Post-cardiac Arrest Research Articles

The impact of real-time feedback on ventilation quality during out-of-hospital cardiac arrest: A before-and-after study

IntroductionVentilations are a critical component of cardiopulmonary resuscitation (CPR). There is conflicting evidence, however, on the most appropriate method of ventilation during cardiac arrest management. Recent evidence has suggested that regardless of the optimal ventilation strategy, ventilations are often not delivered compliant with guideline recommendations. Recent technological advancements have allowed for accurate measurement and real-time feedback of ventilation rate and volume during resuscitation. Simulation studies have found significant improvements in ventilations with the use of real-time feedback during simulated cardiac arrest. The use of feedback has not been studied in clinical practice.The objective of this study was to determine whether the use of real-time feedback improves compliance with pre-defined targets for ventilation rate and volume during out-of-hospital cardiac resuscitation. MethodsThis was a before-and-after study with four paramedic services in Ontario, Canada. We enrolled adult, out-of-hospital cardiac arrest (OHCA) patients where the ZOLL Accuvent® device was utilized to measure ventilation rate and volume. In the before phase (without feedback), the Accuvent® was used to measure ventilations, however, providers were blinded to the real-time feedback. In the after phase (with feedback), the feedback dashboard was activated and providers used the real-time feedback to guide their ventilations. All other aspects of resuscitation remained consistent throughout the study. The main objective of the study was to compare the proportion of each case that was compliant with pre-defined ventilation targets with real-time feedback and without real-time feedback. We also examined the use of advanced airways on ventilation quality and examined for associations between ventilation parameters and return of circulation. ResultsWe enrolled 412 patients in the study (191 in the before phase without feedback and 221 in the after phase with feedback). Overall, we found significant improvements in both ventilation rate and volume in the after phase (with real-time feedback) compared to the before phase (without real-time feedback). We did not find any differences in ventilation compliance with or without advanced airways, or intra-arrest or post-cardiac arrest. ConclusionThe use of real-time feedback was associated with an increased proportion of ventilations that were compliant with pre-defined targets during cardiac resuscitation. Further work is required to improve the use of real-time ventilation feedback, and to determine the impact of ventilations on patient outcomes.

A larval zebrafish model of cardiac physiological recovery following cardiac arrest and myocardial hypoxic damage.

Contemporary cardiac injury models in zebrafish larvae include cryoinjury, laser ablation, pharmacological treatment and cardiac dysfunction mutations. Although effective in damaging cardiomyocytes, these models lack the important element of myocardial hypoxia, which induces critical molecular cascades within cardiac muscle. We have developed a novel, tractable, high throughput in vivo model of hypoxia-induced cardiac damage that can subsequently be used in screening cardioactive drugs and testing recovery therapies. Our potentially more realistic model for studying cardiac arrest and recovery involves larval zebrafish (Danio rerio) acutely exposed to severe hypoxia (PO2=5-7 mmHg). Such exposure induces loss of mobility quickly followed by cardiac arrest occurring within 120 min in 5 days post fertilization (dpf) and within 40 min at 10 dpf. Approximately 90% of 5 dpf larvae survive acute hypoxic exposure, but survival fell to 30% by 10 dpf. Upon return to air-saturated water, only a subset of larvae resumed heartbeat, occurring within 4 min (5 dpf) and 6-8 min (8-10 dpf). Heart rate, stroke volume and cardiac output in control larvae before hypoxic exposure were 188±5 bpm, 0.20±0.001 nL and 35.5±2.2 nL/min (n=35), respectively. After briefly falling to zero upon severe hypoxic exposure, heart rate returned to control values by 24 h of recovery. However, reflecting the severe cardiac damage induced by the hypoxic episode, stroke volume and cardiac output remained depressed by ∼50% from control values at 24 h of recovery, and full restoration of cardiac function ultimately required 72 h post-cardiac arrest. Immunohistological staining showed co-localization of Troponin C (identifying cardiomyocytes) and Capase-3 (identifying cellular apoptosis). As an alternative to models employing mechanical or pharmacological damage to the developing myocardium, the highly reproducible cardiac effects of acute hypoxia-induced cardiac arrest in the larval zebrafish represent an alternative, potentially more realistic model that mimics the cellular and molecular consequences of an infarction for studying cardiac tissue hypoxia injury and recovery of function.

Coinfection of Klebsiella pneumoniae and Aspergillus in a patient with chronic obstructive pulmonary disease post cardiac arrest: a case report

IntroductionChronic obstructive pulmonary disease is a lung condition characterized by chronic respiratory symptoms (breathlessness, cough, and expectoration). In the advanced stages, patients often report to the Accident & Emergency department due to worsening of symptoms. Because of the repeated exposure to corticosteroids during the management of exacerbations, these patients are susceptible to super additional infections. Pulmonary aspergillosis can be divided into three main categories: invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Aspergillus overlap syndrome is defined as the presence of more than one form of Aspergillus in a single patient. However, coinfection with Klebsiella and pulmonary aspergillosis overlap syndrome is rare and poses a treatment challenge. As per a pub med search, no such case report has been reported in a case of chronic obstructive pulmonary disease.Case reportWe report the case of a 66-year-old male, Punjabi Hindu by ethnicity, who was a reformed smoker with a known case of COPD. He presented with a history of breathlessness (mMRC grade 4) associated with cough with expectoration and wheezing for 15 days and intermittent episodes of hemoptysis for more than 6 months. The examination revealed tachypnea and wheezing throughout the lung fields. He was initially managed with parenteral steroids and frequent nebulization with bronchodilators. On day 5 of hospitalization, the patient experienced worsening of symptoms and cardiac arrest; he was intubated and return of spontaneous circulation was achieved within 5 minutes of cardio pulmonary resuscitation. Tracheal aspirate and culture revealed Aspergillus fumigatus and Klebsiella pneumoniae respectively. He underwent chest CT, which showed features suggestive of allergic bronchopulmonary aspergillosis and invasive pulmonary aspergillosis. He was found to have elevated β-d-glucan, galactomannan, and aspergillus IgE and IgG. Severe pneumonia and pulmonary Aspergillus overlap syndrome were managed with antibiotics, steroids, and antifungals. Over the next 15–20 days, his general condition improved. He was discharged after 45 days of hospitalization and continued on oral corticosteroids, antifungals, and inhaled bronchodilators.ConclusionCoinfection with bacteria and fungi worsens the outcome. Clinicians should be aware of the polymicrobial manifestations and various drug interactions involved. Timely diagnosis aids in better management strategies and improved patient outcomes.

Evaluation of levetiracetam loading dose in adult patients with benzodiazepine-refractory status epilepticus

BackgroundStatus epilepticus (SE) is a neurologic emergency defined as continued seizure activity greater than five minutes or recurrent seizure activity without return to baseline. Benzodiazepine-refractory SE is continuous seizure activity despite treatment with a benzodiazepine. Treatment of benzodiazepine-refractory SE includes levetiracetam with loading doses ranging from 20 mg/kg to 60 mg/kg up to a maximum dose of 4500 mg. While levetiracetam has minimal adverse effects, there is currently a lack of studies directly comparing the safety and efficacy of various loading doses of levetiracetam. ObjectiveThe objective of this study was to evaluate the safety and efficacy of three loading doses of levetiracetam in the setting of benzodiazepine-refractory SE. MethodsThis was a single center, retrospective cohort study of adult patients with benzodiazepine-refractory SE who were treated with levetiracetam from April 1, 2016, to August 31, 2023. Patients with documented hypersensitivity to levetiracetam, those who were pregnant or incarcerated and patients who received an alternative antiepileptic drug (AED) prior to levetiracetam were excluded. Patients with other identifiable causes of SE including hyperglycemia, hypoglycemia, hyponatremia or who were post cardiac arrest were also excluded. Patients were divided into three arms based on loading dose of levetiracetam administered (≤20 mg/kg [LEVlow], 21‐–39 mg/kg [LEVmed] or ≥40 mg/kg [LEVhigh]). The primary endpoint was the rate of seizure termination, defined as the lack of need for an additional AED within 60 min following levetiracetam administration. Secondary outcomes included the rate of intubation, and recurrent seizure activity 60 min to 24 h post seizure termination as defined by positive EEG results or need for an additional AED. Subgroup analyses were performed to assess the influence of adequate loading doses of benzodiazepines, and outpatient levetiracetam use. ResultsOverall, 740 patients were screened for inclusion, with 218 patients being included in the primary analysis. Patients were divided into three groups with an average levetiracetam loading dose of 14.5 mg/kg in the LEVlow group, 28.8 mg/kg in the LEVmed group, and 48.8 mg/kg in the LEVhigh group. There was no difference in rates of seizure termination at 60 min (92.9% LEVlow vs 89.3% LEVmed vs 84.7% LEVhigh; p = 0.377). Additionally, no difference was found in rates of recurrent seizure activity between 60 min and 24 h post levetiracetam loading dose (32.1% LEVlow vs 32.0% LEVmed vs 28.8% LEVhigh; p = 0.899). However, the LEVhigh group did have a higher rate of intubation (45.8%) compared to the LEVmed (28.2%) and LEVlow (26.8%) group (p = 0.040). ConclusionThe loading of levetiracetam did not result in a statistically significant difference in rate of seizure termination at 60 min nor did it appear to impact the rate of recurrent seizures at 24 h. However, we did find higher rates of intubation in patients who received levetiracetam >40 mg/kg. Further research is warranted to determine the optimal loading dose of levetiracetam in benzodiazepine-refractory SE.

High-sensitivity troponin T for detection of culprit lesions in patients with out-of-hospital cardiac arrest.

Patients with an out-of-hospital cardiac arrest (OHCA) often undergo coronary angiography, although a culprit lesion is found in only 30%-40% of patients. The aim of this study was to investigate high-sensitivity troponin T (hsTnT) levels in post cardiac arrest patients with and without coronary culprit lesions; factors affecting hsTnT levels after return of spontaneous circulation (ROSC); and the diagnostic ability of hsTnT in identifying patients with culprit lesions. We hypothesized that peak hsTnT levels were higher during the initial 48 h after cardiac arrest in patients with a coronary culprit lesion. This was a retrospective observational study, which included patients admitted to the Intensive Care Unit after an OHCA and who received a coronary angiography. Peak values and dynamic changes in hsTnT were analyzed in relation to the presence of a culprit lesion at coronary angiography. A total of 238 patients were studied, of whom 140 had a culprit lesion. HsTnT levels during the initial 48 h were higher in patients with culprit lesions, longer time to ROSC and an unwitnessed cardiac arrest. At 6 to 12 h after ROSC, a hsTnT cut-off level of 1690 ng/L had a sensitivity of 64% and specificity of 84% to identify a culprit lesion. In patients without ST-elevations, hsTnT measured between 6 and 12 h after ROSC had a specificity above 90%, with a sensitivity of 46%. HsTnT levels after cardiac arrest are higher in patients with coronary culprit lesions. Presence of a culprit lesion, witnessed status and the duration of CPR are important factors affecting hsTnT levels. Repeated measurement of hsTnT within the first 12 h after admission improved diagnostic accuracy but the value of hsTnT as a predictor of culprit lesions early after OHCA is limited.

Practice survey on recent changes in post cardiac arrest care and temperature management in French intensive care units

BackgroundRecent guidelines for post-cardiac arrest (CA) management have undergone significant changes regarding targeted therapeutic management (TTM), transitioning from hypothermia to temperature control. We aimed to assess changes in post-CA management in French intensive care units following the new recommendations. MethodsTwo declarative web surveys were conducted from March to August 2023. We compared the doctors' survey to that previously published in 2015. We contacted 389 departments from 276 French centers. ResultsThree hundred thirty-four physicians from 189 distinct ICUs departments participated in the survey. TTM was used by 95.5 % of respondents. TTM with temperature feedback device was used by 64 % of respondents. In multivariate analysis, use of TTM with temperature feedback was associated with university hospital responder [OR 1.99 (1.19–3.34, p = 0.009)], high CA admissions rate [OR 2.25 (1.13–4.78, p = 0.026)], use of a written CA procedure [OR 1.76 (1.07–2.92, p = 0.027)] and presence of a cath-lab performing coronary angiography [OR 2.42 (1.33–4.44, p = 0.004)]. The targeted temperature rose from 32 to 34 °C in 2015, to 35–36 °C in 2023 (p < 0.001). Proportions of TTM with temperature feedback devices switched from 45 % to 65 % (p < 0.001). 660 nurses responses from 150 ICUs were analyzed. According to TTM users, gel-coated water circulating pads and intravascular cooling were considered the most effective devices and were found to be easily adjustable. ConclusionsThese surveys provide insights into post-resuscitation care and TTM practice in France. One year after their publication, the latest recommendations concerning TTM have not been fully implemented, as the majority of ICUs continue to use moderate hypothermia. They widely reported employing specific TTM, with the use of TTM with temperature feedback devices increasing significantly. Heterogeneity exists regarding the TTM systems used, with a significant proportion lacking temperature feedback. This aspect requires specific attention, depending on local constraints and devices costs.

Development and evaluation of the model for acute kidney injury in patients with cardiac arrest after successful resuscitation

BackgroundThis study aims to construct a clinical prediction model and create a visual line chart depicting the risk of acute kidney injury (AKI) following resuscitation in cardiac arrest (CA) patients. Additionally, the study aims to validate the clinical predictive accuracy of the developed model.MethodsData were retrieved from the Dryad database, and publicly shared data were downloaded. This retrospective cohort study included 347 successfully resuscitated patients post-cardiac arrest from the Dryad database. Demographic and clinical data of patients in the database, along with their renal function during hospitalization, were included. Through data analysis, the study aimed to explore the relevant influencing factors of acute kidney injury (AKI) in patients after cardiopulmonary resuscitation. The study constructed a line chart prediction model using multivariate logistic regression analysis with post-resuscitation shock status (Post-resuscitation shock refers to the condition where, following successful cardiopulmonary resuscitation after cardiac arrest, some patients develop cardiogenic shock.), C reactive protein (CRP), Lactate dehydrogenase (LDH), and Alkaline phosphatase (ALP) identified as predictive factors. The predictive efficiency of the fitted model was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.ResultsMultivariate logistic regression analysis showed that post-resuscitation shock status, CRP, LDH, and PAL were the influencing factors of AKI after resuscitation in CA patients. The calibration curve test indicated that the prediction model was well-calibrated, and the results of the Decision Curve Analysis (DCA) demonstrated the clinical utility of the model constructed in this study.ConclusionPost-resuscitation shock status, CRP, LDH, and ALPare the influencing factors for AKI after resuscitation in CA patients. The clinical prediction model constructed based on the above indicators has good clinical discriminability and practicality.

Monitoring of Cerebral Blood Flow Autoregulation after Cardiac Arrest.

Background: Cardiac arrest remains one of the leading causes of death. After successful resuscitation of patients in cardiac arrest, post-cardiac arrest syndrome develops, part of it being an impaired cerebral blood flow autoregulation. Monitoring cerebral blood flow autoregulation after cardiac arrest is important for optimizing patient care and prognosticating patients' survival, yet remains a challenge. There are still gaps in clinical implications and everyday use. In this article, we present a systematic review of studies with different methods of monitoring cerebral blood flow autoregulation after non-traumatic cardiac arrest. Methods: A comprehensive literature search was performed from 1 June 2024 to 27 June 2024 by using multiple databases: PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were studies with an included description of the measurement of cerebral blood flow autoregulation in adult patients after non-traumatic cardiac arrest. Results: A total of 16 studies met inclusion criteria. Our data show that the most used methods in the reviewed studies were near-infrared spectroscopy and transcranial Doppler. The most used mathematical methods for calculating cerebral autoregulation were cerebral oximetry index, tissue oxygenation reactivity index, and mean flow index. Conclusions: The use of various monitoring and mathematical methods for calculating cerebral blood flow autoregulation poses a challenge for standardization, validation, and daily use in clinical practice. In the future studies, focus should be considered on clinical validation and transitioning autoregulation monitoring techniques to everyday clinical practice, which could improve the survival outcomes of patients after cardiac arrest.

Perioperative cardiopulmonary resuscitation in a prone position: A case report

Post-cardiac arrest brain injury remains a major cause of mortality in perioperative cardiac arrest, although intraoperative events are uncommon due to pre-procedural preparations, risk-benefit anticipation, and a controlled working environment. Herein, we describe the successful cardiopulmonary resuscitation of a 57-year-old male with a C2-C3 schwannoma who experienced intraoperative cardiac arrest due to massive blood loss during a C2-C3 laminectomy and excision of tumor while in a prone position. The intricacies and effectiveness of resuscitation in a prone position, as well as neuroprotective strategies in the perioperative setting to optimize functional outcomes, will be discussed.

Venous return physiology applied to post-cardiac arrest haemodynamic management: a post hoc analysis of the NEUROPROTECT trial

BackgroundThe European Resuscitation Council 2021 guidelines for haemodynamic monitoring and management during post-resuscitation care from cardiac arrest call for an individualised approach to therapeutic interventions. Combining the cardiac function and venous return curves with the inclusion of the mean systemic filling pressure enables a physiological illustration of intravascular volume, vasoconstriction and inotropy. An analogue mean systemic filling pressure (Pmsa) may be calculated once cardiac output, mean arterial and central venous pressure are known. The NEUROPROTECT trial compared targeting a mean arterial pressure of 65 mmHg (standard) versus an early goal directed haemodynamic optimisation targeting 85 mmHg (high) in ICU for 36 h after cardiac arrest. The trial data were used in this study to calculate post hoc Pmsa and its expanded variables to comprehensively describe venous return physiology during post-cardiac arrest management. A general estimating equation model was used to analyse continuous variables split by standard and high mean arterial pressure groups.ResultsData from 52 patients in each group were analysed. The driving pressure for venous return, and thus cardiac output, was higher in the high MAP group (p < 0.001) along with a numerically increased estimated stressed intravascular volume (mean difference 0.27 [− 0.014–0.55] L, p = 0.06). The heart efficiency was comparable (p = 0.43) in both the standard and high MAP target groups, suggesting that inotropy was similar despite increased arterial load in the high MAP group (p = 0.01). The efficiency of fluid boluses to increase cardiac output was increased in the higher MAP compared to standard MAP group (mean difference 0.26 [0.08–0.43] fraction units, p = 0.01).ConclusionsCalculation of the analogue mean systemic filling pressure and expanded variables using haemodynamic data from the NEUROPROTECT trial demonstrated an increased venous return, and thus cardiac output, as well as increased volume responsiveness associated with targeting a higher MAP. Further studies of the analogue mean systemic filling pressure and its derived variables are warranted to individualise post-resuscitation care and evaluate any clinical benefit associated with this monitoring approach.

Simultaneous prognostic score validation in patients with out-of-hospital cardiac arrest by a post-hoc analysis based on national multicenter registry

Using a nationwide multicenter prospective registry in Japan’s data, we calculated prognostic and predictive scores, including the Out-of-Hospital Cardiac Arrest (OHCA); Cardiac Arrest Hospital Prognosis (CAHP); Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH < 7.2, Lactate > 7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥ 85 years, Still resuscitation, and Extracardiac cause (NULL-PLEASE); revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST); and MIRACLE2 scores, for adult patients with cardiac arrest. The MIRACLE2 score was validated with the modified MIRACLE2 score, which excludes information of pupillary reflexes. Each score was calculated only for the cases with no missing data for the variables used. These scores’ accuracies were compared using neurological outcomes 30 days after out-of-hospital cardiac arrest (OOHCA). Patients with a cerebral performance category scale of 1 or 2 were designated as having favorable neurological outcomes. Each score’s discrimination ability was evaluated by the receiver operating characteristic curve’s area under the curve (AUC). To assess in detail in areas of high specificity and high sensitivity, which are areas of interest to clinicians, partial AUCs were also used. The analysis included 11,924 hospitalized adult patients. The AUCs of the OHCA, MIRACLE2, CAHP, rCAST, and NULL-PLEASE scores for favorable neurological outcomes were 0.713, 0.727, 0.785, 0.761, and 0.831, respectively. The CAHP and NULL-PLEASE scores were significantly more accurate than the rest. Accuracies did not differ significantly between the CAHP and NULL-PLEASE scores. The NULL-PLEASE score was significantly better at discriminating favorable neurological prognoses at 30 days in patients with OOHCA compared to other scoring systems.

Transcranial doppler in post-cardiac arrest management: a systematic review

Transcranial doppler in post-cardiac arrest management: a systematic review

Combination of Hydrogen Inhalation and Hypothermic Temperature Control After Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During PostCardiac Arrest Care II Trial.

The Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID) II trial (jRCTs031180352) suggested that hydrogen inhalation may reduce post-cardiac arrest brain injury (PCABI). However, the combination of hypothermic target temperature management (TTM) and hydrogen inhalation on outcomes is unclear. The aim of this study was to investigate the combined effect of hydrogen inhalation and hypothermic TTM on outcomes after out-of-hospital cardiac arrest (OHCA). Post hoc analysis of a multicenter, randomized, controlled trial. Fifteen Japanese ICUs. Cardiogenic OHCA enrolled in the HYBRID II trial. Hydrogen mixed oxygen (hydrogen group) versus oxygen alone (control group). TTM was performed at a target temperature of 32-34°C (TTM32-TTM34) or 35-36°C (TTM35-TTM36) per the institutional protocol. The association between hydrogen + TTM32-TTM34 and 90-day good neurologic outcomes was analyzed using generalized estimating equations. The 90-day survival was compared between the hydrogen and control groups under TTM32-TTM34 and TTM35-TTM36, respectively. The analysis included 72 patients (hydrogen [ n = 39] and control [ n = 33] groups) with outcome data. TTM32-TTM34 was implemented in 25 (64%) and 24 (73%) patients in the hydrogen and control groups, respectively ( p = 0.46). Under TTM32-TTM34, 17 (68%) and 9 (38%) patients achieved good neurologic outcomes in the hydrogen and control groups, respectively (relative risk: 1.81 [95% CI, 1.05-3.66], p < 0.05). Hydrogen + TTM32-TTM34 was independently associated with good neurologic outcomes (adjusted odds ratio 16.10 [95% CI, 1.88-138.17], p = 0.01). However, hydrogen + TTM32-TTM34 did not improve survival compared with TTM32-TTM34 alone (adjusted hazard ratio: 0.22 [95% CI, 0.05-1.06], p = 0.06). Hydrogen + TTM32-TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32-TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32-TTM34.

Abstract Tu002: Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Mitochondrial DNA-Induced Activation of Porcine Peripheral Blood Mononuclear Cells

Objective: Systemic inflammation is a well-established component of post-cardiac arrest syndrome (PCAS), a condition responsible for significant morbidity and mortality in patients that are initially resuscitated from sudden cardiac arrest. Immune cell activation is pivotal in PCAS pathophysiology, with emerging evidence implicating mitochondrial DNA (mtDNA) as a potent pro-inflammatory stimulus in this context. Given the paucity of available interventions to inhibit mtDNA-induced immune cell activation, we investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to modulate the inflammatory response of porcine peripheral blood mononuclear cells (PBMCs) activated by mtDNA in vitro . Methods: Porcine bone marrow-derived mesenchymal stem cells (MSCs; P2) were cultured for 5 days and serum-starved for 3 days to collect MSC-EVs. These EVs were isolated from conditioned media (CM) using size exclusion chromatography and ultracentrifugation, then characterized by nanoparticle tracking analysis (ZetaView) and ExoCheck. Naïve PBMCs from healthy swine were cultured for 1 week before stimulation with lipofectamine 2000 (TR-control) or 2 µg/mL mtDNA+TR. MSC-EVs were added to activated PBMCs (2.5e8–2e9 EVs/well) and inflammatory surface marker expression (flow cytometry), inflammatory cytokine transcripts (qPCR) and release (ELISA), and reactive oxygen/nitrogen species (ROS/RNS) production were assessed 24 hours later. Results: mtDNA-stimulated PBMC populations exhibited altered surface marker expression consistent with enrichment of inflammatory granulocytes (CD172+CD163-), macrophages (CD14+CD163+), and adhesion molecules (CD172+) compared to TR-control (all p&lt;0.05). Addition of MSC-EVs significantly reduced the number of all inflammatory cell populations, with the most prominent effects achieved at the highest EV dose (2e9 EVs/well). Likewise, MSC-EVs significantly attenuated mtDNA-activated PBMC expression and secretion of TNFα, IL-1β, and IL-6 ( Figure) and decreased ROS/RNS production in a dose-dependent manner. Conclusion: MSC-EVs attenuate mtDNA-induced activation of PBMCs in a dose-dependent manner, as determined by reductions in pro-inflammatory surface marker expression, inflammatory cytokine gene expression and secretion, and ROS/RNS production. These findings indicate that MSC-EVs may be a viable therapeutic for the inhibition of mtDNA-mediated immune activation in PCAS.

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Checkpoint for Considering Interleukin-6 as a Potential Target to Mitigate Secondary Brain Injury after Cardiac Arrest.

Interleukin-6 (IL-6) was suggested as a potential target for intervention to mitigate brain injury. However, its neuro-protective effect in post-resuscitation care has not been proven. We investigated the time-course of changes in IL-6 and its association with other markers (systemic inflammation and myocardial and neuronal injury), according to the injury severity of the cardiac arrest. This retrospective study analyzed IL-6 and other markers at baseline and 24, 48, and 72 h after the return of spontaneous circulation. The primary outcome was the association of IL-6 with injury severity as assessed using the revised Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia scoring system (low, moderate, and high severity). Of 111 patients, 22 (19.8%), 61 (55.0%), and 28 (25.2%) had low-, moderate-, and high-severity scores, respectively. IL-6 levels were significantly lower in the low-severity group than in the moderate- and high-severity groups at baseline and at 24 h and 72 h (p < 0.005). While IL-6 was not independently associated with neuronal injury markers in the low-severity group, it was demonstrated to be associated with it in the moderate-severity (β [95% CI] = 4.3 [0.1-8.6], R2 = 0.11) and high-severity (β [95% CI] = 7.9 [3.4-12.5], R2 = 0.14) groups. IL-6 exhibits distinct patterns across severity and shows differential associations with systemic inflammation or neuronal injury.

Inflammatory response after prehospital high-dose glucocorticoid to patients resuscitated from out-of-hospital cardiac arrest: A sub-study of the STEROHCA trial

BackgroundThe post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized “STERoid for OHCA” (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission. MethodsThe STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences. ResultsThe 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49–5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03–0.10), p < 0.001), IL-8 (ratio 0.53 (0.38–0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13–0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18–0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4–0.8), p = 0.01). ConclusionAdministering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h. Trial registrationEudraCT number: 2020–000855-11; submitted March 30, 2020.URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04624776.

Circulating glycocalyx shedding products as biomarkers for evaluating prognosis of patients with out-of-hospital cardiac arrest after return of spontaneous circulation

The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan–Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes.

The impact of pediatric post-cardiac arrest care on survival: A multicenter review from the AHA get with the Guidelines®-resuscitation post-cardiac arrest care registry

AimAdherence to post-cardiac arrest care (PCAC) recommendations is associated with improved outcomes for adults. We aimed to describe the survival impact of meeting American Heart Association (AHA) PCAC guidelines in children after cardiac arrest. MethodsWe conducted a retrospective study using Get With The Guidelines® Resuscitation’s (GWTG®-R) registry to describe the PCAC of patients ≤ 18 years old who suffered an in-hospital or out-of-hospital cardiac arrest (IHCA or OHCA). We evaluated the association between the absence of hypotension and fever in the initial 24 h following return of circulation (ROC) with survival to hospital discharge. We reviewed the utilization of monitoring/evaluation tools recommended in pediatric PCAC guidelines: electrocardiogram (ECG), electroencephalogram (EEG), and neuro-imaging. ResultsWe found 385 pediatric patients who suffered an IHCA or OHCA from 2015 through 2019 and survived at least 6 h post-ROC. Sixty-six percent of patients survived to hospital discharge. Following ROC, 56% of patients had EEG monitoring, 80% had an ECG performed, 47% had a head CT, and 26% had a cerebral MRI. In the initial 24 h post-ROC, 92% of patients did not have hypotension and 79% were afebrile. Patients without hypotension in the initial 24 h post-ROC had higher odds of survival to hospital discharge than those with hypotension (aOR 4.96; 95% CI 2.07, 11.90; p = 0.0003), adjusting for age and cardiac arrest location. Patients without hypotension and without fever in the initial 24 h post-ROC had higher odds of survival to hospital discharge compared to patients who had either hypotension or fever or both (aOR 1.98; 95% CI 1.06,3.71; p = 0.034). ConclusionIn this retrospective multicenter registry study, absence of both post-cardiac arrest hypotension and fever were associated with increased odds of survival to hospital discharge. Further research is needed to understand the full impact of PCAC recommendation compliance on survival outcomes.

The Lived Experience of Cardiac Arrest Survivors: A Scoping Review.

Survival rates after cardiac arrest have steadily increased over the past few decades because of the adoption of cardiopulmonary resuscitation, public access to automated external defibrillators, and an increase in public education on how to perform cardiopulmonary resuscitation. The lived experiences of post-cardiac arrest survival have been underexplored. The themes that resulted from the analysis in this scoping review can inform clinical practice and propose strategies to improve the patients' quality of life. The objective of this scoping review was to map out qualitative literature that explores the lived experience of individuals who have survived cardiac arrest. In this scoping review, the authors examined peer-reviewed qualitative studies identified in the PubMed, CINAHL, and MEDLINE databases. Arksey and O'Malley's methodological framework for conducting a scoping study was followed. The search yielded 174 articles, with 16 meeting inclusion criteria for this scoping review. Initially, 14 articles were selected, and 2 additional articles were identified through references. Themes extracted from these 16 articles include the need for support and information, emotional challenges, and acceptance of a new reality. Cardiac arrest survivors often experience loss of control, vulnerability, and insecurity. These emotional changes can be significant and may include physical challenges, cognitive impairments, and psychological distress, which can cause individuals to reevaluate their perspectives on life and accept a new reality, potentially leading to changes in their future outlook.