Department of Anaesthesiology and Intensive Care, University of Turku, Turku, Finland2Division of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.
Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki, Helsinki, Finland4Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki.
JAMA. 2016 Mar 15;315(11):1120-8. doi: 10.1001/jama.2016.1933.
Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies.
To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI).
DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized.
Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group).
The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months.
Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053).
Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest.
clinicaltrials.gov Identifier: NCT00879892.
临床前模型的证据表明，氙气可以预防急性全脑缺氧缺血性脑损伤后的脑损伤发展，但迄今为止，这些潜在的神经保护作用在人类研究中尚未得到报道。
确定吸入氙气对磁共振成像 (MRI) 评估的缺血性白质损伤的影响。
设计、设置和参与者：这是一项在芬兰的 2 个多用途重症监护病房于 2009 年 8 月至 2015 年 3 月期间进行的随机、单盲、2 期临床药物试验。110 名处于昏迷状态的患者（年龄 24-76 岁）经历了院外心脏骤停，被随机分配。
患者被随机分配接受吸入氙气联合 33°C 低温治疗 24 小时（氙气组 55 例）或单独低温治疗（对照组 55 例）。
主要终点是通过心脏骤停后 36-52 小时进行的扩散张量 MRI 评估的脑白质损伤的分数各向异性。次要终点包括使用改良 Rankin 量表（评分 0 [无症状]至 6 [死亡]）评估的神经功能预后和 6 个月时的死亡率。
在 110 名随机患者中（平均年龄 61.5 岁；80 名男性[72.7%]），所有人都完成了研究。中位数为心脏骤停后 53 小时（四分位距 [IQR]，47-64 小时）有 97 名患者有 MRI 数据。在氙气组和对照组中，全球平均分数各向异性值分别为 0.433（标准差 [SD]，0.028）和 0.419（SD，0.033）。年龄、性别和地点调整后的全球平均分数各向异性值在氙气组中高 3.8%（95%置信区间 [CI]，1.1%-6.4%）（调整平均差异，0.016 [95% CI，0.005-0.027]，P =.006）。6 个月时，75 名患者（68.2%）存活。6 个月时的次要终点在组间没有显示出统计学上的显著差异。在改良 Rankin 量表的有序分析中，中位数（IQR）值在氙气组中为 1（1-6），在对照组中为 1（0-6）（中位数差值为 0 [95% CI，0-0]；P =.68）。6 个月死亡率在氙气组为 27.3%（15/55），在对照组为 34.5%（19/55）（调整后的危险比，0.49 [95% CI，0.23-1.01]；P =.053）。
在院外心脏骤停的昏迷幸存者中，与单独低温治疗相比，吸入氙气联合低温治疗可通过扩散张量 MRI 的分数各向异性测量结果显示白质损伤程度较低。然而，在 6 个月时的神经功能预后或死亡率方面没有统计学上的显著差异。这些初步发现需要在设计用于评估院外心脏骤停幸存者吸入氙气相关临床结局的充分有效性临床试验中进一步评估。
clinicaltrials.gov 标识符：NCT00879892。
