American Academy of Hospice and Palliative Medicine (AAHPM): Annual Assembly

DENVER – Morphine sulfate can be readily formulated into a gel for effective topical analgesia in patients with painful skin ulcers and other wounds.

All that’s necessary is for a compounding pharmacist to mix 10 mg of intravenous morphine sulfate in 8 g of IntraSite Gel, a hydrogel widely used in wound care. The morphine gel can be applied to the wound one to three times daily, according to Mary Lynn McPherson, professor and vice chair of the department of pharmacy practice and science at the University of Maryland, Baltimore.

There is very little systemic absorption of the morphine. External irritation that manifests as burning or itching is the only side effect. This therapy works despite the limited systemic absorption because there are both central and peripheral opioid receptors.

Dressing changes can be excruciating for hospice patients. Administering an oral dose of ketamine beforehand provides effective pain relief.

"We’ve been doing this frequently in our inpatient hospice unit for patients who have these horrific, horrific wounds. We’ll give them 10, 20, or even 30 mg of ketamine orally 15-20 minutes before wound care. It has made absolutely all the difference in the world. The results have been spectacular," she said at the meeting.

The oral dose consists of intravenous ketamine solution, the only form in which the drug is available. The taste is awful, so the medication should be mixed with cherry syrup, spearmint, orange juice, or another masking flavor.

Dr. McPherson reported having no financial conflicts.

DENVER – Morphine sulfate can be readily formulated into a gel for effective topical analgesia in patients with painful skin ulcers and other wounds.

All that’s necessary is for a compounding pharmacist to mix 10 mg of intravenous morphine sulfate in 8 g of IntraSite Gel, a hydrogel widely used in wound care. The morphine gel can be applied to the wound one to three times daily, according to Mary Lynn McPherson, professor and vice chair of the department of pharmacy practice and science at the University of Maryland, Baltimore.

There is very little systemic absorption of the morphine. External irritation that manifests as burning or itching is the only side effect. This therapy works despite the limited systemic absorption because there are both central and peripheral opioid receptors.

Dressing changes can be excruciating for hospice patients. Administering an oral dose of ketamine beforehand provides effective pain relief.

"We’ve been doing this frequently in our inpatient hospice unit for patients who have these horrific, horrific wounds. We’ll give them 10, 20, or even 30 mg of ketamine orally 15-20 minutes before wound care. It has made absolutely all the difference in the world. The results have been spectacular," she said at the meeting.

The oral dose consists of intravenous ketamine solution, the only form in which the drug is available. The taste is awful, so the medication should be mixed with cherry syrup, spearmint, orange juice, or another masking flavor.

Dr. McPherson reported having no financial conflicts.

DENVER – Morphine sulfate can be readily formulated into a gel for effective topical analgesia in patients with painful skin ulcers and other wounds.

All that’s necessary is for a compounding pharmacist to mix 10 mg of intravenous morphine sulfate in 8 g of IntraSite Gel, a hydrogel widely used in wound care. The morphine gel can be applied to the wound one to three times daily, according to Mary Lynn McPherson, professor and vice chair of the department of pharmacy practice and science at the University of Maryland, Baltimore.

There is very little systemic absorption of the morphine. External irritation that manifests as burning or itching is the only side effect. This therapy works despite the limited systemic absorption because there are both central and peripheral opioid receptors.

Dressing changes can be excruciating for hospice patients. Administering an oral dose of ketamine beforehand provides effective pain relief.

"We’ve been doing this frequently in our inpatient hospice unit for patients who have these horrific, horrific wounds. We’ll give them 10, 20, or even 30 mg of ketamine orally 15-20 minutes before wound care. It has made absolutely all the difference in the world. The results have been spectacular," she said at the meeting.

The oral dose consists of intravenous ketamine solution, the only form in which the drug is available. The taste is awful, so the medication should be mixed with cherry syrup, spearmint, orange juice, or another masking flavor.

Dr. McPherson reported having no financial conflicts.

DENVER – More than three-quarters of the general public have no idea what palliative care is, according to a national survey. And that, as it turns out, is actually excellent for the field’s future growth prospects, according to one of the nation’s top palliative care specialists.

"This is good news for us. We can create the cognitive frame where there isn’t one already in place," said Dr. Diane E. Meier, director of the Center to Advance Palliative Care and professor of geriatrics and internal medicine at Mount Sinai School of Medicine, New York.

Bruce Jancin/IMNG Medical Media

While the public is largely a blank slate with regard to palliative care, nonpalliative care physicians and other health care professionals tend to believe that palliative care is simply end of life care. Many don’t understand that palliative care is actually about relieving the pain, symptoms, and stress of serious illness in patients of any age and at any stage of disease, and that palliative care can be delivered alongside curative or life-prolonging therapies, Dr. Meier said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

The consumer survey sponsored by the Center to Advance Palliative Care and the American Cancer Society involved 800 adults; 70% indicated they were "not at all knowledgeable" about palliative care, and another 8% had never heard of the term. Only 5% were categorized as "very knowledgeable" about palliative care.

Once they were informed about what palliative care truly is, however, survey participants of all political persuasions were very positive about it.

For example, once they were educated about palliative care, 95% of those surveyed said it’s important for patients with serious illnesses and their families to learn about palliative care. Most (92%) indicated they would likely consider it for themselves or a loved one, and an equal percentage said it’s important that palliative care services be available at all hospitals, Dr. Meier reported.

She and other leaders in the palliative care field are now seeking funding for an ambitious 5-year, multimillion-dollar social marketing campaign to increase public awareness regarding palliative care.

"We’ve recognized that we’re not going to see policy change without public support," Dr. Meier said.

Among the policy changes she and her colleagues seek is a big boost in the palliative care workforce, which at present is so small as to constitute a major barrier to access. While there is one oncologist for every 145 patients in the United States with a new cancer diagnosis, and one cardiologist for every 71 patients who have a myocardial infarction, there is just one palliative care specialist for every 1,300 people with a serious illness. And in nearly half of the states, no postgraduate training in palliative care is available.

Dr. Meier would like to see an increased number of physician and nurse practitioner fellowship programs established in palliative care. Another priority is to develop a midcareer board certification track in palliative care across all medical disciplines.

"We have a lot of people coming in from oncology, surgery, and other fields who are seeking work with meaning and purpose," she observed.

Starting in 2013, the specialty will require fellowship training for board certification in palliative care. "Grandfathering in" will no longer be possible.

Dr. Meier reported having no financial conflicts.

DENVER – More than three-quarters of the general public have no idea what palliative care is, according to a national survey. And that, as it turns out, is actually excellent for the field’s future growth prospects, according to one of the nation’s top palliative care specialists.

"This is good news for us. We can create the cognitive frame where there isn’t one already in place," said Dr. Diane E. Meier, director of the Center to Advance Palliative Care and professor of geriatrics and internal medicine at Mount Sinai School of Medicine, New York.

Bruce Jancin/IMNG Medical Media

While the public is largely a blank slate with regard to palliative care, nonpalliative care physicians and other health care professionals tend to believe that palliative care is simply end of life care. Many don’t understand that palliative care is actually about relieving the pain, symptoms, and stress of serious illness in patients of any age and at any stage of disease, and that palliative care can be delivered alongside curative or life-prolonging therapies, Dr. Meier said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

The consumer survey sponsored by the Center to Advance Palliative Care and the American Cancer Society involved 800 adults; 70% indicated they were "not at all knowledgeable" about palliative care, and another 8% had never heard of the term. Only 5% were categorized as "very knowledgeable" about palliative care.

Once they were informed about what palliative care truly is, however, survey participants of all political persuasions were very positive about it.

For example, once they were educated about palliative care, 95% of those surveyed said it’s important for patients with serious illnesses and their families to learn about palliative care. Most (92%) indicated they would likely consider it for themselves or a loved one, and an equal percentage said it’s important that palliative care services be available at all hospitals, Dr. Meier reported.

She and other leaders in the palliative care field are now seeking funding for an ambitious 5-year, multimillion-dollar social marketing campaign to increase public awareness regarding palliative care.

"We’ve recognized that we’re not going to see policy change without public support," Dr. Meier said.

Among the policy changes she and her colleagues seek is a big boost in the palliative care workforce, which at present is so small as to constitute a major barrier to access. While there is one oncologist for every 145 patients in the United States with a new cancer diagnosis, and one cardiologist for every 71 patients who have a myocardial infarction, there is just one palliative care specialist for every 1,300 people with a serious illness. And in nearly half of the states, no postgraduate training in palliative care is available.

Dr. Meier would like to see an increased number of physician and nurse practitioner fellowship programs established in palliative care. Another priority is to develop a midcareer board certification track in palliative care across all medical disciplines.

"We have a lot of people coming in from oncology, surgery, and other fields who are seeking work with meaning and purpose," she observed.

Starting in 2013, the specialty will require fellowship training for board certification in palliative care. "Grandfathering in" will no longer be possible.

Dr. Meier reported having no financial conflicts.

DENVER – More than three-quarters of the general public have no idea what palliative care is, according to a national survey. And that, as it turns out, is actually excellent for the field’s future growth prospects, according to one of the nation’s top palliative care specialists.

"This is good news for us. We can create the cognitive frame where there isn’t one already in place," said Dr. Diane E. Meier, director of the Center to Advance Palliative Care and professor of geriatrics and internal medicine at Mount Sinai School of Medicine, New York.

Bruce Jancin/IMNG Medical Media

While the public is largely a blank slate with regard to palliative care, nonpalliative care physicians and other health care professionals tend to believe that palliative care is simply end of life care. Many don’t understand that palliative care is actually about relieving the pain, symptoms, and stress of serious illness in patients of any age and at any stage of disease, and that palliative care can be delivered alongside curative or life-prolonging therapies, Dr. Meier said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

The consumer survey sponsored by the Center to Advance Palliative Care and the American Cancer Society involved 800 adults; 70% indicated they were "not at all knowledgeable" about palliative care, and another 8% had never heard of the term. Only 5% were categorized as "very knowledgeable" about palliative care.

Once they were informed about what palliative care truly is, however, survey participants of all political persuasions were very positive about it.

For example, once they were educated about palliative care, 95% of those surveyed said it’s important for patients with serious illnesses and their families to learn about palliative care. Most (92%) indicated they would likely consider it for themselves or a loved one, and an equal percentage said it’s important that palliative care services be available at all hospitals, Dr. Meier reported.

She and other leaders in the palliative care field are now seeking funding for an ambitious 5-year, multimillion-dollar social marketing campaign to increase public awareness regarding palliative care.

"We’ve recognized that we’re not going to see policy change without public support," Dr. Meier said.

Among the policy changes she and her colleagues seek is a big boost in the palliative care workforce, which at present is so small as to constitute a major barrier to access. While there is one oncologist for every 145 patients in the United States with a new cancer diagnosis, and one cardiologist for every 71 patients who have a myocardial infarction, there is just one palliative care specialist for every 1,300 people with a serious illness. And in nearly half of the states, no postgraduate training in palliative care is available.

Dr. Meier would like to see an increased number of physician and nurse practitioner fellowship programs established in palliative care. Another priority is to develop a midcareer board certification track in palliative care across all medical disciplines.

"We have a lot of people coming in from oncology, surgery, and other fields who are seeking work with meaning and purpose," she observed.

Starting in 2013, the specialty will require fellowship training for board certification in palliative care. "Grandfathering in" will no longer be possible.

Dr. Meier reported having no financial conflicts.

DENVER – Methylphenidate and oral ketamine show considerable promise as extremely rapid-acting, safe, and cost-effective treatments for depression in the hospice setting.

Moreover, early indications are that ketamine might be even more effective as the treatment of anxiety disorders than as an antidepressant in this population nearing end of life, Dr. Scott A. Irwin said at the conference.

This is off-label therapy. But standard antidepressant medications and guideline-recommended treatment algorithms for depression just don’t cut it in the hospice setting. The reason is quite simple: "We don’t have that kind of time," noted Dr. Irwin, director of psychiatry programs at the Institute for Palliative Medicine at San Diego Hospice.

For example, current American Psychiatric Association guidelines for treatment of moderate to severe depression call for 6-8 weeks of antidepressant medication and psychotherapy before switching agents or adding a second one in the event there hasn’t been at least moderate improvement. Patients are then supposed to be monitored for another 6-8 weeks. Yet, the median time in hospice care in the United States is only about 3 weeks. One-third of patients at San Diego Hospice die within the first week.

In one study of more than 1,000 consecutive patients in a palliative care unit, three-quarters of those who were prescribed an antidepressant got the medication only during their last 2 weeks of life. That’s not enough time to allow relief of symptoms, the psychiatrist said.

The prevalence of major depressive disorder in palliative care patients has been estimated at about 15%. No published randomized controlled trials have examined methylphenidate for treatment of such episodes in palliative care settings. But mechanistically, it is sound, Dr. Irwin said, since the psychostimulant blocks reuptake of dopamine in central adrenergic neurons and inhibits reuptake of serotonin and norepinephrine as well, just like standard antidepressants. There have been encouraging review articles, and Dr. Irwin presented his own highly promising retrospective blinded chart review study.

His study included 64 palliative care patients with psychiatrist-diagnosed depressive disorders treated in various ways, with treatment efficacy and side effects evaluated using the Clinical Global Impressions Scale (CGI).

Twenty of 21 methylphenidate-treated patients (95%) were blindly rated as having a significant clinical response, as were 4 of 9 (44%) treated with selective serotonin reuptake inhibitors (SSRIs), 3 of 13 (23%) who received other antidepressants, and 0 of 21 who received usual care alone. The time to response was 4 days with methylphenidate, 10 days with SSRIs, and about 5 days with other antidepressants. Those response times for standard antidepressants are much shorter than expected and require further study, according to Dr. Irwin.

Methylphenidate was blindly rated as significantly more effective than were the nonstimulant antidepressants. The mean score on the CGI 0-4 efficacy scale, in which lower is better, was 2.33 in methylphenidate-treated patients, compared with 3.06 with nonstimulant antidepressants.

On the other hand, side effects were significantly greater with methylphenidate: a mean score of 1.72, compared with 1.13. However, Dr. Irwin characterized side effects in the 1.0-2.0 range on the CGI as being in the "mild and don’t worry about-it" level.

It’s readily apparent within the first day or two if methylphenidate is going to be effective, he continued.

Somatic symptoms, which are very common in palliative care patients, typically improve markedly in methylphenidate-treated patients as their depression improves. However, anxiety increases in a minority of treated patients as depression wanes, sometimes requiring methylphenidate discontinuation, said Dr. Irwin, who is also a faculty psychiatrist at the University of California, San Diego.

He is now conducting a prospective open-label study of methylphenidate in hospice patients having a current major depressive episode. The study employs a flexible dosing schedule with dosing changes on days 3, 7, and 14, and a maximum dose of 20 mg b.i.d. But he finds it extremely challenging to conduct clinical trials in hospice patients because of their high death rate, its unpredictable timing, and informed consent issues.

Turning to ketamine for depression, Dr. Irwin said exciting preliminary evidence in nonhospice patients suggests that a single intravenous infusion of the anesthetic improves depression literally within minutes and that the effect lasts for weeks.

As it turns out, hospice physicians already have long experience using ketamine, not as an antidepressant but for treatment of pain, including cancer pain. They view ketamine as a familiar and inexpensive analgesic that they’re comfortable giving by the oral, subcutaneous, and transdermal routes.

Dr. Irwin is in the midst of conducting an open label pilot study to evaluate the efficacy and tolerability of oral ketamine for the treatment of major depression in hospice patients. Fourteen of a planned 20 patients have completed the 28-day study. The dosing is 0.5 mg/kg of the intravenous ketamine solution mixed in cherry syrup to hide the universally loathed taste. Treatment is once daily.

The therapeutic efficacy has been impressive, as reflected in a drop in average scores on the Hospital Anxiety and Depression Scale from about 20 to 5.

"Interestingly, several patients had diagnosable severe anxiety disorders that went away completely. We’re finding that anxiety may be even more affected by ketamine than depression," Dr. Irwin said.

The high burden of somatic symptoms present in these patients also lightened significantly, with scores on the Adverse Symptom Checklist falling from about 28 to 5. This doesn’t appear to be a result of the drug’s analgesic effect, because some patients didn’t have significant pain, while in others the somatic symptoms improved while pain scores remained unchanged.

Another 30 or so San Diego Hospice patients have received oral ketamine outside of the pilot study, with similar benefits.

"We’ve gone to nightly dosing. And if you see a decrement in benefit, bump up the dose by 20%," Dr. Irwin advised in response to audience questions.

He called depression near the end of life a major yet widely underappreciated public health problem. The consequences of untreated depression in these patients include longer inpatient hospital stays, worsening medical illness, greater difficulty in treating pain and nausea, and interference with making preparations for death. Untreated depression also impedes interactions with caregivers and, most importantly, with loved ones.

Dr. Irwin recalled one of the first hospice patients for whom he prescribed methylphenidate. After 24 hours on treatment, the man no longer met criteria for major depressive disorder. He lived for another week with newly restored enjoyment of nature and his family. Dr. Irwin learned of his death when he ran into the patient’s daughter in the parking lot.

"She said, ‘I want to thank you for giving me my father back. I will now remember him as the great man he always was, and not the miserable man that he’d become for the last 6 months,’ "

Dr. Irwin said. "So we changed her life for decades.

"If anyone asks you, ‘Why bother treating depression in hospice when you’re only changing the last few days?’ tell them it’s a family experience. It’s not just about the patient."

He reported having no financial conflicts.

DENVER – Methylphenidate and oral ketamine show considerable promise as extremely rapid-acting, safe, and cost-effective treatments for depression in the hospice setting.

Moreover, early indications are that ketamine might be even more effective as the treatment of anxiety disorders than as an antidepressant in this population nearing end of life, Dr. Scott A. Irwin said at the conference.

This is off-label therapy. But standard antidepressant medications and guideline-recommended treatment algorithms for depression just don’t cut it in the hospice setting. The reason is quite simple: "We don’t have that kind of time," noted Dr. Irwin, director of psychiatry programs at the Institute for Palliative Medicine at San Diego Hospice.

For example, current American Psychiatric Association guidelines for treatment of moderate to severe depression call for 6-8 weeks of antidepressant medication and psychotherapy before switching agents or adding a second one in the event there hasn’t been at least moderate improvement. Patients are then supposed to be monitored for another 6-8 weeks. Yet, the median time in hospice care in the United States is only about 3 weeks. One-third of patients at San Diego Hospice die within the first week.

In one study of more than 1,000 consecutive patients in a palliative care unit, three-quarters of those who were prescribed an antidepressant got the medication only during their last 2 weeks of life. That’s not enough time to allow relief of symptoms, the psychiatrist said.

The prevalence of major depressive disorder in palliative care patients has been estimated at about 15%. No published randomized controlled trials have examined methylphenidate for treatment of such episodes in palliative care settings. But mechanistically, it is sound, Dr. Irwin said, since the psychostimulant blocks reuptake of dopamine in central adrenergic neurons and inhibits reuptake of serotonin and norepinephrine as well, just like standard antidepressants. There have been encouraging review articles, and Dr. Irwin presented his own highly promising retrospective blinded chart review study.

His study included 64 palliative care patients with psychiatrist-diagnosed depressive disorders treated in various ways, with treatment efficacy and side effects evaluated using the Clinical Global Impressions Scale (CGI).

Twenty of 21 methylphenidate-treated patients (95%) were blindly rated as having a significant clinical response, as were 4 of 9 (44%) treated with selective serotonin reuptake inhibitors (SSRIs), 3 of 13 (23%) who received other antidepressants, and 0 of 21 who received usual care alone. The time to response was 4 days with methylphenidate, 10 days with SSRIs, and about 5 days with other antidepressants. Those response times for standard antidepressants are much shorter than expected and require further study, according to Dr. Irwin.

Methylphenidate was blindly rated as significantly more effective than were the nonstimulant antidepressants. The mean score on the CGI 0-4 efficacy scale, in which lower is better, was 2.33 in methylphenidate-treated patients, compared with 3.06 with nonstimulant antidepressants.

On the other hand, side effects were significantly greater with methylphenidate: a mean score of 1.72, compared with 1.13. However, Dr. Irwin characterized side effects in the 1.0-2.0 range on the CGI as being in the "mild and don’t worry about-it" level.

It’s readily apparent within the first day or two if methylphenidate is going to be effective, he continued.

Somatic symptoms, which are very common in palliative care patients, typically improve markedly in methylphenidate-treated patients as their depression improves. However, anxiety increases in a minority of treated patients as depression wanes, sometimes requiring methylphenidate discontinuation, said Dr. Irwin, who is also a faculty psychiatrist at the University of California, San Diego.

He is now conducting a prospective open-label study of methylphenidate in hospice patients having a current major depressive episode. The study employs a flexible dosing schedule with dosing changes on days 3, 7, and 14, and a maximum dose of 20 mg b.i.d. But he finds it extremely challenging to conduct clinical trials in hospice patients because of their high death rate, its unpredictable timing, and informed consent issues.

Turning to ketamine for depression, Dr. Irwin said exciting preliminary evidence in nonhospice patients suggests that a single intravenous infusion of the anesthetic improves depression literally within minutes and that the effect lasts for weeks.

As it turns out, hospice physicians already have long experience using ketamine, not as an antidepressant but for treatment of pain, including cancer pain. They view ketamine as a familiar and inexpensive analgesic that they’re comfortable giving by the oral, subcutaneous, and transdermal routes.

Dr. Irwin is in the midst of conducting an open label pilot study to evaluate the efficacy and tolerability of oral ketamine for the treatment of major depression in hospice patients. Fourteen of a planned 20 patients have completed the 28-day study. The dosing is 0.5 mg/kg of the intravenous ketamine solution mixed in cherry syrup to hide the universally loathed taste. Treatment is once daily.

The therapeutic efficacy has been impressive, as reflected in a drop in average scores on the Hospital Anxiety and Depression Scale from about 20 to 5.

"Interestingly, several patients had diagnosable severe anxiety disorders that went away completely. We’re finding that anxiety may be even more affected by ketamine than depression," Dr. Irwin said.

The high burden of somatic symptoms present in these patients also lightened significantly, with scores on the Adverse Symptom Checklist falling from about 28 to 5. This doesn’t appear to be a result of the drug’s analgesic effect, because some patients didn’t have significant pain, while in others the somatic symptoms improved while pain scores remained unchanged.

Another 30 or so San Diego Hospice patients have received oral ketamine outside of the pilot study, with similar benefits.

"We’ve gone to nightly dosing. And if you see a decrement in benefit, bump up the dose by 20%," Dr. Irwin advised in response to audience questions.

He called depression near the end of life a major yet widely underappreciated public health problem. The consequences of untreated depression in these patients include longer inpatient hospital stays, worsening medical illness, greater difficulty in treating pain and nausea, and interference with making preparations for death. Untreated depression also impedes interactions with caregivers and, most importantly, with loved ones.

Dr. Irwin recalled one of the first hospice patients for whom he prescribed methylphenidate. After 24 hours on treatment, the man no longer met criteria for major depressive disorder. He lived for another week with newly restored enjoyment of nature and his family. Dr. Irwin learned of his death when he ran into the patient’s daughter in the parking lot.

"She said, ‘I want to thank you for giving me my father back. I will now remember him as the great man he always was, and not the miserable man that he’d become for the last 6 months,’ "

Dr. Irwin said. "So we changed her life for decades.

"If anyone asks you, ‘Why bother treating depression in hospice when you’re only changing the last few days?’ tell them it’s a family experience. It’s not just about the patient."

He reported having no financial conflicts.

DENVER – Methylphenidate and oral ketamine show considerable promise as extremely rapid-acting, safe, and cost-effective treatments for depression in the hospice setting.

Moreover, early indications are that ketamine might be even more effective as the treatment of anxiety disorders than as an antidepressant in this population nearing end of life, Dr. Scott A. Irwin said at the conference.

This is off-label therapy. But standard antidepressant medications and guideline-recommended treatment algorithms for depression just don’t cut it in the hospice setting. The reason is quite simple: "We don’t have that kind of time," noted Dr. Irwin, director of psychiatry programs at the Institute for Palliative Medicine at San Diego Hospice.

For example, current American Psychiatric Association guidelines for treatment of moderate to severe depression call for 6-8 weeks of antidepressant medication and psychotherapy before switching agents or adding a second one in the event there hasn’t been at least moderate improvement. Patients are then supposed to be monitored for another 6-8 weeks. Yet, the median time in hospice care in the United States is only about 3 weeks. One-third of patients at San Diego Hospice die within the first week.

In one study of more than 1,000 consecutive patients in a palliative care unit, three-quarters of those who were prescribed an antidepressant got the medication only during their last 2 weeks of life. That’s not enough time to allow relief of symptoms, the psychiatrist said.

The prevalence of major depressive disorder in palliative care patients has been estimated at about 15%. No published randomized controlled trials have examined methylphenidate for treatment of such episodes in palliative care settings. But mechanistically, it is sound, Dr. Irwin said, since the psychostimulant blocks reuptake of dopamine in central adrenergic neurons and inhibits reuptake of serotonin and norepinephrine as well, just like standard antidepressants. There have been encouraging review articles, and Dr. Irwin presented his own highly promising retrospective blinded chart review study.

His study included 64 palliative care patients with psychiatrist-diagnosed depressive disorders treated in various ways, with treatment efficacy and side effects evaluated using the Clinical Global Impressions Scale (CGI).

Twenty of 21 methylphenidate-treated patients (95%) were blindly rated as having a significant clinical response, as were 4 of 9 (44%) treated with selective serotonin reuptake inhibitors (SSRIs), 3 of 13 (23%) who received other antidepressants, and 0 of 21 who received usual care alone. The time to response was 4 days with methylphenidate, 10 days with SSRIs, and about 5 days with other antidepressants. Those response times for standard antidepressants are much shorter than expected and require further study, according to Dr. Irwin.

Methylphenidate was blindly rated as significantly more effective than were the nonstimulant antidepressants. The mean score on the CGI 0-4 efficacy scale, in which lower is better, was 2.33 in methylphenidate-treated patients, compared with 3.06 with nonstimulant antidepressants.

On the other hand, side effects were significantly greater with methylphenidate: a mean score of 1.72, compared with 1.13. However, Dr. Irwin characterized side effects in the 1.0-2.0 range on the CGI as being in the "mild and don’t worry about-it" level.

It’s readily apparent within the first day or two if methylphenidate is going to be effective, he continued.

Somatic symptoms, which are very common in palliative care patients, typically improve markedly in methylphenidate-treated patients as their depression improves. However, anxiety increases in a minority of treated patients as depression wanes, sometimes requiring methylphenidate discontinuation, said Dr. Irwin, who is also a faculty psychiatrist at the University of California, San Diego.

He is now conducting a prospective open-label study of methylphenidate in hospice patients having a current major depressive episode. The study employs a flexible dosing schedule with dosing changes on days 3, 7, and 14, and a maximum dose of 20 mg b.i.d. But he finds it extremely challenging to conduct clinical trials in hospice patients because of their high death rate, its unpredictable timing, and informed consent issues.

Turning to ketamine for depression, Dr. Irwin said exciting preliminary evidence in nonhospice patients suggests that a single intravenous infusion of the anesthetic improves depression literally within minutes and that the effect lasts for weeks.

As it turns out, hospice physicians already have long experience using ketamine, not as an antidepressant but for treatment of pain, including cancer pain. They view ketamine as a familiar and inexpensive analgesic that they’re comfortable giving by the oral, subcutaneous, and transdermal routes.

Dr. Irwin is in the midst of conducting an open label pilot study to evaluate the efficacy and tolerability of oral ketamine for the treatment of major depression in hospice patients. Fourteen of a planned 20 patients have completed the 28-day study. The dosing is 0.5 mg/kg of the intravenous ketamine solution mixed in cherry syrup to hide the universally loathed taste. Treatment is once daily.

The therapeutic efficacy has been impressive, as reflected in a drop in average scores on the Hospital Anxiety and Depression Scale from about 20 to 5.

"Interestingly, several patients had diagnosable severe anxiety disorders that went away completely. We’re finding that anxiety may be even more affected by ketamine than depression," Dr. Irwin said.

The high burden of somatic symptoms present in these patients also lightened significantly, with scores on the Adverse Symptom Checklist falling from about 28 to 5. This doesn’t appear to be a result of the drug’s analgesic effect, because some patients didn’t have significant pain, while in others the somatic symptoms improved while pain scores remained unchanged.

Another 30 or so San Diego Hospice patients have received oral ketamine outside of the pilot study, with similar benefits.

"We’ve gone to nightly dosing. And if you see a decrement in benefit, bump up the dose by 20%," Dr. Irwin advised in response to audience questions.

He called depression near the end of life a major yet widely underappreciated public health problem. The consequences of untreated depression in these patients include longer inpatient hospital stays, worsening medical illness, greater difficulty in treating pain and nausea, and interference with making preparations for death. Untreated depression also impedes interactions with caregivers and, most importantly, with loved ones.

Dr. Irwin recalled one of the first hospice patients for whom he prescribed methylphenidate. After 24 hours on treatment, the man no longer met criteria for major depressive disorder. He lived for another week with newly restored enjoyment of nature and his family. Dr. Irwin learned of his death when he ran into the patient’s daughter in the parking lot.

"She said, ‘I want to thank you for giving me my father back. I will now remember him as the great man he always was, and not the miserable man that he’d become for the last 6 months,’ "

Dr. Irwin said. "So we changed her life for decades.

"If anyone asks you, ‘Why bother treating depression in hospice when you’re only changing the last few days?’ tell them it’s a family experience. It’s not just about the patient."

He reported having no financial conflicts.

DENVER – The variety of administration routes and dosing protocols for ketamine make it useful for analgesia in the palliative care setting.

Ketamine seems effective in a variety of difficult pain syndromes commonly encountered in hospice and palliative medicine, Dr. Eric Prommer observed at the conference. Multiple routes of administration make ketamine a valuable weapon in the setting of refractory pain.

The most common and best-studied routes of administration are the intravenous, oral, and subcutaneous approaches. Uncommon routes come in handy when others become problematic and include sublingual, intranasal, and topical administration.

"Ketamine is both water and lipid soluble. That’s the beauty of ketamine: It’s what allows multiple routes of administration and generally reliable absorption," explained Dr. Prommer, director of palliative care at the Mayo Clinic Hospital in Scottsdale, Ariz.

Ketamine is on the World Health Organization’s essential drug list for refractory cancer pain, but there is no agreement on the best protocol, dose, or method of administration for optimal analgesia. Perhaps that element of uncertainty drew the packed house for Dr. Prommer’s plenary lecture, in which he filled in the blanks in a ketamine analgesia literature dominated by uncontrolled studies leavened by a limited number of randomized trials and growing anecdotal experience.

At present, ketamine’s best role is as an adjuvant analgesic prescribed in order to avoid escalation of opioid dosing.

"There is really only limited data looking at giving ketamine instead of opioids. That needs to be studied further," he stressed.

Ketamine’s main method of action involves binding to the NMDA receptor. This receptor mirrors the opioid receptor such that everywhere in the CNS that there’s an opioid receptor, there is also an NMDA receptor. As an NMDA antagonist, ketamine reverses opioid tolerance. So when a patient on both ketamine and opioids develops sedation as a prominent adverse effect, look to reduce the opioid dose. It’s unlikely that ketamine prescribed in the subanesthetic doses used for pain relief is the culprit.

Unlike methadone, ketamine has no major drug interactions that could affect its bioavailability.

Adverse effects occur in dose-dependent fashion in up to 20%-30% of patients on intravenous ketamine at 200-350 mg/day. The chief side effects are psychomimetic and involve altered visuospatial perceptions, or a "spaced out" feeling. Delirium, dizziness, altered hearing, tachycardia, hypertension, and nausea and vomiting can also occur. Adverse effects are less frequent with oral dosing. Prophylactic administration of haloperidol at 0.5 mg or lorazepam at 0.5 mg for the first few doses of ketamine lessens the risk of side effects.

Urinary toxicity is a recently recognized side effect of ketamine. Manifestations include interstitial cystitis, hydronephrosis, vesicoureteric reflux, and renal impairment, including irreversible renal failure. Mostly, however, urinary toxicity occurs in long-term "street" ketamine abusers.

"We don’t see a lot of this in our population because they’re typically not on ketamine for a prolonged time," he noted.

The starting intravenous bolus dose of ketamine is typically 0.25-0.50 mg/kg given over 30 minutes. Onset of effect is within 60 seconds, with a duration of 3-4 hours.

Oral ketamine is simply the intravenous solution mixed in a flavored syrup to mask the unpleasant taste; spearmint and cherry flavorings are popular. Oral dosing is 0.5 mg/kg. Onset is in about 20 minutes. The dose can be repeated three or four times per 24 hours. A recent study showed that a 1:1 dose ratio for conversion from subcutaneous to oral dosing is safe and effectively maintains analgesia in patients with cancer pain (J. Pain Symptom Manage. 2011;41:1098-105).

Sublingual ketamine at 25 mg works well for breakthrough pain. "That number – 25 mg – comes up a lot in the literature. If you extrapolate that to a 70-kg person that’s a nice subanesthetic dose," according to Dr. Prommer.

The intranasal route is another really important backup option for breakthrough pain. The dose is 50 mg.

Topical 1%-2% ketamine cream compounded in a pharmacy and applied three times daily to affected areas is effective for neuropathic pain. Another topical option in neuropathic pain syndromes – and one supported by an open-label study – is topical 2% amitriptyline/1% ketamine, which was well tolerated and associated with moderate to complete patient satisfaction over 6-12 months (J. Pain 2005;6:644-9).

"The beauty of the topical route is there is minimal systemic absorption, so you don’t have to worry about any kind of significant adverse effects. There seems to be a dose-response relationship. I’ve given up to 10% ketamine topically and patients have tolerated it," Dr. Prommer said.

A particularly exciting method of giving ketamine for refractory pain is the so-called "burst technique." It entails a 3- to 5-day continuous subcutaneous infusion with dose escalation. Upon stopping the ketamine, pain relief lasting 2 weeks or longer is common.

"Once you silence that NMDA receptor you might get prolonged effects. This is really wonderful for our palliative care/hospice population because it means they get one less medication while it adds to their comfort. You can’t get better than that: a medicine that you can stop and still get some mileage out of it," he continued.

In the Australian multicenter VCOG PM 1-00 study, the burst ketamine protocol used in palliative care patients with refractory cancer pain began with a continuous subcutaneous infusion of 100 mg/24 hours. If that proved ineffective after 24 hours, the dose was increased to 300 mg/24 hours. And if patients didn’t have good analgesia after 24 hours on ketamine at 300 mg/24 hours, the dose was bumped to 500 mg/24 hours. When the effective or maximum tolerated dose was reached, it was continued for 3 days and then stopped. Thus, patients ceased taking ketamine after a maximum of 5 days whether it was effective or not.

Half of patients were rated as responders using strict criteria and 9% became pain free. Moreover, 50% of responders experienced pain relief lasting 2 weeks or longer while off ketamine. The toxicities were mainly neurologic and occurred at 300 or 500 mg/24 hours dosing (J. Palliat. Care 2010;26:176-83).

"It was very interesting: There really weren’t a lot of cardiovascular adverse effects in this study," Dr. Prommer commented.

A variant of the burst technique proved effective in patients with complex regional pain syndrome type 1 in a Dutch placebo-controlled study. The 60 participants had a median 7.4-year disease duration. Investigators utilized a 4.2-day intravenous infusion of low-dose ketamine with individualized stepwise tailoring of dosage based upon pain relief and side effects. The final dose was 22.2 mg/hour/70 kg. Pain relief in the ketamine group lasted for nearly 12 weeks after the drug was stopped (Pain 2009;145:304-11).

Other randomized studies show efficacy for ketamine in patients with post-herpetic neuralgia or ischemic pain. But Dr. Prommer stressed that while it’s clear ketamine provides relief in patients with chronic noncancer pain, he believes the drug’s long-term use should be restricted to the clinical trial setting.

"There are just no good long-term safety data for 6-8 months of therapy," he emphasized.

Dr. Prommer said a single dose of ketamine is helpful for painful dressing changes when adequate analgesia can’t be gained with opioids alone. Case reports attest to the usefulness of ketamine as an oral rinse in patients with mucositis; however, Dr. Prommer has tried it and found it didn’t work.

He reported having no financial conflicts.

DENVER – The variety of administration routes and dosing protocols for ketamine make it useful for analgesia in the palliative care setting.

Ketamine seems effective in a variety of difficult pain syndromes commonly encountered in hospice and palliative medicine, Dr. Eric Prommer observed at the conference. Multiple routes of administration make ketamine a valuable weapon in the setting of refractory pain.

The most common and best-studied routes of administration are the intravenous, oral, and subcutaneous approaches. Uncommon routes come in handy when others become problematic and include sublingual, intranasal, and topical administration.

"Ketamine is both water and lipid soluble. That’s the beauty of ketamine: It’s what allows multiple routes of administration and generally reliable absorption," explained Dr. Prommer, director of palliative care at the Mayo Clinic Hospital in Scottsdale, Ariz.

Ketamine is on the World Health Organization’s essential drug list for refractory cancer pain, but there is no agreement on the best protocol, dose, or method of administration for optimal analgesia. Perhaps that element of uncertainty drew the packed house for Dr. Prommer’s plenary lecture, in which he filled in the blanks in a ketamine analgesia literature dominated by uncontrolled studies leavened by a limited number of randomized trials and growing anecdotal experience.

At present, ketamine’s best role is as an adjuvant analgesic prescribed in order to avoid escalation of opioid dosing.

"There is really only limited data looking at giving ketamine instead of opioids. That needs to be studied further," he stressed.

Ketamine’s main method of action involves binding to the NMDA receptor. This receptor mirrors the opioid receptor such that everywhere in the CNS that there’s an opioid receptor, there is also an NMDA receptor. As an NMDA antagonist, ketamine reverses opioid tolerance. So when a patient on both ketamine and opioids develops sedation as a prominent adverse effect, look to reduce the opioid dose. It’s unlikely that ketamine prescribed in the subanesthetic doses used for pain relief is the culprit.

Unlike methadone, ketamine has no major drug interactions that could affect its bioavailability.

Adverse effects occur in dose-dependent fashion in up to 20%-30% of patients on intravenous ketamine at 200-350 mg/day. The chief side effects are psychomimetic and involve altered visuospatial perceptions, or a "spaced out" feeling. Delirium, dizziness, altered hearing, tachycardia, hypertension, and nausea and vomiting can also occur. Adverse effects are less frequent with oral dosing. Prophylactic administration of haloperidol at 0.5 mg or lorazepam at 0.5 mg for the first few doses of ketamine lessens the risk of side effects.

Urinary toxicity is a recently recognized side effect of ketamine. Manifestations include interstitial cystitis, hydronephrosis, vesicoureteric reflux, and renal impairment, including irreversible renal failure. Mostly, however, urinary toxicity occurs in long-term "street" ketamine abusers.

"We don’t see a lot of this in our population because they’re typically not on ketamine for a prolonged time," he noted.

The starting intravenous bolus dose of ketamine is typically 0.25-0.50 mg/kg given over 30 minutes. Onset of effect is within 60 seconds, with a duration of 3-4 hours.

Oral ketamine is simply the intravenous solution mixed in a flavored syrup to mask the unpleasant taste; spearmint and cherry flavorings are popular. Oral dosing is 0.5 mg/kg. Onset is in about 20 minutes. The dose can be repeated three or four times per 24 hours. A recent study showed that a 1:1 dose ratio for conversion from subcutaneous to oral dosing is safe and effectively maintains analgesia in patients with cancer pain (J. Pain Symptom Manage. 2011;41:1098-105).

Sublingual ketamine at 25 mg works well for breakthrough pain. "That number – 25 mg – comes up a lot in the literature. If you extrapolate that to a 70-kg person that’s a nice subanesthetic dose," according to Dr. Prommer.

The intranasal route is another really important backup option for breakthrough pain. The dose is 50 mg.

Topical 1%-2% ketamine cream compounded in a pharmacy and applied three times daily to affected areas is effective for neuropathic pain. Another topical option in neuropathic pain syndromes – and one supported by an open-label study – is topical 2% amitriptyline/1% ketamine, which was well tolerated and associated with moderate to complete patient satisfaction over 6-12 months (J. Pain 2005;6:644-9).

"The beauty of the topical route is there is minimal systemic absorption, so you don’t have to worry about any kind of significant adverse effects. There seems to be a dose-response relationship. I’ve given up to 10% ketamine topically and patients have tolerated it," Dr. Prommer said.

A particularly exciting method of giving ketamine for refractory pain is the so-called "burst technique." It entails a 3- to 5-day continuous subcutaneous infusion with dose escalation. Upon stopping the ketamine, pain relief lasting 2 weeks or longer is common.

"Once you silence that NMDA receptor you might get prolonged effects. This is really wonderful for our palliative care/hospice population because it means they get one less medication while it adds to their comfort. You can’t get better than that: a medicine that you can stop and still get some mileage out of it," he continued.

In the Australian multicenter VCOG PM 1-00 study, the burst ketamine protocol used in palliative care patients with refractory cancer pain began with a continuous subcutaneous infusion of 100 mg/24 hours. If that proved ineffective after 24 hours, the dose was increased to 300 mg/24 hours. And if patients didn’t have good analgesia after 24 hours on ketamine at 300 mg/24 hours, the dose was bumped to 500 mg/24 hours. When the effective or maximum tolerated dose was reached, it was continued for 3 days and then stopped. Thus, patients ceased taking ketamine after a maximum of 5 days whether it was effective or not.

Half of patients were rated as responders using strict criteria and 9% became pain free. Moreover, 50% of responders experienced pain relief lasting 2 weeks or longer while off ketamine. The toxicities were mainly neurologic and occurred at 300 or 500 mg/24 hours dosing (J. Palliat. Care 2010;26:176-83).

"It was very interesting: There really weren’t a lot of cardiovascular adverse effects in this study," Dr. Prommer commented.

A variant of the burst technique proved effective in patients with complex regional pain syndrome type 1 in a Dutch placebo-controlled study. The 60 participants had a median 7.4-year disease duration. Investigators utilized a 4.2-day intravenous infusion of low-dose ketamine with individualized stepwise tailoring of dosage based upon pain relief and side effects. The final dose was 22.2 mg/hour/70 kg. Pain relief in the ketamine group lasted for nearly 12 weeks after the drug was stopped (Pain 2009;145:304-11).

Other randomized studies show efficacy for ketamine in patients with post-herpetic neuralgia or ischemic pain. But Dr. Prommer stressed that while it’s clear ketamine provides relief in patients with chronic noncancer pain, he believes the drug’s long-term use should be restricted to the clinical trial setting.

"There are just no good long-term safety data for 6-8 months of therapy," he emphasized.

Dr. Prommer said a single dose of ketamine is helpful for painful dressing changes when adequate analgesia can’t be gained with opioids alone. Case reports attest to the usefulness of ketamine as an oral rinse in patients with mucositis; however, Dr. Prommer has tried it and found it didn’t work.

He reported having no financial conflicts.

DENVER – The variety of administration routes and dosing protocols for ketamine make it useful for analgesia in the palliative care setting.

Ketamine seems effective in a variety of difficult pain syndromes commonly encountered in hospice and palliative medicine, Dr. Eric Prommer observed at the conference. Multiple routes of administration make ketamine a valuable weapon in the setting of refractory pain.

The most common and best-studied routes of administration are the intravenous, oral, and subcutaneous approaches. Uncommon routes come in handy when others become problematic and include sublingual, intranasal, and topical administration.

"Ketamine is both water and lipid soluble. That’s the beauty of ketamine: It’s what allows multiple routes of administration and generally reliable absorption," explained Dr. Prommer, director of palliative care at the Mayo Clinic Hospital in Scottsdale, Ariz.

Ketamine is on the World Health Organization’s essential drug list for refractory cancer pain, but there is no agreement on the best protocol, dose, or method of administration for optimal analgesia. Perhaps that element of uncertainty drew the packed house for Dr. Prommer’s plenary lecture, in which he filled in the blanks in a ketamine analgesia literature dominated by uncontrolled studies leavened by a limited number of randomized trials and growing anecdotal experience.

At present, ketamine’s best role is as an adjuvant analgesic prescribed in order to avoid escalation of opioid dosing.

"There is really only limited data looking at giving ketamine instead of opioids. That needs to be studied further," he stressed.

Ketamine’s main method of action involves binding to the NMDA receptor. This receptor mirrors the opioid receptor such that everywhere in the CNS that there’s an opioid receptor, there is also an NMDA receptor. As an NMDA antagonist, ketamine reverses opioid tolerance. So when a patient on both ketamine and opioids develops sedation as a prominent adverse effect, look to reduce the opioid dose. It’s unlikely that ketamine prescribed in the subanesthetic doses used for pain relief is the culprit.

Unlike methadone, ketamine has no major drug interactions that could affect its bioavailability.

Adverse effects occur in dose-dependent fashion in up to 20%-30% of patients on intravenous ketamine at 200-350 mg/day. The chief side effects are psychomimetic and involve altered visuospatial perceptions, or a "spaced out" feeling. Delirium, dizziness, altered hearing, tachycardia, hypertension, and nausea and vomiting can also occur. Adverse effects are less frequent with oral dosing. Prophylactic administration of haloperidol at 0.5 mg or lorazepam at 0.5 mg for the first few doses of ketamine lessens the risk of side effects.

Urinary toxicity is a recently recognized side effect of ketamine. Manifestations include interstitial cystitis, hydronephrosis, vesicoureteric reflux, and renal impairment, including irreversible renal failure. Mostly, however, urinary toxicity occurs in long-term "street" ketamine abusers.

"We don’t see a lot of this in our population because they’re typically not on ketamine for a prolonged time," he noted.

The starting intravenous bolus dose of ketamine is typically 0.25-0.50 mg/kg given over 30 minutes. Onset of effect is within 60 seconds, with a duration of 3-4 hours.

Oral ketamine is simply the intravenous solution mixed in a flavored syrup to mask the unpleasant taste; spearmint and cherry flavorings are popular. Oral dosing is 0.5 mg/kg. Onset is in about 20 minutes. The dose can be repeated three or four times per 24 hours. A recent study showed that a 1:1 dose ratio for conversion from subcutaneous to oral dosing is safe and effectively maintains analgesia in patients with cancer pain (J. Pain Symptom Manage. 2011;41:1098-105).

Sublingual ketamine at 25 mg works well for breakthrough pain. "That number – 25 mg – comes up a lot in the literature. If you extrapolate that to a 70-kg person that’s a nice subanesthetic dose," according to Dr. Prommer.

The intranasal route is another really important backup option for breakthrough pain. The dose is 50 mg.

Topical 1%-2% ketamine cream compounded in a pharmacy and applied three times daily to affected areas is effective for neuropathic pain. Another topical option in neuropathic pain syndromes – and one supported by an open-label study – is topical 2% amitriptyline/1% ketamine, which was well tolerated and associated with moderate to complete patient satisfaction over 6-12 months (J. Pain 2005;6:644-9).

"The beauty of the topical route is there is minimal systemic absorption, so you don’t have to worry about any kind of significant adverse effects. There seems to be a dose-response relationship. I’ve given up to 10% ketamine topically and patients have tolerated it," Dr. Prommer said.

A particularly exciting method of giving ketamine for refractory pain is the so-called "burst technique." It entails a 3- to 5-day continuous subcutaneous infusion with dose escalation. Upon stopping the ketamine, pain relief lasting 2 weeks or longer is common.

"Once you silence that NMDA receptor you might get prolonged effects. This is really wonderful for our palliative care/hospice population because it means they get one less medication while it adds to their comfort. You can’t get better than that: a medicine that you can stop and still get some mileage out of it," he continued.

In the Australian multicenter VCOG PM 1-00 study, the burst ketamine protocol used in palliative care patients with refractory cancer pain began with a continuous subcutaneous infusion of 100 mg/24 hours. If that proved ineffective after 24 hours, the dose was increased to 300 mg/24 hours. And if patients didn’t have good analgesia after 24 hours on ketamine at 300 mg/24 hours, the dose was bumped to 500 mg/24 hours. When the effective or maximum tolerated dose was reached, it was continued for 3 days and then stopped. Thus, patients ceased taking ketamine after a maximum of 5 days whether it was effective or not.

Half of patients were rated as responders using strict criteria and 9% became pain free. Moreover, 50% of responders experienced pain relief lasting 2 weeks or longer while off ketamine. The toxicities were mainly neurologic and occurred at 300 or 500 mg/24 hours dosing (J. Palliat. Care 2010;26:176-83).

"It was very interesting: There really weren’t a lot of cardiovascular adverse effects in this study," Dr. Prommer commented.

A variant of the burst technique proved effective in patients with complex regional pain syndrome type 1 in a Dutch placebo-controlled study. The 60 participants had a median 7.4-year disease duration. Investigators utilized a 4.2-day intravenous infusion of low-dose ketamine with individualized stepwise tailoring of dosage based upon pain relief and side effects. The final dose was 22.2 mg/hour/70 kg. Pain relief in the ketamine group lasted for nearly 12 weeks after the drug was stopped (Pain 2009;145:304-11).

Other randomized studies show efficacy for ketamine in patients with post-herpetic neuralgia or ischemic pain. But Dr. Prommer stressed that while it’s clear ketamine provides relief in patients with chronic noncancer pain, he believes the drug’s long-term use should be restricted to the clinical trial setting.

"There are just no good long-term safety data for 6-8 months of therapy," he emphasized.

Dr. Prommer said a single dose of ketamine is helpful for painful dressing changes when adequate analgesia can’t be gained with opioids alone. Case reports attest to the usefulness of ketamine as an oral rinse in patients with mucositis; however, Dr. Prommer has tried it and found it didn’t work.

He reported having no financial conflicts.

DENVER – The routine administration of oxygen to terminally ill patients who are near death is unwarranted, according to the results of a randomized, double-blind trial.

"I would suggest that we always use the patient in respiratory distress as their own control in an n-of-1 trial of oxygen. If oxygen does reduce their distress, then that patient should have oxygen, but if it does not – if there’s no change in patient distress – then that oxygen can be discontinued, or certainly not initiated in the first place," Mary L. Campbell, Ph.D., declared at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Oxygen has well-established benefits in hypoxemic patients with acute or chronic exacerbations of an underlying pulmonary condition, but without ever having been subjected to scientific scrutiny, oxygen administration has become routine for patients who are near death, asserted Dr. Campbell of Wayne State University, Detroit.

"Oxygen has become almost an iconic intervention at the end of life – as common as golf clubs on a Wednesday afternoon," she said.

And oxygen support is not a benign intervention. It’s expensive, particularly in home care, where it requires additional personnel and materials in the home, including a noisy, intrusive concentrator at the bedside. It also causes nasal drying and nosebleeds as well as feelings of suffocation, Dr. Campbell said.

["Comfort Seldom Comes from Cannula" -- Commentary, Hospitalist News, 4/6/12]

To assess the value of routine oxygen administration, she conducted a double-blind, randomized, crossover study involving 32 terminally ill patients. None was in respiratory distress at baseline, but all were at high risk for distress because of underlying COPD, heart failure, pneumonia, or lung cancer. All participants had a Palliative Performance Scale score of 30 or less, which is associated with a median 9- to 14-day survival.

Each patient received a capnoline – that is, a nasal cannula with a piece of plastic hanging down over the patient’s mouth to capture exhaled carbon dioxide. Next, randomly alternating 10-minute intervals of oxygen, medical air, and no flow were administered for 90 minutes.

The key finding: 29 of 32 patients experienced no distress during the 90-minute protocol, indicating that they didn’t need the oxygen. Yet, at enrollment, 27 patients had oxygen flowing, reflecting this widespread clinical practice at the end of life, Dr. Campbell said.

The remaining three patients rapidly became hypoxemic and distressed when crossed over from oxygen to no flow. They were returned to baseline oxygen and respiratory comfort.

As many of the study participants were unconscious or cognitively impaired and couldn’t self report their distress, the Respiratory Distress Observation Scale was assessed at baseline and for 10 minutes after every flow change. A score of 4 or less on the 0-16 scale indicates little or no distress; the average baseline score was 1.47, and it didn’t vary significantly during the different flow conditions, she reported.

The average oxygen saturation at baseline was 93.6%, and it didn’t change significantly during the 90-minute protocol.

Dr. Campbell said that she determines the need for oxygen in an end-of-life patient by taking the patient off oxygen for 10 minutes and watching for distress.

Several audience members predicted that the patient’s family is likely to object to this approach because oxygen has become an expected part of end-of-life care. Dr. Campbell responded that the solution to that problem is simply good communication.

"I think if you explain to families that this is a treatment that can be helpful but has side effects, and we always take away the things that aren’t helping when they’re no longer helping, you won’t have pushback from family members," she said.

Dr. Campbell’s study was funded by the Blue Cross/Blue Shield of Michigan Foundation. She reported having no financial conflicts.

DENVER – The routine administration of oxygen to terminally ill patients who are near death is unwarranted, according to the results of a randomized, double-blind trial.

"I would suggest that we always use the patient in respiratory distress as their own control in an n-of-1 trial of oxygen. If oxygen does reduce their distress, then that patient should have oxygen, but if it does not – if there’s no change in patient distress – then that oxygen can be discontinued, or certainly not initiated in the first place," Mary L. Campbell, Ph.D., declared at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Oxygen has well-established benefits in hypoxemic patients with acute or chronic exacerbations of an underlying pulmonary condition, but without ever having been subjected to scientific scrutiny, oxygen administration has become routine for patients who are near death, asserted Dr. Campbell of Wayne State University, Detroit.

"Oxygen has become almost an iconic intervention at the end of life – as common as golf clubs on a Wednesday afternoon," she said.

And oxygen support is not a benign intervention. It’s expensive, particularly in home care, where it requires additional personnel and materials in the home, including a noisy, intrusive concentrator at the bedside. It also causes nasal drying and nosebleeds as well as feelings of suffocation, Dr. Campbell said.

["Comfort Seldom Comes from Cannula" -- Commentary, Hospitalist News, 4/6/12]

To assess the value of routine oxygen administration, she conducted a double-blind, randomized, crossover study involving 32 terminally ill patients. None was in respiratory distress at baseline, but all were at high risk for distress because of underlying COPD, heart failure, pneumonia, or lung cancer. All participants had a Palliative Performance Scale score of 30 or less, which is associated with a median 9- to 14-day survival.

Each patient received a capnoline – that is, a nasal cannula with a piece of plastic hanging down over the patient’s mouth to capture exhaled carbon dioxide. Next, randomly alternating 10-minute intervals of oxygen, medical air, and no flow were administered for 90 minutes.

The key finding: 29 of 32 patients experienced no distress during the 90-minute protocol, indicating that they didn’t need the oxygen. Yet, at enrollment, 27 patients had oxygen flowing, reflecting this widespread clinical practice at the end of life, Dr. Campbell said.

The remaining three patients rapidly became hypoxemic and distressed when crossed over from oxygen to no flow. They were returned to baseline oxygen and respiratory comfort.

As many of the study participants were unconscious or cognitively impaired and couldn’t self report their distress, the Respiratory Distress Observation Scale was assessed at baseline and for 10 minutes after every flow change. A score of 4 or less on the 0-16 scale indicates little or no distress; the average baseline score was 1.47, and it didn’t vary significantly during the different flow conditions, she reported.

The average oxygen saturation at baseline was 93.6%, and it didn’t change significantly during the 90-minute protocol.

Dr. Campbell said that she determines the need for oxygen in an end-of-life patient by taking the patient off oxygen for 10 minutes and watching for distress.

Several audience members predicted that the patient’s family is likely to object to this approach because oxygen has become an expected part of end-of-life care. Dr. Campbell responded that the solution to that problem is simply good communication.

"I think if you explain to families that this is a treatment that can be helpful but has side effects, and we always take away the things that aren’t helping when they’re no longer helping, you won’t have pushback from family members," she said.

Dr. Campbell’s study was funded by the Blue Cross/Blue Shield of Michigan Foundation. She reported having no financial conflicts.

DENVER – The routine administration of oxygen to terminally ill patients who are near death is unwarranted, according to the results of a randomized, double-blind trial.

"I would suggest that we always use the patient in respiratory distress as their own control in an n-of-1 trial of oxygen. If oxygen does reduce their distress, then that patient should have oxygen, but if it does not – if there’s no change in patient distress – then that oxygen can be discontinued, or certainly not initiated in the first place," Mary L. Campbell, Ph.D., declared at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Oxygen has well-established benefits in hypoxemic patients with acute or chronic exacerbations of an underlying pulmonary condition, but without ever having been subjected to scientific scrutiny, oxygen administration has become routine for patients who are near death, asserted Dr. Campbell of Wayne State University, Detroit.

"Oxygen has become almost an iconic intervention at the end of life – as common as golf clubs on a Wednesday afternoon," she said.

And oxygen support is not a benign intervention. It’s expensive, particularly in home care, where it requires additional personnel and materials in the home, including a noisy, intrusive concentrator at the bedside. It also causes nasal drying and nosebleeds as well as feelings of suffocation, Dr. Campbell said.

["Comfort Seldom Comes from Cannula" -- Commentary, Hospitalist News, 4/6/12]

To assess the value of routine oxygen administration, she conducted a double-blind, randomized, crossover study involving 32 terminally ill patients. None was in respiratory distress at baseline, but all were at high risk for distress because of underlying COPD, heart failure, pneumonia, or lung cancer. All participants had a Palliative Performance Scale score of 30 or less, which is associated with a median 9- to 14-day survival.

Each patient received a capnoline – that is, a nasal cannula with a piece of plastic hanging down over the patient’s mouth to capture exhaled carbon dioxide. Next, randomly alternating 10-minute intervals of oxygen, medical air, and no flow were administered for 90 minutes.

The key finding: 29 of 32 patients experienced no distress during the 90-minute protocol, indicating that they didn’t need the oxygen. Yet, at enrollment, 27 patients had oxygen flowing, reflecting this widespread clinical practice at the end of life, Dr. Campbell said.

The remaining three patients rapidly became hypoxemic and distressed when crossed over from oxygen to no flow. They were returned to baseline oxygen and respiratory comfort.

As many of the study participants were unconscious or cognitively impaired and couldn’t self report their distress, the Respiratory Distress Observation Scale was assessed at baseline and for 10 minutes after every flow change. A score of 4 or less on the 0-16 scale indicates little or no distress; the average baseline score was 1.47, and it didn’t vary significantly during the different flow conditions, she reported.

The average oxygen saturation at baseline was 93.6%, and it didn’t change significantly during the 90-minute protocol.

Dr. Campbell said that she determines the need for oxygen in an end-of-life patient by taking the patient off oxygen for 10 minutes and watching for distress.

Several audience members predicted that the patient’s family is likely to object to this approach because oxygen has become an expected part of end-of-life care. Dr. Campbell responded that the solution to that problem is simply good communication.

"I think if you explain to families that this is a treatment that can be helpful but has side effects, and we always take away the things that aren’t helping when they’re no longer helping, you won’t have pushback from family members," she said.

Dr. Campbell’s study was funded by the Blue Cross/Blue Shield of Michigan Foundation. She reported having no financial conflicts.

DENVER – Low-dose adjunctive benzodiazepines are effective in combination with opioids for dyspnea in palliative care patients who don’t respond to opioids alone, according to Dr. Patama Gomutbutra.

When opioids alone aren’t bringing significant improvement, adding a benzodiazepine is worthwhile, she said. The question of whether benzodiazepines alone are effective in the management of dyspnea must await answers from randomized clinical trials.

Dr. Gomutbutra conducted a retrospective chart review of 303 inpatients with dyspnea evaluated by members of the University of California, San Francisco, palliative care program. These were seriously ill patients: Twenty-three percent had primary lung cancer, 32% had cancer outside the lung, 12% had heart failure, and 7% had chronic obstructive pulmonary disease. Of these patients, 47% died in the hospital and 25% were discharged to hospice.

At baseline, physicians rated dyspnea as severe in 19% of patients, moderate in 28%, and mild in 53%. At baseline, 49% of patients were already on opioids at a median dose of 52 mg/day; 87% of these patients remained on opioids at 24 hours, with a bump up in dose to a median of 60 mg/day. Of the patients not initially taking an opioid, 41% were placed on the medication at a median dose of 22 mg/day.

"Our results should not dissuade people from using opioids as the first-line treatment."

At baseline, 17% of patients were on a benzodiazepine at a median dose of 1 mg/day of oral lorazepam or its equivalent. At 24 hours, 24% of patients were on a benzodiazepine, again at a median daily dose of 1 mg.

At follow-up 24 hours after adjustment of dosages or addition of an opioid or a benzodiazepine, the population with severe dyspnea had fallen from 19% to 4%. Dyspnea was rated moderate in 18% and mild in 44%, and was absent in 34%.

Overall, 57% of patients had a clinically meaningful improvement in dyspnea of one severity grade or more, 37% remained the same, and the rest became worse, according to Dr. Gomutbutra of Chiang Mai (Thailand) University.

Taking an opioid and a benzodiazepine at follow-up was independently associated with a 2.1-fold increased likelihood of significant improvement in dyspnea. Having moderate or severe dyspnea at baseline was associated with 4.1- and 4.5-fold increased likelihoods of improvement, respectively.

Surprisingly, being on an opioid at baseline wasn’t associated with significant improvement at follow-up, even though opioids are guideline-recommended therapy for dyspnea.

Dr. Gomutbutra cautioned against overinterpretation of this finding, given that her study was retrospective and thus vulnerable to confounding. For example, she noted, the respiratory rate typically slows near death, so affected patients may not have received continued or increased doses of opioids.

"Our results should not dissuade people from using opioids as the first-line treatment," Dr. Gomutbutra emphasized.

Dr. Gomutbutra carried out this study after observing big differences in how dyspnea is managed in palliative care settings in the United States, compared with Thailand. While the median daily dose of opioids at baseline in the San Francisco study was 52 mg/day, a typical dose in Thailand would be 6 mg/day. And benzodiazepines are far more widely used in treating dyspnea there, she added.

She reported having no financial conflicts.

DENVER – Low-dose adjunctive benzodiazepines are effective in combination with opioids for dyspnea in palliative care patients who don’t respond to opioids alone, according to Dr. Patama Gomutbutra.

When opioids alone aren’t bringing significant improvement, adding a benzodiazepine is worthwhile, she said. The question of whether benzodiazepines alone are effective in the management of dyspnea must await answers from randomized clinical trials.

Dr. Gomutbutra conducted a retrospective chart review of 303 inpatients with dyspnea evaluated by members of the University of California, San Francisco, palliative care program. These were seriously ill patients: Twenty-three percent had primary lung cancer, 32% had cancer outside the lung, 12% had heart failure, and 7% had chronic obstructive pulmonary disease. Of these patients, 47% died in the hospital and 25% were discharged to hospice.

At baseline, physicians rated dyspnea as severe in 19% of patients, moderate in 28%, and mild in 53%. At baseline, 49% of patients were already on opioids at a median dose of 52 mg/day; 87% of these patients remained on opioids at 24 hours, with a bump up in dose to a median of 60 mg/day. Of the patients not initially taking an opioid, 41% were placed on the medication at a median dose of 22 mg/day.

"Our results should not dissuade people from using opioids as the first-line treatment."

At baseline, 17% of patients were on a benzodiazepine at a median dose of 1 mg/day of oral lorazepam or its equivalent. At 24 hours, 24% of patients were on a benzodiazepine, again at a median daily dose of 1 mg.

At follow-up 24 hours after adjustment of dosages or addition of an opioid or a benzodiazepine, the population with severe dyspnea had fallen from 19% to 4%. Dyspnea was rated moderate in 18% and mild in 44%, and was absent in 34%.

Overall, 57% of patients had a clinically meaningful improvement in dyspnea of one severity grade or more, 37% remained the same, and the rest became worse, according to Dr. Gomutbutra of Chiang Mai (Thailand) University.

Taking an opioid and a benzodiazepine at follow-up was independently associated with a 2.1-fold increased likelihood of significant improvement in dyspnea. Having moderate or severe dyspnea at baseline was associated with 4.1- and 4.5-fold increased likelihoods of improvement, respectively.

Surprisingly, being on an opioid at baseline wasn’t associated with significant improvement at follow-up, even though opioids are guideline-recommended therapy for dyspnea.

Dr. Gomutbutra cautioned against overinterpretation of this finding, given that her study was retrospective and thus vulnerable to confounding. For example, she noted, the respiratory rate typically slows near death, so affected patients may not have received continued or increased doses of opioids.

"Our results should not dissuade people from using opioids as the first-line treatment," Dr. Gomutbutra emphasized.

Dr. Gomutbutra carried out this study after observing big differences in how dyspnea is managed in palliative care settings in the United States, compared with Thailand. While the median daily dose of opioids at baseline in the San Francisco study was 52 mg/day, a typical dose in Thailand would be 6 mg/day. And benzodiazepines are far more widely used in treating dyspnea there, she added.

She reported having no financial conflicts.

DENVER – Low-dose adjunctive benzodiazepines are effective in combination with opioids for dyspnea in palliative care patients who don’t respond to opioids alone, according to Dr. Patama Gomutbutra.

When opioids alone aren’t bringing significant improvement, adding a benzodiazepine is worthwhile, she said. The question of whether benzodiazepines alone are effective in the management of dyspnea must await answers from randomized clinical trials.

Dr. Gomutbutra conducted a retrospective chart review of 303 inpatients with dyspnea evaluated by members of the University of California, San Francisco, palliative care program. These were seriously ill patients: Twenty-three percent had primary lung cancer, 32% had cancer outside the lung, 12% had heart failure, and 7% had chronic obstructive pulmonary disease. Of these patients, 47% died in the hospital and 25% were discharged to hospice.

At baseline, physicians rated dyspnea as severe in 19% of patients, moderate in 28%, and mild in 53%. At baseline, 49% of patients were already on opioids at a median dose of 52 mg/day; 87% of these patients remained on opioids at 24 hours, with a bump up in dose to a median of 60 mg/day. Of the patients not initially taking an opioid, 41% were placed on the medication at a median dose of 22 mg/day.

"Our results should not dissuade people from using opioids as the first-line treatment."

At baseline, 17% of patients were on a benzodiazepine at a median dose of 1 mg/day of oral lorazepam or its equivalent. At 24 hours, 24% of patients were on a benzodiazepine, again at a median daily dose of 1 mg.

At follow-up 24 hours after adjustment of dosages or addition of an opioid or a benzodiazepine, the population with severe dyspnea had fallen from 19% to 4%. Dyspnea was rated moderate in 18% and mild in 44%, and was absent in 34%.

Overall, 57% of patients had a clinically meaningful improvement in dyspnea of one severity grade or more, 37% remained the same, and the rest became worse, according to Dr. Gomutbutra of Chiang Mai (Thailand) University.

Taking an opioid and a benzodiazepine at follow-up was independently associated with a 2.1-fold increased likelihood of significant improvement in dyspnea. Having moderate or severe dyspnea at baseline was associated with 4.1- and 4.5-fold increased likelihoods of improvement, respectively.

Surprisingly, being on an opioid at baseline wasn’t associated with significant improvement at follow-up, even though opioids are guideline-recommended therapy for dyspnea.

Dr. Gomutbutra cautioned against overinterpretation of this finding, given that her study was retrospective and thus vulnerable to confounding. For example, she noted, the respiratory rate typically slows near death, so affected patients may not have received continued or increased doses of opioids.

"Our results should not dissuade people from using opioids as the first-line treatment," Dr. Gomutbutra emphasized.

Dr. Gomutbutra carried out this study after observing big differences in how dyspnea is managed in palliative care settings in the United States, compared with Thailand. While the median daily dose of opioids at baseline in the San Francisco study was 52 mg/day, a typical dose in Thailand would be 6 mg/day. And benzodiazepines are far more widely used in treating dyspnea there, she added.

She reported having no financial conflicts.

DENVER – It would seem logical to loosen the reins and manage diabetes less intensively in patients with comorbid dementia. That’s what American Geriatrics Society guidelines recommend. After all, the cognitive impairment in such patients renders them less able to manage a complicated medical regimen, and less communicative in describing complications when they arise.

But is less-stringent metabolic control in diabetic patients with comorbid dementia actually what happens in clinical practice? Mostly not, according to Dr. Paul Tatum of the University of Missouri, Columbia.

He pointed to a massive cross-sectional study involving 497,900 veterans aged 65 and older with type 2 diabetes. The combined prevalence of dementia and cognitive impairment was 13.1% in those aged 65-74, climbing to 24.2% among those aged 75 and older.

The veterans with dementia/cognitive impairment had more intensive diabetes management than did patients with neither condition. Their mean HbA_1c value was lower. More of them were on insulin (30%, compared with 24% in elderly patients without dementia or cognitive impairment). And among all subjects on insulin, 26.5% of those with dementia and 19.5% with cognitive impairment experienced hypoglycemic episodes during the 2-year study period, significantly higher rates than the 14.4% among insulin-using diabetic patients without either condition.

The unadjusted odds ratio for hypoglycemia was 2.4 in veterans with dementia and 1.7 for those with cognitive impairment. After adjustment for other comorbid conditions, demographics, nursing home stays, and other potential confounders, the adjusted odds ratios for hypoglycemia were attenuated but still significant, at 1.58 for dementia and 1.13 for cognitive impairment (J. Am. Geriatr. Soc. 2011;59:2263-72).

"We can help change that paradigm," Dr. Tatum urged at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

The American Geriatrics Society guideline on diabetes can be an ally in this regard. It states that "for frail older adults, persons with life expectancy of less than 5 years, and other in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target such as 8% is appropriate" (J. Am. Geriatr. Soc. 2003;51[5 suppl. guidelines]:S265-80).

The average life expectancy from the initial diagnosis of Alzheimer’s dementia is 4.5 years (Ann. Intern. Med. 2004;140:501-9).

The American Geriatrics Society guideline also emphasizes the importance of screening for cognitive impairment in older patients with diabetes. This point was driven home in a large, longitudinal cohort study conducted at Kaiser Permanente in Northern California.

The investigators followed 16,667 patients with type 2 diabetes, no cognitive impairment at baseline, and a mean age of 65 years. Subjects who experienced one or more acute hypoglycemic episodes severe enough to require hospitalization during 1980-2002 turned out to have an increased risk of being diagnosed with dementia in 2003-2007.

The risk was graded. Patients with a single episode of severe hypoglycemia had a fully adjusted 1.26-fold greater likelihood of later being diagnosed with dementia, compared with patients who had no episodes. Those with two episodes had a 1.8-fold increased risk, and three or more episodes placed an individual at a 1.94-fold increased risk. A similar relationship held true for emergency department visits for hypoglycemia and subsequent dementia risk. These findings were independent of HbA_1c level, diabetes comorbidities, and diabetes medications (JAMA 2009;301:1565-72).

It’s unclear whether hypoglycemia increases the risk of dementia in older type 2 diabetes patients because severe hypoglycemia can cause lasting neurologic insult, or whether severe hypoglycemia is an early marker for cognitive decline.

For busy clinicians who say they simply can’t fit in cognitive assessments in older patients, diabetic or otherwise, Dr. Tatum recommended the Mini-Cog as a 3-minute test that approximates the Mini-Mental State Exam, which takes at least twice as long. The Mini-Cog involves a three-item recall test for memory, along with a simply scored clock-drawing test.

"It’s at least a start for that busy physician who says, ‘I just don’t have time,’ " according to Dr. Tatum.

The Mini-Mental State Exam is not a great instrument for assessing executive function, which often deteriorates well before memory. He recommended the Montreal Cognitive Assessment as a useful tool for a more detailed evaluation of executive function as part of cognitive testing.

Dr. Tatum said that the American Geriatrics Society recommendations regarding diabetes and dementia are consistent with the U.K. National Institute for Health and Clinical Excellence (NICE) guidelines on dementia, which he finds quite helpful. Among the best practices highlighted in the NICE guidelines: "Adopt a palliative care approach from diagnosis until death to support the quality of life of people with dementia and to enable them to die with dignity and in the place of their choosing."

Dr. Tatum reported having no relevant financial conflicts.

DENVER – It would seem logical to loosen the reins and manage diabetes less intensively in patients with comorbid dementia. That’s what American Geriatrics Society guidelines recommend. After all, the cognitive impairment in such patients renders them less able to manage a complicated medical regimen, and less communicative in describing complications when they arise.

But is less-stringent metabolic control in diabetic patients with comorbid dementia actually what happens in clinical practice? Mostly not, according to Dr. Paul Tatum of the University of Missouri, Columbia.

He pointed to a massive cross-sectional study involving 497,900 veterans aged 65 and older with type 2 diabetes. The combined prevalence of dementia and cognitive impairment was 13.1% in those aged 65-74, climbing to 24.2% among those aged 75 and older.

The veterans with dementia/cognitive impairment had more intensive diabetes management than did patients with neither condition. Their mean HbA_1c value was lower. More of them were on insulin (30%, compared with 24% in elderly patients without dementia or cognitive impairment). And among all subjects on insulin, 26.5% of those with dementia and 19.5% with cognitive impairment experienced hypoglycemic episodes during the 2-year study period, significantly higher rates than the 14.4% among insulin-using diabetic patients without either condition.

The unadjusted odds ratio for hypoglycemia was 2.4 in veterans with dementia and 1.7 for those with cognitive impairment. After adjustment for other comorbid conditions, demographics, nursing home stays, and other potential confounders, the adjusted odds ratios for hypoglycemia were attenuated but still significant, at 1.58 for dementia and 1.13 for cognitive impairment (J. Am. Geriatr. Soc. 2011;59:2263-72).

"We can help change that paradigm," Dr. Tatum urged at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

The American Geriatrics Society guideline on diabetes can be an ally in this regard. It states that "for frail older adults, persons with life expectancy of less than 5 years, and other in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target such as 8% is appropriate" (J. Am. Geriatr. Soc. 2003;51[5 suppl. guidelines]:S265-80).

The average life expectancy from the initial diagnosis of Alzheimer’s dementia is 4.5 years (Ann. Intern. Med. 2004;140:501-9).

The American Geriatrics Society guideline also emphasizes the importance of screening for cognitive impairment in older patients with diabetes. This point was driven home in a large, longitudinal cohort study conducted at Kaiser Permanente in Northern California.

The investigators followed 16,667 patients with type 2 diabetes, no cognitive impairment at baseline, and a mean age of 65 years. Subjects who experienced one or more acute hypoglycemic episodes severe enough to require hospitalization during 1980-2002 turned out to have an increased risk of being diagnosed with dementia in 2003-2007.

The risk was graded. Patients with a single episode of severe hypoglycemia had a fully adjusted 1.26-fold greater likelihood of later being diagnosed with dementia, compared with patients who had no episodes. Those with two episodes had a 1.8-fold increased risk, and three or more episodes placed an individual at a 1.94-fold increased risk. A similar relationship held true for emergency department visits for hypoglycemia and subsequent dementia risk. These findings were independent of HbA_1c level, diabetes comorbidities, and diabetes medications (JAMA 2009;301:1565-72).

It’s unclear whether hypoglycemia increases the risk of dementia in older type 2 diabetes patients because severe hypoglycemia can cause lasting neurologic insult, or whether severe hypoglycemia is an early marker for cognitive decline.

For busy clinicians who say they simply can’t fit in cognitive assessments in older patients, diabetic or otherwise, Dr. Tatum recommended the Mini-Cog as a 3-minute test that approximates the Mini-Mental State Exam, which takes at least twice as long. The Mini-Cog involves a three-item recall test for memory, along with a simply scored clock-drawing test.

"It’s at least a start for that busy physician who says, ‘I just don’t have time,’ " according to Dr. Tatum.

The Mini-Mental State Exam is not a great instrument for assessing executive function, which often deteriorates well before memory. He recommended the Montreal Cognitive Assessment as a useful tool for a more detailed evaluation of executive function as part of cognitive testing.

Dr. Tatum said that the American Geriatrics Society recommendations regarding diabetes and dementia are consistent with the U.K. National Institute for Health and Clinical Excellence (NICE) guidelines on dementia, which he finds quite helpful. Among the best practices highlighted in the NICE guidelines: "Adopt a palliative care approach from diagnosis until death to support the quality of life of people with dementia and to enable them to die with dignity and in the place of their choosing."

Dr. Tatum reported having no relevant financial conflicts.

DENVER – It would seem logical to loosen the reins and manage diabetes less intensively in patients with comorbid dementia. That’s what American Geriatrics Society guidelines recommend. After all, the cognitive impairment in such patients renders them less able to manage a complicated medical regimen, and less communicative in describing complications when they arise.

But is less-stringent metabolic control in diabetic patients with comorbid dementia actually what happens in clinical practice? Mostly not, according to Dr. Paul Tatum of the University of Missouri, Columbia.

He pointed to a massive cross-sectional study involving 497,900 veterans aged 65 and older with type 2 diabetes. The combined prevalence of dementia and cognitive impairment was 13.1% in those aged 65-74, climbing to 24.2% among those aged 75 and older.

The veterans with dementia/cognitive impairment had more intensive diabetes management than did patients with neither condition. Their mean HbA_1c value was lower. More of them were on insulin (30%, compared with 24% in elderly patients without dementia or cognitive impairment). And among all subjects on insulin, 26.5% of those with dementia and 19.5% with cognitive impairment experienced hypoglycemic episodes during the 2-year study period, significantly higher rates than the 14.4% among insulin-using diabetic patients without either condition.

The unadjusted odds ratio for hypoglycemia was 2.4 in veterans with dementia and 1.7 for those with cognitive impairment. After adjustment for other comorbid conditions, demographics, nursing home stays, and other potential confounders, the adjusted odds ratios for hypoglycemia were attenuated but still significant, at 1.58 for dementia and 1.13 for cognitive impairment (J. Am. Geriatr. Soc. 2011;59:2263-72).

"We can help change that paradigm," Dr. Tatum urged at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

The American Geriatrics Society guideline on diabetes can be an ally in this regard. It states that "for frail older adults, persons with life expectancy of less than 5 years, and other in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target such as 8% is appropriate" (J. Am. Geriatr. Soc. 2003;51[5 suppl. guidelines]:S265-80).

The average life expectancy from the initial diagnosis of Alzheimer’s dementia is 4.5 years (Ann. Intern. Med. 2004;140:501-9).

The American Geriatrics Society guideline also emphasizes the importance of screening for cognitive impairment in older patients with diabetes. This point was driven home in a large, longitudinal cohort study conducted at Kaiser Permanente in Northern California.

The investigators followed 16,667 patients with type 2 diabetes, no cognitive impairment at baseline, and a mean age of 65 years. Subjects who experienced one or more acute hypoglycemic episodes severe enough to require hospitalization during 1980-2002 turned out to have an increased risk of being diagnosed with dementia in 2003-2007.

The risk was graded. Patients with a single episode of severe hypoglycemia had a fully adjusted 1.26-fold greater likelihood of later being diagnosed with dementia, compared with patients who had no episodes. Those with two episodes had a 1.8-fold increased risk, and three or more episodes placed an individual at a 1.94-fold increased risk. A similar relationship held true for emergency department visits for hypoglycemia and subsequent dementia risk. These findings were independent of HbA_1c level, diabetes comorbidities, and diabetes medications (JAMA 2009;301:1565-72).

It’s unclear whether hypoglycemia increases the risk of dementia in older type 2 diabetes patients because severe hypoglycemia can cause lasting neurologic insult, or whether severe hypoglycemia is an early marker for cognitive decline.

For busy clinicians who say they simply can’t fit in cognitive assessments in older patients, diabetic or otherwise, Dr. Tatum recommended the Mini-Cog as a 3-minute test that approximates the Mini-Mental State Exam, which takes at least twice as long. The Mini-Cog involves a three-item recall test for memory, along with a simply scored clock-drawing test.

"It’s at least a start for that busy physician who says, ‘I just don’t have time,’ " according to Dr. Tatum.

The Mini-Mental State Exam is not a great instrument for assessing executive function, which often deteriorates well before memory. He recommended the Montreal Cognitive Assessment as a useful tool for a more detailed evaluation of executive function as part of cognitive testing.

Dr. Tatum said that the American Geriatrics Society recommendations regarding diabetes and dementia are consistent with the U.K. National Institute for Health and Clinical Excellence (NICE) guidelines on dementia, which he finds quite helpful. Among the best practices highlighted in the NICE guidelines: "Adopt a palliative care approach from diagnosis until death to support the quality of life of people with dementia and to enable them to die with dignity and in the place of their choosing."

Dr. Tatum reported having no relevant financial conflicts.

DENVER – A structured approach to giving pain medications to agitated nursing home residents with moderate to severe dementia – regardless of their pain scores – significantly reduced their agitation and aggression in a randomized trial.

"The assumption is that their agitation was related to pain and because they had cognitive impairment they couldn’t really express [their condition]," Dr. Nathan E. Goldstein of Mount Sinai School of Medicine, New York, said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Bruce Jancin/IMNG Medical Media

He was one of several experts at the meeting who singled out the Norwegian nursing home study as one of the most important scientific advances in palliative care during the past year.

Agitation and other behavioral disturbances are common in patients with dementia. Haloperidol or another antipsychotic agent is often employed as first-line therapy, but these drugs have significant side effects, particularly in elderly demented patients who are often already on many other medications.

Investigators at the University of Bergen (Norway) opted to think outside the box. They randomized 352 subjects in 60 nursing home units within 18 nursing homes to 8 weeks of pain medication delivered according to a structured protocol or to usual care. Participants had moderate to severe dementia, with a median Mini-Mental State Examination score of 7. Cluster randomization was utilized, such that all patients in a given nursing home unit were randomized to the same study arm.

The primary study end point was agitation as measured by the Cohen-Mansfield Agitation Inventory. This instrument requires nurses to rate each of 29 behaviors on a 1-7 scale, with 1 indicating the behavior is not present and 7 meaning the behavior occurs several times per hour. A score of 39 or more is considered clinically significant agitation.

The mean agitation score in the pain medication group dropped steadily from a baseline of 56.2 to a nadir of 46.9 at week 8, when the intervention ended. The mean score as assessed by blinded evaluators rebounded to 50.3 at week 12, after 4 weeks off the intervention. Agitation scores in the control group didn’t change significantly over time.

The pain treatment group also demonstrated significant decreases in overall aggression and pain scores, but no significant changes in cognition or activities of daily living. The lower a patient’s pain score at the end of treatment, the lower the aggression score.

The stepwise pain treatment protocol was based upon American Geriatrics Society guidelines. Patients who were on no analgesics or only on low-dose acetaminophen at baseline were bumped up to full-dose oral acetaminophen at a maximum of 3 g/day. Those who were on full-dose acetaminophen or low-dose morphine at baseline received short-acting oral morphine to a maximum of 20 mg/day. Patients on low-dose buprenorphine at baseline or who were unable to swallow were placed on transdermal buprenorphine at 5-10 mcg/hour. And subjects with neuropathic pain were placed on adjuvant pregabalin at a maximum daily dose of 300 mg (BMJ 2011;343:d4065 [doi: 10.1136/bmj.d4065]).

Dr. Goldstein praised the Norwegian analgesia protocol as straightforward and easy to implement.

"It could be standardized and used routinely by nursing staff based upon their assessment. This means they wouldn’t have to wait for a physician order," he observed.

The only possible hang-up is that staff education and reorientation would definitely be required to make this work, and the Norwegian investigators did not discuss how they accomplished this.

"All patients in the intervention arm received the pain medication regardless of their pain assessment. There would need to be quite a bit of culture change in nursing homes to actually implement a protocol like this," the geriatrician noted.

Dr. Eric Widera of the University of California, San Francisco, said ample evidence indicates that pain in patients with dementia is common, underrecognized, and undertreated. The Norwegian pain medication protocol overcomes these barriers in novel fashion by treating everybody.

He stressed that the reduction in agitation and aggressive behavior wasn’t accomplished by merely sedating participants. After all, 69% of subjects in the intervention arm received only full-dose acetaminophen. And of the roughly one-quarter of patients who got opioids, only three withdrew from the study due to nausea or sedation.

The randomized trial was funded by the Norwegian Research Council, the University of Bergen, and Kavli’s Center for Aging and Dementia. Dr. Goldstein and Dr. Widera reported having no financial conflicts.

DENVER – A structured approach to giving pain medications to agitated nursing home residents with moderate to severe dementia – regardless of their pain scores – significantly reduced their agitation and aggression in a randomized trial.

"The assumption is that their agitation was related to pain and because they had cognitive impairment they couldn’t really express [their condition]," Dr. Nathan E. Goldstein of Mount Sinai School of Medicine, New York, said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Bruce Jancin/IMNG Medical Media

He was one of several experts at the meeting who singled out the Norwegian nursing home study as one of the most important scientific advances in palliative care during the past year.

Agitation and other behavioral disturbances are common in patients with dementia. Haloperidol or another antipsychotic agent is often employed as first-line therapy, but these drugs have significant side effects, particularly in elderly demented patients who are often already on many other medications.

Investigators at the University of Bergen (Norway) opted to think outside the box. They randomized 352 subjects in 60 nursing home units within 18 nursing homes to 8 weeks of pain medication delivered according to a structured protocol or to usual care. Participants had moderate to severe dementia, with a median Mini-Mental State Examination score of 7. Cluster randomization was utilized, such that all patients in a given nursing home unit were randomized to the same study arm.

The primary study end point was agitation as measured by the Cohen-Mansfield Agitation Inventory. This instrument requires nurses to rate each of 29 behaviors on a 1-7 scale, with 1 indicating the behavior is not present and 7 meaning the behavior occurs several times per hour. A score of 39 or more is considered clinically significant agitation.

The mean agitation score in the pain medication group dropped steadily from a baseline of 56.2 to a nadir of 46.9 at week 8, when the intervention ended. The mean score as assessed by blinded evaluators rebounded to 50.3 at week 12, after 4 weeks off the intervention. Agitation scores in the control group didn’t change significantly over time.

The pain treatment group also demonstrated significant decreases in overall aggression and pain scores, but no significant changes in cognition or activities of daily living. The lower a patient’s pain score at the end of treatment, the lower the aggression score.

The stepwise pain treatment protocol was based upon American Geriatrics Society guidelines. Patients who were on no analgesics or only on low-dose acetaminophen at baseline were bumped up to full-dose oral acetaminophen at a maximum of 3 g/day. Those who were on full-dose acetaminophen or low-dose morphine at baseline received short-acting oral morphine to a maximum of 20 mg/day. Patients on low-dose buprenorphine at baseline or who were unable to swallow were placed on transdermal buprenorphine at 5-10 mcg/hour. And subjects with neuropathic pain were placed on adjuvant pregabalin at a maximum daily dose of 300 mg (BMJ 2011;343:d4065 [doi: 10.1136/bmj.d4065]).

Dr. Goldstein praised the Norwegian analgesia protocol as straightforward and easy to implement.

"It could be standardized and used routinely by nursing staff based upon their assessment. This means they wouldn’t have to wait for a physician order," he observed.

The only possible hang-up is that staff education and reorientation would definitely be required to make this work, and the Norwegian investigators did not discuss how they accomplished this.

"All patients in the intervention arm received the pain medication regardless of their pain assessment. There would need to be quite a bit of culture change in nursing homes to actually implement a protocol like this," the geriatrician noted.

Dr. Eric Widera of the University of California, San Francisco, said ample evidence indicates that pain in patients with dementia is common, underrecognized, and undertreated. The Norwegian pain medication protocol overcomes these barriers in novel fashion by treating everybody.

He stressed that the reduction in agitation and aggressive behavior wasn’t accomplished by merely sedating participants. After all, 69% of subjects in the intervention arm received only full-dose acetaminophen. And of the roughly one-quarter of patients who got opioids, only three withdrew from the study due to nausea or sedation.

The randomized trial was funded by the Norwegian Research Council, the University of Bergen, and Kavli’s Center for Aging and Dementia. Dr. Goldstein and Dr. Widera reported having no financial conflicts.

DENVER – A structured approach to giving pain medications to agitated nursing home residents with moderate to severe dementia – regardless of their pain scores – significantly reduced their agitation and aggression in a randomized trial.

"The assumption is that their agitation was related to pain and because they had cognitive impairment they couldn’t really express [their condition]," Dr. Nathan E. Goldstein of Mount Sinai School of Medicine, New York, said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Bruce Jancin/IMNG Medical Media

He was one of several experts at the meeting who singled out the Norwegian nursing home study as one of the most important scientific advances in palliative care during the past year.

Agitation and other behavioral disturbances are common in patients with dementia. Haloperidol or another antipsychotic agent is often employed as first-line therapy, but these drugs have significant side effects, particularly in elderly demented patients who are often already on many other medications.

Investigators at the University of Bergen (Norway) opted to think outside the box. They randomized 352 subjects in 60 nursing home units within 18 nursing homes to 8 weeks of pain medication delivered according to a structured protocol or to usual care. Participants had moderate to severe dementia, with a median Mini-Mental State Examination score of 7. Cluster randomization was utilized, such that all patients in a given nursing home unit were randomized to the same study arm.

The primary study end point was agitation as measured by the Cohen-Mansfield Agitation Inventory. This instrument requires nurses to rate each of 29 behaviors on a 1-7 scale, with 1 indicating the behavior is not present and 7 meaning the behavior occurs several times per hour. A score of 39 or more is considered clinically significant agitation.

The mean agitation score in the pain medication group dropped steadily from a baseline of 56.2 to a nadir of 46.9 at week 8, when the intervention ended. The mean score as assessed by blinded evaluators rebounded to 50.3 at week 12, after 4 weeks off the intervention. Agitation scores in the control group didn’t change significantly over time.

The pain treatment group also demonstrated significant decreases in overall aggression and pain scores, but no significant changes in cognition or activities of daily living. The lower a patient’s pain score at the end of treatment, the lower the aggression score.

The stepwise pain treatment protocol was based upon American Geriatrics Society guidelines. Patients who were on no analgesics or only on low-dose acetaminophen at baseline were bumped up to full-dose oral acetaminophen at a maximum of 3 g/day. Those who were on full-dose acetaminophen or low-dose morphine at baseline received short-acting oral morphine to a maximum of 20 mg/day. Patients on low-dose buprenorphine at baseline or who were unable to swallow were placed on transdermal buprenorphine at 5-10 mcg/hour. And subjects with neuropathic pain were placed on adjuvant pregabalin at a maximum daily dose of 300 mg (BMJ 2011;343:d4065 [doi: 10.1136/bmj.d4065]).

Dr. Goldstein praised the Norwegian analgesia protocol as straightforward and easy to implement.

"It could be standardized and used routinely by nursing staff based upon their assessment. This means they wouldn’t have to wait for a physician order," he observed.

The only possible hang-up is that staff education and reorientation would definitely be required to make this work, and the Norwegian investigators did not discuss how they accomplished this.

"All patients in the intervention arm received the pain medication regardless of their pain assessment. There would need to be quite a bit of culture change in nursing homes to actually implement a protocol like this," the geriatrician noted.

Dr. Eric Widera of the University of California, San Francisco, said ample evidence indicates that pain in patients with dementia is common, underrecognized, and undertreated. The Norwegian pain medication protocol overcomes these barriers in novel fashion by treating everybody.

He stressed that the reduction in agitation and aggressive behavior wasn’t accomplished by merely sedating participants. After all, 69% of subjects in the intervention arm received only full-dose acetaminophen. And of the roughly one-quarter of patients who got opioids, only three withdrew from the study due to nausea or sedation.

The randomized trial was funded by the Norwegian Research Council, the University of Bergen, and Kavli’s Center for Aging and Dementia. Dr. Goldstein and Dr. Widera reported having no financial conflicts.

DENVER – Electrocutaneous direct nerve stimulation via a device that scrambles "pain" and "no pain" signals reduced pain scores in preliminary studies involving patients with refractory chemotherapy-induced peripheral neuropathy, post-herpetic neuralgia, and other forms of chronic, disabling neuropathic pain.

"What I saw in our pilot study in patients with chemotherapy-induced peripheral neuropathy was about a 60% reduction in pain, and you knew right away – within the first 3 days – whether it was going to work," said Dr. Thomas J. Smith, professor of oncology and director of palliative care at Johns Hopkins University, Baltimore.

The device, known as the MC5-A Calmare Scrambler, received Food and Drug Administration clearance in February 2009 and has a Medicare payment code. The Scrambler has been used worldwide to treat more than 4,000 patients with no reported serious side effects. Yet few American physicians have heard of the therapy because Medicare fixed the payment so low (at $44) that there is little financial incentive to adopt it, according to Dr. Smith.

"There’s not much you can do in the hospital outpatient setting for $44. That barely covers the cost of the electrodes and maybe a technician’s time," he said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine. "They set the reimbursement so low that it’s almost guaranteed not to be accepted by physicians until we get more evidence. But there are a significant number of studies in the works."

Chemotherapy-induced peripheral neuropathy affects up to 30%-40% of treated cancer patients. Dr. Smith’s pilot study involved 16 patients with refractory chemotherapy-induced peripheral neuropathy that lasted from 3 months to 8 years. The most common drugs involved were taxanes, platinum-based agents, and bortezomib (Velcade). Patients received hour-long Scrambler sessions daily on 10 consecutive working days.

Pain scores fell from a mean baseline score of 5.8 on a 10-point scale to 2.4 at the end of 10 days. Four patients had a pain score of 0, and 15 of the 16 patients had at least a 20% reduction in their pain score on day 10. There was no toxicity (J. Pain Symptom Manage. 2010;40:883-91).

"When you see that sort of effect size, you can’t believe it’s real," Dr. Smith observed. "That’s in fact what the first reviewer said of the article. He said, ‘I’ve never heard of this therapy, and I don’t believe it.’ I volunteered to give him the case reports."

Neuropathic pain reductions in the 60% range are what are seen with permanent implanted spinal cord stimulation devices, a therapy that runs about $40,000, he added.

Dr. Smith’s Scrambler pilot study results were confirmed in an Italian study involving 40 patients with refractory cancer and 33 with non–cancer-related pain. Their mean pretreatment pain scale score was 6.2, plunging to 1.6 after the 10th day of treatment, and rebounding to 2.9 at follow-up 2 weeks after the final treatment session. Again, there were no side effects (Support Care Cancer. 2012;20:405-12).

Separately, a group led by the Scrambler’s inventor, Giuseppe Marineo, Ph.D., of the University of Rome Tor Vergata, reported on a randomized but unblinded trial involving 52 patients with chronic failed back syndrome, post-herpetic neuralgia, or spinal cord stenosis. Subjects assigned to the control arm received pharmacotherapy according to European Federation of Neurological Societies guidelines (Eur. J. Neurol. 2010;17:1113-e88), while the intervention arm received 10 daily Scrambler sessions.

The pretreatment mean visual analog pain score fell in 1 month from 8.1 in a control group and 8.0 in a group treated with the Scrambler to 5.8 in controls and to 0.7 in the Scrambler group. At 2 and 3 months of follow-up, the mean pain scores were 1.4 and 2.0 points, respectively, in the Scrambler group but were still 5.7 and 5.9 points in controls. A marked and persistent reduction in allodynia was also documented in response to Scrambler therapy (J. Pain Symptom Manage. 2012;43:87-95).

With regard to post-herpetic neuralgia, Dr. Smith presented a series of 10 treated patients. Their mean pain scores dropped from 8 at baseline to less than 1 at 1 month, holding steady with a score of 2 at 2 and 3 months’ follow-up.

The Scrambler entails application of 16 ECG-like electrode pads placed along the dermatome above and below the site of pain. The Scrambler machine is designed to feed 16 different nerve potentials in rapid sequence, essentially in order to confuse a firing nerve. The electrical charge is individually adjusted to patient tolerance. It feels like a bee sting, according to Dr. Smith. The mechanism of benefit isn’t well defined as yet.

"It’s likely acting like direct spinal cord stimulation, raising the gate threshold," he continued. "My hypothesis – and the inventor’s hypothesis as well – is that the therapy resets the damaged nerves at several sites. You see some effect within the first 30 minutes, and that rapid onset suggests biochemical change. And the long-lasting nature of the pain relief suggests remodeling as well as adaptation to the pain."

Clearly, further studies need to be done – free of industry sponsorship, on larger numbers of patients, and with sham-treated controls – in order to fully assess the Scrambler therapy’s efficacy, mechanism of action, and optimal schedule.

"The Scrambler is one of several neurocutaneous direct nerve stimulation techniques that are interesting but absolutely require further testing," Dr. Smith said.

Dr. Charles L. Loprinzi, professor of oncology at the Mayo Clinic, Rochester, Minn., has started such studies, he noted. "He was at least as skeptical of this as I was, and he’s been impressed with results from this machine," Dr. Smith said, adding that Dr. Loprinzi’s research team is expected to present data later this year at the annual meeting of the American Society of Clinical Oncology.

Competitive Technologies Inc., based in Fairfield, Conn., has worldwide rights to the device. Dr. Smith reported having no financial conflicts.

DENVER – Electrocutaneous direct nerve stimulation via a device that scrambles "pain" and "no pain" signals reduced pain scores in preliminary studies involving patients with refractory chemotherapy-induced peripheral neuropathy, post-herpetic neuralgia, and other forms of chronic, disabling neuropathic pain.

"What I saw in our pilot study in patients with chemotherapy-induced peripheral neuropathy was about a 60% reduction in pain, and you knew right away – within the first 3 days – whether it was going to work," said Dr. Thomas J. Smith, professor of oncology and director of palliative care at Johns Hopkins University, Baltimore.

The device, known as the MC5-A Calmare Scrambler, received Food and Drug Administration clearance in February 2009 and has a Medicare payment code. The Scrambler has been used worldwide to treat more than 4,000 patients with no reported serious side effects. Yet few American physicians have heard of the therapy because Medicare fixed the payment so low (at $44) that there is little financial incentive to adopt it, according to Dr. Smith.

"There’s not much you can do in the hospital outpatient setting for $44. That barely covers the cost of the electrodes and maybe a technician’s time," he said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine. "They set the reimbursement so low that it’s almost guaranteed not to be accepted by physicians until we get more evidence. But there are a significant number of studies in the works."

Chemotherapy-induced peripheral neuropathy affects up to 30%-40% of treated cancer patients. Dr. Smith’s pilot study involved 16 patients with refractory chemotherapy-induced peripheral neuropathy that lasted from 3 months to 8 years. The most common drugs involved were taxanes, platinum-based agents, and bortezomib (Velcade). Patients received hour-long Scrambler sessions daily on 10 consecutive working days.

Pain scores fell from a mean baseline score of 5.8 on a 10-point scale to 2.4 at the end of 10 days. Four patients had a pain score of 0, and 15 of the 16 patients had at least a 20% reduction in their pain score on day 10. There was no toxicity (J. Pain Symptom Manage. 2010;40:883-91).

"When you see that sort of effect size, you can’t believe it’s real," Dr. Smith observed. "That’s in fact what the first reviewer said of the article. He said, ‘I’ve never heard of this therapy, and I don’t believe it.’ I volunteered to give him the case reports."

Neuropathic pain reductions in the 60% range are what are seen with permanent implanted spinal cord stimulation devices, a therapy that runs about $40,000, he added.

Dr. Smith’s Scrambler pilot study results were confirmed in an Italian study involving 40 patients with refractory cancer and 33 with non–cancer-related pain. Their mean pretreatment pain scale score was 6.2, plunging to 1.6 after the 10th day of treatment, and rebounding to 2.9 at follow-up 2 weeks after the final treatment session. Again, there were no side effects (Support Care Cancer. 2012;20:405-12).

Separately, a group led by the Scrambler’s inventor, Giuseppe Marineo, Ph.D., of the University of Rome Tor Vergata, reported on a randomized but unblinded trial involving 52 patients with chronic failed back syndrome, post-herpetic neuralgia, or spinal cord stenosis. Subjects assigned to the control arm received pharmacotherapy according to European Federation of Neurological Societies guidelines (Eur. J. Neurol. 2010;17:1113-e88), while the intervention arm received 10 daily Scrambler sessions.

The pretreatment mean visual analog pain score fell in 1 month from 8.1 in a control group and 8.0 in a group treated with the Scrambler to 5.8 in controls and to 0.7 in the Scrambler group. At 2 and 3 months of follow-up, the mean pain scores were 1.4 and 2.0 points, respectively, in the Scrambler group but were still 5.7 and 5.9 points in controls. A marked and persistent reduction in allodynia was also documented in response to Scrambler therapy (J. Pain Symptom Manage. 2012;43:87-95).

With regard to post-herpetic neuralgia, Dr. Smith presented a series of 10 treated patients. Their mean pain scores dropped from 8 at baseline to less than 1 at 1 month, holding steady with a score of 2 at 2 and 3 months’ follow-up.

The Scrambler entails application of 16 ECG-like electrode pads placed along the dermatome above and below the site of pain. The Scrambler machine is designed to feed 16 different nerve potentials in rapid sequence, essentially in order to confuse a firing nerve. The electrical charge is individually adjusted to patient tolerance. It feels like a bee sting, according to Dr. Smith. The mechanism of benefit isn’t well defined as yet.

"It’s likely acting like direct spinal cord stimulation, raising the gate threshold," he continued. "My hypothesis – and the inventor’s hypothesis as well – is that the therapy resets the damaged nerves at several sites. You see some effect within the first 30 minutes, and that rapid onset suggests biochemical change. And the long-lasting nature of the pain relief suggests remodeling as well as adaptation to the pain."

Clearly, further studies need to be done – free of industry sponsorship, on larger numbers of patients, and with sham-treated controls – in order to fully assess the Scrambler therapy’s efficacy, mechanism of action, and optimal schedule.

"The Scrambler is one of several neurocutaneous direct nerve stimulation techniques that are interesting but absolutely require further testing," Dr. Smith said.

Dr. Charles L. Loprinzi, professor of oncology at the Mayo Clinic, Rochester, Minn., has started such studies, he noted. "He was at least as skeptical of this as I was, and he’s been impressed with results from this machine," Dr. Smith said, adding that Dr. Loprinzi’s research team is expected to present data later this year at the annual meeting of the American Society of Clinical Oncology.

Competitive Technologies Inc., based in Fairfield, Conn., has worldwide rights to the device. Dr. Smith reported having no financial conflicts.

DENVER – Electrocutaneous direct nerve stimulation via a device that scrambles "pain" and "no pain" signals reduced pain scores in preliminary studies involving patients with refractory chemotherapy-induced peripheral neuropathy, post-herpetic neuralgia, and other forms of chronic, disabling neuropathic pain.

"What I saw in our pilot study in patients with chemotherapy-induced peripheral neuropathy was about a 60% reduction in pain, and you knew right away – within the first 3 days – whether it was going to work," said Dr. Thomas J. Smith, professor of oncology and director of palliative care at Johns Hopkins University, Baltimore.

The device, known as the MC5-A Calmare Scrambler, received Food and Drug Administration clearance in February 2009 and has a Medicare payment code. The Scrambler has been used worldwide to treat more than 4,000 patients with no reported serious side effects. Yet few American physicians have heard of the therapy because Medicare fixed the payment so low (at $44) that there is little financial incentive to adopt it, according to Dr. Smith.

"There’s not much you can do in the hospital outpatient setting for $44. That barely covers the cost of the electrodes and maybe a technician’s time," he said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine. "They set the reimbursement so low that it’s almost guaranteed not to be accepted by physicians until we get more evidence. But there are a significant number of studies in the works."

Chemotherapy-induced peripheral neuropathy affects up to 30%-40% of treated cancer patients. Dr. Smith’s pilot study involved 16 patients with refractory chemotherapy-induced peripheral neuropathy that lasted from 3 months to 8 years. The most common drugs involved were taxanes, platinum-based agents, and bortezomib (Velcade). Patients received hour-long Scrambler sessions daily on 10 consecutive working days.

Pain scores fell from a mean baseline score of 5.8 on a 10-point scale to 2.4 at the end of 10 days. Four patients had a pain score of 0, and 15 of the 16 patients had at least a 20% reduction in their pain score on day 10. There was no toxicity (J. Pain Symptom Manage. 2010;40:883-91).

"When you see that sort of effect size, you can’t believe it’s real," Dr. Smith observed. "That’s in fact what the first reviewer said of the article. He said, ‘I’ve never heard of this therapy, and I don’t believe it.’ I volunteered to give him the case reports."

Neuropathic pain reductions in the 60% range are what are seen with permanent implanted spinal cord stimulation devices, a therapy that runs about $40,000, he added.

Dr. Smith’s Scrambler pilot study results were confirmed in an Italian study involving 40 patients with refractory cancer and 33 with non–cancer-related pain. Their mean pretreatment pain scale score was 6.2, plunging to 1.6 after the 10th day of treatment, and rebounding to 2.9 at follow-up 2 weeks after the final treatment session. Again, there were no side effects (Support Care Cancer. 2012;20:405-12).

Separately, a group led by the Scrambler’s inventor, Giuseppe Marineo, Ph.D., of the University of Rome Tor Vergata, reported on a randomized but unblinded trial involving 52 patients with chronic failed back syndrome, post-herpetic neuralgia, or spinal cord stenosis. Subjects assigned to the control arm received pharmacotherapy according to European Federation of Neurological Societies guidelines (Eur. J. Neurol. 2010;17:1113-e88), while the intervention arm received 10 daily Scrambler sessions.

The pretreatment mean visual analog pain score fell in 1 month from 8.1 in a control group and 8.0 in a group treated with the Scrambler to 5.8 in controls and to 0.7 in the Scrambler group. At 2 and 3 months of follow-up, the mean pain scores were 1.4 and 2.0 points, respectively, in the Scrambler group but were still 5.7 and 5.9 points in controls. A marked and persistent reduction in allodynia was also documented in response to Scrambler therapy (J. Pain Symptom Manage. 2012;43:87-95).

With regard to post-herpetic neuralgia, Dr. Smith presented a series of 10 treated patients. Their mean pain scores dropped from 8 at baseline to less than 1 at 1 month, holding steady with a score of 2 at 2 and 3 months’ follow-up.

The Scrambler entails application of 16 ECG-like electrode pads placed along the dermatome above and below the site of pain. The Scrambler machine is designed to feed 16 different nerve potentials in rapid sequence, essentially in order to confuse a firing nerve. The electrical charge is individually adjusted to patient tolerance. It feels like a bee sting, according to Dr. Smith. The mechanism of benefit isn’t well defined as yet.

"It’s likely acting like direct spinal cord stimulation, raising the gate threshold," he continued. "My hypothesis – and the inventor’s hypothesis as well – is that the therapy resets the damaged nerves at several sites. You see some effect within the first 30 minutes, and that rapid onset suggests biochemical change. And the long-lasting nature of the pain relief suggests remodeling as well as adaptation to the pain."

Clearly, further studies need to be done – free of industry sponsorship, on larger numbers of patients, and with sham-treated controls – in order to fully assess the Scrambler therapy’s efficacy, mechanism of action, and optimal schedule.

"The Scrambler is one of several neurocutaneous direct nerve stimulation techniques that are interesting but absolutely require further testing," Dr. Smith said.

Dr. Charles L. Loprinzi, professor of oncology at the Mayo Clinic, Rochester, Minn., has started such studies, he noted. "He was at least as skeptical of this as I was, and he’s been impressed with results from this machine," Dr. Smith said, adding that Dr. Loprinzi’s research team is expected to present data later this year at the annual meeting of the American Society of Clinical Oncology.

Competitive Technologies Inc., based in Fairfield, Conn., has worldwide rights to the device. Dr. Smith reported having no financial conflicts.

DENVER – Playing a musical instrument, singing, or simply listening to recorded music resulted in significant reduction in anxiety scores in patients with cancer, according to a Cochrane Database systematic review and meta-analysis.

The various music interventions offered by medical staff or trained music therapists also achieved significant improvements in the secondary end points of pain, mood, and quality of life scores, according to the review by investigators in the department of creative arts therapies at Drexel University in Philadelphia.

Photo Bruce Jancin/IMNG Medical Media

At the annual meeting of the American Academy of Hospice and Palliative Care Medicine, Dr. Wendy Anderson highlighted the Cochrane review findings as particularly on-point for her colleagues in oncology and palliative medicine.

"In palliative care we’re always trying to make the best of a difficult situation, and sometimes the best way to do this is through a nonpharmacologic intervention, even though it means doing something outside of our comfort zone," commented Dr. Anderson of the University of California, San Francisco.

Prior studies of music interventions in patients with cancer have been quite small. The Cochrane meta-analysis was designed to yield stronger, more definitive conclusions by incorporating those small studies which were sufficiently similar to combine.

The Cochrane report included 30 randomized clinical trials in seven countries with a total of 1,891 participating patients of all ages and with all types of cancer. In all, 13 trials involved the use of trained music therapists, while in the other 17 in the intervention consisted of listening to various genres of prerecorded music selected by the patients. Sessions were typically 30-45 minutes in length. The number of sessions varied widely from study to study. Subjects in the control arm received usual care or in some studies listened to white noise through headphones.

Sixteen randomized trials assessed anxiety. Collectively they showed that music interventions achieved statistically and clinically meaningful reductions in anxiety scores, with median to large effect sizes. For example, mean scores on the State Trait Anxiety Inventory fell by a mean of 11.2 units following the various music interventions while remaining unchanged in controls.

Similarly, the reduction in pain scores and improvements in structured measures of mood and quality of life in participants in the music interventions as compared to controls were also in the moderate to large range.

"Those are important outcomes in our patients with cancer," Dr. Anderson observed.

Music therapy is an established profession. Trained music therapists can perform a detailed patient evaluation and provide a tailored music experience. Although the Drexel researchers sought to learn whether the more elaborate, active participation music interventions provided by trained music therapists result in bigger improvements in psychologic and physical outcomes than the simpler music-listening interventions offered by medical staff, the investigators found that the research database wasn’t sufficiently large to draw any conclusions on that score (Cochrane Database Syst. Rev. 2011 [doi:10.1002/14651858.CD006911]).

The Cochrane group self-rated the quality of evidence on which the music intervention meta-analysis was based as low because these were nonblinded randomized trials. Patient awareness of whether they received a music intervention may have biased the results.

"Usually a low quality of evidence would, I think, make us reluctant to admit some innovations into our practices, but what’s interesting here is there’s a low potential for harm from music, and the patients feel the music improves their symptoms. That may be enough for us to implement music interventions in our practices," Dr. Anderson concluded.

The Cochrane review was funded by the State of Pennsylvania Formula Fund.

Dr. Anderson reported having no financial conflicts.

DENVER – Playing a musical instrument, singing, or simply listening to recorded music resulted in significant reduction in anxiety scores in patients with cancer, according to a Cochrane Database systematic review and meta-analysis.

The various music interventions offered by medical staff or trained music therapists also achieved significant improvements in the secondary end points of pain, mood, and quality of life scores, according to the review by investigators in the department of creative arts therapies at Drexel University in Philadelphia.

Photo Bruce Jancin/IMNG Medical Media

At the annual meeting of the American Academy of Hospice and Palliative Care Medicine, Dr. Wendy Anderson highlighted the Cochrane review findings as particularly on-point for her colleagues in oncology and palliative medicine.

"In palliative care we’re always trying to make the best of a difficult situation, and sometimes the best way to do this is through a nonpharmacologic intervention, even though it means doing something outside of our comfort zone," commented Dr. Anderson of the University of California, San Francisco.

Prior studies of music interventions in patients with cancer have been quite small. The Cochrane meta-analysis was designed to yield stronger, more definitive conclusions by incorporating those small studies which were sufficiently similar to combine.

The Cochrane report included 30 randomized clinical trials in seven countries with a total of 1,891 participating patients of all ages and with all types of cancer. In all, 13 trials involved the use of trained music therapists, while in the other 17 in the intervention consisted of listening to various genres of prerecorded music selected by the patients. Sessions were typically 30-45 minutes in length. The number of sessions varied widely from study to study. Subjects in the control arm received usual care or in some studies listened to white noise through headphones.

Sixteen randomized trials assessed anxiety. Collectively they showed that music interventions achieved statistically and clinically meaningful reductions in anxiety scores, with median to large effect sizes. For example, mean scores on the State Trait Anxiety Inventory fell by a mean of 11.2 units following the various music interventions while remaining unchanged in controls.

Similarly, the reduction in pain scores and improvements in structured measures of mood and quality of life in participants in the music interventions as compared to controls were also in the moderate to large range.

"Those are important outcomes in our patients with cancer," Dr. Anderson observed.

Music therapy is an established profession. Trained music therapists can perform a detailed patient evaluation and provide a tailored music experience. Although the Drexel researchers sought to learn whether the more elaborate, active participation music interventions provided by trained music therapists result in bigger improvements in psychologic and physical outcomes than the simpler music-listening interventions offered by medical staff, the investigators found that the research database wasn’t sufficiently large to draw any conclusions on that score (Cochrane Database Syst. Rev. 2011 [doi:10.1002/14651858.CD006911]).

The Cochrane group self-rated the quality of evidence on which the music intervention meta-analysis was based as low because these were nonblinded randomized trials. Patient awareness of whether they received a music intervention may have biased the results.

"Usually a low quality of evidence would, I think, make us reluctant to admit some innovations into our practices, but what’s interesting here is there’s a low potential for harm from music, and the patients feel the music improves their symptoms. That may be enough for us to implement music interventions in our practices," Dr. Anderson concluded.

The Cochrane review was funded by the State of Pennsylvania Formula Fund.

Dr. Anderson reported having no financial conflicts.

DENVER – Playing a musical instrument, singing, or simply listening to recorded music resulted in significant reduction in anxiety scores in patients with cancer, according to a Cochrane Database systematic review and meta-analysis.

The various music interventions offered by medical staff or trained music therapists also achieved significant improvements in the secondary end points of pain, mood, and quality of life scores, according to the review by investigators in the department of creative arts therapies at Drexel University in Philadelphia.

Photo Bruce Jancin/IMNG Medical Media

At the annual meeting of the American Academy of Hospice and Palliative Care Medicine, Dr. Wendy Anderson highlighted the Cochrane review findings as particularly on-point for her colleagues in oncology and palliative medicine.

"In palliative care we’re always trying to make the best of a difficult situation, and sometimes the best way to do this is through a nonpharmacologic intervention, even though it means doing something outside of our comfort zone," commented Dr. Anderson of the University of California, San Francisco.

Prior studies of music interventions in patients with cancer have been quite small. The Cochrane meta-analysis was designed to yield stronger, more definitive conclusions by incorporating those small studies which were sufficiently similar to combine.

The Cochrane report included 30 randomized clinical trials in seven countries with a total of 1,891 participating patients of all ages and with all types of cancer. In all, 13 trials involved the use of trained music therapists, while in the other 17 in the intervention consisted of listening to various genres of prerecorded music selected by the patients. Sessions were typically 30-45 minutes in length. The number of sessions varied widely from study to study. Subjects in the control arm received usual care or in some studies listened to white noise through headphones.

Sixteen randomized trials assessed anxiety. Collectively they showed that music interventions achieved statistically and clinically meaningful reductions in anxiety scores, with median to large effect sizes. For example, mean scores on the State Trait Anxiety Inventory fell by a mean of 11.2 units following the various music interventions while remaining unchanged in controls.

Similarly, the reduction in pain scores and improvements in structured measures of mood and quality of life in participants in the music interventions as compared to controls were also in the moderate to large range.

"Those are important outcomes in our patients with cancer," Dr. Anderson observed.

Music therapy is an established profession. Trained music therapists can perform a detailed patient evaluation and provide a tailored music experience. Although the Drexel researchers sought to learn whether the more elaborate, active participation music interventions provided by trained music therapists result in bigger improvements in psychologic and physical outcomes than the simpler music-listening interventions offered by medical staff, the investigators found that the research database wasn’t sufficiently large to draw any conclusions on that score (Cochrane Database Syst. Rev. 2011 [doi:10.1002/14651858.CD006911]).

The Cochrane group self-rated the quality of evidence on which the music intervention meta-analysis was based as low because these were nonblinded randomized trials. Patient awareness of whether they received a music intervention may have biased the results.

"Usually a low quality of evidence would, I think, make us reluctant to admit some innovations into our practices, but what’s interesting here is there’s a low potential for harm from music, and the patients feel the music improves their symptoms. That may be enough for us to implement music interventions in our practices," Dr. Anderson concluded.

The Cochrane review was funded by the State of Pennsylvania Formula Fund.

Dr. Anderson reported having no financial conflicts.