Pharmacokinetics of sedative medicine during brain hypothermia therapy and its proper use

点击翻译按钮获取中文摘要

Control of sedation level is important during brain hypothermia therapy (BHT) that is expected to provide neuroprotection for severe brain injury. Hypothermia is known to induce some physiological changes. To gain the optimal sedation using midazolam during BHT, we examined the influence of hypothermia on pharmacokinetics of midazolam in patients undergoing BHT. During hypothermic period (33℃-35℃), total clearance of midazolam was decreased, resulting in that the half-life of serum disappearance of midazolam was prolonged and serum concentration was increased compared to when body temperature rose to 36℃. In some patients hepatic blood flow was reduced. Furthermore, in vitro study, Vmax value for metabolism of midazolam by CYP3A5 decreased to about 60% and 40% at 33℃ and 25℃, respectively, compared to that at 37℃. The value by CYP3A4 was decreased to 50% at 25℃, but not affected at 33℃. These results suggest that hypothermia induces the decrease of CYP3A5 activity and/or hepatic blood flow, which contributes to the increase of serum concentration of midazolam during hypothermic period.