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ObjectiveTo determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.Data sourcesMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.Study selectionCase-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract.Data extractionStudy characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.Data synthesisOne hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).ConclusionsStrong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

Original publication





Critical care medicine

Publication Date



Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada. Pediatric and Neonatal ICU, University Children`s Hospital Zurich, Zurich, Switzerland, and Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia. KEMRI Wellcome Trust Research Program, Nairobi, Kenya. Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa. Department of Paediatrics, Verona University Hospital, Verona, Italy. Department of Clinical Infection Microbiology and Immunology, University of Liverpool Institute of Infection, Veterinary and Ecological Sciences, Liverpool, United Kingdom. Children's Hospital of Philadelphia, Philadelphia, PA. International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, and The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, PA. Paediatric Intensive Care Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. Departments of Emergency Medicine and Pediatrics, University of California San Diego School of Medicine, La Jolla, CA. Department of Pediatrics, University of British Columbia and British Columbia Children's Hospital, Vancouver, BC, Canada. All India Institute of Medical Sciences, Delhi, India. St. Mary's Hospital, Imperial College Healthcare NHS Trust, and Imperial College London, London, United Kingdom. Associação de Medicina Intensiva Brasileira, São Paulo, Brazil. University College London Great Ormond Street Institute of Child Health, London, United Kingdom. Departments of Anesthesia and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada. Departments of Pediatrics and Emergency Medicine, University of Colorado School of Medicine, Aurora, CO. Departments of Pediatrics, Hospital Sírio-Libanês and Hospital Universitário da Universidade de São Paulo, São Paolo, Brazil. Pediatric Intensive Care, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA. University of British Columbia, Vancouver, BC, Canada. Mbarara University of Science and Technology, Mbarara, Uganda. Department of Pediatrics, University of Florida, Gainesville, FL. Ann & Robert H. Lurie Children's Hospital and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Lurie Children's Pediatric Research & Evidence Synthesis Center (PRECIISE): A JBI Affiliated Group, Chicago, IL.


Pediatric Sepsis Definition Taskforce of the Society of Critical Care Medicine