Patients with severe pain who use opioid-based medications may suffer sleep apnea and its complications, including greater likelihood of death, according to a study in Pain Medicine, the journal of the American Academy of Pain Medicine.

The research shows that three-fourths of patients on chronic opioid therapy have some degree of sleep apnea, said Dr. Lynn R. Webster of Lifetree Clinical Research and Pain Clinic in Salt Lake City, who is lead author on the study. They also found a "direct dose-response relationship" between central sleep apnea and methadone used with benzodiazepines.

Webster said sleep apnea may be an underlying factor in the increase in unintentional overdose deaths linked to opioid pain medications, especially methadone.

The research also showed that as many as one-third of patients being treated with opioids had a component of sleep apnea called central sleep apnea, rather than the more common obstructive sleep apnea. Central apnea is when the body makes no effort to breathe, the part of the brain responsible for respiration malfunctioning. It's also harder to spot, because some of the telltale hints with obstructive sleep apnea, such as being overweight and loud snoring, are absent.

"With central sleep apnea, we don't know what the indicators are," Webster said.

Anyone with sleep apnea is at greater risk of heart disease and stroke. And Webster said it also has been shown that people with sleep apnea have more intense pain, "which makes pain medicine less effective, which leads to more pain medicine, which leads to more sleep apnea, which increases the risk of heart disease and stroke. ... It's a cycle. There are a lot of different factors that are interrelated that can contribute to other problems."

While someone on moderate to high-dose opioid medications may have significant problems with sleep apnea, Webster said, not all of them will. It is important that patients are assessed to spot cases of sleep apnea and treat it.

"If you can't modify the sleep apnea and make sure it's safe, you may have to provide less medication," he said. However, he noted the research is not a call to reduce use of opioids, but rather to understand the risks they may bring and deal with them.

There are a number of treatments for patients with sleep apnea, including a continuous positive airway pressure (CPAP) mask, use of oxygen and others. "The best treatment for this we do not know yet. You can't necessarily use the treatments used for other populations for this problem, because the mechanisms are different for them."

Central sleep apnea in the past has been most strongly linked to heart failure or neurologic disorders like stroke. In these cases it's presumably a combination of chronic pain and the opioid treatment prescribed for it.

The first step is making sure that those who treat patients in chronic severe pain are aware of how common the problem with sleep apnea is, Webster said. He's working to develop protocols looking at the most appropriate treatment for the degrees of both obstructive and central sleep apnea. Treating the sleep apnea may reduce the amount of pain someone experiences and thus the amount of medication needed to cope with it.

"The recent flurry of news reports of deaths associated with methadone use and the synergy of opioids and benzodiazepines in causing respiratory depression highlight the importance of Dr. Webster's research," said Dr. Rollin M. Gallagher, editor of Pain Medicine. "Clearly we need more studies of these mechanisms as well as ways of identifying those at risk. Doctors and patients who are considering opioid medication for pain control must balance this risk against the potential for improved quality of life."

The researchers examined sleep lab data on 140 patients who were taking around-the-clock opioid therapy for chronic pain. All patients had been on the opioid therapy at least six months, with stable dosing for at least four weeks.


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