scholarly journals Update: Microdialysis for Monitoring Cerebral Metabolic Dysfunction after Subarachnoid Hemorrhage

2020 ◽  
Vol 10 (1) ◽  
pp. 100
Author(s):  
Pierce Spencer ◽  
Yinghua Jiang ◽  
Ning Liu ◽  
Jinrui Han ◽  
Yadan Li ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Cerebral Metabolism ◽  
Experimental Studies ◽  
Cerebral Microdialysis ◽  
Secondary Brain Injury ◽  
Metabolic Dysfunction ◽  
Monitoring Tools ◽  
The Relationship ◽  
The Brain

Cerebral metabolic dysfunction has been shown to extensively mediate the pathophysiology of brain injury after subarachnoid hemorrhage (SAH). The characterization of the alterations of metabolites in the brain can help elucidate pathophysiological changes occurring throughout SAH and the relationship between secondary brain injury and cerebral energy dysfunction after SAH. Cerebral microdialysis (CMD) is a tool that can measure concentrations of multiple bioenergetics metabolites in brain interstitial fluid. This review aims to provide an update on the implication of CMD on the measurement of metabolic dysfunction in the brain after SAH. A literature review was conducted through a general PubMed search with the terms “Subarachnoid Hemorrhage AND Microdialysis” as well as a more targeted search using MeSh with the search terms “Subarachnoid hemorrhage AND Microdialysis AND Metabolism.” Both experimental and clinical papers were reviewed. CMD is a suitable tool that has been used for monitoring cerebral metabolic changes in various types of brain injury. Clinically, CMD data have shown the dramatic changes in cerebral metabolism after SAH, including glucose depletion, enhanced glycolysis, and suppressed oxidative phosphorylation. Experimental studies using CMD have demonstrated a similar pattern of cerebral metabolic dysfunction after SAH. The combination of CMD and other monitoring tools has also shown value in further dissecting and distinguishing alterations in different metabolic pathways after brain injury. Despite the lack of a standard procedure as well as the presence of limitations regarding CMD application and data interpretation for both clinical and experimental studies, emerging investigations have suggested that CMD is an effective way to monitor the changes of cerebral metabolic dysfunction after SAH in real-time, and alternatively, the combination of CMD and other monitoring tools might be able to further understand the relationship between cerebral metabolic dysfunction and brain injury after SAH, determine the severity of brain injury and predict the pathological progression and outcomes after SAH. More translational preclinical investigations and clinical validation may help to optimize CMD as a powerful tool in critical care and personalized medicine for patients with SAH.

Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 133 (1) ◽  
pp. 152-158 ◽  
Author(s):  
Umeshkumar Athiraman ◽  
Diane Aum ◽  
Ananth K. Vellimana ◽  
Joshua W. Osbun ◽  
Rajat Dhar ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Secondary Brain Injury ◽  
Large Artery ◽  
Inhalational Anesthetics ◽  
Angiographic Vasospasm ◽  
Inhalational Anesthetic

OBJECTIVEDelayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI—a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH.METHODSAfter IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints.RESULTSThe cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic–only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic–only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic–only technique (OR 0.35, 95% CI 0.14–0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03–2.22), and diabetes (OR 0.19, 95% CI 0.06–0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic–only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI.CONCLUSIONSThese data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

scholarly journals The Association Between Arterial Oxygen Level and Outcome in Neurocritically Ill Patients is not Affected by Blood Pressure

2021 ◽  
Author(s):  
Jaana Humaloja ◽  
Markus B. Skrifvars ◽  
Rahul Raj ◽  
Erika Wilkman ◽  
Pirkka T. Pekkarinen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intensive Care ◽  
Brain Injury ◽  
Hemodynamic Instability ◽  
Arterial Oxygen ◽  
Admission Diagnosis ◽  
Secondary Brain Injury ◽  
Multivariable Logistic Regression Model ◽  
Mechanically Ventilated ◽  
The Relationship

Abstract Background In neurocritically ill patients, one early mechanism behind secondary brain injury is low systemic blood pressure resulting in inadequate cerebral perfusion and consequent hypoxia. Intuitively, higher partial pressures of arterial oxygen (PaO2) could be protective in case of inadequate cerebral circulation related to hemodynamic instability. Study purpose We examined whether the association between PaO2 and mortality is different in patients with low compared to normal and high mean arterial pressure (MAP) in patients after various types of brain injury. Methods We screened the Finnish Intensive Care Consortium database for mechanically ventilated adult (≥ 18) brain injury patients treated in several tertiary intensive care units (ICUs) between 2003 and 2013. Admission diagnoses included traumatic brain injury, cardiac arrest, subarachnoid and intracranial hemorrhage, and acute ischemic stroke. The primary exposures of interest were PaO2 (recorded in connection with the lowest measured PaO2/fraction of inspired oxygen ratio) and the lowest MAP, recorded during the first 24 h in the ICU. PaO2 was grouped as follows: hypoxemia (< 8.2 kPa, the lowest 10th percentile), normoxemia (8.2–18.3 kPa), and hyperoxemia (> 18.3 kPa, the highest 10th percentile), and MAP was divided into equally sized tertiles (< 60, 60–68, and > 68 mmHg). The primary outcome was 1-year mortality. We tested the association between hyperoxemia, MAP, and mortality with a multivariable logistic regression model, including the PaO2, MAP, and interaction of PaO2*MAP, adjusting for age, admission diagnosis, premorbid physical performance, vasoactive use, intracranial pressure monitoring use, and disease severity. The relationship between predicted 1-year mortality and PaO2 was visualized with locally weighted scatterplot smoothing curves (Loess) for different MAP levels. Results From a total of 8290 patients, 3912 (47%) were dead at 1 year. PaO2 was not an independent predictor of mortality: the odds ratio (OR) for hyperoxemia was 1.16 (95% CI 0.85–1.59) and for hypoxemia 1.24 (95% CI 0.96–1.61) compared to normoxemia. Higher MAP predicted lower mortality: OR for MAP 60–68 mmHg was 0.73 (95% CI 0.64–0.84) and for MAP > 68 mmHg 0.80 (95% CI 0.69–0.92) compared to MAP < 60 mmHg. The interaction term PaO2*MAP was nonsignificant. In Loess visualization, the relationship between PaO2 and predicted mortality appeared similar in all MAP tertiles. Conclusions During the first 24 h of ICU treatment in mechanically ventilated brain injured patients, the association between PaO2 and mortality was not different in patients with low compared to normal MAP.

scholarly journals Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Roland Roelz ◽  
Fabian Schubach ◽  
Volker A. Coenen ◽  
Carolin Jenkner ◽  
Christian Scheiwe ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Standard Of Care ◽  
Secondary Brain Injury ◽  
Ringer’S Solution ◽  
Randomized Controlled ◽  
Therapy Protocol

Abstract Background Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer’s solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. Methods This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0–3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. Discussion New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer’s solution. Trial registration Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645. Registered on 8 May 2019

scholarly journals A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yong-Peng Yu ◽  
Xiang-Lin Chi ◽  
Li-Jun Liu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
The Brain

Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.

Use of hemoglobin-based oxygen-carrying solution–201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage

2008 ◽  
Vol 108 (3) ◽  
pp. 575-587 ◽  
Author(s):  
Guy Rosenthal ◽  
Diane Morabito ◽  
Mitchell Cohen ◽  
Annina Roeytenberg ◽  
Nikita Derugin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mr Imaging ◽  
Swine Model ◽  
Secondary Brain Injury ◽  
Large Animal ◽  
Fluoro Jade B ◽  
Significant Difference ◽  
Impact Injury ◽  
The Brain

Object Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. Methods Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. Results Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. Conclusions The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

scholarly journals Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury

2021 ◽  
Vol 1 ◽  
pp. 100310
Author(s):  
K. Akeret ◽  
R.M. Buzzi ◽  
C.A. Schaer ◽  
B.R. Thomson ◽  
F. Vallelian ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Secondary Brain Injury

A Model of Metabolic Supply-Demand Mismatch Leading to Secondary Brain Injury

2021 ◽  
Author(s):  
Jiangling Song ◽  
Jennifer A. Kim ◽  
Aaron Frank Struck ◽  
Rui Zhang ◽  
M. Brandon Westover
Keyword(s):  
Brain Injury ◽  
Mechanistic Model ◽  
Acute Brain Injury ◽  
Extracellular Potassium ◽  
Secondary Brain Injury ◽  
Proposed Model ◽  
The Common ◽  
High Level ◽  
The Brain ◽  
Common Association

Secondary brain injury (SBI) is defined as new or worsening injury to the brain after an initial neurologic insult, such as hemorrhage, trauma, ischemic stroke, or infection. It is a common and potentially preventable complication following many types of primary brain injury (PBI). However, mechanistic details about how PBI leads to additional brain injury and evolves into SBI are poorly characterized. In this work, we propose a mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH) of SBI. Our model, based on the Hodgkin-Huxley model, supplemented with additional dynamics for extracellular potassium, oxygen concentration and excitotoxity, provides a high-level unified explanation for why patients with acute brain injury frequently develop SBI. We investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, and seizures can induce SBI, and suggest three underlying paths for how events following PBI may lead to SBI. The proposed model also helps explain several important empirical observations, including the common association of acute brain injury with seizures, the association of seizures with tissue hypoxia and so on. In contrast to current practices which assume that ischemia plays the predominant role in SBI, our model suggests that metabolic crisis involved in SBI can also be non-ischemic. Our findings offer a more comprehensive understanding of the complex interrelationship among potassium, oxygen, excitotoxicity, seizures and SBI.

Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional ‘H’ therapy in vasospasm treatment

2017 ◽  
Vol 9 (7) ◽  
pp. 659-663 ◽  
Author(s):  
Markus Bruder ◽  
Sae-Yeon Won ◽  
Sepide Kashefiolasl ◽  
Marlies Wagner ◽  
Nina Brawanski ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Favorable Outcome ◽  
Matched Pair ◽  
Control Group ◽  
High Morbidity ◽  
Secondary Brain Injury ◽  
Heparin Group ◽  
Vasomotor Function

ObjectiveSecondary brain injury leads to high morbidity and mortality rates in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, evidence-based treatment strategies are sparse. Since heparin has various effects on neuroinflammation, microthromboembolism and vasomotor function, our objective was to determine whether heparin can be used as a multitarget prophylactic agent to ameliorate morbidity in SAH.MethodsBetween June 1999 and December 2014, 718 patients received endovascular treatment after rupture of an intracranial aneurysm at our institution; 197 of them were treated with continuous unfractionated heparin in therapeutic dosages after the endovascular procedure. We performed a matched pair analysis to evaluate the effect of heparin on cerebral vasospasm (CVS), cerebral infarction (CI), and outcome.ResultsThe rate of severe CVS was significantly reduced in the heparin group compared with the control group (14.2% vs 25.4%; p=0.005). CI and multiple ischemic lesions were less often present in patients with heparin treatment. These effects were enhanced if patients were treated with heparin for >48 hours, but the difference was not significant. Favorable outcome at 6-month follow-up was achieved in 69% in the heparin group and in 65% in the control group.ConclusionsPatients receiving unfractionated continuous heparin after endovascular aneurysm occlusion have a significant reduction in the rate of severe CVS, have CI less often, and tend to have a favorable outcome more often. Our findings support the potential beneficial effects of heparin as a multitarget therapy in patients with SAH, resulting in an additional ‘H’ therapy in vasospasm treatment.

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