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Outline of the experimental protocol. VF, ventricular fibrillation; CCPR, conventional cardiopulmonary resuscitation; ECMO, extracorporeal membrane oxygenation; EP, epinephrine
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Introduction:
Despite decades of improved strategy in conventional cardiopulmonary resuscitation (CCPR), survival rates of favorable neurological outcome after cardiac arrest (CA) remains poor. It is indicated that the survival rate of successful resuscitation of extracorporeal membrane oxygenation (ECMO) is superior to that of CCPR. But the effec...
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A 24-year-old man suffered a witnessed cardiac arrest after a padel game. Basic life support was immediately provided. The pre-hospital emergency services team continued the resuscitation efforts, and the patient was accepted for extracorporeal cardiopulmonary resuscitation. The return of spontaneous circulation was achieved in 45 minutes. The init...
Citations
... While there are numerous established neurological models for conventional CPR, [15][16][17][18] and some models that investigate the survival and organ function preservation in ECPR, [19][20][21] little is known regarding a mature and reproducible neurological ECPR model. Therefore, there is an urgent need for a translational ECPR model that can answer mechanistic questions and lead to intervention and monitoring strategies to ultimately improve neurological outcomes in ECPR. ...
Background
Despite the high prevalence of neurological complications and mortality associated with extracorporeal cardiopulmonary resuscitation (ECPR), neurologically-focused animal models are scarce. Our objective is to review current ECPR models investigating neurological outcomes and identify key elements for a recommended model.
Methods
We searched PubMed and four other engines for animal ECPR studies examining neurological outcomes. Inclusion criteria were: animals experiencing cardiac arrest, ECPR/ECMO interventions, comparisons of short versus long cardiac arrest times, and neurological outcomes.
Results
Among 20 identified ECPR animal studies (n = 442), 13 pigs, 4 dogs, and 3 rats were used. Only 10% (2/20) included both sexes. Significant heterogeneity was observed in experimental protocols. 90% (18/20) employed peripheral VA-ECMO cannulation and 55% (11/20) were survival models (median survival = 168 hours; ECMO duration = 60 minutes). Ventricular fibrillation (18/20, 90%) was the most common method for inducing cardiac arrest with a median duration of 15 minutes (IQR = 6–20). In two studies, cardiac arrests exceeding 15 minutes led to considerable mortality and neurological impairment. Among seven studies utilizing neuromonitoring tools, only four employed multimodal devices to evaluate cerebral blood flow using Transcranial Doppler ultrasound and near-infrared spectroscopy, brain tissue oxygenation, and intracranial pressure. None examined cerebral autoregulation or neurovascular coupling.
Conclusions
The substantial heterogeneity in ECPR preclinical model protocols leads to limited reproducibility and multiple challenges. The recommended model includes large animals with both sexes, standardized pre-operative protocols, a cardiac arrest time between 10–15 minutes, use of multimodal methods to evaluate neurological outcomes, and the ability to survive animals after conducting experiments.
... The integrity of mitochondrial structure and function is the premise and basis of normal cell metabolism, and mitochondria can also regulate intracellular ion balance, and then participate in the processes of cell apoptosis and necrosis (40). In the animal model of ventricular fibrillationinduced cardiac arrest, ECMO can prevent oxidative damage, regulate energy metabolism, inhibit cardiomyocyte apoptosis, and improve survival (41). We also found that, the two hub genes, ASB13 and CDCA7, were both apoptosis-related genes, suggesting that ECMO may affect the prognosis of patients through apoptosis, in the AMI complicated by cardiogenic shock. ...
Background
Extracorporeal membrane oxygenation (ECMO) is an important clinical treatment for acute myocardial infarction (AMI) combined with cardiogenic shock, but the role of programmed cell death (PCD)-related genes in prognostication has not yet been investigated. Therefore, we explored the key prognostic biomarkers and immune infiltration in ECMO treatment in AMI combined with cardiogenic shock.
Methods
The GSE93101 dataset was analyzed from the Gene Expression Omnibus (GEO) database, and the expression levels of PCD-related genes in AMI under ECMO were identified. Differentially expressed PCD-related genes between successful and failed treatment samples were analyzed, and Least absolute shrinkage and selection operator (LASSO) logistic regression and random forest were used to screen PCD-related molecular markers for ECMO treatment in AMI combined with cardiogenic shock. Co-expressed regulatory network and enrichment functions of the hub PCD-related genes were performed. In addition, the single-sample gene set enrichment analysis (ssGSEA) algorithm was used to calculate the immune cell infiltration of the ECMO treatment samples.
Results
A total of 115 differentially expressed genes were identified from the GSE93101 dataset, and 76 genes were associated with PCD. Then, two hub PCD-related genes, Cell division cycle associated 7 (CDCA7), ankyrin repeat and SOCS box containing 13 (ASB13) were identified as prognostic markers of ECMO treatment in AMI combined with cardiogenic shock. The most significant Gene Ontology (GO) enriched terms of the co-expressed protein of ASB13 are related to post-translational protein modification, cullin-RING ubiquitin ligase complex, and cullin family protein binding, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that ubiquitin mediated proteolysis is the most enriched pathway. The results of GO and KEGG analysis in CDCA7 were mainly involved in DNA and cell cycle related activities and pathways. Moreover, we found that the successful treatment samples contained a lower proportion of nature killer T cells using immune infiltration analysis. Immune cell infiltration analysis revealed that ASB13 was positively correlated with natural killer cell ( r = 0.591, p = 0.026), monocyte ( r = 0.586, p = 0.028), and gamma delta T cell ( r = 0.562, p = 0.036).
Conclusion
The results of this study showed that ASB13 and CDCA7 may contribute to the occurrence and progression of AMI with cardiogenic shock under ECMO.
... With the development of more portable ECMO devices and percutaneous implantation, ECPR has become possible in medical intensive care units and emergency rooms, expanding its potential use in patients with out-of-hospital cardiac arrest (OHCA) [5,6]. Multiple animal models have demonstrated improved survival and end-organ protection with ECPR, compared with CCPR, after CA [7][8][9] Since the mid-2000s, the number of ECMO-capable centers participating in the Extracorporeal Life Support Organization (ELSO) has tripled, increasing the feasibility of ECPR [10][11][12]. Two meta-analyses of observational studies comparing ECPR and CCPR for patients with CA occurring in and outside of the hospital demonstrated an improvement in both survival and neurologic outcomes with ECPR. ...
The addition of extracorporeal membrane oxygenation (ECMO) to conventional cardiopulmonary resuscitation (CPR), termed extracorporeal cardiopulmonary resuscitation (ECPR), has significantly improved survival in selected patient populations. Despite this advancement, significant neurological impairment persists in approximately half of survivors. ECPR represents a potential advancement for patients who experience refractory cardiac arrest (CA) due to a reversible etiology and do not regain spontaneous circulation. Important risk factors for acute brain injury (ABI) in ECPR include lack of perfusion, reperfusion, and altered cerebral autoregulation. The initial hypoxic-ischemic injury caused by no-flow and low-flow states after CA and during CPR is compounded by reperfusion, hyperoxia during ECMO support, and nonpulsatile blood flow. Additionally, ECPR patients are at risk for Harlequin syndrome with peripheral cannulation, which can lead to preferential perfusion of cerebral vessels with deoxygenated blood. Lastly, the oxygenator membrane is prothrombotic and requires systemic anticoagulation. The two competing phenomena result in thrombus formation, hemolysis, and thrombocytopenia, increasing the risk of ischemic and hemorrhagic ABI. In addition to clinical studies, we assessed available ECPR animal models to identify the mechanisms underlying ABI at the cellular level. Standardized multimodal neurological monitoring may facilitate early detection of and intervention for ABI. With the increasing use of ECPR, it is critical to understand the pathophysiology of ABI, its prevention, and the management strategies for improving the outcomes of ECPR. Translational and clinical research focusing on acute ABI immediately after ECMO cannulation and its short- and long-term neurological outcomes are warranted.
Peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used in patients suffering from refractory cardiogenic shock (CS). Although considered life-saving, peripheral VA-ECMO may also be responsible for intracardiac hemodynamic changes, including left ventricular overload and dysfunction. Venoarterial extracorporeal membrane oxygenation may also increase myocardial wall stress and stroke work, possibly affecting the cellular cardioprotective and apoptosis signaling pathways, and thus the infarct size. To test this hypothesis, we investigated the effects of increasing the peripheral VA-ECMO blood flow (25–100% of the baseline cardiac output) on systemic and cardiac hemodynamics in a closed-chest CS model. Upon completion of the experiment, the hearts were removed for assessment of infarct size, histology, apoptosis measurements, and phosphorylation statuses of p38 and protein Kinase B (Akt), and extracellular signal-regulated kinase mitogen-activated protein kinases (ERK-MAPK). Peripheral VA-ECMO restored systemic perfusion but induced a significant and blood flow-dependent increase in left ventricular preload and afterload. Venoarterial extracorporeal membrane oxygenation did not affect infarct size but significantly decreased p38-MAPK phosphorylation and cardiac myocyte apoptosis in the border zone.
This study compared the effects of extracorporeal cardiopulmonary resuscitation (ECPR) using propensity-score matching (PSM) analyses. A nationwide registry of out-of-hospital cardiac arrest (OHCA) patients in Korea between 2013 and 2016 was used. Patients with OHCA aged ≥15 years with cardiac etiology and resuscitation time >30 minutes were enrolled. Resuscitation-related variables before the initiation of ECPR were included. Two PSM analyses were performed separately, with and without post-ECPR variables. The primary outcome (PO) was a favorable neurologic outcome at hospital discharge. The rate of PO was 8.1% (13/161) in the ECPR group and 1.5% (247/16,489) in the conventional CPR (CCPR) group. In the matched cohort with post-ECPR variables, there was no significant difference in the rate of PO between the ECPR and CCPR groups (7.9% vs. 7.9%; p = 0.982). In the matched cohort without post-ECPR variables, the rate of PO was higher in the ECPR group than that in the CCPR group (8.3% vs. 3.6%; p = 0.012). PSM analysis without post-ECPR variables compared outcomes of all patients experiencing OHCA and treated with ECPR versus CCPR, which showed better neurologic outcomes for ECPR. PSM analysis with post-ECPR variables compared outcomes between ECPR survivors and CCPR survivors, which exhibited similar neurologic outcomes.
Elderly patients affected by suspected infection and declining clinical conditions can be admitted to stepdown units (SDU), but a risk stratification is necessary to optimize their management. Admission troponin I (aTnI) has a prognostic role, however, one of the most commonly used stratification tools, the Sequential Organ Failure Assessment score (SOFA), does not consider myocardial injury. With this paper, we aimed to evaluate the prognostic accuracy of a new score, named SOFA-T, considering both SOFA score and aTnI in a cohort of elderly patients admitted to the stepdown beds of two Internal Medicine departments. Patients aged > 65 years admitted in SDU of two different hospitals of the same region in a 12-months timeframe were retrospectively assessed obtaining age, sex, days of admission, in-hospital death, SOFA, aTnI and comorbidities. The best aTnI cutoff for in-hospital death was calculated with ROC curve analysis; dichotomous variables were compared with chi-squared test; continuous variables were compared with t test or Mann–Whitney test. We obtained a cohort of 390 patients. The best aTnI cutoff was 0.31 ng/ml: patients with increased aTnI had higher risk of in-hospital death (OR: 1.834; 95% CI 1.160–2.900; p = 0.009), and higher SOFA (6.81 ± 2.71 versus 5.97 ± 3.10; p = 0.010). Adding aTnI to SOFA increased significantly the area under the curve (AUCSOFA = 0.68; 95% CI 0.64–0.73; AUCSOFA-T = 0.71; 95% CI 0.65–0.76; p = 0.0001), with a slight improvement of the prognostic performance. In elderly patients admitted to SDU for suspected infection, sepsis or septic shock, aTnI slightly improves the accuracy of SOFA score of the in-hospital death prediction.
Background
More than 640,000 combined in-hospital and out-of-hospital cardiac arrests occur annually in the United States. However, survival rates and meaningful neurologic recovery remain poor. Although “shockable” rhythms (i.e., ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)) have the best outcomes, many of these ventricular dysrhythmias fail to return to a perfusing rhythm (resistant VF/VT), or recur shortly after they are resolved (recurrent VF/VT).
Objective
This review discusses 4 emerging therapies in the emergency department for treating these resistant or recurrent ventricular dysrhythmias: beta-blocker therapy, dual simultaneous external defibrillation, stellate ganglion blockade, and extracorporeal cardiopulmonary resuscitation. We discuss the underlying physiology of each therapy, review relevant literature, describe when these approaches should be considered, and provide evidence-based recommendations for these techniques.
Discussion
Esmolol may mitigate some of epinephrine's negative effects when used during resuscitation, improving both postresuscitation cardiac function and long-term survival. Dual simultaneous external defibrillation targets the region of the heart where ventricular fibrillation typically resumes and may apply a more efficient defibrillation across the heart, leading to higher rates of successful defibrillation. Stellate ganglion blocks, recently described in the emergency medicine literature, have been used to treat patients with recurrent VF/VT, resulting in significant dysrhythmia suppression. Finally, extracorporeal cardiopulmonary resuscitation is used to provide cardiopulmonary support while clinicians correct reversible causes of arrest, potentially resulting in improved survival and good neurologic functional outcomes.
Conclusion
These emerging therapies do not represent standard practice; however, they may be considered in the appropriate clinical scenario when standard therapies are exhausted without success.
