Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)
Navin P. Boeddha,
Luregn J. Schlapbach,
Gertjan J. Driessen,
Jethro A. Herberg,
Irene Rivero-Calle,
Miriam Cebey-López,
Daniela S. Klobassa,
Ria Philipsen,
Ronald de Groot,
David P. Inwald,
Simon Nadel,
Stéphane Paulus,
Eleanor Pinnock,
Fatou Secka,
Suzanne T. Anderson,
Rachel S. Agbeko,
Christoph Berger,
Colin G. Fink,
Enitan D. Carrol,
Werner Zenz,
Michael Levin,
Michiel van der Flier,
Federico Martinón-Torres,
Jan A. Hazelzet,
Marieke Emonts,
on behalf of the EUCLIDS consortium
Affiliations
Navin P. Boeddha
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam
Luregn J. Schlapbach
Faculty of Medicine, The University of Queensland
Gertjan J. Driessen
Department of Pediatrics, Division of Pediatric Infectious Diseases & Immunology, Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam
Jethro A. Herberg
Section of Pediatrics, Imperial College London
Irene Rivero-Calle
Translational Pediatrics and Infectious Diseases Section- Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela
Miriam Cebey-López
Genetics- Vaccines- Infectious Diseases and Pediatrics research group GENVIP, Health Research Institute of Santiago IDIS/SERGAS
Daniela S. Klobassa
Department of General Paediatrics, Medical University of Graz
Ria Philipsen
Radboudumc Technology Center Clinical Studies, Radboudumc
Ronald de Groot
Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences
David P. Inwald
Department of Paediatrics, Faculty of Medicine, Imperial College London, South Kensington Campus
Simon Nadel
Department of Paediatrics, Faculty of Medicine, Imperial College London, South Kensington Campus
Stéphane Paulus
Division of Paediatric Infectious Diseases, Alder Hey Children’s NHS Foundation Trust
Eleanor Pinnock
Micropathology Ltd, University of Warwick Science Park
Fatou Secka
Medical research Council Unit
Suzanne T. Anderson
Medical research Council Unit
Rachel S. Agbeko
Department of Paediatric Intensive Care, Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Victoria Wing
Christoph Berger
Division of Infectious Diseases and Hospital Epidemiology, and Children’s Research Center, University Children’s Hospital Zurich
Colin G. Fink
Micropathology Ltd, University of Warwick Science Park
Enitan D. Carrol
Institute of Infection & Global Health, University of Liverpool
Werner Zenz
Department of General Paediatrics, Medical University of Graz
Michael Levin
Section of Pediatrics, Imperial College London
Michiel van der Flier
Radboudumc Technology Center Clinical Studies, Radboudumc
Federico Martinón-Torres
Translational Pediatrics and Infectious Diseases Section- Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela
Jan A. Hazelzet
Department of Public Health, Erasmus MC, University Medical Center Rotterdam
Marieke Emonts
Institute of Cellular Medicine, Newcastle University
Abstract Background Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability. Methods Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis. Results Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3–6.1, P < 0.01; disability OR 3.4, 95% CI 1.8–6.4, P < 0.001). Conclusions Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.