Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017-2021.

OBJECTIVES: To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation). DESIGN: Retrospective database study. SETTINGS: Data reported to the Extracorporeal Life Support Organization (ELSO), 2017-2021. PATIENTS: Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards' regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year ( p < 0.001), arterial blood carbon dioxide tension (Pa co2 ) greater than 82 mm Hg ( p = 0.022), baseline lactate greater than 15 mmol/L ( p = 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L ( p < 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39-0.83] p = 0.004). CONCLUSIONS: In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Pa co2 management in E-cardiopulmonary resuscitation warrants further studies.

Longitudinal Trends in Bleeding Complications on Extracorporeal Life Support Over the Past Two Decades-Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: Data about inhospital outcomes in bleeding complications during extracorporeal life support (ECLS) have been poorly investigated. DESIGN: Retrospective observational study. SETTING: Patients reported in Extracorporeal Life Support Organization Registry. PATIENTS: Data of 53.644 adult patients (greater than or equal to 18 yr old) mean age 51.4 ± 15.9 years, 33.859 (64.5%) male supported with single ECLS run between 01.01.2000 and 31.03.2020, and 19.748 cannulated for venovenous (V-V) ECLS and 30.696 for venoarterial (V-A) ECLS. INTERVENTIONS: Trends in bleeding complications, bleeding risk factors, and mortality. MEASUREMENT AND MAIN RESULTS: Bleeding complications were reported in 14.786 patients (27.6%), more often in V-A ECLS compared with V-V (30.0% vs 21.9%; p < 0.001). Hospital survival in those who developed bleeding complications was lower in both V-V ECLS (49.6% vs 66.6%; p < 0.001) and V-A ECLS (33.9 vs 44.9%; p < 0.001). Steady decrease in bleeding complications in V-V and V-A ECLS was observed over the past 20 years (coef., -1.124; p < 0.001 and -1.661; p < 0.001). No change in mortality rates was reported over time in V-V or V-A ECLS (coef., -0.147; p = 0.442 and coef., -0.195; p = 0.139).Multivariate regression revealed advanced age, ecls duration, surgical cannulation, renal replacement therapy, prone positioning as independent bleeding predictors in v-v ecls and female gender, ecls duration, pre-ecls arrest or bridge to transplant, therapeutic hypothermia, and surgical cannulation in v-a ecls. CONCLUSIONS: A steady decrease in bleeding over the last 20 years, mostly attributable to surgical and cannula-site-related bleeding has been found in this large cohort of patients receiving ECLS support. However, there is not enough data to attribute the decreasing trends in bleeding to technological refinements alone. Especially reduction in cannulation site bleeding is also due to changes in timing, patient selection, and ultrasound guided percutaneous cannulation. Other types of bleeding, such as CNS, have remained stable, and overall bleeding remains associated with a persistent increase in mortality.

Extracorporeal Life Support for Respiratory Failure in Patients With Electronic Cigarette or Vaping Product Use-Associated Lung Injury.

OBJECTIVES: Electronic cigarette or vaping product use-associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use-associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use-associated lung injury who received extracorporeal life support. DESIGN: We performed a retrospective review of records of electronic cigarette or vaping product use-associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed. SETTING: This was a multi-institutional, international case series with patients from 10 different institutions in three different countries. PATIENTS: Patients who met criteria for confirmed electronic cigarette or vaping product use-associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers. MEASUREMENTS AND MAIN RESULTS: Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0-6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock. CONCLUSIONS: Electronic cigarette or vaping product use-associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use-associated lung injury.

HEROES V-A: HEmoRrhagic cOmplications in veno-arterial Extracorporeal life Support: Development and internal validation of a multivariable prediction model in adult patients.

BACKGROUND: Risk factors for bleeding complications during extracorporeal life support (ECLS) indicated for cardiac support remain poorly investigated. The aim is to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving veno-arterial (V-A) ECLS. METHODS: Data of the Extracorporeal Life Support Organization registry of adult patients undergoing V-A ECLS between 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-A ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the prediction model. Performance of the model was tested by discriminative ability and calibration with receiver operator characteristic, area under the curve, and visual inspection of the calibration plot. Internal validation was performed to detect overfitting of the model. RESULTS: In total 28 767 adult patients were included, of which 29.0% developed bleeding complications. Sex, body mass index, surgical cannulation, pre-ECLS respiratory and hemodynamic variables, pre-ECLS support and interventions, and different type of diagnosis were included in the prediction model. This prediction model showed a predictive capability with an AUC of 0.66. CONCLUSION: The model is based on the largest cohort of V-A ECLS patients and is the best available predictive model for bleeding events given the predictors that are available in V-A ECLS compared to current literature. The model can help in identifying patients at high risk for bleeding complications and will help in developing further research and decision-making in terms of anticoagulation management. External validation is warranted to extrapolate this model in the clinical setting.

HEROES V-V-HEmorRhagic cOmplications in Veno-Venous Extracorporeal life Support-Development and internal validation of multivariable prediction model in adult patients.

BACKGROUND: During extracorporeal life support (ECLS), bleeding is one of the most frequent complications, associated with high morbidity and increased mortality, despite continuous improvements in devices and patient care. Risk factors for bleeding complications in veno-venous (V-V) ECLS applied for respiratory support have been poorly investigated. We aim to develop and internally validate a prediction model to calculate the risk for bleeding complications in adult patients receiving V-V ECLS support. METHODS: Data from adult patients reported to the extracorporeal life support organization (ELSO) registry between the years 2010 and 2020 were analyzed. The primary outcome was bleeding complications recorded during V-V ECLS. Multivariable logistic regression with backward stepwise elimination was used to develop the predictive model. The performance of the model was tested by discriminative ability and calibration with receiver operating characteristic curves and visual inspection of the calibration plot. RESULTS: In total, 18 658 adult patients were included, of which 3 933 (21.1%) developed bleeding complications. The prediction model showed a prediction of bleeding complications with an AUC of 0.63. Pre-ECLS arrest, surgical cannulation, lactate, pO2 , HCO3 , ventilation rate, mean airway pressure, pre-ECLS cardiopulmonary bypass or renal replacement therapy, pre-ECLS surgical interventions, and different types of diagnosis were included in the prediction model. CONCLUSIONS: The model is based on the largest cohort of V-V ECLS patients and reveals the most favorable predictive value addressing bleeding events given the predictors that are feasible and when compared to the current literature. This model will help identify patients at risk of bleeding complications, and decision making in terms of anticoagulation and hemostatic management.

Extracorporeal membrane oxygenation outcomes in children with Williams syndrome: a review of the ELSO registry.

INTRODUCTION: Williams syndrome (WS) results from a microdeletion that usually involves the elastin gene, leading to generalized arteriopathy. Cardiovascular anomalies are seen in 80% of WS patients, including supravalvular aortic stenosis (SVAS), pulmonary artery stenosis (PAS), and pulmonary stenosis (PS). Sudden death associated with procedural sedation and in the perioperative period in WS children have been reported. This study aims to describe extracorporeal membrane oxygenation (ECMO) use in WS children, identify risk factors for hospital mortality of WS patients, and compare outcomes between WS children and non-WS children with SVAS, PAS, and PS. METHODS: Children 0-18 years-old in the Extracorporeal Life Support Organization (ELSO) Registry with a primary or secondary diagnosis of WS, SVAS, PAS, or PAS were included. RESULTS: Included were 50 WS children and 1222 non-WS children with similar cardiac diagnoses. ECMO use increased over time in both groups (p = 0.93), with most cases occurring in the current era. WS children were younger (p = 0.004), weighed less (p = 0.048), had a pulmonary indication for ECMO (50% vs 10%, p < 0.001), and were placed more on high frequency ventilation (p < 0.001) than non-WS patients. Despite reporting a respiratory indication, most (84%) WS patients were placed on VA-ECMO. There were no significant differences between the two groups in terms of pre-ECMO cardiac arrest, ECMO duration, or reason for ECMO discontinuation. Both groups had a mortality rate of 48% (p = 1.00). No risk factors for WS mortality were identified.

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

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

Association Between Arterial Carbon Dioxide Tension and Clinical Outcomes in Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: The manipulation of arterial carbon dioxide tension is associated with differential mortality and neurologic injury in intensive care and cardiac arrest patients; however, few studies have investigated this relationship in patients on venoarterial extracorporeal membrane oxygenation. We investigated the association between the initial arterial carbon dioxide tension and change over 24 hours on mortality and neurologic injury in patients undergoing venoarterial extracorporeal membrane oxygenation for cardiac arrest and refractory cardiogenic shock. DESIGN: Retrospective cohort analysis of adult patients recorded in the international Extracorporeal Life Support Organization Registry. SETTING: Data reported to the Extracorporeal Life Support Organization from all international extracorporeal membrane oxygenation centers during 2003-2016. PATIENTS: Adult patients (≥ 18 yr old) supported with venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 7,168 patients had sufficient data for analysis at the initiation of venoarterial extracorporeal membrane oxygenation, 4,918 of these patients had arterial carbon dioxide tension data available at 24 hours on support. The overall in-hospital mortality rate was 59.9%. A U-shaped relationship between arterial carbon dioxide tension tension at extracorporeal membrane oxygenation initiation and in-hospital mortality was observed. Increased mortality was observed with a arterial carbon dioxide tension less than 30 mm Hg (odds ratio, 1.26; 95% CI, 1.08-1.47; p = 0.003) and greater than 60 mm Hg (odds ratio, 1.28; 95% CI, 1.10-1.50; p = 0.002). Large reductions (> 20 mm Hg) in arterial carbon dioxide tension over 24 hours were associated with important neurologic complications: intracranial hemorrhage, ischemic stroke, and/or brain death, as a composite outcome (odds ratio, 1.63; 95% CI, 1.03-2.59; p = 0.04), independent of the initial arterial carbon dioxide tension. CONCLUSIONS: Initial arterial carbon dioxide tension tension was independently associated with mortality in this cohort of venoarterial extracorporeal membrane oxygenation patients. Reductions in arterial carbon dioxide tension (> 20 mm Hg) from the initiation of extracorporeal membrane oxygenation were associated with neurologic complications. Further prospective studies testing these associations are warranted.

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

OBJECTIVES: To assess in-hospital neurologic (CNS) complications in adult patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization's data registry. SETTING: Data reported to Extracorporeal Life Support Organization from 350 international extracorporeal membrane oxygenation centers during 1992-2015. PATIENTS: Adults (≥ 18 yr old) supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 4,988 adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure. Neurologic injury was defined as brain death, seizures, stroke, and intracranial hemorrhage occurring during extracorporeal membrane oxygenation support. We used multivariable logistic regression to explore patient and extracorporeal membrane oxygenation factors associated with neurologic injury. Median age of the study cohort was 46 (interquartile range, 32-58). Four hundred twenty-six neurologic complications were reported in 356 patients (7.1%), and included 181 intracranial hemorrhage (42.5%), 100 brain deaths (23.5%), 85 stroke (19.9%), and 60 seizure events (14.1%). In-hospital mortality was significantly higher for those with CNS complications (75.8% vs 37.8%; p < 0.001) and varied by type of CNS injury; mortality was 79.6% in patients with intracranial hemorrhage, 68.2% in patients with stroke, and 50% in patients with seizures. Pre-extracorporeal membrane oxygenation cardiac arrest, continuous veno-venous hemofiltration, and hyperbilirubinemia during extracorporeal membrane oxygenation were associated with increased odds of neurologic injury. CONCLUSIONS: Approximately 7% of adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure had neurologic injury. Intracranial hemorrhage was the most frequent type, and survival for patients with neurologic injury was poor. Future investigations should evaluate anticoagulation management as well as brain/extracorporeal membrane oxygenation interaction to reduce these life-threatening events.

Shifting Risks and Conflicting Outcomes-ECMO for Neonates with Congenital Diaphragmatic Hernia in the Modern Era.

OBJECTIVES: To update previously described trends for neonates with congenital diaphragmatic hernia (CDH) receiving ECMO with changes in recommendations for care, and to determine how recent advancements in respiratory care have affected this patient population. STUDY DESIGN: This study is a retrospective review of more than 2500 neonates with CDH who received ECMO listed in the Extracorporeal Life Support Organization (ELSO) registry. Cochran-Armitage and multivariate regression analyses were used to analyze changes in the patient population over time and in mortality-related risk factors. RESULTS: Almost one-half (48.1%) of the term neonates survived to discharge, representing a 13.8% decline in survival over the past 25 years (P < .0001). Over the past 10 years, the prevalence of respiratory acidosis more than doubled (P < .0001) and the prevalence of major complications increased (P < .001). During the same period, the number of ECMO courses longer than 1 week increased (P < .001), whereas the prevalence of multiple complications (>4) decreased (P < .0001). Surgeries performed on ECMO were associated with worse outcomes than those performed off ECMO. ECMO duration no longer represents a mortality-related risk factor. CONCLUSIONS: Survival rates for neonates with CDH receiving ECMO have continued to drop in the modern era. Although the safety of ECMO has improved over the last decade, the number of patients experiencing significant respiratory acidosis has more than doubled-increasing the risk of intracranial hemorrhage and overall mortality. The evidence for permissive hypercapnia remains mixed; nonetheless, we believe that the risks outweigh the rewards in this patient population.

Extracorporeal membrane oxygenation outcomes in children with hemophagocytic lymphohistiocytosis.

INTRODUCTION: Pediatric patients with hemophagocytic lymphohistiocytosis (HLH) may develop refractory respiratory or cardiac failure that warrants consideration for extracorporeal membrane oxygenation (ECMO) support. The purposes of this study were to describe the use and outcomes of ECMO in pediatric HLH patients, to identify risk factors for hospital mortality and to compare their ECMO use and outcomes to the ECMO population as a whole. METHODS: Pediatric patients (⩽ 18 years) with a diagnosis of HLH in the Extracorporeal Life Support Organization (ELSO) Registry were included. RESULTS: Between 1983 and 2014, data for 30 children with HLH were available in the ELSO registry and all were included in this study. All cases occurred in the last decade. Of the 30 HLH patients, 24 (80%) had a respiratory indication for ECMO and six (20%) had a cardiac indication (of which 4 were E-CPR and 2 cardiac failure). Of the 24 respiratory ECMO patients, 63% were placed on VA ECMO. Compared with all pediatric patients in the ELSO registry during the study period (n=17,007), HLH patients had worse hospital survival (non-HLH 59% vs HLH 30%, p=0.001). In pediatric HLH patients, no pre-ECMO risk factors for mortality were identified. The development of a hemorrhagic complication on ECMO was associated with decreased mortality (p=0.01). Comparing HLH patients with respiratory failure to patients with other immune compromised conditions, the overall survival rate is similar (HLH 38% vs. non-HLH immune compromised 31%, p=0.64). CONCLUSIONS: HLH is an uncommon indication for ECMO and these patients have increased mortality compared to the overall pediatric ECMO population. These data should be factored into decision-making when considering ECMO for pediatric HLH patients.

Outcome of Adult Respiratory Failure Patients Receiving Prolonged (≥14 Days) ECMO.

OBJECTIVE: To examine the outcomes of prolonged (≥14 days) extracorporeal membrane oxygenation (P-ECMO) for adult severe respiratory failure and to assess characteristics associated with survival. BACKGROUND: The use of ECMO for treatment of severe respiratory adult patients is associated with overall survival rates of 50% to 70% with median ECMO duration of 10 days. No prior multi-institutional studies have examined outcomes of P-ECMO for severe respiratory failure. METHODS: Data on all adult (≥18 years) patients who required P-ECMO for severe respiratory failure from 1989 to 2013 were extracted from the Extracorporeal Life Support Organization international multi-institutional registry. We examined outcomes over 23 years and compared the 2 more recent time periods of 1989 to 2006 versus 2007 to 2013. RESULTS: Up to 974 patients, mean age 40.2 (18-83) years, had ECMO duration of mean 25.2 days/median 21.0 days (range: 14-208 days). Venovenous ECMO support was most common (venovenous: 79.5%, venoarterial: 9.9%). Reason for ECMO discontinuation included native lung recovery (54%), organ failure (23.7%), family request (6.7%), hemorrhage (2.7%), and diagnosis incompatible with life (5.6%). Forty patients (4.1%) underwent lung transplant with 50% postoperative in-hospital mortality. Increased prevalence of P-ECMO was noted with 72% (701/974) of all cases reported since 2008. Survival to hospital discharge was 45.4% (443/974) and did not vary with ECMO duration. Multivariate logistic regression analysis confirmed that P-ECMO patients 2007 to 2013 had a lower risk of death [odds ratio (OR): 0.650; 95% confidence interval (CI), 0.454-0.929; P = 0.010] compared with 1989 to 2006. Factors independently associated with survival were younger age (OR: 0.983; 95% CI, 0.974-0.993; P < 0.001) and lower PaCO2 (OR, 0.991; 95% CI, 0.986-0.996; P < 0.001). CONCLUSIONS: Prolonged ECMO use for adult respiratory failure was associated with a lower (45.4%) hospital survival rate, compared with prior reported survival rates of short duration ECMO. Prolonged ECMO survival significantly increased in recent years, and increasing ECMO duration did not alter the survival fraction in the 1989 to 2013 study cohort. Although P-ECMO survival rates are less than short ECMO runs, P-ECMO support is justified.

In-Hospital Neurologic Complications in Adult Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To elucidate the epidemiology, complication profiles, hospital outcome, and predisposing factors of CNS complications occurring during venoarterial extracorporeal membrane oxygenation in adults. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization registry. SETTING: Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers from 1992 to 2013. PATIENTS: Patients more than 16 years old supported with a single-run of venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined 4,522 adult patients supported with venoarterial extracorporeal membrane oxygenation and included in the Extracorporeal Life Support Organization registry. Venoarterial extracorporeal membrane oxygenation was used for cardiac dysfunction in 3,005 patients (66.5%), cardiopulmonary resuscitation in 877 patients (19.4%), and respiratory failure in 640 patients (14.1%), respectively. Multivariate logistic regression was performed to identify factors independently associated with CNS injury. Neurologic complications occurred in 682 patients (15.1%), and included brain death in 358 patients (7.9%), cerebral infarction in 161 patients (3.6%), seizures in 83 patients (1.8%), and cerebral hemorrhage in 80 patients (1.8%). Multiple CNS complications in the same patient occurred in 70 cases. Hospital mortality in patients with CNS complications was 89%, compared with 57% in patients without (p < 0.001). In a multivariable model, age, pre-extracorporeal membrane oxygenation cardiac arrest, the use of inotropes on extracorporeal membrane oxygenation, and post-extracorporeal membrane oxygenation hypoglycemia were shown to be associated with CNS complications. CONCLUSIONS: Neurologic complications in adult patients on venoarterial extracorporeal membrane oxygenation support are common and associated with poor survival. Further research should focus on better understanding and management of brain/extracorporeal membrane oxygenation interaction to avoid such catastrophic complications.

Factors Associated With Mortality in Neonates Requiring Extracorporeal Membrane Oxygenation for Cardiac Indications: Analysis of the Extracorporeal Life Support Organization Registry Data.

OBJECTIVES: Survival among neonates supported with extracorporeal membrane oxygenation for cardiac indications is 39%. Previous single-center studies have identified factors associated with mortality, but a comprehensive multivariate analysis is not available for this population. Understanding factors associated with mortality may help design treatment strategies, determine optimal timing for cannulation, and inform patient selection. This study identifies factors associated with mortality in neonates supported with extracorporeal membrane oxygenation for cardiac indications. DESIGN: Retrospective cohort study. SETTING: Two hundred and thirty U.S. and international centers reporting extracorporeal membrane oxygenation data to the Extracorporeal Life Support Organization. SUBJECTS: Four thousand and four seventy one neonates with congenital and acquired cardiac disease supported with extracorporeal membrane oxygenation for cardiac indications during 2001-2011. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The primary outcome measure was mortality prior to hospital discharge. Overall hospital mortality was 59%. Demographic and preextracorporeal membrane oxygenation factors associated with mortality were evaluated in a multivariable model. Factors associated with death prior to hospital discharge included lower body weight, earlier era, single ventricle physiology, lower preextracorporeal membrane oxygenation arterial pH, and longer time from intubation to extracorporeal membrane oxygenation cannulation. Lower pH was associated with increased mortality regardless of cardiac diagnosis and surgical complexity. The majority of survivors separated from extracorporeal membrane oxygenation less than 8 days after extracorporeal membrane oxygenation deployment. CONCLUSIONS: Mortality for neonates supported with extracorporeal membrane oxygenation for cardiac indications is high. Severity of preextracorporeal membrane oxygenation acidosis was independently associated with increased risk of mortality. Earlier initiation of extracorporeal membrane oxygenation may reduce the degree and duration of acidosis and may improve survival. Further studies are needed to determine optimal timing of cannulation in this population.

Global Trends in Extracorporeal Membranous Oxygenation Use and Survival of Patients With Influenza-Associated Illness.

OBJECTIVES: To determine the overall use of extracorporeal membranous oxygenation for influenza-associated illness and describe risk factors associated with mortality in these patients. DESIGN: Retrospective multicenter cohort analysis. SETTING: The international Extracorporeal Life Support Organization database was queried for patients with influenza-associated illness on extracorporeal membranous oxygenation from 1992 to 2014. PATIENTS: In total, 1,654 patients with influenza-associated illness on extracorporeal membranous oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data collected included age, type of support, duration of support, type of microbial codetection, complications, and survival status at discharge. The primary outcome of interest was survival to hospital discharge. From 1992 to 2014, 1,688 (3%) of the 61,336 extracorporeal membranous oxygenation runs were due to influenza-associated illness reflecting 1,654 unique patients: 30 (2%) were neonates, 521 (31%) were pediatric patients, and 1,103 (67%) were adults. Extracorporeal membranous oxygenation use for influenza-associated illness increased from 1992 to 2014, with a marked increase in use after the 2009 H1N1 pandemic. Survival to hospital discharge of patients with influenza-associated illness on extracorporeal membranous oxygenation was 63% and was not affected by bacterial codetection. However, when patients with Staphylococcus aureus codetection were compared with those with another bacterial codetection, their survival to hospital discharge was significantly lower (52% vs 67%; p < 0.01). In a logistic regression model, the effect of S. aureus on in-hospital mortality varied by age group, with younger patients with S. aureus having increased in-hospital mortality. CONCLUSIONS: Extracorporeal membranous oxygenation use for individuals with influenza increased over time, particularly after the 2009 H1N1 pandemic, most notably among older adults. Survival to hospital discharge for patients with influenza on extracorporeal membranous oxygenation was slightly higher than survival to hospital discharge for respiratory illness due to any cause. Bacterial codetection was common among patients with influenza on extracorporeal membranous oxygenation and was associated with increased days on extracorporeal membranous oxygenation but not increased mortality. Only S. aureus codetection in children was associated with increased in-hospital mortality.

Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) may provide mechanical pulmonary and circulatory support for patients with cardiogenic shock refractory to conventional medical therapy. Prediction of survival in these patients may assist in management of these patients and comparison of results from different centers. AIMS: To identify pre-ECMO factors which predict survival from refractory cardiogenic shock requiring ECMO and create the survival after veno-arterial-ECMO (SAVE)-score. METHODS AND RESULTS: Patients with refractory cardiogenic shock treated with veno-arterial ECMO between January 2003 and December 2013 were extracted from the international Extracorporeal Life Support Organization registry. Multivariable logistic regression was performed using bootstrapping methodology with internal and external validation to identify factors independently associated with in-hospital survival. Of 3846 patients with cardiogenic shock treated with ECMO, 1601 (42%) patients were alive at hospital discharge. Chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO3) were risk factors associated with mortality. Younger age, lower weight, acute myocarditis, heart transplant, refractory ventricular tachycardia or fibrillation, higher diastolic blood pressure, and lower peak inspiratory pressure were protective. The SAVE-score (area under the receiver operating characteristics [ROC] curve [AUROC] 0.68 [95%CI 0.64-0.71]) was created. External validation of the SAVE-score in an Australian population of 161 patients showed excellent discrimination with AUROC = 0.90 (95%CI 0.85-0.95). CONCLUSIONS: The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www.save-score.com).

Extracorporeal membrane oxygenation for the support of adults with acute myocarditis.

OBJECTIVES: To characterize survival outcomes for adult patients with acute myocarditis supported with extracorporeal membrane oxygenation and identify risk factors for in-hospital mortality. DESIGN: Retrospective review of Extracorporeal Life Support Organization registry database. SETTING: Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers. PATIENTS: Patients 16 years old or older supported with extracorporeal membrane oxygenation for myocarditis during 1995 to 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 150 separate runs of extracorporeal membrane oxygenation for 147 patients with a diagnosis of acute myocarditis in the Extracorporeal Life Support Organization database from 1995 through 2011. Survival to hospital discharge was 61%. Nine patients underwent heart transplantation, and transplant-free survival to discharge was 56%. Extracorporeal membrane oxygenation was deployed during extracorporeal cardiopulmonary resuscitation in 31 patients (21% of the cohort). In a multivariate model evaluating pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation support factors, pre-extracorporeal membrane oxygenation arrest (adjusted odds ratio, 2.4; 95% CI, 1.1-5.0) and need for higher extracorporeal membrane oxygenation flows at 4 hours post-extracorporeal membrane oxygenation cannulation (odds ratio, 2.8; 95% CI, 1.1-7.3) were associated with increased odds of in-hospital mortality. In a second multivariate model evaluating adverse events while on extracorporeal membrane oxygenation, central nervous system injury (odds ratio, 26.5; 95% CI, 7.3-96.6), renal failure (odds ratio, 3.6; 95% CI, 1.4-9.3), arrhythmia (odds ratio, 5.8; 95% CI, 2.2-15.1), and hyperbilirubinemia (odds ratio, 9.1; 95% CI, 2.6-31.8) were associated with increased odds of in-hospital mortality. CONCLUSIONS: Extracorporeal membrane oxygenation can be used effectively in adults with myocarditis to support the circulation while awaiting myocardial recovery. Early extracorporeal membrane oxygenation deployment prior to cardiac arrest may be associated with better outcomes.

Extracorporeal Membrane Oxygenation in Pediatric Trisomy 21: 30 Years of Experience from the Extracorporeal Life Support Organization Registry.

OBJECTIVES: To describe the use of extracorporeal membrane oxygenation (ECMO) in patients with trisomy 21 (T21), to identify risk factors for hospital mortality, and to compare outcomes with those of patients without T21. STUDY DESIGN: Children under age 18 years registered in the Extracorporeal Life Support Organization Registry were included. Comparisons between patients with T21 and patients without T21 were performed using the χ(2) or Wilcoxon rank-sum test and multivariable logistic regression. RESULTS: The study cohort included 623 patients with T21 and 46 239 patients without T21. The prevalence of T21 was 13.5/1000 patients receiving ECMO. ECMO utilization in patients with T21 increased over time, with 60% of cases occurring in the last decade. There was no significant difference in survival between patients without T21 and those with T21 (63% vs 57%; P = .23). In patients with T21, independent risk factors for mortality before cannulation were a cardiac indication for ECMO support and milrinone use (P ≤ .001 for both). Multivariable risk factors for mortality on ECMO included hemorrhagic, neurologic, renal, and pulmonary complications (P < .04 for all). CONCLUSION: The use of ECMO in patients with T21 has increased over time. Patients with a cardiac indication for ECMO have higher mortality compared with those supported for respiratory indications. Despite differences in indications for ECMO, patients with T21 have similar hospital survival as those without T21; thus, by itself, a diagnosis of T21 should not be considered a risk factor for in-hospital mortality when contemplating ECMO cannulation.

Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score.

RATIONALE: Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. OBJECTIVES: To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. METHODS: Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. MEASUREMENTS AND MAIN RESULTS: Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72-0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89-0.97). CONCLUSIONS: The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

Extracorporeal cardiopulmonary resuscitation outcomes in term and premature neonates*.

OBJECTIVE: Extracorporeal cardiopulmonary resuscitation appears to improve survival in patients with acute refractory cardiopulmonary failure. This analysis was performed to determine survival outcomes and predictors of in-hospital mortality for term and preterm neonates who received extracorporeal cardiopulmonary resuscitation. DESIGN: Retrospective review of data from the Extracorporeal Life Support Organization international registry. SETTING: Pediatric and neonatal ICUs. PATIENTS: Infants less than or equal to 30 days. INTERVENTIONS: Extracorporeal cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and survival data from patients who received extracorporeal cardiopulmonary resuscitation between 1998 and 2010 were analyzed to determine factors that affect in-hospital mortality. Overall survival to hospital discharge for the 641 neonates who received extracorporeal cardiopulmonary resuscitation was 39%. In univariate analysis, gestational age correlated inversely with stroke (odds ratio, 0.84 [95% CI, 0.75-0.95]; p = 0.006) and death (odds ratio, 0.87 [95% CI, 0.78-0.96]; p = 0.005) as did corrected gestational age (odds ratio, 0.89 [95% CI, 0.81-0.97]; p = 0.006) and birth weight (odds ratio, 0.53 [95% CI, 0.38-0.74]; p < 0.001). Dysrhythmia as the primary diagnosis had significantly lower odds of death than single-ventricle cardiac disease (odds ratio, 0.24 [95% CI, 0.06-0.95]; p = 0.04). Higher pre-extracorporeal cardiopulmonary resuscitation oxygenation decreased the odds of death (odds ratio, 0.996 [95% CI, 0.994-0.999]; p = 0.01), whereas complications occurring on extracorporeal life support increased the odds of death. In the multivariate analysis, lower birth weight and pre-extracorporeal cardiopulmonary resuscitation oxygenation, as well as complications including CNS hemorrhage, pulmonary hemorrhage, acidosis, renal replacement therapy, and mechanical complications, increased the odds of death. CONCLUSIONS: Overall survival for neonates receiving extracorporeal cardiopulmonary resuscitation is similar to older pediatric patients but decreases with lower gestational age and weight. Despite this, many low-birth weight neonates survive to hospital discharge.