Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study

Opioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjects with untreated OSA have increased sensitivity to opioids compared with subjects without OSA, or with OSA treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP).

This was a single-centre, prospective cohort study in subjects without OSA (n=20), with untreated OSA (n=33), or with treated OSA (n=21). OSA diagnosis was verified using type III (in-home) polysomnography. Subjects received a stepped-dose remifentanil infusion (target effect-site concentrations of 0.5, 1, 2, 3, 4 ng ml^-1). Primary outcome was miosis (pupil area fractional change), the most sensitive opioid effect. Secondary outcomes were ventilatory rate, end-expired CO₂, sedation, and thermal analgesia.

There were no differences in miosis between untreated OSA subjects (mean=0.51, 95% confidence interval [CI] 0.41-0.61) and subjects without OSA (mean=0.49, 95% CI 0.36-0.62) (mean difference=0.02, 95% CI -0.18 to 0.22); between treated OSA subjects (mean=0.56, 95% CI 0.43-0.68) and subjects without OSA (difference=0.07, 95% CI -0.16 to 0.29); or between untreated OSA and treated OSA (difference=-0.05, 95% CI -0.25 to 0.16). There were no significant differences between subjects without OSA, untreated OSA, and treated OSA in ventilatory rate, end-expired CO₂, sedation, or thermal analgesia responses to remifentanil. There was no relationship between OSA severity and magnitude of opioid effects.

Neither obstructive sleep apnoea nor obstructive sleep apnoea treatment affected sensitivity to the miotic, sedative, analgesic, or respiratory depressant effects of the opioid remifentanil in awake adults. These results challenge conventional notions of opioid effects in obstructive sleep apnoea.

NCT02898792 (clinicaltrials.gov).