RSS-Feed abonnieren

DOI: 10.1055/a-2411-1000
Characteristics of Bleeding Complications in Patients with Severe COVID-19 Requiring Veno-venous Extracorporeal Membrane Oxygenation in Japan
Funding This research was funded by the Japan Agency for Medical Research and Development (grant number: JP22fk0108654).

Abstract
Background Complications during veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with in-hospital mortality. Asian patients on extracorporeal membrane oxygenation (ECMO) have higher risks of bleeding and in-hospital mortality than Caucasian patients. This study aimed to characterize and identify bleeding complications and their associated factors related to in-hospital mortality in patients with severe coronavirus disease 2019 (COVID-19) requiring VV-ECMO in Japan.
Methods In this retrospective observational analysis, the prospective nationwide multicenter registry was used to track real-time information from intensive care units throughout Japan during the COVID-19 pandemic. VV-ECMO patients' registry data between February 1, 2020 and October 31, 2022 were used.
Results This study included 441 patients; 178 (40%) had bleeding complications in the following sites: 20% at the cannulation site, 16% in the gastrointestinal tract, 16% in the ear–nose–throat, 13% at the tracheostomy site, 9% intrathoracic, 6% intracranial, and 5% in the iliopsoas. Anticoagulation was discontinued in >50% of patients with intracranial, iliopsoas, and gastrointestinal tract bleeding. ECMO was discontinued in one-third of patients with intracranial, intramuscular, and iliopsoas hemorrhages. Multivariable logistic regression analysis revealed that only gastrointestinal tract bleeding was associated with in-hospital mortality (odds ratio: 2.49; 95% confidence interval: 1.11–5.60; p = 0.03).
Conclusion Incidence of bleeding complications was 40% in the Japanese population. Gastrointestinal tract bleeding emerged as a significant predictor of adverse outcomes, necessitating further research into preventive strategies and optimized care protocols. These findings can guide the management of VV-ECMO patients with COVID-19.
Keywords
bleeding - coronavirus disease 2019 - gastrointestinal tract - respiratory distress syndrome - mortalityEthical Approval Statement
This study was approved by the Institutional Review Board of Yokohama City University (approval number: B200700034), and the need for informed consent was waived owing to its retrospective nature. Instead, an opt-out statement was posted on the Web site. The study was conducted according to the principles of the Declaration of Helsinki.
Publikationsverlauf
Eingereicht: 18. Juni 2024
Angenommen: 02. September 2024
Accepted Manuscript online:
06. September 2024
Artikel online veröffentlicht:
27. September 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Stuttgart · New York
-
References
- 1 Peek GJ, Mugford M, Tiruvoipati R. et al; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374 (9698) 1351-1363
- 2 Combes A, Hajage D, Capellier G. et al; EOLIA Trial Group, REVA, and ECMONet. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 2018; 378 (21) 1965-1975
- 3 Ramanathan K, Shekar K, Ling RR. et al. Correction to: extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Crit Care 2021; 25 (01) 375
- 4 Urner M, Barnett AG, Bassi GL. et al; COVID-19 Critical Care Consortium Investigators. Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study. BMJ 2022; 377: e068723
- 5 Ohshimo S, Liu K, Ogura T. et al; Japan ECMO Network. Trends in survival during the pandemic in patients with critical COVID-19 receiving mechanical ventilation with or without ECMO: analysis of the Japanese national registry data. Crit Care 2022; 26 (01) 354
- 6 Nunez JI, Gosling AF, O'Gara B. et al. Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis. Intensive Care Med 2022; 48 (02) 213-224
- 7 Willers A, Swol J, Buscher H. et al. Longitudinal trends in bleeding complications on extracorporeal life support over the past two decades-extracorporeal life support organization registry analysis. Crit Care Med 2022; 50 (06) e569-e580
- 8 Fanning JP, Weaver N, Fanning RB. et al; COVID-19 Critical Care Consortium. Hemorrhage, disseminated intravascular coagulopathy, and thrombosis complications among critically ill patients with COVID-19: an international COVID-19 critical care consortium study. Crit Care Med 2023; 51 (05) 619-631
- 9 Martucci G, Giani M, Schmidt M. et al; International ECMO Network (ECMONet). Anticoagulation and bleeding during veno-venous extracorporeal membrane oxygenation: insights from the PROTECMO study. Am J Respir Crit Care Med 2024; 209 (04) 417-426
- 10 Willers A, Swol J, van Kuijk SMJ. et al. HEROES V-V-HEmorRhagic cOmplications in Veno-Venous Extracorporeal life Support-Development and internal validation of multivariable prediction model in adult patients. Artif Organs 2022; 46 (05) 932-952
- 11 Schmidbauer ML, Ferse C, Salih F. et al; On Behalf Of The Ignite Study Group. COVID-19 and intracranial hemorrhage: a multicenter case series, systematic review and pooled analysis. J Clin Med 2022; 11 (03) 605
- 12 Kim HK, Tantry US, Smith Jr SC. et al. The East Asian paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease. Thromb Haemost 2021; 121 (04) 422-432
- 13 Richardson S, Verma A, Sanaiha Y. et al. Racial disparities in outcomes for extracorporeal membrane oxygenation in the United States. Am J Surg 2023; 225 (01) 113-117
- 14 Yusuff H, Zochios V, Brodie D. Thrombosis and coagulopathy in COVID-19 patients rceiving ECMO: a narrative review of current literature. J Cardiothorac Vasc Anesth 2022; 36 (8, Pt B): 3312-3317
- 15 Mansour A, Flecher E, Schmidt M. et al; ECMOSARS Investigators. Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study. Intensive Care Med 2022; 48 (08) 1039-1052
- 16 Shaefi S, Brenner SK, Gupta S. et al; STOP-COVID Investigators. Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19. Intensive Care Med 2021; 47 (02) 208-221
- 17 Arachchillage DJ, Rajakaruna I, Scott I. et al. Impact of major bleeding and thrombosis on 180-day survival in patients with severe COVID-19 supported with veno-venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study. Br J Haematol 2022; 196 (03) 566-576
- 18 Li C, Cai T, Xie H. et al. Risk factors and outcomes for patients with bleeding complications receiving extracorporeal membrane oxygenation: an analysis of the Chinese Extracorporeal Life Support Registry. Artif Organs 2022; 46 (12) 2432-2441
- 19 Malas J, Chen Q, Shen T. et al. Outcomes of extremely prolonged (> 50 d) venovenous extracorporeal membrane oxygenation support. Crit Care Med 2023; 51 (07) e140-e144
- 20 Thomas J, Kostousov V, Teruya J. Bleeding and thrombotic complications in the use of extracorporeal membrane oxygenation. Semin Thromb Hemost 2018; 44 (01) 20-29
- 21 de Oliveira GLV, Oliveira CNS, Pinzan CF, de Salis LVV, Cardoso CRB. Microbiota modulation of the gut-lung axis in COVID-19. Front Immunol 2021; 12: 635471
- 22 Nichi-Iko Pharmaceutical Co. L. Pharmaceutical interview form for FUTHAN 10 INJ., FUTHAN 50 INJ. 6th ed. [Internet]. 2019 . Accessed August 10, 2024 at: https://www.nichiiko.co.jp/medicine/file/31050/interview
- 23 Hernández-Mitre MP, Tong SYC, Denholm JT. et al. Nafamostat mesylate for treatment of COVID-19 in hospitalised patients: a structured, narrative review. Clin Pharmacokinet 2022; 61 (10) 1331-1343
- 24 Minakata D, Fujiwara SI, Ikeda T. et al. Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies. Int J Hematol 2019; 109 (02) 141-146
- 25 Doi K, Ikeda M, Hayase N, Moriya K, Morimura N. COVID-UTH Study Group. Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with Covid-19: a case series. Crit Care 2020; 24 (01) 392
- 26 Yoshioka T, Daizumoto K, Tada K. et al. Retroperitoneal hemorrhage in a patient with coronavirus disease 2019 (COVID-19): a case report. J Med Invest 2022; 69 (1.2): 148-151
- 27 Doi S, Akashi YJ, Takita M. et al. Preventing thrombosis in a COVID-19 patient by combined therapy with nafamostat and heparin during extracorporeal membrane oxygenation. Acute Med Surg 2020; 7 (01) e585
- 28 Hunsicker O, Beck L, Krannich A. et al. Timing, outcome, and risk factors of intracranial hemorrhage in acute respiratory distress syndrome patients during venovenous extracorporeal membrane oxygenation. Crit Care Med 2021; 49 (02) e120-e129
- 29 Fletcher-Sandersjöö A, Thelin EP, Bartek Jr J. et al. Incidence, outcome, and predictors of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation: a systematic and narrative review. Front Neurol 2018; 9: 548
- 30 Arachchillage DRJ, Passariello M, Laffan M. et al. Intracranial hemorrhage and early mortality in patients receiving extracorporeal membrane oxygenation for severe respiratory failure. Semin Thromb Hemost 2018; 44 (03) 276-286
- 31 Fletcher-Sandersjöö A, Thelin EP, Bartek Jr J, Elmi-Terander A, Broman M, Bellander BM. Management of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation (ECMO): an observational cohort study. PLoS One 2017; 12 (12) e0190365
- 32 Taniguchi H, Ikeda T, Takeuchi I, Ichiba S. Iliopsoas hematoma in patients undergoing venovenous ECMO. Am J Crit Care 2021; 30 (01) 55-63
- 33 Taniguchi H, Rätsep I, Heinsar S. et al. Iliopsoas haematoma during extracorporeal membrane oxygenation: a registry report from the COVID-19 critical care consortium across 30 countries. Perfusion 2024; 39 (05) 891-895