Background: Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support. Methods: We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. Patients were allocated to the PP group if PP was performed during VV ECMO treatment or the supine positioning group. VV ECMO weaning success and hospital survival were analysed before and after propensity score matching. Results: A total of 158 patients could be analysed, and 38 patients (24.1%) received PP. There were no significant differences in VV ECMO weaning rate (47.4% vs. 46.7%, p = 0.94) and hospital survival (36.8% vs. 36.7%, p = 0.98) between the prone and supine groups, respectively. The analysis of 38 propensity score matched pairs also showed no difference in hospital survival (36.8% vs. 36.8%, p = 1.0) or VV ECMO weaning rate (47.4% vs. 44.7%, p = 0.82). Hospital survival was superior in the subgroup of patients treated with early PP (cutoff < 17 h via Youden’s Index) as compared to late or no PP (81.8% vs. 33.3%, p = 0.02). Conclusion: In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. However, early initiation of prone positioning was linked to a significant reduction of hospital mortality.

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.

Objectives: SARS-CoV2 infection leads to a concomitant pulmonary inflammation. This inflammation is supposed to be the main driver in the pathogenesis of lung failure (Acute Respiratory Distress Syndrome) in COVID-19. Objective of this study is to evaluate the efficacy and safety of a single dose treatment with Tocilizumab in patients with severe COVID-19. We hypothesize that Tocilizumab slows down the progression of SARS-CoV-2 induced pneumonia and inflammation. We expect an improvement in pulmonary function compared to placebo-treated patients. Desirable outcomes would be that tocilizumab reduces the number of days that patients are dependent on mechanical ventilation and reduces the invasiveness of breathing assistance. Furthermore, this treatment might result in fewer admissions to intensive care units. Next to these efficacy parameters, safety of a therapy with Tocilizumab in COVID-19 patients has to be monitored closely, since immunosuppression could lead to an increased rate of bacterial infections, which could negatively influence the patient’s outcome. Trial design: Multicentre, prospective, 2-arm randomised (ratio 1:1), double blind, placebo-controlled trial with parallel group design. Participants: Inclusion criteria Proof of SARS-CoV2 (Symptoms and positive polymerase chain reaction (PCR)) Severe respiratory failure: Ambient air SpO₂ ≤ 92% or Need of ≥ 6l O2/min or NIV (non-invasive ventilation) or IMV (invasive mechanical ventilation) Age ≥ 18 years Exclusion criteria Non-invasive or invasive mechanical ventilation ≥ 48 hours Pregnancy or breast feeding Liver injury or failure (AST/ALT ≥ 5x ULN) Leukocytes < 2 × 10³/μl Thrombocytes < 50 × 10³/μl Severe bacterial infection (PCT > 3ng/ml) Acute or chronic diverticulitis Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine) Known active or chronic tuberculosis Known active or chronic viral hepatitis Known allergic reactions to tocilizumab or its ingredients Life expectation of less than 1 year (independent of COVID-19) Participation in any other interventional clinical trial within the last 30 days before the start of this trial Simultaneous participation in other interventional trials (except for participation in COVID-19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception. The data collection of the primary follow up (28 days after randomisation) takes place during the hospital stay. Subsequently, a telephone interview on the quality of life is conducted after 6 and 12 months. Participants will be recruited from inpatients at ten medical centres in Germany. Intervention and comparator: Intervention arm: Application of 8mg/kg body weight (BW) Tocilizumab i.v. once immediately after randomisation (12 mg/kg for patients with <30kg BW; total dose should not exceed 800 mg) AND conventional treatment. Control arm: Placebo (NaCl) i.v. once immediately after randomisation AND conventional treatment. Main outcomes: Primary endpoint is the number of ventilator free days (d) (VFD) in the first 28 days after randomisation. Non-invasive ventilation (NIV), Invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO) are defined as ventilator days. VFD’s are counted as zero if the patient dies within the first 28 days. Randomisation: The randomisation code will be generated by the CTU (Clinical Trials Unit, ZKS Freiburg) using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. Randomisation will be stratified by centre and will be performed in blocks of variable length in a ratio of 1:1 within each centre. The block lengths will be documented separately and will not be disclosed to the investigators. The randomisation code will be produced by validated programs based on the Statistical Analysis System (SAS). Blinding (masking): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. Numbers to be randomised (sample size): 100 participants will be randomised to each group (thus 200 participants in total). Trial Status: Protocol Version: V 1.2, 16.04.2020. Recruitment began 27th April 2020 and is anticipated to be completed by December 2020. Trial registration: The trial was registered before trial start in trial registries (EudraCT: No. 2020-001408-41, registered 21st April 2020, and DRKS: No. DRKS00021238, registered 22nd April 2020). Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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. Graphical

Veno‐venous extracorporeal membrane oxygenation (V‐V ECMO) is used to sustain blood oxygenation and decarboxylation in severe acute respiratory distress syndrome (ARDS). It is under debate if V‐V ECMO is as appropriate for coronavirus disease 2019 (Covid‐19) ARDS as it is for influenza. In this retrospective study, we analyzed all patients with confirmed SARS‐CoV‐2 or influenza A/B infection, ARDS and V‐V ECMO, treated at our medical intensive care unit (ICU) between October 2010 and June 2020. Baseline and procedural characteristics as well as survival 30 days after ECMO cannulation were analyzed. A total of 62 V‐V ECMO patients were included (15 with Covid‐19 and 47 with influenza). Both groups had similar baseline characteristics at cannulation. Thirty days after ECMO cannulation, 13.3% of all patients with Covid‐19 were discharged alive from our ICU compared to 44.7% with influenza (P = .03). Patients with Covid‐19 had fewer ECMO‐free days (0 (0‐9.7) days vs. 13.2 (0‐22.1) days; P = .05). Cumulative incidences of 30‐day‐survival showed no significant differences (48.6% in Covid‐19 patients, 63.7% in influenza patients; P = .23). ICU treatment duration was significantly longer in ARDS patients with V‐V ECMO for Covid‐19 compared to influenza. Thirty‐day mortality was higher in Covid‐19, but not significant.

Background: Hemodynamic response to successful extracorporeal cardiopulmonary resuscitation (eCPR) is not uniform. Pulse pressure (PP) as a correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients. Methods: We report retrospective data of a single-centre registry of eCPR patients, treated at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP [low (0–9 mmHg), mid (10–29 mmHg) and high (≥ 30 mmHg)] at each time point. Results: One hundred forty-three patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 h) and after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 h to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5–20%), moderate (20–40%) and high (50–70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 h was an independent predictor for survival (p = 0.008). Conclusion: In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR. Graphic