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)

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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.

Electronic supplementary material

The online version of this article (10.1186/s13054-018-2052-7) contains supplementary material, which is available to authorized users.

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Most cited references 31

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Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation

Chris Feudtner, James Feinstein, Wenjun Zhong … (2014)

Background The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. Results The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. Conclusions The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

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Long-term mortality and quality of life in sepsis: a systematic review.

Bradford D Winters, Michael Eberlein, Janice Leung … (2010)

Long-term outcomes from sepsis are poorly understood, and sepsis in patients may have different long-term effects on mortality and quality of life. Long-term outcome studies of other critical illnesses such as acute lung injury have demonstrated incremental health effects that persist after hospital discharge. Whether patients with sepsis have similar long-term mortality and quality-of-life effects is unclear. We performed a systematic review of studies reporting long-term mortality and quality-of-life data (>3 months) in patients with sepsis, severe sepsis, and septic shock using defined search criteria. Systematic review of the literature. None. Patients with sepsis showed ongoing mortality up to 2 yrs and beyond after the standard 28-day inhospital mortality end point. Patients with sepsis also had decrements in quality-of-life measures after hospital discharge. Results were consistent across varying severity of illness and different patient populations in different countries, including large and small studies. In addition, these results were consistent within observational and randomized, controlled trials. Study quality was limited by inadequate control groups and poor adjustment for confounding variables. Patients with sepsis have ongoing mortality beyond short-term end points, and survivors consistently demonstrate impaired quality of life. The use of 28-day mortality as an end point for clinical studies may lead to inaccurate inferences. Both observational and interventional future studies should include longer-term end points to better-understand the natural history of sepsis and the effect of interventions on patient morbidities.

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Assessing the outcome of pediatric intensive care.

D H Fiser (1992)

To describe the short-term outcome of pediatric intensive care by quantifying overall functional morbidity and cognitive impairment, I developed the Pediatric Overall Performance Category (POPC) and the Pediatric Cerebral Performance Category (PCPC) scales, respectively. A total of 1469 subjects (1539 admissions) were admitted to the pediatric intensive care unit of Arkansas Children's Hospital from July 1989 through December 1990. Patients were assigned baseline POPC and PCPC scores derived from historical information and discharge scores at the time of discharge from the hospital (or from the pediatric intensive care unit for patients with multiple hospitalizations). Delta scores were calculated as the difference between the discharge scores and the baseline scores. The changes in POPC and PCPC scores were associated with several measures of morbidity (length of stay in the pediatric intensive care unit, total hospital charges, and discharge care needs) and with severity of illness (pediatric risk of mortality score) or severity of injury (pediatric trauma score) (p less than 0.0001). Interrater reliability was excellent (r = 0.88 to 0.96; p less than 0.001). The POPC and PCPC scales are apparently reliable and valid tools for assessing the outcome of pediatric intensive care.

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Author and article information

Contributors

Navin P. Boeddha: n.boeddha@erasmusmc.nl

Luregn J. Schlapbach: l.schlapbach@uq.edu.au

Gertjan J. Driessen: g.driessen@hagaziekenhuis.nl

Jethro A. Herberg: j.herberg@imperial.ac.uk

Irene Rivero-Calle: irina667@hotmail.com

Miriam Cebey-López: Miriam.Cebey.Lopez@sergas.es

Daniela S. Klobassa: daniela.klobassa@medunigraz.at

Ria Philipsen: Ria.Philipsen@radboudumc.nl

Ronald de Groot: R.deGroot@cukz.umcn.nl

David P. Inwald: d.inwald@imperial.ac.uk

Simon Nadel: s.nadel@imperial.ac.uk

Stéphane Paulus: Stephane.Paulus@alderhey.nhs.uk

Eleanor Pinnock: E.Pinnock@micropathology.com

Fatou Secka: fsecka@mrc.gm

Suzanne T. Anderson: sanderson@mrc.gm

Rachel S. Agbeko: Rachel.Agbeko@nuth.nhs.uk

Christoph Berger: christoph.berger@kispi.uzh.ch

Colin G. Fink: colinfink@micropathology.com

Enitan D. Carrol: edcarrol@liverpool.ac.uk

Werner Zenz: werner.zenz@medunigraz.at

Michael Levin: m.levin@imperial.ac.uk

Michiel van der Flier: michiel.vanderflier@radboudumc.nl

Federico Martinón-Torres: Federico.Martinon.Torres@sergas.es

Jan A. Hazelzet: +31107030049 , j.a.hazelzet@erasmusmc.nl

Marieke Emonts: Marieke.Emonts@ncl.ac.uk

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 31 May 2018

Publication date PMC-release: 31 May 2018

Publication date Collection: 2018

Volume: 22

Electronic Location Identifier: 143

Affiliations

[1 ]GRID grid.416135.4, Intensive Care and Department of Pediatric Surgery, , Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam, ; Wytemaweg 80, 3015 CN Rotterdam, The Netherlands

[2 ]GRID grid.416135.4, 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

[3 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, Faculty of Medicine, , The University of Queensland, ; St Lucia Queensland, Brisbane, 4072 Australia

[4 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, Paediatric Critical Care Research Group, Mater Research Institute, , The University of Queensland, ; Aubigny Place, Raymond Terrace, Brisbane, Australia

[5 ]GRID grid.240562.7, Paediatric Intensive Care Unit, , Lady Cilento Children’s Hospital, Children’s Health Queensland, ; 501 Stanley St, Brisbane, Australia

[6 ]Department of Pediatrics, Bern University Hospital, Inselspital, University of Bern, Freiburgstrasse 8, 3010 Bern, Switzerland

[7 ]Department of Paediatrics, Juliana Children’s Hospital/Haga Teaching Hospital, Els Borst-Eilersplein 275, 2545 AA The Hague, The Netherlands

[8 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Section of Pediatrics, Imperial College London, ; Level 2, Faculty Building South Kensington Campus, London, SW7 2AZ UK

[9 ]ISNI 0000 0000 8816 6945, GRID grid.411048.8, Translational Pediatrics and Infectious Diseases Section- Pediatrics Department, , Hospital Clínico Universitario de Santiago de Compostela, ; Travesía da Choupana, 15706 Santiago de Compostela, Spain

[10 ]Genetics- Vaccines- Infectious Diseases and Pediatrics research group GENVIP, Health Research Institute of Santiago IDIS/SERGAS, Travesía da Choupana, 15706 Santiago de Compostela, Spain

[11 ]ISNI 0000 0000 8988 2476, GRID grid.11598.34, Department of General Paediatrics, , Medical University of Graz, ; Auenbruggerplatz 34/2, A-8036 Graz, Austria

[12 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Radboudumc Technology Center Clinical Studies, Radboudumc, ; Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands

[13 ]GRID grid.461760.2, 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

[14 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Radboud Center for Infectious Diseases, Radboudumc, ; Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands

[15 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Department of Paediatrics, Faculty of Medicine, , Imperial College London, South Kensington Campus, ; London, SW7 2AZ UK

[16 ]St Mary’s Hospital, Imperial College Healthcare NHS Trust, Praed Street, London, W2 1NY UK

[17 ]ISNI 0000 0004 0421 1374, GRID grid.417858.7, Division of Paediatric Infectious Diseases, , Alder Hey Children’s NHS Foundation Trust, ; Eaton Rd, Liverpool, L12 2AP UK

[18 ]ISNI 0000 0004 1936 8470, GRID grid.10025.36, Institute of Infection & Global Health, , University of Liverpool, ; 8 West Derby St, Liverpool, L7 3EA UK

[19 ]ISNI 0000 0000 8809 1613, GRID grid.7372.1, Micropathology Ltd, , University of Warwick Science Park, ; Venture Centre, Sir William Lyons Road, Coventry, CV4 7EZ UK

[20 ]ISNI 0000 0004 0606 294X, GRID grid.415063.5, Medical research Council Unit, ; Atlantic Boulevard, Fajara, P. O. Box 273, Banjul, The Gambia

[21 ]ISNI 0000 0004 4904 7256, GRID grid.459561.a, 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

[22 ]ISNI 0000 0001 0462 7212, GRID grid.1006.7, Institute of Cellular Medicine, , Newcastle University, ; 4th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK

[23 ]ISNI 0000 0001 0726 4330, GRID grid.412341.1, Division of Infectious Diseases and Hospital Epidemiology, and Children’s Research Center, , University Children’s Hospital Zurich, ; Steinwiesenstrasse 75, 8032 Zurich, Switzerland

[24 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, 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

[25 ]ISNI 000000040459992X, GRID grid.5645.2, Department of Public Health, Erasmus MC, , University Medical Center Rotterdam, ; Wytemaweg 80, 3015 CN Rotterdam, The Netherlands

[26 ]ISNI 0000 0004 4904 7256, GRID grid.459561.a, 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

[27 ]GRID grid.454379.8, NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, ; Westgate Rd, Newcastle upon Tyne, NE4 5PL UK

Article

Publisher ID: 2052

DOI: 10.1186/s13054-018-2052-7

PMC ID: 5984383

PubMed ID: 29855385

SO-VID: f5543d73-6a2e-4ed0-b00f-7836d2ffb30a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), 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 ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 30 January 2018

Date accepted : 29 April 2018

Funding

Funded by: European Seventh Framework Programme for Research and Technological Development (FP7)

Award ID: 279185

Award Recipient : Michael Levin

Funded by: Swiss National Science Foundation

Award ID: 342730_153158/1