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镁,另一个失败的神经保护剂?
原作者: Wan-Tsu Wendy Chang, 发布日期:2015-12-07

Title: Magnesium, another failed neuroprotectant?
题目:镁,另一个失败的神经保护剂?
Author: Wan-Tsu Wendy Chang
作者:Wan-Tsu Wendy Chang
翻译:江利冰 校对:肖锋

Stroke is a leading cause of adult disability and the second leading cause of death worldwide. Currently available therapies for acute ischemic stroke are based on restoring perfusion to the ischemic penumbra. However, they are only moderately effective.
中风是成年人首位致残原因同时也是第二位死亡原因。对于急性缺血性中风目前的治疗策略均是基于恢复缺血半暗区的再灌注。但是这些策略仅仅具有中等疗效。

A series of pathological cascades leading to neuronal death are triggered in acute ischemia. Thus it may be logical to suggest that if one can interrupt the propagation of these cascades, perhaps part of the brain tissue can be protected and salvaged.
在急性缺血过程中,会激发一系列导致神经元死亡的病理性瀑布反应。因此,如果能够中断这些病理性瀑布,就有可能保护和抢救部分神经元。

Magnesium has been shown in various animal models to have pluripotent neuroprotective properties. It is also widely available, simple to administer, and has a favorable risk profile. A prior study of magnesium in acute ischemic stroke (IMAGES) did not show a benefit when the agent was administered a median 7.4 hours after symptom onset. However, a subgroup of patients treated within 3 hours of symptom onset showed possible benefit.
镁在很多动物模型中已经显示出了多功能的神经保护特性。它来源广泛,使用简单而且使用安全。之前一项报道(IMAGES)研究了在急性缺血中风中使用镁,发现当在症状出现后的7.4个小时后使用镁,没有显示出任何优势。然而亚组分析中当在症状出现3个小时内使用镁时,患者可能会受益。

The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) trial, funded by the NIH, looked at magnesium administered within 2 hours after symptom onset on the degree of disability at 90 days after stroke as measured by the modified Rankin scale.
FAST-MAG研究是NIH资助的一项的研究,主要研究在中风症状出现后2个小时内使用镁对中风患者90天功能障碍的影响,使用改良Rankin评分表示。
• A total of 1700 patients were included in the study.
• 该研究共纳入了1700例患者。
• 73.3% of patients had a final diagnosis of ischemic stroke, compared with 22.8% with intracranial hemorrhage and 3.9% with stroke-mimicking condition.
• 73.3%患者最终诊断为缺血性中风,22.8%的患者存在颅内出血,3.9%的患者为类中风情况。
• Of the patients with ischemic stroke, 52.4% were treated with tPA.
• 对于缺血性中风的患者,52.4%的患者接受了组织纤溶酶原激活剂的治疗

Magnesium was not found to have any benefit in functional outcome at 90 days.
镁对中风患者90天的功能恢复没有任何的益处。

This study was unique in several ways:
这个研究在一些方面是独一无二的:

It examined the use of a neuroprotective agent in the hyperacute window of 2 hours, as a common criticism of prior neuroprotective studies is that those agents may not have been administered within the optimal therapeutic window
该研究探查了在超急性期(2h内)使用神经保护剂的作用,否定了之前研究认为神经保护剂没有在最佳的治疗窗内使用的说法。
Administration of the neuroprotective agent began in the prehospital setting. Logistically, this was done with a pre-randomized study kit containing the initial bolus dose to be administered by EMS and the maintenance dose to be given to the receiving hospital for administration in the ED.
在院前开始使用神经保护剂。初始计量在院前由EMS工作人员提供,维持剂量在入院后,急诊室内给予。
Despite the short window for enrollment and drug administration, patients were screened using a previously validated prehospital stroke scale and 98.7% of patients were enrolled after explicit written informed consent from the patient or a legally authorized representative.
尽管患者纳入以及药物使用的窗口期很短,患者筛选使用的是经过验证的院前中风量表,而且98.7%的患者或者合法授权代理人签署了知情同意书。

However, despite this study being very well executed, demonstrating the feasibility of conducting a phase 3 trial with targeted intervention within the hyperacute window, it is another neuroprotective agent that failed to translate from the laboratory bench to the clinical realm.
但是,尽管该研究执行的很严谨,预示着在超急性期使用目标干预的3期临床试验的可行性,但是也说明了另一种神经保护剂无法从实验室的疗效转化为临床疗效。
Potential explanations for the discrepancies between preclinical and clinical outcomes of neuroprotective agents thus far include discrepancies on outcome measures, functional assessments, pre-morbid conditions, therapeutic windows, and drug-dosing schedules between animal studies and clinical trials.
目前可以解释临床前期和临床研究结果矛盾的原因包括:结局测量指标的不同、功能评估的方法、发病前的基础疾病、治疗窗以及动物实验和临床研究之间不同的药物剂量时间表。

Take Home Point: Magnesium does not have any clear benefit in acute ischemic stroke at this time.
要点:目前镁对于急性缺血性中风还没有发现任何明显的益处。