Leukocyte filtration and leukocyte modulation therapy during extracorporeal cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest.

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation.

Online training to improve BLS performance with dispatcher assistance? Results of a cluster-randomised controlled simulation trial.

BACKGROUND: The prognosis for patients improves significantly with effective cardiopulmonary resuscitation (CPR) performed by bystanders. Current research indicates that individuals who receive CPR from trained bystanders have a greater likelihood of survival compared to those who receive dispatcher-assisted CPR from untrained laypersons. This cluster-randomised controlled trial assessed the impact of a 30-min online training session prior to a simulated cardiac arrest situation with dispatcher-assisted CPR (DA-CPR) on enhancing Basic Life Support (BLS) performance. METHODS: This study was performed in 2018 in Hamburg, Germany. The primary outcome was the practical BLS skills of high school students in simulated out-of-hospital cardiac arrest scenarios with dispatcher assistance. The intervention group participants underwent a 30-min online BLS training session, while the control group did not receive an intervention. It was hypothesized that the average practical BLS scores of the intervention group would be 1.5 points higher than those of the control group. RESULTS: BLS assessments of 286 students of 16 different classes were analysed. The estimated mean BLS score in the intervention group was 7.60 points (95% CI: 6.76 to 8.44) compared to 6.81 (95% CI: 5.97 to 7.65) in the control group adjusted for BLS training and class. Therefore, the estimated mean difference between the groups was 0.79 (95% CI: -0.40 to 1.97) and not significantly different (p-value: 0.176). Based on a logistic regression analysis the intervention had only a significant effect on the chance to pass the item "vertically above the chest" (OR = 4.99; 95% CI: 1.46 to 17.12) adjusted for BLS training and class. CONCLUSION: Prior online training exhibits beneficial impacts on the BLS performance of bystanders during DA-CPR. To maximise the effect size, online training should be incorporated into a set of interventions that are mutually complementary and specifically designed for the target participants. TRIAL REGISTRATION: DRKS00033531 . "Kann online Training Laien darauf vorbereiten Reanimationsmaßnahmen unter Anleitung der Leitstelle adäquat durchzuführen? " Registered on January 29, 2024.

Standard cardiopulmonary resuscitation versus chest compressions only after out-of-hospital cardiac arrest: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The 2020 American Heart Association guidelines encourage lay rescuers to provide chest compression-only cardiopulmonary resuscitation to simplify the process and encourage cardiopulmonary resuscitation initiation. However, recent clinical trials had contradictory results about chest compression-only cardiopulmonary resuscitation. This study will aim to compare standard and chest compressions-only cardiopulmonary resuscitation after out-of-hospital cardiac arrest. METHODS AND ANALYSIS: This study will retrieve only randomised and quasi-randomised controlled trials from the Cochrane Library, PubMed, Web of Science and Embase databases. Data on study design, participant characteristics, intervention details and outcomes will be extracted by a unified standard form. Primary outcomes to be assessed are hospital admission, discharge, and 30-day survival, and return of spontaneous circulation. The Grading of Recommendations, Assessment, Development and Evaluation framework will evaluate the quality of evidence. Cochrane's tool for assessing the risk of bias will evaluate risk deviation. If the I2 statistic is lower than 40%, the fixed-effects model will be used for meta-analysis. Otherwise, the random-effects model will be used. The search will be performed following the publication of this protocol (estimated to occur on 30 December 2024). DISCUSSION: This study will evaluate the effect of chest compression-only cardiopulmonary resuscitation after out-of-hospital cardiac arrest and provide evidence for cardiopulmonary resuscitation guidelines. ETHICS AND DISSEMINATION: No patient or public entity will be involved in this study. Therefore, the study does not need to be ethically reviewed. The results of the study will be disseminated through peer-reviewed journal publications and committee conferences. PROSPERO REGISTRATION NUMBER: CRD42021295507.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. METHODS AND RESULTS: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Efficacy of bougie first approach for endotracheal intubation with video laryngoscopy during continuous chest compression: a randomized crossover manikin trial.

BACKGROUND: Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression. METHODS: This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute. RESULTS: A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants. CONCLUSIONS: The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings. TRIAL REGISTRATION: Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.

Ventilation during cardiopulmonary resuscitation with mechanical chest compressions: How often are two insufflations being given during the 3-second ventilation pauses?

BACKGROUND: Mechanical chest compression devices in 30:2 mode provide 3-second pauses to allow for two insufflations. We aimed to determine how often two insufflations are provided in these ventilation pauses, in order to assess if prehospital providers are able to ventilate out-of-hospital cardiac arrest (OHCA) patients successfully during mechanical chest compressions. METHODS: Data from OHCA cases of the regional ambulance service of Utrecht, The Netherlands, were prospectively collected in the UTrecht studygroup for OPtimal registry of cardIAc arrest database (UTOPIA). Compression pauses and insufflations were visualized on thoracic impedance and waveform capnography signals recorded by manual defibrillators. Ventilation pauses were analyzed for number of insufflations, duration of the subintervals of the ventilation cycles, and ratio of successfully providing two insufflations over the course of the resuscitation. Generalized linear mixed effects models were used to accurately estimate proportions and means. RESULTS: In 250 cases, 8473 ventilation pauses were identified, of which 4305 (51%) included two insufflations. When corrected for non-independence of the data across repeated measures within the same subjects with a mixed effects analysis, two insufflations were successfully provided in 45% of ventilation pauses (95% CI: 40-50%). In 19% (95% CI: 16-22%) none were given. CONCLUSION: Providing two insufflations during pauses in mechanical chest compressions is mostly unsuccessful. We recommend developing strategies to improve giving insufflations when using mechanical chest compression devices. Increasing the pause duration might help to improve insufflation success.

Effectiveness of innovative chest compression on the emergency department stretcher by an alternative method: a randomized controlled crossover trial.

Comparison of the three methods standing-on-a-stool (SS), one knee kneeling on a stretcher (KS), and kneeling at the same height as the patient's bed on the kneeling stool (KK) to evaluate the yielded of highest CPR quality and rescuer comfortability. A prospective randomized cross-over study which compares the three different rescuer positions for their effectiveness of chest compression. Conducted at a tertiary care between 19 and 22 Aug 2022. Emergency personnel aged 18 years or older, who completed the AHA-approved BLS course. The chest compression data was obtained by the ALIVE AED manikin® and AED reporting system. The information on the CPR quality and post-test questionnaires assessing the participants' preference, satisfaction and modified Borg's scale score was collected. The three methods shown no statistically significant difference in adequate chest compression depth (percentage). KK was not superior than SS at chest compression rate (P = 0.05). The adequate full chest recoil achieved with KK and KS were significantly higher than that of SS. However, there were no statistical difference between the three methods in the modified Borg's scale score. Based on the satisfying score, the rescuers preferred KK to either SS (p 0.007) or KS (p 0.012). The three methods shown no statistically significant difference in adequate chest compression depth (percentage). Still, both KK and KS provided more adequate chest recoil, so we would recommend using these two methods in the ED.Clinical trial registry: This study was retrospective registration in thaiclinicaltrials.org (TCTR20230119002, 19/1/2023).