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Importance: 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., Objective: 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., Interventions: 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)., Main Outcomes and Measures: 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., Results: 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)., Conclusions and Relevance: 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., Trial Registration: clinicaltrials.gov Identifier: NCT00879892.

BACKGROUND:The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). OBJECTIVES:A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. METHODS:A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. RESULTS:Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). CONCLUSIONS:Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T.