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; Riitta Parkkola; Victor Vorobyev; Jani Saunavaara; Ruut Laitio; Olli Arola; Marja Hynninen; Minna Bäcklund; Juha Martola; Emmi Ylikoski; Risto O Roine; Marjaana Tiainen; Harry Scheinin; Mervyn Maze; Tero Vahlberg; Timo T Laitio

doi:10.1007/s12028-024-02053-8

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

Neurocrit Care. 2024 Jul 9. doi: 10.1007/s12028-024-02053-8. Online ahead of print.

Authors

Affiliations

¹ Department of Radiology, Turku University Hospital, University of Turku, Turku, Finland.
² Department of Medical Physics, Turku University Hospital, University of Turku, Turku, Finland.
³ Division of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, University of Turku, POB 52, 20521, Turku, Finland.
⁴ Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁵ Department of Radiology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁶ Division of Clinical Neurosciences, Turku University Hospital, University of Turku, Turku, Finland.
⁷ Department of Neurology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁸ Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA, USA.
⁹ Department of Biostatistics, University of Turku and Turku University Hospital, Turku, Finland.
¹⁰ Division of Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, University of Turku, POB 52, 20521, Turku, Finland. timo.laitio@varha.fi.

^# Contributed equally.

PMID: 38982000
DOI: 10.1007/s12028-024-02053-8

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.

Associated data

ClinicalTrials.gov/NCT00879892