PURPOSE: Extracorporeal Membrane Oxygenation (ECMO) support is being employed with increasing frequency for patients with severe respiratory and/or cardiac failure.Elevations of serum bilirubin, sometimes to extremely high values, are commonly encountered when caring for patients on ECMO support.Several single center retrospective studies have described elevated bilirubin as associated with increased mortality in ECMO supported patients.In fact, one study cited a 90% mortality in patients with total serum bilirubin greater than 11 mg/dL.(ASAIO 2019; 65:812-818).We sought to systematically describe the experience with bilirubin elevation at our center in the ECMO population.METHODS: A retrospective chart review was performed on all adult patients supported with ECMO at Inova Fairfax Medical Center from January 1, 2018 to March 1, 2023.Patients were divided by support with venovenous (VV) or venoarterial (VA) ECMO.Patients were divided into three groups based on highest total serum bilirubin value following initiation of ECMO support: 0-3 mg/dL, 3-10 mg/dL, and > 10 mg/dL.In-hospital mortality was assessed for each group.RESULTS: A total of 527 adult patients were supported with ECMO during the specified timeframe (123 VV (23.3%), 404 VA (76.7%).The distribution of peak total serum bilirubin levels among patients was as follows: VV-ECMO -0-3 mg/dl (82, 66.6%), 3-10 mg/dL (29, 23.6%), and >10 mg /dL (12, 9.8%); VA-ECMO --0-3 mg/dl (235, 58.2%), 3-10 mg/dL (113, 28.0%), and >10 mg /dL (56, 13.9%).In-hospital mortality amongst these groups was as follows: VV-ECMO -0-3 mg/dl (10, 12.2%), 3-10 mg/dL (17, 58.6%), and >10 mg /dL (6, 50%); VA-ECMO -0-3 mg/dl (81, 34.5%), 3-10 mg/dL (57, 50.4%), and >10 mg /dL (41, 73.2%).The highest total bilirubin in a VV-ECMO survivor was 14.8 mg/dL, while the highest total bilirubin in a VA survivor was 46.3 mg/dL.Eight of twenty-four (33.3%)VA ECMO patients with total bilirubin over 20 mg/dL survived their hospitalization.No patients appeared to have fulminant hepatic failure despite elevations of serum bilirubin.CONCLUSIONS: Elevations of bilirubin are commonly encountered in patients on ECMO support and appear to be associated with increased mortality.Further survival analysis controlling for additional clinical characteristics is warranted.Despite the association between bilirubin and mortality it does not appear that deaths are due to liver disease and elevations in bilirubin may be more reflective of overall clinical status.CLINICAL IMPLICATIONS: Elevations of bilirubin seem to carry prognostic significance in ECMO but should not be solely relied upon to make decisions regarding ongoing extracorporeal support.

The impact of the duration of noninvasive respiratory support (RS) including high-flow nasal cannula and noninvasive ventilation before the initiation of extracorporeal membrane oxygenation (ECMO) is unknown. We reviewed data of patients with coronavirus disease 2019 (COVID-19) treated with V-V ECMO at two high-volume tertiary care centers. Survival analysis was used to compare the effect of duration of RS on liberation from ECMO. A total of 78 patients required ECMO and the median duration of RS and invasive mechanical ventilation (IMV) before ECMO was 2 days (interquartile range [IQR]: 0, 6) and 2.5 days (IQR: 1, 5), respectively. The median duration of ECMO support was 24 days (IQR: 11, 73) and 59.0% (N = 46) remained alive at the time of censure. Patients that received RS for ≥3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26-0.83), IMV (HR: 0.42; 95% CI: 0.20-0.89) or be discharged from the hospital (HR: 0.52; 95% CI: 0.27-0.99) compared to patients that received RS for <3 days. There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56-2.26). These relationships persisted after adjustment for age, gender, and duration of IMV. Prolonged duration of RS before ECMO may result in lung injury and worse subsequent outcomes.

To the Editor: We read with great interest the article published in a recent issue of Critical Care Medicine on the prevalence of intracranial hemorrhage (ICH) in COVID-19 patients on extracorporeal membrane oxygenation (ECMO) by Seeliger et al (1). We were struck by the high prevalence of ICH in COVID-19 patients on ECMO. This retrospective article analyzes ICH occurrence rate and clinical outcomes in patients on ECMO due to COVID-19–induced acute respiratory distress syndrome (C-ARDS) compared with other viral acute respiratory distress syndrome (ARDS). The article reported ICH in 29 of 142 COVID-19 patients (20%), including 15 major bleeds. We have not observed a similar predilection to ICH in COVID-19 at our institution. We have cared for 69 COVID patients requiring venovenous ECMO support for C-ARDS, of whom 66.6% survived to hospital discharge. Of these patients, only two patients (2.9%) suffered ICH, one while on ECMO and the other following her ECMO run. Both patients recovered completely without neurologic sequelae. The reason for the discrepant rates of ICH in C-ARDS patients is unclear. Our patient population was younger, with a mean age of 43 (range, 16–68). Severity of ARDS at the time of cannulation appears similar between the groups. Our practices for screening for ICH mirror those of Seeliger et al (1). However, only 13 patients in our cohort had head imaging which is a lower percentage of imaging than the authors’ report, so some subclinical bleeds could be missed. Regardless, the rate of major/fatal bleeds observed by Seeliger et al (1) still far exceeds our observed rate. Perhaps the biggest difference between cohorts is the anticoagulation strategy. Unfractionated heparin (UFH) was primarily used by Seeliger et al (1). In contrast, ~80% (n = 55) of our patients were anticoagulated with bivalirudin targeting an activated partial thromboplastin time between 50 and 80 seconds. In our patients, 14.5% (n = 10) started out with UFH and were transitioned to bivalirudin, whereas only 5.8% (n = 4) were anticoagulated with UFH exclusively. Our institutional data does not show an increased prevalence of ICH in C-ARDS patients on venovenous ECMO. Based on our experience, we postulate that bivalirudin may represent a safer strategy for anticoagulation in C-ARDS patients on VV-ECMO. Further study with prospective clinical trials is warranted to confirm these findings.

PURPOSE: Prolonged duration of invasive mechanical ventilation (IMV) prior to veno-venous extracorporeal membrane oxygenation (VV-ECMO) initiation has been associated with poor clinical outcomes.It has also been proposed that spontaneously breathing patients with acute respiratory distress syndrome are at risk of self-inflicted lung injury.The impact of the duration of non-invasive respiratory support (RS) including high-flow nasal cannula and non-invasive positive pressure ventilation prior to the initiation of ECMO is not known.We hypothesized prolonged RS is a risk factor for worse outcomes in patients with severe COVID-19 that require ECMO support. METHODS:We reviewed data of all patients with COVID-19 treated with ECMO at two high-volume tertiary care centers.Patients were stratified by the duration of RS received prior to ECMO initiation.Survival analysis with the Kaplan-Meier method and the Cox proportional hazards model were used to compare the effect of duration of RS on liberation from ECMO and secondary outcomes included in-hospital mortality, liberation from mechanical ventilation, and hospital discharge.Sensitivity analysis with Fine-Gray regression was also performed to account for the competing risk of death for relevant endpoints.RESULTS: 78 patients with COVID-19 required ECMO support.The median duration of RS and IMV prior to ECMO was 2 days (IQR: 0, 6) and 2.5 days (IQR: 1, 5) respectively.The median duration of ECMO support was 24 days and 57.1% (N¼44) remained alive at the time of censure.In univariate analysis, duration of RS prior was associated with a reduced rate of subsequent ECMO liberation (HR: 0.91; 95% CI: 0.85-0.98).Duration of IMV prior to ECMO was not statistically associated with ECMO liberation (HR: 0.96; 95% CI: 0.87-1.06).Patients were stratified by the median duration of RS in the cohort.Those that received RS for $3 days were significantly less likely to be liberated from ECMO (HR: 0.46; 95% CI: 0.26-0.83),IMV (HR: 0.42; 95% CI: 0.20-0.89),or be discharged from the hospital (HR: 0.52; 95% CI: 0.27-0.99)compared to patients that received RS for <3 days.There was no difference in hospital mortality between the groups (HR: 1.12; 95% CI: 0.56-2.26).These relationships persisted when the Cox model was adjusted for age and gender and when death was treated as a competing risk. CONCLUSIONS:In our cohort of severely ill patients with COVID-19 requiring ECMO, $3 days of RS prior to ECMO initiation was associated with a 50% reduction in the rate of liberation from ECMO, IMV, and subsequent hospital discharge.Prolonged duration of RS prior to ECMO may result in lung injury and worse subsequent outcomes. CLINICAL IMPLICATIONS:In patients with severe COVID-19 meeting institutional criteria for ECMO utilization, earlier initiation of IMV and ECMO and avoidance of prolonged use of RS may improve outcomes.

Objective: The successful use of ECMO in adult patients with severe respiratory failure from COVID-19 has been reported, but there is little data in children or adolescents except those with cardiac manifestations. Thus, the utility of ECMO in pediatric patients with severe respiratory failure is not well established. Describe the clinical course and outcome of three pediatric patients with COVID-19 who progressed to Acute Respiratory Distress Syndrome (ARDS) requiring ECMO. Methods: Data related to demographics, clinical course, ECMO course and outcome from three consecutive pediatric patients who received venovenous (VV) ECMO due to COVID-19-associated respiratory failure were analyzed from electronic health records. IRB approval was given. Results: We describe three patients (see Figure 1) aged 14 to 16 who all had acute COVID-19 leading to the acute respiratory distress syndrome - one patient whose father died from COVID following ECMO and two brothers. The patients presented between days 4 and 10 of symptoms and rapidly required escalation of care including intubation, nitric oxide and VV ECMO. All three patients were treated with methylprednisolone, though with differing regimens;two received remdesivir through a clinical trial;and two required tracheostomy placement for respiratory support, with one having the tracheostomy tube removed prior to discharge. ECMO was continued for 9 to 24 days, with no episodes of recannulation, major bleeding events or other complications from the ECMO therapy. All three patients were eventually discharged;two were discharged home and one transferred to acute rehabilitation. Conclusions: These cases show the safe and effective use of VV ECMO in COVID-19-associated ARDS. Pediatric critical care physicians should be aware of the ability to use VV ECMO for pulmonary support in patients with COVID-19 illness and should consider early transfer to ECMO capable units to improve survival from ARDS related mortality.

As the world learned about Covid-19, the application of ECMO also evolved as health systems in the United States had some time to prepare.We report our initial experience using extracorporeal support for Covid-19 patients with the resource challenges that attend a worldwide pandemic. Background:Extracorporeal support has improved survival in select neonatal and pediatric patients for over forty years.Over the last two decades, extracorporeal membrane oxygenation (ECMO) has emerged as an acceptable and potentially beneficial rescue modality in select adult populations.In severe respiratory failure, ECMO provides time for the lungs to rest and recover by augmenting gas exchange with the extracorporeal circuit.A review of the outcomes in patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) treated with ECMO demonstrated a decrease in hospital mortality rate and length of intensive care unit (ICU) stay compared to those managed with conventional therapy alone (1).Early reports regarding the use of ECMO in patients with Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-COV-2 or Covid-19) pneumonia have been mixed.Despite the similarities of MERS-CoV and the current novel coronavirus disease, recent reports have raised concerns regarding the high mortality rates observed in an early series of ECMO supported Covid-19 patients (2, 3).Similarly, a pooled analysis of five recent studies (4, 5, 6, 7, 8) suggested ECMO produced neither harm nor benefit in Covid-19 patients with ARDS.The authors of these analysis compared mortality in patients supported with ECMO for both MERS and Covid-19 and concluded Covid-19 patients had a significantly higher mortality than MERS (94.1% vs. 65.0%)when treated with ECMO.The authors further state that this data raises "questions about the real utility of ECMO in this outbreak" (8).Initial reports from United States hospital systems that had been both surprised and overrun with critically ill Covid-19 patients, demonstrated unfavorable results with supporting patients with ECMO, leading centers to abandon this support modality for these patients (9).We present a single-center analysis and preliminary outcomes regarding the use of ECMO in 15 patients with severe respiratory failure due to Covid-19 all of which had failed maximal conventional ventilatory management and interventions as presented.These initial promising results prompted communication of our experience, despite its preliminary nature.