BackgroundAcute respiratory distress syndrome is a heterogeneous syndrome that complicates risk stratification, therapy monitoring and personalised treatment during veno-venous extracorporeal membrane oxygenation. This study aims to identify discrete acute respiratory distress syndrome subphenotypes among veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients using high-resolution electronic health record clustering, and to assess differences in clinical outcomes.Materials and methodsWe conducted a study of 598 adult patients with acute respiratory distress syndrome treated with VV-ECMO. Twenty-six clinically relevant parameters spanning inflammation, coagulation, kidney/liver function, mechanical ventilation, and ECMO parameters were analysed using K-means clustering. Shapley Additive Explanations models were used to identify key differentiating parameters between clusters and independent survival factors. Clinical outcomes were compared between clusters, including treatment duration and survival rates in intensive care.ResultsCluster analysis revealed distinct subphenotypes primarily driven by differences in inflammation (procalcitonin and C-reactive protein), kidney/liver function (creatinine and urea), coagulation (fibrinogen and D-dimer), and mechanical ventilation (positive end-expiratory pressure). Survival rates varied considerably between clusters, most notably within the kidney/liver function (32%) and combined parameter categories (21%). Subphenotypes defined solely by ECMO or ventilator settings showed smaller differences. Intensive care unit length of stay was longer in clusters with multi-organ dysfunction.ConclusionsEarly data-driven clustering of electronic health record parameters identifies clinically meaningful acute respiratory distress syndrome subphenotypes among veno-venous extracorporeal membrane oxygenation patients. Renal, hepatic, and inflammatory dysfunctions are critical determinants of survival. Subphenotype-based stratification may refine risk stratification and management in severe acute respiratory distress syndrome treated with VV-ECMO.

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) requiring invasive mechanical ventilation (IMV) are associated with high mortality and long-term disability. Extracorporeal CO₂ removal (ECCO₂R) using modern high-capacity devices may facilitate early endotracheal extubation and reduce IMV-related complications. To evaluate whether ECCO2R-facilitated early extubation improves clinical outcomes compared with standard IMV in patients with severe AE-COPD requiring IMV. Adults with acute hypercapnic respiratory failure due to AE-COPD requiring IMV who failed or were ineligible for extubation within 24 hours of intubation were randomized to ECCO2R or no ECCO2R. The primary endpoint was a composite of death or severe disability at day 60. 18 patients were randomized before the trial was terminated early by the sponsor for financial reasons (planned enrollment: 192). The primary composite endpoint occurred in 0/8 ECCO2R-treated patients versus 3/9 evaluable IMV-treated patients (33

This study introduces a virtual patient generation model as online tool through the generation of high-quality synthetic data, addressing challenges like privacy cocerns and limited dataset sizes. Using a Conditional Tabular Generative Adversarial Network (CTGAN), we generated synthetic data from the Electronic Health Records (EHR) of 767 veno-venous extracorporeal membrane oxygenation (ECMO) patients, focusing on 55 critical therapy parameters. Rigorous preprocessing, imputation, and model tuning ensured that the synthetic data closely mirrored real patient records, achieving a 86.6% coverage score and minimal deviations in data correlations. The tool is integrated into a web platform - , allowing researchers to generate and visualize virtual patient cohorts, potentially enhancing ECMO research and reducing the need for extensive clinical trials. ### Competing Interest Statement The authors have declared no competing interest.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become standard of care in patients with the most severe forms of acute respiratory distress syndrome. However, hemolysis and bleeding are one of the most frequent side effects, affecting mortality. Despite the widespread use of VV ECMO, current protocols lack detailed, in-vivo data-based recommendations for safe ECMO pump operating conditions. This study aims to comprehensively analyze the impact of VV ECMO pump operating conditions on hemolysis by combining in-silico modeling and clinical data analysis. We combined data from 580 patients treated with VV ECMO in conjunction with numerical predictions of hemolysis using computational fluid dynamics and reduced order modeling of the Rotaflow (Getinge) and DP3 (Xenios) pumps. Blood trauma parameters across 94,779 pump operating points were associated with numerical predictions of shear induced hemolysis. Minimal hemolysis was observed at low pump pressures and low circuit resistance across all flow rates, whereas high pump pressures and circuit resistance consistently precipitated substantial hemolysis, irrespective of flow rate. However, the lower the flow rate, the more pronounced the influence of circuit resistance on hemolysis became. Numerical models validated against clinical data demonstrated a strong association (Spearman’s r = 0.8) between simulated and observed hemolysis, irrespective of the pump type. Integrating in-silico predictions with clinical data provided a novel approach in understanding and potentially reducing blood trauma in VV ECMO. This study further demonstrated that a key factor in lowering side effects of ECMO support is the maintenance of low circuit resistance, including oxygenators with the lowest possible resistance, the shortest feasible circuit tubing, and cannulae with an optimal diameter.

INTRODUCTION:Survivors of severe COVID-19 face complex challenges and a high degree of pulmonary sequelae. Therefore, we aim to describe their ongoing health burden. METHODS:In this single-center prospective cohort study, COVID-19 ICU survivors were invited 3 and 6 months after ICU discharge. We examined pulmonary function with pulmonary function tests (PFT) and cardiopulmonary exercise testing (CPET), and we established health-related quality of life (HRQL) and health status (HS) with the EuroQol five-dimension five-level (EQ-5D-5L), the short-form health survey 12 (SF-12), and the modified British Medical Research Council dyspnea scale (mMRC) questionnaires. RESULTS:Out of the 53 individuals screened, 23 participated in this study. Throughout both assessment points, participants maintained PFT results within range, apart from a decline in the transfer factor of the lung for carbon monoxide (TLCO). CPET showed improved fitness but persistent ventilatory deficiencies, indicated by altered dead space ventilation (VD/VT) and elevated arterial-alveoli gradient for oxygen (AaDO2). HRQL and HS remained compromised, with both physical (PCS) and mental component summary (MCS) scores significantly lower than the standardized norm population scores. Also, there was a rise in the prevalence of issues related to mobility, pain/discomfort, and anxiety/depression, and an increase in reported dyspnea. CONCLUSION:These results enhance our comprehension of the complex difficulties faced by COVID-19 ICU survivors. Six months post-discharge, CPET revealed the presence of ventilatory insufficiencies. Additionally, there was a decline in HRQL and HS, notably affected by mental health concerns and an increase in the level of dyspnea.

Moderne ECMO-Systeme sind grundsätzlich aus einer Pumpe, einem Oxygenator mit Frischgaszufuhr (Sweepgas) sowie einem zum System zu- und einem wegführenden Blutschlauchsystem aufgebaut (Abb. 1). Der Blutfluss über das System, der Frischgasfluss über den Oxygenator sowie die Größe und der Aufbau des Oxygenators bestimmen die Gasaustauschleistung des Systems. Die in modernen Systemen eingesetzten Pumpen sind heutzutage aufgrund ihres geringeren Bluttraumas häufig Rotationsblutpumpen, meist Zentrifugalpumpen und nicht wie in den Anfängen der ECMO-Therapie oder im operativen herzchirurgischen Bereich Rollerpumpen. Mit Rotations- oder Zentrifugalblutpumpen kann der Blutfluss stabil und relativ atraumatisch bis zu einer Leistung von etwa 6 l/min gehalten werden.

Extracorporeal membrane oxygenation (ECMO) is an established treatment option for severe acute respiratory failure (1). In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic with the occurrence of many severe acute respiratory distress syndrome cases, ECMO is increasingly being used worldwide depending on the available resources. Data from high-volume centers show that ECMO therapy may reduce the in-hospital mortality rate of ventilated patients who would otherwise reach more than 50–80% mortality (2, 3). When 10,021 hospitalized patients being treated in 920 different German hospitals during the first wave of the pandemic were analyzed, ECMO was reportedly used in 119 patients (1.2%) with a mortality rate of 71% (4). In contrast, a recent worldwide meta-analysis revealed a lower in-hospital mortality rate of 37% in 1,896 patients (5). The recent data of the European Extracorporeal Life Support Organization point in the same direction (6). The aim of the current research letter was to determine the in-hospital mortality rate during the first and second coronavirus disease (COVID-19) waves in Germany, a country that maintained quantitively sufficient healthcare resources during the pandemic without major restrictions. We therefore report unbiased and unselected follow-up claims data of the largest German health insurance company, including a total of 768 patients with COVID-19 who underwent ECMO admitted to hospitals between February and December 2020. The largest German health insurance provider, Allgemeine Ortskrankenkasse, provides statutory health insurance for roughly 32% of the German population. All patients included in the study completed the hospital treatment and either died or were discharged from the hospital. Baseline characteristics of the patients are depicted in Table 1. All patients included into the analysis had SARS-CoV-2 infection confirmed by PCR at a time when variants of concern were almost not present in Germany. The mean age of the patients reached 58 years (SD: 11 yr), 78% of whomwere men with a median length of hospital stay of 44 days (SD: 39 d) and a mean length of ventilation time of 31 days (SD: 24 d). Sixty-one percent of patients were tracheotomized and 60% required dialysis. Unfortunately, in-hospital mortality reached 73%. In more detail, in-hospital mortality was 56% for patients 18–49 years of age, 67% for patients 50–59 years of age, 83% for patients 60–69, and 88% for patients.69 years of age (Figure 1A, P, 0.05 for all groups compared with the youngest age group). We found no significant survival difference between men and women (Figure 1B, P=0.47). Regarding the time of initiation of ECMO therapy after onset of mechanical ventilation (either noninvasive or invasive, Figure 1C), we found the lowest mortality in those patients with early onset of ECMO therapy within the first 3 days after initiation of mechanical ventilation. However, no linear relation was observed, although all other groups demonstrated significantly higher mortality rates (Figure 1C, P, 0.05). We also had no information on the time from infection to intubation or ECMO therapy.

Extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R) provide respiratory support aimed at gaining time to allow patient’s recovery from hypoxemic and/or hypercapnic respiratory failure, respectively.1 However, in recent years, very few new oxygenators have been developed.2–4 In this report, we describe a newly designed oxygenator, a component of the MOBYBOX (Hemovent, Aachen, Germany). This oxygenator has a membrane lung surface area of 1.6 m2 consisting of typical polymethylpentene fibers. The fibers are arranged in a stacked design with perpendicular blood flow in theory characterized by a low-pressure difference across the oxygenator. The corners of the oxygenator have been sealed, and the blood flow is directed in a helical fashion into the fiber bundle to eliminate stagnant regions and optimize washout. Limited stagnation was achieved by means of computational flow dynamics (CFD) in silico. Recent long-term sheep experiments revealed a high carbon dioxide (CO2) removal capacity. 5 The aim of the current animal study was to evaluate the pressure gradient across the oxygenator and the gas exchange performance within a blood flow rate (BFR) range of 1–4 L/min, typically used in clinical practice for ECMO and ECCO2R.

Abstract Background In thoracic surgery, utilization of extracorporeal membrane oxygenation (ECMO) is mainly established for patients undergoing lung transplantation. The aim of our study was to summarize our single-center experience with intraoperative use of veno-venous- or veno-arterial-ECMO in patients undergoing complex lung surgery involving the main carina, or the left atrium or the descending aorta. Methods A total of 24 patients underwent combined complex lung, carinal, aortal, or left atrial resections. In cases of carinal resection, percutaneous veno-venous, jugular–femoral cannulation was considered suitable. For combined resection of lung and descending aorta, a percutaneous femoral veno-arterial cannulation was used. In cases of extended left atrial resection, a percutaneous jugular–femoral veno-venous-arterial cannulation was favored. Results Procedures were divided into three groups: carinal resections and reconstruction (n = 8), resections of the descending aorta and left lung (n = 7), resections of lung and left atrium (n = 9). No intraoperative complications occurred. Overall 30-day mortality was 25%. A complete resection was achieved in 18 patients. Median survival was 12 months. One- and 5-year survival were 48.1 and 22.7%, respectively. Conclusion The present study shows that intraoperative use of ECMO for extended carinal, aortic, or atrial resections is feasible with minimal intraoperative complications allowing surgeons increased operating-field safety. Perioperative mortality is high, but this is rather an attribute of local extended disease and patient comorbidities.

Background. Extracorporeal membrane oxygenation (ECMO) is rapidly becoming a mainstream technology for lung or heart/lung support. Current ECMO devices mostly consist of a power-driven centrifugal pump and a dedicated oxygenator. We studied the safety and efficacy of a novel, fully pneumatically driven ECMO device, which could be used in both venovenous or venoarterial mode in an animal model. Methods. Six healthy, awake sheep were treated with the Mobybox ECMO device (Hemovent, Aachen, Germany) over a 7-day period in a venovenous mode. Gas exchange, coagulation parameters, and safety were assessed. Results. Using a blood flow rate of 2 L/min and a low sweep gas flow rate of 0.3 L/min, the PCO2 ranged from 38 to 44 mm Hg pre oxygenator and dropped to 32 to 36 mm Hg post oxygenator, whereas the PaO2 post oxygenator increased to 600 mm Hg. Higher levels of sweep gas flow resulted in cessation of spontaneous breathing in some animals, consistent with high-efficiency carbon dioxide removal; thus, the sweep gas flow rate was maintained at a low level. Platelets dropped from 177 +/- 53/mL to 107 +/- 28/mL on day 2, while returning to baseline by day 7 (180 +/- 51/mL). Plasma-free hemoglobin remained low (2-9 mg/dL), whereas fibrinogen slightly increased, and then remained stable throughout the period. Neither the pump nor the oxygenator showed any visible clotting after 7 days. Conclusions. The pneumatically driven ECMO device provided excellent safety and physiologic efficacy in a 7-day sheep experiment without visible clotting, hemolysis, or sustained reductions in fibrinogen or platelets. (C) 2020 by The Society of Thoracic Surgeons

OBJECTIVES:Measurement tools of health-related quality of life (HRQL) that are specific for the underlying disorder are inevitably needed to assess HRQL changes following specific treatment strategies. The aim of the current study was to develop a questionnaire assessing HRQL in patients with unilateral diaphragmatic paresis.METHODS:Firstly, topics of health impairments covering physical, psychological, social and functional aspects were predefined by a physician expert panel to ensure face validity. Secondly, all predefined topics were rated by a patient group with unilateral diaphragmatic paresis (untreated: n = 11; postoperative: n = 9) using a 5-point Likert scale ranging from 'not relevant at all' (-2) to 'absolutely relevant' (+2) to guarantee content validity. Thirdly, only relevant topics (0 to +2) were used for item development, while non-relevant items (<0) were not subject for item development.RESULTS:In total, 20 patients rated a total of 43 topics covering a broad spectrum of health impairment. 21 were considered as relevant for item development. Items are answered on a 5-point Likert scale ranging from 'completely untrue' (-2) to 'always true' (+2). The Diaphragmatic Paralysis Questionnaire (DPQ) Summary Score ranges from 0 (worst HRQL) to 100 (best HRQL). Finally, the German DPQ was professionally translated and transculturally adapted into English, Italian, Dutch, French, Greek and Spanish, using translation/back-translation procedures.CONCLUSIONS:The DPQ is the first diseases-specific HRQL measure developed for patients with diaphragmatic paresis. In addition, the DPQ is available in 7 languages free of charge for non-profit purposes.CLINICAL TRIAL REGISTRATION:German clinical trials register: DRKS00017056.

Veno-venous extracorporeal carbon dioxide (CO2) removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates range in clinical practice from 200 mL/min to more than 1500 mL/min, and sweep gas flow rates range from less than 1 to more than 10 L/min. The present porcine model study was aimed at determining the impact of varying sweep gas flow rates on CO2 removal under different blood flow conditions and membrane lung surface areas.

The current study investigates the effect of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) on the evolution of respiratory acidosis depending on endotracheal tube (ET) sizes. In addition, the impact of increasing tidal volumes during the intervention was investigated. Two groups of ICU-patients undergoing bronchoscopy-guided PDT with varying tidal volumes and tube sizes were consecutively investigated: 6 ml/kg (N = 29, mean age 57.4 ± 14.5 years) and 12 ml/kg predicted body weight (N = 34, mean age 59.5 ± 12.8 years). The mean intervention time during all procedures was 10 ± 3 min. The combination of low tidal volumes and ETs of 7.5 mm internal diameter resulted in the most profound increase in PaCO2 (32.2 ± 11.6 mmHg) and decrease in pH-value (− 0.18 ± 0.05). In contrast, the combination of high tidal volumes and ETs of 8.5 mm internal diameter resulted in the least profound increase in PaCO2 (8.8 ± 9.0 mmHg) and decrease of pH (− 0.05 ± 0.04). The intervention-related increase in PaCO2 was significantly lower when using higher tidal volumes for larger ET: internal diameter 7.5, 8.0 and 8.5: P > 0.05, =0.006 and = 0.002, respectively. Transcutaneous PCO2 monitoring revealed steadily worsening hypercapnia during the intervention with a high correlation of 0.87 and a low bias of 0.7 ± 9.4 mmHg according to the Bland-Altman analysis when compared to PaCO2 measurements. Profound respiratory acidosis following bronchoscopy-guided PDT evolves in a rapid and dynamic process. Increasing the tidal volume from 6 to 12 ml/kg PBW was capable of attenuating the evolution of respiratory acidosis, but this effect was only evident when using larger ETs. DRKS00011004 . Registered 20th September 2016.

Veno-venous extracorporeal CO2 removal (vv-ECCO2R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD. A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA. Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO2R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO2R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO2R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 μV vs. 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO2 and pH values stable. Edi was the best predictor for vv-ECCO2R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively. This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO2R and NIV-NAVA. The Edi during vv-ECCO2R weaning was found to be the best predictor of tolerance to removing vv-ECCO2R.

Zusammenfassung Hintergrund Die außerklinische Beatmung erfährt in Deutschland eine rasante Entwicklung. Patienten mit chronischer respiratorischer Insuffizienz werden in deutlich zunehmender Zahl nichtinvasiv oder invasiv in einem häuslichen Setting beatmet. Diese Patienten müssen im Rahmen von Kontrolluntersuchungen oder Akut-Problemen immer wieder stationär behandelt werden. Die für die Steuerung des Gesundheitswesens wichtige Entwicklung der stationären Behandlungsfälle ist bislang ebenso unbekannt wie die Morbidität und Krankenhaussterblichkeit der häuslich beatmeten Patienten. Methode Von 2006 – 2016 wurden alle stationären Aufnahmen analysiert, bei denen eine Langzeit-Abhängigkeit vom Respirator (mindestens 3 Monate) bestand (Daten des Deutschen Statistischen Bundesamtes). Ergebnisse Es zeigte sich eine exponentielle Zunahme von stationären Behandlungsfällen, wobei 2006 noch 24 845 Patienten stationär behandelt werden mussten, im Jahr 2016 hingegen 86 117 Patienten. Im gleichen Zeitraum zeigte sich eine Abnahme der Krankenhaussterblichkeit von 13,2 % (2006) auf 5,7 % (2016). Im Jahr 2016 wurden zudem 47 % der Patienten auf einer Intensiv-, Weaning- oder Überwachungsstation behandelt. Es bestand eine Vielzahl von internistischen und neurologischen Komorbiditäten, welche in Verbindung mit der chronischen respiratorischen Insuffizienz die große Patientenkohorte als schwer krankes Patientenkollektiv charakterisierte. Führende Diagnosen waren die COPD mit 58 % und eine Vielzahl kardiologischer Diagnosen. Auffällig viele Patienten (24 %) zeigten eine Einschränkung der Nierenfunktion bis hin zur Dialysepflichtigkeit. Diskussion Die rasante Zunahme der außerklinischen Beatmung hat wesentlichen Einfluss auf die Entwicklung der Krankenhauslandschaft in Deutschland. Der exponentielle Anstieg der sehr pflegeintensiven Patienten stellt das Gesundheitssystem vor extreme Herausforderungen und erfordert eine gesundheitspolitische Diskussion über die Grenzen des Systems.

Electrical impedance tomography (EIT) has been used to guide mechanical ventilation in ICU patients with lung collapse. Its use in patients with obstructive pulmonary diseases has been rare since obstructions could not be monitored on a regional level at the bedside. The current study therefore determines breath-by-breath regional expiratory time constants in intubated patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS).

Veno-venous extracorporeal CO2 removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m2. The present study in an animal model with similar CO2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO2R.

A clinical case of fatal HBoV infection in an adult cystic-fibrosis patient awaiting lung transplantation is reported. The case is important as the genetic background of the underlying disease is congruent with the background of the sole permissive permanent cell culture CuFi-8 which originates also from a CF patient donor.

The evolution of the epidemiology and mortality of extracorporeal membrane oxygenation (ECMO) remains unclear. The present study investigates the evolving epidemiology and mortality of various ECMO techniques in Germany over time, used for both severe respiratory and cardiac failure.