The widely-held belief that opioids worsen OSA severity has been debunked in a randomised controlled trial by Australian researchers.

Professional guidelines currently advise that opioids are relatively contraindicated in people with OSA due to their respiratory depression effects, but clinicians from NSW say this recommendation is based on weak and indirect evidence of effects on sleep disordered breathing.

Researchers at the NHMRC Centre for Sleep and Chronobiology and the Woolcock Institute, Sydney say their trial findings, published in Thorax, suggest that opioids only worsen OSA in a small proportion of people with specific clinical phenotypes and genotypes.

In a study of 60 male patients with OSA, they showed that the commonly used dose of morphine (40mg MS Contin) did not worsen severity of the condition overall.

In the randomised crossover trial involving two visits to a sleep clinic, there was no difference in sleep time with oxygen saturation below 90% (T90) or in apnoea-hypopnoea index (AHI) between participants after morphine and placebo.

Despite the overall lack of difference there were large inter-individual responses, with some patients paradoxically showing improvements in OSA with morphine and others showing worsening.

Of the 60 men in the trial, 12 showed no change in T90, 13 had a small improvement (<5% total sleep time), 30 had minor worsening, three had improvements in T90 of >5% of TST and two had worsening of >5% TST.

Notably, the patients who showed more pronounced positive and responses had differences in baseline chemoreflex sensitivity (CO2 response threshold) and also OPRM1 genotypes for OSA.

The researchers said their findings contradicted previous results from small trials that may have been confounded by  being in the perioperative setting and using higher disease of opioids as well as other anaesthetic agents and sedatives.

“In conclusion, as the first major RCT in this field, we found that 40 mg oral slow release morphine did not worsen OSA in men, challenging traditional thinking that OSA will be generally worsened with opioid use,” they wrote.

And while the wide variation in responses meant they could not conclude that this dose of opioid is safe for all patients with OSA, “our findings in opioid response phenotype and genotype may pave the way for a precision medicine approach to develop strategies to avoid excess complications and deaths in those patients most vulnerable to opioid-related harm,” they said.