Off-label use of opioids can provide relief in refractory dyspnea

CHICAGO – Low doses of opioids titrated based on patient ratings of breathing difficulty are effective in managing refractory dyspnea, according to Dr. Donald Mahler.

Because refractory dyspnea is a neuromechanical dissociation, treating more than the pulmonary system can be beneficial, Dr. Mahler said at the annual meeting of the American College of Chest Physicians. "We have targets for the lungs to relieve dyspnea, but we may also have potential targets in the central nervous system that may also provide benefit."

Referring to published data from two randomized controlled studies about the effect of naloxone on blocking opioid signals in patients with COPD who reported breathlessness and perceived "unpleasantness" of dyspnea after exercise, Dr. Mahler said that endogenous opioids modulate the perception of dyspnea; exogenous opioids could therefore do the same (Eur. Respir. J. 2009;33:771-7 and COPD 2011;8:160-6).

Opioid receptors in the limbic system have 100 times greater binding density in the bronchioles and alveolar walls. "That may play a role when thinking about a nebulized approach," said Dr. Mahler of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. The number of side effects, including constipation, was lower with this approach, he added.

Because opioids are known to decrease respiratory drive, there is a "presumable" effect on corollary discharge, which can lead to less perception of breathlessness, according to Dr. Mahler. Narcotics’ dulling effect on the perception of pain and anxiety might also contribute. "Maybe by relieving symptoms, there’s less anxiety as a result," said Dr. Mahler.

He addressed concerns over the "double effect" whereby opioids used to lessen symptoms might actually hasten death in a patient with refractory dyspnea, saying the studies "don’t really support that." Dr. Mahler cited data indicating that higher doses of benzodiazepines used in withdrawal of life-sustaining treatment were not associated with a decreased time from withdrawal of life support to death (CHEST 2004;126:286-93).

As for respiratory depression, Dr. Mahler said he had reviewed 11 studies and found only one report of any change in oxygen saturation after opioid administration.

In deciding whether a patient should be given opioid therapy, Dr. Mahler said physicians should be sure that standard therapies are inadequate and that the risk/benefit ratio favors trial treatment. Establishing treatment goals and confirming that the patient and/or the patient’s family are on board with a trial of opioid treatment is key, he added.

To determine titration, physicians should ask the patients to rate their breathing difficulty. "This is a critical part of the assessment," said Dr. Mahler, noting that the level of breathlessness determines the dose and duration of action.

If dyspnea is episodic, he said, "it doesn’t make sense to administer a long-acting opioid" and so an immediate-release or short-acting form should be considered. If it’s constant, sustained release may be effective, he said.

Dr. Mahler, who said his presentation was related to the off-label use of morphine only, said that the important thing is to "titrate the opioid to achieve the lower effective dose based on the patient’s rating of the dyspnea." Adding an anxiolytic could also be considered, he said. "It’s pretty straightforward that you should discontinue the opioid if there is an unsatisfactory response or if there is an adverse effect."

Dr. Mahler disclosed ties with numerous pharmaceutical manufacturers and other medical organizations, including GlaxoSmithKline, Novartis, and Sunovion.

[email protected]

CHICAGO – Low doses of opioids titrated based on patient ratings of breathing difficulty are effective in managing refractory dyspnea, according to Dr. Donald Mahler.

Because refractory dyspnea is a neuromechanical dissociation, treating more than the pulmonary system can be beneficial, Dr. Mahler said at the annual meeting of the American College of Chest Physicians. "We have targets for the lungs to relieve dyspnea, but we may also have potential targets in the central nervous system that may also provide benefit."

Referring to published data from two randomized controlled studies about the effect of naloxone on blocking opioid signals in patients with COPD who reported breathlessness and perceived "unpleasantness" of dyspnea after exercise, Dr. Mahler said that endogenous opioids modulate the perception of dyspnea; exogenous opioids could therefore do the same (Eur. Respir. J. 2009;33:771-7 and COPD 2011;8:160-6).

Opioid receptors in the limbic system have 100 times greater binding density in the bronchioles and alveolar walls. "That may play a role when thinking about a nebulized approach," said Dr. Mahler of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. The number of side effects, including constipation, was lower with this approach, he added.

Because opioids are known to decrease respiratory drive, there is a "presumable" effect on corollary discharge, which can lead to less perception of breathlessness, according to Dr. Mahler. Narcotics’ dulling effect on the perception of pain and anxiety might also contribute. "Maybe by relieving symptoms, there’s less anxiety as a result," said Dr. Mahler.

He addressed concerns over the "double effect" whereby opioids used to lessen symptoms might actually hasten death in a patient with refractory dyspnea, saying the studies "don’t really support that." Dr. Mahler cited data indicating that higher doses of benzodiazepines used in withdrawal of life-sustaining treatment were not associated with a decreased time from withdrawal of life support to death (CHEST 2004;126:286-93).

As for respiratory depression, Dr. Mahler said he had reviewed 11 studies and found only one report of any change in oxygen saturation after opioid administration.

In deciding whether a patient should be given opioid therapy, Dr. Mahler said physicians should be sure that standard therapies are inadequate and that the risk/benefit ratio favors trial treatment. Establishing treatment goals and confirming that the patient and/or the patient’s family are on board with a trial of opioid treatment is key, he added.

To determine titration, physicians should ask the patients to rate their breathing difficulty. "This is a critical part of the assessment," said Dr. Mahler, noting that the level of breathlessness determines the dose and duration of action.

If dyspnea is episodic, he said, "it doesn’t make sense to administer a long-acting opioid" and so an immediate-release or short-acting form should be considered. If it’s constant, sustained release may be effective, he said.

Dr. Mahler, who said his presentation was related to the off-label use of morphine only, said that the important thing is to "titrate the opioid to achieve the lower effective dose based on the patient’s rating of the dyspnea." Adding an anxiolytic could also be considered, he said. "It’s pretty straightforward that you should discontinue the opioid if there is an unsatisfactory response or if there is an adverse effect."

Dr. Mahler disclosed ties with numerous pharmaceutical manufacturers and other medical organizations, including GlaxoSmithKline, Novartis, and Sunovion.

[email protected]

CHICAGO – Low doses of opioids titrated based on patient ratings of breathing difficulty are effective in managing refractory dyspnea, according to Dr. Donald Mahler.

Because refractory dyspnea is a neuromechanical dissociation, treating more than the pulmonary system can be beneficial, Dr. Mahler said at the annual meeting of the American College of Chest Physicians. "We have targets for the lungs to relieve dyspnea, but we may also have potential targets in the central nervous system that may also provide benefit."

Referring to published data from two randomized controlled studies about the effect of naloxone on blocking opioid signals in patients with COPD who reported breathlessness and perceived "unpleasantness" of dyspnea after exercise, Dr. Mahler said that endogenous opioids modulate the perception of dyspnea; exogenous opioids could therefore do the same (Eur. Respir. J. 2009;33:771-7 and COPD 2011;8:160-6).

Opioid receptors in the limbic system have 100 times greater binding density in the bronchioles and alveolar walls. "That may play a role when thinking about a nebulized approach," said Dr. Mahler of Dartmouth-Hitchcock Medical Center, Lebanon, N.H. The number of side effects, including constipation, was lower with this approach, he added.

Because opioids are known to decrease respiratory drive, there is a "presumable" effect on corollary discharge, which can lead to less perception of breathlessness, according to Dr. Mahler. Narcotics’ dulling effect on the perception of pain and anxiety might also contribute. "Maybe by relieving symptoms, there’s less anxiety as a result," said Dr. Mahler.

He addressed concerns over the "double effect" whereby opioids used to lessen symptoms might actually hasten death in a patient with refractory dyspnea, saying the studies "don’t really support that." Dr. Mahler cited data indicating that higher doses of benzodiazepines used in withdrawal of life-sustaining treatment were not associated with a decreased time from withdrawal of life support to death (CHEST 2004;126:286-93).

As for respiratory depression, Dr. Mahler said he had reviewed 11 studies and found only one report of any change in oxygen saturation after opioid administration.

In deciding whether a patient should be given opioid therapy, Dr. Mahler said physicians should be sure that standard therapies are inadequate and that the risk/benefit ratio favors trial treatment. Establishing treatment goals and confirming that the patient and/or the patient’s family are on board with a trial of opioid treatment is key, he added.

To determine titration, physicians should ask the patients to rate their breathing difficulty. "This is a critical part of the assessment," said Dr. Mahler, noting that the level of breathlessness determines the dose and duration of action.

If dyspnea is episodic, he said, "it doesn’t make sense to administer a long-acting opioid" and so an immediate-release or short-acting form should be considered. If it’s constant, sustained release may be effective, he said.

Dr. Mahler, who said his presentation was related to the off-label use of morphine only, said that the important thing is to "titrate the opioid to achieve the lower effective dose based on the patient’s rating of the dyspnea." Adding an anxiolytic could also be considered, he said. "It’s pretty straightforward that you should discontinue the opioid if there is an unsatisfactory response or if there is an adverse effect."

Dr. Mahler disclosed ties with numerous pharmaceutical manufacturers and other medical organizations, including GlaxoSmithKline, Novartis, and Sunovion.

[email protected]