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The influence of opioids and non-opioid central nervous system active medications on central sleep apnea: a case-control study.

STUDY OBJECTIVES
Opioids are known to contribute to central sleep apnea (CSA), but the influence of non-opioid central nervous system active medications (CNSAM) on CSA remains unclear. In light of the hypothesized impact of non-opioid CNSAM on respiration, we examined the relationships between the use of opioids only, non-opioid CNSAM alone, and their combination with CSA.


METHODS
Among all adults who underwent polysomnography testing at the University of Michigan's Sleep laboratory between 2013-2018 (N=10,606), we identified 212 CSA cases and randomly selected 300 controls. Participants were classified into four groups based on their medication use: opioids alone, non-opioid CNSAM only, their combination, and a reference group, including those who did not use any of these medications. We defined CSA as a binary outcome and as a continuous variable using central apnea index (CAI) data. Logistic and linear regression were used to examine associations between medication use, CSA diagnosis, and CAI.


RESULTS
Study participants included 58% men, and mean age was 50 (±14 SD) years. Nearly half of study participants did not use opioids or non-opioid CNSAM, 6% used opioids alone, 27% non-opioid CNSAM alone, and 16% used a combination of these medications. In adjusted analyses, opioids only users had nearly 2-fold increase in CSA odds, while those who used a combination of opioids and non-opioid CNSAM had 5-fold higher odds of CSA relative to the reference group. In contrast, use of non-opioid CNSAM alone had protective associations with CSA.


CONCLUSIONS
This report showed increased odds of CSA, particularly among patients with sleep complaints who were prescribed opioids in combination with non-opioid CNSAM compared with those who did not use any of these medications.