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Extracorporeal cardiopulmonary resuscitation (ECPR) is an invasive and resource-intensive therapy used to care for patients with refractory cardiac arrest. In this review, we highlight considerations for the establishment of an ECPR system of care for patients suffering refractory out-of-hospital cardiac arrest (OHCA).ECPR has been shown to improve neurologically favorable outcomes in patients with refractory cardiac arrest in numerous studies, including a single randomized control trial. Successful ECPR programs are typically part of a comprehensive system of care that optimizes all phases of OHCA management. Given the resource-intensive and time-sensitive nature of ECPR, patient selection criteria, timing of ECPR, and location must be well defined. Many knowledge gaps remain within ECPR systems of care, postcardiac arrest management, and neuroprognostication strategies for ECPR patients.To be consistently successful, ECPR must be a part of a comprehensive OHCA system of care that optimizes all phases of cardiac arrest management. Future investigation is needed for the knowledge gaps that remain.

BackgroundDespite advances in pre- and post-resuscitation care, percentage of survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) was extremely low. Development of an accurate system to predict the daily incidence of OHCA might provide a significant public health benefit. Here, we developed and validated a machine learning (ML) predictive model for daily OHCA incidence using high-resolution meteorological, chronological, and geographical data.MethodsWe analyzed a dataset from the United States that combined an OHCA nationwide registry, high-resolution meteorological data, chronological data, and geographical data. We developed a model to predict daily OHCA incidence with a training dataset for 2013–2017 using the eXtreme Gradient Boosting algorithm. A dataset for 2018–2019 was used to test the predictive model. The main outcome was the predictive accuracy for the number of daily OHCA events, based on root mean squared error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE). In general, a model with MAPE less than 10% is considered highly accurate.ResultsAmong the 446,830 OHCAs of non-traumatic cause where resuscitative efforts were initiated by a 911 responder, 264,916 in the training dataset and 181,914 in the testing dataset were included in the analysis. The ML model with combined meteorological, chronological, and geographical data had high predictive accuracy in relation to nationwide incidence rate per 100,000 at the nationwide level) in the training dataset (RMSE, 0.016; MAE, 0.013; and MAPE, 7.61%) and in the testing dataset (RMSE, 0.018; MAE, 0.014; and MAPE, 6.52%).ConclusionsA ML predictive model using comprehensive daily meteorological, chronological, and geographical data allows for highly precise estimates of OHCA incidence in the United States.Clinical PerspectiveWhat is new?A machine learning predictive model developed with a high-resolution meteorological dataset and chronological and geographical variables predicted the daily incidence of out-of-hospital cardiac arrest (OHCA) in the U.S. population with high precision. The predictive accuracy at the state level was greater in medium and high-temperature areas than in the low-temperature area.What are the clinical implications?This predictive model revealed complex associations between meteorological, chronological, and geographic variables in relation to predicting daily incidence of OHCA. It might be useful for public health strategies in temperate regions, for example, by providing a warning system for citizens and emergency medical services agencies on high-risk days.

his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

Recent reports have questioned the efficacy of intraosseous (IO) drug administration for out-of-hospital cardiac arrest (OHCA) resuscitation. Our aim was to determine whether prehospital administration of resuscitative medications via the IO route was associated with lower rates of return of spontaneous circulation (ROSC) and survival to hospital discharge than peripheral intravenous (IV) infusion in the setting of OHCA.We obtained data on all OHCA patients receiving prehospital IV or IO drug administration from the three most populous counties in Michigan over three years. Data was from the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) database. The association between route of drug administration and outcomes was tested using a matched propensity score analysis.From a total of 10,626 OHCA patients, 6869 received parenteral drugs during their prehospital resuscitation (37.8% by IO) and were included in analysis. Unadjusted outcomes were lower in patients with IO vs. IV access: 18.3% vs. 23.8% for ROSC (p0.001), 3.2% vs. 7.6% for survival to hospital discharge (p0.001), and 2.0% vs. 5.8% for favorable neurological function (p0.001). After adjustment, IO route remained associated with lower odds of sustained ROSC (OR 0.72, 95% CI 0.63-0.81, p0.001), hospital survival (OR 0.48, 95% CI 0.37-0.62, p0.001), and favorable neurological outcomes (OR 0.42, 95% CI 0.30-0.57, p0.001).In this cohort of OHCA patients, the use of prehospital IO drug administration was associated with unfavorable clinical outcomes.

Publisher Copyright: © 2021 Elsevier Ltd As more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.

BACKGROUND Exception from informed consent (EFIC) enables the enrollment of research subjects with emergent conditions to clinical trials without prior consent. EFIC study approval requires community consultation and public disclosure. We hypothesized that the integration of social media with targeted emails and in-person outreach is an effective community consultation strategy. METHODS We utilized social media with targeted emails and in-person outreach for the community consultation of the ACCESS cardiac arrest trial. Study advertisements were disseminated using Facebook and Instagram, and targeted emails were sent to emergency medicine, prehospital, and cardiology providers. We also interviewed at-risk individuals with cardiac conditions, their caretakers, and patient advocacy groups. Participants were asked to complete a survey about their opinions about the study. RESULTS We collected 559 surveys over an 8-week period, and 70.5% of the surveys were obtained using social media. The median (IQR) age of survey respondents was 44 (33-57) years; 89.9% were White and 60.1% were women. A total of 91.3% believed ACCESS was an important study. Compared to the in-person group, more from social media (81.8% vs. 63.3%, p

Study objective Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients. Methods In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes. Results Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome. Conclusion The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.

ObjectivesTo evaluate a predictive model for robust estimation of daily out-of-hospital cardiac arrest (OHCA) incidence using a suite of machine learning (ML) approaches and high-resolution meteorological and chronological data.MethodsIn this population-based study, we combined an OHCA nationwide registry and high-resolution meteorological and chronological datasets from Japan. We developed a model to predict daily OHCA incidence with a training dataset for 2005–2013 using the eXtreme Gradient Boosting algorithm. A dataset for 2014–2015 was used to test the predictive model. The main outcome was the accuracy of the predictive model for the number of daily OHCA events, based on mean absolute error (MAE) and mean absolute percentage error (MAPE). In general, a model with MAPE less than 10% is considered highly accurate.ResultsAmong the 1 299 784 OHCA cases, 661 052 OHCA cases of cardiac origin (525 374 cases in the training dataset on which fourfold cross-validation was performed and 135 678 cases in the testing dataset) were included in the analysis. Compared with the ML models using meteorological or chronological variables alone, the ML model with combined meteorological and chronological variables had the highest predictive accuracy in the training (MAE 1.314 and MAPE 7.007%) and testing datasets (MAE 1.547 and MAPE 7.788%). Sunday, Monday, holiday, winter, low ambient temperature and large interday or intraday temperature difference were more strongly associated with OHCA incidence than other the meteorological and chronological variables.ConclusionsA ML predictive model using comprehensive daily meteorological and chronological data allows for highly precise estimates of OHCA incidence.

To investigate whether intentional cooling, achieved temperature and hypothermia duration were associated with in-hospital death in patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest.This is a retrospective analysis of the Extracorporeal Life Support Organization Registry. Patients 18-79 years of age who received ECPR between 2010 and 2019 were included. We compared outcomes for intentional cooling versus no intentional cooling. Then, among those who completed intentional cooling, we compared the outcomes between i) achieved temperature ≤ 34 °C, 34-36 °C, and 36 °C, and ii) duration ≤ 36 °C for 12 h, 12-48 h, and ≥ 48 h. The primary outcome was in-hospital mortality within 90 days. Cox proportional hazard models were generated with adjustment for covariates.Among 4,214 ECPR patients, 1,511 patients were included in the final analysis. After multivariable adjustment, there was no significant difference in in-hospital mortality between patients with intentional cooling and no intentional cooling (hazard ratio [HR], 1.06 [95% CI 0.93-1.21]; p = 0.394). In the 609 patients who completed intentional cooling, temperature at 34-36 °C had a significantly lower adjusted HR for in-hospital mortality compared with 36 °C (HR, 0.73 [0.55-0.96]; p = 0.025). Moreover, temperature ≤ 36 °C for 12-48 h had a significantly lower adjusted HR for in-hospital mortality compared with ≤ 36 °C for 12 h (HR, 0.69 [0.53-0.90]; p = 0.005).Intentional cooling was not associated with lower in-hospital mortality in ECPR patients. However, among patients with intentional cooling, achieving temperature of 34-36 °C for 12-48 h was associated with lower in-hospital mortality.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 20 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 3 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

This2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendationsfor advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results.Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy.There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004).This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

Telecommunicator cardiopulmonary resuscitation (T-CPR) is a critical component of optimized out-of-hospital cardiac arrest (OHCA) care. We assessed a pilot tool to capture American Heart Association (AHA) T-CPR measures and T-CPR coaching by telecommunicators using audio review.Using a pilot tool, we conducted a retrospective review of 911 call audio from 65 emergency medical services-treated out-of-hospital cardiac arrest (OHCA) patients. Data collection included events (e.g., OHCA recognition), time intervals, and coaching quality measures. We calculated summary statistics for all performance and quality measures.Among 65 cases, the patients' mean age was 64.7 years (SD: 14.6) and 17 (26.2%) were women. Telecommunicator recognition occurred in 72% of cases (47/65). Among 18 non-recognized cases, reviewers determined 12 (66%) were not recognizable based on characteristics of the call. Median time-to-recognition was 76 seconds (n = 40; IQR:39-138), while median time-to-first-instructed-compression was 198 seconds (n = 26; IQR:149-233). In 36 cases where coaching was needed, coaching on compression-depth occurred in 27 (75%); -rate in 28 (78%); and chest recoil in 10 (28%) instances. In 30 cases where repositioning was needed, instruction to position the patient's body flat occurred in 18 (60%) instances, on-back in 22 (73%) instances, and on-ground in 22 (73%) instances.Successful collection of data to calculate AHA T-CPR measures using a pilot tool for audio review revealed performance near AHA benchmarks, although coaching instructions did not occur in many instances. Application of this standardized tool may aid in T-CPR quality review.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival of patients with prolonged cardiac arrest (CA) that is refractory to standard CPR and ACLS. It has been proposed that ECPR accentuates inflammation after CA, potentially limiting its effectiveness. The benefits of leukocyte filters or leukocyte-modulating devices in conjunction with ECPR have not been studied. Hypothesis: When paired with ECPR, inflammation-modulating devices targeting leukocytes may improve recovery of cardiac function after prolonged cardiac arrest. Methods: In a randomized study, 24 swine (40±5kg) underwent 8min of untreated ventricular fibrillation CA followed by CPR with mechanical chest compressions and impedance threshold device for 30 min (total arrest time = 38min), immediately followed by 8h of ECPR with heparin anticoagulation and temperature maintained at 33°C. Group 1 (n=8) had standard ECPR system (control), Group 2 (n=8) had a leukocyte filter device (LF) added to the ECPR circuit, an and Group 3 (n=8) had a leukocyte modulation device (LMOD) added to the ECPR circuit. Recovery of cardiac function was measured using a cardiac resuscitablity score (CRS) and left ventricular ejection fraction (LVEF) via transthoracic echocardiography. Data was collected at baseline (prior CA) and after 8h of ECPR. Data analysis: single-factor ANOVA test (p Results: There were no statically significant differences between the groups in CRS (Control = 3.3 ± 2.4, LF = 4.0 ± 2.8, LMOD = 2.1 ± 2.6; p=0.37) or LVEF (Control = 59% ± 27%, LF = 49% ± 29% LMOD = 34% ± 38%: p=0.34) at 8 hours after ECPR initiation (Table 1). Discussion: In this swine model of prolonged cardiac arrest treated with ECPR, addition of a leukocyte filter or leukocyte modulation device to the ECPR circuit did not improve recovery of cardiac function during the first 8 hours after initiating ECPR.

Introduction: Sudden Cardiac Arrest (CA) affects more than 400,000 people per year in the United States. Although a third of these patients survive to hospital admission, another 60-70% go on to die due to failed recovery of vital organ function. Microvascular thrombosis has been suggested as a potential contributor to prolonged organ dysfunction, but no antithrombotic therapies have been shown to be beneficial and coagulofibrinolytic abnormalities in prolonged CA remain poorly understood. Objectives: To establish key biomarkers of porcine coagulation and fibrinolysis in the setting of prolonged CA and cardiopulmonary resuscitation (CPR) and test the ability of ART-123 (recombinant human thrombomodulin alpha) to reverse these abnormalities. Methods: 15 pigs (n=5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR. Animals were randomized to receive saline or ART-123 (~1mg/kg) pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Results: Robust and ongoing activation of coagulation and fibrinolysis were detected throughout the resuscitation. After 50 minutes of CPR, plasma tests suggested consumptive coagulopathy, while whole blood testing (thromboelastography) indicated a persistent hypercoagulable state. ART-123 had a clear anticoagulant effect irrespective of timing (TAT complexes 381±25 vs. 238±18 vs. 226±12, p Conclusion: Our porcine CA model provides an excellent platform for evaluating antithrombotic interventions. Plasma testing after prolonged CA/CPR suggests consumptive coagulopathy, although TEG indicates a persistent hypercoagulable state. ART-123 given before no-flow or just after CPR demonstrates antithrombotic effects, although the specific modes of action depending on the timing of administration.

ImportanceValue in health care is quality per unit cost (V = Q/C), and an emergency department–based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care.ObjectiveTo determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter.Design, Setting, and ParticipantsThis retrospective economic analysis evaluated the cost of care delivery to patients in the ED before and after deployment of the Joyce and Don Massey Family Foundation Emergency Critical Care Center, an ED-ICU, on February 16, 2015, at a large academic medical center in the US with approximately 75 000 adult ED visits per year. The pre–ED-ICU cohort was defined as all documented ED visits by patients 18 years or older with a complete financial record from September 8, 2012, through June 30, 2014 (660 days); the post–ED-ICU cohort, all visits from July 1, 2015, through April 21, 2017 (660 days). Fiscal year 2015 was excluded from analysis to phase in the new care model. Statistical analysis was performed March 1 through December 30, 2021.ExposuresImplementation of an ED-ICU.Main Outcomes and MeasuresInflation-adjusted direct cost of care, net revenue, and direct margin per patient encounter in the ED.ResultsA total of 234 884 ED visits during the study period were analyzed, with 115 052 patients (54.7% women) in the pre–ED-ICU cohort and 119 832 patients (54.5% women) in the post–ED-ICU cohort. The post–ED-ICU cohort was older (mean [SD] age, 49.1 [19.9] vs 47.8 [19.6] years; P P P P P = .98). Inflation-adjusted net revenue per encounter increased by 7.0% (95% CI, 3.4%-10.6%; P P Conclusions and RelevanceImplementation of an ED-ICU was associated with no significant change in inflation-adjusted total direct cost per ED encounter. Holding delivery costs constant while improving quality demonstrates improved value via the ED-ICU model of care.

Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective compound which protects neurons from ischemic injury by reducing neuronal calcium overload via NMDA receptor modulation and preventing calcium-induced mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO(4) during CPR has the potential to target these mechanisms within an early therapeutic window. We hypothesize that IM MgSO(4) administrated during CPR could achieve therapeutic serum magnesium levels within 15 min after ROSC and improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Male Long Evans rats were subjected to 8-min asphyxial cardiac arrest and block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO(4) IM at the onset of CPR. Serum magnesium concentrations increased rapidly with IM delivery during CPR, achieving twofold to fourfold increase by 15 min after ROSC in all magnesium dose groups. Rats subjected to cardiac arrest or sham surgery were block randomized to treatment groups for assessment of neurological outcomes. We found that IM MgSO(4) during CPR had no effect on ROSC rate (p > 0.05). IM MgSO(4) treatment had no statistically significant effect on 10-day survival with good neurologic function or hippocampal CA1 pyramidal neuron survival compared to placebo treatment. In conclusion, a single dose IM MgSO(4) during CPR achieves up to fourfold baseline serum magnesium levels within 15 min after ROSC; however, this treatment strategy did not improve survival, recovery of neurologic function, or neuron survival. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.

All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percentage of medical school faculty who are National Institutes of Health (NIH)-funded principal investigators (PIs; 1.7%) and the percentage of medical school departments with NIH-funded PIs (33%). Although there has been a steady increase in the number of NIH-funded projects and total NIH dollars, the slowing growth in the number of NIH-funded PIs and lack of growth in the number of EM departments with NIH-funded PIs is cause for concern. In response, the Association of Academic Chairs of Emergency Medicine (AACEM) Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH funding. These goals have been endorsed by the AACEM Executive Committee and the boards of Society for Academic Emergency Medicine (SAEM), American College of Emergency Physicians (ACEP), and American Academy of Emergency Medicine (AAEM). The 2030 strategic goals include 200 NIH-funded projects led by 150 EM PIs in at least 50 EM departments with over $100M in annual funding resulting in over 3% of EM faculty being NIH-funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.

The mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.

Introduction: For out-of-hospital cardiac arrests (OHCAs) unwitnessed by emergency responders, contact with the 911 system provides the earliest point for consistent data collection. Building upon previous tools, we developed a 911 call data abstraction instrument and tested it to see if it reliably tracked key metrics from 911 calls for dispatch assisted CPR in order to guide quality initiatives for OHCA. Methods: Data abstractors applied this tool to a random sample of 23 emergency medical services (EMS)-confirmed, second-party, non-traumatic, non-overdose adult OHCAs occurring prior to first responder arrival from November 2017 to November 2019 in Washtenaw County, Michigan. For each call, data elements were collected by 2 independent reviewers. We focused on key variables: 1) whether the arrest was recognized by dispatch in eligible cases (n=23), 2) whether instructed compressions were provided in eligible cases (n=23), and 3) the 911-time-to-first-instructed-compression (n=11). To evaluate interrater reliability, we calculated kappa statistics for categorical variables and intraclass correlation coefficients (ICC) for continuous variables. Results: We included 23 calls with an average patient age of 64.2 (SD: 10.9) lasting an average of ~5 mins. Overall, 16 patients were men and 7 were women. Thirteen calls originated from private residences, 9 from a public place, and 1 could not be identified. We found that OHCA was recognized by dispatch in 18 of the 23 calls (78%). Reviewers reported instructed compressions occurred in 14 of 23 calls (61%). The median 911-time-to-first-instructed-compression of calls where consistent measurement was possible (n=11) was 197.5 seconds (IQR: 2:30.0-4:44.0). Among calls, kappa statistics for recognition of cardiac arrest and provision of instruction compressions was 1.00 (n=23) and 0.91 (n=23), respectively, while the ICC for time-to-first instructed compression was >0.99 (n=11). Conclusions: Reviewing 911 calls with this tool was capable of collecting reliable information from independent reviewers on key events including critically important times. Collection of these data is a critical first step for evaluating system performance to improve survival from OHCA.

Introduction: Respiratory infections can occur through the transmission of virus-containing aerosols from infected individuals. It remains unclear whether cardiac arrest (CA) resuscitation generates aerosols that have the potential to transmit diseases including COVID-19. Hypothesis: In a swine CA model, chest compression and defibrillation generate aerosols (≤10 μm) that could contain respiratory viruses. Methods: To simulate witnessed CA with bystander-initiated CPR, 3 female non-intubated swine underwent 4 minutes of untreated ventricular fibrillation CA followed by ten 2-minute cycles of mechanical chest compression and defibrillation without ventilation. The diameter (0.3 - 10 μm) and quantity of aerosols generated during 45-second intervals of no-flow, chest compression, and after each defibrillation were collected via a nose cone by the TSI Optical Particle Sizer. Aerosol generated from the coughs of 4 healthy human subjects were also compared to the swine data. Results: There was no significant difference between the total aerosols generated during chest compression compared to no-flow. In contrast, defibrillation followed by chest compression generated significantly more aerosols than chest compression or no-flow alone (72.4 ± 41.6 x10 4 vs 12.3 ± 8.3 x10 4 vs 10.5 ± 11.2 x10 4 ; p < 0.0001), particularly at the larger-sized aerosols. Two consecutive human coughs generated 54.7 ± 33.9 x10 4 aerosols with a size distribution much smaller than post-defibrillation CPR (Table). Conclusion: Chest compression generated comparable aerosols to no-flow in a swine CA model. In contrast, defibrillation followed by chest compression generated significantly more aerosols than chest compression or no-flow alone, with a distribution shift toward larger aerosols. Additional research is needed to elucidate the mechanisms by which aerosol generation during chest compression is modified by defibrillation and to assess rescuer risk during CA resuscitation.

Background: Following prolonged cardiac arrest treated with extracorporeal cardiopulmonary resuscitation (ECPR), recovery of organ function and survival are potentially impaired due to a “no reflow” phenomenon associated with microvascular thrombosis. This study evaluated the effects of antithrombotic interventions on coagulation parameters in a in a porcine model of out-of-hospital cardiac arrest (OHCA). Hypothesis: We hypothesized that anticoagulant therapy (argatroban) during CPR and/or thrombolytic (streptokinase) therapy at onset of ECPR would prevent consumptive coagulopathy after prolonged cardiac arrest. Methods: In a blinded and randomized study, 48 swine (40±5kg) were subjected to 8min of ventricular fibrillation cardiac arrest followed by 30min of goal-directed CPR (gdCPR), and 8hr of ECPR (33°C) with heparin anticoagulation during ECPR titrated to ACT values (200-300s). Animals were randomized to one of 4 groups (n=12) with 350mg/kg argatroban (Arg) or placebo (20mL NSS) administered 12min after arrest and 1.5 MU streptokinase (STK) or placebo (50mL NSS) at ECPR initiation: Group 1 (placebo and placebo); Group 2 (Arg and placebo); Group 3 (placebo and STK); and Group 4 (Arg and STK). Blood samples were drawn at baseline and at 8hr of ECPR (or earlier if the experiment ended). Data was analyzed using t-tests and ANOVA (p Results: Average platelet count and fibrinogen levels significantly decreased between baseline and at the end of ECPR ( p =p =0.6315 and p =0.7692, respectively). D-dimer levels significantly increased across groups from baseline to the end of ECPR ( p =p =0.1881). Discussion: These results indicate that this OHCA model induces consumptive coagulopathy and the effects of antithrombotic therapies did not mitigate it in this porcine model.

Introduction: Dispatch processes for prehospital management of out-of-hospital cardiac arrest (OHCA) vary greatly by region, and so do the barriers and facilitators of rapid time-to-first-treatment within those systems. In order to optimize local OHCA response, we sought to identify improvement targets by tracking time intervals during OHCA 911 calls and evaluating associated barriers and facilitators to timely OHCA prehospital care delivery. Methods: We developed a data abstraction tool to collect quantitative and qualitative data regarding key events in a random sample of 23 of emergency medical services (EMS)-confirmed, second-party, non-traumatic, non-overdose, non-facility adult OHCAs occurring prior to first responder arrival from November 2017 to November 2019 in Washtenaw County, Michigan. Trained abstractors double reviewed calls. We calculated descriptive statistics of key event times to summarize a timeline of care and evaluated qualitative data using thematic analysis to assess event intervals. Results: Based on quantitative and qualitative analyses, we created a timeline with summary data of dispatcher OHCA response based on an aggregate of 23 calls to 911 dispatch (see Figure 1). Data abstractors identified two intervals-of-interest as containing barriers to optimizing time-to-first treatment: 1) time between the first report of abnormal breathing and call taker statement of CPR need (Interval 1), and 2) time from patient positioning to the first compression instruction (Interval 2). Qualitative data suggested that these interval delays were a result of extensive efforts on the part of the call taker to reconfirm breathing status in particular. Additional barriers, such as the callers misunderstanding instruction, and on-scene physical limitations, were also identified. Conclusions: We identified two primary time intervals to target for improvement as well as barriers present in our local 911 system. These data may serve as a foundation to develop targeted interventions to optimize local systems of care for 911 dispatch workflows. Figure 1

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) is promising but unproven. We developed a concept for a randomized Bayesian adaptive clinical trial to define the interval after arrest during which patients derive benefit. Hypotheses: We hypothesized that the simulated design characteristics of the adaptive design would efficiently confirm or refute the existence of a therapeutic window for ECPR in a future trial. Methods: Through iterative simulation and design modification, we developed a Bayesian adaptive trial of ECPR for adults with OHCA. The goals of the trial design were to address the uncertainty surrounding the OHCA-to-ECPR interval within which clinical benefit might be preserved and the difference in prognosis between patients with non-shockable vs shockable rhythms. The treatment effect was defined as the mean 90-day utility-weighted Modified Rankin Scale (uwmRS) for each rhythm subgroup and estimated CA-to-ECPR interval. The trial adaptively lengthens or contracts the estimated CA-to-ECPR eligibility window depending on the probability of benefit from ECPR. We simulated trial performance under six potential ECPR efficacy scenarios. We compared the adaptive design to a fixed design. Results: The trial had 91-100% power to detect a benefit from ECPR for non-shockable rhythms and 69-98% power for shockable rhythms under the scenarios simulated (figure). The design had a high probability of identifying the maximum CA-to-ECPR interval within which ECPR produces a clinically significant benefit of 0.2 on the uwMRS. In null scenarios, the 97-99% of the simulated trials ended early declaring futility. Conclusions: The adaptive trial design helps to ensure the patient population most likely to benefit from treatment—as defined by rhythm subgroup and estimated CA-to-ECPR interval—are enrolled. The design also promotes early termination of the trial if continuation is likely to be futile.

Background: The effectiveness of CPR declines over time during prolonged cardiac arrest (CA). Intravascular thrombosis may be a contributing factor. As part of a larger study examining antithrombotic therapy in a porcine model of prolonged CA, the impact of early administration of argatroban on CPR hemodynamics is reported. Hypothesis: Early administration of argatroban during CPR improves the quality of goal-directed CPR (gdCPR). Methods: In a blinded and randomized study, 48 swine (40±5kg) underwent an 8min untreated period of ventricular fibrillation CA followed by a gdCPR protocol for 30min (total arrest time 38min). Manual and mechanical chest compressions with the use of an impedance threshold device (ITD) were introduced to maintain end-tidal CO 2 (Et-CO 2 ) >20mmHg. Argatroban (350mg/kg) or placebo (20mL NSS) were administered to respective groups (n=24 per group) 12mins after initiation of CA. Et-CO 2 , coronary perfusion pressure (CPP), end-diastolic pressure (EDP), and intracranial pressure (ICP) were monitored continuously. Averages were taken over the course of gdCPR for hemodynamic parameters. Arterial blood gases (ABGs) were obtained at the end of gdCPR. Analysis between groups was performed using an unpaired t-test (significance = p Results: Average hemodynamic parameters were not statistically different between argatroban vs. placebo groups (Et-CO 2 22.6±6.7 vs. 21.5±5.9 mmHg; EDP 25.6±10.7 vs. 23.7±9.6 mmHg; ICP 25.7±2.0 vs.20.9±2.7 cmH 2 O; CPP 8.7±11.2 vs. 7.0±11.2 mmHg). Final ABG values were also not statistically different between argatroban vs. placebo groups (pH 7.23±0.1 vs. 7.23±0.2; PaO 2 187.4±146.3 vs. 132.2±187.4 mmHg; PaCO 2 38.8±16.6 vs. 43.0±26.1 mmHg; lactate 8.5±1.7 vs. 8.8±1.4 mmol/L). Conclusion: These results demonstrate that early administration of argatroban during CPR did not have a significant effect on gdCPR quality in a porcine model of prolonged CA.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) is promising but is unproven, and outcomes are strongly dependent on time to initiation of therapy. Expedited transport may facilitate opportunities for ECPR in clinical practice and future trials. Hypotheses: We hypothesized that a real-time dispatch-based computer algorithm could select refractory OHCA patients who could be reliably transported to the emergency department (ED) within 30 min of the 911 call, and that Emergency Medicine physicians could initiate ECPR in eligible patients within 30 min of ED arrival. Methods: In a 2-tiered EMS system serving a US city of 100k in 29 square miles with an ECPR capable primary destination hospital, adults with refractory shockable or witnessed OHCA were randomized 4:1 to expedited transport (ET) or standard prehospital care (SC) if the predicted 911 to ED arrival time was Results: Out of 156 cardiac arrest runs, 15 participants (10%) were randomized prior to ending the trial for slow accrual. Five of 12 patients randomized to expedited transport had an ED arrival time of Conclusions: EROCA demonstrated a functional model for selecting patients with refractory OHCA for ET in an ECPR capable system but did not meet predefined time-interval targets. These results provide important insight into the feasibility of ECPR clinical trials and clinical practice based on selected target intervals.