Association of sepsis and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage

Background: 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 of sepsis with DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition. Methods: Patients admitted to our hospital between 11/2014-11/2018 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%) developed sepsis and 74 (31%) 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% (76/135) in patients with neither sepsis nor DCI, to 43% (21/48) in those with no sepsis but DCI, to 34% (10/29) with sepsis but no DCI and to 8% (2/26) in patients with both sepsis and DCI. Conclusions: 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. ### Competing Interest Statement Dr. Centner, Dr. Schoettler and Prof. Dr. Thiel report funding from the Klaus Tschira Stiftung, grant number 00.277.2015. Dr. Maros 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) and unrelated consultancy for Siemens Healthineers GmbH and EppData GmbH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors have no conflicts of interest to declare. ### Clinical Protocols ### Funding Statement Dr. Centner, Dr. Schoettler and Prof. Dr. Thiel report funding from the Klaus Tschira Stiftung, grant number 00.277.2015. Dr. Maros 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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Medical Ethics Commission II of Medical Faculty Mannheim, University of Heidelberg, approved the study design as well as reanalysis of neuroradiological reports and imaging data (reference nr.: 2019-1096R, 2017-825R-MA and 2017-828R-MA; date of approval: 01/10/2019). The need for informed consent was waived because of the retrospective nature of the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Study design and reporting adhered to the STROBE guidelines. All data produced in the present study are available upon reasonable request to the authors.