The Impact of Head Position on Neurological and Histopathological Outcome Following Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model.

Introduction: Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model. Methods: After 20 min of ventricular fibrillation, 46 domestic pigs underwent CARL, including high, pulsatile extracorporeal blood flow, pH-stat acid-base management, priming with a colloid, mannitol and citrate, targeted oxygen, carbon dioxide and blood pressure management, rapid cooling and slow rewarming. N = 25 were head-up (HUP) during CARL, and N = 21 were supine (SUP). After weaning from ECC, the pigs were extubated and followed up in the animal care facility for up to seven days. Neuronal density was evaluated in neurohistopathology. Results: More animals in the HUP group survived and achieved a favorable neurological recovery, 21/25 (84%) versus 6/21 (29%) in the SUP group. Head positioning was an independent factor in neurologically favorable survival (p < 0.00012). Neurohistopathology showed no significant structural differences between HUP and SUP. Distinct, partly transient clinical neurologic deficits were blindness and ataxia. Conclusions: Head elevation during CARL after 20 min of cardiac arrest independently improved survival and neurologic outcome in pigs. Clinical follow-up revealed transient neurologic deficits potentially attributable to functions localized in the posterior perfusion area, whereas histopathologic findings did not show corresponding differences between the groups. A possible explanation of our findings may be venous congestion and edema as modifiable contributing factors of neurologic injury following prolonged cardiac arrest.

Data-driven sudden cardiac arrest research in Europe: Experts' perspectives on ethical challenges and governance strategies.

Background: Observational studies using large-scale databases and biobanks help improve prevention and treatment of sudden cardiac arrest (SCA) but the lack of guidance on data protection issues in this setting may harm patients' rights and the research enterprise itself. This qualitative study explored the ethical aspects of observational SCA research, as well as solutions. Methods: European experts in SCA research, medical ethics and health law reflected on this topic through semi-structured interviews (N = 29) and a virtual roundtable conference (N = 18). The ESCAPE-NET project served as a discussion case. Findings were coded and thematically analysed. Results: The first theme concerned the potential benefits and harms (at individual and group level) of observational data-based SCA studies and included the following sub-themes: societal value, scientific validity, data privacy, disclosure of genetic findings, stigma and discrimination, and medicalisation of sudden death. The second theme involved governance through 'privacy by design', 'privacy by policy' and associated regulation and oversight. Sub-themes were: de-identification of data, informed consent (broad and deferred), ethics review, and harmonisation. Conclusions: Researchers and scientific societies should be aware that ethico-legal issues may arise during data-driven studies in SCA and other emergencies. These can be mitigated by combining technical data protection safeguards with appropriate informed consent policies and proportional ethics oversight. To ensure responsible conduct of data research in emergency medicine, we recommend the establishment of 'codes of conduct' which should be developed in interdisciplinary groups and together with patient representatives.

Limiting calcium overload after cardiac arrest: The role of human albumin in controlled automated reperfusion of the whole body.

BACKGROUND: Regarding the overall inadequate results after cardiopulmonary resuscitation, the development of new treatment concepts is urgently needed. Controlled Automated Reperfusion of the whoLe body (CARL) represents a therapy bundle to control the conditions of reperfusion and the composition of the reperfusate after cardiac arrest (CA). The aim of this study was to investigate the plasma expander's role in the CARL priming solution and examine its mechanism of action. METHODS: Viscosity, osmolality, colloid osmotic pressure (COP), pH and calcium binding of different priming solutions were measured in vitro and compared to in vivo data. N = 16 pigs were allocated to receive CARL following 20 min of untreated CA with either human albumin 20% (HA, N = 8) or gelatin polysuccinate 4% (GP, N = 8). Blood gas analyses were performed during the first hour of reperfusion and catecholamine and fluid requirements were recorded. Neurological outcome was assessed by neurological deficit scoring (NDS) on the seventh day. RESULTS: In vitro, addition of HA to the CARL priming solution resulted in higher COP and higher calcium-binding than GP. In vivo, treatment with HA led to greater reduction of ionized calcium and higher extracorporeal flows within the first 30 min of reperfusion with no difference in catecholamine support and fluid requirement. Seven-day survival of 75% with no difference in NDS was observed in both groups. CONCLUSIONS: Our data show that the plasma expander in the CARL priming solution has a significant effect on the initial reperfusate and can potentially influence the course of resuscitation. However, seven-day survival and NDS did not differ between groups.

New International Guidelines and Consensus on the Use of Lung Ultrasound.

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point-of-care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements.

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study.

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6-26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.

Observational study on implications of the COVID-19-pandemic for cardiopulmonary resuscitation in out-of-hospital cardiac arrest: qualitative and quantitative insights from a model region in Germany.

BACKGROUND: The city of Freiburg has been among the most affected regions by the COVID-19 pandemic in Germany. In out of hospital cardiac arrest (OHCA) care, all parts of the rescue system were exposed to profound infrastructural changes. We aimed to provide a comprehensive overview of these changes in the resuscitation landscape in the Freiburg region. METHODS: Utstein-style quantitative data on OHCA with CPR initiated, occurring in the first pandemic wave between February 27th, 2020 and April 30th, 2020 were compared to the same time periods between 2016 and 2019. Additionally, qualitative changes in the entire rescue system were analyzed and described. RESULTS: Incidence of OHCA with attempted CPR did not significantly increase during the pandemic period (11.1/100.000 inhabitants/63 days vs 10.4/100.000 inhabitants/63 days, p = 1.000). In witnessed cases, bystander-CPR decreased significantly from 57.7% (30/52) to 25% (4/16) (p = 0.043). A severe pre-existing condition (PEC) was documented more often, 66.7% (16/24) vs 38.2% (39/102) there were longer emergency medical services (EMS) response times, more resuscitation attempts terminated on scene, 62.5% (15/24) vs. 34.3% (35/102) and less patients transported to hospital (p = 0.019). Public basic life support courses, an app-based first-responder alarm system, Kids Save Lives activities and a prehospital extracorporeal CPR (eCPR) service were paused during the peak of the pandemic. CONCLUSION: In our region, bystander CPR in witnessed OHCA cases as well as the number of patients transported to hospital significantly decreased during the first pandemic wave. Several important parts of the resuscitation landscape were paused. The COVID-19 pandemic impedes OHCA care, which leads to additional casualties. Countermeasures should be taken.

Serum proteome alterations during conventional and extracorporeal resuscitation in pigs.

BACKGROUND: Only a small number of patients survive an out-of-hospital cardiac arrest (CA) and can be discharged from hospital alive with a large percentage of these patients retaining neurological impairments. In recent years, extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a beneficial strategy to optimize cardiac arrest treatment. However, ECPR is still associated with various complications. To reduce these problems, a profound understanding of the underlying mechanisms is required. This study aims to investigate the effects of CA, conventional cardiopulmonary resuscitation (CPR) and ECPR using a whole-body reperfusion protocol (controlled and automated reperfusion of the whole body-CARL) on the serum proteome profiles in a pig model of refractory CA. METHODS: N = 7 pigs underwent 5 min of untreated CA followed by 30 min CPR and 120 min perfusion with CARL. Blood samples for proteomic analysis were drawn at baseline, after CPR and at the end of the CARL period. Following albumin-depletion, proteomic analysis was performed using liquid chromatography-tandem mass spectrometry. RESULTS: N = 21 serum samples were measured resulting in the identification and quantification of 308-360 proteins per sample and 388 unique proteins in total. The three serum proteome profiles at the investigated time points clustered individually and segregated almost completely when considering a 90% confidence interval. Differential expression analysis showed significant abundance changes in 27 proteins between baseline and after CPR and in 9 proteins after CARL compared to CPR. Significant findings were further validated through a co-abundance cluster analysis corroborating the observed abundance changes. CONCLUSIONS: The presented data highlight the impact of systemic ischemia and reperfusion on the entire serum proteome during resuscitation with a special focus on changes regarding haemolysis, coagulation, inflammation, and cell-death processes. Generally, the observed changes contribute to post-ischemic complications. Better understanding of the underlying mechanisms during CA and resuscitation may help to limit these complications and improve therapeutic options.

Beneficial Effects of Adjusted Perfusion and Defibrillation Strategies on Rhythm Control within Controlled Automated Reperfusion of the Whole Body (CARL) for Refractory Out-of-Hospital Cardiac Arrest.

Survival and neurological outcomes after out-of-hospital cardiac arrest (OHCA) remain low. The further development of prehospital extracorporeal resuscitation (ECPR) towards Controlled Automated Reperfusion of the Whole Body (CARL) has the potential to improve survival and outcome in these patients. In CARL therapy, pulsatile, high blood-flow reperfusion is performed combined with several modified reperfusion parameters and adjusted defibrillation strategies. We aimed to investigate whether pulsatile, high-flow reperfusion is feasible in refractory OHCA and whether the CARL approach improves heart-rhythm control during ECPR. In a reality-based porcine model of refractory OHCA, 20 pigs underwent prehospital CARL or conventional ECPR. Significantly higher pulsatile blood-flow proved to be feasible, and critical hypotension was consistently prevented via CARL. In the CARL group, spontaneous rhythm conversions were observed using a modified priming solution. Applying potassium-induced secondary cardioplegia proved to be a safe and effective method for sustained rhythm conversion. Moreover, significantly fewer defibrillation attempts were needed, and cardiac arrhythmias were reduced during reperfusion via CARL. Prehospital CARL therapy thus not only proved to be feasible after prolonged OHCA, but it turned out to be superior to conventional ECPR regarding rhythm control.

[Implementation of a smartphone-based first-responder alerting system]. / Implementierungsprozess einer Smartphone-basierten Ersthelferalarmierung: Herausforderungen bei der Einführung, Weiterentwicklung zum System 2.0.

Background: Shortening the resuscitation-free interval in cardiac arrest increases the survival rate. Smartphone-based systems can locate and alert nearby rescuers. Objectives: Implementation of a first responder system, technical development and adaption to regional structures. Materials and methods: The system "Region der Lebensretter" was successfully established in July 2018 in Freiburg. The need of optimization was evaluated every half year and realized according to the PDCA (plan-do-check-act) cycle. The necessary functions were specified (plan), programmed, tested and released (do). Afterwards the changes were evaluated (check) and, if necessary, further optimizations were implemented (act). Results: The number of registered rescuers increased from 276 (2nd half year 2018) to 794 (1st half year 2020). The rate of alarm acceptance increased from 30% (2nd half year 2018) to 49% (1st half year 2020). The following features were designed and released: dynamic adjustment of the alarm radius (DAA), critical alert function, connection to automated external defibrillator (AED) database, digital rescuer identification (ID), feedback button "arrived on scene", choice of means of transport for algorithm optimization. The number of existing AEDs increased from 190 to 270. Conclusion: The resuscitation-free interval can be shortened by smartphone-based alerting systems. For successful operation, the total number of rescuers and the technical realization is crucial. Further studies are necessary to investigate whether the survival rate of out-of-hospital cardiac arrest can be increased. It appears extremely appropriate to adapt these systems to databases of quality management or research registers.

Association of GPS-Based Logging and Manual Confirmation of the First Responders' Arrival Time in a Smartphone Alerting System: An Observational Study.

The latest guidelines for cardiopulmonary resuscitation recommend that in case of suspected cardiac arrest first responders, who are close to the emergency location, should be notified by a smartphone app or text message. Smartphone Alerting Systems (SAS) aim to reduce the resuscitation-free interval. Thus, there is a need for uniform reporting of process times. Objective: To compare the response times in a SAS either by using global positioning system (GPS) data or by manual confirmation of first responders arriving at the scene. Methods: In the region of Freiburg (Southern Germany, 1,531 km2, 493,000 inhabitants), a SAS is activated when the emergency dispatch center receives a call regarding suspected cardiac arrest. First responders who accept a mission are tracked using GPS. GPS-based times are logged for each responder when their position is within a radius of 100, 50, or 10 meters around the geographical position of the reported emergency. When arriving at the patient location, the first responders manually confirm "arrived" via their app. GPS-based and manually confirmed response arrival times were compared for all cases between 1 October and 31 March. Results: 192 missions with correct manual logging of the arrival time were included. GPS-based times were available in 175 (91%), 100 (52%), and 30 (16%) cases within radii of 100, 50, and 10 meters, respectively. GPS arrival times were approximately 1.5 minutes shorter when using a 100-meter radius and significantly longer when using a 10-meter radius. No difference was found for a 50-meter radius, but this would result in a lack of data in nearly half of the cases. Conclusion: GPS-based logging of arrival times leads to missing data. A 100-meter circle is associated with a low number of missing values, but 1.5 minutes must be added for the last 100 meters the first responder has to move. A wide range of the difference in response times (GPS vs. manual confirmation) must be regarded as a disadvantage. Manual confirmation reveals precise response times, but first responders may forget to confirm when they arrive. Trial registration: DRKS00016625 (14 April 2019).

Monitoring Mitochondrial Partial Oxygen Pressure During Cardiac Arrest and Extracorporeal Cardiopulmonary Resuscitation. An Experimental Pilot Study in a Pig Model.

Introduction: Ischemia and reperfusion are crucial in determining the outcome after cardiac arrest and can be influenced by extracorporeal cardiopulmonary resuscitation (ECPR). The effect of ECPR on the availability and level of oxygen in mitochondria remains unknown. The aim of this study was to find out if skin mitochondrial partial oxygen pressure (mitoPO2) measurements in cardiac arrest and ECPR are feasible and to investigate its course. Materials and Methods: We performed a feasibility test to determine if skin mitoPO2 measurements in a pig are possible. Next, we aimed to measure skin mitoPO2 in 10 experimental pigs. Measurements were performed using a cellular oxygen metabolism measurement monitor (COMET), at baseline, during cardiac arrest, and during ECPR using the controlled integrated resuscitation device (CIRD). Results: The feasibility test showed continuous mitoPO2 values. Nine experimental pigs could be measured. Measurements in six experimental pigs succeeded. Our results showed a delay until the initial spike of mitoPO2 after ECPR initiation in all six experimental tests. In two experiments (33%) mitoPO2 remained present after the initial spike. A correlation of mitoPO2 with mean arterial pressure (MAP) and arterial partial oxygen pressure measured by CIRD (CIRD-PaO2) seemed not present. One of the experimental pigs survived. Conclusions: This experimental pilot study shows that continuous measurements of skin mitoPO2 in pigs treated with ECPR are feasible. The delay in initial mitoPO2 and discrepancy of mitoPO2 and MAP in our small sample study could point to the possible value of additional measurements besides MAP to monitor the quality of tissue perfusion during cardiac arrest and ECPR.

Smartphone based alerting of first responders during the corona virus disease-19 pandemic: An observational study.

ABSTRACT: Smartphone alerting systems (SAS) for first responders potentially shorten the resuscitation-free interval of patients with acute cardiac arrest. During the corona virus disease-19 (COVID-19) pandemic, many systems are suspended due to potential risks for the responders.Objective of the study was to establish a concept for SAS during the COVID-19 pandemic and to evaluate whether a SAS can safely be operated in pandemic conditions.A SAS had been implemented in Freiburg (Germany) in 2018 alerting nearby registered first responders in case of emergencies with suspected cardiac arrest. Due to the pandemic, SAS was stopped in March 2020. A concept for a safe restart was elaborated with provision of a set with ventilation bag/mask, airway filter, and personal protective equipment (PPE) for every volunteer. A standard operating procedure was elaborated following the COVID-19 guidelines of the European Resuscitation Council.Willingness of the participants to respond alarms during the pandemic was investigated using an online survey. The response rates of first responders were monitored before and after deactivation, and during the second wave of the pandemic.The system was restarted in May 2020. The willingness to respond to alarms was lower during the pandemic without PPE. It remained lower than before the pandemic when the volunteers had been equipped with PPE, but the alarm response rate remained at approximately 50% during the second wave of the pandemic.When volunteers are equipped with PPE, the operation of a SAS does not need to be paused, and the willingness to respond remains high among first responders.

Brain vulnerability and viability after ischaemia.

The susceptibility of the brain to ischaemic injury dramatically limits its viability following interruptions in blood flow. However, data from studies of dissociated cells, tissue specimens, isolated organs and whole bodies have brought into question the temporal limits within which the brain is capable of tolerating prolonged circulatory arrest. This Review assesses cell type-specific mechanisms of global cerebral ischaemia, and examines the circumstances in which the brain exhibits heightened resilience to injury. We suggest strategies for expanding such discoveries to fuel translational research into novel cytoprotective therapies, and describe emerging technologies and experimental concepts. By doing so, we propose a new multimodal framework to investigate brain resuscitation following extended periods of circulatory arrest.

Lung ultrasound in the emergency department - a valuable tool in the management of patients presenting with respiratory symptoms during the SARS-CoV-2 pandemic.

BACKGROUND: Typical lung ultrasound (LUS) findings in patients with a COVID-19 infection were reported early on. During the global SARS-CoV-2 pandemic, LUS was propagated as a useful instrument in triage and monitoring. We evaluated LUS as a rapid diagnostic triage tool for the management of patients with suspected COVID-19 in the emergency department (ED). METHODS: The study retrospectively enrolled patients with suspected COVID-19, who were admitted from 1st April to 25th of April 2020 to the ED of a tertiary care center in Germany. During clinical work-up, patients underwent LUS and polymerase chain reaction (PCR) testing for SARS-CoV-2. The recorded ultrasound findings were analyzed and judged regarding typical signs of viral pneumonia, blinded for clinical information of the patients. The results were compared with PCR test and chest computed tomography (CT). RESULTS: 2236 patients were treated in the ED during the study period. 203 were tested for SARS-CoV-2 using PCR, 135 (66.5%) underwent LUS and 39 (28.9%) of the patients were examined by chest CT scan. 39 (28.9%) of the 135 patients were tested positive for SARS-CoV-2 with PCR. In 52 (38.5%) COVID-19 was suspected from the finding of the LUS, resulting in a sensitivity of 76.9% and a specificity of 77.1% compared with PCR results. The negative predictive value reached 89.2%. The findings of the LUS had - compared to a positive chest CT scan for COVID-19 - a sensitivity of 70.6% and a specificity of 72.7%. CONCLUSIONS: LUS is a rapid and useful triage tool in the work-up of patients with suspected COVID-19 infection during a pandemic scenario. Still, the results of the LUS depend on the physician's experience and skills.

Education, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

For this 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.

[German recommendations on lung and thoracic ultrasonography in patients with COVID-19]. / Empfehlungen zur Lungen- und Thoraxsonographie bei Patienten mit COVID-19-Erkrankung.

Lung and chest ultrasound are further examination modalities in addition to computed tomography and laboratory diagnostics in patients with COVID-19. It extends the clinical-physical examination because it can examine lung surface sensitively. Lung surface pattern changes have been found in sonograms of patients with COVID-19 pneumonia and during the course of the disease. German specialist societies of clinical acute, emergency and intensive care medicine as well as imaging, which are concerned with the care of patients with SARS-CoV­2 infection and COVID-19, have coordinated recommendations for lung and thorax sonography. This document has been created within a transparent process, led by the German Society of Interdisciplinary Emergency and Acute Medicine e. V. (DGINA), and worked out by an expert panel and delegates from the societies. Sources of the first 200 cases were summarized. Typical thorax sonographic findings are presented. International sources or standards that were available in PubMed until May 24, 2020 were included. Using case studies and multimedia content, the document is intended to not only support users but also demonstrate quality features and the potential of chest and lung sonography. The German Society for Ultrasound in Medicine (DEGUM) is carrying out a multicenter study (study coordination at the TU Munich).

[Pulmonary Sonography in Patients With Suspected COVID-19 - Step-by-Step]. / Lungensonografie bei Patienten mit Verdacht auf COVID-19 ­ Schritt-für-Schritt.

Pulmonary sonography can be a valuable aid in the differential diagnosis of a variety of cardiopulmonary diseases, including patients with COVID-19. Pulmonary sonography is an examination method that is also quickly available at the bedside without additional risks for the patient. When COVID-19 is suspected, lung sonography is a valuable component of initial diagnosis when used systematically, performed hygienically and correctly. However, the findings of pulmonary sonography must be placed in the clinical context; sonography does not replace the gold standard of PCR diagnosis. The article shows how this sonography is performed and which findings in COVID-19 are relevant.