Groeben H, Foster W M, Brown R H
Department of Anesthesiology and Environmental Health Services, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):885-8. doi: 10.1164/ajrccm.154.4.8887580.
Stimulation of the airways of asthmatic individuals causes severe bronchoconstriction, which is in part neurally mediated via the vagus nerve. Local anesthetics are commonly administered to prevent this reflex-induced bronchoconstriction. Therefore, in a double-blind, placebo-controlled prospective study, we tested the effectiveness of oral mexiletine and intravenous lidocaine at blocking histamine-induced reflex bronchoconstriction. Fifteen subjects with mild asthma were selected (for whom the provocative concentration of histamine aerosol causing a 20% decrease in FEV1 (PC20) was less than 18 mg/ml). Subsequently, the subjects were pretreated with oral mexiletine, intravenous lidocaine, or placebo, and the histamine challenges were repeated. The baseline PC20 for histamine was 8.8 +/- 1.8 mg/ml. Mexiletine and lidocaine at therapeutic serum concentrations blocked reflex bronchoconstriction. Oral mexiletine increased the PC20 to 21.1 +/- 5.0 mg/ml (serum concentration: 0.7 +/- 0.05 microg/ml). Likewise, intravenous lidocaine increased the PC20 to 24.5 +/- 4.9 mg/ml (serum concentration: 2.6 +/- 0.15 microg/ml). Oral mexiletine and intravenous lidocaine block reflex-induced bronchoconstriction. Furthermore, mexiletine may have additional airway benefits when selected for the treatment of dysrhythmias or chronic pain in patients with coexisting lung diseases.
刺激哮喘患者的气道会导致严重的支气管收缩，这部分是通过迷走神经进行神经介导的。通常会使用局部麻醉剂来预防这种反射性诱导的支气管收缩。因此，在一项双盲、安慰剂对照的前瞻性研究中，我们测试了口服美西律和静脉注射利多卡因对组胺诱导的反射性支气管收缩的阻断效果。选取了15名轻度哮喘患者（其引起第一秒用力呼气容积（FEV1）下降20%的组胺气雾剂激发浓度（PC20）小于18mg/ml）。随后，对这些受试者分别用口服美西律、静脉注射利多卡因或安慰剂进行预处理，然后重复组胺激发试验。组胺的基线PC20为8.8±1.8mg/ml。治疗性血清浓度的美西律和利多卡因可阻断反射性支气管收缩。口服美西律使PC20增加至21.1±5.0mg/ml（血清浓度：0.7±0.05μg/ml）。同样，静脉注射利多卡因使PC20增加至24.5±4.9mg/ml（血清浓度：2.6±0.15μg/ml）。口服美西律和静脉注射利多卡因可阻断反射性诱导的支气管收缩。此外，当选择美西律用于治疗合并肺部疾病患者的心律失常或慢性疼痛时，它可能对气道还有其他益处。
