Effect of Xenon and Therapeutic Hypothermia, on the Brain and on Neurological Outcome Following Brain Ischemia in Cardiac Arrest Patients

Summary

The main purpose of this study is to explore whether xenon is neuroprotective in humans. In addition, the purpose is to explore the underlying mechanisms for the possible synergistic neuroprotective interaction of xenon and hypothermia in patients suffering cerebral ischemia post cardiac arrest, by undertaking brain imaging to evaluate their effects on cerebral hypoxia, neuronal loss and mitochondrial dysfunction. In addition, the investigators aim to correlate these findings with neurological outcome to determine surrogate markers of favourable clinical outcome at six months.

Timeline

Start

2009-05

Primary completion

2014-09

Completion

2014-09

Publications

• Background Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. doi: 10.1056/NEJMoa012689.
• Hollmen CC, Vorobyev V, Parkkola R, Posti JP, Saunavaara J, Laitio R, Arola O, Hynninen M, Backlund M, Blennow K, Zetterberg H, Martola J, Ylikoski E, Roine RO, Tiainen M, Scheinin H, Maze M, Vahlberg T, Laitio TT; Xe-HYPOTHECA Consortium. Grey matter volume reduction and its association with brain-enriched blood biomarkers in out-of-hospital cardiac arrest survivors. Sci Rep. 2025 Nov 26;15(1):42219. doi: 10.1038/s41598-025-26322-4.
• Hollmen C, Parkkola R, Vorobyev V, Saunavaara J, Laitio R, Arola O, Hynninen M, Backlund M, Martola J, Ylikoski E, Roine RO, Tiainen M, Scheinin H, Maze M, Vahlberg T, Laitio TT. 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. 2025 Feb;42(1):131-141. doi: 10.1007/s12028-024-02053-8. Epub 2024 Jul 9.
• Nummela AJ, Scheinin H, Perola M, Joensuu A, Laitio R, Arola O, Gronlund J, Roine RO, Backlund M, Vahlberg TJ, Laitio T; Xe-Hypotheca Collaboration Group. A metabolic profile of xenon and metabolite associations with 6-month mortality after out-of-hospital cardiac arrest: A post-hoc study of the randomised Xe-Hypotheca trial. PLoS One. 2024 Jun 4;19(6):e0304966. doi: 10.1371/journal.pone.0304966. eCollection 2024.
• Koskensalo K, Virtanen S, Saunavaara J, Parkkola R, Laitio R, Arola O, Hynninen M, Silvasti P, Nukarinen E, Martola J, Silvennoinen HM, Tiainen M, Roine RO, Scheinin H, Saraste A, Maze M, Vahlberg T, Laitio TT; XeHYPOTHECA Research Group. Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrest-a substudy of the XeHypotheca trial. Neuroradiology. 2023 Feb;65(2):349-360. doi: 10.1007/s00234-022-03063-z. Epub 2022 Oct 17.
• Laitio R, Hynninen M, Arola O, Virtanen S, Parkkola R, Saunavaara J, Roine RO, Gronlund J, Ylikoski E, Wennervirta J, Backlund M, Silvasti P, Nukarinen E, Tiainen M, Saraste A, Pietila M, Airaksinen J, Valanne L, Martola J, Silvennoinen H, Scheinin H, Harjola VP, Niiranen J, Korpi K, Varpula M, Inkinen O, Olkkola KT, Maze M, Vahlberg T, Laitio T. Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2016 Mar 15;315(11):1120-8. doi: 10.1001/jama.2016.1933.
• Arola OJ, Laitio RM, Roine RO, Gronlund J, Saraste A, Pietila M, Airaksinen J, Perttila J, Scheinin H, Olkkola KT, Maze M, Laitio TT. Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest. Crit Care Med. 2013 Sep;41(9):2116-24. doi: 10.1097/CCM.0b013e31828a4337.

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