Paediatric survivors of extracorporeal life support functional outcomes at one-year follow-up

Abstract

Objective:

To investigate functional outcomes in children who survived extracorporeal life support at 12 months follow-up post-discharge.

Background:

Some patients who require extracorporeal life support acquire significant morbidity during their hospitalisation. The Functional Status Scale is a validated tool that allows quantification of paediatric function.

Methods:

A retrospective study that included children placed on extracorporeal life support at a quaternary children’s hospital between March 2020 and October 2021 and had follow-up encounter within 12 months post-discharge.

Results:

Forty-two patients met inclusion criteria: 33% female, 93% veno-arterial extracorporeal membrane oxygenation (VA ECMO), and 12% with single ventricle anatomy. Median age was 1.7 years (interquartile range 10 days–11.9 years). Median hospital stay was 51 days (interquartile range 34–91 days), and median extracorporeal life support duration was 94 hours (interquartile range 56–142 hours). The median Functional Status Scale at discharge was 8.0 (interquartile range 6.3–8.8). The mean change in Functional Status Scale from discharge to follow-up at 9 months (n = 37) was −0.8 [95% confidence interval (CI) −1.3 to −0.4, p < 0.001] and at 12 months (n = 34) was −1 (95% confidence interval −1.5 to −0.4, p < 0.001); the most improvement was in the feeding score. New morbidity (Functional Status Scale increase of ≥3) occurred in 10 children (24%) from admission to discharge. Children with new morbidity were more likely to be younger (p = 0.01), have an underlying genetic syndrome (p = 0.02), and demonstrate evidence of neurologic injury by electroencephalogram or imaging (p = 0.05).

Conclusions:

In survivors of extracorporeal life support, the Functional Status Scale improved from discharge to 12-month follow-up, with the most improvement demonstrated in the feeding score.

Introduction

Utilisation of extracorporeal life support has increased over the last several years, ¹ with increasingly complex patients being placed on extracorporeal life support. ² As the population of survivors expands, it amplifies the concern for understanding and preventing acquired morbidity in these children while undergoing extracorporeal life support. ³ In addition to the interventions inherent to critical care such as mechanical ventilation, vasopressors, and central access, children who are placed on extracorporeal life support are uniquely exposed to a myriad of potential insults, including hypoxia, thrombosis, bleeding, neurologic, and end-organ injury. ^4–6 Studies have shown that in the short term, central nervous system morbidity has been noted in more than a fifth of the population. ^7,8 As survival in this population improves, studies have focused on optimisation of outcomes after extracorporeal life support. ^9–11

The Functional Status Scale is a validated measure of paediatric function developed by Pollack and colleagues. ¹² This framework is modelled from adult measures of activities of daily living. The Functional Status Scale is designed to be applicable to the full spectrum of paediatric patients and minimally dependent on subjective assessment. In children supported with extracorporeal life support, Functional Status Scale scores have been utilised to assess function upon admission and at discharge; ^13,14 however, there are limited data evaluating the long-term function of survivors. This study characterises the Functional Status Scale of survivors supported with extracorporeal life support at admission, discharge, and within one-year post-discharge. We hypothesise that some survivors develop significant morbidity while undergoing extracorporeal life support but that this morbidity improves in the medium to long-term.

Methods

Study design

This study was approved by The Children’s Healthcare of Atlanta Institutional Review Board (STUDY 00001443, Approved 6/22/22), and informed consent was waived. We performed a single-centre retrospective study of paediatric patients who underwent extracorporeal life support between March 2020 and October 2021 at Children’s Healthcare of Atlanta, a free-standing paediatric university-affiliated hospital. Included were survivors who had outpatient follow-up within 9–12 months of hospital discharge.

Patient population

Children aged 0–21 years placed on extracorporeal life support in the cardiac ICU, paediatric ICU, and neonatal ICU were included. Patients were excluded if they died prior to the follow-up period or if there was no clinical follow-up encounter in either the 9- or 12 month- windows (Figure 1).

Figure 1. Study flowchart.

Data collection

Patients were identified from an institutional clinical database of extracorporeal life support patients stored in REDCap. Patient electronic medical records were retrospectively reviewed. Patient demographics and clinical characteristics (hospital length of stay, genetic syndrome, and primary cardiac diagnosis) were collected. Neurological imaging was collected, including evidence of clinical seizures, electroencephalogram, and evidence of ischaemic changes on imaging. Of note, neurological imaging and electroencephalogram were only obtained if there was a clinical concern. Extracorporeal life support variables (hours on extracorporeal life support, initial mode of extracorporeal life support, lowest pH, and cardiac or respiratory arrest in the 24 hours prior to extracorporeal life support) were collected.

Functional status scale

The Functional Status Scale consists of six domains, including mental status, sensory, communication, motor function, feeding, and respiratory, as previously published by Pollack et al. ¹² Functional status for each domain is scored from 1 which is considered “normal” to 5 which reflects “very severe dysfunction.” A patient without any morbidity and normal function across all domains would receive a Functional Status Scale of 6, and patients with very severe dysfunction across all domains would receive a Functional Status Scale of 30. The patient admission notes were reviewed to assign baseline Functional Status Scale, discharge summaries were used to assign discharge Functional Status Scale, and any routine clinical outpatient visits that included a physical exam at 9- and 12-month visit windows were used to assign follow-up Functional Status Scale. If the child had multiple clinical visits in that time period, the most detailed physical exam was used to assign the follow-up Functional Status Scale. Newborns transferred from outside hospitals at day of life 10 or younger were assigned a scale of 6, similar to methodology used in other studies. ^13,14 The primary outcome was change in Functional Status Scale from discharge to follow-up within 12 months. An increase in the total Functional Status Scale by 3 or more was considered “new morbidity” as previously described by Pollack and colleagues. ¹⁵

Statistical analysis

Statistical analysis was performed using SAS 9.4 (Cary, NC). p < 0.05 were considered significant. Median values and interquartile ranges were presented with descriptive statistics. Continuous variables were analysed with Mann–Whitney U for non-normal data.

Results

There were 58 patients placed on extracorporeal life support during the study period, with 42 patients meeting inclusion criteria (Figure 1). Patient characteristics are presented in Table 1. The median age at admission was 1.7 years (interquartile range 10 days–11.9 years). Paediatric patients undergoing extracorporeal life support accounted for 71% (n = 30) compared with neonatal patients 29% (n = 12). There were 37 patients (88%) with biventricular circulation and 5 patients (12%) with single ventricle circulation. Most patients were placed on extracorporeal life support for a cardiac indication (n = 21, 50%), while others were placed on extracorporeal life support for a respiratory indication (n = 7, 17%) or for extracorporeal cardiopulmonary resuscitation (n = 14, 33%). A significant proportion (n = 19, 45%) of patients experience pre-ECMO cardiac/respiratory arrest, which was defined as cardiopulmonary resuscitation occurring within 24 hours prior to xtracorporeal life support. Genetic syndromes were present in 6 patients (14%): trisomy 18 (n = 1, 2%), trisomy 21 (n = 2, 5%), and DiGeorge syndrome (n = 3, 7%). The median duration of extracorporeal life support was 94 hours (interquartile range 56–142 hours).

Table 1. Patient characteristics

Displayed as n (%) or median (IQR).

The median total Functional Status Scale at admission was 6.0 (interquartile range 6–6) and 8.0 (interquartile range 6.3–8.8) at discharge (p < 0.001). There were 10 patients (24%) who acquired new morbidity from admission to discharge (Functional Status Scale ≥3).

Hospital functional outcomes

Patients with an increase in Functional Status Scale ≥3 from admission to discharge were younger than patients without a significant change in Functional Status Scale, 6 days (interquartile range 1 day–1.3 years) versus 7.4 years (interquartile range 114 days–12.6 years) (p = 0.01) (Table 2). Children with an increase in Functional Status Scale ≥3 were more likely to be those with genetic syndromes, 40% (n = 4), whereas a majority of children without a genetic syndrome did not have a change in their Functional Status Scale, 94% (n = 30, p = 0.02). All children who experienced seizures and cerebral ischaemia had an increase in their Functional Status Scale ≥3 from admission to discharge (n = 2, p = 0.05, for both). There was a trend towards a longer hospital length of stay in children who developed a new morbidity during their hospitalisation and those who did not, but this did not reach statistical significance, p = 0.08.

Table 2. Acquired morbidity during hospitalisation

Displayed as n (%) or median (IQR).

Follow-up outcomes

Most patients (79%) were discharged home rather than to a rehabilitation facility. 30% (n = 3) of patients who acquired a new morbidity (Functional Status Scale≥3) were discharged to rehab in comparison to patients with no significant difference in their Functional Status Scale at discharge (n = 6, 19%), p = 0.66. A majority of children (74%) required subsequent readmission after initial discharge. Children who had acquired new morbidity (Functional Status Scale ≥3) during their hospitalisation spent more time hospitalised in the first year after discharge, 40 days (interquartile range 13–79 days), as compared to children who did not experience a significant change in their Functional Status Scale, 4 days (interquartile range 0–15 days), p = 0.003. Total Functional Status Scale improved from 8.0 (6.3–8.8) at discharge to 6.0 (6.0–8.0) at the 12-month follow-up, p = 0.001 (Table 3). There was no significant difference between the 9-month and one-year time points (p = 0.48). The improvement in Functional Status Scale from discharge to 12-month follow-up as primarily driven by the improvement in feeding score (p = 0.001).

Table 3. Improved functional status post-discharge

Discussion

This study demonstrates that this population of extracorporeal life support survivors accrued significant morbidity during the initial hospitalisation followed by improvement in Functional Status Scale throughout follow-up. In our population, younger age, genetic syndrome, and evidence of neurologic injury (electroencephalogram-determined seizures and central nervous system diffuse ischaemic changes) were each individually associated with an increase in the Functional Status Scale by ≥3 from admission to discharge. Children demonstrated improvement in the 12-month follow-up period, which was predominantly driven by improvement in the feeding domain. Functional Status Scale scores in our population increased from admission to discharge but then significantly improved from discharge to follow-up within 12 months.

Our finding of significant neurologic morbidity during hospitalisation was similar to findings previously reported. ^16,17 These studies showed that 5.5–8.4% of patients experienced seizures during their hospitalisation, similar to the 5% of patients who experienced seizures in our population. ^16,17 In contrast, Okochi and colleagues found a significantly greater proportion of patients experienced seizures detectable by continuous electroencephalogram, 23%. ¹⁸ Okochi and colleagues specifically only included patients with at least 24 hours of continuous electroencephalogram monitoring while on extracorporeal life support, whereas in our population, a continuous electroencephalogram was only performed for a clinical concern. Thus, it is possible that a greater number of children experience seizures during their extracorporeal life support hospitalisation than are detected by routine clinical practice.

In contrast to our study that found that neurologic morbidity was the most common among survivors of extracorporeal life support, Beshish and colleagues found cardiovascular complications as the most common (59%) with acquired neurologic morbidity in just 14%. ¹⁴ Overall, Beshish and colleagues ¹⁴ also found a higher rate of new morbidity, with 40% of patients developing a new morbidity during their hospitalisation, whereas we found 24%. This may be secondary to our population being older. The median age in our study was 1.7 years, and theirs was just 3.1 months. Beshish and colleagues also found that longer duration of the extracorporeal life support run has previously been associated with worse functional outcomes. ¹⁴ We saw a trend in increased duration on extracorporeal life support being associated with an Functional Status Scale ≥3 from admission to discharge, but this did not reach statistical significance, which may be a consequence of our smaller sample size.

As an additional marker of morbidity, we investigated the readmission rate of our patient population within the first year of hospital discharge. A majority of our patients were readmitted within the first year, 73%. This is similar to previous studies, which have found that 36–62% of paediatric extracorporeal life support survivors required hospital readmission after their initial discharge. ^3,19 Specifically, we found that children who developed a new morbidity during their admission also had a longer cumulative hospital day burden in their first year post-discharge than children who did not acquire a new morbidity. Similarly, children with an increased number of complex chronic conditions have also been found to have a higher readmission rate. ¹⁹

While a substantial proportion of patients developed new morbidity during their hospitalisation, there was significant improvement in the Functional Status Scale score at one year. This is consistent with previous literature that has shown that most newborn infants treated with extracorporeal life support will have a normal neurodevelopmental assessment at 11–19 months of age. ²⁰ However, this does not preclude children from developing neuropsychological impairments and school problems in longer-term follow-up, known as the growing into deficit phenomenon. ²¹

Perhaps the most meaningful impact of our findings is the improvement in the feeding Functional Status Scale score, which represents that a significant portion of children improved from requiring tube feeds to being able to complete age-appropriate feeding. Previous literature has found that a majority of children (87%) who are tube-fed have been found to experience at least one adverse effect from tube-feeding, such as nausea, vomiting, retching, and gagging. ²² The burden on caregivers is also significant. Though caregivers of children with a gastrostomy tube (G-tube) have not been found to be more depressed than caregivers of children without G-tubes, ²³ a substantial portion of parents (23%) describe a feeding as an anxious or intrusive experience. ²² Thus, this improvement during outpatient follow-up is impactful for both patients and their families.

The study has several limitations; its generalisability is limited given the inherent nature of the single-centre study. Some associations may be absent in our analysis given our sample size but may be exposed in larger, multi-centre studies. Additionally, Functional Status Scale scores have been previously shown to be easily reproducible with minimal interobserver variability ¹² ; however, when obtained retrospectively, they rely upon the documentation of clinical providers, and thus subtle findings may not have been detected. Our study used a standardised approach for transferred neonates, as reported in previous literature ^13,14 ; however, this approach does not account for pre-existing functional deficits, particularly in patients found to have a genetic syndrome.

Conclusion

Children who are supported with extracorporeal life support continue to make significant improvements in their overall functional status after discharge, particularly in their feeding scores. During their hospitalisation, a majority of children who survived to the follow-up period had a favourable outcome (76%). Younger age, genetic syndromes, and evidence of neurologic injury were associated with an increase in Functional Status Scale by ≥3. As both survivorship improves and utilisation of extracorporeal life support increases, further studies are imperative to elucidate modifiable factors that will improve long-term outcomes in these patients.