Left-Ventricular Unloading With Impella During Refractory Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) is the implementation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) during refractory cardiac arrest. The role of left-ventricular (LV) unloading with Impella in addition to VA-ECMO ("ECMELLA") remains unclear during ECPR. This is the first systematic review and meta-analysis to characterize patients with ECPR receiving LV unloading and to compare in-hospital mortality between ECMELLA and VA-ECMO during ECPR. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, and abstract websites of the three largest cardiology societies (American Heart Association, American College of Cardiology, and European Society of Cardiology). STUDY SELECTION: Observational studies with adult patients with refractory cardiac arrest receiving ECPR with ECMELLA or VA-ECMO until July 2023 according to the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist. DATA EXTRACTION: Patient and treatment characteristics and in-hospital mortality from 13 study records at 32 hospitals with a total of 1014 ECPR patients. Odds ratios (ORs) and 95% CI were computed with the Mantel-Haenszel test using a random-effects model. DATA SYNTHESIS: Seven hundred sixty-two patients (75.1%) received VA-ECMO and 252 (24.9%) ECMELLA. Compared with VA-ECMO, the ECMELLA group was comprised of more patients with initial shockable electrocardiogram rhythms (58.6% vs. 49.3%), acute myocardial infarctions (79.7% vs. 51.5%), and percutaneous coronary interventions (79.0% vs. 47.5%). VA-ECMO alone was more frequently used in pulmonary embolism (9.5% vs. 0.7%). Age, rate of out-of-hospital cardiac arrest, and low-flow times were similar between both groups. ECMELLA support was associated with reduced odds of mortality (OR, 0.53 [95% CI, 0.30-0.91]) and higher odds of good neurologic outcome (OR, 2.22 [95% CI, 1.17-4.22]) compared with VA-ECMO support alone. ECMELLA therapy was associated with numerically increased but not significantly higher complication rates. Primary results remained robust in multiple sensitivity analyses. CONCLUSIONS: ECMELLA support was predominantly used in patients with acute myocardial infarction and VA-ECMO for pulmonary embolism. ECMELLA support during ECPR might be associated with improved survival and neurologic outcome despite higher complication rates. However, indications and frequency of ECMELLA support varied strongly between institutions. Further scientific evidence is urgently required to elaborate standardized guidelines for the use of LV unloading during ECPR.

Mortality and healthcare resource utilisation after cardiac arrest in the United States - A 10-year nationwide analysis prior to the COVID-19 pandemic.

AIM: Understanding the public health burden of cardiac arrest (CA) is important to inform healthcare policies, particularly during healthcare crises such as the COVID-19 pandemic. This study aimed to analyse outcomes of in-hospital mortality and healthcare resource utilisation in adult patients with CA in the United States over the last decade prior to the COVID-19 pandemic. METHODS: The United States (US) National Inpatient Sample was utilised to identify hospitalised adult patients with CA between 2010 and 2019. Logistic and Poisson regression models were used to analyse outcomes by adjusting for 47 confounders. RESULTS: 248,754 adult patients with CA (without "Do Not Resuscitate"-orders) were included in this study, out of which 57.5% were male. In-hospital mortality was high with 51.2% but improved significantly from 58.3% in 2010 to 46.4% in 2019 (P < 0.001). Particularly, elderly patients, non-white patients and patients requiring complex therapy had a higher mortality rate. Although the average hospital LOS decreased by 11%, hospital expenses have increased by 13% between 2010 and 2019 (each P < 0.001), presumably due to more frequent use of mechanical circulatory support (MCS, e.g. ECMO from 2.6% to 8.7% or Impella® micro-axial flow pump from 1.8% to 14.2%). Strong disparities existed among patient age groups and ethnicities across the US. Of note, the number of young adults with CA and opioid-induced CA has almost doubled within the study period. CONCLUSION: Over the last ten years prior to the COVID-19 pandemic, CA-related survival has incrementally improved with shorter hospitalisations and increased medical expenses, while strong disparities existed among different age groups and ethnicities. National standards for CA surveillance should be considered to identify trends and differences in CA treatment to allow for standardised medical care.

Safety and Healthcare Resource Utilization in Patients Undergoing Left Atrial Appendage Closure-A Nationwide Analysis.

Percutaneous left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. The aim of this study was to analyze outcomes of peri-procedural safety and healthcare resource utilization in 11,240 adult patients undergoing LAAC in the United States between 2016 and 2019. Primary outcomes (safety) were in-hospital ischemic stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolization and mortality. Secondary outcomes (resource utilization) were adverse discharge disposition, hospital length of stay (LOS) and costs. Logistic and Poisson regression models were used to analyze outcomes by adjusting for 10 confounders. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (p = 0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality (0.14%) remained stable. Hospital LOS decreased by 17% (0.78-0.87, p < 0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, p = 0.005) between 2016 and 2019, while hospital costs did not significantly change (p = 0.2). Female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]) while multi-morbid patients had higher risks of major bleeding (p < 0.001) and mortality (p = 0.031), longer hospital LOS (p < 0.001) and increased treatment costs (p = 0.073). Significant differences in all outcomes were observed between male and female patients across US regions. In conclusion, LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.

Case report: Refractory cardiac arrest supported with veno-arterial-venous extracorporeal membrane oxygenation and left-ventricular Impella CP®-Physiological insights and pitfalls of ECMELLA.

Introduction: To the best of our knowledge, this is the first case report which provides insights into patient-specific hemodynamics during veno-arterio-venous-extracorporeal membrane oxygenation (VAV ECMO) combined with a left-ventricular (LV) Impella® micro-axial pump for therapy-refractory cardiac arrest due to acute myocardial infarction, complicated by acute lung injury (ALI). Patient presentation: A 54-year-old male patient presented with ST-segment elevation acute coronary syndrome complicated by out-of-hospital cardiac arrest with ventricular fibrillation upon arrival of the emergency medical service. As cardiac arrest was refractory to advanced cardiac life support, the patient was transferred to the Cardiac Arrest Center for immediate initiation of extracorporeal cardiopulmonary resuscitation (ECPR) with peripheral VA ECMO and emergency percutaneous coronary intervention using drug eluting stents in the right coronary artery. Due to LV distension and persistent asystole after coronary revascularization, an Impella® pump was inserted for LV unloading and additional hemodynamic support (i.e., "ECMELLA"). Despite successful unloading by ECMELLA, post-cardiac arrest treatment was further complicated by sudden differential hypoxemia of the upper body. This so called "Harlequin phenomenon" was explained by a new onset of ALI, necessitating escalation of VA ECMO to VAV ECMO, while maintaining Impella® support. Comprehensive monitoring as derived from the Impella® console allowed to illustrate patient-specific hemodynamics of cardiac unloading. Ultimately, the patient recovered and was discharged from the hospital 28 days after admission. 12 months after the index event the patient was enrolled in the ECPR Outpatient Care Program which revealed good recovery of neurologic functions while physical exercise capacities were impaired. Conclusion: A combined mechanical circulatory support strategy may successfully be deployed in complex cases of severe cardio-circulatory and respiratory failure as occasionally encountered in clinical practice. While appreciating potential clinical benefits, it seems of utmost importance to closely monitor the physiological effects and related complications of such a multimodal approach to reach the most favorable outcome as illustrated in this case.

Comparison of Hemostatic Changes in Pump-driven Extracorporeal Carbon Dioxide Removal and Venovenous Extracorporeal Membrane Oxygenation.

Extracorporeal carbon dioxide removal (ECCO 2 R) has gained widespread use as a supposedly less invasive alternative for hypercapnic respiratory failure besides venovenous extracorporeal membrane oxygenation (VV ECMO). Despite technological advances, coagulation-related adverse events remain a major challenge in both therapies. The overlapping operating areas of VV ECMO and pump-driven ECCO 2 R could allow for a device selection targeted at the lowest risk of such complications. This retrospective analysis of 47 consecutive patients compared hemostatic changes between pump-driven ECCO 2 R (n = 23) and VV ECMO (n = 24) by application of linear mixed effect models. A significant decrease in platelet count, increase in D-dimer levels, and decrease of fibrinogen levels were observed. However, except for fibrinogen, the type of extracorporeal support did not have a significant effect on the time course of these parameters. Our findings suggest that in terms of hemocompatibility, pump-driven ECCO 2 R is not significantly different from VV ECMO.

Heparin-induced thrombocytopaenia diagnostic testing after adult cardiac surgery: a single-centre experience and development.

OBJECTIVES: To assess the incidence and outcome of heparin-induced thrombocytopaenia (HIT) in patients after cardiac surgery on cardiopulmonary bypass (CPB) and to review the time course of platelet counts and the use of different immunological diagnostic tests. METHODS: All patients ≥18 years of age who underwent CPB from 2006 to 2015 and who were postoperatively admitted to our cardiac intensive care unit (ICU) were included in this retrospective study. Screening for heparin/platelet factor-4 antibodies was performed using an antibody test, which was later replaced with a screening test specific for IgG antibodies without IgA/IgM cross-reactivity. The enzyme immunoassay (EIA) for the detection of antibodies of all immunoglobulin classes against heparin/PF4 complexes was replaced with an IgG-specific EIA. HIT was confirmed by a heparin-induced platelet aggregation test until 2014. RESULTS: Among 4978 patients admitted between 2006 and 2015, 539 (11%) patients were evaluated for HIT. Patients were excluded because of age <18 years (n = 9), non-cardiac surgery without CPB (n = 10) or incomplete data (n = 3). Of the remaining 517 patients, 43 (8.3%) patients were HIT-positive. HIT incidence was 0.86%. The proportion of HIT-positive patients was similar in men and women (8.4% and 8.2%, respectively). Men and women with suspected HIT also had similar in-hospital mortality (odds ratio ≈ 1; P = 0.926). CONCLUSIONS: The incidence of HIT was lower in our study than previously reported. Novel immunological tests have improved to specifically detect IgG antibodies. Furthermore, they are able to detect anti-protamine antibodies, which may be present in patients with high clinical probability of testing negative for HIT. Incidence and clinical relevance of heparin/protamine antibodies will be subjects of future investigation.

Extracorporeal immunoadsorption in heparin- and protamine-induced thrombocytopaenia prior to cardiac surgery.

Exposure to heparin and protamine during cardiac surgery on cardiopulmonary bypass (CPB) may trigger heparin-induced thrombocytopaenia and/or protamine-induced thrombocytopaenia. Further surgery on CPB with heparin and protamine in the presence of these antibodies implies increased thromboembolic risk. We present the successful application of extracorporeal immunoadsorption to deplete antibodies causing heparin-induced and protamine-induced thrombocytopaenia preoperatively.

Diagnostic value of 18F-fluordesoxyglucose positron emission tomography for patients with brain metastasis from unknown primary site.

BACKGROUND: In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS. METHODS: We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation. RESULTS: FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10-5, Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10-5; Wilcoxon's test). All observations were confirmed in the validation cohort. CONCLUSIONS: Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA.

Performance and skill retention of five supraglottic airway devices for the pediatric difficult airway in a manikin.

Supraglottic airway devices (SADs) have been introduced to assist medical professionals in emergency situations with limited experience in securing airways via conventional endotracheal intubation (ETI). Literature on the use of SADs for securing an airway during pediatric critical settings is scarce, and there is a lack of studies comparing different SADs to each other and to conventional ETI. We conducted a study comparing five different SADs to ETI with regard to success rate, time to first ventilation, and personal rating in a pediatric manikin under simulated physiologic and pathologic airway conditions in 41 pediatricians of varying clinical experience and training. Only the AirQ, AuraG, and laryngeal tube (LT) were inserted within 30 s correctly by all participants under physiologic conditions. In tongue edema (TE), AirQ and LT had the highest success rate. In limited mobility of the cervical spine (CS), AirQ, AuraG, and LT again all were inserted within 30 s. In a multivariate analysis, factors influencing the success were experience with the respective device and level of medical education. Under TE conditions, there were significantly longer insertion times for the ETI, laryngeal mask airway (LMA), and EzT. Under CS conditions, there were significantly longer insertion times for the ETI, LMA, LT, and EzT. A multivariate analysis showed experience with the respective device to be the only factor of influence on time to first ventilation. CONCLUSION: LT, AuraG, and AirQ were superior in providing fast and effective ventilation during simulated difficult airway situations in pediatricians. What is Known: • Supraglottic airway devices have been introduced for medical professionals who lack experience for managing difficult airway situations. • A variety of these devices have been developed so far, but not compared to each other yet. What is New: • We compared five different supraglottic airway devices with regard to success rate, time to first ventilation, and personal rating in a pediatric manikin under simulated physiologic and pathologic airway conditions. • Laryngeal tube, AuraG, and AirQ were superior in providing fast and effective ventilation during simulated difficult airway situations in pediatricians with varying clinical experience.

Inter-center comparison of EasyTube and endotracheal tube during general anesthesia in minor elective surgery.

BACKGROUND: The EasyTube® (EzT) is a supraglottic airway device (SAD) enabling ventilation irrespective of its placement into the esophagus or trachea. Data obtained on SADs from multicenter studies, performed in highly specialized centers cannot always be transferred to other sites. However, data on comparability of different sites are scarce. This study focused on inter-site variability of ventilatory and safety parameters during general anesthesia with the EzT. METHODS: 400 patients with ASA physical status I-II undergoing general anesthesia for elective surgery in four medical centers (EzT group (n = 200), ETT group (n = 200)). Mallampati classification, success of insertion, insertion time, duration of ventilation, number of insertion attempts, ease of insertion, tidal volumes, leakage, hemodynamic parameters, oxygenation, and complications rates with the EasyTube (EzT) or endotracheal tube (ETT) in comparison within the sites and in between the sites were recorded. RESULTS: Intra-site and inter-site comparison of insertion success as primary outcome did not differ significantly. The inter-site comparison of expiratory minute volumes showed that the volumes achieved over the course of anesthesia did not differ significantly, however, mean leakage at one site was significantly higher with the EzT (0.63 l/min, p = 0.02). No significant inter-site differences in heart rate, blood pressure, or oxygenation were observed. Sore throat and blood on the cuff after removal of the device were the most frequent complications with significantly more complications at one site with the EzT (p = 0.01) where insertion was also reported significantly more difficult (p = 0.02). CONCLUSION: Performance of the EzT but not the ETT varied between sites with regard to insertion difficulty, leakage, and complications but not insertion success, ventilation, hemodynamics, and oxygenation parameters in patients with ASA physical status 1-2 during general anesthesia undergoing minor elective surgery.

Descriptive statistical analysis of a real life cohort of 2419 patients with brain metastases of solid cancers.

AIM: We provide a descriptive statistical analysis of baseline characteristics and the clinical course of a large real-life cohort of brain metastases (BM) patients. METHODS: We performed a retrospective chart review for patients treated for BM of solid cancers at the Medical University of Vienna between 1990 and 2011. RESULTS: We identified a total of 2419 BM patients (50.5% male, 49.5% female, median age 59 years). The primary tumour was lung cancer in 43.2%, breast cancer in 15.7%, melanoma in 16.4%, renal cell carcinoma in 9.1%, colorectal cancer in 9.3% and unknown in 1.4% of cases. Rare tumour types associated with BM included genitourinary cancers (4.1%), sarcomas (0.7%). gastro-oesophageal cancer (0.6%) and head and neck cancers (0.2%). 48.7% of patients presented with a singular BM, 27.7% with 2-3 and 23.5% with >3 BM. Time from primary tumour to BM diagnosis was shortest in lung cancer (median 11 months; range 1-162) and longest in breast cancer (median 44 months; 1-443; p<0.001). Multiple BM were most frequent in breast cancer (30.6%) and least frequent in colorectal cancer (8.5%; p<0.001). Patients with breast cancer had the longest median overall survival times (8 months), followed by patients with lung cancer (7 months), renal cell carcinoma (7 months), melanoma (5 months) and colorectal cancer (4 months; p<0.001; log rank test). Recursive partitioning analysis and graded prognostic assessment scores showed significant correlation with overall survival (both p<0.001, log rank test). Evaluation of the disease status in the past 2 months prior to patient death showed intracranial progression in 35.9%, extracranial progression in 27.5% and combined extracranial and intracranial progression in 36.6% of patients. CONCLUSIONS: Our data highlight the heterogeneity in presentation and clinical course of BM patients in the everyday clinical setting and may be useful for rational planning of clinical studies.