Management of Extracorporeal Membrane Oxygenation Anticoagulation in the Perioperative Period: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic review-informed, modified Delphi consensus regarding the management of children on extracorporeal membrane oxygenation (ECMO) undergoing invasive procedures or interventions developed by the Pediatric Anticoagulation on ECMO CollaborativE (PEACE) Consensus Conference. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: ECMO anticoagulation and hemostasis management in the perioperative period and during procedures. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. Seventeen references were used for data extraction and informed recommendations. 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 for the management of bleeding and thrombotic complications in pediatric ECMO patients. 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. Four good practice statements, 7 recommendations, and 18 consensus statements are presented. CONCLUSIONS: Although agreement among experts was strong, important future research is required in this population for evidence-informed recommendations.

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

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.

Characterizing the Racial Discrepancy in Hypoxemia Detection in Venovenous Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Analysis.

PURPOSE: Skin pigmentation influences peripheral oxygen saturation (SpO2) compared to arterial saturation of oxygen (SaO2). Occult hypoxemia (SaO2 ≤ 88% with SpO2 ≥ 92%) is associated with increased in-hospital mortality in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO2-SaO2 discrepancy due to significant hemolysis. METHODS: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO2 and SaO2 measurements from over 500 centers in the Extracorporeal Life Support Organization Registry (1/2018-5/2023) were included. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO2-SaO2 calculations. RESULTS: Of 13,171 VV-ECMO patients, there were 7772 (59%) White, 2114 (16%) Hispanic, 1777 (14%) Black, and 1508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic patients versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively). In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18-2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95% CI = 1.16-2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95% CI = 1.15-2.55, P = 0.008) had higher risk versus White patients. Higher pump flow rates (aOR = 1.29, 95% CI = 1.08-1.55, P = 0.005) and on-ECMO 24-h lactate (aOR = 1.06, 95% CI = 1.03-1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia. CONCLUSION: SaO2 should be carefully monitored if using SpO2 during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia.

Cardiac Tamponade Complicating Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: Cardiac tamponade is a potentially life-threatening complication during extracorporeal membrane oxygenation (ECMO). In this study, the authors assessed the incidence, patient characteristics, and risk factors for mortality of cardiac tamponade during ECMO. DESIGN: The authors queried the Extracorporeal Life Support Organization (ELSO) Registry from 1997 to 2021 for all adults with cardiac tamponade as a reported complication during ECMO. PARTICIPANTS: Cardiac tamponade was reported in 2,176 (64% men; 53.8 ± 0.33 years) of 84,430 adults (2.6%). MEASUREMENTS AND MAIN RESULTS: Venoarterial ECMO was the main configuration (78%), followed by venovenous ECMO (VV ECMO) (18%), for cardiac (67%), pulmonary (21%) support, and extracorporeal cardiopulmonary resuscitation (ECPR) (12%). Percutaneous cannulation was performed in 51%, with the femoral vein and femoral artery as the most common sites for drainage and return cannulae, with dual-lumen cannulae in 39% of VV ECMO. Hospital survival was lower (35% v 49%; p < 0.01) when compared with that of all adults from the ELSO Registry. In multivariate analysis, age, aortic dissection and/or rupture, COVID-19, ECPR, pre-ECMO renal-replacement therapy, and prone position are associated with hospital mortality, whereas ECMO for pulmonary support is associated with hospital survival. Similarly, renal, cardiovascular, metabolic, neurologic, and pulmonary complications occurred more frequently in nonsurvivors. CONCLUSIONS: Cardiac tamponade is a rare complication during ECMO that, despite being potentially reversible, is associated with high hospital mortality. Venoarterial ECMO is the most common configuration. ECMO for pulmonary support was associated with higher survival, and ECPR was associated with higher mortality. In these patients, other ECMO-related complications were frequently reported and associated with hospital mortality.

Comparison of Platelet Mass Index to Platelet Count as Transfusion Trigger in Neonatal Extracorporeal Membrane Oxygenation.

BACKGROUND: Platelet transfusions are routinely administered to neonates in intensive care units when there are concerns of bleeding, including high-risk situations like Extracorporeal Membrane Oxygenation (ECMO). Most platelets in ICUs are transfused prophylactically for thrombocytopenia based solely on the platelet count. Platelet Mass Index (PMI) has been proposed as an alternative to platelet count (PC) as a transfusion trigger. The objective of this study was to determine the relationship between PMI and platelet-specific maximal clot firmness (PMCF) in Rotational thromboelastometry (ROTEM), which gives an indication of platelet contribution to clot firmness and to investigate whether PMI may be a better choice as a trigger for platelet transfusions than PC. METHODS: Retrospective review of medical records of neonates with congenital heart disease placed on ECMO support in the cardiovascular intensive care unit (CVICU) from 2015 to 2018 was conducted. Platelet count (PC), platelet mean volume (PMV), ROTEM parameters along with demographic data including gestation age, birth weight, gender and survival were collected. Mixed effects linear models with a first order autoregressive covariance structure were used to assess the associations of PMI, PC, and MPV against PMCF. In addition, generalized estimating equations with a first order auto-regressive covariance structure were used to compare odds of transfusion using PC versus PMI triggers. RESULTS: A total of 92 tests on consecutive days were obtained for 12 ECMO patients (5 male, GA = 38.1 ± 1.6 weeks, BW = 3.1 ± 0.4 kgs, mean ± SD). A variation of 40.1% in PMCF was explained by platelet count (p < 0.001) while 38.5% of the variation in PMCF was explained by PMI (p < 0.001). If the platelet transfusion trigger was PC < 100 x 103 platelets/µL vs. PMI < 800. Using the PC trigger yielded significantly higher odds of transfusion compared to the PMI trigger (odds ratio = 1.31, 95% confidence interval: 1.18 - 1.45, p < 0.001). CONCLUSIONS: While our study failed to demonstrate a superior correlation of PMI with PMCF than PC, our study did reveal that using PMI as transfusion trigger would result in significantly less platelet transfusions, when compared with the current practice of using PC as a trigger.

Vasoplegic Shock Represents a Dominant Hemodynamic Profile of Multisystem Inflammatory Syndrome Following COVID-19 in Children and Adolescents.

OBJECTIVES: The hemodynamic profile of multisystem inflammatory syndrome in children (MIS-C)-related shock remains poorly defined and, therefore, challenging to support with pharmacotherapy in the ICU. We aimed to evaluate the hemodynamic profile and vasoactive medication management used in MIS-C patients presenting to the ICU in shock and provide data from high-fidelity continuous cardiac output monitoring. DESIGN: Single-center retrospective case-cohort study. SETTING: Pediatric and cardiac ICU in a quaternary-care hospital. PATIENTS: All patients who met U.S. Centers for Disease Control and Prevention criteria for MIS-C and who were admitted to the ICU between March 2020 and May 2021 required vasoactive support and were placed on continuous cardiac index (CCI) monitoring. Patients requiring extracorporeal life support were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 52 children with MIS-C presenting in shock and requiring vasoactive support, 14 patients (27%) were placed on CCI monitoring. These 14 patients had hyperdynamic cardiac index (CI) and low indexed systemic vascular resistance (SVRi) in the first 24 hours with normalization of CI and improved SVRi within the subsequent 24 hours. CONCLUSIONS: Further studies are needed to evaluate the difference between the use of vasoconstrictor versus vasodilators in pediatric patients with MIS-C because a phenotype with high CI and low SVRi may be important.

Cardiovascular sequelae from COVID-19: perspectives from a paediatric cardiac ICU.

OBJECTIVE: Paediatric ICUs have shared the burden of the COVID-19 pandemic, including subspecialty cardiac ICUs. We sought to address knowledge gaps regarding patient characteristics, acuity, and sequelae of COVID-19 in the paediatric cardiac ICU setting. DESIGN: Retrospective review of paediatric cardiac ICU admissions with COVID-19-related disease. SETTING: Single centre tertiary care paediatric cardiac ICU. PATIENTS: All patients with PCR/antibody evidence of primary COVID-19 infection, and/or Multisystem Inflammatory Syndrome in Children, were admitted between 26 March, 2020 and 31 March, 2021. INTERVENTIONS: None. MAIN OUTCOMES MEASURES: Patient-level demographics, pre-existing conditions, clinical symptoms, and outcomes related to ICU admission were captured from medical records. RESULTS: Among 1064 patients hospitalised with COVID-19/Multisystem Inflammatory Syndrome in Children, 102 patients (9.5%) were admitted to cardiac ICU, 76 of which were symptomatic (median age 12.5 years [IQR 7.5-16.0]). The primary system involved at presentation was cardiovascular in 48 (63%). Vasoactive infusions were required in 62% (n = 47), with eight patients (11%) requiring VA ECMO. Severity of disease was categorised as mild/moderate in 16 (21%) and severe/critical in 60 patients (79%). On univariate analysis, African-American race, presentation with gastrointestinal symptoms or elevated inflammatory markers were associated with risk for severe disease. All-cause death was observed in five patients (7%, n = 5/72) with four patients remaining hospitalised at the time of data query. CONCLUSION: COVID-19 and its cardiovascular sequelae were associated with important morbidity and significant mortality in a notable minority of paediatric patients admitted to a paediatric cardiac ICU. Further study is required to quantify the risk of morbidity and mortality for COVID-19 and sequelae.

Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry.

BACKGROUND: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. METHODS: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. FINDINGS: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4-40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20-2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6-41·5). INTERPRETATION: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. FUNDING: None.

Improving Outcomes for Children Requiring Extracorporeal Membrane Oxygenation Therapy Following Hematopoietic Stem Cell Transplantation.

OBJECTIVES: The objective of this study was to provide an updated review of survival for pediatric hematopoietic stem cell transplantation patients requiring extracorporeal membrane oxygenation therapy as well as characterize the demographics, clinical variables, and complications associated with mortality. DESIGN: Retrospective database review of the Extracorporeal Life Support Organization Registry from 1990 to 2019. SETTING: Extracorporeal membrane oxygenation centers reporting to Extracorporeal Life Support Organization. PATIENTS: Patients treated with extracorporeal membrane oxygenation greater than 28 days to 18 years old with International Classification of Diseases Ninth Revision, International Classification of Diseases Tenth Revision, and current procedural terminology codes consistent with hematopoietic stem cell transplantation were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, year of extracorporeal membrane oxygenation run, clinical variables, comorbid diagnoses, and extracorporeal membrane oxygenation complications were assessed in relation to the primary study outcome of survival to hospital discharge. Ninety patients were included in the final analysis. The overall survival rate for the study period was 19%. However, the survival rate in the last decade (2010-2019) improved to 26% (p = 0.01; odds ratio 9.4 [1.2-74.8]). Factors associated with decreased survival included comorbid malignancy, elevated peak inspiratory pressure in conventionally ventilated patients, and pulmonary and metabolic complications on extracorporeal membrane oxygenation. CONCLUSIONS: Pediatric patients posthematopoietic stem cell transplantation supported with extracorporeal membrane oxygenation have improving survival rates over time. With 26% of patients (16/62) surviving to hospital discharge in the last decade (2010-2019), history of hematopoietic stem cell transplantation may no longer be considered an absolute contraindication to extracorporeal membrane oxygenation. As advancements are made in hematopoietic stem cell transplantation therapies and extracorporeal membrane oxygenation management, the indications for life-saving extracorporeal membrane oxygenation support among patients posthematopoietic stem cell transplantation may expand accordingly.

Epidemiology of Pediatric Heart Failure in the USA-a 15-Year Multi-Institutional Study.

The epidemiology of pediatric heart failure (HF) has been characterized for congenital heart disease (CHD) and cardiomyopathies (CM), but the impact of CM associated with CHD has not been studied. This study aims to describe the characteristics and outcomes of inpatient pediatric HF patients with CHD, CM, and CHD with CM (CHD + CM) across the USA. We included all HF patients with CM diagnoses with and without CHD using ICD 9/10 codes ≤ 19 years old from January 2004 to September 2019 using the Pediatric Health Information System database. We identified 67,349 unique patients ≤ 19 years old with HF, of which 87% had CHD, 7% had CHD + CM, and 6% had CM. Pediatric HF admissions increased significantly from 2004 to 2018 with an associated increase in extracorporeal circulatory support (ECLS) use. Heart transplantation (HTX) increased only in the CHD and CHD + CM groups. CHD patients required less ECLS with and without HTX; however, they had significantly higher inpatient mortality after those procedures than the other groups (p < 0.001). CM patients were older (median 115 months) and had the lowest inpatient mortality after HTX with and without ECLS (p < 0.05). CHD + CM showed the highest overall inpatient mortality (15%), and cumulative hospital billed charges (median US$ 541,374), all p < 0.001. Pediatric HF admissions have increased from 2004 to 2018. ECLS use and HTX have expanded in this population, with an associated decrease in inpatient mortality in the CHD and CM groups. CHD + CM patients are a growing population with the highest inpatient mortality.

Extracorporeal Membrane Oxygenation in Pregnancy: An Analysis of the Extracorporeal Life Support Organization Registry.

OBJECTIVES: We examined data from the International Registry of the Extracorporeal Life Support Organization to identify risk factors for mortality in pregnant and peripartum patients receiving extracorporeal membrane oxygenation. DESIGN: Retrospective analysis. SETTING: International Registry of Extracorporeal Life Support Organization. PATIENTS: We collected de-identified data on all peripartum patients who needed extracorporeal membrane oxygenation between 1997 and 2017 using International Classification of Diseases, 9th and 10th Edition criteria. INTERVENTIONS: Our primary outcome measure was in-hospital mortality. We also collected data on demographics, preextracorporeal membrane oxygenation ventilator, hemodynamic and biochemical parameters, extracorporeal membrane oxygenation mode, duration, and complications. Initial bivariate analysis assessed potential associations between survival and various preextracorporeal membrane oxygenation as well as extracorporeal membrane oxygenation-related factors. Variables with p values of less than 0.1 were considered for logistic regression analysis which identified predictors of mortality. MEASUREMENTS AND MAIN RESULTS: There were 280 peripartum patients who received extracorporeal membrane oxygenation. Overall maternal survival was 70%, with observed mortality for these patients decreasing over the 21-year time period. Multivariate regression identified extracorporeal cardiopulmonary resuscitation (odds ratio, 3.674; 95% CI, 1.425-9.473; overall p = 0.025), duration of extracorporeal membrane oxygenation (< 66 hr: odds ratio, 1; 66-128 hr: odds ratio, 0.281; 95% CI, 0.101-0.777; p = 0.014; 128-232 hr: odds ratio, 0.474; 95% CI, 0.191-1.174; p = 0.107; and > 232 hr: odds ratio, 1.084; 95% CI, 0.429-2.737; p = 0.864; overall p = 0.017), and renal complications on extracorporeal membrane oxygenation (odds ratio, 2.346; 95% CI, 1.203-4.572; p = 0.012) as significant risk factors for mortality. There was no statistically significant difference in mortality between venovenous versus venoarterial versus mixed group extracorporeal membrane oxygenation (23.9 vs 34.4 vs 29.4%; p = 0.2) or between pulmonary versus cardiac indications (1.634; 95% CI, 0.797-3.352; p = 0.18) for extracorporeal membrane oxygenation. CONCLUSIONS: On analysis of this multicenter database, pregnant and peripartum patients with refractory cardiac or respiratory failure supported on extracorporeal membrane oxygenation had survival rates of 70%. We identified preextracorporeal membrane oxygenation as well as extracorporeal membrane oxygenation-related factors that are associated with mortality.

Population Pharmacokinetics of Vancomycin in the Pediatric Ventricular Assist Device Population.

OBJECTIVES: Determine the pharmacokinetic disposition of vancomycin in the pediatric ventricular assist device population. DESIGN: A retrospective, population pharmacokinetic study. SETTING: Large, quaternary care children's hospital. PATIENTS: Less than 19 years old initiated on vancomycin while undergoing ventricular assist device therapy from 2011 to 2018 in our institution. INTERVENTIONS: Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM (Icon, PLC, Dublin, Ireland). Simulation was performed to identify a vancomycin dosing strategy that resulted in a trough concentration less than 15 mg/L and an area under the curve0-24:minimum inhibitory concentration ratio of greater than 400. MEASUREMENTS AND MAIN RESULTS: A total of 69 patients (male 50.7%, median age 7.1 years [interquartile range, 2.4-11.9]) met study criteria (HeartWare [Framingham, MA] = 37, Berlin Heart [Berlin, Germany] = 22, Impella [Abiomed, Danvers, MA] = 4, RotaFlow [Maquet, Hirrlingen, Germany] right ventricular assist device = 3, HeartMate II [Abbott Laboratories, Abbott Park, IL] = 2, Berlin Heart biventricular assist device = 1). Patients received a median of 21 doses (interquartile range, 13-44 doses) of IV vancomycin (14.8 ± 1.8 mg/kg/dose) along with vancomycin as an intrathoracic irrigation (n = 48; 69.6%). The mean serum concentration was 12.2 ± 5.2 mg/L at 11.2 ± 6.9 hours after a dose. A one-compartment pharmacokinetic model best fit the data with allometric scaling on clearance and volume of distribution. Clearance was characterized by total body weight and serum creatinine, and volume of distribution was characterized by total body weight. Simulation identified doses greater than 15 mg/kg/dose with extended intervals were necessary to achieve endpoints. CONCLUSIONS: Vancomycin dosing in pediatric ventricular assist device patients should be altered in comparison to nonventricular assist device patients and should be accompanied with frequent serum concentration monitoring.

Central Venous Catheter-Related Deep Vein Thrombosis in the Pediatric Cardiac Intensive Care Unit.

BACKGROUND: Central venous catheter (CVC) use is common in the management of critically ill children, especially those with congenital heart disease. CVCs are known to augment the risk of deep vein thrombosis (DVT), but data on CVC-associated DVTs in the pediatric cardiac intensive care unit (CICU) are limited. In this study, we aim to identify the incidence of and risk factors for CVC-related DVT in this high-risk population, as its complications are highly morbid. MATERIALS AND METHODS: The PC4 database and a radiologic imaging database were retrospectively reviewed for the demographics and outcomes of patients admitted to the Texas Children's Hospital CICU requiring CVC placement, as well as the incidence of DVT and its complications. RESULTS: Between January 2017 and December 2017, 1215 central lines were placed over 851 admissions. DVT was diagnosed in 8% of admissions with a CVC, 29% of which demonstrated thrombus in the inferior vena cava. The risk factors significantly associated with DVT included the presence of >1 line, higher total line hours, longer intubation times, and extended CICU stay. A diagnosis of low cardiac output syndrome, sepsis, central line-associated bloodstream infection, and cardiac catheterization were also significant risk factors. Interestingly, cardiac surgery with cardiopulmonary bypass appeared to be protective of clot development. DVT was a highly significant risk factor for mortality in these patients. CONCLUSIONS: CVC-related DVTs in critically ill children with congenital heart disease are associated with higher risks of morbidity and mortality, highlighting the need for well-designed studies to determine the best preventative and treatment strategies and to establish guidelines for appropriate monitoring and follow-up of these patients.

Antithrombin Population Pharmacokinetics in Pediatric Ventricular Assist Device Patients.

OBJECTIVES: Describe the pharmacokinetics of antithrombin in pediatric patients undergoing ventricular assist device therapy and provide dosing recommendations for antithrombin in this population. DESIGN: A retrospective population pharmacokinetic study was designed. SETTING: Large tertiary care children's hospital Subject inclusion criteria consisted of less than 19 years old. PATIENTS: Subjects less than 19 years old undergoing therapy with a HeartWare ventricular assist device (HeartWare, Framingham, MA) or Berlin EXCOR ventricular assist device (Berlin GmbH, Berlin, Germany), who received a dose of antithrombin with a postdose antithrombin activity level from January 1, 2011, to June 30, 2017. INTERVENTIONS: Population pharmacokinetic analysis and simulation using NONMEM v.7.4 (Icon, PLC, Dublin, Ireland). MEASUREMENTS AND MAIN RESULTS: A total of 41 patients met study criteria (median age, 5.8 years [interquartile range, 1.6-9.9 yr]), and 53.7% underwent therapy with the pulsatile Berlin EXCOR pediatric ventricular assist device (Berlin Heart GmbH, Berlin, Germany). All patients received unfractionated heparin continuous infusion at a mean ± SD dose of 29 ± 14 U/kg/hr. A total of 181 antithrombin doses (44.1 ± 24.6 U/kg/dose) were included, and baseline antithrombin activity levels were 77 ± 12 U/dL. Antithrombin activity levels were drawn a median 19.9 hours (interquartile range, 8.8-41.6 hr) after antithrombin dose. A one-compartment proportional error model best fit the data, with allometric scaling of fat-free mass providing a better model fit than actual body weight. Unfractionated heparin and baseline antithrombin were identified as significant covariates. A 50 U/kg dose of antithrombin had a simulated half-life 13.2 ± 6.6 hours. CONCLUSIONS: Antithrombin should be dosed on fat-free mass in pediatric ventricular assist device patients. Unfractionated heparin dose and baseline antithrombin activity level should be considered when dosing antithrombin in pediatric ventricular assist device patients.

Outcomes of Infants Supported With Extracorporeal Membrane Oxygenation Using Centrifugal Versus Roller Pumps: An Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To determine whether mortality differs between roller and centrifugal pumps used during extracorporeal membrane oxygenation in infants weighing less than 10 kg. DESIGN: Retrospective propensity-matched cohort study. SETTING: All extracorporeal membrane oxygenation centers reporting to the Extracorporeal Life Support Organization. PATIENTS: All patients less than 10 kg supported on extracorporeal membrane oxygenation during 2011-2016 within Extracorporeal Life Support Organization Registry. INTERVENTIONS: Centrifugal and roller pump recipients were propensity matched (1:1) based on predicted probability of receiving a centrifugal pump using demographic variables, indication for extracorporeal membrane oxygenation, central versus peripheral cannulation, and pre-extracorporeal membrane oxygenation patient management. MEASUREMENTS AND MAIN RESULTS: A total of 12,890 patients less than 10 kg were supported with extracorporeal membrane oxygenation within the Extracorporeal Life Support Organization registry during 2011-2016. Patients were propensity matched into a cohort of 8,366. Venoarterial and venovenous extracorporeal membrane oxygenation runs were propensity matched separately. The propensity-matched cohorts were similar except earlier year of extracorporeal membrane oxygenation (standardized mean difference, 0.49) in the roller pump group. Within the propensity-matched cohort, survival to discharge was lower in the centrifugal pump group (57% vs 59%; odds ratio, 0.91; 95% CI, 0.83-0.99; p = 0.04). Hemolytic, infectious, limb injury, mechanical, metabolic, neurologic, pulmonary, and renal complications were more frequent in the centrifugal pump group. Hemorrhagic complications were similar between groups. Hemolysis mediated the relationship between centrifugal pumps and mortality (indirect effect, 0.023; p < 0.001). CONCLUSIONS: In this propensity score-matched cohort study of 8,366 extracorporeal membrane oxygenation recipients weighing less than 10 kg, those supported with centrifugal pumps had increased mortality and extracorporeal membrane oxygenation complications. Hemolysis was evaluated as a potential mediator of the relationship between centrifugal pump use and mortality and met criteria for full mediation.

Characteristics and Outcomes of Pediatric Patients Supported With Ventricular Assist Device-A Multi-Institutional Analysis.

OBJECTIVES: The use of ventricular assist devices for pediatric patients with heart failure is increasing, but is associated with significant morbidity and mortality. Our objectives were to describe the admission outcomes and resource utilization of pediatric patients supported with ventricular assist devices, utilizing a multicenter database. DATA SOURCES: Pediatric Health Information System database (comprising 49 nonprofit children's hospitals). STUDY SELECTION: Retrospective cohort analysis of the database from January 2006 to September 2015 for all admissions less than or equal to 21 years old with ventricular assist device implantation. DATA EXTRACTION: The primary outcome was hospital mortality. The secondary outcomes were hospital length of stay and adjusted cost. DATA SYNTHESIS: We analyzed 744 ventricular assist device implantations (740 patients), 422 (57%) males, and 363 (49%) non-Hispanic white. Median age at admission was 5.9 years (interquartile range, 0.9-13.5 yr), and median length of stay was 69 days (interquartile range, 36-122 d). The overall hospital mortality was 188 (25%), whereas 395 (53%) were transplanted and 141 (19%) were discharged on ventricular assist device. Extracorporeal membrane oxygenation was used, in addition to ventricular assist device, in 340 (46%). The majority of ventricular assist device implantations (453, 61%) were from 2011 to 2015 (compared to 2006-2010). More patients discharged on ventricular assist device from 2011 to 2015 (23% vs 13% in 2006-2010; p = 0.001). There was no difference in median age, mortality, length of stay, or adjusted costs between these time periods. On multivariable analysis, underlying congenital heart disease, renal failure, liver congestion, sepsis, cerebrovascular accident, and extracorporeal membrane oxygenation were associated with hospital mortality. Sepsis and ventricular assist device replacement/repair were associated with higher adjusted cost and longer length of stay. CONCLUSIONS: The pediatric ventricular assist device experience continues to grow, with a significant increase in the number of patients undergoing ventricular assist device implantation and a higher proportion being discharged from hospital on ventricular assist device support in recent years. Underlying congenital heart disease, renal failure, sepsis, cerebrovascular accident, and extracorporeal membrane oxygenation are significantly associated with hospital mortality.

Cardiovascular recurrence of high-grade osteosarcoma presenting as atrial thrombosis and pulmonary embolism: A case report and review of the pediatric literature.

In the era of neoadjuvant and adjuvant chemotherapy, extrapulmonary involvement by high-grade osteosarcoma (HGOS) is rare. Importantly however, HGOS metastasis in the form of cardiovascular tumor thrombus portends a dismal prognosis. Thus, prompt and accurate identification of tumor thrombus is crucial. We report here two unique cases of recurrent HGOS, presenting as thrombotic events, in order to increase awareness and index of suspicion among practitioners regarding this presentation. Additionally, we review 14 previously reported pediatric cases of cardiovascular metastatic HGOS.

Pediatric Highlights From the Extracorporeal Life Support Organization Registry: 2017-2022.

The Extracorporeal Life Support Organization (ELSO) registry which collects data from hundreds of participating centers supports research in ECMO to help improve patient outcomes. The ELSO Scientific Oversight Committee, an international and diverse group of ECMOlogists ( https://www.elso.org/registry/socmembers.aspx ), selected the most impactful and innovative research articles on pediatric ECMO emerging from ELSO data. Here they present brief highlights of these publications.

Adult Highlights From the Extracorporeal Life Support Organization Registry: 2017-2022.

The Extracorporeal Life Support Organization (ELSO) registry captures clinical data and outcomes on patients receiving extracorporeal membrane oxygenation (ECMO) support across the globe at participating centers. It provides a very unique opportunity to benchmark outcomes and analyze the clinical course to help identify ways of improving patient outcomes. In this review, we summarize select adult ECMO articles published using the ELSO registry over the past 5 years. These articles highlight innovative utilization of the registry data in generating hypotheses for future clinical trials. Members of the ELSO Scientific Oversight Committee can be found here: https://www.elso.org/registry/socmembers.aspx .