丙戊酸
医学
创伤性脑损伤
神经保护
麻醉
生理盐水
药代动力学
病变
磁共振成像
休克(循环)
脑血流
血流动力学
复苏
外科
药理学
内科学
癫痫
放射科
精神科
作者
Guang Jin,Jessie W Ho,Toby Philip Keeney-Bonthrone,Manjunath P. Pai,Bo Wen,Rebecca Ober,Deanna Dimonte,Kiril Chtraklin,Theodore Alan Joaquin,Zahid Latif,Claire A Vercruysse,Hasan B. Alam
出处
期刊:The journal of trauma and acute care surgery
[Ovid Technologies (Wolters Kluwer)]
日期:2023-06-14
卷期号:95 (5): 657-663
标识
DOI:10.1097/ta.0000000000004022
摘要
It has previously been shown that administration of valproic acid (VPA) can improve outcomes if given within an hour following traumatic brain injury (TBI). This short therapeutic window (TW) limits its use in real-life situations. Based upon its pharmacokinetic data, we hypothesized that TW can be extended to 3 hours if a second dose of VPA is given 8 hours after the initial dose.Yorkshire swine (40-45 kg; n = 10) were subjected to TBI (controlled cortical impact) and 40% blood volume hemorrhage. After 2 hours of shock, they were randomized to either (1) normal saline resuscitation (control) or (2) normal saline-VPA (150 mg/kg × two doses). First dose of VPA was started 3 hours after the TBI, with a second dose 8 hours after the first dose. Neurologic severity scores (range, 0-36) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging on postinjury day 3.Hemodynamic and laboratory parameters of shock were similar in both groups. Valproic acid-treated animals had significantly less neurologic impairment on days 2 (16.3 ± 2.0 vs. 7.3 ± 2.8) and 3 (10.9 ± 3.6 vs. 2.8 ± 1.1) postinjury and returned to baseline levels 54% faster. Magnetic resonance imaging showed no differences in brain lesion size on day 3. Pharmacokinetic data confirmed neuroprotective levels of VPA in the circulation.This is the first study to demonstrate that VPA can be neuroprotective even when given 3 hours after TBI. This expanded TW has significant implications for the design of the clinical trial.
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