Sepsis and delayed cerebral ischemia are associated and have a cumulative effect on poor functional outcome in aneurysmal subarachnoid hemorrhage

Franz-Simon Centner; Holger Wenz; Mariella Eliana Oster; Franz-Joseph Dally; Johannes Sauter-Servaes; Tanja Pelzer; Jochen J Schoettler; Bianka Hahn; Amr Abdulazim; Katharian A M Hackenberg; Christoph Groden; Joerg Krebs; Manfred Thiel; Nima Etminan; Máté E Maros

doi:10.3389/fneur.2024.1393989

Sepsis and delayed cerebral ischemia are associated and have a cumulative effect on poor functional outcome in aneurysmal subarachnoid hemorrhage

Front Neurol. 2024 May 31:15:1393989. doi: 10.3389/fneur.2024.1393989. eCollection 2024.

Authors

Franz-Simon Centner¹, Holger Wenz², Mariella Eliana Oster¹, Franz-Joseph Dally^{1

3}, Johannes Sauter-Servaes¹, Tanja Pelzer^{1

4}, Jochen J Schoettler¹, Bianka Hahn¹, Amr Abdulazim⁵, Katharian A M Hackenberg⁵, Christoph Groden², Joerg Krebs¹, Manfred Thiel¹, Nima Etminan⁵, Máté E Maros^{2

6}

Affiliations

¹ Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
² Department of Neuroradiology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
³ Department of Orthopedics and Trauma Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁴ Department of Neonatology, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁵ Department of Neurosurgery, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁶ Department of Biomedical Informatics at the Center for Preventive Medicine and Digital Health (CPD), University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Abstract

Objective: Although sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association between sepsis and DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition.

Methods: Patients admitted to our hospital between 11/2014 and 11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed.

Results: Of 238 patients with aSAH, 55 (23.1%) developed sepsis and 74 (31.1%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p < 0.01) and longer ICU stay (p = 0.046). Sepsis was independently associated with DCI (OR = 2.46, 95%CI: 1.28-4.72, p < 0.01). However, after exclusion of patients who developed sepsis before (OR = 1.59, 95%CI: 0.78-3.24, p = 0.21) or after DCI (OR = 0.85, 95%CI: 0.37-1.95, p = 0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56.3% (76/135) in patients with neither sepsis nor DCI, to 43.8% (21/48) in those with no sepsis but DCI, to 34.5% (10/29) with sepsis but no DCI and to 7.7% (2/26) in patients with both sepsis and DCI.

Conclusion: Our study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.

Keywords: delayed cerebral ischemia; propensity score (PS) matching (PSM); sepsis; sepsis criteria; subarachnoid hemorrhage.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. F-SC, JS, and MT report funding from the Klaus Tschira Stiftung, grant number 00.277.2015. MM reports funding from the German Ministry for Education and Research (BMBF) within the framework of the Medical Informatics Initiative (MII) MIRACUM Consortium (Medical Informatics for Holistic Disease Models in Personalized and Preventive Medicine, MIDorAI; 01ZZ2020). For the publication fee, we acknowledge the financial support from the Open Access Publication Funding of Heidelberg University and the German Research Foundation (DFG).