Prehospital use of magnesium sulfate as neuroprotection in acute stroke.
Prehospital use of magnesium sulfate as neuroprotection in acute stroke.
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DOI：
10.1056/nejmoa1408827
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发表时间：
2015-02-05
期刊：
影响因子：
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通讯作者：
FAST-MAG Investigators and Coordinators
中科院分区：
文献类型：
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作者：
Saver JL;Starkman S;Eckstein M;Stratton SJ;Pratt FD;Hamilton S;Conwit R;Liebeskind DS;Sung G;Kramer I;Moreau G;Goldweber R;Sanossian N;FAST-MAG Investigators and Coordinators
硫酸镁在中风的临床前模型中具有神经保护作用，并且在人类中风发作后早期给予时显示出潜在疗效的信号，具有可接受的安全性特征。神经保护剂的延迟启动阻碍了神经保护剂的早期3期试验。我们将疑似中风的患者随机分配接受静脉注射硫酸镁或安慰剂，在症状发作后2小时内开始。在患者到达医院之前，护理人员开始负荷剂量，并在患者到达医院时开始24小时维持输注。主要结局是90天时的残疾程度，通过改良兰金量表评分（范围0 - 6分，评分越高表示残疾越严重）进行测量。在1700例入组患者（镁组857例，安慰剂组843例）中，平均（±SD）年龄为69±13岁，42.6%为女性，治疗前卒中严重程度洛杉矶运动量表评分（范围0 - 10，评分越高表示运动缺陷越严重）平均为3.7±1.3。合格事件的最终诊断为73.3%的患者为脑缺血，22.8%的患者为颅内出血，3.9%的患者为拟卒中状态。患者最后一次已知无卒中症状与研究药物输注开始之间的中位时间间隔为45分钟（四分位距，35 - 62），74.3%的患者在症状发作后1小时内接受了研究药物输注。镁组和安慰剂组患者的90天残疾结局分布在总体改良兰金量表上没有显著变化（Cochran-Mantel-Haenszel检验P = 0.28）;镁组和安慰剂组的90天平均评分没有差异（每组2.7，P = 1.00）。在死亡率（镁组为15.4%，安慰剂组为15.5%，P = 0.95）或所有严重不良事件方面，未观察到显著的组间差异。院前开始硫酸镁治疗是安全的，并允许在卒中症状发作后2小时内开始治疗，但在90天时并未改善残疾结局。（由国家神经疾病和中风研究所资助; FAST-MAG ClinicalTrials.gov编号，NCT 00059332。
Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient’s arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P = 0.28 by the Cochran–Mantel–Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P = 1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P = 0.95) or all serious adverse events. Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days. (Funded by the National Institute of Neurological Disorders and Stroke; FAST-MAG ClinicalTrials.gov number, NCT00059332.)