Improvement of Idiopathic Central Sleep Apnea with Zolpidem

Abstract

Scientific inveStigAtionSStudy Objectives: We hypothesized that the non-benzodiazepine hypnotic zolpidem would improve idiopathic central sleep apnea (ICSA) by enhancing sleep stability, resulting in fewer arousals, which in turn would lessen oscillation in arterial CO 2 and produce a decrease in central apnea/hypopnea events. Zolpidem might also decrease ventilatory control responsiveness during arousals, thereby reducing hyperpnea, hypocapnia, and subsequent apneas. Patients and Study Design: This was a case series in which all patients with ICSA seen in the Henry Ford Sleep Disorders Clinic from January 1, 2004, to December 31, 2006, were offered zolpidem, as well as other therapeutic options of acetazolamide, continuous positive airway pressure (CPAP), bilevel pressure support, or assist control ventilatory support. Those 20 patients who chose zolpidem were prescribed 10 mg at bedtime Measurements and Results: After a therapeutic trial averaging 9 weeks, a follow-up polysomnogram showed that the overall apnea/ hypopnea index (AHI) and central AHI (CAHI) decreased, 30.0 ± 18.1 (SD) to 13.5 ± 13.3 (p = 0.001), and 26.0 ± 17.2 to 7.1 ± 11.8 (p < 0.001), respectively, without an overall change in obstructive AHI or arterial oxygen saturation. The total number of arousals per hour decreased with zolpidem use, 24.0 ± 11.6 to 15.1 ± 7.7 (p < 0.001), leading to a significant improvement in sleep efficiency. There was a positive correlation between the decrease in CAHI and the arousal index. Consistent with the hypnotic effect of zolpidem, sleep latency decreased, stage 1 sleep percentage decreased, and stage 2 percentage increased (all significant), without changes in stage 3-4 or REM sleep. Excessive daytime sleepiness, measured by the Epworth Sleepiness Scale (ESS) decreased from 13 ± 5 to 8 ± 5 (p < 0.001). Three patients experienced a significant increase in obstructive events. Conclusion:In an open-label trial, ICSA patients studied experienced a decrease in central apnea/hypopneas with zolpidem. They also had improved sleep continuity and decreased subjective daytime sleepiness, without a worsening of oxygenation or obstructive events in the majority of patients. However, in the absence of a randomized, controlled trial, zolpidem cannot be recommended for treatment of ICSA at this time.

The effects of zolpidem in obstructive sleep apnea – An open‐label pilot study

“…Consistent with the current findings of reduced central apnea frequency, 10 mg of zolpidem has been shown to reduce central apnea (Quadri, Drake, & Hudgel, 2009). This effect may be mediated via decreased respiratory control instability (lower loop gain), but this requires further investigation.…”

Role of common hypnotics on the phenotypic causes of obstructive sleep apnoea: paradoxical effects of zolpidem

“…The paradoxical increase in genioglossus muscle responsiveness with zolpidem is intriguing. Improvements in central sleep apnoea and daytime sleepiness have been observed with zolpidem [41]. These effects are likely mediated via sleep promotion and arousal prevention rather than pharyngeal dilator muscle activation.…”

Primary central sleep apnea and anesthesia: a retrospective case series

“…In two small nonrandomized trials, acetazolamide decreased the central apnea and central hypopnea indices and decreased daytime sleepiness. 23,27 In a small nonrandomized trial with zolpidem 22 and a small, randomized cross-over trial with triazolam, 21 these medications decreased the central apnea indices and attenuated PCSA symptoms. Nevertheless, concerns that these medications could worsen respiratory depression and hypoxemia (e.g., from other underlying sleep disorders such as OSA or a concomitant pulmonary condition) have resulted in recommendations that they be used as second-line agents only and in patients under close clinical observation.…”

“…Nevertheless, concerns that these medications could worsen respiratory depression and hypoxemia (e.g., from other underlying sleep disorders such as OSA or a concomitant pulmonary condition) have resulted in recommendations that they be used as second-line agents only and in patients under close clinical observation. 6,22 In this cohort, zolpidem was used in only one patient, and this patient used it long term. There is no evidence regarding de novo use of pharmacologic sleep aids in such patients, and the use of these aids in the postoperative period should be done cautiously.…”

“…All patients had a manual review of their medical records and sleep evaluation, including clinical notes, medications, polysomnographic findings, and laboratory and other test results to confirm eligibility and assign the CSA syndrome subtype. Severity of CSA was determined by the apneahypopnea index as mild (\ 15 eventsÁhr -1 ), moderate, [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] or severe (C 30). 1 Patients were designated as having PCSA if no known cause was found for CSA at the time of diagnosis after comprehensive review of the medical record by a sleep medicine clinician (M.P.M.).…”