Systemic Coagulation Derangement as an Early Sign of Oxygenator Failure in Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) Without Anticoagulation

The Right Ventricle in COVID-19 Lung Injury: Proposed Mechanisms, Management, and Research Gaps

Peripartum use of Extracorporeal Membrane Oxygenation (ECMO) in a Patient Suffering from COVID-19 Severe Acute Respiratory Distress Syndrome (ARDS): A Case Report

Lung transplantation for coronavirus disease 2019 (COVID-19): The who, what, where, when, and why

BackgroundThe survival benefit of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with severe acute respiratory distress syndrome (ARDS) remains controversial. This study aimed to investigate the efficiency and potential prognostic factors of VV-ECMO for severe ARDS in adults by evaluating our institutional experience and results.Materials and methodsThis research studied ARDS patients receiving VV-ECMO between June 2011 and May 2023. The inclusion criteria were PaO2/FiO2 < 100 mmHg at FiO2 of 1.0. Retrospective data was analyzed to identify factors associated with successful ECMO weaning and hospital discharge survival.ResultsA total of 18 patients were included in this study, with 7 cases (38.9%) successfully weaned from ECMO and 5 cases (27.8%) surviving hospital discharge. The overall complication rate was 77.8%. After treatment with VV ECMO, there were statistically significant improvements in both PaO2 and PaCO2 (P < 0.05). Patients in the successful weaning group had a lower pTB value, less accumulative volume of sodium bicarbonate during ECMO, and lower accumulative volume of intravenous immunoglobulin in the hospital compared to the unsuccessful weaning group (all P < 0.05). Furthermore, compared to the non-survivors, the survivors had less severe acidosis, higher mean arterial pressure before ECMO, a lower level of pCr, and a lower pTB value during ECMO (all P < 0.05).ConclusionECMO can effectively promote oxygenation and carbon dioxide (CO2) removal in patients with severe ARDS. Early initiation of ECMO with appropriate management could benefit in reducing comorbidities and mortality.

Essential Topics in the Management of Venovenous Extracorporeal Membrane Oxygenation in COVID-19 Acute Respiratory Distress Syndrome

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was officially declared a global pandemic on March 11, 2020, by the World Health Organization (WHO). The majority of patients with COVID-19 have mild disease, but approximately 14% develop severe respiratory failure and acute respiratory distress syndrome (ARDS), which is associated with high mortality.1–3 Extracorporeal membrane oxygenation (ECMO) could potentially improve survival in COVID-19-associated severe ARDS and has been incorporated in the WHO recommendation for management of severe COVID-19 disease.4–8 In this issue of ASAIO J, Slepian et al.9 report on the early experience of a multicenter cohort of patients undergoing ECMO for COVID-19 severe respiratory or cardiorespiratory failure. Their study, the largest cohort of COVID ECMO patients to date, describes 32 patients who were provided extracorporeal support either with veno-venous (VV), veno-arterial-venous (VAV), or veno-arterial (VA) ECMO. This initial description provides some insights into the use of ECMO for COVID-19 disease. Notably, the authors provide a glimpse at the median duration of ECMO in the five patients successfully weaned from ECMO (8 days, interquartile range [IQR] = 2–5), in addition to spending several days in endotracheally intubated before initiation of ECMO (median = 4 days, IQR = 2–5). Further, there is a trend toward higher mortality in those patients who require VA-ECMO or VAV-ECMO, in contrast to those patients who only require VV-ECMO, which could potentially be explained by the concomitant cardiac component of their COVID-19 disease, as well as the likely low-flow state and end-organ hypoperfusion before initiating VA-ECMO. However, as the authors note, outcomes are unclear from this cohort as the majority of the patients in the cohort were still receiving ECMO at the time of publication. The report is also limited in that detailed data on patient characteristics and detailed ventilatory data before the provision of ECMO are challenging to come by. These data will be crucial for further tailoring of both ECMO referral and cannulation criteria to identify those most likely to benefit from ECMO support.9 There is currently limited guidance on ECMO use and patient selection in a pandemic surge, particularly for COVID-19. The role of ECMO depends not only on patient factors (such as disease severity) but also on resource availability, as it consumes a large portion of hospital, critical care, and personnel resources.10–13 Moreover, ECMO capacity at these levels of systemic stress may be very limited at centers capable of providing this technology. ECMO growth was catalyzed following the efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure trial successfully demonstrating a mortality benefit in patients referred to an ECMO center for respiratory failure as well as the influenza A (H1N1) viral pandemic in 2009.14–16 Data on the effectiveness of ECMO during previous coronavirus outbreaks, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), remains limited, particularly during SARS. ECMO for MERS demonstrated an association with improved survival.17 Based on this historical experience, it is plausible that ECMO may improve survival outcomes for selected COVID-19 patients with severe ARDS. Given the significant resources required to provide ECMO, it is conceivable that during a pandemic it may become too burdensome to the system to be possible or justifiable. Principles of precision clinical medicine should be applied to patient selection and determining who is likely to most benefit from ECMO support during the COVID-19 pandemic. Early reports have determined several patient factors that are associated with high mortality in COVID-19, which include advanced age (>65 years), presence of comorbidities, extrapulmonary organ failures (assessed through Sequential Organ Failure Assessment score), hyperinflammation (elevated C-reactive protein, ferritin, or d-dimer), leukopenia, and myocardial injury (elevated troponin).18,19 Patients with one or more of the aforementioned risk factors for poor outcomes are less likely to be successfully supported with VV-ECMO. Eligible patients who develop COVID-19-related myocarditis leading to refractory cardiogenic shock may benefit from VA-ECMO, shown to confer survival benefit in patients with isolated myocarditis.20–22 Prospectively validated survival prediction models at ECMO initiation (e.g., RESP and PRESET scores) can assist in the assessment of candidacy for ECMO; however, these scores have not specifically been validated for COVID-19-associated ARDS.23,24 Initial criteria for consideration for ECMO should be based on current evidence and guidance. Patients with very severe ARDS who have been invasively ventilated for 7 days or less meeting the ECMO to rescue lung injury in severe ARDS (EOLIA) trial criteria and recent Extracorporeal Life Support Organization (ELSO) general guidance (ratio of arterial oxygen partial pressure to fractional inspired oxygen [PaO2:FiO2] <50 mmHg for >3 hours, or PaO2:FiO2 <80 mmHg for >6 hours or pH <7.25 with partial pressure of carbon dioxide [PCO2] ≥60 mmHg for more than 6 hours)5,10 without extrapulmonary organ failures could be considered for ECMO support. It is likely that these criteria can be further refined. We know that VV-ECMO is able to provide two major benefits to patients with ARDS. The first is that it can improve oxygenation when the patient has exhausted conventional strategies.5,25 The second, and likely more important mechanism, is that it facilitates extended lung-protective ventilation for patients who are already receiving conventional lung-protective ventilation. The EOLIA trial suggested that patients who were hypercarbic despite maximizing lung-protective ventilation were the group of patients with the greatest survival benefit that ECMO facilitates lung protection through a reduction in driving pressure and mechanical power.5 Patients with COVID-19-associated ARDS often present with notable hypoxemia, yet some may have relatively well-preserved lung compliance.26 The majority of these patients could potentially be managed with conventional methods and without ECMO unless compliance worsens (e.g., due to worsening underlying pathology, patient self-inflicted lung injury, or ventilator-induced lung injury) or hypoxemia is very severe and refractory to conventional management. These are the patients who are most likely to benefit from facilitated lung rest through VV-ECMO. Given the complexity of patient selection, a multidisciplinary approach to patient selection should be undertaken. Collaboration between ECMO centers is crucial to ensure appropriate service delivery and capacity to those patients with confirmed COVID-19 ARDS. Thorough assessment before accepting a patient for ECMO will also ensure that ECMO should only be considered after all conventional measures (lung-protective ventilation, moderate-to-high levels of positive-end expiratory pressure as tolerated, prone positioning, possible neuromuscular blockade, and negative fluid balance, as appropriate) fail to maintain adequate oxygenation and ventilation.27,28 Collaborative decision making between referring centers and the ECMO centers could potentially increase precision of clinical practice by reducing variabilities in the management of ARDS. The decision to offer or decline ECMO during COVID-19 pandemic is a difficult one. ECMO centers need to be highly selective aiming to enhance the precision of individual treatment benefit. This approach will potentially allow judicious planning, resource allocation, and a safe delivery of ECMO service. Prospective data will enable clinicians to better characterize this disease and successfully personalize therapies including ECMO.

BackgroundThere were relatively few studies about the incidence and risk factors for bloodstream infection (BSI) in patients with severe acute respiratory distress syndrome (ARDS) supported by veno–venous extracorporeal membrane oxygenation (VV–ECMO).MethodsPatients who were diagnosed with severe ARDS and received VV–ECMO treatment in the medical intensive care unit of China–Japan Friendship Hospital from August 2013 to March 2019 were retrospectively studied. The pathogens isolated from blood culture (BC) were identified and analyzed for drug sensitivity. The risk factors for BSI were analyzed by logistic regression.ResultsA total of 105 patients were included in this single–center retrospective cohort study. Among them, 23 patients (22%) had BSIs. 19 cases were identified as primary BSI; while the other 4 cases were as secondary BSI. A total of 23 pathogenic strains were isolated from BCs, including gram–negative (G–) bacilli in 21 (91%) cases, gram–positive (G+) cocci in 1 case, fungus in 1 case, and multidrug–resistant (MDR) organisms in 8 cases. Compared with patients without BSI, patients with BSI had a higher Murray score (odds ratio = 6.29, P = 0.01) and more blood transfusion (odds ratio = 1.27, P = 0.03) during ECMO.ConclusionsThe incidence of BSI in patients with severe ARDS supported by VV–ECMO was 22%. G– bacilli was the main pathogen, and most of them were MDR–G– bacilli (MDR–GNB). Higher Murray score and more blood transfusion may be the independent risk factors for BSI.

Patients with acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation benefit from higher positive end-expiratory pressure combined with conventional ventilation during the early extracorporeal membrane oxygenation period. The role of incremental positive end-expiratory pressure titration in patients with severe acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation remains unclear. This study aimed to determine the preferred method for setting positive end-expiratory pressure in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation support. We retrospectively reviewed all subjects supported with veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from 2009 to 2019 in the intensive care units in Tianjin Third Central Hospital. Subjects were divided into two groups according to the positive end-expiratory pressure titration method used: P-V curve (quasi-static pressure-volume curve-guided positive end-expiratory pressure setting) group or Crs (respiratory system compliance-guided positive end-expiratory pressure setting) group. Forty-three subjects were included in the clinical outcome analysis: 20 in the P-V curve group and 23 in the Crs group. Initial positive end-expiratory pressure levels during veno-venous extracorporeal membrane oxygenation were similar in both groups. Incidence rates of barotrauma and hemodynamic events were significantly lower in the Crs group (all p < 0.05). Mechanical ventilation duration, intensive care unit length of stay, and hospital length of stay were significantly shorter in the Crs group than the P-V curve group (all p < 0.05). Subjects in the Crs group showed non-significant improvements in the duration of extracorporeal membrane oxygenation support and 28-day mortality (p > 0.05). Respiratory system compliance-guided positive end-expiratory pressure setting may lead to more optimal clinical outcomes for patients with severe acute respiratory distress syndrome supported by veno-venous extracorporeal membrane oxygenation. Moreover, the operation is simple, safe, and convenient in clinical practice.

VV-ECMO in severe COVID-19: multidimensional perspectives on the use of a complex treatment

Venovenous extracorporeal membrane oxygenation is an effective intervention to improve gas exchange in patients with severe acute respiratory distress syndrome. However, the mortality of patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation remains high, and this may be due in part to a lack of standardized mechanical ventilation strategies aimed at further minimizing ventilator-induced lung injury. We tested whether a continuous positive airway pressure ventilation strategy mitigates ventilator-induced lung injury in patients with severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation, compared with current ventilation practice that employs tidal ventilation with limited driving pressure. We used plasma biomarkers as a surrogate outcome for ventilator-induced lung injury. Randomized crossover physiologic study. Single-center ICU. Ten patients with severe acute respiratory distress syndrome supported on venovenous extracorporeal membrane oxygenation. The study included four phases. After receiving pressure-controlled ventilation with driving pressure of 10 cm H2O for 1 hour (phase 1), patients were randomly assigned to receive first either pressure-controlled ventilation 20 cm H2O for 2 hours (phase 2) or continuous positive airway pressure for 2 hours (phase 3), and then crossover to the other phase for 2 hours; during phase 4 ventilation settings returned to baseline (pressure-controlled ventilation 10 cm H2O) for 4 hours. There was a linear relationship between the change in driving pressure and the plasma concentration of interleukin-6, soluble receptor for advanced glycation end products, interleukin-1ra, tumor necrosis factor alpha, surfactant protein D, and interleukin-10. Ventilator-induced lung injury may occur in acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation despite the delivery of volume- and pressure-limited mechanical ventilation. Reducing driving pressure to zero may provide more protective mechanical ventilation in acute respiratory distress syndrome patients supported with venovenous extracorporeal membrane oxygenation. However, the risks versus benefits of such an approach need to be confirmed in studies that are designed to test patient centered outcomes.

Early Initiation of Physical Therapy While on Extracorporeal Life Support Improves Patients’ Functional Activity on Discharge

Meld Scoring System to Predict Outcomes in Patients Who Undergo VV ECMO Implantation

Aim: To report the clinical courses of two patients, one with Hodgkin’s lymphoma (HL) and one with Non-Hodgkin’s lymphoma (NHL), who developed severe refractory acute respiratory distress syndrome (ARDS) and were treated with veno-venous extracorporeal membrane oxygenation (VV ECMO). Case report: Both patients developed chemotherapy-associated febrile neutropenia followed by pneumonia and ARDS, after which they were transferred to the intensive care unit. Their respiratory failure deteriorated despite endotracheal intubation with protective mechanical ventilation, at which point a decision for VV ECMO initiation was made. Both patients had complicated treatment courses and developed severe ECMO-associated complications. The most important complications of ECMO support in our HL patient were cardiac arrest; right atrial laceration with pericardial tamponade which needed surgical treatment; right leg ischemia which required transfemoral amputation; thrombosis within the membrane oxygenator; several septic episodes with severe hemodynamic instability; and right sided tension pneumothorax. Despite all difficulties, the patient was successfully weaned from ECMO. Unfortunately, he died prior to hospital discharge as a result of sepsis with multiple organ failure. The most significant ECMO-induced complications in our NHL patient were severe bleeding incidents, most notably diffuse oropharyngeal and continuous bilateral pulmonary hemorrhage; superimposed bacterial pneumonia; extensive pneumomediastinum and subcutaneous emphysema. Despite all therapeutic efforts, the patient died during ECMO treatment because of respiratory decompensation. Conclusions: The patients with hematologic malignancies (HMs) undergoing ECMO support have poor outcomes, with high rates of severe ECMO-induced complications. Further studies focusing on patient selection and issues concerning prevention, diagnosis and treatment of ECMO-associated complications are needed.

BackgroundA combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO.MethodsIn this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching.ResultsA total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035).ConclusionsPatients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO.Trial RegistrationClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.

Introduction: Veno-venous extracorporeal membrane oxygenation (VV ECMO) is an indicated treatment for severe acute respiratory distress syndrome (ARDS) refractory to conventional medical treatment. Severe ARDS is a common complication of CoVID-19 infection. Subsequently, the efficacy of VV ECMO in CoVID-19 severe ARDS patients must be investigated. ECMO is a resource-intensive treatment modality, meaning that its use must be reserved for patients with robust indications and paucity of contraindications. Methods: We performed retrospective chart review of three patients at the University of Nebraska Medical Center that were placed on VV ECMO secondary to severe ARDS from CoVID-19 infection. Results: All patients were male with a median age of 39 years. Two patients were of Hispanic descent, and the third was of Asian descent. No patients had underlying lung disease, and all patients had type II diabetes mellitus. Median time on mechanical ventilation prior to ECMO cannulation was six days. Median duration of ECMO treatment was 21 days with a range of 17 to 27 days. All patients were decannulated from ECMO during their hospital stay, and all patients survived to 60 days post-hospital discharge. Complications while on ECMO included GI bleeding in two patients, hematuria in one patient, necessitation of vasodilator and vasopressor support in all patients, AKI in two patients, secondary bacterial pneumonia in two patients, and blood cultures positive for gram-positive organisms in all patients. No patients suffered DVT or CVA. All patients required pRBC transfusion during ECMO treatment. Two patients were treated with remdesivir and one patient received baricitinib, a JAK-inhibitor. Conclusion: VV ECMO is a viable treatment for patients with severe ARDS secondary to CoVID-19 infection that have failed conventional therapy. Stringent adherence to inclusion and exclusion criteria is imperative. VV ECMO combined with lung protective ventilation strategies with a focus on minimizing driving pressure can provide life-saving treatment to patients with severe ARDS secondary to CoVID-19 infection