How I manage differential gas exchange in peripheral venoarterial extracorporeal membrane oxygenation.

Dual circulation is a common but underrecognized physiological occurrence associated with peripheral venoarterial extracorporeal membrane oxygenation (ECMO). Competitive flow will develop between blood ejected from the heart and blood travelling retrograde within the aorta from the ECMO reinfusion cannula. The intersection of these two competitive flows is referred to as the "mixing point". The location of this mixing point, which depends upon the relative strengths of the native and extracorporeal pumps, will determine which regions of the body are perfused with blood ejected from the left ventricle and which regions are perfused by reinfused blood from the ECMO circuit, effectively establishing dual circulations. Because gas exchange within these circulations is dictated by the native lungs and membrane lung, respectively, oxygenation and carbon dioxide removal may differ between regions-depending on how well gas exchange is preserved within each circulation-potentially leading to differential oxygenation or differential carbon dioxide, each of which may have important clinical implications. In this perspective, we address the identification and management of dual circulation and differential gas exchange through various clinical scenarios of venoarterial ECMO. Recognition of dual circulation, proper monitoring for differential gas exchange, and understanding the various strategies to resolve differential oxygenation and carbon dioxide may allow for more optimal patient management and improved clinical outcomes.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

Ten-year outcomes of extracorporeal life support for in-hospital cardiac arrest at a tertiary center.

Extracorporeal cardiopulmonary resuscitation (ECPR) is controversial, given both the lack of evidence for improved outcomes and clarity on appropriate candidacy during time-sensitive cardiac arrest situations. The primary objective of our study was to identify factors predicting successful outcomes in ECPR patients.Between March 2007 and November 2018, 112 patients were placed on extracorporeal life support (ECLS) during active CPR (ECPR) at our institution. The primary outcome was survival to hospital discharge. Survivors and non-survivors were compared in terms of pre-cannulation comorbidities, laboratory values, and overall outcomes. Multivariable logistic regression was used to identify pre-cannulation predictors of in-hospital mortality. Among 112 patients, 44 (39%) patients survived to decannulation and 31 (28%) survived to hospital discharge. The median age was 60 years (IQR 45-72) with a median ECLS duration of 2.2 days (IQR 0.6-5.1). Patients who survived to discharge had lower rates of chronic kidney disease than non-survivors (19% vs. 41%, p = 0.046) and lower baseline creatinine values [median 1.2 mg/dL (IQR 0.8-1.7) vs. 1.7 (0.7-2.7), p = 0.008]. Median duration from CPR initiation to cannulation was 40 min (IQR 30-50) with no difference between survivors and non-survivors (p = 0.453). When controlling for age and CPR duration, multivariable logistic regression with pre-procedural risk factors identified pre-arrest serum creatinine as an independent predictor of mortality [OR 3.25 (95% CI 1.22-8.70), p = 0.019] and higher pre-arrest serum albumin as protective [OR 0.32 (95% CI 0.14-0.74), p = 0.007]. In our cohort, pre-arrest creatinine and albumin were independently predictive of in-hospital mortality during ECPR, while age and CPR duration were not.

Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

BACKGROUND: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. METHODS: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. FINDINGS: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5). INTERPRETATION: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. FUNDING: None.

Increasing Opportunity for Lung Transplant in Interstitial Lung Disease With Pulmonary Hypertension.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation for end-stage interstitial lung disease (ILD) and pulmonary hypertension (PH) has varying results based on ECMO configuration. We compare our experience using venovenous (VV) and venoarterial (VA) ECMO bridge to transplantation for ILD with PH on survival to successful transplantation. METHODS: A single-center retrospective review was done of patients with ILD and secondary PH who were placed on either VV or VA ECMO as bridge to transplantation from 2010 to 2016. Comparisons for factors associated with survival to transplantation between VV and VA ECMO strategies were made using Cox proportional hazards model. Subgroup analysis included comparisons of VV ECMO patients who remained on VV or were converted to VA ECMO. RESULTS: A total of 50 patients with ILD and PH were treated initially with either VV (n = 19) or VA (n = 31) ECMO as bridge to lung transplantation. Initial VA ECMO had a significantly higher survival to transplantation compared with initial VV ECMO (p = 0.03). Cox proportional hazards modeling showed a 59% reduction in risk of death for VA compared with VV ECMO (hazard reduction 0.41, 95% confidence interval: 0.18 to 0.92, p = 0.03). Patients converted from VV to VA ECMO had significantly longer survival awaiting transplant than patients who remained on VV ECMO (p = 0.03). Ambulation on ECMO before transplantation was associated with an 80% reduction in the risk of death (hazard reduction 0.20, 95% confidence interval: 0.08 to 0.48, p < 0.01). CONCLUSIONS: Venoarterial ECMO upper body configuration for patients with end stage ILD and PH significantly improves overall survival to transplantation.

Extracorporeal membrane oxygenation in the management of diffuse alveolar hemorrhage.

Extracorporeal membrane oxygenation (ECMO) may be used to support patients with severe hypoxemic respiratory failure refractory to conventional mechanical ventilation. However, because systemic anticoagulation is generally required to maintain circuit patency, severe bleeding is often seen as a contraindication to ECMO. We describe our center's experience with four patients who received ECMO for refractory hypoxemic respiratory failure due to diffuse alveolar hemorrhage (DAH), a condition for which anticoagulation is typically contraindicated, and provide a review of the literature. The mean age was 35.8 ± 16.4 years. The mean pre-ECMO PaO2 to FIO2 ratio was 52.3 ± 9.4 mm Hg. All patients were treated with continuous infusions of heparin with a goal-activated partial thromboplastin time between 40 and 60 seconds (mean, 47.4 ± 11.6 seconds). All four subjects (100%) survived to decannulation, and three subjects (75%) survived to discharge. The results from this case series, along with previously published data, suggest that ECMO is a reasonable management option for patients with DAH-associated severe, refractory hypoxemic respiratory failure. This is especially true in the era of modern ECMO technology where lower levels of anticoagulation are able to maintain circuit patency while minimizing bleeding risk.

Blood conservation in extracorporeal membrane oxygenation for acute respiratory distress syndrome.

BACKGROUND: Extracorporeal membrane oxygenation support (ECMO) typically requires multiple blood transfusions and is associated with frequent bleeding complications. Blood transfusions are known to increase morbidity and mortality in critically ill patients, which may extend to patients receiving ECMO. Aiming to reduce transfusion requirements, we implemented a blood conservation protocol in adults with severe acute respiratory distress syndrome (ARDS) receiving ECMO. METHODS: This was a retrospective study of adults receiving ECMO for ARDS after initiation of a blood conservation protocol that included a transfusion trigger of hemoglobin of less than 7.0 g/dL, use of low-dose anticoagulation targeting an activated partial thromboplastin time of 40 to 60 seconds, and autotransfusion of circuit blood during decannulation. The primary objective was to evaluate transfusion requirements during ECMO support. Clinical outcomes included survival, neurologic function, renal function, bleeding, and thrombotic complications. RESULTS: The analysis included 38 patients; of these, 24 (63.2%) received a transfusion while receiving ECMO. Median hemoglobin was 8.29 g/dL. A median of 1.0 units (range, 250 to 300 mL) was transfused during ECMO support over a median duration of 9.0 days, equivalent to 0.11 U/d (range, 27.5 to 33.3 mL/d). The median activated partial thromboplastin time was 46.5 seconds. Bleeding occurred in 10 patients (26.3%); severe bleeding occurred in 2 patients (5.3%). Twenty-eight patients (73.7%) survived to hospital discharge. CONCLUSIONS: Implementation of a blood conservation protocol in adults receiving ECMO for ARDS resulted in lower transfusion requirements and bleeding complications than previously reported in the literature and was associated with comparable survival and organ recovery.

ECMO for adult respiratory failure: current use and evolving applications.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used to support adults with severe forms of respiratory failure. Fueling the explosive growth is a combination of technological improvements and accumulating, although controversial, evidence. Current use of ECMO extends beyond its most familiar role in the support of patients with severe acute respiratory distress syndrome (ARDS) to treat patients with various forms of severe hypoxemic or hypercapnic respiratory failure, ranging from bridging patients to lung transplantation to managing pulmonary hypertensive crises. The role of ECMO used primarily for extracorporeal carbon dioxide removal (ECCO2R) in the support of patients with hypercapnic respiratory failure and less severe forms of ARDS is also evolving. Select patients with respiratory failure may be liberated from invasive mechanical ventilation altogether and some may undergo extensive physical therapy while receiving extracorporeal support. Current research may yield a true artificial lung with the potential to change the paradigm of treatment for adults with chronic respiratory failure.

Early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study.

INTRODUCTION: Critical illness is a well-recognized cause of neuromuscular weakness and impaired physical functioning. Physical therapy (PT) has been demonstrated to be safe and effective for critically ill patients. The impact of such an intervention on patients receiving extracorporeal membrane oxygenation (ECMO) has not been well characterized. We describe the feasibility and impact of active PT on ECMO patients. METHODS: We performed a retrospective cohort study of 100 consecutive patients receiving ECMO in the medical intensive care unit of a university hospital. RESULTS: Of the 100 patients receiving ECMO, 35 (35%) participated in active PT; 19 as bridge to transplant and 16 as bridge to recovery. Duration of ECMO was 14.3 ± 10.9 days. Patients received 7.2 ± 6.5 PT sessions while on ECMO. During PT sessions, 18 patients (51%) ambulated (median distance 175 feet, range 4 to 2,800) and 9 patients were on vasopressors. Whilst receiving ECMO, 23 patients were liberated from invasive mechanical ventilation. Of the 16 bridge to recovery patients, 14 (88%) survived to discharge; 10 bridge to transplant patients (53%) survived to transplantation, with 9 (90%) surviving to discharge. Of the 23 survivors, 13 (57%) went directly home, 8 (35%) went to acute rehabilitation, and 2 (9%) went to subacute rehabilitation. There were no PT-related complications. CONCLUSIONS: Active PT, including ambulation, can be achieved safely and reliably in ECMO patients when an experienced, multidisciplinary team is utilized. More research is needed to define the barriers to PT and the impact on survival and long-term functional, neurocognitive outcomes in this population.

Extracorporeal membrane oxygenation as a novel bridging strategy for acute right heart failure in group 1 pulmonary arterial hypertension.

Patients with group 1 pulmonary arterial hypertension (PAH) and decompensated right heart failure (RHF) were not previously considered for extracorporeal membrane oxygenation (ECMO) as bridge to transplantation (BTT) or bridge to recovery (BTR) because options were limited by long transplantation wait times and perceived inability to wean ECMO. In a retrospective review, we describe our center's multidisciplinary mechanical-medical approach to ECMO as a bridging therapy for PAH (2009-2012). Suitability for ECMO was determined using a defined algorithm. Six patients (age, 32 ± 11 years) underwent mechanical-medical bridging. Two transplant-eligible patients underwent successful BTT. The four patients ineligible for transplantation underwent BTR with escalation of targeted medical therapies before weaning off ECMO. Three of four BTR patients survived to ECMO decannulation (duration, 12 ± 7; range, 7-23 days). In this single-institution experience, mechanical-medical BTT and BTR with ECMO and targeted PAH therapies were used as a novel treatment strategy to successfully manage acute RHF in PAH.

Upper-body extracorporeal membrane oxygenation as a strategy in decompensated pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disease with significant morbidity and mortality, particularly during an acute decompensation. We describe a single-center experience of three patients with severe Group 1 PAH, refractory to targeted medical therapy, in which an extubated, nonsedated, extracorporeal membrane oxygenation (ECMO) strategy with an upper-body configuration was used as a bridge to recovery or lung transplantation. All three patients were extubated within 24 hours of ECMO initiation. Two patients were successfully bridged to lung transplantation, and the other patient was optimized on targeted PAH therapy with subsequent recovery from an acute decompensation. The upper-body ECMO configuration allowed for daily physical therapy, including one patient, who would otherwise have been unsuitable for transplantation, ambulating over 850 meters daily. This series demonstrates the feasibility of using ECMO to bridge PAH patients to recovery or transplantation while avoiding the complications of immobility and invasive mechanical ventilation.

Pilot study of extracorporeal carbon dioxide removal to facilitate extubation and ambulation in exacerbations of chronic obstructive pulmonary disease.

RATIONALE: Acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring invasive mechanical ventilation (IMV) are associated with significant morbidity and mortality. Extracorporeal carbon dioxide removal (ECCO2R) may facilitate extubation and ambulation in these patients and potentially improve outcomes. OBJECTIVES: We assessed the feasibility of achieving early extubation and ambulation in subjects requiring IMV for exacerbations of COPD using single-site ECCO2R. METHODS: Five subjects with exacerbations of COPD with uncompensated hypercapnia requiring IMV were enrolled in this single-center, prospective, feasibility trial using a protocol of ECCO2R, extubation, and physical rehabilitation. The primary endpoint was extubation within 72 hours of starting ECCO2R. MEASUREMENTS AND MAIN RESULTS: Mean preintubation pH and PaCO2 were 7.23 ± 0.05 and 81.6 ± 15.9 mm Hg, respectively. All subjects met the primary endpoint (median duration, 4 h; range, 1.5-21.5 h). Mean duration of extracorporeal support was 193.0 ± 76.5 hours. Mean time to ambulation after extracorporeal initiation was 29.4 ± 12.6 hours. Mean maximal ambulation on extracorporeal support was 302 feet (range, 70-600). Four subjects were discharged home, and one underwent planned lung transplantation. Two minor bleeding complications occurred. There were no complications from mobilization on extracorporeal support. CONCLUSIONS: ECCO2R facilitates early extubation and ambulation in exacerbations of COPD requiring IMV and has the potential to serve as a new paradigm for the management of a select group of patients. Rigorous clinical trials are needed to corroborate these results and to investigate the effect on long-term outcomes and cost effectiveness over conventional management.