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Cerebral Hemodynamics and Levosimendan Use in Patients with Cerebral Vasospasm and Subarachnoid Hemorrhage: An Observational Perfusion CT-Based Imaging Study

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Abstract

Background

Delayed cerebral ischemia associated with cerebral vasospasm (CVS) in aneurysmal subarachnoid hemorrhage significantly affects patient prognosis. Levosimendan has emerged as a potential treatment, but clinical data are lacking. The aim of this study is to decipher levosimendan’s effect on cerebral hemodynamics by automated quantitative measurements of brain computed tomography perfusion (CTP).

Methods

We conducted a retrospective analysis of a database of a neurosurgical intensive care unit. All patients admitted from January 2018 to July 2022 for aneurysmal subarachnoid hemorrhage and treated with levosimendan for CVS who did not respond to other therapies were included. Quantitative measurements of time to maximum (Tmax), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) were automatically compared with coregistered CTP before and after levosimendan administration in oligemic regions.

Results

Of 21 patients included, CTP analysis could be performed in 16. Levosimendan improved Tmax from 14.4 s (interquartile range [IQR] 9.1–21) before treatment to 7.1 s (IQR 5.5–8.1) after treatment (p < 0.001). rCBV (94% [IQR 79–103] before treatment and 89% [IQR 72–103] after treatment, p = 0.63) and rCBF (85% [IQR 77–90] before treatment and 87% [IQR 73–98] after treatment, p = 0.98) remained stable. The subgroup of six patients who did not develop cerebral infarction attributed to delayed cerebral ischemia showed an approximately 10% increase (rCBV 85% [IQR 79–99] before treatment vs. 95% [IQR 88–112] after treatment, p = 0.21; rCBF 81% [IQR 76–87] before treatment vs. 89% [IQR 84–99] after treatment, p = 0.4).

Conclusions

In refractory CVS, levosimendan use was associated with a significant reduction in Tmax in oligemic regions. However, this value remained at an abnormal level, indicating the presence of a persistent CVS. Further analysis raised the hypothesis that levosimendan causes cerebral vasodilation, but other studies are needed because our design does not allow us to quantify the effect of levosimendan from that of the natural evolution of CVS.

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Funding

This study did not have funding.

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Authors and Affiliations

  1. Service d’Anesthésie-Réanimation Tripode, CHU de Bordeaux, Bordeaux, France

    Grégoire Cane, Hugues de Courson, Caroline Robert & Matthieu Biais

  2. Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Hikaru Fukutomi

  3. CHU de Bordeaux, Bordeaux, France

    Gaultier Marnat & Thomas Tourdias

  4. INSERM-U1215, Neurocentre Magendie, Bordeaux, France

    Thomas Tourdias

  5. INSERM Biologie des Maladies Cardiovasculaires U1034, University of Bordeaux, 33600, Pessac, France

    Matthieu Biais

Authors
  1. Grégoire Cane
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  2. Hugues de Courson
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Contributions

GC and CR collected clinical, biological, and radiological data to build the analyzed database. GC, HDC, and MB conceived and designed this study. GM and TT designed the analysis of the radiological perfusion data and reviewed all the images. HF performed the offline analysis of the perfusion CT scans, realigning the individual perfusion scans and propagating the ROIs of the oligemic regions from one CT scan to the other. GC reprocessed with Olea software all perfusion data. GC wrote the first manuscript. HDC, MB, GM, and TT contributed heavily to the review. All authors read, revised, and approved the final manuscript.

Corresponding author

Correspondence to Grégoire Cane.

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Conflict of interest

All authors have no competing interests.

Ethical Approval/Informed Consent

This study complies with national and European guidelines on the protection of personal health data (RGPD), as our clinical data warehouse is quality certified in EHDEN. Approval for this study was obtained from the local ethics committee (Comité d’Ethique de la Recherche du Centre Hospitalier Universitaire de Bordeaux). The nonopposition of patients to the use of their data was systematically sought, as required by national regulations for retrospective observational studies.

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Cane, G., de Courson, H., Robert, C. et al. Cerebral Hemodynamics and Levosimendan Use in Patients with Cerebral Vasospasm and Subarachnoid Hemorrhage: An Observational Perfusion CT-Based Imaging Study. Neurocrit Care (2024). https://doi.org/10.1007/s12028-023-01928-6

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  • DOI: https://doi.org/10.1007/s12028-023-01928-6

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