The History of Extracorporeal Membrane Oxygenation and the Development of Extracorporeal Membrane Oxygenation Anticoagulation

Abstract

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the “Father of ECMO”—Dr. Robert Bartlett, describe the history and advances of ECMO.

Keywords

ECMO - History - Anticoagulation

Author Contributions

All authors participated in writing and review of the entire manuscript. J.T. planned the structure of this manuscript and wrote the abstract and conclusion; R.B. wrote section 1, D.J.A. wrote section 2; M.C., S.K.R.H., and C.N. wrote section 3; A.D., A.R., and B.H. wrote section 4, H.S.L. wrote section 5; A.S. wrote section 6; and T.R. wrote section 7. V.K. reviewed the entire manuscript and assisted with reference citations. All authors are responsible for the entire content of this article.

Publikationsverlauf

Artikel online veröffentlicht:
07. Februar 2023

• References

• 1 Hessel II EA. A brief history of cardiopulmonary bypass. Semin Cardiothorac Vasc Anesth 2014; 18 (02) 87-100
• 2 Bartlett RH, Isherwood J, Moss RA, Olszewski WL, Polet H, Drinker PA. A toroidal flow membrane oxygenator: four day partial bypass in dogs. Surg Forum 1969; 20: 152-153
• 3 Bartlett RH, Kittredge D, Noyes Jr BS, Willard III RH, Drinker PA. Development of a membrane oxygenator: overcoming blood diffusiolimitation. J Thorac Cardiovasc Surg 1969; 58 (06) 795-800
• 4 Bartlett RH, Drinker PA, Burns NE, Fong SW, Hyans T. The toroidal membrane oxygenator: design, performance, and prolonged bypass testing of a clinical model. Trans Am Soc Artif Intern Organs 1972; 18 (00) 369-374
• 5 Lenahan JG, Phillips GE. Some variables which influence the activated partial thromboplastin time assay. Clin Chem 1966; 12 (05) 269-273
• 6 Fong SW, Burns NE, Williams G, Woldanski C, Gazzaniga AB, Bartlett RH. Changes in coagulation and platelet function during prolonged extracorporeal circulation (ECC) in sheep and man. Trans Am Soc Artif Intern Organs 1974; 20A: 239-247
• 7 Bartlett RH, Burns NE, Fong SW, Gazzaniga AB, Achauer BM, Fraile J. Prolonged partial venoarterial bypass: physiologic, biochemical, and hematologic responses. Surg Forum 1972; 23 (00) 178-180
• 8 Kolobow T, Zapol WM, Sigman RL, Pierce J. Partial cardiopulmonary bypass lasting up to seven days in alert lambs with membrane lung blood oxygenation. J Thorac Cardiovasc Surg 1970; 60 (06) 781-788
• 9 Bramson ML, Hill JD, Osborn JJ, Gerbode F. Partial veno-arterial perfusion with membrane oxygenation and diastolic augmentation. Trans Am Soc Artif Intern Organs 1969; 15: 412-416
• 10 Hill JD, O'Brien TG, Murray JJ. et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med 1972; 286 (12) 629-634
• 11 Bartlett RH, Gazzaniga AB, Fong SW, Burns NE. Prolonged extracorporeal cardiopulmonary support in man. J Thorac Cardiovasc Surg 1974; 68 (06) 918-932
• 12 Bartlett RH, Andrews AF, Toomasian JM, Haiduc NJ, Gazzaniga AB. Extracorporeal membrane oxygenation for newborn respiratory failure: forty-five cases. Surgery 1982; 92 (02) 425-433
• 13 Bartlett RH, Gazzaniga AB, Toomasian J, Coran AG, Roloff D, Rucker R. Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg 1986; 204 (03) 236-245
• 14 Bartlett RH, Roloff DW, Cornell RG, Andrews AF, Dillon PW, Zwischenberger JB. Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics 1985; 76 (04) 479-487
• 15 O'Rourke PP, Crone RK, Vacanti JP. et al. Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study. Pediatrics 1989; 84 (06) 957-963
• 16 UK Collaborative ECMO Trail Group. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet 1996; 348 (9020): 75-82
• 17 MacLaren G, Brodie D, Lorusso R. et al, Eds. Extracorporeal Life Support: The ELSO Red Book. 6th ed. Ann Arbor, MI: Extracorporeal Life Support Organization; 2022
• 18 Annich G, Barbaro R, Cornell T. et al. Adverse effects of extracorporeal life support: the blood biomaterial interaction. In: Brogan T, Laquier L, Lorusso R. et al. (eds) Extracorporeal Life Support: The ELSO Red Book. 5th ed. Ann Arbor, MI: : ELSO, 2017: 81-92
• 19 Kurihara C, Walter JM, Karim A. et al. Feasibility of venovenous extracorporeal membrane oxygenation without systemic anticoagulation. Ann Thorac Surg 2020; 110 (04) 1209-1215
• 20 Wood KL, Ayers B, Gosev I. et al. Venoarterial-extracorporeal membrane oxygenation without routine systemic anticoagulation decreases adverse events. Ann Thorac Surg 2020; 109 (05) 1458-1466
• 21 Willers A, Arens J, Mariani S. et al. New trends, advantages and disadvantages in anticoagulation and coating methods used in extracorporeal life support devices. Membranes (Basel) 2021; 11 (08) 617
• 22 Brisbois EJ, Kim M, Wang X. et al. Improved hemocompatibility of multi-lumen catheters via nitric oxide (NO) release from s-nitroso-N-acetylpenicillamine (SNAP) composite filled lumen. ACS Appl Mater Interfaces 2016; 8 (43) 29270-29279
• 23 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
• 24 Arachchillage DRJ, Kamani F, Deplano S, Banya W, Laffan M. Should we abandon the APTT for monitoring unfractionated heparin?. Thromb Res 2017; 157: 157-161
• 25 Arachchillage DRJ, Laffan M, Khanna S. et al. Frequency of thrombocytopenia and heparin-induced thrombocytopenia in patients receiving extracorporeal membrane oxygenation compared with cardiopulmonary bypass and the limited sensitivity of pretest probability score. Crit Care Med 2020; 48 (05) e371-e379
• 26 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
• 27 Burstein B, Wieruszewski PM, Zhao YJ, Smischney N. Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation. World J Crit Care Med 2019; 8 (06) 87-98
• 28 Geli J, Capoccia M, Maybauer DM, Maybauer MO. Direct thrombin inhibition in extracorporeal membrane oxygenation. Int J Artif Organs 2022; 45 (07) 652-655
• 29 Rey Y Formoso V, Barreto Mota R, Soares H. Developmental hemostasis in the neonatal period. World J Pediatr 2022; 18 (01) 7-15
• 30 Toulon P. Developmental hemostasis: laboratory and clinical implications. Int J Lab Hematol 2016; 38 (Suppl. 01) 66-77
• 31 Male C, Lensing AWA, Palumbo JS. et al; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7 (01) e18-e27
• 32 Monagle P, Chan AKC, Goldenberg NA. et al. Antithrombotic therapy in neonates and children antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012. 141. e737S-801S
• 33 Witt DM, Nieuwlaat R, Clark NP. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv 2018; 2 (22) 3257-3291
• 34 Goldenberg NA, Kittelson JM, Abshire TC. et al; Kids-DOTT Trial Investigators and the ATLAS Group. Effect of anticoagulant therapy for 6 weeks vs 3 months on recurrence and bleeding events in patients younger than 21 years of age with provoked venous thromboembolism: the kids-DOTT Randomized Clinical Trial. JAMA 2022; 327 (02) 129-137
• 35 Taylor T, Campbell CT, Kelly B. A review of bivalirudin for pediatric and adult mechanical circulatory support. Am J Cardiovasc Drugs 2021; 21 (04) 395-409
• 36 Pollak U. Heparin-induced thrombocytopenia complicating extracorporeal membrane oxygenation support: review of the literature and alternative anticoagulants. J Thromb Haemost 2019; 17 (10) 1608-1622
• 37 Ma M, Liang S, Zhu J. et al. The efficacy and safety of bivalirudin versus heparin in the anticoagulation therapy of extracorporeal membrane oxygenation: a systematic review and meta-analysis. Front Pharmacol 2022; 13: 771563
• 38 Neunert C, Chitlur M, van Ommen CH. The changing landscape of anticoagulation in pediatric extracorporeal membrane oxygenation: use of the direct thrombin inhibitors. Front Med (Lausanne) 2022; 9: 887199
• 39 McMichael ABV, Hornik CP, Hupp SR, Gordon SE, Ozment CP. Correlation among antifactor xa, activated partial thromboplastin time, and heparin dose and association with pediatric extracorporeal membrane oxygenation complications. ASAIO J 2020; 66 (03) 307-313
• 40 Liveris A, Bello RA, Friedmann P. et al. Anti-factor Xa assay is a superior correlate of heparin dose than activated partial thromboplastin time or activated clotting time in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med 2014; 15 (02) e72-e79
• 41 Henderson N, Sullivan JE, Myers J. et al. Use of thromboelastography to predict thrombotic complications in pediatric and neonatal extracorporeal membranous oxygenation. J Extra Corpor Technol 2018; 50 (03) 149-154
• 42 Martin AA, Bhat R, Chitlur M. Hemostasis in pediatric extracorporeal life support: overview and challenges. Pediatr Clin North Am 2022; 69 (03) 441-464
• 43 Love JE, Ferrell C, Chandler WL. Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost 2007; 98 (01) 234-242
• 44 Beyer JT, Lind SE, Fisher S, Trujillo TC, Wempe MF, Kiser TH. Evaluation of intravenous direct thrombin inhibitor monitoring tests: correlation with plasma concentrations and clinical outcomes in hospitalized patients. J Thromb Thrombolysis 2020; 49 (02) 259-267
• 45 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
• 46 Sutter R, Tisljar K, Marsch S. Acute neurologic complications during extracorporeal membrane oxygenation: a systematic review. Crit Care Med 2018; 46 (09) 1506-1513
• 47 Parzy G, Daviet F, Persico N. et al. Prevalence and risk factors for thrombotic complications following venovenous extracorporeal membrane oxygenation: A CT scan study. Crit Care Med 2020; 48 (02) 192-199
• 48 Hartley EL, Singh N, Barrett N, Wyncoll D, Retter A. Screening pulmonary angiogram and the effect on anticoagulation strategies in severe respiratory failure patients on venovenous extracorporeal membrane oxygenation. J Thromb Haemost 2020; 18 (01) 217-221
• 49 Le Guennec L, Schmidt M, Clarençon F. et al. Mechanical thrombectomy in acute ischemic stroke patients under venoarterial extracorporeal membrane oxygenation. J Neurointerv Surg 2020; 12 (05) 486-488
• 50 Tran D, Hays N, Shah A. et al. Ultrasound-assisted catheter directed thrombolysis for pulmonary embolus during extracorporeal membrane oxygenation. J Card Surg 2021; 36 (08) 2685-2691
• 51 Moerer O, Huber-Petersen JF, Schaeper J, Binder C, Wand S. Factor XIII activity might already be impaired before veno-venous ECMO in ARDS patients: a prospective, observational single-center cohort study. J Clin Med 2021; 10 (06) 1203
• 52 Panholzer B, Bajorat T, Haneya A. et al. Acquired von Willebrand syndrome in ECMO patients: a 3-year cohort study. Blood Cells Mol Dis 2021; 87: 102526
• 53 Jiritano F, Serraino GF, Ten Cate H. et al. Platelets and extra-corporeal membrane oxygenation in adult patients: a systematic review and meta-analysis. Intensive Care Med 2020; 46 (06) 1154-1169
• 54 Kalbhenn J, Wittau N, Schmutz A, Zieger B, Schmidt R. Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy. Perfusion 2015; 30 (08) 675-682
• 55 Lotz C, Streiber N, Roewer N, Lepper PM, Muellenbach RM, Kredel M. Therapeutic interventions and risk factors of bleeding during extracorporeal membrane oxygenation. ASAIO J 2017; 63 (05) 624-630
• 56 Olson SR, Murphree CR, Zonies D. et al. Thrombosis and bleeding in extracorporeal membrane oxygenation (ECMO) without anticoagulation: a systematic review. ASAIO J 2021; 67 (03) 290-296
• 57 Shakur H, Roberts I, Bautista R. et al; CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376 (9734): 23-32
• 58 Myles PS, Smith JA, Forbes A. et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic acid in patients undergoing coronary-artery surgery. N Engl J Med 2017; 376 (02) 136-148
• 59 Coleman M, Davis J, Maher KO, Deshpande SR. Clinical and hematological outcomes of aminocaproic acid use during pediatric cardiac ECMO. J Extra Corpor Technol 2021; 53 (01) 40-45
• 60 Becher PM, Schrage B, Sinning CR. et al. Venoarterial extracorporeal membrane oxygenation for cardiopulmonary support. Insights from a German Registry. Circulation 2018; 138 (20) 2298-2300
• 61 Jawitz OK, Fudim M, Raman V. et al. Reassessing recipient mortality under the new heart allocation system: an updated UNOS Registry Analysis. JACC Heart Fail 2020; 8 (07) 548-556
• 62 Jentzer JC, Ahmed AM, Vallabhajosyula S. et al. Shock in the cardiac intensive care unit: changes in epidemiology and prognosis over time. Am Heart J 2021; 232: 94-104
• 63 Acharya D, Torabi M, Borgstrom M. et al; Analysis of the ELSO Registry. Extracorporeal membrane oxygenation in myocardial infarction complicated by cardiogenic shock. J Am Coll Cardiol 2020; 76 (08) 1001-1002
• 64 Freund A, Jobs A, Lurz P. et al. Frequency and impact of bleeding on outcome in patients with cardiogenic shock. JACC Cardiovasc Interv 2020; 13 (10) 1182-1193
• 65 Moghaddam N, van Diepen S, So D, Lawler PR, Fordyce CB. Cardiogenic shock teams and centres: a contemporary review of multidisciplinary care for cardiogenic shock. ESC Heart Fail 2021; 8 (02) 988-998
• 66 Panigada M, EIapichino G, Brioni M. et al. Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study. Ann Intensive Care 2018; 8 (01) 7
• 67 Cartwright B, Bruce HM, Kershaw G. et al. Hemostasis, coagulation and thrombin in venoarterial and venovenous extracorporeal membrane oxygenation: the HECTIC study. Sci Rep 2021; 11 (01) 7975
• 68 Willers A, Arens J, Mariani S. et al. New trends, advantages and disadvantages in anticoagulation and coating methods used in extracorporeal life support devices. Membranes (Basel) 2021; 11 (08) 617
• 69 Ontaneda A, Annich GM. Novel surfaces in extracorporeal membrane oxygenation circuits. Front Med (Lausanne) 2018; 5: 321
• 70 Chung M, Cabezas FR, Nunez JI. et al. Hemocompatibility-related adverse events and survival on venoarterial extracorporeal life support: an ELSO Registry Analysis. JACC Heart Fail 2020; 8 (11) 892-902
• 71 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
• 72 Gerlach M, Föhre B, Keh D, Riess H, Falke KJ, Gerlach H. Global and extended coagulation monitoring during extracorporeal lung assist with heparin-coated systems in ARDS patients. Int J Artif Organs 1997; 20 (01) 29-36
• 73 Ichinose K, Okamoto T, Tanimoto H. et al. Comparison of a new heparin-coated dense membrane lung with nonheparin-coated dense membrane lung for prolonged extracorporeal lung assist in goats. Artif Organs 2004; 28 (11) 993-1001
• 74 Nojiri C, Hagiwara K, Yokoyama K. et al. Evaluation of a new heparin bonding process in prolonged extracorporeal membrane oxygenation. ASAIO J 1995; 41 (03) M561-M567
• 75 Irwin C, Roberts W, Naseem KM. Nitric oxide inhibits platelet adhesion to collagen through cGMP-dependent and independent mechanisms: the potential role for S-nitrosylation. Platelets 2009; 20 (07) 478-486
• 76 Skrzypchak AM, Lafayette NG, Bartlett RH. et al. Effect of varying nitric oxide release to prevent platelet consumption and preserve platelet function in an in vivo model of extracorporeal circulation. Perfusion 2007; 22 (03) 193-200
• 77 Ashcraft M, Douglass M, Chen Y, Handa H. Combination strategies for antithrombotic biomaterials: an emerging trend towards hemocompatibility. Biomater Sci 2021; 9 (07) 2413-2423
• 78 Major TC, Brant DO, Burney CP. et al. The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model. Biomaterials 2011; 32 (26) 5957-5969
• 79 Gerling K, Ölschläger S, Avci-Adali M. et al. A novel C1-Esterase inhibitor oxygenator coating prevents FXII activation in human blood. Biomolecules 2020; 10 (07) 1042
• 80 Yu J, Brisbois E, Handa H. et al. The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation. J Mater Chem B Mater Biol Med 2016; 4 (13) 2264-2272
• 81 Liu T, Liu S, Zhang K, Chen J, Huang N. Endothelialization of implanted cardiovascular biomaterial surfaces: the development from in vitro to in vivo. J Biomed Mater Res A 2014; 102 (10) 3754-3772
• 82 Maul TM, Massicotte MP, Wearden PD. ECMO biocompatibility: surface coatings, anticoagulation, and coagulation monitoring. In: Firstenberg MS. ed. Extracorporeal Membrane Oxygenation—Advances in Therapy [Internet]. London: IntechOpen; 2016. [cited 2022 Aug 20].
• 83 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
• 84 Renné T, Pozgajová M, Grüner S. et al. Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med 2005; 202 (02) 271-281
• 85 Long AT, Kenne E, Jung R, Fuchs TA, Renné T. Contact system revisited: an interface between inflammation, coagulation, and innate immunity. J Thromb Haemost 2016; 14 (03) 427-437
• 86 Mailer RK, Allende M, Heestermans M. et al. Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate. Blood 2021; 137 (10) 1392-1405
• 87 Kleinschnitz C, Stoll G, Bendszus M. et al. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 2006; 203 (03) 513-518
• 88 Larsson M, Rayzman V, Nolte MW. et al. A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci Transl Med 2014; 6 (222): 222ra17
• 89 Heestermans M, Naudin C, Mailer RK. et al. Identification of the factor XII contact activation site enables sensitive coagulation diagnostics. Nat Commun 2021; 12 (01) 5596
• 90 Craig T, Magerl M, Levy DS. et al. Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2022; 399 (10328): 945-955