Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: A comparison between midazolam, diazepam, and lorazepam
Short-term effects of intravenous benzodiazepines on autonomic neurocardiac regulation in humans: A comparison between midazolam, diazepam, and lorazepam
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DOI：
10.1097/00003246-200205000-00008
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发表时间：
2002-05-01
影响因子：
8.8
通讯作者：
Mueck-Weymann, M
中科院分区：
文献类型：
--
作者：
Agelink, MW;Majewski, TB;Mueck-Weymann, M
目的：评估静脉应用安定，劳拉西泮，咪达唑仑对自主神经心脏调节的影响评估标准化测量的心率variable.Design：前瞻性，随机临床研究。设置：大学教学hospital.Patients：45例患者，谁接受了胃镜检查，随机分配到静脉前驱用药咪达唑仑（5毫克），地西泮（10毫克），或劳拉西泮（4毫克）。6名受试者拒绝注射，并作为非术前用药对照。在术前用药前、用药后15分钟和30分钟连续记录5分钟静息心率变异性。7例苯二氮卓类药物治疗的患者接受静脉注射氟马西尼（0.5 mg）。测量和主要结果：平均剂量为咪达唑仑0.07 mg/kg，地西泮0.13 mg/kg，劳拉西泮0.06 mg/kg。静脉注射苯二氮卓类药物后15分钟，我们发现与基线相比，所有三个苯二氮卓类药物治疗亚组的静息心率增加，迷走神经张力降低。对实验过程中心率变异性指数变化的多变量分析（协变量年龄）显示，咪达唑仑或地西泮与未术前用药受试者相比，绝对高频功率显著降低。此外，咪达唑仑治疗受试者的相对高频功率降低幅度显著大于未治疗受试者，也大于劳拉西泮或地西泮治疗受试者。即使在苯二氮卓类药物应用后30分钟，迷走神经张力仍较基线降低，然而，静息心率降至基线水平。氟马西尼给药后，高频功率的增加与静息心率的相应降低呈线性相关。苯二氮卓类药物可能通过与γ-氨基丁酸（A）-受体氯离子通道复合物相互作用影响人体自主神经心脏调节。研究结果表明，静脉注射咪达唑仑，地西泮，劳拉西泮影响人体自主神经心脏调节的双相方式。首先，它们会导致中枢迷走神经张力降低，其次，它们可能会直接降低心脏起搏点。氟马西尼完全消除了苯二氮卓类药物的自主神经心脏调节作用。
Objectives: To evaluate the effects of intravenously applied diazepam, lorazepam, and midazolam on autonomic neurocardiac regulation assessed by standardized measurements of heart rate variability.Design: Prospective, randomized clinical study.Setting: University teaching hospital.Patients: Forty-five patients, who underwent a gastroscopy, were randomly assigned to intravenous premedication with midazolam (5 mg), diazepam (10 mg), or lorazepam (4 mg). Six subjects refused an injection and served as nonpremedicated controls.Interventions., Serial recordings of the 5-min resting heart rate variability were obtained before and 15 and 30 mins after premedication. Seven benzodiazepine-treated patients received intravenous flumazenil (0.5 mg).Measurements and Main Results: The average doses applied were 0.07 mg/kg for midazolam, 0.13 mg/kg for diazepam, and 0.06 mg/kg for lorazepam. Fifteen minutes after intravenous benzodiazepines were administered, we found an increase in resting heart rate and a reduction of vagal tone compared with baseline in all three benzodiazepine-treated subgroups. Multivariate analysis (covariate age) of the changes in heart rate variability indices over the experimental course revealed a significant reduction in absolute high-frequency power with midazolam or diazepam compared with nonpremedicated subjects. Moreover, midazolam-treated subjects showed a significantly larger reduction in relative high-frequency power not only compared with nontreated subjects, but also compared with lorazepam- or diazepam-treated subjects. Vagal tone remained reduced compared with baseline even 30 mins after benzodiazepine application, however, the resting heart rate decreased toward baseline levels. After flumazenil administration, there was a linear correlation between an increase in high-frequency power and a corresponding decrease in resting heart rate.Conclusions. Benzodiazepines can influence autonomic neurocardiac regulation in man, probably through their interaction with the gamma-aminobutyric acid(A)-receptor chloride ion channel complex. The pattern of findings suggests that intravenous midazolam, diazepam, and lorazepam influence human autonomic neurocardiac regulation in a biphasic way. First, they cause a reduction of central vagal tone, and second, they may decrease the cardiac pacemaker directly. Flumazenil completely abolished the autonomic neurocardiac regulation effects of benzodiazepines.