Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP)-A single center, open-label, three-arm, randomized, controlled intervention pilot trial.

BACKGROUND: To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute-on-chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT). METHODS: A prospective, randomized, single-center, open-label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT). In the hemoadsorption group, the CytoSorb adsorber was incorporated into the CRRT system, replaced after 12, 24, and 48 h, and removed after 72 h. The primary endpoint was the serum bilirubin level after 72 h. RESULTS: CYTOHEP was terminated early due to difficulties in recruiting patients and ethical concerns. Three of 9 patients (33%) were treated in each group. Comparing the three groups, mean bilirubin levels after 72 h were lower by -8.0 mg/dL in the "CRRT with hemoadsorption" group compared to "CRRT without hemoadsorption" (95% CI, -21.3 to 5.3 mg/dL; p = 0.17). The corresponding mean difference between "CRRT without hemoadsorption" and "no CRRT" was -1.4 mg/dL (95% CI, -14.2 to 11.5 mg/dL; p = 0.78). Comparing "CRRT with hemoadsorption" and "no CRRT," it was -9.4 mg/dL (95% CI, -20.8 to 2.1 mg/dL; p = 0.0854). Only 1/9 patients (11%, "no CRRT" group) survived day 30 after study inclusion but died on day 89. IL-6, liver function parameters, and clinical scores were similar between the study groups. CONCLUSIONS: CYTOHEP failed to demonstrate that extracorporeal hemoadsorption combined with CRRT can reduce serum bilirubin in ACLF patients with acute kidney failure.

Secondary Sclerosing Cholangitis Following Coronavirus Disease 2019 (COVID-19): A Multicenter Retrospective Study.

BACKGROUND: Secondary sclerosing cholangitis (SSC) is a rare disease with poor prognosis. Cases of SSC have been reported following coronavirus disease 2019 (COVID-SSC). The aim of this study was to compare COVID-SSC to SSC in critically ill patients (SSC-CIP) and to assess factors influencing transplant-free survival. METHODS: In this retrospective, multicenter study involving 127 patients with SSC from 9 tertiary care centers in Germany, COVID-SSC was compared to SSC-CIP and logistic regression analyses were performed investigating factors impacting transplant-free survival. RESULTS: Twenty-four patients had COVID-SSC, 77 patients SSC-CIP, and 26 patients other forms of SSC. COVID-SSC developed after a median of 91 days following COVID-19 diagnosis. All patients had received extensive intensive care treatment (median days of mechanical ventilation, 48). Patients with COVID-SSC and SSC-CIP were comparable in most of the clinical parameters and transplant-free survival was not different from other forms of SSC (P = .443, log-rank test). In the overall cohort, the use of ursodeoxycholic acid (UDCA) (odds ratio [OR], 0.36 [95% confidence interval {CI}, .16-.80], P = .013; log-rank P < .001) and high serum albumin levels (OR, 0.40 [95% CI, .17-.96], P = .040) were independently associated with an increased transplant-free survival, while the presence of liver cirrhosis (OR, 2.52 [95% CI, 1.01-6.25], P = .047) was associated with worse outcome. Multidrug-resistant organism (MDRO) colonization or infection did not impact patients' survival. CONCLUSIONS: COVID-SSC and CIP-SSC share the same clinical phenotype, course of the disease, and risk factors for its development. UDCA may be a promising therapeutic option in SSC, though future prospective trials are needed to confirm our findings.

Timing of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess the association of timing to prone positioning (PP) during venovenous extracorporeal membrane oxygenation (V-V ECMO) with the probability of being discharged alive from the ICU at 90 days (primary endpoint) and the improvement of the respiratory system compliance (Cpl,rs). DESIGN: Pooled individual data analysis from five original observational cohort studies. SETTING: European extracorporeal membrane oxygenation (ECMO) centers. PATIENTS: Acute respiratory distress syndrome (ARDS) patients who underwent PP during ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Time to PP during V-V ECMO was explored both as a continuous and a categorical variable with Cox proportional hazard models. Three hundred patients were included in the analysis. The longer the time to PP during V-V ECMO, the lower the adjusted probability of alive ICU discharge (adjusted hazard ratio [HR] 0.90 for each day increase; 95% CI, 0.87-0.93). Two hundred twenty-three and 77 patients were included in the early PP (≤ 5 d) and late PP (> 5 d) groups, respectively. The cumulative 90-day probability of being discharged alive from the ICU was 61% in the early PP group vs 36% in the late PP group (log-rank test, p <0.001). This benefit was maintained after adjustment for confounders (adjusted HR, 2.52; 95% CI, 1.66-3.81; p <0.001). In the early PP group, PP was associated with a significant improvement of Cpl,rs (4 ± 9 mL/cm H2O vs 0 ± 12 in the late PP group, p=0.038). CONCLUSIONS: In a large cohort of ARDS patients on ECMO, early PP during ECMO was associated with a higher probability of being discharged alive from the ICU at 90 days and a greater improvement of Cpl,rs.

The serum proteome of VA-ECMO patients changes over time and allows differentiation of survivors and non-survivors: an observational study.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is applied in patients with refractory hemodynamic failure. Exposure of blood components to high shear stress and the large extracorporeal surfaces in the ECMO circuit trigger a complex inflammatory response syndrome and coagulopathy which are believed to worsen the already poor prognosis of these patients. Mass spectrometry-based proteomics allow a detailed characterization of the serum proteome as it provides the identity and concentration of large numbers of individual proteins at the same time. In this study, we aimed to characterize the serum proteome of patients receiving VA-ECMO. METHODS: Serum samples were collected on day 1 and day 3 after initiation of VA-ECMO. Samples underwent immunoaffinity based depletion for the 14 most abundant serum proteins, in-solution digestion and PreOmics clean-up. A spectral library was built with multiple measurements of a master-mix sample using variable mass windows. Individual samples were measured in data independent acquisition (DIA) mode. Raw files were analyzed by DIA-neural network. Unique proteins were log transformed and quantile normalized. Differential expression analysis was conducted with the LIMMA-R package. ROAST was applied to generate gene ontology enrichment analyses. RESULTS: Fourteen VA-ECMO patients and six healthy controls were recruited. Seven patients survived. Three hundred and fifty-one unique proteins were identified. One hundred and thirty-seven proteins were differentially expressed between VA-ECMO patients and controls. One hundred and forty-five proteins were differentially expressed on day 3 compared to day 1. Many of the differentially expressed proteins were involved in coagulation and the inflammatory response. The serum proteomes of survivors and non-survivors on day 3 differed from each other according to partial least-squares discriminant analysis (PLS-DA) and 48 proteins were differentially expressed. Many of these proteins have also been ascribed to processes in coagulation and inflammation (e.g., Factor IX, Protein-C, Kallikrein, SERPINA10, SEMA4B, Complement C3, Complement Factor D and MASP-1). CONCLUSION: The serum proteome of VA-ECMO patients displays major changes compared to controls and changes from day 1 until day 3. Many changes in the serum proteome are related to inflammation and coagulation. Survivors and non-survivors can be differentiated according to their serum proteomes using PLS-DA analysis on day 3. Our results build the basis for future studies using mass-spectrometry based serum proteomics as a tool to identify novel prognostic biomarkers. TRIAL REGISTRATION: DRKS00011106.

The effect of recombinant versus plasma-derived von Willebrand factor on prolonged PFA closure times in ECMO patients with acquired von Willebrand syndrome - an observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is applied in patients with respiratory or cardiopulmonary failure, but bleeding is a frequent complication contributing to the high mortality rates in this patient collective. A major factor predisposing patients to bleeding events is an acquired von Willebrand syndrome (aVWS). So far, specific treatment options for this phenomenon are lacking. In hereditary von Willebrand disease (VWD), treatment with recombinant or plasma-derived von Willebrand factor (rVWF or pVWF) is common practice. Closure time measured by the Platelet Function Analyser-200 (PFA-200) is an established assay to detect defects in primary hemostasis and the method is useful to monitor the effect of hemostatic therapy. The aim of this study was to assess the effect of recombinant (rVWF) vs. plasma-derived von Willebrand factor (pVWF) on closure times measured by PFA in blood obtained from ECMO patients with aVWS. METHODS: Blood was sampled from thirteen patients receiving extracorporeal membrane oxygenation and three patients with hereditary VWD. Diagnosis of aVWS was made by conventional coagulation parameters and by multimeric structure analysis. PFA analysis of blood spiked with rVWF or pVWF was performed. RESULTS: Thirteen patients receiving ECMO were recruited. Ten patients survived and three patients suffered major bleeding complications. PFA closure times in ECMO patients with aVWS spiked with rVWF were significantly shorter at all concentrations than with pVWF (e.g., rVWF vs. pVWF: 1 U/ml: 150.4 ± 21.7 s vs. 263.8 ± 11.7 s; 4 U/ml: 97.8 ± 9.8 s vs. 195.8 ± 15.4 s, p<0.001). PFA closure times were also significantly shorter in three patients with hereditary VWD treated with rVWF compared to pVWF (e.g., 1 U/ml rVWF vs. pVWF: 73.7±1.33 s vs. 231.3±43.4 s, p<0.01) CONCLUSION: In summary, this study shows that rVWF compared to pVWF more effectively reduced PFA closures times in blood samples of ECMO patients with aVWS. Higher doses of VWF are needed to normalize PFA closure time in blood samples of patients with ECMO-induced aVWS compared to hereditary VWD. These data support the use of PFA-200 to monitor hemostatic effects in a future clinical trial involving ECMO patients with aVWS.

Dual lumen cannulation and mobilization of patients with venovenous extracorporeal membrane oxygenation.

BACKGROUND: Mobilization is important in longer courses in intensive care unit (ICU), typical for patients requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). For patients supported with ECMO, especially out-of-bed mobilizations improve outcome. We hypothesized that utilization of a dual lumen cannula (DLC) for V-V ECMO would facilitate out-of-bed mobilization compared to single lumen cannulas (SLC). METHODS: Retrospective single center registry study including all V-V ECMO patients cannulated between 10/2010 and 05/2021 for respiratory failure. RESULTS: The registry included 355 V-V ECMO patients (median age 55.6 years, 31.8% female, 27.3% with preexisting pulmonary disease), 289/355 (81.4%) primary cannulated with DLC, and 66/355 (18.6%) using SLC. Both groups had similar pre-ECMO characteristics. The runtime of the first ECMO cannula was significantly longer in DLC compared to SLC (169 vs. 115 h, p = 0.015). The frequency of prone positioning during V-V ECMO was similar in both groups (38.4 vs. 34.8%, p = 0.673). There was no difference in in-bed mobilization (41.2 vs. 36.4%, for DLC and SLC, respectively, p = 0.491). Patients with DLC were more often mobilized out-of-bed (25.6 vs. 12.1%, OR 2.495 [95% CI 1.150 to 5.268], for DLC and SLC, respectively, p = 0.023). Hospital survival was similar in both groups (46.4 vs. 39.4%, for DLC and SLC, respectively, p = 0.339). CONCLUSION: Patients cannulated with a dual lumen cannula for V-V ECMO support were significantly more often mobilized out-of-bed. Since mobilization is important in prolonged ICU courses typical for ECMO patients, this might be an important benefit. Other benefits of DLC were the longer runtime of the initial cannula set and fewer suction events.

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis.

BACKGROUND: Prone positioning (PP) reduces mortality of patients with acute respiratory distress syndrome (ARDS). The potential benefit of prone positioning maneuvers during venovenous extracorporeal membrane oxygenation (ECMO) is unknown. The aim of this study was to evaluate the association between the use of prone positioning during extracorporeal support and ICU mortality in a pooled population of patients from previous European cohort studies. METHODS: We performed a pooled individual patient data analysis of European cohort studies which compared patients treated with prone positioning during ECMO (Prone group) to "conventional" ECMO management (Supine group) in patients with severe ARDS. RESULTS: 889 patients from five studies were included. Unadjusted ICU mortality was 52.8% in the Supine Group and 40.8% in the Prone group. At a Cox multiple regression analysis PP during ECMO was not significantly associated with a reduction of ICU mortality (HR 0.67 95% CI: 0.42-1.06). Propensity score matching identified 227 patients in each group. ICU mortality of the matched samples was 48.0% and 39.6% for patients in the Supine and Prone group, respectively (p = 0.072). CONCLUSIONS: In a large population of ARDS patients receiving venovenous extracorporeal support, the use of prone positioning during ECMO was not significantly associated with reduced ICU mortality. The impact of this procedure will have to be definitively assessed by prospective randomized controlled trials.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Extracorporeal membrane oxygenation during the first three waves of the coronavirus disease 2019 pandemic: A retrospective single-center registry study.

BACKGROUND: Despite increasing knowledge about the optimal treatment for patients with severe COVID-19, data from different cohorts suggested that survival of patients treated with ECMO seemed to decline over the course of the pandemic. METHODS: In this non-interventional retrospective single-center registry study we analyzed all consecutive patients tested positive for SARS-CoV-2 infection and supported with VV ECMO in our center during the first three waves of the pandemic. From March 2020 through June 2021, 59 patients have been included. RESULTS: Overall 90-day survival was 32%. Besides changes in drug treatment for COVID-19 and a lower PaO2 /FiO2 ratio before ECMO initiation during the third wave, all other patient baseline characteristics were similar during the three waves. Survival rate was highest during the first wave and lowest during the third wave, yet this difference was not statistically significant. CONCLUSIONS: VV ECMO has shown to be a feasible and safe support option for patients with severe respiratory failure due to COVID-19. The results from this single-center study confirm findings from other cohorts showing declining survival rates of patients treated with VV ECMO during the COVID-19 pandemic, however, the specific reasons for this finding remain unclear.

Annual hospital procedural volume and outcome in extracorporeal membrane oxygenation for respiratory failure.

BACKGROUND: The hospital mortality of patients suffering from pulmonary failure requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) or extracorporeal carbon dioxide removal (ECCO2 R) is high. It is unclear whether outcome correlates with a hospital's annual procedural volume. METHODS: Data on all V-V ECMO and ECCO2 R cases treated from 2007 to 2019 were retrieved from the German Institute for Medical Documentation and Information. Comorbidities and outcomes were assessed by DRG, OPS, and ICD codes. The study population was divided into 5 groups depending on annual hospital V-V ECMO and ECCO2 R volumes (<10 cases; 10-19 cases; 20-29 cases; 30-49 cases; ≥50 cases). Primary outcome was hospital mortality. RESULTS: A total of 25 096 V-V ECMO and 3607 ECCO2 R cases were analyzed. V-V ECMO hospitals increased from 89 in 2007 to 214 in 2019. Hospitals handling <10 cases annually increased especially (64 in 2007 to 149 in 2019). V-V ECMO cases rose from 807 in 2007 to 2597 in 2019. Over 50% of cases were treated in hospitals handling ≥30 cases annually. Hospital mortality was independent of the annual hospital procedural volume (55.3%; 61.3%; 59.8%; 60.2%; 56.3%, respectively, p = 0.287). We detected no differences when comparing hospitals handling <30 cases to those with ≥30 annually (p = 0.659). The numbers of ECCO2 R hospitals and cases has dropped since 2011 (287 in 2007 to 48 in 2019). No correlation between annual hospital procedural volume and hospital mortality was identified (p = 0.914). CONCLUSION: The number of hospitals treating patients requiring V-V ECMO and V-V ECMO cases rose from 2007 to 2019, while ECCO2 R hospitals and their case numbers decreased. We detected no correlation between annual hospital V-V ECMO or ECCO2 R volume and hospital mortality.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Harmonizing Heterogeneous Endpoints in Coronavirus Disease 2019 Trials Without Loss of Information.

OBJECTIVES: Many trials investigate potential effects of treatments for coronavirus disease 2019. To provide sufficient information for all involveddecision-makers (clinicians, public health authorities, and drug regulatory agencies), a multiplicity of endpoints must be considered. The objectives are to provide hands-on statistical guidelines for harmonizing heterogeneous endpoints in coronavirus disease 2019 clinical trials. DESIGN: Randomized controlled trials for patients infected with coronavirus disease 2019. SETTING: General methods that apply to any randomized controlled trial for patients infected with coronavirus disease 2019. PATIENTS: Coronavirus disease 2019 positive individuals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We develop a multistate model that is based on hospitalization, mechanical ventilation, death, and discharge. These events are both categories of the ordinal endpoint recommended by the World Health Organization and also within the core outcome set of the Core Outcome Measures in Effectiveness Trials initiative for coronavirus disease 2019 trials. To support our choice of states in the multistate model, we also perform a brief review of registered coronavirus disease 2019 clinical trials. Based on the multistate model, we give recommendation for compact, informative illustration of time-dynamic treatment effects and explorative statistical analysis. A majority of coronavirus disease 2019 clinical trials collect information on mechanical ventilation, hospitalization, and death. Using reconstructed and real data of coronavirus disease 2019 trials, we show how a stacked probability plot provides a detailed understanding of treatment effects on the patients' course of hospital stay. It contributes to harmonizing multiple endpoints and differing lengths of follow-up both within and between trials. CONCLUSIONS: All ongoing clinical trials should include a stacked probability plot in their statistical analysis plan as descriptive analysis. While primary analysis should be on an early endpoint with appropriate capability to be a surrogate (parameter), our multistate model provides additional detailed descriptive information and links results within and between coronavirus disease 2019 trials.

Incidence and predictors of delirium on the intensive care unit after acute myocardial infarction, insight from a retrospective registry.

OBJECTIVES: This study aimed to identify the incidence and potential risk factors for delirium after myocardial infarction (MI). BACKGROUND: Delirium is a common complication on intensive care units. Data on incidence and especially on predictors of delirium in patients after acute MI are rare. METHODS: In this retrospective study, all patients hospitalized for MI treated with coronary angiography in an university hospital in 2018 were included and analyzed. Onset of delirium within the first 5 days after MI was attributed to the MI and was defined by a Nursing Delirium screening scale (NuDesc) ≥2. This score is taken as part of daily care in every patient on intensive care unit three times a day by especially trained nurses. RESULTS: A total of 624 patients with MI (age 68.5 ± 13.2 years, ST-elevation MI 41.6%, hospital mortality 3.2%) were included in the study. Delirium was detected in 10.9% of all patients. In the subgroup of patients with a stay on the intensive care unit (ICU) for more than 24 hr (n = 229), delirium was detected in 29.7%. Hospital and ICU stay were significantly longer in patients with delirium (p < .001). Delirium was an independent predictor of prolonged ICU-stay. Independent predictors of delirium were age, dementia, alcohol abuse, cardiac arrest, hypotension, and leucocytosis. Infarct size or presentation with ST-elevation were not associated with incidence of delirium. CONCLUSION: Development of delirium is frequent after acute MI and prolongs hospitalization. Incidence of delirium is associated with clinical instability, preexisting comorbidity, and age rather than MI type or size.

Long-term survival and health-related quality of life in patients with severe acute respiratory distress syndrome and veno-venous extracorporeal membrane oxygenation support.

BACKGROUND: There is limited information about the long-term outcome of patients suffering from acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Most studies focused on short- to mid-term follow-up. We aimed to investigate long-term survival and health-related quality of life (HRQL) in these patients. METHODS: We report retrospective data from a single-centre registry of patients with severe ARDS treated with VV ECMO at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 10/2010 and 06/2019. Follow-up data of all patients that survived the index hospitalisation were collected by telephone interviews from 02/2020 till 09/2020. Long-term survival, HRQL (Short-Form Health Survey-36 (SF-36), St. Georges Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS)) and the return to work rate were documented. RESULTS: In total, 289 patients were treated with VV ECMO during the study period (median age 55 years, 67% males, hospital survival 45%). After a median duration of 3.9 years, follow-up assessment was complete in 94 of 129 hospital survivors (73%). Fifty-three patients completed the HRQL assessment. Hospital survivors showed a high 6- and 12-month survival rate (89% and 85%, respectively). Estimated survival rate of those discharged alive from ICU was 68.5% (95%-CI 56.9-80.1%) after 9.7 years. These patients reported high levels of HRQL (median SF-36 total score 73) and only few pulmonary (median SGRQ total score 19) and mental limitations (median HAD-D score 2 and HAD-A score 3). In total, 80% of the patients were able to resume employment. CONCLUSION: This analysis of VV ECMO patients showed favourable long-term survival and high levels of HRQL suggesting promising prospects for VV ECMO survivors.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Medical history of coronary artery disease and time to electrocardiogram in the emergency department: a real-life, single-center, retrospective analysis.

BACKGROUND: Timely acquisition of 12-lead Electrocardiogram (ECG) in the emergency department (ED) is crucial and recommended by current guidelines. OBJECTIVES: To evaluate the association of medical history of coronary artery disease (hCAD) on door-to-ECG time in the ED. METHODS: In this single center, retrospective cohort study, patients admitted to ED for cardiac evaluation were grouped according to hCAD and no hCAD. The primary outcome was door-to-ECG time. A multivariate analysis adjusted for the cofounders sex, age, type of referral and shift was performed to evaluate the association of hCAD with door-to-ECG time. RESULTS: 1101 patients were included in this analysis. 362 patients (33%) had hCAD. Patients with hCAD had shorter door-to-ECG time (20 min. [Inter Quartile Range [IQR] 13-30] vs. 22 min. [IQR 14-37]; p < 0.001) when compared to patients with no hCAD. In a multivariable regression analysis hCAD was significantly associated with a shorter door-to-ECG time (- 3 min [p = 0.007; 95% confidence Interval [CI] - 5.16 to - 0.84 min]). CONCLUSION: In this single center registry, hCAD was associated with shorter door-to-ECG time. In patients presenting in ED for cardiac evaluation, timely ECG diagnostic should be facilitated irrespective of hCAD.

Incidence of Barotrauma in Patients With COVID-19 Pneumonia During Prolonged Invasive Mechanical Ventilation - A Case-Control Study.

BACKGROUND: SARS-CoV2 can cause pulmonary failure requiring prolonged invasive mechanical ventilation (MV). Lung protective ventilation strategies are recommended in order to minimize ventilator induced lung injury. Whether patients with COVID-19 have the same risk for complications including barotrauma is still unknown. Therefore, we investigated barotrauma in patients with COVID-19 pneumonia requiring prolonged MV. METHODS: All patients meeting diagnosis criteria for ARDS according to the Berlin Definition, with PCR positive SARS-CoV2 infection and prolonged mechanical ventilation, defined as ≥2 days, treated at our ARDS referral center between March and April 2020 were included in a retrospective registry analysis. Complications were detected by manual review of all patient data including respiratory data, imaging studies, and patient files. RESULTS: A total of 20 patients with severe COVID-19 pulmonary failure (Overall characteristics: median age: 61 years, female gender 6, median duration of MV 22 days) were analyzed. Eight patients (40%) developed severe barotrauma during MV (after median 18 days, range: 1-32) including pneumothorax (5/20), pneumomediastinum (5/20), pneumopericard (1/20), and extended subcutaneous emphysema (5/20). Median respirator settings 24 hours before barotrauma were: Peak inspiratory pressure (Ppeak) 29 cm H2O (range: 27-35), positive end-expiratory pressure (PEEP) 14 cm H2O (range: 5-24), tidal volume (VT) 5.4ml/kg predicted body weight (range 0.4-8.6), plateau pressure (Pplateau) 27 cm H2O (range: 19-30). Mechanical ventilation was significantly more invasive on several occasions in patients without barotrauma. CONCLUSION: Barotrauma in COVID-19 induced respiratory failure requiring mechanical ventilation was found in 40% of patients included in this registry. Our data suggest that barotrauma in COVID-19 may occur even when following recommendations for lung protective MV.

Thrombotic circuit complications during venovenous extracorporeal membrane oxygenation in COVID-19.

The novel coronavirus SARS-CoV-2 and the resulting disease COVID-19 causes pulmonary failure including severe courses requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). Coagulopathy is a known complication of COVID-19 leading to thrombotic events including pulmonary embolism. It is unclear if the coagulopathy also increases thrombotic circuit complications of the ECMO. Aim of the present study therefor was to investigate the rate of V-V ECMO complications in COVID-19. We conducted a retrospective registry study including all patients on V-V ECMO treated at our centre between 01/2018 and 04/2020. COVID-19 cases were compared non- COVID-19 cases. All circuit related complications resulting in partial or complete exchange of the extracorporeal system were registered. In total, 66 patients were analysed of which 11 (16.7%) were SARS-CoV-2 positive. The two groups did not differ in clinical parameters including age (COVID-19 59.4 vs. non-COVID-19 58.1 years), gender (36.4% vs. 40%), BMI (27.8 vs. 24.2) and severity of illness as quantified by the RESP Score (1pt. vs 1pt.). 28 days survival was similar in both groups (72.7% vs. 58.2%). While anticoagulation was similar in both groups (p = 0.09), centrifugal pump head thrombosis was more frequent in COVID-19 (9/11 versus 16/55 p < 0.01). Neither the time to first exchange (p = 0.61) nor blood flow at exchange (p = 0.68) did differ in both groups. D-dimer levels prior to the thrombotic events were significantly higher in COVID-19 (mean 15.48 vs 26.59, p = 0.01). The SARS-CoV-2 induced infection is associated with higher rates of thrombotic events of the extracorporeal system during V-V ECMO therapy.

Combining lung ultrasound and Wells score for diagnosing pulmonary embolism in critically ill COVID-19 patients.

Subpleural consolidations have been found in lung ultrasound in patients with COVID-19, possibly deriving from pulmonary embolism (PE). The diagnostic utility of impact of lung ultrasound in critical-ill patients with COVID-19 for PE diagnostics however is unclear. We retrospectively evaluated all SARS-CoV2-associated ARDS patients admitted to our ICU between March 8th and May 31th 2020. They were enrolled in this study, when a lung ultrasound and a computed tomography pulmonary angiography (CTPA) were documented. In addition, wells score was calculated to estimate the probability of PE. The CTPA was used as the gold standard for the detection of PE. Twenty out of 25 patients met the inclusion criteria. In 12/20 patients (60%) (sub-) segmental PE were detected by CT-angiography. Lung ultrasound found subpleural consolidations in 90% of patients. PE-typical large supleural consolidations with a size ≥ 1 cm were detectable in 65% of patients and were significant more frequent in patients with PE compared to those without (p = 0.035). Large consolidations predicted PE with a sensitivity of 77% and a specificity of 71%. The Wells score was significantly higher in patients with PE compared to those without (2.7 ± 0.8 and 1.7 ± 0.5, respectively, p = 0.042) and predicted PE with an AUC of 0.81. When combining the two modalities, comparing patients with considered/probable PE using LUS plus a Wells score ≥ 2 to patients with possible/unlikely PE in LUS plus a Wells score < 2, PE could be predicted with a sensitivity of 100% and a specificity of 80%. Large consolidations detected in lung ultrasound were found frequently in COVID-19 ARDS patients with pulmonary embolism. In combination with a Wells score > 2, this might indicate a high-risk for PE in COVID-19.

Mobile ECMO retrieval of patients during the COVID-19 pandemic.

ECMO support is particularly resource-intensive and should be provided in highly specialized centers. Occasionally, ECMO needs to be initiated in non-ECMO centers by mobile ECMO retrieval teams. Subsequently, patients must be transferred on ECMO to the ECMO center. We report single-center data from out-of-center initiations of ECMO during the COVID-19 pandemic. From March 2020 through February 2021, nine patients were connected to ECMO before transfer to our center. Median travel distance (IQR) from the referring hospital to our center was 66 km (20-92), median land travel time (IQR) was 51 minutes (26-92). Personal protective equipment was available for all team members and used throughout the missions. No infections of team members with SARS-CoV-2 occurred. Three patients survived until hospital discharge. Median duration of ECMO (IQR) was 18 days (2-78) in survivors and 19 days (9-42) in non-survivors, respectively. Out-of-center initiation of ECMO during the COVID-19 pandemic was feasible and safe for patients and staff.