Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Claire Rummage, Mercer University College of Pharmacy

International guidelines recommend therapeutic hypothermia for comatose survivors of out-of-hospital cardiac arrest.1 It is stated that the inhalation of xenon has favorable cardiovascular properties when given to patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest.2

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial3
Design Randomized, two-group, single-blind, phase two clinical trial at two multipurpose intensive care units in Finland; N= 110
Objective To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imagining (MRI)
Study Groups Inhaled xenon combined with hypothermia (33°C) for 24 hours (n= 55) or hypothermia treatment alone (n= 55)
Methods Patients were scheduled to undergo brain MRI within 16 hours after rewarming; ranging from 36 to 52 hours after out-of-hospital cardiac arrest. Fractional anisotropy and diffusivity maps were calculated for each patient to represent the centers of all major white matter structures. These images were used to identify significant differences in diffusion parameters.
Duration August 2009 – March 2015
Primary Outcome Measure Cerebral white matter damage evaluated by fractional anisotropy
Baseline Characteristics   Xenon (n= 55) Control (n= 55)
Age, years 63 (55-70) 60 (54-67)
Male sex, n 41 (74.5%) 39 (70.9%)
Coronary artery disease 38 (69.1%) 40(72.7%)
Hypertension 22 (40%) 26 (47.3)
Fazekas score 0-1 39 (81.3) 38 (77.6)
Fazekas score 2-3 9 (18.8) 11(22.4)
Core temperature before start of cooling median (°C ) 34.9 (34.4-35.8) 35.4 (34.0-36.3)
Time from out-of-hospital cardiac arrest to target temperature, median (min) 290 (263-338) 336 (254-395)
Time from out-of-hospital cardiac arrest to initiation of xenon median (min) 247 (209-278)  
Results   Xenon (n=48) Control (n=49) p value unadjusted
Fractional Anisotropy, mean (SD) 0.433 (0.028) 0.419 (0.033) 0.03
Adverse Events Common Adverse Events: N/A  
Serious Adverse Events: N/A  
Percentage that Discontinued due to Adverse Events: 0.9%  
Study Author Conclusions Among the survivors, inhaled xenon combined with hypothermia compared with hypothermia alone resulting in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. There was no statistically significant difference in neurological outcomes or mortality at 6 months.  

The main outcome of this study showed that inhaled xenon in combination with therapeutic hypothermia treatment preserved white matter tracts better than hypothermia treatment alone in survivors of cardiac arrest. Although 80% of the deaths in this study were due to severe ischemic brain injury, underlying cardiac disease may have also contributed to poor outcomes. Therefore, subsequent studies could evaluate if cardiovascular disease is a confounding variable.

 

 

References

  1. Hypothermia after Cardiac Arrest Study Group.  Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549-556.

 

  1. Arola  OJ, Laitio  RM, Roine  RO,  et al.  Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest. Crit Care Med. 2013;41(9):2116-2124.

 

  1. Laitio R, Hynninen M, Arola O, et al. Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2016;315(11):1120-8.
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