Eggleston, Reid

Abstract Introduction Tizanidine is an alpha-2 receptor adrenergic agonist employed for treatment of musculoskeletal pain and muscle spasticity. Drowsiness, xerostomia, and, less frequently, sleep disturbance are notable side effects. Central sleep apnea (CSA) occurs in patients taking other alpha-2 receptor agonists such as clonidine but the frequency of CSA among users of tizanidine is less well-known. Rarer still is the presence of central apneic episodes during wakefulness in patients without heart failure who have an intact brainstem and are not taking opioids or benzodiazepines. We report a case of a patient with central apneic episodes during wakefulness in the setting of tizanidine use. Report of case A 60-year-old white male was referred to our sleep center for sleep apnea. He was previously diagnosed with severe obstructive sleep apnea (apnea-hypopnea index of 104 events per hour) but was not adherent to continuous positive airway pressure (CPAP) due to a previous head injury which made use of CPAP straps intolerably painful. Thus, he had undergone a modified uvulopalatopharyngoplasty 3 months prior to evaluation. Despite UPPP he continued to have excessive daytime sleepiness. A repeat polysomnogram revealed frequent central apneic episodes during periods of wakefulness that did not persist after sleep onset. The patient had taken his nightly tizanidine 8 mg prior to testing. Echocardiogram prior to testing showed mild diastolic dysfunction and brain magnetic resonance imaging was unremarkable. A polysomnogram was repeated 1 month later, this time with tizanidine held for 1 week prior to testing. Wake-onset central apneic episodes had resolved without any other changes in medication or health status. Conclusion Certain medications such as opioids, benzodiazepines, and baclofen are known to induce CSA. However, to the best of our knowledge this is the first case of a commonly prescribed alpha-2 agonist implicated in the development of wake-onset central apneic episodes. More study is needed to elucidate the impact of tizanidine on ventilatory function in the wake and sleep states and whether similar effects may occur among other centrally acting medications. Support (if any)