Pediatric Extracorporeal Membrane Oxygenation Patients Research Articles

Pharmacokinetics of Human Plasma-Derived Antithrombin in Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off-label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma-derived AT. We demonstrated that a two-compartment turnover model appropriately described the PK of AT, and the parameter estimates for clearance, central volume, intercompartmental clearance, peripheral volume, and basal AT input under non-ECMO conditions were 0.338 dL/h/70 kg, 38.5 dL/70 kg, 1.16 dL/h/70 kg, 40.0 dL/70 kg, and 30.4 units/h/70 kg, respectively. Also, ECMO could reduce bioavailable AT by 50% resulting in 2-fold increase of clearance and volume of distribution. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in older infants and children, we proposed potential replacement regimens for each age group, accompanied by therapeutic drug monitoring.

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

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. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. ECMO anticoagulation and hemostasis management in the perioperative period and during procedures. 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. 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. Although agreement among experts was strong, important future research is required in this population for evidence-informed recommendations.

Prophylactic Transfusion Strategies in Children Supported by Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding prophylactic transfusions in neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021. Included studies assessed use of prophylactic blood product transfusion in pediatric ECMO. Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Thirty-three references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-informed recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for prophylactic transfusion strategies for children supported with ECMO. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was based on a modified Delphi process with agreement defined as greater than 80%. We developed two good practice statements, 4 weak recommendations, and three expert consensus statements. Despite the frequency with which pediatric ECMO patients are transfused, there is insufficient evidence to formulate evidence-based prophylactic transfusion strategies.

Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. The management of bleeding and thrombotic complications of ECMO. Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. 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. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented. Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.

Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs). Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. 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. One weak recommendation and three consensus statements are presented. Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

Research progress on nutritional support in the neonatal and pediatric populations receiving extracorporeal membrane oxygenation.

Nutritional support is crucial for the prognosis of children supported by extracorporeal membrane oxygenation (ECMO). This article discusses the latest research progress and guideline recommendations for nutritional support during ECMO. We summarize the nutritional status and evaluation of ECMO patients, nutritional support methods and timing, trace elements, the impact of continuous renal replacement therapy (CRRT), and energy requirements and algorithms. The article shows that malnutrition is high in ECMO patients compared to other critically ill patients, with nearly one-third of patients experiencing a decrease in nutritional indicators. The timing of the initiation of nutrition is very important for the nutritional status of the child. Early enteral nutrition can improve patient prognosis, which is the most commonly used, with parenteral nutrition as a supplement. However, the proportion of enteral nutrition is relatively low, and a stepwise nutrition algorithm can determine when to initiate early enteral nutrition and parenteral nutrition. Malnourishment during critical illness have been associated with increased morbidity as well as increased mortality. Nutritional status should be evaluated at admission by screening tools. In addition, changes in the levels of several metabolites in vivo, such as blood lipids, carnitine, and thiamine, can also reflect the degree of nutritional deficiency in critically ill children. This article provides a reference for the implementation of nutrition of pediatric ECMO patients and further research on nutritional support.

In vivo measurement of pediatric extracorporeal oxygenator insensible losses; a single center pilot study.

Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous in vitro studies have attempted to quantify oxygenator-related insensible losses, as failure to account for this fluid loss may lead to inaccurate fluid balance assessment and potentially harmful clinical management, such as unnecessary exposure to diuretics, slow continuous ultrafiltration (SCUF), or continuous kidney replacement therapy (CKRT). We performed a novel in vivo study to measure insensible fluid losses in pediatric ECMO patients. Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow. Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m2 IQR [0.315, 1.3725]. Overall, the cohort had a median sweep of 2.5 L/min [0.9, 4], ECMO flow of 3.975 L/m2/min [0.75, 4.51], and a set ECMO temperature of 37 degrees Celsius [36.6, 37.2]. The calculated net water loss per L/min of sweep was 75.93 ml/day, regardless of oxygenator size or patient weight. There was a significant difference in median documented vs. calculated fluid balance incorporating the insensible fluid loss, irrespective of oxygenator size (pediatric oxygenator: 7.001 ml/kg/day [-12.37, 28.59] vs. -6.11 ml/kg/day [-17.44, 13.01], respectively, p = 0.005 and adult oxygenator: 14.36 ml/kg/day [1.54, 25.77] and 9.204 ml/kg/day [-1.28, 22.05], respectively, p = <0.001). We present this pilot study of measured oxygenator-associated insensible fluid losses on ECMO. Our results are consistent with prior in vitro methods and provide the basis for future studies evaluating the impact of incorporating these fluid losses into patients' daily fluid balance on patient management and outcomes.

"Extracorporeal membrane oxygenation outcomes in multisystem inflammatory syndrome of childhood - An extracorporeal life support organization registry study".

Multisystem inflammatory disease in childhood (MIS-C) is a novel pediatric syndrome after a COVID-19 infection that causes systemic injury, with potential life-threatening hemodynamic compromise requiring Extracorporeal Membrane Oxygenation (ECMO) support. We performed an observational retrospective cohort study in children aged 0-18 years with MIS-C and non-MIS-C myocarditis on ECMO between January 2020 and December 2021, using the ELSO Registry database. We aimed to compare the outcomes of both populations and to identify factors for decreased survival in MIS-C patients on ECMO. The Extracorporeal Life Support Organization (ELSO) Registry reported 310 pediatric ECMO patients with MIS-C (56.1%) and non-MIS-C myocarditis (43.9%). No difference was found in survival to hospital discharge between groups (67.2% for MIS-C vs 69.1% for non-MIS-C myocarditis, p 0.725). Multivariable analysis demonstrated that ECPR and co-infection were significantly associated with decreased survival to hospital discharge in MIS-C patients (OR 0.138, p 0.01 and OR 0.44, p 0.02, respectively). Outcomes of children with MIS-C on ECMO support are similar to those of non-MIS-C myocarditis despite higher infectious, multiorgan dysfunction and respiratory complications accompanying COVID-19 infections. The use of ECMO for MIS-C patients seems to be feasible and safe. Prospective studies on the use of ECMO support in MIS-C patients may improve outcomes in this pediatric population.

100: Invasive Surgical Procedures Impact Mortality in Pediatric Extracorporeal Membrane Oxygenation Patients

100: Invasive Surgical Procedures Impact Mortality in Pediatric Extracorporeal Membrane Oxygenation Patients

Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature.

Although intravenous (IV) direct thrombin inhibitors (DTI) have gained interest in pediatric extracorporeal membrane oxygenation (ECMO), dosing and safety information is limited. The objective of this systematic review was to characterize DTI types, dosing, monitoring, and outcomes (bleeding and thromboembolic) in pediatric ECMO patients managed with IV DTIs. We conducted searches of MEDLINE (Ovid) and Embase (Elsevier) from inception through December 2022. Case reports, retrospective studies, and prospective studies providing per-patients or summary data for patient(s) <18 years of age receiving IV DTI for ECMO anticoagulation were included. Study selection and data extraction were conducted independently by two reviewers. A total of 28 studies: 14 case reports, 13 retrospective studies, and 1 prospective study were included, totaling 329 patients. Bivalirudin was utilized in 318 (96.7%), argatroban in 9 (2.7%), and lepirudin in 2 (0.6%) patients. Infusion dosing included: bivalirudin 0.14 ± 0.37 mg/kg, argatroban 0.69 ± 0.73 µg/kg/min, lepirudin 0.14 ± 0.02 mg/kg/h. Laboratory monitoring tests utilized were the activated clotting time, activated partial thromboplastin time (aPTT), diluted thrombin time, and thromboelastography measures. The aPTT was utilized in most patients (95%). Thromboembolism, bleeding, or death were observed in 17%, 17%, and 23% of bivalirudin, argatroban, and lepirudin patients, respectively. Bivalirudin appears to be the most frequently used DTI in pediatric ECMO. Dosing and laboratory monitoring varied, and bleeding and thromboembolic events were reported in 17% of patients. Prospective studies are warranted to establish dosing, monitoring, safety, and efficacy of bivalirudin and other IV DTI in pediatric ECMO.

Pediatric venoarterial and venovenous ECMO

Extracorporeal membrane oxygenation (ECMO) is an invaluable resource in the treatment of critically ill children with cardiopulmonary failure. To date, over 36,000 children have been placed on ECMO and the utilization of this life saving treatment continues to expand with advances in ECMO technology. This article offers a review of pediatric ECMO including modes and sites of ECMO cannulation, indications and contraindications, and cannulation techniques. Furthermore, it summarizes the basic principles of pediatric ECMO including circuit maintenance, nutritional support, and clinical decision making regarding weaning pediatric ECMO and decannulation. Finally, it gives an overview of common pediatric ECMO complications including overall mortality and long-term outcomes of ECMO survivors. The goal of this article is to provide a comprehensive review for healthcare professionals providing care for pediatric ECMO patients.

PEDS9: Bleeding in Pediatric Patients on Extracorporeal Membrane Oxygenation-Use of Procoagulant Factors

Background: Bleeding complications remain common in extracorporeal membrane oxygenation (ECMO) and can be associated with adverse outcomes. Effect of excessive shear stress on vasculature may increase bleeding risk associated with preferential loss of high molecular weight von Willebrand factor (high molecular weight (vWF) multimers; acquired vW syndrome, AVWS) and may also be associated with platelet dysfunction. Some pediatric patients may have a pre-existing increased risk of shear-related abnormalities which may further increase bleeding risk on ECMO. We aimed to review bleeding events requiring intervention in a pediatric ECMO cohort. Methods: Retrospective review of pediatric ECMO patients who underwent treatment of bleeding beyond simple transfusion in conjunction with ECMO anticoagulation consultation (EAC) between June 2020 and December 2022 was conducted. Results: Fifty patients required ECMO for 53 runs (52 VA, 2 VV, 1 VAV). Median weight was 4.3 kg (2.4-131 kg). Mean duration of ECMO was 11 days (2-97). 60% (30/50) of patients had congenital heart disease (CHD), and within these 30 patients, 27% of them had bleeding requiring procedural intervention. Ten patients with bleeding were screened for AVWS guided by EAC with 100% meeting criteria for AVWS. Platelet transfusions were administered as first line bleeding therapy with thrombocytopenia or platelet dysfunction and plasma or prothrombin complex concentrate (PCCC) in volume-sensitive patients for coagulopathy. With ongoing bleeding despite transfusion, antihemophilic factor/vWF complex (Humate P) was administered to 4 patients guided by EAC (figure 1). Of these 4 patients, 75% had CHD and 100% had valve abnormalities with 50% having new mechanical valves placed within 1 month prior to ECMO. Initial Humate P dose was given on mean day 14, with mean number of 8 doses. No circuit or mechanical valve thrombosis occurred. Platelet counts and function improved with a decrease in platelet transfusions and clinical bleeding in all patients following Humate P. Conclusion: Bleeding remains a common complication but is often multifactorial and may be difficult to determine specific etiologies. AVWS and thrombocytopenia commonly occur during pediatric ECMO. However, not all patients have clinical bleeding, such that additional risk factors may contribute to increased bleeding risk in these patients. Given impact of recurrent transfusions due to bleeding on morbidity and mortality, as well as cost consideration and potential thrombosis risk of vWF or PCCC supplementation, development of an expert-guided (EAC) algorithm for screening and treatment criteria for such agents appears to be safe, cost-effective and may be associated with decreased bleeding and transfusions. Further research into etiologies and consequences of ECMO-induced bleeding as well as treatment is needed.Figure 1. Algorithm for Assessment of Persistent Bleeding and Consideration of Humate P Administration (pilot).

Tickle Me ECMO…Differences and Outcomes Unearthed for Kids Requiring Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Syndrome Coronavirus 2-Associated Disease.

Tickle Me ECMO…Differences and Outcomes Unearthed for Kids Requiring Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Syndrome Coronavirus 2-Associated Disease.

A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Single-Center Experience Using the Cardiohelp System for Neonatal and Pediatric Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) systems have continued to evolve and improve with the development of smaller and portable systems. The Cardiohelp (Maquet Getinge Cardiopulmonary AG, Rastatt, Germany) portable life support device is a compact ECMO system used widely in adults and for ECMO transport. Reports of its use in neonatal and pediatric centers remain limited. In this single-center retrospective review, we describe our institutional experience with the Cardiohelp. Single-center retrospective review. Neonatal ICUs and PICUs in a tertiary-care children's hospital. Seventeen pediatric patients on ECMO. None. Median (interquartile range, IQR) of patient age was 0.5 years (0-7 yr). Eleven of 17 patients were on veno-arterial ECMO, five on veno-venous ECMO, and one on veno-venoarterial ECMO. All veno-venous and veno-venoarterial runs ( n = 6) were accomplished with bicaval, dual-lumen cannulae. Median duration on Cardiohelp was 113 hours (IQR 50-140 hr). Median anti-Xa level for patients was 0.43 IU/mL (IQR 0.35-0.47 IU/mL), with median heparin dose of 23.6 U/kg/hr (IQR 17.6-28.1 U/kg/hr). Median plasma-free hemoglobin was 41.4 mg/dL (IQR 30-60 mg/dL). Circuit change was required in three cases. Fourteen patients survived ECMO, with 13 patients surviving to discharge. We have used the Cardiohelp system to support 17 neonatal and pediatric ECMO patients, without complications. Further studies are warranted to compare complications, outcomes, and overall cost with other institutions and other existing ECMO systems.

349: EVALUATING CONCORDANCE BETWEEN LAB HEMOGLOBIN/HEMATOCRIT AND POINT-OF-CARE TESTS IN PEDIATRIC ECMO

Introduction: Accuracy of point-of-care (POC) hemoglobin (Hgb) and hematocrit (Hct) testing in critically ill patients on extracorporeal membrane oxygenation (ECMO) support is unknown. Advantages of POC testing include immediate results and smaller blood volume, however inaccurate results can lead to repeat testing and could contribute to increased blood transfusion. The objectives of this study were to quantify agreement between lab-based and POC tests for Hgb and Hct in critically ill pediatric patients on ECMO. Methods: A single center retrospective study from January 1, 2013 to December 31, 2021. Lab and POC results were recorded if obtained within 5 minutes of each other. A single set of values was recorded per day, using the values closest to 4AM if multiple sets were obtained, and up to 10 days of an individual ECMO course were included. POC measures included in-line hematocrit monitor and bedside blood gas analyzer. Discordance was a priori defined as > 0.5g/dL (Hgb) or > 1.5% (Hct) discrepancy. Exclusion criteria were: > 18 years of age, cannulated at outside hospital, converted to other mechanical circulatory support, ECMO support during OR only, and subsequent ECMO courses during the study. Results: 136 patients were included with an average age of 2 months. 51% were female. 66% VA ECMO and 34% VV ECMO. Diagnoses included sepsis (8.1%), trauma (2.9%), cardiac s/p CPB (29%), cardiac non-CPB (15%), congenital diaphragmatic hernia (CDH) (12%), and non-CDH respiratory (31%). The average ECMO duration included in analyses was 7 days. 279 values compared lab-based to in-line, of which 27% were discordant for Hgb and 24% for Hct. 59 values compared lab-based to blood gas analyzer, of which 32% were discordant for Hgb and 36% for Hct. All discordant results had a lower POC value. Conclusions: Lab-based hemoglobin and hematocrit values compared to both blood gas analyzer and in-line hematocrit monitor were often discordant. In all cases, POC measures were lower, raising concerns that use of POC to guide transfusions could increase transfusion burden. Further study is needed to evaluate factors predictive of discordance and to determine effects of POC hemoglobin/hematocrit measures on transfusion burden in pediatric ECMO patients.

283: PREDICTING ETHICS CONSULTATIONS IN PEDIATRIC PATIENTS SUPPORTED ON ECMO

Introduction: No publications quantify or characterize patient-level ethical issues in pediatric extracorporeal membrane oxygenation (ECMO). We sought to examine characteristics associated with referral to a hospital ethics consult (EC) service for pediatric ECMO patients. Methods: This is a single center retrospective study in a quaternary pediatric hospital. Local ECMO and ethics databases and records were cross referenced to include all patients on ECMO from 2012 through 2021 and identify those with EC. We compared demographic and clinical variables according to EC. To define optimal cutoffs for EC for run duration, length of stay (LOS) and sum of procedures and complications, we fit receiver operating characteristics (ROC) curves. To identify independent predictors of EC in ECMO patients we used forward stepwise selection including 7 a priori defined covariates in a multivariable logistic regression model (age, ECMO location, ECPR and multiple runs as well as the three optimal cutoff variables). Results: Of 601 ECMO patients, 27 received EC (4.5%). EC was associated with multiple ECMO runs, more complications/procedures, longer LOS and ECMO duration, cardiac service cannulation location, decannulation outcomes (bypass or recannulation) and higher in-hospital mortality (p< 0.05). Cutoffs for EC were LOS >52 days, run duration >160hrs and >6 procedures and complications. Independent associations with EC included LOS>52 days (adjusted odds ratio (aOR) 7.9, 95% CI [3.0, 21.1]), run >160hrs (aOR 3.3, 95%CI [1.1, 9.7]), procedure and complication sum >6 (aOR 2.5, 95%CI [1.0, 6.0]) and age (adjusted coefficient 1.3, 95%CI [1.1, 1.5]). The model showed good discrimination (area under the ROC curve 0.88), fit (Hosmer Lemeshow test p = 0.723) and no collinearity (VIF < 1.4). Conclusions: We observed a low EC rate compared to adult studies. Older age, longer LOS, prolonged runs and multiple procedures or complications were predictors of EC. These data may guide earlier identification of patients at risk for significant ethical issues and inform ethically supportable frameworks around this invasive care. Future work should include model validation and quality improvement projects to improve EC utilization and evaluate the influence on patient experience and quality of care.

Use of a Calibrated, Drug-Specific DTT Assay to Improve Bivalirudin Monitoring in Pediatric Extracorporeal Membrane Oxygenation (ECMO)

Background: Balancing the hemostatic system in anticoagulated ECMO patients to optimally prevent thrombosis and bleeding is challenging. Although the traditional anticoagulant of choice for ECMO has been unfractionated heparin (UFH), use of the direct thrombin inhibitor bivalirudin is growing, due to reported reductions in bleeding and thrombotic complications. Bivalirudin monitoring remains problematic, as the most widely available and commonly used assay, the activated partial thromboplastin time (aPTT), correlates poorly with other assays of bivalirudin effect. An accurate, standardized monitoring test is needed. In a prior study we investigated use of a research-only dilute thrombin time (dTT) assay calibrated to bivalirudin concentration (Hemoclot, Hyphen-Biomed, FR) in a pediatric ventricular assist device (VAD) population. This bivalirudin dTT had excellent correlation with both the clinical dTT (R2 = 0.991) and with a research-only, drug-calibrated factor IIa chromogenic assay (BiophenDT, Hyphen-Biomed, FR) (R2 = 0.94), but poor correlation with the aPTT (R2 =0.1). This led to an institutional practice change to utilize the clinical dTT and the bivalirudin dTT assay for monitoring bivalirudin in VAD patients. Clinicians started to include these tests as well as the aPTT for patients on ECMO; however, validation of the test in the ECMO population has not been reported. Aim: The aim of this quality improvement project was to validate how the bivalirudin dTT correlated with the clinically ordered dTT (c-dTT) and aPTT in pediatric ECMO patients. Methods: A retrospective review of pediatric ECMO patients ages 0-18 years treated with bivalirudin was conducted. Bivalirudin dosing, monitoring and titration was at the discretion of the treating physician. Clinically ordered laboratory testing of interest included c-dTT, bivalirudin dTT, and aPTT. The bivalirudin dTT uses a known quantity of human thrombin added to a 1:10 diluted plasma sample to initiate clotting. Clotting time (seconds) is related to bivalirudin concentration using drug-specific controls and calibrators of low and high (1.5 and 4 microgram/mL) bivalirudin (Biophen, Hyphen-Biomed, FR). Clinical data is reported descriptively. The bivalirudin dTT was compared to aPTT and c-dTT results using Pearson correlation and an R2 coefficient determined by simple linear regression. Data analysis on clinical outcomes including circuit thrombosis, patient thrombosis, and bleeding events is ongoing. Results: In total, 124 clinically obtained, concurrent c-dTT, aPTT, and bivalirudin dTT results from 6 pediatric ECMO patients receiving bivalirudin were evaluated. Ages ranged from 0-14 years (mean 3.5 years) with 4 patients started on ECMO in the neonatal period (<1 month of age). Indications for ECMO included congenital heart disease, congenital diaphragmatic hernia, respiratory failure, and cardiogenic shock. Mean bivalirudin infusion rate was 0.6 mg/kg/hr (range 0.15-0.84mg/kg/hr). Average duration on bivalirudin was 8 days (range 4-11) for 5 of the 6 patients, with 1 patient on for > 150 days. The mean aPTT was 78.5 seconds (range 55.9-105.5 seconds). The mean c-dTT was 51 seconds (range 25.4-71.1 seconds). The bivalirudin assay had poor correlation with aPTT (R2 = 0.273, Fig 1) and excellent correlation with the c-dTT (R2 = 0.899, Fig 2). A c-dTT range of 35-65 seconds corresponded with a bivalirudin dTT level of 0.55-1.8mcg/mL. Discussion: Here we report results of the clinical use of a bivalirudin dTT monitoring assay in pediatric ECMO patients. Similar to prior results in VADs, the aPTT showed poor correlation with the bivalirudin dTT. The c-dTT had excellent correlation with the bivalirudin dTT and results were so stable for an infusion rate that clinicians ordered less frequent monitoring labs, compared to their practice for UFH. More research and outcomes data is needed to determine the appropriate therapeutic range for optimizing bivalirudin effect and minimizing complications. Validation of a bivalirudin-specific assay that can be used by many institutions will facilitate collaboration on outcomes-based research. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bivalirudin in pediatric extracorporeal membrane oxygenation.

This review summarizes the current literature surrounding the use of bivalirudin as an alternative anticoagulant for pediatric extracorporeal membrane oxygenation (ECMO) patients. Recent single center studies describe that bivalirudin may be associated with decreased blood product transfusion, decreased cost and similar clinical outcomes for pediatric ECMO patients who have failed unfractionated heparin (UFH) anticoagulation. aPTT is the most common test to monitor bivalirudin but has several limitations. Other tests including dilute thrombin time (dTT) and viscoelastic assays are promising but more study is needed. Current evidence suggests that bivalirudin is a well tolerated and effective alternative anticoagulant for pediatric ECMO patients who have failed UFH anticoagulation but prospective studies are needed to confirm these results. Bivalirudin is a promising alternative anticoagulant for pediatric ECMO patients who have failed UFH. Large prospective, multicenter studies are needed to confirm safety and efficacy.

Transfusion policy in pediatric extracorporeal membrane oxygenation patients: Less could be more.

To evaluate a restrictive transfusion policy of red blood cells (RBC) and platelets in pediatric patients submitted to extracorporeal membrane oxygenation (ECMO). Retrospective descriptive study of pediatric patients supported with ECMO, from January 2010 to December 2019. Hemoglobin, platelet, lactate and mixed venous oxygen saturation (SvO2) values of each patient while on ECMO, were collected. Transfusion efficiency and tissue oxygenation were statistically evaluated comparing pre-transfusion hemoglobin, lactate and SvO2 with post-transfusion values. Ranges of hemoglobin and platelets were established, and the number of transfusions registered. The bleeding complications and outcome were documented. Of a total of 1016 hemoglobin values, the mean value before transfusion was 8.6g/dl. Hemoglobin and SvO2 increased significantly post-transfusion. Red blood cell transfusion varied with hemoglobin values: when hemoglobin value was less than 7g/dl, 89% (41/46) were transfused but just 23% (181/794) when greater or equal to 7g/dl. In the presence of active bleeding, the frequency of RBC transfusion increased from 32% to 62%, with hemoglobin between 7g/dl and 8g/dl.The mean value for platelet transfusion was 32 x 109/L. Thirty-eight (43%) platelet values between 20 x 109/L and 30x109/L, and 31 (40%) between 30 x 109/L and 40 x 109/L led to platelet transfusion; between 40 x 109/L and 50 x 109/L, only 7 (9%) prompted platelet transfusion.Comparing the 2010-2015 to 2016-2019 periods there was a decrease in RBC and platelet transfusion threshold with similar survival (p = .528). Survival to discharge was 68%. Using a restrictive RBC and platelet transfusion policy was safe and allowed a good outcome in this case series. The presence of active bleeding was an important decision factor when hemoglobin was above 7g/dl and platelets were above 30 x 109/L.