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InternalMed_Harrison. disease and treatment registries. For example, by 2008, the use of acute and discharge medications for myocardial infarction had largely been equalized among racial and ethnic groups; however, African-American and Hispanic patients still experienced longer delays before reperfusion, with door-to-balloon times of <90 min for 83% of white patients as opposed to 75% and 76% of black and Hispanic patients, respectively.


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InternalMed_Harrison. The Institute of Medicine (IOM) report Unequal Treatment, released in March 2002, remains the preeminent study of racial and ethnic disparities in health care in the United States. The IOM was charged with assessing the extent of racial/ethnic differences in health care that are not otherwise attributable to known factors, such as access to care. To provide recommendations regarding interventions aimed at eliminating health care disparities, the IOM studied health system, provider, and patient factors. The study found the following: Racial and ethnic disparities in health care exist and, because they are associated with worse health outcomes, are unacceptable. Racial and ethnic disparities in health care occur in the context of (1) broader historic and contemporary social and economic inequality and (2) evidence of persistent racial and ethnic discrimination in many sectors of American life.


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InternalMed_Harrison. Many sources—including health systems, health care providers, patients, and utilization managers—may contribute to racial and ethnic disparities in health care. Bias, stereotyping, prejudice, and clinical uncertainty on the part of health care providers may contribute to racial and ethnic disparities in health care. A small number of studies suggest that minority patients may be more likely to refuse treatments, yet these refusal rates are generally small and do not fully explain health care disparities. Unequal Treatment went on to identify a set of root causes that included the following: Health system factors: These include issues related to the complexity of the health care system, the difficulty that minority patients may have in navigating this complex system, and the lack of availability of interpreter services to assist patients with limited English proficiency. In addition, health care systems are generally ill prepared to identify and address disparities.


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InternalMed_Harrison. Provider-level factors: These include issues related to the health care provider, including stereotyping, the impact of race/ethnicity on clinical decision-making, and clinical uncertainty due to poor communication. 0.75 1 1.25 1994–1996 0.53 (0.51, 0.54) 1997–1999 0.52 (0.50, 0.53) 2000–2002 0.55 (0.53, 0.56) 2003–2006 0.54 (0.52, 0.56) Whites more likely to receive 0.25 0.5 0.75 1998–1999 0.92 (0.89, 0.96) 2000–2002 0.84 (0.82, 0.86) 2003–2006 0.76 (0.75, 0.81) likely to receive likely to receive 1 1.25 0.25 0.5 0.75 1 1.25


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InternalMed_Harrison. Whites more likely to receive 0.25 0.5 0.75 1998–1999 0.92 (0.89, 0.96) 2000–2002 0.84 (0.82, 0.86) 2003–2006 0.76 (0.75, 0.81) likely to receive likely to receive 1 1.25 0.25 0.5 0.75 1 1.25 FIgURE 16e-4 Racial differences in guideline-based treatments for acute myocardial infarction (AMI). The reference population consisted of 2,515,106 patients with AMI admitted to U.S. hospitals between July 1990 and December 2006. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention. (From ED Peterson et al: Am Heart J 156:1045, 2008.) • Patient-level factors: These include patients’ mistrust of the health care system leading to refusal of services, poor adherence to treatment, and delay in seeking care. A more detailed analysis of these root causes is presented below.


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InternalMed_Harrison. Health System Factors • HEALTH SYSTEM COMPLEXITY Even among persons who are insured and educated and who have a high degree of health literacy, navigating the U.S. health care system can be complicated and confusing. Some individuals may be at higher risk for receiving substandard care because of their difficulty navigating the system’s complexities. These individuals may include those from cultures unfamiliar with the Western model of health care delivery, those with limited English proficiency, those with low health literacy, and those who are mistrustful of the health care system. These individuals may have difficulty knowing how and where to go for a referral to a specialist; how to prepare for a procedure such as a colonoscopy; or how to follow up on an abnormal test result such as a mammogram. Since people of color in the United States tend to be overrepresented among the groups listed above, the inherent complexity of navigating the health care system has been seen as a root


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InternalMed_Harrison. a mammogram. Since people of color in the United States tend to be overrepresented among the groups listed above, the inherent complexity of navigating the health care system has been seen as a root cause for racial/ethnic disparities in health care.


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InternalMed_Harrison. OTHER HEALTH SYSTEM FACTORS Racial/ethnic disparities are due not only to differences in care provided within hospitals but also to where and


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InternalMed_Harrison. FIgURE 16e-5 Racial trends in age-adjusted total knee replacement in Medicaid enrollees from 2000 to 2006. The reference population consisted of Medicaid part A enrollees ≥65 years of age who were not members of a managed-care plan. (From the Centers for Disease Control and Prevention, 2009.) from whom minorities receive their care; i.e., certain specific providers, geographic regions, or hospitals are lower-performing on certain aspects of quality. For example, one study showed that 25% of hospitals cared for 90% of black Medicare patients in the United States and that these hospitals tended to have lower performance scores on certain quality measures than other hospitals. That said, health systems generally are not well prepared to measure, report, and intervene to reduce disparities in care. Few hospitals or health plans stratify their quality data by race/ethnicity or language to measure disparities, and even fewer use data of this type to develop disparity-targeted interventions.


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InternalMed_Harrison. care. Few hospitals or health plans stratify their quality data by race/ethnicity or language to measure disparities, and even fewer use data of this type to develop disparity-targeted interventions. Similarly, despite regulations concerning the need for professional interpreters, research demonstrates that many health care organizations and providers fail to routinely provide this service for patients with limited English proficiency. Despite the link between limited English proficiency and health-care quality and safety, few providers or institutions monitor performance for patients in these areas.


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InternalMed_Harrison. Provider-Level Factors • PROVIDER–PATIENT COMMUNICATION Significant evidence highlights the impact of sociocultural factors, race, ethnicity, and limited English proficiency on health and clinical care. Health care professionals frequently care for diverse populations with varied perspectives, values, beliefs, and behaviors regarding health and wellbeing. The differences include variations in the recognition of symptoms, thresholds for seeking care, comprehension of management strategies, expectations of care (including preferences for or against diagnostic and therapeutic procedures), and adherence to preventive measures and medications. In addition, sociocultural differences between patient and provider influence communication and clinical decision-making and are especially pertinent: evidence clearly links provider–patient communication to improved patient satisfaction, regimen adherence, and better health outcomes (Fig. 16e-6). Thus, when sociocultural differences between patient


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InternalMed_Harrison. clearly links provider–patient communication to improved patient satisfaction, regimen adherence, and better health outcomes (Fig. 16e-6). Thus, when sociocultural differences between patient and provider are not appreciated, explored, understood, or communicated effectively during the medical encounter, patient dissatisfaction, poor adherence, poorer health outcomes, and racial/ethnic disparities in care may result.


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InternalMed_Harrison. A survey of 6722 Americans ≥18 years of age is particularly relevant to this important link between provider–patient communication and health outcomes. Whites, blacks, Hispanics/Latinos, and Asian Americans who had made a medical visit in the past 2 years were asked whether they had trouble understanding their doctors; whether they felt the doctors did not listen; and whether they had medical questions they were afraid to ask. The survey found that 19% of all patients experienced one or more of these problems, yet whites experienced them 16% of the time as opposed to 23% of the time for blacks, 33% for Hispanics/Latinos, and 27% for Asian Americans (Fig. 16e-7). How do we link communication to outcomes? Communication FIgURE 16e-6 The link between effective communication and patient satisfaction, adherence, and health outcomes. (From the Institute of Medicine: Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Washington, DC, National Academy Press, 2002.)


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InternalMed_Harrison. In addition, in the setting of even a minimal language barrier, provider–patient communication without an interpreter is recognized as a major challenge to effective health care delivery. These communication barriers for patients with limited English proficiency lead to frequent misunderstanding of diagnosis, treatment, and follow-up plans; inappropriate use of medications; lack of informed consent for surgical procedures; high rates of serious adverse events; and a lower-quality health care experience than is provided to patients who speak fluent English. Physicians who have access to trained interpreters report a significantly higher quality of patient–physician communication than physicians who use other methods. Communication issues related to discordant language disproportionately affect minorities and likely contribute to racial/ethnic disparities in health care.


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InternalMed_Harrison. CLINICAL DECISION-MAKING Theory and research suggest that variations in clinical decision-making may contribute to racial and ethnic disparities in health care. Two factors are central to this process: clinical uncertainty and stereotyping. First, a doctor’s decision-making process is nested in clinical uncertainty. Doctors depend on inferences about severity based on what they understand about illness and the information obtained from the patient. A doctor caring for a patient whose symptoms he or she has difficulty understanding and whose “signals”—the set of clues and indications that physicians rely on to make clinical decisions—are hard to read may make a decision different from the one that would be made Percent of adults with one or more communication problems* *Problems include understanding doctor, feeling doctor listened, had questions but did not ask.


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InternalMed_Harrison. FIgURE 16e-7 Communication difficulties with physicians, by race/ethnicity. The reference population consisted of 6722 Americans ≥18 years of age who had made a medical visit in the previous 2 years and were asked whether they had had trouble understanding their doctors, whether they felt that the doctors had not listened, and whether they had had medical questions they were afraid to ask. (From the Commonwealth Fund Health Care Quality Survey, 2001.) for another patient who presents with exactly the same clinical condition. Given that the expression of symptoms may differ among cultural and racial groups, doctors—the overwhelming majority of whom are white—may understand symptoms best when expressed by patients of their own racial/ethnic groups. The consequence is that white patients may be treated differently from minority patients. Differences in clinical decisions can arise from this mechanism even when the doctor has the same regard for each patient (i.e., is not prejudiced).


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InternalMed_Harrison. Second, the literature on social cognitive theory highlights how natural tendencies to stereotype may influence clinical decision-making. Stereotyping can be defined as the way in which people use social categories (e.g., race, gender, age) in acquiring, processing, and recalling information about others. Faced with enormous information loads and the need to make many decisions, people often subconsciously simplify the decision-making process and lessen cognitive effort by using “categories” or “stereotypes” that bundle information into groups or types that can be processed more quickly. Although functional, stereotyping can be systematically biased, as people are automatically classified into social categories based on dimensions such as race, gender, and age. Many people may not be aware of their attitudes, may not consciously endorse specific stereotypes, and paradoxically may consider themselves egalitarian and not prejudiced.


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InternalMed_Harrison. Stereotypes may be strongly influenced by the messages presented consciously and unconsciously in society. For instance, if the media and our social/professional contacts tend to present images of minorities as being less educated, more violent, and nonadherent to health care recommendations, these impressions may generate stereotypes that unnaturally and unjustly impact clinical decision-making. As signs of racism, classism, gender bias, and ageism are experienced (consciously or unconsciously) in our society, stereotypes may be created that impact the way doctors manage patients from these groups. On the basis of training or practice location, doctors may develop certain perceptions about race/ethnicity, culture, and class that may evolve into stereotypes. For example, many medical students and residents are often trained—and minorities cared for—in academic health centers or public hospitals located in socioeconomically disadvantaged areas. As a result, doctors may begin to equate


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InternalMed_Harrison. and residents are often trained—and minorities cared for—in academic health centers or public hospitals located in socioeconomically disadvantaged areas. As a result, doctors may begin to equate certain races and ethnicities with specific health beliefs and behaviors (e.g., “these patients” engage in risky behaviors, “those patients” tend to be noncompliant) that are more associated with the social environment (e.g., poverty) than with a patient’s racial/ethnic background or cultural traditions. This “conditioning” phenomenon may also be operative if doctors are faced with certain racial/ethnic patient groups who frequently do not choose aggressive forms of diagnostic or therapeutic intervention. The result over time may be that doctors begin to believe that “these patients” do not like invasive procedures; thus they may not offer these procedures as options. A wide range of studies have documented the potential for provider biases to contribute to racial/ethnic disparities in health


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InternalMed_Harrison. procedures; thus they may not offer these procedures as options. A wide range of studies have documented the potential for provider biases to contribute to racial/ethnic disparities in health care. For example, one study measured physicians’ unconscious (or implicit) biases and showed that these were related to differences in decisions to provide thrombolysis for a hypothetical black or white patient with a myocardial infarction.


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InternalMed_Harrison. It is important to differentiate stereotyping from prejudice and discrimination. Prejudice is a conscious prejudgment of individuals that may lead to disparate treatment, and discrimination is conscious and intentional disparate treatment. All individuals stereotype subconsciously, yet, if left unquestioned, these subconscious assumptions may lead to lower-quality care for certain groups because of differences in clinical decision-making or differences in communication and patientcenteredness. For example, one study tested physicians’ unconscious racial/ethnic biases and showed that patients perceived more biased physicians as being less patient-centered in their communication. What is particularly salient is that stereotypes tend to be activated most in environments where the individual is stressed, multitasking, and under time pressure—the hallmarks of the clinical encounter.


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InternalMed_Harrison. Patient-Level Factors Lack of trust has become a major concern for many health care institutions today. For example, an IOM report, To Err Is Human: Building a Safer Health System, documented alarming rates of medical errors that made patients feel vulnerable and less trustful of the U.S. health care system. The increased media and academic attention to problems related to quality of care (and of disparities themselves) has clearly diminished trust in doctors and nurses.


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InternalMed_Harrison. Trust is a crucial element in the therapeutic alliance between patient and health care provider. It facilitates open communication and is directly correlated with adherence to the physician’s recommendations and the patient’s satisfaction. In other words, patients who mistrust their health care providers are less satisfied with the care they receive, and mistrust of the health care system greatly affects patients’ use of services. Mistrust can also result in inconsistent care, “doctor-shopping,” self-medication, and an increased demand by patients for referrals and diagnostic tests.


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InternalMed_Harrison. On the basis of historic factors such as discrimination, segregation, and medical experimentation, blacks may be especially mistrustful of providers. The exploitation of blacks by the U.S. Public Health Service during the Tuskegee syphilis study from 1932 to 1972 left a legacy of mistrust that persists even today among this population. Other populations, including Native Americans/Alaskan Natives, Hispanics/ Latinos, and Asian Americans, also harbor significant mistrust of the health care system. A national Kaiser Family Foundation survey of 3884 individuals found that 36% of Hispanics and 35% of blacks (compared with 15% of whites) felt they had been treated unfairly in the health care system in the past because of their race/ethnicity. Perhaps even more alarming, 65% of blacks and 58% of Hispanics (compared with 22% of whites) were afraid of being treated unfairly in the future on that basis (Fig. 16e-8).


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InternalMed_Harrison. This mistrust may contribute to wariness in accepting or following recommendations, undergoing invasive procedures, or participating in clinical research, and these choices, in turn, may lead to misunderstanding and the perpetuation of stereotypes among health professionals. The publication Unequal Treatment provides a series of recommendations to address racial and ethnic disparities in health care, focusing on a broad set of stakeholders. These recommendations include health system interventions, provider interventions, patient interventions, and general recommendations, which are described in more detail below. Health System Interventions • COLLECTION AND REPORTING OF DATA ON HEALTH CARE ACCESS AND USE, bY PATIENTS’ RACE/ETHNICITY Unequal Treatment found that the appropriate systems to track and monitor racial and ethnic disparities in health care are lacking and that less is known about the disparities affecting minority groups other than African


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InternalMed_Harrison. FIgURE 16e-8 Patient perspectives regarding unfair treatment (Tx) based on race/ethnicity. The reference population consisted of 3884 individuals surveyed about how fairly they had been treated in the health care system in the past and how fairly they felt they would be treated in the future on the basis of their race/ethnicity. (From Race, Ethnicity & Medical Care: A Survey of Public Perceptions and Experiences. Kaiser Family Foundation, 2005.)


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InternalMed_Harrison. Americans (Hispanics, Asian Americans, Pacific Islanders, Native 16e-5 Americans, and Alaskan Natives). For instance, only in the mid-1980s did the Medicare database begin to collect data on patient groups outside the standard categories of “white,” “black,” and “other.” Federal, private, and state-supported data-collection efforts are scattered and unsystematic, and many health care systems and hospitals still do not collect data on the race, ethnicity, or primary language of enrollees or patients. A survey by Regenstein and Sickler in 2006 found that 78% of 501 U.S. hospitals collected information on race, 50% collected data on ethnicity, and 50% collected data on primary language. However, the information was not collected by standard categories or collection methods and thus was of questionable accuracy. Surveys by America’s Health Insurance Plans in 2003 and 2006 showed that the proportion of enrollees in plans that collected race/ethnicity data of some type increased from 54% to


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InternalMed_Harrison. accuracy. Surveys by America’s Health Insurance Plans in 2003 and 2006 showed that the proportion of enrollees in plans that collected race/ethnicity data of some type increased from 54% to 67%; however, the total percentage of plan enrollees whose race/ethnicity and language are recorded is still much lower than these figures.


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InternalMed_Harrison. ENCOURAGEMENT OF THE USE OF EVIDENCE-bASED GUIDELINES AND QUALITY IMPROVEMENT Unequal Treatment highlights the subjectivity of clinical decision-making as a potential cause of racial and ethnic disparities in health care by describing how clinicians—despite the existence of well-delineated practice guidelines—may offer (consciously or unconsciously) different diagnostic and therapeutic options to different patients on the basis of their race or ethnicity. Therefore, the widespread adoption and implementation of evidence-based guidelines is a key recommendation in eliminating disparities. For instance, evidence-based guidelines are now available for the management of diabetes, HIV/AIDS, cardiovascular diseases, cancer screening and management, and asthma—all areas where significant disparities exist. As part of ongoing quality-improvement efforts, particular attention should be paid to the implementation of evidence-based guidelines for all patients, regardless of their race and


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InternalMed_Harrison. exist. As part of ongoing quality-improvement efforts, particular attention should be paid to the implementation of evidence-based guidelines for all patients, regardless of their race and ethnicity.


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InternalMed_Harrison. SUPPORT FOR THE USE OF LANGUAGE INTERPRETATION SERVICES IN THE CLINICAL SETTING As described previously, a lack of efficient and effective interpreter services in a health care system can lead to patient dissatisfaction, to poor comprehension and adherence, and thus to ineffective/lower-quality care for patients with limited English proficiency. Unequal Treatment’s recommendation to support the use of interpretation services has clear implications for delivery of quality health care by improving doctors’ ability to communicate effectively with these patients.


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InternalMed_Harrison. INCREASES IN THE PROPORTION OF UNDERREPRESENTED MINORITIES IN THE HEALTH CARE WORKFORCE Data for 2004 from the Association of American Medical Colleges indicate that, of the 72.4% of U.S. physicians whose race and ethnicity are known, Hispanics make up 2.8%, blacks 3.3%, and Native American and Alaskan Natives 0.3%. Furthermore, U.S. national data show that minorities (excluding Asians) compose just 7.5% of medical school faculty. In addition, minority faculty in 2007 were more likely to be at or below the rank of assistant professor, while whites composed the highest proportion of full professors. Despite representing ∼26% of the U.S. population (a number projected to almost double by 2050), minority students are still underrepresented in medical schools. In 2007, matriculants to U.S. medical schools were 7.2% Latino, 6.4% African American, 0.2% Native Hawaiian or Other Pacific Islander, and 0.3% Native American or Alaskan Native. These percentages have decreased or remained the same


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InternalMed_Harrison. schools were 7.2% Latino, 6.4% African American, 0.2% Native Hawaiian or Other Pacific Islander, and 0.3% Native American or Alaskan Native. These percentages have decreased or remained the same since 2007. It will be difficult to develop a diverse health-care workforce that can meet the needs of an increasingly diverse population without dramatic changes in the racial and ethnic composition of medical student bodies.


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InternalMed_Harrison. Provider Interventions • INTEGRATION OF CROSS-CULTURAL EDUCATION INTO THE TRAINING OF ALL HEALTH CARE PROFESSIONALS The goal of cross-cultural education is to improve providers’ ability to understand, communicate with, and care for patients from diverse backgrounds. Such education focuses on enhancing awareness of sociocultural influences on health beliefs and behaviors and on building skills to facilitate understanding and management of these factors in the medical encounter. Cross-cultural education includes curricula on health care disparities, use of interpreters, and effective communication and negotiation across cultures. These curricula can be incorporated into health-professions training in medical schools, residency programs, and nursing schools and can be offered as a component of continuing education. Despite the importance of this area of education and the attention it has attracted from medical education accreditation bodies, a national survey of senior resident


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InternalMed_Harrison. of continuing education. Despite the importance of this area of education and the attention it has attracted from medical education accreditation bodies, a national survey of senior resident physicians by Weissman and colleagues found that up to 28% felt unprepared to deal with cross-cultural issues, including caring for patients who have religious beliefs that may affect treatment, patients who use complementary medicine, patients who have health beliefs at odds with Western medicine, patients who mistrust the health care system, and new immigrants. In a study at one medical school, 70% of fourth-year students felt inadequately prepared to care for patients with limited English proficiency. Efforts to incorporate cross-cultural education into medical education will contribute to improving communication and to providing a better quality of care for all patients.


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InternalMed_Harrison. INCORPORATION OF TEACHING ON THE IMPACT OF RACE, ETHNICITY, AND CULTURE ON CLINICAL DECISION-MAKING Unequal Treatment and more recent studies found that stereotyping by health care providers can lead to disparate treatment based on a patient’s race or ethnicity. The Liaison Committee on Medical Education, which accredits medical schools, issued a directive that medical education should include instruction on how a patient’s race, ethnicity, and culture might unconsciously impact communication and clinical decision-making. Patient Interventions Difficulty navigating the health care system and obtaining access to care can be a hindrance to all populations, particularly to minorities. Similarly, lack of empowerment or involvement in the medical encounter by minorities can be a barrier to care. Patients need to be educated on how to navigate the health care system and how best to access care. Interventions should be used to increase patients’ participation in treatment decisions.


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InternalMed_Harrison. general Recommendations • INCREASE AWARENESS OF RACIAL/ETHNIC DISPARITIES IN HEALTH CARE Efforts to raise awareness of racial/ethnic health care disparities have done little for the general public but have been fairly successful among physicians, according to a Kaiser Family Foundation report. In 2006, nearly 6 in 10 people surveyed believed that blacks received the same quality of care as whites, and 5 in 10 believed that Latinos received the same quality of care as whites. These estimates are similar to findings in a 1999 survey. Despite this lack of awareness, most people believed that all Americans deserve quality care, regardless of their background. In contrast, the level of awareness among physicians has risen sharply. In 2002, the majority (69%) of physicians said that the health care system “rarely or never” treated people unfairly on the basis of their racial/ethnic background. In 2005, less than one-quarter (24%) of physicians disagreed with the statement that “minority


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InternalMed_Harrison. care system “rarely or never” treated people unfairly on the basis of their racial/ethnic background. In 2005, less than one-quarter (24%) of physicians disagreed with the statement that “minority patients generally receive lower-quality care than white patients.” Increasing awareness of racial and ethnic health disparities among health care professionals and the public is an important first step in addressing these disparities. The ultimate goals are to generate discourse and to mobilize action to address disparities at multiple levels, including health policy makers, health systems, and the community.


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InternalMed_Harrison. CONDUCT FURTHER RESEARCH TO IDENTIFY SOURCES OF DISPARITIES AND PROMISING INTERVENTIONS While the literature that formed the basis for the findings reported and recommendations made in Unequal Treatment provided significant evidence for racial and ethnic disparities, additional research is needed in several areas. First, most of the literature on disparities focuses on black-versus-white differences; much less is known about the experiences of other minority groups. Improving the ability to collect racial and ethnic patient data should facilitate this process. However, in instances where the necessary systems are not yet in place, racial and ethnic patient data may be collected prospectively in the setting of clinical or health services research to more fully elucidate disparities for other populations. Second, much of the literature on disparities to date has focused on defining areas in which these disparities exist, but less has been done to identify the multiple factors that


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InternalMed_Harrison. other populations. Second, much of the literature on disparities to date has focused on defining areas in which these disparities exist, but less has been done to identify the multiple factors that contribute to the disparities or to test interventions to address these factors. There is clearly a need for research that identifies promising practices and solutions to disparities.


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InternalMed_Harrison. Individual health care providers can do several things in the clinical encounter to address racial and ethnic disparities in health care. Be Aware that Disparities Exist Increasing awareness of racial and ethnic disparities among health care professionals is an important first step in addressing disparities in health care. Only with greater awareness can care providers be attuned to their behavior in clinical practice and thus monitor that behavior and ensure that all patients receive the highest quality of care, regardless of race, ethnicity, or culture.


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InternalMed_Harrison. Practice Culturally Competent Care Previous efforts have been made to teach clinicians about the attitudes, values, beliefs, and behaviors of certain cultural groups—the key practice “dos and don’ts” in caring for “the Hispanic patient” or the “Asian patient,” for example. In certain situations, learning about a particular local community or cultural group, with a goal of following the principles of community-oriented primary care, can be helpful; when broadly and uncritically applied, however, this approach can actually lead to stereotyping and oversimplification of culture, without respect for its complexity.


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InternalMed_Harrison. Cultural competence has thus evolved from merely learning information and making assumptions about patients on the basis of their backgrounds to focusing on the development of skills that follow the principles of patient-centered care. Patient-centeredness encompasses the qualities of compassion, empathy, and responsiveness to the needs, values, and expressed preferences of the individual patient. Cultural competence aims to take things a step further by expanding the repertoire of knowledge and skills classically defined as “patient-centered” to include those that are especially useful in cross-cultural interactions (and that, in fact, are vital in all clinical encounters). This repertoire includes effectively using interpreter services, eliciting the patient’s understanding of his or her condition, assessing decision-making preferences and the role of family, determining the patient’s views about biomedicine versus complementary and alternative medicine, recognizing sexual and


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InternalMed_Harrison. or her condition, assessing decision-making preferences and the role of family, determining the patient’s views about biomedicine versus complementary and alternative medicine, recognizing sexual and gender issues, and building trust. For example, while it is important to understand all patients’ beliefs about health, it may be particularly crucial to understand the health beliefs of patients who come from a different culture or have a different health care experience. With the individual patient as teacher, the physician can adjust his or her practice style to meet the patient’s specific needs.


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InternalMed_Harrison. Avoid Stereotyping Several strategies can allow health care providers to counteract, both systemically and individually, the normal tendency to stereotype. For example, when racially/ethnically/culturally/socially diverse teams in which each member is given equal power are assembled and are tasked to achieve a common goal, a sense of camaraderie develops and prevents the development of stereotypes based on race/ ethnicity, gender, culture, or class. Thus, health care providers should aim to gain experiences working with and learning from a diverse set of colleagues. In addition, simply being aware of the operation of social cognitive factors allows providers to actively check up on or monitor their behavior. Physicians can constantly reevaluate to ensure that they are offering the same things, in the same ways, to all patients. Understanding one’s own susceptibility to stereotyping—and how disparities may result—is essential in providing equitable, high-quality care to all patients.


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InternalMed_Harrison. Work to Build Trust Patients’ mistrust of the health care system and of health care providers impacts multiple facets of the medical encounter, with effects ranging from decreased patient satisfaction to delayed care. Although the historic legacy of discrimination can never be erased, several steps can be taken to build trust with patients and to address disparities. First, providers must be aware that mistrust exists and is more prevalent among minority populations, given the history of discrimination in the United States and other countries. Second, providers must reassure patients that they come first, that everything possible will be done to ensure that they always get the best care available, and that their caregivers will serve as their advocates. Third, interpersonal skills and communication techniques that demonstrate honesty, openness, compassion, and respect on the part of the health care provider are essential tools in dismantling mistrust. Finally, patients indicate that


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InternalMed_Harrison. techniques that demonstrate honesty, openness, compassion, and respect on the part of the health care provider are essential tools in dismantling mistrust. Finally, patients indicate that trust is built when there is shared, participatory decision-making and the provider makes a concerted effort to understand the patient’s background. When the doctor–patient relationship is reframed as one of solidarity, the patient’s sense of vulnerability can be transformed into one of trust. The successful elimination of disparities requires trust-building interventions and strengthening of this relationship.


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InternalMed_Harrison. The issue of racial and ethnic disparities in health care has gained national prominence, both with the release of the IOM report Unequal Treatment and with more recent articles that have confirmed their persistence and explored their root causes. Furthermore, another 16e-7 influential IOM report, Crossing the Quality Chasm, has highlighted the importance of equity—i.e., no variations in quality of care due to personal characteristics, including race and ethnicity—as a central principle of quality. Current efforts in health care reform and transformation, including a greater focus on value (high-quality care and cost-control), will sharpen the nation’s focus on the care of populations who experience low-quality, costly care. Addressing disparities will become a major focus, and there will be many obvious opportunities for interventions to eliminate them. Greater attention to addressing the root causes of disparities will improve the care provided to all patients, not just those who


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InternalMed_Harrison. be many obvious opportunities for interventions to eliminate them. Greater attention to addressing the root causes of disparities will improve the care provided to all patients, not just those who belong to racial and ethnic minorities.


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InternalMed_Harrison. The authors thank Marina Cervantes for her contributions to this chapter.


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InternalMed_Harrison. Ethical Issues in Clinical Medicine Bernard Lo, Christine Grady Twenty-first-century physicians face novel ethical dilemmas that can be perplexing and emotionally draining. For example, electronic medical records, handheld personal devices, and provision of care by interdisciplinary teams all hold the promise of more coordinated and 17e comprehensive care but also raise new concerns about confidentiality, appropriate boundaries of the doctor–patient relationship, and responsibility. Chapter 1 puts the practice of medicine into a professional and historical context. The current chapter presents approaches and principles that physicians can use to address the ethical issues they encounter in their work. Physicians make ethical judgments about clinical situations every day. Traditional professional codes and ethical principles provide instructive guidance for physicians but need to be interpreted and applied to each situation. Physicians need to be prepared for lifelong learning about


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InternalMed_Harrison. codes and ethical principles provide instructive guidance for physicians but need to be interpreted and applied to each situation. Physicians need to be prepared for lifelong learning about ethical issues and dilemmas as well as about new scientific and clinical developments. When struggling with difficult ethical issues, physicians may need to reevaluate their basic convictions, tolerate uncertainty, and maintain their integrity while respecting the opinions of others. Discussing perplexing ethical issues with other members of the health care team, ethics consultation services, or the hospital ethics committee can clarify issues and reveal strategies for resolution, including improving communication and dealing with strong or conflicting emotions.


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InternalMed_Harrison. Several approaches may be useful for resolving ethical issues. Among these approaches are those based on ethical principles, virtue ethics, professional oaths, and personal values. These various sources of guidance encompass precepts that may conflict in a particular case, leaving the physician in a quandary. In a diverse society, different individuals may turn to different sources of moral guidance. In addition, general moral precepts often need to be interpreted and applied in the context of a particular clinical situation. When facing an ethical challenge, physicians should articulate their concerns and reasoning, discuss and listen to the views of others involved in the case, and call on available resources as needed. Through these efforts, physicians can gain deeper insight into the ethical issues they face and often can reach mutually acceptable resolutions to complex problems.


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InternalMed_Harrison. Ethical principles can serve as general guidelines to help physicians determine the right thing to do. Respecting Patients Physicians should always treat patients with respect, which entails understanding patients’ goals, communicating effectively, obtaining informed and voluntary consent for interventions, respecting informed refusals, and protecting confidentiality. Different clinical goals and approaches are often feasible, and interventions can cause both benefit and harm. Individuals place different values on health and medical care and weigh the benefits and risks of medical interventions differently. Generally, the values and informed choices of patients should be respected.


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InternalMed_Harrison. OBTAINING INFORMED CONSENT To help patients make informed decisions, physicians should discuss with them the nature of the proposed care; the alternatives; and the risks, benefits, and likely consequences of each option. Informed consent involves more than obtaining signatures on consent forms. Physicians should promote shared decision-making by educating patients, answering their questions, making recommendations, and helping them deliberate. Patients can be overwhelmed by medical jargon, needlessly complicated explanations, or the provision of too much information at once. Patients can make informed decisions only if they receive honest and understandable information. Competent, informed patients may refuse recommended interventions and choose among reasonable alternatives. If patients cannot give consent in an emergency and if delay of treatment while 17e-1 surrogates are contacted will place their lives or health in peril, treatment can be given without informed consent. People


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InternalMed_Harrison. cannot give consent in an emergency and if delay of treatment while 17e-1 surrogates are contacted will place their lives or health in peril, treatment can be given without informed consent. People are presumed to want such emergency care unless they have previously indicated otherwise.


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InternalMed_Harrison. Respect for patients does not entitle the patients to insist on any care they want. Physicians are not obligated to provide interventions that have no physiologic rationale, that have already failed, or that are contrary to evidence-based practice recommendations, good clinical judgment, or public policies. National policies and laws also dictate certain decisions—e.g., allocating cadaveric organs for transplantation and, in most states, prohibiting physician-assisted suicide.


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InternalMed_Harrison. Physicians should disclose and discuss relevant and accurate information about diagnosis, prognosis, and treatment options. To help patients cope with bad news, doctors can adjust the pace of disclosure, offer empathy and hope, provide emotional support, and call on other resources such as spiritual care or social work. Physicians may be tempted to withhold a serious diagnosis, misrepresent it by using ambiguous terms, or limit discussions of prognosis or risks for fear that certain information will make patients anxious or depressed. Providing honest information about clinical situations preserves patients’ autonomy and trust and promotes sound communication with patients and colleagues. However, patients may choose not to receive such information, asking surrogates to make decisions on their behalf, as is common with serious diagnoses in some traditional cultures.


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InternalMed_Harrison. AVOIDING DECEPTION Health care providers sometimes consider using lies or deception to obtain benefits for patients. Lying refers to statements known to be false and intended to mislead the listener. Deception includes statements and actions intended to mislead the listener, whether or not they are literally true. For example, a physician might sign a disability form for a patient who does not meet disability criteria. Although motivated by a desire to help the patient, such deception is ethically problematic because it undermines physicians’ credibility and trustworthiness.


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InternalMed_Harrison. MAINTAINING CONFIDENTIALITY Maintaining confidentiality is essential in respecting patients’ autonomy and privacy, encourages them to seek treatment and to discuss problems candidly, and prevents discrimination. However, confidentiality may be overridden to prevent serious harm to third parties or to the patient. Exceptions to confidentiality are justified if the risk is serious and probable, if there are no less restrictive measures by which to avert risk, if the adverse effects of overriding confidentiality are minimized, and if these adverse effects are deemed acceptable by society. For example, the law requires physicians to report cases of tuberculosis, sexually transmitted infection, elder or child abuse, and domestic violence.


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InternalMed_Harrison. CARING FOR PATIENTS WHO LACK DECISION-MAKING CAPACITY Some patients are not able to make informed decisions because of unconsciousness, dementia, delirium, or other medical conditions. Although only the courts have the legal authority to determine that a patient is incompetent for making medical decisions, in practice, physicians determine when patients lack the capacity to make health care decisions and arrange for surrogates to make decisions for them, without involving the courts. Patients with decision-making capacity can express a choice and appreciate the medical situation; the nature of the proposed care; the alternatives; and the risks, benefits, and consequences of each alternative. Their choices should be consistent with their values and not the result of delusions or hallucinations. Psychiatrists may help assess decision-making capacity in difficult cases. When impairments are fluctuating or reversible, decisions should be postponed if possible until the patient recovers


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InternalMed_Harrison. Psychiatrists may help assess decision-making capacity in difficult cases. When impairments are fluctuating or reversible, decisions should be postponed if possible until the patient recovers decision-making capacity.


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InternalMed_Harrison. If a patient lacks decision-making capacity, physicians should ask: Who is the appropriate surrogate, and what would the patient want done? Patients may designate someone to serve as their health care proxy or to assume durable power of attorney for health care; such choices should be respected. (See Chap. 10 for further details about advance care planning.) Unless a patient without decision-making capacity has previously designated a health care proxy, physicians usually ask family members to serve as surrogates. Many patients want family members as surrogates, and family members generally have the patient’s best interests at heart. Statutes in most U.S. states delineate a prioritized list of relatives who may serve as surrogates if the patient has not designated a proxy. Surrogates’ decisions should be guided by the patient’s values, goals, and previously expressed preferences. However, it may be appropriate to override previous preferences in favor of the patient’s current best


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InternalMed_Harrison. decisions should be guided by the patient’s values, goals, and previously expressed preferences. However, it may be appropriate to override previous preferences in favor of the patient’s current best interests if an intervention is highly likely to provide a significant benefit, if previous statements do not fit the situation well, or if the patient expressed a desire for the surrogate to have leeway in making decisions.


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InternalMed_Harrison. ACTING IN THE BEST INTERESTS OF PATIENTS Respect for patients is broader than respecting their autonomy to make informed choices about their medical care and promoting shared decision-making. Physicians should also be compassionate and dedicated and should act in the best interests of their patients.


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InternalMed_Harrison. The principle of beneficence requires physicians to act for the patient’s benefit. Patients typically lack medical expertise and may be vulnerable because of their illness. They rely on physicians to provide sound recommendations and to promote their well-being. Physicians encourage such trust and have a fiduciary duty to act in the best interests of the patient, which should prevail over the physicians’ own self-interest or the interests of third parties, such as hospitals or insurers. Physicians’ fiduciary obligations contrast sharply with business relationships, which are characterized by “let the buyer beware,” not by reliance and trust. A related principle, “first do no harm,” forbids physicians to provide ineffective interventions or to act without due care. Although often cited, this precept alone provides only limited guidance because many beneficial interventions pose serious risks. Physicians should prevent unnecessary harm by recommending interventions that maximize benefit


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InternalMed_Harrison. precept alone provides only limited guidance because many beneficial interventions pose serious risks. Physicians should prevent unnecessary harm by recommending interventions that maximize benefit and minimize harm.


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InternalMed_Harrison. MANAGING CONFLICTS BETWEEN RESPECTING PATIENTS AND ACTING IN THEIR BEST INTERESTS Conflicts can arise when patients’ refusal of interventions thwarts their own goals for care or causes them serious harm. For example, if a young woman with asthma refuses mechanical ventilation for reversible respiratory failure, simple acceptance of this decision by the physician, in the name of respecting autonomy, is morally constricted. Physicians should elicit patients’ expectations and concerns, correct their misunderstandings, and try to persuade them to accept beneficial therapies. If disagreements persist after such efforts, patients’ informed choices and views of their own best interests should prevail. While refusing recommended care does not render a patient incompetent, it may lead the physician to probe further to ensure that the patient has the capacity to make informed decisions.


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InternalMed_Harrison. Acting Justly The principle of justice provides guidance to physicians about how to ethically treat patients and to make decisions about allocating important resources, including their own time. Justice in a general sense means fairness: people should receive what they deserve. In addition, it is important to act consistently in cases that are similar in ethically relevant ways. Otherwise, decisions may be arbitrary, biased, and unfair. Justice forbids discrimination in health care based on race, religion, gender, sexual orientation, or other personal characteristics (Chap. 16e).


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InternalMed_Harrison. Justice also requires that limited health care resources be allocated fairly. Universal access to medically needed health care remains an unrealized moral aspiration in the United States and much of the rest of the world. Patients without health insurance often cannot afford health care and lack access to safety-net services. Even among insured patients, insurers may deny coverage for interventions recommended by the physician. In this situation, physicians should advocate for patients and try to help them obtain needed care. Doctors might consider—or patients might request—the use of deception to obtain such benefits. However, avoiding deception is a basic ethical guideline that sets limits on advocating for patients.


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InternalMed_Harrison. Allocation of health care resources is unavoidable because these resources are limited. Ideally, decisions about allocation are made at the level of public policy, with physician input. For example, the United Network for Organ Sharing (www.unos.org) provides criteria for allocating scarce organs. Ad hoc resource allocation at the bedside is problematic because it may be inconsistent, unfair, and ineffective. Physicians have an important role, however, in avoiding unnecessary interventions. Evidence-based lists of tests and procedures that physicians and patients should question and discuss were developed through the recent initiative Choosing Wisely (http://www.choosingwisely.org/). At the bedside, physicians should act as patient advocates within constraints set by society, reasonable insurance coverage, and evidence-based practice. For example, if a patient’s insurer has a higher copayment for nonformulary drugs, it still may be reasonable for physicians to advocate for


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InternalMed_Harrison. insurance coverage, and evidence-based practice. For example, if a patient’s insurer has a higher copayment for nonformulary drugs, it still may be reasonable for physicians to advocate for nonformulary products for good reasons (e.g., when the formulary drugs are ineffective or not tolerated).


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InternalMed_Harrison. Virtue ethics focuses on physicians’ character and qualities, with the expectation that doctors will cultivate such virtues as compassion, dedication, altruism, humility, and integrity. Proponents argue that, if such characteristics become ingrained, they help guide physicians in novel situations. Moreover, merely following ethical precepts or principles without these virtues leads to uncaring doctor–patient relationships.


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InternalMed_Harrison. Professional oaths and codes are useful guides for physicians. Most physicians take oaths at student white-coat ceremonies and at medical school graduation, and many are members of professional societies that have professional codes. Members of the profession pledge to the public and to their patients that they will be guided by the principles and values in these oaths or codes. Oaths and codes focus physicians on ethical ideals rather than on daily pragmatic concerns. However, professional oaths and codes—even the Hippocratic tradition—have been criticized for lack of patient or public input and the limited role given to patients in making decisions.


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InternalMed_Harrison. Personal values, cultural traditions, and religious beliefs are important sources of personal morality that help physicians address ethical issues and cope with the moral distress they may experience in practice. While essential, personal morality is a limited ethical guide in clinical practice. Physicians have role-specific ethical obligations that go beyond their obligations as good people, including the duties to obtain informed consent and maintain confidentiality discussed earlier in this chapter. Furthermore, in a culturally and religiously diverse world, patients and colleagues have personal moral beliefs that commonly differ from their physicians’.


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InternalMed_Harrison. Claims of Conscience Some physicians have conscientious objections to providing or referring patients for certain treatments, such as contraception. While physicians should not be asked to violate deeply held moral beliefs or religious convictions, patients need to receive medically appropriate, timely care. Institutions such as clinics and hospitals have a collective duty to provide care that patients need while making reasonable attempts to accommodate health care workers’ conscientious objections—for example, by arranging for another professional to provide the service in question. Patients seeking a relationship with a doctor or health care institution should be notified in advance of any conscientious objections to the provision of specific interventions. Since patients commonly must select providers for insurance purposes, switching providers when a specific service is needed would be burdensome. There are important limits on claims of conscience. Health care workers may not


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InternalMed_Harrison. select providers for insurance purposes, switching providers when a specific service is needed would be burdensome. There are important limits on claims of conscience. Health care workers may not insist that patients receive unwanted medical interventions and may not refuse to treat patients because of their race, ethnicity, national origin, gender, or religion. Such discrimination is illegal and violates the physician’s duty to respect patients.


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InternalMed_Harrison. Moral Distress Physicians and other health care providers may experience moral distress when they feel they know the ethically correct action to take in a particular situation but are constrained by institutional policies, limited resources, or a position subordinate to the ultimate decision-maker. Moral distress can lead to anger, anxiety, frustration, fatigue, and work dissatisfaction. Discussing complex clinical situations with colleagues and seeking assistance with difficult decisions helps to alleviate moral distress, as does a healthy work environment characterized by open communication and mutual respect.


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InternalMed_Harrison. These various sources of guidance contain precepts that may conflict in a particular case, leaving the physician in a quandary. In a diverse society, different individuals may turn to different sources of moral guidance. In addition, general moral precepts often need to be interpreted and applied in the context of a particular clinical situation. When facing an ethical challenge, physicians should articulate their concerns and reasoning, discuss and listen to the views of others involved in the case, and call on available resources as needed. Through these efforts, physicians can gain deeper insight into the ethical issues they face and often reach mutually acceptable resolutions to complex problems. Recent changes in the organization and delivery of health care have led to new ethical challenges for physicians.


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InternalMed_Harrison. The Accreditation Council for Graduate Medical Education requires medical students and residents to observe work-hour limitations, which are intended to help prevent physician burnout, reduce mistakes, and create a better balance between work and private life. In addition to continuing controversy over their effectiveness, some ethical concerns are raised by work-hour limitations. One concern is that physicians may develop a shift-worker mentality that undermines their dedication to the well-being of patients. Forced handoffs to colleagues may actually increase the risk of errors, and inflexibility can be detrimental. In some cases, trainees could provide an irreplaceable benefit to a patient or family by going beyond work-hour limits, especially if there is rapport with the patient or family that is not easily transferred to another provider. For example, a resident may want to discuss decisions about life-sustaining interventions or to comfort a family member over a patient’s death


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InternalMed_Harrison. that is not easily transferred to another provider. For example, a resident may want to discuss decisions about life-sustaining interventions or to comfort a family member over a patient’s death (Chap. 10). Thus strict adherence to work-hour limits is not always consistent with the ideal of acting for the good of the patient and with compassion. Exceptions to work-hour limits, however, should remain exceptions and should not be allowed to undercut work-hour policies.


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InternalMed_Harrison. Physicians’ roles are changing as care is increasingly provided by multidisciplinary teams. The traditional hierarchy in which the physician is the “captain of the ship” may be inappropriate, particularly in areas such as prevention, disease management and its coordination, and patient education. Physicians should respect team members and acknowledge the expertise of those from other disciplinary backgrounds. Team-based care promises to provide more comprehensive and higher-quality care. However, regular communication and planning are critical to avoid diffusion of responsibility and to ensure that someone is accountable for the completion of patient-care tasks.


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InternalMed_Harrison. The increasing use of evidence-based practice guidelines and benchmarking of performance raises the overall quality of care. However, practice guideline recommendations may be inappropriate for an individual patient, while another option may provide substantially greater benefits. In such situations, physicians’ duty to act in the patient’s best interests should take priority over benefits to society as a whole. Physicians need to understand practice guidelines, to recognize situations in which exceptions might be reasonable, and to be prepared to justify an exception.


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InternalMed_Harrison. With the growing importance of and interest in global health, ods. Typically, physicians gain valuable experience while providing service to patients in need. Such arrangements, however, can raise ethical challenges—for example, because of differences in beliefs 17e-3 about health and illness, expectations regarding health care and the physician’s role, standards of clinical practice, and norms for disclosure of serious diagnoses. Additional dilemmas arise if visiting physicians take on responsibilities beyond their level of training or if donated drugs and equipment are not appropriate to local needs. Visiting physicians and trainees should exercise due diligence in obtaining needed information about the cultural and clinical practices in the host community, should work closely with local professionals and team members, and should be explicit about their skills, knowledge, and limits. In addition, these arrangements can pose risks. The visiting physician may face personal risk from


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InternalMed_Harrison. professionals and team members, and should be explicit about their skills, knowledge, and limits. In addition, these arrangements can pose risks. The visiting physician may face personal risk from infectious disease or motor vehicle accident. The host institution incurs administrative and supervisory costs. Advance preparation for these possibilities minimizes harm, distress, and misunderstanding.


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InternalMed_Harrison. Increasingly, physicians use social and electronic media to share information with patients and other providers. Social networking may be especially useful in reaching young or otherwise hard-toaccess patients. However, the use of social media, including blogs, social networks, and websites, raises ethical challenges and can have harmful consequences if not approached prudently. Injudicious use of social media can pose risks to patient confidentiality, expose patients to intimate details of physicians’ personal lives, cross professional boundaries, and jeopardize therapeutic relationships. Posts may be considered unprofessional and lead to adverse consequences for a provider’s reputation, safety, or even employment, especially if they express frustration or anger over work incidents, disparage patients or colleagues, use offensive or discriminatory language, reveal highly personal information, or picture a physician intoxicated, using illegal drugs, or in sexually suggestive poses.


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InternalMed_Harrison. patients or colleagues, use offensive or discriminatory language, reveal highly personal information, or picture a physician intoxicated, using illegal drugs, or in sexually suggestive poses. Physicians should remember that, in the absence of highly restrictive privacy settings, postings on the Internet in general and on social networking sites in particular are usually permanent and may be accessible to the public, their employers, and their patients. Physicians should separate professional from personal websites, social networking accounts, and blogs and should follow guidelines developed by institutions and professional societies on using social media to communicate with patients.


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InternalMed_Harrison. Acting in patients’ best interests may conflict with the physician’s self-interest or the interests of third parties such as insurers or hospitals. From an ethical viewpoint, patients’ interests should be paramount. Even the appearance of a conflict of interest may undermine trust in the profession. Health care providers may be offered financial incentives to improve the quality or efficiency of care. Such pay-for-performance incentives, however, could lead physicians to avoid sicker patients with more complicated cases or to focus on benchmarked outcomes even when such a focus is not in the best interests of an individual patient. In contrast, fee-for-service payments offer physicians incentives to order more interventions than may be necessary or to refer patients to laboratory or imaging facilities in which they have a financial stake. Regardless of financial incentives, physicians should recommend available care that is in the patient’s best interests—no more and no less.


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InternalMed_Harrison. Financial relationships between physicians and industry are increasingly scrutinized. Gifts from drug and device companies may create an inappropriate risk of undue influence, induce subconscious feelings of reciprocity, impair public trust, and increase the cost of health care. Many academic medical centers have banned drug-company gifts of pens, notepads, and meals to physicians. Under the new Physician Payment Sunshine Act, companies must disclose publicly the names of physicians to whom they have made payments or transferred material goods and the amount of those payments or transfers. The challenge will be to distinguish payments for scientific consulting and research contracts—which are consistent with professional and academic missions and should be encouraged—from those for promotional speaking and consulting whose goal is to increase sales of company products.


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InternalMed_Harrison. Some health care workers, fearing fatal occupational infections, have refused to care for certain patients, such as those with HIV infection or severe acute respiratory syndrome (SARS). Such fears about personal safety need to be acknowledged. Health care institutions should reduce occupational risk by providing proper training, protective equipment, and supervision. To fulfill their mission of helping patients, physicians should provide appropriate care within their clinical expertise, despite some personal risk.


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InternalMed_Harrison. Errors are inevitable in clinical medicine, and some errors cause serious adverse events that harm patients. Most errors are caused by lapses of attention or flaws in the system of delivering health care; only a few result from blameworthy individual behavior (Chaps. 3 and 12e). Physicians and students may fear that disclosing errors will damage their careers. However, patients appreciate being told when an error occurs, receiving an apology, and being informed about efforts to prevent similar errors in the future. Physicians and health care institutions show respect for patients by disclosing errors, offering appropriate compensation for harm done, and using errors as opportunities to improve the quality of care. Overall, patient safety is more likely to be improved through a quality improvement approach to errors rather than a punitive one except in cases of gross incompetence, physician impairment, boundary violations, or repeated violations of standard procedures.


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InternalMed_Harrison. Physicians’ interest in learning, which fosters the long-term goal of benefiting future patients, may conflict with the short-term goal of providing optimal care to current patients. When trainees learn to carry out procedures on patients, they lack the proficiency of experienced physicians, and patients may experience inconvenience, discomfort, longer procedures, or even increased risk. Although patients’ consent for trainee participation in their care is always important, it is particularly important for intimate examinations, such as pelvic, rectal, breast, and testicular examinations, and for invasive procedures. To ensure patients’ cooperation, some care providers introduce students as physicians or do not tell patients that trainees will be performing procedures. Such misrepresentation undermines trust, may lead to more elaborate deception, and makes it difficult for patients to make informed choices about their care. Patients should be told who is providing care and how


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InternalMed_Harrison. undermines trust, may lead to more elaborate deception, and makes it difficult for patients to make informed choices about their care. Patients should be told who is providing care and how trainees are supervised. Most patients, when informed, allow trainees to play an active role in their care.


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InternalMed_Harrison. Physicians may hesitate to intervene when colleagues impaired by alcohol abuse, drug abuse, or psychiatric or medical illness place patients at risk. However, society relies on physicians to regulate themselves. If colleagues of an impaired physician do not take steps to protect patients, no one else may be in a position to do so.


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InternalMed_Harrison. Clinical research is essential to translate scientific discoveries into beneficial tests and therapies for patients. However, clinical research raises ethical concerns because participants face inconvenience and risks in research that is designed not specifically to benefit them but rather to advance scientific knowledge. Ethical guidelines for researchers require them to obtain informed and voluntary consent from participants and approval from an institutional review board, which determines that risks to participants are acceptable and have been minimized and recommends appropriate additional protections when research includes vulnerable participants. Physicians may be involved as clinical research investigators or may be in a position to refer or recommend clinical trial participation to their patients. Physicians should be critical consumers of clinical research results and keep up with advances that change standards of practice. Courses and guidance on the ethics of clinical


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InternalMed_Harrison. to their patients. Physicians should be critical consumers of clinical research results and keep up with advances that change standards of practice. Courses and guidance on the ethics of clinical research are widely available.


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InternalMed_Harrison. Pain: Pathophysiology and Management James P. Rathmell, Howard L. Fields The province of medicine is to preserve and restore health and to relieve suffering. Understanding pain is essential to both of these goals. Because pain is universally understood as a signal of disease, it 18 SEC Tion 1 PAin FIguRE 18-1 Components of a typical cutaneous nerve. There are two distinct functional cat-egories of axons: primary afferents with cell bodies in the dorsal root ganglion, and sympathetic postganglionic fibers with cell bodies in the sympathetic ganglion. Primary afferents include those with large-diameter myelinated (Aβ), small-diameter myelinated (Aδ), and unmyelinated (C) axons. All sympathetic postganglionic fibers are unmyelinated.


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InternalMed_Harrison. CHAPTER 18 Pain: Pathophysiology and Management is the most common symptom that brings a patient to a physician’s attention. The function of the pain sensory system is to protect the body and maintain homeostasis. It does this by detecting, localizing, and identifying potential or actual tissue-damaging processes. Because different diseases produce characteristic patterns of tissue damage, the quality, time course, and location of a patient’s pain lend important diagnostic clues. It is the physician’s responsibility to provide rapid and effective pain relief.


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InternalMed_Harrison. Pain is an unpleasant sensation localized to a part of the body. It is often described in terms of a penetrating or tissue-destructive process (e.g., stabbing, burning, twisting, tearing, squeezing) and/or of a bodily or emotional reaction (e.g., terrifying, nauseating, sickening). Furthermore, any pain of moderate or higher intensity is accompanied by anxiety and the urge to escape or terminate the feeling. These properties illustrate the duality of pain: it is both sensation and emotion. When it is acute, pain is characteristically associated with behavioral arousal and a stress response consisting of increased blood pressure, heart rate, pupil diameter, and plasma cortisol levels. In addition, local muscle contraction (e.g., limb flexion, abdominal wall rigidity) is often present.


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InternalMed_Harrison. PERIPHERAL MECHANISMS The Primary Afferent Nociceptor A peripheral nerve consists of the axons of three different types of neurons: primary sensory afferents, motor neurons, and sympathetic postganglionic neurons (Fig. 18-1). The cell bodies of primary sensory afferents are located in the dorsal root ganglia within the vertebral foramina. The primary afferent axon has two branches: one projects centrally into the spinal cord and the other projects peripherally to innervate tissues. Primary afferents are classified by their diameter, degree of myelination, and conduction velocity. The largest diameter afferent fibers, A-beta (Aβ), respond maximally to light touch and/or moving stimuli; they are present primarily in nerves that innervate the skin. In normal individuals, the activity of these fibers does not produce pain. There are two other classes of primary afferent nerve fibers: the small diameter myelinated A-delta (Aδ) and the unmyelinated (C) axons (Fig. 18-1). These fibers are


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InternalMed_Harrison. fibers does not produce pain. There are two other classes of primary afferent nerve fibers: the small diameter myelinated A-delta (Aδ) and the unmyelinated (C) axons (Fig. 18-1). These fibers are present in nerves to the skin and to deep somatic and visceral structures. Some tissues, such as the cornea, are innervated only by Aδ and C fiber afferents. Most Aδ and C fiber afferents respond maximally only to intense (painful) stimuli and produce the subjective experience of pain when they are electrically stimulated; this defines them as primary afferent nociceptors (pain receptors). The ability to detect painful stimuli is completely abolished when conduction in Aδ and C fiber axons is blocked.


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InternalMed_Harrison. Individual primary afferent nociceptors can respond to several different types of noxious stimuli. For example, most nociceptors respond to heat; intense cold; intense mechanical distortion, such as a pinch; changes in pH, particularly an acidic environment; and application of chemical irritants including adenosine triphosphate (ATP), serotonin, bradykinin, and histamine.


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InternalMed_Harrison. Sensitization When intense, repeated, or prolonged stimuli are applied to damaged or inflamed tissues, the threshold for activating primary afferent nociceptors is lowered, and the frequency of firing is higher for all stimulus intensities. Inflammatory mediators such as bradykinin, nerve-growth factor, some prostaglandins, and leukotrienes contribute to this process, which is called sensitization. Sensitization occurs at the level of the peripheral nerve terminal (peripheral sensitization) as well as at the level of the dorsal horn of the spinal cord (central sensitization). Peripheral sensitization occurs in damaged or inflamed tissues, when inflammatory mediators activate intracellular signal transduction in nociceptors, prompting an increase in the production, transport, and membrane insertion of chemically gated and voltage-gated ion channels. These changes increase the excitability of nociceptor terminals and lower their threshold for activation by mechanical, thermal, and


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InternalMed_Harrison. insertion of chemically gated and voltage-gated ion channels. These changes increase the excitability of nociceptor terminals and lower their threshold for activation by mechanical, thermal, and chemical stimuli. Central sensitization occurs when activity, generated by nociceptors during inflammation, enhances the excitability of nerve cells in the dorsal horn of the spinal cord. Following injury and resultant sensitization, normally innocuous stimuli can produce pain (termed allodynia). Sensitization is a clinically important process that contributes to tenderness, soreness, and hyperalgesia (increased pain intensity in response to the same noxious stimulus; e.g., moderate pressure causes severe pain). A striking example of sensitization is sunburned skin, in which severe pain can be produced by a gentle slap on the back or a warm shower.


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InternalMed_Harrison. Sensitization is of particular importance for pain and tenderness in deep tissues. Viscera are normally relatively insensitive to noxious mechanical and thermal stimuli, although hollow viscera do generate significant discomfort when distended. In contrast, when affected by a disease process with an inflammatory component, deep structures such as joints or hollow viscera characteristically become exquisitely sensitive to mechanical stimulation.


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InternalMed_Harrison. A large proportion of Aδ and C fiber afferents innervating viscera are completely insensitive in normal noninjured, noninflamed tissue. That is, they cannot be activated by known mechanical or thermal stimuli and are not spontaneously active. However, in the presence of inflammatory mediators, these afferents become sensitive to mechanical stimuli. Such afferents have been termed silent nociceptors, and their characteristic properties may explain how, under pathologic conditions, the relatively insensitive deep structures can become the source of severe and debilitating pain and tenderness. Low pH, prostaglandins, leukotrienes, and other inflammatory mediators such as bradykinin play a significant role in sensitization.


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InternalMed_Harrison. Nociceptor-Induced Inflammation Primary afferent nociceptors also have a neuroeffector function. Most nociceptors contain polypeptide mediators that are released from their peripheral terminals when they are activated (Fig. 18-2). An example is substance P, an 11-amino-acid peptide. Substance P is released from primary afferent nociceptors and has multiple biologic activities. It is a potent vasodilator, degranulates mast cells, is a chemoattractant for leukocytes, and increases the production and release of inflammatory mediators. Interestingly, depletion of substance P from joints reduces the severity of experimental arthritis. Primary afferent nociceptors are not simply passive messengers of threats to tissue injury but also play an active role in tissue protection through these neuroeffector functions.


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InternalMed_Harrison. CENTRAL MECHANISMS The Spinal Cord and Referred Pain The axons of primary afferent nociceptors enter the spinal cord via the dorsal root. They terminate in the dorsal horn of the spinal gray matter (Fig. 18-3). The terminals of primary afferent axons contact spinal neurons that transmit the pain signal to brain sites involved in pain perception. When primary afferents are activated by noxious stimuli, they release neurotransmitters from their terminals that excite the spinal cord neurons. The major neurotransmitter released is glutamate, which rapidly excites dorsal horn neurons. Primary afferent nociceptor terminals also release peptides, including substance P and calcitonin gene-related peptide, which produce a slower and longer-lasting excitation of the dorsal horn neurons. The axon of each primary afferent contacts many spinal neurons, and each spinal neuron receives convergent inputs from many primary afferents.


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InternalMed_Harrison. The convergence of sensory inputs to a single spinal pain-transmission neuron is of great importance because it underlies the phenomenon of referred pain. All spinal neurons that receive input from the viscera and deep musculoskeletal structures also receive input from the skin. The convergence patterns are determined by the spinal segment of the dorsal root ganglion that supplies the afferent innervation of a structure. For example, the afferents that supply the central diaphragm are derived from the third and fourth cervical dorsal root ganglia. Primary afferents with cell bodies in these same ganglia supply the skin of the shoulder and lower neck. Thus, sensory inputs from both the shoulder skin and the central diaphragm converge on pain-transmission neurons in the third and fourth cervical spinal segments.


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InternalMed_Harrison. Because of this convergence and the fact that the spinal neurons are most often activated by inputs from the skin, activity evoked in spinal neurons by input from deep structures is mislocalized by the patient to a place that roughly corresponds with the region of skin innervated by the same spinal segment. Thus, inflammation near the central diaphragm is often reported as shoulder discomfort. This spatial displacement of pain sensation from the site of the injury that produces it is known as referred pain. PART 2 Cardinal Manifestations and Presentation of Diseases


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InternalMed_Harrison. PART 2 Cardinal Manifestations and Presentation of Diseases FIguRE 18-2 Events leading to activation, sensitization, and spread of sensitization of primary afferent nociceptor terminals. A. Direct activation by intense pressure and consequent cell damage. Cell damage induces lower pH (H+) and leads to release of potassium (K+) and to synthesis of prostaglandins (PG) and bradykinin (BK). Prostaglandins increase the sensitivity of the terminal to bradykinin and other pain-producing substances. B. Secondary activation. Impulses generated in the stimulated terminal propagate not only to the spinal cord but also into other terminal branches where they induce the release of peptides, including substance P (SP). Substance P causes vasodilation and neurogenic edema with further accumulation of bradykinin (BK). Substance P also causes the release of histamine (H) from mast cells and serotonin (5HT) from platelets.


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InternalMed_Harrison. Ascending Pathways for Pain A majority of spinal neurons contacted by primary afferent nociceptors send their axons to the contralateral thalamus. These axons form the contralateral spinothalamic tract, which lies in the anterolateral white matter of the spinal cord, the lateral edge of the medulla, and the lateral pons and midbrain. The spinothalamic pathway is crucial for pain sensation in humans. Interruption of this pathway produces permanent deficits in pain and temperature discrimination. Spinothalamic tract axons ascend to several regions of the thalamus. There is tremendous divergence of the pain signal from these thalamic sites to several distinct areas of the cerebral cortex that subserve different aspects of the pain experience (Fig. 18-4). One of the thalamic projections is to the somatosensory cortex. This projection mediates the purely sensory aspects of pain, i.e., its location, intensity, and quality. Other thalamic neurons project to cortical regions that are linked


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InternalMed_Harrison. FIguRE 18-3 The convergence-projection hypothesis of referred pain. According to this hypothesis, visceral afferent nociceptors converge on the same pain-projection neurons as the afferents from the somatic structures in which the pain is perceived. The brain has no way of knowing the actual source of input and mistakenly “projects” the sensation to the somatic structure. to emotional responses, such as the cingulate gyrus and other areas of the frontal lobes, including the insular cortex. These pathways to the frontal cortex subserve the affective or unpleasant emotional dimension of pain. This affective dimension of pain produces suffering and exerts potent control of behavior. Because of this dimension, fear is FIguRE 18-4 Pain transmission and modulatory pathways.


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InternalMed_Harrison. FIguRE 18-4 Pain transmission and modulatory pathways. A. Transmission system for nociceptive messages. Noxious stimuli activate the sensitive peripheral ending of the primary afferent nociceptor by the process of transduction. The message is then transmitted over the peripheral nerve to the spinal cord, where it synapses with cells of origin of the major ascending pain pathway, the spinothalamic tract. The message is relayed in the thalamus to the anterior cingulate (C), frontal insular (F), and somatosensory cortex (SS). B. Pain-modulation network. Inputs from frontal cortex and hypothalamus activate cells in the midbrain that control spinal pain-transmission cells via cells in the medulla. a constant companion of pain. As a consequence, injury or surgical lesions to areas of the frontal cortex activated by painful stimuli can diminish the emotional impact of pain while largely preserving the individual’s ability to recognize noxious stimuli as painful.


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InternalMed_Harrison. The pain produced by injuries of similar magnitude is remarkably variable in different situations and in different individuals. For example, athletes have been known to sustain serious fractures with only minor pain, and Beecher’s classic World War II survey revealed that many soldiers in battle were unbothered by injuries that would have produced agonizing pain in civilian patients. Furthermore, even the suggestion that a treatment will relieve pain can have a significant analgesic effect (the placebo effect). On the other hand, many patients find even minor injuries (such as venipuncture) frightening and unbearable, and the expectation of pain can induce pain even without a noxious stimulus. The suggestion that pain will worsen following administration of an inert substance can increase its perceived intensity (the nocebo effect).


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InternalMed_Harrison. The powerful effect of expectation and other psychological variables on the perceived intensity of pain is explained by brain circuits that modulate the activity of the pain-transmission pathways. One of these circuits has links to the hypothalamus, midbrain, and medulla, and it selectively controls spinal pain-transmission neurons through a descending pathway (Fig. 18-4). Human brain–imaging studies have implicated this painmodulating circuit in the pain-relieving effect of attention, suggestion, and opioid analgesic medications (Fig. 18-5). Furthermore, each of the component structures of the pathway contains opioid receptors and is sensitive to the direct application of opioid drugs. In animals, lesions of this descending modulatory system reduce the analgesic effect of systemically administered opioids such as morphine. Along with the opioid receptor, the component nuclei of this pain-modulating circuit contain endogenous opioid peptides such as the enkephalins and β-endorphin.


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InternalMed_Harrison. The most reliable way to activate this endogenous opioid-mediated modulating system is by suggestion of pain relief or by intense emotion directed away from the pain-causing injury (e.g., during severe threat or an athletic competition). In fact, pain-relieving endogenous opioids are released following surgical procedures and in patients given a placebo for pain relief.


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InternalMed_Harrison. Pain-modulating circuits can enhance as well as suppress pain. Both pain-inhibiting and pain-facilitating neurons in the medulla project to and control spinal pain-transmission neurons. Because pain-transmission neurons can be activated by modulatory neurons, it is theoretically possible to generate a pain signal with no peripheral noxious stimulus. In fact, human functional imaging studies have demonstrated increased activity in this circuit during migraine headaches. A central circuit that facilitates pain could account for the finding that pain can be induced by suggestion or enhanced by expectation and provides a framework for understanding how psychological factors can contribute to chronic pain.


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InternalMed_Harrison. Lesions of the peripheral or central nociceptive pathways typically result in a loss or impairment of pain sensation. Paradoxically, damage to or dysfunction of these pathways can also produce pain. For example, damage to peripheral nerves, as occurs in diabetic neuropathy, or to primary afferents, as in herpes zoster infection, can result in pain that is referred to the body region innervated by the damaged nerves. Pain may also be produced by damage to the central nervous system (CNS), for example, in some patients following trauma or vascular injury to the spinal cord, brainstem, or thalamic areas that contain central nociceptive pathways. Such neuropathic pains are often severe and are typically resistant to standard treatments for pain.


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InternalMed_Harrison. Neuropathic pain typically has an unusual burning, tingling, or electric shock–like quality and may be triggered by very light touch. These features are rare in other types of pain. On examination, a sensory deficit is characteristically present in the area of the patient’s pain. Hyperpathia, a greatly exaggerated pain sensation to innocuous CHAPTER 18 Pain: Pathophysiology and Management


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InternalMed_Harrison. FIguRE 18-5 Functional magnetic resonance imaging (fMRI) demonstrates placebo-enhanced brain activity in anatomic regions correlating with the opioidergic descending pain control system. Top panel: Frontal fMRI image shows placebo-enhanced brain activity in the dorsal lateral prefrontal cortex (DLPFC). Bottom panel: Sagittal fMRI images show placebo-enhanced responses in the rostral anterior cingulate cortex (rACC), the rostral ventral medullae (RVM), the periaqueductal gray (PAG) area, and the hypothalamus. The placebo-enhanced activity in all areas was reduced by naloxone, demonstrating the link between the descending opioidergic system and the placebo analgesic response. (Adapted with permission from F Eippert et al: Neuron 63:533, 2009.) or mild nociceptive stimuli, is also characteristic of neuropathic pain; patients often complain that the very lightest moving stimulus evokes exquisite pain (allodynia). In this regard, it is of clinical interest that a topical preparation of 5%


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InternalMed_Harrison. of neuropathic pain; patients often complain that the very lightest moving stimulus evokes exquisite pain (allodynia). In this regard, it is of clinical interest that a topical preparation of 5% lidocaine in patch form is effective for patients with postherpetic neuralgia who have prominent allodynia.


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InternalMed_Harrison. A variety of mechanisms contribute to neuropathic pain. As with sensitized primary afferent nociceptors, damaged primary afferents, including nociceptors, become highly sensitive to mechanical stimulation and may generate impulses in the absence of stimulation. Increased sensitivity and spontaneous activity are due, in part, to an increased concentration of sodium channels in the damaged nerve fiber. Damaged primary afferents may also develop sensitivity to nor-epinephrine. Interestingly, spinal cord pain-transmission neurons cut off from their normal input may also become spontaneously active. PART 2 Cardinal Manifestations and Presentation of Diseases Thus, both CNS and peripheral nervous system hyperactivity contribute to neuropathic pain.


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InternalMed_Harrison. Sympathetically Maintained Pain Patients with peripheral nerve injury occasionally develop spontaneous pain in the region innervated by the nerve. This pain is often described as having a burning quality. The pain typically begins after a delay of hours to days or even weeks and is accompanied by swelling of the extremity, periarticular bone loss, and arthritic changes in the distal joints. The pain may be relieved by a local anesthetic block of the sympathetic innervation to the affected extremity. Damaged primary afferent nociceptors acquire adrenergic sensitivity and can be activated by stimulation of the sympathetic outflow. This constellation of spontaneous pain and signs of sympathetic dysfunction following injury has been termed complex regional pain syndrome (CRPS). When this occurs after an identifiable nerve injury, it is termed CRPS type II (also known as posttraumatic neuralgia or, if severe, causalgia). When a similar clinical picture appears without obvious nerve injury,


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InternalMed_Harrison. after an identifiable nerve injury, it is termed CRPS type II (also known as posttraumatic neuralgia or, if severe, causalgia). When a similar clinical picture appears without obvious nerve injury, it is termed CRPS type I (also known as reflex sympathetic dystrophy). CRPS can be produced by a variety of injuries, including fractures of bone, soft tissue trauma, myocardial infarction, and stroke (Chap. 446). CRPS type I typically resolves with symptomatic treatment; however, when it persists, detailed examination often reveals evidence of peripheral nerve injury. Although the pathophysiology of CRPS is poorly understood, the pain and the signs of inflammation, when acute, can be rapidly relieved by blocking the sympathetic nervous system. This implies that sympathetic activity can activate undamaged nociceptors when inflammation is present. Signs of sympathetic hyperactivity should be sought in patients with post-traumatic pain and inflammation and no other obvious explanation.


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InternalMed_Harrison. The ideal treatment for any pain is to remove the cause; thus, while treatment can be initiated immediately, efforts to establish the underlying etiology should always proceed as treatment begins. Sometimes, treating the underlying condition does not immediately relieve pain. Furthermore, some conditions are so painful that rapid and effective analgesia is essential (e.g., the postoperative state, burns, trauma, cancer, or sickle cell crisis). Analgesic medications are a first line of treatment in these cases, and all practitioners should be familiar with their use. ASPIRIN, ACETAMINOPHEN, AND NONSTEROIDAL ANTI-INFLAMMATORY AgENTS (NSAIDs)


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InternalMed_Harrison. ASPIRIN, ACETAMINOPHEN, AND NONSTEROIDAL ANTI-INFLAMMATORY AgENTS (NSAIDs) These drugs are considered together because they are used for similar problems and may have a similar mechanism of action (Table 18-1). All these compounds inhibit cyclooxygenase (COX), and, except for acetaminophen, all have anti-inflammatory actions, especially at higher dosages. They are particularly effective for mild to moderate headache and for pain of musculoskeletal origin.


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InternalMed_Harrison. Because they are effective for these common types of pain and are available without prescription, COX inhibitors are by far the most commonly used analgesics. They are absorbed well from the gastrointestinal tract and, with occasional use, have only minimal side effects. With chronic use, gastric irritation is a common side effect of aspirin and NSAIDs and is the problem that most frequently limits the dose that can be given. Gastric irritation is most severe with aspirin, which may cause erosion and ulceration of the gastric mucosa leading to bleeding or perforation. Because aspirin irreversibly acetylates platelet cyclooxygenase and thereby interferes with coagulation of the blood, gastrointestinal bleeding is a particular risk. Older age and history of gastrointestinal disease increase the risks of aspirin and NSAIDs. In addition to the well-known gastrointestinal toxicity of NSAIDs, nephrotoxicity is a significant problem for patients using these drugs on a chronic basis. Patients


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InternalMed_Harrison. the risks of aspirin and NSAIDs. In addition to the well-known gastrointestinal toxicity of NSAIDs, nephrotoxicity is a significant problem for patients using these drugs on a chronic basis. Patients at risk for renal insufficiency, particularly those with significant contraction of their intravascular volume as occurs with chronic diuretic use or


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InternalMed_Harrison. Generic Name Dose, mg Interval Comments Nonnarcotic analgesics: usual doses and intervals Codeine 30–60 q4h 30–60 q4h Nausea common Oxycodone — 5–10 q4–6h Usually available with acetaminophen or aspirin Morphine 5 q4h 30 q4h Morphine sustained — 15–60 bid to tid Oral slow-release preparation release Hydromorphone 1–2 q4h 2–4 q4h Shorter acting than morphine sulfate Levorphanol 2 q6–8h 4 q6–8h Longer acting than morphine sulfate; absorbed well PO Methadone 5–10 q6–8h 5–20 q6–8h Delayed sedation due to long half-life; therapy should not be initiated with >40 mg/d, and dose escalation should be made no more frequently than every 3 days Meperidine 50–100 q3–4h 300 q4h Poorly absorbed PO; normeperidine is a toxic metabolite; routine use of this agent is 7-day transdermal patch Buprenorphine 0.3 q6–8h CHAPTER 18 Pain: Pathophysiology and Management Anticholinergic Orthostatic Cardiac Ave. Dose, Generic Name 5-HT NE Sedative Potency Potency Hypotension Arrhythmia mg/d Range, mg/d