nach oben

Erschienen in:

18.12.2021 | Original

Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis

verfasst von: Jose I. Nunez, Andre F. Gosling, Brian O’Gara, Kevin F. Kennedy, Peter Rycus, Darryl Abrams, Daniel Brodie, Shahzad Shaefi, A. Reshad Garan, E. Wilson Grandin

Erschienen in: Intensive Care Medicine | Ausgabe 2/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

This study aimed at analyzing the prevalence, mortality association, and risk factors for bleeding and thrombosis events (BTEs) among adults supported with venovenous extracorporeal membrane oxygenation (VV-ECMO).

Methods

We queried the Extracorporeal Life Support Organization registry for adults supported with VV-ECMO from 2010 to 2017. Multivariable logistic regression modeling was used to assess the association between BTEs and in-hospital mortality and the predictors of BTEs.

Results

Among 7579 VV-ECMO patients meeting criteria, 40.2% experienced ≥ 1 BTE. Thrombotic events comprised 54.9% of all BTEs and were predominantly ECMO circuit thrombosis. BTE rates decreased significantly over the study period (p < 0.001). The inpatient mortality rate was 34.9%. Bleeding events (1.69 [1.49–1.93]) were more strongly associated with in-hospital mortality than thrombotic events (1.23 [1.08–1.41]) p < 0.01 for both. The BTEs most strongly associated with mortality were ischemic stroke (4.50 [2.55–7.97]) and medical bleeding, including intracranial (5.71 [4.02–8.09]), pulmonary (2.02 [1.54–2.67]), and gastrointestinal (1.54 [1.2–1.98]) hemorrhage, all p < 0.01. Risk factors for bleeding included acute kidney injury and pre-ECMO vasopressor support and for thrombosis were higher weight, multisite cannulation, pre-ECMO arrest, and higher PaCO₂ at ECMO initiation. Longer time on ECMO, younger age, higher pH, and earlier year of support were associated with bleeding and thrombosis.

Conclusions

Although decreasing over time, BTEs remain common during VV-ECMO and have a strong, cumulative association with in-hospital mortality. Thrombotic events are more frequent, but bleeding carries a higher risk of inpatient mortality. Differential risk factors for bleeding and thrombotic complications exist, raising the possibility of a tailored approach to VV-ECMO management.

Nur mit Berechtigung zugänglich

Thiagarajan RR, Barbaro RP, Rycus PT, McMullan DM, Conrad SA, Fortenberry JD, Paden ML (2017) Extracorporeal life support organization registry international report 2016. ASAIO J 63(1):60–67. https://doi.org/10.1097/mat.0000000000000475CrossRefPubMed

Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A (2018) Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 378(21):1965–1975. https://doi.org/10.1056/NEJMoa1800385CrossRefPubMed

Munshi L, Walkey A, Goligher E, Pham T, Uleryk EM, Fan E (2019) Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Lancet Respir Med 7(2):163–172. https://doi.org/10.1016/s2213-2600(18)30452-1CrossRefPubMed

Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D (2009) Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 374(9698):1351–1363. https://doi.org/10.1016/s0140-6736(09)61069-2CrossRefPubMed

Combes A, Peek GJ, Hajage D, Hardy P, Abrams D, Schmidt M, Dechartres A, Elbourne D (2020) ECMO for severe ARDS: systematic review and individual patient data meta-analysis. Intensive Care Med 46(11):2048–2057. https://doi.org/10.1007/s00134-020-06248-3CrossRefPubMed

Vaquer S, de Haro C, Peruga P, Oliva JC, Artigas A (2017) Systematic review and meta-analysis of complications and mortality of veno-venous extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome. Ann Intensive Care 7(1):51. https://doi.org/10.1186/s13613-017-0275-4CrossRefPubMedPubMedCentral

Ramanathan K, Tan CS, Rycus P, MacLaren G (2017) Extracorporeal Membrane Oxygenation for Adult Community-Acquired Pneumonia: Outcomes and Predictors of Mortality*. Crit Care Med 45(5):814–821. https://doi.org/10.1097/ccm.0000000000002320CrossRefPubMed

Schmidt M, Bailey M, Sheldrake J, Hodgson C, Aubron C, Rycus PT, Scheinkestel C, Cooper DJ, Brodie D, Pellegrino V, Combes A, Pilcher D (2014) Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score. Am J Respir Crit Care Med 189(11):1374–1382. https://doi.org/10.1164/rccm.201311-2023OCCrossRefPubMed

Mazzeffi M, Greenwood J, Tanaka K, Menaker J, Rector R, Herr D, Kon Z, Lee J, Griffith B, Rajagopal K, Pham S (2016) Bleeding, transfusion, and mortality on extracorporeal life support: ECLS Working Group on Thrombosis and Hemostasis. Ann Thorac Surg 101(2):682–689. https://doi.org/10.1016/j.athoracsur.2015.07.046CrossRefPubMed

10.

Schmidt M, Hodgson C, Combes A (2015) Extracorporeal gas exchange for acute respiratory failure in adult patients: a systematic review. Crit Care 19:99. https://doi.org/10.1186/s13054-015-0806-zCrossRefPubMedPubMedCentral

11.

Oliver WC (2009) Anticoagulation and coagulation management for ECMO. Semin Cardiothorac Vasc Anesth 13(3):154–175. https://doi.org/10.1177/1089253209347384CrossRefPubMed

12.

Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, Murphy D, Scheinkestel C, Cooper DJ, Capellier G, Pellegrino V, Pilcher D, McQuilten Z (2016) Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care 6(1):97. https://doi.org/10.1186/s13613-016-0196-7CrossRefPubMedPubMedCentral

13.

Krueger K, Schmutz A, Zieger B, Kalbhenn J (2017) Venovenous extracorporeal membrane oxygenation with prophylactic subcutaneous anticoagulation only: an observational study in more than 60 patients. Artif Organs 41(2):186–192. https://doi.org/10.1111/aor.12737CrossRefPubMed

14.

Wu MY, Lin PJ, Tseng YH, Kao KC, Hsiao HL, Huang CC (2014) Venovenous extracorporeal life support for posttraumatic respiratory distress syndrome in adults: the risk of major hemorrhages. Scand J Trauma Resusc Emerg Med 22:56. https://doi.org/10.1186/s13049-014-0056-0CrossRefPubMedPubMedCentral

15.

Annich GM (2015) Extracorporeal life support: the precarious balance of hemostasis. J Thromb Haemost 13(Suppl 1):S336-342. https://doi.org/10.1111/jth.12963CrossRefPubMed

16.

Kreyer S, Muders T, Theuerkauf N, Spitzhüttl J, Schellhaas T, Schewe J-C, Guenther U, Wrigge H, Putensen C (2017) Hemorrhage under veno-venous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients: a retrospective data analysis. J Thorac Dis 9(12):5017–5029. https://doi.org/10.21037/jtd.2017.11.05CrossRefPubMedPubMedCentral

17.

Wu MY, Chang YS, Huang CC, Wu TI, Lin PJ (2017) The impacts of baseline ventilator parameters on hospital mortality in acute respiratory distress syndrome treated with venovenous extracorporeal membrane oxygenation: a retrospective cohort study. BMC Pulm Med 17(1):181. https://doi.org/10.1186/s12890-017-0520-5CrossRefPubMedPubMedCentral

18.

Lee YJ, Kim DJ, Kim JS, Lee JH, Lee CT, Jheon S, Cho YJ (2015) Experience and results with VV-ECMO for severe acute respiratory failure: weaning versus nonweaning. ASAIO J 61(2):184–189. https://doi.org/10.1097/mat.0000000000000174CrossRefPubMed

19.

Shaefi S, Brenner SK, Gupta S, O’Gara BP, Krajewski ML, Charytan DM et al (2021) Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19. Intensive Care Med 47(2):208–221. https://doi.org/10.1007/s00134-020-06331-9CrossRefPubMed

20.

Sy E, Sklar MC, Lequier L, Fan E, Kanji HD (2017) Anticoagulation practices and the prevalence of major bleeding, thromboembolic events, and mortality in venoarterial extracorporeal membrane oxygenation: A systematic review and meta-analysis. J Crit Care 39:87–96. https://doi.org/10.1016/j.jcrc.2017.02.014CrossRefPubMed

21.

Cooper E, Burns J, Retter A, Salt G, Camporota L, Meadows CI, Langrish CC, Wyncoll D, Glover G, Ioannou N, Daly K, Barrett NA (2015) Prevalence of venous thrombosis following venovenous extracorporeal membrane oxygenation in patients with severe respiratory failure. Crit Care Med 43(12):e581-584. https://doi.org/10.1097/ccm.0000000000001277CrossRefPubMed

22.

Luyt CE, Brechot N, Demondion P, Jovanovic T, Hekimian G, Lebreton G, Nieszkowska A, Schmidt M, Trouillet JL, Leprince P, Chastre J, Combes A (2016) Brain injury during venovenous extracorporeal membrane oxygenation. Intensive Care Med 42(5):897–907. https://doi.org/10.1007/s00134-016-4318-3CrossRefPubMed

23.

Lorusso R, Gelsomino S, Parise O, Di Mauro M, Barili F, Geskes G, Vizzardi E, Rycus PT, Muellenbach R, Mueller T, Pesenti A, Combes A, Peek G, Frenckner B, Di Nardo M, Swol J, Maessen J, Thiagarajan RR (2017) Neurologic injury in adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure: findings from the extracorporeal life support organization database. Crit Care Med 45(8):1389–1397. https://doi.org/10.1097/ccm.0000000000002502CrossRefPubMed

24.

Chung M, Cabezas FR, Nunez JI, Kennedy KF, Rick K, Rycus P, Mehra MR, Garan AR, Kociol RD, Grandin EW (2020) Hemocompatibility-related adverse events and survival on venoarterial extracorporeal life support. JACC Heart Fail 8(11):892–902. https://doi.org/10.1016/j.jchf.2020.09.004CrossRefPubMedPubMedCentral

25.

Dalton HJ, Garcia-Filion P, Holubkov R, Moler FW, Shanley T, Heidemann S, Meert K, Berg RA, Berger J, Carcillo J, Newth C, Harrison R, Doctor A, Rycus P, Dean JM, Jenkins T, Nicholson C (2015) Association of bleeding and thrombosis with outcome in extracorporeal life support. Pediatr Crit Care Med 16(2):167–174. https://doi.org/10.1097/pcc.0000000000000317CrossRefPubMedPubMedCentral

26.

Cavayas YA, Munshi L, Sorbo Ld, Fan E (2020) The early change in PaCO₂ after extracorporeal membrane oxygenation initiation is associated with neurological complications. Am J Respir Crit Care Med 201(12):1525–1535. https://doi.org/10.1164/rccm.202001-0023OCCrossRefPubMed

27.

Khoshbin E, Roberts N, Harvey C, Machin D, Killer H, Peek GJ, Sosnowski AW, Firmin RK (2005) Poly-methyl pentene oxygenators have improved gas exchange capability and reduced transfusion requirements in adult extracorporeal membrane oxygenation. ASAIO J 51(3):281–287. https://doi.org/10.1097/01.mat.0000159741.33681.f1CrossRefPubMed

28.

Peek GJ, Killer HM, Reeves R, Sosnowski AW, Firmin RK (2002) Early experience with a polymethyl pentene oxygenator for adult extracorporeal life support. ASAIO J 48(5):480–482. https://doi.org/10.1097/00002480-200209000-00007CrossRefPubMed

29.

Toomasian JM, Schreiner RJ, Meyer DE, Schmidt ME, Hagan SE, Griffith GW, Bartlett RH, Cook KE (2005) A polymethylpentene fiber gas exchanger for long-term extracorporeal life support. Asaio j 51(4):390–397. https://doi.org/10.1097/01.mat.0000169111.66328.a8CrossRefPubMed

30.

Ontaneda A, Annich GM (2018) Novel surfaces in extracorporeal membrane oxygenation circuits. Front Med (Lausanne) 5:321. https://doi.org/10.3389/fmed.2018.00321CrossRef

31.

Kohler K, Valchanov K, Nias G, Vuylsteke A (2013) ECMO cannula review. Perfusion 28(2):114–124. https://doi.org/10.1177/0267659112468014CrossRefPubMed

32.

Ganslmeier P, Philipp A, Rupprecht L, Diez C, Arlt M, Mueller T, Pfister K, Hilker M, Schmid C (2011) Percutaneous cannulation for extracorporeal life support. Thorac Cardiovasc Surg 59(2):103–107. https://doi.org/10.1055/s-0030-1250635CrossRefPubMed

33.

Rupprecht L, Lunz D, Philipp A, Lubnow M, Schmid C (2015) Pitfalls in percutaneous ECMO cannulation. Heart Lung Vessel 7(4):320–326PubMedPubMedCentral

34.

Kurihara C, Walter JM, Karim A, Thakkar S, Saine M, Odell DD, Kim S, Tomic R, Wunderink RG, Budinger GRS, Bharat A (2020) Feasibility of venovenous extracorporeal membrane oxygenation without systemic anticoagulation. Ann Thorac Surg. https://doi.org/10.1016/j.athoracsur.2020.02.011CrossRefPubMedPubMedCentral

35.

Lamarche Y, Chow B, Bédard A, Johal N, Kaan A, Humphries KH, Cheung A (2010) Thromboembolic events in patients on extracorporeal membrane oxygenation without anticoagulation. Innovations (Phila) 5(6):424–429. https://doi.org/10.1097/IMI.0b013e3182029a83CrossRef

36.

Hermann A, Schellongowski P, Bojic A, Robak O, Buchtele N, Staudinger T (2019) ECMO without anticoagulation in patients with disease-related severe thrombocytopenia: feasible but futile? Artif Organs 43(11):1077–1084. https://doi.org/10.1111/aor.13514CrossRefPubMed

37.

Agerstrand CL, Burkart KM, Abrams DC, Bacchetta MD, Brodie D (2015) Blood conservation in extracorporeal membrane oxygenation for acute respiratory distress syndrome. Ann Thorac Surg 99(2):590–595. https://doi.org/10.1016/j.athoracsur.2014.08.039CrossRefPubMed

38.

Aubron C, McQuilten Z, Bailey M, Board J, Buhr H, Cartwright B, Dennis M, Hodgson C, Forrest P, McIlroy D, Murphy D, Murray L, Pellegrino V, Pilcher D, Sheldrake J, Tran H, Vallance S, Cooper DJ (2019) Low-dose versus therapeutic anticoagulation in patients on extracorporeal membrane oxygenation: a pilot randomized trial. Crit Care Med 47(7):e563–e571. https://doi.org/10.1097/ccm.0000000000003780CrossRefPubMed

39.

Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J (1999) Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 27(12):2812–2817. https://doi.org/10.1097/00003246-199912000-00034CrossRefPubMed

40.

MacLaren R, Reynolds PM, Allen RR (2014) Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 174(4):564–574. https://doi.org/10.1001/jamainternmed.2013.14673CrossRefPubMed

41.

An SJ, Kim TJ, Yoon BW (2017) Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: an update. J Stroke 19(1):3–10. https://doi.org/10.5853/jos.2016.00864CrossRefPubMedPubMedCentral

42.

Boccardo P, Remuzzi G, Galbusera M (2004) Platelet dysfunction in renal failure. Semin Thromb Hemost 30(5):579–589. https://doi.org/10.1055/s-2004-835678CrossRefPubMed

43.

Boyle AJ, Jorde UP, Sun B, Park SJ, Milano CA, Frazier OH, Sundareswaran KS, Farrar DJ, Russell SD (2014) Pre-operative risk factors of bleeding and stroke during left ventricular assist device support: an analysis of more than 900 HeartMate II outpatients. J Am Coll Cardiol 63(9):880–888. https://doi.org/10.1016/j.jacc.2013.08.1656CrossRefPubMed

44.

Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Myers S, Acker MA, Rogers J, Slaughter MS, Stevenson LW (2015) Pump thrombosis in the Thoratec HeartMate II device: an update analysis of the INTERMACS Registry. J Heart Lung Transplant 34(12):1515–1526. https://doi.org/10.1016/j.healun.2015.10.024CrossRefPubMed

45.

Blokhin IO, Lentz SR (2013) Mechanisms of thrombosis in obesity. Curr Opin Hematol 20(5):437–444. https://doi.org/10.1097/MOH.0b013e3283634443CrossRefPubMedPubMedCentral

46.

Yang Y, Tang H (2016) Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia. Cell Mol Immunol 13(4):432–442. https://doi.org/10.1038/cmi.2016.1CrossRefPubMedPubMedCentral

47.

Engström M, Schött U, Romner B, Reinstrup P (2006) Acidosis impairs the coagulation: a thromboelastographic study. J Trauma 61(3):624–628. https://doi.org/10.1097/01.ta.0000226739.30655.75CrossRefPubMed

48.

Ramaker AJ, Meyer P, van der Meer J, Struys MM, Lisman T, van Oeveren W, Hendriks HG (2009) Effects of acidosis, alkalosis, hyperthermia and hypothermia on haemostasis: results of point of care testing with the thromboelastography analyser. Blood Coagul Fibrinol 20(6):436–439. https://doi.org/10.1097/MBC.0b013e32832dc327CrossRef

49.

Vincent JL, Taccone FS, He X (2017) Harmful effects of hyperoxia in postcardiac arrest, sepsis, traumatic brain injury, or stroke: the importance of individualized oxygen therapy in critically ill patients. Can Respir J 2017:2834956. https://doi.org/10.1155/2017/2834956CrossRefPubMedPubMedCentral

50.

Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P (2015) Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care 5(1):42. https://doi.org/10.1186/s13613-015-0084-6CrossRefPubMedPubMedCentral

51.

Parzy G, Daviet F, Persico N, Rambaud R, Scemama U, Adda M, Guervilly C, Hraiech S, Chaumoitre K, Roch A, Papazian L, Forel JM (2019) Prevalence and risk factors for thrombotic complications following venovenous extracorporeal membrane oxygenation: a CT scan study. Crit Care Med. https://doi.org/10.1097/ccm.0000000000004129CrossRef

52.

Bidar F, Lancelot A, Lebreton G, Pineton de Chambrun M, Schmidt M, Hékimian G, Juvin C, Bréchot N, Schoell T, Leprince P, Combes A, Bouglé A, Luyt CE (2021) Venous or arterial thromboses after venoarterial extracorporeal membrane oxygenation support: frequency and risk factors. J Heart Lung Transplant 40(4):307–315. https://doi.org/10.1016/j.healun.2020.12.007CrossRefPubMed

Titel: Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis
verfasst von: Jose I. Nunez
Andre F. Gosling
Brian O’Gara
Kevin F. Kennedy
Peter Rycus
Darryl Abrams
Daniel Brodie
Shahzad Shaefi
A. Reshad Garan
E. Wilson Grandin
Publikationsdatum: 18.12.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Intensive Care Medicine / Ausgabe 2/2022
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-021-06593-x

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

hier abonnieren

Springer Medizin

Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis