Medication-Induced Central Sleep Apnea: A Unifying Concept

Shahrokh Javaheri; W J Randerath; M Safwan Badr; Sogol Javaheri

doi:10.1093/sleep/zsae038

Medication-Induced Central Sleep Apnea: A Unifying Concept

Sleep. 2024 Feb 9:zsae038. doi: 10.1093/sleep/zsae038. Online ahead of print.

Authors

Shahrokh Javaheri¹, W J Randerath², M Safwan Badr³, Sogol Javaheri⁴

Affiliations

¹ Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, OH, Adjunct Professor of Medicine, Division of Cardiology, The Ohio State University, Columbus, Ohio, and Emeritus Professor of Medicine, Division of Pulmonary and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio , USA.
² Professor and Head Physician, Institute of Pneumology, University of Cologne, Bethanien Hospital, Solingen, Germany, USA.
³ Professor and Chair, Department of Internal Medicine, Wayne State University School of Medicine Detroit, Staff Physician, John D. Dingell VA Medical Center, MI, USA.
⁴ Assistant Professor of Sleep Medicine, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

PMID: 38334297
DOI: 10.1093/sleep/zsae038

Abstract

Medication-induced central sleep apnea (CSA) is one of the 8 categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioids medications including sodium oxybate, baclofen, valproic acid, gabapentin and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.

Keywords: baclofen; central sleep apnea; gabapentin; opioids; respiratory control; ticagrelor; valproic acid.