Subcutaneous Enoxaparin for Systemic Anticoagulation of COVID-19 Patients During Extracorporeal Life Support.
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ABSTRACT: Background
Extracorporeal membrane oxygenation, with an inherent requirement for anticoagulation to avoid circuit thrombosis, is a key element in the treatment of respiratory failure associated with COVID-19. Anticoagulation remains challenging, the standard of care being intravenous continuous administration of unfractionated heparin. Yet regimens vary. Some intensive care units in our center have successfully used enoxaparin subcutaneously in recent years and throughout the pandemic.Methods
We retrospectively analyzed adult COVID-19 patients with respiratory failure who had been systemically anticoagulated using either enoxaparin or unfractionated heparin. The choice of anticoagulant therapy was based on the standard of the intensive care unit. Defined thromboembolic and hemorrhagic events were analyzed as study endpoints.Results
Of 98 patients, 62 had received enoxaparin and 36 unfractionated heparin. All hazard ratios for the thromboembolic (3.43; 95% CI: 1.08-10.87; p = 0.04), hemorrhagic (2.58; 95% CI: 1.03-6.48; p = 0.04), and composite (2.86; 95% CI: 1.41-5.92; p = 0.007) endpoints favored enoxaparin, whose efficient administration was verified by peak levels of anti-factor Xa (median: 0.45 IU ml-1; IQR: 0.38; 0.56). Activated partial thromboplastin time as well as thrombin time differed significantly (both p<0.001) between groups mirroring the effect of unfractionated heparin.Conclusions
This study demonstrates the successful use of subcutaneous enoxaparin for systemic anticoagulation in patients with COVID-19 during extracorporeal membrane oxygenation. Our findings are to be confirmed by future prospective, randomized, controlled trials.
SUBMITTER: Wiegele M
PROVIDER: S-EPMC9309531 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe Society of Thoracic Surgeons Workforce on Critical Care and the Extracorporeal Life Support Organization sought to identify how the coronavirus disease 2019 (COVID-19) pandemic has changed the practice of venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO) programs across North America.MethodsA 26-question survey covering 6 categories (ECMO initiation, cannulation, management, anticoagulation, triage/protocols, and credentialing) was emailed to 276 North American Extracorporeal Life Support Organization centers. ECMO practices before and during the COVID-19 pandemic were compared.ResultsResponses were received from 93 (34%) programs. The percentage of high-volume (>20 cases per year) VV ECMO programs increased during the pandemic from 29% to 41% (P < .001), as did institutions requiring multiple clinicians for determining initiation of ECMO (VV ECMO, 25% to 43% [P = .001]; VA ECMO, 20% to 32% [P = .012]). During the pandemic, more institutions developed their own protocols for resource allocation (23% before to 51%; P < .001), and more programs created sharing arrangements to triage patients and equipment with other centers (31% to 57%; P < .001). Direct thrombin inhibitor use increased for both VA ECMO (13% to 18%; P = .025) and VV ECMO (12% to 24%; P = .005). Although cardiothoracic surgeons remained the primary cannulating proceduralists, VV ECMO cannulations performed by pulmonary and critical care physicians increased (13% to 17%; P = .046).ConclusionsThe Society of Thoracic Surgeons/Extracorporeal Life Support Organization collaborative survey indicated that the pandemic has affected ECMO practice. Further research on these ECMO strategies and lessons learned during the COVID-19 pandemic may be useful in future global situations.
| S-EPMC9618293 | biostudies-literature
Project description:BackgroundMultiple 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.MethodsWe 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.FindingsData 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).InterpretationIn 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.FundingNone.
| S-EPMC7518880 | biostudies-literature
Project description:Background Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity.Objective We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity.Methods This is a cohort study simulating an intention-to-treat clinical trial, by analyzing the effect on mortality of anticoagulation therapy chosen in the first 48 hours of hospitalization. We analyzed 3,625 COVID-19+ inpatients, controlling for age, gender, glomerular filtration rate, oxygen saturation, ventilation requirement, intensive care unit admission, and time period, all determined during the first 48 hours.Results Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (odds ratio [OR] 0.46, p = 0.001) and enoxaparin (OR = 0.49, p = 0.001). Therapeutic apixaban was also associated with decreased mortality (OR 0.57, p = 0.006) but was not more beneficial than prophylactic use when analyzed over the entire cohort or within D-dimer stratified categories. Higher D-dimer levels were associated with increased mortality (p < 0.0001). When adjusted for these same comorbidities within D-dimer strata, patients with D-dimer levels < 1 µg/mL did not appear to benefit from anticoagulation while patients with D-dimer levels > 10 µg/mL derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used.Conclusion We conclude that COVID-19+ patients with moderate or severe illness benefit from anticoagulation and that apixaban has similar efficacy to enoxaparin in decreasing mortality in this disease.
| S-EPMC7869055 | biostudies-literature
Project description:BackgroundOver the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date.MethodsWe retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres-ie, those using ECMO support for COVID-19 throughout 2020-we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups.FindingsIn 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1-39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0-53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4-62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70-0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17-1·73]).InterpretationMortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers.FundingNone.
| S-EPMC8480964 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exist regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients show poor overall outcomes. This report describes our institutional practice regarding the application and management of ECMO support for patients with COVID-19 and reports promising early outcomes.MethodsAll critically ill patients with confirmed COVID-19 evaluated for ECMO support from March 10, 2020, to April 24, 2020, were retrospectively reviewed. Patients were evaluated for ECMO support based on a partial pressure of arterial oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg or pH of less than 7.25 with a partial pressure of arterial carbon dioxide exceeding 60 mm Hg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies, and proning, as clinically indicated.ResultsAmong 321 patients intubated for COVID-19, 77 patients (24%) were evaluated for ECMO support, and 27 patients (8.4%) were placed on ECMO. All patients were supported with venovenous ECMO. Current survival is 96.3%, with only 1 death to date in more than 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, and 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital, of which 4 are on room air. No health care workers who participated in ECMO cannulation developed symptoms of or tested positive for COVID-19.ConclusionsThe early outcomes presented here suggest that the judicious use of ECMO support in severe COVID-19 may be clinically beneficial.
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Project description:Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID-19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID-19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient's recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID-19-induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID-19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID-19 benefitted from ECLS.
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Project description:Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and oxygen exchange performance, and assessment of clotting-related laboratory parameters. However, these observations do not provide a quantitative assessment of oxygenator clot formation. By measuring changes in the dynamic oxygenator blood volume this study aimed to evaluate the relation to oxygenator resistance and oxygen transfer performance. Sixty-seven oxygenators were studied during adult extracorporeal life support. Oxygenator blood volume, oxygenator resistance, and oxygen transfer efficiency were monitored. Oxygenator blood volume decreased with increasing runtime (r = -0.462; p <0.001). There was a statistically significant, fair negative correlation between oxygenator blood volume and oxygenator resistance (r = -0.476; p<0.001) in all oxygenators, which became stronger analyzing only exchanged oxygenators (r = -0.680; p<0.001) and oxygenators with an oxygenator blood volume <187 mL (r = 0.831; p<0.001). No relevant correlation between oxygenator blood volume and O2 transfer was found. Oxygenator blood volume declined over time and was clearly associated with an increasing oxygenator resistance during prolonged extracorporeal life support, though O2 transfer was less affected.
| S-EPMC8809600 | biostudies-literature
Project description:BackgroundVenovenous extracorporeal membrane oxygenation (ECMO) is increasingly being used for acute respiratory distress syndrome and as a bridge to lung transplantation. After initiation of venovenous ECMO, systemic anticoagulation therapy is traditionally administered and can cause bleeding diathesis. Here, we investigated whether venovenous ECMO can be administered without continuous systemic anticoagulation administration for patients with acute respiratory distress syndrome.MethodsThis is a retrospective review of an institutional ECMO database. We included consecutive patients from January 2015 through February 2019. Overall, 38 patients received low levels of continuous systemic anticoagulation (AC+) whereas the subsequent 36 patients received standard venous thromboprophylaxis (AC-). Published Extracorporeal Life Support Organization guidelines were used for the definition of outcomes and complications.ResultsOverall, survival was not different between the two groups (P = .58). However, patients in the AC+ group had higher rates of gastrointestinal bleeding (28.9%, vs AC- group 5.6%; P < .001). The events per patient-day of gastrointestinal bleeding was 0.00025 in the AC- group and 0.00064 in the AC+ group (P < .001). In addition, oxygenator dysfunction was increased in the AC+ group (28.9% and 0.00067 events per patient-day, vs AC- 11.1% and 0.00062 events per patient-day; P = .02). Furthermore, the AC+ group received more transfusions: packed red blood cells, AC+ group 94.7% vs AC- group 55.5% (P < .001); fresh frozen plasma, AC+ 60.5% vs AC- 16.6% (P = .001); and platelets, AC+ 84.2% vs AC- 27.7% (P < .001). There was no circuit thrombosis in either groups throughout the duration of ECMO support.ConclusionsOur results suggest that venovenous ECMO can be safely administered without continuous systemic anticoagulation therapy. This approach may be associated with reduced bleeding diathesis and need for blood transfusions.
| S-EPMC7486253 | biostudies-literature
Project description:BackgroundVeno-venous extracorporeal membrane oxygenation (V-V ECMO) support is increasingly used in the management of COVID-19-related acute respiratory distress syndrome (ARDS). However, the clinical decision-making to initiate V-V ECMO for severe COVID-19 still remains unclear. In order to determine the optimal timing and patient selection, we investigated the outcomes of both COVID-19 and non-COVID-19 patients undergoing V-V ECMO support.MethodsOverall, 138 patients were included in this study. Patients were stratified into two cohorts: those with COVID-19 and non-COVID-19 ARDS.ResultsThe survival in patients with COVID-19 was statistically similar to non-COVID-19 patients (p = .16). However, the COVID-19 group demonstrated higher rates of bleeding (p = .03) and thrombotic complications (p < .001). The duration of V-V ECMO support was longer in COVID-19 patients compared to non-COVID-19 patients (29.0 ± 27.5 vs 15.9 ± 19.6 days, p < .01). Most notably, in contrast to the non-COVID-19 group, we found that COVID-19 patients who had been on a ventilator for longer than 7 days prior to ECMO had 100% mortality without a lung transplant.ConclusionsThese findings suggest that COVID-19-associated ARDS was not associated with a higher post-ECMO mortality than non-COVID-19-associated ARDS patients, despite longer duration of extracorporeal support. Early initiation of V-V ECMO is important for improved ECMO outcomes in COVID-19 ARDS patients. Since late initiation of ECMO was associated with extremely high mortality related to lack of pulmonary recovery, it should be used judiciously or as a bridge to lung transplantation.
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Project description:Cardiopulmonary support is frequently required during lung transplantation. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been recently shown to be an acceptable and, perhaps, safer alternative to cardiopulmonary bypass machine (CBM) for lung transplantation. However, therapeutic anticoagulation used during both these techniques can cause significant bleeding diathesis, especially in the setting of re-transplantation or when severe adhesions are encountered. Technological advances have reduced the thrombogenic potential of VA-ECMO circuits and unlike CBM, VA-ECMO does not include a reservoir containing a stagnant column of blood. Here, we demonstrate that VA-ECMO can be used without therapeutic anticoagulation for short-term intraoperative support.
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