Molecular genetic evaluation of the clinical effect of sedatives

2000年，Yoichi Kurasawa和他的同事首次报道了在口腔内同时注射局麻药和镇静剂以减少和预防与牙科治疗期间局麻药相关的并发症（例如，过度通气综合征和脑贫血症状）。然而，目前还没有关于这种麻醉过程的详细证据。今年，我们对口腔局部注射镇静剂（主要是咪达唑仑）后的生命体征进行了记录和分析。经皮动脉血氧饱和度在镇静组和对照组之间有显著差异，但呼吸频率、心率或血压没有差异。注射后5分钟，咪达唑仑血药浓度达到最高值（101.0±31.1 ng/ml）， 80分钟后，咪达唑仑血药浓度逐渐下降至43.0±14.5 ng/ml。在感染后10（79.1±4.7）分钟、20（64.6±7.5）分钟、30（56.3±15.0）分钟、40（58.1±17.6）分钟、60（60.5±24.6）分钟和80（92.2±5.8）分钟，咪达唑仑组BIS指数明显低于对照组。注射后30分钟记录最小BIS指数。对血药浓度和脑电图变化的详细记录和分析是本研究最重要的成果，将有助于预防事故和并发症，实现更安全的牙科治疗。本研究结果于2009年8月在日本神户举行的第56届日本麻醉师学会年会上发表。第二个研究课题是与基因组DNA序列相关的镇静作用差异，我们纯化DNA，利用限制性片段长度多态性聚合酶链反应分析GABAα6受体和细胞色素P450 3A亚家族基因的突变；然而，我们没有发现这些突变与镇静程度之间有任何显著的相关性。我们将继续进行分析以进一步澄清这一点。少

Simultaneous injection of a local anesthetic and a sedative in the oral cavity to reduce and prevent complications associated with local anesthesia during dental treatment (e.g., hyperventilation syndrome and cerebral anemia symptoms) was first reported by Yoichi Kurasawa and his colleagues in 2000. However, there has been no detailed evidence regarding this anesthetic procedure. This year, we performed recording and analysis of vital signs following local injection of sedatives (mainly midazolam) in the oral cavity. Percutaneous arterial oxygen saturation, but not respiratory rate, heart rate or blood pressure, showed significant differences between the sedative and control groups. Plasma midazolam concentration reached the maximum level 5 minutes after injection (101.0 ± 31.1 ng/ml), and then decreased over time to an 80-minute value of 43.0 ± 14.5 ng/ml. BIS index as measured with a BIS monitor were significantly lower in the midazolam group than in the control group at the followin … More g time points: 10 (79.1 ± 4.7), 20 (64.6 ± 7.5), 30 (56.3 ± 15.0), 40 (58.1 ± 17.6), 60 (60.5 ± 24.6) and 80 (92.2 ± 5.8) minutes after infection. The minimum BIS index was recorded 30 minutes after injection. The demonstration of the detailed recording and analysis of blood concentrations and electroencephalographic changes was the most important achievement of the present study and should lead to the prevention of accidents and complications and the realization of safer dental treatment. The present results were presented at the 56th Annual Meeting of the Japan Society of Anesthesiologists (August 2009, Kobe, Japan). For the second research subject regarding differences in sedative effect related to the genomic DNA sequence, we purified DNA and analyzed for mutations in the GABAα6 receptor and cytochrome P450 3A subfamily genes using restriction fragment length polymorphism polymerase chain reaction; however, we have not found any significant correlation between these mutations and degree of sedation. We will continue to perform analyses to further clarify this. Less