Multimodal monitoring guided management of blood and cerebral perfusion pressure in aneurysmal subarachnoid hemorrhage – a prospective multicenter observational cohort study.

• Applicant: Privatdozent Michael Veldeman, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546970303

Aneurysmal subarachnoid hemorrhage remains a poorly understood and devastating disease. Due to the fact that it affects relatively young patients, the disease generates a socio-economic burden comparable to ischemic stroke. Apart from initial hemorrhage severity, the main determining factor of patient’s outcome is the occurrence of delayed cerebral ischemia (DCI). Research focus has shifted towards a better understanding of DCI on a microvasculatory level. Translational as well as clinical research have identified microvasospasm, microthrombosis, neuroinflammation and loss of autoregulation (among others) as drivers of DCI. The loss of autoregulation and the endogenous mechanisms compensation for it, have been insufficiently assessed in the SAH population. Treatment of DCI to date consists out of somewhat paradoxical infusion of noradrenaline which causes arteriolar vasoconstriction driven blood pressure increase. Though, often leading to a positive clinical response, the treatment is still controversially discussed and non-individualized pressure targets possibly lead to overtreatment and unnecessary side effects. For this project we will have three databases of continuous physiological (heart rate, blood pressure, intracranial pressure, and derivatives) and multimodal (brain tissue oxygen and cerebral microdialysis) datamonitoring at our disposable. The database collected at the RWTH Aachen University Hospital will be fused with the Cambridge and Zürich database, cleaned from artifacts, and analyzed using ICM+ software (developed at Cambridge University). The objectives of this research project are -To characterized and define the temporal changes of autoregulatory indices in relation to identified DCI events. Special attention will be directed towards patients with so called “permissive hypertension” who develop endogenous hypertension counteracting their DCI-induced reduced cerebral blood flow. This is presumed to be a subgroup of patients able to compensate for macro/micro vascular vasospasm by a demand driven response which is most possible related to autoregulation. -To characterized metabolic intraparenchymal changes leading up to DCI events. Multimodal neuromonitoring using brain oxygen measurement and microdialysis are susceptible to artifacts and the delay in data acquisition may lead to treatment decisions coming to late. Relative temporal changes of partial oxygen pressure and microdialysis parameters might prove more valuable than absolute cut-offs, triggering action. We wish to define the slopes of change leading up to DCI and DCI-related infarction, in order to provide earlier warning signs for impending DCI. A combined better understanding of cerebral autoregulation and metabolic changes preceding DCI can help tailer blood pressure management of SAH patients and identify new treatment targets for future research.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Peter Smielewski, Ph.D.