Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children.
Therapeutic hypothermia preserves antioxidant defenses after severe traumatic brain injury in infants and children.
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DOI：
10.1097/ccm.0b013e318194abf2
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发表时间：
2009-02
影响因子：
8.8
通讯作者：
Kochanek PM
中科院分区：
文献类型：
--
作者：
Bayir H;Adelson PD;Wisniewski SR;Shore P;Lai Y;Brown D;Janesko-Feldman KL;Kagan VE;Kochanek PM
氧化应激导致创伤性脑损伤（TBI）后的继发性损害。低温降低实验性脑损伤后内源性抗氧化剂消耗和脂质过氧化作用。我们的目的是确定治疗性低温对婴儿和儿童严重TBI后氧化损伤的影响，随机分为中度低温组和常温组。前瞻性随机对照研究。匹兹堡儿童医院的儿科ICU该研究包括28名患者，我们比较了在一个多中心随机对照试验中低温治疗严重儿科TBI（GCS评分≤ 8）的患者中低温（32-33°C）与常温治疗的效果。随机分为亚低温组（n=13），在24 h ~ 24 h内降温至目标温度，持续48 h，然后复温。通过测量总抗氧化储备[AOR]和谷胱甘肽来评估抗氧化状态。蛋白质氧化和脂质过氧化分别通过测量损伤后第1 -3天获得的脑室CSF样本（n=76）中的蛋白质巯基和F2-异前列烷进行评估。通过双变量和多元回归模型评估GCS评分、年龄、性别、治疗、体温、损伤后时间与CSF AOR、谷胱甘肽、蛋白硫醇、F2-异前列烷水平之间的相关性。两个治疗组的人口统计学和临床特征相似。损伤机制包括意外损伤和非意外损伤。多元回归模型显示低温可保护CSF抗氧化储备（p = 0.001）。同样，多元回归模型显示谷胱甘肽水平与采样时患者体温呈负相关（p = 0.002）。F2-异前列烷水平在损伤后第1天达到峰值，此后逐渐下降。尽管随机分配至低温组的患者的F2-异前列烷水平比正常体温组低1.3倍，但该差异无统计学显著性。据我们所知，这是第一个研究表明，低温减弱氧化应激后，严重的创伤性脑损伤的婴儿和儿童。我们的数据还支持CSF是监测TBI后氧化应激治疗效果的有价值的工具的概念。
Oxidative stress contributes to secondary damage after traumatic brain injury (TBI). Hypothermia decreases endogenous antioxidant consumption and lipid peroxidation after experimental cerebral injury. Our objective was to determine the effect of therapeutic hypothermia on oxidative damage after severe TBI in infants and children randomized to moderate hypothermia vs normothermia. Prospective randomized controlled study. Pediatric ICU of Pittsburgh Children’s Hospital The study included 28 patients We compared the effects of hypothermia (32-33°C) vs normothermia in patients treated in a single center involved in a multi-center randomized controlled trial of hypothermia in severe pediatric TBI (GCS score ≤ 8). The patients randomized to hypothermia (n=13) were cooled to target temperature within ∼6h-24h for 48h and then re-warmed. Antioxidant status was assessed by measurements of total antioxidant reserve [AOR] and glutathione. Protein oxidation and lipid peroxidation were assessed by measurements of protein-thiols and F2-isoprostane, respectively in ventricular CSF samples (n=76) obtained on day1-3 after injury. The association between GCS score, age, gender, treatment, temperature, time after injury, and CSF AOR, glutathione, protein-thiol, F2-isoprostane levels were assessed by bivariate and multiple regression models. Demographic and clinical characteristics were similar between the two treatment groups. Mechanism of injury included both accidental injury and nonaccidental injury. Multiple regression models revealed preservation of CSF antioxidant reserve by hypothermia (p = 0.001). Similarly, a multiple regression model showed that glutathione levels were inversely associated with patient temperature at the time of sampling (p = 0.002). F2-isoprostane levels peaked on day 1 after injury and were progressively decreased thereafter. Although F2-isoprostane levels were ∼3-fold lower in patients randomized to hypothermia vs. normothermia, this difference was not statistically significant. To our knowledge this is the first study demonstrating that hypothermia attenuates oxidative stress after severe TBI in infants and children. Our data also support the concept that CSF represents a valuable tool for monitoring treatment effects on oxidative stress after TBI.