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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).
Crit Care. 2018 05 31; 22(1):143.CC

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.

Authors+Show Affiliations

Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. Department of Pediatrics, Division of Pediatric Infectious Diseases & Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.Faculty of Medicine, The University of Queensland, St Lucia Queensland, Brisbane, 4072, Australia. Paediatric Critical Care Research Group, Mater Research Institute, The University of Queensland, Aubigny Place, Raymond Terrace, Brisbane, Australia. Paediatric Intensive Care Unit, Lady Cilento Children's Hospital, Children's Health Queensland, 501 Stanley St, Brisbane, Australia. Department of Pediatrics, Bern University Hospital, Inselspital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland.Department of Pediatrics, Division of Pediatric Infectious Diseases & Immunology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. Department of Paediatrics, Juliana Children's Hospital/Haga Teaching Hospital, Els Borst-Eilersplein 275, 2545 AA, The Hague, The Netherlands.Section of Pediatrics, Imperial College London, Level 2, Faculty Building South Kensington Campus, London, SW7 2AZ, UK.Translational Pediatrics and Infectious Diseases Section- Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Travesía da Choupana, 15706, Santiago de Compostela, Spain. Genetics- Vaccines- Infectious Diseases and Pediatrics research group GENVIP, Health Research Institute of Santiago IDIS/SERGAS, Travesía da Choupana, 15706, Santiago de Compostela, Spain.Genetics- Vaccines- Infectious Diseases and Pediatrics research group GENVIP, Health Research Institute of Santiago IDIS/SERGAS, Travesía da Choupana, 15706, Santiago de Compostela, Spain.Department of General Paediatrics, Medical University of Graz, Auenbruggerplatz 34/2, A-8036, Graz, Austria.Radboudumc Technology Center Clinical Studies, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. Radboud Center for Infectious Diseases, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.Department of Paediatrics, Faculty of Medicine, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. St Mary's Hospital, Imperial College Healthcare NHS Trust, Praed Street, London, W2 1NY, UK.Department of Paediatrics, Faculty of Medicine, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. St Mary's Hospital, Imperial College Healthcare NHS Trust, Praed Street, London, W2 1NY, UK.Division of Paediatric Infectious Diseases, Alder Hey Children's NHS Foundation Trust, Eaton Rd, Liverpool, L12 2AP, UK. Institute of Infection & Global Health, University of Liverpool, 8 West Derby St, Liverpool, L7 3EA, UK.Micropathology Ltd, University of Warwick Science Park, Venture Centre, Sir William Lyons Road, Coventry, CV4 7EZ, UK.Medical research Council Unit, Atlantic Boulevard, Fajara, P. O. Box 273, Banjul, The Gambia.Medical research Council Unit, Atlantic Boulevard, Fajara, P. O. Box 273, Banjul, The Gambia.Department of Paediatric Intensive Care, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Victoria Wing, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK. Institute of Cellular Medicine, Newcastle University, 4th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.Division of Infectious Diseases and Hospital Epidemiology, and Children's Research Center, University Children's Hospital Zurich, Steinwiesenstrasse 75, 8032, Zurich, Switzerland.Micropathology Ltd, University of Warwick Science Park, Venture Centre, Sir William Lyons Road, Coventry, CV4 7EZ, UK.Institute of Infection & Global Health, University of Liverpool, 8 West Derby St, Liverpool, L7 3EA, UK.Department of General Paediatrics, Medical University of Graz, Auenbruggerplatz 34/2, A-8036, Graz, Austria.Section of Pediatrics, Imperial College London, Level 2, Faculty Building South Kensington Campus, London, SW7 2AZ, UK.Radboudumc Technology Center Clinical Studies, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. Section of Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. Pediatric Infectious Diseases and Immunology Amalia Children's Hospital, and Radboudumc Expertise Center for Immunodeficiency and Autoinflammation (REIA), Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.Translational Pediatrics and Infectious Diseases Section- Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Travesía da Choupana, 15706, Santiago de Compostela, Spain. Genetics- Vaccines- Infectious Diseases and Pediatrics research group GENVIP, Health Research Institute of Santiago IDIS/SERGAS, Travesía da Choupana, 15706, Santiago de Compostela, Spain.Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. j.a.hazelzet@erasmusmc.nl.Institute of Cellular Medicine, Newcastle University, 4th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. Paediatric Infectious Diseases and Immunology Department, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Victoria Wing, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK. NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Westgate Rd, Newcastle upon Tyne, NE4 5PL, UK.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29855385

Citation

Boeddha, Navin P., et al. "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)." Critical Care (London, England), vol. 22, no. 1, 2018, p. 143.
Boeddha NP, Schlapbach LJ, Driessen GJ, et al. 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). Crit Care. 2018;22(1):143.
Boeddha, N. P., Schlapbach, L. J., Driessen, G. J., Herberg, J. A., Rivero-Calle, I., Cebey-López, M., Klobassa, D. S., Philipsen, R., de Groot, R., Inwald, D. P., Nadel, S., Paulus, S., Pinnock, E., Secka, F., Anderson, S. T., Agbeko, R. S., Berger, C., Fink, C. G., Carrol, E. D., ... Emonts, M. (2018). 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). Critical Care (London, England), 22(1), 143. https://doi.org/10.1186/s13054-018-2052-7
Boeddha NP, et al. 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). Crit Care. 2018 05 31;22(1):143. PubMed PMID: 29855385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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). AU - Boeddha,Navin P, AU - Schlapbach,Luregn J, AU - Driessen,Gertjan J, AU - Herberg,Jethro A, AU - Rivero-Calle,Irene, AU - Cebey-López,Miriam, AU - Klobassa,Daniela S, AU - Philipsen,Ria, AU - de Groot,Ronald, AU - Inwald,David P, AU - Nadel,Simon, AU - Paulus,Stéphane, AU - Pinnock,Eleanor, AU - Secka,Fatou, AU - Anderson,Suzanne T, AU - Agbeko,Rachel S, AU - Berger,Christoph, AU - Fink,Colin G, AU - Carrol,Enitan D, AU - Zenz,Werner, AU - Levin,Michael, AU - van der Flier,Michiel, AU - Martinón-Torres,Federico, AU - Hazelzet,Jan A, AU - Emonts,Marieke, AU - ,, Y1 - 2018/05/31/ PY - 2018/01/30/received PY - 2018/04/29/accepted PY - 2018/6/2/entrez PY - 2018/6/2/pubmed PY - 2019/5/29/medline KW - Bacteremia KW - Meningococcal infections KW - Morbidity KW - Mortality KW - Pneumococcal infections SP - 143 EP - 143 JF - Critical care (London, England) JO - Crit Care VL - 22 IS - 1 N2 - 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. SN - 1466-609X UR - https://www.unboundmedicine.com/medline/citation/29855385/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__ L2 - https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2052-7 DB - PRIME DP - Unbound Medicine ER -