Expert consensus statement on venovenous extracorporeal membrane oxygenation ECMO for COVID-19 severe ARDS: an international Delphi study.

BACKGROUND: The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. OBJECTIVES: To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. METHODS: The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel's questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. RESULTS: In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. CONCLUSION: Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations.

Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2. FINDINGS: Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05]. INTERPRETATION: The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO. FUNDING: None.

Extracorporeal membrane oxygenation for COVID-19-related acute respiratory distress syndrome: a narrative review.

A growing body of evidence supports the use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) refractory to maximal medical therapy. ARDS may develop in a proportion of patients hospitalized for coronavirus disease 2019 (COVID-19) and ECMO may be used to manage patients refractory to maximal medical therapy to mitigate the risk of ventilator-induced lung injury and provide lung rest while awaiting recovery. The mortality of COVID-19-related ARDS was variously reassessed during the pandemic. Veno-venous (VV) ECMO was the default choice to manage refractory respiratory failure; however, with concomitant severe right ventricular dysfunction, venoarterial (VA) ECMO or mechanical right ventricular assist devices with extracorporeal gas exchange (Oxy-RVAD) were also considered. ECMO has also been used to manage special populations such as pregnant women, pediatric patients affected by severe forms of COVID-19, and, in cases with persistent and seemingly irreversible respiratory failure, as a bridge to successful lung transplantation. In this narrative review, we outline and summarize the most recent evidence that has emerged on ECMO use in different patient populations with COVID-19-related ARDS.

Respiratory system mechanics, gas exchange, and outcomes in mechanically ventilated patients with COVID-19-related acute respiratory distress syndrome: a systematic review and meta-analysis.

The association of respiratory mechanics, particularly respiratory system static compliance (CRS), with severity of hypoxaemia in patients with COVID-19-related acute respiratory distress syndrome (ARDS) has been widely debated, with some studies reporting distinct ARDS phenotypes based on CRS. Ascertaining whether such phenotypes exist is important, because they might indicate the need for ventilation strategies that differ from those used in patients with ARDS due to other causes. In a systematic review and meta-analysis of studies published between Dec 1, 2019, and March 14, 2022, we evaluated respiratory system mechanics, ventilator parameters, gas exchange parameters, and clinical outcomes in patients with COVID-19-related ARDS. Among 11 356 patients in 37 studies, mean reported CRS, measured close to the time of endotracheal intubation, was 35·8 mL/cm H2O (95% CI 33·9-37·8; I2=96·9%, τ2=32·6). Pooled mean CRS was normally distributed. Increasing ARDS severity (assessed by PaO2/FiO2 ratio as mild, moderate, or severe) was associated with decreasing CRS. We found no evidence for distinct CRS-based clinical phenotypes in patients with COVID-19-related ARDS, and we therefore conclude that no change in conventional lung-protective ventilation strategies is warranted. Future studies should explore the personalisation of mechanical ventilation strategies according to factors including respiratory system mechanics and haemodynamic status in patients with ARDS.

Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long-term outcomes in COVID-19 patients.

Sustained hypercoagulability and endotheliopathy are present in convalescent COVID-19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID-19 patients were evaluated up to 16 months after recovery from COVID-19. These values were compared with a control group of healthy volunteers (n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID-19 acute ischaemic limb. Elevated D-dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D-dimer 0.34 FEU µg/mL (IQR 0.28, 0.46) (p < .001) and Factor VIII 150% (IQR 171, 203) (p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) (p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) (p = 0.01) and delayed lag time 2.4 min (1.42-2.97) (p = 0.0002) versus controls. Raised vWF:Ag and ICAM-1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) (p = 0.02) and ICAM-1 54.1 ng/mL (IQR 43.8, 64.1) (p = .004) than controls. IL-6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL-6 of 1.5 pg/mL (IQR 0.6, 3.0) (p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID-19 severity and COVID-19 vaccination preceding SARS-CoV-2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID-19.

Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature.

BACKGROUND: A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS. METHODS: MEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data. RESULTS: Ten studies reporting 421 patients (PaO2:FiO2 141.03 mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p < .001) and a 1.89 mL/kg (95%-CI: 1.75-2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy. CONCLUSIONS: Venovenous ECCO2R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. METHODS: We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. RESULTS: Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8-52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. CONCLUSIONS: The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

Myopericarditis following COVID-19 vaccination and non-COVID-19 vaccination: a systematic review and meta-analysis.

BACKGROUND: Myopericarditis is a rare complication of vaccination. However, there have been increasing reports of myopericarditis following COVID-19 vaccination, especially among adolescents and young adults. We aimed to characterise the incidence of myopericarditis following COVID-19 vaccination, and compare this with non-COVID-19 vaccination. METHODS: We did a systematic review and meta-analysis, searching four international databases from Jan 1, 1947, to Dec 31, 2021, for studies in English reporting on the incidence of myopericarditis following vaccination (the primary outcome). We included studies reporting on people in the general population who had myopericarditis in temporal relation to receiving vaccines, and excluded studies on a specific subpopulation of patients, non-human studies, and studies in which the number of doses was not reported. Random-effects meta-analyses (DerSimonian and Laird) were conducted, and the intra-study risk of bias (Joanna Briggs Institute checklist) and certainty of evidence (Grading of Recommendations, Assessment, Development and Evaluations approach) were assessed. We analysed the difference in incidence of myopericarditis among subpopulations, stratifying by the type of vaccine (COVID-19 vs non-COVID-19) and age group (adult vs paediatric). Among COVID-19 vaccinations, we examined the effect of the type of vaccine (mRNA or non-mRNA), sex, age, and dose on the incidence of myopericarditis. This study was registered with PROSPERO (CRD42021275477). FINDINGS: The overall incidence of myopericarditis from 22 studies (405 272 721 vaccine doses) was 33·3 cases (95% CI 15·3-72·6) per million vaccine doses, and did not differ significantly between people who received COVID-19 vaccines (18·2 [10·9-30·3], 11 studies [395 361 933 doses], high certainty) and those who received non-COVID-19 vaccines (56·0 [10·7-293·7], 11 studies [9 910 788 doses], moderate certainty, p=0·20). Compared with COVID-19 vaccination, the incidence of myopericarditis was significantly higher following smallpox vaccinations (132·1 [81·3-214·6], p<0·0001) but was not significantly different after influenza vaccinations (1·3 [0·0-884·1], p=0·43) or in studies reporting on various other non-smallpox vaccinations (57·0 [1·1-3036·6], p=0·58). Among people who received COVID-19 vaccines, the incidence of myopericarditis was significantly higher in males (vs females), in people younger than 30 years (vs 30 years or older), after receiving an mRNA vaccine (vs non-mRNA vaccine), and after a second dose of vaccine (vs a first or third dose). INTERPRETATION: The overall risk of myopericarditis after receiving a COVID-19 vaccine is low. However, younger males have an increased incidence of myopericarditis, particularly after receiving mRNA vaccines. Nevertheless, the risks of such rare adverse events should be balanced against the risks of COVID-19 infection (including myopericarditis). FUNDING: None.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study.

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.

Convalescent Plasma for Patients Hospitalized With Coronavirus Disease 2019: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

Current evidence from randomized controlled trials (RCTs) and systematic reviews on the utility of convalescent plasma (CP) in patients with coronavirus disease 2019 (COVID-19) suggests a lack of benefit. We conducted an updated meta-analysis of RCTs with trial sequential analysis to investigate whether convalescent plasma is futile in reducing mortality in patients hospitalized with COVID-19. We searched 6 databases from December 1, 2019 to August 1, 2021 for RCTs comparing the use of CP with standard of care or transfusion of non-CP standard plasma in patients with COVID-19. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 Tool. Random effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the aggregate risk for in-hospital mortality between both arms. We conducted a trial sequential analysis (TSA) based on the pooled relative risks (RRs) for in-hospital mortality. Secondary outcomes included the pooled RR for receipt of mechanical ventilation and mean difference in hospital length of stay. We included 18 RCTs (8702 CP, 7906 control). CP was not associated with a significant mortality benefit (RR: 0.95, 95%-CI: 0.86-1.04, P = .27, high certainty). Subgroup analysis did not find any significant differences (pinteraction = 0.30) between patients who received CP within 8 days of symptom onset (RR: 0.97, 95%-CI: 0.79-1.19, P = .80), or after 8 days (RR: 0.79, 95%-CI: 0.57-1.10, P = .16). TSA based on a RR reduction of 10% from a baseline mortality of 20% found that CP was not effective, with the pooled effect within the boundary for futility. CP did not significantly reduce the requirement for mechanical ventilation (RR: 1.00, 95%-CI: 0.91-1.10, P = .99, moderate certainty) or hospital length of stay (+1.32, 95%-CI: -1.86 to +4.52, P = .42, low certainty). CP does not improve relevant clinical outcomes in patients with COVID-19, especially in severe disease. The pooled effect of mortality was within the boundary of futility, suggesting the lack of benefit of CP in patients hospitalized with COVID-19.

Prone Positioning of Nonintubated Patients With Coronavirus Disease 2019-A Systematic Review and Meta-Analysis.

OBJECTIVES: Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019-related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes. DESIGN AND SETTING: We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020. SUBJECTS AND INTERVENTION: Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included. MEASUREMENTS AND MAIN RESULTS: Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao2 to the Fio2 (mean difference, 39; 95% CI, 25-54), Pao2 (mean difference, 20 mm Hg; 95% CI, 14-25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3-6%). Respiratory rate decreased post prone positioning (mean difference, -3.2 breaths/min; 95% CI, -4.6 to -1.9). Intubation and mortality rates were 24% (95% CI, 17-32%) and 13% (95% CI, 6-19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them. CONCLUSIONS: Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.

Comprehensive assessment of a nationwide simulation-based course for artificial life support.

BACKGROUND: Successful implementation of medical technologies applied in life-threatening conditions, including extracorporeal membrane oxygenation (ECMO) requires appropriate preparation and training of medical personnel. The pandemic has accelerated the creation of new ECMO centers and has highlighted continuous training in adapting to new pandemic standards. To reach high standards of patients' care, we created the first of its kind, National Education Centre for Artificial Life Support (NEC-ALS) in 40 million inhabitants' country in the Central and Eastern Europe (CEE). The role of the Center is to test and promote the novel or commonly used procedures as well as to develop staff skills on management of patients needing ECMO. METHOD: In 2020, nine approved and endorsed by ELSO courses of "Artificial Life Support with ECMO" were organized. Physicians participated in the three-day high-fidelity simulation-based training that was adapted to abide by the social distancing norms of the COVID-19 pandemic. Knowledge as well as crucial cognitive, behavioral and technical aspects (on a 5-point Likert scale) of management on ECMO were assessed before and after course completion. Moreover, the results of training in mechanical chest compression were also evaluated. RESULTS: There were 115 participants (60% men) predominantly in the age of 30-40 years. Majority of them (63%) were anesthesiologists or intensivists with more than 5-year clinical experience, but 54% had no previous ECMO experience. There was significant improvement after the course in all cognitive, behavioral, and technical self-assessments. Among aspects of management with ECMO that all increased significantly following the course, the most pronounced was related to the technical one (from approximately 1.0 to more 4.0 points). Knowledge scores significantly increased post-course from 11.4 ± SD to 13 ± SD (out of 15 points). The quality of manual chest compression relatively poor before course improved significantly after training. CONCLUSIONS: Our course confirmed that simulation as an educational approach is invaluable not only in training and testing of novel or commonly used procedures, skills upgrading, but also in practicing very rare cases. The implementation of the education program during COVID-19 pandemic may be helpful in founding specialized Advanced Life Support centers and teams including mobile ones. The dedicated R&D Innovation Ecosystem established in the "ECMO for Greater Poland" program, with developed National Education Center can play a crucial role in the knowledge and know-how transfer but future research is needed.

Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Prone positioning (PP) improves oxygenation and respiratory mechanics and is associated with lower mortality in patients with moderate to severe acute respiratory distress syndrome (ARDS). Despite this, some patients develop refractory hypoxemia and hypercapnia requiring venovenous extracorporeal membrane oxygenation (VV ECMO) support and are usually cared for in supine position. The physiologic and outcome benefits of routine PP of patients during VV ECMO remains unclear. Hence, we conducted the systematic review and meta-analysis to evaluate the outcome benefits of PP for patients with ARDS being treated with VV ECMO. METHODS: After registration with PROSPERO (CRD42020199723), MEDLINE, EMBASE, Scopus and Cochrane databases were searched for relevant studies that reported PP in more than 10 adult patients supported with VV ECMO from origin to 1 March 2021. Studies were reviewed for quality using appropriate Joanna Briggs Institute (JBI) checklists, and certainty of evidence was assessed using the GRADE approach. The random-effects model (DerSimonian and Laird) was used. The primary outcome of interest was cumulative survival. Secondary outcomes were intensive care unit length of stay (ICU LOS) and ECMO duration. Changes in arterial blood gas (ABG) values, ventilator mechanics and complication rates were also studied. RESULTS: Of 812 potentially relevant publications, 12 studies (640 patients) met our inclusion criteria. Due to overlapping study populations, 11 studies were included in the final meta-analysis. Cumulative survival in patients that underwent PP was 57% (95% CI 41.9-71.4, high certainty). Patients that underwent PP had longer ICU LOS (+ 14.5 days, 95% CI 3.4-25.7, p = 0.01) and ECMO duration (+ 9.6 days, 95% CI 5.5-13.7, p < 0.0001). After PP, patients had significantly higher PaO2/FiO2 ratio, lower PaCO2 and reduced ventilator driving pressure, and no major complications were reported. CONCLUSIONS: PP during VV ECMO appears safe with a cumulative survival of 57% and may result in longer ECMO runs and ICU LOS. However, evidence from appropriately designed randomized trials is needed prior to widespread adoption of PP on VV ECMO.

Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study.

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.