Pharmacogenetic and pharmacokinetic factors for dexmedetomidine-associated hemodynamic instability in pediatric patients

The reported incidence of hemodynamic instability for dexmedetomidine (DEX) sedation exceeds 50%. The risk of hemodynamic instability caused by DEX necessitates a better understanding of its pharmacogenetics in young children. The purpose of this study was to investigate the factors that associated with DEX-induced hemodynamic instability. As a result, genetic variants in UGT2B10, CYP2A6, ADRA2B, CACNA2D2, NR1I2 and CACNB2 influenced the incidence of DEX-induced hemodynamic instability, and polymorphism analyses in associated genes might be beneficial to optimize DEX treatment. Hemodynamic instability is likely to occur after 35-min DEX initiation in patients with lower DEX clearance after propofol induction.<br>

右美托咪定（dexmedetomidine，DEX）镇静相关血流动力学不稳定的报道发生率已超50%。鉴于DEX诱导血流动力学不稳定的风险，亟需深化对儿童群体中该药药物遗传学特征的认识。本研究旨在探究与DEX诱导的血流动力学不稳定相关的影响因素。研究结果显示，UGT2B10、CYP2A6、ADRA2B、CACNA2D2、NR1I2及CACNB2的基因变异会影响DEX诱导的血流动力学不稳定的发生率；对相关基因开展多态性分析，或可优化DEX的临床治疗方案。在接受丙泊酚诱导后DEX清除率较低的患者中，血流动力学不稳定多在DEX给药启动35分钟后发生。