Extracorporeal Membrane Oxygenation Run Research Articles

Outcomes of extracorporeal life support for respiratory failure in children with primary immunodeficiencies.

Extracorporeal Membrane Oxygenation (ECMO) may serve as a life-saving rescue therapy in critically ill children with respiratory failure. While survival rates of ECMO in children with secondary immunodeficiency is considered relatively poor, survival rates in children with primary immunodeficiencies (PID) has yet to be thoroughly investigated. Retrospective analysis of prospectively collected data from children (29 days-18 years old). PID patients were identified by using International Classification of Diseases (ICD) codes. Data were retrieved from Extracorporeal Life Support Organization Registry (1989-2018). ECMO for a pulmonary support indication. The survival-to-discharge rate was calculated and factors influencing outcomes were compared between survivors and non-survivors. A total of 73 eligible ECMO runs were included. The survival-to-discharge rate in pediatric PID patients was 45.2%. No differences were noted in survival based on type of immunodeficiency (p = 0.42) or decade of support (p = 0.98). There was no difference in the rate of pre-ECMO infection in survivors versus non-survivors (p = 0.69). The survival-to-discharge rate in patients with a culture positive infection during the ECMO run was 45.0% versus 45.3% in those with no infection (p = 0.98). In multivariate analysis, only cardiac complications (OR 5.09, 95% CI: 1.15-22.53), pulmonary complications (OR: 13.00, 95% CI: 1.20-141.25), and neurologic complications (OR: 9.86, 95% CI: 1.64-59.21) were independently associated with increased mortality. Children with a PID who require extracorporeal life support due to respiratory failure have a reasonable chance of survival and should be considered candidates for ECMO. The presence of a pre-ECMO infection should not be considered an ECMO contraindication.

Extracorporeal Membrane Oxygenation Complications in Heparin- and Bivalirudin-Treated Patients.

Retrospective cohort study. Johns Hopkins Hospital patients between January 2016 and July 2019. Adult (> 18 yr) extracorporeal membrane oxygenation patients. Patients were anticoagulated either with heparin or bivalirudin. We compared rates of hemorrhagic and thrombotic complications by time on heparin versus bivalirudin and characterized the average time to each complication. Of 144 extracorporeal membrane oxygenation patients (mean age 55.3 yr; 58% male), 41% were on central venoarterial extracorporeal membrane oxygenation, 40% on peripheral venoarterial extracorporeal membrane oxygenation, and 19% on venovenous extracorporeal membrane oxygenation. Thirteen patients (9%) received bivalirudin during their extracorporeal membrane oxygenation run, due to concern for (n = 8) or diagnosis of (n = 4) heparin-induced thrombocytopenia or for heparin resistance (n = 1). The rate of hemorrhagic or thrombotic complications did not differ between heparin (0.13/d) and bivalirudin (0.06/d; p = 0.633), but patients on bivalirudin received significantly fewer blood transfusions (1.0 U of RBCs/d vs 2.9/d on heparin; p < 0.001). Our results confirm the safety and efficacy of bivalirudin as an alternative anticoagulant in extracorporeal membrane oxygenation and suggest a potential benefit in less blood product transfusion, although prospective studies are needed to evaluate the true effect of bivalirudin versus the disease processes that prompted its use in our study population.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

ELSO Interim Guidelines for Venoarterial Extracorporeal Membrane Oxygenation in Adult Cardiac Patients.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation.

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p = .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p < .01, Rho = .439), AST (p < .01, Rho = .439), RDW (p < .01, Rho = .190), LDH (p < .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p < .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p= .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p&lt; .01, Rho = .439), AST (p&lt; .01, Rho = .439), RDW (p&lt; .01, Rho = .190), LDH (p&lt; .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p&lt; .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Application of extracorporeal membrane oxygenation in critically ill pregnant women

To investigate the safety and effectiveness of extracorporeal membrane oxygenation (ECMO) in emergency treatment of critically ill pregnant women. Clinical data of 8 pregnant women with severe cardiopulmonary dysfunction during the perinatal period treated by ECMO in the department of intensive care unit (ICU) of Nanjing Drum Tower Hospital, the Affiliated Hospital to Nanjing University Medical School from September 2017 to November 2020 were retrospectively analyzed. For the 8 pregnant women, the mean age was (32.5±6.3) years old. Body weight was (73.5±8.1) kg. Gestational age was (31.0±4.4) weeks. Acute physiology and chronic health evaluation II (APACHE II) score was 13.0±6.6, and sequential organ failure assessment (SOFA) score was 8.3±3.8. Among them, 5 pregnant women suffered from severe pneumonia and were treated with venous-venous ECMO (VV-ECMO). Another 3 pregnant women with heart failure underwent venous-arterial ECMO (VA-ECMO). The initial ECMO flow rate was set to 2.0-3.0 L/min. Then the highest flow rate was (3.1±0.6) L/min, and the average ECMO running time was (174±36) hours. The length of ICU stay was (16.0±5.4) days. Six pregnant women (5 with severe pneumonia and 1 with peripartum cardiomyopathy) successfully evacuated from ECMO and survived. Two pregnant women with pulmonary hypertension showed poor prognosis. In total, seven babies survived. Two of them were delivered after ECMO evacution, and one underwent emergency cesarean section with ECMO support. In another case, the fetus could not be delivered due to under-gestational weeks. During this period, there were no serious bleeding complications. One pregnant woman developed heparin-induced thrombocytopenia and thrombosis (HITT), then she received another anticoagulant treatment. One pregnant woman got sequential anticoagulation therapy for 3 months on account of thrombosis in the puncture vessel. ECMO has played an active role in the rescue of critically ill pregnant women. For those with reversible severe cardiopulmonary dysfunction, it is necessary to evaluate the application of ECMO as early as possible to improve the survival rate of mothers and infants.

Emergency department extracorporeal membrane oxygenation may also include noncardiac arrest patients

Background/aimThe primary purpose of this study is to report the experience on the extracorporeal membrane oxygenation (ECMO) process for patients in the critical care unit (CCU) of an emergency department of a tertiary hospital in Turkey, from cannulation to decannulation, including follow-up procedures.Materials and methodsThis retrospective and observational study included eight patients who received ECMO from January 2018 to January 2020. We evaluated the demographics, indications for ECMO, laboratory values, Respiratory ECMO Survival Prediction, Survival After Veno-Arterial ECMO and ECMO net scores, the management process, and patient outcomes. Blood gas analyses done after the first hour of ECMO initiation and the reevaluation of the patients’ Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores in the 24th hour of ECMO were recorded.ResultsThe mean age was 52.7 ± 14.2 years. The median duration of the ECMO run was 81 (min–max: 4–267) h, and the mean length of CCU stay was 10.2 ± 6.7 days. Of the 8 patients studied, 5 (62.5%) had veno-arterial and 3 (37.5%) had veno-venous ECMO. Three patients were successfully weaned (37.5%). The overall survival-to-discharge rate was 25%. Carbon dioxide levels were significantly decreased 1 h after ECMO initiation (P = 0.038) as well as the need for vasopressors. Lactate levels were lower in decannulated patients. Changes in the APACHE II score were more consistent with the clinical deterioration in patients than SOFA score changes were.ConclusionsIn the early phase of ECMO, vital signs improve, and the need for vasopressors and carbon dioxide levels decrease. Thus, CCUs in Emergency Departments with ECMO capabilities could potentially be designed, and emergency department ECMO algorithms could be tailored for critically ill patients in addition to out-of-hospital cardiac arrest patients.

A Systematic Literature Review of Packed Red Cell Transfusion Usage in Adult Extracorporeal Membrane Oxygenation.

Background: Blood product administration plays a major role in the management of patients treated with extracorporeal membrane oxygenation (ECMO) and may be a contributor to morbidity and mortality. Methods: We performed a systematic review of the published literature to determine the current usage of packed red cell transfusions. Predefined search criteria were used to identify journal articles reporting transfusion practice in ECMO by interrogating EMBASE and Medline databases and following the PRISMA statement. Results: Out of 1579 abstracts screened, articles reporting ECMO usage in a minimum of 10 adult patients were included. Full texts of 331 articles were obtained, and 54 were included in the final analysis. All studies were observational (2 were designed prospectively, and two were multicentre). A total of 3808 patients were reported (range 10–517). Mean exposure to ECMO was 8.2 days (95% confidence interval (CI) 7.0–9.4). A median of 5.6% was not transfused (interquartile range (IQR) 0–11.3%, 19 studies). The mean red cell transfusion per ECMO run was 17.7 units (CI 14.2–21.2, from 52 studies) or 2.60 units per day (CI 1.93–3.27, from 49 studies). The median survival to discharge was 50.8% (IQR 40.0–64.9%). Conclusion: Current evidence on transfusion practice in ECMO is mainly drawn from single-centre observational trials and varies widely. The need for transfusions is highly variable. Confounding factors influencing transfusion practice need to be identified in prospective multicentre studies to mitigate potential harmful effects and generate hypotheses for interventional trials.

Vitamin K and ECMO for neonatal hypoxic respiratory failure.

The objectives of this retrospective cohort study were to examine the effect of vitamin K administration on hemorrhagic and thrombotic complications, blood product utilization, and outcomes in neonatal extracorporeal membrane oxygenation (ECMO). In the pilot study, complications, blood product use, and outcome data for neonates who received (n = 21) or did not receive (n = 18) a single dose of vitamin K (5 mg) immediately after initiation of ECMO for respiratory failure between 2006 and 2010 were compared. In the validation cohort, complications and outcomes were compared for 74 consecutive neonates supported with ECMO for respiratory failure who received (n = 45) or did not receive (n = 29) additional vitamin K once daily for prothrombin time (PT) ⩾14 seconds during ECMO from 2014 to 2019. In the pilot study, vitamin K at ECMO initiation was associated with fewer thrombotic complications and similar hemorrhagic complications. The volume of fresh frozen plasma was higher in neonates who received vitamin K, but total blood product and other component volume did not differ between groups. ECMO run time, survival off ECMO, survival to discharge, and length of stay did not differ between cohorts. In the validation cohort, neonates who received additional vitamin K during ECMO had longer ECMO run time and length of stay, but no difference in mortality was observed. Further, thrombotic and hemorrhagic complications as well as blood product exposure were similar between cohorts. These data suggest that routine vitamin K administration may have limited or no benefit during neonatal ECMO.

Impact of Arterial Carbon Dioxide and Oxygen Content on Cerebral Autoregulation Monitoring Among Children Supported by ECMO.

Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO2 (PaCO2) and O2 (PaO2) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied. Retrospective analysis of data collected prospectively from 30 children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France. A correlation coefficient between the variations of regional cerebral oxygen saturation (rSO2) and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). Cox-MAP plots were investigated allowing determining lower limit of autoregulation (LLA) and upper limit of autoregulation (ULA) limits of autoregulation. Age-based normal blood pressure was used to adjust the MAP, LLA, and ULA data from each patient and then reported as percentage (nMAP, nLLA, and nULA, respectively). RSO2, COx, nMAP, nLLA, and nULA values were averaged over one hour before each arterial blood gas (ABG) sample during ECMO run. Thirty children (median age 4.8months [Interquartile range (IQR) 0.7-39.1], median weight 5kg [IQR 4-15]) experiencing 31 ECMO runs were included in the study. Three hundred and ninety ABGs were analyzed. The highest values of COx were observed on day 1 (D1) of ECMO. The relationship between COx and PaCO2 was nonlinear, but COx values tended to be lower in case of hypercapnia compared to normocapnia. During the whole ECMO run, a weak but significant correlation between PaCO2 and nULA was observed (R = 0.432, p = 0.02). On D1 of ECMO, this correlation was stronger (R = 0.85, p = 0.03) and a positive correlation between nLLA and PaCO2 was also found (R = 0.726, p < 0.001). A very weak negative correlation between PaO2 and nULA was observed within the whole ECMO run and on D1 of ECMO (R = -0.07 p = 0.04 and R = -0.135 p = <0.001, respectively). The difference between nULA and nLLA representing the span of the autoregulation plateau was positively correlated with PaCO2 and negatively correlated with PaO2 (R = 0.224, p = 0.01 and R = -0.051, p = 0.004, respectively). We observed a complex relationship between PaCO2 and CA, influenced by the level of blood pressure. Hypercapnia seems to be globally protective in normotensive or hypertensive condition, while, in case of very low MAP, hypercapnia may disturb CA as it increases LLA. These data add additional arguments for very cautiously lower PaCO2, especially after ECMO start.

Outcome of Repeat Venoarterial Extracorporeal Membrane Oxygenation in Postcardiotomy Cardiogenic Shock

Data on patients requiring a second run of venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in patients affected by postcardiotomy cardiogenic shock (PCS) are very limited. The authors aimed to investigate the effect of a second run of VA-ECMO on PCS patient survival. Retrospective analysis of an international registry. Multicenter study, tertiary university hospitals. Data on adult PCS patients receiving a second run of VA-ECMO. A total of 674 patients with a mean age of 62.9 ± 12.7 years were analyzed, and 21 (3.1%) patients had a second run of VA-ECMO. None of them required more than two VA-ECMO runs. The median duration of VA-ECMO therapy was 135 hours (interquartile range [IQR] 61-226) in patients who did not require a VA-ECMO rerun. In the rerun VA-ECMO group the median overall duration of VA-ECMO therapy was 183 hours (IQR 107-344), and the median duration of the first run was 114 hours (IQR 66-169). Nine (42.9%) of the patients who required a second run of VA-ECMO died during VA-ECMO therapy, whereas five (23.8%) survived to hospital discharge. No differences between patients treated with single or second VA-ECMO runs were observed in terms of hospital mortality and late survival. In patients requiring a second VA-ECMO run, the actuarial survival estimates at three and 12 months after VA-ECMO weaning were 23.8% ± 9.3% and 19.6% ± 6.4%, respectively. Repeat VA-ECMO therapy is a valid treatment strategy for PCS patients. Early and late survivals are similar between patients who have undergone a single or second run of VA-ECMO.

P0385 / #744: THE VALUE OF INSPIRATORY AND EXPIRATORY CHEST CT TO GUIDE VENTILATORY STRATEGY FOR CHILDREN REQUIRING RESPIRATORY ECMO SUPPORT

Aims & Objectives: To describe a single institution experience on inspiratory and expiratory computed tomography (CT) to determine lung recruitability in children requiring respiratory extracorporeal membrane oxygenation (ECMO) support. Methods: Retrospective review of 5 cases referred for respiratory ECMO to tertiary children’s ICU from 2018 to 2019. All patients had oxygen saturation <80% despite maximal conventional ventilation (Peak pressure >35) or high frequency oscillation. A chest CT was performed in all cases either before or on ECMO to define ventilatory strategy. The CT was used to determine how much lung was recruitable between expiration (pressure 0 to 5 cmH20) and maximum inspiration (pressure 45 cmH20). Results: Five patients (median weight 8 kg, range 3 – 23) and age (median 4.0 years, range 0.1 to 12.0 years) developed severe hypoxic hypercarbic respiratory failure requiring ECMO. The Table 1 shows the summary of the CT chest findings and their clinical outcomes.FIGURE 1FIGURE 2Patients with non-recruitable lungs either died (Case 1) or had a prolonged ECMO run of six weeks. (Case 2, Figure 2). When lung was recuritable, we used an aggressive physiotherapy and bronchoscopy regime and promoted ventilation rather than lung resting strategy(Figure 1). Case 3 required selective intubation of the right lung. Conclusions: CT chest with inspiratory and expiratory views provide useful information in severe ARDS to help define ventilation strategy, especially on ECMO. Lack of lung recruitability on CT suggests a prolonged or futile ECMO course. Further studies are warranted

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

Disclaimer:This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19–related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19–related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

Hybrid and parallel extracorporeal membrane oxygenation circuits

Hybrid and parallel extracorporeal membrane oxygenation circuits

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

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. Retrospective database review of the Extracorporeal Life Support Organization Registry from 1990 to 2019. Extracorporeal membrane oxygenation centers reporting to Extracorporeal Life Support Organization. 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. None. 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. 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.

Outcomes of Multiple Runs of Extracorporeal Membrane Oxygenation: An analysis of the Extracorporeal Life Support Registry

When patients deteriorate after decannulation from extracorporeal membrane oxygenation (ECMO), a second run of extracorporeal support may be considered. However, repeat cannulation can be difficult and poor outcomes associated with multiple ECMO runs are a concern. The aim of this study was to evaluate outcomes and identify factors associated with survival and mortality in cases of multiple runs of extracorporeal membrane oxygenation. Retrospective cohort analysis of the Extracorporeal Life Support Organization Registry. The Extracorporeal Life Support Organization's registry was queried for neonates, children, and adults receiving 2 or more runs of ECMO during the same hospitalization, for any indication, from 1998 to 2015. 1,818 patients from the Extracorporeal Life Support Organization Registry. Of the 1,818 patients, 1,648 underwent 2 runs and 170 underwent 3 or more runs of ECMO. The survival to discharge rate was 36.7% for 2 runs and 29.4% for 3 or more runs. No significant differences in survival were detected in analysis by decade of ECMO run (p = 0.21). Pediatric patients had less mortality than adults (OR: 0.45, 95%CI: 0.24-0.82). Cardiac support on the first run portrayed worse mortality than pulmonary support regardless of final run indication (OR:1.38, 95%CI: 1.09-1.75). Across all age groups, patients receiving pulmonary support on the last run tended to have higher survival rates regardless of support type on the first run. The only first run complication independently predictive of mortality on the final run was renal complications (OR: 1.60, 95%CI: 1.28-1.99). Though the use of multiple runs of ECMO is growing, outcomes remain poor for most cohorts. Survival decreases with each additional run. Patients requiring additional runs for a pulmonary indication should be considered prime candidates. Renal complications on the first run significantly increases the risk of mortality on subsequent runs, and as such, careful consideration should be applied in these cases.

Evaluation of Coagulation and Inflammatory Markers in Pediatric Patients on Extracorporeal Membrane Oxygenation (ECMO)

Background: Bleeding and thrombosis remain the primary complications related to the use of extracorporeal membrane oxygenation (ECMO). To date, no single test or parameter has been identified to accurately predict the risk of these hemostatic complications. Thrombin generation may be the key marker for both thrombosis and bleeding, and may be influenced by inflammation. The aims of this study were to evaluate if novel laboratory tests including thrombin generation assay, neutrophil extracellular traps (NETs), microparticles (MPs), and red blood cell (RBC) membrane fragility/adhesion could better predict patients at risk for bleeding and/or thrombosis compared to routine laboratory tests. We hypothesized that ECMO related thrombosis is associated with increased thrombin generation and ECMO related bleeding is associated with decreased thrombin generation. Methods: An IRB approved prospective pilot study of patients requiring ECMO was conducted at Children's Hospital of Michigan. Patients were enrolled within 24 hours of ECMO cannulation after informed consent. Patients aged 0-17 years placed on venoarterial (VA) or venovenous (VV) ECMO were included. Patient demographics, baseline laboratory, clinical data, and novel assays were collected. Presented is the preliminary data of the first 16 patients enrolled. SPSS was used for data analysis. Results: Of the 16 patients, there were 9 males and 7 females with the majority being cannulated for primary respiratory etiologies. Median age was 8.5 months with 6 patients being neonates (38%). Twelve patients (75%) survived the ECMO run, and 11 patients (69%) survived to hospital discharge. Laboratory data was grouped based on "no event" (N=94), "bleeding event" (N=13) and "clotting event" (N=21) days. There were no differences in the number of RBC, fresh frozen plasma, or cryoprecipitate transfusions between events. Platelet transfusions were used at higher volumes in bleeding events, p=0.011. Platelet counts did not differ between groups, whereas fibrinogen levels were significantly lower on days of bleeding events, p≤0.001 (Figure 1A). There were no differences seen in the activated partial thromboplastin time (aPTT) or activated clotting time (ACT) which are routinely used for monitoring anticoagulation. However, the prothrombin time (PT) was significantly prolonged in bleeding events with a median of 16 seconds (p=0.001), which may be related to the lower fibrinogen levels (Figure 1B). Thrombin generation was assessed using the maximum rate of thrombin generation (MRTG) value from the thromboelastograph (TEG) generated velocity curve (Figure 1D). Bleeding events had a significantly lower median MRTG of 7.93 mm/min compared to 12.36 mm/min in the no event group and 12.14 mm/min in the clotting event group (p=0.004). The thrombin generation assay results are in process. NETs were analyzed using an ELISA to detect citrullinated histone-3 (CitH3) levels (ng/mL). There were no significant differences seen in our population, however there is a trend toward increased levels in thrombotic events (Figure 1E). Both absolute MPs and platelet MPs were significantly increased in clotting events compared to bleeding events, p=0.003 and p≤0.001 respectively (Figure 1C). In our population, there was no evidence that hemolysis played a role in thrombosis as assessed by flow based RBC mechanical fragility testing. Of note, flow based RBC adhesion showed a non-significant trend toward increased adhesion to P-selectin. This finding requires further investigation because P-selectin is a primary site for adhesion on endothelial cells and plays a crucial role in coagulation (Figure 1F). Conclusions: Bleeding events on ECMO are associated with increased mortality. Our findings suggest that lower fibrinogen levels, prolonged PT and decreased thrombin generation (as assessed by the TEG) are associated with an increased risk for major bleeding. Increased levels of NETs, MPs and RBC adhesion have a trend towards increased thrombotic events. Thus, although preliminary, our results suggest that novel laboratory tests were effective in identifying bleeding events, and the trends seen in thrombotic events may allow for the use of new medications to reduce clotting in ECMO. The results illustrate the challenges in monitoring ECMO anticoagulation and additional study of novel tests are needed to identify and avoid clinical complications. Disclosures Tarasev: Functional Fluidics:Current Employment, Current equity holder in private company.Hines:Functional Fluidics:Current equity holder in private company.Chitlur:Biovertiv:Honoraria;Pfizer:Honoraria;Novo Nordisk:Consultancy, Honoraria;Takeda:Honoraria;Agios Pharmaceuticals:Research Funding.

Risk Factors of Ischemic and Hemorrhagic Strokes During Venovenous Extracorporeal Membrane Oxygenation: Analysis of Data From the Extracorporeal Life Support Organization Registry.

Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support. Retrospective analysis. Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019. Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation. None. Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03-0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22-4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12-3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51-8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12-0.65; p = 0.003), preextracorporeal membrane oxygenation Po2 (adjusted odds ratio = 0.96; 95% CI, 0.93-0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15-2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22-2.02; p < 0.001) were independently associated with hemorrhagic stroke. Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Seizures Are Associated With Brain Injury in Infants Undergoing Extracorporeal Membrane Oxygenation.

Determine seizure frequency and association with neurologic outcomes in infants undergoing extracorporeal membrane oxygenation. Identify patient or clinical factors associated with seizures or brain injury on imaging. Retrospective, single-center study including infants less than 1 year of age, who underwent extracorporeal membrane oxygenation between 2012 and 2017. A total of 104 infants met study criteria including 45 patients with continuous electroencephalographic (EEG) monitoring during their extracorporeal membrane oxygenation run and 59 infants without EEG. Seizures (electrographic-only or electro-clinical) were identified in 18 of the 45 (40%). Among the 18 infants with seizures, 14 (78%) had moderate to severe brain injury, whereas only 44% of those without seizures (12 of 27) on EEG had moderate to severe brain injury (P = .03). Cardiopulmonary resuscitation prior to extracorporeal membrane oxygenation (ECPR), mode of extracorporeal membrane oxygenation, length of stay, survival to discharge, and congenital heart disease were not associated with seizures. One of 10 patients with cyanotic congenital heart disease due to hypoplastic left heart syndrome had seizures compared with 7 of 10 patients with non-hypoplastic left heart syndrome lesions (P = .02). Seizures were associated with moderate to severe brain injury, after adjusting for ECPR and congenital heart disease (P = .04). Electrographic seizures were common in patients undergoing extracorporeal membrane oxygenation and higher than previously reported. Seizures were associated with moderate to severe abnormalities on imaging, after adjusting for ECPR and congenital heart disease. This study adds to recent literature describing the risk of seizures in patients on extracorporeal membrane oxygenation and highlights the presence of brain injuries that may be identified by routine EEG surveillance.

Successful Establishment of the First Neonatal Respiratory Extracorporeal Membrane Oxygenation (ECMO) Program in the Middle East, in Collaboration With Pediatric Services.

Background: Extracorporeal membrane oxygenation (ECMO) is a complex life-saving support for acute cardio-respiratory failure, unresponsive to medical treatment. Starting a new ECMO program requires synergizing different aspects of organizational infrastructures and appropriate extensive training of core team members to deliver the care successfully and safely.Objectives: To describe the process of establishing a new neonatal ECMO program and to evaluate the program by benchmarking the ECMO respiratory outcomes and mechanical complications to the well-established Extracorporeal Life Support Organization (ELSO) registry data.Materials and Methods: We reviewed the processes and steps involved in planning and setting up the new ECMO program. To assess the success of the ECMO implementation program, we retrospectively reviewed data of clinical outcomes and technical complications for the first 11 patients who have received ECMO therapy for respiratory indications since program activation (July 2018–May 2020). We analyzed mechanical complications as a tool to measure infrastructures and our effective training for the core team of ECMO specialists. We also looked at all clinical complications and benchmarked these numbers with the last 10 years of ELSO registry data (2009–2019) in the corresponding categories for comparison. Chi-square test was used to compare, and outcomes are presented in percentage; a p-value of <0.05 is considered significant.Results: A total of 27 patients underwent ECMO in the hospital, out of which 11 (six neonatal and five pediatric) patients had acute respiratory failure treated with venovenous (VV) ECMO or veno-arterial (VA) ECMO over a 22-month period. We had a total of 3,360 h of ECMO run with a range from 1 day to 7 weeks on ECMO. Clinical outcomes and mechanical complications are comparable to ELSO registry data (no significant difference); there were no pump failure, oxygenator failure, or pump clots.Conclusions: Establishing the ECMO program involved a multisystem approach with particular attention to the training of ECMO team members. The unified protocols, equipment, and multistep ECMO team training increased staff knowledge, technical skills, and teamwork, allowing the successful development of a neonatal respiratory ECMO program with minimal mechanical complications during ECMO runs, showing a comparable patient flow and mechanical complications.