis A H. Use of cardiopulmonCIIJI bypass in high-risk patients is a predictor of adverse outcome. Seminars in Cardiotlzoracic and Vascu lar Anesthesia 2000: 4:86-9 I .

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UWOMJ 71(2) 2001 37

Surgical options for the correction of craniofacial soft tissue defects

Vickram Chahal. Meds 2002

Ma rtin Lacey, MD, FRCS(C) Assistant Professor of Surgery, The University of Western On tario Consultant, Division of Plastic & Reconstructive Surge1y, Department of Surgery, London Health Sciences Centre Victoria Campus (Weshninster Site)

Craniofacial soft tissue defects can be both physically and psychologically debilitating. Soft tissue facial defects arise from various causes including congenital deformities, tumour extirpation, trauma, and degenerative diseases. The ideal substance for the reconstruction of soft tissue defects would be biologically inert, predictable, readily available, inexpensive, easily tailored and sculpted, and suitable for single stage implantation. Over the past few decades, numerous methods for correction of soft tissue deficits of the face have been explored. The techniques employed can be divided into two broad categories: the use of alloplastic materials and the use of autologous tissue. The discussion on autologous tissue includes the use of free flaps and free fat grafts. Numerous free flaps have been used for craniofacial contour correction including omentum , groin, pectoralis major, latissimus dorsi, transverse rectus abdominis muscle (TRAM), deep inferior epigastric perforator (DIEP), radial forearm , lateral intercostal, scapular and parascapular, and the inframammary extended circumflex scapular (IMECS). Two types of fat grafts that can be used in the restoration of facial contour defects are free dermal fat grafts (FDFG) and free fat grafts (FFG). Free fat transplantation is emerging as a popular choice for facial tissue augmentation. This paper discusses the advantages and disadvlfntages of all three basic surgical procedures from alloplastic implants to autologous tissue including free flap transplantation and free fat grafts.

INTRODUCTION Crani ofac ial so ft tissue defects can be both phys ically and psychol ogically debilitating. The conspicuous nature of fa cial contour defects often causes patients to seek surgical restoration. Soft tiss ue facial defects ari se from vari ous causes including congerutal deformities, tumour extirpati on, trauma, and degenerative di seases. Congenital soft ti ssue defects include hemifac ial microsomia and Crouzon's di sease . Extirpative surgery can result in postsurgical contour defects in patients with squamous cell carcinoma , eos in ophili c g ranul oma, cysti c hyg roma, cavern ous hemangioma, rhabdomyosarcoma, invasive blue cellular nevus, and pleomorphic adenoma. Penetrating and blunt injuri es as well as burn injuri es are tra umati c ca uses of contour defects.

UWOMJ 71(2) 200 1

Degenerative changes include hemifacial atrophy, polio-induced musc le wasting, Bell 's palsy, and steroid-induced fat necrosis. Fac ial deformiti es can be due to bony abnormalities, soft tissue defi ciency, or both. Due to the broad range of causes, many poss ibl e treatments ex ist. Regardless of the approach taken, a fundam ental principle exi sts. Obwegeser and colleagues state that the " in to out" principle stipul ates the correction of the bony problem before the soft tissue defect. I The idea l substance for the reconstruction of soft tissue defects would be biologically inert (noninununogeruc with a low infection rate), predi ctable, readily available, inexpensive, easily tailored and sculpted, and suitable for single stage implantation. For facial contour defects, secure tissue f ixation and lasting fl exibility are critical due to the constant demands of facial expression.2

Over the past few decades, numerous methods for correction of soft tissue deficits of the face have been explored. The techniques employed can be divided into two broad categories, the use of alloplastic materials and the use of autologous tissue. The discussion on autologous tissue includes the use of free flaps and free fat grafts .

ALLOPLASTIC MATERIALS In the search for an ideal soft tissue filler, a wide variety of alloplastic materials have been tried including silicone and Teflon.3.4 Despite the early enthusiasm for silicone in the correction of facial contour defects, its use has decreased due to significant complications.5-7 Teflon has been found to cause a foreign body granulomatous reaction.4 Generally, alloplastic materials have suboptimal texture, and are considered to be expensive, scarce, and poorly tolerated by the host.2 The use of alloplastic materials in children has been limited due to their inability to accommodate growth .S Roddi et al (1994) report complications including infection, stiffness, and mobility of the prostheses. Patient dissatisfaction and eventual poor comesis led to the removal of the implants within six months to a year.9

AUTOLOGOUS TISSUE Autologous tissue affords several advantages over alloplastic tissue that stem from their inherent biological properties. Complete histocompatibility leaves autogenous transplants free offoreign body reactions. As living vascularized tissue, the autologous tissue remains supple and can accommodate long-term growth. Autologous transplants are relatively free of infection,2.8 The use of autogenous tissue in the correction of facial soft tissue defects can be separated into two different groupings: free flaps and fat grafts.

Free Flaps Numerous free flaps have been used for craniofacial contour correction including omentum,I0-12 groin,l3-16 pectoralis major, l7 latissimus dorsi,9, 18 transverse rectus abdominis muscle, (TRAM)17,19 deep inferior epigastric perforator (DIEP),20 radial forearm,l 7,20,2 1 lateral intercostal,22 scapular and parascapular,23-28 and the inframammary extended circumflex scapular (IMECS) .29 One of the original free flap used for the correction of facial soft tissue defects, the omentum flap, allows easy vascular division and minimal donor site morbidity. However, the flap has fallen out of favour due to its unpredictable fat content, need for laparotomy, and requirement of a fascial sling to prevent long term gravitational sagging,3.20.22 The groin flap results in a relatively satisfactory donor scar. I I A portion of the iliac bone can be included if a concurrent bone graft is necessary.22 Unfortunately, the groin flap has a small , short pedicle that makes it difficult to work with , especially if an anastomosis to the neck is required ) It cannot be selectively trimmed, 11 often making it too bulky. Also, the groin flap does not permit much contouring.22 The pectoralis major flap is rarely mentioned in the literature for the correction of craniofacial soft tissue defects. Hasegawa and colleagues (1992) address three concerns with the flap . It is bulky, the vascularity of the skin paddle is unreliable, and there is

a high incidence of orocutaneou fistulas. I7 While the latissimus dorsi flap can be used as muscle alone, the drawbacks include unavo idable late muscular atrophy, loss of the posterior push off movement (i.e. getting out of a chair), winged scapu la, donor site pain, and seroma fonnation .9 The TRAM flap has distinct advantages and disadvantages giving it the potential to be either an excellent or poor choice depending on the c linical situation. The TRAM flap improved upon the pectoralis major flap . It has reliable vascu larity; the perforators are well anastomosed. Only one or two perforators are needed to supply the large ski n paddle. The TRAM flap is easi ly dissected and can be raised in various forms and design . The greater part of the skin paddle can remain lined with the rectus sheath and muscle much like the pectoralis major flap . The skin paddle can be extended from the underlying muscle in variation directions. Only a small segment of musc le from around the main perforators can be taken. The subcutaneous fat can be removed, thirming the skin paddle. In addition, the TRAM flap has been found to have a low incidence of necrotic change and fistula formation.17 However, the TRAM flap has been criticized for its bulkiness. I7,20 This can be corrected by selecting the thinned type of TRAM flap where the subcutaneous tissue has been removed. The rectus abdominis shows larger atrophic volume changes than the cutaneous part. I7 Further, Kashima and colleagues (2000) state that the TRAM flap cannot be used in females wishing to have children in the future because the rectus abdominis muscle is sacrificed .20 The deep inferior epigastric perforator (DIEP) flap is an improvement on the TRAM flap. While the DIEP flap can also be thinned by removing superficial and deep fatty tissue, unlike the TRAM flap , the rectus abdominis is preserved. The preservation of the rectus abdominis affords several advantages including minimal donor site morbidity, accommodation of future pregnancy in female patients, and prevention of weakness, bulging, and herniation of the abdominal waii. 20 The DIEP is preferred over the superficial inferior epigastric perforator (SIEP) which is often absent and hence unpredictable. The DIEP flap produces a greater tissue yield than the scapular, parascapular, or groin flaps. 20 Operating time can be reduced with the simultaneous elevation of the flap when preparing the recipient site.2o The muscle perforator of this flap is, however, technically difficult to dissect and skin grafting of donor defects is required.20 The radial forearm flap has been used to correct small facial contour defects but has significant limitations. I7,20 This flap cannot be used for larger defects because only a small volume offatty tissue is available. The radial artery should not be sacrificed if the patient has poor collateral circulation in the hand (i.e. positive Allen's test). A long, linear scar in the forearm leaves an unpleasant donor site.20 While difficult to harvest, the lateral intercostal flap offers a number of benefits. There are several pedicles a surgeon can choose to raise. A central position of a vascular pedicle in the flap allows primary defatting and beveling of the periphery of the flap without compromising the vascularity.22 A well-tailored flap reduces the need for future revisions. The diameter of the facial and superficial temporal arteries are comparable to the diameter

UWOMJ 71(2) 200 I 39

of the posterior intercostal artery22 and allows for good anastomoses. When skeletal augmentation is necessary in conjunction with soft tissue restoration, a rib bone can be included in the flap. The scapular and parascapular flaps are based on the branches of the circumflex scapular artery. These flaps have a constant proximal vascular anatomy. A long vascular pedicle, with large caliber vessels, can be dissected. Large amounts of tissue are available allowing for the correction of large craniofacial defects . Aesthetically speaking, the skin transplanted to the facial area is relatively hairless .24 Despite the advantages of scapular and parascapular flaps , the disadvantages associated with them have limited their use . Upton and colleagues ( 1992) reported hypertrophic scarring at the donor site.24 They found the donor site scars widened with time particularly those in a transverse direction (i.e. scapular flap ).24 Although billed as an option to fill large facial defects, a subcutaneous contour deformity in the donor region develops if large amounts of fat and fascia are harvested.24 Scapular and parascapular flaps cannot be selectively trimmed.20 An increased amount of operating time is required since the proximity of the donor site to the face makes the simultaneous elevation of the donor and recipient site difficult.20 Siebert and Longaker ( 1997) described the inframammary extended circumflex scapular (IMECS) flap as an improvement on the scapular and parascapular flaps.29 The IMECS flap places the donor site scar within the inframammary fold, leaving it well hidden. This technique also minimizes the hypertrophy of the widening scar because of decreased motion and tension at the donor site. The presence of a relatively thin dermal layer in the axilla and lateral chest accounts for less scarring.29 There are disadvantages that apply to all free flap transfers despite the technique used. A visible preauricular scar is unavoidable. If the tissue is not adequately fixed, the graft experiences downward sliding due to the effect of gravity. The use of a highly skilled team and a lengthy operating time is required, which make these procedures tend to be very costly. Also, despite deepithelialization, future epidermal cyst formation can occur.

Fat Grafts Two types of fat grafts that can be used in the restoration of facial contour defects are free dermal fat grafts (FDFG) and free fat grafts (FFG). The main difference between the two techniques is the inclusion of the dermal layer in the FDFG . When the dermis of the graft is placed superficially, a large contact area with the overlying well vascularized subdermal plexus is achieved ) By incorporating the dermal layer, FDFGs provide a stronger tissue to secure sutures with than fat alone, resulting in greater stability than FFG.JOHowever, the FDFG has not gained widespread clinical acceptance. A major drawback to the FDFG is the occurrence of epithelial cyst formation . Davis and colleagues ( 1995) reported a preauricular fistula occurring three years after implantation ) On examination, the fistula revealed a hair-bearing, epithelialized cavity containing keratinous debris .2 The authors also documented recurrent abscess formation .2 These problems point to the inability to achieve complete de-epithelialization. Free fat transplantation is emerging as a popular choice for facial tissue augmentation. The use of free fat grafts has distinct benefits over other autologous transplants. The technique of

UWOMJ 71 (2) 200 I

lipofilling involves the aspiration of subcutaneous fat from a suitable donor site and subsequent injection into the facial defect. The transplanted fat readily acquires a blood supply.JI Illouz, a pioneer of the technique, believed the facial area offered the best chance of success for free fat grafts due to the rich blood supply in the face .J2 The FFG can be adjusted to any shape desired to meet the demands of the defect.JI The transplanted fat does not displace inferiorly under the influence of gravity.JI Since the subcutaneous fat from the donor site is transplanted to the subcutaneous layer of the face, the transplant material is nearly identical to the consistency of the surrounding structures. The advantages of the FFGs in comparison to free flaps are numerous . First, FFGs can be repeated. Fat injections can be done in 4-6 week intervals resulting in an accumulation of fat to counteract any resorption that may occur.33 This allows the surgeon to fine tune the correction of the defect by adding supplemental fat. During the repeated injections, any scar tissue laid down will serve to counteract gravitational pull.33 Also, there are few morbidities at the numerous donor sites that are available, where deep subcutaneous fat is preferred for harvesting to superficial fat because of its tendency to resist lipolysis and the difficulty in removing it from dieting alone.JO Similarly, there are no complications at the recipient site. There is no scar left on the face, no bleeding, and no necrosis.9 The recipient vascular bed does not need to be undermined, leaving the fasciocutaneous vascular and neuronal plexus intact.9 Moreover, the procedure does not require a highly skilled team and can be performed on an outpatient basis in a short amount of time. This greatly reduces the cost associated with correcting facial contour defects. Other cosmetic advantages include intact facial expression and equal distribution of future weight gain on both sides of the face.J3 FFGs also have valuable implications for correction of pediatric craniofacial contour defects . The innocuous nature of the fat graft permits early correction of the facial defect and there is no need to delay treatment until after the completion of facial growth. Peer found that children are better candidates for fat grafting than adults.34 Despite their abundant advantages, FFGs have received their share of criticism. Fir t and foremost, the use of fat transplants is often criticized for the substantial fat resorption that occurs over time. Long term studies have found that 20-80% of the volume of grafted fat is resorbed.JS-39 Reichel-Fischel et al (2000) stated several factors that may account for the loss in the graft volume. They include resorption from excessive graft thickness, traumatic harvesting and handling, hematoma formation, wound infection, inadequate immobilization, and poor vascularity of the recipient site.s Fortunately, the repeatability of the transplant allows for modification when necessary. Little is known of the mechanism involved in the uptake and absorption of grafted fat. 40 -42 Nishimura and colleagues (2000) have recently found that fat graft survival can be improved with the clinical application of angiogenic factors as vascular endothelial growth factors (VEGF).4 Another criticism of FFGs is their dependency on revascularization for graft survival after transplantation because they are not harvested with a blood supply. Also, FFGs catmot be used to correct all sizes of soft tissue defects. Histologic studies have shown that adipose tissue survives by plasmatic imbibition.43 The

transplanted fat is vascularized in a centripetal manner and is able to survive by plasmatic imbibition for a distance ranging from 0.5 to 1.5 mm.44 This limits the maximum diameter of free fat transp~ants to 3mm. A transplant larger than this size would predictably result in increased resorption . The use ofFFGs should be limited for the correction of small facial soft tissue defects. Furthermore, the aspiration and injection of the graft can cause trauma to the fat cells.33 The amount of trauma can be reduced by usmg the same syringe to extract and inject, minimizing handling of the graft.9 Temporary discolouration of the skin distal to the injection site, presumably due to inadvertent intravascular injectiOn of fat, has been reported.45 Finally, FFGs are contraindicated ~or heavy smokers, psycholabile patients, obese patients, diabetIcs, and patients with active collagen vascular disease.9 Craniofacial soft tissue defects have a considerable impact on self-perception of body image. Most patients find facial contour defects to be aesthetically unacceptable and seek surgical correction. There are numerous techniques available to the plastic surgeon for the reconstruction of the soft tissue in the facial area. This paper has discussed the advantages and disadvantages of all three basic surgical procedures from alloplastic implants to autologous tissue including free flap transplantation and free fat grafts. Alloplastic materials have fallen out of use due to their deleterious effects. Free flaps are useful for the correction oflarge, severe defects while free fat grafts represent the best choice for small, moderate facial contour defects. REFERENCES Obwegeser HL, Sailer F. E1jahrungen mit der freien Fettransplantation :::ur Konturkorrektur im Gesichtsbereich. Kiefer Gesichts Chir 1979; 24:5 1. 2. Davis RE, Guida RA, Cook TA . Autologous Free Dermal Fat Graft. Arch Oto/01y ngol Head Neck Surgey 1995; 121:95-100. 3. Mordick TG II, Larossa D, Whitaker L. Soft-Tissue Reconsh·uction of th e Face: A Comparison of Dermal-Fat Grafting and Vascu lari:::ed Tissue Transfa Annals of Plastic Surgery 1992;29:390-396. 4. Nishimura T, Hashimoto H, Nakanishi 1, Furukawa M. Microvascular Angiogenesis and Apotosis in th e Surviva l of Free Fat Grafts. LOIJmgoscope 2000;110:1333-1338. 5. Rees TD, Ashley FL, Delgado JP Silicone fluid injections for facia l ah·ophy. ?last Reconsn· Surg 1973;55:11 8-1 27. 6. Edgerton MT, Wells JH. Indications for and pitfalls of soft tissue augmentation with liquid silicone. ?last Reconstr Swg 1976;58: 15 7-165. 7. Achauer BM. A serious complication following medical-grade silicone injection of the face. Plast Reconsn· Sw g 1983; 71:251-254. 8. Reiche-Fischel 0 , Wolford LM, PittaM. Facial Contour Reconstruction Using an Autologous Free Fat Graft: A Case Report with 18-year Follow-up. J Oral Maxi/lofac Surg 2000;58: 103-106. 9. Roddi R, Riggio E, Gilbert PM. Clinical evaluation of techniques used in the surgical treatment of progressive hemifacial atrophy. Journal of Crania-Maxillo-Facial Sw·ge1y 1994;22:23-32. 10. Walla ce JG, Schneider WJ, Brown RG, Nahai FM. Reconstruction of hemifacial atrophy with a .fi"ee flap of omentum. Br J Plast Surg 1979;32:15. 11. Upton J, Mulliken JB, Hicks PD, Murray JE. Restoration offacia l contour using .fi"ee vascularized omental transfel: P/ast Reconsn· Surg 1980;66:560. 12. Jurt.:iewicz MJ, Na hai FM. Th e use of.fi"ee revascularized grafts in the amelioration of hemifacial atrophy. ?last Reconstr Surg 1985; 76:44. 13. Shintomi Y, Ohura T, Honda K, /ida K. The reconstruction ofprogressive 1.

14. 15.

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facial hemi-atrophy by .fi"ee vasculari:::ed dermis-fat flaps . Br J ?last Surg 1981;34:398. Marashina T. Nakajima T. Yoshimura Y. A free groin flap reconstruction in progressive facia l hemiatrophy. Br J ?last Surg 1977;30: 14. Dunkley MP. Stevenson JH. Experience with the free .. inverted " groin flap in facial soft tissue contouring: A report on 6 flaps . Br J ?last Surg 1990;43: 154. Enigo F. Rojo P. Ysunza A. Aesthetic treatment of Rombe1g's disease: Experience with 35 cases. Br J Plast Surg 1993;46: 194. Hasegawa K, Amagasa T, Araida T. Miyamoto H, Morita K. Oral and ma.xilofacial reconstruction using the free rectus abdominis myocutaneous flap . Journal of Crania-Max illo-Facial Surge')' 1994;22:236244. Poole MD. A composite flap fo r early n·eahnent of hemifacial microsomia. Br J ?last Surg 1989;42: 163. Coessens BC, Van Geertruyden JP Simultan eous bilateral facial reco nstruction of a Barraquer-Simon lipodystrophy with free TRAM flaps. P/ast Reconstr Surg 1995;95:911 . Kashima 1, lnagawa K, Urushibara K, Ohtsuki M, Moriguichi T. Deep inferior Epigastric Pe1jorator Dermal-Fat or Adiposal Flap for Correction of Craniofacial Contour Deformities. ?last Reconstr Surg 2000: 106:10. Koshy CE, Evans J. Facial contour reconstruction in localized lipodystrophy using .fi"ee radial forearm adipofascial flap s. Br J Plast Surg 1998;51:499. Badran HA , Youssef MKH, Shaker AA . Management of Facial Contour Deformities with Deepitheliali:::ed Lateral Intercostal Free Flap. Annals of Plastic Surge')' 1996:37:94-101. Stern HS, Elliott LF, Beegle PH fl. Progressive hemifacial ah·ophy associated with Lyme disease. Plast Reconsn· Surg 1992;90:479. Upton J, Albin RE, Mulliken JB, Murray JE. Th e use of sacpular and parascapular flaps for cheek reconstruction. Plast Reconstr Surg 1992;90:959. Longaker MT, Siebert JW Microvasculr free flap correction of severe hemifacial an·ophy. ?last Reconsh· Surg 1995;96:800. Siebert JW Anson G, Longaker MT. Microsurgical correction offacial asymmet1y in 60 consecutive cases. Plast Reconstr SLag 1996;97:354. Longaker MT. Siebert JW Microsurgical correcton offacia l contour in congenital craniofacial malformations: Th e marriage of hard and soft tissue. Plast Reconsn· Surg 1996;98:942. Longaker MT, Flynn A, Seibert JW Microsurgical correction of bilateral facia l contour deformities. Plast Reconstr Surg 1996;98:951. Siebert JW, Longaker MT, Angrigiani C. The !nframammO/y Extended Circumflex Scapular Flap : An Aesthetic improvement of th e Parascapular Flap. Plast Reconstr Surg 1997;99:70. Boyce RG, Nuss DW, Kluka EA . The use of autogenous fa t, fascia, and nonvascularized muscle grafts in the head and neck. Otol01y ngologic Climes of North America 1994;27:39-68. Drommer RB, Mende U Free fat transplantation in th e face. Journal of Crania-Maxillo-Facial Surge!)' 1995;23:228-232. 11/ou::: YG. De Villiers YT. Body sculpturing by /ipoplasty. ChurchillLivingston. London, 1989. Moscona R, Ullman Y. Har-Shai Y. Hirshowit::: B. Free-fat Injections fo r the Correction ofHemifacial An·ophy. ?last Reconh· Surg 1989;501-506. Peer LA . The neglected free fat graft. ?last Reconstr Surg 1956; 18:233. Nguyen A, Pasyk KA , Bouvier TH. Comparative study of survival of autologous adipose tissue taken and transplanted by different techniques. Plast Reconstr Surg 1990;85:378-386. Mif..."US JL, Kaufman JA , Kilpatrick SE. Fate of liposuctioned and purified autologous fat injections in the canine vocal fold. L01y ngoscope 1995;105:17-22. Bauer CA, Valentino J, Hoffman HT. Long-term result of vocal cord augmentation with autogenous fat . Ann Otol L01y ngol 1995; 104:871-875. Zaretsky LS, ShidoML, DeTar M, Rice DH. Autologous fat injection for vocal fo ld paralyszs: long-term histologic evaluation. Ann Otol Rhino/ LO/yngo/1995:104:1-4.

UWOMJ 71(2) 2001 41

39. Shindo ML, Zaretsky LS. Rice DH. Autologous fat injection for unilateral vocal fo ld paralysis. Ann Otol Rhino/ Laryngol 1996; 105:602-606. 40. Kononas TC, Bucky LP. Hurley C. May Jw. Th e fate of suctioned and surgically removed fat after reimplantation for soft-tissue augmentation: a volum etric and histologic study in rabbits. Plast Reconstr Surg 1993;91: 763- 768. 41 . Niechajev I, Sevcuk 0. Long-term results off at transplantation: clinical and histologic studies. Plast Reconstr Surg 1994;94:496-506. 42. Chajchir A. Benzaquen I. Fat-grafting injection for soft-tissue augm entation. Plast Reconstr Surg 1989;84:92 1-934. 43 . Billings E II, May Jw. Historical revieHJ and present status of free f at graft autotransplantation in plastic and reconstructive surge1y . Plast Reconstr Sw g 1989;83:368. 44. Cortese A, Savastano G, Felicetta L. Free Fat Transplantation fo r Facial Tissue Augmentation. J Oral Maxilofa c Stag 2000: 58: 164-169. 45. Asken S. Autologous fat transplantation: Micro and macro techniques. Am J Cosm Surg 1987; 4:1 11-1 21.

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UWOMJ 7 1(2) 200 I

Diagnosis of the acute abdomen: Back to basics

Peter Kim, Meds 2002

Acute abdomen is a clinical disorder characterized by a sudden onset of undiagnosed abdominal pain of less than one week in duration, accompanied by other signs and symptoms focussed on the abdominal area.l, 2 It is a relatively common problem that has a potential to inflict significant morbidity and mortality to a patient. Sound history and physical examination are essential for an early diagnosis. History inquires about the various aspects of abdominal pain, associated symptoms, and co-existing medical problems. Physical exam focuses on the general appearance of the patient, vital signs, and a thorough abdominal exam. Relevant laboratory and radiological tests can aid patient assessment to secure an early diagnosis and promptly initiate treatment.

EPIDEMIOLOGY

A monumental survey was conducted by Research Committee of the World Organization of Gastroenterology from 1979 to 1986 to outline causes of acute abdominal pain.J,4,5 According to the study, the most common diagnosis of acute abdorllinal pain was non-specific abdominal pain (34%), followed by acute appendicitis (28% ) , acute cholecystitis (9 .7% ), small bowel obstruction (4 . 1%), acute gynecological conditions (4.0% ), acute pancreatitis (2 .9% ), and renal colic (2 .9%) _3 ,4,5

PAIN Anatomy of the abdominal organs

The gastrointestinal tract is derived from three main embryological structures: foregut, midgut and illndgut, which are lined with endodermal layers (Table 1). The mesodermal layer develops into peritoneum, which is named visceral or parietal according to the structures it covers.6 Types of Pain There are two types of abdominal pain: visceral and parietal (somatic). Visceral pain refers to pain originating from distention, compression and torsion of the abdominal viscera. 7,8.9 Ischerllia

and inflammation can also cause visceral pain. Typically, it is midline, poorly localized, and dull and vague in character. Most abdominal organs are insensitive to typical forms of stimulation including cutting, burning, and crusillng; it is possible to cut and tear the intestine without causing any pain to the fully conscious patient. 7,8 Pain from a tubular structure, such as intestine, is due to distention of the visceral peritoneum that covers it. Pain from so lid organs originates from capsular stretching as a result of blood, pus or tumor.7 Distribution of visceral pain follows the structures of the embryological origin (Figure 1). Pain from structures derived from the foregut is transmitted via the celiac plexus and perceived as a discomfort in the epigastric area; therefore, pain arising from gastric ulcer or pancreatitis is perceived in tills area.IO,II Pain impulses from the midgut structures are transmitted along nerve fibers that follow the pathways of superior mesenteric artery and it is perceived in the umbilical area. Tills is the reason beillnd umbilical pain in early appendicitis.'' Pain impulses from the hindgut structures are transmitted via the inferior mesenteric plexus and sacral plexus;I2 thus, it is perceived in the suprapubic area. Clinically, the presence of poorly localized visceral pain implies that the disease process has not yet markedly inflamed the parietal peritoneum or the pathology is insulated from the parietal peritoneum.s

UWOMJ 71 (2) 2001 43

GO Tract Structures

Blood Supply

Nerve Plexus

Foregut

oropharynx, esophagus stomach, diodenum ( I st and 2nd)

celiac trunk

celiac plexus

Midgut

distal duodenum, jejunum ileum, appendix, cecum ascending colon proximal transverse colon

superior mesenteric artery

nerves along the superior mesenteric artery

Hindgut

distal transverse co lon descending colon sigmoid colon rectum to the dentate line

inferior mesenteric artery

nerves along the inferior mesenteric artery

Mesoder01al layers

visceral peri toneum parietal peritoneum

splanchnic nerves spinothalamic tract

Table I. Outline of the embryolog ical structures and their corresponding anatomica l structures of the gastrointestinal tract. Parietal pa in of the abdomen is pain from irritation of the parietal peritoneum. It is sharp, we ll localized pain felt directly over the site of peritoneal irritation and is often an indi cation that the visceral process has become transmural and the inflammation has extended to the parietal peritoneum .8,II Colic Co lic is defined as " rhythmic attacks or paroxysms of pain w ith periods of intermittent or complete relief "? True colic is always a result of violent peri staltic contractions of the tubular structures in the abdomen (i ntestines, ureters, ducts, uterus and fall opian tubes). It usually occurs in attempt to overcome an obstruction or resistance. Thi s is di stinguished from normal peristalsis that is not painful.7

Referred Pain Referred pain is pain from a visceral organ perceived at a s ite distant from it due to parallel innervati ons by the same nerve roots. The site of referred pa in is distributed in a dermatomal fas hion of the afferent splanchi c f ibers suppl ying the specif ic abdominal organ. For exampl e, the pa in from a perfo rated ulcer that irritates the di aphragm , is fe lt in the ipsil atera l shoulder (Kehr's sign) .I3,I4

Figure 1. The distribution of visceral pain of the abdomen. The pain from the stomach is perceived in the epigastrium, from the small intestine in the umbilicus, and fro m the co lon in the hypogastrium, respectively.

I. acute cho lecystiti s 2. leaking duodenal ulcer 3. appendiciti s with high appendix

HISTORY

Patient Profile Age, a component of the patient profil e, is of importance since some conditions are more commo n in one age group than in others. For example, acute intussuscepti on is more likely to arise in infants less than 2 years old, 7, 8 obstruction of the large intestines from the co lon cancer occurs ra re ly before age 30 or 40,7,8 and appendiciti s is more commo n in adolescents '' w ith peak incidence between 10 to 30 years. IS

I. pencreatiti s 2. perfo rated gastric ul cer 3. leaking aneurysm of sple Âˇc artery

I. appendicitis 2. leaking duodenal ulcer 3. regional il eiti s

â&#x20AC;˘ â&#x20AC;˘

I. diverticuliti s 2. percolitis around colon CA 3. renal pain

History of the Pain The location, onset, duration, character, intensity, radiation, prog ress ion, agg ravating and alleviating fac tors of the pain should be expl o red . The location of the pain m ay give clues to the diagnosis, as shown in Figure 1 and 2. The changing of location of 44

UWOMJ 7 1(2) 200 I

Figure 2. The location and orne examples of pathologic processes underlying local peritonitis presenting in the four quadrants: right upper quadrant (RU Q), left upper quadrant (L UQ), right lower quadrant (RLQ) and the left lower quadrant (LLQ).

pain from the umbilicus and to the right lower quadrant, observed in classic presentation of acute appendicitis, is present in about 50% of cases.t 6 Abdomina l pain of sudden onset usually indicates viscus perforations or strangu lations,s whereas insidious onset of pain usually indicates inflammation of the visceral or parietal peritoneum.8 Nitroglycerin al leviates pain from angina pectoris as well as some intra-abdominal causes such as esophageal spasm and cho lecystitis.''

Anorexia, Nausea and Vomiting Abdomi nal pain is often accompan ied by anorexia nausea and vomiting. These are different grades of the same stimulus arising due to severe irritation of the afferent nerves in the peritoneum or obstruction of structures such as the biliary duct, the ureter, and the intestineJ,S It is a reflex response to afferent impulses to the vomiting centre.s Vomiting without nausea usually implies increased intracranial pressure.t 2 In the case of peptic ulcers , vomiting provides pain relief whereas the pain in cho lecystitis or pancreatitis is not altered by vomiting.? Episodic, projectile vomiting is seen in mechanical intestinal obstruction, and fecu lent emesis is seen in distal small bowel obstruction . Retching is seen in local or generalized peritonitis.t2

Bowel Movement Although the information on the nature, the pattern and any changes of the patient's bowel movement is important, it is interesting to note that the " normal" number of bowel movements in a "normal" population ranges from three times a day to once every three weeks.t7

Medications Patients receiving adrenal steroid treatment do not present with the typical symptoms of acute abdomen. It is well known that steroid treatment decreases inflammation JS and it may allow diminution of symptoms and signs of peritonitis. With these patients, the index of suspicion for a major pathology shou ld be high even with mild abdominal pain .7

Past Medical History Medical conditions such as diabetic ketoacidosis , Addisonian crisis, porphyria, sickle cell crisis can present with acute abdominal pain.7

PHYSICAL EXAM General Appearance The patient's mood, color (pallor, facial flushing, jaundice, cyanosis), respiratory effort and position shou ld be noted. Typically, patients with uretera l lithiasis writhe in agony, patients with peritonitis lie very still , and patients with acute pancreatitis feel less uncomfortable while sitting up. Observation of the patient's pattern of facial expressions can often detern1ine if the pain is colicky or constant.?. 19 Pallor may suggest internal hemorrhage and sweating ofthe face may suggest the presence of perforated gastric ulcer.

Vital Signs The vital signs are crucial in determining the patient 's overall condition. As in other conditions, tachycardia and hypotension signify shock or hypovolemia from internal hemorrhage. This

presentation of cardiovasc ular coll ap e seco ndary to intra-abdominal cause has traditionally been ca ll ed "abdominal apoplexy."'

ABDOMINAL EXAM Inspection The abdomen should be inspected for scars, di sco loration, hernias, and gross distention . The presence of jaundice indicates that th e pathological proce s involves the liver and the biliary tree. Old surgical scars may provide information about an organ that the patient may be mi ss ing or suggest intra-abdominal adhesions as an etiology of intestinal obstruction. The cutaneous manifestations of acute pancreatitis such as Grey Turner 's sign (flank discoloration)20 and Cu ll en's sign (umbilical discoloration) may be present.2 '

Auscultation In general, a quiet abdomen is suggestive of peritonitis and loud borborygmi are suggestive of mechanical obstruction . Abdominal bruits may be heard in ruptured abdominal aortic aneurysm.t9

Percussion In the diagnosis of acute abdomen, percussion is used either to demonstrate peritoneal irritation or to distinguish between gas and fluid causes of distention.' ,2, t9

Palpation Palpation shou ld begin with light touch while avoiding the painful area until the end of the examination. A ll possible sites of hernia should be exp lored. Palpable, yet non-tender gallbladder in the face of the obstructive jaundice is known as the Courvoisier's sign .zs. 26, 27 The site of local tenderness may give clues to the underlying etio logy as illustrated in Figure 2. The presence of rebound tenderness indicates the presence of peritonitis. Rebound tenderness is eli cited by continual pressure on the site of the tenderness until the patient adjusts to the pain (this may take 30 to 60 seconds), then suddenly release the pressure and look for any signs of pain.t.z Up to 20% of non-surgical abdomen exhibit rebound tenderness ) Tenderness at the McBurney's point (one third away on the line from the right anterior superior ili ac spine to the umbilicus) described by McBurney in 1889, is a class ic sign ofappendicitis, t,2,7 although it is present in only about 50 % of patients with the diagnosis .2 Rebound tenderness in the right lower quadrant from palpation of the left lower quadrant (Rovsing 's sign) is often present in appendicitis.22 Murphy 's sign is the observation of inspiratory arrest during palpation of right upper quadrant. It is sensitive (48-62%) and specific (62-96%) for cholecystitis.23,24 Rigidity is defined as an involuntary, reflexive palpable spasm in the abdominal musculature in attempt to defend the inflamed parts. It is indicative of peritonitis I and cannot be overcome by reassurance or tact. Rigidity is a relative term , and its degree depends on the underlying condition and the involved parts.7 In generalized peritonitis from perforated ulcer, a "boardlike" abdomen is present; however, in pelvic inflammatory lesions or intestinal obstruction, the amount of rigidity is minimal or even absent.7 The degree of rigidity does not necessarily correspond with the degree of peritonitis.

UWOMJ 71(2) 2001 45

Digital Rectal Exam

Generalized Peritonitis

Examination of the abdomen in the assessment of acute abdomen is not complete without a proper digital rectal exam . An adequate visual inspection of the anal margin, perianal skin is fo llowed by palpation of all fo ur aspects (posterior, anterior, left and right lateral) of the rectum for pain, tenderness, and masses . Any blood or mucus in the bowel contents should be noted.

The clinical pi cture in generalized peritoniti s is a sick patient with diffuse abdominal pain and tenderness) ' On physical exam, several "peritonea l signs" can be demonstrated: board-like rigidity, rebound tenderness, referred tenderness, and voluntary guarding J.8,3 I Adult causes include perforated ulcer and colonic perforation whereas perforated appendiciti s is the most common cause in the pediatric population) '

AnciUary Maneuvers The psoas sign is elicited by asking the patient to lift his or her thigh against resistance in supine posi ti on or with the patient in the left lateral decubitus position, by applying hip extension on the pati ent's right leg. Pain fro m these maneuvers is a pos itive sign and indi cates irritation of the psoas musc le by infl amed retroperitoneal appendi x. IS The obturator sign is positive when pai n is eli cited by pass ive internal rotation of the fl exed thigh whil e the pati ent is supine. This indicates an inflam ed pelvic appendix.2o Described by Fothergi ll in 1926, the Fothergill 's sign di stinguishes anterior abdominal wall les ions fro m intra-abdominal lesions.25 To eli cit thi s sign , ask the patient to lift hi s or her head in the supine pos ition, and then re-examine the abdominal les ion. The sign is pos itive when the anterior abdominal lesion becomes more palpable or the intra-abdominal les ion becomes less palpabl e and tenderJ .26, 21

CLINICAL PATTERNS

Abdominal Pain and Shock This is the least common, yet most dramatic presentation of acute abdomen that calls for urgent management. The patient is very sick, and presents with abdominal pain and cardiovascul ar coll apse. Two most common causes are ruptured abdominal aorti c aneurysm and ectopic pregnancy.7.3I

Pain with vomiting and distention but no rigidity Th is presentati on is characteristic of intestinal obstruction. Some of the common causes of the small bowel obstruction include intra-abdominal adhesions, herni as, and neoplasms. IO,I9 Possi ble conditions precipitating large bowel obstruction are colonic neopl asm, diverticul iti s and volvulus.IO,I9

LABORATORY TESTS Routine laboratory blood tests such as the compl ete blood cell count (CBC), electrolytes, urea, creatinine, g lucose are usefu l ai ds in the di agnosis of acute abdomen. Urinalysis may play a role when ureteral co lic is suspected.

Visceral Pain Most common causes of visceral epigastric pain are cholecystitis, gastri tis, acute pancreati tis, hepati ti s and perforating gastri c or duodenal ulcers7, II In additi on to the stomach, liver, pancreas, bil e ducts, duodenum and the spleen, non-abdominal structures such as the heart, the lungs , and the pleura should be kept in mind as potenti al causes of the pain in the epigastrium . Pain in the umb ili cus usually ind icates di sease of the small intestine. Some causes of pain in this area are early appendi citi s, small intestine obstruction, and mesenteric adeniti s7,II Pain in the suprapubi c a'rea indi cates a di sease process occurring in the colon, uterus and adnexal structures. Co lonic obstruction and salpingitis can cause pain in thi s area.

Localized Peritonitis Some of the common ca uses of localized peritoni tis are illustrated in Figure 2. Tenderness and rigidi ty in the ri ght upper quadrant is usually secondary to infl ammati on of the ga llbladder, li ver or the duodenum . Some of the common causes are acute cho lecystiti s, parenchymal liver di sease and leaki ng duodenal ul cer.? Tenderness and rigidity in the right lower quadrant is most commonly due to acute appendi citis, but may be due to condi tions such as regional il eiti s or leaki ng duodenal ulcer.? Tenderness and rigidi ty in the left lower quadrant is most commonly due to acute diverticuliti s.? Tenderness and rig idi ty localized to the left upper quadran t is not common; however, conditions such as pancreati tis, perforated gastric ulcer f ixed w ith adhesions, and spontaneously ruptured spleen should be considered .?

UWOMJ 71(2) 200 I

IMAGING Plain Chest Radiograph Pl ain f ilm of the chest is ordered routinely in evaluation of acute abdominal pain to investigate thoracic causes of abdominal pain , and the presence of free air under the di aphragm .

Plain Abdominal Radiograph Supine, upright and lateral views of the plain abdominal radiograph are done routinely in evaluation of acute abdominal pain. This radiological technique is helpfu l and j ustified in the following suspected abdominal conditions: intestinal obstruction, perforation of the viscus, renal colic, gall bl adder disease, ischemia, and trauma.7.8

Ultrasound U ltrasonography is a useful too l in evaluati on of the acute abdomen. In the literature, the initial imaging study of choice for suspected cases of cholelith iasis and cholecystiti s remain s right upper quadrant ultrasound .8 It is also useful in evaluation of possible gynecological causes of acute abdomen and to rule out of causes that can mimic appendiciti s. 7.8

CT abdomen CT scan of the abdomen has been established to be an important part of evaluati on of acute abdomen for appendiciti s, diverticuliti s,33 intestinal ischemia, pancreatiti s, intestinal obstruction and perforated viscus.34

CONCLUSIONS The topic of acute abdomen includes an array of abdominal and non-abdominal conditions. The abi li ty to cover this topic in depth is beyond the scope of this article. However, it should be emphasized that early diagnosis of the acute abdomen is cruc ial for a positive outcome and is heavily dependent on sound hjstory and physical exam that allow one to recognize the relevant clini cal presentations .

ACKNOWLEDGEMENT The author would like to sincerely thank Dr. Robert Zhong for reviewing the manuscript. Dr. Zhong is a professor of surgery and the director of the experimental surgery division of the multiorgan transp lant program at the London Health Sciences Centre. REFERENCES I.

2. 3. 4. 5. 6.

7. 8. 9. I 0. II . 12. 13. 14. 15. 16.

17. 18. 19. 20. 21. 22. 23.

Judge RD, Woolliscroft JO, Zelenock GB, Znidema GD. The Michigan manual of clinical diagnosis. Philadelphia: Lippincott-Raven; 1998. p. 199-210. de Dombal FT. Diagnosis of acute abdominal pain. 2nd ed. New York (NY): Churchill Livingstone; 1991. de Dombal FT. Acute abdominal pain-an O.M.G.E. Survey. Scand J Gastroenterol 1979; 56(suppl) :29-43. de Dombal FT. The O.M.G.E. acute abdominal pain survey-progress report, 1982. Scand J Gastroenterol 1984; 95(supp/) :28-40. de Do mba/ FT. The OM. G.E. acute abdominal pain survey-progress report, 1986. Scand J Gastroenteroll 988; 144(s uppl) :35-42. Sadler TW Langman 's Medica l Embryology. 7th ed. Baltimore: Williams and Wilkins; 1995. Silen W, editor. Cope 's early diagnosis of the acute abdomen. 20th ed. Oxford: Oxford University Press; 2000. Martin RF, Rossi RL. Abdominal emergencies. Has any thing changed? Surg Clin North Am 1997;7: 1227-43. Screenivas VI. Acute disorders of the abdomen. Diagnosis and treatment. New York: Springer-Verlag; 1980. p. 1-29. Sabiston Jr DC. Sabiston textbook of surgery. 15th ed. Philadelphia: WB. Saunders Company; 1997. p.825-846. Nyhus LM, Vitello JM, Condon RE. Abdominal pain. A guide to rapid diagnosis. Norwalk (Connecticu t): Appleton and Lange; 1995. p. J-48. Kirkpatrick JR . The acute abdomen. Diagnosis and management. Baltimore: Williams and Wilkins; 1984. p.l-5 7. Hickey MS, Kierman GJ, Weaver KE. Acute abdominal disorders. Emerg Clin NorthAm 1989;7:437-52. Aldea PA , Meehan JP, Sternbach G. The acute abdomen and Murphy's signs. J Emerg Med 1986; 4:5 7-63. Hardin Jr. M. Acute appendicitis: review and update. Am Fam Physician 1999; 60: 2027-34. Liu CD, McFadden DW Acute abdomen and appendix. In : Greenfield CJ et al. , editors, Surgery scientific principles and practice. 2nd ed. Philadelphia: Lippincott-Raven; 1997. p./ 246-61. Connell AM, Milton C, Irvin e G, Lennard Jones JR. Miscienitz JJ Br Med J 1965; 2: 1095-9. Katzung BG. Basic and Clinical Pharmacology, 7th ed. Stamford (Connecticut) : Appleton and Lange; 1998. p. 635-47. Schwartz Sf eta/. Principles of surgery. 7th ed. New York: McGraw-Hill; 1999. p.103 3-79. Grey Turner G. Local discoloration of the abdominal wall as a sign of acute pancreatitis. Br 1 Surg 1919; 7:394-395. Meyers MA, Feldberg MAM, Oliphant M. Grey Turner's sign and Cullen's sign in acute pancreatitis. Gastrointest Radio! 1989; 14:31-37. Wagner JM, McKinney WP, Carpenter JL. Does this patient have appendicitis ? lAMA 1996; 276:1589-94. Eskelinen M, Jkonen J, Lipponen P. A multiparameter diagnostic score

in clinical diagnosis of acute cholecystitis. Theor Surg !993; 8:90-4. 24. Eskelin en M, lkonen J, Lipponen P. Diagnostic approaches in acute cholecystitis. Theor Surg 1993; 8: 15-20. 25. Chen JJ, Changch ien CS, Tai Dl, Kuo CH. Gallbladder volum e in patients with common hepatic duct dilatation . An evaluation of Courvoisier 's sign. Scand J Gastroenterol/ 994; 29:284-8. 26. Ludwig Co urvoisier (1 843-1918) Courvoisier 's sign [editorial}. lAMA 1968; 240:165. 27. Courvoisier LG. Th e pathology and surge1y of th e biliaiJ' tract. Leipzig, FCW Vogel; 1890. 28. Foth ergill WE. Hematoma in the abdominal wall stimulating pelvic new growth . Br Med J 1926; 1:941-2. 29. Zainea GG, Jordan F Rectus sheath hematomas: the pathogenesis. diagnosis and managment. Am Surg 1985;54:630-633. 30. Ed/ow JA , Juang P, Margulies S, Burstein J Rectus sheath hematoma. Ann Emerg Med 1999; 34:671-675. 31 . Schein M. Schein 's common sense emergency abdomina l surgery. New York: Springer-Verlag; 2000. p. 1-28. 32. Field S. Plain abdomen. ln : diagnostic and interventional radiology in surgical practice. Armstrong P, Wastie ML, editors. 1997. Philadelphia; Chapman and Hall. p./5-46. 33. Birnbaum BA, Baltha::ar EJ CT of appendicitis and diverticulitis. Radio! Clin North Am 1994; 32:885-98 34. Fukuya T. Ha wes DR, Lu CC, Chang PJ Barloon TJ CT diagnosis of small bowel obstruction : efficacy in 60 patients. Am 1 Roentgenol 1992;158: 765-72.

TIMMINS AND DISTRICT HOSPITAL TIMMINS, ONTARIO Timmins and District Hospital, (TDH) is a fu ll y accredited 147 bed facility situated in the City ofTimmins. The Timmins and District Hospital serve an immediate population of 50,000 and a catchment area of I00,000. Timmins is a friendly, family oriented community situated in a clean wide-open environment with more than 200 lake,. Attractions in the area include fi shing, camping, boating. downhill and eros -country skiing. golfing, curling. amateur theatre and the Timmins Symphony Orchestra. Timmins and District Hospital offers excellent income opportunities and financial incenti ves. Assistance with moving expense will be offered. Locum support is provided by the Ministry of Health, Underservi ced Area Program. $300.00 per day honorarium. travel and accommodations plus 590.00 tipend or fee for service. We have full time and locum positions avai lable for:

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UWOMJ 71(2) 2001 47

Guglielmi detachable coils and the subarachniod haemorrhage: Radiology's encroachment on neurosurgery

Jason Ashley, Meds 2003

Subarachnoid hemorrhage (SAH) has an incidence of 2.0 to 22.5 per 100 000. Surgery, the current gold standard in the treatment of SAH, is being replaced by less invasive endovascular procedures performed by neuroradiologists. Guglielmi Detachable Coils (GDC) are used by most centres around the world for SAH. The procedure involves placing a soft, flexible platinum coil within the lumen of a cerebral aneurysm. The coil, which stimulates thrombus formation , is then detached and the aneurysm is occluded. Success rates approach those of surgery and results consistently improve as better technology and techniques emerge in this ten-year-old method. Mortality and morbidity rates approach those reported for surgery intervention. While few studies have looked at costs of GDC, they are reported to be consistently lower than surgery for the treatment of saccular SAH. Indications for GDC for SAH are currently in flux. It is the intent of this article to discuss GDC techniques and demonstrate this procedure as the safer and cheaper alternative to microneurosurgery.

INTRODUCTION Cerebral vascu lature was elucidated in 1927 by a Portuguese neurologist, Egas Moniaz.l He performed the first cerebral angiography via an internal carotid puncture and was the first to demonstrate an anterior communi cating artery aneurysm. This work acted as a foundation for Dandy and hi s first pl anned clipping of a cerebral aneurysm with a sil ver clip des igned by Harvey Cushing in 19362 in attempt to reduce the high mortality rates fro m subarac hnoid hae morrage (SAH) due to cere bra l aneurysms .3 SAH is relatively common and has an incidence of 2.0 to 22.5 per 100 000. 4 Rinke! demonstrated that the preva lence of aneurysms in the general population is high. He indi cated that aneurysms occur in 0.4% in retrospective autopsy studies, 3.6% in prospective autopsy studies, and 3.7% for retrospective angiographi c studi es and 6% for prospective angiog raphy studi es.5 In an effort to treat surg ica ll y inaccessi bl e cerebral aneurysms , Serb inenko proposed and used endovascular tech-

UWOMJ71(2)2001

niques in the mid-l 970's.6 His techniques invo lved parent vessel occlusion with detachable latex balloons via sheaths introduced into the cervical internal carotid artery. In 1987, Fox et a! further va lidated parent vessel occlusion in 68 patients with large and giant surgically unc lippable aneurysms .7 However, sequellea from this procedure can be significant (persistent paralysis and parasthesia) and patient populations were quite specific.s,9 As the procedure evolved, avai lability of smaller instruments made direct aneurysm occlusion poss ibl e. Thi s reduced the sequellae assoc iated with compl ete parent artery embo li zation. Early methods of vessel occlusion used latex balloons which were unfortunately subjected to deflation , biodegradation, a~d were stiff and unyielding.9, IO In 1979, Taki described the use of silicone balloons in an effort to reduce the level of biodegradation and proVIde a more permanent so lution.'' Silicone is more pliable and puts less lateral stress on the fragile aneurysm waJJ.I 2 However, the "Water-hammer" effect through the balloon can put stresses at the weakest, and hence most I ikely to ruph1re, part of the aneurysm . 13

In efforts to develop alternative procedures with a better costto-risk ratio, other methods such as laser thermal coagulation,14,15 stenting, l6,17,18 liquid polymer injection, l9,20,2 1 and meta llic coils22 have been exp lored. Figure 1 demonstrates parent artery occlusion, direct balloon occlusion, coiling, and stenting. Each of these perform well , but have their individua l draw backs. For examp le, laser thermal coagulation may form an unstable thrombus, stenting eventually causes parent vessel stenosis due to endothelial trauma, and liquid polymers can eventually cana lize. However, these procedures are all in experimental stages and wi ll not be discussed in this artic le. They may become increasingly evident in the future and most like ly will be used in conjunction with the most influential technique in aneurysm embo lization: detachable balloons and e lectrica lly detachable platinum coi ls.23,24

THE GUGLIELMI ELECTRICALLY DETACHABLE COIL (GDC) Most recently, the development of detachable platinum coi ls has offered the Neuroradio logist insight into the future of cerebra l aneurysm treatment. The GDC is the most widely used coi l and has been used in more than 15 000 procedures.25 The coil was developed by Guglielmi et al in 19924 and was tested from 1991 to 1995 .26 In the United States, FDA approval was granted in 1996. The GDC (Figure 2) consists of a soft platinum coi I that stimulates thrombogenesis .27 The platinum co il is attached to a stainless steel wire via a microsolder. When the coil is in the desired position, an electrical current is run through the guidewire and the microsolder dissolves, releasing the coi l in the aneurysm. The electrical detachment also produces a positive charge in the platinum coil further facilitating thrombogenesis by attraction of platelets, fibrin, and other negatively charged cellular components. The stainless steel guidewire all ows positioning, repositioning and withdrawal of the coil as desired, providing a definite advantage to the previous coiling strategies that all owed on ly one deployment.2 7 The wire used to construct the coil is very thin (0.05 mm in diameter). The width of the assembled wire helix can range from 0.25 mm to 0.375 mm .27 The length (from 2 to 30 em) and diameter (from 2 to 20 mm) used is highly dependent on the volume of the aneurysm . The GDC is coiled to produce easy infolding within the aneurysm since previous attempts using straight wires resulted in wire prolapse and parent artery occlusion.28

Figure I. Modes of Aneurysm embolization: A) parent artery occlusion , B) baloon emboli zati on, C) platinum co il embolization, D) stent

act as a road map for the guidewire placement and microcatheter navigation. A micro catheter is introduced and follows the guidewire to the neck of the aneurysm . The guidewire is then removed and the microcatheter navigated into the aneurysm . Once inside, the f irst GDC coi l is introduced. The first coi l should be a larger diameter coi l that provides a peripheral base and to all ows sequential f illing of the central regions of the aneurysm with subsequent coils . When it is in proper position, an electrical current is appli ed and the coi l is detached 20 to 60 seconds later.27-29 A so lid thrombus forms as a result of flow dynamics within the aneurysm .27 The patient is heparinised for 2 days post-operatively to reduce thromboembolic events.29

SUCCESS RATES WITH THE GDC Success of coi l embolization is highly dependent on experience.26 Results have been very promising and perhaps indicate possibility of being the first line treatment for most aneurysms . In a preliminary study of 15 hi gh ri sk saccular aneurysms by Gugli elmi et al, 2 were occl uded 100% and the remaining were occluded 70 to 90%.30 In 124 coiled aneurysms, Horowitz indicated that 115 were completely obliterated and only 9 required retreatment. 31 Vifiuela et al, in a patient population with 60.8% small , 34.7% large and 4 .5% giant aneurysms , obtained complete occlusion in 70.8%, 35%, and 50% of aneurysms in their respective size categories. Neck remnants were apparent in 21.4% of sma ll , 57 . I% of large, and 50% of giant aneurysms .32 In the United States, there is a 75 % success rate with >90% occlusion in 735 coi led aneurysms .33 Current studies indicates that there is now 80% success rate with a complication rate of only 5 to 10% .4

TECHNIQUE USING THE GDC Almost all centres use genera l anaesthetic for this procedure.28,29 This a llows better patient monitoring and position.28,29 The patient's status is monitored via haemodynamic parameters, continuous encephalographic monitoring and evoked brainstem responses. The catheter is inserted through the femoral artery and placed as far up the cervical vascu lature as possible. Diagnostic angiography is then performed through a transfemoral guide catheter. Visualization of the cerebral vasculature is achieved through subtraction digital imaging and the visualization of the neck of the aneurysm is then optimised through fluoroscope repositioning to allow for precise placement of the guidewire and microcatheter. The guidewire is fed into the cerebral vasculature to the neck of the aneurysm. The digitally subtracted image will

Figure 2. G ug liemi Detachable Coil : A) coil diameter, B) coil length, C+D) so lder, E) sheath

UWOMJ 71 (2) 2001 49

These values are currently approachi ng those obtained via surg ical management. Success rates currently are lower th an those for surgery and are possibly due to patient selection criteria,26-3 1 si nce on ly those who are unwilling to undergo surgery or considered a surgica l risk are used in the studi es for GDC. A randomi sed contro l trial must be performed to adequately compare GDC coi l embolization to surgery. 25-29

a rupture rate of 6%, and thus it might be concluded that surgery would be indicated.J7, 38 Thus, aneurysm rupture must be a significant risk before surgery is considered. However, the conclusions made for the treatment of smaller aneurysms have been challenged recently.40, 41 This is because the natural rustory of aneurysms and the rate of rupture both relate to cost effectiveness and cost per year42 and it is necessary in today 's economical atmosphere to reduce costs by prevention or cost effective procedures.

INDICATIONS FOR GDC

Indications for GDC

Indications for Surgery

Medically unstable

Large and G iant Aneurysms

Poor neurologic grade

Wide neck Aneurysms

Small neck aneurysms in posterior fossa

Vessels emanating fro m the aneurysm dome

Early vasospasm

Hematoma or mass effect assoc iated with aneurysm

Multipl e Aneurysms in different arterial territori es

Recurrent aneurysms after GDC embolization

Table 1. Indications of GDC and SurgeryJ-1 Arguments can be made for choosi ng surgical intervention for cerebral aneurysms when mass effect is present or when vesse ls emanate from the aneurysm dome. However, thi s is not clear for large and giant aneurysms. In a multicentre clinica l trial , 43 posterior fossa aneurysms were treated. Of the 43 aneurysms , 26 had a wide neck (>4mm) and 4 of these 26 were obliterated while the remaining were occluded 70-90%.30 In the United States, 26, 30% of the large or giant aneurysms were compl etely occluded and 50% had a persistent neck.J3 At six month fo llow-up , 29% of the large and 30% of the giant recanalised and 42 % of all aneurysms contained signifi cant recanali sation .J3 More recently, initi al trial s in the use of balloon assisted coi l emboli zation have been quite successfuJ.3 5 At a mean of 19 months follow-up , aneurysm occ lusion was obtained in 17 of20 patients (85 %), with a cerebrovascu lar event occurring in 4 of the 22 treated (2 di ed subsequently after treatment of co-morbid illnesses) with one permanent deficit. 20 of the 22 had exce ll ent to good clini ca l outcomes. In giant, very wi de-neck aneurysms that are surgically and endovascularly untreatabl e, it has been suggested that parti al surgica l clipping and subsequent GDC embolization may be indi cated.J 1,36 Recurrent aneurysms after GDC emboli zation have also been an indication for surgery. Surgery may not be necessa ry, given th at reemboli sation may be indi cated in certain circumstances ) ! Thus, indications for GDC are cu rrently in flux and cannot be standardi zed unti l the full limits of the procedure can be demonstrated. TREATMENT: RUPTURED OR UNRUPTURED ANEURYSMS? Raaymakers eta! indicated that screening is recommended for fir t degree fami ly members wi th fami li al SAH.J7 Screening and subsequent detection do not translate to surgery or endovascul ar procedure because of the mortali ty (2.6%) and morbidity rates ( 10.9%) of aneurysm surgery.J9 Aneurysms less than 10 mm in diameter have a 0.05 % chance of rupture annually while aneurysm 10-25 mrn had a 1% annual rupture rate. Aneurysms >25 nun have 50

UWOMJ 7 1(2) 200 1

There is also a debate about the timing of intervention for ruptured SAH. Increasi ng evidence suggests that early intervention is best for both surgery and endovascular procedures 25-29 This will reduce the rate of rehaemorrhage. The Cooperative Aneurysm Study showed that the rate of rehaemorrhage is 4.1% for day 1 and 1.5% for days 2 and 3, with a cumulative risk of 19% at 2 weeks43 and overall mortality rate of 70%. Endovascular procedures have the advantage of being performed days after the SAH, without the ri sk of vasospasm - a definite ri sk in surgical clipping >72 hours after rupture.-1-1 Furthermore vasospasm is responsible for 7% of total overall morbidity of surgical procedures.J2,-14 Medical management is usua lly indicated in vasospasm and includes induced hypervolemi a, haemodilution, hypertension, and a co urse of calcium channel blockers. 29 Endovascular procedures can also be utilized to dil ate vasculature via a balloon catheter. 29 COST OF SURGERY AND ENDOVASCULAR PROCEDURES Very few studi es exam1mng the cost effectiveness of endovascular procedures are availab\e .J l,45,-16 One of these studies reported that costs of surgery are approximately $ 11 000 US with $2 570 US cost for the routine and $8 430 US ancillary fees .Jl These fees include costs for hospital nursing care and other postoperative care fees . Length of stay (LOS) in hospital was an average 6.5 days. GDC averaged a total cost of $9 000 US with $1 360 US in routine fees and $7 640 US in ancillary fees . Average LOS was 4 days . These trends in reduced costs are not solely a result of GDC but is evident in most of the endovascular procedures.47, 48 CONCLUSION While surgery is still indicated as the gold standard, the future might tell a different story for the treatment of cerebral aneurysms. Results from experienced Neuroradiologists have indi cated that endovascular procedures are as effective as open

procedures in small neck aneurysms. With current trends in adapti~g .balloon and liquid polymer techniques with coil

embolizatiOn, large and giant aneurysms with wide necks are being effectively treated. Costs of the procedures are low, and can be convertedto open procedures with relative ease. It will be on ly a m~tter of time before the aneurysm becomes the domain , primanly, of the Neuroradiologist. REFERENCES

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19. Berenstein, A. Lasjaunias, P Indications and Results of Enclovascular Treatmen t of Anew J•sms. In Surgica l Neuroangiograp hy, Vol 5. Berenstein, A, Lasjaunias, P (eels): New York, Springer-Verlag, 1992, pp 149-84. 20. Mandai, S, Kinugasa . K. Ohmoto, T. Direct thrombosis of anew)'sms with cellulose acetate polyme1: Part 1: Results of thrombosis in experimental aneurysms. Journal ofNeurosw geiJ'. 77(4):497-500, 1992 Oct. 21. Kinugasa, K, Mandai, S, Terai. Y, et a/. Direct thrombosis of aneurysms with cellulose acetate polyme1: Part II: PreliminGi y clinical experience. Journal ofNeurosurgeiJ'· 77(4):50 1- 7, 1992 Oct. 22. Mu llan, S, Raimondi, AJ, Dobben, G, et a/. Electrically Induced Thrombosis in Intracranial Anewysms. Journal of Neuros urgetJ' 22:539-547, 1965. 23. Guglielmi, G. Vinuela. F, Duclovile1; G, eta/. Endovascular Treatm ent of Posterior Circulation Aneurysms by Electro th rombos is using Elecn·ically detachable coils. Jouma/ of Neuros w ge1y 77:5 15-524, 1992. 24. Guglielmi. G, Vinuela, F, Sepetka, I. eta/. Electrothrombosis ofSaccular Anew ysms via Endovascular Approach, Part I : Electrochemical basis and experimental results. Journal of Neurosurgery 75: 1- 7, 1991. 15. BIJ'an. RN. Rigamonti, D. Mathis, JM. Th e Treann ent of Acutely Ruptured Cerebral Anewysms: Endovascular Th erapy versus Surge1y. American Journal ofNeuroracliology 18: 1826-30, November 1997. 26. Guglielmi, G, Vinuela, F. Dion, J, et a/. Electrothrombosis of saccular aneW) 1SII1S via endovascu/ar approach, Part II: PreliminGi y Clinical Experience. Journal ofNeurosurgerJ' 75:8- 14, 1991. 27. Nichols, DA , Meye1; FB. Piepgras, DG, Smith, PL. Endovascu/ar Treatment ofi ntracranial Aneu1ysms. Mayo Clinic Proceedings 69:27285, 1994. 28. Thomas, J E. Armonda, RA. Rosenwasse1; RH. Endosaccu/ar Thrombosis of Cerebral Anelii )'Sms. Neurostuge1y Clinics of North America JJ(J) :J01-21 JanuCII y2000. 29. Pruvo, JP Leclerc, X, Ares, GS, et a/. Endovascular Treatment of Ruptured Intra cranial Anewysms. Journal of Neurology 246:244-49, 1999. 30. Standard, SC, Guterman, LR. Chavis, TD. et a /. Endo vascular Management of Gia nt Intracranial Aneurysms. Clinical Neurostu ge1y 42:267-93 1995. 31. Horowit::., M, Purdy. P, Kopitnik, T, eta/. Anew ysm Retreahnent after Guglielmi Detachable Coil Emboli::.ation: Report of Nine Cases and Review of Literature. Neuroswgery 44(4): 712-20 Apri/ / 999. 32. Vinu ela, F. Duc!.:wile1; G, Mawad, M. Guglielmi Detachable Co il Emboli::.ation ofAcute intracranial Anewysm: Perioperative anatomical and clinical outcome in 403 patients. Journal of Ne urosurge1y 86:475482, 1997. 33. Vinuela, F. Endovascular Occlusion ofIntra cranial Anewysms using the GDC SystemL The USA exp erience. Presented at the GDC In vestigators Meeting During the 31st annual meting of the American Society of Ne uroradiology, Vancouve1; BC: May 1993. 34. Vespa, PM. Gobin. YP Endovascular Treatment and Neurointensive Care of Ruptured Aneurysms. Critical Care Clinics 15(4) : 667-84, October 1999. 35. Nelson, PK, Levya, Dl. Balloon-assisted Coil Emboli::.ation of Widenecked anewysms of the internal carotid arte1y: medium-term angiograpluc and chmcal fo llow-up in 22 pateints. American Journal of Neuroradio logy 22(1) :19-26, Janua'J' 2001 . 36. Ha cein-Bey, L, Connolly. ES J1 ; Maye1; SA , et a/. Complex intracranial aneurysms: co mbined operative and enclovascular approa ches . Neurosurge1y. 43{6):1304-12, 1998 Dec. 37. Raay makers TWRinkel GJ Ramos LM. Initial and fo llow-up screening for aneliiJ1Sms m /Gimhes w1th fam ilial subarachnoid hemorrhage. Neurology. 51(4) :1125-30, 1998 Oct. 38. fnt emational Study fo Unruptured ln n·acranial Anew ysm Investigators. Unruptured Intracramal Anewy ms - Risk of Rupture and Risks of Swg1ca/ Intervention. New England Journal of Medicine 339(24)' 1725-33. .

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39. Raaymakers, Tl¥, Rinke/, GJ, Limburg, M, Algra, A. Morta lity and morbidity of surgery for unruptured inn·acranial an ewysms: a meta-analysis. Stroke. 29(8): 1531-8, 1998A ug. 40. Berenstein, A, Flamm , ES, Kupersmith, MJ Unruptured intracranial anewysms.New England Journal of Medicine. 340(1 8): 1439-40, 1999 May. 41 . Stieg, PE, Friedlande1; R. Unruptured intracranial anewysms. New England Journal of Medicine. 340(1 8): 1441, 1999 May. 42. Kallmes, DF, Kallm es, MH, C/oft, HJ, Dian, JE. Guglielmi detachable coil embolization for unruptured anewysms in non-surgical candidates: a cost effectiveness exploration. American Journal of Neuroradiology 19(1) : 167-1 76. 43. Kassel/, NF, Torn e1; J C. Anewysmal Rebleeding: A Prelimina1y Report from the Cooperative Anewysm Study. Neurosw gel)' 13:479-81, 1983. 44. Raymond, J, Roy, D. Safety and Eflcacy of Endovascular Treatment of Acutely Ruptured Aneurysm. Neurosurgery 41 : 1235-46, 1997. 45. Johnston , SC, Gress, DR, Kahn , J G. Which Ruptured cerebral Anewysms should be n·eated? A cost utility analysis. Ne urology 52(9): 1806-1 5, Jun e 1999. 46. Yoshimoto, Y, Wakai, S. Cost-effectiveness analysis of screening for asymptomatic, unruptured inn·acrania/ anewysms. A mathematical model. Stroke 30(8): 1621-7 1999Aug. 4 7. Blum, U. eta /. Endolumina/ Sten-graftsfor Infra renal Abdominal Aortic Aneurysms. New England Journal of Medicine, 336(1) : 13-20, Jan ua~y 1997. 48. Ohki, T, Veith, FJ Endovascular Grafts and Other Im age-Guided Catheter-Based Adjuncts to Improve th e Treatm ent of Ruptured Aortoiliac Aneurysms. Annals of SwgeiJ' 232(4) :466-79.

WILLIAM OSLER HEALTH

At Wi ll iam Osler H eal th Centre, we are passionate about the way we do b usiness. We are looking for physicians that can help us shape the fUture of heal thcare in a corporation poised for co nsiderable growth and development.

Wi ll iam Osler Health Centre has more than 640 physicians and serves a population in excess of 700,000. This population base gives William Osler H eal th Centre the critical mass to provide regio nal specialized services in such areas as Paediatrics, Neonatology, MRI, Dialys is and Orthopaedics. Together th e Etobicoke H ospital , Brampton M emorial Hospital and Georgetown H ospital Campuses provide care to Canada's fastes t growi ng co mmunities.

CENTRE The largest comm unity hospitaf in Outario is looking for pl1ysiciam in .. . Family & Emergency Medicine Psychiatry Cardiology Dermatology Gastroenterology Neurology Geriatrics !nfoctious Diseases

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UWOMJ 71(2) 200 I

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A comparison of open surgery versus endovascular repair in the treatment of abdominal aortic aneurysms

Radu Butan, Meds 2003

Abdominal aortic aneurysms (AAA) have an incidence of 3-4% in adults over 65 years old. Untreated, they pose the catastrophic complication of rupturing. For many years, open surgery was the gold standard for treating such patients. However, endovascular repair of abdominal aortic aneurysms has evolved dramatically in recent years. This paper compares recent studies looking at the outcome of open surgery versus endoluminal stent grafting in the repair of AAA. Both surgery and endoluminal grafting have a low mortality rate. However, endovascular repair of AAA reduced the number of medical complications, such as myocardial infarction, respiratory failure and colon ischemia. Further, endografting offers the advantage of a quicker recovery, a reduction in hospital stay, a decrease in blood loss and a decrease in extubation time. In terms of costs, it remains unclear as to which modality is more economical. Endovascular procedure is expensive because of the expenses of the graft and necessary imaging. Although it is appealing, more studies looking at long-term outcomes are needed before it can replace open surgery as the standard procedure in the repair of AAA.

A BACKGROUND TO ABDOMINAL AORTIC ANEURYSMS (AAA) An aortic aneurysm is the dilatation of a blood vesse l and can be fusiform or sac-like. Aneurysms can occur anywhere along the vascular tree although the infrarenal part of the aorta is the most common site. Aneurysms are thought to be the result of degenerative and atherosclerotic processes, hence they are most common in older men who also tend to have coexisting coronary and vascular disease. Other risk factors include a family history of AAA, connective tissue disease, long term smoking and hypertension.' The incidence of AAA is about 3-4% in adults over 65 years in the United States. In fact, it has been reported that the incidence of AAA has tripled in the past 30 years.2 This reflects the more widespread use of imaging modalities allowing physicians to diagnose this condition earlier. Most abdominal aneurysms are detected by coincidence when an abdominal ultrasound or com-

puted tomography is done. Mass population screening programs have been proposed in order to better detect AAA.2 For the general population, these clinical trials have shown to be cost ineffective , however, screening using an abdominal examination and ultrasound is merited for those at risk. The detection and repair of AAA is critical because untreated aneurysms can rupture with a fatality rate of 50-90% . Clinically, the most important predictor of the aneurysm outcome is its maximal diameter. For example, if the aneurysm is 4-5cm in diameter, the risk of rupture in the next year is 1%, and 5-6 em, 11 %, and 6-7cm, 21 %.2 Current guidelines recommend that aneurysms in a healthy person that exceed 5-6cm should be treated.3 Nowadays, the controversy is not whether we should treat, but rather how we can best treat AAAs. In particular, this article will discuss the advantages and disadvantages of the more traditional open surgery versus the newer techniques of endoluminal grafting in the management of abdominal aortic aneurysms. UWOMJ 71 (2) 2001 53

OPEN SURGERY Since the first repair by Dubost in 1951 , open surgery has been the go ld standard of AAA repair.3 In healthy patients, the operative mortality is 3-5%. However, concurrent medica l cond itions such as chronic renal failure, chronic lung disease and hepatic cirrhosis can double or even triple this risk. 2.4 Coronary artery disease is the most important illness contributing to mortali ty and morbidity during and after the surgery. Elective AAA surgery is considered high-risk surgery and all patients undergo a cardi ovascular assessment to ensure that they are fit for surgery. Despite this, about 5% of patients suffe r fro m myocardial infa rction or heart fa ilure during the peri-operati ve period.5 Open surgery is perfo rmed under general anesthesia. A midline transabdominal incision is made, although some surgeons prefer a retroperitoneal approach.6 With the bowel moved to the side, one locates the aorta which is then clamped both proximally and distally to the aneurysm . The aneurysmal sac is opened, the thrombus is scooped out and the collateral lumbar arteri es and possibly the infe rior mesenteric artery are ligated prior to the insertion of the graft .7 An appropriately sized Dacron graft is chosen, and this is sewn to the hea lthy portion of the aorta. The clamps are then carefull y removed, and the surgeon checks for any leakage before the abdomen is closed.7 In most cases, a straight tubul ar graft is used. A bifurcated graft is used if the aneurysmal sac extends down to the iliac arteries. Open surgery has stood as the gold standard of treating AAA to which all other methods are compared. It has a relatively low mortality and morbidity rate, and has decreased the number of ruptured AAAs since its debut 40 years ago .3 However, it remains a costly procedure that is very invas ive and is not suitabl e to many patients wi th medica l comorbidities. Endoluminal grafting as a repair method of AAAs offers the hope of being less intrusive, better tolerated by the patient, and more cost effective while hopefu lly j ust as effective.

ENDOGRAFT REPAIR The concept of remote depl oyment of an en dog raft to treat an AAA is attributed to Juan Parodi in 199 1.8 Aneurysms are thought to expand and rupture due to the weakness of the arterial wall and high arteri al blood pressure. The concept behind endografting is to remotely insert a prostheti c device that seals and excl udes the ane urysm from ci rcu lation. Preoperati vely, one begins by imaging of the aneurysm, preferably by contrast-enhanced spi ral CT or by angiography.9 As in open surgery, one must carefully select a properly sized graft, and decide between a tubul ar and bifurcated graft, whi ch depends on the pos iti on and the anatomy of the aneurysm. The procedure is typi ca lly perfo rmed under general anesthes ia, though with experi ence many centers have increas ingly re lied on local anesthes ia.9 One of the fe moral arteri es is entered percutaneously, a catheter is pushed to the aneurysm and an arteriography is perfo rm ed to conf irm the anatomi c dimensions and to determine the proximal site of attachm ent. Consequently, a sheath containing the stent graft device i introduced into the fe moral artery though a s urg ically created arteriotomy. Under flu oroscopi c gu idance the graft is pushed to the proposed site of attachment. Next, the

UWOMJ 7 1(2) 200 I

sheath is carefully withdrawn, and the graft self-expands and embeds within the aorta .9 The deployed graft may be further modeled onto the arterial wall by an inflatable balloon.5 Bifurcated grafts consist of two parts: main and single limb. The single limb is introduced through the contralateral femoral artery and is joined to the main part inside the aneurysm. Lastly, a contrast angiogram or intravascular ultrasound is done to verify the absence of leakage and to confirm complete stent deployment.9 Postoperatively, a contrast enhanced CT scan confirms graft placement and the absence of leakage . Endovascular grafting can offer many potential advantages. Since they are less invasive, they can be applied more universally and can reduce hospita l stay and the utilization of ICU. Endografting is hoped to reduce the number of medical and surgica l complications, and perhaps even mortality. Furthermore, one has to consider the shortening of hospital stay after an endograft procedure. However, thi s new technology did come without its problems. The most common complication is an endoleak, which is defined as the persistence of blood outside the graft but inside the original intact aneurysm.9 Endoleaks are cl ass ified as primary if they occur in the first 30 days and secondary if they occur thereafter. The most common cause of primary endoleaks are incomplete sealing of the graft, while graft migration is the leading cause of late endoleaks.9 The incidence of endoleaks varied among studi es and has been reported as 29% and 23%.5,10 However, most of them closed spontaneously, and at 1 month after surgery, the endoleak rate was between 6% to 9% .5,10 If an endoleak persists fo r 3 months, they are unlikely to seal on their own, and further endovascular procedures are advisable. Other complications of endograftin g are limited access to aneurysm through narrow and tortuous iliac arteries, perforation of artery during inserti on, increased risk of mi croembolization and postoperative bl eeding. 5.11 .12 These complications can usually be corrected by secondary endovascular interventions, otherwise, they are resolved wi th open surgery. Overall , 3 year graft survival has been estimated to be around 70-80% .12

OPEN SURGERY VS. ENDOGRAFTING To date, there has been no completed prospective randomized tri al that compares open AAA repair with endoluminal stent grafting. Pati of the di fficulty in comparing open AAA repair to endog rafting is that endograft repair is offered only to those unfit fo r open surgery, which makes an inaccurate comparison between the two groups. In various retrospective studi es, when compared to open surgery, endog raftin g results in decreased surgical time, blood loss, bl ood repl acement, extubation time and an earlier return to funcf ton.56 .路路路 10 I n a dd ttton, endovascul ar gro up decreased intensive care unit stay from 2 to 0 days , and hospital stay from 7 to 2 days .5 It was also fo und that endoluminal graftin g decreased the number of medical. ~o mpli catio ns . Whether the reduction in hospital stay and the uttltzatt? n of resources translates into cost savings has been controverstal. One study found that hospital costs were reduced by 40% in the endovascular group, whil e hospital profits m crease~ by 50% .5 However, ~hi s study did not include the high co ts of tmag mg that are requtred pre-operatively and post-oper-

atively. It is important to remem ber that unl ike open surgica l pati ents, endografti ng requ ires regu lar fo llow ups to ens ure that the graft has not fa il ed . Another hi nderi ng factor is the hi gh cost of the g raft : between $5 ,000 and $6,000 (US do ll ars).6 T herefore, mo re comprehen ive stud ies are needed to accurately compare the costs of surgery versus e ndovasc ul arization . When comparing surgica l mortali ty, there was no stati stically signif icant differe nces between the two interventio ns.5,12 Whil e the short term results of endog raft ing seem prom is ing, there ha been a lack of studies looking at long term outcomes. A recent study by Wesley Moore at UCLA was the firs t to fo llow the two groups over a longer timefram e.s Mortali ty curves over 5 years were constructed and the surv ival of the two gro ups was shown to be stati sti ca lly identica l. T here were no deaths attribu ta bl e to a ruptured AAA in the endograft stentin g group . In addition, there is a trend for lower m orbidi ty rates in patients undergo ing endovascular repair fo r incidence of myocardial infa rction, respiratory fa ilure and colon ischemi a.s.1o

CONCLUSIONS E ndolumina l stent grafting has emerged as a pro mi sing technique in the treatment of AAAs. While it is an alternative form of treatment in non-surgical candidates, recent studi es have advocated its success on a w ider basis. Long term m ortality and surv iva l curves is similar between open surg ical repair and endovascular technique. However, endoluminal g rafting is less invasive, better tolerated by the patient, and has lower rates of medical compli cations, which may arguably be mo re cost effective. Despite these early successes, many clinical and technica l issues have to be addressed . A t the fo refront is the need to desig n g rafts o r implantation techniqu es that redu ces th e numbe r of endo lea ks. Furthermo re, there needs to be g reater uniformity among g raft s, since at the present a w ide spectrum are used by different centers. This makes it mo re difficult to compare results among centers and have a uni for m training in the manipulati on of these g rafts. As well, the cost of the g raft itse lf has to decrease in order for it be widely used . As techno logy improves and experience is ga ined, endoluminal stent grafting may one day replace open surgery as the go ld standard in treating AAAs.

ACKNOWLEDGEMENT This paper has been kindly rev iewed by D r. Thomas F. Lindsay who is a vascul ar surgeon at the Toronto General Hospital. REFRENCES i . Andreoli TE, Cwpenter CJ. Griggs RC, Loscal::o J Vascular diseases and hyp ertension. In: Cecil Essentials of Medicine. Philadelphia : WB. Saunders Company, 2001:i 45- I 63. 2. Hallett JW Management of abdominal aortic aneliiJ'Sms. Mayo Clin Proc. 2000; 75:395-399. 3. Ernst CB. Current therapy for infra renal aortic anewysms. Editorial New England Journal of Medicine i997: 336:59-60. 4. Herbert LM. Paterson IS Caring for the patient undergoing abdominal aortic aneurysm repail: In: Caring for the Vascular Patient. New York: Churchill Livingstone, I 997:207-220. 5. Moore WS, Vikram SK, Candace LY; Quinones-Baldrich WJ Abdominal aortic aneurysm a 6-year comparison of endovascular versus transabdominal repail: Annals ofSurgel)' 1999; 230:298-308.

Quinon es-Baldrich WJ Gamer C. Cas11'ell D, A/111 SS, Celabert HA , Ma ch/eder Hi, Moore WS. Endom sculw; transperitoneal. and retroperiton eal abdominal aortic cmew :J'SIII repair: Results and costs. J Vas e Surg i999; 30:59-67. 7. Ouriel K, Rutherford RB. Abdominal Aorttc Anew :rsm Resection . i n: Atlas of Vascular Sw gel) '. Philadelphia : WB. Saunders Company, i 997:94-i05 . 8. Parodi JC. Palma:: J C, Barone HD. Transjim10ral intraluminal graft implantation for abdominal aortic anelii) 'Sms. Ann Vase Swg. 1991 : 5:491-499. 9. Seelig MH. 0 /denbwg ff'/1. Hakaim AC. Halle// JW Chow/a A . Andrews JC. Chen J' KJ Endovascular repair of abdominal aortic an elii)'Sms: Where do we stancf? Mayo Clin Proc. 1999: 74:999- 1010. 10. Zarins CK, White RA . Sclmarten D, Kin11ey E. Diethrich EB, Hodgson KJ. Fogarty TJ AneuR.x stent graft versus open sw g ical repair of abdominal aortic aneUI J'SIIIS: Multicenter prospecti ve clinical trial. J Vase Surg I 999: :?9::?92-308. 11 . Blum U. Voshage C, Lammer J. Bey ersdorf F. Tolln er D. Kretschmer C. Spillner C. Polerauer P, Nagel C. Hol::enbein T. Thumher S. Langer M. Endolwnina/ stent-grafts fo r infra renal abdominal aortic aneurysms. N Eng/ J Med 1997: 336: 13-:?0. I:?. May J. White CH. Yu W Ly CN. Waugh R. Stephen MS. Arulchelvam M, Harris JP Concurrent comparison of endolum inal versus open repair in the treatment of abdominal aortic anew :J'SIIIS: Analysis of303 patients by life table method. J Vase St og / 998; 2 7::? 13-22 i .

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UWOMJ 71(2) 2001 55

Role of imaging in the diagnosis of acute appendicitis

Eric Wong , Meds 2002

Early clinical diagnosis and aggressive surgical intervention are crucial in the traditional management of acute appendicitis (AA). This approach aims to minimize perforation but is accompanied by a high negative appendectomy rate and a moderate perforation rate. Radiological and nuclear medicine imaging provide the opportunity to lower the negative appendectomy and perforation rate. Various methods of imaging and their usefulness in diagnosing AA are discussed. Ultrasonography (US) and computed tomography (CT) have both emerged as useful radiological investigations that help diagnose or rule out AA in patients with equivocal clinical findings. In general, CT is superior to US in diagnosing acute appendicitis because it is more sensitive, specific, and accurate. However, the most suitable imaging modality primarily depends on the availability of the necessary technology, technicians at the healthcare centre involved, and the characteristics of the patients suspected to have AA. Before routine usage of US and CT in diagnosing AA can be recommended, further studies are needed to accurately delineate the costs and benefits of US and CT in this setting.

INTRODUCTION The appendix was first described by Leonardo da Vinci in 1492 as an ear-like structure arising from the caecum l, but it was not until 1886 that Reginald H. Fitz first used the term "appendicitis" to accurately describe the primary source of inflammation in acute typhilitis.1,2 Fitz's description of the progression of appendicitis from right-lower-quadrant (RLQ) pain to peritonitis and iliac fossa abscess formation prompted surgeons to establish the tradition of early intervention in acute appendicitis to prevent appendiceal perforation and peritonitis.2 This, in turn, necessitated the need for early diagnosis of acute appendicitis (AA), which has historically been, and remains mainly, clinical. Classic presentation of AA involves poorly localized periumbilical pain early on in the disease process, which is followed by nausea, vomiting and migration of pain from the periumbilical region to the RLQ. These findings occur only in about 50-60% of patients with AA.l-3 The accuracy of clinical diagnosis of AA has been reported to be approximately 80%, and is slightly higher for men than women 56

UWOMJ 71(2) 2001

because acute gynecological conditions can present simi larly as AA. Meanwhile, the negative appendectomy rate is between 15-23% and the perforation rate 16-39%.2 The high negative appendectomy rate has been traditionally accepted as the result of surgical aggressiveness with the intention to minimize appendiceal perforations.1 ,2,4 However, there has been a tremendous amount of recent efforts to lower the high negative appendectomy rate without increasing the perforation rate. These efforts chiefly centred on the use of radiological imaging, especially ultrasonography (US) and computed tomography (CT). The goal of these modalities is to improve the diagnostic accuracy of AA, reduce costs, and decrease patient complications of unnecessary appendectomies and hospitalizations.

PLAIN RADIOGRAPHS The value of plain radiographs in the diagnosis of AA is poor.I ,S-7, 9, Jo This is primarily because plain radiographs have a low sensitivity and specificity for AA and normal radiograph of

an abdomen cannot rule out appendicitisJ,IO Although numerous findings are associated with AA, such as distended cecum with fluid levels, gas in the appendiceal lumen, scoliosis of the lumbar spine to the right, and loss of right psoas shadow, all of them are non-specific for AA6,7 and can be found in up to 38-60% of patients without AA. 6 The only specific sign for AA is the presence of calcified appendicoliths, but this is only present in 10% of patients who have AA.6.7,IO Thus, it is recommended that plain radiographs of the abdomen should not be used to diagnose AA, but to identify other causes of abdominal pain.s.B. II

BARIUM ENEMA Barium enema (BE) is now seldom used as a diagnostic tool for acute abdominal pain because of advancements made in US and CT. Nonetheless, it has been used and studied in the past as a radiographic tool in diagnosing AA. Findings on BE that is suggestive of AA includes filling defect of the cecum and appendix.I.6,7,9 The sensitivity and specificity of BE for AA have been reported to be highi .7 and BE has been associated with the ability to decrease negative appendectomy rate to 9%.6 But its usage remained unpopular because 1) it cannot visualize the appendix in about 10% of normal patients, 2) it does not provide information about extraluminal structures of the abdomen, 3) an inflamed appendix can have normal filling , 4) there is a high incidence of technical failure , and 5) the risk of contrast extravasation.I.6

NUCLEAR MEDICINE IMAGING Diagnosis of AA using radioisotopic-labelled leukocytes has yielded a wide-range of sensitivity, specificity, and accuracy. I Because of these reported variability in its effectiveness and the delay of scanning after radiolabelled leukocytes injection, this modality is not recommended for use in the diagnosis of AA.I .6,7

ULTRASONOGRAPHY The use of US in the diagnosis of AA did not become popular until Puylaerti2 published successful visualization of the inflamed appendix with a graded compression technique and a high-resolution transducer. Graded compression technique refers to the application of a constant pressure on the region of interest of the abdomen through a transducer to determine the compressibility of underlying bowel loops. This technique is based on the premise that normal bowel is compressible while obstructed and inflamed ones are not.2 Since Puylaert'si2 initial publication, numerous studies have evaluated the diagnostic usefulness and practicality of US in AA. The most illustrative piece of literature in this regard was the meta-analysis conducted by Orr et al.I 3 of 17 studies that evaluated the usage of US in the diagnosis of AA. Orr et al.I 3 concluded that graded compression US is most useful in the setting where there is an indeterminate probability of AA because of its high positive and negatively predictive values, 87.3% and 89.9%, respectively. The authors did not recommend using US in diagnosing AA where the clinically determined probability is high because of a high falsenegative rate and where the clinically determined probability is low because of a high false-positive rate. The overall sensitivity and specificity were determined to be 84.7% and 92 .I %, respectively. Other studies have reported a range of sensitivities between 75-90%, specificities between 86-100%, and accuracies between 87-96%. 2

The adjunct of Doppler in diagnosing AA has also been studied. This technique is based on the principl e that the activity of inflammation is proportional to the amount of co lor signal (i. e. blood flow) within the gut wall, as blood flow is obscured by the compliance and peristaltic activity of normal bowel waiJ.2 One study by Quillin and Siegel1 4 directly compared the effi cacy of graded compression US with graded compression US with Doppler. It found that graded compression US with Doppler was equal in sensitivity (87%) compared to graded compression US, but superior in specificity (97% vs. 92%) and accuracy (93% vs. 90%). A more recent study Is reported that the sensitivity of graded compression US with Doppler as 90% and specificity as 94%. The diagnostic criteria of AA in US primarily involves the identification of an aperistaltic and non-compressible appendix greater than 6 mm in diameter (with circumferential colour in the wall of the appendix on Doppler if Doppler is used) or the identification of appendicoliths.I-3,7,8, 11 AA can be ruled out if a normal appendix is visualized. Drawbacks of using US in diagnosing AA include the need of an experienced ultrasonographer2,3, lower sensitivity and specificity in perforated AA2, and the inability to image abdomens with severe pain and guarding. Despite these shortcomings, US has numerous advantages such as availability, low cost, lack of ionizing radiation and ability to provide information about gynecological organs. In practice, abdominal graded compression US is useful in the following situations when there is an indeterminate probability of AA: 1) pediatric population - because of the lack of ionizing radiationi ,8, II and lack of intraperitoneal and mesenteric fat for contrast in CTI 8 2) young women in reproductive age and pregnant women because of the possibility of gynecological conditions that can mimic appendicitis, the lack of ionizing radiation to the fetus and reproductive organsi ,8,II and the lack of intraperitoneal and mesenteric fat for contrast in CTI 8 3) individuals with thin habitus - because of the lack of intraperitoneal and mesenteric fat for contrast in CT2,I8 4) individuals suspected for AA where CT results are equivocal8

COMPUTED TOMOGRAPHY Interest in using CT to help diagnose AA blossomed after early descriptions of CT findings of advanced appendicitis and subsequent reports that demonstrated the ability of CT to detect milder forms of AA.9 Since then, different CT techniques that image the appendix have been investigated. These included conventional CT of entire abdomen and pelvis after oral and intravenous (IV) contrast, conventional appendiceal CT (CT scans from L3 to pubic symphysis) without contrast, helical or spiral CT of the entire abdomen and pelvis without contrast, and spiral appendiceal CT (limited to the abdominopelvic junction) after oral and colon contrast, and spiral appendiceal CT with colon contrast only. The general conclusion from the comparisons of these various techniques is that spiral appendiceal CT with oral and colon contrast has the highest accuracy (98%), sensitivity ( 100%), rate of normal appendix visualization (100%), and rate of alternate diagnosis (80%). This is followed closely by spiral

UWOMJ 71 (2) 2001 57

appendiceal CT with colon contrast only with an identical accuracy, 98% sensitivity, 94% visualization rate of normal appendix, and 62% rate of alternate diagnosis .I6 Overall, spiral CT diagnosis of AA, regardless of technique, has been quoted to have a sensitivity between 90-100%, specificity 91-99%, accuracy of 94-98%, positive predictive va lue of 92-98%, and negative predictive value of 95-100%. Conventional CT is recommended only if it is accompanied with oral and IV contrast, as the sensitivity drops to 87% if no contrast is used.2 These impressive results are primarily due to enhanced visualization of the appendix and detection of periappendiceal inflammatory changes .'' Spiral CT findings that are diagnostic of AA includes an appendix greater 6 rnm in diameter, filling defect of the appendix (if oral or colon contrast is used), cecal apical changes, appendoliths , and periappendiceal inflammation.2,9.I6- I8 Obvious advantages in using spiral CT in diagnosing AA is its efficacy and ability to provide alternate diagnosis. However, exposure to ionizing radiation makes CT undesirable in children, pregnant women and women of reproductive age. In addition, it is more expensive than US , requires preparation of patients with contrasts, and lacks contrast ability in patients with decreased intraperitoneal and mesenteric fat ,2,6 There is some evidence that spiral CT is able to favourably impact clinical and financial outcomes in the management of patients suspected to have AA . A few studies have shown that the rputine use of spiral CT in patients with an indeterminate probability of having AA based on clinical examination resulted in decreased negative appendectomy rates without increasing perforation rates, and positively influenced the management of these patients. I9-22 In particular, economic analyses by Rao et al.20 and Schuler et.22 found that routine use of spiral CT in patients with equivocal findings for AA can reduce costs in the management of these patients. Nonetheless, more similar studies are needed to further validate these results . At the present time, spiral CT is useful in the diagnosi s of AA in the following settings when there is an indeterminate probability of AA: 1) obese patients - boca use of enhanced contrast resulting in better visualization of the cecum and appendix due to the presence of intraperitoneal and mesenteric fat in adequate amoutn s2.6,7, I8 2) any patient for whom US has not been recommended as a first imaging tool 3) any case of suspected AA where the results of US is equivocal - because of high sensitivity, specificity and accuracy2.6.7

MAGNETIC RESONANCE IMAGING Although gadolinium-enhanced magnetic resonance imaging has high sensitivity (97%) and accuracy (95 %)8, its high cost and unavailability renders it a negligible role in the diagnosis of AA at presentJ,S.IO

SUMMARY AND CONCLUSIONS US and spiral CT have emerged as useful imaging tool s in the diagnosis of AA when there are equivoca l clinical findings in the past decade . Appendiceal spiral CT with oral and colon contrast or colon contrast alone has been shown to have excellent 58

UWOMJ 71 (2) 2001

accuracy, sensitivity, specificity, visualization of the appendix and ability to provide alternate diagnosis that are superior to that of graded compression US. Nonetheless, the choice of whether US or CT should be used depends on various factors: age, sex, body habitus, availability of imaging machinery, and availability of experienced ultrasonographer in the diagnosis of AA using US. Despite the potential ability of US and CT in reducing negative appendectomy rates, perforation rates and costs of patient management, more studies are required to further examine the benefits and clinical impact of US and CT in equivocal cases of suspected AA before routine usage can be recommended. REFERENCES 1. Graffeo CS, Counselman FL. Appendicitis. Emergency Medicine Clinics of No rth America 1996; 14(4) :653-671. 2. Birnbaum BA , Wilson SR. Appendicitis at th e M illennium. Radiology 2000; 215(2):337-348. 3. Hudso n PA , Pron es SB. Abdominal ultrasonography. Emergency Medicine Clinics of No rth America 1997; 15(4) :825-848. 4. Birnbaum BA , Baltha::ar EJ CT of appendicitis and diverticulitis. Radiologic Clin ics of No rth America 1994; 32(5):885-898. 5. Ma on JD. Th e evaluation of acute abdominal pain in children. Emergency Medicine Clinics of North America 1996; 14(3):629-643. 6. Eriksson S. Acute appendicitis - Ways to improve diagnostic accuracy. European Journa l ofSurgeJy 1996; 162(6): 435-442. 7. Rao PM, Boland GWL. Imaging of acute right lower abdominal quadrant pain. Clinical Radiology 1998; 53(9) :639-649. 8. Gupta H, Dupuy DE. Advances in imag ing of the acute abdom en. Surgical Clinics ofNorthAm erica 1997; 77(6) :1245-1 263. 9. Birnbaum BA, Baltha::ar EJ. CT of appendicitis and diverticulitis. Radiologic Clinics of North America 1994; 32(5):885-898. 10. Rao PM. Rhea JT, Nove/lin e RA . Helical CT of appendicitis and diverticulitis. Radiologic Clinics of No rth America 1999; 3 7(5):895-910. 11 . Ha rdin J1: DM. Appendicitis. American Family Physician 1999; 60(7):2027-2034. 12. Puylaert JB. Acute appendicitis: US evaluation using graded compre sion. Radiology 1986; 158:355-360. 13. Orr RK. Porter D. Hartman D. Ultrasonography to evaluate adults for appendicitis: decision making based on meta-analysis and probabilistic reasoning. Academic Emergency Medicine 1995; 2(7):644-650. 14. Quillin SP. Siegel MJ Appendicitis: efficacy of color Doppler sonography. Radiology 1994: 191(2) .557-560. 15. Gulierre:: CJ, Mariano MC. Faddis DM. Sullivan RR, Wo ng RS, Lourie DJ. Sta in C. Doppler ultrasound accurately screens patients with appendicitis. American Surgeon 1999: 65(1 1): 1015- 7, 1999. 16. Rao PM. Rhea JT, Nove/lin e RA . Helical CT of appendicitis and diverticulitis. Radiologic Clinics of North America 1999; 3 7(5) :895-91 0. 17. Urban BA, Fishman EK. Targeted helical CT of the acute abdomen: Appendicitis, diverticulitis. and small bowel obstruction. Seminars in Ultrasound. CT. and MRI 2000; 2 1(1):20-39. 18. Lane MJ, Mindel;;un RE. Appendicitis and its mimickers. Seminars in Ultrasound, CT. and MRI 1999; 20(2): 77-85. 19. Baltha::ar EJ. Rofsky NM. Zucker R. Appendicitis: Th e impact of computed tomography imaging on negative appendectomy and pe1joration rates. American Journal of Gastroenterology 1998; 93(5): 768-71. 20. Rao PM, Rhea JT, Nove/lin e RA , Mostafavi AA. McCabe CJ Effect of computed tomography of the appendix on treatment ofpatients and use of hospital resources. New Eng land Journal of Medicin e. 1998; 338(3): 141 -6. 21. WalkerS, Haun W. Clark J, McMillin K, Zeren F, Gilliland T. Th e value of lim ited computed tomography with rectal contrast in th e diagnosis of acute appendicitis. American Journal of Surgery 2000: 180(6):450-455. 22. Schuler JG, Shortsleeve MJ, GoldellSon RS, Pere::-Rossel/o JM, Perlmutter RA , Th orsen A. Is there a role for abdominal computed tomographic scans in appendicitis? Archives of Surge1y 1998; 133:373-376.

Miscellaneous Articles

Differences in prescribing practice between board certified prescribing psychologists and psychiatrists

Lany C. Litman PhD, CPsych, FPPR Board Certified, Diplomate-Fellow in Psychopharmacology Psychological Physician (American Psychologist Physicians 路 Register) Adjunct Professor of Psychiatty, University of Western Ontario, London, Ontario, Canada Forensic- and Neuro-Psychologist, Forensic Services, London I St. Thomas Psychiatric Hospital, St. Thomas, Ontario, Canada.

Differences in the both the medical training programmes and in the practice of pharmacotherapy between doctors trained within the psychological and medical models are adumbrated, with the implications of the use of the psychological model in the pharmacological management of patients propounded as being quite profound. Each model is tendered as offering an orthogonally distinct cluster of benefits that should not be overlooked.

Practice differences between doctors within the medical and psychological specialties have been adumbrated in those areas in which they are found to labour in the same vineyard. For example, Grisso' investigated how forensic psychologists and forensic psychiatrists, in general, differ (as well as how they are alike) in such areas as theory and research data base sources, professional mentoring systems, the content to which each group predominantly attends in the understanding of forensic cases, methods for constructing a forensic case, and epistemological (i.e., clinical research) differences. He points out that these differences are rooted in the historical purposes of the two professions, with each having their own unique sets of strengths that counterbalance the weaknesses of the other when they engage in consociation (i.e., an anthropological term referring to collaboration between two cultural groups, while maintaining their separate identities and a concern for their independent interests). He also points out the vulnerability of these chronicled similarities and differences as generalizations, while maintaining that, beyond certain types of knowledge and abilities that they share, forensic psychiatry and forensic psychology are especially good at different things, and that the world will benefit most from each group striving to perfect what they do best. While the background of forensic psychiatrists were found to favour a focus on the diagnosis of serious mental disorder, forensic psychologists were observed to go beyond the matter of mental disorder to describe the person - that is, the individual's abilities, personality, social role, and interpersonal life as a context within which mental disorder is manifested. This eventuality was descried as arising out of the fact that mental illness historically has been the true purpose

and reason for psychiatry but something that has not been true for psychology. Psychiatry developed as a branch of medicine for the purpose of diagnosing and treating illness, while its closest counterpart in psychology, clinical psychology, arose from general psychology, which developed (out of philosophy) with a mission to better understand human behaviour generally (i.e., including the range of "normal" behaviour). Hence, psychology's historical purpose is identified with the development of scientific principles regarding broader matters than illness, such as human development, cognitive and intellectual abilities, and the adaptive and maladaptive aspects of personality and social-emotional functioning, all of which are brought to bear upon the development of forensic (as well as general clinical) cases. In other words, if there were no mental illness, there might be no psychiatry, but there would still be a field called psychology. In general, Dr. Grisso 's findings indicated that forensic psychiatrists were seen as better able to use interviews, on-the-ward observations, and record reviews to reach diagnostic and forensic conclusions. These skills are emphasized early in their intern and residency experiences to facilitate efficient and practical decision-making with confidence under circumstances of limited clinical information. In contrast, the average forensic psychologist was perceived by both psychiatrists and psychologists alike as better prepared to obtain and use standardized, quantitative assessment data, as well as theory and method in the process of case analysis, which are rooted in their pre-specialisation training. They devote more time to discussing not merely what they know, but how they know it, and how they can support the reliability and validity of their claims about

UWOMJ 71(2) 200 I 59

their cases. Their training is designed to sensitize them to sources of bias in their interpretations of what they have observed. In other words, rather than making decisions with confidence, as psychiatrists are socialized to do, they are taught to mistrust their senses or ideas, and to expetience confidence in their hypotheses about a case only when they are supported by some standardized data sources, preferably from several quantitative methods. Although this offers especially convincing fo rensic evidence when the standard can be met, such a standard is very demanding and sometimes impractical when applied to forensic cases. Dr. Grizzo also observed that, while both psychologists and psychiatrists engage in fine research and that both f ields are empirica lly minded, there is an epistemological difference between the two groups. The research tradition of psychi atry is rooted in medicine's reliance upon applied clinica l experience in the evo luti on of knowledge, with the know ledge base for the field tending to evolve through doing cases and by cumulative crossreferencing of them in search of generalizations. Its data base is drawn fro m the world as it presents itself in clinical circumstances, and forensic psychiatrists wi ll typically use their fo rensic experiences to contribute to their f ield 's knowledge base via case studies or observations based on larger patient samples. In contrast, the research tradition of fo rensic psychologists are rooted in psychology's tradition, which pl aces a puissant value on knowledge that evolves fro m controlled experimentation and is derived fro m the cumul ative res ults of studies in which various conditions are held constant, or are systematically varied, in order to examine their relationship to other conditions or outcomes. As training in the proficiency of clinical psychopharmacology by doctors within the appli ed psychological spec ialties mushrooms2, and the numbers of board-certified prescribing psychologists and psychologica l phys icians3 continues to proliferate at an accelerating rate4.s, di ffere nces between the psycholog ical and medi cal models in the area of pharmacotherapy has also, ineluctably, arisen as fodder for profess ional discourse. Newman6 has noted that the implications of the use of the psychologica l model, in contrast to a medi ca l model, in the pharmaco logic management of patients are quite profound. While the current medical trainirtg programmes fo r psychologists include the bas ic content fo und in traditi onal med ica l schoo l co urses, the obj ective is not to transform psycholog ical physicians into carbon copies of physicians who graduate fro m these prog rammes, but to provide a tailored programme addressing the medi ca l training needs of doctors operating wi thin a psychologica l model of treatment Dr. Newman prov ides a few exampl es of how the medical and psycholog ical models can be di ffe renti ated. For example, one operational definition of the medi ca l model is diagnos ing a "defect or disease" and then intervening to remove it surgically or medi cate it away chemically. Further, thi s model presumes the reducti onistic presence of a di screte illness, equates health with the absence of di sease, and in sofar as surgery is not appropri ate, assumes medication is the interventi on. In contrast, the psychologica l model can be depicted as a system-oriented, holistic, integrative approach. It presumes a continuati on of fun ctions and adaptability and, to the extent that medication is appropri ate, assumes that it is but one aspect of treatment. Another example of the difference between the two models is 60

UWOMJ 7 1(2) 2001

the role of the patient. In the traditional medical model , the patient is, by and large, a passive recipient of care and of a " Dr. knows best" approach to treatment. A good patient is a compliant patient In contrast, the psychological model maximizes patient empowerment and treatment anticipates an active, problem-solving approach by the patient Collaboration between the doctor and the patient and, where appropriate, the patient's family, is the norm rather than the exception. Such di fferences in the two models also create practical variations in how medication is used. For example , while there is often no alternative treatment other than medication in the medical model, medicine is only one of a number of possible interventions, and one that is likely to be combined with other interventi ons, in the psychological modeL In addition, the collaborative aspect involved in the relationship between prescriber and patient may lead to more di scussion, explanation, and psychoeducation supporting the use of medicine. Not prescribirtg, as well as prescribing, is also viewed as a treatment option. In addition, practical diffe rences in how symptoms are conceptualized are generated by the two treatment models. The medical model often assumes that the severity of a patient's symptoms is an indicator of di sease severity. As a result, as mental healthrelated symptoms increase, so does the likelihood that medication will be prescribed. In the psychological model, however, symptom increase does not on its own mean that the di sorder is worsening, as worsening of symptoms can also result fro m successful treatment that is prog ressively helping patients to better confront problems. When symptoms are interfering with psychological treatment, then a trial of medication is considered to help in this area. However, when symptoms are not interfering with treatment medication may not be viewed as necessary or even appropriate. Hence, the actual use of medication di ffe rs dependent upon whether a psychologica l or medical model is adopted. In surrunary, there are important qualitative differences in the prescribing practices of doctors depending upon whether they are trained within either the psychological or medical models of diagnos is, treatment and patient management. While neither model is intrinsically superior to the other, each provides an orthogonally distinct cluster of benefits that should not be overlooked. Rather, as Dr. Grisso pointed out, a consociational type of collaboration between the practitioners of the two models will yield the optimum benefit for both the practitioners (in terms of credibility) and their patients (in terms of care). REFERENCES I . Grisso T Th e differences between fo rensic psychiatry and f orensic psychology. Bulletin of the American Acaden1y of Psychiatry and the Law 1993;2 1(2): 133-145. 2. Foxhall K Training in psychopharmacology gathers steam. APA Monitor 2000;31(3) :42-44. 3. Levant RF Th e psychological physician: On ward to the fu ture. Journal of Clinical Psychology in Medical Sellings 1996;3(2) : 167-172. 4. Litman L C The Prescribing Psychologists' Reg ister. Th e International College of Prescribing Psychologists, and the birth of the p sychological physician. Ontario Psychology. In press. 5. Litman LC Medically trained psychologists and psychological physicians proliferate. ? synopsis. In Press 6. Newman R. A p sycholog ical model for prescribing. APA Mo nitor 2000;31(3) :45.

The end of the shift

Pat Marley-Forster MD, FRCPC Associate Professor, The University of Western Ontario Earl Russell Chair, Th e University of Western Ontario Interdisciplinary Pain Program Department ofAnesth esia, St. Joseph s Health Care London

It was nearing the end of my long and busy twelve hour shift

on the Labour Floor as the anesthesiologist on call. The charge nurse informed me that a young woman, 32 weeks pregnant, had just been transferred to our tertiary unit from an outlying hospital. She was displaying the classic features of pre-eclampsia, or pregnancy-induced hypertension. Her blood pressure was extremely !Ugh at 180/ 120 and she was complaining of a headache. The INR was elevated, the platelet count had dropped to only 50 000. The obstetrician planned to deliver her baby by urgent Caesarean section in order to control the rising blood pressure. I visited her in her labour room to assess her and to discuss the anaesthetic. In most cases, it is preferable to give either an epidural or spinal for Cesarean section. This reduces fhe risks of aspiration, minimizes the amount of drug transferred to the fetus , and allows the mother to witness the birth. However, it is unsafe to do this in the face of an abnormal coagulation profile because of the risk of epidural hematoma and permanent neurological damage. I had to give her a genera l anaesthetic. My concern increased when I saw her. She was quite overweight on a short frame . I chatted and reassured her as well as obtained her medical !Ustory. She was still dazed by the turn events had taken, since 24 hours ago she had felt fine . I assessed her airway for ease of intubation by asking her to open her mouth wide. She opened her mouth no more than an inch and a half, saying that 路 was all she could manage with her temperomandibular joint (TMJ) pain syndrome. Her headache was worsening and she asked to be given something for it. I ordered Fentanyl , an intravenous pain killer, to ease the pain rapidly without causing nausea. I prepared the operating room by setting up an arterial line monitor to provide beat to beat reading of her blood pressure. Pre-

eclamptic patients often have wild swings of blood pressure under anaesthesia wnich must be rapidly corrected with medication. Aside from her blood pressure, my main concern was her airway. When a patient is given an intravenous induction agent, apnea occurs within seconds. The anaesthesiologist becomes responsible for ensuring oxygenation by placing an endotracheal tube and mechanically inflating the lungs. Usually tnis is routine. Given her obesity, short neck and reduced mouth opening, I knew intubation would be a significant tecnnical chall enge in this patient. Ifl fai led to do it quickly, it could be life threatening both for her and the fetus totally dependent on maternal oxygen supply. My plan was to sedate her lightly, topically anesthetize the airway and gently introduce the tube while she was still conscious and breathing on her own. She was wheeled in on a stretcher to the Operating Room. The nurses helped her to move over to the narrow operating table. I had placed some folded sheets under her neck and shoulders to put her in the best possible position to see the vocal cords on laryngoscopy. Despite the late hour, a number of people materialized to assist with the anaesthetic - a first -year medical student considering a career in anaesthesia, the anesthesia resident and a family doctor also thinking of doing the Family Practice/ Anesthesia Program. Just as she was settled on the operating room table, events began to unfold very quickly. Without warning she began to have a violent grand-mal seizure that rendered her unconscious and apneic. This is one of the most feared and serious complications of pre-eclampsia. It became my responsibility, and mine alone, to ensure that the seizure was terminated and that she received oxygen quickly. Not only was her life at stake, but that of the unborn UWOMJ 71 (2) 2001 61

baby. I quickly drew up Midazo lam, a benzodi azepine, and injected it through her intravenous tubing to terminate the se izure. It worked with in seconds. The seizure stopped anrl she began to breathe spontaneously. However, now she was only semi -consc ious. At this point the thought fl ew through my mind that if she vomited, it would probably be aspirated into her lungs and result in a fatal pneumoni a. The only thing that would protect her lungs from aspirati on of stomach contents was an endotrachea l tube. I was not sure I could accompli sh thi s in her. My plan to sedate her lightly since an awake look was no longer feas ible. If intubati on proved impossibl e, she would need an emergency tracheotomy. To make matters worse, her intravenous tubing had become interstitial during her seizure. To start another IV in thi s woman was a chall enge almost as great as the airway - and aga in my so le responsibility. The veins on her hand were imposs ibl e to see. Whi le the resident held the oxygen mask tightly on her and maintained a clear airway with a j aw- thrust, I searched frantically for another vei n. I inserted the needle blindly to the radi al aspect of her wri st where I knew a vein should be located. Mi raculously it worked ! The obstetrician waited patiently and quietly, full of concern . The only thing he said was "Tell me as soon as I can start." Thank God he was not the type to vent anxiety by shouting at the anesthes io logist to hurry it up . The ex ternal fetal heart rate monitor was recording a fe tal heart rate of only 60 beats per minute, indicating fetal hypoxia. If the baby was not delivered quickly, brain damage wou ld occur. I gave the mother intravenous thiopental to induce unconsc iousness foll owed immedi ately by succ inylcholine for muscle relaxation . I took over the patient's airway from the resident. Thi s wo uld demand all my skill and experience. Besides, if things went seriously wrong, I did not want him to fee l responsible. I inserted the laryngoscope, searching for the fa mili ar anatomica l landmarks. She had bitten her tongue during the se izure so her mouth was full of blood. Nothing looked normal but I managed to locate the vocal cords and insert the tube between them. The exhaled ca rbon diox ide monitor instantly told me that the tube was in the trachea, not the esophagus . I told the ob tetrician to go ahead . Within a couple of minutes, the surgeons had delivered a small , drowsy, but otherwise hea lthy, baby girl. Immediately, she was whi sked off to the Neonatal Intensive Care Unit. After the surgery was f ini shed, I took my pati ent to the Intensive Care Unit, still sedated and unconscious. It would have been ri sky to awaken her and remove the endotrachea l tube since the seizures could recur for up to 48 hours after deli very. Two days later I went to check on her prog ress in the ICU. A few minutes earli er the baby had just arrived for her first visit with Mom. Her attention was naturally diverted. " I remember you - You 're the doctor who gave me something fo r my headache." she said. She had no other memory of me or of the Operating Room . She returned to examining every square inch of the new baby in her arms. The little girl, in turn, stared at her mother's face with the pure, unblinking gaze of the newborn . Did her lack of appreciation of the rol e I had played bother me? No and yes . No .. . because seeing the contented mother and baby gave me a fee ling of profound thankfulness that l had been 62

UWOMJ 71(2) 2001

abl e to do the right thing. My resuscitation skills developed in just such life-threatening situations had stood me in good stead. Yes ... because anesthes iologists seem fated to be cloaked in anonymity. As I took my unheralded leave, I reflected that, had I failed I would have had attention enough focused on me by the media and the lawyers asking what went wrong and who was to blame. As so often happens in the life of an anesthesiologist, the feeling of a j ob well done must be its own reward. ACKNOWLEDGEMENT The author would like to thank Dr. Indu Singh and Mr. Eric Forster for reviewing the manuscript.

London Regional Cancer Centre Centre Regional de Cancerologie de London 790 Commissioners Road East London. Ontario N6A 4L6 Tel: (519) 685-8600 Ext. 54007 Fax: (519) 685-8611 London Region al Cance r Centre

The UNIVERSITY of WESTERN ONTARIO Facu lty of Med icin e & Denti try • Department of Oncology 790 Commi ss ioners Road East London, Ontario N6A 4L6 (5 19) 685-8600

Dr. J. Gregory Cairncross, MD Chief Executive Officer London Regional Cancer Centre Professor and Chair, Department of Oncology The London Reg ional Cancer Centre is a modern , we ll equipped, ambul atory treatment facility. The opportunity exi ts to participate in c linical and bas ic re earch programs. The Department of Onco logy offers postgradu ating training in Medica l and Radi ati on Oncology.

For details, contact: Dr. Eric Winquist, MD, FRCPC Residency Program Director • Department of Medi ca l Oncology Dr. Barbara Fisher, MD, FRCPC Residency Program Director • Department of Radi ati on Oncology (5 19) 685-8600 Ext. 54007

ZIPIIDR* A TOR0::!S7A77N CALOUM EFFICACY TO REACH TARGET THE FIRST TIME

" LIPITOR• (at01vastabn calcium) 10 mg, 20 mg, 40 mg and 80 mg tablets THERAPEUTIC CLASSIFICATION: Liprd Metabolism Regulator ACTIONS AND CLINICAL PHARMACOLOGY LIPITOR (atorvastatin calcium) is a synthetic lipid-lowering agent It rs a selecfive. competitive rnhrbrtor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase This enzyme catalyzes the conversron of HMG-CoA to mevalonate. whrch rs an early and rate-limiting step rn the biosynthesis of cholesterol. LIPITOR lowers plasma cholesterc> and lipoprotem levels by rnhibrting HMG-CoA reductase and cholesterc> synthesrs rn the liver and by rncreasing the number of hepatic Low Oensrty Upoprotern (LDL) receptors on the cell-surface for enhanced uptake and catabolism of Low Densrty Lipoprotern (LDL) LIPITOR reduces LDL-Cholesterol (LOL -C) and the number of LDL pa~icles LIPITOR also reduces Very Low Density LrpoproternCholesterol (VLOL-C). serum triglycendes (TG) and lntermedrate Oensrty Lipoproteins (IOL), as well as the number of apohpoprotern B (apo B) contarnrng partJcles, but increases Hrgh Oensrty l.Jpoprotern-Chc>esterol (HDL-C) Elevated serum cholesterol due to elevated LDL-C is a ma1or risk factor for the development of cardiovascular drsease Elevated plasma TG is also a risk factor for cardiovascular drsease. pa~rcularly rf due to increased IDL, or associated with decreased HOL-C or rncreased LDL -C Atorvastabn is rapidly absorbed after oral administranon, maxrmum plasma concentrations occur wrthrn 1 to 2 hours Atorvastatin tablets are 95% to 99% broava1lable compared to solutions Mean drstnbubon of atorvastatrn rs approxrmately 381 lltres Atorvastafin rs ;,98% bound to plasma proterns Atorvastatrn is extensively metabolized by cytochrome P-450 3A4 to ortho- and para-hydroxylated denvatives and to vanous beta-oxrdabon products Approxrmately 70% of crrculanng rnhrbrtory actrvrty for HMG-CoA reductase rs attnbuted to act1ve metabolites Atorvastatin and rts metabolites are elimrnated by brhary excretron. Less than 2% of a dose of atorvastatin rs recovered rn unne following oral administration. Mean plasma eliminatron half-life of atorvastatrn in humans rs approximately 14 hours, but the half-hie of rnhrbrtory acfivrty for HMG-CoA reductase is 20 to 30 hours due to the contnbubon of longer-lived active metabolites. INDICATIONS AND CLINICAL USE LIPITOR (atorvastann calcium) rs rndrcaled as an adtunct to dret, at least equrvalent to the American Hea~ Assocratron (AHA) Step 1 dret, for the reducnon of elevated total cholesterol, (total-C), LOL-C, TG and apolipoprotern B (apo B) rn hyperliprdemic and dysliprdemrc condrtions, when response to dret and other nonpharmacological measures alone has been rnadequate, rncludrng • Primary hypercholesterolemra (Type lla); • Combrned (mixed) hyperllprdemra (Type lib), rncludrng familial combrned hyperliprdemia, regardless of whether cholesterol or triglycerides are the lipid abnormality of concern, • Oysbetalipoproternemia (Type IIQ, • Hypertnglycendemra (Type IV); • Famrlial hypercholesterolemra (homozygous and heterozygous). For homozygous famrhal hypercholesterotemra, UPtTOR should be used as an adjunct to treatments such as lDL apheres.s, or as monotherapy rf such treatments are not avarlable In cllnrcal trials, UPITOR (10 to 80 mglday) srgnrficantly rmproved hprd profiles in patients with a wide vanety of hyperlrprdemrc and dyslipidemic condrbons. In 2 dose-response studres rn mrldly to moderately hyperhprdemic patients (Frednckscn Types lla and lib), UPITOR reduced the levels of total cholesterol (29-45%), LDL-C (39-60%), apo B (32-50%), TG (19-37%), and rncreased high density lipoprotern cholesterol (HOL-C) levels (5-9%) Comparable responses were achreved rn patients wrth heterozygous familial hypercholesterolemra, non-famrlial forms of hypercholesterolemra, combined hyperhprdemra, rncludrng famrllal combrned hyperlrprdemra and pafients With non-rnsulin dependent diabetes mellitus In pabents with hypertngtycendemia (Type IV), LIPITOR (10 to 80 mg darly) reduced TG (25- 56%) and LOL-C levels (23- 40%) Chy\omrcrons, whrch charactenze Types I and V, have not been measured rn drnical studres rn panents With hrgh TG levels(> 11 mmoVL) In an open-label study rn pabents WJth dysbetalipoproternemra (Type Ill), LIPITOR (10 to 80 mg darly) reduced totai-C (40-57%), TG (40-56%) and IOL-C + VLOL-C levels (34-58%) In an open label study in pafients wrth homozygous famrlial hypercholesterolemra (FH) UPITOR (1 0 to 80 mg daily) reduced mean LDL-C levels (22%). In a pilot study, UPITOR SO mglday showed a mean LOL-C lowering of 30% for pafients not on plasmapheresrs and of 31% for patients who continued plasmapheresrs A mean LDL-C lowering of 35% was observed in receptor defecnve patients and of 19% rn receptor negafive pabents (see PHARMACOLOGY, Clinical Studies). For more detarls on efficacy results by pre-defined classification and pooled data by Fredrickson types. see PHARMACOLOGY, Clinrcal Studies Pnor to rnrtiabng therapy With LIPITOR. secondary causes should be excluded forr elevations in plasma llprd levels (e g poorly controlled drabetes mellitus. hypothyrordrsm, nephrotic syndrome, dysproternemras. obstnuctive liver disease. and alcoholism), and a hprd profile pertonmed to measure total cholesterol, LDL-C, HOL-C, and TG For pafients wrth TG <4.52 mmoVL (<400 mgldL), LDL -C can be esfimated us1ng the following equation. LDL -C (mmoi/L) ; totai -C - [(0.37 x (TG) + HOL -C)) LOL-C (mg/dL); totai-C- [(0.2 x (TG) + HDL-C)]' For patients with TG levels >4 52 mmoii/L (>400 mg/dL), this equation is less accurate and LOL-C concentratrons should be measured directly or by ultracentrrfugation The Atorvastatin Versus Revascularizafion Treatments (AVERT) study exammed the effect of rntensrve lrprd-lowenng rn patients with stable coronary a~ery disease and LDL -C at least 3 0 mmoVL rn patrents referred for percutaneous translumrnal coronary angioplasty (PTCA). Panents were randomrsed for 18 months to LIPITOR 80 mg darly or to PTCA with usual medical care which could include lipid metabolism regulators. The results of the AVERT study should be considered as exploratory since several limitations may affect its desrgn and conduct In the medical-treated group wrth LIPITOR there was a trend for a reduced incidence of ischemic events and a delayed time to first ischemic event. The results also suggest thatrntensive treatment to targetlDL-C levels with LIPITOR is additive and complementary to angroptasty and would benefit patients referred for thrs procedure (see SELECTED BIBLIOGRAPHY in product monograph) CONTRAINDICATIONS Hypersensifivity to any component of this medrcafion Actrve liver drsease or unexplained persistent elevabons of serum transamrnases exceeding 3 times the upper limrt of normal (see WARNINGS) Pregnancy and lactation (see PRECAUTIONS). WARNINGS Pharmacokinetic Interactions The use of HMG-CoA reductase inhrbitors has been assocrated wrth severe myopathy, rncludrng rhabdorrnyolysrs, whiCh may be more frequent when they are coadmrnistered wrth drugs that rnhibil the cytochrorrne P-450 enzyme system. Atorvastatin is metabc>rzed by cytochrome P-450 isoform 3A4 and as such may rnteract with agents that inhrbrtthrs enzyme. (See WARNINGS, Muscle effects and PRECAUTIONS, Drug Interactions and Cyiochrome P-450-medrated Interactions). Hepatic Effects In clinical trials, persistent increases in serum transamrnases greater than three nmes the upper limit of normal occurred in <1% of patients who received LIPITOR. When the dosage of LIPITOR was reduced, or when drug treatment was interrupted or discontinued. serum transaminase levels returned to pretreatment levels The rncreases were generally not associated with jaundice or other clinical signs or symptoms. Most pabents continued treatment with a reduced dose of UPfTOR without clinical sequelae. LNer !unction tests should be oertormed before the rnrtialion of treatment and oenodrcallv thereafter. Special attention should be paid to pafients who develop elevated serum transamrnase levels, and in these patients measurements should be repeated promptly and then pertonmed more frequently If increases in alanine aminotransferase (All) or aspartate aminotransferase (AST) show evidence of progression, particularly ff they rise to greater than 3 times the upper limit of normal and are persistent, the dosage should be reduced or the drug discontinued. UPITOR should be used with caution in patients who consume substantial quantrties of alcohol and/or have a past history of liver disease Active liver disease or unexplained transaminase elevations are contraindrcations to the use of UPfTOR; rf such a condilion should develop during therapy, the drug should be discontinued. 1 Fnedewald WT era/ C/111 Chem 1972; 18(6) 489-502

Muscle Effects Myopathy, defrned as muscle achrng or muscle weakness rn contunction With rncreases rn creaMe phosphokinase (CPK) values to greater than ten trmes the upper limrt of normal, should be consrdered rn any patrent wrth drffuse myalgra, muscle tenderness or weakness. and/or marked elevation of CPK Panents should be advrsed to repo~ promptly unexplarned muscle parn, tenderness or weakness, partJcularly rf accompanred by malarse or fever UPITOR therapy should be drsconfinued rt markedly elevated CPK levels occur or myopathy is dragnosed orr suspected The risk of myopathy and rhabdomyolysrs dunng treatment wrth HMG-CoA reductase rnhrbrtors rs rncreased wrth concurrent admrnrstrafion of cyclosponn, fibnc acrd denvatives, erythromycrn. clanthromycin, nracrn (nrcotinic acrd), azote anti!ungals or nefazodone As there rs no expenence to date WJth the use of UPfTOR grven concurrently With these drugs, With the excepuon of pharmacokmefic studres conducted rn healthy subJects wrth erythromycrn and clanthromycrn, the benefits and nsks of such combined therapy should be carefully consrdered (see PRECALfTIONS, PharmacolonebC Interaction Studres and Potential Drug Interactions) Rhabdorrnyolysrs has been repo~ed rn very rare cases Wlt!1 UPITOR (see PRECAUTIONS, Drug Interactions). RhalbdomyolySIS With renal dysfunction secondary to myoglobrnuna has also been reported wrth HMG-CoA reductase rnhrbrtors LIPfTOR therapy should be temporrarily wrthheld or drscontinued rn any patrent with an acute senous condrtion suggestrve of a myopathy or havrng a nsk factor predrsposrng to the development of renal failure secondary to rhabdomyolysrs (such as severe acute rnfectron, hypotensron, mator surgery, trauma. severe metabolic, endocnne and electrolyte disorders, and uncontrolled serzures) PRECAUTIONS General The effects of atorvastatin-induced changes in lipoprotein levels, including reduction of serum cholesterol on cardiovascular morbidity or mortality or total mortality have not been established. Before rnstrtutrng therapy with UPITOR (atorvastafin calcrum), an anempt should be made to control elevated serum lipoprote1n levels wrth appropnate dret, exercrse, and werght reductron 1n overwerght pat1ents, and to treat other underly1ng medical problems (see INDICATIONS AND CLINICAL USE). Patrems should be acMsed to rnform subsequent physrcians of the prior use ol LIPITOR or any other liprd-lowenng agents

Elf Current long-term data from clinrcal tnals do not rndicate an adverse effect of atorvastaM on the human lens Effect on Ubiguinone ICoOrol Levels Srgnlfrcant decreases rn crrculafing ubrqurnone levels rn panents treated wrth atorrvastatin and other stafins have been observed The clrnrcal srgnrficance of a potentral long-term statrn -rnduced deficrency of ubrqurnone has not been established It has been repo~ed that a decrease rn myocardral ubrquinone levels could lead to imparred cardiac function rn patrents wrth borderline congesfive heart farlure (see SELECTED BIBLIOGRAPHY rn product monograph) Effect on lipoprotein Ia\ In some patients, the beneficial effect of lowered total cholesterol and LOL-C levels may be partly blunted by a concomrtant rncrease rn Lp(a) levels Unlit further expenence is obtained, rt rs suggested, where feasible, that measurements of serum lp(a) be followed up rn patients placed on atorvastatin therapy (see SELECTED BIBLIOGRAPHY rn product monograph) Hypersensitivity An apparent hypersensrtrv1ty syndrome has been repo~ed wrth other HMG-CoA reductase rnhrbrtors whrch has rncluded 1 or more of the following features anaphylaxrs, angioedema, lupus erythematous-like syndrome, polymyalgra rheumatica, vasculitis, purpura, thrombocytopenia. leukopenra, hemrnytic anemra. posrtive ANA, ESR increase, eosinophilia, aMntis, aMralgra, urtJcaria, asthenra, photosensitivity, fever, chills, flushing , malaise, dyspnea. to~c epidenmal necrolysis, erythema multrfonme, rncluding Stevens-Johnson syndrorrne I>Jthough to date hypersensrtivrty syndrome has not been descnbed as such, UPITOR should be discontinued if hypersensitiVlty is suspected Use in Pregnancy LIPITOR is contraindicated during pregnancy (see CONTRAINDICATIONS). Atherosclerosrs rs a chrome process and drsconfinuation of liprd-lowenng drugs dunng pregnancy should have little rmpact on the outcome of long-term therapy ol primary hypercholesterolemra Cholesterol and other products of cholesterol brosynthesis are essential components for Jetal development uncluding synthesis of steroids and cell membranes) Srnce HMG-CoA reductase rnhib1tors decrease cholesterol synthesrs and possrbly the synthesis of other b<ologrcally actrve substances denved from cholesterol, they may cause hanm to the fetus when admrnistered to pregnant women There are no data on the use of UPITOR during pregnancy UPITOR should be admrnrstered to women of chrldbearing age only when such patients are hrghly unlikely to concerve and have been rnfonmed of the potentral hazar<Js If the patient becomes pregnant whrle taking UPITOR. the drug should be discontinued and the pabent apprised of the potenfial nsk to the fetus

Nursing Mothers In rats. mrlk concentratrons of atorvastafin are srmilar to t!lose rn plasma It rs not known whether thrs drug is excreted 1n human mrlk Because of the potential for adverse reactrons rn nursing infants, women taking UPfTOR should not breast-feed (see CONTRANDICATIONS). Pediatric Use Treatment expenence in a pedratric populatron rs limrted to doses of LIPITOR up to 80 mg/day for 1 year in 8 patients with homozygous famrllal hyperchrnesterolemra No chnrcal or bochemrcal abnorrmalities were repo~ed rn these patients Geriatric Use Treatment expenence in adults 70 years or older (N=221) with doses of UPITOR up to 80 mglday has demonstrated that the safety and effectiveness of atorvastatrn 1n this population was srmilar to that of patients <70 years of age Phanmacokinetic evaluation of atorvastafin rn subtects over the age of 65 years rndrcates an rncreased AUC As a precautionary measure, the lowest dose should be administered initially (see PHARMACOLOGY, Human Pharmacolonencs, SELECTED BIBLIOGRAPHY rn product monograph). Renal Insufficiency Plasma concentrations and LDL -C lowenng efficacy of LIPITOR was shown to be Similar rn pafients with moderate renal rnsufficrency corrnpared With pahents WJth nonmal renal funcbon However, srnce several cases of rhabdomyolysrs have been repo~ed rn patients with a hrstory of renal insufficrency of unknown seventy, as a precautronary measure and pendrng fu~her expenence rn renal drsease. the lowest dose (10 mg/day) of UPITOR should be used rn these patients Srmilar precautions apply rn panents wrth severe renalrnsufficrency [creatrnrne clearance <30 mUmrn (<0 5 mUsec)] ; the lowest dosage should be used and implemented cautiously (see WARNINGS, Muscle Effects; PRECAUTIONS, Drug Interactions). Refer also to DOSAGE AND ADMINISTRATION. Endocrine Function HMG-CoA reductase inhibitors rntertere with cholesterol synt!lesrs and as such mrght theorreticaly blunt adrenal and/or gonadal sterord producnon Clrnrcal studres With atorvastatin and other HMG-CoA reductase rnhrb<tors have suggested that these agents do not reduce ~asma corfisol concentration or rmparr adrenra reserve and do not reduce basal plasma testosterone concentration However, the effects of HMG-CoA reductase rnhrbrtors on male fertJhty have not been studied rn adequate numbers of panents The effects, rf any, on the ~tuitary-gonadal axrs in premenopausal worrnen are unknown Patients treated with atorvastatin who develop clinrcal evidence of endocnne dysfunctron should be evaluated appropriately. Caution should be exercised if an HMG-CoA reductase inhibitor or other agent used to tower cholesterol levels rs admrnistered to patrents receivrng other drugs (e g ketoconazole, sprronolactone or crmetrdrne) that may decrease the levels of endogenous steroid hormones Pharmacokinetic Interaction Studies and Potential Drug Interactions Pharmacokinetrc interactron studres conducted With drugs rn healthy subJects may not detect the possrbrlity of a potential drug interaction in some patients due to drfferences in underlying drseases and use of concomrtant medrcalions (see also Genatnc Use; Renal Insufficiency, Patients With Severe Hypercholesterolemia). Concomitant Therapy with Other Lipid Metabolism Regulators: Combrned drug therapy should be approached with cautron as rnfonmation from controlled stud1es rs limited. Bile Acid Sequestrants: Patients With mrkf to moderate hyoerchc>estero!em~a: LDL-C redUCtion was greater when UPtTOR 10 mg and colestrpof 20 g were coadmrnrstered (-45%) t!lan when either drug was administered alone (-35% for UPtTOR and -22% for colestrpoQ

Panents W1th severe hypercholesterolemra LDL-C reductron was srmrlar (-53%) when UPITOR 40 mg and colestipol 20 g were coadministered when compared to that wrth LIPITOR 80 mg alone Plasma concentration of atQMistatin was lower (appro~mately 26%) when UPITOR 40 mg plus colestrpol 20 g were coadmrmstered compared W1th UPITOR 40 mg alone However. the combmanon drug therapy was less effective rn lowenng the tng~ndes than UPITOR monotherapy in both types of hYPercholesterolemiC patients (see PHARMACOLOGY, Clincal Studres). When UPITOR is used concurrently W1th colesbpol or any other resrn, an rnteMI of at least tv.o hours should be marntarned between the tv.o drugs, srnce the absorpbOn of LIPITOR may be impared by the resin. Fibric Acid Derivatives (Gemfibrozil, Fenofibrate, Bezafibrate) and Niacin (Nicotinic Acid): Although there rs no experience W1th the use of UPITOR grven concurrently Wlth fibnc acrd denvaoves and macrn. the benefits and nsks of such combrned therapy should be carefully consrdered The nsk of myopathy during treaonent Wlth other drugs in thrs class rs rncreased wrth concurrent admrmstration (see WARNINGS, Muscle Effects) Coumarin Anticoagulants: UPITOR had no cllnrcally srgnrfrcant effect on prothrombrn nme when admrmstered to patients receivmg chrome wartann therapy (see SELECTED BIBLIOGRAPHY rn product monograph) Digoxin: In healthy subjects, digoxrn pharmaco~neocs at steady-state were not srgnificantly altered by coadmrnistration of drgoxrn 0 25 mg and UPITOR 10 mg darly However, drgoxrn steady-state coocentranons rncreased approxrmately 20% f<JIDWing coadmrnrstrabon of drgoxrn 0 25 mg and LIPITOR 80 mg darly (see Human Pharrna~neOcs) Paoents ta~ng drgoxrn should be monrtored appropnately Antihypertensive agents (amlodipine): In clinical studres. LIPITOR was used concomrtan~y Wlth antihypertensrve agents wrthout evrdence to date of clinrcally srgnrfrcant adverse interactions. In healthy subjects, atorvastatrn pharmaco~neocs were not altered by the coadmrn~tratron of LIPITOR 80 mg and amlodiprne 10 mg at steady-state (see Human Pha~nebcs) (quinapril): In a randomrzed, open-label study rn healthy subjects, steady-state qurnapnl dosrng (80 mg 00) drd not ~gnrtican~y affect the pharrna~neoc profile of atoMstann tablets (1 0 mg 00) (see Human Pharrna~neocs) Oral Contraceptives and Honmone Replacement Therapy: Coadministration of UPITOR wrth an oral contraceptrve. containrng 1 mg norethrndrone and 35~g ethrn~ estradrol, rncreased plasma concentrations (AUG levels) of norethrndrone and ethr~ estradiol by appr@mately 30% and 20%, respectvely These rncreases should be consrdered when selecting an oral contraceptive In clrnrcal studres, UPITOR was used concomrtantly wrth estrogen replacement therapy wrthout evrdence to date of cliniCally ~nrficant adverse rnteracoons Antacids: Admrmstraoon of alumrnum and magnesium based antacrds, such as Maalox" TC Suspensron, Wlth UPITOR decreased plasma concentrations of UPITOR by approxrmately 35%. LDL-C reduction was not altered but the tnglycendelowering effect of UPITOR may be affected Cimetidine: Admrnrstranon of crmeodrne Wlth UPITOR drd not alter plasma concentratrons or LDL-C lowenng efficacy of UPITOR, however, the trrglycende·lowenng effect of UPITOR was reduced from 34% to 26% C>jtochrome P-450-mediated Interactions: Atorvastaon rs metabolized by the cytochrome P-450 rsoenzyme, GYP 3A4 Erythrornyon, a GYP 3A4 rnhibltor, rncreased atorvastann plasma levels by 40% Coadmrnrstrabon of GYP 3A4 rnhrbitors, such as grapefruit JUCe, some macrolide antibiotics Qe erythromycn, danthromycin), Immunosuppressants (cyclosporrne). azole anotungal agents e rtraconazole, ketoconazole). protease rnhrbitors. or the antrdepressant, nefazodone. may have the potential to rncrease plasma concentranons of HMG-CoA reductase rnhrbrtors. includrng LIPITOR (see SELECTED BIBUOGRAPHY rn product monograph) Cauoon should thus be exerciSed W1th ooncomrtant use of these agents (see WARNINGS, Pharma~nellc lnteracbQns. Muscle Effects; PRECAUTIONS, Renal lnsufficrency and Endocnne Function. DOSAGE AND AOMINISTRATlON, SELECTED BIBLIOGRAPHY rn product monograph) In healthy subjects. coadmrnistraoon of maxrmum doses of both atorvastann (80 mg) and tertenad1ne (120 mg), a CYP 3A4 substrate, was shoW1n to produce a modest increase in tertenadme AUG. The Ol e rnteMI remarned unchanged However, srnce an rnteraction between these tv.o drugs cannot be excluded in patients w1th predrspos1ng factors for arrhythmia, (e.g preexrsong prolonged OT 1nterval, severe coronary anery d~ . hypokalemra). caunon should be exercised when these agents are coadm1mstered (see WARNINGS, Pharmacokmenc lnteracMns; DOSAGE AND ADMINISTRATlON) Antipyrine: Anopynne was used as a non-specific model for drugs metaboliZed by the microsomal hepatic enzyme system (cytochrome P-450 system). UPITOR had no effect on the pharmaco~nencs of antipyrine. thus 1nteractrons with other drugs metabolized v1a the same cytochrome rsozymes are not expected Macrolide Antibiotics (azithromycin, cfarithromycin, erythromycin): In healthy adults, coadm1nistratron of UPITOR (10 mg 00) and azrthrornycn (500 mg 00) d1d not ~gnrticantly al1er the plasma concentranons of atOMistann However. coadmrmstraoon of atorvastaon (1 0 mg 00) W1th erythromycrn (500 mg 010) or clarithromycin (500 mg BID), which are both GYP 3A4 1nh1bltors, Increased plasma concentrations of atorvastatin approxrmate~ 40% and 80%, respectively (see WARNINGS, Muscle Effects. Human Pharrna~neocs) Protease Inhibitors (nelfinavir mesylate): In healthy adults, coadm1mstration of nelfinavir mesylate (1250 mg BID), a known GYP 3A4 1nh1brtor, and atorvastatin (1 0 mg 00) resulted rn 1ncreased plasma concentratrons of atorvastaon AUG and C...... of atorvastatin were mcreased by 74% and 122% respectvely Patients wi!!J Severe HyPercholesterolemia· H1gher drug dosages (80 mg/day) required for some patients wr1h severe hYPfrcholester<Jem'a Qncludrng familial hypercholesterolemia) are aSSCICrated With increased plasma levels of atorvastahn Caution should be exercised in such patierrts who are also severely renalfy impaired, elderly, or are concomitantly being administered digoxin or CYP 3A4 inhibitors (see WARNINGS, Phanmacokinetic Interactions, Mu~e Effects; PRECAUTIONS, Orug lrrteractions; DOSAGE AND ADMINISTRATION).

Drug/l.i!boratory Test Interactions UPITOR may elevate serum transamrnase and creanmne phospho~nase levels (from skeletal muscle) In the d1fferenbal drag~s of chest pan 1n a patient on therapy with UPITOR. card1ac and noncardrac fractions of these enzymes should be determined ADVERSE REACTIONS UPITOR rs generally well -tolerated Adverse reacoons have usually been m1ld and transient In controlled clincal studies (placebo-contr<Jied and actrve-controlled comparali'fe stud1es w1th other lipid-lowering agents) involVIng 2502 patrents, <2% of patrents were d1scontrnued due to adverse expenences alfnbutable to UPITOR Of these 2502 patients. 1721 were treated for at least 6 months and 1253 for 1 year or more Adverse experiences •occurrrng at an IIICidence ~1% 1n patients participating In placebo controlled Cl1n1cal studies of UPITOR and reponed to be ~b~. probably or definitely drug related are shown in Table 1 below TABLE 1. Associated Adverse Events Reported In ~ 1 % of Patients in Placebo-Controlled Clinical Trials Placebo % (n-2701 UPITOR % (n- 1122 I GASTROINTESTINAL Constipation D1arrhea Dyspepsia Flatulence Nausea NERVOUS SYSTEM Headache MISCEULANEOUS Pain <1 Myalgia 1 Asthenia <1 The followrng additional adverse events were reported in Cl1n1cal trrals, not all events listed below have been assocrated with a causal relationship to UPITOR therapy Muscle cramps, myosrns, myopathy, paresthesia, penpheral neuropathy, pancreatitis, hep· antis. cholestatic jaundice. anorexra. vomi1ing, alopecia, pruntus. rash, rmpotence. hyperglycemia, and hypoglycemia l'ost-ma!l<e)lng exoenence· Very rare reports severe myopathy W1th or Without rhabldomyoflysls (see WARNINGS, Muscle Effects, PRECAUTONS. Renal InsuffiCiency and Drug Interactions) Isolated reports: thrombocytopenia, arthralgia and allergic reactions including urticana, ang1oneurotic edema, anaphylaxis and bullous rashes (including erytheme mul!lforme, Stevens-.JOilnson syndrome and toxrc epidermal necroflys~). These may have no causal relationship to atorvastatin Ophthalmologrc observatrons see PRECAUTIONS Laboratory Tests Increases rn serum transaminase levels have been noted In clinical trials (see WARNINGS) SYMPTOMS AND TREATMENT OF OVERDOSAGE There is no specific treaonent for atorvastatin overdosage Should an overdose occur, the patient should be treated symptomatically and supportive measures instituted as required Due to extensrve drug binding to plasma proteins, hemod~ysrs rs not expected to slgn,ficantly enhance atorvastatrn clearance. DOSAGE AND ADMINISTRATION Patients should be placed on a standard cholesterol lowenng d1et [a I least equivalent to the American Heart Association (AHA)

Step 1 diet] before receiving LIPITOR. and should continue on thiS diet duri ng treatment with UPITOR. If appropriate, a program of weight control and physical exercise should be implemented. Primarv Hypercholesterolemia and Combmed !Mixed\ Hyperlipidemia Including Familial Combined Hyoertipidemia. The recommended dose of LIPITOR rs 10 mg once a day The majority of patients achieve and maintain targe1 cholesterol levels with LIPITOR 10 mg/day. A s1gmficant therapeuoc response IS evident w1thin 2 weeks. and the m~mum response is usually achieved within 2-4 weeks. The response is marntarned dunng chronic therapy. Doses can be gwen at any time of the day, with or without food, and should preferably be given in the evening. Doses should be indwrdualized according to baseline LDL ·C and/or TG levels. the desired LDL-C and/or TG target (see the Detection and Management of Hlypercholesterolemia, Wor1<ing Group on Hlypercholesterolemia and other Oyslipidemias ]Canada] and/or the US National Ch<Jesterol Education Program [NCEP[). the goal of therapy and the patient's response Adjustments of dosage, 1f necessary, should be made at Intervals of 4 weeks or more The recommended dose range for most patients is 10 to 40 mg/day The maxrmum dosa IS 80 mg/day, which may be required 1n a minority of patients (see section below). Lipid levels should be monitored periodically and, if necessary, the dose of LIPITOR adjusted based on target lipid levels recommended by guidelines. The following reductions 1n total cholesterol and LDL -C levels have been observed in 2 dose-response studies, and may serve as a guide to treatrnen1 of patients Wlth m1ld to moderate hypercholesterolemia. TABLE 2. Dose-Response in Patients With Mild to Moderate Hypercholesterolemia (Mean Percent Change from Baseline)' UPITOR Dose (mgiday) Lipid Parameter 40 10 (N- 21) (N -22)

80 (N-23)

-29

-33

-37

-45

-39

-43

·50

-60

a. Results are pooled from 2 dose-response stud1es. b. Mean baseline values Severe Oyslipidemias In patrents with severe dys1ip1demias, Including homozygous and heterozygous familial hypercholesterolemia and dysbetalipoprote1nemia (Type IIQ, h1gher dosages (up to 80 mg/day) may be required (see WARNINGS, Pharmacokinetic ln1eracoons, Muscle Effects, PRECAUTlONS, Drug ln1eractions) Concomitant Therapy See PRECAUTlONS, Drug Interactions. Dosage in Patients With Renal lnsurtificiency See PRECAUTlONS. PHARMACEUTICAL INFORMATION Drug Substance Proper Name Atorvastatin calcrum Chemical Name [R-[R' ,W)]-2·(4-fluorophenyf}·B, o-dlhydroxy-5-(1 -methytethyf)-3-phenyl-4-[(phenylamlno) cartlonyl]1t!·pyrrole-1·heptanorc ac1d, calcrum salt (21) tnhydrate Emprncal Formula (C,HJ.I FN 1 0~ 1 Ca •3H 1 0 M<Jecular We1ght 1209 42 Structural Formula

Oescnption Atorvastatin calc1um rs a white to off-white crystalline powder that rs practically 1ns<Juble in aqueous solut1ons of pH 4 and below Atorvastaon caloum IS very slighlly soluble 1n distilled water, pH 7.4 phospha1e buffer and acetomtr11e. slighlly soluble rn ethanol, and freely soluble 1n methanol Tablet Comoosition: Each tablet contarns erther 10 mg. 20 mg. 40 mg or 80 mg a1orvastabn as the active 1ngredrent Each tablet also coo1a1ns the followrng non-mediCinallngredrents calaum carbonate, candelilla wax, croscarmellose sodium, hydroxyprop~ cellulose, lactose monohydrate, magnesrum stearate. mrcrocrystalhne cellulose, hydroxyprop~ methytcellulose, polye1hylene glyc<J, talc, titanium d1oxrde. polysorbate 80 and s1meth1cone emuls1on Stabilitv and Storage Recommendations: Store at controlled room temperature 15 to 30 C AVAILABILITY OF DOSAGE FORMS UPITOR (atorvastatin calc1um) rs available rn dosage strengths of 10 mg, 20 mg, 40 mg and 80 mg atorvastatin per tablet 10 mg:Whlte, elhpt1cal, film-coated tablet, coded "10" on one side and "PO 155" on the other Available 1n bolfles of 90 tablets 20 mg: Wh1te, elliptical. film coated tablet. coded "20" on one side and "PO 156" on the other Available in bottles of 90 tablets 40 mg: Wh1te, ell1ptlcal, film-coated tablet, coded "40" on one side and "PO 157" on the other. Available rn bottles of 90 tablets 80 mg: White, elliptical. film -coated table1, coded "BO" on one side and "PO 158" on the other. Blisters of 30 tablets (3 strips x 10) References: 1 Smrth el al Cost of Treating to a Modified European Atherosclerosrs Socrety LDL -C Target- Comparison of A10Mistatin with Fluvastalln. Pravastatrn and Simvastalln Clm Drug /nves/1999 Mar;17(3):185-193. 2. UPITOR (atorvastatin calcium) Product Monograph, Pfizer Canada Inc .. May 2001. 3 Bertolini S, Brtollo Bon G. Campbell LM, Farnier M, Langan J, Mahla G, Pauciullo P, Sirton C. Egros F, Fayyad R. Nawrocki J The efficacy and safely of atorvastatrn compared to pravastatin in patients with hypercholesterolemia. Alheroscleros1s 1997; 130.191-197. 4. Dart A, Jerums G. Nicholson G, d'Emden M, Hamil1on-Cra1g I, Tallis G. Best J, West M. Sullivan 0, Braes P, Black D. A multicenter. double-blind, 1-year study comparing safety and efficacy of atorvastatin versus srmvastatin 1n patients with hypercholesterolemia. Am J Carriro/1997;8039-44 5 Ontario Drug Benefit Formulary, March 2001 For a copy of the Product Monograph or full Prescribing Information, please contact.

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