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In the best interests of the patient. In accordance with the patient’s wishes. Preserving patient autonomy. These concepts are at the core of modern medical decision-making.
Traditionally medical decisions are made by hospitalists and communicated to patients. This approach has shifted to an emphasis on patient autonomy and input in decision-making.
But what about the patient unable to make decisions or provide input to the medical caregivers? How can the comatose or incompetent patient participate in his or her own care decisions? What happens when half of a team is no longer able to share team functions?
In these instances, hospitalists rely on surrogates. A surrogate is empowered not only to speak for but also to make legal decisions for a patient. The relationship becomes a triad of hospitalist, surrogate, and patient. This triad must include:
- A hospitalist who brings the same degree of trust, respect, and open communication to the new relationship;
- A surrogate who is an active participant rather than a passive spokesperson; and
- A patient whose interests are the primary goal.
Key Issues
The aging of the population and the increased prevalence of medical conditions causing cognitive impairment point up the need to take a closer look at the hospitalist-surrogate relationship. A study this year outlined four key issues:
- There are unique challenges for both parties in creating a hospitalist-surrogate relationship;
- The hospitalist and surrogate are dealing not only with each other but also with the decision-making role each will play in regard to the patient;
- The surrogate must understand that serving as a surrogate for a loved one is completely different from making decisions for oneself; and
- There may be more than one surrogate decision maker.1
The first challenge facing hospitalist and surrogate is establishing a foundation of trust, respect, and a treatment plan. Their perspectives play a critical role: The surrogate knows the patient as a lively, engaged, and interesting individual, while the hospitalist has seen the patient only in a nonresponsive, incapacitated state. Opening an immediate line of communication is the best way to assume their respective responsibilities.
Second, even after the hospitalist and surrogate develop an initial working relationship, they may still need to outline mutually satisfying ways to share decision-making with the patient. Both must balance their concern for the patient, their understanding of the patient’s status, and their perspectives of what the patient would want. With time pressures and the capabilities of modern technology, this mutual decision-making responsibility may seem daunting.
Third, surrogates may discover a conflict between their personal values and their patient’s. They may have to make a decision that reflects their patient’s wishes yet contradicts their own beliefs. Sometimes hospitalists can help the surrogate resolve this dilemma by suggesting consultations with other family members or professionals.
The fourth issue, multiple surrogates, may magnify the challenges but can also be an advantage. In most cases families, even those with members who have differing belief systems, tend to support each other during crises to reach a consensus in the patient’s best interests.
Tom Baudendistel, MD, a hospitalist at California Pacific Medical Center in San Francisco, says that although engaging in a dialogue with the multiple surrogates may reveal a family conflict, mistrust, or other issues, the problem is usually resolved. “One surrogate comes around after we make sure the one disagreeing sees in person what the patient is going through, the low quality of life,” says Dr. Baudendistel.
Howard Epstein, MD, medical director, Care Management and Palliative Care, Regions Hospital, St. Paul, Minn., suggests a different approach. “We ask the surrogate to imagine that if the patient could stand outside his or her body, hearing everything that is being said, what would he or she say?” says Dr. Epstein.
The Process
While these issues affect all hospitalists who work with surrogates, hospitalists often encounter additional circumstances that require special attention. These are not always problems but may be situations unique to the hospital setting or the hospitalist’s job.
The hospitalist’s first contact with a patient is often the patient’s admission to the hospital. The hospitalist is most often starting with a blank page with no background information. Gathering information quickly about an unknown patient is critical.
This duty often falls to hospitalists. Donald Krause, MD, medical director for quality assurance at St. Joseph Hospital in Bangor, Maine, and a hospitalist for 11 years, points out that “hospitalists take care of 90% of medical admissions and as part of this job arrange for surrogates if needed as well as anything else to help the patient.”
Beginning with the admission of a patient, the hospitalist may take on the responsibility of finding a surrogate.
Find a surrogate: When a patient is admitted, the hospitalist questions everyone connected to the patient about the existence of a surrogate or family spokesperson. If there is no information available, many hospitalists turn to other staff experts, such as social workers or chaplains, to seek people who know the patient.
Dr. Baudendistel says his medical center resuscitates “unbefriended” patients admitted to the emergency department to allow time to find a family member or surrogate. “Social workers then search the Internet, call shelters, and contact other hospitals and institutions to learn anything they can about the patient,” he says. If the search is unsuccessful, the hospitalist usually consults the institution’s ethics committee for additional suggestions.
Don C. Postema, PhD, ethics consultant for Regions Hospital, chair of the HealthPartners Ethics Committee, and ethicist-in-residence at Gillette Children’s Specialty HealthCare in St. Paul, Minn., proposes that an ethics committee look beyond the standard candidates in searching for a surrogate. “The legal relationship of a potential surrogate to the patient is secondary to what I consider to be the primary relationship, that is, the person who knows the patient best,” says Dr. Postema. “It could be the patient’s landlord or a neighbor who sees the patient on a regular basis.”
What about the patient whose family lives too far away to see the patient on a regular basis? Look into hiring a local geriatric case manager, Dr. Epstein advises.
There is one person who should not serve as a patient’s surrogate: the attending physician, whether a hospitalist or the primary caregiver. Erin Egan, MD, JD, assistant professor of hospital medicine, University of Colorado Hospitals, warns that a hospitalist acting as a surrogate has a conflict of interest. “Most states prohibit hospitalists from acting as surrogates,” Dr. Egan warns. “In some cases a doctor can presume consent for a short time before a surrogate is appointed in order to make an immediate medical decision. As a general rule, however, a clinician should never assume the surrogate’s role.”
Look for advance directives: Ideally, every patient’s file would contain an advance directive indicating a surrogate or a note that there is no surrogate.2 In addition, there should be a healthcare advance directive, also known as a healthcare power of attorney, that appoints a surrogate. It is often accompanied by a living will, an instruction sheet stipulating what treatment the patient wants if he or she is unable to speak or communicate. Unfortunately, many hospitalists cannot find these documents when they admit a patient.
In this case, the hospitalist must search. Most hospitals, nursing homes, or home healthcare agencies are required by the federal Patient Self-Determination Act (PSDA) to offer information about advance directives at the time of admission. This information states the patient’s healthcare decision-making rights under state law and the institution’s policy about adhering to advance directives. Contacting these agencies is a starting point.
Make difficult decisions: While some advance directives carry legal power, they often are not helpful to hospitalists or surrogates making end-of-life decisions. Because a medical crisis cannot always be predicted and treatment options change rapidly, a specific directive may not be as helpful as a written description of a patient’s beliefs, religious convictions, and cultural values. Equally valuable are notes about conversations among patients, family members, friends, and caregivers.3 This creates a picture of the patient’s feelings about quality of life, treatment preferences, and end-of-life outcomes.
The hospitalist’s role in this situation is to facilitate such discussions among all family and friends involved. The goal is to develop an accurate picture of the patient to make appropriate decisions. The hospitalist should explore the cultural values and religious beliefs of the patient, surrogate, family, and friends. “Different ethnic groups view medical care differently,” says Richard L. Heinrich, MD, medical director of Hospice of the Lakes, Bloomington, Minn. “Some religions believe that suffering in this life is rewarded in the next life, which makes a difference when making treatment decisions,” he says. “We must honor and work with cultural values unless in our view the individual is suffering needlessly.”
The hospitalist should be alert to the need for an interpreter and anything else that will promote a meaningful discussion. And, the hospitalist and the medical staff should be prepared to share as much medical information as is possible, including individual staff opinions, the rationale behind recommendations, and the pros and cons of each suggestion. The surrogate and family cannot make any meaningful contribution without all the pertinent information.
The goal should be a consensus about the patient’s best interests, how certain medical decisions will provide benefit or burden to the patient, and if the decision is what the patient would want. It’s especially critical to call a family conference to allow everyone the opportunity to discuss the patient’s concept of his or her death.
“Most people are afraid of getting caught in an end-of-life situation where they lose control,” says Dr. Postema. TH
Ann Kepler is a medical writer based in Chicago.
References
- Torke AM, Alexander GC, Lantos J, et al. The physician-surrogate relationship. Arch Intern Med. 2007 Jun 11;167(11):1117-1121.
- Wenger NS, Rosenfeld K. Quality indicators for end-of-life care in vulnerable elders. Ann Intern Med. 2001 Oct 16;135(8):677-685.
- Bloche MG. Managing conflict at the end of life. N Engl J Med. 2005 Jun 9;352:2371-2373.
In the best interests of the patient. In accordance with the patient’s wishes. Preserving patient autonomy. These concepts are at the core of modern medical decision-making.
Traditionally medical decisions are made by hospitalists and communicated to patients. This approach has shifted to an emphasis on patient autonomy and input in decision-making.
But what about the patient unable to make decisions or provide input to the medical caregivers? How can the comatose or incompetent patient participate in his or her own care decisions? What happens when half of a team is no longer able to share team functions?
In these instances, hospitalists rely on surrogates. A surrogate is empowered not only to speak for but also to make legal decisions for a patient. The relationship becomes a triad of hospitalist, surrogate, and patient. This triad must include:
- A hospitalist who brings the same degree of trust, respect, and open communication to the new relationship;
- A surrogate who is an active participant rather than a passive spokesperson; and
- A patient whose interests are the primary goal.
Key Issues
The aging of the population and the increased prevalence of medical conditions causing cognitive impairment point up the need to take a closer look at the hospitalist-surrogate relationship. A study this year outlined four key issues:
- There are unique challenges for both parties in creating a hospitalist-surrogate relationship;
- The hospitalist and surrogate are dealing not only with each other but also with the decision-making role each will play in regard to the patient;
- The surrogate must understand that serving as a surrogate for a loved one is completely different from making decisions for oneself; and
- There may be more than one surrogate decision maker.1
The first challenge facing hospitalist and surrogate is establishing a foundation of trust, respect, and a treatment plan. Their perspectives play a critical role: The surrogate knows the patient as a lively, engaged, and interesting individual, while the hospitalist has seen the patient only in a nonresponsive, incapacitated state. Opening an immediate line of communication is the best way to assume their respective responsibilities.
Second, even after the hospitalist and surrogate develop an initial working relationship, they may still need to outline mutually satisfying ways to share decision-making with the patient. Both must balance their concern for the patient, their understanding of the patient’s status, and their perspectives of what the patient would want. With time pressures and the capabilities of modern technology, this mutual decision-making responsibility may seem daunting.
Third, surrogates may discover a conflict between their personal values and their patient’s. They may have to make a decision that reflects their patient’s wishes yet contradicts their own beliefs. Sometimes hospitalists can help the surrogate resolve this dilemma by suggesting consultations with other family members or professionals.
The fourth issue, multiple surrogates, may magnify the challenges but can also be an advantage. In most cases families, even those with members who have differing belief systems, tend to support each other during crises to reach a consensus in the patient’s best interests.
Tom Baudendistel, MD, a hospitalist at California Pacific Medical Center in San Francisco, says that although engaging in a dialogue with the multiple surrogates may reveal a family conflict, mistrust, or other issues, the problem is usually resolved. “One surrogate comes around after we make sure the one disagreeing sees in person what the patient is going through, the low quality of life,” says Dr. Baudendistel.
Howard Epstein, MD, medical director, Care Management and Palliative Care, Regions Hospital, St. Paul, Minn., suggests a different approach. “We ask the surrogate to imagine that if the patient could stand outside his or her body, hearing everything that is being said, what would he or she say?” says Dr. Epstein.
The Process
While these issues affect all hospitalists who work with surrogates, hospitalists often encounter additional circumstances that require special attention. These are not always problems but may be situations unique to the hospital setting or the hospitalist’s job.
The hospitalist’s first contact with a patient is often the patient’s admission to the hospital. The hospitalist is most often starting with a blank page with no background information. Gathering information quickly about an unknown patient is critical.
This duty often falls to hospitalists. Donald Krause, MD, medical director for quality assurance at St. Joseph Hospital in Bangor, Maine, and a hospitalist for 11 years, points out that “hospitalists take care of 90% of medical admissions and as part of this job arrange for surrogates if needed as well as anything else to help the patient.”
Beginning with the admission of a patient, the hospitalist may take on the responsibility of finding a surrogate.
Find a surrogate: When a patient is admitted, the hospitalist questions everyone connected to the patient about the existence of a surrogate or family spokesperson. If there is no information available, many hospitalists turn to other staff experts, such as social workers or chaplains, to seek people who know the patient.
Dr. Baudendistel says his medical center resuscitates “unbefriended” patients admitted to the emergency department to allow time to find a family member or surrogate. “Social workers then search the Internet, call shelters, and contact other hospitals and institutions to learn anything they can about the patient,” he says. If the search is unsuccessful, the hospitalist usually consults the institution’s ethics committee for additional suggestions.
Don C. Postema, PhD, ethics consultant for Regions Hospital, chair of the HealthPartners Ethics Committee, and ethicist-in-residence at Gillette Children’s Specialty HealthCare in St. Paul, Minn., proposes that an ethics committee look beyond the standard candidates in searching for a surrogate. “The legal relationship of a potential surrogate to the patient is secondary to what I consider to be the primary relationship, that is, the person who knows the patient best,” says Dr. Postema. “It could be the patient’s landlord or a neighbor who sees the patient on a regular basis.”
What about the patient whose family lives too far away to see the patient on a regular basis? Look into hiring a local geriatric case manager, Dr. Epstein advises.
There is one person who should not serve as a patient’s surrogate: the attending physician, whether a hospitalist or the primary caregiver. Erin Egan, MD, JD, assistant professor of hospital medicine, University of Colorado Hospitals, warns that a hospitalist acting as a surrogate has a conflict of interest. “Most states prohibit hospitalists from acting as surrogates,” Dr. Egan warns. “In some cases a doctor can presume consent for a short time before a surrogate is appointed in order to make an immediate medical decision. As a general rule, however, a clinician should never assume the surrogate’s role.”
Look for advance directives: Ideally, every patient’s file would contain an advance directive indicating a surrogate or a note that there is no surrogate.2 In addition, there should be a healthcare advance directive, also known as a healthcare power of attorney, that appoints a surrogate. It is often accompanied by a living will, an instruction sheet stipulating what treatment the patient wants if he or she is unable to speak or communicate. Unfortunately, many hospitalists cannot find these documents when they admit a patient.
In this case, the hospitalist must search. Most hospitals, nursing homes, or home healthcare agencies are required by the federal Patient Self-Determination Act (PSDA) to offer information about advance directives at the time of admission. This information states the patient’s healthcare decision-making rights under state law and the institution’s policy about adhering to advance directives. Contacting these agencies is a starting point.
Make difficult decisions: While some advance directives carry legal power, they often are not helpful to hospitalists or surrogates making end-of-life decisions. Because a medical crisis cannot always be predicted and treatment options change rapidly, a specific directive may not be as helpful as a written description of a patient’s beliefs, religious convictions, and cultural values. Equally valuable are notes about conversations among patients, family members, friends, and caregivers.3 This creates a picture of the patient’s feelings about quality of life, treatment preferences, and end-of-life outcomes.
The hospitalist’s role in this situation is to facilitate such discussions among all family and friends involved. The goal is to develop an accurate picture of the patient to make appropriate decisions. The hospitalist should explore the cultural values and religious beliefs of the patient, surrogate, family, and friends. “Different ethnic groups view medical care differently,” says Richard L. Heinrich, MD, medical director of Hospice of the Lakes, Bloomington, Minn. “Some religions believe that suffering in this life is rewarded in the next life, which makes a difference when making treatment decisions,” he says. “We must honor and work with cultural values unless in our view the individual is suffering needlessly.”
The hospitalist should be alert to the need for an interpreter and anything else that will promote a meaningful discussion. And, the hospitalist and the medical staff should be prepared to share as much medical information as is possible, including individual staff opinions, the rationale behind recommendations, and the pros and cons of each suggestion. The surrogate and family cannot make any meaningful contribution without all the pertinent information.
The goal should be a consensus about the patient’s best interests, how certain medical decisions will provide benefit or burden to the patient, and if the decision is what the patient would want. It’s especially critical to call a family conference to allow everyone the opportunity to discuss the patient’s concept of his or her death.
“Most people are afraid of getting caught in an end-of-life situation where they lose control,” says Dr. Postema. TH
Ann Kepler is a medical writer based in Chicago.
References
- Torke AM, Alexander GC, Lantos J, et al. The physician-surrogate relationship. Arch Intern Med. 2007 Jun 11;167(11):1117-1121.
- Wenger NS, Rosenfeld K. Quality indicators for end-of-life care in vulnerable elders. Ann Intern Med. 2001 Oct 16;135(8):677-685.
- Bloche MG. Managing conflict at the end of life. N Engl J Med. 2005 Jun 9;352:2371-2373.
In the best interests of the patient. In accordance with the patient’s wishes. Preserving patient autonomy. These concepts are at the core of modern medical decision-making.
Traditionally medical decisions are made by hospitalists and communicated to patients. This approach has shifted to an emphasis on patient autonomy and input in decision-making.
But what about the patient unable to make decisions or provide input to the medical caregivers? How can the comatose or incompetent patient participate in his or her own care decisions? What happens when half of a team is no longer able to share team functions?
In these instances, hospitalists rely on surrogates. A surrogate is empowered not only to speak for but also to make legal decisions for a patient. The relationship becomes a triad of hospitalist, surrogate, and patient. This triad must include:
- A hospitalist who brings the same degree of trust, respect, and open communication to the new relationship;
- A surrogate who is an active participant rather than a passive spokesperson; and
- A patient whose interests are the primary goal.
Key Issues
The aging of the population and the increased prevalence of medical conditions causing cognitive impairment point up the need to take a closer look at the hospitalist-surrogate relationship. A study this year outlined four key issues:
- There are unique challenges for both parties in creating a hospitalist-surrogate relationship;
- The hospitalist and surrogate are dealing not only with each other but also with the decision-making role each will play in regard to the patient;
- The surrogate must understand that serving as a surrogate for a loved one is completely different from making decisions for oneself; and
- There may be more than one surrogate decision maker.1
The first challenge facing hospitalist and surrogate is establishing a foundation of trust, respect, and a treatment plan. Their perspectives play a critical role: The surrogate knows the patient as a lively, engaged, and interesting individual, while the hospitalist has seen the patient only in a nonresponsive, incapacitated state. Opening an immediate line of communication is the best way to assume their respective responsibilities.
Second, even after the hospitalist and surrogate develop an initial working relationship, they may still need to outline mutually satisfying ways to share decision-making with the patient. Both must balance their concern for the patient, their understanding of the patient’s status, and their perspectives of what the patient would want. With time pressures and the capabilities of modern technology, this mutual decision-making responsibility may seem daunting.
Third, surrogates may discover a conflict between their personal values and their patient’s. They may have to make a decision that reflects their patient’s wishes yet contradicts their own beliefs. Sometimes hospitalists can help the surrogate resolve this dilemma by suggesting consultations with other family members or professionals.
The fourth issue, multiple surrogates, may magnify the challenges but can also be an advantage. In most cases families, even those with members who have differing belief systems, tend to support each other during crises to reach a consensus in the patient’s best interests.
Tom Baudendistel, MD, a hospitalist at California Pacific Medical Center in San Francisco, says that although engaging in a dialogue with the multiple surrogates may reveal a family conflict, mistrust, or other issues, the problem is usually resolved. “One surrogate comes around after we make sure the one disagreeing sees in person what the patient is going through, the low quality of life,” says Dr. Baudendistel.
Howard Epstein, MD, medical director, Care Management and Palliative Care, Regions Hospital, St. Paul, Minn., suggests a different approach. “We ask the surrogate to imagine that if the patient could stand outside his or her body, hearing everything that is being said, what would he or she say?” says Dr. Epstein.
The Process
While these issues affect all hospitalists who work with surrogates, hospitalists often encounter additional circumstances that require special attention. These are not always problems but may be situations unique to the hospital setting or the hospitalist’s job.
The hospitalist’s first contact with a patient is often the patient’s admission to the hospital. The hospitalist is most often starting with a blank page with no background information. Gathering information quickly about an unknown patient is critical.
This duty often falls to hospitalists. Donald Krause, MD, medical director for quality assurance at St. Joseph Hospital in Bangor, Maine, and a hospitalist for 11 years, points out that “hospitalists take care of 90% of medical admissions and as part of this job arrange for surrogates if needed as well as anything else to help the patient.”
Beginning with the admission of a patient, the hospitalist may take on the responsibility of finding a surrogate.
Find a surrogate: When a patient is admitted, the hospitalist questions everyone connected to the patient about the existence of a surrogate or family spokesperson. If there is no information available, many hospitalists turn to other staff experts, such as social workers or chaplains, to seek people who know the patient.
Dr. Baudendistel says his medical center resuscitates “unbefriended” patients admitted to the emergency department to allow time to find a family member or surrogate. “Social workers then search the Internet, call shelters, and contact other hospitals and institutions to learn anything they can about the patient,” he says. If the search is unsuccessful, the hospitalist usually consults the institution’s ethics committee for additional suggestions.
Don C. Postema, PhD, ethics consultant for Regions Hospital, chair of the HealthPartners Ethics Committee, and ethicist-in-residence at Gillette Children’s Specialty HealthCare in St. Paul, Minn., proposes that an ethics committee look beyond the standard candidates in searching for a surrogate. “The legal relationship of a potential surrogate to the patient is secondary to what I consider to be the primary relationship, that is, the person who knows the patient best,” says Dr. Postema. “It could be the patient’s landlord or a neighbor who sees the patient on a regular basis.”
What about the patient whose family lives too far away to see the patient on a regular basis? Look into hiring a local geriatric case manager, Dr. Epstein advises.
There is one person who should not serve as a patient’s surrogate: the attending physician, whether a hospitalist or the primary caregiver. Erin Egan, MD, JD, assistant professor of hospital medicine, University of Colorado Hospitals, warns that a hospitalist acting as a surrogate has a conflict of interest. “Most states prohibit hospitalists from acting as surrogates,” Dr. Egan warns. “In some cases a doctor can presume consent for a short time before a surrogate is appointed in order to make an immediate medical decision. As a general rule, however, a clinician should never assume the surrogate’s role.”
Look for advance directives: Ideally, every patient’s file would contain an advance directive indicating a surrogate or a note that there is no surrogate.2 In addition, there should be a healthcare advance directive, also known as a healthcare power of attorney, that appoints a surrogate. It is often accompanied by a living will, an instruction sheet stipulating what treatment the patient wants if he or she is unable to speak or communicate. Unfortunately, many hospitalists cannot find these documents when they admit a patient.
In this case, the hospitalist must search. Most hospitals, nursing homes, or home healthcare agencies are required by the federal Patient Self-Determination Act (PSDA) to offer information about advance directives at the time of admission. This information states the patient’s healthcare decision-making rights under state law and the institution’s policy about adhering to advance directives. Contacting these agencies is a starting point.
Make difficult decisions: While some advance directives carry legal power, they often are not helpful to hospitalists or surrogates making end-of-life decisions. Because a medical crisis cannot always be predicted and treatment options change rapidly, a specific directive may not be as helpful as a written description of a patient’s beliefs, religious convictions, and cultural values. Equally valuable are notes about conversations among patients, family members, friends, and caregivers.3 This creates a picture of the patient’s feelings about quality of life, treatment preferences, and end-of-life outcomes.
The hospitalist’s role in this situation is to facilitate such discussions among all family and friends involved. The goal is to develop an accurate picture of the patient to make appropriate decisions. The hospitalist should explore the cultural values and religious beliefs of the patient, surrogate, family, and friends. “Different ethnic groups view medical care differently,” says Richard L. Heinrich, MD, medical director of Hospice of the Lakes, Bloomington, Minn. “Some religions believe that suffering in this life is rewarded in the next life, which makes a difference when making treatment decisions,” he says. “We must honor and work with cultural values unless in our view the individual is suffering needlessly.”
The hospitalist should be alert to the need for an interpreter and anything else that will promote a meaningful discussion. And, the hospitalist and the medical staff should be prepared to share as much medical information as is possible, including individual staff opinions, the rationale behind recommendations, and the pros and cons of each suggestion. The surrogate and family cannot make any meaningful contribution without all the pertinent information.
The goal should be a consensus about the patient’s best interests, how certain medical decisions will provide benefit or burden to the patient, and if the decision is what the patient would want. It’s especially critical to call a family conference to allow everyone the opportunity to discuss the patient’s concept of his or her death.
“Most people are afraid of getting caught in an end-of-life situation where they lose control,” says Dr. Postema. TH
Ann Kepler is a medical writer based in Chicago.
References
- Torke AM, Alexander GC, Lantos J, et al. The physician-surrogate relationship. Arch Intern Med. 2007 Jun 11;167(11):1117-1121.
- Wenger NS, Rosenfeld K. Quality indicators for end-of-life care in vulnerable elders. Ann Intern Med. 2001 Oct 16;135(8):677-685.
- Bloche MG. Managing conflict at the end of life. N Engl J Med. 2005 Jun 9;352:2371-2373.