Extracorporeal Membrane Oxygenation in Patients With COVID-19:An International Multicenter Cohort Study

BACKGROUND: To report and compare the characteristics and outcomes of COVID-19 patients on extracorporeal membrane oxygenation (ECMO) to non-COVID-19 acute respiratory distress syndrome (ARDS) patients on ECMO. METHODS: We performed an international retrospective study of COVID-19 patients on ECMO from 13 intensive care units from March 1 to April 30, 2020. Demographic data, ECMO characteristics and clinical outcomes were collected. The primary outcome was to assess the complication rate and 28-day mortality; the secondary outcome was to compare patient and ECMO characteristics between COVID-19 patients on ECMO and non-COVID-19 related ARDS patients on ECMO (non-COVID-19; January 1, 2018 until July 31, 2019). RESULTS: During the study period 71 COVID-19 patients received ECMO, mostly veno-venous, for a median duration of 13 days (IQR 7-20). ECMO was initiated at 5 days (IQR 3-10) following invasive mechanical ventilation. Median PaO(2)/FiO(2) ratio prior to initiation of ECMO was similar in COVID-19 patients (58 mmHg [IQR 46-76]) and non-COVID-19 patients (53 mmHg [IQR 44-66]), the latter consisting of 48 patients. 28-day mortality was 37% in COVID-19 patients and 27% in non-COVID-19 patients. However, Kaplan-Meier curves showed that after a 100-day follow-up this non-significant difference resolves. Non-surviving COVID-19 patients were more acidotic prior to initiation ECMO, had a shorter ECMO run and fewer received muscle paralysis compared to survivors. CONCLUSIONS: No significant differences in outcomes were found between COVID-19 patients on ECMO and non-COVID-19 ARDS patients on ECMO. This suggests that ECMO could be considered as a supportive therapy in case of refractory respiratory failure in COVID-19

Plasma Transfusion and Procoagulant Product Administration in Extracorporeal Membrane Oxygenation:A Secondary Analysis of an International Observational Study on Current Practices

OBJECTIVES: To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO.DESIGN: A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications. SETTING: Sixteen international ICUs.PATIENTS: Adult patients on VA-ECMO or VV-ECMO.INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 420 VA-ECMO patients, 59% (n = 247) received plasma, 20% (n = 82) received fibrinogen concentrate, 17% (n = 70) received TXA, and 7% of patients (n = 28) received PCC. Fifty percent of patients (n = 208) suffered bleeding complications and 27% (n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p &lt; 0.001), fibrinogen concentrate (28% vs 11%, p &lt; 0.001), and TXA (23% vs 10%, p &lt; 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% (n = 81) received plasma, 6% (n = 12) fibrinogen concentrate, 7% (n = 14) TXA, and 5% (n = 10) PCC. Thirty-nine percent (n = 80) of VV-ECMO patients suffered bleeding complications and 23% (n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p &lt; 0.001), fibrinogen concentrate (13% vs 2%, p &lt; 0.01), and TXA (11% vs 2%, p &lt; 0.01). CONCLUSIONS: The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided.</p

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19-Induced Acute Respiratory Distress Syndrome: An Inverse Probability Weighted Analysis

IMPORTANCE: Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19-induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN, SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a "control" non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19-related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19-associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27; 95% CI, 0.82-1.98; p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19-Induced Acute Respiratory Distress Syndrome:An Inverse Probability Weighted Analysis

IMPORTANCE: Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19-induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN, SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a "control" non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19-related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19-associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27; 95% CI, 0.82-1.98; p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study

Abstract Background Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO. Methods This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018–Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100–150·109/L), moderate (50–100·109/L) and severe (< 50·109/L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models. Results Of the 419 patients included, median platelet count at admission was 179·109/L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9–56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34–360). Conclusions Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding. Trial registration: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45–62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5–14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8g/dL (8.9–13.0g/dL), decreasing to 8.7g/dL (7.7–9.8g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1g/dL [7.4–9.3g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3–2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation:A multicenter retrospective observational cohort study

BACKGROUND: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients. METHODS: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run &gt;24?h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion. RESULTS: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5?days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders. CONCLUSION: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45–62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5–14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8g/dL (8.9–13.0g/dL), decreasing to 8.7g/dL (7.7–9.8g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1g/dL [7.4–9.3g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3–2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45–62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5–14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8g/dL (8.9–13.0g/dL), decreasing to 8.7g/dL (7.7–9.8g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1g/dL [7.4–9.3g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3–2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation