Fort Hamilton Hospital, Fort Hamilton, OH, USA.
J Clin Sleep Med. 2009 Apr 15;5(2):122-9.
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 CO2 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.
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.
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.
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.
我们假设非苯二氮䓬类催眠药唑吡坦可通过增强睡眠稳定性来改善特发性中枢性睡眠呼吸暂停（ICSA），从而减少觉醒次数，进而减少动脉二氧化碳的波动，并减少中枢性呼吸暂停/低通气事件。唑吡坦还可能降低觉醒时的呼吸控制反应性，从而减少过度通气、低碳酸血症和随后的呼吸暂停。
这是一项病例系列研究，纳入 2004 年 1 月 1 日至 2006 年 12 月 31 日期间在亨利福特睡眠障碍诊所就诊的所有 ICSA 患者，他们均接受唑吡坦治疗，以及乙酰唑胺、持续气道正压通气（CPAP）、双水平压力支持或辅助控制通气支持等其他治疗选择。选择唑吡坦的 20 例患者每晚睡前服用 10mg。
经过平均 9 周的治疗试验后，随访多导睡眠图显示，总的呼吸暂停/低通气指数（AHI）和中枢性 AHI（CAHI）分别从 30.0±18.1（标准差）降至 13.5±13.3（p=0.001）和 26.0±17.2 降至 7.1±11.8（p<0.001），而阻塞性 AHI 或动脉血氧饱和度无总体变化。使用唑吡坦后，每小时的总觉醒次数减少，从 24.0±11.6 降至 15.1±7.7（p<0.001），从而显著提高睡眠效率。CAHI 的下降与觉醒指数呈正相关。与唑吡坦的催眠作用一致，睡眠潜伏期缩短，1 期睡眠百分比降低，2 期百分比增加（均有统计学意义），而 3-4 期或 REM 睡眠无变化。Epworth 嗜睡量表（ESS）评估的日间嗜睡程度从 13±5 降至 8±5（p<0.001）。3 例患者出现阻塞性事件显著增加。
在开放性试验中，研究中的 ICSA 患者使用唑吡坦后，中枢性呼吸暂停/低通气减少。他们的睡眠连续性也得到改善，白天嗜睡程度减轻，而大多数患者的氧合或阻塞性事件无恶化。然而，由于缺乏随机对照试验，目前不能推荐唑吡坦治疗 ICSA。
