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Defining benefit threshold for extracorporeal membrane oxygenation in children with sepsis-a binational multicenter
Luregn J Schlapbach1,2,3, Roberto Chiletti4,5, Lahn Straney6,7
1Paediatric Critical Care Research Group, Child Health Research Centre, The University of Queensland, Brisbane, Australia. l.schlapbach@uq.edu.au.
Insights
Extracorporeal membrane oxygenation (ECMO) may benefit pediatric septic shock patients if their predicted mortality risk exceeds 47.1%. Central cannulation improved survival on ECMO, suggesting a randomized trial is not feasible.
Area of Science:
- Pediatric Critical Care Medicine
- Cardiopulmonary Support
- Septic Shock Management
Background:
- The Surviving Sepsis Campaign suggests extracorporeal membrane oxygenation (ECMO) for refractory septic shock.
- Defining the benefit threshold for ECMO in pediatric septic shock is crucial.
Purpose of the Study:
- To establish benefit thresholds for ECMO in pediatric septic shock.
- To identify predictors of survival in children treated with ECMO.
Main Methods:
- Retrospective binational multicenter cohort study (2002-2016) of pediatric patients (<16 years) with sepsis and septic shock.
- Developed sepsis-specific risk-adjusted models to determine ECMO benefit thresholds using early clinical variables.
- Performed multivariate analyses to identify survival predictors in ECMO-treated children.
Main Results:
- A model using 12 variables predicted mortality with high accuracy (AUROC 0.879).
- The benefit threshold was a 47.1% predicted mortality risk.
- Observed mortality was lower than predicted for patients above this threshold (SMR 0.61).
- Lower lactate, no prior cardiac arrest, and central cannulation predicted survival on ECMO.
Conclusions:
- A predictive model can define ECMO benefit thresholds in pediatric septic shock.
- Central cannulation is associated with improved survival on ECMO.
- A large randomized controlled trial on ECMO for sepsis is likely not feasible.
Background:
The surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.
Methods:
Retrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.
Results:
Five thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864-0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89-2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39-0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10-0.98, p = 0.046) as significant predictors of survival for those treated with VA-ECMO.
Conclusions:
This binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.
