2. What therapies appear most effective for the treatment of vasovagal syncope?
3. Why the difficulty in studying and reporting treatment therapies?
4. Have more invasive therapies been suggested for the treatment of vasovagal syncope?
1. 血管迷走神经性晕厥的治疗措施有哪些？
2. 血管迷走神经性晕厥的治疗措施中哪种方法最有效？
3. 为什么关于血管迷走神经性晕厥的研究和报道的治疗很难？
4. 有没有侵入性治疗推荐用于血管迷走神经性晕厥的治疗？
1.血管迷走神经性晕厥的治疗措施有哪些？
因为血管迷走神经性晕厥的确切作用机制尚不清楚，因此对其的治疗更大程度上是建立在经验和尚未证实的假设的基础上[1]。因为存在与具有预测性的前驱症状相关的一些少见情况的出现，因此常常建议对于怀疑有血管迷走神经性晕厥者采取留观措施。在手术室，患者应该处于斜卧位并给与监护。此类患者常前负荷减少，如没有禁忌症，可以静脉输液。很少有建议取消手术，除非出现明显和延长的血流动力学变化。
对于大多数情况，虽然有很多措施被推荐使用，包括增加前负荷（通过饮食疗法）、血管收缩药、抗胆碱能药物、负性心脏肌力药、中枢神经系统药物和机械装置（如起搏器），但是这些治疗措施的大多数是通过观察、非盲和/或随机试验获得的[2]。近期有综述发现，只有3种治疗药物（见下）接受了前瞻性、随机、安慰剂对照的临床研究[1]。
2.血管迷走神经性晕厥的治疗措施中哪种方法最有效？
虽然α-激动剂（甲氧胺、苯福林）、sertotonin重吸收阻滞剂（帕罗西汀，中枢神经系统药物）和抗胆碱能药（丙吡胺，抗心律失常药）是通过随机、对照试验进行了研究，但是只有甲氧胺[2]和帕罗西汀[3]在控制症状方面最有效。但是这些研究均是通过小样本进行的，因此在治疗上是否有明确的效果尚缺乏有效的说服力。
3.为什么关于血管迷走神经性晕厥的研究和治疗的报道很难？
对于这些患者研究的困难（以及分析一些研究结果）包括以下方法的差异：
●诊断
●患者选择标准
●样本大小和统计学
●研究终点
●研究持续时间
●药理学目标
4.有哪些侵入性治疗推荐用于血管迷走神经性晕厥的治疗？
采用永久性起搏器治疗血管迷走神经性晕厥得到推广和支持，但没有对照研究[5]。在试图更简单的证明起搏器在治疗上的优点时，北美起搏器研究组[6]对此类患者进行了研究，入选标准为至少发作6次晕厥且倾斜台试验阳性，安装永久起搏器，随机的设定起搏器为（或非）“rate-drop”特性。这种特定的起搏特性，在心率出现急剧下降达到设定目标时，可提供高速起搏，即心率速降反应。在出现晕厥复发时，终止试验的有54名患者（284名中），因为使用起搏器（rate-drop特性）而出现晕厥的几率明显降低（相对危险降低85.4%，95%可信区间59.7%～94.7%；P=0.000022）。有趣的是，研究因为样本量小和缺乏标准的医学治疗[7]而遭到质疑，缺乏真正的对照组（起搏器被植入到所有患者以预防出现心动过缓，但只有一半采用了rate-drop特性）。后续的研究对此进行了改正。
What therapies have been advocated for the treatment of vasovagal syncope?
As specific triggers for vasovagal syncope have not been clearly identified and may be variable, treatment is largely empirical and based on putative (but unproven) mechanisms (1). For infrequent episodes associated with a warning prodrome, counseling and observation have been suggested as a worthy regimen. In the perioperative setting, the patient should be placed (if not already so) in a recumbent position and monitored. As decreased preload is believed at least partially responsible, intravenous fluids, if not contraindicated, should be given. Few recommend the cancellation of a surgical case, unless significant and prolonged hemodynamic aberrations are noted.
For more frequent episodes, although a number of agents have been suggested, including increasing preload (through salt and diet modifications), vasoconstrictors, anticholinergic agents, negative cardiac inotropes, central nervous system agents, and mechanical devices (i.e. pacemakers), the majority of these therapies are supported by observational, unblinded, and/or uncontrolled studies (2). A recent review found only 3 agents (see below) which have undergone prospective, randomized, placebo-controlled clinical trials (1).
What therapies appear most effective for the treatment of vasovagal syncope?
Although randomized and controlled trials have been performed for alpha-agonists (midodrine, etilefrine), sertotonin reuptake blockers (paroxetine) and an anticholinergic (disopyramide), significantly more symptom free days were noted only with midodrine (2) and paroxetine (3). These studies however, were in small samples of patients and thus remain underpowered to make significant conclusions on these therapies.
Why the difficulty in studying and reporting treatment therapies?
The difficulty in studying this patient population (and analyzing the results of any studies) include differences in the use of:
• diagnosis (especially with an entity of variable expression and incidence)
• patient selection criteria
• size and statistical power
• study end points
• study duration
• pharmacologic targets
Have more invasive therapies been suggested for the treatment of vasovagal syncope?
The use of permanent pacing for the treatment of vasovagal syncope has been advocated and supported by an anecdotal series (5). In attempting to more robustly demonstrate the benefits of pacing therapy in this population of patients, the North American Pacemaker Study enrolled patients with at least 6 lifetime episodes of syncope and positive tilt table testing results, to receive a permanent pacemaker randomly assigned to include (or not to include) a “rate-drop” feature. This specific pacer feature provided high-rate pacing if a predetermined precipitous drop in heart rate occurred (rate-drop response). With the main outcome being the time to first recurrence of syncope, the study was terminated at the first formal interim analysis of 54 (of 284 planned) patients, due to the marked reduction in the postrandomization risk of syncope in pacemaker (with rate drop feature) patients (relative risk reduction 85.4%, 95% confidence interval 59.7% to 94.7%; p=0.000022). While interesting, the study has been criticized for the small patient population, lack of a true control group (pacemakers were implanted in all patients to prevent bradycardia in all, but only half with the rate drop feature), and the lack of standardized medical therapy (7). A second trial is now under way.
Question Author: Lawrence Tsen, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1. Fenton AM, Hammill SC, Rea RF, Low PA, Shen WK. Vasovagal Syncope. Ann Intern Med. 2000;133(9):714-725.
2. Calkins H. Pharmacologic approaches to therapy for vasovagal syncope. Am J Cardiol 1999;84(8A):20Q-25Q
3. Ward CR, Gray JC, Gilroy JJ, Kenny RA. Midodrine: a role in the management of neurocardiogenic syncope. Heart 1998;79(1):45-9
4. Di Girolamo E, Di Iorio C, Sabatini P, et al. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 1999;33(5):1227-30.
5. Petersen ME, Chamberlain-Webber R, Fitzpatrick AP, et al. Permanent pacing for cardioinhibitory malignant vasovagal syndrome. Br Heart J. 1994;71(3):274-81.
6. Connolly SJ, Sheldon R, Roberts RS, Gent M. The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cardiol 1999;33(1):16-20.
7. Benditt DG. Cardiac pacing for prevention of vasovagal syncope. J Am Coll Cardiol 1999;33(1):21-3.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
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