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The importance of preoperative cardiac function in pediatric lung transplantation is unknown. We hypothesized that worse preoperative right ventricular (RV) systolic and worse left ventricular (LV) diastolic function would be associated with a higher risk of primary graft dysfunction grade 3 (PGD 3) between 48 and 72 hours. We performed a single center, retrospective pilot study of children (<18 years) who had echocardiograms <1 year prior to lung transplantation between 2006 and 2019. Conventional and strain echocardiography parameters were measured, and PGD was graded. Area under the receiver operating characteristic (AUROC) curves and logistic regression were performed. Forty‐one patients were included; 14 (34%) developed PGD 3 and were more likely to have pulmonary hypertension (PH) as the indication for transplant (P =.005). PGD 3 patients had worse RV global longitudinal strain (P =.01), RV free wall strain (FWS) (P =.003), RV fractional area change (P =.005), E/e' (P =.01) and lateral e' velocity (P =.004) but not tricuspid annular plane systolic excursion (P =.61). RV FWS (AUROC 0.79, 95% CI 0.62‐0.95) and lateral e' velocity (AUROC 0.87, 95% CI 0.68‐1.00) best discriminated PGD 3 development and showed the strongest association with PGD 3 (RV FWS OR 3.87 [95% CI 1.59‐9.43], P =.003; lateral e' velocity OR 0.10 [95% CI 0.01‐0.70], P =.02). These associations remained when separately adjusting for age, weight, primary PH diagnosis, ischemic time, and bypass time. In this pilot study, worse preoperative RV systolic and worse LV diastolic function were associated with PGD 3 and may be modifiable recipient risk factors in pediatric lung transplantation. [ABSTRACT FROM AUTHOR]

Severe primary graft dysfunction (PGD) is associated with the development of bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), in adults. However, PGD associations with long-term outcomes following pediatric lung transplantation are unknown. We hypothesized that PGD grade 3 (PGD 3) at 48- or 72-hours would be associated with shorter CLAD-free survival following pediatric lung transplantation. This was a single center retrospective cohort study of patients ≤ 21 years of age who underwent bilateral lung transplantation between 2005 and 2019 with ≥ 1 year of follow-up. PGD and CLAD were defined by published criteria. We evaluated the association of PGD 3 at 48- or 72-hours with CLAD-free survival by using time-to-event analyses. Fifty-one patients were included (median age 12.7 years; 51% female). The most common transplant indications were cystic fibrosis (29%) and pulmonary hypertension (20%). Seventeen patients (33%) had PGD 3 at either 48- or 72-hours. In unadjusted analysis, PGD 3 was associated with an increased risk of CLAD or mortality (HR 2.10, 95% CI 1.01-4.37, p =0.047). This association remained when adjusting individually for multiple potential confounders. There was evidence of effect modification by sex (interaction p = 0.055) with the association of PGD 3 and shorter CLAD-free survival driven predominantly by males (HR 4.73, 95% CI 1.44-15.6) rather than females (HR 1.23, 95% CI 0.47-3.20). PGD 3 at 48- or 72-hours following pediatric lung transplantation was associated with shorter CLAD-free survival. Sex may be a modifier of this association. [ABSTRACT FROM AUTHOR]

Objectives: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus., Data Sources: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children., Study Selection: The management of ECMO anticoagulation for critically ill neonates and children., Data Extraction: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts., Data Synthesis: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis)., Conclusions: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population., Competing Interests: Drs. Muszynski and Alexander’s institutions received funding from the National Institutes of Health (NIH). Drs. Muszynski, Bembea, Himebauch, Barbaro, and Alexander received support for article research from the NIH. Dr. Bembea’s institution received funding from the National Institute of Neurologic Disorder and Stroke (R01NS106292) and a Grifols Investigator Sponsored Research Grant. Drs. Bembea, Steiner, and Thiagarajan’s institutions received funding from the Department of Defense. Dr. Cheifetz received funding from UptoDate. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation (ECMO) Concepts, Entegrion, and Hemocue; she disclosed the off-label product use of ECMO equipment and drugs for anticoagulation. Dr. Himebauch receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL153759. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Said acknowledges research support from the Children’s Discovery Institute Faculty Development Award at Washington University in St. Louis. Dr. Ozment received funding from Kaufman & Canoles Law Firm, Wiseman Ashworth Law Group, and Social Cascade; she disclosed the off-label product use of Heparin and bivalirudin use in neonatal and pediatric patients on ECMO. Dr. Steiner received funding from Octapharma, MedTronic, and PumpKIN DSMB; she disclosed the off-label product use of rFVIIA, TXA, Amicar, Kcentra. Dr. Thiagarajan received funding from the Society of Critical Care Medicine and the Extracorporeal Life Support Organization (ELSO). Dr. Zantek received funding from the North American Specialized Coagulation Laboratory Association (NASCOLA), the American Society for Apheresis (ASFA), and BloodNet; she disclosed that she is a Board Member of External Quality Assurance in Thrombosis and Hemostasis, a committee member of NASCOLA, ASFA, the Association for the Advancement of Blood and Biotherapies, the College of American Pathologists, and the International Society for Laboratory Hematology; she disclosed that her spouse is an employee of Boston Scientific and has a financial interest in Boston Scientific and Endo International. Dr. Barbaro’s institution received funding from the NIH (R01 HL153519 and K12 HL138039); he disclosed that he is a Board Member for ELSO and Co-Chair for Pedi-ECMO. Dr. Alexander’s institution received funding from ELSO and Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE., Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021., Study Selection: Management of ECMO anticoagulation in the setting of different ECMO circuit components., Data Extraction: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. Evidence tables were constructed using a standardized data extraction form., Data Synthesis: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for the influence of ECMO circuit and components on anticoagulation management. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented., Conclusions: The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes., Competing Interests: Dr. Himebauch receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) under award number K23HL153759. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr. Said acknowledges research support from the Children’s Discovery Institute Faculty Development Award at Washington University in St. Louis. Dr. Turner is used by the American Board of Pediatrics, and the content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the American Board of Pediatrics. Drs. Muszynski, and Alexander received support for article research from the NIH. Dr. Alexander’s institution received funding from the National Institute of Child Health and Human Development (1R13HD104432), Extracorporeal Life Support Organization (ELSO), and Novartis. Dr. Paden received funding from ELSO, he disclosed that he is past president and board member of ELSO, and he disclosed the off-label product use of extracorporeal membrane oxygenation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)