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.

Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Evidence of cerebrovascular complications in COVID-19 requiring venovenous extracorporeal membrane oxygenation (ECMO) is limited. Our study aims to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on venovenous ECMO. DESIGN: We analyzed prospectively collected observational data, using univariable and multivariable survival modeling to identify risk factors for stroke. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. SETTING: Three hundred eighty institutions in 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. PATIENTS: Adult COVID-19 patients who were supported by venovenous ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five hundred ninety-five patients (median age [interquartile range], 51 yr [42-59 yr]; male: 70.8%) had venovenous ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity (adjusted hazard ratio [aHR], 2.19; 95% CI, 1.05-4.59) and use of vasopressors before ECMO (aHR, 2.37; 95% CI, 1.08-5.22) were associated with an increased risk of stroke. Forty-eight-hour post-ECMO Pa co2 -pre-ECMO Pa co2 /pre-ECMO Pa co2 (relative ΔPa co2 ) of negative 26% and 48-hour post-ECMO Pa o2 -pre-ECMO Pa o2 /pre-ECMO Pa o2 (relative ΔPa o2 ) of positive 24% at 48 hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPa co2 of negative 17% and relative ΔPa o2 of positive 7% in the nonstroke group. Patients with acute stroke had a 79% in-hospital mortality compared with 45% mortality for stroke-free patients. CONCLUSIONS: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on venovenous ECMO. Also, the importance of relative decrease in Pa co2 and moderate hyperoxia within 48 hours after ECMO initiation were additional risk factors.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Heparin-based versus bivalirudin-based anticoagulation in pediatric extracorporeal membrane oxygenation: A systematic review.

Introduction: Optimal anticoagulation therapy is essential for the prevention of thrombotic and hemorrhagic complications in pediatric patients supported with extracorporeal membrane oxygenation (ECMO). Recent data have demonstrated bivalirudin has the potential to surpass and replace heparin as the anticoagulant of choice. Methods: We conducted a systematic review comparing the outcomes of heparin-based versus bivalirudin-based anticoagulation in pediatric patients supported on ECMO to identify the preferred anticoagulant to minimize bleeding events, thrombotic complications, and associated mortality. We referenced the PubMed, Cochrane Library, and Embase databases. These databases were searched from inception through October 2022. Our initial search identified 422 studies. All records were screened by two independent reviewers using the Covidence software for adherence to our inclusion criteria, and seven retrospective cohort studies were identified as appropriate for inclusion. Results: In total, 196 pediatric patients were anticoagulated with heparin and 117 were anticoagulated with bivalirudin while on ECMO. Across the included studies, it was found that for patients treated with bivalirudin, trends were noted toward lower rates of bleeding, transfusion requirements, and thrombosis with no difference in mortality. Overall costs associated with bivalirudin therapy were lower. Time to therapeutic anticoagulation varied between studies though institutions had different anticoagulation targets. Conclusion: Bivalirudin may be a safe, cost-effective alternative to heparin in achieving anticoagulation in pediatric ECMO patients. Prospective multicenter studies and randomized control trials with standard anticoagulation targets are needed to accurately compare outcomes associated with heparin versus bivalirudin in pediatric ECMO patients.

Iliopsoas haematoma during extracorporeal membrane oxygenation: A registry report from the COVID-19 critical care consortium across 30 countries.

INTRODUCTION: Iliopsoas haematoma (IPH) during extracorporeal membrane oxygenation (ECMO) is a rare bleeding complication that can be fatal due to its progression to abdominal compartment syndrome, but its incidence and risk factors are not well known. We have previously reported an IPH incidence rate of 16% in Japan. Among possible reasons for this high incidence, ethnicity has been hypothesised to play a role. Therefore, we used an international multi-centre cohort registry to test this hypothesis by determining the incidence rate of IPH. METHODS: This study was performed using the COVID-19 Critical Care Consortium database, conducted in 30 countries across five continents between 3 January 2020, and 20 June 2022. RESULTS: Overall, 1102 patients received ECMO for COVID-19-related acute respiratory distress syndrome. Of them, only seven were reported to have IPH, indicating an incidence rate of 0.64%, with comparable rates between the countries. The IPH group tended to have a higher mortality rate (71.4%) than the non-IPH group (51%). CONCLUSIONS: Overall incidence of IPH in the studied COVID-19 ECMO cohort was 0.64%. Most cases were reported from Japan, Belgium, and Italy. In our study, this rare complication did not appear to be confined to Asian patients. Due to the high fatality rate, awareness about the occurrence of IPH should be recognised.

Morbid obesity's impact on COVID-19 patients requiring venovenous extracorporeal membrane oxygenation: The covid-19 critical care consortium database review.

Introduction: Obesity is associated with a worse prognosis in COVID-19 patients with acute respiratory distress syndrome (ARDS). Veno-venous (V-V) Extracorporeal Membrane Oxygenation (ECMO) can be a rescue option, however, the direct impact of morbid obesity in this select group of patients remains unclear.Methods: This is an observational study of critically ill adults with COVID-19 and ARDS supported by V-V ECMO. Data are from 82 institutions participating in the COVID-19 Critical Care Consortium international registry. Patients were admitted between 12 January 2020 to 27 April 2021. They were stratified based on Body Mass Index (BMI) at 40 kg/m2. The endpoint was survival to hospital discharge.Results: Complete data available on 354 of 401 patients supported on V-V ECMO. The characteristics of the high BMI (>40 kg/m2) and lower BMI (≤40 kg/m2) groups were statistically similar. However, the 'high BMI' group were comparatively younger and had a lower APACHE II score. Using survival analysis, older age (Hazard Ratio, HR 1.49 per-10-years, CI 1.25-1.79) and higher BMI (HR 1.15 per-5 kg/m2 increase, CI 1.03-1.28) were associated with a decreased patient survival. A safe BMI threshold above which V-V ECMO would be prohibitive was not apparent and instead, the risk of an adverse outcome increased linearly with BMI.Conclusion: In COVID-19 patients with severe ARDS who require V-V ECMO, there is an increased risk of death associated with age and BMI. The risk is linear and there is no BMI threshold beyond which the risk for death greatly increases.

Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study.

OBJECTIVE: To estimate the effect of extracorporeal membrane oxygenation (ECMO) compared with conventional mechanical ventilation on outcomes of patients with covid-19 associated respiratory failure. DESIGN: Observational study. SETTING: 30 countries across five continents, 3 January 2020 to 29 August 2021. PARTICIPANTS: 7345 adults admitted to the intensive care unit with clinically suspected or laboratory confirmed SARS-CoV-2 infection. INTERVENTIONS: ECMO in patients with a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio <80 mm Hg compared with conventional mechanical ventilation without ECMO. MAIN OUTCOME MEASURE: The primary outcome was hospital mortality within 60 days of admission to the intensive care unit. Adherence adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for competing events and for baseline and time varying confounding. RESULTS: 844 of 7345 eligible patients (11.5%) received ECMO at any time point during follow-up. Adherence adjusted mortality was 26.0% (95% confidence interval 24.5% to 27.5%) for a treatment strategy that included ECMO if the PaO2/FiO2 ratio decreased <80 mm Hg compared with 33.2% (31.8% to 34.6%) had patients received conventional treatment without ECMO (risk difference -7.1%, 95% confidence interval -8.2% to -6.1%; risk ratio 0.78, 95% confidence interval 0.75 to 0.82). In secondary analyses, ECMO was most effective in patients aged <65 years and with a PaO2/FiO2 <80 mm Hg or with driving pressures >15 cmH2O during the first 10 days of mechanical ventilation. CONCLUSIONS: ECMO was associated with a reduction in mortality in selected adults with covid-19 associated respiratory failure. Age, severity of hypoxaemia, and duration and intensity of mechanical ventilation were found to be modifiers of treatment effectiveness and should be considered when deciding to initiate ECMO in patients with covid-19.

Beneficial Effect of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019.

OBJECTIVES: The study investigated the impact of prone positioning during venovenous extracorporeal membrane oxygenation support for coronavirus disease 2019 acute respiratory failure on the patient outcome. DESIGN: An observational study of venovenous extracorporeal membrane oxygenation patients. We used a multistate survival model to compare the outcomes of patients treated with or without prone positioning during extracorporeal membrane oxygenation, which incorporates the dynamic nature of prone positioning and adjusts for potential confounders. SETTING: Seventy-two international institutions participating in the Coronavirus Disease 2019 Critical Care Consortium international registry. PATIENTS: Coronavirus disease 2019 patients who were supported by venovenous extracorporeal membrane oxygenation during the study period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: There were 232 coronavirus disease 2019 patients at 72 participating institutions who were supported with venovenous extracorporeal membrane oxygenation during the study period from February 16, 2020, to October 31, 2020. Proning was used in 176 patients (76%) before initiation of extracorporeal membrane oxygenation and in 67 patients (29%) during extracorporeal membrane oxygenation. Survival to hospital discharge was 33% in the extracorporeal membrane oxygenation prone group versus 22% in the extracorporeal membrane oxygenation supine group. Prone positioning during extracorporeal membrane oxygenation support was associated with reduced mortality (hazard ratio, 0.31; 95% CI, 0.14-0.68). CONCLUSIONS: Our study highlights that prone positioning during venovenous extracorporeal membrane oxygenation support for refractory coronavirus disease 2019-related acute respiratory distress syndrome is associated with reduced mortality. Given the observational nature of the study, a randomized controlled trial of prone positioning on venovenous extracorporeal membrane oxygenation is needed to confirm these findings.

Mobile Extracorporeal Membrane Oxygenation for Covid-19 Does Not Pose Extra Risk to Transport Team.

Previous experience has shown that transporting patients on extracorporeal membrane oxygenation (ECMO) is a safe and effective mode of transferring critically ill patients requiring maximum mechanical ventilator support to a quaternary care center. The coronavirus disease 2019 (COVID-19) pandemic posed new challenges. This is a multicenter, retrospective study of 113 patients with confirmed severe acute respiratory syndrome coronavirus 2, cannulated at an outside hospital and transported on ECMO to an ECMO center. This was performed by a multidisciplinary mobile ECMO team consisting of physicians for cannulation, critical care nurses, and an ECMO specialist or perfusionist, along with a driver or pilot. Teams practised strict airborne contact precautions with eyewear while caring for the patient and were in standard Personal Protective Equipment. The primary mode of transportation was ground. Ten patients were transported by air. The average distance traveled was 40 miles (SD ±56). The average duration of transport was 133 minutes (SD ±92). When stratified by mode of transport, the average distance traveled for ground transports was 36 miles (SD ±52) and duration was 136 minutes (SD ±93). For air, the average distance traveled was 66 miles (SD ±82) and duration was 104 minutes (SD ±70). There were no instances of transport-related adverse events including pump failures, cannulation complications at outside hospital, or accidental decannulations or dislodgements in transit. There were no instances of the transport team members contracting COVID-19 infection within 21 days after transport. By adhering to best practices and ACE precautions, patients with COVID-19 can be safely cannulated at an outside hospital and transported to a quaternary care center without increased risk to the transport team.

Case report: double lung en bloc procurement from a donor after arterial switch operation.

The growing unmet demand for suitable organ donors increases each year. Despite relative contraindications for thoracic organ donation after previous cardiac surgery, experienced programmes and surgeons can successfully utilise the lungs from select donors who have undergone prior cardiac surgery. This is the first reported case of double lung en bloc procurement from a donor who had a previous arterial switch operation as an infant.

Implementation of new ECMO centers during the COVID-19 pandemic: experience and results from the Middle East and India.

PURPOSE: Extracorporeal membrane oxygenation (ECMO) use for severe coronavirus disease 2019 (COVID-19) patients has increased during the course of the pandemic. As uncertainty existed regarding patient's outcomes, early guidelines recommended against establishing new ECMO centers. We aimed to explore the epidemiology and outcomes of ECMO for COVID-19 related cardiopulmonary failure in five countries in the Middle East and India and to evaluate the results of ECMO in 5 new centers. METHODS: This is a retrospective, multicenter international, observational study conducted in 19 ECMO centers in five countries in the Middle East and India from March 1, 2020, to September 30, 2020. We included patients with COVID-19 who received ECMO for refractory hypoxemia and severe respiratory acidosis with or without circulatory failure. Data collection included demographic data, ECMO-related specific data, pre-ECMO patient condition, 24 h post-ECMO initiation data, and outcome. The primary outcome was survival to home discharge. Secondary outcomes included mortality during ECMO, survival to decannulation, and outcomes stratified by center type. RESULTS: Three hundred and seven COVID-19 patients received ECMO support during the study period, of whom 78 (25%) were treated in the new ECMO centers. The median age was 45 years (interquartile range IQR 37-52), and 81% were men. New center patients were younger, were less frequently male, had received higher PEEP, more frequently inotropes and prone positioning before ECMO and were less frequently retrieved from a peripheral center on ECMO. Survival to home discharge was 45%. In patients treated in new and established centers, survival was 55 and 41% (p = 0.03), respectively. Multivariable analysis retained only a SOFA score < 12 at ECMO initiation as associated with survival (odds ratio, OR 1.93 (95% CI 1.05-3.58), p = 0.034), but not treatment in a new center (OR 1.65 (95% CI 0.75-3.67)). CONCLUSIONS: During pandemics, ECMO may provide favorable outcomes in highly selected patients as resources allow. Newly formed ECMO centers with appropriate supervision of regional experts may have satisfactory results.

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

DISCLAIMER: This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers.

Disclaimer: The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.