Paden, Matthew L.*; Conrad, Steven A.†; Rycus, Peter T.‡; Thiagarajan, Ravi R.§; on Behalf of the ELSO Registry
The Extracorporeal Life Support Organization (ELSO) was formed in 1989, as a group of centers using extracorporeal life support (ECLS) in the management of cardiopulmonary failure unresponsive to conventional medical and surgical therapies. The ELSO maintains a registry of ECLS cases and provides annual ECLS survival information and center-based performance reports. Other functions of ELSO include enhancing communication, developing guidelines for ECLS, and promoting research to improve ECLS outcomes and develop newer ECLS devices. In 2011, ELSO had 170 domestic and international centers actively reporting data to the registry.
Maintaining a registry of ECLS cases is one of the major functions of ELSO. The ELSO Registry is funded solely by ELSO and receives no external funding. A data use agreement is in place with each individual ECLS center to provide ELSO member centers with a limited data set for research or quality assurance purposes. Entry of patient data into the registry is strongly encouraged to all ELSO members. Initially, the registry was implemented as a system of handwritten paper forms filled out by individual centers that were manually entered at ELSO into a flat file database. Recognizing the growth of ECLS and the needs of ELSO members, the registry has evolved into a secure, encrypted web-based data entry system (http://www.elsonet.org) with integrated data integrity monitoring that stores data in a Microsoft SQL Server (Microsoft Corporation, Redmond, WA). Addition of disease- and condition-specific data, including specific surgical information for the cardiac support patients, International Classification of Diseases (ICD-9), and Current Procedural Terminology (CPT) values to the database, allows a standard structure that promotes consistency in query results. This modernization has provided multiple benefits to the ELSO Registry and the ECLS community. It has allowed a more rapid response to urgent clinically needed queries of the database. In addition, it allows for rapid collection and distribution of worldwide outcome data as was seen during the H1N1 influenza pandemic. In addition, ELSO Registry data were instrumental in providing matched pairs for the studies that led to the approval of the Berlin Heart EXCOR pediatric ventricular assist device by the US Food and Drug Administration. Standardized reporting of both international and center-specific patient outcomes and complications are reported to member centers twice a year. There have been seven official ELSO Registry reports published since 1988, with the last complete registry report being published in 2005.1–7 In 2009, a more focused discussion of neonatal and pediatric cardiac ECLS outcomes using registry data was completed.7
Data reported to ELSO include basic patient descriptive information, perinatal information (for neonatal patients), pre-ECLS physiologic data, ECLS equipment and implementation data, complications (both mechanical and patient related), and outcome information. In addition to that data, for specific patient conditions, addendums have been created for cardiac failure patients (2001), extracorporeal cardiopulmonary resuscitation (ECPR) (2011), and renal failure patients (2012).
All cases submitted to the Registry through June 2012 are included in this analysis. The Registry captures the majority of ECLS cases performed in the United States. The registry also captures cases from many international centers and thus represents a broad cross-section of ECLS cases. With expanding membership from international centers, international cases are being increasingly reported to ELSO. The ELSO actively seeks out nonmember centers that are performing ECLS to obtain cases for the registry.
The Registry categorizes cases as neonatal, pediatric, or adult. Neonatal cases are defined as those aged 30 days or less at the time of ECLS initiation. Pediatric cases are those more than 30 days old and younger than 18 years at the time of ECLS initiation. Adult cases include all cases 18 years and older.
Patients are also categorized by reason for ECLS support. These choices are limited to pulmonary, cardiac, or ECPR. Pulmonary cases are defined as those in which the primary indication for support is hypoxemic or hypercapnic acute respiratory failure, even with some degree of concomitant cardiac dysfunction. Extracorporeal life support used as a bridge to lung transplantation is defined as a pulmonary case even if concomitant cardiac dysfunction is present. Similarly, cardiac cases are defined as those in which the primary reason for ECLS is cardiac dysfunction. This includes patients with primary cardiomyopathies, myocarditis, and postoperative cardiac surgical cases (congenital and noncongenital). Patients where ECLS is being used as a bridge to a cardiac transplant are defined as cardiac cases even in the presence of lung failure. Extracorporeal cardiopulmonary resuscitation captures cases where rapid ECLS deployment is used to support cardiopulmonary resuscitation.8 Guidelines for ECLS patient selection, technique, and timing of initiation have been promulgated by ELSO (http://www.elsonet.org/index.php/resources/guidelines.html).9 Although there may be variation by center, all patients have acute, potentially reversible cardiorespiratory failure in which conventional support has been deemed inadequate and the patient faces a predicted risk of mortality greater than 50%. Conventional support includes pressure-limited ventilation, airway pressure release ventilation, high-frequency ventilation, inhaled nitric oxide, surfactant administration, prone positioning, recruitment maneuvers, fluid management, and optimization of circulatory function with pharmacologic support as appropriate for age and type of organ dysfunction.
The modes of support defined by the Registry are variations of either venoarterial (VA) or venovenous (VV) ECLS. Venoarterial ECLS provides partial to total cardiopulmonary support by drainage of blood from major venous structures and returning the postgas exchanged blood to the arterial system. Venovenous ECLS provides no direct cardiac support, but instead provides gas exchange to venous blood and subsequently returns that blood before entry to the pulmonary circuit. Venovenous double lumen (VVDL) cannulas are commonly used for VV ECLS and have the advantage of single-site insertion. Regardless of mode, additional venous drainage cannulas, if used, are indicated as “+V.” Conversion from one mode of ECLS to another during therapy is represented in the Registry by a mode of “VV→VA” or “VA→VV.”
Complications related to or attributed to ECLS are defined as either mechanical (involving ECLS circuit components including cannulae) or patient related. In general, a complication is recorded if it requires active management such as equipment change, change in therapy, or results in organ dysfunction. The complications recorded are predefined by ELSO and are standardized across centers. Survival is recorded in the ELSO Registry in two categories. Survival to completion of ECLS is obtained and survival to discharge or transfer. For the purposes of this article, all survival data presented are survival to discharge or transfer.
Data were extracted from the Registry using Structured Query Language queries. All patients entered into the database before July 1, 2012, were included for analysis. Statistical procedures used included descriptive statistics and Fisher’s exact test/chi-square with Yates’ correction as appropriate for sample size for analysis of categorical variables. Note that in all figures in this article, 2012 data will be underrepresented because of delays in reporting patients to the Registry.
Survival outcomes for all patients reported to the ELSO Registry through July 1, 2012, and provided in the July 2012 ELSO International Summary are categorized by age and support are shown in Table 1. By age, the majority of the patients (62%) are neonatal, with an overall survival of 68%. Extracorporeal life support is mostly used for pulmonary indications, representing 68% of the patients in the registry with 70% survival. Although the number of ELSO centers was stable between 110 and 120 from 1993 to 2004, growth has been seen since that time with 160 centers in 2010 and 170 in 2011.
Neonatal Respiratory ECLS
Neonatal respiratory ECLS patients compose the largest group (25,746 patients, 75% overall survival) in the ELSO registry. As noted in the 2004 ELSO Registry report by Conrad et al.,6 the number of neonatal respiratory support cases reported showed a decreasing trend that existed from 1992 to 1998 and has remained steady at approximately 800 cases (69% survival) per year since that time (Figure 1). In 2011, the last complete year of data collection, there were 787 runs with 65% survival. The three most common indications for neonatal respiratory ECLS are meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), and persistent pulmonary hypertension of the newborn (PPHN). Extracorporeal life support use by pulmonary diagnoses is shown in Figure 2. Despite having the best outcome (94% survival in 7,842 patients) in the ELSO Registry, use of ECLS for MAS has decreased since the 1990s owing to improvement in ventilatory techniques, equipment, and therapeutics.10,11 Extracorporeal life support use for PPHN (4,292 patients with 77% survival) and CDH (6,458 patients) have been stable over the past decade. A decrease in survival is seen comparing CDH survival between 1990–2000 (53.4%) and 2001–2011 (45.4%; p < 0.0001). The factors behind the decreased survival in these patients are not clear from registry data and may reflect differences in local practices, severity of illness, and patient condition before ECLS deployment. The mean time on ECLS is 168 hours (7 days) with the longest neonatal respiratory ECLS run being 2,549 hours (106 days).
Mode of ECLS support is summarized in Table 2. Venoarterial ECLS is the predominate (72%) mode of neonatal respiratory patients in the Registry with 71% survival. Venovenous ECLS is most commonly provided via a double lumen cannula. Venovenous ECLS has a higher rate of survival (84%) compared with VA ECLS (p < 0.0001). Currently, there is no severity of illness scoring system in the Registry to aid in determining whether this survival difference is owing to patient factors or mode of ECLS used.
Pediatric Respiratory ECLS
The number of pediatric patients (30 days to <18 years) supported for respiratory failure is presented in Figure 3. Although previously stable at 200 patients a year, an increase has been occurring in the 2000s and approximately 350 patients have received ECLS in the past 2 years. In 2011, the last complete year of data collection, there were 382 runs with 58% survival. The 444 cases treated in 2009 represent the single largest yearly usage of ECLS for pediatric respiratory patients. This increase in usage is partially attributable to the 78 pediatric respiratory ECLS patients with novel H1N1 influenza that year. The 60% survival of novel H1N1 ECLS patients that year was not different from other indications for pediatric respiratory ECLS (55%; p = 0.3823). Extracorporeal life support use in novel H1N1 influenza has been reviewed elsewhere extensively.12,13
Overall survival is unchanged comparing time periods from 1990–2000 to 2001–2011 (55.6% vs. 56.1%; p = 0.7113). Although no severity of illness scoring system currently exists in the ELSO Registry, it has been noted that that the number of pediatric respiratory ECLS patients with comorbidities increased from 19% in 1993 to 47% in 2007, implying that more complicated patients are being cared for without subsequent increase in mortality.14 The mean duration of ECLS is 193 hours (8 days) with 2,968 hours (4 months) being the longest reported ECLS time in the Registry. In the pediatric respiratory group of patients, diagnosis does not appear to have a large impact on survival (Table 3). However, analysis is made more difficult by the large number of patients with diverse etiologies of disease categorized as “Other.”
Although the majority of patients are still supported with VA ECLS, there has been a substantial shift regarding the chosen mode of ECLS since the last Registry report. Omitting those patients who switched modes during their course, the 2004 Registry report showed 32% of cases being supported with VV (VV, VVDL, VVDL+V) mode.6 Since that report, an increase to 43% in VV support has been noted in the recent cohort of 2,492 pediatric patients. The recent cohort of pediatric patients supported with VV ECLS for respiratory failure is significantly larger than the cohort in the 2004 report (p < 0.0001). For the first time, in 2011 VV ECLS outnumbered VA ECLS for pediatric respiratory cases (Figure 4).
Adult Respiratory ECLS
Extracorporeal life support for adult respiratory failure remained stable at approximately 100 cases a year until the mid-2000s when usage started increasing (Figure 5). As was seen in the pediatric population, a large increase in utilization occurred in 2009 caused by the novel H1N1 influenza pandemic. During this pandemic, owing to a large influx of requests for information on the utility of ECLS with novel H1N1 influenza, the ELSO Registry rapidly put together a short form registry to collect clinical and outcome information about these patients. Participation in this Registry was open to both ELSO members and non-ELSO members. A total of 237 adult respiratory failure patients with novel H1N1 influenza treated with ECLS were entered into this registry with 159 surviving (67%). Multiple individual centers worldwide have published their individual experiences using ECLS during a pandemic.15,16
After the pandemic subsided, ECLS usage continued to remain more than 400 cases per year. This subsequent increase in ECLS usage likely stems from the publication of the Conventional ventilation or ECMO for Severe Adult Respiratory failure (CESAR) trial results showing increased survival (63% vs. 47%; relative risk, 0.69; confidence interval, 0.05–0.97; p = 0.03) without disability at 6 months in severe acute respiratory distress syndrome patients randomized to be transported to an ECLS center.17 Overall survival for adult respiratory ECLS is 55% and survival varies by diagnosis with again a large population of patients coded as “Other” (Table 4). In 2011, the last complete year of data collection, there were 507 runs with 58% survival. In contrast to the other populations examined, VV ECLS predominates (78%) in the adult patients. Most patients are multiple-site VV ECLS (72%); however, the introduction of a large percutaneously placed double lumen cannula that allows single-site VV ECLS has become increasingly used. In 2008, the first year where more than five VVDL cannulas were used in this population, they represented 20% of VV cannulations. This percentage continues to increase, with VVDL usage rates of 40%, 49%, and 47% in VV ECLS for years 2009–2011. The mean time on ECLS is 177 hours (7 days) with the longest adult respiratory ECLS run being 5,014 hours (7 months).
Cardiac ECLS cases are one of the fastest growing populations, and data are presented by age range in Figures 6–9. Despite new innovations in pediatric ventricular assist device and artificial heart technology, ECLS remains the primary modality of support for infants and small pediatric patients with cardiac failure refractory to medical therapy. Overall, cardiac ECLS survival (44%) is less than what is seen with respiratory ECLS indications. However, survival in the overall cardiac population is increasing when comparing cohorts from 1990–2000 (38%) to 2001–2011 (45%; p < 0.0001). In 2011, the last complete year of data collection, there were 1,219 runs with 46% survival. Case data and survival percentage, stratified by indication and age group, are provided in Table 5. Outside the neonatal age group, ECLS for myocarditis has the best survival of the cardiac indications. As seen with the respiratory cohorts, a large number of cases are classified as “Other,” making further analysis more difficult. Because cardiac support is by definition necessary in this population, more than 95% of cases use VA ECLS. Exceptions tend to be occasional uses of VV ECLS to aid patients with failing Fontan physiology and patients converted from VA to VV ECLS when their cardiac function has returned, but the patient still needs aid with gas exchange. As demonstrated in Figure 9, adult cardiac ECLS usage has been rapidly increasing since 2004. This growth stems from both development of new programs providing this therapy and existing neonatal/pediatric programs which have extended their scope of practice. Median duration of ECLS for cardiac ECLS (114 hours for <30 days, 115 hours for 31–364 days, 113 hours for 1 year to <16 years, and 93 hours for >16 years) is shorter than ECLS for respiratory failure (144 hours).
A major function of the ELSO Registry is to capture data on complications that occur when using this complex patient support technology. These data allow individual centers to benchmark themselves against the whole of international centers and serve as a platform to foster both local and international quality improvement programs. Currently, ELSO collects data on 46 different complications. The ELSO presents to member centers complication data for both respiratory and cardiac ECLS, and the complications are stratified into mechanical (device-related) and patient-related events (a subset of complication data is shown in Tables 6 and 7). As with previous reports, bleeding from cannula and surgical sites remains a significant problem and is associated with worse survival. Intracranial hemorrhage and seizures remain more common in the younger population, with a decline in incidence as patients get older.
Extracorporeal life support utilization has stabilized in the neonatal respiratory population, after the decline seen in the 1990s attributable to improvement in respiratory technologies and therapeutics. However, ECLS use overall continues to increase, with yearly increases in the pediatric respiratory, adult respiratory, and cardiac ECLS populations. This trend is expected to continue, being driven largely by the increasing utilization of adult respiratory ECLS since the publication of the CESAR trial results. The ELSO centers and ECLS played an important role in responding to clinical needs during the 2009 novel H1N1 influenza pandemic, supporting 317 respiratory patients worldwide with 65% overall survival.
The ELSO Registry is a comprehensive database of extracorporeal support data and remains a valuable resource to the ECLS community, clinicians, industry, and regulatory agencies. In response to the changing populations and numbers of patients being treated with ECLS, additions are being made to the current ELSO Registry infrastructure. The recent addition of web-based data entry with automatic data integrity monitoring will lower the barrier to data entry, thus improving response rates, and aid in ensuring accuracy of the entered values. In 2013, standardized real-time query capability of the Registry will be added to allow ELSO member centers access to the latest data. One criticism of the ELSO registry is that it lacks the ability to stratify patients by severity of illness which impairs ability to make comparisons between different patient populations. Addition of six commonly used severity of illness scoring systems (Pediatric Risk of Mortality 3 [PRISM3], Paediatric Logistic Organ Dysfunction [PELOD], Pediatric Index of Mortality 2 [PIM2], Acute Physiology and Chronic Health Evaluation II [APACHE II], SAPS [Simplified Acute Physiology Score], and Sequential Organ Failure Assessment [SOFA]) for neonatal, pediatric, and adult patients will be added in 2013 to aid in future analysis of patients treated at different centers or time periods. Efforts to validate these scoring systems in the ECLS population will also be pursued. The ELSO Registry reporting to member centers will be restructured in 2013 to include improved categorization of patients and reduction of patients in the “Other” categories to less than 5%. A limited version of Registry summary data will be provided to the public on the ELSO community Web site (http://www.elsonet.org/index.php/registry/statistics/limited.html). Linkage of ELSO Registry data with that of other large patient databases, such as that run by the Society of Thoracic Surgeons, would allow a greater understanding of cardiac ECLS patients by potentially allowing better and more specific information collected by these databases (but not by ELSO) to be available for a more comprehensive analysis of factors associated with survival. In addition, linkage with the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database allows the opportunity to evaluate outcomes more complex than survival, such as long-term follow-up data regarding level of function and quality of life. These linkages can help with better patient selection, determining timing of ECLS deployment, and understanding patient management issues that can help improve ECLS outcomes for patients supported with cardiac ECLS.
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extracorporeal membrane oxygenation; cardiopulmonary failure; mechanical support