When sleep stops: subtherapeutic buprenorphine-naloxone and severe central sleep apnea

Central sleep apnea (CSA) is a recognized complication of opioid use, yet its occurrence in individuals using subtherapeutic and/or inconsistent doses of buprenorphine-naloxone remain underreported. This case highlights the development of severe CSA in a patient with opioid use disorder despite only partial adherence to a subtherapeutic maintenance dose of buprenorphine-naloxone. Additionally, our case report demonstrates the efficacy during the ASV titration study and subsequent intolerance to ASV and full face/ hybrid mask in treating coexisting CSA and obstructive sleep apnea (OSA) and discusses phrenic nerve stimulation (PNS) as an alternative therapy in cases of ASV non-compliance. A 43-year-old male with a history of opioid use disorder was inconsistently using a self-reduced subtherapeutic maintenance dose of buprenorphine-naloxone of 2 mg/0.5 mg daily when he presented with excessive daytime sleepiness and witnessed apneas. The diagnostic portion of the split-night polysomnogram (PSG) revealed severe OSA with an obstructive AHI of 44.1 events/hour of sleep and severe CSA with a central apnea index of 67.6 events/hour of sleep, with approximately 60% of all events being central events. Standard therapies, including CPAP and BPAP, failed to control either his central or obstructive sleep apnea. While ASV achieved optimal resolution of both OSA and CSA during the ASV titration study, the patient later developed intolerance to both the ASV pressure settings and the mask interface despite adjustment of the pressure settings and switching from full face mask to hybrid mask respectively. This led to poor adherence, recurrence of symptoms, and eventual consideration for PNS as an alternative treatment approach. Our case highlights the risk of CSA in patients who are using subtherapeutic or inconsistent doses of buprenorphine-naloxone. It also highlights that ASV can be highly effective in managing opioid-related CSA, but intolerance to pressure or mask interface may limit long-term use. In such cases, PNS represents a promising alternative. Clinicians should maintain a high index of suspicion for CSA in patients with opioid use disorder, regardless of buprenorphine-naloxone dose or adherence pattern.