阻塞性睡眠呼吸暂停患者在前往高原地区时会出现心脏复极紊乱：乙酰唑胺的随机、安慰剂对照试验。
Patients with Obstructive Sleep Apnea Have Cardiac Repolarization Disturbances when Travelling to Altitude: Randomized, Placebo-Controlled Trial of Acetazolamide.
作者信息
Latshang Tsogyal Daniela, Kaufmann Barbara, Nussbaumer-Ochsner Yvonne, Ulrich Silvia, Furian Michael, Kohler Malcolm, Thurnheer Robert, Saguner Ardan Muammer, Duru Firat, Bloch Konrad Ernst
机构信息
Sleep Disorders Center and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
出版信息
Sleep. 2016 Sep 1;39(9):1631-7. doi: 10.5665/sleep.6080.
STUDY OBJECTIVES
Obstructive sleep apnea (OSA) promotes myocardial electrical instability and may predispose to nocturnal sudden cardiac death. We evaluated whether hypobaric hypoxia during altitude travel further impairs cardiac repolarization in patients with OSA, and whether this is prevented by acetazolamide, a drug known to improve oxygenation and central sleep apnea at altitude.
METHODS
Thirty-nine OSA patients living < 600 m, discontinued continuous positive airway pressure therapy during studies at 490 m and during two sojourns of 3 days at altitude (2 days at 1860 m, 1 day at 2590 m). During one altitude sojourn, patients took acetazolamide, during the other placebo, or vice versa, according to a randomized, double-blind crossover design. Twelve-lead electrocardiography and pulse oximetry (SpO2) were recorded during nocturnal polysomnography. Heart rate corrected mean QT intervals during the entire night (meanQTc) and during 1 min of the night with the longest meanQTc (maxQTc) were determined.
RESULTS
At 490 m the median nocturnal SpO2 was 93%, medians of meanQTc and maxQTc were 420 ms and 478 ms. At 2590 m, on placebo, SpO2 was lower (85%), and meanQTc and maxQTc were prolonged to 430 ms and 510 ms (P < 0.02 vs. 490 m, all corresponding comparisons). At 2590 m on acetazolamide, median SpO2 was increased to 88% (P < 0.05 vs. placebo), meanQTc was reduced to 427 ms (P < 0.05 vs. placebo), whereas maxQTc remained increased at 502 ms (P = ns vs. placebo).
CONCLUSIONS
At 2590 m OSA patients experienced cardiac repolarization disturbances in association with hypoxemia. Prolongation of meanQTc at altitude was prevented and hypoxemia was improved by acetazolamide, whereas maxQTc remained increased suggesting imperfect protection from repolarization disturbances.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov ID: NTC-00714740. URL: www.clinicaltrials.gov.
研究目的
阻塞性睡眠呼吸暂停（OSA）会促进心肌电不稳定，并可能导致夜间心源性猝死。我们评估了高原旅行期间的低压缺氧是否会进一步损害OSA患者的心脏复极，以及乙酰唑胺（一种已知可改善高原地区氧合和中枢性睡眠呼吸暂停的药物）是否能预防这种情况。
方法
39名居住在海拔<600米的OSA患者，在490米的研究期间以及在高原地区进行的两次为期3天的停留（在1860米停留2天，在2590米停留1天）期间停止持续气道正压通气治疗。根据随机、双盲交叉设计，在一次高原停留期间，患者服用乙酰唑胺，在另一次停留期间服用安慰剂，反之亦然。在夜间多导睡眠图期间记录12导联心电图和脉搏血氧饱和度（SpO2）。确定整个夜间的心率校正平均QT间期（meanQTc）以及夜间平均QTc最长的1分钟内的平均QT间期（maxQTc）。
结果
在490米处，夜间SpO2的中位数为93%，meanQTc和maxQTc的中位数分别为420毫秒和478毫秒。在2590米处，服用安慰剂时，SpO2较低（85%），meanQTc和maxQTc延长至430毫秒和510毫秒（与490米处相比，所有相应比较P<0.02）。在2590米处服用乙酰唑胺时，SpO2中位数增加到88%（与安慰剂相比P<0.05），meanQTc降至427毫秒（与安慰剂相比P<0.05），而maxQTc仍增加至502毫秒（与安慰剂相比P=无显著性差异）。
结论
在2590米处，OSA患者出现与低氧血症相关的心脏复极紊乱。乙酰唑胺可预防高原地区meanQTc延长并改善低氧血症，而maxQTc仍增加，提示对复极紊乱的保护不完善。
临床试验注册
ClinicalTrials.gov标识符：NTC-00714740。网址：www.clinicaltrials.gov。
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