Visualizing the burden of brain tissue hypoxia and metabolic dysfunction assessed by multimodal neuromonitoring in subarachnoid hemorrhage patients: the TITAN study

Elisa Gouvêa Bogossian¹, Bavo Kempen^{2

3}, Michael Veldeman⁴, Soojin Park^{5

6}, Verena Rass⁷, Stephane Marinesco⁸, Miriam Weiss^{9

10}, Gerrit Alexander Schubert^{4

9}, Nick Kastenholz^{4

11}, Jan Claassen⁵, Philipp Kindl⁷, Anna Berek⁷, Marco Anderloni^{12

13}, Catharina Conzen-Dilger⁴, Sophie Schuind¹⁴, Baptiste Balança^{8

15}, Yannick Tholance^{16

17}, E Sander Connolly¹⁸, Geert Meyfroidt¹⁹, Raimund Helbok^{7

20

21}, Giorgia Carra²², Fabio Silvio Taccone¹²

Affiliations

¹ Department of Intensive Care, Hôpital Universitaire de Bruxelles-Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium. elisagobog@gmail.com.
² Department of Neurosciences, KU Leuven, Leuven, Belgium.
³ Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium.
⁴ Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany.
⁵ Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, USA.
⁶ Department of Biomedical Informatics, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, NY, USA.
⁷ Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
⁸ Université Claude Bernard Lyon 1, CNRS, INSERM, Centre de Recherche en Neurosciences de Lyon CRNL U1028, UMR5292, TIGER, Bron, France.
⁹ Department of Neurosurgery, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁰ Department of Neurosurgery, Inselspital, University Hospital Bern, Bern, Switzerland.
¹¹ Department of Neurosurgery, University of Cologne, Cologne, Germany.
¹² Department of Intensive Care, Hôpital Universitaire de Bruxelles-Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
¹³ Department of Anesthesiology and Intensive Care, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
¹⁴ Department of Neurosurgery, Hôpital Universitaire de Bruxelles-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
¹⁵ Département d'anesthésie-Réanimation Neurologique, Hospices Civils de Lyon, Bron, France.
¹⁶ Synaptopathies and Autoantibodies, Faculté de Médecine Jacques Lisfranc, University Jean-Monnet, University Claude Bernard Lyon 1, MeLis, CNRS UMR 5284 INSERM U1314, Institut Neuromyogène, Saint-Étienne, France.
¹⁷ Department of Biochemistry, University Hospital, Saint-Etienne, France.
¹⁸ Department of Neurosurgery, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, USA.
¹⁹ Laboratory and Departement of Intensive Care Medicine, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
²⁰ Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
²¹ Clinical Research Institute of Neuroscience, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
²² Biomedical Data Science Center and Department of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland.

PMID: 40261381
DOI: 10.1007/s00134-025-07888-z

Multicenter Study

Visualizing the burden of brain tissue hypoxia and metabolic dysfunction assessed by multimodal neuromonitoring in subarachnoid hemorrhage patients: the TITAN study

Elisa Gouvêa Bogossian et al. Intensive Care Med. 2025 Apr.

. 2025 Apr;51(4):708-720.

doi: 10.1007/s00134-025-07888-z. Epub 2025 Apr 22.

Authors

Affiliations

¹ Department of Intensive Care, Hôpital Universitaire de Bruxelles-Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium. elisagobog@gmail.com.
² Department of Neurosciences, KU Leuven, Leuven, Belgium.
³ Department of Electrical Engineering (ESAT), KU Leuven, Leuven, Belgium.
⁴ Department of Neurosurgery, RWTH Aachen University Hospital, Aachen, Germany.
⁵ Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, USA.
⁶ Department of Biomedical Informatics, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, NY, USA.
⁷ Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
⁸ Université Claude Bernard Lyon 1, CNRS, INSERM, Centre de Recherche en Neurosciences de Lyon CRNL U1028, UMR5292, TIGER, Bron, France.
⁹ Department of Neurosurgery, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁰ Department of Neurosurgery, Inselspital, University Hospital Bern, Bern, Switzerland.
¹¹ Department of Neurosurgery, University of Cologne, Cologne, Germany.
¹² Department of Intensive Care, Hôpital Universitaire de Bruxelles-Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium.
¹³ Department of Anesthesiology and Intensive Care, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
¹⁴ Department of Neurosurgery, Hôpital Universitaire de Bruxelles-Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
¹⁵ Département d'anesthésie-Réanimation Neurologique, Hospices Civils de Lyon, Bron, France.
¹⁶ Synaptopathies and Autoantibodies, Faculté de Médecine Jacques Lisfranc, University Jean-Monnet, University Claude Bernard Lyon 1, MeLis, CNRS UMR 5284 INSERM U1314, Institut Neuromyogène, Saint-Étienne, France.
¹⁷ Department of Biochemistry, University Hospital, Saint-Etienne, France.
¹⁸ Department of Neurosurgery, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian Hospital, New York, USA.
¹⁹ Laboratory and Departement of Intensive Care Medicine, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
²⁰ Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
²¹ Clinical Research Institute of Neuroscience, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
²² Biomedical Data Science Center and Department of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland.

PMID: 40261381
DOI: 10.1007/s00134-025-07888-z

Abstract

Purpose: Brain tissue hypoxia and metabolic dysfunction are common in patients with subarachnoid hemorrhage (SAH) and may worsen prognosis. We aimed to assess the impact of episodes of low brain tissue partial pressure of oxygen (PbtO₂) and metabolic dysfunction (elevated lactate pyruvate ratio-LPR measured by cerebral microdialysis, CMD) on neurological outcome at 6 months.

Methods: This is a multicentric retrospective cohort study of SAH patients admitted to 5 neurocritical care units who required invasive multimodal neuromonitoring. The relationship between episodes of low PbtO₂ combined with elevated LPR and 6-month Glasgow Outcome Scale (GOS) was visualized in a color-coded plot. We performed a multivariate analysis of the association between the percentage of time spent with the low PbtO₂ and/or high LPR and neurological outcome and mortality at 6 months.

Results: We included 232 SAH patients with a median of 117 (IQR 77-154) h of monitoring per patient. The color-coded plot illustrated that combined episodes of low PbtO₂ and elevated LPR were prevalent in patients with unfavorable neurological outcome (e.g., GOS 1-3). This association was less evident in patients with isolated low PbtO₂ or isolated elevated LPR_. In a multivariate model, the cumulative PbtO₂/LPR burden was independently associated with unfavorable neurological outcome.

Conclusions: In this study, low PbtO₂ and metabolic insults were more prevalent among SAH patients with unfavorable long-term neurological outcome at 6 months. The role of multimodal neuromonitoring in guiding therapies and potentially influencing the outcome of these patients warrants further studies.

Keywords: Brain metabolism; Brain oxygenation; Invasive multimodal monitoring; Stroke.

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Conflict of interest statement

Declarations. Conflicts of interest: EGB was supported by the governmental grant “Mandat de Recherche Scientific -Fonds National de recherche Scientific (FNRS) Wallonie-Bruxelles”, Belgium. SP was supported by the US National Institutes of Health R01NS131606 and R01NS129760. BK was supported by a PhD fellowship basic research grant from the Foundation for Scientific Research Flanders (FWO 1S12525N). MV was supported by a grant (Grant No. VE 1274/1-1) from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). GM was supported by a senior clinical researcher grant (1843123N) from the Research Foundation Flanders (FWO). Ethical approval: This study complied with the declaration of Helsinki and was approved by the local ethics committees: Lyon institutional review board: Comité de Protection des Personnes Sud-Est IV, ref12-135, “Biothèque du service de neurobiologie du centre de Biologie Pathologie Est des Hospices Civils de Lyon”, approved 09/06/2012. Brussels institutional review board: Erasme Hospital Ethics committee: P2021/589. Innsbruck institutional review board: Innsbruck University Hospital Ethics Committee: AM4091-292/4.6. Aachen institutional review board: Medical Faculty of RWTH Aachen University Ethics Committee (EK 14/062 and EK 22/378). Columbia University Institutional Review Board (IRB) Protocol # AAAL4106.

References

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Visualizing the burden of brain tissue hypoxia and metabolic dysfunction assessed by multimodal neuromonitoring in subarachnoid hemorrhage patients: the TITAN study

Affiliations

Visualizing the burden of brain tissue hypoxia and metabolic dysfunction assessed by multimodal neuromonitoring in subarachnoid hemorrhage patients: the TITAN study

Authors

Affiliations

Abstract

Conflict of interest statement

References

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