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.

Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Using Cerebral Blood Flow Velocities and Cerebral Autoregulation Assessment

2015 ◽  
Vol 23 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Lionel Calviere ◽  
Nathalie Nasr ◽  
Catherine Arnaud ◽  
Marek Czosnyka ◽  
Alain Viguier ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Autoregulation ◽  
Delayed Cerebral Ischemia ◽  
Blood Flow Velocities ◽  
Flow Velocities

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.

Abstract TP418: Red Blood Cell Transfusion Increases Cerebral Oxygen Delivery After Subarachnoid Hemorrhage Regardless of Hemoglobin Level

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rajat Dhar ◽  
Allyson Zazulia ◽  
Tom Videen ◽  
Colin P Derdeyn ◽  
Michael Diringer
Keyword(s):  
At Risk ◽  
Subarachnoid Hemorrhage ◽  
Oxygen Delivery ◽  
Delayed Cerebral Ischemia ◽  
Brain Regions ◽  
Oxygen Extraction Fraction ◽  
Red Blood Cell Transfusion ◽  
Cerebral Oxygen ◽  
Arterial Blood ◽  
Patients At Risk

Introduction: Impaired oxygen delivery (DO 2 ), as a result of reduced cerebral blood flow (CBF), is the hallmark of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). Anemia further contributes to reductions in DO 2 and places the brain at risk for infarction. Transfusion, by raising hemoglobin (Hgb) and oxygen content of arterial blood, may be able to reduce the risk of ischemia. However, it is unknown whether an Hgb threshold exists above which CBF will fall sufficient to negate any benefit of transfusion on DO 2 . In this physiologic proof-of-principle study we evaluated whether transfusion improves DO 2 and reduces brain vulnerable to ischemia across a broad range of Hgb values. Methods: 47 SAH patients with/at-risk for DCI with Hgb 7-13 g/dl were transfused 1 unit of red blood cells (RBCs). 15 O-PET imaging was used to measure CBF, DO 2 , and oxygen extraction fraction (OEF) before and after transfusion. Vulnerable brain regions were defined as those with baseline DO 2 < 4.5 ml/100g/min (equivalent to CBF of 25 ml/100g/min at low-normal Hgb). Results: Baseline Hgb was 9.7 g/dl (range 6.9-12.5) and CBF was 43±11 ml/100g/min. After transfusion, Hgb rose by 12% and global DO 2 by 10% (from 5.0 to 5.5 ml/100g/min, p=0.001), with CBF only marginally lower; response to transfusion was not dependent on Hgb level. Transfusion resulted in a greater (16%) rise in DO 2 , associated with a larger reduction in OEF, in vulnerable brain regions (p=0.005 for low vs. normal regions), even after adjusting for Hgb. Number of vulnerable regions was reduced from median 9 to 4 per patient (p=0.005). Conclusions: Transfusion of RBCs to patients at-risk for DCI improves cerebral oxygen delivery, preferentially to vulnerable regions and reduces brain at-risk for ischemia. This physiologic benefit does not appear limited to those with severe anemia but persists to Hgb as high as 13 g/dl. Our findings suggest that restrictive transfusion practices may not be appropriate in this population. Prospective trials are needed to determine if these physiologic benefits outweigh risks of transfusion and translate into clinical prevention of DCI.

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.

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