O'Meara Katherine, Puccio Ava M, Ren Dianxu, Deslouches Sandra, Jha Ruchira, Okonkwo David O, Conley Yvette P
University of Pittsburgh School of Nursing, Pittsburgh, Pennsylvania, USA.
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Neurotrauma Rep. 2024 Jul 16;5(1):680-685. doi: 10.1089/neur.2024.0025. eCollection 2024.
Management of severe traumatic brain injury (sTBI) typically involves the use of sedation, which inherently results in benefits and risks. The cytochrome P450 enzyme CYP2B6 is involved in the biotransformation of particular drug classes, including many intravenous sedatives. Variants of the gene can lead to decreased systemic clearance of some sedatives, including propofol. This study aimed to investigate the relationship of gene variation and patient outcomes after TBI while also considering propofol administration. Patients who sustained a non-penetrating sTBI and admitted to a single-center Level 1 trauma hospital were included in this study ( = 440). The *6 functional allele of that leads to reduced enzyme expression and activity required genotyping two single nucleotide polymorphisms, rs3745274 and rs2279343. Patient outcomes were evaluated using the Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) at 3 and 6 months post-injury. Data on sedative administration were abstracted from medical records. Individuals homozygous for the alleles coding for the reduced enzyme expression and activity were more likely to have worse outcomes. A relationship between propofol administration and 3-month GOS and 6-month DRS was noted when controlling for genotype. These findings suggest that genetic variation in may influence the impact of intravenous sedation on patient outcomes after TBI and warrants further investigation.
重度创伤性脑损伤（sTBI）的治疗通常涉及使用镇静剂，这本身会带来益处和风险。细胞色素P450酶CYP2B6参与特定药物类别的生物转化，包括许多静脉镇静剂。该基因的变异可导致某些镇静剂的全身清除率降低，包括丙泊酚。本研究旨在调查TBI后CYP2B6基因变异与患者预后的关系，同时考虑丙泊酚的使用情况。本研究纳入了在一家单中心一级创伤医院就诊的非穿透性sTBI患者（n = 440）。导致酶表达和活性降低的CYP2B6 *6功能等位基因需要对两个单核苷酸多态性rs3745274和rs2279343进行基因分型。在受伤后3个月和6个月时，使用格拉斯哥预后量表（GOS）和残疾评定量表（DRS）评估患者预后。从医疗记录中提取镇静剂使用数据。编码酶表达和活性降低的等位基因纯合个体更有可能有更差的预后。在控制CYP2B6基因型时，发现丙泊酚使用与3个月GOS和6个月DRS之间存在关联。这些发现表明，CYP2B6基因变异可能会影响静脉镇静对TBI后患者预后的影响，值得进一步研究。
