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. 2024 Feb 27;331(8):665-674.
doi: 10.1001/jama.2024.0179.

International Consensus Criteria for Pediatric Sepsis and Septic Shock

Luregn J Schlapbach  1   2 , R Scott Watson  3   4 , Lauren R Sorce  5   6 , Andrew C Argent  7   8 , Kusum Menon  9   10 , Mark W Hall  11   12 , Samuel Akech  13 , David J Albers  14   15 , Elizabeth R Alpern  5   16 , Fran Balamuth  17   18 , Melania Bembea  19 , Paolo Biban  20 , Enitan D Carrol  21 , Kathleen Chiotos  22   23 , Mohammod Jobayer Chisti  24 , Peter E DeWitt  25 , Idris Evans  26   27 , Cláudio Flauzino de Oliveira  28   29 , Christopher M Horvat  26   27 , David Inwald  30 , Paul Ishimine  31 , Juan Camilo Jaramillo-Bustamante  32   33 , Michael Levin  34   35 , Rakesh Lodha  36 , Blake Martin  37   38 , Simon Nadel  39   40 , Satoshi Nakagawa  41 , Mark J Peters  42   43 , Adrienne G Randolph  44   45 , Suchitra Ranjit  46 , Margaret N Rebull  25 , Seth Russell  25 , Halden F Scott  47   48 , Daniela Carla de Souza  29   49   50 , Pierre Tissieres  51 , Scott L Weiss  52   53 , Matthew O Wiens  54   55 , James L Wynn  56 , Niranjan Kissoon  57 , Jerry J Zimmerman  3   4 , L Nelson Sanchez-Pinto  5   58 , Tellen D Bennett  37 ; Society of Critical Care Medicine Pediatric Sepsis Definition Task Force
Collaborators, Affiliations

International Consensus Criteria for Pediatric Sepsis and Septic Shock

Luregn J Schlapbach et al. JAMA. .

Abstract

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children.

Objective: To update and evaluate criteria for sepsis and septic shock in children.

Evidence review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria.

Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively.

Conclusions and relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Schlapbach reported receiving grants from Medical Research Future Funds (MRFF), National Health and Research Council (NHMRC), NOMIS Foundation, and Swiss Personalized Health Network (SPHN) outside the submitted work. Dr Watson reported receiving support to his institution from the National Institutes of Health (NIH) and nonfinancial support from the SCCM during the conduct of the study. Dr Argent reported receiving payments for providing expert evidence for medicolegal matters in South Africa. Dr Menon reported receiving grants from the Canadian Institutes of Health Research (CIHR) funding outside the submitted work. Dr Hall reported serving on the data and safety monitoring board for Abbvie and on a subboard of the American Board of Pediatrics; receiving nonfinancial support from Sobi and Partner Therapeutics and personal fees from Kiadis Licensing that is unrelated to the submitted work. Dr Balamuth reported receiving grants from the NIH and the Children's Hospital of Philadelphia Research Institute, Global Lyme Alliance, and the Kleberg Foundation. Dr Bembea reported receiving grants from the National Institute of Child Health and Human Development (NICHD), Grifols Research, Department of Defense, and the National Heart, Lung, and Blood Institute (NHLBI) to her institution outside the submitted work. Dr Carrol reported serving on the committee for UK National Institute for Health and Care Excellence (NICE) sepsis guidelines 2016 and SCCM International guidelines for pediatric sepsis. Dr Chiotos reported receiving grants from Centers for Disease Control and Prevention (CDC) and the Agency for Healthcare Research and Quality (AHRQ) outside the submitted work and serving as a member of the Infectious Diseases Society of America (IDSA) Sepsis Taskforce. Dr Horvat reported receiving grants from the NICHD and grants from National Institute of Neurological Disorders and Stroke (NINDS) outside the submitted work. Dr Martin reported receiving grants from the Thrasher Research Fund outside the submitted work. Dr Nakagawa reported receiving grants from the Japan Blood Products Organization outside the submitted work. Dr Peters reported receiving grants from the National Institute of Health and Care Research UK for clinical trials from the Heath Technology Assessment, Research for Patient Benefit, and Programme Grants for Applied Research programmes outside of the submitted work. Dr Randolph reported serving as the chair of the International Sepsis Forum; receiving institutional grants from the CDC, NIH, and NIAID; serving as a section editor of UpToDate and on the advisory board of ThermoFisher Pediatric; attending a scientific advisory meeting for Volition Inc; and receiving nonfinancial support from Illumina Inc in the form of reagents to Boston Children’s Hospital outside the submitted work. Dr Scott reported receiving grants from AHRQ outside the submitted work. Dr Tissieres reported receiving grants from Baxter, honoraria from a Baxter symposium, advisory fees from Sedana, ThermoFisher, and Sanofi outside the submitted work. Dr Wynn reported serving as a consultant to Sobi outside the submitted work. Dr Zimmerman reported receiving grants from Immunexpress, research funding and personal fees and royalties from Elsevier Publishing, and royalties outside the submitted work. Dr Bennett reported receiving grants from the National Center for Advancing Translational Sciences and the NHLBI outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Proposed Diagnostic Flow to Characterize Patients Using the New Criteria for Sepsis and Septic Shock in Children
Sepsis diagnosis is operationalized as 2 points or more on the Phoenix Sepsis Score, and septic shock as sepsis with cardiovascular dysfunction (see the Table). aInstitutionally available procedures to identify deteriorating patients with infection should be followed for screening. There is a need for data-driven tools to screen children at risk of development of sepsis, which must be rigorously evaluated in different populations and contexts. The Phoenix Sepsis Score is not intended for early screening or recognition of possible sepsis and management before organ dysfunction is overt. bPlease refer to the Table for the Phoenix Sepsis Score.
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Comment in

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