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Clinical Trial
. 2025 Feb;42(1):131-141.
doi: 10.1007/s12028-024-02053-8. Epub 2024 Jul 9.

Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial

Carita Hollmén #  1 , Riitta Parkkola #  1 , Victor Vorobyev  1 , Jani Saunavaara  2 , Ruut Laitio  3 , Olli Arola  3 , Marja Hynninen  4 , Minna Bäcklund  4 , Juha Martola  5 , Emmi Ylikoski  4 , Risto O Roine  6 , Marjaana Tiainen  7 , Harry Scheinin  3 , Mervyn Maze  8 , Tero Vahlberg  9 , Timo T Laitio  10
Affiliations
Clinical Trial

Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial

Carita Hollmén et al. Neurocrit Care. 2025 Feb.

Abstract

Background: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA.

Methods: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA.

Results: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups.

Conclusions: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone.

Clinical trial registration: ClinicalTrials.gov: NCT00879892.

Keywords: Gray matter injury; Neuroprotection; Out-of-hospital cardiac arrest; Targeted temperature management; Voxel-based morphometry; Xenon.

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Conflict of interest statement

Conflicts of interest: TL reports funding from State Research Funding, Finland. RL is a paid governmental consultant official for the National Supervisory Authority for Welfare and Health. ROR reports funding from the Academy of Finland. For the remaining authors, none were declared. Ethical Approval/Informed Consent: The study was approved by the ethics committee of the Hospital District of Southwest Finland on March 17, 2009 (approval Number 10/2009/§65; study title: Effect of Xenon, in Combination with Therapeutic Hypothermia, on the Brain and on Neurological Outcome following Brain Ischemia in Cardiac Arrest Patients) and the institutional review boards of Helsinki University Hospital and the Finnish Medicines Agency. All patients’ next of kin or legal representatives gave written informed assent within four hours after hospital arrival. Consent was obtained from patients when they regained consciousness.

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