Opioid use and sleep apnoea

Opioid prescriptions in the USA have fallen over the past decade or so. But the numbers are still enormous. In 2020, US pharmacies filled more than 140 million prescriptions for opioids, enough to medicate 43% of the population. Some 10 million Americans are thought to misuse opioids, a category of drug that includes heroin, methadone, and morphine. The opioid epidemic, which has its roots in irresponsible prescription practices, shows no sign of abating. Communities across the USA have been devastated, especially in the rural Appalachians and midwest. More than half a million people have died from opioid overdoses in the country since the late 1990s. Deaths are mostly related to fentanyl, a synthetic opioid 50-times more potent than heroin. The risk of overdose is enhanced if an opioid is taken with other central nervous system depressants, such as benzodiazepines; the combination has a synergetic effect on suppressing the respiratory drive. In September, 2022, the US Government announced it would provide nearly US$1·5 billion for the State Opioid Response grant. Lynn Webster, Senior Fellow at the Center for US Policy, was one of the first researchers to establish the link between sleep apnoea and opioid use. “People thought that central sleep apnoea [CSA] was only associated with conditions such as cardiac disease and neurologic disorders”, he said. “We published a paper in 2008, which documented the relationship between the incidence and severity of CSA and prescription opioids.” Researchers have yet to reach a consensus on prevalence of sleep apnoea in opioid users, however. “We know that sleep apnoea is widespread in this patient population, but we do not have exact figures”, explained Webster. Studies have tended to focus on small groups, and clinicians do not routinely assess their patients' sleep habits. “We still do not have any criteria with which to screen for CSA in patients you are prescribing opioids to”, said Webster. “You cannot go on body-mass index or neck circumference. The only confirmed link is with dosage—the higher the dose, the greater the risk of sleep apnoea.” Much else is also unclear, including the mechanism by which opioids trigger or exacerbate sleep apnoea. More is known about the relationship between CSA and opioids than the relationship between obstructive sleep apnoea (OSA) and opioids, though Webster noted that individuals who already have OSA, or are borderline cases, can be pushed to more severe states by opioid use. The optimal treatment for sleep apnoea in patients taking opioids has yet to be determined. Continuous positive airway pressure does not appear to work, but there are indications that adaptive servo-ventilation might be effective. Webster speculated that sleep apnoea might help explain why patients who are prescribed opioids mostly die at night. “The normal respiratory system does not have the same drive at night”, he said. “Respiration rate is lower, as are tidal volumes. Opioids depress the respiratory drive, so patients who are on the precipice of experiencing a fatal lack of ventilation might not be able to overcome the opioid-associated sleep apnoea.” But it is uncertain whether individuals who are using opioids illicitly are at the same risk. There is not a large difference between a lethal dose of fentanyl and one that provides the sought-after high, so overdoses usually occur soon after the drug has been taken. Moreover, people prescribed opioids for pain relief are more likely to take them just before going to bed, so as to help them sleep. Individuals who use opioids recreationally, or because of addiction issues, tend to take them during the day, so by the time they fall asleep, the depressive effects of the drugs on the respiratory system are less pronounced. Winfried Randerath is Chief Physician and Medical Director at the Clinic for Pneumology and Allergology at the Center for Sleep Medicine and Respiratory Care (Hospital Bethanien, Solingen, Germany). He stressed the importance of only prescribing opioids when necessary and monitoring patients' sleep patterns, particularly when their dosage reaches a particular threshold. Randerath pointed out that prescription rates for opioids in European nations, such as Germany, are far lower than in the USA. “Reluctance in prescriptions habits might be responsible for lower numbers of overdoses and deaths [in Europe]. On the other hand, we must not withhold using opioids for pain or for patients in severe end-stage disease—eg, for chronic obstructive pulmonary disease or lung fibrosis”, he told The Lancet Respiratory Medicine. Randerath added that patients prescribed opioids for legitimate medical reasons do not typically overuse the drugs. “We should not be blaming opioids for most of the problems we see with overuse and misuse, we should be blaming mis-prescription”, he concluded.