Directed Hypercapnia as a Strategy to Wean Extracorporeal Membrane Oxygenation in COVID-19 Pneumonia.

Coronavirus disease 2019 pneumonia with respiratory failure refractory to maximum medical therapy has been successfully managed with venovenous extracorporeal membrane oxygenation. This report describes a process of using directed hypercapnia in 5 patients to wean them from prolonged extracorporeal support secondary to refractory hypercarbic respiratory failure.

Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Extracorporeal membrane oxygenation for respiratory failure in phases of COVID-19 variants.

BACKGROUND: Adaptive mutations of the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) virus have emerged throughout the coronavirus disease 2019 (COVID-19) pandemic. The characterization of outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory distress from COVID-19 during the peak prevalence of different variants is not well known. METHODS: There were 131 patients with laboratory-confirmed SARS-CoV-2 infection supported by ECMO at two referral centers within a large healthcare system. Three predominant variant phase time windows (Pre-Alpha, Alpha, and Delta) were determined by a change-point analyzer based on random population sampling and viral genome sequencing. Patient demographics and outcomes were compared. RESULTS: The average age of patients was 46.9 ± 10.5 years and 70.2% (92/131) were male. Patients cannulated for ECMO during the Delta variant wave were younger compared to earlier Pre-Alpha (39.3 ± 7.8 vs. 48.0 ± 11.1 years) and Alpha phases (39.3 ± 7.8 vs. 47.2 ± 7.7 years) (p < .01). The predominantly affected race in the Pre-Alpha phase was Hispanic (52.2%; 47/90), while in Alpha (61.5%; 16/26) and Delta (40%; 6/15) variant waves, most patients were White (p < .01). Most patients received a tracheostomy (82.4%; 108/131) with a trend toward early intervention in later phases compared to Pre-Alpha (p < .01). There was no significant difference between the duration of ECMO, mechanical support, intensive care unit (ICU) length of stay (LOS), or hospital LOS over the three variant phases. The in-hospital mortality was overall 41.5% (54/131) and was also similar. Six-month survival of patients who survived to discharge was 92.2% (71/77). CONCLUSIONS: There was no significant difference in survival or time on ECMO support in patients during the peak prevalence of the three variants.

Blood Product Utilization in Patients With COVID-19 on ECMO.

INTRODUCTION: Although extracorporeal membrane oxygenation (ECMO) has been associated with improved outcomes in COVID patients with respiratory failure, data regarding the need for blood product utilization in this population is inadequate. METHODS: We conducted a retrospective review of all COVID patients requiring ECMO support at our facility. Patient demographics, co-morbidities, measures of acuity, and blood product utilization were identified. Patients were stratified by the presence of a major bleed and the need for dialysis. The primary outcome was blood product utilization. Linear regression models were used to assess predictors of the need for blood products. RESULTS: From 2020 to 2021, 41 patients with COVID-19 were included in our study. Overall 1601 d of support, COVID ECMO patients received 755 units of packed red blood cells (PRBC), 51 units of fresh frozen plasma (FFP), 326 platelets, and 1702 cryoprecipitate, amounting to 18.4 units PRBC per patient or 3.30 units per week of ECMO support. Both major bleeding and the need for dialysis were associated with higher rates of transfusion of PRBC, FFP, and platelets. The average non-bleeding COVID ECMO patient who did not need dialysis required 2.17 units of PRBC, 0.12 units of FFP, 0.76 platelets, and 8.36 of cryoprecipitate per week of ECMO support. On multivariable linear regression analysis, each day on ECMO was associated with 0.30 [0.19-0.42, P < 0.01] units of PRBC. CONCLUSIONS: In conclusion, COVID ECMO is associated with a significant need for blood and blood products. Major bleeding and dialysis are important drivers of blood product requirements.

Treatment of acute respiratory distress syndrome from COVID-19 with extracorporeal membrane oxygenation in obstetrical patients.

BACKGROUND: Extracorporeal membrane oxygenation therapy has been used as a rescue therapy for patients with severe acute respiratory distress syndrome from COVID-19 who have failed conventional ventilatory strategies. Little is known about the outcome of pregnant and postpartum patients on extracorporeal membrane oxygenation therapy. OBJECTIVE: To describe the medical and surgical outcomes of pregnant and postpartum patients who were placed on extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome from COVID-19. STUDY DESIGN: A case series reviewing pregnant or postpartum patients with laboratory-confirmed COVID-19 who were placed on extracorporeal membrane oxygenation therapy was conducted within the Baylor Scott & White Healthcare system. The demographics and the medical and surgical outcomes were collected and reviewed. RESULTS: Between March 2020 and October 2021, 5 pregnant and 5 postpartum women were supported with venovenous extracorporeal membrane oxygenation therapy. The median age was 30 years (interquartile range, 26-33.5) and the median body mass index was 36.6 kg/m2 (interquartile range, 29.5-42.0). There was a median of 4.5 days (interquartile range, 1.5-6.8) from admission to any hospital to intubation and 9 days (interquartile range, 7-13) to extracorporeal membrane oxygenation therapy cannulation. One patient had an ischemic stroke, 1 patient had a presumed hemorrhagic stroke, and 9 patients developed bleeding while on extracorporeal membrane oxygenation therapy. Of the 5 pregnant women, 2 patients had intrauterine fetal demise and 3 underwent delivery for maternal hemodynamic instability. The 5 postpartum women were initiated on extracorporeal membrane oxygenation therapy a median of 10 days (interquartile range, 3-11) after delivery. The median length of time on extracorporeal membrane oxygenation therapy was 22 days (interquartile range, 11-31). At the time of the study, there were 2 inpatient mortalities, 6 patients survived to discharge from the extracorporeal membrane oxygenation therapy hospital, and 2 patients were still admitted. CONCLUSION: There is limited information regarding the use of extracorporeal membrane oxygenation therapy for COVID-19 acute respiratory distress syndrome in obstetrical patients. This case series describes the use of extracorporeal membrane oxygenation therapy and survival in pregnant and postpartum patients with COVID-19.

Outcomes of Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Distress Syndrome Caused by COVID-19 Versus Influenza.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be effective for refractory acute respiratory distress syndrome (ARDS) in patients with influenza, but its utility in patients with coronavirus disease 2019 (COVID-19) is uncertain. We compared outcomes of patients with refractory ARDS from COVID-19 and influenza placed on ECMO. METHODS: We conducted a retrospective analysis of 120 patients with refractory ARDS due to COVID-19 or influenza placed on ECMO at 2 referral centers from January 2013 to October 2020. Patient characteristics and clinical outcomes were compared. The primary endpoint was survival to discharge. RESULTS: Baseline characteristics and comorbidities were similar. During the study period, 53 patients with COVID-19 and 67 patients with influenza were supported. Venovenous ECMO was the predominant initial cannulation strategy in both groups (COVID 92.5% vs influenza 95.5%; P = .5). Survival to hospital discharge was 62.3% (33 of 53 patients) in the COVID-19 group and 64.2% (43 of 67 patients) in the influenza group (P = .8). In patients successfully decannulated, median length of time on ECMO was longer in COVID-19 patients (14 [interquartile range (IQR), 9-30] days vs influenza 10.5 [IQR, 6.8-14.3] days; P = .004). Among patients discharged alive, COVID-19 patients had longer overall length of stay (COVID-19 37 [IQR, 27-62] days vs influenza 13.5 [IQR, 9.3-24] days; P = .007). CONCLUSIONS: In patients with refractory ARDS from COVID-19 or influenza placed on ECMO, there was no significant difference in survival to hospital discharge. In patients surviving to decannulation, the duration of ECMO support and total length of stay were longer in COVID-19 patients.

Venovenous extracorporeal membrane oxygenation for patients with refractory coronavirus disease 2019 (COVID-19): Multicenter experience of referral hospitals in a large health care system.

BACKGROUND: The benefit of extracorporeal membrane oxygenation (ECMO) for patients with severe acute respiratory distress from coronavirus disease 2019 refractory to medical management and lung-protective mechanical ventilation has not been adequately determined. METHODS: We reviewed the clinical course of 37 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection supported by venovenous ECMO at 4 ECMO referral centers within a large health care system. Patient characteristics, progression of hemodynamics and inflammatory markers, and clinical outcomes were evaluated. RESULTS: The patients had median age of 51 years (interquartile range, 40-59), and 73% were male. Peak plateau pressures, vasopressor requirements, and arterial partial pressure of carbon dioxide all improved with ECMO support. In our patient population, 24 of 37 patients (64.8%) survived to decannulation and 21 of 37 patients (56.8%) survived to discharge. Among patients discharged alive from the ECMO facility, 12 patients were discharged to a long-term acute care or rehabilitation facility, 2 were transferred back to the referring hospital for ventilatory weaning, and 7 were discharged directly home. For patients who were successfully decannulated, median length of time on ECMO was 17 days (interquartile range, 10-33.5). CONCLUSIONS: Venovenous ECMO represents a useful therapy for patients with refractory severe acute respiratory distress syndrome from coronavirus disease 2019.