SANGUINATE™ (PEGylated Carboxyhemoglobin Bovine) Improves Cerebral Blood Flow to Vulnerable Brain Regions at Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

2017 ◽  
Vol 27 (3) ◽  
pp. 341-349 ◽  
Author(s):  
Rajat Dhar ◽  
Hemant Misra ◽  
Michael N. Diringer
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Brain Regions

Abstract 196: Sanguinate (PEGylated-carboxyhemoglobin-bovine) Improves Cerebral Blood Flow and Oxygen Extraction to Vulnerable Brain Regions in Patients at Risk for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rajat Dhar ◽  
Hemant Misra ◽  
Michael Diringer
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Brain Regions ◽  
Oxygen Extraction ◽  
Patients At Risk ◽  
Higher Doses

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.

Sustained Increased Cerebral Blood Flow with Prophylactic Hypertensive Hypervolemic Hemodilution (“Triple-H” Therapy) after Subarachnoid Hemorrhage

Neurosurgery ◽  
1990 ◽  
Vol 27 (5) ◽  
pp. 729-740 ◽  
Author(s):  
Thomas C. Origitano ◽  
Thomas M. Wascher ◽  
Howard O. Reichman ◽  
Douglas E. Anderson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Inhalation Technique ◽  
Hypervolemic Hemodilution ◽  
Consistent Method ◽  
Triple H

Abstract Delayed cerebral ischemia is the major cause of death and disability in patients who initially survive an aneurysmal subarachnoid hemorrhage (SAH). In the present study, a protocol for prophylactic hypertensive hypervolemic hemodilution (“triple-H” therapy) was utilized in the treatment of SAH, and the response of cerebral blood flow (CBF) was evaluated. Serial CBF measurements, f1 and CBF15, were performed using the xenon-133 inhalation technique to maximize therapy. Surgery within 24 hours of subarachnoid hemorrhage was preferred. In 43 patients with SAH, mean hemoglobin and hematocrit were lowered 3.0 ± 0.3 g/dL and 8.9 ± 0.5%, respectively, over the first 24 hours. Mean f1 and mean CBF15 over the same period increased 34.2 ± 5.8% and 21.2 ± 3.6%, respectively. The maximum mean increase in CBF was 47.2 ± 4.7% for f1 and 30.1 ± 3.2% for CBF15. Cerebral blood flow remained elevated during the 21 days after SAH, irrespective of neurological grade on admission, age, sex, or angiographic arterial narrowing. This is the first report of a consistent method for establishing sustained improvement in CBF after SAH. All patients managed in total compliance with the protocol remained neurologically stable or improved. Two patients developed delayed ischemia and infarction because of the inability to sustain protocol requirements. Thirty-six of the 43 patients (84%) were discharged capable of an independent lifestyle. Triple-H therapy is a safe and effective modality for elevating and sustaining CBF after SAH. In combination with early aneurysm surgery, it can minimize delayed cerebral ischemia and lead to an improved overall outcome.

scholarly journals Early low cerebral blood flow and high cerebral lactate: prediction of delayed cerebral ischemia in subarachnoid hemorrhage

2018 ◽  
Vol 128 (6) ◽  
pp. 1762-1770 ◽  
Author(s):  
Elham Rostami ◽  
Henrik Engquist ◽  
Timothy Howells ◽  
Ulf Johnson ◽  
Elisabeth Ronne-Engström ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Disease Onset ◽  
Delayed Cerebral Ischemia ◽  
Warning Signs ◽  
Xenon Ct ◽  
High Lactate ◽  
Pyruvate Ratio

OBJECTIVEDelayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is one of the major contributors to poor outcome. It is crucial to be able to detect early signs of DCI to prevent its occurrence. The objective of this study was to determine if low cerebral blood flow (CBF) measurements and pathological microdialysis parameters measured at the bedside can be observed early in patients with SAH who later developed DCI.METHODSThe authors included 30 patients with severe SAH. The CBF measurements were performed at Day 0–3 after disease onset, using bedside xenon-CT. Interstitial glucose, lactate, pyruvate, glycerol, and glutamate were measured using microdialysis.RESULTSNine of 30 patients developed DCI. Patients with DCI showed significantly lower global and regional CBF, and lactate was significantly increased in these patients. A high lactate/pyruvate ratio was also detected in patients with DCI.CONCLUSIONSEarly low CBF measurements and a high lactate and lactate/pyruvate ratio may be early warning signs of the risk of developing DCI. The clinical value of these findings needs to be confirmed in larger studies.

scholarly journals Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Vasilios E. Papaioannou ◽  
Karol P. Budohoski ◽  
Michal M. Placek ◽  
Zofia Czosnyka ◽  
Peter Smielewski ◽  
...  
Keyword(s):  
Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Flow Velocity ◽  
Transcranial Doppler ◽  
Blood Flow Velocity ◽  
Cerebral Blood Flow Velocity ◽  
Delayed Cerebral Ischemia ◽  
Area Under The Curve ◽  
Slow Waves

Abstract Background Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia. Methods A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn). Results In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13). Conclusions In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia.

scholarly journals The diagnostic value of 3D-ASL in vertebral artery stenosis among individuals at risk of stroke

2019 ◽  
Author(s):  
DanDan Xu ◽  
XinMing Huang ◽  
GuoEn Cai ◽  
XiaoXia Yang ◽  
YingQing Wang ◽  
...  
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vertebral Artery ◽  
Occipital Lobe ◽  
Brain Regions ◽  
Artery Stenosis ◽  
Vertebral Artery Stenosis ◽  
Left And Right ◽  
The Difference

Abstract Background: This study explored the predictive value of 3D-ASL for vertebral artery stenosis (VAS) in individuals at risk of stroke. Methods: A total of 43 participants at risk of stroke were enrolled in our study. All participants underwent 3D-ASL and carotid artery computed tomography angiography (CTA) or cervical vascular ultrasound. Cerebral blood flow (CBF) was measured in the left and right frontal lobes, temporal lobes, parietal lobes, occipital lobes, basal ganglia, thalamus, cerebellum, and hippocampus. Calculate the CBF BI (CBF BI means: The absolute value of the difference in cerebral blood flow in the corresponding brain regions on the left and right sides of the enrolled personnel) of the corresponding brain regions of the left and right between the VAS group and the non-VAS group respectively. To evaluate the predictive value of 3D-ASL for vascular stenosis in participants at risk of stroke, we used two-sample t-tests to determine if there were significant differences in BI. Results: Among 43 participants at risk of stroke we recruited, 20 participants with vertebral artery stenosis (the VAS group) and 23 without vertebral artery stenosis (the non-VAS group). There were significant differences in BI of the occipital lobe between the VAS group and the non-VAS group (p < 0.05). According to the occipital lobe BI value, the receiver operating characteristic curve (ROC) demonstrated best diagnostic limits of 10.46 ml/(100g×min). Conclusion: Using 3D-ASL to detect cerebral blood flow and calculate the difference of bilateral occipital cerebral blood flow which can help to diagnose vertebral artery stenosis in high risk population of stroke.

Burden of cerebral hypoperfusion in patients with delayed cerebral ischemia after subarachnoid hemorrhage

2020 ◽  
Vol 132 (6) ◽  
pp. 1872-1879
Author(s):  
Hussain Jafri ◽  
Michael N. Diringer ◽  
Michelle Allen ◽  
Allyson R. Zazulia ◽  
Gregory J. Zipfel ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Area Under The Curve ◽  
Brain Regions ◽  
Cerebral Hypoperfusion ◽  
Neurological Deficits ◽  
Contralateral Hemisphere ◽  
The Brain ◽  
Abnormal Brain

OBJECTIVEDelayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) may result in focal neurological deficits and cerebral infarction, believed to result from critical regional rather than global impairments in cerebral blood flow (CBF). However, the burden of such regional hypoperfusion has not been evaluated by gold-standard voxel-by-voxel CBF measurements. Specifically, the authors sought to determine whether the proportion of brain affected by hypoperfusion was greater in patients with DCI than in SAH controls without DCI and whether the symptomatic hemisphere (in those with lateralizing deficits) exhibited a greater cerebral hypoperfusion burden.METHODSSixty-one patients with aneurysmal SAH underwent 15O PET to measure regional CBF during the period of risk for DCI (median 8 days after SAH, IQR 7–10 days). Regions of visibly abnormal brain on head CT studies, including areas of hemorrhage and infarction, were excluded. Burden of hypoperfusion was defined as the proportion of PET voxels in normal-appearing brain with CBF < 25 ml/100 g/min. Global CBF and hypoperfusion burden were compared between patients with and those without DCI at the time of PET. For patients with focal impairments from DCI, the authors also compared average CBF and hypoperfusion burden in symptomatic versus asymptomatic hemispheres.RESULTSTwenty-three patients (38%) had clinical DCI at the time of PET. Those with DCI had higher mean arterial pressure (MAP; 126 ± 14 vs 106 ± 12 mm Hg, p < 0.001) and 18 (78%) were on vasopressor therapy at the time of PET study. While global CBF was not significantly lower in patients with DCI (mean 39.4 ± 11.2 vs 43.0 ± 8.3 ml/100 g/min, p = 0.16), the burden of hypoperfusion was greater (20%, IQR 12%–23%, vs 12%, 9%–16%, p = 0.006). Burden of hypoperfusion performed better than global CBF as a predictor of DCI (area under the curve 0.71 vs 0.65, p = 0.044). Neither global CBF nor hypoperfusion burden differed in patients who responded to therapy compared to those who had not improved by the time of PET. Although hemispheric CBF was not lower in the symptomatic versus contralateral hemisphere in the 13 patients with focal deficits, there was a trend toward greater burden of hypoperfusion in the symptomatic hemisphere (21% vs 18%, p = 0.049).CONCLUSIONSThe burden of hypoperfusion was greater in patients with DCI, despite hemodynamic therapies, higher MAP, and equivalent global CBF. Similarly, hypoperfusion burden was greater in the symptomatic hemisphere of DCI patients with focal deficits even though the average CBF was similar to that in the contralateral hemisphere. Evaluating the proportion of the brain with critical hypoperfusion after SAH may better capture the extent of DCI than averaging CBF across heterogenous brain regions.

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