Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce

doi:10.1097/CCM.0000000000005294

Meta-Analysis

. 2022 Jan 1;50(1):21-36.

doi: 10.1097/CCM.0000000000005294.

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce

Kusum Menon¹, Luregn J Schlapbach², Samuel Akech³, Andrew Argent⁴, Paolo Biban⁵, Enitan D Carrol⁶, Kathleen Chiotos⁷, Mohammod Jobayer Chisti⁸, Idris V R Evans⁹, David P Inwald¹⁰, Paul Ishimine¹¹, Niranjan Kissoon¹², Rakesh Lodha¹³, Simon Nadel¹⁴, Cláudio Flauzino Oliveira¹⁵, Mark Peters¹⁶, Benham Sadeghirad¹⁷, Halden F Scott¹⁸, Daniela C de Souza¹⁹, Pierre Tissieres²⁰, R Scott Watson²¹, Matthew O Wiens^{22

23}, James L Wynn²⁴, Jerry J Zimmerman²¹, Lauren R Sorce²⁵; Pediatric Sepsis Definition Taskforce of the Society of Critical Care Medicine

Affiliations

¹ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
² Pediatric and Neonatal ICU, University Children`s Hospital Zurich, Zurich, Switzerland, and Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia.
³ KEMRI Wellcome Trust Research Program, Nairobi, Kenya.
⁴ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.
⁵ Department of Paediatrics, Verona University Hospital, Verona, Italy.
⁶ Department of Clinical Infection Microbiology and Immunology, University of Liverpool Institute of Infection, Veterinary and Ecological Sciences, Liverpool, United Kingdom.
⁷ Children's Hospital of Philadelphia, Philadelphia, PA.
⁸ International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
⁹ 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.
¹⁰ Paediatric Intensive Care Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
¹¹ Departments of Emergency Medicine and Pediatrics, University of California San Diego School of Medicine, La Jolla, CA.
¹² Department of Pediatrics, University of British Columbia and British Columbia Children's Hospital, Vancouver, BC, Canada.
¹³ All India Institute of Medical Sciences, Delhi, India.
¹⁴ St. Mary's Hospital, Imperial College Healthcare NHS Trust, and Imperial College London, London, United Kingdom.
¹⁵ Associação de Medicina Intensiva Brasileira, São Paulo, Brazil.
¹⁶ University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
¹⁷ Departments of Anesthesia and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁸ Departments of Pediatrics and Emergency Medicine, University of Colorado School of Medicine, Aurora, CO.
¹⁹ Departments of Pediatrics, Hospital Sírio-Libanês and Hospital Universitário da Universidade de São Paulo, São Paolo, Brazil.
²⁰ Pediatric Intensive Care, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
²¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
²² University of British Columbia, Vancouver, BC, Canada.
²³ Mbarara University of Science and Technology, Mbarara, Uganda.
²⁴ Department of Pediatrics, University of Florida, Gainesville, FL.
²⁵ 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.

PMID: 34612847
PMCID: PMC8670345
DOI: 10.1097/CCM.0000000000005294

Free PMC article

Meta-Analysis

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce

Kusum Menon et al. Crit Care Med. 2022.

Free PMC article

. 2022 Jan 1;50(1):21-36.

doi: 10.1097/CCM.0000000000005294.

Authors

Affiliations

¹ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
² Pediatric and Neonatal ICU, University Children`s Hospital Zurich, Zurich, Switzerland, and Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia.
³ KEMRI Wellcome Trust Research Program, Nairobi, Kenya.
⁴ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.
⁵ Department of Paediatrics, Verona University Hospital, Verona, Italy.
⁶ Department of Clinical Infection Microbiology and Immunology, University of Liverpool Institute of Infection, Veterinary and Ecological Sciences, Liverpool, United Kingdom.
⁷ Children's Hospital of Philadelphia, Philadelphia, PA.
⁸ International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
⁹ 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.
¹⁰ Paediatric Intensive Care Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
¹¹ Departments of Emergency Medicine and Pediatrics, University of California San Diego School of Medicine, La Jolla, CA.
¹² Department of Pediatrics, University of British Columbia and British Columbia Children's Hospital, Vancouver, BC, Canada.
¹³ All India Institute of Medical Sciences, Delhi, India.
¹⁴ St. Mary's Hospital, Imperial College Healthcare NHS Trust, and Imperial College London, London, United Kingdom.
¹⁵ Associação de Medicina Intensiva Brasileira, São Paulo, Brazil.
¹⁶ University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
¹⁷ Departments of Anesthesia and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁸ Departments of Pediatrics and Emergency Medicine, University of Colorado School of Medicine, Aurora, CO.
¹⁹ Departments of Pediatrics, Hospital Sírio-Libanês and Hospital Universitário da Universidade de São Paulo, São Paolo, Brazil.
²⁰ Pediatric Intensive Care, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
²¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
²² University of British Columbia, Vancouver, BC, Canada.
²³ Mbarara University of Science and Technology, Mbarara, Uganda.
²⁴ Department of Pediatrics, University of Florida, Gainesville, FL.
²⁵ 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.

PMID: 34612847
PMCID: PMC8670345
DOI: 10.1097/CCM.0000000000005294

Abstract

Objective: To 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 sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.

Study selection: Case-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 extraction: Study 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 synthesis: One 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).

Conclusions: Strong 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.

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Conflict of interest statement

Dr. Menon has a Canadian Institutes of Health Research grant for the study of corticosteroids in pediatric septic shock. Dr. Menon’s institution received funding from Crowdsourcing; he disclosed that he is a principal investigator on an international trial on Steroids in Pediatric Sepsis Shock. Drs. Menon and Watson received funding from Society of Critical Care Medicine. Dr. Argent received funding from the World Federation of Pediatric Intensive and Critical Care Societies as a part of the process of working with the Pediatric Sepsis Definitions working group. Dr. Biban received funding from Chiesi and Getinge. Dr. Nadel received funding from Abbvie. Dr. Sadeghirad received funding from the Pre-Interventional Preventative Risk Assessment AG, Mitacs Canada, and Accelerate internship in partnership with Nestlé Canada. Dr. Scott’s institution received funding from the Agency for Healthcare Research and Quality (AHRQ K08HS025696); he received support for article research from the AHRQ. Dr. Tissieres received funding from Sedana, Inotrem, and Baxter. Dr. Wynn received funding from the National Institutes of Health (NIH) (R01GM128452; R01HD089939, R01HD097081, R43EB029863). Dr. Zimmerman’s institution received funding from the NIH, the National Institute of Child Health and Human Development, and Immunexpress; he received funding from Elsevier Publishing. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

**Figure 1.**
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for included studies.

**Figure 2.**
Pooled mortality rates for sepsis, severe sepsis, and septic shock in included studies across World Bank Income classifications. HIC = high-income country, LMIC = low-middle-income country, UMIC = upper-middle-income country.

See this image and copyright information in PMC

Comment in

Sepsis Definitions: I Know It When I See It.
Parker MM. Parker MM. Crit Care Med. 2022 Jan 1;50(1):148-150. doi: 10.1097/CCM.0000000000005350. Crit Care Med. 2022. PMID: 34914644 No abstract available.

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References

1. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396:1204–1222 - PMC - PubMed
1. Rudd KE, Johnson SC, Agesa KM, et al. . Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet. 2020; 395:200–211 - PMC - PubMed
1. Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005; 6:2–8 - PubMed
1. Weiss SL, Peters MJ, Alhazzani W, et al. . Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med. 2020; 21:e52–e106 - PubMed
1. Shankar-Hari M, Phillips GS, Levy ML, et al. ; Sepsis Definitions Task Force. Developing a new definition and assessing new clinical criteria for septic shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315:775–787 - PMC - PubMed

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[1] GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396:1204–1222 - PMC - PubMed

[2] GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396:1204–1222 - PMC - PubMed

[3] Rudd KE, Johnson SC, Agesa KM, et al. . Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet. 2020; 395:200–211 - PMC - PubMed

[4] Rudd KE, Johnson SC, Agesa KM, et al. . Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet. 2020; 395:200–211 - PMC - PubMed

[5] Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005; 6:2–8 - PubMed

[6] Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005; 6:2–8 - PubMed

[7] Weiss SL, Peters MJ, Alhazzani W, et al. . Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med. 2020; 21:e52–e106 - PubMed

[8] Weiss SL, Peters MJ, Alhazzani W, et al. . Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med. 2020; 21:e52–e106 - PubMed

[9] Shankar-Hari M, Phillips GS, Levy ML, et al. ; Sepsis Definitions Task Force. Developing a new definition and assessing new clinical criteria for septic shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315:775–787 - PMC - PubMed

[10] Shankar-Hari M, Phillips GS, Levy ML, et al. ; Sepsis Definitions Task Force. Developing a new definition and assessing new clinical criteria for septic shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315:775–787 - PMC - PubMed

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Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce

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Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce

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