The Wolf Creek Conference, initiated in 1975, is a well-established tradition providing a unique forum for robust intellectual exchange between thought leaders and scientists from academia and ...industry focused on advancing the science and practice of cardiac arrest resuscitation. The Wolf Creek XVII Conference was hosted by the Max Harry Weil Institute for Critical Care Research and Innovation in Ann Arbor, Michigan, USA on June 15–17, 2023. A major focus of the conference proceedings was to identify and prioritize the knowledge gaps, barriers to translation, and research priorities for six major domains in the field of resuscitation: (1) automated cardiac arrest diagnosis, (2) amplifying lay-responder response, (3) mobile AEDs, (4) physiology-guided CPR, (5) extracorporeal support, and (6) neuroprotection. In addition, industry scientists were given the opportunity to present and discuss cutting edge innovations. Finally, building off of the conference’s theme of “The Future of Cardiac Arrest Resuscitation”, the Weil Institute introduced the “Wolf Creek Innovator in Cardiac Arrest and Resuscitation Award” to recognize early career investigators who were challenging current paradigms in resuscitation science. Similar to the early Wolf Creek Conferences, the goal was to fuel active discussion and debate among leading experts to determine where future research efforts should be focused. This manuscript provides an overview of the Wolf Creek XVII conference, and the individual manuscripts within this special edition of Resuscitation Plus describe the conference proceedings and outcomes in more detail. It is our intent that these publications will provide a roadmap for important academic and commercial advances in the field of cardiac arrest resuscitation.
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.
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.
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.
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.
Abstract In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after ...transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca 2 + -dependent protease calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo , we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 h after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration.
Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging therapy for refractory cardiac arrest. The purpose of this study was to analyze and report characteristics and outcomes of adult ...patients treated with ECPR after out-of-hospital cardiac arrest (OHCA) in a large international registry.
The Extracorporeal Life Support Organization’s Extracorporeal Life Support Registry was queried for adult cardiac arrests with arrest location of “EMT Transport” or “Outside Hospital.”
From 2010–2016, 217 cases of ECPR following OHCA were reported in Europe (47%), Asia-Pacific (29%), and North America (24%). The median age was 52 years (IQR 45–62, range 18–87); 73% were male. The median duration of ECPR was 47h (IQR 17–94, range 0–711). Reported complications included hemorrhage (31.3%), limb complications (11.1%), circuit complications (8.8%), infection (7.4%), and seizures (5.5%). The rate of percutaneous coronary intervention (PCI) was higher in Europe (35.6%) and Asia-Pacific (25.8%) than North America (9.4%; p<0.01). Survival to hospital discharge was 27.6% (95% CI 22.1–34.0%), and male gender was independently associated with mortality (adjusted odds ratio 2.1 95% CI 1.1–4.2, p<0.05). Survival did not differ by region, race, age, or year. Brain death was reported in 16.6% 95% CI 12.2–22.1%; organ donation rate was not reported.
This international analysis of ECPR for refractory OHCA reveals a survival rate of 27.6%, demonstrates association of male gender with mortality, and highlights regional differences in PCI utilization. These results will help inform implementation and research of this potentially life-saving strategy for refractory OHCA.
Coronary artery disease is prevalent in different causes of out-of-hospital cardiac arrest (OHCA), especially in individuals presenting with shockable rhythms of ventricular fibrillation/pulseless ...ventricular tachycardia (VF/pVT). The purpose of this report is to review the known prevalence and potential importance of coronary artery disease in patients with OHCA and to describe the emerging paradigm of treatment with advanced perfusion/reperfusion techniques and their potential benefits on the basis of available evidence. Although randomized clinical trials are planned or ongoing, current scientific evidence rests principally on observational case series with their potential confounding selection bias. Among patients resuscitated from VF/pVT OHCA with ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 70% to 85%. More than 90% of these patients have had successful percutaneous coronary intervention. Conversely, among patients resuscitated from VF/pVT OHCA without ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 25% to 50%. For these patients, early access to the cardiac catheterization laboratory is associated with a 10% to 15% absolute higher functionally favorable survival rate compared with more conservative approaches of late or no access to the cardiac catheterization laboratory. In patients with VF/pVT OHCA refractory to standard treatment, a new treatment paradigm is also emerging that uses venoarterial extracorporeal membrane oxygenation to facilitate return of normal perfusion and to support further resuscitation efforts, including coronary angiography and percutaneous coronary intervention. The burden of coronary artery disease is high in this patient population, presumably causative in most patients. The strategy of venoarterial extracorporeal membrane oxygenation, coronary angiography, and percutaneous coronary intervention has resulted in functionally favorable survival rates ranging from 9% to 45% in observational studies in this patient population. Patients with VF/pVT should be considered at the highest severity in the continuum of acute coronary syndromes. These patients have a significant burden of coronary artery disease and acute coronary thrombotic events. Evidence from randomized trials will further define optimal clinical practice.
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