Identifying opioid outliers in OSA

Thursday, 19 May 2016

Physiological testing can help identify patients with obstructive sleep apnoea who are at the highest risk of respiratory depression when using opioid analgesics, Associate Professor David Wang from the Woolcock Institute has told ATS delegates.

He told the meeting that prescription opioid use, and associated deaths, continue to increase worldwide.

“Deaths are nearly always due to respiratory arrest and often occur during sleep when breathing is primarily regulated by automatic neurochemical control,” he said.

“Some guidelines suggest that OSA is worsened by opioid use, but the theory has not been backed by any randomised controlled trials.

“There is also large inter-individual variability in opioid metabolism, making certain patients more vulnerable.”

Professor Wang and his colleagues recruited 60 males with OSA and, in a double-blind randomised crossover design, administered a single dose of slow release oral morphine (40 mg MS Contin) or placebo at 5:30 pm.

They had awake ventilatory chemoreflex tests at 9 pm, near the peak concentration of the opioid, and then overnight polysomnography.

On average the morphine dose did not modify sleep time with oxygen saturation <90% (T90) or the apnoea hypopnoea index (AHI).

However, there was a large variability between individuals in the response to morphine: the change in T90 ranged from an increase of 94 minutes to a reduction of 53 minutes.

In the 45 patients who had severe OSA, lower CO2 ventilatory recruitment threshold (VRT) in the awake chemoreflex test correlated with worsening of T90, AHI, oxygen desaturation index and arousal index with morphine use. It could, potentially, be used to identify those at highest risk without necessarily requiring a sleep study.

“Morphine has complex effects on sleep in OSA patients,” Professor Wang said. “In some cases it can improve the stability of breathing which counters the respiratory depression caused by opioids, but in other cases it increases the risk.

“The aim is to identify patients who are the outliers who have marked changes in response to an opioid. Younger age and lower VRT seem to be predictors of worsening OSA,” he added.

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