Opioid-Induced Respiratory Depression, Central Sleep Apnea Remain a Major Clinical Challenge

PALM SPRINGS, CA — Patients on chronic opioid treatment should be assessed for sleep-disordered breathing, as central apnea can result in a higher risk of morbidity and mortality, according to a presentation during the 2012 American Academy of Pain Medicine Annual Meeting.

In the hospital setting, incidence of opiate-induced respiratory depression is 10–15%, representing a major clinical challenge for anesthesiologists, pain medicine specialists, and intensivists. Balancing the trade-off between analgesia and sedation and respiratory depression is critically important because risk of central sleep apnea due to sleep-disordered breathing — another result of opioid usage in patients with chronic pain — can be increased with no physiological “cue,” said Lynn R. Webster, MD, Lifetree Clinical Research, Salt Lake City, UT. Case studies have found that even a single dose of an opioid can push patients into the severe category of central sleep apnea that would otherwise go undetected unless the patient was being monitored.

Risk factors for sleep apnea with chronic opioid therapy include the opioid dose, concomitant use of benzodiazepines, and age, he said, with body mass index having an inverse relationship. “Every opioid for every individual is unique; start low and titrate up,” he said.

Now that “we know where respiratory rhythm is generated,” the task remains to develop agents that can increase effectiveness of an opioid without interfering with its underlying analgesic effects, said John J. Greer, PhD, of the University of Alberta, Edmonton, Canada.

One new class of agents being explored is the ampakines, which have been shown to have respiratory stimulant effects on the brain's pre-Bötzinger complex. Specifically, an intravenous formulation of the ampakine CX717 is being developed; ideally, it could be used in conjunction with opioid drugs to reduce respiratory depression without affecting analgesia. Ampakines may also find a use in apnea of prematurity, Dr. Greer concluded.