Extracorporeal Membrane Oxygenation for COVID-19: Collaborative Experience From the Texas Medical Center in Houston With 2 Years Follow-Up.

Patients with severe refractory hypoxemic respiratory failure may benefit from extracorporeal membrane oxygenation (ECMO) for salvage therapy. The Coronavirus disease 2019 (COVID-19) pandemic offered three high-volume independent ECMO programs at a large medical center the chance to collaborate to optimize ECMO care at the beginning of the pandemic in Spring 2020. Between March 15, 2020, and May 30, 2020, 3,615 inpatients with COVID-19 were treated at the Texas Medical Center. During this time, 35 COVID-19 patients were cannulated for ECMO, all but one in a veno-venous configuration. At hospital discharge, 23 (66%) of the 35 patients were alive. Twelve patients died of vasodilatory shock (n = 9), intracranial hemorrhage (n = 2), and cannulation-related bleeding and multiorgan dysfunction (n = 1). The average duration of ECMO was 13.6 days in survivors and 25.0 days in nonsurvivors ( p < 0.04). At 1 year follow-up, all 23 discharged patients were still alive, making the 1 year survival rate 66% (23/35). At 2 years follow-up, the overall rate of survival was 63% (22/35). Of those patients who survived 2 years, all were at home and alive and well at follow-up.

Extracorporeal membrane oxygenation as rescue therapy for severe hypoxemic respiratory failure.

Extracorporeal membrane oxygenation (ECMO) has been used for more than 50 years as salvage therapy for patients with severe cardiopulmonary failure refractory to conventional treatment. ECMO was first used in the 1960s to treat hypoxemic respiratory failure in newborns. On the basis of its success in that population, ECMO began to be used in the early 1970s to treat adult hypoxemic respiratory failure. However, outcomes for adults were, somewhat perplexingly, quite poor. By the 1980s, use of ECMO for severe hypoxemia was rare outside of the pediatric population. ECMO technology, however, continued to evolve and improve. Multiple case reports and small series describing ECMO use as rescue for adults with severe hypoxemia from various lung pathologies have appeared in the literature over the past three decades. Adult respiratory distress syndrome (ARDS) is often the final common pathway of various pathologies affecting adults and causing hypoxemic respiratory failure. It is prevalent in intensive care units throughout the world and has, since it was first described in 1967, carried a high mortality. No specific therapy for ARDS has been found, and current care is supportive, primarily by mechanical ventilation. Results from recent randomized controlled trials, however, suggest that ECMO may have a place in the treatment of these patients. This article reviews these studies and recommends adding severe ARDS to the list of established indications for ECMO in patients with hypoxemic respiratory failure.

Evaluation of a heparin monitoring protocol for extracorporeal membrane oxygenation and review of the literature.

BACKGROUND: Bleeding complications are common with extracorporeal membrane oxygenation (ECMO). We investigated whether a heparin monitoring protocol using activated partial thromboplastin time (aPTT) and thromboelastography (TEG) affected clinical outcomes. METHODS: This retrospective chart review stratified cohorts by study interval: pre-protocol (January 2016-March 2017) or post-protocol (March 2017-December 2017). The protocol defined therapeutic anticoagulation as aPTT of 60-80 seconds and a TEG reaction (TEG-R) time of 2-4× baseline; pre-protocol management used aPTT alone. The primary endpoints were the rates of bleeding and thrombotic events (clinical/device thrombosis) as defined by Extracorporeal Life Support Organization (ELSO) guidelines. Secondary endpoints included time in therapeutic aPTT range, rate of physician compliance with the protocol, time to heparin initiation, intensive care unit length of stay, mortality, and antithrombin III (ATIII) supplementation. RESULTS: The pre-protocol (n=72) and post-protocol (n=51) groups (age 60±12 years; 80% on venoarterial ECMO; average ECMO duration of 6 days) showed no difference in baseline characteristics. Major bleeding events occurred in 69% of pre-protocol patients, versus 67% of post-protocol patients (P=0.85). The post-protocol group had fewer retroperitoneal bleeds (P=0.01) and had a non-significantly lower rate of pulmonary or central nervous system (CNS) bleeding (P=0.07). Thrombotic events occurred in 21% of the pre-protocol group, versus 28% of the post-protocol group (P=0.39). Mortality during ECMO support was significantly lower in the post-protocol group (56.9% vs. 33.3%, P=0.01). The thrombosis rate was higher in patients who received ATIII than in those who did not (48.2% vs. 15.9%, P<0.01). CONCLUSIONS: Major bleeding did not differ between the treatment groups. However, we observed significantly less mortality and retroperitoneal bleeding in the post-protocol group, suggesting an important gain from the intervention. Further study of the value of ATIII supplementation in ECMO patients is needed since we observed that a lower baseline ATIII level may indicate higher risk for thrombosis.

Proposed diagnostic criteria for the case definition of amniotic fluid embolism in research studies.

Amniotic fluid embolism is a leading cause of maternal mortality in developed countries. Our understanding of risk factors, diagnosis, treatment, and prognosis is hampered by a lack of uniform clinical case definition; neither histologic nor laboratory findings have been identified unique to this condition. Amniotic fluid embolism is often overdiagnosed in critically ill peripartum women, particularly when an element of coagulopathy is involved. Previously proposed case definitions for amniotic fluid embolism are nonspecific, and when viewed through the eyes of individuals with experience in critical care obstetrics, would include women with a number of medical conditions much more common than amniotic fluid embolism. We convened a working group under the auspices of a committee of the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation whose task was to develop uniform diagnostic criteria for the research reporting of amniotic fluid embolism. These criteria rely on the presence of the classic triad of hemodynamic and respiratory compromise accompanied by strictly defined disseminated intravascular coagulopathy. It is anticipated that limiting research reports involving amniotic fluid embolism to women who meet these criteria will enhance the validity of published data and assist in the identification of risk factors, effective treatments, and possibly useful biomarkers for this condition. A registry has been established in conjunction with the Perinatal Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development to collect both clinical information and laboratory specimens of women with suspected amniotic fluid embolism in the hopes of identifying unique biomarkers of this condition.

Randomized, double-blind pilot study of transendocardial injection of autologous aldehyde dehydrogenase-bright stem cells in patients with ischemic heart failure.

BACKGROUND: The optimal type of stem cell for use in patients with ischemic heart disease has not been determined. A primitive population of bone marrow-derived hematopoietic cells has been isolated by the presence of the enzyme aldehyde dehydrogenase and comprises a multilineage mix of stem and progenitor cells. Aldehyde dehydrogenase-bright (ALDH(br)) cells have shown promise in promoting angiogenesis and providing perfusion benefits in preclinical ischemia studies. We hypothesize that ALDH(br) cells may be beneficial in treating ischemic heart disease and thus conducted the first randomized, controlled, double-blind study to assess the safety of the transendocardial injection of autologous ALDH(br) cells isolated from the bone marrow in patients with advanced ischemic heart failure. METHODS: Aldehyde dehydrogenase-bright cells were isolated from patients' bone marrow on the basis of the expression of a functional (aldehyde dehydrogenase) marker. We enrolled 20 patients (treatment, n = 10; control, n = 10). Safety (primary end point) and efficacy (secondary end point) were assessed at 6 months. RESULTS: No major adverse cardiovascular or cerebrovascular events occurred in ALDH(br)-treated patients in the periprocedural period (up to 1 month); electromechanical mapping-related ventricular tachycardia (n = 2) and fibrillation (n = 1) occurred in control patients. Aldehyde dehydrogenase-bright-treated patients showed a significant decrease in left ventricular end-systolic volume at 6 months (P = .04) and a trend toward improved maximal oxygen consumption. The single photon emission computed tomography delta analysis showed a trend toward significant improvement in reversibility in cell-treated patients (P = .053). CONCLUSIONS: We provide preliminary evidence that treatment with the novel cell population, ALDH(br) cells, is safe and may provide perfusion and functional benefits in patients with chronic myocardial ischemia.

A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF).

BACKGROUND: Autologous bone marrow mononuclear cell (ABMMNC) therapy has shown promise in patients with heart failure (HF). Cell function analysis may be important in interpreting trial results. METHODS: In this prospective study, we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF. Efficacy was assessed by maximal myocardial oxygen consumption, single photon emission computed tomography, 2-dimensional echocardiography, and quality-of-life assessment (Minnesota Living with Heart Failure and Short Form 36). We also characterized patients' bone marrow cells by flow cytometry, colony-forming unit, and proliferative assays. RESULTS: Cell-treated (n = 20) and control patients (n = 10) were similar at baseline. The procedure was safe; adverse events were similar in both groups. Canadian Cardiovascular Society angina score improved significantly (P = .001) in cell-treated patients, but function was not affected. Quality-of-life scores improved significantly at 6 months (P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36) over baseline in cell-treated but not control patients. Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients. The proportion of fixed defects significantly increased in control (P = .02) but not in treated patients (P = .16). Function of patients' bone marrow mononuclear cells was severely impaired. Stratifying cell results by age showed that younger patients (≤60 years) had significantly more mesenchymal progenitor cells (colony-forming unit fibroblasts) than patients >60 years (20.16 ± 14.6 vs 10.92 ± 7.8, P = .04). Furthermore, cell-treated younger patients had significantly improved maximal myocardial oxygen consumption (15 ± 5.8, 18.6 ± 2.7, and 17 ± 3.7 mL/kg per minute at baseline, 3 months, and 6 months, respectively) compared with similarly aged control patients (14.3 ± 2.5, 13.7 ± 3.7, and 14.6 ± 4.7 mL/kg per minute, P = .04). CONCLUSIONS: ABMMNC therapy is safe and improves symptoms, quality of life, and possibly perfusion in patients with chronic HF.