Clinical Review

With the number of aging Americans projected to grow dramatically in the next several years, the need for primary palliative care and advance care planning (ACP) is more important than ever. Patients and their families want and expect palliative care when needed, but initial conversations about ACP can be difficult for them. Appropriate timing in raising this subject and clear communication can give patients the opportunity, while they are still independent, to set their goals for medical care.

For the past several decades, political decisions and judicial cases have shaped palliative care as we know it today. And its shape is still evolving. In support of ACP, advocacy groups at a national level are developing models that practitioners can use to engage patients in setting goals. And Medicare is now reimbursing primary care providers for this work that they have been doing for years (although many still may not be billing for the service).

Finally, the busy primary care office may have its own set of challenges in addressing ACP. Our aim in this review is to identify the barriers we face and the solutions we can implement to make a difference in our patients’ end-of-life care planning.

LANDMARK EVENTS HAVE DEFINED ACP TODAY

In 1969, Luis Kutner, an Illinois attorney, proposed the idea of a “living will,” envisioned as a document specifying the types of treatment a person would be willing to receive were he or she unable at a later time to participate in making a decision.¹ In 1976, California became the first state to give living wills the power of the law through the Natural Death Act.²

Throughout the 1970s and ‘80s, several high-profile court cases brought this idea into the national spotlight. In 1975, the New Jersey Supreme Court granted the parents of 21-year-old Karen Ann Quinlan the right to discontinue the treatment sustaining her in a persistent vegetative state. Ms. Quinlan was removed from the ventilator and lived nine more months before dying in a nursing home.

In 1983, age 25, Nancy Cruzan was involved in a motor vehicle accident that left her in a persistent vegetative state. She remained so until 1988, when her parents asked that her feeding tube be removed. The hospital refused, indicating that it would lead to her death. The family sued, and the case eventually went to the US Supreme Court in 1989.

In a 5-to-4 decision, the Supreme Court ruled that a state was legally able to require “clear and convincing evidence” of a patient’s wish for removal of life-sustaining therapies. Cruzan’s family was able to provide such evidence, and her artificial nutrition was withheld. She died 12 days later.

The Cruzan case was instrumental in furthering ACP, leading to the passage of the Patient Self Determination Act by ­Congress in 1990. All federally funded health care facilities were now required to educate ­patients of their rights in determining their medical care and to ask about advance directives.³ The ACP movement gained ad­ditional momentum from the landmark SUPPORT study that documented short­comings in communication between phys­icians and patients/families about treat­ment preferences and end-of-life care in US hospitals.⁴

In the Terri Schiavo case, the patient’s husband disagreed with the life-sustaining decisions of his wife’s parents, given her persistent vegetative state and the fact that she had no chance of meaningful recovery. After a prolonged national debate, it was ultimately decided that the husband could elect to withhold artificial nutrition. (She died in 2005.) The Schiavo case, as well as the Institute of Medicine’s report on Dying in America, influenced Congress in 2016 to pass legislation funding ACP conversations.⁵

THE DEMONSTRATED BENEFITS OF ACP

When done comprehensively, ACP yields many benefits for patients and families and for the health care system. A systematic review demonstrated that, despite the few studies examining the economic cost of ACP, the process may lead to decreased health care costs in certain populations (nursing home residents, community-dwelling adults with dementia, and those living in high health care–spending regions) and at the very least does not increase health care costs.⁶ ACP has increased the number of do-not-resuscitate orders and has decreased hospitalizations, admissions to intensive care units, and rates of cardiopulmonary resuscitation, mechanical ventilation, and use of tube feeding.^6-8

More noteworthy than the decrease in resource utilization and potential cost savings is the impact that ACP can have on a patient’s quality of life. Patients who receive aggressive care at the end of life tend to experience decreased quality of life compared with those receiving hospice care.⁷ Quality-of-life scores for patients in hospice improved with the length of enrollment in that care.⁷ When ACP discussions have taken place, the care patients receive at the end of life tends to conform more closely to their wishes and to increase family satis­faction.^9-11

One reason that practitioners often give for not completing ACP is the fear of increasing patient or family anxiety or post-traumatic stress disorder (PTSD). However, studies have shown this concern to be unfounded.^7,12 While ACP studies have not shown a decrease in rates of anxiety or PTSD, no study has shown an increase in these psychologic morbidities.⁸

Caveats to keep in mind. Not all studies have shown unambiguous benefits related to ACP. Among the systematic reviews previously noted, there was significant variability in quality of data. Additionally, some experts argue that the traditional view of ACP (ie, completion of a single advance directive/living will) is outdated and should be replaced with a method that prepares patients and families to anticipate “in-the-moment decision making.”¹³ While we still believe that completion of an advance directive is useful, the experts’ point is well taken, especially since many patients change their preferences over time (and typically toward more aggressive care).^14,15 While the advance directive serves a role, it is more important to help patients recognize their goals and preferences and to facilitate ongoing discussions between the patient and his or her family/surrogate decision-maker and providers.

A SNAPSHOT OF PARTICIPATION IN ACP

Despite the ACP movement and the likely benefits associated with it, most individuals have not participated. Rates of completion do seem to be rising, but there is still room for improvement. Among all individuals older than 18, only 26.3% have an advance directive.¹⁶ In a cohort of older patients seen in an emergency department, only 40% had a living will, while nearly 54% had a designated health care power of attorney.¹⁷ Perhaps more alarming is the lack of ACP for those patients almost all providers would agree need it: the long-term care population. The National Center for Health Statistics has reported that only 28% of home health care patients, 65% of nursing home residents, and 88% of hospice patients have an advance directive on file.¹⁸

PROVIDER AND PATIENT BARRIERS TO ACP

If ACP can decrease resource utilization and improve caregiver compliance with a patient’s wishes for end of life, the obvious question is: Why isn’t it done more often? A longstanding barrier for providers has been that these types of discussions are time intensive and have not been billable. However, since January 1, 2016, we are now able to bill for these discussions. (More on this in a bit.) Providers do cite other barriers, though.

A recent systematic review showed that ACP is hindered by time constraints imposed by other clinical and administrative tasks that are heavily monitored.¹⁹ Barriers to engaging in ACP reported by patients include a reluctance to think about dying, a belief that family or providers will know what to do, difficulty understanding ACP forms, and the absence of a person who can serve as a surrogate decision-maker.^20,21

NATIONAL MODELS TO HELP WITH IMPLEMENTATION

The percentage of individuals with an advance directive in the US has not increased significantly over the past decade.²² The lack of traction in completion and use of advance directives has led several authors to question the utility of this older model of ACP.²² Several experts in the field believe that more robust, ongoing goals-of-care conversations between patients, families, and providers are equally, or even more, important than the completion of actual advance directive documents.^23,24

National models such as the POLST (Physician Orders for Life-Sustaining Treatment) paradigm have become popular in several states (www.polst.org). Intended for those with estimated life expectancy of less than one year, POLST is not an advance directive but a physician order for these seriously ill patients. Emergency medical service workers are legally able to follow a POLST document but not a living will or advance directive—a significant reason for those with end-stage illness to consider completing a POLST document with their health care provider. Programs such as “Respecting Choices” have incorporated POLST documentation as part of ongoing goals-of-care conversations between patients and health care providers (www.gundersenhealth.org/respecting-choices).

Many groups have developed products to encourage patients and their families to initiate conversations at home. An example is the Conversation Project, a free online resource available in multiple languages that can help break the ice for patients and get them talking about their wishes for end-of-life care (www.theconversationproject.org). It poses simple stimulating questions such as “What kind of role do you want to have in the decision-making process?” and “What are your concerns about treatment?”

HOW-TO TIPS FOR ACP IN OUTPATIENT SETTINGS

When approaching the topic of ACP with patients, it’s important to do so over time, starting as soon as possible with older patients and those with chronic illness that confers a high risk for significant morbidity or mortality. Assess each patient’s understanding of ACP and readiness to discuss the topic. Many patients think of ACP in the context of a document (eg, living will), so asking about the existence of a living will may help to start the conversation. Alternatively, consider inquiring about whether the patient has had experience with family or friends at the end of life or during a difficult medical situation, and whether the patient has thought about making personal plans for such a situation.²⁵

When a patient is ready to have this conversation, your goal should be three-fold:²⁶

1. Help the patient articulate personal values, goals, and preferences.
2. Ask the patient to formally assign health care power of attorney (POA) to a trusted individual or to name a surrogate decision-maker. Document this decision in the medical record.
3. Help the patient translate expressed values into specific medical care plans, if applicable.

Because ACP conversations are often time consuming, it’s a good idea to schedule separate appointments to focus on this alone. If, however, a patient is unable to return for a dedicated ACP visit, a first step that can be completed in a reasonably short period would be choosing a surrogate decision-maker.

Helping a patient articulate personal values may be eased by asking such questions as, “Have you ever thought about what kind of care you would want if the time came when you could not make your own decisions?” or “What worries you the most about possibly not being able to make your own decisions?”²⁷ If the patient is able to identify a surrogate decision-maker before the ACP appointment, ask that this person attend. A family member or close friend may remember instances in which the patient expressed health care preferences, and their presence can help to minimize gaps in communication.

Once the patient’s preferences are clear, document them in the medical record. Some preferences may be suitable for translation into POLST orders or an advance directive, but this is less important than the overall discussion. ACP should be an ongoing conversation, since a patient’s goals may change over time. And encourage the patient to share any desired change in plans with their surrogate decision-maker or update the POA document.

BE SURE TO BILL FOR ACP SERVICES

To encourage office-based providers to conduct ACP, the Centers for Medicare and Medicaid Services (CMS) implemented payment for CPT codes 99497 and 99498.

CPT code 99497 covers the first 30 minutes of face-to-face time with patients or their family members or medical decision-makers. This time can be used to discuss living wills or advance directives.

CPT code 99498 can be applied to each additional 30 minutes of ACP services. Typically, this billing code would be used as an add-on for a particular diagnosis, such as heart failure, chronic obstructive pulmonary disease, or pancreatic cancer.

CPT Code 99497 equates to 2.40 relative-value units (RVU) with an estimated payment of $85.99, while CPT code 99498 equates to 2.09 RVU with an estimated payment of $74.88.²⁸

According to CMS, there is no annual limit to the number of times the ACP codes can be billed for a particular patient. And there are no restrictions regarding location of service, meaning a provider could perform this in an outpatient setting, an inpatient setting, or a long-term care facility. All health care providers are allowed to bill with this code. Also worth noting: You don’t need to complete any particular documentation for a visit to be billed as an ACP service. CMS provides a helpful Q & A at www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PhysicianFeeSched/Downloads/FAQ-Advance-Care-Planning.pdf.

With the number of aging Americans projected to grow dramatically in the next several years, the need for primary palliative care and advance care planning (ACP) is more important than ever. Patients and their families want and expect palliative care when needed, but initial conversations about ACP can be difficult for them. Appropriate timing in raising this subject and clear communication can give patients the opportunity, while they are still independent, to set their goals for medical care.

For the past several decades, political decisions and judicial cases have shaped palliative care as we know it today. And its shape is still evolving. In support of ACP, advocacy groups at a national level are developing models that practitioners can use to engage patients in setting goals. And Medicare is now reimbursing primary care providers for this work that they have been doing for years (although many still may not be billing for the service).

Finally, the busy primary care office may have its own set of challenges in addressing ACP. Our aim in this review is to identify the barriers we face and the solutions we can implement to make a difference in our patients’ end-of-life care planning.

LANDMARK EVENTS HAVE DEFINED ACP TODAY

In 1969, Luis Kutner, an Illinois attorney, proposed the idea of a “living will,” envisioned as a document specifying the types of treatment a person would be willing to receive were he or she unable at a later time to participate in making a decision.¹ In 1976, California became the first state to give living wills the power of the law through the Natural Death Act.²

Throughout the 1970s and ‘80s, several high-profile court cases brought this idea into the national spotlight. In 1975, the New Jersey Supreme Court granted the parents of 21-year-old Karen Ann Quinlan the right to discontinue the treatment sustaining her in a persistent vegetative state. Ms. Quinlan was removed from the ventilator and lived nine more months before dying in a nursing home.

In 1983, age 25, Nancy Cruzan was involved in a motor vehicle accident that left her in a persistent vegetative state. She remained so until 1988, when her parents asked that her feeding tube be removed. The hospital refused, indicating that it would lead to her death. The family sued, and the case eventually went to the US Supreme Court in 1989.

In a 5-to-4 decision, the Supreme Court ruled that a state was legally able to require “clear and convincing evidence” of a patient’s wish for removal of life-sustaining therapies. Cruzan’s family was able to provide such evidence, and her artificial nutrition was withheld. She died 12 days later.

The Cruzan case was instrumental in furthering ACP, leading to the passage of the Patient Self Determination Act by ­Congress in 1990. All federally funded health care facilities were now required to educate ­patients of their rights in determining their medical care and to ask about advance directives.³ The ACP movement gained ad­ditional momentum from the landmark SUPPORT study that documented short­comings in communication between phys­icians and patients/families about treat­ment preferences and end-of-life care in US hospitals.⁴

In the Terri Schiavo case, the patient’s husband disagreed with the life-sustaining decisions of his wife’s parents, given her persistent vegetative state and the fact that she had no chance of meaningful recovery. After a prolonged national debate, it was ultimately decided that the husband could elect to withhold artificial nutrition. (She died in 2005.) The Schiavo case, as well as the Institute of Medicine’s report on Dying in America, influenced Congress in 2016 to pass legislation funding ACP conversations.⁵

THE DEMONSTRATED BENEFITS OF ACP

When done comprehensively, ACP yields many benefits for patients and families and for the health care system. A systematic review demonstrated that, despite the few studies examining the economic cost of ACP, the process may lead to decreased health care costs in certain populations (nursing home residents, community-dwelling adults with dementia, and those living in high health care–spending regions) and at the very least does not increase health care costs.⁶ ACP has increased the number of do-not-resuscitate orders and has decreased hospitalizations, admissions to intensive care units, and rates of cardiopulmonary resuscitation, mechanical ventilation, and use of tube feeding.^6-8

More noteworthy than the decrease in resource utilization and potential cost savings is the impact that ACP can have on a patient’s quality of life. Patients who receive aggressive care at the end of life tend to experience decreased quality of life compared with those receiving hospice care.⁷ Quality-of-life scores for patients in hospice improved with the length of enrollment in that care.⁷ When ACP discussions have taken place, the care patients receive at the end of life tends to conform more closely to their wishes and to increase family satis­faction.^9-11

One reason that practitioners often give for not completing ACP is the fear of increasing patient or family anxiety or post-traumatic stress disorder (PTSD). However, studies have shown this concern to be unfounded.^7,12 While ACP studies have not shown a decrease in rates of anxiety or PTSD, no study has shown an increase in these psychologic morbidities.⁸

Caveats to keep in mind. Not all studies have shown unambiguous benefits related to ACP. Among the systematic reviews previously noted, there was significant variability in quality of data. Additionally, some experts argue that the traditional view of ACP (ie, completion of a single advance directive/living will) is outdated and should be replaced with a method that prepares patients and families to anticipate “in-the-moment decision making.”¹³ While we still believe that completion of an advance directive is useful, the experts’ point is well taken, especially since many patients change their preferences over time (and typically toward more aggressive care).^14,15 While the advance directive serves a role, it is more important to help patients recognize their goals and preferences and to facilitate ongoing discussions between the patient and his or her family/surrogate decision-maker and providers.

A SNAPSHOT OF PARTICIPATION IN ACP

Despite the ACP movement and the likely benefits associated with it, most individuals have not participated. Rates of completion do seem to be rising, but there is still room for improvement. Among all individuals older than 18, only 26.3% have an advance directive.¹⁶ In a cohort of older patients seen in an emergency department, only 40% had a living will, while nearly 54% had a designated health care power of attorney.¹⁷ Perhaps more alarming is the lack of ACP for those patients almost all providers would agree need it: the long-term care population. The National Center for Health Statistics has reported that only 28% of home health care patients, 65% of nursing home residents, and 88% of hospice patients have an advance directive on file.¹⁸

PROVIDER AND PATIENT BARRIERS TO ACP

If ACP can decrease resource utilization and improve caregiver compliance with a patient’s wishes for end of life, the obvious question is: Why isn’t it done more often? A longstanding barrier for providers has been that these types of discussions are time intensive and have not been billable. However, since January 1, 2016, we are now able to bill for these discussions. (More on this in a bit.) Providers do cite other barriers, though.

A recent systematic review showed that ACP is hindered by time constraints imposed by other clinical and administrative tasks that are heavily monitored.¹⁹ Barriers to engaging in ACP reported by patients include a reluctance to think about dying, a belief that family or providers will know what to do, difficulty understanding ACP forms, and the absence of a person who can serve as a surrogate decision-maker.^20,21

NATIONAL MODELS TO HELP WITH IMPLEMENTATION

The percentage of individuals with an advance directive in the US has not increased significantly over the past decade.²² The lack of traction in completion and use of advance directives has led several authors to question the utility of this older model of ACP.²² Several experts in the field believe that more robust, ongoing goals-of-care conversations between patients, families, and providers are equally, or even more, important than the completion of actual advance directive documents.^23,24

National models such as the POLST (Physician Orders for Life-Sustaining Treatment) paradigm have become popular in several states (www.polst.org). Intended for those with estimated life expectancy of less than one year, POLST is not an advance directive but a physician order for these seriously ill patients. Emergency medical service workers are legally able to follow a POLST document but not a living will or advance directive—a significant reason for those with end-stage illness to consider completing a POLST document with their health care provider. Programs such as “Respecting Choices” have incorporated POLST documentation as part of ongoing goals-of-care conversations between patients and health care providers (www.gundersenhealth.org/respecting-choices).

Many groups have developed products to encourage patients and their families to initiate conversations at home. An example is the Conversation Project, a free online resource available in multiple languages that can help break the ice for patients and get them talking about their wishes for end-of-life care (www.theconversationproject.org). It poses simple stimulating questions such as “What kind of role do you want to have in the decision-making process?” and “What are your concerns about treatment?”

HOW-TO TIPS FOR ACP IN OUTPATIENT SETTINGS

When approaching the topic of ACP with patients, it’s important to do so over time, starting as soon as possible with older patients and those with chronic illness that confers a high risk for significant morbidity or mortality. Assess each patient’s understanding of ACP and readiness to discuss the topic. Many patients think of ACP in the context of a document (eg, living will), so asking about the existence of a living will may help to start the conversation. Alternatively, consider inquiring about whether the patient has had experience with family or friends at the end of life or during a difficult medical situation, and whether the patient has thought about making personal plans for such a situation.²⁵

When a patient is ready to have this conversation, your goal should be three-fold:²⁶

1. Help the patient articulate personal values, goals, and preferences.
2. Ask the patient to formally assign health care power of attorney (POA) to a trusted individual or to name a surrogate decision-maker. Document this decision in the medical record.
3. Help the patient translate expressed values into specific medical care plans, if applicable.

Because ACP conversations are often time consuming, it’s a good idea to schedule separate appointments to focus on this alone. If, however, a patient is unable to return for a dedicated ACP visit, a first step that can be completed in a reasonably short period would be choosing a surrogate decision-maker.

Helping a patient articulate personal values may be eased by asking such questions as, “Have you ever thought about what kind of care you would want if the time came when you could not make your own decisions?” or “What worries you the most about possibly not being able to make your own decisions?”²⁷ If the patient is able to identify a surrogate decision-maker before the ACP appointment, ask that this person attend. A family member or close friend may remember instances in which the patient expressed health care preferences, and their presence can help to minimize gaps in communication.

Once the patient’s preferences are clear, document them in the medical record. Some preferences may be suitable for translation into POLST orders or an advance directive, but this is less important than the overall discussion. ACP should be an ongoing conversation, since a patient’s goals may change over time. And encourage the patient to share any desired change in plans with their surrogate decision-maker or update the POA document.

BE SURE TO BILL FOR ACP SERVICES

To encourage office-based providers to conduct ACP, the Centers for Medicare and Medicaid Services (CMS) implemented payment for CPT codes 99497 and 99498.

CPT code 99497 covers the first 30 minutes of face-to-face time with patients or their family members or medical decision-makers. This time can be used to discuss living wills or advance directives.

CPT code 99498 can be applied to each additional 30 minutes of ACP services. Typically, this billing code would be used as an add-on for a particular diagnosis, such as heart failure, chronic obstructive pulmonary disease, or pancreatic cancer.

CPT Code 99497 equates to 2.40 relative-value units (RVU) with an estimated payment of $85.99, while CPT code 99498 equates to 2.09 RVU with an estimated payment of $74.88.²⁸

According to CMS, there is no annual limit to the number of times the ACP codes can be billed for a particular patient. And there are no restrictions regarding location of service, meaning a provider could perform this in an outpatient setting, an inpatient setting, or a long-term care facility. All health care providers are allowed to bill with this code. Also worth noting: You don’t need to complete any particular documentation for a visit to be billed as an ACP service. CMS provides a helpful Q & A at www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PhysicianFeeSched/Downloads/FAQ-Advance-Care-Planning.pdf.

With the number of aging Americans projected to grow dramatically in the next several years, the need for primary palliative care and advance care planning (ACP) is more important than ever. Patients and their families want and expect palliative care when needed, but initial conversations about ACP can be difficult for them. Appropriate timing in raising this subject and clear communication can give patients the opportunity, while they are still independent, to set their goals for medical care.

For the past several decades, political decisions and judicial cases have shaped palliative care as we know it today. And its shape is still evolving. In support of ACP, advocacy groups at a national level are developing models that practitioners can use to engage patients in setting goals. And Medicare is now reimbursing primary care providers for this work that they have been doing for years (although many still may not be billing for the service).

Finally, the busy primary care office may have its own set of challenges in addressing ACP. Our aim in this review is to identify the barriers we face and the solutions we can implement to make a difference in our patients’ end-of-life care planning.

LANDMARK EVENTS HAVE DEFINED ACP TODAY

In 1969, Luis Kutner, an Illinois attorney, proposed the idea of a “living will,” envisioned as a document specifying the types of treatment a person would be willing to receive were he or she unable at a later time to participate in making a decision.¹ In 1976, California became the first state to give living wills the power of the law through the Natural Death Act.²

Throughout the 1970s and ‘80s, several high-profile court cases brought this idea into the national spotlight. In 1975, the New Jersey Supreme Court granted the parents of 21-year-old Karen Ann Quinlan the right to discontinue the treatment sustaining her in a persistent vegetative state. Ms. Quinlan was removed from the ventilator and lived nine more months before dying in a nursing home.

In 1983, age 25, Nancy Cruzan was involved in a motor vehicle accident that left her in a persistent vegetative state. She remained so until 1988, when her parents asked that her feeding tube be removed. The hospital refused, indicating that it would lead to her death. The family sued, and the case eventually went to the US Supreme Court in 1989.

In a 5-to-4 decision, the Supreme Court ruled that a state was legally able to require “clear and convincing evidence” of a patient’s wish for removal of life-sustaining therapies. Cruzan’s family was able to provide such evidence, and her artificial nutrition was withheld. She died 12 days later.

The Cruzan case was instrumental in furthering ACP, leading to the passage of the Patient Self Determination Act by ­Congress in 1990. All federally funded health care facilities were now required to educate ­patients of their rights in determining their medical care and to ask about advance directives.³ The ACP movement gained ad­ditional momentum from the landmark SUPPORT study that documented short­comings in communication between phys­icians and patients/families about treat­ment preferences and end-of-life care in US hospitals.⁴

In the Terri Schiavo case, the patient’s husband disagreed with the life-sustaining decisions of his wife’s parents, given her persistent vegetative state and the fact that she had no chance of meaningful recovery. After a prolonged national debate, it was ultimately decided that the husband could elect to withhold artificial nutrition. (She died in 2005.) The Schiavo case, as well as the Institute of Medicine’s report on Dying in America, influenced Congress in 2016 to pass legislation funding ACP conversations.⁵

THE DEMONSTRATED BENEFITS OF ACP

When done comprehensively, ACP yields many benefits for patients and families and for the health care system. A systematic review demonstrated that, despite the few studies examining the economic cost of ACP, the process may lead to decreased health care costs in certain populations (nursing home residents, community-dwelling adults with dementia, and those living in high health care–spending regions) and at the very least does not increase health care costs.⁶ ACP has increased the number of do-not-resuscitate orders and has decreased hospitalizations, admissions to intensive care units, and rates of cardiopulmonary resuscitation, mechanical ventilation, and use of tube feeding.^6-8

More noteworthy than the decrease in resource utilization and potential cost savings is the impact that ACP can have on a patient’s quality of life. Patients who receive aggressive care at the end of life tend to experience decreased quality of life compared with those receiving hospice care.⁷ Quality-of-life scores for patients in hospice improved with the length of enrollment in that care.⁷ When ACP discussions have taken place, the care patients receive at the end of life tends to conform more closely to their wishes and to increase family satis­faction.^9-11

One reason that practitioners often give for not completing ACP is the fear of increasing patient or family anxiety or post-traumatic stress disorder (PTSD). However, studies have shown this concern to be unfounded.^7,12 While ACP studies have not shown a decrease in rates of anxiety or PTSD, no study has shown an increase in these psychologic morbidities.⁸

Caveats to keep in mind. Not all studies have shown unambiguous benefits related to ACP. Among the systematic reviews previously noted, there was significant variability in quality of data. Additionally, some experts argue that the traditional view of ACP (ie, completion of a single advance directive/living will) is outdated and should be replaced with a method that prepares patients and families to anticipate “in-the-moment decision making.”¹³ While we still believe that completion of an advance directive is useful, the experts’ point is well taken, especially since many patients change their preferences over time (and typically toward more aggressive care).^14,15 While the advance directive serves a role, it is more important to help patients recognize their goals and preferences and to facilitate ongoing discussions between the patient and his or her family/surrogate decision-maker and providers.

A SNAPSHOT OF PARTICIPATION IN ACP

Despite the ACP movement and the likely benefits associated with it, most individuals have not participated. Rates of completion do seem to be rising, but there is still room for improvement. Among all individuals older than 18, only 26.3% have an advance directive.¹⁶ In a cohort of older patients seen in an emergency department, only 40% had a living will, while nearly 54% had a designated health care power of attorney.¹⁷ Perhaps more alarming is the lack of ACP for those patients almost all providers would agree need it: the long-term care population. The National Center for Health Statistics has reported that only 28% of home health care patients, 65% of nursing home residents, and 88% of hospice patients have an advance directive on file.¹⁸

PROVIDER AND PATIENT BARRIERS TO ACP

If ACP can decrease resource utilization and improve caregiver compliance with a patient’s wishes for end of life, the obvious question is: Why isn’t it done more often? A longstanding barrier for providers has been that these types of discussions are time intensive and have not been billable. However, since January 1, 2016, we are now able to bill for these discussions. (More on this in a bit.) Providers do cite other barriers, though.

A recent systematic review showed that ACP is hindered by time constraints imposed by other clinical and administrative tasks that are heavily monitored.¹⁹ Barriers to engaging in ACP reported by patients include a reluctance to think about dying, a belief that family or providers will know what to do, difficulty understanding ACP forms, and the absence of a person who can serve as a surrogate decision-maker.^20,21

NATIONAL MODELS TO HELP WITH IMPLEMENTATION

The percentage of individuals with an advance directive in the US has not increased significantly over the past decade.²² The lack of traction in completion and use of advance directives has led several authors to question the utility of this older model of ACP.²² Several experts in the field believe that more robust, ongoing goals-of-care conversations between patients, families, and providers are equally, or even more, important than the completion of actual advance directive documents.^23,24

National models such as the POLST (Physician Orders for Life-Sustaining Treatment) paradigm have become popular in several states (www.polst.org). Intended for those with estimated life expectancy of less than one year, POLST is not an advance directive but a physician order for these seriously ill patients. Emergency medical service workers are legally able to follow a POLST document but not a living will or advance directive—a significant reason for those with end-stage illness to consider completing a POLST document with their health care provider. Programs such as “Respecting Choices” have incorporated POLST documentation as part of ongoing goals-of-care conversations between patients and health care providers (www.gundersenhealth.org/respecting-choices).

Many groups have developed products to encourage patients and their families to initiate conversations at home. An example is the Conversation Project, a free online resource available in multiple languages that can help break the ice for patients and get them talking about their wishes for end-of-life care (www.theconversationproject.org). It poses simple stimulating questions such as “What kind of role do you want to have in the decision-making process?” and “What are your concerns about treatment?”

HOW-TO TIPS FOR ACP IN OUTPATIENT SETTINGS

When approaching the topic of ACP with patients, it’s important to do so over time, starting as soon as possible with older patients and those with chronic illness that confers a high risk for significant morbidity or mortality. Assess each patient’s understanding of ACP and readiness to discuss the topic. Many patients think of ACP in the context of a document (eg, living will), so asking about the existence of a living will may help to start the conversation. Alternatively, consider inquiring about whether the patient has had experience with family or friends at the end of life or during a difficult medical situation, and whether the patient has thought about making personal plans for such a situation.²⁵

When a patient is ready to have this conversation, your goal should be three-fold:²⁶

1. Help the patient articulate personal values, goals, and preferences.
2. Ask the patient to formally assign health care power of attorney (POA) to a trusted individual or to name a surrogate decision-maker. Document this decision in the medical record.
3. Help the patient translate expressed values into specific medical care plans, if applicable.

Because ACP conversations are often time consuming, it’s a good idea to schedule separate appointments to focus on this alone. If, however, a patient is unable to return for a dedicated ACP visit, a first step that can be completed in a reasonably short period would be choosing a surrogate decision-maker.

Helping a patient articulate personal values may be eased by asking such questions as, “Have you ever thought about what kind of care you would want if the time came when you could not make your own decisions?” or “What worries you the most about possibly not being able to make your own decisions?”²⁷ If the patient is able to identify a surrogate decision-maker before the ACP appointment, ask that this person attend. A family member or close friend may remember instances in which the patient expressed health care preferences, and their presence can help to minimize gaps in communication.

Once the patient’s preferences are clear, document them in the medical record. Some preferences may be suitable for translation into POLST orders or an advance directive, but this is less important than the overall discussion. ACP should be an ongoing conversation, since a patient’s goals may change over time. And encourage the patient to share any desired change in plans with their surrogate decision-maker or update the POA document.

BE SURE TO BILL FOR ACP SERVICES

To encourage office-based providers to conduct ACP, the Centers for Medicare and Medicaid Services (CMS) implemented payment for CPT codes 99497 and 99498.

CPT code 99497 covers the first 30 minutes of face-to-face time with patients or their family members or medical decision-makers. This time can be used to discuss living wills or advance directives.

CPT code 99498 can be applied to each additional 30 minutes of ACP services. Typically, this billing code would be used as an add-on for a particular diagnosis, such as heart failure, chronic obstructive pulmonary disease, or pancreatic cancer.

CPT Code 99497 equates to 2.40 relative-value units (RVU) with an estimated payment of $85.99, while CPT code 99498 equates to 2.09 RVU with an estimated payment of $74.88.²⁸

According to CMS, there is no annual limit to the number of times the ACP codes can be billed for a particular patient. And there are no restrictions regarding location of service, meaning a provider could perform this in an outpatient setting, an inpatient setting, or a long-term care facility. All health care providers are allowed to bill with this code. Also worth noting: You don’t need to complete any particular documentation for a visit to be billed as an ACP service. CMS provides a helpful Q & A at www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/PhysicianFeeSched/Downloads/FAQ-Advance-Care-Planning.pdf.

ED Visits by Older Patients Increase in the Weeks After a Disaster

BY KELLIE DESANTIS

Visits to an ED by adults ages 65 years and older increase significantly in the weeks following a disaster, according to a study published in Disaster Medicine and Public Health Preparedness.¹

Older adults are vulnerable to the effects of disasters because of their diminished ability to adequately prepare for and respond to the effects of a disaster. Older adults suffering from visual, auditory, proprioceptive, and cognitive impairments are especially vulnerable and have the most difficulty complying with evacuation and preparatory warnings. Individuals with multiple chronic diseases, living in long-term care facilities or suffering from cognitive impairments are among the most vulnerable.

To better understand the impact of natural disasters on this vulnerable population, researchers examined the effects of the 2012 disaster, Hurricane Sandy, on older adults living in New York City (NYC) during the disaster. Researchers turned to the New York State Department of Health (NYSDOH) for data. The NYSDOH compiles a comprehensive database of claims from all ED visits in the Statewide Planning and Research Cooperative System (SPARCS), which is the most complete source for ED utilization in New York state, and includes primary and secondary diagnosis codes and patient addresses.

Researchers evaluated ED utilization by adults 65 years and older in the weeks immediately before and after the Hurricane Sandy landfall. They excluded patients who lived in a nursing home, were incarcerated, or visited an ED associated with a specialty hospital (surgical subspecialty, oncological, or Veterans Administration). By using geographic distribution information available from SPARCS and the NYC Office of Emergency Management evacuation zones, researchers were able to compare the ED utilization for older adults living in the evacuation zones before the landfall of Hurricane Sandy and in the weeks shortly after the storm.

The analysis revealed a significant increase in ED utilization for older adults living in the evacuation zones in the 3 weeks after the storm compared to ED use before the storm. The number of weekly ED visits by older adults from all evacuation zones was 9,852 in the weeks before Hurricane Sandy and increased in the first week after the storm to 10,073. Among the most severely impacted were older adults in evacuation zone one, where ED utilization increased from 552 visits to 1,111 visits. The number of ED visits remained elevated for 3 weeks after the storm but returned to normal by the fourth week.

Researchers suggested several reasons for this increase in ED visits, including seeking refuge in the ED as a result of homelessness due to the disaster, the interruption of ongoing care for chronic illness, environmental exposure, and the lack of preparation for the lasting effect of the disaster.

To improve the response to such a disaster in the future, a NYC Hurricane Sandy Assessment report² recommended developing a door-to-door service task force for older adults to improve preparedness for this vulnerable population. The task force would be responsible for implementing an action plan to ensure that healthcare services, communication, and provisions for this population continue without interruption in the weeks following a disaster. Legal and regulatory changes would allow for Medicare recipients to be eligible for "early medication refill" and pre-storm "early dialysis" programs to improve the continuity of care of the chronically ill.

1. Malik S, Lee DC, Doran KM, et al. Vulnerability of older adults in disasters: emergency department utilization by geriatric patients after hurricane sandy. Disaster Med Public Health Prep. 2017:1-10. doi:10.1017/dmp.2017.44

2. The City of New York, Office of the Mayor. Hurricane Sandy After Action Report. Published May 2013. http://www.nyc.gov/html/recovery/downlaods/pdf/sandy_aar_5.2.13.pdf. Accessed September 1, 2017.

Digital Rectal Examination of ED Patients with Acute GI Bleeding Cuts Rates of Admissions, Pharmacotherapy, and Endoscopy

BY JEFF BAUER

Patients presenting to the ED with acute gastrointestinal (GI) bleeding who receive a digital rectal examination have significantly lower rates of admissions, pharmacotherapy, and endoscopies, according to a retrospective study published in The American Journal of Medicine. Digital rectal examinations are an established part of the physical examination of a patient with GI bleeding, but physicians often are reluctant to conduct such examinations. Previous studies have found that 10% to 35% of patients with acute GI bleeding do not receive digital rectal examinations.

In the current study, researchers analyzed data from the electronic health records (EHRs) of patients ages 18 years and older who presented to the ED of a single institution with acute GI bleeding, as identified by International Classification of Diseases, Ninth Edition codes. They collected patients’ medical histories, demographic information, and clinical and laboratory data. ED clinician notes were used to determine which patients received a digital rectal examination. The outcomes researchers assessed were hospital admission, intensive care unit (ICU) admission, initiation of medical therapy (a proton pump inhibitor or octreotide), inpatient endoscopy (upper endoscopy or colonoscopy), and packed red blood cell (RBC) transfusion.

Overall, 1237 patients presented with acute GI bleeding. Most patients were Caucasian (49.2%) or Hispanic (38.4%), 44.9% were female, and the median age was 53 years.

Slightly more than one-half of patients (55.6%) received a digital rectal examination. In total, 736 patients were admitted—including 222 admissions to the ICU; 751 were started on a proton pump inhibitor or octreotide, 274 underwent endoscopy, and 321 received an RBC transfusion.

Patients were more likely to receive a digital rectal examination if they were older, Hispanic, or receiving an anticoagulant. Patients were less likely to undergo such examinations if they presented with altered mental status or hematemesis. Compared to patients who did not receive a digital rectal examination, those who did were significantly less likely to be admitted to the hospital (P = .004), to be starting on medical therapy (P = .04), or to undergo endoscopy (P = .02). There were no significant differences between these two groups in terms of ICU admissions, gastroenterology consultations, or transfusions.

Researchers suggested that the 44% rate of patients with acute GI bleeding who did not receive digital rectal examinations was higher than had been reported in previous studies. The difference had been the result of relying solely on ED clinician notes for this data, without including notes from admitting or consulting clinicians. The authors also were unable to determine the reasons these examinations were not conducted.

Shrestha MP, Borgstrom M, Trowers E. Digital rectal examination reduces hospital admissions, endoscopies, and medical therapy in patients with acute gastrointestinal bleeding. Am J Med. 2017;130(7):819-825. doi: 10.1016/j.amjmed.2017.01.036.

ED Visits by Older Patients Increase in the Weeks After a Disaster

BY KELLIE DESANTIS

Visits to an ED by adults ages 65 years and older increase significantly in the weeks following a disaster, according to a study published in Disaster Medicine and Public Health Preparedness.¹

Older adults are vulnerable to the effects of disasters because of their diminished ability to adequately prepare for and respond to the effects of a disaster. Older adults suffering from visual, auditory, proprioceptive, and cognitive impairments are especially vulnerable and have the most difficulty complying with evacuation and preparatory warnings. Individuals with multiple chronic diseases, living in long-term care facilities or suffering from cognitive impairments are among the most vulnerable.

To better understand the impact of natural disasters on this vulnerable population, researchers examined the effects of the 2012 disaster, Hurricane Sandy, on older adults living in New York City (NYC) during the disaster. Researchers turned to the New York State Department of Health (NYSDOH) for data. The NYSDOH compiles a comprehensive database of claims from all ED visits in the Statewide Planning and Research Cooperative System (SPARCS), which is the most complete source for ED utilization in New York state, and includes primary and secondary diagnosis codes and patient addresses.

Researchers evaluated ED utilization by adults 65 years and older in the weeks immediately before and after the Hurricane Sandy landfall. They excluded patients who lived in a nursing home, were incarcerated, or visited an ED associated with a specialty hospital (surgical subspecialty, oncological, or Veterans Administration). By using geographic distribution information available from SPARCS and the NYC Office of Emergency Management evacuation zones, researchers were able to compare the ED utilization for older adults living in the evacuation zones before the landfall of Hurricane Sandy and in the weeks shortly after the storm.

The analysis revealed a significant increase in ED utilization for older adults living in the evacuation zones in the 3 weeks after the storm compared to ED use before the storm. The number of weekly ED visits by older adults from all evacuation zones was 9,852 in the weeks before Hurricane Sandy and increased in the first week after the storm to 10,073. Among the most severely impacted were older adults in evacuation zone one, where ED utilization increased from 552 visits to 1,111 visits. The number of ED visits remained elevated for 3 weeks after the storm but returned to normal by the fourth week.

Researchers suggested several reasons for this increase in ED visits, including seeking refuge in the ED as a result of homelessness due to the disaster, the interruption of ongoing care for chronic illness, environmental exposure, and the lack of preparation for the lasting effect of the disaster.

To improve the response to such a disaster in the future, a NYC Hurricane Sandy Assessment report² recommended developing a door-to-door service task force for older adults to improve preparedness for this vulnerable population. The task force would be responsible for implementing an action plan to ensure that healthcare services, communication, and provisions for this population continue without interruption in the weeks following a disaster. Legal and regulatory changes would allow for Medicare recipients to be eligible for "early medication refill" and pre-storm "early dialysis" programs to improve the continuity of care of the chronically ill.

1. Malik S, Lee DC, Doran KM, et al. Vulnerability of older adults in disasters: emergency department utilization by geriatric patients after hurricane sandy. Disaster Med Public Health Prep. 2017:1-10. doi:10.1017/dmp.2017.44

2. The City of New York, Office of the Mayor. Hurricane Sandy After Action Report. Published May 2013. http://www.nyc.gov/html/recovery/downlaods/pdf/sandy_aar_5.2.13.pdf. Accessed September 1, 2017.

Digital Rectal Examination of ED Patients with Acute GI Bleeding Cuts Rates of Admissions, Pharmacotherapy, and Endoscopy

BY JEFF BAUER

Patients presenting to the ED with acute gastrointestinal (GI) bleeding who receive a digital rectal examination have significantly lower rates of admissions, pharmacotherapy, and endoscopies, according to a retrospective study published in The American Journal of Medicine. Digital rectal examinations are an established part of the physical examination of a patient with GI bleeding, but physicians often are reluctant to conduct such examinations. Previous studies have found that 10% to 35% of patients with acute GI bleeding do not receive digital rectal examinations.

In the current study, researchers analyzed data from the electronic health records (EHRs) of patients ages 18 years and older who presented to the ED of a single institution with acute GI bleeding, as identified by International Classification of Diseases, Ninth Edition codes. They collected patients’ medical histories, demographic information, and clinical and laboratory data. ED clinician notes were used to determine which patients received a digital rectal examination. The outcomes researchers assessed were hospital admission, intensive care unit (ICU) admission, initiation of medical therapy (a proton pump inhibitor or octreotide), inpatient endoscopy (upper endoscopy or colonoscopy), and packed red blood cell (RBC) transfusion.

Overall, 1237 patients presented with acute GI bleeding. Most patients were Caucasian (49.2%) or Hispanic (38.4%), 44.9% were female, and the median age was 53 years.

Slightly more than one-half of patients (55.6%) received a digital rectal examination. In total, 736 patients were admitted—including 222 admissions to the ICU; 751 were started on a proton pump inhibitor or octreotide, 274 underwent endoscopy, and 321 received an RBC transfusion.

Patients were more likely to receive a digital rectal examination if they were older, Hispanic, or receiving an anticoagulant. Patients were less likely to undergo such examinations if they presented with altered mental status or hematemesis. Compared to patients who did not receive a digital rectal examination, those who did were significantly less likely to be admitted to the hospital (P = .004), to be starting on medical therapy (P = .04), or to undergo endoscopy (P = .02). There were no significant differences between these two groups in terms of ICU admissions, gastroenterology consultations, or transfusions.

Researchers suggested that the 44% rate of patients with acute GI bleeding who did not receive digital rectal examinations was higher than had been reported in previous studies. The difference had been the result of relying solely on ED clinician notes for this data, without including notes from admitting or consulting clinicians. The authors also were unable to determine the reasons these examinations were not conducted.

Shrestha MP, Borgstrom M, Trowers E. Digital rectal examination reduces hospital admissions, endoscopies, and medical therapy in patients with acute gastrointestinal bleeding. Am J Med. 2017;130(7):819-825. doi: 10.1016/j.amjmed.2017.01.036.

ED Visits by Older Patients Increase in the Weeks After a Disaster

BY KELLIE DESANTIS

Visits to an ED by adults ages 65 years and older increase significantly in the weeks following a disaster, according to a study published in Disaster Medicine and Public Health Preparedness.¹

Older adults are vulnerable to the effects of disasters because of their diminished ability to adequately prepare for and respond to the effects of a disaster. Older adults suffering from visual, auditory, proprioceptive, and cognitive impairments are especially vulnerable and have the most difficulty complying with evacuation and preparatory warnings. Individuals with multiple chronic diseases, living in long-term care facilities or suffering from cognitive impairments are among the most vulnerable.

To better understand the impact of natural disasters on this vulnerable population, researchers examined the effects of the 2012 disaster, Hurricane Sandy, on older adults living in New York City (NYC) during the disaster. Researchers turned to the New York State Department of Health (NYSDOH) for data. The NYSDOH compiles a comprehensive database of claims from all ED visits in the Statewide Planning and Research Cooperative System (SPARCS), which is the most complete source for ED utilization in New York state, and includes primary and secondary diagnosis codes and patient addresses.

Researchers evaluated ED utilization by adults 65 years and older in the weeks immediately before and after the Hurricane Sandy landfall. They excluded patients who lived in a nursing home, were incarcerated, or visited an ED associated with a specialty hospital (surgical subspecialty, oncological, or Veterans Administration). By using geographic distribution information available from SPARCS and the NYC Office of Emergency Management evacuation zones, researchers were able to compare the ED utilization for older adults living in the evacuation zones before the landfall of Hurricane Sandy and in the weeks shortly after the storm.

The analysis revealed a significant increase in ED utilization for older adults living in the evacuation zones in the 3 weeks after the storm compared to ED use before the storm. The number of weekly ED visits by older adults from all evacuation zones was 9,852 in the weeks before Hurricane Sandy and increased in the first week after the storm to 10,073. Among the most severely impacted were older adults in evacuation zone one, where ED utilization increased from 552 visits to 1,111 visits. The number of ED visits remained elevated for 3 weeks after the storm but returned to normal by the fourth week.

Researchers suggested several reasons for this increase in ED visits, including seeking refuge in the ED as a result of homelessness due to the disaster, the interruption of ongoing care for chronic illness, environmental exposure, and the lack of preparation for the lasting effect of the disaster.

To improve the response to such a disaster in the future, a NYC Hurricane Sandy Assessment report² recommended developing a door-to-door service task force for older adults to improve preparedness for this vulnerable population. The task force would be responsible for implementing an action plan to ensure that healthcare services, communication, and provisions for this population continue without interruption in the weeks following a disaster. Legal and regulatory changes would allow for Medicare recipients to be eligible for "early medication refill" and pre-storm "early dialysis" programs to improve the continuity of care of the chronically ill.

1. Malik S, Lee DC, Doran KM, et al. Vulnerability of older adults in disasters: emergency department utilization by geriatric patients after hurricane sandy. Disaster Med Public Health Prep. 2017:1-10. doi:10.1017/dmp.2017.44

2. The City of New York, Office of the Mayor. Hurricane Sandy After Action Report. Published May 2013. http://www.nyc.gov/html/recovery/downlaods/pdf/sandy_aar_5.2.13.pdf. Accessed September 1, 2017.

Digital Rectal Examination of ED Patients with Acute GI Bleeding Cuts Rates of Admissions, Pharmacotherapy, and Endoscopy

BY JEFF BAUER

Patients presenting to the ED with acute gastrointestinal (GI) bleeding who receive a digital rectal examination have significantly lower rates of admissions, pharmacotherapy, and endoscopies, according to a retrospective study published in The American Journal of Medicine. Digital rectal examinations are an established part of the physical examination of a patient with GI bleeding, but physicians often are reluctant to conduct such examinations. Previous studies have found that 10% to 35% of patients with acute GI bleeding do not receive digital rectal examinations.

In the current study, researchers analyzed data from the electronic health records (EHRs) of patients ages 18 years and older who presented to the ED of a single institution with acute GI bleeding, as identified by International Classification of Diseases, Ninth Edition codes. They collected patients’ medical histories, demographic information, and clinical and laboratory data. ED clinician notes were used to determine which patients received a digital rectal examination. The outcomes researchers assessed were hospital admission, intensive care unit (ICU) admission, initiation of medical therapy (a proton pump inhibitor or octreotide), inpatient endoscopy (upper endoscopy or colonoscopy), and packed red blood cell (RBC) transfusion.

Overall, 1237 patients presented with acute GI bleeding. Most patients were Caucasian (49.2%) or Hispanic (38.4%), 44.9% were female, and the median age was 53 years.

Slightly more than one-half of patients (55.6%) received a digital rectal examination. In total, 736 patients were admitted—including 222 admissions to the ICU; 751 were started on a proton pump inhibitor or octreotide, 274 underwent endoscopy, and 321 received an RBC transfusion.

Patients were more likely to receive a digital rectal examination if they were older, Hispanic, or receiving an anticoagulant. Patients were less likely to undergo such examinations if they presented with altered mental status or hematemesis. Compared to patients who did not receive a digital rectal examination, those who did were significantly less likely to be admitted to the hospital (P = .004), to be starting on medical therapy (P = .04), or to undergo endoscopy (P = .02). There were no significant differences between these two groups in terms of ICU admissions, gastroenterology consultations, or transfusions.

Researchers suggested that the 44% rate of patients with acute GI bleeding who did not receive digital rectal examinations was higher than had been reported in previous studies. The difference had been the result of relying solely on ED clinician notes for this data, without including notes from admitting or consulting clinicians. The authors also were unable to determine the reasons these examinations were not conducted.

Shrestha MP, Borgstrom M, Trowers E. Digital rectal examination reduces hospital admissions, endoscopies, and medical therapy in patients with acute gastrointestinal bleeding. Am J Med. 2017;130(7):819-825. doi: 10.1016/j.amjmed.2017.01.036.

In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.¹ Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.^1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.^4-6

Background

In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.⁴ Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.⁷ The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.⁸

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).³ Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.³ According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.³

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.³

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.⁴ However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).⁴ Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).⁴ Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.^1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.⁵ One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.⁹ Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.⁹

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.^4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.¹⁰ Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.¹¹ Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.⁴ Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.⁴ Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).⁹ Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

Ketamine

Recently, researchers have identified ketamine as a potential therapeutic option for depression and SI. A single ketamine infusion treatment has a rapid response, minimal AEs, and potentially long-lasting efficacy with SI, which would make it ideal for the treatment of acutely suicidal patients.⁴ Ketamine is an N-methyl-D-aspartate receptor (NMDAR) inhibitor that also has been found to be a weak μ- and κ-opioid receptor agonist and an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. Inhibition of the NMDAR results in analgesia, and ketamine is approved for the induction of anesthesia, pain relief, and sedation.¹²

Although AEs such as hallucinations and sedation create the potential for dangerous recreational use, ketamine is safely used in health care settings for a variety of indications. Effects are noted within 5 minutes of administration if given by infusion, and the main effects can last between 20 and 40 minutes.

Ketamine has a complex pharmacology and plays a role in other cell signaling mechanisms, but the significance of these additional mechanisms in the therapeutic effects of ketamine have only recently been elucidated. Preclinical studies indicate a probable NMDAR inhibition-independent mechanism responsible for the antidepressant response to ketamine.^13,14 The complex associations with rapamycin signaling, eukaryotic elongation factor 2 dephosphorylation, increased synthesis of brain-derived neurotrophic factor, and activation of glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors have been linked to its rapid antidepressant effect and ketamine’s induction of synaptogenesis within the limbic system.^13,14

Clinical Research

Ketamine was studied as an adjunctive treatment to psychotherapy for addictions as far back as the 1970s.¹⁵ The available reports indicate a universally positive result, with increased rates of remission and decreased rates of relapse attributed to ketamine’s ability to alter one’s thought processes by reinforcing limbic-cortex interactions that facilitate the growth of more positive cognitive schemas and improved emotional attitudes about the self in support of the recovery process.¹⁵

Neurobiologic studies have shown that treatment with ketamine has a direct and immediate effect on neuronal pathways of the limbic system. It is known to regulate the mind’s reaction to positive stimuli by reversing the depressed subject’s blunted reaction to positive faces.¹⁶ This rapid normalization of the positive faces test is unique to ketamine infusion and is not seen in tests with traditional antidepressants.

In 2000, the first placebo-controlled trial using ketamine for treatment resistant depression (TRD) demonstrated the rapid antidepressant effects of a single dose of ketamine, but this study only looked at these effects for 1 week.¹⁷ In multiple double blind, placebo-controlled trials since then, IV infusion of ketamine was shown to be an effective intervention for TRD.^13,18,19 More recently, a published investigation involving the treatment of MDD showed that ketamine in conjunction with a selective serotonin reuptake inhibitor (SSRI) accelerated and enhanced the effectiveness of the SSRI in reducing depressive symptoms.²⁰

Based on the rapid resolution of depressive symptoms using ketamine, researchers have looked at its effect on suicidality as a secondary measure. A case study of a patient with severe depressive episodes and multiple previous suicidal attempts reported that the patient responded to a single dose of ketamine, described the experience as “being reborn,” and maintained complete remission of SI for the 6-month study period.²¹ In a larger study, 133 TRD patients received a single IV dose of ketamine with significant reductions in SI independent of depressive and anxiety symptoms.²²

Depression Treatment

These results have led to an excitement for ketamine therapy as a novel treatment of depression, and off-label use by treatment centers now exists in several countries to aid those with TRD.²³ This off-label use continues to be controversial, as research has yet to determine the safest most effective route and duration of treatment and whether the ketamine treatment AEs will exceed any accrued therapeutic benefit.¹³

The American Psychological Association Council of Research Task Force on Novel Biomarkers and Treatment critically examined the clinical evidence of ketamine use and has raised important concerns about the use of ketamine in the outpatient setting, administered in the absence of consensus therapeutic monitoring guidelines, and ambitiously marketed as a panacea for TRD.^13,24 A study showed permanent impairment of brain function for both groups compared with monkeys treated with saline infusions.²⁵ In 2016, the FDA gave fast-track approval for an intranasal ketamine that would make the treatment more easily available in the outpatient setting, but this could lead to certain patients developing a dependency on ketamine or engaging in its diversion for recreational use. There are case reports and anecdotes in the literature of patients and research subjects developing drug-seeking behaviors and overuse of ketamine.²⁴ Additionally, the comorbidities associated with TRD and SI have not been fully evaluated. For instance, there is evidence that depressed patients with obsessive compulsive disorder may have worse outcomes that include delayed onset SI.²⁶

There also is concern for the use of ketamine for chronic opioid users. The combination of ketamine with opioids may increase the response to the opioid in an otherwise drug tolerant patient, leading to risk of death by overdose in patients who have not increased their usual dose.²⁷ However, this effect was noted only when ketamine and opioids were administered together, and the effect does not seem to last postinfusion.²⁷

The challenges in treatment of TRD include finding an effective formulation—IV infusion of ketamine requires cardiovascular monitoring and is administered by anesthesiologists. The short duration of action for depression requires repeated infusions, and the frequency and quantity of infusions have not been determined. Efforts to find other NMDAR inhibitors (eg, memantine, nitrous oxide, D-cycloserine, and others) that match ketamine’s antidepressant efficacy but with easier delivery methods and fewer risks have thus far been unsuccessful.¹³ It is now believed that ketamine’s unique ability to activate intracellular signaling pathways linked to synaptic plasticity gives it the antidepressant function. Recent studies have further narrowed ketamine’s antidepressant function to the R- enantiomer of the ketamine metabolite, hydroxynorketamine.¹⁴ The nasal spray for ketamine is the S- enantiomer, which has better bioavailability but may have less antidepressant efficacy compared with the racemic mixture used in ketamine infusions.

Suicide Ideation Treatment

The many challenges faced by researchers and clinicians trying to develop ketamine treatment for TRD may not apply to the treatment of SI. Whereas repeated doses of ketamine cannot reliably produce sustained remission of depression, the few studies that have looked at the long-term effects of ketamine treatment on SI indicate the potential for long-term efficacy after a single IV infusion.^21,22 Although treatment with IV infusions have additional costs and logistics, if it is found beneficial, it could be given in the emergency department (ED) prior to hospitalization and potentially lead to better outcomes.

In 2011, a small preliminary observational study of patients with depression and SI presenting to the ED indicated that SI was rapidly reduced following an infusion of ketamine.²⁸ This study showed that both depressive symptoms and suicidality rapidly and significantly diminished within 40 minutes with no evidence of the recurrence of symptoms 10 days postadministration.

A more recent study used ketamine in a military field hospital to treat SI and also concluded that it could be effective and safe when administered in an ED setting. This preliminary study suggests that ketamine could be a safe and potentially effective medication for rapid reduction of depression and suicidality in a busy ED setting.²⁹ These limited studies involving the use of ketamine in patients with SI show promise with long-term effectiveness. However, more research is needed to clarify whether the efficacy with SI will be similar to the clinical experience seen in TRD; a duration of effect limited to 2 weeks with recurrence after treatment discontinued.²⁴

Conclusion

There has been a compelling accumulation of scientific data since 2000 to support the use of ketamine for the treatment of depression and SI. Ketamine use in patients with these diagnoses showed a rapid decrease of symptoms and minimal AEs among a significant number of patients.^22,30

Although the initial findings involving the use of ketamine in suicidal patients are promising, the clinical use of ketamine needs further research, using larger sample sizes and exploring both the short-term and long-term effects of this medication. Researchers need to further establish the safe and effective route, point of care, and patient type that would best respond to this novel treatment. The initial evidence would suggest that health care providers have every right to be hopeful that ketamine will become the first pharmacologic treatment of acute SI in a majority of patients presenting to EDs, mental health clinics, community hospitals, and VA medical centers.

In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.¹ Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.^1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.^4-6

Background

In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.⁴ Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.⁷ The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.⁸

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).³ Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.³ According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.³

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.³

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.⁴ However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).⁴ Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).⁴ Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.^1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.⁵ One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.⁹ Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.⁹

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.^4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.¹⁰ Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.¹¹ Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.⁴ Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.⁴ Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).⁹ Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

Ketamine

Recently, researchers have identified ketamine as a potential therapeutic option for depression and SI. A single ketamine infusion treatment has a rapid response, minimal AEs, and potentially long-lasting efficacy with SI, which would make it ideal for the treatment of acutely suicidal patients.⁴ Ketamine is an N-methyl-D-aspartate receptor (NMDAR) inhibitor that also has been found to be a weak μ- and κ-opioid receptor agonist and an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. Inhibition of the NMDAR results in analgesia, and ketamine is approved for the induction of anesthesia, pain relief, and sedation.¹²

Although AEs such as hallucinations and sedation create the potential for dangerous recreational use, ketamine is safely used in health care settings for a variety of indications. Effects are noted within 5 minutes of administration if given by infusion, and the main effects can last between 20 and 40 minutes.

Ketamine has a complex pharmacology and plays a role in other cell signaling mechanisms, but the significance of these additional mechanisms in the therapeutic effects of ketamine have only recently been elucidated. Preclinical studies indicate a probable NMDAR inhibition-independent mechanism responsible for the antidepressant response to ketamine.^13,14 The complex associations with rapamycin signaling, eukaryotic elongation factor 2 dephosphorylation, increased synthesis of brain-derived neurotrophic factor, and activation of glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors have been linked to its rapid antidepressant effect and ketamine’s induction of synaptogenesis within the limbic system.^13,14

Clinical Research

Ketamine was studied as an adjunctive treatment to psychotherapy for addictions as far back as the 1970s.¹⁵ The available reports indicate a universally positive result, with increased rates of remission and decreased rates of relapse attributed to ketamine’s ability to alter one’s thought processes by reinforcing limbic-cortex interactions that facilitate the growth of more positive cognitive schemas and improved emotional attitudes about the self in support of the recovery process.¹⁵

Neurobiologic studies have shown that treatment with ketamine has a direct and immediate effect on neuronal pathways of the limbic system. It is known to regulate the mind’s reaction to positive stimuli by reversing the depressed subject’s blunted reaction to positive faces.¹⁶ This rapid normalization of the positive faces test is unique to ketamine infusion and is not seen in tests with traditional antidepressants.

In 2000, the first placebo-controlled trial using ketamine for treatment resistant depression (TRD) demonstrated the rapid antidepressant effects of a single dose of ketamine, but this study only looked at these effects for 1 week.¹⁷ In multiple double blind, placebo-controlled trials since then, IV infusion of ketamine was shown to be an effective intervention for TRD.^13,18,19 More recently, a published investigation involving the treatment of MDD showed that ketamine in conjunction with a selective serotonin reuptake inhibitor (SSRI) accelerated and enhanced the effectiveness of the SSRI in reducing depressive symptoms.²⁰

Based on the rapid resolution of depressive symptoms using ketamine, researchers have looked at its effect on suicidality as a secondary measure. A case study of a patient with severe depressive episodes and multiple previous suicidal attempts reported that the patient responded to a single dose of ketamine, described the experience as “being reborn,” and maintained complete remission of SI for the 6-month study period.²¹ In a larger study, 133 TRD patients received a single IV dose of ketamine with significant reductions in SI independent of depressive and anxiety symptoms.²²

Depression Treatment

These results have led to an excitement for ketamine therapy as a novel treatment of depression, and off-label use by treatment centers now exists in several countries to aid those with TRD.²³ This off-label use continues to be controversial, as research has yet to determine the safest most effective route and duration of treatment and whether the ketamine treatment AEs will exceed any accrued therapeutic benefit.¹³

The American Psychological Association Council of Research Task Force on Novel Biomarkers and Treatment critically examined the clinical evidence of ketamine use and has raised important concerns about the use of ketamine in the outpatient setting, administered in the absence of consensus therapeutic monitoring guidelines, and ambitiously marketed as a panacea for TRD.^13,24 A study showed permanent impairment of brain function for both groups compared with monkeys treated with saline infusions.²⁵ In 2016, the FDA gave fast-track approval for an intranasal ketamine that would make the treatment more easily available in the outpatient setting, but this could lead to certain patients developing a dependency on ketamine or engaging in its diversion for recreational use. There are case reports and anecdotes in the literature of patients and research subjects developing drug-seeking behaviors and overuse of ketamine.²⁴ Additionally, the comorbidities associated with TRD and SI have not been fully evaluated. For instance, there is evidence that depressed patients with obsessive compulsive disorder may have worse outcomes that include delayed onset SI.²⁶

There also is concern for the use of ketamine for chronic opioid users. The combination of ketamine with opioids may increase the response to the opioid in an otherwise drug tolerant patient, leading to risk of death by overdose in patients who have not increased their usual dose.²⁷ However, this effect was noted only when ketamine and opioids were administered together, and the effect does not seem to last postinfusion.²⁷

The challenges in treatment of TRD include finding an effective formulation—IV infusion of ketamine requires cardiovascular monitoring and is administered by anesthesiologists. The short duration of action for depression requires repeated infusions, and the frequency and quantity of infusions have not been determined. Efforts to find other NMDAR inhibitors (eg, memantine, nitrous oxide, D-cycloserine, and others) that match ketamine’s antidepressant efficacy but with easier delivery methods and fewer risks have thus far been unsuccessful.¹³ It is now believed that ketamine’s unique ability to activate intracellular signaling pathways linked to synaptic plasticity gives it the antidepressant function. Recent studies have further narrowed ketamine’s antidepressant function to the R- enantiomer of the ketamine metabolite, hydroxynorketamine.¹⁴ The nasal spray for ketamine is the S- enantiomer, which has better bioavailability but may have less antidepressant efficacy compared with the racemic mixture used in ketamine infusions.

Suicide Ideation Treatment

The many challenges faced by researchers and clinicians trying to develop ketamine treatment for TRD may not apply to the treatment of SI. Whereas repeated doses of ketamine cannot reliably produce sustained remission of depression, the few studies that have looked at the long-term effects of ketamine treatment on SI indicate the potential for long-term efficacy after a single IV infusion.^21,22 Although treatment with IV infusions have additional costs and logistics, if it is found beneficial, it could be given in the emergency department (ED) prior to hospitalization and potentially lead to better outcomes.

In 2011, a small preliminary observational study of patients with depression and SI presenting to the ED indicated that SI was rapidly reduced following an infusion of ketamine.²⁸ This study showed that both depressive symptoms and suicidality rapidly and significantly diminished within 40 minutes with no evidence of the recurrence of symptoms 10 days postadministration.

A more recent study used ketamine in a military field hospital to treat SI and also concluded that it could be effective and safe when administered in an ED setting. This preliminary study suggests that ketamine could be a safe and potentially effective medication for rapid reduction of depression and suicidality in a busy ED setting.²⁹ These limited studies involving the use of ketamine in patients with SI show promise with long-term effectiveness. However, more research is needed to clarify whether the efficacy with SI will be similar to the clinical experience seen in TRD; a duration of effect limited to 2 weeks with recurrence after treatment discontinued.²⁴

Conclusion

There has been a compelling accumulation of scientific data since 2000 to support the use of ketamine for the treatment of depression and SI. Ketamine use in patients with these diagnoses showed a rapid decrease of symptoms and minimal AEs among a significant number of patients.^22,30

Although the initial findings involving the use of ketamine in suicidal patients are promising, the clinical use of ketamine needs further research, using larger sample sizes and exploring both the short-term and long-term effects of this medication. Researchers need to further establish the safe and effective route, point of care, and patient type that would best respond to this novel treatment. The initial evidence would suggest that health care providers have every right to be hopeful that ketamine will become the first pharmacologic treatment of acute SI in a majority of patients presenting to EDs, mental health clinics, community hospitals, and VA medical centers.

In 2014 the suicide rate in the U.S. was 13/100,000, the highest recorded in 28 years.¹ Suicide is now considered the 10th leading cause of death for all ages, and the rate has increased every year from 2000 to 2014 among both women and men and in every age group except those aged ≥ 75 years.^1-3 For those aged 15 to 44 years, suicide is among the top 3 causes of death worldwide.^4-6

Background

In 2013, more than 490,000 hospital visits related to suicide attempts were reported in the U.S.⁴ Health care expenditures related to suicide are estimated at $56.9 billion in combined medical and work loss costs annually and an unmeasurable cost to the affected families.⁷ The mental health care community is desperate for ways to address this epidemic, and the National Academies of Medicine (NAM) has declared that research that directly addresses comparative effectiveness of treatment strategies following a suicide attempt should be a national priority.⁸

The most recent reports from 2014 indicate that the suicide rates are higher for male veterans than for male nonveterans (32.1 vs 20.9 per 100,000, respectively) and are much higher for female veterans than for female nonveterans (28.7 vs 5.2 per 100,000, respectively).³ Suicide rates also may be associated with veteran-specific comorbidities, such as higher rates of depression, anxiety, posttraumatic stress disorder (PTSD), and war-related trauma.³ According to the VHA, the suicide rate for veterans aged > 30 years also is rapidly increasing, and VHA has echoed the calls from NAM to make suicide prevention research a national priority.³

The VA has tried to stem the tide of suicides in veterans by implementing many advances in suicide prevention, including hiring suicide prevention coordinators at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services. Yet the suicide rates for veterans continue to rise and remain higher than the rates in the general population.³

About 90% of deaths by suicide are by persons who have a treatable psychiatric disorder, most commonly a mood disorder, such as depression.⁴ However, most studies show that antidepressant therapy does not provide rapid or significant relief of suicidal ideation (SI).⁴ Therefore, the current standard of care for the treatment of acutely suicidal patients includes a combination of hospitalization, cognitive behavioral therapy or psychotherapy, case management, antidepressant medications, and electroconvulsive therapy (ECT).⁴ Even though these therapies have become more widely available over the past decade, rates of suicide continue to increase.^1,4 These interventions have limited effectiveness in acute settings. Although both intensive outpatient follow-up and routine outpatient care have been studied in relation to the decrease of suicidal behavior, neither intervention has been shown to immediately reduce suicidal behavior significantly in patients.

Suicidality Interventions

Therapy and case management require patients to be well enough to make office visits and follow through with care for periods as long as 1 year, which is often not possible for individuals with severe depression.⁵ One-third of patients who attended 6 months of outpatient therapy consistently still met the criteria for major depressive disorder (MDD), a major risk for suicide attempt.⁹ Antidepressant medications take a minimum of 4 weeks to reach full efficacy, and many patients stop taking the medications before that point because of concern that the medication is not helping or because of adverse effects (AEs), such as sleep disturbance, sexual dysfunction, or weight gain.⁹

Electroconvulsive therapy has been shown to be an effective treatment for patients with depression and suicidal behavior, but adherence with 12 weeks of recommended therapy has been a barrier for this intervention. Additionally, ECT may not provide reduction in SI for 1 to 2 weeks.^4,10 A review of research studies showed that nearly 50% of patients with high-expressed SI did not complete the prescribed amount of ECT due to the length of time to complete the recommended 12 sessions.¹⁰ Therefore, current treatment barriers for suicidal patients include: (1) long periods in treatment for therapy, medication, and ECT before any relief of symptoms is noted; (2) high recidivism rates for MDD symptoms and risk of suicide following treatment; and (3) high treatment dropout rates.

Pharmacologic treatments currently used in suicidal patients have not fared much better. Many have received FDA approval for treatment of associated mental health diagnoses such as bipolar disorder, schizophrenia, or MDD, but there are no approved treatments that specifically target suicidal behavior. Lithium is approved for reducing the long-term risk of SI primarily because it reduces the risk of mood disorders associated with SI, but lithium has not been shown to be effective in acute settings.¹¹ Clozapine is approved for reducing the long-term risk of recurrent suicide in patients with schizophrenia or schizoaffective disorder.⁴ Clozapine has not been shown to be effective in patients with mood disorders, which make up the majority of patients who attempt suicide.⁴ Additionally, both medications are plagued by the same barriers listed earlier, such as long time to effect (it takes an average 4 weeks to reach efficacy), lack of efficacy in acute settings, and AEs (eg, sleep problems, weight gain, and sexual dysfunction).⁹ Thus finding better pharmacologic interventions for suicidal patients is a priority for current research.

Ketamine

Recently, researchers have identified ketamine as a potential therapeutic option for depression and SI. A single ketamine infusion treatment has a rapid response, minimal AEs, and potentially long-lasting efficacy with SI, which would make it ideal for the treatment of acutely suicidal patients.⁴ Ketamine is an N-methyl-D-aspartate receptor (NMDAR) inhibitor that also has been found to be a weak μ- and κ-opioid receptor agonist and an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. Inhibition of the NMDAR results in analgesia, and ketamine is approved for the induction of anesthesia, pain relief, and sedation.¹²

Although AEs such as hallucinations and sedation create the potential for dangerous recreational use, ketamine is safely used in health care settings for a variety of indications. Effects are noted within 5 minutes of administration if given by infusion, and the main effects can last between 20 and 40 minutes.

Ketamine has a complex pharmacology and plays a role in other cell signaling mechanisms, but the significance of these additional mechanisms in the therapeutic effects of ketamine have only recently been elucidated. Preclinical studies indicate a probable NMDAR inhibition-independent mechanism responsible for the antidepressant response to ketamine.^13,14 The complex associations with rapamycin signaling, eukaryotic elongation factor 2 dephosphorylation, increased synthesis of brain-derived neurotrophic factor, and activation of glutamatergic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors have been linked to its rapid antidepressant effect and ketamine’s induction of synaptogenesis within the limbic system.^13,14

Clinical Research

Ketamine was studied as an adjunctive treatment to psychotherapy for addictions as far back as the 1970s.¹⁵ The available reports indicate a universally positive result, with increased rates of remission and decreased rates of relapse attributed to ketamine’s ability to alter one’s thought processes by reinforcing limbic-cortex interactions that facilitate the growth of more positive cognitive schemas and improved emotional attitudes about the self in support of the recovery process.¹⁵

Neurobiologic studies have shown that treatment with ketamine has a direct and immediate effect on neuronal pathways of the limbic system. It is known to regulate the mind’s reaction to positive stimuli by reversing the depressed subject’s blunted reaction to positive faces.¹⁶ This rapid normalization of the positive faces test is unique to ketamine infusion and is not seen in tests with traditional antidepressants.

In 2000, the first placebo-controlled trial using ketamine for treatment resistant depression (TRD) demonstrated the rapid antidepressant effects of a single dose of ketamine, but this study only looked at these effects for 1 week.¹⁷ In multiple double blind, placebo-controlled trials since then, IV infusion of ketamine was shown to be an effective intervention for TRD.^13,18,19 More recently, a published investigation involving the treatment of MDD showed that ketamine in conjunction with a selective serotonin reuptake inhibitor (SSRI) accelerated and enhanced the effectiveness of the SSRI in reducing depressive symptoms.²⁰

Based on the rapid resolution of depressive symptoms using ketamine, researchers have looked at its effect on suicidality as a secondary measure. A case study of a patient with severe depressive episodes and multiple previous suicidal attempts reported that the patient responded to a single dose of ketamine, described the experience as “being reborn,” and maintained complete remission of SI for the 6-month study period.²¹ In a larger study, 133 TRD patients received a single IV dose of ketamine with significant reductions in SI independent of depressive and anxiety symptoms.²²

Depression Treatment

These results have led to an excitement for ketamine therapy as a novel treatment of depression, and off-label use by treatment centers now exists in several countries to aid those with TRD.²³ This off-label use continues to be controversial, as research has yet to determine the safest most effective route and duration of treatment and whether the ketamine treatment AEs will exceed any accrued therapeutic benefit.¹³

The American Psychological Association Council of Research Task Force on Novel Biomarkers and Treatment critically examined the clinical evidence of ketamine use and has raised important concerns about the use of ketamine in the outpatient setting, administered in the absence of consensus therapeutic monitoring guidelines, and ambitiously marketed as a panacea for TRD.^13,24 A study showed permanent impairment of brain function for both groups compared with monkeys treated with saline infusions.²⁵ In 2016, the FDA gave fast-track approval for an intranasal ketamine that would make the treatment more easily available in the outpatient setting, but this could lead to certain patients developing a dependency on ketamine or engaging in its diversion for recreational use. There are case reports and anecdotes in the literature of patients and research subjects developing drug-seeking behaviors and overuse of ketamine.²⁴ Additionally, the comorbidities associated with TRD and SI have not been fully evaluated. For instance, there is evidence that depressed patients with obsessive compulsive disorder may have worse outcomes that include delayed onset SI.²⁶

There also is concern for the use of ketamine for chronic opioid users. The combination of ketamine with opioids may increase the response to the opioid in an otherwise drug tolerant patient, leading to risk of death by overdose in patients who have not increased their usual dose.²⁷ However, this effect was noted only when ketamine and opioids were administered together, and the effect does not seem to last postinfusion.²⁷

The challenges in treatment of TRD include finding an effective formulation—IV infusion of ketamine requires cardiovascular monitoring and is administered by anesthesiologists. The short duration of action for depression requires repeated infusions, and the frequency and quantity of infusions have not been determined. Efforts to find other NMDAR inhibitors (eg, memantine, nitrous oxide, D-cycloserine, and others) that match ketamine’s antidepressant efficacy but with easier delivery methods and fewer risks have thus far been unsuccessful.¹³ It is now believed that ketamine’s unique ability to activate intracellular signaling pathways linked to synaptic plasticity gives it the antidepressant function. Recent studies have further narrowed ketamine’s antidepressant function to the R- enantiomer of the ketamine metabolite, hydroxynorketamine.¹⁴ The nasal spray for ketamine is the S- enantiomer, which has better bioavailability but may have less antidepressant efficacy compared with the racemic mixture used in ketamine infusions.

Suicide Ideation Treatment

The many challenges faced by researchers and clinicians trying to develop ketamine treatment for TRD may not apply to the treatment of SI. Whereas repeated doses of ketamine cannot reliably produce sustained remission of depression, the few studies that have looked at the long-term effects of ketamine treatment on SI indicate the potential for long-term efficacy after a single IV infusion.^21,22 Although treatment with IV infusions have additional costs and logistics, if it is found beneficial, it could be given in the emergency department (ED) prior to hospitalization and potentially lead to better outcomes.

In 2011, a small preliminary observational study of patients with depression and SI presenting to the ED indicated that SI was rapidly reduced following an infusion of ketamine.²⁸ This study showed that both depressive symptoms and suicidality rapidly and significantly diminished within 40 minutes with no evidence of the recurrence of symptoms 10 days postadministration.

A more recent study used ketamine in a military field hospital to treat SI and also concluded that it could be effective and safe when administered in an ED setting. This preliminary study suggests that ketamine could be a safe and potentially effective medication for rapid reduction of depression and suicidality in a busy ED setting.²⁹ These limited studies involving the use of ketamine in patients with SI show promise with long-term effectiveness. However, more research is needed to clarify whether the efficacy with SI will be similar to the clinical experience seen in TRD; a duration of effect limited to 2 weeks with recurrence after treatment discontinued.²⁴

Conclusion

There has been a compelling accumulation of scientific data since 2000 to support the use of ketamine for the treatment of depression and SI. Ketamine use in patients with these diagnoses showed a rapid decrease of symptoms and minimal AEs among a significant number of patients.^22,30

Although the initial findings involving the use of ketamine in suicidal patients are promising, the clinical use of ketamine needs further research, using larger sample sizes and exploring both the short-term and long-term effects of this medication. Researchers need to further establish the safe and effective route, point of care, and patient type that would best respond to this novel treatment. The initial evidence would suggest that health care providers have every right to be hopeful that ketamine will become the first pharmacologic treatment of acute SI in a majority of patients presenting to EDs, mental health clinics, community hospitals, and VA medical centers.

In the current health care environment, there is an increasing demand for objective assessment of disease states.¹ This is particularly apparent in the realm of behavioral health, where documentation of outcomes lags that of other areas of medicine.

In 2012, the additional health care costs incurred by persons with mental health diagnoses were estimated to be $293 billion among commercially insured, Medicaid, and Medicare beneficiaries in the United States—a figure that is 273% higher than the cost for those without psychiatric diagnoses.² Psychiatric and medical illnesses can be so tightly linked that accurate diagnosis and treatment of psychiatric disorders becomes essential to control medical illnesses. It is not surprising that there is increased scrutiny to the ways in which behavioral health care can be objectively assessed and monitored, and payers such as the Centers for Medicare and Medicaid Services increasingly require objective documentation of disease state improvement for payment.³

Support for objective assessment of disease derives from the collaborative care model. This model is designed to better integrate mental health and primary care (among other practices) by establishing the Patient-Centered Medical Home and emphasizing screening and monitoring patient-reported outcomes over time to assess treatment response.⁴ This approach, which is endorsed by the American Psychiatric Association, is associated with significant improvements in outcomes compared with usual care.⁵ It tracks patient progress using validated clinical rating scales and other screening tools (eg, Patient Health Questionnaire [PHQ-9] for depression), an approach that is analogous to how patients with type 2 diabetes are monitored by A1C lab tests.⁶ An extensive body of research supports the impact of this approach on treatment. A 2012 Cochrane review associated collaborative care with significant improvements in depression and anxiety outcomes compared with usual treatment.⁷

Despite these findings, a recent Kennedy Forum brief asserts that behavioral health is characterized by a "lack of systematic measurement to determine whether patients are responding to treatment."⁸ That same brief points to the many validated, easy-to-administer rating scales and screening tools that can reliably measure the frequency and severity of psychiatric symptoms over time, and likens the lack of their use to "treating high blood pressure without using a blood pressure cuff to measure if a patient's blood pressure is improving."⁸ In fact, it is estimated that only 18% of psychiatrists and 11% of psychologists use rating scales routinely.^9,10 This lack of use denies clinicians important information that can help detect deterioration or lack of improvement in their patients; implementing these scales in primary care can help early detection of behavioral health problems.

Behavioral health is replete with rating scales and screening tools, and the number of competing scales can make choosing a measure difficult.¹ Nonetheless, not all scales are appropriate for clinical use; many are designed for research, for instance, and are lengthy and difficult to administer.

Let's review a number of rating scales that are brief, useful, and easy to administer. A framework for the screening tools addressed in this article is available on the federally funded Center for Integrated Health Solutions website (www.integration.samhsa.gov). This site promotes the use of tools designed to assist in screening and monitoring for depression, anxiety, bipolar disorder, substance use, and suicidality.¹¹

QUALITY CRITERIA FOR RATING SCALES

The quality of a rating scale is determined by the following attributes.

Objectivity. The ability of a scale to obtain the same results, regardless of who administers, analyzes, or interprets it.

Reliability. The ability of a scale to convey consistent and reproducible information across time, patients, and raters.

Validity. The degree to which the scale measures what it is supposed to measure (eg, depressive symptoms). Sensitivity and specificity are measures of validity and provide additional information about the rating scale; namely, whether the scale can detect the presence of a disease (sensitivity) and whether it detects only that disease or condition and not another (specificity).

Establishment of norms. Whether a scale provides reference values for different clinical groups.

Practicability. The resources required to administer the assessment instrument in terms of time, staff, and material.¹²

In addition to meeting these quality criteria, selection of a scale can be based on whether it is self-rated or observer-rated. Advantages to self-rated scales, such as the PHQ-9, Mood Disorder Questionnaire (MDQ), and Generalized Anxiety Disorder 7-item (GAD-7) scale, are their practicability—they are easy to administer and don't require much time—and their use in evaluating and raising awareness of subjective states.

However, reliability may be a concern, as some patients may lack insight or exaggerate or mask symptoms when completing such scales.¹³ Both observer- and self-rated scales can be used together to minimize bias, identify symptoms that might have been missed/not addressed in the clinical interview, and drive clinical decision-making. Both can also help patients communicate with their providers and make them feel more involved in clinical decision-making.⁸

ENDORSED RATING SCALES

The following scales have met many of the quality criteria described here and are endorsed by the government payer system. They can easily be incorporated into clinical practice and will provide useful clinical information that can assist in diagnosis and monitoring patient outcomes.

Patient Health Questionnaire

PHQ-9 is a nine-item self-report questionnaire that can help to detect depression and supplement a thorough mental health interview. It scores the nine DSM-IV criteria for depression on a scale of 0 (not at all) to 3 (nearly every day). It is a public resource that is easy to find online, available without cost in several languages, and takes just a few minutes to complete.¹⁴

PHQ-9 has shown excellent test-retest reliability in screening for depression, and normative data on the instrument's use are available in various clinical populations.¹⁵ Research has shown that as PHQ-9 depression scores increase, functional status decreases, while depressive symptoms, sick days, and health care utilization increase.¹⁵ In one study, a PHQ-9 score of ≥ 10 had 88% sensitivity and specificity for detecting depression, with scores of 5, 10, 15, and 20 indicating mild, moderate, moderately severe, and severe depression, respectively.¹⁶ In addition to its use as a screening tool, PHQ-9 is a responsive and reliable measure of depression treatment outcomes.¹⁷

Mood Disorder Questionnaire

MDQ is another brief, self-report questionnaire that is available online. It is designed to identify and monitor patients who are likely to meet diagnostic criteria for bipolar disorder.^18,19

The first question on the MDQ asks if the patient has experienced any of 13 common mood and behavior symptoms. The second question asks if these symptoms have ever occurred at the same time, and the third asks the degree to which the patient finds the symptoms to be problematic. The remaining two questions provide additional clinical information, addressing family history of manic-depressive illness or bipolar disorder and whether a diagnosis of either disorder has been made.

The MDQ has shown validity in assessing bipolar disorder symptoms in a general population, although recent research suggests that imprecise recall bias may limit its reliability in detecting hypomanic episodes earlier in life.^20,21 Nonetheless, its specificity of > 97% means that it will effectively screen out just about all true negatives.¹⁸

Generalized Anxiety Disorder 7-item scale

The GAD-7 scale is a brief, self-administered questionnaire for screening and measuring severity of GAD.²² It asks patients to rate seven items that represent problems with general anxiety and scores each item on a scale of 0 (not at all) to 3 (nearly every day). Similar to the other measures, it is easily accessible online.

Research evidence supports the reliability and validity of GAD-7 as a measure of anxiety in the general population. Sensitivity and specificity are 89% and 82%, respectively. Normative data for age- and sex-specific subgroups support its use across age groups and in both males and females.²³ The GAD-7 performs well for detecting and monitoring not only GAD but also panic disorder, social anxiety disorder, and posttraumatic stress disorder.²⁴

CAGE questionnaire for detection of substance use

The CAGE questionnaire is a widely used screening tool that was originally developed to detect alcohol abuse but has been adapted to assess other substance abuse.^25,26 The omission of substance abuse from diagnostic consideration can have a major effect on quality of care, because substance abuse can be the underlying cause of other diseases. Therefore, routine administration of this instrument in clinical practice can lead to better understanding and monitoring of patient health.²⁷

Similar to other instruments, CAGE is free and available online.²⁷ It contains four simple questions, with 1 point assigned to each positive answer (see Table); the simple mnemonic makes the questions easy to ­remember and to administer in a clinical setting.

CAGE has demonstrated validity, with one study determining that scores ≥ 2 had a specificity and sensitivity of 76% and 93%, respectively, for identifying excessive drinking, and a specificity and sensitivity of 77% and 91%, respectively, for identifying alcohol abuse.²⁸

Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS was developed by researchers at Columbia University to assess the severity of and track changes over time in suicidal ideation and behavior. C-SSRS is two pages and takes only a few minutes to administer; however, it also may be completed as a self-report measure. The questions are phrased in an interview format, and while clinicians are encouraged to receive training prior to its administration, specific training in mental health is not required.

The "Lifetime/Recent" version allows practitioners to gather lifetime history of suicidality as well as any recent suicidal ideation and/or behavior, whereas the "Since Last Visit" version of the scale assesses suicidality in patients who have completed at least one Lifetime/Recent C-SSRS assessment. A truncated, six-item "Screener" version is typically used in emergency situations. A risk assessment can be added to either the Full or Screener version to summarize the answers from C-SSRS and document risk and protective factors.²⁹

Several studies have found C-SSRS to be reliable and valid for identifying suicide risk in children and adults.^30,31USA Today reported that an individual exhibiting even a single behavior identified by the scale is eight to 10 times more likely to complete suicide.³² In addition, the C-SSRS has helped reduce the suicide rate by 65% in one of the largest providers of community-based behavioral health care in the United States.³²

USING SCALES TO AUGMENT CARE

Each of the scales described in this article can easily be incorporated into clinical practice. The information the scales provide can be used to track progression of symptoms and effectiveness of treatment. Although rating scales should never be used alone to establish a diagnosis or clinical treatment plan, they can and should be used to augment information from the clinician's assessment and follow-up interviews.⁵

In the current health care environment, there is an increasing demand for objective assessment of disease states.¹ This is particularly apparent in the realm of behavioral health, where documentation of outcomes lags that of other areas of medicine.

In 2012, the additional health care costs incurred by persons with mental health diagnoses were estimated to be $293 billion among commercially insured, Medicaid, and Medicare beneficiaries in the United States—a figure that is 273% higher than the cost for those without psychiatric diagnoses.² Psychiatric and medical illnesses can be so tightly linked that accurate diagnosis and treatment of psychiatric disorders becomes essential to control medical illnesses. It is not surprising that there is increased scrutiny to the ways in which behavioral health care can be objectively assessed and monitored, and payers such as the Centers for Medicare and Medicaid Services increasingly require objective documentation of disease state improvement for payment.³

Support for objective assessment of disease derives from the collaborative care model. This model is designed to better integrate mental health and primary care (among other practices) by establishing the Patient-Centered Medical Home and emphasizing screening and monitoring patient-reported outcomes over time to assess treatment response.⁴ This approach, which is endorsed by the American Psychiatric Association, is associated with significant improvements in outcomes compared with usual care.⁵ It tracks patient progress using validated clinical rating scales and other screening tools (eg, Patient Health Questionnaire [PHQ-9] for depression), an approach that is analogous to how patients with type 2 diabetes are monitored by A1C lab tests.⁶ An extensive body of research supports the impact of this approach on treatment. A 2012 Cochrane review associated collaborative care with significant improvements in depression and anxiety outcomes compared with usual treatment.⁷

Despite these findings, a recent Kennedy Forum brief asserts that behavioral health is characterized by a "lack of systematic measurement to determine whether patients are responding to treatment."⁸ That same brief points to the many validated, easy-to-administer rating scales and screening tools that can reliably measure the frequency and severity of psychiatric symptoms over time, and likens the lack of their use to "treating high blood pressure without using a blood pressure cuff to measure if a patient's blood pressure is improving."⁸ In fact, it is estimated that only 18% of psychiatrists and 11% of psychologists use rating scales routinely.^9,10 This lack of use denies clinicians important information that can help detect deterioration or lack of improvement in their patients; implementing these scales in primary care can help early detection of behavioral health problems.

Behavioral health is replete with rating scales and screening tools, and the number of competing scales can make choosing a measure difficult.¹ Nonetheless, not all scales are appropriate for clinical use; many are designed for research, for instance, and are lengthy and difficult to administer.

Let's review a number of rating scales that are brief, useful, and easy to administer. A framework for the screening tools addressed in this article is available on the federally funded Center for Integrated Health Solutions website (www.integration.samhsa.gov). This site promotes the use of tools designed to assist in screening and monitoring for depression, anxiety, bipolar disorder, substance use, and suicidality.¹¹

QUALITY CRITERIA FOR RATING SCALES

The quality of a rating scale is determined by the following attributes.

Objectivity. The ability of a scale to obtain the same results, regardless of who administers, analyzes, or interprets it.

Reliability. The ability of a scale to convey consistent and reproducible information across time, patients, and raters.

Validity. The degree to which the scale measures what it is supposed to measure (eg, depressive symptoms). Sensitivity and specificity are measures of validity and provide additional information about the rating scale; namely, whether the scale can detect the presence of a disease (sensitivity) and whether it detects only that disease or condition and not another (specificity).

Establishment of norms. Whether a scale provides reference values for different clinical groups.

Practicability. The resources required to administer the assessment instrument in terms of time, staff, and material.¹²

In addition to meeting these quality criteria, selection of a scale can be based on whether it is self-rated or observer-rated. Advantages to self-rated scales, such as the PHQ-9, Mood Disorder Questionnaire (MDQ), and Generalized Anxiety Disorder 7-item (GAD-7) scale, are their practicability—they are easy to administer and don't require much time—and their use in evaluating and raising awareness of subjective states.

However, reliability may be a concern, as some patients may lack insight or exaggerate or mask symptoms when completing such scales.¹³ Both observer- and self-rated scales can be used together to minimize bias, identify symptoms that might have been missed/not addressed in the clinical interview, and drive clinical decision-making. Both can also help patients communicate with their providers and make them feel more involved in clinical decision-making.⁸

ENDORSED RATING SCALES

The following scales have met many of the quality criteria described here and are endorsed by the government payer system. They can easily be incorporated into clinical practice and will provide useful clinical information that can assist in diagnosis and monitoring patient outcomes.

Patient Health Questionnaire

PHQ-9 is a nine-item self-report questionnaire that can help to detect depression and supplement a thorough mental health interview. It scores the nine DSM-IV criteria for depression on a scale of 0 (not at all) to 3 (nearly every day). It is a public resource that is easy to find online, available without cost in several languages, and takes just a few minutes to complete.¹⁴

PHQ-9 has shown excellent test-retest reliability in screening for depression, and normative data on the instrument's use are available in various clinical populations.¹⁵ Research has shown that as PHQ-9 depression scores increase, functional status decreases, while depressive symptoms, sick days, and health care utilization increase.¹⁵ In one study, a PHQ-9 score of ≥ 10 had 88% sensitivity and specificity for detecting depression, with scores of 5, 10, 15, and 20 indicating mild, moderate, moderately severe, and severe depression, respectively.¹⁶ In addition to its use as a screening tool, PHQ-9 is a responsive and reliable measure of depression treatment outcomes.¹⁷

Mood Disorder Questionnaire

MDQ is another brief, self-report questionnaire that is available online. It is designed to identify and monitor patients who are likely to meet diagnostic criteria for bipolar disorder.^18,19

The first question on the MDQ asks if the patient has experienced any of 13 common mood and behavior symptoms. The second question asks if these symptoms have ever occurred at the same time, and the third asks the degree to which the patient finds the symptoms to be problematic. The remaining two questions provide additional clinical information, addressing family history of manic-depressive illness or bipolar disorder and whether a diagnosis of either disorder has been made.

The MDQ has shown validity in assessing bipolar disorder symptoms in a general population, although recent research suggests that imprecise recall bias may limit its reliability in detecting hypomanic episodes earlier in life.^20,21 Nonetheless, its specificity of > 97% means that it will effectively screen out just about all true negatives.¹⁸

Generalized Anxiety Disorder 7-item scale

The GAD-7 scale is a brief, self-administered questionnaire for screening and measuring severity of GAD.²² It asks patients to rate seven items that represent problems with general anxiety and scores each item on a scale of 0 (not at all) to 3 (nearly every day). Similar to the other measures, it is easily accessible online.

Research evidence supports the reliability and validity of GAD-7 as a measure of anxiety in the general population. Sensitivity and specificity are 89% and 82%, respectively. Normative data for age- and sex-specific subgroups support its use across age groups and in both males and females.²³ The GAD-7 performs well for detecting and monitoring not only GAD but also panic disorder, social anxiety disorder, and posttraumatic stress disorder.²⁴

CAGE questionnaire for detection of substance use

The CAGE questionnaire is a widely used screening tool that was originally developed to detect alcohol abuse but has been adapted to assess other substance abuse.^25,26 The omission of substance abuse from diagnostic consideration can have a major effect on quality of care, because substance abuse can be the underlying cause of other diseases. Therefore, routine administration of this instrument in clinical practice can lead to better understanding and monitoring of patient health.²⁷

Similar to other instruments, CAGE is free and available online.²⁷ It contains four simple questions, with 1 point assigned to each positive answer (see Table); the simple mnemonic makes the questions easy to ­remember and to administer in a clinical setting.

CAGE has demonstrated validity, with one study determining that scores ≥ 2 had a specificity and sensitivity of 76% and 93%, respectively, for identifying excessive drinking, and a specificity and sensitivity of 77% and 91%, respectively, for identifying alcohol abuse.²⁸

Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS was developed by researchers at Columbia University to assess the severity of and track changes over time in suicidal ideation and behavior. C-SSRS is two pages and takes only a few minutes to administer; however, it also may be completed as a self-report measure. The questions are phrased in an interview format, and while clinicians are encouraged to receive training prior to its administration, specific training in mental health is not required.

The "Lifetime/Recent" version allows practitioners to gather lifetime history of suicidality as well as any recent suicidal ideation and/or behavior, whereas the "Since Last Visit" version of the scale assesses suicidality in patients who have completed at least one Lifetime/Recent C-SSRS assessment. A truncated, six-item "Screener" version is typically used in emergency situations. A risk assessment can be added to either the Full or Screener version to summarize the answers from C-SSRS and document risk and protective factors.²⁹

Several studies have found C-SSRS to be reliable and valid for identifying suicide risk in children and adults.^30,31USA Today reported that an individual exhibiting even a single behavior identified by the scale is eight to 10 times more likely to complete suicide.³² In addition, the C-SSRS has helped reduce the suicide rate by 65% in one of the largest providers of community-based behavioral health care in the United States.³²

USING SCALES TO AUGMENT CARE

Each of the scales described in this article can easily be incorporated into clinical practice. The information the scales provide can be used to track progression of symptoms and effectiveness of treatment. Although rating scales should never be used alone to establish a diagnosis or clinical treatment plan, they can and should be used to augment information from the clinician's assessment and follow-up interviews.⁵

In the current health care environment, there is an increasing demand for objective assessment of disease states.¹ This is particularly apparent in the realm of behavioral health, where documentation of outcomes lags that of other areas of medicine.

In 2012, the additional health care costs incurred by persons with mental health diagnoses were estimated to be $293 billion among commercially insured, Medicaid, and Medicare beneficiaries in the United States—a figure that is 273% higher than the cost for those without psychiatric diagnoses.² Psychiatric and medical illnesses can be so tightly linked that accurate diagnosis and treatment of psychiatric disorders becomes essential to control medical illnesses. It is not surprising that there is increased scrutiny to the ways in which behavioral health care can be objectively assessed and monitored, and payers such as the Centers for Medicare and Medicaid Services increasingly require objective documentation of disease state improvement for payment.³

Support for objective assessment of disease derives from the collaborative care model. This model is designed to better integrate mental health and primary care (among other practices) by establishing the Patient-Centered Medical Home and emphasizing screening and monitoring patient-reported outcomes over time to assess treatment response.⁴ This approach, which is endorsed by the American Psychiatric Association, is associated with significant improvements in outcomes compared with usual care.⁵ It tracks patient progress using validated clinical rating scales and other screening tools (eg, Patient Health Questionnaire [PHQ-9] for depression), an approach that is analogous to how patients with type 2 diabetes are monitored by A1C lab tests.⁶ An extensive body of research supports the impact of this approach on treatment. A 2012 Cochrane review associated collaborative care with significant improvements in depression and anxiety outcomes compared with usual treatment.⁷

Despite these findings, a recent Kennedy Forum brief asserts that behavioral health is characterized by a "lack of systematic measurement to determine whether patients are responding to treatment."⁸ That same brief points to the many validated, easy-to-administer rating scales and screening tools that can reliably measure the frequency and severity of psychiatric symptoms over time, and likens the lack of their use to "treating high blood pressure without using a blood pressure cuff to measure if a patient's blood pressure is improving."⁸ In fact, it is estimated that only 18% of psychiatrists and 11% of psychologists use rating scales routinely.^9,10 This lack of use denies clinicians important information that can help detect deterioration or lack of improvement in their patients; implementing these scales in primary care can help early detection of behavioral health problems.

Behavioral health is replete with rating scales and screening tools, and the number of competing scales can make choosing a measure difficult.¹ Nonetheless, not all scales are appropriate for clinical use; many are designed for research, for instance, and are lengthy and difficult to administer.

Let's review a number of rating scales that are brief, useful, and easy to administer. A framework for the screening tools addressed in this article is available on the federally funded Center for Integrated Health Solutions website (www.integration.samhsa.gov). This site promotes the use of tools designed to assist in screening and monitoring for depression, anxiety, bipolar disorder, substance use, and suicidality.¹¹

QUALITY CRITERIA FOR RATING SCALES

The quality of a rating scale is determined by the following attributes.

Objectivity. The ability of a scale to obtain the same results, regardless of who administers, analyzes, or interprets it.

Reliability. The ability of a scale to convey consistent and reproducible information across time, patients, and raters.

Validity. The degree to which the scale measures what it is supposed to measure (eg, depressive symptoms). Sensitivity and specificity are measures of validity and provide additional information about the rating scale; namely, whether the scale can detect the presence of a disease (sensitivity) and whether it detects only that disease or condition and not another (specificity).

Establishment of norms. Whether a scale provides reference values for different clinical groups.

Practicability. The resources required to administer the assessment instrument in terms of time, staff, and material.¹²

In addition to meeting these quality criteria, selection of a scale can be based on whether it is self-rated or observer-rated. Advantages to self-rated scales, such as the PHQ-9, Mood Disorder Questionnaire (MDQ), and Generalized Anxiety Disorder 7-item (GAD-7) scale, are their practicability—they are easy to administer and don't require much time—and their use in evaluating and raising awareness of subjective states.

However, reliability may be a concern, as some patients may lack insight or exaggerate or mask symptoms when completing such scales.¹³ Both observer- and self-rated scales can be used together to minimize bias, identify symptoms that might have been missed/not addressed in the clinical interview, and drive clinical decision-making. Both can also help patients communicate with their providers and make them feel more involved in clinical decision-making.⁸

ENDORSED RATING SCALES

The following scales have met many of the quality criteria described here and are endorsed by the government payer system. They can easily be incorporated into clinical practice and will provide useful clinical information that can assist in diagnosis and monitoring patient outcomes.

Patient Health Questionnaire

PHQ-9 is a nine-item self-report questionnaire that can help to detect depression and supplement a thorough mental health interview. It scores the nine DSM-IV criteria for depression on a scale of 0 (not at all) to 3 (nearly every day). It is a public resource that is easy to find online, available without cost in several languages, and takes just a few minutes to complete.¹⁴

PHQ-9 has shown excellent test-retest reliability in screening for depression, and normative data on the instrument's use are available in various clinical populations.¹⁵ Research has shown that as PHQ-9 depression scores increase, functional status decreases, while depressive symptoms, sick days, and health care utilization increase.¹⁵ In one study, a PHQ-9 score of ≥ 10 had 88% sensitivity and specificity for detecting depression, with scores of 5, 10, 15, and 20 indicating mild, moderate, moderately severe, and severe depression, respectively.¹⁶ In addition to its use as a screening tool, PHQ-9 is a responsive and reliable measure of depression treatment outcomes.¹⁷

Mood Disorder Questionnaire

MDQ is another brief, self-report questionnaire that is available online. It is designed to identify and monitor patients who are likely to meet diagnostic criteria for bipolar disorder.^18,19

The first question on the MDQ asks if the patient has experienced any of 13 common mood and behavior symptoms. The second question asks if these symptoms have ever occurred at the same time, and the third asks the degree to which the patient finds the symptoms to be problematic. The remaining two questions provide additional clinical information, addressing family history of manic-depressive illness or bipolar disorder and whether a diagnosis of either disorder has been made.

The MDQ has shown validity in assessing bipolar disorder symptoms in a general population, although recent research suggests that imprecise recall bias may limit its reliability in detecting hypomanic episodes earlier in life.^20,21 Nonetheless, its specificity of > 97% means that it will effectively screen out just about all true negatives.¹⁸

Generalized Anxiety Disorder 7-item scale

The GAD-7 scale is a brief, self-administered questionnaire for screening and measuring severity of GAD.²² It asks patients to rate seven items that represent problems with general anxiety and scores each item on a scale of 0 (not at all) to 3 (nearly every day). Similar to the other measures, it is easily accessible online.

Research evidence supports the reliability and validity of GAD-7 as a measure of anxiety in the general population. Sensitivity and specificity are 89% and 82%, respectively. Normative data for age- and sex-specific subgroups support its use across age groups and in both males and females.²³ The GAD-7 performs well for detecting and monitoring not only GAD but also panic disorder, social anxiety disorder, and posttraumatic stress disorder.²⁴

CAGE questionnaire for detection of substance use

The CAGE questionnaire is a widely used screening tool that was originally developed to detect alcohol abuse but has been adapted to assess other substance abuse.^25,26 The omission of substance abuse from diagnostic consideration can have a major effect on quality of care, because substance abuse can be the underlying cause of other diseases. Therefore, routine administration of this instrument in clinical practice can lead to better understanding and monitoring of patient health.²⁷

Similar to other instruments, CAGE is free and available online.²⁷ It contains four simple questions, with 1 point assigned to each positive answer (see Table); the simple mnemonic makes the questions easy to ­remember and to administer in a clinical setting.

CAGE has demonstrated validity, with one study determining that scores ≥ 2 had a specificity and sensitivity of 76% and 93%, respectively, for identifying excessive drinking, and a specificity and sensitivity of 77% and 91%, respectively, for identifying alcohol abuse.²⁸

Columbia Suicide Severity Rating Scale (C-SSRS)

C-SSRS was developed by researchers at Columbia University to assess the severity of and track changes over time in suicidal ideation and behavior. C-SSRS is two pages and takes only a few minutes to administer; however, it also may be completed as a self-report measure. The questions are phrased in an interview format, and while clinicians are encouraged to receive training prior to its administration, specific training in mental health is not required.

The "Lifetime/Recent" version allows practitioners to gather lifetime history of suicidality as well as any recent suicidal ideation and/or behavior, whereas the "Since Last Visit" version of the scale assesses suicidality in patients who have completed at least one Lifetime/Recent C-SSRS assessment. A truncated, six-item "Screener" version is typically used in emergency situations. A risk assessment can be added to either the Full or Screener version to summarize the answers from C-SSRS and document risk and protective factors.²⁹

Several studies have found C-SSRS to be reliable and valid for identifying suicide risk in children and adults.^30,31USA Today reported that an individual exhibiting even a single behavior identified by the scale is eight to 10 times more likely to complete suicide.³² In addition, the C-SSRS has helped reduce the suicide rate by 65% in one of the largest providers of community-based behavioral health care in the United States.³²

USING SCALES TO AUGMENT CARE

Each of the scales described in this article can easily be incorporated into clinical practice. The information the scales provide can be used to track progression of symptoms and effectiveness of treatment. Although rating scales should never be used alone to establish a diagnosis or clinical treatment plan, they can and should be used to augment information from the clinician's assessment and follow-up interviews.⁵

Atopic dermatitis (AD) is a disease that finally is coming of age in dermatology research. New topical agents and systemic biologic agents offer patients with AD other options for medical management. This article provides a practical review of prevention strategies and treatment guidelines for AD.

PREVENTION

Prevention strategies for AD have been largely unsuccessful in the past, which may relate to factors such as prenatal triggers.¹ However, some newer interventional studies have shown some promise in AD prevention in specific settings. For example, a randomized trial of infants in the United States and United Kingdom at high risk for AD (ie, family history of atopy) reported that the AD risk was reduced by 50% when patients were treated with at least once-daily application of full-body emollients for 6 months (beginning by 3 weeks of life).² The strategy of daily application of emollients for avoidance of AD in infants with a family history of AD is reasonable but may not offer lifetime prevention, and the benefit in children not from AD families is unknown.

Other trials to prevent AD have included usage of dust avoidance and dust covers for mattresses. This strategy showed modest benefit in reducing the incidence of atopic diatheses in the first year³ but did not gain endorsement by the most recent guidelines of the American Academy of Dermatology (AAD).⁴

Prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus has shown promise in prevention.⁵ The exact regimen likely makes an impact on efficacy. An early study showed the usage of probiotics (eg, Lactobacillus reuteri) prenatally in pregnant women and postnatally in infants resulted in no reduction in occurrence of AD and possible reduction in IgE-associated AD.⁶ Kalliomäki et al⁷ demonstrated that L rhamnosus GG alone reduced AD by half in at-risk infants in a double-blind, placebo-controlled trial. On the other hand, Taylor et al⁸ performed a study of probiotic supplementation in which patients at high risk for AD developed higher rates of allergen sensitization. The most successful recent trial involved the randomization of 415 pregnant women to receive interventions from 36 weeks’ gestation until 3 months postpartum.⁹ The intervention was a randomized comparison of milk without probiotics versus a blend of probiotic milk containing L rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp lactis Bb-12. At 6 years of age, 81 babies who consumed probiotic milk and 82 babies who consumed milk without probiotics were available for testing. The strategy caused a statistically significant reduction in AD in the complete case analysis (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P=.027; number needed to treat, 6). Sadly, other allergic diseases were not prevented in this study.⁹

MANAGEMENT OF AD

There currently is no cure or perfected prevention technique for AD. As a result, therapy focuses on avoiding triggers and alleviating symptoms.¹⁰ Recent guidelines from the AAD state that“[t]he ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the disease.”¹¹ Skin-directed therapies are the first line of treatment including emollients, gentle skin care, and topical medicaments. In AD, therapies are needed to reduce disease activity and flare severity, clear flares, and provide relief.

Parental education and written eczema action plans are recommended to help patients and parents/guardians follow recommended regimens¹²; Tollefson and Bruckner¹³ for the American Academy of Pediatrics provide an action plan to guide the care of children with atopic dermatitis that is simple, but many others exist online. The eczema action plan usually provides information on how to bathe and what to do when the skin is actively inflamed.

In 2014, a 4-part series of guidelines of care for the management of AD was published by the AAD, replacing prior guidelines.^4,11,14,15 The following sections review some of the important parameters of care highlighted in these management guidelines.

Psychological Support

Appropriate psychological support for AD patients can be sought through counselors, therapists, psychiatrists, and support groups such as the National Eczema Association (https://nationaleczema.org/).

Education

Education is the leading form of medical therapy in patients with AD. Eczema schools are popular in Europe and are just beginning to form in the United States (http://tuh.templehealth.org/content/eczema_school.htm), which can be helpful to educate caregivers and patients with AD. Patient resources online and through support groups with an online presence, in-person meetings, and patient/family conventions can be helpful to AD patients. Often, an initial office visit with a dermatologist involves a review of avoidance of triggers, usage of gentle skin care including bland emollients, and therapeutic regimens for disease activity. This form of verbal education is to be paired with an eczema action plan, a written document that allows individuals to reference recommendations and share information with other caregivers.^12,13,16

Emollients and Gentle Skin Care

Gentle skin care regimens, which includes the usage of synthetic cleansers with a low pH to help maintain the acidity (acid mantle) of the skin, seek to reduce irritation and have been rated as level IA (highest level) in recent AAD guidelines.¹⁴ Although bathing frequency has been emphasized in the guidelines, AD severity as reflected by SCORAD (SCORing Atopic Dermatitis) was not different for daily bathing versus twice weekly.¹⁷ The American Academy of Pediatrics recommended a skin care regimen of bathing every 2 to 3 days in lukewarm water for 10 to 15 minutes, followed by application of emollients that are fragrance free and have few preservatives.¹³ Topical emollients with additives such as colloidal oatmeal, avenanthramides, or ceramides can be used to enhance the skin barrier and are well tolerated in all age groups.^18,19 Despite enhanced emollients, the therapy of AD still requires usage of prescription or over-the-counter TCs and/or topical calcineurin inhibitors (TCIs) in many cases.²⁰

Topical Medication

Children have a relatively higher body surface area–to-weight ratio, allowing for greater potential absorption of topical medicaments and potential side effects from absorption. Types of vehicle, cost, site of application, and availability may impact patient and physician preference in choice of therapeutic topical agent.¹⁴

Topical Corticosteroids
Topical corticosteroids (TCs) are the mainstay of treatment for AD and have been used for more than 60 years^.14,20 Topical corticosteroids provide anti-inflammatory effects on T cells, monocytes, and macrophages, producing altered cytokine activity locally. Topical corticosteroids inhibit collagen synthesis, potentially causing skin atrophy. They also inhibit IL-1, IL-2, IL-6, IFN-α, and tumor necrosis factor α.²¹ Topical corticosteroids are classified as class I (ultra-high potency) to class VII (low potency). In children, low-potency TCs generally are applied to the face, intertriginous areas, groin, and genitalia, and mid-potency corticosteroids are applied to the body, arms, and legs. An even higher-strength agent can be prescribed as a rescue medication in severe cases. After clearance with once- or twice-daily therapy, twice-weekly usage can benefit disease activity.²² Topical corticosteroids reduce inflammation as well as Staphylococcus aureus load through inhibition of cytokines that inhibit antimicrobial peptides. Topical corticosteroids have been endorsed as level IA evidence therapy by the AAD guidelines.¹⁴

Topical corticosteroids, particularly prolonged usage of mid- to high-potency products, have been associated with side effects such as skin atrophy, striae, telangiectases, hypopigmentation, rosacea, acneiform eruptions, focal hypertrichosis, perioral dermatitis, and acne²³; potential systemic side effects include hypothalamic-pituitary-adrenal axis suppression, cataracts, glaucoma (with periocular application), Cushing syndrome, hyperglycemia, hypertension,²³ and growth retardation.¹⁴ Long-term corticosteroid therapy is associated with tachyphylaxis and potential rebound of disease with discontinuation.²⁴ Based on the potential risk of side effects with TCs, the least potent product for the shortest time needed is recommended, with special care for thin skin. Discontinuation when clearance occurs is advised. Allergy to TCs and/or vehicle ingredients such as propylene glycol should be suspected in severe unremitting cases.¹⁴ A recent registry review of children screened for contact dermatitis demonstrated that children with AD had higher sensitization to the steroid tixocortol pivalate.²⁵

Topical Calcineurin Inhibitors
Topical calcineurin inhibitors include pimecrolimus cream 1%, which is approved for mild to moderate AD in adults and children 2 years and older, and tacrolimus ointment 0.03% and 0.1%, which are approved for moderate to severe AD in adults and children aged 2 to 15 years (0.03% formulation only). Topical calcineurin inhibitors can be used as second-line agents in AD in patients who have inadequate response to TCs or who may not be able to use TCs due to the disease site.^10,13,14 Guidelines from the AAD also have endorsed TCIs as level IA evidence for steroid-sparing agents.

Concerns about the reporting of cancers and lymphomas prompted the US Food and Drug Administration to issue a black box warning on TCIs more than 10 years ago. Pimecrolimus, which has little absorption and no notable immunosuppressive effects, has been used without detrimental effect on vaccination and delayed-type hypersensitivities, but many decades of data are lacking.^{10,13,14,17,26-29} Topical calcineurin inhibitors can be used as steroid-sparing agents in lieu of corticosteroids in specific locations such as the face and eyelids and for long-term suppressive therapy twice weekly.³⁰ Intermittent usage and cycling with corticosteroids is advisable,²⁸ but usage intermittently beyond 1 year has not been evaluated.

Topical calcineurin inhibitors are recommended as effective for acute and chronic AD. Their use as maintenance therapy in adults and children, for AD recalcitrant to steroids, for AD in sensitive areas, for steroid-induced atrophy, and for long-term uninterrupted topical steroid usage carries a level IA evidence recommendation. Furthermore, the AAD guidelines have recommended TCIs as steroid-sparing agents with level IA evidence and off-label use of TCIs in children younger than 2 years with level IA evidence. Pretreatment with TCs to reduce stinging has level IIB evidence. Usage for flare prevention is level IA evidence. Routine blood monitoring of TCI-treated patients was not recommended; in fact, the AAD guidelines provided this recommendation as level IA evidence against routine laboratory monitoring of TCI-treated patients.¹⁴

Topical Antibiotics
Topical antibiotics are indicated for the therapy of impetigo and can be used in the setting of impetiginized AD in conjunction with TCs. Recent AAD guidelines suggested against routine usage of topical antistaphylococcal agents as level IA evidence.¹⁴ There is one study supporting usage of topical mupirocin in addition to TCs to heal children with eczema area and severity index scores more than 7 more rapidly in the first week of AD therapy, but in the same study, additive benefit was not demonstrated in AD beyond the first week.³¹ There also are data supporting usage of intranasal mupirocin adjunctively with bleach baths in patients with moderate to severe AD, which was rated as level IIB evidence in the AAD guidelines.^14,32 There are limited data on the long-term utility of topical anti-infectives in AD. The risks of long-term usage could include resistance formation to agents such as mupirocin, contact dermatitis, and lack of efficacy.

Additional Therapeutics

Wet Wraps
Penetration through the stratum corneum is needed for drug activity in AD. Penetration can be enhanced using wet wrap therapy or using ointments, which produce higher relative potency.¹³ Wet wraps overlying a dilute topical medicament have been described as effective in AD and are recommended in AAD guidelines as level IIB evidence.¹⁴ Different wet wrap techniques can be used, including wet pajamas covered by dry pajamas or saline-soaked gauze wrapped around the affected areas and then dry gauze applied over the wet gauze. The methodology used should be tailored to the patient as well as to whether the individual is an inpatient or outpatient.

Bleach Baths
Dilute sodium hypochlorite solution 0.005% (one-quarter cup bleach in 20 gallons of water) has been demonstrated to be beneficial in reduction of disease activity in AD patients with recurrent bacterial infections.³² This simple technique in addition to intranasal mupirocin can reduce AD severity and improve quality of life and is the only ongoing S aureus therapeutic management endorsed by the AAD guidelines for the management of AD.^14,32

Topical and Oral Delivery

Antihistamines
Topical antihistamines are ineffective in AD. Oral antihistamines can be used to reduce pruritus and are most effective when given as sedating agents for sleep enhancement but may be given as nonsedating agents for patients with concomitant allergic disorders such as allergic rhinoconjunctivitis. Paradoxical hyperreactivity with sedating antihistamines is not uncommon in small children, and sedating antihistamine usage should be discontinued in these instances.¹³ Parents of children with AD have reported giving the child antihistamines to sleep was helpful, as well as putting on creams, using special clothes (eg, all cotton), and keeping the room cool.³³ There is level IIIC evidence against use of systemic antihistamines and level IIA evidence for sedating and nonsedating, according to the AAD guidelines.¹⁴

Systemic Therapeutics

Oral therapeutics range from oral antihistamines to oral antibiotics and immunosuppressive medications. Oral antibiotics (level IIB evidence) are reserved for superinfected AD, which is not easily defined for the following reasons: there is no consensus definition of superinfected AD; the majority of active AD lesions when cultured will demonstrate S aureus growth; and most AD lesions ooze, thereby creating the appearance of superinfection. In real-world practice, superinfection can be diagnosed based on the presence of pustules; furuncles; or signs of infection such as tracking erythema, tenderness, severe erosions, or maceration. Clinical judgment is always required.

The immunosuppressive medications used in AD include leukotriene inhibitors, which rarely are effective for AD.³⁴ More effective systemic agents for AD include cyclosporine (level I to IIB evidence), azathioprine (level IIB evidence), mycophenolate mofetil (level IIIC evidence), and methotrexate (level IIB evidence). These agents are indicated for pediatric or adult patients when topical agents and/or phototherapy have failed.¹⁵ Monitoring these agents for side effects includes ongoing evaluation for renal and liver toxicity. Short courses (ie, 6 months) are preferred to minimize side effects.³⁵

Dupilumab, an injectable AD therapy, is approved in the United States. This agent is injected every 2 weeks and binds to the IL-4Rα shared by IL-4 and IL-13. In 4 weeks of monotherapy, 85% of adult patients treated had 50% or greater clearance.³⁶ Recently published consensus opinion from the International Eczema Council recommends assessment of a variety of factors before initiating systemic therapy including comorbid illnesses such as contact allergy, trigger avoidance, superinfection, and impact on quality of life.³⁷

Oral Corticosteroids
Systemic corticosteroids clear patients quickly but provide no sustained improvement; in fact, many patients rebound or have tachyphylaxis. Although short-term corticosteroid usage can break the itch-scratch cycle, long-term usage is associated with osteoporosis, Cushing syndrome, and aseptic necrosis of the femoral head. Decreased linear growth will occur during therapy in children; therefore, systemic steroids are not recommended in children with AD, except for additional or comorbid conditions (eg, asthma or contact dermatitis).⁴

Phototherapy
Phototherapy has been recommended in the AAD guidelines as a second-line treatment after failure of first-line agents (ie, TCIs and TCs) for clearance and or maintenance and should be tailored to the patient’s skin tone by an experienced physician. Narrowband UVB phototherapy may act through the suppression of T-cell activity in the skin and possibly via suppression of staphylococcal superantigens; however, many phototherapy types have been described for AD.^38,39 Usage can be effective in school-aged children and teenagers but may be limited due to school attendance. Phototherapy was graded as level IIB evidence in the AAD guidelines.¹⁵ Side effects include aggravation of AD by exposure to heat and UV light, actinic damage, tenderness, erythema, pruritus, burning, and stinging. Lentigines; skin cancers (melanoma and nonmelanoma); folliculitis; and ocular toxicity, especially cataracts, can occur.¹⁵ Children younger than 6 years will find it difficult to stand in a phototherapy booth and may be poor candidates.^15,38,39

Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) also has been used for AD in the United States. In a review of the 2007 National Health Interview Survey of 9417 children aged 0 to 17 years, CAM was used for AD by 0.99% of children. Some CAM techniques were associated with worsening severity of AD, including herbal therapy, vitamins, homeopathic agents, diet, and movement techniques.⁴⁰ Usage of Chinese herbal medications for AD can be associated with liver toxicity.⁴¹ Only one CAM therapy—massage therapy—has some mild supportive data.⁴²

Allergen Avoidance and Diet
Bronsnick et al⁴³ discussed the possible benefit of prenatal and postnatal probiotics for prevention of AD, which were not supported in the AAD guidelines for management of AD⁴; postnatal prebiotic supplementation; and exclusive breastfeeding and/or supplementation with hydrolyzed formula in at-risk children. Elimination diets for children and mothers were not recommended. The authors found no beneficial role of supplements including vitamin D, selenium, fish oil, borage oil, and zinc sulfate.⁴³

A National Institute of Allergy and Infectious Diseases consensus group recommended avoidance of proven but not random elimination of food allergens in AD, asthma, and/or eosinophilic esophagitis.⁴⁴ Restricted maternal diet was not recommended, and breastfeeding exclusively for the first 4 to 6 months was recommended. Hydrolyzed formulas were suggested as a possible preventive strategy in at-risk infants as a breastfeeding alternative, with cost of these formulas being a problem.⁴⁴

In children younger than 5 years, food allergy screening for the most common allergens (eg, milk, eggs, peanuts, wheat, soy) should be considered in children with persistent unremitting dermatitis and/or known food challenge–induced reactions.⁴ Conservative measures to avoid house dust mite exposure in known sensitized individuals including dust covers for pillows and mattresses may be beneficial.^4,45

Emerging Therapies

Recently approved therapies include better-targeted agents that appear to have a reasonable safety profile and may fulfill unmet needs in AD care. Of these agents, crisaborole, a topical boron-based phosphodiesterase 4 inhibitor, was approved in December 2016 for mild to moderate AD in patients 2 years and older.Topically, this agent seems to be efficacious in the absence of notable carcinogenicity.⁴⁶

The systemic (injectable) biologic agent dupilumab was approved in March 2017 for moderate to severe AD. Phase 3 studies in adults with AD showed excellent success in adults with moderate to severe AD.³⁷ This agent is a monoclonal antibody targeted at blockade of the crucial atopic inflammatory triggering pathway via blockade of the IL-4A receptor site, targeting IL-4 and IL-13 activity.^36,47 There are many medications in the pipeline, which Renert-Yuval and Guttman-Yassky⁴⁸ review. However, an overview of the landscape demonstrates that Janus kinase (JAK) inhibitors⁴⁹ and biologic medications in addition to dupilumab affecting targeted inflammatory cascades in AD are in development. In particular, the JAK inhibitors appear promising due to availability both as oral and topical agents.⁴⁹

Need for Ongoing Care and Monitoring

Atopic dermatitis is a chronic inflammatory skin disorder with a genetic basis. Once initiated, the process of AD may persist throughout the patient’s life and become a systemic disorder with comorbidities including sleep disturbance, reduced quality of life, and cardiovascular disease.⁵⁰ Ongoing management of AD includes topical reduction in irritants and triggers, topical medicaments, and management of pruritus and infections. At this time, emollients and irritant avoidance paired with judicious topical medicaments including TCs and second-line or site-specific (eg, eyelids) usage of TCIs or phosphodiesterase 4 inhibitors remain the backbone of therapy. Ongoing review of therapeutics for associated morbidities is underway, which may guide future therapeutic interventions into AD. The future of prevention and therapy look bright, but time will tell.

Atopic dermatitis (AD) is a disease that finally is coming of age in dermatology research. New topical agents and systemic biologic agents offer patients with AD other options for medical management. This article provides a practical review of prevention strategies and treatment guidelines for AD.

PREVENTION

Prevention strategies for AD have been largely unsuccessful in the past, which may relate to factors such as prenatal triggers.¹ However, some newer interventional studies have shown some promise in AD prevention in specific settings. For example, a randomized trial of infants in the United States and United Kingdom at high risk for AD (ie, family history of atopy) reported that the AD risk was reduced by 50% when patients were treated with at least once-daily application of full-body emollients for 6 months (beginning by 3 weeks of life).² The strategy of daily application of emollients for avoidance of AD in infants with a family history of AD is reasonable but may not offer lifetime prevention, and the benefit in children not from AD families is unknown.

Other trials to prevent AD have included usage of dust avoidance and dust covers for mattresses. This strategy showed modest benefit in reducing the incidence of atopic diatheses in the first year³ but did not gain endorsement by the most recent guidelines of the American Academy of Dermatology (AAD).⁴

Prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus has shown promise in prevention.⁵ The exact regimen likely makes an impact on efficacy. An early study showed the usage of probiotics (eg, Lactobacillus reuteri) prenatally in pregnant women and postnatally in infants resulted in no reduction in occurrence of AD and possible reduction in IgE-associated AD.⁶ Kalliomäki et al⁷ demonstrated that L rhamnosus GG alone reduced AD by half in at-risk infants in a double-blind, placebo-controlled trial. On the other hand, Taylor et al⁸ performed a study of probiotic supplementation in which patients at high risk for AD developed higher rates of allergen sensitization. The most successful recent trial involved the randomization of 415 pregnant women to receive interventions from 36 weeks’ gestation until 3 months postpartum.⁹ The intervention was a randomized comparison of milk without probiotics versus a blend of probiotic milk containing L rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp lactis Bb-12. At 6 years of age, 81 babies who consumed probiotic milk and 82 babies who consumed milk without probiotics were available for testing. The strategy caused a statistically significant reduction in AD in the complete case analysis (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P=.027; number needed to treat, 6). Sadly, other allergic diseases were not prevented in this study.⁹

MANAGEMENT OF AD

There currently is no cure or perfected prevention technique for AD. As a result, therapy focuses on avoiding triggers and alleviating symptoms.¹⁰ Recent guidelines from the AAD state that“[t]he ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the disease.”¹¹ Skin-directed therapies are the first line of treatment including emollients, gentle skin care, and topical medicaments. In AD, therapies are needed to reduce disease activity and flare severity, clear flares, and provide relief.

Parental education and written eczema action plans are recommended to help patients and parents/guardians follow recommended regimens¹²; Tollefson and Bruckner¹³ for the American Academy of Pediatrics provide an action plan to guide the care of children with atopic dermatitis that is simple, but many others exist online. The eczema action plan usually provides information on how to bathe and what to do when the skin is actively inflamed.

In 2014, a 4-part series of guidelines of care for the management of AD was published by the AAD, replacing prior guidelines.^4,11,14,15 The following sections review some of the important parameters of care highlighted in these management guidelines.

Psychological Support

Appropriate psychological support for AD patients can be sought through counselors, therapists, psychiatrists, and support groups such as the National Eczema Association (https://nationaleczema.org/).

Education

Education is the leading form of medical therapy in patients with AD. Eczema schools are popular in Europe and are just beginning to form in the United States (http://tuh.templehealth.org/content/eczema_school.htm), which can be helpful to educate caregivers and patients with AD. Patient resources online and through support groups with an online presence, in-person meetings, and patient/family conventions can be helpful to AD patients. Often, an initial office visit with a dermatologist involves a review of avoidance of triggers, usage of gentle skin care including bland emollients, and therapeutic regimens for disease activity. This form of verbal education is to be paired with an eczema action plan, a written document that allows individuals to reference recommendations and share information with other caregivers.^12,13,16

Emollients and Gentle Skin Care

Gentle skin care regimens, which includes the usage of synthetic cleansers with a low pH to help maintain the acidity (acid mantle) of the skin, seek to reduce irritation and have been rated as level IA (highest level) in recent AAD guidelines.¹⁴ Although bathing frequency has been emphasized in the guidelines, AD severity as reflected by SCORAD (SCORing Atopic Dermatitis) was not different for daily bathing versus twice weekly.¹⁷ The American Academy of Pediatrics recommended a skin care regimen of bathing every 2 to 3 days in lukewarm water for 10 to 15 minutes, followed by application of emollients that are fragrance free and have few preservatives.¹³ Topical emollients with additives such as colloidal oatmeal, avenanthramides, or ceramides can be used to enhance the skin barrier and are well tolerated in all age groups.^18,19 Despite enhanced emollients, the therapy of AD still requires usage of prescription or over-the-counter TCs and/or topical calcineurin inhibitors (TCIs) in many cases.²⁰

Topical Medication

Children have a relatively higher body surface area–to-weight ratio, allowing for greater potential absorption of topical medicaments and potential side effects from absorption. Types of vehicle, cost, site of application, and availability may impact patient and physician preference in choice of therapeutic topical agent.¹⁴

Topical Corticosteroids
Topical corticosteroids (TCs) are the mainstay of treatment for AD and have been used for more than 60 years^.14,20 Topical corticosteroids provide anti-inflammatory effects on T cells, monocytes, and macrophages, producing altered cytokine activity locally. Topical corticosteroids inhibit collagen synthesis, potentially causing skin atrophy. They also inhibit IL-1, IL-2, IL-6, IFN-α, and tumor necrosis factor α.²¹ Topical corticosteroids are classified as class I (ultra-high potency) to class VII (low potency). In children, low-potency TCs generally are applied to the face, intertriginous areas, groin, and genitalia, and mid-potency corticosteroids are applied to the body, arms, and legs. An even higher-strength agent can be prescribed as a rescue medication in severe cases. After clearance with once- or twice-daily therapy, twice-weekly usage can benefit disease activity.²² Topical corticosteroids reduce inflammation as well as Staphylococcus aureus load through inhibition of cytokines that inhibit antimicrobial peptides. Topical corticosteroids have been endorsed as level IA evidence therapy by the AAD guidelines.¹⁴

Topical corticosteroids, particularly prolonged usage of mid- to high-potency products, have been associated with side effects such as skin atrophy, striae, telangiectases, hypopigmentation, rosacea, acneiform eruptions, focal hypertrichosis, perioral dermatitis, and acne²³; potential systemic side effects include hypothalamic-pituitary-adrenal axis suppression, cataracts, glaucoma (with periocular application), Cushing syndrome, hyperglycemia, hypertension,²³ and growth retardation.¹⁴ Long-term corticosteroid therapy is associated with tachyphylaxis and potential rebound of disease with discontinuation.²⁴ Based on the potential risk of side effects with TCs, the least potent product for the shortest time needed is recommended, with special care for thin skin. Discontinuation when clearance occurs is advised. Allergy to TCs and/or vehicle ingredients such as propylene glycol should be suspected in severe unremitting cases.¹⁴ A recent registry review of children screened for contact dermatitis demonstrated that children with AD had higher sensitization to the steroid tixocortol pivalate.²⁵

Topical Calcineurin Inhibitors
Topical calcineurin inhibitors include pimecrolimus cream 1%, which is approved for mild to moderate AD in adults and children 2 years and older, and tacrolimus ointment 0.03% and 0.1%, which are approved for moderate to severe AD in adults and children aged 2 to 15 years (0.03% formulation only). Topical calcineurin inhibitors can be used as second-line agents in AD in patients who have inadequate response to TCs or who may not be able to use TCs due to the disease site.^10,13,14 Guidelines from the AAD also have endorsed TCIs as level IA evidence for steroid-sparing agents.

Concerns about the reporting of cancers and lymphomas prompted the US Food and Drug Administration to issue a black box warning on TCIs more than 10 years ago. Pimecrolimus, which has little absorption and no notable immunosuppressive effects, has been used without detrimental effect on vaccination and delayed-type hypersensitivities, but many decades of data are lacking.^{10,13,14,17,26-29} Topical calcineurin inhibitors can be used as steroid-sparing agents in lieu of corticosteroids in specific locations such as the face and eyelids and for long-term suppressive therapy twice weekly.³⁰ Intermittent usage and cycling with corticosteroids is advisable,²⁸ but usage intermittently beyond 1 year has not been evaluated.

Topical calcineurin inhibitors are recommended as effective for acute and chronic AD. Their use as maintenance therapy in adults and children, for AD recalcitrant to steroids, for AD in sensitive areas, for steroid-induced atrophy, and for long-term uninterrupted topical steroid usage carries a level IA evidence recommendation. Furthermore, the AAD guidelines have recommended TCIs as steroid-sparing agents with level IA evidence and off-label use of TCIs in children younger than 2 years with level IA evidence. Pretreatment with TCs to reduce stinging has level IIB evidence. Usage for flare prevention is level IA evidence. Routine blood monitoring of TCI-treated patients was not recommended; in fact, the AAD guidelines provided this recommendation as level IA evidence against routine laboratory monitoring of TCI-treated patients.¹⁴

Topical Antibiotics
Topical antibiotics are indicated for the therapy of impetigo and can be used in the setting of impetiginized AD in conjunction with TCs. Recent AAD guidelines suggested against routine usage of topical antistaphylococcal agents as level IA evidence.¹⁴ There is one study supporting usage of topical mupirocin in addition to TCs to heal children with eczema area and severity index scores more than 7 more rapidly in the first week of AD therapy, but in the same study, additive benefit was not demonstrated in AD beyond the first week.³¹ There also are data supporting usage of intranasal mupirocin adjunctively with bleach baths in patients with moderate to severe AD, which was rated as level IIB evidence in the AAD guidelines.^14,32 There are limited data on the long-term utility of topical anti-infectives in AD. The risks of long-term usage could include resistance formation to agents such as mupirocin, contact dermatitis, and lack of efficacy.

Additional Therapeutics

Wet Wraps
Penetration through the stratum corneum is needed for drug activity in AD. Penetration can be enhanced using wet wrap therapy or using ointments, which produce higher relative potency.¹³ Wet wraps overlying a dilute topical medicament have been described as effective in AD and are recommended in AAD guidelines as level IIB evidence.¹⁴ Different wet wrap techniques can be used, including wet pajamas covered by dry pajamas or saline-soaked gauze wrapped around the affected areas and then dry gauze applied over the wet gauze. The methodology used should be tailored to the patient as well as to whether the individual is an inpatient or outpatient.

Bleach Baths
Dilute sodium hypochlorite solution 0.005% (one-quarter cup bleach in 20 gallons of water) has been demonstrated to be beneficial in reduction of disease activity in AD patients with recurrent bacterial infections.³² This simple technique in addition to intranasal mupirocin can reduce AD severity and improve quality of life and is the only ongoing S aureus therapeutic management endorsed by the AAD guidelines for the management of AD.^14,32

Topical and Oral Delivery

Antihistamines
Topical antihistamines are ineffective in AD. Oral antihistamines can be used to reduce pruritus and are most effective when given as sedating agents for sleep enhancement but may be given as nonsedating agents for patients with concomitant allergic disorders such as allergic rhinoconjunctivitis. Paradoxical hyperreactivity with sedating antihistamines is not uncommon in small children, and sedating antihistamine usage should be discontinued in these instances.¹³ Parents of children with AD have reported giving the child antihistamines to sleep was helpful, as well as putting on creams, using special clothes (eg, all cotton), and keeping the room cool.³³ There is level IIIC evidence against use of systemic antihistamines and level IIA evidence for sedating and nonsedating, according to the AAD guidelines.¹⁴

Systemic Therapeutics

Oral therapeutics range from oral antihistamines to oral antibiotics and immunosuppressive medications. Oral antibiotics (level IIB evidence) are reserved for superinfected AD, which is not easily defined for the following reasons: there is no consensus definition of superinfected AD; the majority of active AD lesions when cultured will demonstrate S aureus growth; and most AD lesions ooze, thereby creating the appearance of superinfection. In real-world practice, superinfection can be diagnosed based on the presence of pustules; furuncles; or signs of infection such as tracking erythema, tenderness, severe erosions, or maceration. Clinical judgment is always required.

The immunosuppressive medications used in AD include leukotriene inhibitors, which rarely are effective for AD.³⁴ More effective systemic agents for AD include cyclosporine (level I to IIB evidence), azathioprine (level IIB evidence), mycophenolate mofetil (level IIIC evidence), and methotrexate (level IIB evidence). These agents are indicated for pediatric or adult patients when topical agents and/or phototherapy have failed.¹⁵ Monitoring these agents for side effects includes ongoing evaluation for renal and liver toxicity. Short courses (ie, 6 months) are preferred to minimize side effects.³⁵

Dupilumab, an injectable AD therapy, is approved in the United States. This agent is injected every 2 weeks and binds to the IL-4Rα shared by IL-4 and IL-13. In 4 weeks of monotherapy, 85% of adult patients treated had 50% or greater clearance.³⁶ Recently published consensus opinion from the International Eczema Council recommends assessment of a variety of factors before initiating systemic therapy including comorbid illnesses such as contact allergy, trigger avoidance, superinfection, and impact on quality of life.³⁷

Oral Corticosteroids
Systemic corticosteroids clear patients quickly but provide no sustained improvement; in fact, many patients rebound or have tachyphylaxis. Although short-term corticosteroid usage can break the itch-scratch cycle, long-term usage is associated with osteoporosis, Cushing syndrome, and aseptic necrosis of the femoral head. Decreased linear growth will occur during therapy in children; therefore, systemic steroids are not recommended in children with AD, except for additional or comorbid conditions (eg, asthma or contact dermatitis).⁴

Phototherapy
Phototherapy has been recommended in the AAD guidelines as a second-line treatment after failure of first-line agents (ie, TCIs and TCs) for clearance and or maintenance and should be tailored to the patient’s skin tone by an experienced physician. Narrowband UVB phototherapy may act through the suppression of T-cell activity in the skin and possibly via suppression of staphylococcal superantigens; however, many phototherapy types have been described for AD.^38,39 Usage can be effective in school-aged children and teenagers but may be limited due to school attendance. Phototherapy was graded as level IIB evidence in the AAD guidelines.¹⁵ Side effects include aggravation of AD by exposure to heat and UV light, actinic damage, tenderness, erythema, pruritus, burning, and stinging. Lentigines; skin cancers (melanoma and nonmelanoma); folliculitis; and ocular toxicity, especially cataracts, can occur.¹⁵ Children younger than 6 years will find it difficult to stand in a phototherapy booth and may be poor candidates.^15,38,39

Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) also has been used for AD in the United States. In a review of the 2007 National Health Interview Survey of 9417 children aged 0 to 17 years, CAM was used for AD by 0.99% of children. Some CAM techniques were associated with worsening severity of AD, including herbal therapy, vitamins, homeopathic agents, diet, and movement techniques.⁴⁰ Usage of Chinese herbal medications for AD can be associated with liver toxicity.⁴¹ Only one CAM therapy—massage therapy—has some mild supportive data.⁴²

Allergen Avoidance and Diet
Bronsnick et al⁴³ discussed the possible benefit of prenatal and postnatal probiotics for prevention of AD, which were not supported in the AAD guidelines for management of AD⁴; postnatal prebiotic supplementation; and exclusive breastfeeding and/or supplementation with hydrolyzed formula in at-risk children. Elimination diets for children and mothers were not recommended. The authors found no beneficial role of supplements including vitamin D, selenium, fish oil, borage oil, and zinc sulfate.⁴³

A National Institute of Allergy and Infectious Diseases consensus group recommended avoidance of proven but not random elimination of food allergens in AD, asthma, and/or eosinophilic esophagitis.⁴⁴ Restricted maternal diet was not recommended, and breastfeeding exclusively for the first 4 to 6 months was recommended. Hydrolyzed formulas were suggested as a possible preventive strategy in at-risk infants as a breastfeeding alternative, with cost of these formulas being a problem.⁴⁴

In children younger than 5 years, food allergy screening for the most common allergens (eg, milk, eggs, peanuts, wheat, soy) should be considered in children with persistent unremitting dermatitis and/or known food challenge–induced reactions.⁴ Conservative measures to avoid house dust mite exposure in known sensitized individuals including dust covers for pillows and mattresses may be beneficial.^4,45

Emerging Therapies

Recently approved therapies include better-targeted agents that appear to have a reasonable safety profile and may fulfill unmet needs in AD care. Of these agents, crisaborole, a topical boron-based phosphodiesterase 4 inhibitor, was approved in December 2016 for mild to moderate AD in patients 2 years and older.Topically, this agent seems to be efficacious in the absence of notable carcinogenicity.⁴⁶

The systemic (injectable) biologic agent dupilumab was approved in March 2017 for moderate to severe AD. Phase 3 studies in adults with AD showed excellent success in adults with moderate to severe AD.³⁷ This agent is a monoclonal antibody targeted at blockade of the crucial atopic inflammatory triggering pathway via blockade of the IL-4A receptor site, targeting IL-4 and IL-13 activity.^36,47 There are many medications in the pipeline, which Renert-Yuval and Guttman-Yassky⁴⁸ review. However, an overview of the landscape demonstrates that Janus kinase (JAK) inhibitors⁴⁹ and biologic medications in addition to dupilumab affecting targeted inflammatory cascades in AD are in development. In particular, the JAK inhibitors appear promising due to availability both as oral and topical agents.⁴⁹

Need for Ongoing Care and Monitoring

Atopic dermatitis is a chronic inflammatory skin disorder with a genetic basis. Once initiated, the process of AD may persist throughout the patient’s life and become a systemic disorder with comorbidities including sleep disturbance, reduced quality of life, and cardiovascular disease.⁵⁰ Ongoing management of AD includes topical reduction in irritants and triggers, topical medicaments, and management of pruritus and infections. At this time, emollients and irritant avoidance paired with judicious topical medicaments including TCs and second-line or site-specific (eg, eyelids) usage of TCIs or phosphodiesterase 4 inhibitors remain the backbone of therapy. Ongoing review of therapeutics for associated morbidities is underway, which may guide future therapeutic interventions into AD. The future of prevention and therapy look bright, but time will tell.

Atopic dermatitis (AD) is a disease that finally is coming of age in dermatology research. New topical agents and systemic biologic agents offer patients with AD other options for medical management. This article provides a practical review of prevention strategies and treatment guidelines for AD.

PREVENTION

Prevention strategies for AD have been largely unsuccessful in the past, which may relate to factors such as prenatal triggers.¹ However, some newer interventional studies have shown some promise in AD prevention in specific settings. For example, a randomized trial of infants in the United States and United Kingdom at high risk for AD (ie, family history of atopy) reported that the AD risk was reduced by 50% when patients were treated with at least once-daily application of full-body emollients for 6 months (beginning by 3 weeks of life).² The strategy of daily application of emollients for avoidance of AD in infants with a family history of AD is reasonable but may not offer lifetime prevention, and the benefit in children not from AD families is unknown.

Other trials to prevent AD have included usage of dust avoidance and dust covers for mattresses. This strategy showed modest benefit in reducing the incidence of atopic diatheses in the first year³ but did not gain endorsement by the most recent guidelines of the American Academy of Dermatology (AAD).⁴

Prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus has shown promise in prevention.⁵ The exact regimen likely makes an impact on efficacy. An early study showed the usage of probiotics (eg, Lactobacillus reuteri) prenatally in pregnant women and postnatally in infants resulted in no reduction in occurrence of AD and possible reduction in IgE-associated AD.⁶ Kalliomäki et al⁷ demonstrated that L rhamnosus GG alone reduced AD by half in at-risk infants in a double-blind, placebo-controlled trial. On the other hand, Taylor et al⁸ performed a study of probiotic supplementation in which patients at high risk for AD developed higher rates of allergen sensitization. The most successful recent trial involved the randomization of 415 pregnant women to receive interventions from 36 weeks’ gestation until 3 months postpartum.⁹ The intervention was a randomized comparison of milk without probiotics versus a blend of probiotic milk containing L rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp lactis Bb-12. At 6 years of age, 81 babies who consumed probiotic milk and 82 babies who consumed milk without probiotics were available for testing. The strategy caused a statistically significant reduction in AD in the complete case analysis (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P=.027; number needed to treat, 6). Sadly, other allergic diseases were not prevented in this study.⁹

MANAGEMENT OF AD

There currently is no cure or perfected prevention technique for AD. As a result, therapy focuses on avoiding triggers and alleviating symptoms.¹⁰ Recent guidelines from the AAD state that“[t]he ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the disease.”¹¹ Skin-directed therapies are the first line of treatment including emollients, gentle skin care, and topical medicaments. In AD, therapies are needed to reduce disease activity and flare severity, clear flares, and provide relief.

Parental education and written eczema action plans are recommended to help patients and parents/guardians follow recommended regimens¹²; Tollefson and Bruckner¹³ for the American Academy of Pediatrics provide an action plan to guide the care of children with atopic dermatitis that is simple, but many others exist online. The eczema action plan usually provides information on how to bathe and what to do when the skin is actively inflamed.

In 2014, a 4-part series of guidelines of care for the management of AD was published by the AAD, replacing prior guidelines.^4,11,14,15 The following sections review some of the important parameters of care highlighted in these management guidelines.

Psychological Support

Appropriate psychological support for AD patients can be sought through counselors, therapists, psychiatrists, and support groups such as the National Eczema Association (https://nationaleczema.org/).

Education

Education is the leading form of medical therapy in patients with AD. Eczema schools are popular in Europe and are just beginning to form in the United States (http://tuh.templehealth.org/content/eczema_school.htm), which can be helpful to educate caregivers and patients with AD. Patient resources online and through support groups with an online presence, in-person meetings, and patient/family conventions can be helpful to AD patients. Often, an initial office visit with a dermatologist involves a review of avoidance of triggers, usage of gentle skin care including bland emollients, and therapeutic regimens for disease activity. This form of verbal education is to be paired with an eczema action plan, a written document that allows individuals to reference recommendations and share information with other caregivers.^12,13,16

Emollients and Gentle Skin Care

Gentle skin care regimens, which includes the usage of synthetic cleansers with a low pH to help maintain the acidity (acid mantle) of the skin, seek to reduce irritation and have been rated as level IA (highest level) in recent AAD guidelines.¹⁴ Although bathing frequency has been emphasized in the guidelines, AD severity as reflected by SCORAD (SCORing Atopic Dermatitis) was not different for daily bathing versus twice weekly.¹⁷ The American Academy of Pediatrics recommended a skin care regimen of bathing every 2 to 3 days in lukewarm water for 10 to 15 minutes, followed by application of emollients that are fragrance free and have few preservatives.¹³ Topical emollients with additives such as colloidal oatmeal, avenanthramides, or ceramides can be used to enhance the skin barrier and are well tolerated in all age groups.^18,19 Despite enhanced emollients, the therapy of AD still requires usage of prescription or over-the-counter TCs and/or topical calcineurin inhibitors (TCIs) in many cases.²⁰

Topical Medication

Children have a relatively higher body surface area–to-weight ratio, allowing for greater potential absorption of topical medicaments and potential side effects from absorption. Types of vehicle, cost, site of application, and availability may impact patient and physician preference in choice of therapeutic topical agent.¹⁴

Topical Corticosteroids
Topical corticosteroids (TCs) are the mainstay of treatment for AD and have been used for more than 60 years^.14,20 Topical corticosteroids provide anti-inflammatory effects on T cells, monocytes, and macrophages, producing altered cytokine activity locally. Topical corticosteroids inhibit collagen synthesis, potentially causing skin atrophy. They also inhibit IL-1, IL-2, IL-6, IFN-α, and tumor necrosis factor α.²¹ Topical corticosteroids are classified as class I (ultra-high potency) to class VII (low potency). In children, low-potency TCs generally are applied to the face, intertriginous areas, groin, and genitalia, and mid-potency corticosteroids are applied to the body, arms, and legs. An even higher-strength agent can be prescribed as a rescue medication in severe cases. After clearance with once- or twice-daily therapy, twice-weekly usage can benefit disease activity.²² Topical corticosteroids reduce inflammation as well as Staphylococcus aureus load through inhibition of cytokines that inhibit antimicrobial peptides. Topical corticosteroids have been endorsed as level IA evidence therapy by the AAD guidelines.¹⁴

Topical corticosteroids, particularly prolonged usage of mid- to high-potency products, have been associated with side effects such as skin atrophy, striae, telangiectases, hypopigmentation, rosacea, acneiform eruptions, focal hypertrichosis, perioral dermatitis, and acne²³; potential systemic side effects include hypothalamic-pituitary-adrenal axis suppression, cataracts, glaucoma (with periocular application), Cushing syndrome, hyperglycemia, hypertension,²³ and growth retardation.¹⁴ Long-term corticosteroid therapy is associated with tachyphylaxis and potential rebound of disease with discontinuation.²⁴ Based on the potential risk of side effects with TCs, the least potent product for the shortest time needed is recommended, with special care for thin skin. Discontinuation when clearance occurs is advised. Allergy to TCs and/or vehicle ingredients such as propylene glycol should be suspected in severe unremitting cases.¹⁴ A recent registry review of children screened for contact dermatitis demonstrated that children with AD had higher sensitization to the steroid tixocortol pivalate.²⁵

Topical Calcineurin Inhibitors
Topical calcineurin inhibitors include pimecrolimus cream 1%, which is approved for mild to moderate AD in adults and children 2 years and older, and tacrolimus ointment 0.03% and 0.1%, which are approved for moderate to severe AD in adults and children aged 2 to 15 years (0.03% formulation only). Topical calcineurin inhibitors can be used as second-line agents in AD in patients who have inadequate response to TCs or who may not be able to use TCs due to the disease site.^10,13,14 Guidelines from the AAD also have endorsed TCIs as level IA evidence for steroid-sparing agents.

Concerns about the reporting of cancers and lymphomas prompted the US Food and Drug Administration to issue a black box warning on TCIs more than 10 years ago. Pimecrolimus, which has little absorption and no notable immunosuppressive effects, has been used without detrimental effect on vaccination and delayed-type hypersensitivities, but many decades of data are lacking.^{10,13,14,17,26-29} Topical calcineurin inhibitors can be used as steroid-sparing agents in lieu of corticosteroids in specific locations such as the face and eyelids and for long-term suppressive therapy twice weekly.³⁰ Intermittent usage and cycling with corticosteroids is advisable,²⁸ but usage intermittently beyond 1 year has not been evaluated.

Topical calcineurin inhibitors are recommended as effective for acute and chronic AD. Their use as maintenance therapy in adults and children, for AD recalcitrant to steroids, for AD in sensitive areas, for steroid-induced atrophy, and for long-term uninterrupted topical steroid usage carries a level IA evidence recommendation. Furthermore, the AAD guidelines have recommended TCIs as steroid-sparing agents with level IA evidence and off-label use of TCIs in children younger than 2 years with level IA evidence. Pretreatment with TCs to reduce stinging has level IIB evidence. Usage for flare prevention is level IA evidence. Routine blood monitoring of TCI-treated patients was not recommended; in fact, the AAD guidelines provided this recommendation as level IA evidence against routine laboratory monitoring of TCI-treated patients.¹⁴

Topical Antibiotics
Topical antibiotics are indicated for the therapy of impetigo and can be used in the setting of impetiginized AD in conjunction with TCs. Recent AAD guidelines suggested against routine usage of topical antistaphylococcal agents as level IA evidence.¹⁴ There is one study supporting usage of topical mupirocin in addition to TCs to heal children with eczema area and severity index scores more than 7 more rapidly in the first week of AD therapy, but in the same study, additive benefit was not demonstrated in AD beyond the first week.³¹ There also are data supporting usage of intranasal mupirocin adjunctively with bleach baths in patients with moderate to severe AD, which was rated as level IIB evidence in the AAD guidelines.^14,32 There are limited data on the long-term utility of topical anti-infectives in AD. The risks of long-term usage could include resistance formation to agents such as mupirocin, contact dermatitis, and lack of efficacy.

Additional Therapeutics

Wet Wraps
Penetration through the stratum corneum is needed for drug activity in AD. Penetration can be enhanced using wet wrap therapy or using ointments, which produce higher relative potency.¹³ Wet wraps overlying a dilute topical medicament have been described as effective in AD and are recommended in AAD guidelines as level IIB evidence.¹⁴ Different wet wrap techniques can be used, including wet pajamas covered by dry pajamas or saline-soaked gauze wrapped around the affected areas and then dry gauze applied over the wet gauze. The methodology used should be tailored to the patient as well as to whether the individual is an inpatient or outpatient.

Bleach Baths
Dilute sodium hypochlorite solution 0.005% (one-quarter cup bleach in 20 gallons of water) has been demonstrated to be beneficial in reduction of disease activity in AD patients with recurrent bacterial infections.³² This simple technique in addition to intranasal mupirocin can reduce AD severity and improve quality of life and is the only ongoing S aureus therapeutic management endorsed by the AAD guidelines for the management of AD.^14,32

Topical and Oral Delivery

Antihistamines
Topical antihistamines are ineffective in AD. Oral antihistamines can be used to reduce pruritus and are most effective when given as sedating agents for sleep enhancement but may be given as nonsedating agents for patients with concomitant allergic disorders such as allergic rhinoconjunctivitis. Paradoxical hyperreactivity with sedating antihistamines is not uncommon in small children, and sedating antihistamine usage should be discontinued in these instances.¹³ Parents of children with AD have reported giving the child antihistamines to sleep was helpful, as well as putting on creams, using special clothes (eg, all cotton), and keeping the room cool.³³ There is level IIIC evidence against use of systemic antihistamines and level IIA evidence for sedating and nonsedating, according to the AAD guidelines.¹⁴

Systemic Therapeutics

Oral therapeutics range from oral antihistamines to oral antibiotics and immunosuppressive medications. Oral antibiotics (level IIB evidence) are reserved for superinfected AD, which is not easily defined for the following reasons: there is no consensus definition of superinfected AD; the majority of active AD lesions when cultured will demonstrate S aureus growth; and most AD lesions ooze, thereby creating the appearance of superinfection. In real-world practice, superinfection can be diagnosed based on the presence of pustules; furuncles; or signs of infection such as tracking erythema, tenderness, severe erosions, or maceration. Clinical judgment is always required.

The immunosuppressive medications used in AD include leukotriene inhibitors, which rarely are effective for AD.³⁴ More effective systemic agents for AD include cyclosporine (level I to IIB evidence), azathioprine (level IIB evidence), mycophenolate mofetil (level IIIC evidence), and methotrexate (level IIB evidence). These agents are indicated for pediatric or adult patients when topical agents and/or phototherapy have failed.¹⁵ Monitoring these agents for side effects includes ongoing evaluation for renal and liver toxicity. Short courses (ie, 6 months) are preferred to minimize side effects.³⁵

Dupilumab, an injectable AD therapy, is approved in the United States. This agent is injected every 2 weeks and binds to the IL-4Rα shared by IL-4 and IL-13. In 4 weeks of monotherapy, 85% of adult patients treated had 50% or greater clearance.³⁶ Recently published consensus opinion from the International Eczema Council recommends assessment of a variety of factors before initiating systemic therapy including comorbid illnesses such as contact allergy, trigger avoidance, superinfection, and impact on quality of life.³⁷

Oral Corticosteroids
Systemic corticosteroids clear patients quickly but provide no sustained improvement; in fact, many patients rebound or have tachyphylaxis. Although short-term corticosteroid usage can break the itch-scratch cycle, long-term usage is associated with osteoporosis, Cushing syndrome, and aseptic necrosis of the femoral head. Decreased linear growth will occur during therapy in children; therefore, systemic steroids are not recommended in children with AD, except for additional or comorbid conditions (eg, asthma or contact dermatitis).⁴

Phototherapy
Phototherapy has been recommended in the AAD guidelines as a second-line treatment after failure of first-line agents (ie, TCIs and TCs) for clearance and or maintenance and should be tailored to the patient’s skin tone by an experienced physician. Narrowband UVB phototherapy may act through the suppression of T-cell activity in the skin and possibly via suppression of staphylococcal superantigens; however, many phototherapy types have been described for AD.^38,39 Usage can be effective in school-aged children and teenagers but may be limited due to school attendance. Phototherapy was graded as level IIB evidence in the AAD guidelines.¹⁵ Side effects include aggravation of AD by exposure to heat and UV light, actinic damage, tenderness, erythema, pruritus, burning, and stinging. Lentigines; skin cancers (melanoma and nonmelanoma); folliculitis; and ocular toxicity, especially cataracts, can occur.¹⁵ Children younger than 6 years will find it difficult to stand in a phototherapy booth and may be poor candidates.^15,38,39

Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) also has been used for AD in the United States. In a review of the 2007 National Health Interview Survey of 9417 children aged 0 to 17 years, CAM was used for AD by 0.99% of children. Some CAM techniques were associated with worsening severity of AD, including herbal therapy, vitamins, homeopathic agents, diet, and movement techniques.⁴⁰ Usage of Chinese herbal medications for AD can be associated with liver toxicity.⁴¹ Only one CAM therapy—massage therapy—has some mild supportive data.⁴²

Allergen Avoidance and Diet
Bronsnick et al⁴³ discussed the possible benefit of prenatal and postnatal probiotics for prevention of AD, which were not supported in the AAD guidelines for management of AD⁴; postnatal prebiotic supplementation; and exclusive breastfeeding and/or supplementation with hydrolyzed formula in at-risk children. Elimination diets for children and mothers were not recommended. The authors found no beneficial role of supplements including vitamin D, selenium, fish oil, borage oil, and zinc sulfate.⁴³

A National Institute of Allergy and Infectious Diseases consensus group recommended avoidance of proven but not random elimination of food allergens in AD, asthma, and/or eosinophilic esophagitis.⁴⁴ Restricted maternal diet was not recommended, and breastfeeding exclusively for the first 4 to 6 months was recommended. Hydrolyzed formulas were suggested as a possible preventive strategy in at-risk infants as a breastfeeding alternative, with cost of these formulas being a problem.⁴⁴

In children younger than 5 years, food allergy screening for the most common allergens (eg, milk, eggs, peanuts, wheat, soy) should be considered in children with persistent unremitting dermatitis and/or known food challenge–induced reactions.⁴ Conservative measures to avoid house dust mite exposure in known sensitized individuals including dust covers for pillows and mattresses may be beneficial.^4,45

Emerging Therapies

Recently approved therapies include better-targeted agents that appear to have a reasonable safety profile and may fulfill unmet needs in AD care. Of these agents, crisaborole, a topical boron-based phosphodiesterase 4 inhibitor, was approved in December 2016 for mild to moderate AD in patients 2 years and older.Topically, this agent seems to be efficacious in the absence of notable carcinogenicity.⁴⁶

The systemic (injectable) biologic agent dupilumab was approved in March 2017 for moderate to severe AD. Phase 3 studies in adults with AD showed excellent success in adults with moderate to severe AD.³⁷ This agent is a monoclonal antibody targeted at blockade of the crucial atopic inflammatory triggering pathway via blockade of the IL-4A receptor site, targeting IL-4 and IL-13 activity.^36,47 There are many medications in the pipeline, which Renert-Yuval and Guttman-Yassky⁴⁸ review. However, an overview of the landscape demonstrates that Janus kinase (JAK) inhibitors⁴⁹ and biologic medications in addition to dupilumab affecting targeted inflammatory cascades in AD are in development. In particular, the JAK inhibitors appear promising due to availability both as oral and topical agents.⁴⁹

Need for Ongoing Care and Monitoring

Atopic dermatitis is a chronic inflammatory skin disorder with a genetic basis. Once initiated, the process of AD may persist throughout the patient’s life and become a systemic disorder with comorbidities including sleep disturbance, reduced quality of life, and cardiovascular disease.⁵⁰ Ongoing management of AD includes topical reduction in irritants and triggers, topical medicaments, and management of pruritus and infections. At this time, emollients and irritant avoidance paired with judicious topical medicaments including TCs and second-line or site-specific (eg, eyelids) usage of TCIs or phosphodiesterase 4 inhibitors remain the backbone of therapy. Ongoing review of therapeutics for associated morbidities is underway, which may guide future therapeutic interventions into AD. The future of prevention and therapy look bright, but time will tell.

Illustration: Kimberly Martens for OBG Management

Sexual function is a complex, multifaceted process mediated by neurologic functions, hormonal regulation, and psychological factors. What could possibly go wrong?

As it turns out, quite a lot. Female sexual dysfunction is a common, vastly undertreated sexual health problem that can have wide-reaching effects on a woman’s life. These effects may include impaired body image, self-confidence, and self-worth. Sexual dysfunction also can contribute to relationship dissatisfaction and leave one feeling less connected with her partner.^1,2 Studies have shown women with sexual dysfunction have higher health care expenditures³ and that depression and fatigue are common comorbidities, as is frequently seen in other chronic conditions such as diabetes and back pain.⁴

Understanding the pathogenesis of female sexual dysfunction helps to guide our approach to its management. Indeed, increased understanding of its pathology has helped to usher in new and emerging treatment options, as well as a personalized, biopsychosocial approach to its management.

Related article:
2016 Update on female sexual dysfunction

In this Update, I discuss the interplay of physiologic and psychological factors that affect female sexual function as well as the latest options for its management. I have also assembled a panel of experts to discuss 2 cases representative of sexual dysfunction that you may encounter in your clinical practice and how prescribing decisions are made for their management.

Read about factors that impact sexual function and agents to help manage dysfunction.

Multiple transmitters in the brain can increase or decrease sexual desire and function

Neurotransmitters involved in sexual excitation include brain dopamine, melanocortin, oxytocin, vasopressin, and norepinephrine, whereas brain opioids, serotonin, prolactin, and endocannabinoids function as sexual inhibitors. Inhibitory transmitters are activated normally during sexual refractoriness but also from primary aversion or secondary avoidance disorders.¹ Drugs or conditions that reduce brain dopamine levels, increase the action of brain serotonin, or enhance brain opioid pathways have been shown to inhibit sexual desire, while those that increase hypothalamic and mesolimbic dopamine or decrease serotonin release have been shown to stimulate sexual desire.¹ 

Estradiol and progesterone can impact sexual function and desire

In addition to the neurotransmitters, hormones are important modulators of female sexual function. Decreasing levels of circulating estrogen after menopause lead to physiologic, biologic, and clinical changes in the urogenital tissues, such as decreased elastin, thinning of the epithelium, reduced vaginal blood flow, diminished lubrication, and decreased flexibility and elasticity. These changes result in the symptoms of genitourinary syndrome of menopause (GSM), which affects as many as half of all menopausal women.^5,6 In clinical trials, dyspareunia and vaginal dryness are the most bothersome GSM symptoms reported.⁷

The role of hormonal regulation in sexual dysfunction among premenopausal women is not yet fully understood, but we do know that estradiol has been shown to improve sexual desire, progesterone tends to dampen sexual desire, and that testosterone at physiological levels has been shown in most studies to have a neutral effect on sexual desire in a well-estrogenized patient.⁸

Related article:
Focus on treating genital atrophy symptoms

Experience and behavior modulate or reinforce sexual dysfunction

The most common psychological factors that trigger or amplify female sexual dysfunction are depression, anxiety, distraction, negative body image, sexual abuse, and emotional neglect.⁹ Contextual or sociocultural factors, such as relationship discord, life-stage stressors (the empty nest syndrome or anxiety and sleep deprivation from a new baby), as well as cultural or religious values that suppress sexuality, also should be considered.⁹ Experience-based neuroplasticity (changes in brain pathways that become solidified by negative or positive experiences) may elucidate how a multimodal approach, utilizing medical and psychological treatment, can be beneficial for patients, particularly those with hypoactive sexual desire disorder (HSDD).¹

New and emerging approaches to managing female sexual dysfunction

Three agents, one of which has been available for prescription for some time, one that is newly available, and one in the pipeline, are or may soon be in the gynecologist's armamentarium.

Flibanserin

Medications that target excitatory pathways or blunt inhibitory pathways are in development, and one, flibanserin (Addyi), has been US Food and Drug Administration (FDA)-approved for the treatment of acquired, generalized HSDD in premenopausal women.^1,10 Flibanserin is a nonhormonal, centrally acting, postsynaptic serotonin 1A receptor agonist and a serotonin 2A receptor antagonist that is taken daily at bedtime (100 mg); several weeks are usually needed before any effects are noted.¹ It is not approved for postmenopausal women and has a boxed warning about the risks of hypotension and syncope; its use is contraindicated in women who drink alcohol, in those who have hepatic impairment, and with the use of moderate or strong CYP3A4 inhibitors.¹¹

Also keep in mind that flibanserin is only available through a Risk Evaluation and Mitigation Strategy program, so clinicians who wish to prescribe it must enroll in and complete training to become certified providers.⁹

Related article:
What you need to know (and do) to prescribe the new drug flibanserin

Prasterone

Prasterone (Intrarosa), a once-daily intravaginal dehydroepiandrosterone (DHEA) product, is a prohormone that increases local estrogen and testosterone and has the advantage of improved sexual function, desire, arousal, lubrication, orgasm, satisfaction, as well as pain at sexual activity.¹² It was approved by the FDA in November 2016 to treat moderate to severe dyspareunia and has been available for prescribing since July 2017. Its cost is comparable to topical estrogen products, with a $25 copay program.

Because prasterone is not an estrogen, it does not have the boxed warning that all estrogen products are mandated by the FDA to have. This may make it more acceptable to patients, who often decline to use an estrogen product after seeing the boxed warning on the package. The Centers for Medicare and Medicaid Services (CMS) does not have prasterone on its list of potentially hazardous drugs for the elderly. However, keep in mind that because its label is for dyspareunia and not specifically for GSM, CMS considers it a drug of choice--in other words, like sildenafil (Viagra), a lifestyle choice and not for treatment of a medical condition. As such, at the present time, Medicare does not cover it.

Bremelanotide

Late-stage trials of bremelanotide, a melanocortin receptor agonist, are underway. Its mechanism of action is somewhat like that of flibanserin in that both drugs increase dopamine and norepinephrine levels. The advantage of bremelanotide is that it is used as needed. It is dosed subcutaneously (1.75 mg) and it can be used as often as a woman would like to use it. The FDA is expected to consider it for approval in about a year. Unpublished data from poster sessions at recent meetings show that, in a phase 3 study of 1,247 premenopausal women with HSDD (who had already been screened for depression and were found to have a physiologic condition), improvements in desire, arousal, lubrication, and orgasm were shown with bremelanotide. About 18% of women stopped using the drug because of adverse effects (nausea, vomiting, flushing, or headache) versus 2% for placebo. Like flibanserin, it is expected to be approved for premenopausal women only. 

Read how 3 experts would manage differing GSM symptoms.

What would you prescribe for these patients? 

CASE Genitourinary syndrome of menopause (GSM) in a 55-year-old woman

A 55-year-old widow is beginning a new relationship. She has not had partnered sexual activity for several years, but she recently has begun a relationship. She describes pain with attempted penetration with her new partner. Her last menstrual period was 3 years ago and she has experienced very minor menopausal symptoms, which are not bothersome. On examination, the vulva and vagina are pale, with thin epithelium and absent rugae. The tissue lacks elasticity. A virginal speculum is needed to visualize the cervix.

How would you go about deciding which of the many options for management of GSM you will recommend for this patient? What do you weigh as you consider DHEA versus estrogen and topical versus oral therapy?
 
JoAnn V. Pinkerton, MD: Vulvovaginal atrophy (VVA), part of GSM, is associated with postmenopausal estrogen deficiency and includes the signs and symptoms seen on this patient's physical exam: vaginal narrowing, pallor, loss of elasticity, as well as pain with intercourse.⁶ Estrogen therapy is the most effective treatment for vaginal atrophy.¹³ Since she does not have significant menopausal symptoms, low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA; these include creams, tablets containing estradiol or conjugated equine estrogen (CEE), and a low-dose vaginal estradiol ring--all available at doses that result in minimal systemic absorption.

Choice is usually made based on patient desire and likely adherence. If the patient prefers nonestrogen therapies that improve VVA and have been approved for relief of dyspareunia in postmenopausal women, I would discuss with the patient the oral selective estrogen receptor modulator ospemifene,¹⁴ and the new intravaginal DHEA suppositories, prasterone.¹⁵ Ospemifene is taken daily as an oral tablet, has a small risk of blood clots, and is my choice for women who do not need systemic hormone therapy and prefer to avoid vaginal therapy.

Andrew M. Kaunitz, MD: GSM is prevalent in menopausal women and, if not treated, causes progressive vaginal dryness and sexual discomfort. When the main indication for hormonal management in a menopausal woman is GSM (as opposed to treatment of vasomotor symptoms or prevention of osteoporosis), the treatment of choice is low-dose local vaginal estrogen, ospemifene, or prasterone (DHEA). Prasterone is a vaginally administered nonestrogen steroid that was approved by the FDA to treat dyspareunia associated with GSM. DHEA is an endogenous inactive steroid that is converted locally into androgens and estrogens; one vaginal insert is placed nightly.^16,17

This 55-year-old widow has not been sexually active for some time. The facts that attempted penetration was painful and only an ultrathin (virginal) speculum could be used for examination indicate that contraction of the pelvic floor muscles is likely present. Simply starting medical management may not lead to comfortable/successful penetrative sex for this woman. In addition to  medical management, she would likely benefit from referral for physical therapy. Using dilators and other strategies, along with the positive impact that medical management will have on the vaginal mucosa, a woman's physical therapist can work with this patient to help the pelvic floor muscles relax and facilitate comfortable penetrative sex.

James A. Simon, MD: With only minor vasomotor symptoms, I would assess the other potential benefits of a systemic therapy. These might include cardiovascular risk reduction (systemic estrogens or estrogens/progesterone in some), breast cancer risk reduction (some data suggesting ospemifene can accomplish this), osteoporosis prevention (systemic estrogens and estrogen/androgens), etc. If there is an option for a treatment to address more than one symptom, in this case GSM, assessing the risks/benefits of each of these therapies should be estimated for this specific patient.

If there are no systemic benefits to be had, then any of the local treatments should be helpful. As there are no head-to-head comparisons available, local estrogen cream, tablets, rings, local DHEA, or systemic ospemifene each should be considered possible treatments. I also feel this patient may benefit from supplementary self-dilation and/or physical therapy.

Related article:
2017 Update on menopause

 
CASE Dyspareunia and vasomotor symptoms in a 42-year-old breast cancer survivor

A 42-year-old woman with a BRCA1 mutation has undergone prophylactic mastectomies as well as hysterectomy with bilateral salpingo-oophorectomy. She reports mild to moderate hot flashes and bothersome vaginal dryness and dyspareunia. Examination confirms GSM.

Would you advise systemic hormone therapy for this patient? What would your recommendation be for management of her GSM symptoms?

Dr. Simon: While one's gut reaction would be to avoid systemic estrogen therapy in a patient with a BRCA1 mutation, the scientific information confirming this fear is lacking.¹⁸ Such patients may benefit significantly from systemic estrogen therapy (reduced risk of cardiovascular disease and cognitive decline, etc.), and with both breasts and both ovaries removed, estrogen's breast cancer risks, if any in this population, are largely avoided. The patient also may benefit from additional local therapy with either estrogens or DHEA.

Dr. Kaunitz: Due to her high lifetime risk of breast and ovarian cancer, this woman has proceeded with risk-reducing breast and gynecologic surgery. As more BRCA mutation carriers are being identified and undergo risk-reducing bilateral mastectomy (usually with reconstruction) and salpingo-oophorectomy, clinicians and mutation carriers more frequently face decisions regarding use of systemic hormone therapy.

Mutation carriers who have undergone bilateral risk-reducing mastectomy experience a very low baseline future risk for breast cancer; accordingly, concerns regarding this disease should not prevent use of systemic hormone therapy. Furthermore, without hormone replacement, induced menopause in women this age is associated with an elevated risk of osteoporosis, persistent vasomotor symptoms, cardiovascular disease, stroke, mood changes, dementia, Parkinson disease, and overall mortality. Recognizing the safety of estrogen therapy in this setting, this 42-year-old BRCA1 mutation carrier can initiate estrogen therapy. Standard dose estrogen therapy refers to oral estradiol 1.0 mg, conjugated equine estrogen 0.625 mg,or transdermal estradiol 0.05 mg. In younger women like this 42-year-old with surgically induced menopause, higher than standard replacement doses of estrogen are often appropriate.¹⁷

Due to concerns the hormone therapy might further increase future risk of breast cancer, some mutation carriers may delay or avoid risk-reducing bilateral salpingo-oophorectomy, a potentially lifesaving surgery which reduces not only future risk of ovarian cancer but also future risk for breast cancer.

Among mutation carriers with intact breasts, several studies address risk of breast cancer with use of systemic hormone therapy. Although limited in numbers of participants and years of follow-up, in aggregate, these studies provide reassurance that short-term use of systemic hormone therapy does not increase breast cancer risk in women with BRCA1 or BRCA2 mutations and intact breasts.¹⁹

Dr. Pinkerton: For this woman with early surgical menopause and hysterectomy, estrogen therapy could improve her vasomotor symptoms and decrease her risk of bone loss and GSM.¹⁷ In the Women's Health Initiative trial, there were 7 fewer breast cancers per 10,000 women-years in the estrogen-onlyarm.²⁰ Observational studies suggest that hormone therapy, when given to the average age of menopause, decreases the risks of heart disease, Parkinson disease, and dementia.²¹ Limited observational evidence suggests that hormone therapy use does not further increase risk of breast cancer in women following oophorectomy for BRCA1 or BRCA2 gene mutation.²²

The absolute risks observed with hormone therapy tended to be small, especially in younger, healthy women. Systemic hormone therapy could treat her hot flashes and her GSM symptoms and potentially decrease health risks associated with premature estrogen deficiency. Nonestrogen therapies for hot flashes include low-dose antidepressants, gabapentin, and mind-body options, such as cognitive behavioral therapy and hypnosis, but these would not decrease her health risks or treat her GSM.

If she only requests treatment of her GSM symptoms, she would be a candidate for low-dose vaginal estrogen therapy, given as a cream, tablet, or ring depending on her choice. I would not choose ospemifene as my first choice as she is having hot flashes, and there are no data yet on the drug's health benefits in early menopause. If she prefers nonestrogen vaginal therapy, the new intravaginal DHEA might be a good choice as both estrogen and testosterone are increased locally in the vagina while hormone levels remain in the postmenopausal range. There is no boxed warning on the patient insert, although safety in women with breast cancer or in those with elevated risk of breast cancer has not been tested.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

Sexual function is a complex, multifaceted process mediated by neurologic functions, hormonal regulation, and psychological factors. What could possibly go wrong?

As it turns out, quite a lot. Female sexual dysfunction is a common, vastly undertreated sexual health problem that can have wide-reaching effects on a woman’s life. These effects may include impaired body image, self-confidence, and self-worth. Sexual dysfunction also can contribute to relationship dissatisfaction and leave one feeling less connected with her partner.^1,2 Studies have shown women with sexual dysfunction have higher health care expenditures³ and that depression and fatigue are common comorbidities, as is frequently seen in other chronic conditions such as diabetes and back pain.⁴

Understanding the pathogenesis of female sexual dysfunction helps to guide our approach to its management. Indeed, increased understanding of its pathology has helped to usher in new and emerging treatment options, as well as a personalized, biopsychosocial approach to its management.

Related article:
2016 Update on female sexual dysfunction

In this Update, I discuss the interplay of physiologic and psychological factors that affect female sexual function as well as the latest options for its management. I have also assembled a panel of experts to discuss 2 cases representative of sexual dysfunction that you may encounter in your clinical practice and how prescribing decisions are made for their management.

Read about factors that impact sexual function and agents to help manage dysfunction.

Multiple transmitters in the brain can increase or decrease sexual desire and function

Neurotransmitters involved in sexual excitation include brain dopamine, melanocortin, oxytocin, vasopressin, and norepinephrine, whereas brain opioids, serotonin, prolactin, and endocannabinoids function as sexual inhibitors. Inhibitory transmitters are activated normally during sexual refractoriness but also from primary aversion or secondary avoidance disorders.¹ Drugs or conditions that reduce brain dopamine levels, increase the action of brain serotonin, or enhance brain opioid pathways have been shown to inhibit sexual desire, while those that increase hypothalamic and mesolimbic dopamine or decrease serotonin release have been shown to stimulate sexual desire.¹ 

Estradiol and progesterone can impact sexual function and desire

In addition to the neurotransmitters, hormones are important modulators of female sexual function. Decreasing levels of circulating estrogen after menopause lead to physiologic, biologic, and clinical changes in the urogenital tissues, such as decreased elastin, thinning of the epithelium, reduced vaginal blood flow, diminished lubrication, and decreased flexibility and elasticity. These changes result in the symptoms of genitourinary syndrome of menopause (GSM), which affects as many as half of all menopausal women.^5,6 In clinical trials, dyspareunia and vaginal dryness are the most bothersome GSM symptoms reported.⁷

The role of hormonal regulation in sexual dysfunction among premenopausal women is not yet fully understood, but we do know that estradiol has been shown to improve sexual desire, progesterone tends to dampen sexual desire, and that testosterone at physiological levels has been shown in most studies to have a neutral effect on sexual desire in a well-estrogenized patient.⁸

Related article:
Focus on treating genital atrophy symptoms

Experience and behavior modulate or reinforce sexual dysfunction

The most common psychological factors that trigger or amplify female sexual dysfunction are depression, anxiety, distraction, negative body image, sexual abuse, and emotional neglect.⁹ Contextual or sociocultural factors, such as relationship discord, life-stage stressors (the empty nest syndrome or anxiety and sleep deprivation from a new baby), as well as cultural or religious values that suppress sexuality, also should be considered.⁹ Experience-based neuroplasticity (changes in brain pathways that become solidified by negative or positive experiences) may elucidate how a multimodal approach, utilizing medical and psychological treatment, can be beneficial for patients, particularly those with hypoactive sexual desire disorder (HSDD).¹

New and emerging approaches to managing female sexual dysfunction

Three agents, one of which has been available for prescription for some time, one that is newly available, and one in the pipeline, are or may soon be in the gynecologist's armamentarium.

Flibanserin

Medications that target excitatory pathways or blunt inhibitory pathways are in development, and one, flibanserin (Addyi), has been US Food and Drug Administration (FDA)-approved for the treatment of acquired, generalized HSDD in premenopausal women.^1,10 Flibanserin is a nonhormonal, centrally acting, postsynaptic serotonin 1A receptor agonist and a serotonin 2A receptor antagonist that is taken daily at bedtime (100 mg); several weeks are usually needed before any effects are noted.¹ It is not approved for postmenopausal women and has a boxed warning about the risks of hypotension and syncope; its use is contraindicated in women who drink alcohol, in those who have hepatic impairment, and with the use of moderate or strong CYP3A4 inhibitors.¹¹

Also keep in mind that flibanserin is only available through a Risk Evaluation and Mitigation Strategy program, so clinicians who wish to prescribe it must enroll in and complete training to become certified providers.⁹

Related article:
What you need to know (and do) to prescribe the new drug flibanserin

Prasterone

Prasterone (Intrarosa), a once-daily intravaginal dehydroepiandrosterone (DHEA) product, is a prohormone that increases local estrogen and testosterone and has the advantage of improved sexual function, desire, arousal, lubrication, orgasm, satisfaction, as well as pain at sexual activity.¹² It was approved by the FDA in November 2016 to treat moderate to severe dyspareunia and has been available for prescribing since July 2017. Its cost is comparable to topical estrogen products, with a $25 copay program.

Because prasterone is not an estrogen, it does not have the boxed warning that all estrogen products are mandated by the FDA to have. This may make it more acceptable to patients, who often decline to use an estrogen product after seeing the boxed warning on the package. The Centers for Medicare and Medicaid Services (CMS) does not have prasterone on its list of potentially hazardous drugs for the elderly. However, keep in mind that because its label is for dyspareunia and not specifically for GSM, CMS considers it a drug of choice--in other words, like sildenafil (Viagra), a lifestyle choice and not for treatment of a medical condition. As such, at the present time, Medicare does not cover it.

Bremelanotide

Late-stage trials of bremelanotide, a melanocortin receptor agonist, are underway. Its mechanism of action is somewhat like that of flibanserin in that both drugs increase dopamine and norepinephrine levels. The advantage of bremelanotide is that it is used as needed. It is dosed subcutaneously (1.75 mg) and it can be used as often as a woman would like to use it. The FDA is expected to consider it for approval in about a year. Unpublished data from poster sessions at recent meetings show that, in a phase 3 study of 1,247 premenopausal women with HSDD (who had already been screened for depression and were found to have a physiologic condition), improvements in desire, arousal, lubrication, and orgasm were shown with bremelanotide. About 18% of women stopped using the drug because of adverse effects (nausea, vomiting, flushing, or headache) versus 2% for placebo. Like flibanserin, it is expected to be approved for premenopausal women only. 

Read how 3 experts would manage differing GSM symptoms.

What would you prescribe for these patients? 

CASE Genitourinary syndrome of menopause (GSM) in a 55-year-old woman

A 55-year-old widow is beginning a new relationship. She has not had partnered sexual activity for several years, but she recently has begun a relationship. She describes pain with attempted penetration with her new partner. Her last menstrual period was 3 years ago and she has experienced very minor menopausal symptoms, which are not bothersome. On examination, the vulva and vagina are pale, with thin epithelium and absent rugae. The tissue lacks elasticity. A virginal speculum is needed to visualize the cervix.

How would you go about deciding which of the many options for management of GSM you will recommend for this patient? What do you weigh as you consider DHEA versus estrogen and topical versus oral therapy?
 
JoAnn V. Pinkerton, MD: Vulvovaginal atrophy (VVA), part of GSM, is associated with postmenopausal estrogen deficiency and includes the signs and symptoms seen on this patient's physical exam: vaginal narrowing, pallor, loss of elasticity, as well as pain with intercourse.⁶ Estrogen therapy is the most effective treatment for vaginal atrophy.¹³ Since she does not have significant menopausal symptoms, low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA; these include creams, tablets containing estradiol or conjugated equine estrogen (CEE), and a low-dose vaginal estradiol ring--all available at doses that result in minimal systemic absorption.

Choice is usually made based on patient desire and likely adherence. If the patient prefers nonestrogen therapies that improve VVA and have been approved for relief of dyspareunia in postmenopausal women, I would discuss with the patient the oral selective estrogen receptor modulator ospemifene,¹⁴ and the new intravaginal DHEA suppositories, prasterone.¹⁵ Ospemifene is taken daily as an oral tablet, has a small risk of blood clots, and is my choice for women who do not need systemic hormone therapy and prefer to avoid vaginal therapy.

Andrew M. Kaunitz, MD: GSM is prevalent in menopausal women and, if not treated, causes progressive vaginal dryness and sexual discomfort. When the main indication for hormonal management in a menopausal woman is GSM (as opposed to treatment of vasomotor symptoms or prevention of osteoporosis), the treatment of choice is low-dose local vaginal estrogen, ospemifene, or prasterone (DHEA). Prasterone is a vaginally administered nonestrogen steroid that was approved by the FDA to treat dyspareunia associated with GSM. DHEA is an endogenous inactive steroid that is converted locally into androgens and estrogens; one vaginal insert is placed nightly.^16,17

This 55-year-old widow has not been sexually active for some time. The facts that attempted penetration was painful and only an ultrathin (virginal) speculum could be used for examination indicate that contraction of the pelvic floor muscles is likely present. Simply starting medical management may not lead to comfortable/successful penetrative sex for this woman. In addition to  medical management, she would likely benefit from referral for physical therapy. Using dilators and other strategies, along with the positive impact that medical management will have on the vaginal mucosa, a woman's physical therapist can work with this patient to help the pelvic floor muscles relax and facilitate comfortable penetrative sex.

James A. Simon, MD: With only minor vasomotor symptoms, I would assess the other potential benefits of a systemic therapy. These might include cardiovascular risk reduction (systemic estrogens or estrogens/progesterone in some), breast cancer risk reduction (some data suggesting ospemifene can accomplish this), osteoporosis prevention (systemic estrogens and estrogen/androgens), etc. If there is an option for a treatment to address more than one symptom, in this case GSM, assessing the risks/benefits of each of these therapies should be estimated for this specific patient.

If there are no systemic benefits to be had, then any of the local treatments should be helpful. As there are no head-to-head comparisons available, local estrogen cream, tablets, rings, local DHEA, or systemic ospemifene each should be considered possible treatments. I also feel this patient may benefit from supplementary self-dilation and/or physical therapy.

Related article:
2017 Update on menopause

 
CASE Dyspareunia and vasomotor symptoms in a 42-year-old breast cancer survivor

A 42-year-old woman with a BRCA1 mutation has undergone prophylactic mastectomies as well as hysterectomy with bilateral salpingo-oophorectomy. She reports mild to moderate hot flashes and bothersome vaginal dryness and dyspareunia. Examination confirms GSM.

Would you advise systemic hormone therapy for this patient? What would your recommendation be for management of her GSM symptoms?

Dr. Simon: While one's gut reaction would be to avoid systemic estrogen therapy in a patient with a BRCA1 mutation, the scientific information confirming this fear is lacking.¹⁸ Such patients may benefit significantly from systemic estrogen therapy (reduced risk of cardiovascular disease and cognitive decline, etc.), and with both breasts and both ovaries removed, estrogen's breast cancer risks, if any in this population, are largely avoided. The patient also may benefit from additional local therapy with either estrogens or DHEA.

Dr. Kaunitz: Due to her high lifetime risk of breast and ovarian cancer, this woman has proceeded with risk-reducing breast and gynecologic surgery. As more BRCA mutation carriers are being identified and undergo risk-reducing bilateral mastectomy (usually with reconstruction) and salpingo-oophorectomy, clinicians and mutation carriers more frequently face decisions regarding use of systemic hormone therapy.

Mutation carriers who have undergone bilateral risk-reducing mastectomy experience a very low baseline future risk for breast cancer; accordingly, concerns regarding this disease should not prevent use of systemic hormone therapy. Furthermore, without hormone replacement, induced menopause in women this age is associated with an elevated risk of osteoporosis, persistent vasomotor symptoms, cardiovascular disease, stroke, mood changes, dementia, Parkinson disease, and overall mortality. Recognizing the safety of estrogen therapy in this setting, this 42-year-old BRCA1 mutation carrier can initiate estrogen therapy. Standard dose estrogen therapy refers to oral estradiol 1.0 mg, conjugated equine estrogen 0.625 mg,or transdermal estradiol 0.05 mg. In younger women like this 42-year-old with surgically induced menopause, higher than standard replacement doses of estrogen are often appropriate.¹⁷

Due to concerns the hormone therapy might further increase future risk of breast cancer, some mutation carriers may delay or avoid risk-reducing bilateral salpingo-oophorectomy, a potentially lifesaving surgery which reduces not only future risk of ovarian cancer but also future risk for breast cancer.

Among mutation carriers with intact breasts, several studies address risk of breast cancer with use of systemic hormone therapy. Although limited in numbers of participants and years of follow-up, in aggregate, these studies provide reassurance that short-term use of systemic hormone therapy does not increase breast cancer risk in women with BRCA1 or BRCA2 mutations and intact breasts.¹⁹

Dr. Pinkerton: For this woman with early surgical menopause and hysterectomy, estrogen therapy could improve her vasomotor symptoms and decrease her risk of bone loss and GSM.¹⁷ In the Women's Health Initiative trial, there were 7 fewer breast cancers per 10,000 women-years in the estrogen-onlyarm.²⁰ Observational studies suggest that hormone therapy, when given to the average age of menopause, decreases the risks of heart disease, Parkinson disease, and dementia.²¹ Limited observational evidence suggests that hormone therapy use does not further increase risk of breast cancer in women following oophorectomy for BRCA1 or BRCA2 gene mutation.²²

The absolute risks observed with hormone therapy tended to be small, especially in younger, healthy women. Systemic hormone therapy could treat her hot flashes and her GSM symptoms and potentially decrease health risks associated with premature estrogen deficiency. Nonestrogen therapies for hot flashes include low-dose antidepressants, gabapentin, and mind-body options, such as cognitive behavioral therapy and hypnosis, but these would not decrease her health risks or treat her GSM.

If she only requests treatment of her GSM symptoms, she would be a candidate for low-dose vaginal estrogen therapy, given as a cream, tablet, or ring depending on her choice. I would not choose ospemifene as my first choice as she is having hot flashes, and there are no data yet on the drug's health benefits in early menopause. If she prefers nonestrogen vaginal therapy, the new intravaginal DHEA might be a good choice as both estrogen and testosterone are increased locally in the vagina while hormone levels remain in the postmenopausal range. There is no boxed warning on the patient insert, although safety in women with breast cancer or in those with elevated risk of breast cancer has not been tested.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

Sexual function is a complex, multifaceted process mediated by neurologic functions, hormonal regulation, and psychological factors. What could possibly go wrong?

As it turns out, quite a lot. Female sexual dysfunction is a common, vastly undertreated sexual health problem that can have wide-reaching effects on a woman’s life. These effects may include impaired body image, self-confidence, and self-worth. Sexual dysfunction also can contribute to relationship dissatisfaction and leave one feeling less connected with her partner.^1,2 Studies have shown women with sexual dysfunction have higher health care expenditures³ and that depression and fatigue are common comorbidities, as is frequently seen in other chronic conditions such as diabetes and back pain.⁴

Understanding the pathogenesis of female sexual dysfunction helps to guide our approach to its management. Indeed, increased understanding of its pathology has helped to usher in new and emerging treatment options, as well as a personalized, biopsychosocial approach to its management.

Related article:
2016 Update on female sexual dysfunction

In this Update, I discuss the interplay of physiologic and psychological factors that affect female sexual function as well as the latest options for its management. I have also assembled a panel of experts to discuss 2 cases representative of sexual dysfunction that you may encounter in your clinical practice and how prescribing decisions are made for their management.

Read about factors that impact sexual function and agents to help manage dysfunction.

Multiple transmitters in the brain can increase or decrease sexual desire and function

Neurotransmitters involved in sexual excitation include brain dopamine, melanocortin, oxytocin, vasopressin, and norepinephrine, whereas brain opioids, serotonin, prolactin, and endocannabinoids function as sexual inhibitors. Inhibitory transmitters are activated normally during sexual refractoriness but also from primary aversion or secondary avoidance disorders.¹ Drugs or conditions that reduce brain dopamine levels, increase the action of brain serotonin, or enhance brain opioid pathways have been shown to inhibit sexual desire, while those that increase hypothalamic and mesolimbic dopamine or decrease serotonin release have been shown to stimulate sexual desire.¹ 

Estradiol and progesterone can impact sexual function and desire

In addition to the neurotransmitters, hormones are important modulators of female sexual function. Decreasing levels of circulating estrogen after menopause lead to physiologic, biologic, and clinical changes in the urogenital tissues, such as decreased elastin, thinning of the epithelium, reduced vaginal blood flow, diminished lubrication, and decreased flexibility and elasticity. These changes result in the symptoms of genitourinary syndrome of menopause (GSM), which affects as many as half of all menopausal women.^5,6 In clinical trials, dyspareunia and vaginal dryness are the most bothersome GSM symptoms reported.⁷

The role of hormonal regulation in sexual dysfunction among premenopausal women is not yet fully understood, but we do know that estradiol has been shown to improve sexual desire, progesterone tends to dampen sexual desire, and that testosterone at physiological levels has been shown in most studies to have a neutral effect on sexual desire in a well-estrogenized patient.⁸

Related article:
Focus on treating genital atrophy symptoms

Experience and behavior modulate or reinforce sexual dysfunction

The most common psychological factors that trigger or amplify female sexual dysfunction are depression, anxiety, distraction, negative body image, sexual abuse, and emotional neglect.⁹ Contextual or sociocultural factors, such as relationship discord, life-stage stressors (the empty nest syndrome or anxiety and sleep deprivation from a new baby), as well as cultural or religious values that suppress sexuality, also should be considered.⁹ Experience-based neuroplasticity (changes in brain pathways that become solidified by negative or positive experiences) may elucidate how a multimodal approach, utilizing medical and psychological treatment, can be beneficial for patients, particularly those with hypoactive sexual desire disorder (HSDD).¹

New and emerging approaches to managing female sexual dysfunction

Three agents, one of which has been available for prescription for some time, one that is newly available, and one in the pipeline, are or may soon be in the gynecologist's armamentarium.

Flibanserin

Medications that target excitatory pathways or blunt inhibitory pathways are in development, and one, flibanserin (Addyi), has been US Food and Drug Administration (FDA)-approved for the treatment of acquired, generalized HSDD in premenopausal women.^1,10 Flibanserin is a nonhormonal, centrally acting, postsynaptic serotonin 1A receptor agonist and a serotonin 2A receptor antagonist that is taken daily at bedtime (100 mg); several weeks are usually needed before any effects are noted.¹ It is not approved for postmenopausal women and has a boxed warning about the risks of hypotension and syncope; its use is contraindicated in women who drink alcohol, in those who have hepatic impairment, and with the use of moderate or strong CYP3A4 inhibitors.¹¹

Also keep in mind that flibanserin is only available through a Risk Evaluation and Mitigation Strategy program, so clinicians who wish to prescribe it must enroll in and complete training to become certified providers.⁹

Related article:
What you need to know (and do) to prescribe the new drug flibanserin

Prasterone

Prasterone (Intrarosa), a once-daily intravaginal dehydroepiandrosterone (DHEA) product, is a prohormone that increases local estrogen and testosterone and has the advantage of improved sexual function, desire, arousal, lubrication, orgasm, satisfaction, as well as pain at sexual activity.¹² It was approved by the FDA in November 2016 to treat moderate to severe dyspareunia and has been available for prescribing since July 2017. Its cost is comparable to topical estrogen products, with a $25 copay program.

Because prasterone is not an estrogen, it does not have the boxed warning that all estrogen products are mandated by the FDA to have. This may make it more acceptable to patients, who often decline to use an estrogen product after seeing the boxed warning on the package. The Centers for Medicare and Medicaid Services (CMS) does not have prasterone on its list of potentially hazardous drugs for the elderly. However, keep in mind that because its label is for dyspareunia and not specifically for GSM, CMS considers it a drug of choice--in other words, like sildenafil (Viagra), a lifestyle choice and not for treatment of a medical condition. As such, at the present time, Medicare does not cover it.

Bremelanotide

Late-stage trials of bremelanotide, a melanocortin receptor agonist, are underway. Its mechanism of action is somewhat like that of flibanserin in that both drugs increase dopamine and norepinephrine levels. The advantage of bremelanotide is that it is used as needed. It is dosed subcutaneously (1.75 mg) and it can be used as often as a woman would like to use it. The FDA is expected to consider it for approval in about a year. Unpublished data from poster sessions at recent meetings show that, in a phase 3 study of 1,247 premenopausal women with HSDD (who had already been screened for depression and were found to have a physiologic condition), improvements in desire, arousal, lubrication, and orgasm were shown with bremelanotide. About 18% of women stopped using the drug because of adverse effects (nausea, vomiting, flushing, or headache) versus 2% for placebo. Like flibanserin, it is expected to be approved for premenopausal women only. 

Read how 3 experts would manage differing GSM symptoms.

What would you prescribe for these patients? 

CASE Genitourinary syndrome of menopause (GSM) in a 55-year-old woman

A 55-year-old widow is beginning a new relationship. She has not had partnered sexual activity for several years, but she recently has begun a relationship. She describes pain with attempted penetration with her new partner. Her last menstrual period was 3 years ago and she has experienced very minor menopausal symptoms, which are not bothersome. On examination, the vulva and vagina are pale, with thin epithelium and absent rugae. The tissue lacks elasticity. A virginal speculum is needed to visualize the cervix.

How would you go about deciding which of the many options for management of GSM you will recommend for this patient? What do you weigh as you consider DHEA versus estrogen and topical versus oral therapy?
 
JoAnn V. Pinkerton, MD: Vulvovaginal atrophy (VVA), part of GSM, is associated with postmenopausal estrogen deficiency and includes the signs and symptoms seen on this patient's physical exam: vaginal narrowing, pallor, loss of elasticity, as well as pain with intercourse.⁶ Estrogen therapy is the most effective treatment for vaginal atrophy.¹³ Since she does not have significant menopausal symptoms, low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA; these include creams, tablets containing estradiol or conjugated equine estrogen (CEE), and a low-dose vaginal estradiol ring--all available at doses that result in minimal systemic absorption.

Choice is usually made based on patient desire and likely adherence. If the patient prefers nonestrogen therapies that improve VVA and have been approved for relief of dyspareunia in postmenopausal women, I would discuss with the patient the oral selective estrogen receptor modulator ospemifene,¹⁴ and the new intravaginal DHEA suppositories, prasterone.¹⁵ Ospemifene is taken daily as an oral tablet, has a small risk of blood clots, and is my choice for women who do not need systemic hormone therapy and prefer to avoid vaginal therapy.

Andrew M. Kaunitz, MD: GSM is prevalent in menopausal women and, if not treated, causes progressive vaginal dryness and sexual discomfort. When the main indication for hormonal management in a menopausal woman is GSM (as opposed to treatment of vasomotor symptoms or prevention of osteoporosis), the treatment of choice is low-dose local vaginal estrogen, ospemifene, or prasterone (DHEA). Prasterone is a vaginally administered nonestrogen steroid that was approved by the FDA to treat dyspareunia associated with GSM. DHEA is an endogenous inactive steroid that is converted locally into androgens and estrogens; one vaginal insert is placed nightly.^16,17

This 55-year-old widow has not been sexually active for some time. The facts that attempted penetration was painful and only an ultrathin (virginal) speculum could be used for examination indicate that contraction of the pelvic floor muscles is likely present. Simply starting medical management may not lead to comfortable/successful penetrative sex for this woman. In addition to  medical management, she would likely benefit from referral for physical therapy. Using dilators and other strategies, along with the positive impact that medical management will have on the vaginal mucosa, a woman's physical therapist can work with this patient to help the pelvic floor muscles relax and facilitate comfortable penetrative sex.

James A. Simon, MD: With only minor vasomotor symptoms, I would assess the other potential benefits of a systemic therapy. These might include cardiovascular risk reduction (systemic estrogens or estrogens/progesterone in some), breast cancer risk reduction (some data suggesting ospemifene can accomplish this), osteoporosis prevention (systemic estrogens and estrogen/androgens), etc. If there is an option for a treatment to address more than one symptom, in this case GSM, assessing the risks/benefits of each of these therapies should be estimated for this specific patient.

If there are no systemic benefits to be had, then any of the local treatments should be helpful. As there are no head-to-head comparisons available, local estrogen cream, tablets, rings, local DHEA, or systemic ospemifene each should be considered possible treatments. I also feel this patient may benefit from supplementary self-dilation and/or physical therapy.

Related article:
2017 Update on menopause

 
CASE Dyspareunia and vasomotor symptoms in a 42-year-old breast cancer survivor

A 42-year-old woman with a BRCA1 mutation has undergone prophylactic mastectomies as well as hysterectomy with bilateral salpingo-oophorectomy. She reports mild to moderate hot flashes and bothersome vaginal dryness and dyspareunia. Examination confirms GSM.

Would you advise systemic hormone therapy for this patient? What would your recommendation be for management of her GSM symptoms?

Dr. Simon: While one's gut reaction would be to avoid systemic estrogen therapy in a patient with a BRCA1 mutation, the scientific information confirming this fear is lacking.¹⁸ Such patients may benefit significantly from systemic estrogen therapy (reduced risk of cardiovascular disease and cognitive decline, etc.), and with both breasts and both ovaries removed, estrogen's breast cancer risks, if any in this population, are largely avoided. The patient also may benefit from additional local therapy with either estrogens or DHEA.

Dr. Kaunitz: Due to her high lifetime risk of breast and ovarian cancer, this woman has proceeded with risk-reducing breast and gynecologic surgery. As more BRCA mutation carriers are being identified and undergo risk-reducing bilateral mastectomy (usually with reconstruction) and salpingo-oophorectomy, clinicians and mutation carriers more frequently face decisions regarding use of systemic hormone therapy.

Mutation carriers who have undergone bilateral risk-reducing mastectomy experience a very low baseline future risk for breast cancer; accordingly, concerns regarding this disease should not prevent use of systemic hormone therapy. Furthermore, without hormone replacement, induced menopause in women this age is associated with an elevated risk of osteoporosis, persistent vasomotor symptoms, cardiovascular disease, stroke, mood changes, dementia, Parkinson disease, and overall mortality. Recognizing the safety of estrogen therapy in this setting, this 42-year-old BRCA1 mutation carrier can initiate estrogen therapy. Standard dose estrogen therapy refers to oral estradiol 1.0 mg, conjugated equine estrogen 0.625 mg,or transdermal estradiol 0.05 mg. In younger women like this 42-year-old with surgically induced menopause, higher than standard replacement doses of estrogen are often appropriate.¹⁷

Due to concerns the hormone therapy might further increase future risk of breast cancer, some mutation carriers may delay or avoid risk-reducing bilateral salpingo-oophorectomy, a potentially lifesaving surgery which reduces not only future risk of ovarian cancer but also future risk for breast cancer.

Among mutation carriers with intact breasts, several studies address risk of breast cancer with use of systemic hormone therapy. Although limited in numbers of participants and years of follow-up, in aggregate, these studies provide reassurance that short-term use of systemic hormone therapy does not increase breast cancer risk in women with BRCA1 or BRCA2 mutations and intact breasts.¹⁹

Dr. Pinkerton: For this woman with early surgical menopause and hysterectomy, estrogen therapy could improve her vasomotor symptoms and decrease her risk of bone loss and GSM.¹⁷ In the Women's Health Initiative trial, there were 7 fewer breast cancers per 10,000 women-years in the estrogen-onlyarm.²⁰ Observational studies suggest that hormone therapy, when given to the average age of menopause, decreases the risks of heart disease, Parkinson disease, and dementia.²¹ Limited observational evidence suggests that hormone therapy use does not further increase risk of breast cancer in women following oophorectomy for BRCA1 or BRCA2 gene mutation.²²

The absolute risks observed with hormone therapy tended to be small, especially in younger, healthy women. Systemic hormone therapy could treat her hot flashes and her GSM symptoms and potentially decrease health risks associated with premature estrogen deficiency. Nonestrogen therapies for hot flashes include low-dose antidepressants, gabapentin, and mind-body options, such as cognitive behavioral therapy and hypnosis, but these would not decrease her health risks or treat her GSM.

If she only requests treatment of her GSM symptoms, she would be a candidate for low-dose vaginal estrogen therapy, given as a cream, tablet, or ring depending on her choice. I would not choose ospemifene as my first choice as she is having hot flashes, and there are no data yet on the drug's health benefits in early menopause. If she prefers nonestrogen vaginal therapy, the new intravaginal DHEA might be a good choice as both estrogen and testosterone are increased locally in the vagina while hormone levels remain in the postmenopausal range. There is no boxed warning on the patient insert, although safety in women with breast cancer or in those with elevated risk of breast cancer has not been tested.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Take-Home Points

• Proper patient selection is critical as extensive postoperative rehabilitation is required to obtain an excellent outcome.
• Open and arthroscopic approaches are effective treatment options for elbow contractures.
• Elbow stability must be restored to obtain a successful outcome.
• Knowledge of neurovascular anatomy is essential to prevent neurologic complications.
• Prophylactic ulnar nerve release should be considered, especially in patients with limited flexion.

Elbow stiffness has several etiologies, posttraumatic being the most common. Elbow stiffness can have debilitating functional effects necessitating treatment. In a biomechanical study of normal elbow function, Morrey and colleagues¹ determined that a flexion extension arc of 100° (30°-130°) and a forearm rotation arc of 100° (50° pronation-50° supination) are required in 90% of activities of daily living. Similarly, elbow flexion of <105° was poorly tolerated, whereas patients could easier adapt to flexion contractures up to 40°.²

The goal of initial evaluation should be to establish the cause of the contracture and the patient’s functional demands and ability to cooperate in the extensive postoperative rehabilitation that is essential in achieving an excellent functional outcome. In a thorough clinical examination, the clinician must note skin, range of motion (ROM), ligamentous stability, and neurovascular structures and give special attention to ulnar nerve function and symptoms. Mid-arc pain suggests additional intra-articular pathology, as stiffness typically causes pain only at the limits of motion as osteophytes impinge and soft tissue is under maximal tension. Routine elbow radiographs are required in all cases, and computed tomography (CT) can be useful in evaluating osseous sources of contracture. Suspected ligamentous instability and cartilaginous defects particularly in the setting of mid-arc pain are best evaluated with magnetic resonance imaging.³

In this 5-point review, we evaluate treatment options as well as rehabilitation protocols in the management of elbow stiffness.

1 Anatomy of Contracture: The Usual Suspects

The cause of elbow stiffness is incompletely understood. Several posited contributing factors include biology, complex intra-articular anatomy, capsular distention favoring a flexed position, and tenuous postoperative fixation necessitating prolonged immobilization. Identifying intrinsic and extrinsic anatomical sources of stiffness can help guide treatment.⁴ Intrinsic pathology includes intra-articular malunion, osteophytes, loose bodies, and adhesions; extrinsic pathology includes soft-tissue contracture, heterotopic ossification, and extra-articular malunion.

Compared with the normal elbow, the capsule becomes thickened and fibrotic and thereby prevents motion. Severe contractures, and extension contractures in particular, may require release of the posterior medial capsule and the posterior medial collateral ligament (MCL) to regain motion. In a series of 42 patients with flexion <100°, Park and colleagues⁵ noted that all patients required release of the posterior band of the MCL to regain flexion. Other muscular impediments to motion include contracture of the brachialis and scarring of the triceps to the posterior humerus. Scarring of the triceps to the humerus can limit flexion.

In the posttrauma setting, intra-articular and extra-articular malunion must be considered. Extension malunion of the distal humerus can reduce flexion,⁶ and shortening with compromise of the olecranon and coronoid fossae can limit both flexion and extension.

Last, heterotopic ossification and osteophytes should be assessed as potential causes of limited ROM. Both the coronoid process and the olecranon can develop osteophytes, and their respective fossae should be assessed with CT. Posterior impingement is rare at the tip of the olecranon; it occurs because of "widening" of the olecranon by "Mickey Mouse ear" osteophytes and bony encroachment along the medial and lateral columns. Thus, the olecranon must be narrowed and the fossa widened and deepened.

In case of concomitant ligament instability, we prefer to reconstruct the ligament first, and then perform contracture release as a staged procedure. We favor a staged approach because the rehabilitation regimens for instability and contracture release are diametrically opposed: Instability requires immobilization, and contracture release requires immediate motion. Last, incision placement and ulnar nerve management are crucial in minimizing the potential complications of the second procedure.

2 Nonoperative Treatment

In the absence of significant bony impediments to motion—such as heterotopic ossification or malunion—initial treatment should commence with nonoperative therapy. Therapy should be initiated as soon as concern for stiffness arises in order to prevent contracture. Initial nonoperative treatment can also serve as an important litmus test of postoperative adherence. Adequate patient relaxation is crucial in avoiding co-contracture resisting stretching forces. Passive ROM exercises use sustained force to allow time-dependent stress relaxation to increase tissue length as well as fatigue antagonist muscles. In addition, hold-and-relax techniques apply isometric resistance to induce relaxation of antagonist muscles.⁷ Active ROM should emphasize triceps isolation and elbow extension to prevent scarring of the triceps to the posterior humerus.

Corrective splinting can be an effective adjuvant to physiotherapy. Static progressive turnbuckle splints was described as an effective treatment for both elbow flexion and extension contractures, effecting an average 43° increase in elbow motion in a series of 15 patients.⁸ Similarly, Gelinas and colleagues⁹ noted improvement among 22 patients treated with turnbuckle splinting for an average of 4.5 months. In addition, serial extension splints may be used in the treatment of elbow flexion contractures.

3 Open Contacture Release and Surgical Approach

When nonoperative therapies fail to restore the functional arc of motion, patients with flexion contractures or extension contractures of >30° may be indicated for contracture release. Surgical approach should be determined by meticulous preoperative planning that notes prior incisions and CT findings. It can be helpful to organize common offending structures and their effects on flexion and extension (Table).

A medial over-the-top approach uses the medial supracondylar ridge as a landmark, subperiosteally reflecting the brachialis anteriorly.¹⁰ The ulnar nerve is neurolyzed and protected posteriorly. The flexor-pronator mass is split distally and elevated along with the brachialis as a single sleeve of muscle. The coronal plane of dissection should be the anterior half of the lateral epicondyle to avoid injury to the MCL. Large Bennett or Hohmann retractors can hinge on the lateral border of the humerus and provide clear visualization of the anterior capsule and the ulnohumeral joint. Exposure of the radiocapitellar joint is possible, but this joint is very deep in the operative field, and caution should be taken excising the anterolateral capsule because of the risk of radial nerve injury. The ulnar nerve can be temporarily transposed anteriorly to dissect posteriorly along the supracondylar ridge of the humerus. The triceps is reflected off the distal humerus. Occasionally, the posterior band of the MCL must be resected in severe extension contractures. If possible, the anterior bundle should be preserved. With this approach, the anterior capsule, distal humerus, coronoid process, posterior MCL, posterior capsule, and triceps can be addressed. The zone anterior to the radial head and the anterolateral and posterolateral capsule cannot be safely exposed with a medial approach. As described by Wada and colleagues,¹¹ a primarily medial approach resulted in an average 64° increase in arc of motion.

4 Arthroscopic Contracture Release and Technique

Recently, arthroscopic elbow contracture release, a technically demanding but effective treatment option, has gained popularity. Knowledge of neurovascular anatomy is a prerequisite to the prevention of devastating neurologic complications (ulnar, median, and radial nerve transections have been described^14,15). Relative contraindications include extensive heterotopic ossification, ulnar nerve transposition, and limited arthroscopic experience. Functional improvements as well as average 26° to 42° increases in arc of motion have been described with arthroscopic release.^16-18 In thin-framed patients with dense elbow capsular scarring (severe loss of elbow motion with hard block) and small joint space, arthroscopic release and particularly arthroscope insertion are notoriously difficult.

The patient may be placed in the prone, lateral decubitus, or supine position, depending on surgeon preference (Figure 5). Before surgery, portals and the ulnar nerve should be carefully outlined.¹⁹

We prefer to start by entering the posterior compartment and using the shaver to create a working space. All bone work and resectioning should be performed before capsular resection. After the joint and the olecranon fossa are identified, soft-tissue and bony débridement of the olecranon and the fossa can be performed. Care should be taken to protect the ulnar nerve when the posteromedial corner or medial gutter is approached.

5 Additional Considerations

After surgery, the elbow is immobilized in maximal extension and supination with an anterior splint, and therapy is initiated either immediately or after temporary immobilization.^16,19,20 Regional anesthesia is crucial in obtaining adequate pain control and establishing an immediate postoperative therapy program. The utility of continuous passive motion (CPM) in postoperative protocols is controversial. A retrospective case-control study of 32 patients matched on age, diagnosis, and contraction severity found no benefit of CPM use, and increased costs and hospital length of stay, leading the authors to recommend against CPM use.²⁰

Neurovascular risks are associated with both open and arthroscopic elbow contracture release. Particularly concerning is the risk of traction ulnar neuropathy, described in upward of 20% of patients.²¹ Anatomical studies have found decreases in cubital tunnel and ulnar nerve area as elbow flexion increases with corresponding increased intraneural pressure,²² leading some authors to recommend prophylactic ulnar nerve release with limited preoperative flexion.¹⁵ Nevertheless, despite transposition, ulnar nerve symptoms were noted in 8 of 40 patients who underwent open contracture release for posttraumatic loss of elbow flexion.⁵ In a retrospective review of 164 open and arthroscopic elbow contracture releases, Williams and colleagues²¹ noted an 8.1% rate of postoperative new-onset ulnar nerve symptoms. The rate of ulnar neuropathy was nonsignificantly elevated among patients with preoperative flexion of <100° (15.2% vs 3.7%; P = .057). Recently, a retrospective review of 564 consecutive arthroscopic contracture releases found a significantly higher rate of delayed-onset ulnar neuritis among patients without prophylactic ulnar nerve decompression or transposition (11% vs 3%; P < .001).²³ Further analysis revealed that, compared with decompression, ulnar nerve transposition did not offer additional benefit but was associated with a significantly higher rate of wound complications (19% vs 4%; P = .03). We favor prophylactic release, particularly in the setting of preoperative extension contracture. For open contracture release from the lateral approach, however, we do not routinely release the ulnar nerve unless there were preoperative symptoms.

Although open and arthroscopic contracture releases can provide durable outcomes in the setting of painless elbow stiffness, options are more limited in the treatment of the painful stiff elbow. Total elbow arthroplasty remains an option in low-demand elderly patients but is not without significant risk of complications.²⁴ In addition, durability concerns and postoperative restrictions make total elbow arthroplasty less attractive to younger patients. Interposition arthroplasty may be indicated as a salvage procedure in the treatment of a young or high-demand patient with a stiff painful elbow.²⁵ Elbow stability is crucial in obtaining a successful outcome, and data on optimal graft choices are limited.

Conclusion

Elbow stiffness, a common complication of trauma, significantly impairs activities of daily living. Early after trauma, therapy should be initiated to prevent contracture. In the absence of symptomatic arthritis, both open and arthroscopic contracture releases are effective surgical treatments in properly selected and motivated patients. Although more research is needed to establish the optimal surgical approach, severity and anatomical cause of contracture should guide decisions as to which approach to use. Having a thorough understanding of neurovascular anatomy and of prophylactic ulnar nerve decompression in the setting of limited preoperative flexion can mitigate complications.

Take-Home Points

• Proper patient selection is critical as extensive postoperative rehabilitation is required to obtain an excellent outcome.
• Open and arthroscopic approaches are effective treatment options for elbow contractures.
• Elbow stability must be restored to obtain a successful outcome.
• Knowledge of neurovascular anatomy is essential to prevent neurologic complications.
• Prophylactic ulnar nerve release should be considered, especially in patients with limited flexion.

Elbow stiffness has several etiologies, posttraumatic being the most common. Elbow stiffness can have debilitating functional effects necessitating treatment. In a biomechanical study of normal elbow function, Morrey and colleagues¹ determined that a flexion extension arc of 100° (30°-130°) and a forearm rotation arc of 100° (50° pronation-50° supination) are required in 90% of activities of daily living. Similarly, elbow flexion of <105° was poorly tolerated, whereas patients could easier adapt to flexion contractures up to 40°.²

The goal of initial evaluation should be to establish the cause of the contracture and the patient’s functional demands and ability to cooperate in the extensive postoperative rehabilitation that is essential in achieving an excellent functional outcome. In a thorough clinical examination, the clinician must note skin, range of motion (ROM), ligamentous stability, and neurovascular structures and give special attention to ulnar nerve function and symptoms. Mid-arc pain suggests additional intra-articular pathology, as stiffness typically causes pain only at the limits of motion as osteophytes impinge and soft tissue is under maximal tension. Routine elbow radiographs are required in all cases, and computed tomography (CT) can be useful in evaluating osseous sources of contracture. Suspected ligamentous instability and cartilaginous defects particularly in the setting of mid-arc pain are best evaluated with magnetic resonance imaging.³

In this 5-point review, we evaluate treatment options as well as rehabilitation protocols in the management of elbow stiffness.

1 Anatomy of Contracture: The Usual Suspects

The cause of elbow stiffness is incompletely understood. Several posited contributing factors include biology, complex intra-articular anatomy, capsular distention favoring a flexed position, and tenuous postoperative fixation necessitating prolonged immobilization. Identifying intrinsic and extrinsic anatomical sources of stiffness can help guide treatment.⁴ Intrinsic pathology includes intra-articular malunion, osteophytes, loose bodies, and adhesions; extrinsic pathology includes soft-tissue contracture, heterotopic ossification, and extra-articular malunion.

Compared with the normal elbow, the capsule becomes thickened and fibrotic and thereby prevents motion. Severe contractures, and extension contractures in particular, may require release of the posterior medial capsule and the posterior medial collateral ligament (MCL) to regain motion. In a series of 42 patients with flexion <100°, Park and colleagues⁵ noted that all patients required release of the posterior band of the MCL to regain flexion. Other muscular impediments to motion include contracture of the brachialis and scarring of the triceps to the posterior humerus. Scarring of the triceps to the humerus can limit flexion.

In the posttrauma setting, intra-articular and extra-articular malunion must be considered. Extension malunion of the distal humerus can reduce flexion,⁶ and shortening with compromise of the olecranon and coronoid fossae can limit both flexion and extension.

Last, heterotopic ossification and osteophytes should be assessed as potential causes of limited ROM. Both the coronoid process and the olecranon can develop osteophytes, and their respective fossae should be assessed with CT. Posterior impingement is rare at the tip of the olecranon; it occurs because of "widening" of the olecranon by "Mickey Mouse ear" osteophytes and bony encroachment along the medial and lateral columns. Thus, the olecranon must be narrowed and the fossa widened and deepened.

In case of concomitant ligament instability, we prefer to reconstruct the ligament first, and then perform contracture release as a staged procedure. We favor a staged approach because the rehabilitation regimens for instability and contracture release are diametrically opposed: Instability requires immobilization, and contracture release requires immediate motion. Last, incision placement and ulnar nerve management are crucial in minimizing the potential complications of the second procedure.

2 Nonoperative Treatment

In the absence of significant bony impediments to motion—such as heterotopic ossification or malunion—initial treatment should commence with nonoperative therapy. Therapy should be initiated as soon as concern for stiffness arises in order to prevent contracture. Initial nonoperative treatment can also serve as an important litmus test of postoperative adherence. Adequate patient relaxation is crucial in avoiding co-contracture resisting stretching forces. Passive ROM exercises use sustained force to allow time-dependent stress relaxation to increase tissue length as well as fatigue antagonist muscles. In addition, hold-and-relax techniques apply isometric resistance to induce relaxation of antagonist muscles.⁷ Active ROM should emphasize triceps isolation and elbow extension to prevent scarring of the triceps to the posterior humerus.

Corrective splinting can be an effective adjuvant to physiotherapy. Static progressive turnbuckle splints was described as an effective treatment for both elbow flexion and extension contractures, effecting an average 43° increase in elbow motion in a series of 15 patients.⁸ Similarly, Gelinas and colleagues⁹ noted improvement among 22 patients treated with turnbuckle splinting for an average of 4.5 months. In addition, serial extension splints may be used in the treatment of elbow flexion contractures.

3 Open Contacture Release and Surgical Approach

When nonoperative therapies fail to restore the functional arc of motion, patients with flexion contractures or extension contractures of >30° may be indicated for contracture release. Surgical approach should be determined by meticulous preoperative planning that notes prior incisions and CT findings. It can be helpful to organize common offending structures and their effects on flexion and extension (Table).

A medial over-the-top approach uses the medial supracondylar ridge as a landmark, subperiosteally reflecting the brachialis anteriorly.¹⁰ The ulnar nerve is neurolyzed and protected posteriorly. The flexor-pronator mass is split distally and elevated along with the brachialis as a single sleeve of muscle. The coronal plane of dissection should be the anterior half of the lateral epicondyle to avoid injury to the MCL. Large Bennett or Hohmann retractors can hinge on the lateral border of the humerus and provide clear visualization of the anterior capsule and the ulnohumeral joint. Exposure of the radiocapitellar joint is possible, but this joint is very deep in the operative field, and caution should be taken excising the anterolateral capsule because of the risk of radial nerve injury. The ulnar nerve can be temporarily transposed anteriorly to dissect posteriorly along the supracondylar ridge of the humerus. The triceps is reflected off the distal humerus. Occasionally, the posterior band of the MCL must be resected in severe extension contractures. If possible, the anterior bundle should be preserved. With this approach, the anterior capsule, distal humerus, coronoid process, posterior MCL, posterior capsule, and triceps can be addressed. The zone anterior to the radial head and the anterolateral and posterolateral capsule cannot be safely exposed with a medial approach. As described by Wada and colleagues,¹¹ a primarily medial approach resulted in an average 64° increase in arc of motion.

4 Arthroscopic Contracture Release and Technique

Recently, arthroscopic elbow contracture release, a technically demanding but effective treatment option, has gained popularity. Knowledge of neurovascular anatomy is a prerequisite to the prevention of devastating neurologic complications (ulnar, median, and radial nerve transections have been described^14,15). Relative contraindications include extensive heterotopic ossification, ulnar nerve transposition, and limited arthroscopic experience. Functional improvements as well as average 26° to 42° increases in arc of motion have been described with arthroscopic release.^16-18 In thin-framed patients with dense elbow capsular scarring (severe loss of elbow motion with hard block) and small joint space, arthroscopic release and particularly arthroscope insertion are notoriously difficult.

The patient may be placed in the prone, lateral decubitus, or supine position, depending on surgeon preference (Figure 5). Before surgery, portals and the ulnar nerve should be carefully outlined.¹⁹

We prefer to start by entering the posterior compartment and using the shaver to create a working space. All bone work and resectioning should be performed before capsular resection. After the joint and the olecranon fossa are identified, soft-tissue and bony débridement of the olecranon and the fossa can be performed. Care should be taken to protect the ulnar nerve when the posteromedial corner or medial gutter is approached.

5 Additional Considerations

After surgery, the elbow is immobilized in maximal extension and supination with an anterior splint, and therapy is initiated either immediately or after temporary immobilization.^16,19,20 Regional anesthesia is crucial in obtaining adequate pain control and establishing an immediate postoperative therapy program. The utility of continuous passive motion (CPM) in postoperative protocols is controversial. A retrospective case-control study of 32 patients matched on age, diagnosis, and contraction severity found no benefit of CPM use, and increased costs and hospital length of stay, leading the authors to recommend against CPM use.²⁰

Neurovascular risks are associated with both open and arthroscopic elbow contracture release. Particularly concerning is the risk of traction ulnar neuropathy, described in upward of 20% of patients.²¹ Anatomical studies have found decreases in cubital tunnel and ulnar nerve area as elbow flexion increases with corresponding increased intraneural pressure,²² leading some authors to recommend prophylactic ulnar nerve release with limited preoperative flexion.¹⁵ Nevertheless, despite transposition, ulnar nerve symptoms were noted in 8 of 40 patients who underwent open contracture release for posttraumatic loss of elbow flexion.⁵ In a retrospective review of 164 open and arthroscopic elbow contracture releases, Williams and colleagues²¹ noted an 8.1% rate of postoperative new-onset ulnar nerve symptoms. The rate of ulnar neuropathy was nonsignificantly elevated among patients with preoperative flexion of <100° (15.2% vs 3.7%; P = .057). Recently, a retrospective review of 564 consecutive arthroscopic contracture releases found a significantly higher rate of delayed-onset ulnar neuritis among patients without prophylactic ulnar nerve decompression or transposition (11% vs 3%; P < .001).²³ Further analysis revealed that, compared with decompression, ulnar nerve transposition did not offer additional benefit but was associated with a significantly higher rate of wound complications (19% vs 4%; P = .03). We favor prophylactic release, particularly in the setting of preoperative extension contracture. For open contracture release from the lateral approach, however, we do not routinely release the ulnar nerve unless there were preoperative symptoms.

Although open and arthroscopic contracture releases can provide durable outcomes in the setting of painless elbow stiffness, options are more limited in the treatment of the painful stiff elbow. Total elbow arthroplasty remains an option in low-demand elderly patients but is not without significant risk of complications.²⁴ In addition, durability concerns and postoperative restrictions make total elbow arthroplasty less attractive to younger patients. Interposition arthroplasty may be indicated as a salvage procedure in the treatment of a young or high-demand patient with a stiff painful elbow.²⁵ Elbow stability is crucial in obtaining a successful outcome, and data on optimal graft choices are limited.

Conclusion

Elbow stiffness, a common complication of trauma, significantly impairs activities of daily living. Early after trauma, therapy should be initiated to prevent contracture. In the absence of symptomatic arthritis, both open and arthroscopic contracture releases are effective surgical treatments in properly selected and motivated patients. Although more research is needed to establish the optimal surgical approach, severity and anatomical cause of contracture should guide decisions as to which approach to use. Having a thorough understanding of neurovascular anatomy and of prophylactic ulnar nerve decompression in the setting of limited preoperative flexion can mitigate complications.

Take-Home Points

• Proper patient selection is critical as extensive postoperative rehabilitation is required to obtain an excellent outcome.
• Open and arthroscopic approaches are effective treatment options for elbow contractures.
• Elbow stability must be restored to obtain a successful outcome.
• Knowledge of neurovascular anatomy is essential to prevent neurologic complications.
• Prophylactic ulnar nerve release should be considered, especially in patients with limited flexion.

Elbow stiffness has several etiologies, posttraumatic being the most common. Elbow stiffness can have debilitating functional effects necessitating treatment. In a biomechanical study of normal elbow function, Morrey and colleagues¹ determined that a flexion extension arc of 100° (30°-130°) and a forearm rotation arc of 100° (50° pronation-50° supination) are required in 90% of activities of daily living. Similarly, elbow flexion of <105° was poorly tolerated, whereas patients could easier adapt to flexion contractures up to 40°.²

The goal of initial evaluation should be to establish the cause of the contracture and the patient’s functional demands and ability to cooperate in the extensive postoperative rehabilitation that is essential in achieving an excellent functional outcome. In a thorough clinical examination, the clinician must note skin, range of motion (ROM), ligamentous stability, and neurovascular structures and give special attention to ulnar nerve function and symptoms. Mid-arc pain suggests additional intra-articular pathology, as stiffness typically causes pain only at the limits of motion as osteophytes impinge and soft tissue is under maximal tension. Routine elbow radiographs are required in all cases, and computed tomography (CT) can be useful in evaluating osseous sources of contracture. Suspected ligamentous instability and cartilaginous defects particularly in the setting of mid-arc pain are best evaluated with magnetic resonance imaging.³

In this 5-point review, we evaluate treatment options as well as rehabilitation protocols in the management of elbow stiffness.

1 Anatomy of Contracture: The Usual Suspects

The cause of elbow stiffness is incompletely understood. Several posited contributing factors include biology, complex intra-articular anatomy, capsular distention favoring a flexed position, and tenuous postoperative fixation necessitating prolonged immobilization. Identifying intrinsic and extrinsic anatomical sources of stiffness can help guide treatment.⁴ Intrinsic pathology includes intra-articular malunion, osteophytes, loose bodies, and adhesions; extrinsic pathology includes soft-tissue contracture, heterotopic ossification, and extra-articular malunion.

Compared with the normal elbow, the capsule becomes thickened and fibrotic and thereby prevents motion. Severe contractures, and extension contractures in particular, may require release of the posterior medial capsule and the posterior medial collateral ligament (MCL) to regain motion. In a series of 42 patients with flexion <100°, Park and colleagues⁵ noted that all patients required release of the posterior band of the MCL to regain flexion. Other muscular impediments to motion include contracture of the brachialis and scarring of the triceps to the posterior humerus. Scarring of the triceps to the humerus can limit flexion.

In the posttrauma setting, intra-articular and extra-articular malunion must be considered. Extension malunion of the distal humerus can reduce flexion,⁶ and shortening with compromise of the olecranon and coronoid fossae can limit both flexion and extension.

Last, heterotopic ossification and osteophytes should be assessed as potential causes of limited ROM. Both the coronoid process and the olecranon can develop osteophytes, and their respective fossae should be assessed with CT. Posterior impingement is rare at the tip of the olecranon; it occurs because of "widening" of the olecranon by "Mickey Mouse ear" osteophytes and bony encroachment along the medial and lateral columns. Thus, the olecranon must be narrowed and the fossa widened and deepened.

In case of concomitant ligament instability, we prefer to reconstruct the ligament first, and then perform contracture release as a staged procedure. We favor a staged approach because the rehabilitation regimens for instability and contracture release are diametrically opposed: Instability requires immobilization, and contracture release requires immediate motion. Last, incision placement and ulnar nerve management are crucial in minimizing the potential complications of the second procedure.

2 Nonoperative Treatment

In the absence of significant bony impediments to motion—such as heterotopic ossification or malunion—initial treatment should commence with nonoperative therapy. Therapy should be initiated as soon as concern for stiffness arises in order to prevent contracture. Initial nonoperative treatment can also serve as an important litmus test of postoperative adherence. Adequate patient relaxation is crucial in avoiding co-contracture resisting stretching forces. Passive ROM exercises use sustained force to allow time-dependent stress relaxation to increase tissue length as well as fatigue antagonist muscles. In addition, hold-and-relax techniques apply isometric resistance to induce relaxation of antagonist muscles.⁷ Active ROM should emphasize triceps isolation and elbow extension to prevent scarring of the triceps to the posterior humerus.

Corrective splinting can be an effective adjuvant to physiotherapy. Static progressive turnbuckle splints was described as an effective treatment for both elbow flexion and extension contractures, effecting an average 43° increase in elbow motion in a series of 15 patients.⁸ Similarly, Gelinas and colleagues⁹ noted improvement among 22 patients treated with turnbuckle splinting for an average of 4.5 months. In addition, serial extension splints may be used in the treatment of elbow flexion contractures.

3 Open Contacture Release and Surgical Approach

When nonoperative therapies fail to restore the functional arc of motion, patients with flexion contractures or extension contractures of >30° may be indicated for contracture release. Surgical approach should be determined by meticulous preoperative planning that notes prior incisions and CT findings. It can be helpful to organize common offending structures and their effects on flexion and extension (Table).

A medial over-the-top approach uses the medial supracondylar ridge as a landmark, subperiosteally reflecting the brachialis anteriorly.¹⁰ The ulnar nerve is neurolyzed and protected posteriorly. The flexor-pronator mass is split distally and elevated along with the brachialis as a single sleeve of muscle. The coronal plane of dissection should be the anterior half of the lateral epicondyle to avoid injury to the MCL. Large Bennett or Hohmann retractors can hinge on the lateral border of the humerus and provide clear visualization of the anterior capsule and the ulnohumeral joint. Exposure of the radiocapitellar joint is possible, but this joint is very deep in the operative field, and caution should be taken excising the anterolateral capsule because of the risk of radial nerve injury. The ulnar nerve can be temporarily transposed anteriorly to dissect posteriorly along the supracondylar ridge of the humerus. The triceps is reflected off the distal humerus. Occasionally, the posterior band of the MCL must be resected in severe extension contractures. If possible, the anterior bundle should be preserved. With this approach, the anterior capsule, distal humerus, coronoid process, posterior MCL, posterior capsule, and triceps can be addressed. The zone anterior to the radial head and the anterolateral and posterolateral capsule cannot be safely exposed with a medial approach. As described by Wada and colleagues,¹¹ a primarily medial approach resulted in an average 64° increase in arc of motion.

4 Arthroscopic Contracture Release and Technique

Recently, arthroscopic elbow contracture release, a technically demanding but effective treatment option, has gained popularity. Knowledge of neurovascular anatomy is a prerequisite to the prevention of devastating neurologic complications (ulnar, median, and radial nerve transections have been described^14,15). Relative contraindications include extensive heterotopic ossification, ulnar nerve transposition, and limited arthroscopic experience. Functional improvements as well as average 26° to 42° increases in arc of motion have been described with arthroscopic release.^16-18 In thin-framed patients with dense elbow capsular scarring (severe loss of elbow motion with hard block) and small joint space, arthroscopic release and particularly arthroscope insertion are notoriously difficult.

The patient may be placed in the prone, lateral decubitus, or supine position, depending on surgeon preference (Figure 5). Before surgery, portals and the ulnar nerve should be carefully outlined.¹⁹

We prefer to start by entering the posterior compartment and using the shaver to create a working space. All bone work and resectioning should be performed before capsular resection. After the joint and the olecranon fossa are identified, soft-tissue and bony débridement of the olecranon and the fossa can be performed. Care should be taken to protect the ulnar nerve when the posteromedial corner or medial gutter is approached.

5 Additional Considerations

After surgery, the elbow is immobilized in maximal extension and supination with an anterior splint, and therapy is initiated either immediately or after temporary immobilization.^16,19,20 Regional anesthesia is crucial in obtaining adequate pain control and establishing an immediate postoperative therapy program. The utility of continuous passive motion (CPM) in postoperative protocols is controversial. A retrospective case-control study of 32 patients matched on age, diagnosis, and contraction severity found no benefit of CPM use, and increased costs and hospital length of stay, leading the authors to recommend against CPM use.²⁰

Neurovascular risks are associated with both open and arthroscopic elbow contracture release. Particularly concerning is the risk of traction ulnar neuropathy, described in upward of 20% of patients.²¹ Anatomical studies have found decreases in cubital tunnel and ulnar nerve area as elbow flexion increases with corresponding increased intraneural pressure,²² leading some authors to recommend prophylactic ulnar nerve release with limited preoperative flexion.¹⁵ Nevertheless, despite transposition, ulnar nerve symptoms were noted in 8 of 40 patients who underwent open contracture release for posttraumatic loss of elbow flexion.⁵ In a retrospective review of 164 open and arthroscopic elbow contracture releases, Williams and colleagues²¹ noted an 8.1% rate of postoperative new-onset ulnar nerve symptoms. The rate of ulnar neuropathy was nonsignificantly elevated among patients with preoperative flexion of <100° (15.2% vs 3.7%; P = .057). Recently, a retrospective review of 564 consecutive arthroscopic contracture releases found a significantly higher rate of delayed-onset ulnar neuritis among patients without prophylactic ulnar nerve decompression or transposition (11% vs 3%; P < .001).²³ Further analysis revealed that, compared with decompression, ulnar nerve transposition did not offer additional benefit but was associated with a significantly higher rate of wound complications (19% vs 4%; P = .03). We favor prophylactic release, particularly in the setting of preoperative extension contracture. For open contracture release from the lateral approach, however, we do not routinely release the ulnar nerve unless there were preoperative symptoms.

Although open and arthroscopic contracture releases can provide durable outcomes in the setting of painless elbow stiffness, options are more limited in the treatment of the painful stiff elbow. Total elbow arthroplasty remains an option in low-demand elderly patients but is not without significant risk of complications.²⁴ In addition, durability concerns and postoperative restrictions make total elbow arthroplasty less attractive to younger patients. Interposition arthroplasty may be indicated as a salvage procedure in the treatment of a young or high-demand patient with a stiff painful elbow.²⁵ Elbow stability is crucial in obtaining a successful outcome, and data on optimal graft choices are limited.

Conclusion

Elbow stiffness, a common complication of trauma, significantly impairs activities of daily living. Early after trauma, therapy should be initiated to prevent contracture. In the absence of symptomatic arthritis, both open and arthroscopic contracture releases are effective surgical treatments in properly selected and motivated patients. Although more research is needed to establish the optimal surgical approach, severity and anatomical cause of contracture should guide decisions as to which approach to use. Having a thorough understanding of neurovascular anatomy and of prophylactic ulnar nerve decompression in the setting of limited preoperative flexion can mitigate complications.

Take-Home Points

• Restore proper anatomic parameters; compare to the other side.
• Don't forget about the DRU joint.
• CT can aide in identifying subtle articular depression and severe comminution to change operative management.
• Remember, there still is a role for external fixators; an alternative remains an internal spanning plate.
• Respect the soft tissues, which can aide in reduction, however don't leave the operating room without feeling confident about your fixation.

Distal radius fracture (DRF), a common fracture, accounts for almost one sixth of all emergency department visits.¹ With the advent of emerging technologies and refined technique, treatment options for DRFs have evolved. Although controversy remains regarding nonoperative vs operative treatment of DRFs in the elderly,^2,3 select situations (open injuries, complex high-energy injuries, young age) warrant definitive fixation. Previously, internal fixation options were limited. Current technologies include locked fixed-angle plating, fragment-specific fixation, and locked variable-angle plating. These modalities aid in achieving and maintaining more anatomical fixation. This article summarizes tips, tricks, and planning for definitive external and internal fixation of complex DRFs.

Anatomical Considerations and Classification

The wrist joint, part of the complex articular network that begins at the forearm and ends at the distal interphalangeal joint, is the foundation for fine- and gross-motor skills. Understanding the anatomy of this network can provide a valuable roadmap for operative reconstruction.

At the wrist level, the radius bears most of the weight-bearing, and in some studies exhibits up to 80% of the load.^1,4 The triangular distal radius bears this weight through a biconcave articular surface with facets for the lunate and scaphoid separated by an anteroposterior ridge.^5-7 The radius also articulates with the ulnar head at the sigmoid notch to form the distal radioulnar (DRU) joint. Restoring the relationships of the DRU joint, the triangular fibrocartilage complex, and the ulnar variance is of paramount importance.^1,8,9

Classical teaching calls for restoration of radial inclination to about 23°, volar tilt to 11° to 12°, and radial length to about 11 mm. Especially regarding volar tilt and radial length, however, cadaveric and clinical studies have found more variance, leading to use of the contralateral extremity as an operative template, particularly when closed reduction thought to be adequate deviates significantly from these parameters.^1,4,7

DRF classification based on these principles has led to abundant representation in the literature.^10-13 Many authors have focused on fracture lines, comminution degree, articular surface violation, and other anatomical or radiographic characteristics of DRF classification and operative fixation approach.^10-13 In 2001, Fernandez⁹ proposed a classification system focused on energy or mechanism of injury. In comparisons,¹⁴ the Fernandez system had the highest interobserver reliability—higher than that of AO (Arbeitsgemeinschaft für Osteosynthesefragen).

Considerations for Operative Treatment: Column Theory

In the restoration of anatomical alignment in complex DRFs, it is important to consider the 3 joints and the 3 columns—radial, intermediate, and ulnar (Figure 1). [[{"fid":"201864","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"1"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 1.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 1.","field_file_image_credit[und][0][value]":""}}}]]In addition, parallels between the distal radius and the tibial plateau can be considered because of similarities in operative goals. Restoration of mechanical axis, length, alignment, rotation, and articular surfaces is paramount.¹⁵ Considering multiple surgical approaches to address "bicolumnar injuries" and reconstructing the "simpler" columnar injury first are common principles.¹⁶

The goals of fracture fixation at the wrist are the same as at any other joint: anatomical reduction, stable fixation, and early range of motion (ROM). Column restoration can result in consistent achievement of those goals. Intuitively, there is a close correlation between anatomical alignment and functional results.¹⁷ Rebuilding the structural foundation of the columns with respect to buttressing and restoring the 3 radial articulations with the ulna, scaphoid, and lunate can consistently yield restoration of length, inclination, and tilt (Figure 2). [[{"fid":"201865","view_mode":"medstat_image_flush_right","attributes":{"class":"media-element file-medstat-image-flush-right","data-delta":"2"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 2.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"2":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 2.","field_file_image_credit[und][0][value]":""}}}]]Next, we discuss the options available and how to use each to an advantage, individually or in hybrid constructs.

External Fixation: Is There Still a Role?

In the setting of highly comminuted, complex fractures, external fixation with Kirschner wires (K-wires) is a reasonable choice, with restoration of motion and strength within 75% to 80% of the uninjured wrist.¹⁸ In a 2-year study of 113 patients with comminuted metaphyseal DRFs randomly assigned to either external fixation or casting, Kreder and colleagues¹⁹ found a trend toward better clinical, functional, and radiographic outcomes with external fixation with or without K-wire fixation. There was improved restoration of radial length and palmar tilt with external fixation. A study of unstable DRF in patients with osteoporosis found that redisplacement was more common after treatment with a cast than after treatment with an external fixator.²⁰ Although closed reduction and casting continue to have a role in the treatment of DRF, Kreder and colleagues¹⁹ found that remanipulation was necessary in at least 9% of cases. According to a meta-analysis²¹ of the literature on DRF treatment, 4 articles directly address the question of the superiority of external fixation over closed reduction and casting, and 3 of the 4 found more favorable radiographic and functional outcomes with external fixation.

External fixation is useful in treating complex DRFs with metaphyseal comminution. It can also be effective in the presence of simple articular involvement without depression of the joint surface. External fixation devices can span areas of soft-
tissue injury and are useful as manipulation tools in achieving anatomical reduction. Although external fixation is effective, its complications include pin-tract infection, nerve injury, loss of reduction, and loss of digital ROM. In a meta-analysis, Li-hai and colleagues²² found that external fixators had a complication rate of 30.9%. With this technique, it is important to avoid midcarpal distraction, excessive ulnar deviation, and excessive palmar flexion. Papadonikolakis and colleagues²³ found that distraction of as little as 2 mm to 5 mm significantly affected the function of the flexor digitorum superficialis at the metacarpophalangeal joint. Over-distraction in wrist flexion can lead to lengthening of the extensor tendons and loss of full digital ROM. Excessive flexion and ulnar deviation can lead to median nerve compression and associated symptoms, as well as poor extensor and radial tendon length. In addition, prolonged distraction in excessive flexion combined with swelling and inflammation during fracture healing causes digital stiffness and contracture.²³ Biomechanical studies have found that proximal pin placement in the radius, along with distal pin fixation in 6 metacarpal cortices through the second and third metacarpals, helps provide the strongest fixation.²⁴

As for technique, pins are placed in the second metacarpal and radial shaft. With respect to the radius, the incision is made just proximal to the edge of the abductor pollicis longus muscle in the "bare area." Ideal pin placement is between the extensor carpi radialis longus and the extensor carpi radialis brevis, with care taken to avoid the radial sensory nerve, which lies between the extensor carpi radialis longus and the brachialis and emerges 9 cm proximal to the radial styloid.²⁵ Next, a 2.5-cm to 3-cm incision is made over the palpable edge of the index metacarpal near the base. During drilling, the guide is placed at intersecting 45° angles, and the distal pin is placed 2 cm to 3 cm from the proximal pin. The proximal metacarpal pin is placed at the base of the metacarpal. The second metacarpal pin can also be placed first, with the external fixator used to judge proximal placement of the radial pin within the bare area.

Various supplements to external fixation have positive outcomes. Wolfe and colleagues¹⁸ found that using K-wires with the external fixation construct added stability in flexion/extension, radial/ulnar deviation, and rotational motion. They noted that fixation stability may depend more on the augmentation to fixation than on the external fixator itself. In a prospective, randomized trial, Moroni and colleagues^26,27 found that, compared with standard pins, hydroxyapatite-coated pins had higher extraction torque, which was associated with improved fixation. When combined with external fixation, calcium phosphate cement also provided additional stability, allowing the bone filler to help maintain articular reduction and cortical continuity.^28,29

External fixation has its disadvantages and complications. It can be bulky, and theoretically it contributes to higher rates of stiffness in the wrist and fingers.^30-32 Higher rates of pin-site infection have been reported, along with hardware failure and associated loss of reduction, in patients treated with external fixation (Figures 3A-3C).^31-33[[{"fid":"201866","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"3"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 3.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"3":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 3.","field_file_image_credit[und][0][value]":""}}}]]In addition, joint overdistraction can adversely affect the length-tension curve and contribute to potential reflex sympathetic dystrophy, which can be devastating (Figures 4A, 4B).^1,21,31,33 Despite these complications, external fixation remains a powerful tool in the treatment of high-energy DRFs. [[{"fid":"201867","view_mode":"medstat_image_flush_right","attributes":{"class":"media-element file-medstat-image-flush-right","data-delta":"4"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 4.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"4":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 4.","field_file_image_credit[und][0][value]":""}}}]]In many cases, authors who compared open reduction and internal fixation (ORIF) with external fixation found no significant differences in outcome scores or function.^31-34 In a meta-analysis of 917 patients, Margaliot and colleagues³³ found no differences in pain, grip strength, wrist ROM, or radiographic parameters. More recently, in prospective randomized trials, both Egol and colleagues³¹ and Grewal and colleagues³⁴ compared hybrid external fixation with ORIF, and, though early outcomes favored ORIF, 1-year follow-up comparisons were even, and there were no significant differences. These consistently reproducible results reaffirm keeping external fixation in the orthopedic toolbox.

Definitive Reconstruction With ORIF

Early nonlocked dorsal plating options for DRF fixation had unacceptable rates of plate failure, poor cosmesis, and extensor tendon complications.^17,35-37 Subsequent technologic advances—multiple approaches, lower profile plating, and rigid, fragment-specific fixation—have allowed even the most complex fracture patterns to be addressed (Table). In malunited fractures, bone graft may not be required if the fracture is extra-articular and treated with a volar locking plate. [[{"fid":"201868","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"5"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Table.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"5":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Table.","field_file_image_credit[und][0][value]":""}}}]]Other options include corticocancellous autograft from the iliac crest, hydroxyapatite synthetic grafts, and osteoconductive bone graft substitutes, such as bone morphogenic proteins. In addition, healing times are similar in cases, regardless of whether a graft was used.³⁸

Involvement of the radial and intermediate columns should be addressed first. Although some may prefer a single volar plate, others may use fragment-specific fixation to buttress a comminuted radial styloid (in orthogonal fashion) and/or a dorsal ulnar fragment to restore the intermediate column and thereby fully restore the radial articular surface.^39,40 Typically, restoring the radial and intermediate columns for radial articular reduction subsequently and simultaneously restores the majority of radial height and length. After the radial and intermediate columns are reduced and stabilized, the need for ulna column fixation can be determined. Important factors in ulna column restoration are severe osteoporosis and ulna head and/or neck comminution. Significant comminution throughout the metaphysis of both the radius and the ulna may also warrant stabilizing the ulna with internal fixation. Finally, any DRU joint instability noted on examination should also favor fixing the ulnar side.

Assessment of the distal ulna in these complex fractures goes beyond the involvement of an ulnar styloid fracture. Typically, fractures at the base of the ulnar styloid have been reported to have little clinical relevance, including a low incidence of associated DRU joint problems.^41-43 Decisions to address the ulnar column are largely swayed by any instability found on DRU joint testing, as laxity caused by severe comminution can dictate the need for distal ring fixation to provide support. Even in the presence of a high-energy fracture in severely osteoporotic bone, the argument can be made to prevent instability by supporting the ulnar column. Stabilization of the ulnar articular surface can also be made more facile by creating an easier "A" fracture pattern (per AO classification) from a complex "C" to further aid in achieving efficient anatomical reduction. After preoperative planning is completed, depending on which columns need to be addressed, several surgical approaches can be considered to achieve maximum exposure and soft-tissue mobilization in order to successfully complete the operative fixation goals.

Volar Approach

An approach is selected for ideal exposure of a facile environment for definitive fixation. Access to the radial column can be gained with the extended flexor carpi radialis (FCR) approach. This approach allows visualization and removal of the appropriate deforming forces on the radial column to allow for fracture reduction by "opening the book," similar to that of tibial plateau reconstruction.^44,45 It may be prudent to perform a preincision Allen test as well as a preoperative DRU joint examination for comparison after ORIF is complete. Compared with the classic Henry approach near the distal radius, going through the volar sheath of the FCR avoids many of the perforating radial artery branches. Avoiding stripping the radial artery of its surrounding fat and lymphatics prevents postoperative "cold intolerance." Retracting the FCR ulnarly and then incising the dorsal FCR sheath provide ready access to the pronator quadratus after collective ulnar mobilization of both the FCR and the flexor pollicis longus.⁴⁴ In addition, for work near the distal FCR sheath, care must be taken to avoid the branch of the palmar cutaneous nerve that emerges about 5 cm proximal to the wrist flexion crease.⁴⁶

Once at the level of the pronator quadratus, an "L-shape" incision can be made to reflect the muscle off the radius. Care must be taken when working too distal to avoid transection of the inserting volar wrist ligaments.⁴⁴ Leaving a cuff for repair of the pronator remains controversial. In a recent case-control series, however, Hershman and colleagues⁴⁷ did not find significant differences in function or complication rate in patients with and without repair. After reflection, adequate exposure of the radial column should be achieved. Ready access to the radial styloid for orthogonal plating can be obtained by releasing the brachioradialis, which simultaneously releases one of the primary fracture deforming forces.⁴⁴ With this incision and exposure, if needed, dorsal bone grafting can be achieved from the volar side; however, care must be taken to protect the first dorsal compartment.⁴⁸ The cutaneous branch of the median nerve may be at risk with this exposure, but avoiding dissection ulnar to the FCR tendon can help to reduce this risk.⁴⁹

Before surgery, if the fracture pattern dictates a more ulnar approach, we prefer the extended carpal tunnel approach. Using the plane between the palmaris longus and the flexor digitorum superficialis medially and the FCR laterally, the extended carpal tunnel approach provides an obvious release of the flexor retinaculum but, more important, allows for extensile access to the sigmoid notch, the DRU joint, and the ulnar column.

Dorsal Approach

The dorsal approach is necessary in a few select cases. With a focus on fragment-specific fixation, presence of a significant dorsal ulnar fragment should warrant a dorsal approach.⁵⁰ In addition, in select, rare cases in which volar access is limited or unavailable, dorsal access is the only option.⁵⁰ Finally, if direct articular visualization is required, the dorsal approach typically is favored as the stronger radiocarpal ligaments found on the volar side are maintained.

Access should begin with an incision centered over the dorsal distal radius; a safe access point is just ulnar to the Lister tubercle. On incision of the retinaculum through a full-thickness excision, the third dorsal compartment is opened and the extensor pollicis longus (EPL) mobilized, fully exposing the dorsal distal radius. Work can be performed on either side of the EPL between the second and fourth dorsal compartments. Exposure typically is not an issue because of the pliable soft tissue of the dorsum, with ready access from styloid to styloid.⁴⁴ Here, low-profile plates and/or mini-fragment-specific plate options should be used to minimize potential tendon damage.⁵¹ Care must also be taken to avoid damaging the radiocarpal or scapholunate ligaments.⁴⁹ On closure, the retinaculum is repaired primarily; however, though some proponents advocate relocating the EPL tendon into its groove, we prefer leaving the EPL free within the surrounding soft tissue to reduce tension and promote unhindered excursion. The dorsal approach, though controversial and used inconsistently, should remain an important tool in anatomical restoration, especially in cases of complex fracture patterns.

Conclusion

Controversy still marks the lack of consensus on deciding which DRF treatment is optimal. Some investigators question moving away from external fixation and cite the lack of significantly better data relative to ORIF.^21,52 The same proponents note that the only advantage over external fixation is earlier return to function and cite reports of tendon rupture and complications with both dorsal and volar fixation options.^34,53-58 Other investigators find that operative treatment generally does not provide a significant improvement over nonoperative treatment.⁵⁹

With the advent of lower profile locked plating, fragment-specific fixation, and variable-angle devices, comparative clinical trials are finding it difficult to keep up.^60-64 Results from ongoing prospective randomized trials like ORCHID (Open Reduction and Internal Fixation Versus Casting for Highly Comminuted Intra-Articular Fractures of the Distal Radius; 500 patients >65 years old, 15 centers) will provide more definitive answers about ideal treatment.⁶⁵

Anatomical restoration involves a versatile array of fragment fixation and reconstruction. Careful preoperative planning and a consistent approach to restoring the radial, intermediate, and ulnar columns, along with a proper surgical approach, are ideal. Many advances in internal fixation have been exceedingly helpful. Use of external fixation, especially in a bridging fashion with or without supplementation, is still valuable in many situations.

Take-Home Points

• Restore proper anatomic parameters; compare to the other side.
• Don't forget about the DRU joint.
• CT can aide in identifying subtle articular depression and severe comminution to change operative management.
• Remember, there still is a role for external fixators; an alternative remains an internal spanning plate.
• Respect the soft tissues, which can aide in reduction, however don't leave the operating room without feeling confident about your fixation.

Distal radius fracture (DRF), a common fracture, accounts for almost one sixth of all emergency department visits.¹ With the advent of emerging technologies and refined technique, treatment options for DRFs have evolved. Although controversy remains regarding nonoperative vs operative treatment of DRFs in the elderly,^2,3 select situations (open injuries, complex high-energy injuries, young age) warrant definitive fixation. Previously, internal fixation options were limited. Current technologies include locked fixed-angle plating, fragment-specific fixation, and locked variable-angle plating. These modalities aid in achieving and maintaining more anatomical fixation. This article summarizes tips, tricks, and planning for definitive external and internal fixation of complex DRFs.

Anatomical Considerations and Classification

The wrist joint, part of the complex articular network that begins at the forearm and ends at the distal interphalangeal joint, is the foundation for fine- and gross-motor skills. Understanding the anatomy of this network can provide a valuable roadmap for operative reconstruction.

At the wrist level, the radius bears most of the weight-bearing, and in some studies exhibits up to 80% of the load.^1,4 The triangular distal radius bears this weight through a biconcave articular surface with facets for the lunate and scaphoid separated by an anteroposterior ridge.^5-7 The radius also articulates with the ulnar head at the sigmoid notch to form the distal radioulnar (DRU) joint. Restoring the relationships of the DRU joint, the triangular fibrocartilage complex, and the ulnar variance is of paramount importance.^1,8,9

Classical teaching calls for restoration of radial inclination to about 23°, volar tilt to 11° to 12°, and radial length to about 11 mm. Especially regarding volar tilt and radial length, however, cadaveric and clinical studies have found more variance, leading to use of the contralateral extremity as an operative template, particularly when closed reduction thought to be adequate deviates significantly from these parameters.^1,4,7

DRF classification based on these principles has led to abundant representation in the literature.^10-13 Many authors have focused on fracture lines, comminution degree, articular surface violation, and other anatomical or radiographic characteristics of DRF classification and operative fixation approach.^10-13 In 2001, Fernandez⁹ proposed a classification system focused on energy or mechanism of injury. In comparisons,¹⁴ the Fernandez system had the highest interobserver reliability—higher than that of AO (Arbeitsgemeinschaft für Osteosynthesefragen).

Considerations for Operative Treatment: Column Theory

In the restoration of anatomical alignment in complex DRFs, it is important to consider the 3 joints and the 3 columns—radial, intermediate, and ulnar (Figure 1). [[{"fid":"201864","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"1"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 1.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 1.","field_file_image_credit[und][0][value]":""}}}]]In addition, parallels between the distal radius and the tibial plateau can be considered because of similarities in operative goals. Restoration of mechanical axis, length, alignment, rotation, and articular surfaces is paramount.¹⁵ Considering multiple surgical approaches to address "bicolumnar injuries" and reconstructing the "simpler" columnar injury first are common principles.¹⁶

The goals of fracture fixation at the wrist are the same as at any other joint: anatomical reduction, stable fixation, and early range of motion (ROM). Column restoration can result in consistent achievement of those goals. Intuitively, there is a close correlation between anatomical alignment and functional results.¹⁷ Rebuilding the structural foundation of the columns with respect to buttressing and restoring the 3 radial articulations with the ulna, scaphoid, and lunate can consistently yield restoration of length, inclination, and tilt (Figure 2). [[{"fid":"201865","view_mode":"medstat_image_flush_right","attributes":{"class":"media-element file-medstat-image-flush-right","data-delta":"2"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 2.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"2":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 2.","field_file_image_credit[und][0][value]":""}}}]]Next, we discuss the options available and how to use each to an advantage, individually or in hybrid constructs.

External Fixation: Is There Still a Role?

In the setting of highly comminuted, complex fractures, external fixation with Kirschner wires (K-wires) is a reasonable choice, with restoration of motion and strength within 75% to 80% of the uninjured wrist.¹⁸ In a 2-year study of 113 patients with comminuted metaphyseal DRFs randomly assigned to either external fixation or casting, Kreder and colleagues¹⁹ found a trend toward better clinical, functional, and radiographic outcomes with external fixation with or without K-wire fixation. There was improved restoration of radial length and palmar tilt with external fixation. A study of unstable DRF in patients with osteoporosis found that redisplacement was more common after treatment with a cast than after treatment with an external fixator.²⁰ Although closed reduction and casting continue to have a role in the treatment of DRF, Kreder and colleagues¹⁹ found that remanipulation was necessary in at least 9% of cases. According to a meta-analysis²¹ of the literature on DRF treatment, 4 articles directly address the question of the superiority of external fixation over closed reduction and casting, and 3 of the 4 found more favorable radiographic and functional outcomes with external fixation.

External fixation is useful in treating complex DRFs with metaphyseal comminution. It can also be effective in the presence of simple articular involvement without depression of the joint surface. External fixation devices can span areas of soft-
tissue injury and are useful as manipulation tools in achieving anatomical reduction. Although external fixation is effective, its complications include pin-tract infection, nerve injury, loss of reduction, and loss of digital ROM. In a meta-analysis, Li-hai and colleagues²² found that external fixators had a complication rate of 30.9%. With this technique, it is important to avoid midcarpal distraction, excessive ulnar deviation, and excessive palmar flexion. Papadonikolakis and colleagues²³ found that distraction of as little as 2 mm to 5 mm significantly affected the function of the flexor digitorum superficialis at the metacarpophalangeal joint. Over-distraction in wrist flexion can lead to lengthening of the extensor tendons and loss of full digital ROM. Excessive flexion and ulnar deviation can lead to median nerve compression and associated symptoms, as well as poor extensor and radial tendon length. In addition, prolonged distraction in excessive flexion combined with swelling and inflammation during fracture healing causes digital stiffness and contracture.²³ Biomechanical studies have found that proximal pin placement in the radius, along with distal pin fixation in 6 metacarpal cortices through the second and third metacarpals, helps provide the strongest fixation.²⁴

As for technique, pins are placed in the second metacarpal and radial shaft. With respect to the radius, the incision is made just proximal to the edge of the abductor pollicis longus muscle in the "bare area." Ideal pin placement is between the extensor carpi radialis longus and the extensor carpi radialis brevis, with care taken to avoid the radial sensory nerve, which lies between the extensor carpi radialis longus and the brachialis and emerges 9 cm proximal to the radial styloid.²⁵ Next, a 2.5-cm to 3-cm incision is made over the palpable edge of the index metacarpal near the base. During drilling, the guide is placed at intersecting 45° angles, and the distal pin is placed 2 cm to 3 cm from the proximal pin. The proximal metacarpal pin is placed at the base of the metacarpal. The second metacarpal pin can also be placed first, with the external fixator used to judge proximal placement of the radial pin within the bare area.

Various supplements to external fixation have positive outcomes. Wolfe and colleagues¹⁸ found that using K-wires with the external fixation construct added stability in flexion/extension, radial/ulnar deviation, and rotational motion. They noted that fixation stability may depend more on the augmentation to fixation than on the external fixator itself. In a prospective, randomized trial, Moroni and colleagues^26,27 found that, compared with standard pins, hydroxyapatite-coated pins had higher extraction torque, which was associated with improved fixation. When combined with external fixation, calcium phosphate cement also provided additional stability, allowing the bone filler to help maintain articular reduction and cortical continuity.^28,29

External fixation has its disadvantages and complications. It can be bulky, and theoretically it contributes to higher rates of stiffness in the wrist and fingers.^30-32 Higher rates of pin-site infection have been reported, along with hardware failure and associated loss of reduction, in patients treated with external fixation (Figures 3A-3C).^31-33[[{"fid":"201866","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"3"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 3.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"3":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 3.","field_file_image_credit[und][0][value]":""}}}]]In addition, joint overdistraction can adversely affect the length-tension curve and contribute to potential reflex sympathetic dystrophy, which can be devastating (Figures 4A, 4B).^1,21,31,33 Despite these complications, external fixation remains a powerful tool in the treatment of high-energy DRFs. [[{"fid":"201867","view_mode":"medstat_image_flush_right","attributes":{"class":"media-element file-medstat-image-flush-right","data-delta":"4"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 4.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"4":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 4.","field_file_image_credit[und][0][value]":""}}}]]In many cases, authors who compared open reduction and internal fixation (ORIF) with external fixation found no significant differences in outcome scores or function.^31-34 In a meta-analysis of 917 patients, Margaliot and colleagues³³ found no differences in pain, grip strength, wrist ROM, or radiographic parameters. More recently, in prospective randomized trials, both Egol and colleagues³¹ and Grewal and colleagues³⁴ compared hybrid external fixation with ORIF, and, though early outcomes favored ORIF, 1-year follow-up comparisons were even, and there were no significant differences. These consistently reproducible results reaffirm keeping external fixation in the orthopedic toolbox.

Definitive Reconstruction With ORIF

Early nonlocked dorsal plating options for DRF fixation had unacceptable rates of plate failure, poor cosmesis, and extensor tendon complications.^17,35-37 Subsequent technologic advances—multiple approaches, lower profile plating, and rigid, fragment-specific fixation—have allowed even the most complex fracture patterns to be addressed (Table). In malunited fractures, bone graft may not be required if the fracture is extra-articular and treated with a volar locking plate. [[{"fid":"201868","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"5"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Table.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"5":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Table.","field_file_image_credit[und][0][value]":""}}}]]Other options include corticocancellous autograft from the iliac crest, hydroxyapatite synthetic grafts, and osteoconductive bone graft substitutes, such as bone morphogenic proteins. In addition, healing times are similar in cases, regardless of whether a graft was used.³⁸

Involvement of the radial and intermediate columns should be addressed first. Although some may prefer a single volar plate, others may use fragment-specific fixation to buttress a comminuted radial styloid (in orthogonal fashion) and/or a dorsal ulnar fragment to restore the intermediate column and thereby fully restore the radial articular surface.^39,40 Typically, restoring the radial and intermediate columns for radial articular reduction subsequently and simultaneously restores the majority of radial height and length. After the radial and intermediate columns are reduced and stabilized, the need for ulna column fixation can be determined. Important factors in ulna column restoration are severe osteoporosis and ulna head and/or neck comminution. Significant comminution throughout the metaphysis of both the radius and the ulna may also warrant stabilizing the ulna with internal fixation. Finally, any DRU joint instability noted on examination should also favor fixing the ulnar side.

Assessment of the distal ulna in these complex fractures goes beyond the involvement of an ulnar styloid fracture. Typically, fractures at the base of the ulnar styloid have been reported to have little clinical relevance, including a low incidence of associated DRU joint problems.^41-43 Decisions to address the ulnar column are largely swayed by any instability found on DRU joint testing, as laxity caused by severe comminution can dictate the need for distal ring fixation to provide support. Even in the presence of a high-energy fracture in severely osteoporotic bone, the argument can be made to prevent instability by supporting the ulnar column. Stabilization of the ulnar articular surface can also be made more facile by creating an easier "A" fracture pattern (per AO classification) from a complex "C" to further aid in achieving efficient anatomical reduction. After preoperative planning is completed, depending on which columns need to be addressed, several surgical approaches can be considered to achieve maximum exposure and soft-tissue mobilization in order to successfully complete the operative fixation goals.

Volar Approach

An approach is selected for ideal exposure of a facile environment for definitive fixation. Access to the radial column can be gained with the extended flexor carpi radialis (FCR) approach. This approach allows visualization and removal of the appropriate deforming forces on the radial column to allow for fracture reduction by "opening the book," similar to that of tibial plateau reconstruction.^44,45 It may be prudent to perform a preincision Allen test as well as a preoperative DRU joint examination for comparison after ORIF is complete. Compared with the classic Henry approach near the distal radius, going through the volar sheath of the FCR avoids many of the perforating radial artery branches. Avoiding stripping the radial artery of its surrounding fat and lymphatics prevents postoperative "cold intolerance." Retracting the FCR ulnarly and then incising the dorsal FCR sheath provide ready access to the pronator quadratus after collective ulnar mobilization of both the FCR and the flexor pollicis longus.⁴⁴ In addition, for work near the distal FCR sheath, care must be taken to avoid the branch of the palmar cutaneous nerve that emerges about 5 cm proximal to the wrist flexion crease.⁴⁶

Once at the level of the pronator quadratus, an "L-shape" incision can be made to reflect the muscle off the radius. Care must be taken when working too distal to avoid transection of the inserting volar wrist ligaments.⁴⁴ Leaving a cuff for repair of the pronator remains controversial. In a recent case-control series, however, Hershman and colleagues⁴⁷ did not find significant differences in function or complication rate in patients with and without repair. After reflection, adequate exposure of the radial column should be achieved. Ready access to the radial styloid for orthogonal plating can be obtained by releasing the brachioradialis, which simultaneously releases one of the primary fracture deforming forces.⁴⁴ With this incision and exposure, if needed, dorsal bone grafting can be achieved from the volar side; however, care must be taken to protect the first dorsal compartment.⁴⁸ The cutaneous branch of the median nerve may be at risk with this exposure, but avoiding dissection ulnar to the FCR tendon can help to reduce this risk.⁴⁹

Before surgery, if the fracture pattern dictates a more ulnar approach, we prefer the extended carpal tunnel approach. Using the plane between the palmaris longus and the flexor digitorum superficialis medially and the FCR laterally, the extended carpal tunnel approach provides an obvious release of the flexor retinaculum but, more important, allows for extensile access to the sigmoid notch, the DRU joint, and the ulnar column.

Dorsal Approach

The dorsal approach is necessary in a few select cases. With a focus on fragment-specific fixation, presence of a significant dorsal ulnar fragment should warrant a dorsal approach.⁵⁰ In addition, in select, rare cases in which volar access is limited or unavailable, dorsal access is the only option.⁵⁰ Finally, if direct articular visualization is required, the dorsal approach typically is favored as the stronger radiocarpal ligaments found on the volar side are maintained.

Access should begin with an incision centered over the dorsal distal radius; a safe access point is just ulnar to the Lister tubercle. On incision of the retinaculum through a full-thickness excision, the third dorsal compartment is opened and the extensor pollicis longus (EPL) mobilized, fully exposing the dorsal distal radius. Work can be performed on either side of the EPL between the second and fourth dorsal compartments. Exposure typically is not an issue because of the pliable soft tissue of the dorsum, with ready access from styloid to styloid.⁴⁴ Here, low-profile plates and/or mini-fragment-specific plate options should be used to minimize potential tendon damage.⁵¹ Care must also be taken to avoid damaging the radiocarpal or scapholunate ligaments.⁴⁹ On closure, the retinaculum is repaired primarily; however, though some proponents advocate relocating the EPL tendon into its groove, we prefer leaving the EPL free within the surrounding soft tissue to reduce tension and promote unhindered excursion. The dorsal approach, though controversial and used inconsistently, should remain an important tool in anatomical restoration, especially in cases of complex fracture patterns.

Conclusion

Controversy still marks the lack of consensus on deciding which DRF treatment is optimal. Some investigators question moving away from external fixation and cite the lack of significantly better data relative to ORIF.^21,52 The same proponents note that the only advantage over external fixation is earlier return to function and cite reports of tendon rupture and complications with both dorsal and volar fixation options.^34,53-58 Other investigators find that operative treatment generally does not provide a significant improvement over nonoperative treatment.⁵⁹

With the advent of lower profile locked plating, fragment-specific fixation, and variable-angle devices, comparative clinical trials are finding it difficult to keep up.^60-64 Results from ongoing prospective randomized trials like ORCHID (Open Reduction and Internal Fixation Versus Casting for Highly Comminuted Intra-Articular Fractures of the Distal Radius; 500 patients >65 years old, 15 centers) will provide more definitive answers about ideal treatment.⁶⁵

Anatomical restoration involves a versatile array of fragment fixation and reconstruction. Careful preoperative planning and a consistent approach to restoring the radial, intermediate, and ulnar columns, along with a proper surgical approach, are ideal. Many advances in internal fixation have been exceedingly helpful. Use of external fixation, especially in a bridging fashion with or without supplementation, is still valuable in many situations.

Take-Home Points

• Restore proper anatomic parameters; compare to the other side.
• Don't forget about the DRU joint.
• CT can aide in identifying subtle articular depression and severe comminution to change operative management.
• Remember, there still is a role for external fixators; an alternative remains an internal spanning plate.
• Respect the soft tissues, which can aide in reduction, however don't leave the operating room without feeling confident about your fixation.

Distal radius fracture (DRF), a common fracture, accounts for almost one sixth of all emergency department visits.¹ With the advent of emerging technologies and refined technique, treatment options for DRFs have evolved. Although controversy remains regarding nonoperative vs operative treatment of DRFs in the elderly,^2,3 select situations (open injuries, complex high-energy injuries, young age) warrant definitive fixation. Previously, internal fixation options were limited. Current technologies include locked fixed-angle plating, fragment-specific fixation, and locked variable-angle plating. These modalities aid in achieving and maintaining more anatomical fixation. This article summarizes tips, tricks, and planning for definitive external and internal fixation of complex DRFs.

Anatomical Considerations and Classification

The wrist joint, part of the complex articular network that begins at the forearm and ends at the distal interphalangeal joint, is the foundation for fine- and gross-motor skills. Understanding the anatomy of this network can provide a valuable roadmap for operative reconstruction.

At the wrist level, the radius bears most of the weight-bearing, and in some studies exhibits up to 80% of the load.^1,4 The triangular distal radius bears this weight through a biconcave articular surface with facets for the lunate and scaphoid separated by an anteroposterior ridge.^5-7 The radius also articulates with the ulnar head at the sigmoid notch to form the distal radioulnar (DRU) joint. Restoring the relationships of the DRU joint, the triangular fibrocartilage complex, and the ulnar variance is of paramount importance.^1,8,9

Classical teaching calls for restoration of radial inclination to about 23°, volar tilt to 11° to 12°, and radial length to about 11 mm. Especially regarding volar tilt and radial length, however, cadaveric and clinical studies have found more variance, leading to use of the contralateral extremity as an operative template, particularly when closed reduction thought to be adequate deviates significantly from these parameters.^1,4,7

DRF classification based on these principles has led to abundant representation in the literature.^10-13 Many authors have focused on fracture lines, comminution degree, articular surface violation, and other anatomical or radiographic characteristics of DRF classification and operative fixation approach.^10-13 In 2001, Fernandez⁹ proposed a classification system focused on energy or mechanism of injury. In comparisons,¹⁴ the Fernandez system had the highest interobserver reliability—higher than that of AO (Arbeitsgemeinschaft für Osteosynthesefragen).

Considerations for Operative Treatment: Column Theory

In the restoration of anatomical alignment in complex DRFs, it is important to consider the 3 joints and the 3 columns—radial, intermediate, and ulnar (Figure 1). [[{"fid":"201864","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"1"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 1.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 1.","field_file_image_credit[und][0][value]":""}}}]]In addition, parallels between the distal radius and the tibial plateau can be considered because of similarities in operative goals. Restoration of mechanical axis, length, alignment, rotation, and articular surfaces is paramount.¹⁵ Considering multiple surgical approaches to address "bicolumnar injuries" and reconstructing the "simpler" columnar injury first are common principles.¹⁶

The goals of fracture fixation at the wrist are the same as at any other joint: anatomical reduction, stable fixation, and early range of motion (ROM). Column restoration can result in consistent achievement of those goals. Intuitively, there is a close correlation between anatomical alignment and functional results.¹⁷ Rebuilding the structural foundation of the columns with respect to buttressing and restoring the 3 radial articulations with the ulna, scaphoid, and lunate can consistently yield restoration of length, inclination, and tilt (Figure 2). [[{"fid":"201865","view_mode":"medstat_image_flush_right","attributes":{"class":"media-element file-medstat-image-flush-right","data-delta":"2"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 2.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"2":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 2.","field_file_image_credit[und][0][value]":""}}}]]Next, we discuss the options available and how to use each to an advantage, individually or in hybrid constructs.

External Fixation: Is There Still a Role?

In the setting of highly comminuted, complex fractures, external fixation with Kirschner wires (K-wires) is a reasonable choice, with restoration of motion and strength within 75% to 80% of the uninjured wrist.¹⁸ In a 2-year study of 113 patients with comminuted metaphyseal DRFs randomly assigned to either external fixation or casting, Kreder and colleagues¹⁹ found a trend toward better clinical, functional, and radiographic outcomes with external fixation with or without K-wire fixation. There was improved restoration of radial length and palmar tilt with external fixation. A study of unstable DRF in patients with osteoporosis found that redisplacement was more common after treatment with a cast than after treatment with an external fixator.²⁰ Although closed reduction and casting continue to have a role in the treatment of DRF, Kreder and colleagues¹⁹ found that remanipulation was necessary in at least 9% of cases. According to a meta-analysis²¹ of the literature on DRF treatment, 4 articles directly address the question of the superiority of external fixation over closed reduction and casting, and 3 of the 4 found more favorable radiographic and functional outcomes with external fixation.

External fixation is useful in treating complex DRFs with metaphyseal comminution. It can also be effective in the presence of simple articular involvement without depression of the joint surface. External fixation devices can span areas of soft-
tissue injury and are useful as manipulation tools in achieving anatomical reduction. Although external fixation is effective, its complications include pin-tract infection, nerve injury, loss of reduction, and loss of digital ROM. In a meta-analysis, Li-hai and colleagues²² found that external fixators had a complication rate of 30.9%. With this technique, it is important to avoid midcarpal distraction, excessive ulnar deviation, and excessive palmar flexion. Papadonikolakis and colleagues²³ found that distraction of as little as 2 mm to 5 mm significantly affected the function of the flexor digitorum superficialis at the metacarpophalangeal joint. Over-distraction in wrist flexion can lead to lengthening of the extensor tendons and loss of full digital ROM. Excessive flexion and ulnar deviation can lead to median nerve compression and associated symptoms, as well as poor extensor and radial tendon length. In addition, prolonged distraction in excessive flexion combined with swelling and inflammation during fracture healing causes digital stiffness and contracture.²³ Biomechanical studies have found that proximal pin placement in the radius, along with distal pin fixation in 6 metacarpal cortices through the second and third metacarpals, helps provide the strongest fixation.²⁴

As for technique, pins are placed in the second metacarpal and radial shaft. With respect to the radius, the incision is made just proximal to the edge of the abductor pollicis longus muscle in the "bare area." Ideal pin placement is between the extensor carpi radialis longus and the extensor carpi radialis brevis, with care taken to avoid the radial sensory nerve, which lies between the extensor carpi radialis longus and the brachialis and emerges 9 cm proximal to the radial styloid.²⁵ Next, a 2.5-cm to 3-cm incision is made over the palpable edge of the index metacarpal near the base. During drilling, the guide is placed at intersecting 45° angles, and the distal pin is placed 2 cm to 3 cm from the proximal pin. The proximal metacarpal pin is placed at the base of the metacarpal. The second metacarpal pin can also be placed first, with the external fixator used to judge proximal placement of the radial pin within the bare area.

Various supplements to external fixation have positive outcomes. Wolfe and colleagues¹⁸ found that using K-wires with the external fixation construct added stability in flexion/extension, radial/ulnar deviation, and rotational motion. They noted that fixation stability may depend more on the augmentation to fixation than on the external fixator itself. In a prospective, randomized trial, Moroni and colleagues^26,27 found that, compared with standard pins, hydroxyapatite-coated pins had higher extraction torque, which was associated with improved fixation. When combined with external fixation, calcium phosphate cement also provided additional stability, allowing the bone filler to help maintain articular reduction and cortical continuity.^28,29

External fixation has its disadvantages and complications. It can be bulky, and theoretically it contributes to higher rates of stiffness in the wrist and fingers.^30-32 Higher rates of pin-site infection have been reported, along with hardware failure and associated loss of reduction, in patients treated with external fixation (Figures 3A-3C).^31-33[[{"fid":"201866","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"3"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 3.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"3":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Figure 3.","field_file_image_credit[und][0][value]":""}}}]]In addition, joint overdistraction can adversely affect the length-tension curve and contribute to potential reflex sympathetic dystrophy, which can be devastating (Figures 4A, 4B).^1,21,31,33 Despite these complications, external fixation remains a powerful tool in the treatment of high-energy DRFs. [[{"fid":"201867","view_mode":"medstat_image_flush_right","attributes":{"class":"media-element file-medstat-image-flush-right","data-delta":"4"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 4.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"4":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Figure 4.","field_file_image_credit[und][0][value]":""}}}]]In many cases, authors who compared open reduction and internal fixation (ORIF) with external fixation found no significant differences in outcome scores or function.^31-34 In a meta-analysis of 917 patients, Margaliot and colleagues³³ found no differences in pain, grip strength, wrist ROM, or radiographic parameters. More recently, in prospective randomized trials, both Egol and colleagues³¹ and Grewal and colleagues³⁴ compared hybrid external fixation with ORIF, and, though early outcomes favored ORIF, 1-year follow-up comparisons were even, and there were no significant differences. These consistently reproducible results reaffirm keeping external fixation in the orthopedic toolbox.

Definitive Reconstruction With ORIF

Early nonlocked dorsal plating options for DRF fixation had unacceptable rates of plate failure, poor cosmesis, and extensor tendon complications.^17,35-37 Subsequent technologic advances—multiple approaches, lower profile plating, and rigid, fragment-specific fixation—have allowed even the most complex fracture patterns to be addressed (Table). In malunited fractures, bone graft may not be required if the fracture is extra-articular and treated with a volar locking plate. [[{"fid":"201868","view_mode":"medstat_image_flush_left","attributes":{"class":"media-element file-medstat-image-flush-left","data-delta":"5"},"fields":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Table.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"5":{"format":"medstat_image_flush_left","field_file_image_caption[und][0][value]":"Table.","field_file_image_credit[und][0][value]":""}}}]]Other options include corticocancellous autograft from the iliac crest, hydroxyapatite synthetic grafts, and osteoconductive bone graft substitutes, such as bone morphogenic proteins. In addition, healing times are similar in cases, regardless of whether a graft was used.³⁸

Involvement of the radial and intermediate columns should be addressed first. Although some may prefer a single volar plate, others may use fragment-specific fixation to buttress a comminuted radial styloid (in orthogonal fashion) and/or a dorsal ulnar fragment to restore the intermediate column and thereby fully restore the radial articular surface.^39,40 Typically, restoring the radial and intermediate columns for radial articular reduction subsequently and simultaneously restores the majority of radial height and length. After the radial and intermediate columns are reduced and stabilized, the need for ulna column fixation can be determined. Important factors in ulna column restoration are severe osteoporosis and ulna head and/or neck comminution. Significant comminution throughout the metaphysis of both the radius and the ulna may also warrant stabilizing the ulna with internal fixation. Finally, any DRU joint instability noted on examination should also favor fixing the ulnar side.

Assessment of the distal ulna in these complex fractures goes beyond the involvement of an ulnar styloid fracture. Typically, fractures at the base of the ulnar styloid have been reported to have little clinical relevance, including a low incidence of associated DRU joint problems.^41-43 Decisions to address the ulnar column are largely swayed by any instability found on DRU joint testing, as laxity caused by severe comminution can dictate the need for distal ring fixation to provide support. Even in the presence of a high-energy fracture in severely osteoporotic bone, the argument can be made to prevent instability by supporting the ulnar column. Stabilization of the ulnar articular surface can also be made more facile by creating an easier "A" fracture pattern (per AO classification) from a complex "C" to further aid in achieving efficient anatomical reduction. After preoperative planning is completed, depending on which columns need to be addressed, several surgical approaches can be considered to achieve maximum exposure and soft-tissue mobilization in order to successfully complete the operative fixation goals.

Volar Approach

An approach is selected for ideal exposure of a facile environment for definitive fixation. Access to the radial column can be gained with the extended flexor carpi radialis (FCR) approach. This approach allows visualization and removal of the appropriate deforming forces on the radial column to allow for fracture reduction by "opening the book," similar to that of tibial plateau reconstruction.^44,45 It may be prudent to perform a preincision Allen test as well as a preoperative DRU joint examination for comparison after ORIF is complete. Compared with the classic Henry approach near the distal radius, going through the volar sheath of the FCR avoids many of the perforating radial artery branches. Avoiding stripping the radial artery of its surrounding fat and lymphatics prevents postoperative "cold intolerance." Retracting the FCR ulnarly and then incising the dorsal FCR sheath provide ready access to the pronator quadratus after collective ulnar mobilization of both the FCR and the flexor pollicis longus.⁴⁴ In addition, for work near the distal FCR sheath, care must be taken to avoid the branch of the palmar cutaneous nerve that emerges about 5 cm proximal to the wrist flexion crease.⁴⁶

Once at the level of the pronator quadratus, an "L-shape" incision can be made to reflect the muscle off the radius. Care must be taken when working too distal to avoid transection of the inserting volar wrist ligaments.⁴⁴ Leaving a cuff for repair of the pronator remains controversial. In a recent case-control series, however, Hershman and colleagues⁴⁷ did not find significant differences in function or complication rate in patients with and without repair. After reflection, adequate exposure of the radial column should be achieved. Ready access to the radial styloid for orthogonal plating can be obtained by releasing the brachioradialis, which simultaneously releases one of the primary fracture deforming forces.⁴⁴ With this incision and exposure, if needed, dorsal bone grafting can be achieved from the volar side; however, care must be taken to protect the first dorsal compartment.⁴⁸ The cutaneous branch of the median nerve may be at risk with this exposure, but avoiding dissection ulnar to the FCR tendon can help to reduce this risk.⁴⁹

Before surgery, if the fracture pattern dictates a more ulnar approach, we prefer the extended carpal tunnel approach. Using the plane between the palmaris longus and the flexor digitorum superficialis medially and the FCR laterally, the extended carpal tunnel approach provides an obvious release of the flexor retinaculum but, more important, allows for extensile access to the sigmoid notch, the DRU joint, and the ulnar column.

Dorsal Approach

The dorsal approach is necessary in a few select cases. With a focus on fragment-specific fixation, presence of a significant dorsal ulnar fragment should warrant a dorsal approach.⁵⁰ In addition, in select, rare cases in which volar access is limited or unavailable, dorsal access is the only option.⁵⁰ Finally, if direct articular visualization is required, the dorsal approach typically is favored as the stronger radiocarpal ligaments found on the volar side are maintained.

Access should begin with an incision centered over the dorsal distal radius; a safe access point is just ulnar to the Lister tubercle. On incision of the retinaculum through a full-thickness excision, the third dorsal compartment is opened and the extensor pollicis longus (EPL) mobilized, fully exposing the dorsal distal radius. Work can be performed on either side of the EPL between the second and fourth dorsal compartments. Exposure typically is not an issue because of the pliable soft tissue of the dorsum, with ready access from styloid to styloid.⁴⁴ Here, low-profile plates and/or mini-fragment-specific plate options should be used to minimize potential tendon damage.⁵¹ Care must also be taken to avoid damaging the radiocarpal or scapholunate ligaments.⁴⁹ On closure, the retinaculum is repaired primarily; however, though some proponents advocate relocating the EPL tendon into its groove, we prefer leaving the EPL free within the surrounding soft tissue to reduce tension and promote unhindered excursion. The dorsal approach, though controversial and used inconsistently, should remain an important tool in anatomical restoration, especially in cases of complex fracture patterns.

Conclusion

Controversy still marks the lack of consensus on deciding which DRF treatment is optimal. Some investigators question moving away from external fixation and cite the lack of significantly better data relative to ORIF.^21,52 The same proponents note that the only advantage over external fixation is earlier return to function and cite reports of tendon rupture and complications with both dorsal and volar fixation options.^34,53-58 Other investigators find that operative treatment generally does not provide a significant improvement over nonoperative treatment.⁵⁹

With the advent of lower profile locked plating, fragment-specific fixation, and variable-angle devices, comparative clinical trials are finding it difficult to keep up.^60-64 Results from ongoing prospective randomized trials like ORCHID (Open Reduction and Internal Fixation Versus Casting for Highly Comminuted Intra-Articular Fractures of the Distal Radius; 500 patients >65 years old, 15 centers) will provide more definitive answers about ideal treatment.⁶⁵

Anatomical restoration involves a versatile array of fragment fixation and reconstruction. Careful preoperative planning and a consistent approach to restoring the radial, intermediate, and ulnar columns, along with a proper surgical approach, are ideal. Many advances in internal fixation have been exceedingly helpful. Use of external fixation, especially in a bridging fashion with or without supplementation, is still valuable in many situations.

Take-Home Points

• Understanding the indications for treatment is essential.
• Identifying the superficial (oblique fibers) and deep layers (transverse fibers) of the LR is very important and can lengthen the LR by as much as 20 mm.
• Open procedures reduce the risk of hematomas and related pain.
• The goal is to obtain 1 or 2 patellar quadrants of medial and lateral patellar glide in extensino and a neutral patella.
• If the Z-plasty is combined with the MPFL reconstruction or tibial tubercle transfer, the LR is set to length after the tubercle transfer and before the MPFL reconstruction (to avoid overconstraint).

Anterior knee pain is a common clinical problem that can be challenging to correct, in large part because of multiple causative factors, including structural/anatomical, functional, alignment, and neuroperception/pain pathway factors. One difficult aspect of anatomical assessment is judging the soft-tissue balance between the medial restraints (medial patellofemoral ligament [MPFL]; medial quadriceps tendon to femoral ligament; medial patellotibial and patellomeniscal ligaments) and the lateral restraints (lateral retinaculum [LR] specifically). Both LR tightness and patellar instability can be interpreted as anterior knee pain. Differentiating these entities is one of the most difficult clinical challenges in orthopedics.

LR release (LRR) has been found to improve patellar mobility and tracking.¹ In the absence of clearly defined guidelines, the procedure quickly gained in popularity because of its technical simplicity and the enticing "one tool fits all" treatment approach suggested in early reviews. Injudicious use of LRR, alone or in combination with other procedures, led to iatrogenic instability and chronic pain. LR lengthening (LRL) was introduced to address LR tightness while maintaining lateral soft-tissue integrity and avoiding some of the severe complications of LRR.²

Today, isolated use of LRR/LRL is recommended only for treatment of LR tightness and pain secondary to lateral patellar hypercompression.³ It can also be used as an adjunct treatment in the setting of patellofemoral instability. LRR/LRL should never be used as primary treatment for patellofemoral instability.

In this review of treatments for LR tightness and patellofemoral disorders, we compare the use of LRR and LRL.

Discussion

LR procedures are indicated for LR tightness, which is assessed by taking a history, performing a physical examination, and obtaining diagnostic imaging. Decisions should be based on all findings considered together and never on imaging findings alone.

Physical Examination

The physical examination should include assessment of limb alignment, patellar mobility, muscle balance, and dynamic patellar tracking.

Limb Alignment. Abnormal valgus, rotational deformities, and increased Q-angle are associated with LR tightness. Valgus alignment can be assessed on standing inspection; rotational deformities with increased hip anteversion by hip motion with the patient in the prone position (increased hip internal rotation, decreased hip external rotation); and Q-angle on weight-bearing standing examination and with the patient flexing and extending the knee while seated.

Patellar Mobility. The patellar glide and tilt tests provide the most direct evaluations of LR tightness. Medial displacement of <1 quadrant is consistent with tightness, and displacement of >3 quadrants is consistent with laxity. In full extension, the patellar glide test evaluates only the soft-tissue restraints; at 30° flexion, it also evaluates patellofemoral engagement. The patellar tilt test measures the lifting of the lateral edge of the patella. With normal elevation being 0° to 20°, lack of patellar tilt means the LR is tight, and tilt of >20° means it is loose. MPFL patency can be examined with the Lachman test; the examiner rapidly moves the patella laterally while feeling for the characteristic hard endpoint of lateral translation.

Muscle Balance. The tone, strength, and tightness of the core (abdomen, dorsal, and hip muscles) and lower extremities (quadriceps, hamstrings, gastrocnemius) should be evaluated.

Dynamic Patellar Tracking. The J-sign is the course (shaped like an inverted J) that the patella takes when it is medialized into the trochlea from its laterally displaced resting position as the knee goes from full extension to flexion. The J-sign can be associated with LR tightness, trochlear dysplasia, and patella alta.

Imaging

Although we cannot provide a comprehensive review of the imaging literature, the following radiologic examinations should be used to assess the patellofemoral joint.

30° Lateral Radiograph.  Increased tilt is seen when the lateral facet is not anterior to the patellar ridge. Also evaluated are trochlear anatomy, patellar height, and other factors involved in patellofemoral disorders.

30° Flexed Axial (Merchant) Radiograph. Patellar tilt, subluxation, and trochlear dysplasia are evaluated. Images obtained with progressive flexion can be very useful in verifying patellar tilt reduction. Lack of reduction during early flexion suggests LR tightness.⁴

Alignment Axial Radiographs (Scanogram). Valgus alignment is assessed with this full-length, standing, long-leg examination.

Computed Tomography/Magnetic Resonance Imaging. Many parameters of patellar alignment have been described. Basic assessment should include evaluation of patellar tilt, angle by the line across posterior condyles and a line through the greatest patellar width (>20° indicates abnormality and LR tightness) and tibial tubercle-trochlear groove distance (computed tomography or magnetic resonance imaging scan of the knee is used to measure this distance, and to confirm a significant amount in light of complex patellofemoral malalignment⁵).

Indications

Lateral compression syndrome with LR tightness is often successfully treated with isolated LRR, and results are reproducible and predictable.⁶ Surgical intervention for patellofemoral pain should be undertaken only after failed extensive nonoperative treatment with physical therapy and bracing/taping. Patients with LR tightness on preoperative examination, lateral patellar tilt on imaging, and normal Q-angle can obtain satisfactory results with this procedure. Patellar subluxation or dislocation history, high Q-angle (>20°), grade 3 or 4 chondral injury, and patellofemoral arthritis are associated with poorer outcomes when the procedure is performed in isolation.⁶International Patellofemoral Study Group members agreed that LRR/LRL is a valid treatment option when indicated, but it is rarely performed in isolation and constitutes only 1% to 2% of surgeries performed by this group of experts.⁷ When lateral compression syndrome progresses to arthritis, LRR/LRL can be performed with lateral patella facetectomy for maximal improvement.⁴ In the setting of patellofemoral instability, LRR/LRL can be combined with proximal and/or distal realignment surgery if the LR is tight. The LR is the last line of defense limiting lateral translation in the setting of an incompetent MPFL. Isolated LRR/LRL in the setting of instability further destabilizes the patella and worsens the instability. Therefore, LRR/LRL
is a poor surgical option as an isolated procedure for this condition and should be used only as an adjunct in cases of patellofemoral instability with LR tightness that does not allow the patella to be centralized into the trochlea.⁸ LRR/LRL can also be performed to improve patellar tracking in patello­femoral arthroplasty and total knee arthroplasty.

Lateral Retinaculum Release Versus Lengthening

LRR was first described for the treatment of patellar instability in 1891.⁹ It was also used for the treatment of lateral patellar hypercompression syndrome associated with LR tightness that led to lateral patellar tracking, joint overload, degeneration, and anterior knee pain.¹⁰ Metcalf¹⁰ further popularized the procedure by describing a minimally invasive arthroscopic version. However, the arthroscopic technique is as aggressive as the open technique and may be performed with less control, potentially making its results more variable. As proximal and distal releases are performed from the "inside out," more capsule and muscle disruption is needed to release the more superficial layers.

Z-plasty lengthening of the LR was described as an alternative for maintaining lateral patellar soft-tissue integrity while reducing the tension of the lateral tissue restraints.³ This is our preferred method.

Performing LRL instead of LRR avoids iatrogenic medial patellar instability, avoids overrelease and muscle injury, and improves soft-tissue balance.³ Open release or lengthening reduces inadvertent injury to the lateral superior/inferior geniculate arteries and allows direct hemostasis. Two prospective randomized studies found functional knee outcomes and return to athletic activities were improved more after LRL than LRR.^11,12 These procedures had similar rates of postoperative knee stiffness, decreased muscle mass, and decreased strength. Each prospective study used an extensive LRR technique for LRR cases (various authors have recommended performing the release until the patella is perpendicular to the trochlea), which may have affected outcomes. In any case, with lengthening, the surgeon is less likely to excessively disrupt the lateral tissues.

Lateral Retinaculum Release.  LRR can be openly performed by lateral parapatellar incision,¹ a mini-open percutaneous technique, or arthroscopy. For these open techniques, incisions of various sizes have been used to access the LR and incise it about 1 cm lateral to the patella starting at the distal end of the vastus lateralis and extending distally until patellar tilt reduction is sufficient. If tightness in deep flexion persists, the LRR can be extended distally to the tibial tubercle. Open techniques have the advantage of sparing the joint capsule. All-arthroscopic techniques involve using electrocautery to cut through the capsule and access the LR.

Lateral Retinaculum Lengthening. 

The LR is sharply divided into a superficial layer of superficial oblique fibers from the anterior iliotibial band and a deep layer of transverse fibers from the femur. For LRR, these 2 layers must be identified separate from the articular capsule.¹³

Complications

Complications of performing LRR/LRL to change the lateral restraint include medial patellar instability, increased lateral pain, repair failure, recurrent lateral instability, quadriceps weakness and atrophy, postoperative hemarthrosis, knee stiffness, wound complications, and thermal skin injury.⁷ These complications often result from poor surgical technique and too aggressive release. Although recommended patellar tilt historically has varied from 45° to 90°, the current goal is to normalize the tight soft-tissue restraints without creating secondary instability.

The most significant complication of LRR is medial patellar instability caused by muscle atrophy and loss of soft-tissue restraint.¹⁴ Medial instability can be difficult to diagnose and should be considered in any patient with patellofemoral pain, popping, or patellar instability after LRR.¹⁵ A positive medial subluxation test or medial patellar apprehension test suggests medial instability.

Medial patellar instability usually requires surgical treatment. Direct LR repair, lateral soft-tissue reconstruction, and other procedures can be used to restore lateral restraint.¹⁵ However, these are salvage techniques, and patients often remain significantly limited by pain or instability. Therefore, the LR must be carefully addressed and preferably should undergo lengthening rather than release.