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Background: The prognosis of patients with coronary artery disease is adversely affected by elevated fasting plasma glucose (FPG) levels. However, the relationship between FPG levels and in-hospital cardiac arrest (IHCA) remains unclear., Objectives: The objective of this study was to investigate the association between FPG levels and IHCA in patients diagnosed with acute coronary syndrome (ACS)., Methods: Data from a total of 31,726 ACS patients fitted with inclusion and exclusion criteria across 241 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from November 2014 to July 2019 were collected. Different logistic regression models were utilized to examine the associations of FPG levels with IHCA. Sensitivity analyses were then conducted to assess the robustness of the findings. Marginal effect analyses were also employed to evaluate the impact of different therapies., Results: A total of 335 cases of IHCA and 293 in-hospital mortality were recorded throughout the study. A non-linear relationship between FPG levels and IHCA was identified after adjusting for the covariates. Specifically, a significant association was found between elevated FPG levels (≥6.1 mmol/L) and an increased risk of IHCA. These findings remained consistent across different subgroup analyses including both the diabetic and non-diabetic patients. Additionally, the marginal effect analyses revealed that percutaneous coronary intervention could lower the high FPG-related risk., Conclusions: The study findings showed a positive correlation between FPG levels and a higher incidence of IHCA, irrespective of the presence of diabetes.

Cardiac arrest (CA) is a serious health concern that often results in mortality or severe neurological dysfunction in the case of survival. Our aim was to explore the neurological prognostic factors in patients with CA. This retrospective observational study included adult patients with CA. We investigated serum neuron-specific enolase (NSE), S100 calcium-binding protein β (S100β), and indices and parameters at 1, 3, 5, 7 and intensive care unit (ICU) discharge days after CA. The primary study endpoint was the Cerebral Performance Category (CPC) scale score at ICU discharge, which was dichotomized as good neurological outcome (CPC 1-2: full recovery or moderate disability) and poor neurological outcome (CPC 3-5: severe disability, vegetative state, or death). Of the 191 adult patients with CA, 42 (22%) had good neurological outcomes, and 149 (78%) had poor neurological outcomes. NSE at 1,3,5,7 and ICU discharge days showed excellent predictive accuracy for neurological outcomes (area under the curve [AUC]: 0.666, 0.716, 0.870, 0.739, and 0.901, respectively). However, S100β exhibited general predictive power (AUC: 0.666, 0.573, 0.607, 0.594, 0.727). Finally, the early warning model, which combined day 1 NSE, day 1 S100β, cardiac arrest time, SOFA scores, APACHE II scores, and age, was used to screen CA patients with poor neurological prognosis at early stages and had an AUC of 0.792. Serum concentrations of NSE and S100β were significantly elevated in CA patients and could be prognostic biomarkers to predict neurological outcomes. Day 1 NSE and S100β combined with multiple indicators could be a decent early warning model for poor neurological prognosis in patients with CA., (© 2024. The Author(s).)

Background: Acute liver failure (ALF) following cardiac arrest (CA) poses a significant healthcare challenge, characterized by high morbidity and mortality rates. This study aims to assess the correlation between serum alkaline phosphatase (ALP) levels and poor outcomes in patients with ALF following CA., Methods: A retrospective analysis was conducted utilizing data from the Dryad digital repository. The primary outcomes examined were intensive care unit (ICU) mortality, hospital mortality, and unfavorable neurological outcome. Multivariable logistic regression analysis was employed to assess the relationship between serum ALP levels and clinical prognosis. The predictive value was evaluated using receiver operator characteristic (ROC) curve analysis. Two prediction models were developed, and model comparison was performed using the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC)., Results: A total of 194 patients were included in the analysis (72.2% male). Multivariate logistic regression analysis revealed that a one-standard deviation increase of ln-transformed ALP were independently associated with poorer prognosis: ICU mortality (odds ratios (OR) = 2.49, 95% confidence interval (CI) 1.31-4.74, P = 0.005), hospital mortality (OR = 2.21, 95% CI 1.18-4.16, P = 0.014), and unfavorable neurological outcome (OR = 2.40, 95% CI 1.25-4.60, P = 0.009). The area under the ROC curve for clinical prognosis was 0.644, 0.642, and 0.639, respectively. Additionally, LRT analyses indicated that the ALP-combined model exhibited better predictive efficacy than the model without ALP., Conclusions: Elevated serum ALP levels upon admission were significantly associated with poorer prognosis of ALF following CA, suggesting its potential as a valuable marker for predicting prognosis in this patient population., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate whether there is a difference in serum nitric oxide levels between patients who return spontaneously after cardiopulmonary resuscitation and those who do not. We also examined the potential of using serum nitric oxide levels as a marker to make an accurate decision about patient survival., Methods: We included 100 consecutive patients who were brought to the emergency clinic due to cardiac arrest. Blood samples were taken from these patients at admission, 30 min after admission, and when resuscitation was terminated., Results: We found that there was a significant difference in NO1 and NO3 values between the group of patients who did not return after cardiopulmonary resuscitation and the group in which spontaneous circulation returned. The NO1 value was significant in the receiver operating characteristic (ROC) analysis, while the NO3 value was not. A higher NO1 value provided a higher rate of survival., Conclusion: Our findings suggest that nitric oxide may be a useful parameter to support the decision about patient survival. A higher NO1 value is associated with a better prognosis and survival rate. Therefore, serum nitric oxide levels may be a suitable indicator to support the decision-making process regarding patient survival.

Importance: Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated., Objectives: To evaluate biomarkers' impact in helping VAP diagnosis after cardiac arrest., Design Setting and Participants: This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included., Main Outcomes and Measures: The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group., Results: Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP ( n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP ( n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C., Conclusions and Relevance: Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction: Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a major health burden worldwide, with brain damage being a significant contributor to disability and mortality. Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly localised in the central nervous system, has been previously shown to inhibit postischemia neuronal apoptosis. Therefore, we aim to observe whether serum L-PGDS can serve as a potential biomarker and explore its role in determining the severity and prognosis of patients who have achieved restoration of spontaneous circulation (ROSC)., Methods and Analysis: This is a prospective observational study. The participants (n = 60) who achieve ROSC will be distributed into two groups (non-survivor and survivor) based on 28-day survival. Healthy volunteers (n = 30) will be enrolled as controls. Each individual's relevant information will be extracted from Electronic Medical Record System in Xinhua Hospital, including demographic characteristics, clinical data, laboratory findings and so on. On days 1, 3 and 7 after ROSC, blood samples will be drawn and batch tested on the level of serum neuron-specific enolase, soluble protein 100β, L-PGDS, procalcitonin, tumour necrosis factor-alpha and interleukin-6. The cerebral performance category score was assessed on the 28th day after ROSC., Ethics and Dissemination: This study was performed with the approval of the Clinical Ethical Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-C-2023-130-1). The results will be published in a peer-reviewed journal., Trial Registration Number: Chinese Clinical Trial Registry (ChiCTR2300078564)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stress hyperglycemia ratio (SHR) has shown a predominant correlation with transient adverse events in critically ill patients. However, there remains a gap in comprehensive research regarding the association between SHR and mortality among patients experiencing cardiac arrest and admitted to the intensive care unit (ICU)., Methods: A total of 535 patients with their initial ICU admission suffered cardiac arrest, according to the American Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were stratified into four categories based on quantiles of SHR. Multivariable Cox regression models were used to evaluate the association SHR and mortality. The association between SHR and mortality was assessed using multivariable Cox regression models. Subgroup analyses were conducted to determine whether SHR influenced ICU, 1-year, and long-term all-cause mortality in subgroups stratified according to diabetes status., Results: Patients with higher SHR, when compared to the reference quartile 1 group, exhibited a greater risk of ICU mortality (adjusted hazard ratio [aHR] = 3.029; 95% CI: 1.802-5.090), 1-year mortality (aHR = 3.057; 95% CI: 1.885-4.958), and long-term mortality (aHR = 3.183; 95% CI: 2.020-5.015). This association was particularly noteworthy among patients without diabetes, as indicated by subgroup analysis., Conclusion: Elevated SHR was notably associated with heightened risks of ICU, 1-year, and long-term all-cause mortality among cardiac arrest patients. These findings underscore the importance of considering SHR as a potential prognostic factor in the critical care management of cardiac arrest patients, warranting further investigation and clinical attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lian, Xue, Lu and Zheng.)

Objective: Although the TyG index is a reliable predictor of insulin resistance (IR) and cardiovascular disease, its effectiveness in predicting major adverse cardiac events in hospitalized acute coronary syndrome (ACS) patients has not been validated in large-scale studies. In this study, we aimed to explore the association between the TyG index and the occurrence of MACEs during hospitalization., Methods: We recruited ACS patients from the CCC-ACS (Improving Cardiovascular Care in China-ACS) database and calculated the TyG index using the formula ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). These patients were classified into four groups based on quartiles of the TyG index. The primary endpoint was the occurrence of MACEs during hospitalization, encompassing all-cause mortality, cardiac arrest, myocardial infarction (MI), and stroke. We performed Cox proportional hazards regression analysis to clarify the correlation between the TyG index and the risk of in-hospital MACEs among patients diagnosed with ACS. Additionally, we explored this relationship across various subgroups., Results: A total of 101,113 patients were ultimately included, and 2759 in-hospital MACEs were recorded, with 1554 (49.1%) cases of all-cause mortality, 601 (21.8%) cases of cardiac arrest, 251 (9.1%) cases of MI, and 353 (12.8%) cases of stroke. After adjusting for confounders, patients in TyG index quartile groups 3 and 4 showed increased risks of in-hospital MACEs compared to those in quartile group 1 [HR = 1.253, 95% CI 1.121-1.400 and HR = 1.604, 95% CI 1.437-1.791, respectively; p value for trend < 0.001], especially in patients with STEMI or renal insufficiency. Moreover, we found interactions between the TyG index and age, sex, diabetes status, renal insufficiency status, and previous PCI (all p values for interactions < 0.05)., Conclusions: In patients with ACS, the TyG index was an independent predictor of in-hospital MACEs. Special vigilance should be exercised in females, elderly individuals, and patients with renal insufficiency., (© 2024. The Author(s).)

Abstract: Previous studies found that high red cell distribution width (RDW) value is associated with poor outcomes among out-of-hospital cardiac arrest survivors. The aim of this study was to investigate whether post-ROSC RDW value was associated with survival and neurological outcomes of in-hospital cardiac arrest (IHCA) patients achieving return of spontaneous circulation (ROSC) but remaining critically ill.This retrospective single-center observational study included IHCA adults with sustained ROSC between January 1, 2017 and January 1, 2021 at an academic medical center in China. PostROSC RDW values were measured within 1 hour after sustained ROSC. The primary outcome was survival to hospital discharge and the secondary outcome was favorable neurological outcome at hospital discharge. The associations between postROSC RDW value and outcomes among IHCA patients with ROSC were evaluated by using multivariate logistic regression.A total of 730 patients with sustained ROSC following IHCA were ultimately included in this study. Of whom 194 (26.6%) survived to hospital discharge and 116 (15.9%) had a favorable neurological outcome at hospital discharge. In multivariable logistic regression analysis, lower postROSC RDW value was independently associated with survival to hospital discharge (odds ratio 0.19, 95% confidence interval 0.15-0.63, P = .017, cut-off value: 15.5%) and favorable neurological outcome at hospital discharge (odds ratio 0.23, 95% confidence interval 0.07-0.87, P < .001, cut-off value: 14.6%). Other independent factors including younger age, initial shockable rhythm, shorter total cardiopulmonary resuscitation duration and post-ROSC percutaneous coronary intervention were also associated with survival to hospital discharge. Regarding favorable neurological outcome at hospital discharge, significant variables other than the aforementioned factors included postROSC targeted temperature management and absence of pre-existing neurological insufficiency.Low postROSC RDW value was associated with survival to hospital discharge and favorable neurological outcome at hospital discharge., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) acting as a novel damage-associated molecular pattern molecule promotes systemic inflammatory responses, including neuroinflammation in cerebral ischemia. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC)., Methods: A total of 73 patients after ROSC were divided into non-survivor (n = 48) and survivor (n = 25) groups based on 28-day survival. Healthy volunteers (n = 25) were enrolled as controls. Serum eCIRP, procalcitonin (PCT), the pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and high mobility group protein (HMGB1), the neurological damage biomarkers neuron-specific enolase (NSE), and soluble protein 100β (S100β) were measured on days 1, 3, and 7 after ROSC. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) were calculated concurrently. Cerebral performance category scores on day 28 after ROSC were recorded., Results: Serum eCIRP, IL-6, TNF-α, PCT, and HMGB1, NSE and S100β were significantly increased within the first week after ROSC. The increased levels of eCIRP were positively correlated with IL-6, TNF-α, lactate, NSE, S100β, CPR time, SOFA score, APACHE II score, and HMGB1 after ROSC. Serum eCIRP on days 1, 3, and 7 after ROSC could predict 28-day mortality and neurological prognosis. Serum eCIRP on day 3 after ROSC had a biggest AUC [0.862 (95% CI: 0.741-0.941)] for 28-day mortality and a biggest AUC [0.807 (95% CI: 0.630-0.981)] for neurological prognosis., Conclusions: Systemic inflammatory response with increased serum eCIRP occurred in patients after ROSC. Increased eCIRP level was positively correlated with the aggravation of systemic inflammatory response and the severity after ROSC. Serum eCIRP serves as a potential predictor for 28-day mortality and poor neurological prognosis after ROSC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p < 0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96 h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (score 0.3 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) and hippocampal microglial activation (6 ± 3 vs. 22 ± 4%, p < 0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (2[1-3] vs. 21[16-52] ng/mL, p < 0.01). In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.

We investigated whether combining the pre-arrest serum albumin level could improve the performance of the Good Outcome Following Attempted Resuscitation (GO-FAR) score for predicting neurologic outcomes in in-hospital cardiac arrest patients. Adult patients who were admitted to a tertiary care hospital between 2013 and 2017 were assessed. Their pre-arrest serum albumin levels were measured within 24 h before the cardiac arrest. According to albumin levels, the patients were divided into quartiles and were assigned 1, 0, 0, and, - 2 points. Patients were allocated to the derivation (n = 419) and validation (n = 444) cohorts. The proportion of favorable outcome increased in a stepwise manner across increasing quartiles (p for trend < 0.018). Area under receiver operating characteristic curve (AUROC) of the albumin-added model was significantly higher than that of the original GO-FAR model (0.848 vs. 0.839; p = 0.033). The results were consistent in the validation cohort (AUROC 0.799 vs. 0.791; p = 0.034). Net reclassification indices of the albumin-added model were 0.059 (95% confidence interval [CI] - 0.037 to 0.094) and 0.072 (95% CI 0.013-0.132) in the derivation and validation cohorts, respectively. An improvement in predictive performance was found by adding the ordinal scale of pre-arrest albumin levels to the original GO-FAR score.

Background: Lactate is a prognostic marker in critically ill patients, although currently available illness severity scores do not include lactate as a predictive parameter. We sought to describe the association between lactate and hospital mortality in patients admitted to the cardiac intensive care unit (CICU) with cardiac arrest (CA) and shock., Methods: Retrospective observational analysis of Mayo Clinic CICU patients admitted from 2007 to 2018 with measured lactate on admission, including patients with and without CA or shock. We examined hospital mortality as a function of admission lactate in patients. Multivariable logistic regression was used to determine predictors of hospital mortality., Results: We included 3,042 patients with a median age of 70 years (IQR 60-80), including 41% females, 26% with CA, and 39% with shock. The median APACHE-IV predicted mortality was 24% (IQR 11-51%), and the median admission lactate was 1.8 mmol/L (IQR 1.1-3.0). Hospital mortality occurred in 23% of patients and rose progressively with higher admission lactate, including in patients with and without CA or shock. After multivariable adjustment for clinical characteristics, therapies, and illness severity, a higher lactate remained associated with increased hospital mortality (adjusted OR 1.13 per mmol/L, 95% CI 1.06-1.20, P < 0.001)., Conclusions: Admission lactate levels are strongly associated with increased hospital mortality among CICU patients, including those with and without CA or shock. The prognostic value of lactate levels is independent of established ICU prognostic scores and dependent on admission diagnosis, which may help inform clinicians caring for CICU patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Background: Critically ill patients with cardiogenic shock could benefit from ventricular assist device support using the Impella microaxial blood pump. However, recent studies suggested Impella not to improve outcomes. We, therefore, evaluated outcomes and predictors in a real-world scenario., Methods: In this retrospective single-center trial, 125 patients suffering from cardiac arrest/cardiogenic shock between 2008 and 2018 were analyzed. 93 Patients had a prior successful cardiopulmonary resuscitation. The primary endpoint was hospital mortality. Associations of covariates with the primary endpoint were assessed by univariable and multivariable logistic regression. Adjusted odds ratios (aOR) and optimal cut-offs (using Youden index) were obtained., Results: Hospital mortality was high (81%). Baseline lactate was 4.7mmol/L [IQR = 7.1mmol/L]. In multivariable logistic regression, only age (aOR 1.13 95%CI 1.06-1.20; p<0.001) and lactate (aOR 1.23 95%CI 1.004-1.516; p = 0.046) were associated with hospital mortality, and the respective optimal cut-offs were >3.3mmol/L and age >66 years. Patients were retrospectively stratified into three risk groups: Patients aged ≤66 years and lactate ≤3.3mmol (low-risk; n = 22); patients aged >66 years or lactate >3.3mmol/L (medium-risk; n = 52); and patients both aged >66 years and lactate >3.3mmol/L (high-risk, n = 51). Risk of death increased from 41% in the low-risk group, to 79% in the medium risk group and 100% in the high-risk group. The predictive abilities of this model were high (AUC 0.84; 95% 0.77-0.92)., Conclusion: Mortality was high in this real-world collective of severely ill cardiogenic shock patients. Better patient selection is warranted to avoid unethical use of Impella. Age and lactate might help to improve patient selection., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Neuron-specific enolase (NSE) is frequently used to predict neurological outcomes in patients with hypoxic brain injury. Hanging can cause hypoxic brain damage, and survivors can suffer from neurological deficits that may impair daily activities. Here, we investigated the utility of the initial serum NSE level as a predictor of neurological outcomes in near-hanging patients with decreased consciousness., Methods: This retrospective multicenter study was conducted in patients who visited the emergency department due to near-hanging injury from October 2013 to February 2019 at three university hospitals in Korea. They were divided into two groups according to the presence of out-of-hospital cardiac arrest. The neurological outcome was determined using the Cerebral Performance Category (CPC) measured at the time of discharge. Multivariate analysis was performed to determine whether initial serum NSE is an independent predictor of neurological outcome., Results: Of the 70 patients included in the study, 44 showed a poor neurological outcome (CPC score = 3-5). Among the 52 patients with cardiac arrest, only 10 (19.2%) were discharged with good neurological outcome (CPC score = 1-2). In the whole cohort, a high serum NSE level was a significant predictor of poor neurological outcome (odds ratio [OR], 1.343; 95% confidence interval [CI], 1.003-1.800, p = 0.048). Among the patients with cardiac arrest, a high serum NSE level was a significant predictor of poor neurological outcome (OR, 1.138; 95% CI, 1.009-1.284, p = 0.036)., Conclusions: In near-hanging patients, a high initial serum NSE level is an independent predictor of poor neurological outcome., Competing Interests: The authors have declared that no competing interests exist.

Background: A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores., Methods: This prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light ® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score., Results: Poor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p < 0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p < 0.001) and CAHP score (from AUC 0.89 to 0.92, p < 0.05). Adding NfL to both scores also resulted in significant improvement in reclassification statistics with a Net Reclassification Index (NRI) of 0.58 (p < 0.001) for OHCA and 0.83 (p < 0.001) for CAHP., Conclusions: Admission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.

Accumulating evidence demonstrated that administration of ω-3 polyunsaturated fatty acid (ω-3 PUFA) or ascorbic acid (AA) following cardiac arrest (CA) improves survival. Therefore, we investigate the effects of ω-3 PUFA combined with AA on myocardial function after CA and cardiopulmonary resuscitation (CPR) in a rat model. Thirty male rats were randomized into 5 groups: (1) sham; (2) control; (3) ω-3 PUFA; (4) AA; (5) ω-3 PUFA + AA. Ventricular fibrillation (VF) was induced and untreated for 6 min followed by defibrillation after 8 min of CPR. Infusion of drug or vehicle occurred at the start of CPR. Myocardial function and sublingual microcirculation were measured at baseline and after return of spontaneous circulation (ROSC). Heart tissues and blood were collected 6 h after ROSC. Myocardial function and sublingual microcirculation improvements were seen with ω-3 PUFA or AA compared to control after ROSC (p < 0.05). ω-3 PUFA + AA shows a better myocardial function than ω-3 PUFA or AA (p < 0.05). ω-3 PUFA or AA decreases pro-inflammatory cytokines, cTnI, myocardium malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) modified proteins compared to control (p < 0.05). ω-3 PUFA and AA combined have lower MDA and 4-HNE modified proteins than alone (p < 0.05). ω-3 PUFA or AA treatment reduces the severity of post-resuscitation myocardial dysfunction, improves sublingual microcirculation, decreases lipid peroxidation and systemic inflammation in the early phase of recovery following CA and resuscitation. A combination of ω-3 PUFA and AA treatment confers an additive effect in suppressing lipid peroxidation and improving myocardial function., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Early prognostication of neurological outcome in comatose patients after cardiac arrest (CA) is vital for clinicians when assessing the survival time of sufferers and formulating appropriate treatment strategies to avoid the withdrawal of life-sustaining treatment (WLST) from patients. However, there is still a lack of sensitive and specific serum biomarkers for early and accurate identification of these patients. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic approach, we discovered 55 differentially expressed proteins, with 39 up-regulated secreted serum proteins and 16 down-regulated secreted serum proteins between three comatose CA survivors with good versus poor neurological recovery. Then, four proteins were selected and were validated via an enzyme-linked immunosorbent assay (ELISA) approach in a larger-scale sample containing 32 good neurological outcome patients and 46 poor neurological outcome patients, and it was confirmed that serum angiotensinogen (AGT) and alpha-1-antitrypsin (SERPINA1) were associated with neurological function and prognosis in CA survivors. A prognostic risk score was developed and calculated using a linear and logistic regression model based on a combination of AGT, SERPINA1 and neuron-specific enolase (NSE) with an area under the curve of 0.865 (P < .001), and the prognostic risk score was positively correlated with the CPC value (R = 0.708, P < .001). We propose that the results of the risk score assessment not only reveal changes in biomarkers during neurological recovery but also assist in enhancing current therapeutic strategies for comatose CA survivors., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Takotsubo cardiomyopathy (TTC) is a rare but life-threatening condition that is still not completely understood. Characterised by rapidly reversible ventricular dysfunction without any prior coronary artery disease, it can imitate a myocardial infarction and lead to death if not managed appropriately. This report examines a case of intraoperative cardiac arrest in a patient with no previous cardiac disease, and discusses the factors that may have precipitated this event, as well as the ways of distinguishing the cause of the arrest based on clinical course and investigations, eventually leading to a diagnosis of TTC., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Total liquid ventilation (TLV) has been shown to prevent neurological damage though ultrafast cooling in animal models of cardiac arrest. We investigated whether its neuroprotective effect could be explained by mitigation of early inflammatory events. Methods and Results Rabbits were submitted to 10 minutes of ventricular fibrillation. After resuscitation, they underwent normothermic follow-up (control) or ultrafast cooling by TLV and hypothermia maintenance for 3 hours (TLV). Immune response, survival, and neurological dysfunction were assessed for 3 days. TLV improved neurological recovery and reduced cerebral lesions and leukocyte infiltration as compared with control (eg, neurological dysfunction score=34±6 versus 66±6% at day 1, respectively). TLV also significantly reduced interleukin-6 blood levels during the hypothermic episode (298±303 versus 991±471 pg/mL in TLV versus control at 3 hours after resuscitation, respectively), but not after rewarming (752±563 versus 741±219 pg/mL in TLV versus control at 6 hours after resuscitation, respectively). In vitro assays confirmed the high temperature sensitivity of interleukin-6 secretion. Conversely, TLV did not modify circulating high-mobility group box 1 levels or immune cell recruitment into the peripheral circulation. The link between interleukin-6 early transcripts (<8 hours) and neurological outcome in a subpopulation of the previously described Epo-ACR-02 (High Dose of Erythropoietin Analogue After Cardiac Arrest) trial confirmed the importance of this cytokine at the early stages as compared with delayed stages (>8 hours). Conclusions The neuroprotective effect of hypothermic TLV was associated with a mitigation of humoral interleukin-6 response. A temperature-dependent attenuation of immune cell reactivity during the early phase of the post-cardiac arrest syndrome could explain the potent effect of rapid hypothermia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00999583.

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague-Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research.

Natriuretic peptides (NPs) regulate blood pressure and fluid homeostasis and exert various effects on the cardiovascular system. Recently, the relationship between NPs and the energy metabolism has been reported, and using a cell culture experiment system, we previously showed that NP activated brown cells in a low temperature environment while also suppressing a decrease in the cell temperature. However, few reports have described the secretion of NPs in cold environments, and there have been almost no studies of B-type natriuretic peptide (BNP) in humans. We investigated how NPs respond to cold environments in 21 patients who underwent therapeutic hypothermia (TH) after cardiac arrest. The plasma BNP levels were significantly increased (more than fivefold) during TH (logarithmically from 1.98 ± 0.79 to 2.63 ± 0.59, P < 0.01). During TH, diastolic pulmonary artery pressure (PAP) significantly decreased, and there were no significant changes in the stroke volume index (SVI). This increase of BNP was not associated with any hemodynamic changes. In contrast to our findings for BNP, the change in A-type NP (ANP) was quite small. We detected a significant increase in the plasma BNP levels during TH, unrelated to hemodynamics. This elevation of BNP levels seems to be potential influenced by hypothermia.

Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed ( p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA.

Background This study investigated whether levosimendan, an inotropic calcium sensitizer, when combined with moderate therapeutic hypothermia, may exert synergistic benefits on post-cardiac arrest myocardial dysfunction and improve outcomes. Methods and Results After 9.5-minute asphyxia-induced cardiac arrest and resuscitation, 48 rats were randomized equally into 4 groups following return of spontaneous circulation (ROSC), including normothermia, hypothermia, normothermia-levosimendan, and hypothermia-levosimendan groups. For the normothermia group, the target temperature was 37°C while for the hypothermia group, the target temperature was 32°C, both of which were to be maintained for 4 hours after ROSC. Levosimendan was administered after ROSC with a loading dose of 10 μg/kg and then infused at 0.1 μg/kg per min for 4 hours. In the hypothermia-levosimendan group, left ventricular systolic function and cardiac output increased significantly, whereas the heart rate and systemic vascular resistance decreased significantly compared with the normothermia group. Also, the concentrations of interleukin 1β at 4 hours post-ROSC and the production of NO between 1 hour and 4 hours post-ROSC were reduced significantly in the hypothermia-levosimendan group compared with the normothermia group. The 72-hour post-ROSC survival and neurological recovery were also significantly better in the hypothermia-levosimendan group compared with the normothermia group (survival, 100% versus 50%, χ 2 test, P =0.006). Conclusions Compared with normothermia, only combined moderate therapeutic hypothermia and levosimendan treatment could consistently improve post-cardiac arrest myocardial dysfunction and decrease the release of pro-inflammatory molecules, thereby improving survival and neurological outcomes. These findings suggest synergistic benefits between moderate therapeutic hypothermia and levosimendan.

Background: Cardiac arrest is a tragic event that causes 1 death roughly every 90 seconds worldwide. Survivors generally undergo a workup to identify the cause of arrest. However, 5% to 10% of cardiac arrests remain unexplained. Because cardiac arrhythmias underlie most cardiac arrests and increasing evidence strongly supports the involvement of autoantibodies in arrhythmogenesis, a large-panel autoantibody screening was performed in patients with cardiac arrest., Methods: This is an observational, cross-sectional study of patients from the Montreal Heart Institute hospital cohort, a single-center registry of participants. A peptide microarray was designed to screen for immunoglobulin G targeting epitopes from all known cardiac ion channels with extracellular domains. Plasma samples from 23 patients with unexplained cardiac arrest were compared with those from 22 patients with cardiac arrest cases of ischemic origin and a group of 29 age-, sex-, and body mass index-matched healthy subjects. The false discovery rate, least absolute shrinkage and selection operator logistic regression, and random forest methods were carried out jointly to find significant differential immunoglobulin G responses., Results: The autoantibody against the pore domain of the L-type voltage-gated calcium channel was consistently identified as a biomarker of idiopathic cardiac arrest ( P =0.002; false discovery rate, 0.007; classification accuracies ≥0.83). Functional studies on human induced pluripotent stem cell-derived cardiomyocytes demonstrated that the anti-L-type voltage-gated calcium channel immunoglobulin G purified from patients with idiopathic cardiac arrest is proarrhythmogenic by reducing the action potential duration through calcium channel inhibition., Conclusions: The present report addresses the concept of autoimmunity and cardiac arrest. Hitherto unknown autoantibodies targeting extracellular sequences of cardiac ion channels were detected. Moreover, the study identified an autoantibody signature specific to patients with cardiac arrest.

Background: Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines (interleukin-17 [IL-8], IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post-cardiac arrest period., Methods: This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated "survivors". The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays., Results: Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC., Conclusion: These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients., Trial Registration: Clinicaltrial.govNCT02297776, 2014-11-21.

Background: Resuscitation guidelines list acidaemia as a potentially reversible cause of cardiac arrest without specifying the threshold defining acidaemia. We examined the association between early intra-arrest arterial blood gas (ABG) data and outcomes of in-hospital cardiac arrest (IHCA)., Methods: This single-centred retrospective study reviewed patients with IHCA between 2006 and 2015. Early intra-arrest ABG data were measured within 10 min of initiating cardiopulmonary resuscitation. The ABG analysis included measurements of blood pH, PaCO 2 , and HCO 3 - ., Results: Among the 1065 included patients, 60 (5.6%) achieved neurologically intact survival. Mean blood pH was 7.2. Mean PaCO 2 and HCO 3 - levels were 59.7 mmHg and 22.1 mmol/L, respectively. A blood pH of 7.2 was identified by a generalised additive models plot to define severe acidaemia. The PaCO 2 level was higher in patients with severe acidaemia (mean: 74.5 vs. 44.1 mmHg) than in those without. Multivariable logistic regression analyses indicated that blood pH > 7.2 was associated with a favourable neurological recovery (odds ratio [OR]: 2.79, 95% confidence interval [CI]: 1.43-5.46; p-value = 0.003) and blood pH was positively associated with survival at hospital discharge (OR: 5.80, 95% CI: 1.62-20.69; p-value = 0.007)., Conclusion: Early intra-arrest blood pH was associated with IHCA outcomes, while levels of PaCO 2 and HCO 3 - were not. A blood pH of 7.2 could be used as the threshold defining severe acidaemia during arrest and help profile patients with IHCA. Innovative interventions should be developed to improve the outcomes of patients with severe acidaemia, such as novel ventilation methods., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC)., Methods: Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays., Results: The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline ( P < 0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors ( P < 0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients., Conclusion: Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yuan-Zhuo Chen et al.)

Aims: Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism., Methods and Results: In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P < 0.05). While sublingual microcirculation was significantly compromised in CPR and E-CPR, CO delivery demonstrated a significant improvement in microvascular function (microvascular flow index: Sham 2.9 ± 0.1; CPR 2.2 ± 0.1; E-CPR 1.8 ± 0.1; CO-E-CPR 2.7 ± 0.1; P < 0.01). Histological and serological myocardial damage markers were significantly reduced (hsTroponin-T Sham 0.01 ± 0.001; CPR 1.9 ± 0.2; E-CPR 3.5 ± 1.2; CO-E-CPR 0.5 ± 0.2 ng/mL; P < 0.05). DAMP signalling was decreased ipse facto leading to influence of cardioprotective heat shock and cyclooxygenase response., Conclusions: CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Sudden cardiac arrest is a major global health concern, and survival of patients with ischemia-reperfusion injury is a leading cause of myocardial dysfunction. The mechanism of this phenomenon is not well understood because of the complex pathophysiological nature of the disease. Aim of the study was to investigate the cardioprotective role of fingolimod in an in vivo model of cardiac arrest and resuscitation., Methods: In this study, an in vivo rat model of cardiac arrest using extracorporeal membrane oxygenation resuscitation monitored by invasive hemodynamic measurement was developed. At the beginning of extracorporeal life support (ECLS), animals were randomly treated with fingolimod (Group A, n = 30) or saline (Group B, n = 30). Half of the animals in each group (Group A1 and B1, n = 15 each) were sacrificed after 1 h, and the remaining animals (Group A2 and B2) after 24 h of reperfusion. Blood and myocardial tissues were collected for analysis of cardiac features, inflammatory biomarkers, and cell signaling pathways., Results: Treatment with fingolimod resulted in activation of survival pathways resulting into reduced inflammation, myocardial oxidative stress and apoptosis of cardiomyocytes. This led to significant improvement in systolic and diastolic functions of the left ventricle and improved contractility index., Conclusions: Sphingosine1phosphate receptor activation with fingolimod improved cardiac function after cardiac arrest supported with ECLS. Present study findings strongly support a cardioprotective role of fingolimod through sphingosine-1-phosphate receptor activation during reperfusion after circulatory arrest.

Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop an assay detecting the neo-epitope generated by caspase-6 cleavage of GFAP (GFAP-C6), and to assess the ability of GFAP-C6 to reflect pathological processes in patients suffering a cardiac arrest and subsequent global cerebral ischemia. Anti-GFAP-C6 antibodies recognized their specific target sequence, and dilution and spike recoveries in serum were within limits of ±20% reflecting high precision and accuracy of measurements. Intra- and inter-assay CVs were below limits of 10% and 15%, respectively. Serological levels of GFAP-C6 were significantly elevated 72 hours after CA (Mean±SD) (20.39±10.59 ng/mL) compared to time of admission (17.79±10.77 ng/mL, p<0.0001), 24 hours (17.40±7.99 ng/mL, p<0.0001) and 48 hours (17.87±8.56 ng/mL, p<0.0001) after CA, but were not related to neurological outcome at day 180. GFAP-C6 levels at admission, 24, 48, and 72 hours after cardiac arrest correlated with two proteolytic fragments of tau, tau-A (r = 0.30, r = 0.40, r = 0.50, r = 0.53, p < 0.0001) and tau-C (r = 54, r = 0.48, r = 0.55, r = 0.54, p < 0.0001), respectively. GFAP-C6 levels did not correlate with other markers of CNS damage; total tau, NSE and S100B. In conclusion, we developed the first assay detecting a caspase-6 cleaved fragment of GFAP in blood. Increased levels at 72 hours after cardiac arrest as well as moderate correlations between GFAP-C6 and two other blood biomarkers of neurodegeneration suggest the ability of GFAP-C6 to reflect pathological processes of the injured brain. Investigations into the potential of GFAP-C6 in other types of CNS injury are warranted., Competing Interests: The authors of this manuscript have read the journal’s policy and have the following competing interests: DSJ, KH and MK are employed by Nordic Bioscience and thus received support in the form of a salary. KH and MK own stocks in Nordic Bioscience and hold patents on biomarkers not measured in the present study. There are no patents, products in development or marketed products to declare in relation to this research. The remaining authors report no competing financial interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation (DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage-associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue-type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor-1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no-flow and low-flow times, patients without return of spontaneous circulation, and non-survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post-cardiac arrest syndrome., (© 2019 International Society on Thrombosis and Haemostasis.)

So far, there remains a controversy regarding the efficacy of epinephrine (Ep) in patients with cardiopulmonary arrest (CPA). In this study, we evaluated the importance of the plasma levels of catecholamines prior to the administration of Ep in patients with CPA. Patients with out-of-hospital cardiac arrest (OHCA) who were transferred to Gunma University Hospital were enrolled prospectively between July 2014 and July 2017. The levels of catecholamines [Ep, norepinephrine (NEp), and dopamine] and vasopressin (antidiuretic hormone) in the plasma were measured using blood samples of cardiogenic patients with OHCA not treated with Ep. Patients were divided into two groups: the return of spontaneous circulation [ROSC (+) ] group and the no return of spontaneous circulation [ROSC (-) ] group. The plasma levels of these agents and the conditions of resuscitation were compared between these two groups. 48 patients with cardiogenic CPA had not been treated with Ep prior to obtaining the blood samples. The ROSC (+) and ROSC (-) groups included 14 and 34 patients, respectively. The frequency of prehospital defibrillation was significantly higher in the ROSC (+) group. However, the prehospital resuscitation time was significantly shorter in the ROSC (+) group. Moreover, the levels of Ep and NEp in the plasma were significantly lower in the ROSC (+) group. The increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with cardiogenic CPA.

Purpose: Postresuscitation neuroprognostication is guided by neurophysiological tests, biomarker measurement, and clinical examination. Recent investigations suggest that circulating microRNAs (miRNA) may help in outcome prediction after cardiac arrest. We assessed the ability of miR-574-5p to predict neurological outcome after cardiac arrest, in a sex-specific manner., Methods: In this substudy of the Target Temperature Management (TTM) Trial, we enrolled 590 cardiac arrest patients for which blood samples were available. Expression levels of miR-574-5p were measured by quantitative PCR in plasma samples collected 48 h after cardiac arrest. The endpoint of the study was poor neurological outcome at 6 months (cerebral performance category scores 3 to 5)., Results: Eighty-one percent of patients were men, and 49% had a poor neurological outcome. Circulating levels of miR-574-5p at 48 h were higher in patients with a poor neurological outcome at 6 months ( p < 0.001), both in women and in men. Circulating levels of miR-574-5p were univariate predictors of neurological outcome (odds ratio (OR) [95% confidence interval (CI)]: 1.5 [1.26-1.78]). After adjustment with clinical variables and NSE, circulating levels of miR-574-5p predicted neurological outcome in women (OR [95% CI]: 1.9 [1.09-3.45]), but not in men (OR [95% CI]: 1.0 [0.74-1.28])., Conclusion: miR-574-5p is associated with neurological outcome after cardiac arrest in women.

Cerebral and cardiac dysfunction cause morbidity and mortality in postcardiac arrest syndrome (PCAS) patients. Predicting clinical outcome is necessary to provide the optimal level of life support for these patients. In this pilot study, we examined whether plasma ATP and adenylate levels have value in predicting clinical outcome in PCAS patients. In total, 15 patients who experienced cardiac arrest outside the hospital setting and who could be reanimated were enrolled in this study. Healthy volunteers (n = 8) served as controls. Of the 15 PCAS patients, 8 died within 4 days after resuscitation. Of the 7 survivors, 2 lapsed into vegetative states, 1 survived with moderate disabilities, and 4 showed good recoveries. Arterial blood samples were drawn immediately after successful resuscitation and return of spontaneous circulation (ROSC). The concentrations of ATP and other adenylates in plasma were assessed with high-performance liquid chromatography. PCAS patients had significantly higher ATP levels than healthy controls. Plasma ATP levels correlated with lactate levels, Acute Physiology and Chronic Health Evaluation II scores, and the time it took to ROSC (time-to-ROSC). Plasma adenylate levels in patients who died after resuscitation were significantly higher than in survivors. Based on our results and receiver-operating characteristic curve analysis, we conclude that plasma adenylate levels may help predict outcome in PCAS patients.

Background: It is not predictable which patients will develop a severe inflammatory response after successful cardiopulmonary resuscitation (CPR), also known as "postcardiac arrest syndrome." This pathology affects only a subgroup of cardiac arrest victims. Whole body ischemia/reperfusion and prolonged shock states after return of spontaneous circulation (ROSC) may both contribute to this devastating condition. The vascular endothelium with its glycocalyx is especially susceptible to initial ischemic damage and may play a detrimental role in the initiation of postischemic inflammatory reactions. It is not known to date if an immediate early damage to the endothelial glycocalyx, detected by on-the-scene blood sampling and measurement of soluble components (hyaluronan and syndecan-1), precedes and predicts multiple organ failure (MOF) and survival after ROSC., Methods: 15 patients after prehospital resuscitation were included in the study. Serum samples were collected on the scene immediately after ROSC and after 6 h, 12 h, 24 h, and 48 h. Hyaluronan and syndecan-1 were measured by ELISA. We associated the development of multiple organ failure and 30-day survival rates with these serum markers of early glycocalyx damage., Results: Immediate serum hyaluronan concentrations show significant differences depending on 30-day survival. Further, the hyaluronan level is significantly higher in patients developing MOF during the initial and intermediate resuscitation period. Also, the syndecan-1 levels are significantly different according to MOF occurrence., Conclusion: Serum markers of glycocalyx shedding taken immediately on the scene after ROSC can predict the occurrence of multiple organ failure and adverse clinical outcome in patients after cardiac arrest.

This study aimed to determine whether the combination of procalcitonin (PCT) and S100B improves prognostic performance compared to either alone in cardiac arrest (CA) patients treated with targeted temperature management (TTM).We performed a prospective cohort study of CA patients treated with TTM. PCT and S100B levels were obtained at 0, 24, 48, and 72 hours after return of spontaneous circulation. The prognostic performance was analyzed using each marker and the combination of the 2 markers for predicting poor neurological outcome at 3 months and mortality at 14 days and 3 months.A total of 97 patients were enrolled, of which 67 (69.1%) had poor neurological outcome. S100B showed a better prognostic performance (area under the curve [AUC], 0.934; sensitivity, 77.6%; and specificity, 100%) than PCT (AUC, 0.861; sensitivity, 70.2%; and specificity, 83.3%) with the highest prognostic value at 24 hours. The combination of 24-hour PCT and S100B values (S100B ≥0.2 μg/L or PCT ≥6.6 ng/mL) improved sensitivity (85.07%) compared with S100B alone. In multivariate analysis, PCT was associated with mortality at 14 days (odds ratio [OR]: 1.064, 95% confidence interval [CI]: 1.014-1.118), whereas S100B was associated with neurological outcomes at 3 months (OR: 9.849, 95% CI: 2.089-46.431).The combination of PCT and S100B improved prognostic performance compared to the use of either biomarker alone in CA patient treated with TTM. Further studies that will identify the optimal cutoff values for these biomarkers must be conducted.

Aim: The aim of our study was to evaluate the potential role of resistin in estimating the 30 days prognosis in patients with hypoxic-ischemic organ injury who survived after a cardiac arrest (CA)., Materials and Methods: The study included 40 patients resuscitated after a non-traumatic out-of-hospital CA admitted in Emergency Department (ED). All patients were followed for 30 days after CA or until death. Clinical data on admission were recorded. Blood samples were collected on admission in ED (0-time interval), and at 6, 12, 24, 48- and 72-hours following resuscitation. Serum concentrations of resistin, S100B and neuron specific enolase (NSE) were measured. Several predictive scores for the mortality at 30 days were created with logistic regressions., Results: At each time interval, median serum levels of resistin and S100 B were significantly higher in non-survivors compared to survivors. For NSE, plasma levels were significantly lower in survivors as compared to non-survivors at 48 and 72 hours, respectively. Accurate predictive scores for 30-days mortality were the ones which included the values of resistin and S100B measured at 12 hours after admittance [AUC 0.938 (0.813-0.989), sensitivity 85.71% (67.3%- 96%), specificity 91.67% (61.5%'99.8%), p<0.001], which included the values of all three markers measured at 12 hours after admittance [AUC 0.955 (0.839-0.995), sensitivity 82.14% (63.1%'93.9%), specificity 100.00% (73.5%'100.0%), p<0.001] and the that included the values of resistin and S-100B at 6 hours together with serum lactate on admission [AUC = 0.994 (0.901-1.0), sensitivity 96.4% (81.7%'99.9%), specificity 100.00% (73.5%'100.0%), p<0.001]., Conclusion: In our study, serum levels of resistin or a combination of resistin with S-100B or resistin with S-100B and lactate, were highly predictive for 30 days mortality in resuscitated patients after CA. Further studies on large number of patients are needed to confirm our data., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUND Patients undergoing cardiac surgery are at risk of adverse perioperative neurological complications. Cerebral oximetry monitoring is increasingly used in these patients to detect intraoperative cerebral hypoxia or ischemic events. Near-infrared spectroscopy (NIRS) uses the near-infrared region of the electromagnetic spectrum for oximetry imaging. A case is reported of the persistence of normal tissue oxygenation monitored by NIRS values despite a prolonged perioperative cardiac arrest. CASE REPORT A 65-year-old man was admitted to the Emergency Department with dysarthria, left facial ptosis, left hemiplegia, and arterial hypotension of 75/50 mmHg. Computed tomography (CT) angiography showed a Stanford type A aortic dissection extending to the right common carotid artery. Shortly after arrival in the operating room, his hemodynamic condition rapidly deteriorated resulting in cardiac arrest. Despite the rapid onset of extracorporeal circulation, adequate systemic blood flow could not be restored. Cerebral NIRS values remained within the normal range (70-80%) from the start of emergency resuscitation, during a prolonged period of extremely low global blood perfusion values, and until all resuscitation ceased. CONCLUSIONS Cerebral oximetry values reflect a balance between cerebral oxygen delivery and consumption. This case demonstrated the persistence of normal tissue oxygenation monitored by NIRS values despite a prolonged perioperative cardiac arrest.

Background: Post-cardiac arrest syndrome, which has no specific curative treatment, contributes to the high mortality rate of victims who suffer traumatic cardiac arrest (TCA) and initially can be resuscitated. In the present study, we investigated the potential of ulinastatin to mitigate multiple organ injury after resuscitation in a swine TCA model., Methods: Twenty-one male pigs were subjected to hemodynamic shock (40% estimated blood loss in 20 min) followed by cardiac arrest (electrically induced ventricular fibrillation) and respiratory suspension for 5 min, and finally manual resuscitation. At 5 min after resuscitation, pigs were randomized to receive 80,000 U/kg ulinastatin ( n  = 7) or the same volume of saline ( n  = 9) in the TCA group. Pigs in the sham group ( n  = 5) were not exposed to bleeding or cardiac arrest. At baseline and at 1, 3, and 6 h after the return of spontaneous circulation, blood samples were collected and assayed for tumor necrosis factor-alpha, interleukin 6, and other indicators of organ injury. At 24 h after resuscitation, pigs were sacrificed and apoptosis levels were assessed in samples of heart, brain, kidney, and intestine., Results: One pig died in the ulinastatin group and one pig died in the TCA group; the remaining animals were included in the final analysis. TCA and resuscitation caused significant increases in multiple organ function biomarkers in serum, increases in tumor necrosis factor-alpha, and interleukin 6 in serum and increases in the extent of apoptosis in key organs. All these increases were lower in the ulinastatin group., Conclusion: Ulinastatin may attenuate multiple organ injury after TCA, which should be explored in clinical studies., Competing Interests: Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background After cardiopulmonary resuscitation, the protective effects of therapeutic hypothermia induced by conventional cooling are limited. Recently, esophageal cooling ( EC ) has been shown to be an effective, easily performed approach to induce therapeutic hypothermia. In this study we investigated the efficacy of EC and its effects on early markers of postresuscitation cardiac and neurological injury in a porcine model of cardiac arrest. Methods and Results Thirty-two male domestic swine were randomized into 4 groups: sham control, normothermia, surface cooling, and EC . Sham animals underwent the surgical preparation only. Ventricular fibrillation was induced and untreated for 8 minutes while defibrillation was attempted after 5 minutes of cardiopulmonary resuscitation. At 5 minutes after resuscitation, therapeutic hypothermia was induced by either EC or surface cooling to reach a target temperature of 33°C until 24 hours postresuscitation, followed by a rewarming rate of 1°C/h for 5 hours. The temperature was normally maintained in the control and normothermia groups. After resuscitation, a significantly faster decrease in blood temperature was observed in the EC group than in the surface cooling group (2.8±0.7°C/h versus 1.5±0.4°C/h; P<0.05). During the maintenance and rewarming phases the temperature was maintained at an even level between the 2 groups. Postresuscitation cardiac and neurological damage was significantly improved in the 2 hypothermic groups compared with the normothermia group; however, the protective effects were significantly greater in the EC group. Conclusions In a porcine model of cardiac arrest, faster hypothermia successfully induced by EC was significantly better than conventional cooling in improving early markers of postresuscitation cardiac and neurological injury.

Objective: High-fidelity simulators can simulate physiological responses to medical interventions. The dynamics of the partial arterial pressure of oxygen (P a O 2 ), partial arterial pressure of carbon dioxide (P a CO 2 ), and oxygen pulse saturation (SpO 2 ) during simulated cardiopulmonary resuscitation (CPR) were observed and compared with the results from the literature., Methods: Three periods of cardiac arrest were simulated using the METI Human Patient Simulator™ (Medical Education Technologies, Inc., Sarasota, FL, USA): cardiac arrest, chest compression-only CPR, and chest compression-only CPR with continuous flow insufflation of oxygen (CFIO)., Results: In the first period, the observed values remained constant. In the second period, P a CO 2 started to rise and peaked at 63.5 mmHg. In the CFIO period, P a CO 2 slightly fell. P a O 2 and S p O 2 declined only in the second period, reaching their lowest values of 44 mmHg and 70%, respectively. In the CFIO period, P a O 2 began to rise and peaked at 614 mmHg. S p O 2 exceeded 94% after 2 minutes of CFIO., Conclusions: The METI Human Patient Simulator™ accurately simulated the dynamics of changes in P a CO 2 . Use of this METI oxygenation model has some limitations because the simulated levels of P a O 2 and S p O 2 during cardiac arrest correlate poorly with the results from published studies.

Aims: Lactate and lactate clearance were supposed to be associated with cardiac arrest outcomes, but studies obtained different results. Thus, we conducted this meta-analysis to investigate the association between lactate or lactate clearance and neurological outcomes and their usefulness for prediction of neurological outcomes., Methods: We conducted a systematic search in PubMed, Web of science, EMBASE, Medline, and Google Scholar until May 1, 2018, for relevant studies. Studies reporting lactate, lactate clearance on admission, or other time points after admission associated with neurological outcomes were included in our analysis. Pooled effect date was shown as weighed mean difference (WMD) and 95% confidence interval (CI). To measure the usefulness of lactate on admission to predict neurological outcomes, we also pooled the data of diagnostic test., Results: 23 studies involving 6720 cardiac arrest (CA) patients were included. Results from our analysis indicated that patients with good neurological outcomes tended to have a lower lactate level on admission (WMD: -2.66 mmol/L, 95%CI: -3.39 to -1.93) and 12h, 24h, and 48h after admission ( P <0.001). Furthermore, the pooled AUC for lactate level on admission to predict neurological outcomes was 0.77 (95%CI: 0.73-0.80). However, a significant association between lactate clearance and neurological outcomes was only found in 24h but not 12h lactate clearance rate., Conclusions: Lactate levels on admission and all time points up to 48h were associated with neurological outcomes after CA, whereas the association between lactate clearance and neurological outcomes was not so stable. Lactate was a more robust surrogate marker than lactate clearance to predict neurological outcomes after CA.

Background: Platelet variables, including platelet distribution width (PDW) and mean platelet volume (MPV), have been associated with outcome in critically ill patients. We evaluated these variables in patients after cardiac arrest (CA)., Methods: All adult CA patients admitted to the intensive care unit (ICU) over an 8-year period (2006-2014) and treated with targeted temperature management were included. We retrieved all data concerning CA characteristics as well as platelet count, PDW and MPV on the first 2 days of admission. Unfavorable 3-month neurological outcome was defined as a cerebral performance category score of 3-5., Results: We included 384 patients (age 62 [52-75] years; 270/384 male): 231 patients (60%) died within 30-days and 246 patients (64%) had an unfavorable 3-month neurological outcome. On admission, platelet count, PDW and MPV were 87 [126-261] *10 3 cells/mm 3 , 17 [16.3-17.3]% and 8.3 [7.6-9.2] μm 3 , respectively. Platelet count decreased significantly over the first 2 days, whereas PDW and MPV did not change significantly. There were no significant differences between the values on admission or time-courses of platelet count, PDW or MPV between survivors and non-survivors or between patients with unfavorable and favorable neurological outcome., Conclusions: In our cohort of post-CA patients, PDW and MPV were not associated with outcome.

Background: Deranged glucose metabolism is frequently observed in trauma patients after moderate to severe traumatic injury, but little data is available about pre-hospital blood glucose and its association with various cardiac rhythms and cardiac arrest following trauma., Methods: We retrospectively investigated adult trauma patients treated by a nationwide helicopter emergency medical service (34 bases) between 2005 and 2013. All patients with recorded initial cardiac rhythms and blood glucose levels were enrolled. Blood glucose concentrations were categorised; descriptive and regression analyses were performed., Results: In total, 18,879 patients were included, of whom 185 (1.0%) patients died on scene. Patients with tachycardia (≥100/min, 7.0 ± 2.4 mmol/L p < 0.0001), pulseless ventricular tachycardia (9.8 ± 1.8, mmol/L, p = 0.008) and those with ventricular fibrillation (9.0 ± 3.2 mmol/L, p < 0.0001) had significantly higher blood glucose concentrations than did patients with normal sinus rhythm between 61 and 99/min (6.7 ± 2.1 mmol/L). In patients with low (≤2.8 mmol/L, 7/79; 8.9%, p < 0.0001) and high (> 10.0 mmol/L, 70/1271; 5.5%, p < 0.0001) blood glucose concentrations cardiac arrest was more common than in normoglycaemic patients (166/9433, 1.8%). ROSC was more frequently achieved in hyperglycaemic (> 10 mmol/L; 47/69; 68.1%) than in hypoglycaemic (≤4.2 mmol/L; 13/31; 41.9%) trauma patients (p = 0.01)., Conclusions: In adult trauma patients, pre-hospital higher blood glucose levels were related to tachycardic and shockable rhythms. Cardiac arrest was more frequently observed in hypoglycaemic and hyperglycaemic pre-hospital trauma patients. The rate of ROSC rose significantly with rising blood glucose concentration. Blood glucose measurements in addition to common vital parameters (GCS, heart rate, blood pressure, breathing frequency) may help identify patients at risk for cardiopulmonary arrest and dysrhythmias.

Background: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome., Methods: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao 2 ) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao 2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao 2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao 2 levels and poor neurological outcome, we used other Pao 2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg)., Results: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg., Conclusions: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge., (© 2018 American Heart Association, Inc.)

One of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams., (Copyright © 2017 by the American Society of Nephrology.)

Background: Lipid emulsion treatment appears to have application in the treatment of local anesthetic-induced cardiac arrest. To examine whether the efficacy of lipid resuscitation in the treatment of local anesthetic-induced cardiac arrest is affected by lipophilicity, the effects of lipid infusions were compared between levobupivacaine-induced (high lipophilicity) and ropivacaine-induced (lower lipophilicity) rat cardiac arrest model., Methods: A total of 28 female Sprague-Dawley rats were anesthetized using sevoflurane, which subsequently underwent tracheostomy, followed by femoral artery and vein cannulation. Two hours after the discontinuation of sevoflurane, either levobupivacaine 0.2% (n = 14) or ropivacaine 0.2% (n = 14) was administered at a rate of 2 mg/kg/min to the awake rats. When the pulse pressure decreased to 0, the infusion of local anesthetic was discontinued, and treatment with chest compressions and ventilation with 100% oxygen were immediately initiated. The total doses of local anesthetics needed to trigger the first seizure and pulse pressure of 0 mm Hg were calculated. The 2 groups were each subdivided into a lipid emulsion group (n = 7) and a control group (n = 7). In the lipid emulsion group, 20% lipid emulsion was administered intravenously (5 mL/kg bolus plus continuous infusion of 0.5 mL/kg/min), while in the control group, the same volume of normal saline was administered. Chest compressions were discontinued when the rate-pressure product had increased by more than 20% of baseline., Results: The cumulative doses of levobupivacaine and ropivacaine that produced seizures and 0 pulse pressure showed no significant difference. Mean arterial blood pressure (MAP) values were higher in the levobupivacaine group than in the ropivacaine group after resuscitation was initiated (P < .05). In levobupivacaine-induced cardiac arrest, heart rate and MAP values were higher in the lipid group than in the control group after starting resuscitation (P < .05); all rats in the lipid group achieved spontaneous circulation (rate-pressure product >20% baseline), while only 2 of 7 rats in the control group achieved spontaneous circulation at 10 minutes. In ropivacaine-induced cardiac arrest, there were no significant differences in heart rate and MAP between the lipid and control groups from the start of resuscitation to 10 minutes; spontaneous circulation returned in 6 of 7 lipid group rats, but in only 2 of 7 control group rats at 10 minutes., Conclusions: Lipid emulsion treatment was more effective for levobupivacaine-induced cardiac arrest than for ropivacaine-induced cardiac arrest. Although lipid therapy is also effective for ropivacaine-induced cardiac arrest, it takes more time than in levobupivacaine-induced cardiac arrest. This suggests that the lipophilicity of local anesthetics influences the efficacy of lipid infusion when treating cardiac arrest caused by these drugs.