Cardiac Arrest Resuscitation Research Articles

Relationship of Public Interest in Cardiopulmonary Resuscitation with Cardiac Arrest Epidemiology and National Socioeconomic Indicators: Exploratory Infodemiology Study.

Web-based big data analytics provides a great opportunity to measure public interest in cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). This study aimed to examine associations of online interest in CPR and CA with epidemiological characteristics of out-of-hospital CA (OHCA) and national socioeconomic indicators in a set of European countries. Country-level online search popularity data for CPR and CA topics measured in relative search volume (RSV) with Google Trends (GT), published OHCA epidemiological indicators, and World Bank's socioeconomic statistics of 28 European countries for the year 2017 were analyzed for correlation using Spearman's rank correlation coefficient (r S ). Whereas OHCA incidence, bystander CPR rate, and hospital survival did not correlate with RSV for CPR or CA, the rate of return of spontaneous circulation (ROSC) demonstrated a positive correlation with RSV for CPR (r S = 0.388; P = .042). Further, RSV for CPR positively correlated with countries' gross domestic product and health expenditure (r S = 0.939 and 0.566; P ≤.002) and negatively correlated with mortality caused by road traffic injury (r S = -0.412; P = .029). For the sample of European countries, public interest in CPR or CA showed no relationship with real bystander CPR rates and therefore could not be recommended as a proxy of community readiness to attempt resuscitation. The association of RSV for CPR with the rate of ROSC and countries' socioeconomic characteristics suggests it could be used for identifying geographies with poor performance of prehospital systems in terms of managing CA, in particular where effective epidemiological surveillance for CA may be unavailable.

Quality indicators for post-resuscitation care after out-of-hospital cardiac arrest: a joint statement from the Association for Acute Cardiovascular Care of the European Society of Cardiology, the European Resuscitation Council, the European Society of Intensive Care Medicine, and the European Society for Emergency Medicine.

Quality of care (QoC) is a fundamental tenet of modern healthcare and has become an important assessment tool for healthcare authorities, stakeholders and the public. However, QoC is difficult to measure and quantify because it is a multifactorial and multidimensional concept. Comparison of clinical institutions can be challenging when QoC is estimated solely based on clinical outcomes. Thus, measuring quality through quality indicators (QIs) can provide a foundation for quality assessment and has become widely used in this context. QIs for the evaluation of QoC in acute myocardial infarction are now well-established, but no such indicators exist for the process from resuscitation of cardiac arrest and post-resuscitation care in Europe. The Association of Acute Cardiovascular Care of the European Society Cardiology, the European Resuscitation Council, European Society of Intensive Care Medicine and the European Society for Emergency Medicine, have reflected on the measurement of QoC in cardiac arrest. A set of QIs have been proposed, with the scope to unify and evolve QoC for the management of cardiac arrest across Europe. We present here the list of QIs (6 primary QIs and 12 secondary Qis), with descriptions of the methodology used, scientific justification and motives for the choice for each measure with the aim that this set of QIs will enable assessment of the quality of postout-of-hospital cardiac arrest management across Europe.

Donors brain-dead after successful resuscitation of cardiac arrest: Early outcome and postoperative complications of lung recipients

BackgroundThe outcomes of lung transplantation (LT) recipients who received a graft from a brain-dead donor after successful resuscitation from cardiac arrest (CA donors) have been poorly described. This study compared the one-year survival of LT recipients depending on the CA status of the donor. MethodsThis prospective observational single-centre study analysed all consecutive patients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and December 2020. All donors who experienced CA prior to organ donation, regardless of rhythm or duration, were considered CA donors. The postoperative complications and outcomes of LT recipients were analysed. The one-year survival was compared using Kaplan-Meier curves and log-rank tests. Independent risk factors for one-year mortality were assessed using multivariate analysis (p < 0.05 was considered significant). The Paris North Hospitals Institutional Review Board approved the study. ResultsA total of 236 LT recipients were analysed and 66 (28%) received a graft from a CA donor. The median durations of no/low flow were 4 [0–10]/20 [15–30] minutes, respectively. Shockable and non-shockable rhythms were observed in 11 (17%) and 47 (72%) of the CA donors, respectively. The characteristics of the grafts and early postoperative complications were not different in the CA and non-CA groups. Receiving a graft from a CA donor was not an independent risk factor for recipient one-year mortality. ConclusionReceiving a graft from a CA donor did not worsen the outcome of LT recipients. Acceptation of these grafts must be systematically considered to increase the pool of available grafts.

Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms

Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA? In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95%CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome. We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95%CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95%CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95%CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95%CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95%CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95%CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95%CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95%CI, 0.39-1.85). Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm. Center for Open Science: (https://osf.io/arxwq).

Effects of the 2020 COVID-19 pandemic on outcomes of out-of-hospital cardiac arrest and bystander resuscitation efforts: a nationwide cohort study in Japan.

Background and importance There is limited knowledge about the nationwide impact of the 2020 COVID-19 pandemic in Japan on out-of -hospital cardiac arrest (OHCA) outcomes.Objectives The aim of this study was to investigate the impact of the 2020 COVID-19 pandemic on OHCA outcomes and bystander resuscitation efforts in Japan. Design Retrospective analysis of a nationwide population-based registry of OHCA cases. Settings and participants To conduct this study, we created a comprehensive database comprising 821 665 OHCA cases by combining and reconciling the OHCA database for 835 197 OHCA cases between 2017 and 2020 with another database, including location and time records. After applying exclusion and inclusion criteria, we analysed 751 617 cases.Outcome measures and analysis The primary outcome measure for this study was survival with neurologically favourable outcome (cerebral performance category 1 or 2). We compare OHCA characteristics and outcomes between prepandemic and pandemic years, and also investigated differences in factors associated with outcomes. Results We found that survival with neurologically favourable outcome and the rates of bystander cardiopulmonary resuscitation (CPR) slightly increased in the pandemic year [2.8% vs. 2.9%; crude odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03-1.10; 54.1% vs. 55.3%, 1.05 (1.04-1.06), respectively], although the incidence of public access defibrillation (PAD) slightly decreased [1.8% vs. 1.6%, 0.89 (0.86-0.93)]. Calls for hospital selection by emergency medical service (EMS) increased during the pandemic. Subgroup analysis showed that the incidence of neurologically favourable outcome increased in 2020 for OHCA cases that occurred on nonstate of emergency days, in unaffected prefectures, with noncardiac cause, nonshockable initial rhythm, and during daytime hours. Conclusions During the 2020 COVID-19 pandemic in Japan, survival with neurologically favourable outcome of OHCA patients and bystander CPR rate did not negatively change, despite the decrement in PAD incidence. However, these effects varied with the state of emergency, region, and characteristics of OHCA, suggesting an imbalance between medical demand and supply, and raising concerns about the pandemic.

A Retrospective Nationwide Comparison of the iGel and King Laryngeal Tube Supraglottic Airways for Out-of-Hospital Cardiac Arrest Resuscitation

Introduction While various supraglottic airway devices are available for use during out-of-hospital cardiac arrest (OHCA) resuscitation, comparisons of patient outcomes by device are limited. In this study, we aimed to compare outcomes of OHCA patients who had airway management by emergency medical services (EMS) with the iGel or King-LT. Methods We used the 2018-2021 ESO Data Collaborative public use research datasets for this retrospective study. All patients with non-traumatic OHCA who had iGels or King-LTs inserted by EMS were included. Our primary outcome was survival to discharge to home, and secondary outcomes included first-pass success, return of spontaneous circulation (ROSC), and prehospital rearrest. We examined the association between airway device and each outcome using two-level mixed effects logistic regression with EMS agency as the random effect, adjusted for standard Utstein variables and failed intubation prior to supraglottic airway insertion. Average treatment effects were calculated through propensity score matching. Results A total of 286,192 OHCA patients were screened, resulting in 93,866 patients eligible for inclusion in this analysis. A total of 9,456 transported patients (59.8% iGel) had associated hospital disposition data. Use of the iGel was associated with greater survival to discharge to home (aOR:1.36 [1.06, 1.76]; ATE: 2.2%[+0.5, +3.8]; n = 7,576), first pass airway success (aOR:1.94 [1.79, 2.09]; n = 73,658), and ROSC (aOR:1.19 [1.13, 1.26]; n = 73,207) in comparison to airway management with the King-LT. iGel use was associated with lower odds of experiencing a rearrest (aOR:0.73 [0.67, 0.79]; n = 20,776). Among patients who received a supraglottic device as a primary airway, use of the iGel was not associated with significantly greater survival to discharge to home (aOR:1.26 [0.95, 1.68]). Among patients who received a supraglottic device as a rescue airway following failed intubation, use of the iGel was associated with greater odds of survival to discharge to home (aOR:2.16 [1.15, 4.04]). Conclusion In this dataset, use of the iGel during adult OHCA resuscitation was associated overall with better outcomes compared to use of the King-LT. Subgroup analyses suggested that use of the iGel was associated with greater odds of achieving the primary outcome than the King-LT when used as a rescue device but not when used as the primary airway management device.

Canagliflozin Pretreatment Attenuates Myocardial Dysfunction and Improves Postcardiac Arrest Outcomes After Cardiac Arrest and Cardiopulmonary Resuscitation in Mice.

The SGLT2 inhibitor, canagliflozin, not only reduces glycemia in patients with type 2 diabetes but also exerts cardioprotective effects in individuals without diabetes. However, its potential beneficial effects in cardiac arrest have not been characterized. The purpose of this study was to examine the protective effect of canagliflozin pretreatment on postresuscitation-induced cardiac dysfunction in vivo. Male C57/BL6 mice were randomized to vehicle (sham and control) or canagliflozin treatment groups. All mice except for the sham-operated mice were subjected to potassium chloride-induced cardiac arrest followed by chest compressions and intravenous epinephrine for resuscitation. Canagliflozin therapy efficacies were evaluated by electrocardiogram, echocardiography, histological analysis, inflammatory response, serum markers of myocardial injury, protein phosphorylation analysis, and immunohistological assessment. Canagliflozin-pretreated mice exhibited a higher survival rate (P < 0.05), a shorter return of spontaneous circulation (ROSC) time (P < 0.01) and a higher neurological score (P < 0.01 or P < 0.001) than control mice after resuscitation. Canagliflozin was effective at improving cardiac arrest and resuscitation-associated cardiac dysfunction, indicated by increased left ventricular ejection fraction and fractional shortening (P < 0.001). Canagliflozin reduced serum levels of LDH, CK-MB and α-HBDH, ameliorated systemic inflammatory response, and diminished the incidence of early resuscitation-induced arrhythmia. Notably, canagliflozin promoted phosphorylation of cardiac STAT-3 postresuscitation. Furthermore, pharmacological inhibition of STAT-3 by Ag490 blunted STAT-3 phosphorylation and abolished the cardioprotective actions of canagliflozin. Canagliflozin offered a strong cardioprotective effect against cardiac arrest and resuscitation-induced cardiac dysfunction. This canagliflozin-induced cardioprotection is mediated by the STAT-3-dependent cell-survival signaling pathway.

Role of initial cardiac activity assessed by point-of-care ultrasonography in predicting cardiac arrest outcomes: A prospective cohort study.

This study was conducted to investigate the association between visible cardiac activity in point-of-care ultrasound (POCUS) and outcomes of cardiac arrest such as the return of spontaneous circulation (ROSC), survival to inpatient admission (SIA), and survival to hospital discharge (STHD). This was a single-center, prospective cohort study conducted in the emergency department (ED). Adult (age >18 years) patients in cardiac arrest were included in the study. Exclusion criteria of the study were - traumatic arrest, out-of-hospital cardiac arrest resuscitated before ED admission, and patients presenting with initial shockable rhythm. Patients whose ultrasound images could not be obtained and whose resuscitation stopped following POCUS were also excluded from the study. POCUS examination was done after 2 min of initiation of cardiopulmonary resuscitation (CPR) and visible cardiac activity was defined as any visible movement of the myocardium, excluding movement of blood within cardiac chambers, or isolated valve movement. The duration of POCUS examinations was limited to 10 s. The association of initial cardiac activity in POCUS with the outcomes of cardiac arrest was investigated. Out of 140 patients screened, 84 patients were included in the study. Rates of ROSC, SIA, and STHD were found in 23 (27.4%), 9 (10.7%), and 2 (2.4%) patients, respectively. Only 15 out of 84 (17.9%) patients had cardiac activity on the initial POCUS examination. Cardiac activity was seen in 52.2% of patients with ROSC, which was significantly higher (P < 0.001) as compared with the no-ROSC group (4.9%). Unlike the above association, there was no difference in the incidence of initial cardiac activity in patient groups who got admitted (SIA) and discharged (STHD) versus those who died. In the multivariate regression analysis, the duration of CPR and initial cardiac activity significantly predicted the rate of ROSC, with an adjusted odds ratio of 0.93 (95% confidence interval [CI]: 0.86-0.99, P = 0.04) and 24.8 (95% CI: 3.17-89.41, P = 0.002), respectively. None of the variables predicted SIA and STHD. The positive likelihood ratio of cardiac activity for predicting ROSC, SIA, and STHD were 10.6, 2.1, and 2.9, respectively. Integration of POCUS in cardiac arrest resuscitation was shown to be helpful in terms of prognostic significance of the presence of initial cardiac activity in terms of ROSC.

TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway.

Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) can cause brain injury, which is one of the factors affecting the recovery of brain function in CA patients. There is increasing evidence that tumor necrosis factor-like weak apoptosis-inducing factor (TWEAK) is associated with the brain injury diseases. This study was aimed to investigate the modulation mechanism of TWEAK involved in brain injury after cardiac arrest/subsequent cardiopulmonary resuscitation (CA/CPR). For in vivo experiments, healthy male Sprague-Dawley (SD) rats were applied to establish CA/CPR model, and oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated neurons model was established in vitro. TWEAK short hairpin RNAs (shRNAs) were injected into the lateral ventricle of CA/CPR rats or transfected into OGD/R cell culture to analyze the consequent alteration in neurological scores, behavioral tests, cell proliferation, cell apoptosis, and neuroinflammation through immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA). There were high expressions of TWEAK and fibroblast growth factor-inducible 14 (Fn14) in the cerebral cortex of CA/CPR rats and OGD/R-stimulated neuronal cells. TWEAK knockdown attenuated cell apoptosis, inflammation and showed better behavioral tests in CA/CPR rats. Furthermore, TWEAK shRNAs obviously facilitated cell proliferation, suppressed apoptosis and inflammation after OGD/R injury. Western blotting results stated that TWEAK silencing promoted phosphorylated p38 (p-p38) and phosphorylated p65 (p-p65) expressions. TWEAK might be involved in the pathogenesis of CA/CPR through inhibiting p38 MAPK/NF-κB pathway.

Shenfu Injection Protects Brain Injury in Rats with Cardiac Arrest through Nogo/NgR Pathway.

The effect of Shenfu injection on brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) along with the underlying mechanism of axonal regeneration was explored. CA/CPR model in rats was established for subsequent experiments. A total of 160 rats were randomly divided into sham group, model group, conventional western medicine (CWM) group, Shenfu group, and antagonist group (n = 32 per group). After 3 hours, 24 hours, 3 days, and 7 days of drug administration, the modified Neurological Severity Score tests were performed. The ultrastructure of the brain and hippocampus was observed by electron microscopy. Real-time quantitative polymerase chain reaction (PCR), western blotting, and immunohistochemistry were used to detect Nogo receptor (NgR) expression in the hippocampus and cerebral cortex, and Nogo-NgR expression in CA/CPR model. Neurological deficits in the model group were severe at 3 hours, 24 hours, 3 days, and 7 days after the recovery of natural circulation, whereas the neurological deficits in CWM, antagonist, and Shenfu group were relatively mild. The ultrastructure of neuronal cells in Shenfu group had relatively complete cell membranes and more vesicles than those in the model group. The results of PCR and western blotting showed lower messenger ribonucleic acid and protein expression of NgR in Shenfu group than the model group and CWM group. Immunohistochemical examination indicated a reduction of Nogo-NgR expression in Shenfu group and antagonist group. Our results suggested that Shenfu injection reduced brain injury by attenuating Nogo-NgR signaling pathway and promoting axonal regeneration.

1156: THE BYSTANDER EFFECT: THE INFLUENCE OF KNOWN BYSTANDER CPR AND WITNESSED ARREST ON ED CPR DURATION

Introduction: Long term outcomes for patients with out-of-hospital cardiac arrest (OHCA) are generally poor, with global 1-month survival rates of just over 10%. Witnessed cardiac arrest and bystander cardiopulmonary resuscitation (CPR) are associated with improved rates of ROSC and survival to hospital discharge. The goal of this study is to evaluate the relationship between known bystander CPR and witnessed cardiac arrest on physician decision to terminate resuscitation in the ED. Methods: We prospectively evaluated a consecutive sample of OHCAs that presented to a single tertiary care emergency department from 2018-2019. Data were collected via video surveillance of ED resuscitation bays in combination with patient chart review. Multivariate linear regression was used to evaluate the relationship between witnessed cardiac arrest, bystander CPR, and time to termination of resuscitation. Results: A total of 71 patients met inclusion criteria of OHCA with EMS CPR and termination of resuscitation in the ED. 51 patients had a non-shockable initial presenting rhythm and 20 patients presented with shockable rhythms. Bystander CPR was associated with an average decrease in ED CPR duration of 7.4 minutes (p = 0.02) for patients with non-shockable rhythms, but was not associated with ED CPR duration for patients with shockable rhythms (y = 0.49; p = 0.95). There was no difference in time to termination between witnessed and unwitnessed cardiac arrests. Conclusions: The performance of bystander CPR is one of the most important links in the chain of survival that improves clinical outcomes in cardiac arrest. In our population, bystander CPR was a significant factor in physician decision to terminate resuscitation for patients presenting in non-shockable rhythms. Patients with shockable rhythms were resuscitated longer and without consideration of bystander CPR or presence of witnessed arrest, which may be related to known better chances of ROSC and overall neurologic outcomes for these patients. These findings suggest that bystander CPR may be factored into the total resuscitation time by emergency clinicians when considering the multifactorial decision to terminate CPR.

Intra-aortic and Intra-caval Balloon Pump Devices in Experimental Non-traumatic Cardiac Arrest and Cardiopulmonary Resuscitation.

Intra-aortic balloon pump (IABP) use during CPR has been scarcely studied. Intra-caval balloon pump (ICBP) may decrease backward venous flow during CPR. Mechanical chest compressions (MCC) were initiated after 10min of cardiac arrest in anesthetized pigs. After 5min of MCC, IABP (n = 6) or ICBP (n = 6) was initiated. The MCC device and the IABP/ICBP had slightly different frequencies, inducing a progressive peak pressure phase shift. IABP inflation 0.15s before MCC significantly increased mean arterial pressure (MAP) and carotid blood flow (CBF) compared to inflation 0.10s after MCC and to MCC only. Coronary perfusion pressure significantly increased with IABP inflation 0.25s before MCC compared to inflation at MCC. ICBP inflation before MCC significantly increased MAP and CBF compared to inflation after MCC but not compared to MCC only. This shows the potential of IABP in CPR when optimally synchronized with MCC. The effect of timing of intra-aortic balloon pump (IABP) inflation during mechanical chest compressions (MCC) on hemodynamics. Data from12 anesthetized pigs.

Ventilation rates measured by capnography during out-of-hospital cardiac arrest resuscitations and their association with return of spontaneous circulation

BackgroundClinical guidelines for adult out-of-hospital cardiac arrest (OHCA) recommend a ventilation rate of 8–10 per minute yet acknowledge that few data exist to guide recommendations. The goal of this study was to evaluate the utility of continuous capnography to measure ventilation rates and the association with return of spontaneous circulation (ROSC). MethodsThis was a retrospective observational cohort study. We included all OHCA during a two-year period and excluded traumatic and pediatric patients. Ventilations were recorded using non-invasive continuous capnography. Blinded medically trained team members manually annotated all ventilations. Four techniques were used to analyze ventilation rate. The primary outcome was sustained prehospital ROSC. Secondary outcomes were vital status at the end of prehospital care and survival to hospital admission. Univariable and multivariable logistic regression models were constructed. ResultsA total of 790 OHCA were analyzed. Only 386 (49%) had useable capnography data. After applying inclusion and exclusion criteria, the final study cohort was 314 patients. The median ventilation rate per minute was 7 (IQR 5.4–8.5). Only 70 (22%) received a guideline-compliant ventilation rate of 8–10 per minute. Sixty-two (20%) achieved the primary outcome. No statistically significant associations were observed between any of the ventilation parameters and patient outcomes in both univariable and multivariable logistic regression models. ConclusionsWe failed to detect an association between intra-arrest ventilation rates measured by continuous capnography and proximal patient outcomes after OHCA. Capnography has poor reliability as a measure of ventilation rate. Achieving guideline-compliant ventilation rates remains challenging.

Early Neurological ASsessment with pupillometrY during Cardiac Arrest REsuscitation (EASY-CARE): protocol for an observational multicentre prospective study

IntroductionOut-of-hospital cardiac arrest is burdened with a high rate of ineffective resuscitation and poor neurological outcome among survivors. To date, there are few perfusion assessment tools during cardiopulmonary resuscitation and...

Ginsenoside-Rg1 mitigates cardiac arrest-induced cognitive damage by modulating neuroinflammation and hippocampal plasticity

Ginsenoside-Rg1 can effectively ameliorate mental disorders, but whether ginsenoside-Rg1 plays a neuroprotective role in cardiac arrest and cardiopulmonary resuscitation (CA/CPR)-induced cognitive impairment remains unclear. In this study, a 5-min asphyxia-based CA/CPR rat model was established to explore the mechanisms underlying the effects of ginsenoside-Rg1 (40 mg·kg-1·d-1, ip, 14 days) on its cognitive alterations. These CA/CPR rats displayed spatial learning and memory impairment in the Morris water maze, as reflected in the compromised basal synaptic transmission and long-term potentiation (LTP) at the Schaffer collateral of hippocampal CA1 area in vivo electrophysiology, whereas the ginsenoside-Rg1 remarkably mitigated these alterations. Next, we found that ginsenoside-Rg1 inhibited hippocampal neuroinflammation by alleviating the CA/CPR-induced hippocampal activation of microglia and astrocytes and the overexpression of related proinflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α). In addition, ginsenoside-Rg1 improved CA/CPR-induced hippocampal neuronal apoptosis, dendritic spines and synaptic ultrastructure defects as associated with the upregulation of the key synaptic regulatory proteins. Furthermore, ginsenoside-Rg1 could ameliorate CA/CPR-induced aberrant expression of the key regulators of hippocampal glutamate signaling pathways, excitatory amino acid transporter 2 (EAAT2), excitatory amino acid transporter 1 (EAAT1), Glutamine Synthetase (GS), GluN2B, and glutamate. In conclusion, ginsenoside-Rg1 exerts its neuroprotective effects by ameliorating hippocampus-dependent neuroglia activation-mediated neuroinflammation and neuroplasticity deficits, shedding new light on the therapeutic intervention of CA/CPR-related cognitive disorders.

BAICALEIN RELIEVES BRAIN INJURY VIA INHIBITING FERROPTOSIS AND ENDOPLASMIC RETICULUM STRESS IN A RAT MODEL OF CARDIAC ARREST.

Background: Cardiac arrest (CA) is one of the leading causes of death worldwide. Endoplasmic reticulum (ER) stress and ferroptosis are proven pathological mechanisms implicated in neuronal damage. Baicalein, a ferroptosis Inhibitor, improved outcomes after traumatic brain injury. We aimed to explore the effects of baicalein on brain injury via ferroptosis and ER stress in a rat model of CA.Methods: Cardiac arrest models were established in Sprague-Dawley (SD) rats. The sham group (n = 6) was untreated with inducing ventricular fibrillation to cardiac arrest and cardiopulmonary resuscitation (CPR). Survival rats were randomly divided into five groups (n = 6). Ferroptosis inhibitor and ER stress agonist were administered separately and together in three groups. There was no drug intervention in the remaining group. The neurological deficit scores were recorded. Characteristics of ferroptosis were observed. And the associated protein of ferroptosis and ER stress were determined by Western blot. Cerebral ROS production was measured by using 2',7'-dichlorofluorescein diacetate as the oxidative fluorescent probe. Results: Baicalein treatment improved neurological outcomes and decreased neurocyte injuries compared with CPR group. The changes of ferroptosis, more specifically, iron content, glutathione peroxidase 4 (GPX4), reactive oxygen species (ROS), arachidonate 15-lipoxygenase (ALOX15) and mitochondrial characteristics, were observed in brain tissue after ROSC. ALOX15 was lower in baicalein group than in CPR group. The morphology and structure of mitochondria in baicalein group were better than in CPR group. The ER stress markers, glucose-regulated protein 78, activating Transcription Factor 4 and C/EBP homologous protein was lower in baicalein group compared with CPR group. ROS in tunicamycin group was higher than in CPR group. And ROS in baicalein +tunicamycin group was lower than in tunicamycin group. Conclusion: Ferroptosis and ER stress are both involved in brain injury after ROSC. Baicalein alleviates brain injury via suppressing the ferroptosis and ER stress, and reduces ROS partly through inhibiting ER stress. Baicalein is a potential drug to relieve brain injury after ROSC.

Left ventricle chest compression improves ETCO2, blood pressure, and cerebral blood velocity in a swine model of cardiac arrest and cardiopulmonary resuscitation

IntroductionDuring cardiopulmonary resuscitation (CPR), high quality chest compressions are critical to organ perfusion, especially the brain. Yet, the optimal location for chest compressions is unclear. It was hypothesized that compared with the standard chest compression (SCC) location, left ventricle chest compressions (LVCCs) would result in greater end-tidal carbon dioxide (ETCO2), blood pressure (BP), and cerebral blood velocity (CBV) during CPR in swine. MethodsFemale Landrace swine (N = 32; 35 ± 2 kg) underwent two mins of untreated asphyxiated cardiac arrest (CA). Thereafter, swine were treated with three 2-min cycles of either SCC or LVCC mechanical basic life support CPR (LUCAS 3). ETCO2 (in-line sampling), BP (arterial catheter line), and CBV (transcranial Doppler) were measured during the pre-CA, untreated-CA, and CPR-treated phases. ResultsETCO2, BP, and CBV were similar between groups at pre- and during untreated-CA (P ≥ 0.188). During CPR, ETCO2 (36 ± 6 versus 24 ± 10 mmHg, P < 0.001), mean arterial BP (MAP; 49 ± 9 versus 37 ± 9 mmHg, P = 0.002), and CBV (11 ± 5 versus 5 ± 2 cm/s, P < 0.001) were significantly greater in the LVCC versus SCC group. Moreover, a greater proportion of animals obtained targets for ETCO2 (ETCO2 ≥ 20 mmHg; 52 % (17/33) versus 100 % (32/32), P < 0.001) and diastolic BP (DBP ≥ 25 mmHg; 82 % (33/40) versus 97 % (48/49), P = 0.020) in the LVCC versus SCC group. ConclusionIndicators of cardiac output, BP, and cerebral perfusion during CPR were greatest in the LVCC group, suggesting the quality of chest compressions during BLS CPR may be improved by performing compressions over the left ventricle compared to the centre of the chest.

Abstract 120: Impact Of Mask Application On Aerosol Generation During Chest Compression And Defibrillation In A Swine Cardiac Arrest Model

Introduction: We previously demonstrated that defibrillation followed by chest compression generates more aerosols than chest compression or no-flow state alone. However, the best strategies to prevent aerosol spread during cardiac arrest (CA) resuscitation remain unknown. We hypothesized that mask applications could reduce aerosol spread during chest compressions and defibrillation in a swine CA model. Methods: To simulate witnessed CA with bystander-initiated CPR, 24 female non-intubated swine (43.8 [2.7] kg) underwent 4 minutes of untreated ventricular fibrillation CA followed by 10 two-minute cycles of mechanical chest compression and defibrillation without ventilation. The animals were randomized to receive no mask, cloth mask, surgical mask, N95 mask, or a sealed nose cone over their snouts during resuscitation (n=5/group except nose cone n=4). The diameter (0.3 - 10 μm) and quantity of particles generated during 45-second intervals of no-flow, chest compression, and after each defibrillation were measured 2 inches anterior to the snout. Results: There were no significant differences between total particles generated during chest compression after defibrillation in unmasked versus masked animals regardless of the mask type, while the nose cone significantly reduced total particles. These findings were consistent across all 10 defibrillations (Fig. 1a) and all particle sizes (Fig. 1b). Furthermore, the minimal pre- and post-defibrillation particles detected outside of the nose cone indicated that the ineffectiveness of masks in preventing aerosol spread during CA resuscitation was likely due to their inadequate fit (Fig. 1c). Conclusion: Mask application did not reduce aerosol spread during defibrillation followed by chest compression in a swine CA model. Our data indicate that mask fit is a critical parameter for reducing aerosol transport and do not support mask application on CA victims during bystander-initiated CPR.

Abstract 15563: Analysis of the Ventricular Fibrillation Waveform Can Guide Resuscitation in Cardiac Arrest by Identifying the Precipitating Cause and Estimating the Underlying Hemodynamics

Background: Patients presenting with out of hospital cardiac arrest (OHCA) and prolonged (&gt;30 min) cardiopulmonary resuscitation (CPR) face nearly 100% mortality. In patients presenting with ventricular fibrillation (VF), coronary ischemia is thought to be the cause in up to 60%. As conventional CPR does not reverse a coronary ischemia, CPR often must be done until a patient can be brought to a cardiac catheterization laboratory (CCL) where the underlying cause (acute ischemia) can be treated. In a porcine model of cardiac arrest, we have previously demonstrated that machine learning (ML) targeting invasive hemodynamic monitoring, could significantly improve CPR quality. To advance the clinical relevance of the machine-controlled CPR methods, we developed ML algorithms that can diagnose coronary ischemia during VF, and infer the underlying hemodynamics while performing CPR. Methods: In a porcine model of cardiac arrest, VF was induced via high-grade coronary occlusion (ischemia) or electrical stimulation (dysrhythmia). The animals (n = 72) were left in VF for 3 minutes prior to intervention and the ECG waveform was collected. The VF signal was converted to the frequency domain using a fast-fourier transformation and an ensemble classifier was developed to detect underlying ischemia. CPR was then initiated and the VF waveform was continuously monitored along with the coronary perfusion pressure (CPP). We then developed a 20-layer convolutional neural network (CNN) to non-invasively infer the CPP from a 10-second VF waveform. Results: Animal studies were split into training and test sets. When using the developed ML technique to detect ischemia from the VF waveform, evaluation of the test set yielded an area under the curve (AUC) of 0.81 on a ROC. When we used the CNN to infer the underlying hemodynamics, we demonstrated a high correlation between measured and predicted CPP in the test set. The AUC for the ROC when predicting a CPP of &gt;15 mmHg was 0.85. Conclusion: Survival for patients with OHCA secondary to coronary ischemia will improve with rapid diagnosis and high quality CPR. Our results demonstrate the proof-of-concept that the VF waveform contains features that can guide resuscitation for cause identification and hemodynamic improvement.

Abstract 155: Intra-arrest Epinephrine Administration is Associated with Increased Myocardial Injury and Inflammation in a Novel Murine Model of Cardiac Arrest

Introduction: Epinephrine (EPI) is routinely administered in cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study aims to assess the effects of epinephrine on myocardial inflammation and injury. Hypothesis: Intra-arrest epinephrine use is associated with increased myocardial injury, inflammation and fibrosis. Methods: A total of 56 mice were included in the study. Both cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (CA only) for 4-minutes prior to delivery of intravenous epinephrine (250ul, 30ug/ml) or saline (250ul) and manual chest compressions (300BPM) for 4-minutes (Fig A). Mice were recovered for assessments at 24- or 72-hour timepoints. Results: Rates of successful ROSC (n=21(96%) vs. n=14(82%), P=0.18) and survival to recovery (n=11(50%) vs. n=12(71%),P=0.19) were similar in CA treated with (CA+EPI) and without (CA-Epi) EPI, respectively. Greater myocardial injury occurred in CA+EPI, compared to CA-Epi, with increased Hs-Troponin levels measured at 24- (26.0±0.9ng/mL vs. 9.4±5.3,P=0.015) and 72-hours (20.9±8.3ng/mL vs. 5.0±2.4,P=0.012) (Fig B). To examine mRNA expression in cardiac tissue, rt-PCR was performed. At 72-hours, CA+EPI, compared to CA-EPI, was associated with significantly increased expression of inflammatory (TNF-α, IL1β, IL10, F4-80 and CD68) and fibrotic (TGFβ, Col1 and Col3) genes. There was no difference between SHAM-EPI and SHAM+EPI at 72-hours (Fig C). Conclusion: In a mouse model of cardiac arrest, the use of epinephrine did not improve rates of ROSC and survival. However, epinephrine exposure was associated with increased biomarkers of myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further pre-clinical studies to assess alternate agents that confer protection to vital organs and improve rates of survival.