Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Pharmacotherapy. 2022 Jun;42(6):453-459. doi: 10.1002/phar.2684. Epub 2022 Apr 20.
Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children.
We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children.
Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom-designed TaqMan® Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3-1.2), GC (1, 0.3-1.3), and GG (0.8, 0.3-1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24-1.07), 0.72 (0.22-0.98), 0.58 (0.3-0.94), (p = 0.67).
These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics.
右美托咪定在儿科和心血管重症监护病房(PICU 和 CVICU)中通过滴定来实现镇静。在成年人中,右美托咪定的反应与 ADRA2A 多态性(rs1800544)有关;与 GC 和 GG 相比,CC 基因型与镇静反应增加有关。迄今为止,这在儿童中尚未进行研究。
我们进行了一项试点研究,以确定 ADRA2A 基因型是否与儿童接受右美托咪定的剂量有关。
40 名接受右美托咪定持续输注至少 2 天的气管插管 PICU 或 CVICU 患者接受了 ADRA2A 基因分型,使用定制的 TaqMan® Assay。10 名(25%)患者为野生型(GG),15 名(37.5%)为杂合型(GC),15 名(37.5%)为纯合型(CC)变异。基因型组 CC(1,0.3-1.2)、GC(1,0.3-1.3)和 GG(0.8,0.3-1.2)的最大右美托咪定剂量(mCg/kg/h)没有差异(p=0.37);这些基因型组的平均右美托咪定剂量分别为 0.68(0.24-1.07)、0.72(0.22-0.98)、0.58(0.3-0.94),差异也无统计学意义(p=0.67)。
这些发现与成人研究结果不一致,成人研究表明 ADRA2A 多态性与右美托咪定反应相关,因此强调在儿科实施前,需要进行儿科研究来验证成人中 PGx 发现。