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. 2024 Jul 1;25(7):643-675.
doi: 10.1097/PCC.0000000000003480. Epub 2024 Jul 3.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference

Peta M A Alexander  1 Melania M Bembea  2 Katherine Cashen  3 Ira M Cheifetz  4 Heidi J Dalton  5 Adam S Himebauch  6 Oliver Karam  7   8 Katie M Moynihan  1   9 Marianne E Nellis  10 Caroline Ozment  11 Lakshmi Raman  12 Natalie E Rintoul  13 Ahmed S Said  14 Arun Saini  15 Marie E Steiner  16 Ravi R Thiagarajan  1 Kevin Watt  17 Ariane Willems  18 Nicole D Zantek  19 Ryan P Barbaro  20 Katherine Steffen  21 Adam M Vogel  22 Christopher Almond  23 Marc M Anders  15 Gail M Annich  24 Leonardo R Brandão  25 Wayne Chandler  26 Megan Delaney  27   28 Robert DiGeronimo  29 Sitaram Emani  30 Samir K Gadepalli  31 Alejandro V Garcia  32 Bereketeab Haileselassie  21 Robert Hyslop  33 Martin C J Kneyber  34 Lisa Baumann Kreuziger  35 Jennifer Le  36 Laura Loftis  15 Ali B V McMichael  12   37 D Michael McMullan  38 Paul Monagle  39 Kathleen Nicol  40 Matthew L Paden  41 Jason Patregnani  42 John Priest  43 Leslie Raffini  44 Lindsay M Ryerson  45 Steven R Sloan  46   47 Jun Teruya  48 Andrew R Yates  49 Alison Gehred  50 Elizabeth Lyman  50 Jennifer A Muszynski  51 Pediatric ECMO Anticoagulation CollaborativE (PEACE), in collaboration with the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric ECMO subgroup of PALISI and the Extracorporeal Life Support Organization (PediECMO)
Affiliations

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference

Peta M A Alexander et al. Pediatr Crit Care Med. .

Abstract

Objectives: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

Data sources: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

Study selection: The management of ECMO anticoagulation for critically ill children.

Data extraction: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts.

Data synthesis: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements.

Conclusions: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

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Conflict of interest statement

Drs. Alexander’s and Muszynski’s institutions received funding from the National Institutes of Health (NIH). Drs. Alexander, Bembea, Himebauch, Barbaro, and Muszynski received support for article research from the NIH. Drs. Alexander’s and Bembea’s institutions received funding from the Extracorporeal Life Support Organization (ELSO). Dr. Alexander’s institution received funding from Novartis (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF [PANORAMA-HF]). Dr. Alexander disclosed that she is Treasurer of the Board of Directors of ELSO, past Co-Chair of Pediatric Extracorporeal Membrane Oxygenation (Pedi-ECMO). Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorders and Stroke and a Grifols Investigator Sponsored Research Grant. Dr. Cheifetz received funding from UptoDate. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts, Medtronic, Entegrion, and Hemocue. Drs. Dalton, Ozment, Barbaro, Almond, Brandão, Baumann Kreuziger, Paden, and Ryerson disclosed the off-label product use of pediatric ECMO-related medications for anticoagulation. Dr. Himebauch’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) (K23HL153759). Drs. Karam’s and Nellis’s institutions received funding from the NHBLI (R34HL159119). Dr. Ozment received funding from Kaufman & Canoles, Social Cascade, and Wiseman Ashworth Law Group. Dr. Steiner’s institution received funding from the Department of Defense (DoD); she received funding from Medtronic and Octapharma; she disclosed that she is a Pumps for Kids, Infantsand Neonates (PumpKIN) trial Data Safety and Monitoring Board member. Dr. Alexander’s and Thiagarajan’s institution received funding from the DoD Clinical Trial Award for Trial of Indication-Based Transfusion of RBCs in ECMO trial (W81XWH2210301). Dr. Thiagarajan received funding from Society of Critical Care Medicine and ELSO. Dr. Zantek disclosed that she is a Board Member and Vice President of the North American Specialized Coagulation Laboratory Association and Board Member of the American Society for Apheresis, the External Quality Assurance in Thrombosis and Hemostasis, and Blood Network subgroup of Pediatric Acute Lung Injury and Sepsis Investigators groups; she disclosed that her spouse is an employee of Boston Scientific and owns stock in Endo International PLC. Dr. Barbaro’s institution received funding from the NHLBI (R01 HL153519 and K12 HL138039); he disclosed that he is ELSO Board of Directors and Pedi-ECMO Co-Chair. Dr. Emani received funding from Chiesi Pharma. Dr. Hyslop disclosed he is Co-Chair of ELSO Registry Database Development Committee and Coordinator Liaison to ELSO Steering Committee. Dr. Baumann Kreuziger received funding from the Health Resources and Services Administration Vaccine Injury Compensation Program. Dr. Paden disclosed that he is past president and board member of ELSO. Dr. Ryerson received an honorarium from Instrumentation Laboratory for consultation work. Dr. Sloan commenced employment with CSL Behring after the consensus process was complete. Dr. Patregnani received funding from Mallinckrodt; he discloses consultation payments from MNK pharmaceuticals and Pfizer. The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict-of-interest management. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Clinical guidance for the anticoagulation management of children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE). Weak recommendations (WRs), consensus statement with weak agreement (CS-W), consensus statement with strong agreement (defined as > 95%), and good practice statements (GPSs) are presented. CPB = cardiopulmonary bypass, DTI = direct thrombin inhibitor, HIT = heparin-induced thrombocytopenia, UFH = unfractionated heparin.
Figure 2.
Figure 2.
Clinical guidance for the transfusion, coagulation factor, and antifibrinolytic management of children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE). Weak recommendations (WRs), consensus statements with weak agreement (CS-W), consensus statements with strong agreement (CS-S, defined as > 95%), and good practice statements (GPSs) are presented. CPB = cardiopulmonary bypass, INR = international normalized ratio, PCC = prothrombin complex concentrate, THA = topical hemostatic agents, UFH = unfractionated heparin, VWF = von Willebrand factor.
Figure 3.
Figure 3.
General clinical guidance for the anticoagulation and transfusion management of children with bleeding or thrombotic complications on extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE). Weak recommendations (WRs), consensus statement with weak agreement (CS-W), consensus statement with strong agreement (CS-S, defined as > 95%), and good practice statements (GPSs) are presented. DIC = disseminated intravascular coagulopathy, GI = gastrointestinal, ICH = intracranial hemorrhage, INR = international normalized ratio, PCC = prothrombin complex concentrate.
Figure 4.
Figure 4.
Organ-specific clinical guidance for the anticoagulation and transfusion management of children with bleeding or thrombotic complications on extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE). Weak recommendations (WRs), consensus statement with weak agreement (CS-W), consensus statement with strong agreement (CS-S, defined as > 95%), and good practice statements (GPSs) are presented. DIC = disseminated intravascular coagulopathy, ICH = intracranial hemorrhage, LA = left atrial, US = ultrasound, VA = venoarterial.
Figure 5.
Figure 5.
Anticoagulation and transfusion algorithm example for children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE). *Clinically significant bleeding is defined as meeting any of the criteria listed for moderate or severe bleeding according to published definitions (4, 7, 8). aPTT = activated partial thromboplastin time, Hb = hemoglobin, INR = international normalized ratio, VA = venoarterial, VV = venovenous.

References

    1. Barbaro RP, Paden ML, Guner YS, et al. ; ELSO member centers: Pediatric extracorporeal life support organization registry international report 2016. ASAIO J 2017; 63:456–463 - PMC - PubMed
    1. Extracorporeal Life Support Organization (ELSO): International Summary—ECLS Registry Report. 2023. Available at: https://www.elso.org/registry/internationalsummaryandreports/internation.... Accessed January 10, 2024
    1. O’Halloran CP, Thiagarajan RR, Yarlagadda VV, et al. : Outcomes of infants supported with extracorporeal membrane oxygenation using centrifugal versus roller pumps: An analysis from the Extracorporeal Life Support Organization Registry. Pediatr Crit Care Med 2019; 20:1177–1184 - PMC - PubMed
    1. Dalton HJ, Reeder R, Garcia-Filion P, et al. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network: Factors associated with bleeding and thrombosis in children receiving extracorporeal membrane oxygenation. Am J Respir Crit Care Med 2017; 196:762–771 - PMC - PubMed
    1. Ozment CP, Scott BL, Bembea MM, et al. : Anticoagulation and transfusion management during neonatal and pediatric extracorporeal membrane oxygenation: A survey of medical directors in the United States. Pediatr Crit Care Med 2021; 22:530–541 - PubMed

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