Long-term survival and costs following extracorporeal membrane oxygenation in critically ill children—a population-based cohort study

Extracorporeal membrane oxygenation (ECMO) provides cardiorespiratory support to patients who have failed initial, conventional treatment [1, 2]. In pediatric populations, ECMO is used for organ support in cases of respiratory failure, cardiac failure, and as an adjunct to cardiopulmonary resuscitation (E-CPR) during cardiac arrest [3‐6]. ECMO can also serve as a bridge to selected medical or surgical therapies, including ventricular assist device (VAD), and heart or lung transplant [7, 8].

With the use of ECMO evolving [9], there is a growing need to understand its impact on long-term patient outcomes and system cost. The majority of evidence surrounding the efficacy of ECMO in the pediatric population comes from institutional cohort studies, as very few randomized trials have been performed [2]. Across the world, ECMO utilization was historically more common among neonates than older children; however, this trend has changed over the last decade with an increase in pediatric cardiac and pediatric respiratory utilization [9]. For patients with respiratory failure, in-hospital mortality among those receiving ECMO (largely venovenous [VV-ECMO]) was approximately 25% and did not differ from propensity-matched controls [10]. However, in the pediatric population, venoarterial ECMO (VA-ECMO) is more common. Hospital mortality in this population has been reported between 45 and 55% [9].

ECMO has been used for critically ill children in Canada since 1989, but little has been published regarding longer-term outcomes or associated costs, and this has been identified as an important avenue for future research in extracorporeal life support [11, 12]. Most importantly, there are key gaps in knowledge related to costs incurred in the long-term. We conducted a population-based cohort analysis to evaluate the short- and long-term outcomes and costs of critically ill children receiving ECMO for cardiorespiratory support. We hypothesized that while many ECMO patients may die in hospital, the large majority who survived to discharge would still be alive at 5 years and that patient costs would largely reflect inpatient costs during the index hospitalization.

We included a total of 342 patients in the analysis. Of these, 103 (30.1%) were neonatal (0–30 days old), 169 (49.4%) were categorized as “Cardiac Failure,” and 70 (20.5%) were categorized as “Respiratory Failure.” Patient characteristics of the study cohort are shown in Table 1. Mean age was 2.9 years (SD 5.0 years), and 54.7% were male. Of the total patient cohort, 25.4% came from the lowest income quintile, compared with 14.3% from the highest income quintile. Median time to ECMO initiation from the date of hospital admission was 5 days (IQR 1–13 days). At least one CCC was present in 274 patients (79.9%), with the most common CCC being cardiovascular, which was present in 217 patients (63.3%).

Table 2 shows patient outcomes for the entire cohort and by individual subgroups. A total of 193 patients (56.4%) survived to hospital discharge. The 1-year, 2-year, and 5-year survival for the cohort were 51.5%, 50.0%, and 42.1%, respectively. Survival to discharge was lower among respiratory failure patients (51.4%), as compared to cardiac failure patients (60.4%). Among neonatal patients, 53.4% survived to hospital discharge. Survival at 1 year, 2 years, and 5 years were 47.6%, 45.6%, and 42.9%, respectively. Median overall hospital length of stay was 26 days (IQR 11–61 days). Fifty-nine patients (17.3%) were transitioned from ECMO to VAD. ECMO was followed by heart transplant in 13 patients (3.8%) and lung transplant in 11 patients (3.2%). Among patients surviving to discharge, 192 (99.5%) were discharged home, though 97 of these patients (50.5%) required homecare. In the year following hospitalization, 57.5% of survivors had at least one Emergency Department visit, and 43.0% of survivors required hospital re-admission. Patient outcomes stratified by age are shown in Fig. 1.

The Kaplan-Meier curves depicting survival in the first year following ECMO initiation for the entire cohort and by ECMO indication are shown in Fig. 2. The greatest proportion of deaths occurred in the first 30–40 days following ECMO initiation. We compared patients who died in-hospital with those that survived to discharge (Supplemental Tables 5, 6, 7). A shorter median time to ECMO initiation was associated with survival among the “Neonatal” and “Cardiac Failure” groups.

Importantly, we evaluated median health system costs among pediatric patients receiving ECMO in the 1-year following hospital admission (including the admission itself) (Table 3). Median total costs among all patients were $147,957 (IQR $70,571–$300,295). The predominant contributor to overall costs was inpatient costs of the index hospitalization (median $119,197, IQR $57,839–$250,675). Mean costs are shown in Supplemental Table 8.

We conducted a population-based cohort study among critically ill children receiving ECMO for cardiorespiratory support to identify long-term outcomes and health system costs in the first year. Survival to hospital discharge in this provincial-wide cohort was 56.4%. This did not decrease substantially after 1 year, but moderate decrease was seen at 2 years and 5 years following ECMO initiation. The number of patients in the cohort from the lowest income quintile was nearly double that of patients from the highest income quintile. Patients predominantly received ECMO for cardiac failure, and survival to hospital discharge was markedly higher in this population, as compared to those with respiratory failure. The large majority of survivors to discharge (99.6%) were ultimately able to be discharged home. Finally, pediatric patients accrued significant hospital-related costs in the year following ECMO initiation, but the majority of these costs were incurred during the inpatient hospitalization, with few costs incurred following discharge. This study provides important information regarding long-term survival and costs following the use of this high-intensity therapy in the care of critically ill pediatric patients.

This cohort represents a contemporary pediatric ECMO sample that spans over 7 years. In-hospital mortality in this overall cohort was similar to that reported in other studies [9]. Reassuringly, there was relatively little mortality following hospital discharge, and survival rates at 1 year were comparable to hospital discharge rates. Survival at 2 years and 5 years following initiation of ECMO showed a moderate decline. Similar 5-year trends have been previously demonstrated in a population-based pediatric cohort from the UK [18] and an adult cohort from Ontario [13]. Therefore, this study supports existing work showing that particularly in patients > 30 days of age, the long-term survival (up to 5 years) following ECMO is very good among those who survive to hospital discharge. This data has particular value in conversations with patients and caregivers, and can be used to convey prognostication and set expectations for survival in both the short- and long-term, given the existing data. Overall mortality rates were higher among patients with respiratory failure, which is contrary to what has been seen previously [8‐10]. Although the reason for this remains unclear, it may reflect the selective use of ECMO at the included centers, as compared to other centers in the ELSO database. For this reason, caution must be exercised in extrapolating the findings from the subgroup analyses to other settings.

Few pediatric patients received heart or lung transplantation following ECMO initiation, which is in large contrast to what is seen in adult patients [13]. This is in keeping, however, with the practice in pediatrics that has shifted away from using ECMO as a bridge to transplantation, and replaced it by using VAD, given the better outcomes with VAD over ECMO [19, 20]. Data from the ELSO Registry shows that among patients for whom ECMO was planned as a bridge to heart transplant, only 45% ultimately survived to transplantation, and a third of transplanted patients died before hospital discharge [19].

Importantly, we investigated long-term costs following utilization of ECMO in critically ill children. While there is emerging literature on the cost-effectiveness of ECMO [21, 22], and hospital costs for pediatric patients receiving ECMO have been previously published [21, 23‐25], our study uniquely describes long-term costs in the year following ECMO initiation. We found that patients supported with ECMO accrued significant costs in the year following their index hospitalization; however, the large majority of these costs reflect the ECMO hospitalization itself, and few costs were incurred following discharge. The median overall costs in our population are similar to what has been previously described among pediatric patients with cardiorespiratory failure [26]. These costs are also consistent with those seen in other high-resource critically ill populations, such as pediatric patients with traumatic brain injury [27], or adults with multi-organ failure [28]. A major focus of current critical care research is the understanding of resource utilization not only in the short-term, but also following discharge [29, 30]. ECMO particularly falls into this conversation given the significant amount of resources required for its use. Our study shows that while the inpatient costs are significant, the downstream costs are less so, and this has particular importance in healthcare settings where downstream costs are paid for by the patients themselves.

Finally, our work identifies important avenues for future research, especially related to patient outcomes, and selection for ECMO. We compared and contrasted factors associated with survival among children receiving ECMO. We also demonstrated that ECMO was associated with significant inpatient costs. Therefore, to appropriately prognosticate outcome, and optimize patient selection, derivation and validation of a clinical decision instrument is necessary. Ideally, this should be performed using a prospective cohort, and separate instruments for patients with respiratory and cardiac failure should be derived, as has been done in the adult population [31, 32]. Furthermore, beyond understanding survival, an effort must be made to understand long-term quality of life, as has been done in the adult population [33]. For patients and caregivers, an appropriate picture of survival following ECMO must also include long-term functional and cognitive outcomes. While this has been performed at the 6-month point following ECMO [34, 35], longer-term follow-up is required.

In this study, we utilized comprehensive population-level data to investigate the short- and long-term outcomes and costs among critically ill pediatric patients receiving ECMO in Ontario, Canada. This study provides some of the first data related both to long-term outcomes and costs following the critical illness hospitalization in a large representative sample of Canadian pediatric ECMO patients. However, there are limitations to this study. First, ECMO is known to be associated with important complications, including cerebral hemorrhage, stroke, renal failure, and infection [36, 37]. We did not have validated data related to these complications and therefore are unable to comment on incidence and impact in our cohort. Second, in Ontario, ECMO in pediatric patients is conducted at only two specialized, regional referral centers for cardiac surgery, solid organ transplantation, trauma, and high-risk neonatal care. Since outcomes from ECMO are associated with center-specific frequency of use and volume [38], these findings are only generalizable to similar organizations with mature ECMO programs in North and South America, Europe, East Asia, Australia, and New Zealand. Third, while we did provide data related to survival and costs incurred following discharge, we did not have data related to quality of life and family burden following discharge. Existing evidence highlights the significant long-term morbidity seen in similar populations [39]. Finally, while the databases held at ICES are robust and have been used extensively for large population-based studies [13, 40], there are inherent limitations to the available administrative data. We did not have complete data related to illness severity at the time of hospital admission or ECMO initiation, nor the duration of ECMO. We also did not have data on parameters prior to ECMO initiation, configuration utilized, nor the specific costs attributable to ECMO use from a patient’s total inpatient costs. Lastly, we did not have data on mode or cause leading to death during the hospitalization or after discharge, the latter particularly pertinent among patients who initially survived to hospital discharge.

We found that 55.5% of critically ill pediatric patients requiring ECMO survive to hospital discharge, with relative stabilization of the survival curve at 1, 2, and 5 years following ECMO initiation. Survival was lower among neonates than older children, and among patients with respiratory failure, as compared to cardiac failure. Reassuringly, in this contemporary cohort of children, nearly all patients surviving to hospital discharge were able to be discharged home. While ECMO patients accrued significant inpatient costs, these costs were less than typical high-cost populations, and most importantly, survivors had low healthcare-associated costs in the year following discharge. This work provides novel data regarding the long-term outcomes and costs of critically ill children receiving ECMO for cardiorespiratory support.