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Review Article

Highlights from the Extracorporeal Life Support Organization Registry: 2006–2017

Nasr, Viviane G.*; Raman, Lakshmi; Barbaro, Ryan P.; Guner, Yigit#; Tonna, Joseph; Ramanathan, Kollengode; PAPPALARDO, FEDERICO§; Thiagarajan, Ravi R.**; Alexander, Peta M.A.**,††; on behalf of the ELSO Registry Scientific Oversight Committee

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doi: 10.1097/MAT.0000000000000863
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Abstract

Extracorporeal membrane oxygenation (ECMO) is a supportive therapy for patients with severe cardiovascular or respiratory failure refractory to conventional medical therapy. Improvements in ECMO technology, easy access to ECMO devices, and a greater understanding of care of ECMO patients have led to increased utilization of ECMO. Recently, indications for ECMO use have expanded to include high-risk patients previously not considered for ECMO support.1,2 However, ECMO patients remain at high risk for both mortality and morbidity.2 The Extracorporeal Life Support Organization (ELSO) registry was established in 1984, to collect data on patients receiving ECMO support to help improve outcomes of these patients. The first report from the ELSO registry was published in ASAIO Journal in 1988.3 Toomasian and colleagues3 described 715 neonates supported with ECMO and provided a description of ECMO techniques used, complications, and outcomes. Since this publication, the ELSO registry has grown to include over 400 contributing centers from 60 countries and contains data for more than 80,000 patients.2,4,5 Many investigators have used the ELSO registry to answer clinical questions on outcomes and care of this vulnerable patient population. Publications from the ELSO registry have increased over the past decade from three published articles in 2006 to 22 articles in 2017 with a cumulative number of 106 publications. Using specific methodology described below, this report provides a brief summary of some of the clinical research published using data from the ELSO registry. These publications have advanced knowledge and improved care of neonates, children, and adults treated with ECMO.

Methods

The ELSO Registry Scientific Oversight Committee members are a diverse group of intensive care physicians, surgeons, and anesthesiologists, with international representation consistent with ELSO contributing centers. Members of the scientific review committee have compiled all articles that acknowledged the ELSO registry database using the PubMed (Extracorporeal life support organization [tiab] OR ELSO [tiab]) AND (registry [tiab] OR registries [MeSH]) and the Web of Science (Extracorporeal life support organization OR ELSO) AND (registry OR registries)) from 2006 until 2017. After compilation, each member chose 10 articles for potential inclusion, based on the potential impact on clinical practice and value to the ECMO literature. Of 21 articles collated for review, the ELSO Steering Committee voted, and the most highly voted articles were included (Table 1). These 16 articles address questions about the clinical care of neonates, pediatric, and adult patients and cover multiple specialties including cardiac and respiratory utilizing data from the ELSO registry. The following section represents a summary of each article.

Table 1.
Table 1.:
List of Articles in Chronological Order with the Most Relevant Findings/Impact

Results

Extracorporeal Life Support Organization Registry Report 2012

Collation and presentation of ELSO registry patients provides important survival and outcomes data.2,6,7–10 This is an example of a retrospective description of ECMO utilization in patients of all ages included in the ELSO registry for all indications (pulmonary, cardiac, and extracorporeal cardiopulmonary resuscitation [ECPR]) providing data on survival and outcomes. All ECMO cases (>50,000) from the inception of the registry through June 2012 were included. The report shows an increase in extracorporeal life support (ECLS) usage over time. Specifically, use of ECMO in pediatric and adult respiratory and cardiac failure populations increased and the use of ECMO for neonatal respiratory failure decreased during this time period. It describes the percent of patients in each group, indications of ECMO, mode of cannulation, and survival rates.

Data on ECMO use, survival, and complication rates can guide clinicians in patient selection and management and in understanding factors associated with survival. Every few years, similar reports are generated and published on behalf of the ELSO registry.2,5

Association of Hospital-Level Volume of Extracorporeal Membrane Oxygenation Cases and Mortality: Analysis of the Extracorporeal Life Support Organization Registry

The aim of this study was to analyze the association between hospital annual ECMO volume with the outcome of mortality. Other aspects of clinical care delivery such as mechanical ventilation have been shown to have a volume-outcome relationship.11,12 This retrospective data analysis from 1989 through 2013 categorized patients into neonatal (0–28 days), pediatric (>28 days–<18 years), and adult (≥18 years) groups. Volume was defined as the total number of annual age group-specific cases per hospital. Covariates included year, age, primary diagnosis, support type, pre-ECMO renal failure, comorbidities, pre-ECMO cardiac arrest, circuit and ventilator management parameters, and blood gases. Overall findings included stable neonatal volumes, linear increases in pediatric volumes, and exponential increases in adult volumes over the study period. Annual case volumes and mortality ranged broadly across populations: neonatal (1–71 years; 18–50% mortality), pediatric (1–40; 22–66%), and adult (1–129; 33–92%). In adjusted analysis, the odds of mortality were significantly lower in centers with higher stratum volume. This study demonstrated the wide breadth of case mix volume and survival among centers and a significant relationship between increasing ECMO volume per hospital and lower mortality. These results have been interpreted as an argument for regionalization of ECMO care. However, the relationship between increasing volume and lower mortality was not significant when isolated to the post-2008 era among the pediatric, neonatal, and adult respiratory populations and persisted only among adult cardiac population. These findings are in contrast to previous pediatric and neonatal findings.13,14

Development and Validation of the Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support

Dr. Bartlett’s neonatal pulmonary insufficiency index was a function of pH and fractional inspired oxygen (FiO2) and one of the earlier attempts of utilizing pre-ECMO clinical parameters to predict ECMO risk.15 In the Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support (PED-RESCUERS) study, a pediatric risk estimate score for children using ECMO was developed to estimate in-hospital mortality in children using pre-ECMO clinical parameters.16 The investigators utilized data from 2009 to 2014 to develop and validate the risk score. Children included in the study were 29 days to <18 years. The outcome of the prediction model was inpatient mortality during or after ECMO. The cohort (n = 2458) was randomly divided into development (n = 1611) and validation (n = 409) sets. Prediction models were developed using Bayesian multivariable logistic regression models, and predictive discrimination was measured by the C-statistic. Overall mortality was 39.8%. Pre-ECMO clinical parameters of pH and arterial pCO2, length of mechanical ventilation, hours of admission to ECMO center before ECMO, type of ventilator, mean airway pressure, and milrinone use were incorporated into the risk prediction model, with a C-statistic of 0.69 from the development and 0.64 from the validation datasets. Other variables that predicted mortality were diagnosis of pertussis, asthma, bronchiolitis, or malignancy. Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support is the first mortality risk adjustment tool that was developed and validated for children requiring respiratory ECMO support and is available online.17

Extracorporeal Membrane Oxygenation in Adults with Severe Respiratory Failure: A Multicenter Database

This analysis from 1986 to 2006 described mortality, temporal trend, and factors associated with survival in adult patients (≥16 years) with respiratory failure requiring ECMO.18 The overall survival of 1473 patients who were supported on ECMO for respiratory failure was 50%. There was no improvement of survival over time despite an increase in the number of patients. The study identified pre-ECMO and ECMO factors associated with mortality. Pre-ECMO factors included elderly patients, prolonged mechanical ventilation, decreasing patient weight, and presence of acidosis (pH<7.18). The mortality of patients diagnosed with acute respiratory failure or asthma was significantly less than that of patients who had acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation factors contributing to mortality included the mode of cannulation and the various complications. Patients supported with veno-venous (VV) ECMO alone had better survival than those with veno-arterial (VA) ECMO or multiple support modes. Presence of neurologic, renal, gastrointestinal, pulmonary, and metabolic complications increased mortality along with mechanical complications, need for cardiopulmonary resuscitation (CPR), and inotropes on ECMO. The investigators observed that the use of adjunctive therapies before ECMO had increased significantly over the years, along with patient numbers, implying that ECMO is being used in patients with increasing clinical complexity. This was one of the early studies reporting outcomes of adult patients supported with ECMO from the ELSO registry. The manuscript outlined modifiable and nonmodifiable risk factors for mortality in adult ECMO patients with respiratory failure in a robust template for future analyses of ELSO registry data.

Outcome of Adult Respiratory Failure Patients Receiving Prolonged (≥14 Days) Extracorporeal Membrane Oxygenation

The use of ECMO for adult respiratory failure increased from approximately 100 cases per year from 1986 through 2008 to approximately 400 cases per year since 2009.2 In addition, an increase in the duration of ECMO support was noted. This study evaluated outcomes and risk factors for survival in adult patients (>18 years) with prolonged (>14 days) ECMO for severe respiratory failure between 1989 and 2013.19 Of the 4,488 patients, 974 (22%) needed prolonged ECMO and survival was 45.4%. Veno-venous ECMO (79.5%) remains the most common cannulation mode in these patients with better survival rates (48.6%) compared with VA ECMO (37.5%; odds ratio [OR], 1.58; 95% CI, 1.02–2.44; p = 0.04). Of those patients supported with prolonged ECMO, the majority (72%) were between 2007 and 2013. There was a significant increase in survival rates with prolonged ECMO from 36.6% (1989–2006) vs. 48.9% (2007–2013). Despite prolonged ECMO support, native lung recovery remained the most common indication (54%) for ECMO cessation in this cohort. Forty patients (4%) underwent lung transplantation after prolonged ECMO and 50% survived post-transplant. Independent factors associated with survival in those adults with severe respiratory failure managed with prolonged ECMO were younger age group, pre-ECMO hypocapnia, and post-2007 era. This study demonstrated that prolonged ECMO in adult patients with respiratory failure is not futile and survival trends have improved, likely attributable to better understanding of the underlying disease process and improvements in technology and critical care management.

Predicting Survival After Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure: The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score

Prediction of survival in adult patients with acute respiratory failure may improve resource utilization, allow risk-adjusted comparison of center-specific outcomes, and help clinicians target patients who are most likely to benefit from ECMO. Based on ELSO registry adult patients from 2000 to 2012 supported on ECMO for acute respiratory failure, this study derived a survival prediction score.20 Extracted covariates included demographics, pre-ECMO variables, International Classification of Diseases-9 diagnosis codes, procedure and complication codes, year, and outcome. Only the first ECMO run was included. Among 3,522 ECMO runs, 2,355 had complete data. The authors used logistic regression analysis of pre-ECMO patient or treatment variables to identify candidate variables associated with mortality (p < 0.1), bootstrap methodology, and external validation.21 Initial multivariate analysis revealed age, pre-ECMO cardiac arrest, central nervous system (CNS) dysfunction, renal dysfunction, immune-compromised state, associated nonpulmonary infection, inhaled nitric oxide, bicarbonate infusion, longer pre-ECMO duration of mechanical ventilation, higher arterial pCO2, and higher peak inspiratory pressure as independent risk factors for mortality. Bacterial, viral, and aspiration pneumonias, trauma, burns, asthma, and use of neuromuscular blockade were found to be protective. The final score is calculated weighing 12 pre-ECMO parameters, facilitating categorization of patients into five risk groups, with escalating associated mortality; categories I–V were associated with 92%, 76%, 57%, 33%, and 18% cumulative predicted hospital mortality. Internal validation C-statistic was 0.73 (95% CI, 0.71–0.75), and external validation performance was excellent (C-statistic = 0.92; 95% CI, 0.89–0.97). Derived from patients within the ELSO registry and externally validated in a small dataset, this was the first international, validated predictive mortality model for patients receiving VV ECMO support for respiratory failure. The Respiratory ECMO Survival Prediction (RESP) score facilitates more accurate prediction of mortality than other models, including the Simplified Acute Physiology Score and Sequential Organ Failure Assessment Score and is available online.22

Predicting Survival After Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock: The Survival After Veno-Arterial Extracorporeal Membrane Oxygenation Score

Cardiogenic shock is a common indication for adult patients receiving ECMO, but mortality risk factors for these patients had not been studied in a large multicenter data. This study aimed to determine predictors of in-hospital survival in patients with refractory cardiogenic shock requiring VA ECMO, to create a survival prediction score (Survival After Veno-Arterial ECMO [SAVE] score), and to perform internal and external score validation.23 The derivation cohort included all adult patients from the ELSO registry who received VA ECMO primarily for cardiogenic shock from 2003 to 2013. Validation was done using a cohort of patients who underwent VA ECMO for refractory cardiogenic shock between 2006 and 2013, at the Alfred Hospital, Melbourne, Australia. Multivariable modeling performed on 3,846 ECMO patients identified chronic renal failure, longer duration of mechanical ventilation before initiation of ECMO, acute pre-ECMO organ failure, pre-ECMO cardiac arrest, congenital heart disease (CHD), lower pulse pressure, and lower serum bicarbonate as independent risk factors associated with hospital mortality. Conversely, younger age, weight between 76 and 89 kg, acute myocarditis, post-transplant, refractory VT/VF, higher DBP, and lower peak inspiratory pressure were protective factors. Based on these findings, 12 items were retained to create the SAVE score. Five risk classes with their corresponding survival rate 75, 58, 42, 30, and 18% were identified. A SAVE score of zero was approximately equivalent to 50% survival with positive scores representing higher chances of survival. Internal validation of the SAVE score demonstrated modest discrimination (C-statistic = 0.68; 95% CI, 0.66–0.69), with excellent performance in the validation cohort C-statistic = 0.90 (95% CI, 0.85–0.95). Using a large cohort of patients treated with ECMO for cardiogenic shock, the study created and validated the first international, well-calibrated, and discriminatory survival prediction score for adult patients with cardiogenic shock supported with VA ECMO comprising 13 pre-ECMO variables. The model is available online and can be used as a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock.24

Descriptive Analysis of Extracorporeal Cardiopulmonary Resuscitation After Out-Of-Hospital Cardiac Arrest: An Extracorporeal Life Support Organization Registry Study

Advances in ECMO technology and ease-of-deployment have allowed extension of ECMO to support resuscitation of out-of-hospital cardiac arrest (OHCA). This study aimed to describe survival and factors associated with survival for extracorporeal cardiopulmonary resuscitation (ECPR) initiated for OHCA.25 Prior single-center studies on the topic had shown poor survival.26 This retrospective cohort study included adults (>18 years) who received ECPR for out-of-hospital cardiac arrest (OHCA) during 2010–2016, and factors associated with survival were identified. Two hundred seventeen patients, median age: 52 years (range 18–87), were included. Percutaneous cannulation (71%) and femoral vessels (98%) were commonly used to initiate ECMO support. Sixty-three (29%) underwent coronary interventions (catheter based or surgical). Median duration of ECMO was 47 (range 0–711) hours. Overall survival to hospital discharge was 27.6%, and male gender was associated with reduced survival. In addition, the authors found variation in ECPR utilization for OHCA and interventions provided after ECMO deployment among ELSO regions (Europe, Asia, and North America). Extracorporeal membrane oxygenation complications were common in nonsurvivors despite shorter ECMO duration suggesting that some complications were related to pre-ECPR illness or quality of CPR provided. Limb ischemia complications occurred in 11% of the cohort suggesting that careful assessment of limb perfusion is crucial. Neurologic complications occurred in 24% and included brain death (16%), seizures (6%), and cerebral infarction (3%). This report is limited by lack of information on CPR details, including location of arrest, duration of CPR, medications used during CPR, and location of ECMO cannulation (in hospital or field). Survival reported in this series is similar to other reports of ECPR for inpatients suggesting that ECPR can be considered for OHCA. These data can be used for benchmarking for future evaluation of ECPR for OHCA.27,28

Extracorporeal Membrane Oxygenation to Aid Cardiopulmonary Resuscitation in Infants and Children

Survival to hospital discharge for children after cardiac arrest is poor, and ECMO had been previously shown to improve survival when used to support patients in refractory cardiac arrest.29 This is the first large multicenter study to describe survival to discharge and factors associated with survival for neonates and children supported with ECPR.7

This is a retrospective cohort study of all children <18 years, including neonates, supported with ECPR, during 1992–2005. Factors associated with survival were evaluated using multivariable logistic regression. Six hundred eighty-two children with median age 3 months (Interquartile Range [IQ] range, 1–28) were included. Cardiac disease (73%) was the most common diagnosis and 38% survived to hospital discharge. Cardiac and neonatal respiratory diagnosis, white race, and arterial blood pH before ECPR support of >7.17 were all associated with improved survival, whereas ECMO complications were associated with reduced survival. Among nonsurvivors, the majority (52%) died <72 h after initiation of ECPR. Brain death and arterial blood pH <6.9 was more common in this group. This suggests that pre-ECPR illness or quality of CPR before ECMO strongly influenced survival. Similarly to the previous reference, details of CPR were not included and constituted a major limitation of the data presented in this study.7,25 Finally, this manuscript demonstrated an increasing trend in the use of ECPR among ECMO centers.

This is the first manuscript to describe outcomes in pediatric ECPR and associated factors. In addition to identifying a suitable population, it demonstrates the influence of pre-ECMO illness and quality of CPR provided before ECMO on patients’ outcomes.

Extracorporeal Membrane Oxygenation for Bridge to Heart Transplantation Among Children in the United States: Analysis of Data from the Organ Procurement and Transplant Network and Extracorporeal Life Support Organization Registry

Extracorporeal membrane oxygenation has been used for more than 20 years for cardiopulmonary support of children with end-stage heart failure not responding to standard therapies as a “bridge to heart transplantation.” In this study, data from two multicenter registries are combined to describe the efficacy and safety profile of ECMO support as a bridge to heart transplantation.30 Data from the ELSO registry and the Organ Procurement Transplant Network (OPTN)9 database were merged to identify all children (<18 yrs) supported with VA ECMO and listed for orthotopic heart transplantation in the United States from 1994 to 2009. Independent predictors of wait-list and post-transplantation in-hospital mortality were identified, and objective performance goals for ECMO developed.

More than 700 children with median age 6 months (IQ range, 1–44 months) with any pediatric cardiac diagnosis were included in this study. Bridge to transplantation was intended at ECMO initiation in 38%. Only 45% of wait-listed subjects reached transplantation and one third of those transplanted died before discharge. Wait-list mortality was independently associated with CHD, CPR before ECMO, and renal dysfunction. In addition, post-transplantation mortality was associated with CHD, renal dysfunction, prolonged ECMO duration (>14 days) and initial ECMO indication as a bridge to recovery. Patients with cardiomyopathy and myocarditis had higher survival to hospital discharge than those with CHD (59–60% compared with 33–40%). Although ECMO is effective for short-term circulatory support, it is not reliable for the long-term circulatory support necessary for children awaiting heart transplantation. Fewer than half of patients bridged with ECMO survive to hospital discharge. With just 1 of every 2 patients bridged with ECMO surviving to hospital discharge, the findings emphasized the urgency behind the National Heart, Lung, and Blood Institute’s initiative to develop more reliable mechanical circulatory support devices for the smallest patients.31

Prospective Trial of a Pediatric Ventricular Assist Device

Sixteen centers in the United States participated in this prospective, single-arm trial of the Berlin Heart EXCOR Pediatric Ventricular Assist Device (VAD).32 Patients ≤16 years were divided into two cohorts according to body surface area (cohort 1, <0.7 m2; cohort 2, 0.7–<1.5 m2), with 24 patients in each group. Survival to transplantation or recovery in the two cohorts was compared with survival in propensity score–matched historical control groups extracted from the ELSO registry. Survival rates in patients managed with the EXCOR Pediatric VAD were significantly higher than the matched ECMO groups (cohort 1: median >174 days compared with 13 days, log rank p < 0.001; cohort 2: median 144 days compared with 10 days, log rank p < 0.001). Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of VAD managed study participants. The sequelae of stroke in this trial did not disqualify the majority of participants from transplantation, and the stroke-related deficits were generally considered to be mild. Lack of equipoise in the medical community precluded a standard randomized control trial design but incorporation of propensity score–matched historical controls of ECMO-supported patients identified from the ELSO registry facilitated comparison. After this study, the Berlin Heart EXCOR Pediatric VAD was approved by the Center for Devices and Radiological Health under Humanitarian Device Exemption (HDE) application and is intended to provide mechanical circulatory support as a bridge to cardiac transplantation for pediatric patients.33–35

Mechanical Component Failures in 28,171 Neonatal and Pediatric Extracorporeal Membrane Oxygenation Courses from 1987 to 2006

ELCS circuitry comprised multiple components with different options such as size/types of cannulas, type of pump (roller/centrifugal) and type of oxygenator, type/length of tubing.7 Mechanical complications in the ECMO circuitry could arise and affect the clinical course of the patient. This is a retrospective analysis of the neonatal and pediatric data from the ELSO registry from 1987 to 2007 divided into two eras (1987–1996 and 1997–2006) describing mechanical component failure during ECMO and identifying risk factors including duration of ECMO, year of ECMO, clinical indication, or center volume.36 Of the 28,171 ECMO cases, the incidence of mechanical complications was 14.9%.37 Oxygenator failure was the most common component to be reported as a complication (6.5%), followed by air in the circuit (4.3%). Raceway ruptures were rarely seen (<1%). Center volume was not associated with rate of mechanical failure. The predictors of mechanical component failures were duration of ECMO, age group, indication, and earlier era. The decrease in complications in the second era may be related to acquired experience and improved technology over time. Future studies may be directed toward identifying areas in which mechanical component failures can be prevented in infants and children who require prolonged ECMO runs.

In-Hospital Neurologic Complications in Adult Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation: Results from the Extracorporeal Life Support Organization Registry

Veno-arterial ECMO is being increasingly used in adults because it provides circulatory and respiratory support.18 However, complications and in particular central nervous system (CNS) complications negatively impact both survival and morbidity. This study was aimed at evaluating CNS complications and their impact on survival in VA ECMO.38 All patients >16 years (4,522 patients) who underwent a single run of VA ECMO from 1992 to 2013 were included. Baseline, pre-ECMO, ECMO, and post-ECMO variables were compared between patients with and without CNS injury. Complications were classified based on the ELSO registry coding into brain death, seizures (clinically or electroencephalographically determined), cerebral infarction, and intracerebral hemorrhage (ICH) determined by computed tomography imaging. Fifteen percent (682 patients) had neurologic complications. There was a significant decline in the rate of CNS injury overtime, mainly due to a decrease in the complications in the ECPR group and a significant decrease in brain death overall. Interestingly, CNS hemorrhage was higher in the VA ECMO group placed on ECMO for respiratory failure. CNS complications had a significant impact on mortality with only 11% survival compared with 54% in patients without CNS complications. Multivariate analysis showed that younger age, pre-ECMO cardiac arrest, post-ECMO hypoglycemia, and inotrope use during ECMO were all factors associated with higher odds of CNS injury.

This is the first study that has described the extent of neurologic complications in the adult population and the trend over 15 years. It also highlighted the significant risk of increased mortality associated with CNS complications. This article paved way for further studies on neurologic complications in adult ECMO patients.

Neurologic Injury in Adults Supported with Veno-Venous Extracorporeal Membrane Oxygenation for Respiratory Failure: Findings from the Extracorporeal Life Support Organization Database

Veno-venous ECMO is being increasingly used to support adult patients with respiratory failure. CNS complications are a well-known complication in VA ECMO as described above.38 However, the occurrence rate and factors associated with neurologic injury are not well studied on VV ECMO support. The purpose of the study was to describe the prevalence, types, in-hospital survival, and factors associated with CNS injury in this population.39 All single run VV ECMO patients ≥18 years of age from 1992 to 2015 for respiratory failure were included in this study. Neurologic injury was defined as brain death, seizures, stroke, and ICH occurring during ECMO support.

The study included 4,988 adults with a total of 426 neurologic events. Of 4,988 adults, 426 suffered CNS injuries comprising seizures (14%), strokes (20%), brain death (23.5%), and ICH (42.5%). Although there was an initial decline from 1992 to 2003, the rate of complications remained the same in the rest of the time period from 2003 to 2015. Patients with neurologic injury were also found to have renal failure, cardiac dysfunction with need for vasopressors, systemic hypertension with need for antihypertensive medications, blood stream infections, pneumothoraces, acidosis pre-ECMO, pulmonary hemorrhage, and hyperbilirubinemia during ECMO. Independent risk factors associated with neurologic injury included hyperbilirubinemia during ECMO, pre-ECMO cardiac arrest, and need for continuous veno-venous hemofiltration. The results of the study emphasized that neurologic complications are lower in VV ECMO compared with VA ECMO. The study also highlighted that cerebral hemorrhage was the most common CNS injury in VV ECMO patients and was associated with poor outcome. The study can help clinicians be vigilant about neurologic complications when risk factors are identified such as pre-ECMO cardiac arrest, need for renal replacement therapy, and presence of hyperbilirubinemia.

Neurologic Complications in Neonates Supported with Extracorporeal Membrane Oxygenation: An Analysis of Extracorporeal Life Support Organization Registry Data

Neurologic complications continue to occur in patients supported with ECMO. Children, especially neonates with immature brains, are vulnerable to neurologic complications. Prior studies reported the incidence of ICH in neonates at 9.9% in 1999.40,41 With recent advances in ECMO technology and experience with management of neonates on ECMO, the goal of this study was to determine the current incidence of neurologic complications and associated patient and ECMO factors.42 All neonates (0–<28 days) from the ELSO registry between 2005 and 2010 were included a total of 7,405 runs. The neurologic complications included brain death, cerebral infarction, ICH, or seizures. Indications for ECMO were respiratory failure, cardiovascular disease, and ECPR. The incidence of neurologic complications of 20% did not change during the study period with the most frequent complication being ICH. Mortality was higher in patients with neurologic complications (62% vs. 36%). Patient factors associated with neurologic events were gestational age ≤36 weeks and weight <3 kg. Veno-arterial ECMO and prior ECMO exposure increased the odds of neurologic complications as well as pre-ECMO severity of illness with cardiac arrest, low pH, and bicarbonate requirement. The major limitations of this study relate to the lack of information on the timing of event, severity of the neurologic complications, and the long-term outcomes and survival of those patients. This study identifies important factors that increase the risk of neurologic complications in neonates, which may guide clinicians in patient selection, and timing of ECMO deployment.

Association of Bleeding and Thrombosis with Outcome in Extracorporeal Life Support

Patients supported with ECLS are at risk of thrombosis and bleeding. Extracorporeal life support induces a state of prothrombosis requiring the administration of anticoagulation, which thereby increases risk for bleeding. These common complications contribute to significant morbidity and mortality. The aim of this study by Dalton and colleagues was to report the rate of bleeding and thrombosis of ECLS and the association of such complications with survival.43 This retrospective study from eight centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN) included all patients less than 19 years and reported to the ELSO registry between 2005 and 2011. The indications for ECLS were respiratory failure, cardiovascular compromise, ECPR, and congenital diaphragmatic hernia (CDH) patients, and the modes described were both VV ECMO and VA ECMO. The outcomes were bleeding, thrombosis, and survival to discharge. Bleeding complications included bleeding at the cannula site, surgical site, intracranial, gastrointestinal, and pulmonary hemorrhage. The thrombotic events were reported as clots in the circuit, disseminated intravascular coagulopathy, CNS infarction, and hemolysis. In non-CDH patients, the complication rates for bleeding (38%) and thrombosis (31%) were associated with decreased survival by 40% and 33%, respectively. The rate of complications decreased over time during the study period. For pediatric patients with respiratory failure, bleeding events (50%) were associated with decreased survival, but thrombotic events (37%) were not. In neonates, both bleeding (25%) and thrombotic events (27%) were associated with reduced survival. Other factors associated with increased risk of bleeding and thrombosis and lower survival are longer duration on ECLS and use of VA ECMO. In both neonates and pediatric patients managed on ECMO for cardiac failure, bleeding and thrombosis are associated with decreased survival. For neonates supported on ECMO for ECPR, bleeding (37%) was associated with reduced survival, whereas in pediatric patients, thrombosis (29%) was associated with reduced survival. Among patients with CDH, bleeding and thrombosis occurred at 45% and 60%, respectively; and only bleeding events were associated with reduced survival. Bleeding and complications are both major complications for patients on ECMO regardless of the indication, and adversely affect survival in neonatal and pediatric populations.

Conclusions

We identified and summarized a compilation of peer-reviewed manuscripts published using data from the ELSO registry and describing important aspects of the care of neonates, children, and adults supported with ECMO. We believe these manuscripts have shaped our knowledge, clinical practice, and have helped identify areas for improvement in the care of children and adults supported with ECMO. The ELSO registry is continually improving data entry, definitions and coding aiming for more granular and meaningful data. Future use of the registry may focus on quality of care and long-term outcomes of patients supported with ECMO.

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Keywords:

extracorporeal membrane oxygenation; extracorporeal life support; outcomes; complications; extracorporeal life support organization Registry

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