CT Perfusion for Identification of Patients at Risk for Delayed Cerebral Ischemia during the Acute Phase after Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis

Introduction: Sanguinate is a dual-action oxygen transfer and carbon monoxide-releasing agent with efficacy in animal models of focal brain ischemia and established safety in health volunteers. We performed a dose-escalation study in subarachnoid hemorrhage (SAH) patients at risk for delayed cerebral ischemia (DCI) to evaluate tolerability and explore efficacy in improving cerebral blood flow (CBF) and flow-metabolism balance to vulnerable brain regions. Methods: 12 subjects were studied over three dose tiers: 160mg/kg, 240 mg/kg, and 320 mg/kg, with close safety evaluation prior to proceeding to higher doses. After baseline 15 O-PET measurement of global and regional CBF and oxygen extraction fraction (OEF), Sanguinate was infused over two hours; PET was repeated immediately after and again at 24-hours. Vulnerable brain regions were defined as those with baseline OEF ≥ 0.5. Results: Sanguinate infusion resulted in a significant but transient rise in mean arterial pressure (115±15 to 127±13 mm Hg) that was not dose-dependent. No adverse physiologic or clinical effects were observed with infusion at any dose. Global CBF did not rise significantly after Sanguinate (42.6±7 to 45.9±9 ml/100g/min, p=0.18). However, in the 28% of regions classified as vulnerable, Sanguinate resulted in a significant rise in CBF (42.2±11 to 51.2±18) and reduction in OEF (0.6±0.1 to 0.5±0.11, both p<0.001). The increase in regional CBF was only seen with the two higher doses but OEF improved in all tiers. However, response was attenuated at 24-hours. Conclusions: We safely administered a novel oxygen transport and vasodilating agent to a cohort of patients with SAH. Sanguinate infusion appeared to improve CBF and flow-metabolism balance in vulnerable brain regions and warrants further study in those at-risk for DCI. Higher or repeat dosing may be required for sustained efficacy.

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Meta-analysis of associations of genetic polymorphisms with cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Acta Neurologica Belgica ◽

10.1007/s13760-021-01829-5 ◽

2021 ◽

Author(s):

Yuliia Solodovnikova ◽

Alina Ivaniuk ◽

Tetiana Marusich ◽

Anatoliy Son

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Genetic Polymorphisms ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Delayed Cerebral Ischemia

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CT Perfusion and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.208 ◽

2013 ◽

Vol 34 (2) ◽

pp. 200-207 ◽

Cited By ~ 59

Author(s):

Charlotte H P Cremers ◽

Irene C van der Schaaf ◽

Emerens Wensink ◽

Jacoba P Greving ◽

Gabriel J E Rinkel ◽

...

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Blood Volume ◽

Cerebral Blood Volume ◽

Ct Perfusion ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Mean Transit Time ◽

Delayed Cerebral Ischemia ◽

Mean Difference

Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem, and can only be confirmed with follow-up imaging. For treatment of DCI a diagnostic tool is needed. We performed a systematic review to evaluate the value of CT perfusion (CTP) in the prediction and diagnosis of DCI. We searched PubMed, Embase, and Cochrane databases to identify studies on the relationship between CTP and DCI. Eleven studies totaling 570 patients were included. On admission, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-peak (TTP) did not differ between patients who did and did not develop DCI. In the DCI time-window (4 to 14 days after subarachnoid hemorrhage (SAH)), DCI was associated with a decreased CBF (pooled mean difference −11.9 mL/100 g per minute (95% confidence interval (CI): −15.2 to −8.6)) and an increased MTT (pooled mean difference 1.5 seconds (0.9–2.2)). Cerebral blood volume did not differ and TTP was rarely reported. Perfusion thresholds reported in studies were comparable, although the corresponding test characteristics were moderate and differed between studies. We conclude that CTP can be used in the diagnosis but not in the prediction of DCI. A need exists to standardize the method for measuring perfusion with CTP after SAH, and optimize and validate perfusion thresholds.

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