Letters

The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: • Include no more than 400 words of text, three authors, and five references • Type with double-spacing • Send with the letter a transfer-of copyright form (see Table of Contents for location) signed by all authors • Provide a self-addressed envelope if they want to be notified that the letter was received Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified only if their letter is accepted. Unpublished letters cannot be returned. Preventive Care Guidelines To the Editors: The preventive care guidelines (1) reached our desks the same week that the President of the United States was hospitalized for atrial fibrillation. The guidelines contain a recommendation against routine screening for thyroid disease in persons over 65 years of age. In such patients, however, hyperthyroidism may not present in the classical manner. The President's atrial fibrillation was found to be secondary to Graves disease in the absence of a palpable goiter. Although President Bush had had a "complete" physical examination only 6 weeks before this episode, thyroid function had not been tested. His doctor felt that "other tests" would almost surely have signalled trouble if there had been a serious problem (2). If routine thyroid testing had been done at the President's annual physical, this anxious period for the country might have been averted. The American Thyroid Association has recently recommended that all patients over 60 years of age have a free thyroxine assay and highly sensitive thyroid-stimulating hormone determination as part of routine follow-up (3). The guidelines for preventive care as outlined in Annals (1) conflict with the American Thyroid Association recommendations. We suggest that the guidelines be modified to conform to the American Thyroid Association's recommendations. Joseph M. Tibaldi, MD Daniel L. Lorber, MD Albert Einstein College of Medicine Bronx, NY 10461 References 1. Hayward RS, Steinberg EP, Ford DE, Roizen MF, Roach KW. Preventive care guidelines: 1991. Ann Intern Med. 1991;114:758-83. 2. Martz L, McDaniel A, Picker L. Curing Bush's thyroid. Newsweek. 1991 ;May 20:27. 3. Surks MT, Chopra IJ, Mariash CN, et al. Thyroid disorders. JAMA. 1990;263:1529-32. To the Editors: The article by Hayward and colleagues (1) contains an astonishing omission. The use of spirometry in the early identification of and intervention for smoking-related diseases is not even mentioned! Spirometric abnormalities are potent predictors of premature mortality from ischemic heart disease (2, 3), lung cancer (4), and chronic obstructive pulmo406

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nary disease (5). Together, these major health problems are responsible for most of the 400 000 smoking-related deaths each year that are due to tobacco abuse and addiction. Because the article speaks forcefully of "opportunities to practice prevention in internal medicine . . . ," and states that " . . . physicians would be aided further by new tools to facilitate the assessment and documentation of health risks in the tailoring of preventative programs to individual patients," why omit spirometry? At least two studies suggest that smoking cessation can be encouraged when spirometric abnormalities are known (5). Another study clearly shows a reduction in the decline in airflow abnormalities with stopping smoking early in the course of emerging airflow obstruction (6). A survival benefit was achieved upon stopping smoking, even in patients who stopped smoking relatively late in the course of chronic obstructive pulmonary disease. Thomas L. Petty, MD University of Colorado School of Medicine Denver, CO 80218 References 1. Hayward RS, Steinberg EP, Ford DE, Roizen MF, Roach KW. Preventive care guidelines: 1991. Ann Intern Med. 1991;114:758-83. 2. Sorlie P, Lakatos E, Kannel WB, et al. Influence of cigarette smoking on lung function at baseline and at follow up in 14 years: the Framingham study. J Chronic Dis. 1987;40:849-56. 3. Tockman MS, Anthonisen NR, Wright EC, Donithan MG. Airways obstruction and the risk for lung cancer. Ann Intern Med. 1987;106: 512-8. 4. Hepper NG, Drage CW, Davies SF, et al. Chronic obstructive pulmonary disease: a community oriented program including professional education and screening by a voluntary health agency. Am Rev Respir Dis. 1980;121:97-104. 5. Peto R, Speizer FE, Cochrane AL, et al. The relevance in adults of airflow obstruction but not of mucus hypersecretion to mortality from chronic lung disease: results from 20 years of prospective observation. Am Rev Respir Dis. 1983;128:491-500. In response: The purpose of our paper (1) was not to develop new practice guidelines but to comprehensively outline existing practice guidelines relevant to screening asymptomatic patients. Drs. Tibaldi and Lorber draw attention to a recent article (2) and suggest that it advocates screening for thyroid disorders with a free thyroxine assay and a highly sensitive thyroid-stimulating hormone assay. The article to which Drs. Tibaldi and Lorber refer, however, focuses on optimal selection of thyroid tests when thyroid disease is suspected, rather than on screening for thyroid disease in asymptomatic patients. The article did not address the topic we addressed, namely screening, and hence was not relevant to our review of preventive practice guidelines. Both the Canadian Task Force and the American College of Physicians, in contrast, explicitly recommend against screening for thyroid disorders in asymptomatic adults. Drs. Tibaldi and Lorber also raise the question of whether there are particular patients, such as the President, or groups of patients, such as airline pilots, with whom the consequences of failing to detect asymptomatic disease might be greater than with other persons. We agree that this is possible, and that such consequences should be compared with the benefit and costs of early detection and treatment of disease and with the clinical and financial costs associated with false-positive results. If the President's physician had treated Bush for hyper-

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thyroidism in the setting of increased free thyroxine but no symptoms, an argument could be made for screening the President with thyroid function tests. In response to Dr. Petty's letter, we omitted spirometry from our review because no major organization has systematically reviewed the costs and benefits of spirometry in screening asymptomatic persons. A physician need not use spirometry to select which patients should be advised to stop smoking. All smokers should be advised to stop smoking (3). Dr. Petty also raises the question of whether abnormal spirometry results would encourage a smoker to comply with a physician's advice to stop smoking. Whether spirometry can be used to help change smokers' behavior, rather than to screen for pulmonary disease, could be evaluated further (4). We encourage Dr. Petty and other physicians to communicate with their professional organizations about which interventions should be assessed. Robert S. A. Hay ward, MD Earl P. Steinberg, MD, MPP Daniel E. Ford, MD, MPH Johns Hopkins University Baltimore, MD 21205 References 1. Hayward RS, Steinberg EP, Ford DE, Roizen MF, Roach KW. Preventive care guidelines: 1991. Ann Intern Med. 1991;114:758-83. 2. Surks MI, Chopra U, Mariash CN, et al. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA. 1990;263:1529-32. 3. Freedman S, Raffin TA, Rothkopf MH, Eddy DM. The value of a stage prop: screening for chronic obstructive pulmonary disease. Chest. 1984;85:406-8. 4. Risser NL, Belcher DW. Adding spirometry, carbon monoxide and pulmonary symptom results to smoking cessation counseling: a randomized trial. J Gen Intern Med. 1990;5:16-22.

Theophylline or Physician Toxicity? To the Editors: Schiff and colleagues' report (1) on preventable factors in inpatient theophylline toxicity documents the many circumstances that may contribute to the development of theophylline toxicity. Also documented are the negligence or incompetence of the responsible physicians at Cook County Hospital. Being a "busy physician" is no excuse for 1) ordering a drug level but failing to check the result; 2) failing to consider factors predisposing to theophylline toxicity (for example, heart failure, liver disease, or coadministration of drugs known to decrease theophylline clearance) when determining dosage; 3) failing to consider drug toxicity in a patient developing psychosis in the hospital as his or her theophylline dosage is advanced; 4) neglecting the past medical history (review of medical records revealed recurrent theophylline toxicity in 25% of the patients); 5) giving a potentially toxic medication without documentation or, at least, historical evidence of subtherapeutic blood levels; 6) simultaneously giving full theophylline dosages both parenterally and orally; or 7) discharging a patient on the same dose of theophylline that previously caused toxicity. There is no a priori reason to believe the authors' results can be generalized. The authors state, "Although we have no data on the generalizability of our findings, we suspect the problems are not isolated because our institution's overall quality of care is rated highly." The Chicago Tribune (the reference for this statement [2]) is not widely known as a forum for scientific discussion. The authors obviously did an excellent job of researching their data. Further, their data provide truly useful information, reminding us of some of the circumstances that predispose patients to theophylline toxicity and of the importance of carefully considering all relevant factors before prescribing any medication. In addition to the authors' conclusions, I believe that some physicians at large public hospitals are practicing a brand of medicine that is not in the best interests of their patients. Identifying circumstances leading to theophylline toxicity allowed the authors to implement measures that will de1 September 1991

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crease the incidence of this problem; however, until the root of the problem, suboptimal physician performance, is attacked, it is sure to appear in other aspects of patient care. Michael J. Henry, MD Cook County Hospital Chicago, IL 60612 References 1. Schiff GD, Hegde HK, LaCloche L, Hryhorczuk DO. Inpatient theophylline toxicity: preventable factors. Ann Intern Med. 1991; 114:74853. 2. Kotulak R. County Hospital care rates with the best, report says. Chicago Tribune. 1986;16 March:!.

To the Editors: In their excellent review of inpatient theophylline toxicity, Schiff and coworkers (1) listed corrective measures for preventing recurrent management errors. We wholeheartedly agree with most of these measures, but we feel that the most appropriate solution to prevent excessive dosing in the emergency department is to stop using theophylline there. Making faster analysis for theophylline levels available in the emergency department is not the answer. Rossing and colleagues (2) first showed in 1980 that intravenous aminophylline was a significantly less potent bronchodilator than frequently used aerosolized or subcutaneous agonists. Since then, many controlled clinical trials have shown that theophyllines give no further benefit in acute airways obstruction but frequently add to the toxicity when added to optimal beta-agonist therapy in the emergency department (3). Theophylline use in hospitalized patients is somewhat less clear and requires further study (4). The authors (1) correctly point out that the risk:benefit ratio for theophylline use may be significantly greater outside the setting of the controlled clinical trial. The lack of benefit for using theophylline in the emergency department treatment of acute airways obstruction has been established; the risk does not appear to be worth taking. This attitude is consistent with the recommendations recently released by the National Heart, Lung and Blood Institute, National Asthma Education Program Expert Panel Report on the diagnosis and management of asthma. They have excluded theophylline from the treatment recommendations for the emergency department management of acute asthma exacerbations in children and adults (5). H. William Kelly, PharmD Shirley Murphy, MD University of New Mexico Albuquerque, NM 87131 References 1. Schiff GD, Hegde HK, LaCloche L, Hryhorczuk DO. Inpatient theophylline toxicity: preventable factors. Ann Intern Med. 1991 ;114:74853. 2. Rossing TH, Fanta CH, Goldstein DH, et al. Emergency therapy of asthma: comparison of the acute effects of parenteral and inhaled sympathomimetics and infused aminophylline. Am Rev Respir Dis. 1980;122:365-71. 3. Siegel D, Sheppard D, Gelb A, Weinberg PF. Aminophylline increases the toxicity but not the efficacy of an inhaled beta-agonist in the treatment of acute exacerbations of asthma. Am Rev Respir Dis. 1985;132:283-6. 4. Kelly HW, Murphy S. Should we stop using theophylline for the treatment of the hospitalized patient with status asthmaticus? Drug Intell Clin Pharm. 1989;23:995-8. 5. National Heart, Lung and Blood Institute, National Asthma Education Program Expert Panel Report. Guidelines for the diagnosis and management of asthma. Bethesda, Maryland: National Heart, Lung and Blood Institute Information Center; 1991.

In response: One of the beauties of the Japanese continuous quality improvement paradigm is that it permits us to examine familiar problems from a new perspective. The blur of irresponsible, negligent, and incompetent physicians and hospitals can be re-examined as processes begging for improvement. Dr. Annals of Internal Medicine • Volume 115 • Number 5

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Henry views these problems and sees the blur; we see the processes. With fail-safe mechanisms in place for rapid toxic drug level reporting and action; standardized concentrations for aminophylline administration; protocols for withholding the drug in the emergency room until a nontoxic level is available; protocols to avoid using theophylline (or using only with extreme caution) in congestive heart failure patients; and protocols to reserve theophylline for use as a third-line (after /3-agonists and steroids) rather than first-line agent, any hospital will be less likely to encounter the problems we documented before our implementation of these corrective measures. Dr. Henry is incorrect in implying that the problems uncovered are isolated to one hospital or type of hospital. Recent studies show that 14% to 28% of deaths and other adverse events in hospitalized patients are attributable to "negligence" or other preventable iatrogenic errors (1-3). Such studies consistently show medication complications heading the list of iatrogenic problems. In 1990, a record number of adverse reactions to theophylline (88, including 4 deaths) were reported to the Food and Drug Administration (FDA) Adverse Drug Reaction Spontaneous Reporting System (Dr. J. Bacsanyi, FDA Division of Epidemiology. Personal communication). Public hospitals, the nation's safety-net hospitals, are straining under expanding demands. They remain, nonetheless, centers of innovation and excellence (4). The Chicago Tribune article was cited for its discussion of the excellent performance of Cook County Hospital on the Health Care Financing Administration's Medicare mortality data release. The hospital continues to show a remarkably low mortality rate in each subsequent release (5). We concur with Drs. Kelly and Murphy that the risks of theophylline in the emergency department might outweigh its benefits. Based on the literature Kelly and Murphy cite and on recent studies done by our emergency department, we now avoid routine use of the drug in this setting. Gordon D. Schiff, MD Daniel O. Hryhorczuk, MD Cook County Hospital Chicago IL 60612 References 1. Dubois RW, Brook RH. Preventable deaths: who, how often, and why? Ann Intern Med. 1988;109:582-9. 2. Brennan TA, Leape LL, Laird NM, et al. Incidence of adverse events and negligence in hospitalized patients: results of the Harvard Malpractice Study I. N Engl J Med. 1991;324:370-6. 3. Bedell SE, Deitz DC, Leeman D, Delbanco TL. Incidence and characteristics of preventable iatrogenic cardiac arrests. JAMA. 1991 ;265: 2815. 4. Gage LS, Weslowski VB, Andrulis DP, et al. America's safety net hospitals: the foundation of our nation's health system. Washington, D.C.: National Association of Public Hospitals; 1991. 5. Sullivan LW, Wilensky GR. Medicare hospital mortality information, 1987, 1988, 1989: vol. 10. Washington, DC: Health Care Financing Administration; 1991; HCFA publication no. 00729.

To the Editors: We commend Schiff and colleagues for their study (1). We want to emphasize the authors' statement that "the drug's clinical indications have been questioned." Two very recent investigations have extended emergency department-based conclusions about the treatment of asthma with theophylline into the hospital setting (2, 3). Double-blind, randomized, placebo-controlled studies in both adults (2) and children (3) have failed to show a significant added benefit of theophylline when added to frequent inhaled albuterol and high-dose glucocorticoid therapies. Although further studies are needed to determine if some subgroups of patients could benefit from theophylline in the hospital treatment of asthma, the considerable risk for toxicity, like that found by Schiff and colleagues and numerous other authors, must be weighed very carefully. We suggest, therefore, that in Table 3 of the article the last "corrective action" should be greatly emphasized for most patients in future drug use evaluations in hospitals. That is, do not use theophylline unless aggressive inhaled albuterol and systemic glucocorticoid therapy have failed. 408

Schiff and coworkers make another excellent point that is frequently overlooked by academicians. Theophylline toxicity in carefully controlled studies probably occurs much less commonly than in routine patient management. In our opinion, this finding is particularly true when the drug is prescribed by clinicians who are not familiar with its dosing and the factors that modify its clearance. Although routine theophylline use should be discouraged in acute care settings, it is still useful for treating selected ambulatory patients, especially those with nocturnal asthma or chronic obstructive pulmonary disease. First-line therapy in ambulatory asthma, however, should be anti-inflammatory medications with inhaled steroids or cromolyn (4). Optimal doses of anti-inflammatory drugs also obviate the need for theophylline in the management of most patients with nocturnal asthma. Most patients with chronic obstructive pulmonary disease respond well to inhaled beta agonists and ipratropium and do not need theophylline; exceptions are patients with chronic respiratory insufficiency, hypercapnia or cor pulmonale (5). As pointed out by Schiff and colleagues, outpatient theophylline toxicity continues to be reported. More selective use of this agent in both outpatient and inpatient settings is needed. Arthur L. Kellermann, MD, MPH Nabil Abou-Shala, MD Timothy Self, PharmD University of Tennessee Memphis, TN 38103

References 1. Schiff GD, Hegde HK, LaCloche L, Hryhorczuk DO. Inpatient theophylline toxicity: preventable factors. Ann Intern Med. 1991; 114:74853. 2. Self TH, Abou-Shala N, Burns R, et al. Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics: does aminophylline add any benefit? Chest. 1990;98:1317-21. 3. Strauss RE, Bonagura VR, Schuval SJ, Valacer DJ. Effects of aminophylline on status asthmaticus in children. J Allergy Clin Immunol. 1991;87:309. 4. Barnes PJ. A new approach to the treatment of asthma. N Engl J Med. 1989;321:1517-27. 5. Lam A, Newhouse MT. Management of asthma and chronic airflow limitations: are methylxanthines obsolete? Chest. 1990;98:44-52.

Diuretic Resistance versus Adaptation To the Editors: Ellison (1), in his excellent study of diuretic resistance, does not consider its most common occurrence— the absence of diuresis with continued administration of a diuretic to a person with heart disease but whose heart failure has been dissipated. In the treatment of heart failure, continued daily administration of a diuretic is common practice to prevent recurrence of edema, attainment of dry weight notwithstanding. In such a circumstance, the body is resistant to the diuretic. The diuretic drug becomes paradoxically not only a salt-retaining agent, but also a stimulator of potentially noxious neurohormones. With subsidence or control of precipitating factors of heart failure, daily administration of a diuretic may be unnecessary to maintain dry weight. For these reasons, intermittent use, in a dose size and interval designed to keep the patient edema-free, is preferable and may avoid diuretic resistance and its undesired effects (2). Jacob Zatuchni, MD Pennsylvania Hospital Philadelphia, PA 19107

References 1. Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991;114:886-94. 2. Zatuchni J. The treatment of congestive heart failure with diuretics and nondiuretic agents. Clin Ther. 1988;10:327-49.

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In response: Dr. Zatuchni suggests that diuretic resistance frequently develops when effective treatment of congestive heart failure reduces extracellular fluid volume. Because "diuretic resistance" was defined as the failure to achieve a desired reduction in extracellular fluid volume (1), the example cited is more appropriately termed "diuretic adaptation." This phenomenon occurs whenever diuretics are given as long-term therapy and is not unique to the treatment of congestive heart failure (1). I agree, nevertheless, that physicians should consider reducing diuretic therapy once the underlying disease has been controlled. The reduction would avoid unnecessary side effects and maintain diuretic responsiveness. David H. Ellison, MD Yale University School of Medicine New Haven, CT 06510 Reference 1. Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991;114:886-94.

Disopyramide and Inducible Arrhythmias To the Editors: Singh (1), in a recent review article on ventricular arrhythmias, lists as unknown the efficacy of disopyramide in suppressing ventricular tachycardia and ventricular fibrillation at programmed electrical stimulation. At least 14 studies have addressed this question. The largest study was done by Lerman and colleagues (2), who studied 50 patients with inducible sustained ventricular tachycardia or ventricular fibrillation. These investigators found that disopyramide rendered 34% of the patients noninducible. Studies involving crossover drug testing have shown disopyramide to be equivalent to quinidine (3) and superior to mexiletine (4) for rendering ventricular tachyarrhythmias noninducible. Singh also stated that the role of class I antiarrhythmic agents will likely diminish because of proarrhythmia and that the use of class III drugs will increase. This statement may be misleading. The incidence of serious proarrhythmia with the class III agent amiodarone is greater than with any class IA or IB antiarrhythmic (5). Marshall S. Stanton, MD Mayo Clinic Rochester, MN 55905 References 1. Singh BN. Principles of pharmacologic and nonpharmacologic therapy, pp. 792-795. In: Weiss JN, moderator. Ventricular arrhythmias in ischemic heart disease. Ann Intern Med. 1991;114:784-97. 2. Lerman BB, Waxman HL, Buxton AE, et al. Disopyramide: evaluation of electrophysiologic effects and clinical efficacy in patients with sustained ventricular tachycardia or ventricular fibrillation. Am J Cardiol. 1983;51:759-64. 3. Rizos I, Brachmann J, Lengfelder W, et al. Effects of intravenous disopyramide and quinidine on normal myocardium and on the characteristics of arrhythmias: intraindividual comparison in patients with sustained ventricular tachycardia. Eur Heart J. 1987;8:154-63. 4. Breithardt G, Seipel L, Abendroth RR. Comparison of the antiarrhythmic efficacy of disopyramide and mexiletine against stimulusinduced ventricular tachycardia. J Cardiovasc Pharmacol. 1981 ;3: 1026-37. 5. Stanton MS, Prystowsky EN, Fineberg NS, et al. Arrhythmogenic effects of antiarrhythmic drugs: a study of 506 patients treated for ventricular tachycardia or fibrillation. J Am Coll Cardiol. 1989;14: 209-15.

In response: In retrospect, we are sorry we did not assign a figure for disopyramide in preventing inducible ventricular tachycardia. We could not confidently do this, because the drug has a high propensity to induce heart failure in patients having electrophysiologic testing (2 of the 11 patients, who responded to the drug given orally, developed heart failure in the series of Lerman and coworkers cited by Dr. Stanton). Thus, disopyramide cannot be compared quantitatively with other agents. We were also influenced by the ongoing Electro-

physiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial in which six class I agents and sotalol were selected for study; disopyramide was not included. The figure of 34%, cited by Stanton, is high; Nattel (1) recently cited a composite figure from the reported literature of about 19%. We are surprised that Dr. Stanton took issue with our perception that "the role of class I antiarrhythmic agents will likely diminish because of proarrhythmia and that the use of class III drugs will increase." His restatement of our tentative conclusions is misleading. We concluded: "The role of class I agents is likely to diminish because of proarrhythmia, and that of class III agents, especially with associated anti-adrenergic effects, to grow. This is suggested by increasing experience with sotalol and amiodarone. . . . The role of newer class III agents is being investigated." We believe these statements are a reasonably accurate reflection of current opinion, especially in the wake of the Cardiac Arrhythmia Suppression Trial and meta-analysis of antiarrhythmic trials in survivors of infarction (2). The statements are also consistent with the fact that over 30 class III agents are currently under development worldwide. We are particularly surprised that Stanton, from his studies, suggested that the incidence of serious proarrhythmia with amiodarone was greater than with any class IA or IB antiarrhythmic. This assertion is not supported by the literature. Scheinman, in his editorial (3) accompanying the Stanton article (4), stated that patients treated with amiodarone may experience tachycardia that usually disappears with further therapy, and the incidence of serious proarrhythmic effects in patients on amiodarone is less than 1%. This mirrors our experience (5). We, of course, agree that such a low incidence of proarrhythmic effects may not be a property of other class III agents. Bramah N. Singh, MD, PhD James N. Weiss, MD University of California, Los Angeles School of Medicine Los Angeles, CA 90073 Koonlawaee Nademanee, MD Denver General Hospital Denver, CO 80204

References 1. Nattel S. Anti-arrhythmic drug classifications: a critical appraisal of their history, present status, and clinical relevance. Drugs. 1991 ;41: 672-701. 2. Teo K, Yusuf S, Furberg C. Effect of antiarrhythmic therapy on mortality from acute myocardial infarction. Circulation. 1990;82:III197. 3. Scheinman MM. Pro-arrhythmia and primum non nocere. J Am Coll Cardiol. 1989;16:216-7. 4. Stanton MS, Prytowsky EN, Fineberg NS, et al. Arrhythmogenic effects of antiarrhythmic drugs: a study of 506 patients treated for ventricular tachycardia or fibrillation. J Am Coll Cardiol. 1989; 14: 209-15. 5. Nademanee K, Singh BN, Hendrickson J, et al. Amiodarone in refractory life-threatening ventricular arrhythmias. Ann Intern Med. 1983;98:577-84.

Lawyer's Advice To the Editors: Lo and Steinbrook's fine article on the Cruzan case (1) suggests troubling issues about physician consultation with hospital attorneys. The authors say "lawyers might advise caregivers . . . to disregard advance directives to withhold artificial feedings unless laws are changed or test cases are decided." They cite cases in which patients were abusively subjected to other life-sustaining procedures after the physician received legal advice. Physicians should resist legal opinions that undermine their duties to patients, including the duty to respect a patient's wish not to be subjected to lifesustaining treatment. Hospital lawyers and physicians have fundamentally different loyalties and goals. A lawyer's duty is to the hospital as a corporate entity. Hospitals might want their lawyers to con-

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sider various interests in advising physicians, but hospitals always want lawyers to manage risk. An essential value for physicians—respect for individual patients—is only incidental to risk management. In that the goal of risk management is avoidance of liability, risk management loves rules. Many hospital attorneys treat absence of an authorizing rule as a prohibition: Without a rule that directly approves withholding or withdrawing specific life-sustaining treatment, lawyers often advise continuing treatment or seeking court approval to withhold or withdraw treatment to avoid any liability exposure. Risk management inherently subordinates patients' (and families') interests to institutional interests, and so undermines physicians' responsibility to patients. Continuing inappropriate treatment is obviously wrong. Going to court for permission to stop such treatment is also wrong. Court action exposes patients and families to emotional and financial trauma; subjects patients to inappropriate treatment during litigation; abdicates physician responsibility to a judge; and risks a bad outcome. Physicians should defer to judges only when the law requires them to do so. To defer unnecessarily, when a physician and patient (or surrogate) concur on a care plan, seems to me to be abandonment. "Do no harm" means just that. It does not mean: "Do no harm unless a lawyer advises it" (including advice that to do right by a patient might expose the physician to a lawsuit). Physicians suggest that patients who feel uncomfortable with medical advice get a second opinion. When a lawyer advises action that a physician feels is against patient interest, the physician should get a second opinion, too. Terry J. Barnett, JD 5212 Second Avenue N.W. Seattle, WA 98107 Reference 1. Lo B, Steinbrook R. Beyond the Cruzan case: the U.S. Supreme Court and medical practice. Ann Intern Med. 1991;114:895-901.

To the Editors: Lo and Steinbrook comment that the Cruzan ruling may increase physicians' legal uncertainties when family surrogates make decisions for incapacitated patients (1). Table 1 was provided to help clarify this issue; several citations, however, are inaccurate. The Barber case from California appears at 147 Cal. App. 3d 1006 (1983); the Hamlin case (Washington) was decided in 1984. The Virginia statute has been recodified as Va. Code Ann. Sec. 54.1-2896 (1990). In the text, reference 26, Eicher v. Dillon, should read 438 N.Y.S. 2d 266. These changes should save research time and possible frustration. Although the authors claim that the Cruzan case might not directly affect legally informed practicing physicians, differences in language and interpretation create pitfalls for the unwary. In some states, family surrogates can render health care decisions only for incapacitated adults. In Arkansas, however, the law also includes minors. A patient's incapacity or terminal illness may be certified by the attending physician in Florida, but requires separate opinions from the attending physician and one other physician in Texas. In Oregon, life-sustaining procedures can be withdrawn only after the patient's medical condition is confirmed by a committee of physicians, excluding the attending physician. Statutes often rank family members for appointment as surrogates, that is, spouse or legal guardian first, followed by a majority of adult children, parents), sibling(s), or other relatives. New Mexico allows withdrawal of treatment only by agreement of all available family members. The authors also suggest that oral statements made to physicians by patients about life support show serious intent and should be considered clear and convincing legal evidence. These oral statements, when they occur, are important, but some patients may be unable to hold meaningful discussions with their physicians. Such oral statements did not appear in the cases cited in the paper. They were either not made to the physicians involved or else were not deemed clear and convincing evidence. Instead, personal values, religious beliefs, 410

previous statements made to loving, caring friends and family, attitudes about the impact of illness on others, and other relevant circumstances are the most important factors considered by courts. The lack of consideration of these factors is what makes the Cruzan case and the more recent Wanglie case in Minnesota unusual. In the Wanglie case, a hospital seeks to discontinue life support for an 87-year-old woman in a persistent vegetative state despite the ethical and religious objections of her spouse and family (2, 3). Kenneth D. Grant, MD, JD Georgetown University School of Medicine Washington, DC 20003 References 1. Lo B, Steinbrook R. Beyond the Cruzan case: the U.S. Supreme Court and medical practice. Ann Intern Med. 1991;114:895-901. 2. Walsh E. Recasting right-to-die: public hospital seeks to end life support. The Washington Post. 1991 ;29 May:Al. 3. Walsh E. Spouse says he'd never agree to cut life support: "miracle" may happen, Minnesota court told. The Washington Post. 1991 ;30 May: A3. In response: We agree with Mr. Barnett's cautions against accepting legal advice uncritically. We thank Dr. Grant for correcting several legal citations. As he points out, laws on surrogate decision making vary from state to state. He also comments on oral statements made by patients to physicians. Currently, few patients complete written advance directives. More should be encouraged to do so. But we also need to consider the larger number of patients who have discussed with their physicians preferences about life-sustaining treatment before they become incompetent. According to medical ethics and practice, these previous oral statements can be accepted as evidence of a patient's wishes. Courts should also accept oral directives as evidence of a patient's wishes about treatment. Bernard Lo, MD University of California, San Francisco School of Medicine San Francisco, CA 94143 Red Man Syndrome after Oral Vancomycin To the Editors: Vancomycin-induced red-man syndrome is characterized by pruritus, erythema, and, in severe cases, angioedema, hypotension, and cardiovascular collapse (1). The frequency and severity of this phenomenon diminish with repeated administration of the drug (2). This reaction is usually associated with rapid intravenous infusions but may occur after slow administration (2). A recent report suggests that intraperitoneal vancomycin may also cause the red-man syndrome (3). We report an association between oral administration of vancomycin and the red-man syndrome. A 67-year-old woman developed profuse diarrhea and abdominal pain during treatment with amoxicillin-clavulanic acid for bronchitis. Results of a flexible sigmoidoscopy suggested pseudomembranous colitis. Vancomycin was prescribed (500 mg every 6 hours by nasogastric tube). Other medications included metronidazole, 500 mg, and ranitidine, 50 mg, intravenously every 8 and 12 hours, respectively, as well as phenytoin, 200 mg, by nasogastric tube every 12 hours. The first vancomycin dose was given at 1650 hours. Fifty minutes later, the patient had intense pruritus over both arms and flushing of her face and neck. Erythema over the face, neck, chest, and arms was noted by a nurse and physician. These symptoms dissipated within 30 minutes of onset. That evening, the patient was transferred to the intensive care unit. She received two doses of vancomycin, 500 mg intravenously over 1 hour at 2340 and 0545 hours. She was not observed during the infusions and could not recall any reactions when questioned the next morning. At 1230 hours, the patient received her second dose of oral vancomycin. One hour later she had intense pruritus over her scalp, face, and

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arms. Erythema over her face, neck, thorax, and arms was noted by a blinded investigator. Vital signs were unchanged from baseline. A 25-mg dose of diphenhydramine was administered intravenously, and 50 minutes later the erythema and pruritus had subsided. The patient denied involvement below the midline of her body for both reactions. Mild pruritus was noted by the patient after her oral vancomycin dose the next day despite diphenhydramine pretreatment. Trough and peak (90 minutes after the sixth vancomycin dose) vancomycin concentrations were 3.3 and 4.1 /ug/mL, respectively. No further reactions were noted. The minimum vancomycin concentration required to cause red-man syndrome is unknown. Significant absorption of vancomycin may occur following oral administration (4), which may result in adverse reactions such as rash (5). A small amount of vancomycin may have been absorbed in our patient, sufficient to incite the syndrome. Aaron D. Killian, BScPharm Jan V. Sahai, PharmD Ziad A. Memish, MD Ottawa General Hospital Ottawa, Ontario K1H 8L6 Canada

of both persons (spanning 18 years) for anti-HCV using the Ortho Diagnostic Systems (Raritan, New Jersey) enzymelinked immunosorbent assay (ELISA). All samples from the patient tested positive, from the first sample obtained in 1972 to the last obtained in November 1989. The original sample from the nurse, drawn immediately after the needlestick, was negative for anti-HCV. The sample became positive 6 weeks after she developed hepatitis and has remained positive to the present. These data indicate that 1) HCV can be transmitted by the small-volume inoculum of a needlestick injury, despite the view that the virus circulates in low concentration; 2) antiHCV persists for prolonged periods, perhaps for life, even in the absence of raised enzyme values and thus describes a reservoir for sustained HCV propagation; and 3) chronic HCV infection can persist for many years in the absence of overt hepatic disease. Finally, it is noteworthy that immune globulin, given to the nurse in a dose of 10 mL on two occasions (immediately after the accident and 30 days later), did not prevent HCV transmission in this instance. Leonard B. Seeff, MD Veterans Administration Medical Center Washington, DC 20422

References 1. Polk RE, Healy DP, Schwartz LB, Rock DT, Garson ML, Roller K. Vancomycin and the red-man syndrome: pharmacodynamics of histamine release. J Infect Dis. 1988;157:502-7. 2. Healy DP, Sahai JV, Fuller SH, Polk RE. Vancomycin-induced histamine release and "red man syndrome": comparison of 1- and 2-hour infusions. Antimicrob Agents Chemother. 1990;34:550-4. 3. Bailie GR, Kowalskv SF, Eisele G. Red-neck syndrome associated with intraperitoneal vancomycin. Clin Pharm. 1990;9:671-2. 4. Dudley MN, Quintiliani R, Nightingale CH, Gontarz N. Absorption of vancomycin. Ann Intern Med. 1984; 101:144. 5. Geraci JE, Heilman FR, Nichols DR, Wellman WE, Ross GT. Some laboratory and clinical experiences with a new antibiotic, vancomycin. Mayo Clin Proc. 1956;31:564-82.

References 1. Alter HJ, Purcell RH, Shih J, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med. 1989;321:14941500. 2. Tabor E, Gerety RJ, Drucker JA, et al. Transmission of non-A, non-B hepatitis from man to chimpanzee. Lancet. 1978;1:463-6. 3. Seeff LB, Wright EC, Zimmerman HJ, et al. Type B hepatitis after needlestick exposure: prevention with hepatitis B immune globulin. Ann Intern Med. 1978;88:285-93. 4. Tabor E, Seeff LB, Gerety RJ. Chronic non-A, non-B hepatitis carrier state: transmissible agent documented in one patient over a six-year period. N Engl J Med. 1980;303:139-43.

"Misconceptions" about AIDS Hepatitis C from a Needlestick Injury To the Editors: Transfusion-associated non-A, non-B hepatitis has recently been shown to result usually from infection with the hepatitis C virus (HCV) (1). Although we recognize that non-A, non-B hepatitis can follow smaller inoculum percutaneous exposure, such as a needlestick injury (2), data implicating HCV in this circumstance are lacking. I report an instance of HCV transmission by a needlestick injury incurred 18 years ago with persistence of circulating anti-HCV to the present. In 1972, a nurse injured her finger removing a hypodermic needle from a patient's arm. We were then doing a multicenter study to evaluate the protective efficacy of hepatitis B immune globulin (3). Evaluation of the patient showed that he had aplastic anemia for which he had received multiple blood transfusions, and that, at the time of the accident, he had apparent acute non-B hepatitis. We recommended that the nurse receive conventional immune globulin, after which we took frequent blood samples. Six weeks later she developed anicteric hepatitis, and her serum enzymes remained abnormal for almost 1 year. In 1975, the assay for hepatitis A virus became available. We then determined that both the patient and the nurse were seronegative for hepatitis A and B markers. The initial serum from the patient was later used to inoculate and infect chimpanzees, a result repeated regularly over a 6-year period and that identified him as a carrier (4). The patient is now entirely well despite fluctuating, mild enzyme elevations; two liver specimens, one obtained within the past year, show chronic persistent hepatitis. The nurse, too, is asymptomatic, although she has had occasional instances of mild enzyme elevation. We have assayed the original, stored, and most recent sera

To the Editors: Why students have misconceptions about the transmission of human immunodeficiency virus (HIV) in health care settings is easy to understand (1). The short, tragic history of the acquired immunodeficiency syndrome (AIDS) epidemic is replete with underappreciation by "the experts" of the potential risks of transmission associated with various body fluids. The number of persons who developed AIDS after receiving a blood transfusion at the start of the epidemic is a case in point. Granich and Mermin (1) criticize the misconception among medical students that HIV could be transmitted through aerosolization of body fluids. Just this past week, an article in the ACP Observer reported that the possibility of a person becoming infected by inhalation of infectious aerosol is still open to question (2). Although the risks for such exposure may be low, I think it would be premature to label as a misconception the idea that exposure to any body fluids might transmit HIV infection. To be fair to our future physicians, education about HIV issues should acknowledge those areas of potential transmissibility that are not fully understood. J. Stephan Stapczynski, MD University of Kentucky Lexington, KY 40536 References 1. Granich R, Mermin J. Students' attitudes about AIDS [Letter]. Ann Intern Med. 1991 ;114:1066. 2. Check WA. When AIDS hits home: HIV infection of health care workers. ACP Observer. 1991 June: 13.

1 September 1991 • Annals of Internal Medicine • Volume 115 • Number 5

Downloaded From: https://annals.org/ by a Tulane University User on 11/28/2018

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