Key findings
This was a small, single-center long-term follow-up study of young patients with ARDS, mainly related to H1N1 influenza A pneumonitis, who received rescue VV-ECMO. The survival rate was similar to other Australian published data [
30], but was higher than in international ECMO cohorts. While these patients had a high incidence of pressure injuries and long stays in the ICU and hospital, the LOS was shorter than comparable ARDS cohorts [
20] and many were discharged directly home. The HRQoL in survivors was significantly less than normal age- and sex-matched Australian people, with physical and mental limitations at the time of follow-up. The SF-36 domains of social function and vitality were also reduced compared to previously reported survivors of ARDS [
20] and other ECMO series [
17,
18]. Only a quarter of patients had returned to previous work at the time of follow-up, which is similar to previously described ARDS cohorts [
20].
Relationship to previous studies
On long-term follow-up, our cohort had substantial physical limitations compared with Australian age- and sex-matched samples. Their SF-36 physical component score was 20% lower than normal, with severe limitations in the domains of physical function, role-physical, social function and mental health, general health and vitality. They also displayed reduced mental wellbeing with their SF-36 mental component score 27% lower than normal. This was more pronounced in the patients with ARDS resulting from H1N1, compared to patients with ARDS pneumonia, and may be caused by the systemic effects of H1N1 virus, rather than differences in ICU management, such as the use of sedatives. This indicates frequent psychological distress and social and role disability due to emotional problems. ARDS survivors have been previously described as having considerable challenges, including reduced exercise capacity, cognitive dysfunction and depression or post-traumatic stress disorder (PTSD) [
31‐
33].
Compared to other groups of ARDS survivors in the literature, HRQoL was statistically reduced in this cohort of patients in the domains of vitality and social function (Table
5) [
17,
20]. However, consistent with previous intensive care HRQoL studies [
2,
29], a five-point difference in SF-36 transformed scores was considered clinically significant. When this definition of clinical significance was applied, this cohort had clinically reduced domains of general health, vitality, social function, and mental health.
Vitality is a lack of fatigue, or feelings of energy, and social function is the degree to which relationships are maintained with friends and family. It is unclear why our cohort would have reduced energy or inability to maintain social relationships compared to other survivors of ARDS. Importantly, only half of this young cohort had returned to work and a quarter of them had returned to previous work levels. Previous studies have reported an important functional association with survivors of ARDS that have moderate-severe depression symptoms and are less likely to have returned to work compared to those with less severe symptoms [
34]. Depression has been reported in up to 50% of ICU survivors 12 months after discharge [
35]. Psychiatric screening is also very important to assess depression and PTSD, which is prevalent in ICU survivors [
2,
29]. However, compared with the French H1N1 cohort who received ECMO [
18], our patients who received ECMO had reduced HRQoL in both domains of vitality and social function at a median of 8 months follow-up. The study by Luyt
et al. (2012)[
18] found no difference between survivors of severe H1N1 who received ECMO and those who did not when assessed at 12 months after the stay in ICU. This important question needs to be further addressed in an Australian population comparing survivors of ARDS who do or do not receive ECMO at the same time point.
Compared to other published series of patients with ARDS receiving ECMO for refractory hypoxemia [
15,
17,
18], our small cohort appeared to have good survival rates. When compared with the UK ECMO study [
17] this difference was not accounted for by illness severity (Apache II, lowest PaO
2/FiO
2 ratio on day 1), nor patient age, which were similar in both series (Table
4). It may have been accounted for by the much higher incidence of influenza A pneumonia in our cohort but when the 56 patients with H1N1 pneumonia from the UK ECMO study were separately analysed, the mortality was still significantly higher than in our cohort (27.5 versus 14.0%) [
36]. Several factors that may have accounted for better outcomes included increased management of viral pneumonitis due to the H1N1 epidemic, improved ambulance retrieval service, the ECMO technology, including ultrasound-guided percutaneous ECMO cannulation, intensivist-driven care from retrieval to decannulation and extensive ECMO experience (10 years) at the center.
Patients were retrieved with severe life-threatening refractory hypoxemia if they did not respond to conventional rescue therapies. These included inhaled nitric oxide and recruitment maneuvers, which are consistent with previously published data [
19] from Australia where the most common rescue therapies used during the H1N1 epidemic were recruitment maneuvers (67%) and inhaled nitric oxide (32%) [
19]. In the majority of patients in both this study (86%) and the UK ECMO study (69%), the need for ECMO arose in an external hospital and the patients were retrieved to the study center hospital. In the UK ECMO study [
17] all such retrievals were performed on conventional ventilation and ECMO was initiated on arrival at the study center hospital after transfer. The UK study described three deaths before the retrieval team reached the initial hospital and two deaths in transit.
ECMO was maintained in this cohort for a long period of time in comparison to other studies of patients receiving ECMO for severe ARDS [
15,
17]. Despite the long duration of ECMO, our cohort had a shorter ICU and hospital LOS at the ECMO center (Table
4) compared to the group of patients with ARDS receiving ECMO [
17] or ARDS without ECMO [
20]. This may be partly explained because a large portion of our cohort (50%) was discharged to other acute-care facilities, mostly the destination from which they were retrieved. It may also be a result of the fact that a large proportion of our cohort had confirmed H1N1. Recent data from the H1N1 registry of the Extracorporeal Life Support Organization (ELSO) [
37] showed 61% survival from 76 international centers of H1N1 requiring ECMO, including adult and pediatric data.
A large number of patients in the current study suffered from pressure injuries probably due to prolonged immobility with no long-term effects as a result. This has led to a change in practice in the ICU that includes decreased time between turning patients receiving ECMO, air mattresses and mechanically rotating beds. One patient died after developing a pneumothorax prior to ECMO, then suffering a severe pulmonary hemorrhage on insertion of an intercostal catheter once ECMO and anticoagulation therapy had been commenced. One survivor suffered severe ICU-acquired weakness, was discharged to a rehabilitation facility and was required to wear a splint long-term for foot drop. No patients required ongoing domiciliary oxygen.
Improved survival with decreased HRQoL places a significant burden on caregivers, patients and infrastructure. Survivors have profound muscle weakness and wasting [
20], which impairs exercise capacity and may be improved with early rehabilitation during the ICU period [
38,
39] and a prolonged hospital stay, which includes inpatient rehabilitation. More than half of our survivors reported some degree of problems with mobility at follow-up (Table
5). Further research is required to establish the physical outcomes, exercise capacity and rehabilitation requirements of survivors and to identify risk factors that predict a poorer HRQoL [
31,
32].
Limitations
This pilot study has a number of limitations. First, our major limitation is the small number of included patients, despite collection during a viral pandemic, which limits the external validity of the results. Second, owing to the nature of the pandemic, there were no injury-matched controls (young, previously well patients without co-morbidities all received ECMO as a rescue therapy if they were severely hypoxemic). Third, the data set was examined retrospectively, and therefore the follow-up period for HRQoL was variable, which limits the comparison to other studies. Fourth, there is limited information on the issues contributing to a decrease in HRQoL as a result of the telephone interview process, with no in-person follow-up, although previous work examining telephone interviews has shown that the response rate is improved but patients may report more favourable health ratings [
40]. Finally, we aimed to compare our results to international data that have inherent differences in the structure and provision of the ECMO service, or the management of ARDS, which may confound the results. Future work in this area, where possible, should include larger numbers with a comparator group without ECMO from the same population.