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Type: Journal article
Title: Defining benefit threshold for extracorporeal membrane oxygenation in children with sepsis–a binational multicenter cohort study
Author: Schlapbach, L.J.
Chiletti, R.
Straney, L.
Festa, M.
Alexander, D.
Butt, W.
MacLaren, G.
Ganeshalingam, A.
Sherring, C.
Erickson, S.
Barr, S.
Schibler, A.
Long, D.
Alexander, J.
George, S.
Williams, G.
Smith, V.
Butt, W.
Delzoppo, C.
Millar, J.
et al.
Citation: Critical Care, 2019; 23(1):429-1-429-10
Publisher: Springer Nature
Issue Date: 2019
ISSN: 1364-8535
Statement of
Luregn J. Schlapbach, Roberto Chiletti, Lahn Straney, Marino Festa, Daniel Alexander, Warwick Butt, Graeme MacLaren, and on behalf of the Australian, New Zealand Intensive Care Society, ANZICS, Centre for Outcomes, Resource Evaluation, CORE, and the Australian, New Zealand Intensive Care Society, ANZICS, Paediatric Study Group (Anusha Ganeshalingam, Claire Sherring, Simon Erickson, Samantha Barr, Andreas Schibler, Debbie Long, Luregn Schlapbach Jan Alexander, Shane George, Gary Williams, Vicky Smith, Warwick Butt, Carmel Delzoppo, Johnny Millar Ben Gelbart, Felix Oberender; Subodh Ganu, Georgia Letton, Jonathan Egan, Gail Harper, Marino Festa)
Abstract: 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.
Keywords: Childhood; extracorporeal life support; extracorporeal membrane oxygenation; infection; mortality; pediatric; prediction; sepsis; septic shock
Rights: © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
RMID: 1000012307
DOI: 10.1186/s13054-019-2685-1
Appears in Collections:Medicine publications

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