Role of Hypothermia in the Protection of Myocardial Metabolism during Cardiopulmonary By-Pass and Elective Cardiac Arrest

Background: Studies suggest that blood lactate differs between survivors and non-survivors of out-of-hospital cardiac arrest who are transported to hospital. The prognostic role of lactate taken during out-of-hospital cardiac arrest remains unexplored. Aims: To measure the association between lactate taken during out-of-hospital cardiac arrest, survival to hospital and 30-day mortality. Methods: This is a feasibility, single-centre, prospective cohort study. Eligible for inclusion are patients aged ≥18 years suffering out-of-hospital cardiac arrest, receiving cardiopulmonary resuscitation, in the catchment of Newcastle or Gateshead hospitals, who are attended to by a study-trained specialist paramedic. Exclusions are known/apparent pregnancy, blunt or penetrating injury as primary cause of out-of-hospital cardiac arrest and an absence of intravenous access. Between February 2020 and March 2021, 100 participants will be enrolled. Primary outcome is survival to hospital; secondary outcomes are return of spontaneous circulation at any time and 30-day mortality.

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Abstract T P295: Neurological Recovery Following Out-of-hospital Cardiac Arrest: Role of Hypothermia

Stroke ◽

10.1161/str.46.suppl_1.tp295 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

I-Chen Yu ◽

Nathan Schleinkofer ◽

Joo-Young Maeng ◽

Yu-Chieh Chen ◽

Riddhi Doshi ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Neurological Outcome ◽

The United States ◽

Neurological Function ◽

Neuroprotective Strategies ◽

Included Review ◽

Initial Rhythm ◽

Hospital Cardiac Arrest

Introduction: Every year about 70% of coronary heart disease deaths in the United States occur out of hospital, usually presenting as ‘sudden death’ due to cardiac arrest. Despite the improvement of survival with advanced cardiac interventions, mortality remains high. Therapeutic hypothermia (TH) has been shown to be neuroprotective after cardiac arrest. We explored factors associated with good recovery of neurological function following out-of-hospital cardiac arrest (OHCA). Methods: This retrospective study included review of electronic medical records from a major healthcare system in Northeast Indiana. Individuals who suffered OHCA from January 2011 to June 2014 were included. Neurological function was evaluated by Modified Rankin Scale (mRS) at discharge. The neurological outcome was defined as good (mRS 0-3), poor (mRS 4-5), and deceased (mRS 6) to assess the association of examined variables. Results: Among the 111 patients meeting inclusion criteria, the mortality at discharge was 68.6% in TH-treated patients and 84% in normothermia patients. For almost half (47.5%) of the patients undergoing TH who died prior to discharge, brain-related causes were the primary cause of death. 21 patients who had imaging or pathological examinations all showed evidences of ischemic brain injury. Among TH-treated survivors, patients with return of spontaneous cardiac rhythm (ROSC) within 20 minutes of onset were 1.4 times the odds more likely to have a good neurological outcome at discharge (p=0.02). Patients with ventricular fibrillation had 2 times the odds more likely retaining good neurological function at discharge after receiving TH treatment (p=0.012). The time to initiate TH (mean 2.3 ± 1.5 hours) and time to reach target temperature (mean 7.2 ± 2.3 hours) were not associated with neurological outcome at discharge. Conclusions: Initial rhythm and time to ROSC were identified as reliable predictors of good neurological function following OHCA. TH has been found to be insufficient in preventing brain injury. This study emphasizes the need for future studies to develop new neuroprotective strategies to improve survival among OHCA patients.

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Abstract 421: Point of Care Ultrasound Sonography (POCUS) in Cardiac Arrest: Predicting Survivorship

Circulation ◽

10.1161/circ.140.suppl_2.421 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

Ada Wong ◽

Hassan Patail ◽

Sahar Ahmad

Keyword(s):

Cardiac Arrest ◽

Tricuspid Valve ◽

Prospective Observational Study ◽

Thrombus Formation ◽

Point Of Care ◽

Spontaneous Circulation ◽

Point Of Care Ultrasound ◽

Short Term ◽

Flow Stasis

Introduction: Survival after in hospital (IH) cardiac arrest (CA) is at 17% suggesting that CA represents an arena of medical practice which deserves more attention. Ultrasound (US) may have a role in both intra-arrest management and peri-arrest prognosis. Very little is known about the role of ultrasound for IH CA. Hypothesis: Intra- arrest POCUS can provide prognostic value. Methods: This was a single center, prospective observational study and we included all IH CA which occurred when a provider was available to perform a standardized POCUS protocol. US and echocardiography imaging was collected during the intra- arrest period and compared with outcome measures of return of spontaneous circulation (ROSC) and survival to 24 hours post-ROSC. Results: Echocardiographic features which may reflect survivorship include cardiac standstill, right ventricle (RV) blood flow stasis, and the appearance of thrombus formation at or around the tricuspid valve. 10 of 16 (62.50%) patients with cardiac standstill alone and 1 of 3 (33.33%) RV stasis alone did not achieve ROSC. Of those that did achieve ROSC in these two groups, none of the patients survived beyond 24 hours of the CA. 11 of 19 (57.89%) patients with RV stasis in combination with cardiac standstill did not achieve ROSC, and of the remaining 8 patients that achieved ROSC, only 1 patient survived past 24 hours. The combination of cardiac standstill, RV stasis, and tricuspid valve thrombus had 2 of 3 (66.67%) patients fail to achieve ROSC, with the remaining 1 patient surviving only to 24 hours. The presence of cardiac standstill alone confers an association with death, with an odds ratio (OR) of 1.212. RV stasis plus cardiac standstill on intra-arrest POCUS confer a markedly higher OR 0.8250 in association with death. Conclusions: Our preliminary work brings to light the role of POCUS for predicting short term survivorship based on echocardiographic patient features. This may have implications for resource utilization in such events.

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Abstract 26: Prevalence and Pattern of Myocardial Injury in Patients With Cardiac vs Non-Cardiac Cause of Out-Of-Hospital Cardiac Arrest: A One-Year Multicenter Clinical Experience With the High-Sensitivity Troponin T Assay

Circulation ◽

10.1161/circ.140.suppl_2.26 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

David E Hamilton ◽

Bradley J Petek ◽

Lindsay G Panah ◽

Sean R Mendez ◽

Philip E Dormish ◽

...

Keyword(s):

Cardiac Arrest ◽

Myocardial Injury ◽

Troponin T ◽

Clinical Care ◽

High Sensitivity ◽

Severity Of Injury ◽

High Sensitivity Troponin T ◽

One Year ◽

Hospital Cardiac Arrest

Introduction: Myocardial injury is common after out-of-hospital-cardiac arrest (OHCA). However, little is known about the role of early serial hs-TnT in patients with OHCA for identifying myocardial injury, and whether the prevalence and severity of injury differs according to cardiac (CV) vs noncardiac (non-CV) cause of OHCA. Hypothesis: Early hs-TnT will demonstrate high rates of myocardial injury after OHCA regardless of etiology. However, in the first 6 hours after OHCA the extent of hs-TnT elevation and rate of rise will be higher in patients with CV vs non-CV etiology. Methods: Multicenter retrospective study including OHCA patients presenting from 4/1/2018 to 4/1/2019. Hs-TnT was drawn as part of routine clinical care. Results: Baseline hs-TnT was measured in 120 patients after OHCA due to CV (n=51) and non-CV (n=69) etiologies, with subsequent serial hs-TnT values at 1hr, 3hrs, and 6hrs. Hs-TnT was greater than the 99 th percentile in 97% (115/120) of patients and myocardial injury (hs-TnT> 52ng/L) was detected in 88% (105/120) of patients (no difference between CV vs non-CV etiology). Median hs-TnT values were compared between CV and non-CV etiologies of OHCA identifying no difference in hs-TnT at baseline (Figure: 54 [IQR 18-134] vs. 41 [IQR 19-100]; p=0.357) but significantly higher hs-TnT in patients with CV etiology at 1hr (159 [IQR 80-392] vs 93 [IQR 42-247]; p=0.049), 3hrs (400 [IQR 168-1005] vs 151 [IQR 75-401] p=0.009), and 6hrs (746 [IQR 248-1965] vs 251 [IQR 75-580]; p=0.001). Additionally, hs-TnT rise from baseline was present in both CV and non-CV etiologies but was significantly higher in patients with CV etiology (p = 0.005). Conclusions: As identified by hs-TnT, myocardial injury was prevalent in patients with both CV and non-CV cause of OHCA. Baseline hs-TnT was no different in patients with CV vs non-CV cause, however, over the first 6 hours both absolute value and rate of hs-TnT rise were significantly higher for patients with CV vs non-CV etiology of OHCA.

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Abstract 288: High Mobility Group Box 1 (HMGB1) is Involved in the Physiopathology of Post-Cardiac Arrest Syndrome

Circulation ◽

10.1161/circ.138.suppl_2.288 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Emilie Boissady ◽

Cynthia El Hedjaj ◽

Matthias Kohlhauer ◽

Bijan Ghaleh ◽

Renaud Tissier

Keyword(s):

Cardiac Arrest ◽

High Mobility ◽

Brain Regions ◽

Clinical Parameter ◽

High Mobility Group ◽

Neurological Dysfunction ◽

Blood Levels ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

Introduction: After cardiac arrest, a sepsis-like syndrome is observed and contributes to poor prognosis. Hypothesis: This syndrome could be provoked by the massive release of Damage Associated Molecular Patterns (DAMP). Our aim was to investigate the role of the High mobility group box 1 (HMGB1), a well-characterized nuclear DAMP, in an experimental model of cardiac arrest. Methods: Rabbits were anesthetized and submitted to 10 min of ventricular fibrillation. After resuscitation, they either received an administration of the inhibitor of HMGB1 release glycyrrhizin (4 mg/kg i.v.. (GL group, n=6), or saline (5 ml, i.v.; CT group, n=6). Two additional groups received glycyrrhizin (n=4) or saline (n=4) alone without cardiac arrest (Sham groups). Blood samples were withdrawn to evaluate the kinetics of HMGB1 release. After awakening, survival and neurological dysfunction were evaluated during 3 days. Animals were then euthanized and brain histologic damages were assessed (fluorojade-C staining). Results: In the Sham groups, glycyrrhizin did not modify hemodynamic nor clinical parameter as compared to saline. In the CT group, HMGB1 blood levels increased since 30 min after cardiac arrest and remained elevated until the end of the follow-up. This increase in HMGB1 concentrations was significantly attenuated in GL vs CR (18±1 vs 29±5 and ng/ml at 30 min after cardiac arrest, respectively). Neurological dysfunction score or survival were not significantly improved in GL vs CT (e.g., survival = 50 vs 33 % at day 3 in GT vs CT group). However, fluorojade C staining showed a dramatic attenuation of degenerating neurons in GL vs CT groups in all brain regions (e.g., 7±3 vs 32±10 neurons/field in cortex, respectively). Conclusion: HMGB1 played a key role in early inflammation and promoted neuronal death after cardiac arrest. Its inhibition alone does not provide sufficient benefits to improve the clinical outcome. It emphasizes the importance of other contributors, beyond inflammation and neurons cell death. Adjunction of HMGB1 inhibitors to other therapies could still be of interest.

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Abstract 144: Role of Iron Metabolism on Outcomes after Cardiac Arrest and Resuscitation in Mice

Circulation ◽

10.1161/circ.142.suppl_4.144 ◽

2020 ◽

Vol 142 (Suppl_4) ◽

Author(s):

Yusuke Miyazaki ◽

Kei Hayashida ◽

Takamitsu Ikeda ◽

Eizo Marutani ◽

Aranya Bagchi ◽

...

Keyword(s):

Lipid Peroxidation ◽

Cardiac Arrest ◽

Cortical Neurons ◽

Glucose Deprivation ◽

Neurological Function ◽

Lipid Peroxidation Product ◽

Iron Loading ◽

Intracellular Iron ◽

Neurological Outcomes

Introduction: Ischemia and reperfusion (I/R) induces hepcidin in neurons and macrophages. Hepcidin downregulates ferroportin, the only known iron exporter, thereby inhibiting iron efflux and increases iron in ferroportin rich cells while decreasing serum iron. Increased intracellular iron after I/R induces ferroptosis, a regulated cell death characterized by iron-dependent lipid peroxidation. We hypothesized that hepcidin-induced sequestration of iron in neurons and macrophages, both of which express ferroportin, worsens post-cardiac arrest (CA) brain injury. Methods: Levels of hepcidin, iron, and a lipid peroxidation product, malondialdehyde; and expression of HAMP that encodes hepcidin, transferrin receptor 1, and markers of ferroptosis, PTGS2 and CHAC1, were measured in naïve and post-CA wild-type (WT) mice. To examine the effects of hepcidin on CA outcomes, hepcidin-deficient and WT mice were subjected to potassium-induced 8 min of CA followed by cardiopulmonary resuscitation (CPR). To determine the role of increased intracellular iron after CA/CPR, we administered iron-dextran (300 mg/kg IP) or vehicle to WT mice 24h before CA. The effect of liproxstatin-1, a ferroptosis inhibitor, on cell viability was assessed in murine primary cortical neurons after oxygen-glucose deprivation/reperfusion (OGD/R) with iron-loading. Results: Post-CA WT mice exhibited increased systemic HAMP expression, intracellular iron in spleen, and ferroptosis in brain. Hepcidin deficiency that decreases intracellular iron improved survival and neurological function after CA/CPR, whereas pre-arrest iron-loading that increases intracellular iron worsened survival and neurological function after CA/CPR (Fig. 1). Liproxstatin-1 improved neuron viability after OGD/R with iron-loading. Conclusions: Our data suggest that inhibiting hepcidin improves post-CA neurological outcomes by reducing intracellular iron and ferroptosis-induced neuronal death.

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