This study demonstrates that patients supported on ECMO for pandemic H1N1 had more severe features of critical illness, despite being younger, with higher weight and having fewer comorbidities than those subsequently managed on ECMO for seasonal influenza A. These findings support increased virulence associated with novel virus triggering the pandemic, but may additionally reflect resource limitation of this invasive support during the associated abrupt increase in critical care utilization. Importantly, despite differences in severity of illness, there was no difference in survival to hospital discharge for those patients with pandemic H1N1 compared with patients subsequently managed on ECMO with seasonal influenza A. We did identify patient characteristics, aspects of patient management before ECMO, and ECMO complications that were associated with survival to hospital discharge.
Igniting the surge in ECMO use for adults with ARDS was the success of ECMO during the H1N1 pandemic (2, 3, 17–25). Our study demonstrates continued ECMO use after the 2009 pandemic, more for seasonal influenza A subtypes than H1N1. Despite the higher severity of illness in the H1N1 patients, we did not find a difference in survival according to viral subtype. Studies evaluating the use of ECMO for other viral etiologies of ARDS continue to emerge (33–38). Since the novel COVID-19 pandemic, investigators have reported successful ECMO support with similar survival to hospital discharge, even when directly compared with influenza cohorts (36, 37).
ECMO support for ARDS continued to evolve after the H1N1 pandemic. A single-center study reported up to 80% survival for H1N1 patients supported on ECMO during 2013–2014 (39). Studies from Japan and Korea demonstrated improved outcomes during a resurgence of H1N1 in 2016 when compared to the 2009 pandemic, which likely reflects improvements in their patient selection and management (40, 41). Our study found that, overall, there was no difference in survival in the pandemic H1N1 subtype patients supported on ECMO during the 2009 pandemic year compared to years thereafter. The abrupt increase in hospitalizations and ECMO use during the 2009 pandemic reflected intensified virulence and amplification of the novel H1N1 virus in the community, which highlights the capacity to surge and allocate resources appropriately to support ECMO patients when needed (10).
Allocation of scarce resources or complex resource-intensive therapies during a pandemic can, however, become problematic. Identification of patient factors, as well as patient management strategies prior to ECMO which may be associated with improved outcomes, can inform prioritization during times of limited resource availability. Many of the mortality prediction scores created to help determine ECMO candidacy were developed using patients during the H1N1 pandemic, and thus, it is not surprising that we have identified similar clinical characteristics as associated with survival to hospital discharge (24, 29, 42, 43). However, the majority of our patients had seasonal influenza and not specifically H1N1, and thus factors associated with mortality in our predictive and explanatory models may be more applicable to other viral subtypes causing ARDS. As in previous studies, younger age, higher weight, and lack of reported comorbidities were associated with survival (2, 6, 19, 22, 32, 34, 42). Additionally, those patients who were managed with a shorter duration of mechanical ventilation, who had not progressed to cardiac arrest prior to ECMO cannulation were found to have improved survival, supporting early initiation of ECMO for viral ARDS (3, 6, 18, 29, 42). Established ECMO programs with integrated systems to prevent and mitigate complications may be best placed to offer this invasive support, even during times of pandemic-associated resource limitation (37, 44).
Study limitations
Our study has the expected limitations inherent in a retrospective observational study. ELSO Registry data is entered voluntarily, without external validation of data in the represented era, however, the institution of a data dictionary, data entry exam, and logic-limited data entry has resulted in improved data quality in the ELSO registry over the duration of this study (45). Our data may be subject to era effect. Some unidentified confounding covariates, such as the older population’s prior exposure to H1N1, may impact our results. Our application of LASSO regression adjusting for predefined comorbidities used in the RESP score is a strength of our analysis; however, we did not specifically include other potential comorbidities (29, 46). Additionally, clinically relevant covariates that had more than 15% missing data were excluded from the analysis.