scholarly journals P001: Proof-of-principle in a large animal pilot: cardiac arrest may be associated with acute, transient coagulopathy that may drive post-cardiac arrest syndrome

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S64-S65
Author(s):  
C. Yeh ◽  
B. Camilotti ◽  
H. Hanif ◽  
R. Mohindra ◽  
C. Sun ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Repeated Measures ◽  
Time Course ◽  
Alpha Angle ◽  
Clot Formation ◽  
Lead Target ◽  
Large Animal ◽  
Early Medical Intervention ◽  
Post Cardiac Arrest Syndrome ◽  
Coagulation And Fibrinolysis

Introduction: Many cardiac arrest survivors die later due to hemorrhage or thromboembolism, thought to be caused by acquired coagulopathy in post-cardiac arrest syndrome (PCAS) from shock and reperfusion injury. Understanding PCAS is a priority identified by the AHA for the prevention of complications in cardiac arrest survivors. Shock dysregulates both coagulation and fibrinolysis. The key effector enzyme thrombin (Th), is responsible for both up- and down-regulating coagulation and fibrinolysis. Measuring early Th activity may allow for predicting PCAS coagulopathy, and early medical intervention in the ED. Therefore, we aimed to characterize the time-course profile of early coagulation using an established pig model of cardiac arrest. Methods: Yorkshire pigs were anaesthetised and intubated, had VF-arrest induced by pacing, and were resuscitated per ACLS. Rotational thromboelastometry (ROTEM) was performed on whole blood at four times: baseline, intra-arrest, post-arrest, and death, using the fibrin-based test with tissue factor to initiate clotting in the presence of a platelet inhibitor cytochalasin D (FIBTEM). Clot time (CT), clot formation time (CFT), alpha-angle during clot formation (Alpha), clot amplitude at 10 min (A10), maximum clot firmness (MCF), and maximum lysis as total percentage (ML%) were quantified. The primary outcome is the overall coagulation initiation measured by CFT, while secondary outcomes include ROTEM parameters reflecting Th activity. Parameters are compared over time in SPSS using repeated measures ANOVA and Bonferroni correction. Results: Pilot data from one experiment show that cardiac arrest causes immediate early changes to coagulation that subsequently normalized with ROSC (Figure 1). CFT was impaired immediately upon cardiac arrest (2.3-fold increase), normalized with ROSC, and impaired again at death when compared with baseline. Consistent with clotting impairment, A10, Alpha, and MCF were all reduced with cardiac arrest, normalized with ROSC, and impaired again at death. Conclusion: Higher initial indices of coagulopathy in patients with cardiac arrest appear to correlate with death and thromboembolism. In this pilot, CFT is acutely modified by cardiac arrest. Since CFT is affected by overall Th activity, early Th dysregulation may be a critical driver of coagulopathy. Th may therefore be a lead target that is modifiable in the emergency post-arrest setting to decrease morbidity and mortality from PCAS in cardiac arrest survivors.

Performance Evaluation Tests for Environmental Research (Peter): Evaluation of 114 Measures

1986 ◽  
Vol 63 (2) ◽  
pp. 683-708 ◽  
Author(s):  
Alvah C. Bittner ◽  
Robert C. Carter ◽  
Robert S. Kennedy ◽  
Mary M. Harbeson ◽  
Michele Krause
Keyword(s):  
Performance Evaluation ◽  
Repeated Measures ◽  
Time Course ◽  
Environmental Studies ◽  
Acceptable Level ◽  
Environmental Research ◽  
Human Capabilities ◽  
Task Definition ◽  
And Task

The goal of the Performance Evaluation Tests for Environmental Research (PETER) Program was to identify a set of measures of human capabilities for use in the study of environmental and other time-course effects. 114 measures studied in the PETER Program were evaluated and categorized into four groups based upon task stability and task definition. The Recommended category contained 30 measures that clearly obtained total stabilization and had an acceptable level of reliability efficiency. The Acceptable-But-Redundant category contained 15 measures. The 37 measures in the Marginal category, which included an inordinate number of slope and other derived measures, usually had desirable features which were outweighed by faults. The 32 measures in the Unacceptable category had either differential instability or weak reliability efficiency. It is our opinion that the 30 measures in the Recommended category should be given first consideration for environmental research applications. Further, it is recommended that information pertaining to preexperimental practice requirements and stabilized reliabilities should be utilized in repeated-measures environmental studies.

Abstract 293: Cardiac Arrest and Resuscitation Causes Immunodeficiency That Involves the Hypothalamic-Pituitary-Adrenal Axis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Yuntian Shen ◽  
Qiang Zhao ◽  
Jiangbo Wu ◽  
Zhuoran Wang ◽  
Wei Yang
Keyword(s):  
Immune Response ◽  
Cardiac Arrest ◽  
Immune System ◽  
Hpa Axis ◽  
Time Course ◽  
Immune Cell ◽  
Infectious Complications ◽  
Hypothalamic Pituitary Adrenal ◽  
Immune Organs ◽  
High Incidence

Introduction: Cardiac arrest (CA) is associated with high mortality and morbidity, which is in part due to infectious complications developed in CA patients. Infection complications, particularly pneumonia, occur in approximately 60% of CA patients. Given this high incidence, we hypothesized that after CA, the immune system is impaired, which increases the susceptibility of CA patients to potential infections. Therefore, in this study, we systematically examined the immune response in the brain and peripheral immune organs after CA. Methods: Mice were subjected to CA and cardiopulmonary resuscitation (CA/CPR). Flow cytometry, ELISA, immunohistochemistry, and quantitative PCR were used to analyze the immune response in various post-CA organs. Results: First, we characterized the time course of the immune response in the spleen after CA/CPR. CA/CPR induced significant changes in all major immune cell populations. Notably, B cell frequencies decreased, while T cell frequencies increased, in various organs on day 3 post-CA. Further, the levels of pro-inflammatory cytokines, eg IL-6, were markedly increased in the blood and brain after CA. Critically, we found that the lymphocyte counts in the spleen and thymus were dramatically lower in CA mice than in sham mice. Interestingly, CA/CPR caused progressive atrophy of the spleen and thymus. Since it has been shown that CA/CPR alters activity of the hypothalamic-pituitary-adrenal (HPA) axis, we speculated that CA-induced atrophy of lymphoid organs is mediated by the HPA axis. Thus, we treated CA mice with RU486, a glucocorticoid receptor antagonist. Indeed, this treatment reversed CA-induced organ atrophy and mitigated immune cell depletion, both in the thymus and spleen. Conclusions: We provided for the first time evidence that CA/CPR rapidly induced a systemic inflammatory response followed by impairment of the immune system, which eventually led to a massive loss of immune cells in the peripheral immune organs. This CA-induced immunodeficiency appears to be mediated by dysregulation of the HPA axis. Our findings here may be of high clinical significance, considering the high incidence of infectious complications in CA patients and their detrimental effects on CA outcome.

Effects of Targeted Temperature Management in Patients with Post-Cardiac Arrest Syndrome after an Out-Of-Hospital Cardiac Arrest Caused by Hanging: A Prospective Observational Cohort Study in Japan

2021 ◽  
Author(s):  
Ryuichiro Kakizaki ◽  
Naofumi Bunya ◽  
Shuji Uemura ◽  
Takehiko Kasai ◽  
Keigo Sawamoto ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cardiac Arrest ◽  
Propensity Score ◽  
Multivariate Logistic Regression Analysis ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Matched Cohort ◽  
Neurological Outcomes ◽  
Post Cardiac Arrest Syndrome ◽  
Hospital Cardiac Arrest

Abstract Background: Targeted temperature management (TTM) is recommended for unconscious patients after a cardiac arrest. However, its effectiveness in patients with post-cardiac arrest syndrome (PCAS) by hanging remains unclear. Therefore, this study aimed to investigate the relationship between TTM and favorable neurological outcomes in patients with PCAS by hanging.Methods: This study was a retrospective analysis of the Japanese Association for Acute Medicine out-of-hospital cardiac arrest (OHCA) registry between June 2014 and December 2017 among patients with PCAS admitted to the hospitals after an OHCA caused by hanging. A multivariate logistic regression analysis was performed to estimate the propensity score and to predict whether patients with PCAS by hanging receive TTM. We compared patients with PCAS by hanging who received TTM (TTM group) and those who did not (non-TTM group) using propensity score analysis.Results: A total of 199 patients with PCAS by hanging were enrolled in this study. Among them, 43 were assigned to the TTM group and 156 to the non-TTM group. Logistic regression model adjusted for propensity score revealed that TTM was not associated with favorable neurological outcome at 1-month (adjusted odds ratio [OR]: 1.38, 95% confidence interval [CI]: 0.27–6.96). Moreover, no difference was observed in the propensity score-matched cohort (adjusted OR: 0, 73, 95% CI: 0.10–4.71) and in the inverse probability of treatment weighting-matched cohort (adjusted OR: 0.63, 95% CI: 0.15–2.69).Conclusions: TTM was not associated with increased favorable neurological outcomes at 1-month in patients with PCAS after OHCA by hanging.

Abstract P14: Estradiol Does Not Improve Survival and Hemodynamic Parameters in Male Piglets after Hemorrhage and Ventricular Fibrillation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Egidijus Semenas ◽  
Lars Wiklund
Keyword(s):  
Gender Differences ◽  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Hemorrhagic Shock ◽  
Repeated Measures ◽  
Troponin I ◽  
Control Group ◽  
Hemodynamic Parameters ◽  
Start Time ◽  
Arterial Blood

Introduction: Gender differences in organ functions and survival have been described in animal models of trauma and hemorrhagic shock. The female gender is associated with better cardiac, hepatic and immune functions compared to males after hemorrhagic shock. However, data about gender differences in hypovolemic normothermic cardiac arrest is lacking. Hypothesis: We hypothesized that the estradiol given during cardiopulmonary resuscitation (CPR) will improve survival and hemodynamic response in hypovolemic cardiac arrest and subsequent CPR. Methods: Twenty anesthetized male piglets (with a weight of 25.7 ± 1.7 kg [mean ± SD]) were bled 30% via the right femoral artery to a mean arterial blood pressure of 35 mm during 15 minutes. In the end of bleeding period estradiol group (n=10) received 17â-estradiol 50 ìg/kg intravenously, while the control group received no estradiol (n=10). Later all piglets were subjected to 4 min of untreated ventricular fibrillation followed by up to 15 min of open chest CPR. At 5 min of cardiac arrest piglets received vasopressin 0.4 U/kg, amiodarone 0.5 mg/kg, and hypertonic-hyperoncotic solution 3 ml/kg infusion for 20 minutes. Internal defibrillation was attempted from 8 min of cardiac arrest to achieve restoration of spontaneous circulation (ROSC). The experiment was terminated at 3 hours after initial resuscitation. Data were analyzed using Fisher’s exact test, Kaplan-Meier and repeated measures ANOVA methods. Results: All piglets were successfully resuscitated. No significant differences were observed in survival between the groups (p=0.24). All piglets needed dobutamine infusion and no differences were observed in either total dobutamin dose, or infusion start time (p=0.05). No significant changes were observed in any hemodynamic parameters (p>0.05). Troponin I levels did not differ between groups (p>0.75). Conclusions: Intravenous 17â-estradiol does not improve survival and hemodynamic parameters in male piglets after experimental hypovolemic cardiac arrest.

scholarly journals Effects of Fibrinogen Levels and Platelet Counts on Viscoelastic Testing in Cirrhotic Patients

2018 ◽  
Vol 4 (3) ◽  
pp. 90-95
Author(s):  
Dana Tomescu ◽  
Mihai Popescu ◽  
Alexander Vitin
Keyword(s):  
Alpha Angle ◽  
Area Under The Curve ◽  
Maximum Velocity ◽  
Clot Formation ◽  
Platelet Counts ◽  
Potential Index ◽  
Severity Scores ◽  
Coagulation Tests ◽  
Cirrhotic Patients ◽  
End Stage

Abstract Introduction. Cirrhotic patients have been considered for decades to have a pro-haemorrhagic pattern and were treated as such based on the results from standard coagulation tests. The aim of our study was to determine the effects of platelet count and fibrinogen levels on rotational thromboelastometry (ROTEM) parameters. Methods. We prospectively included 176 patients with End-Stage Liver Disease (ESLD) admitted to our Intensive Care Unit prior to liver transplantation. Collected data consisted of severity scores, liver, renal and standard coagulation tests, fibrinogen levels, platelet counts and ROTEM parameters. Four ROTEM assays were performed (ExTEM, InTEM, ApTEM and FibTEM) and the following parameters included: CT – clotting time, CFT – clot formation time, MCF – maximum clot firmness, ML – maximum lysis, alpha angle, TPI – thrombin potential index, MaxV - maximum velocity of clot formation (MaxV), MaxVt - time to MaxV, MCE - maximum clot elasticity and AUC - area under the curve. Results. Statistical analysis demonstrated a linear correlation between platelet counts and ExTEM TPI (R2 linear =0.494), ExTEM MaxV (R2 linear =0.253), ExTEM MCE (R2 linear = 0.351) and ExTEM MCF (R2 cubic = 0.498). Fibrinogen levels correlated linearly with ExTEM MCF (R2 linear = 0.426), ExTEM TPI (R2 linear = 0.544), ExTEM MaxV (R2 linear = 0.332), ExTEM MCE (R2 linear = 0.395) and non-linearly with ExTEM CFT (R2 cubic = 0.475). Conclusion. Fibrinogen levels and platelet counts had an important effect on both standard and derived ROTEM parameters. Further analysis is required in order to determine clinically oriented cut-off values below which severe coagulopathy would develop.

Abstract 13: Adenosine Receptor Activation During Extracorporeal Cardiopulmonary Resuscitation Improves Survival After Cardiac Arrest in Swine

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
William Z Chancellor ◽  
Dustin Money ◽  
Jared P Beller ◽  
Matthew R Byler ◽  
Aimee Zhang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Troponin I ◽  
Circulatory Arrest ◽  
Receptor Activation ◽  
Large Animal Model ◽  
Saline Control ◽  
Large Animal ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
A2ar Agonist

Introduction: Despite advances in resuscitation protocols, including the addition of Extracorporeal Cardiopulmonary Resuscitation (ECPR), survival after cardiac arrest remains less than 40% and novel methods are needed to attenuate global injury and improve outcomes. ATL1223, an adenosine 2A receptor (A2AR) agonist has been shown to attenuate organ specific reperfusion injury by modulating the interaction of inflammatory cells. Hypothesis: A2AR activation during ECPR will improve survival and decrease the burden of injury in a large animal model of cardiac arrest. Methods: Adult swine underwent 20 minutes of circulatory arrest followed by defibrillation and 6 hours of ECPR. Animals were randomized to receive saline control (n=5) or the A2AR agonist Regadenoson (0.144 and 14.4mcg/kg/hr, n=5/group). Animals were subsequently weaned from ECPR and monitored for 24 hours. Clinical and biochemical endpoints were compared between groups. Results: The administration of Regadenoson increased survival after cardiac arrest compared to saline controls (10/10, 100% vs 2/5, 40%, p=0.02, Figure 1). Anesthetic administration (p=0.41), fluid resuscitation (p=0.54), and epinephrine required to maintain target arterial pressure (p=0.08) were similar for all subjects. Biochemical markers of organ damage, including creatinine (p=0.87), aspartate aminotransferase (p=0.89), and troponin I (p=0.38), were similar among groups (Figure 2). Conclusions: In a clinically relevant model of cardiac arrest treated with ECPR, selective A2AR agonism increased survival from 40% to 100% at 24 hours. These results suggest A2AR activation is a promising therapeutic target after cardiac arrest.

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