Criteria for Pediatric Sepsis

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

Kusum Menon, MD, MSc; Luregn J. Schlapbach, MD, FCICM, PhD; Samuel Akech, MBChB, MMED, DPhil; Andrew Argent, MBBCh, MD(Paeds); Paolo Biban, MD; Enitan D. Carrol, MBChB, MD; Kathleen Chiotos, MD, MSCE; Mohammod Jobayer Chisti, MBBS, MMed, PhD; Idris V. R. Evans, MD, MSc; David P. Inwald, MB BChir, PhD; Paul Ishimine, MD; Niranjan Kissoon, MD; Rakesh Lodha, MD; Simon Nadel, MRCP; Cláudio Flauzino Oliveira, MD; Mark Peters, MBChB, PhD; Benham Sadeghirad, PharmD, MPH, PhD; Halden F. Scott, MD, MSCS; Daniela C. de Souza, MD; Pierre Tissieres, MD, DSc; R. Scott Watson, MD, MPH; Matthew O. Wiens, PharmD, PhD; James L. Wynn, MD; Jerry J. Zimmerman, MD, PhD; Lauren R. Sorce, RN, PhD

Disclosures

Crit Care Med. 2022;50(1):21-36. 

In This Article

Materials and Methods

The protocol including search strategy has been previously published[13] and is summarized below.

Eligibility Criteria

Inclusion criteria for studies were: 1) the words "sepsis," "septic shock," or "septicemia" present in the title or abstract; 2) publication between January 1, 2004, and November 16, 2020; 3) sepsis, septic shock, septicemia, NPMODS, or mortality reported as an outcome; 4) case-control study, cohort study, or randomized trial; and 5) study population of children greater than or equal to 37-week-old postconception to less than 18 years. Studies meeting the following criteria were excluded: 1) no reported data on children with sepsis, severe sepsis, or septic shock; 2) less than 50 children with sepsis, septicemia, severe sepsis, or septic shock; 3) abstracts, case studies, narrative reviews, or surveys; 4) variable values within 24 hours of admission not provided; 5) no comparator group for variable in question; 6) sepsis criteria not specified; 7) article not available; or 8) focused on criteria only available for research (e.g., gene-expression data). Only 27 non-English language articles (0.4%, 27/7502) were identified by the search (17 at abstract screening and 10 following full-text review). Therefore, non-English language studies were excluded.

Data Sources

We identified eligible studies by searching MEDLINE (including Epub Ahead of Print), Embase, and the Cochrane Central Register of Controlled Trials databases.

Study Selection

The titles, abstracts, and full texts were screened using a previously validated platform Insight Scope.[14] Each title and full-text article were screened by two reviewers, and at each screening level and for data extraction, conflicts were resolved by a third reviewer.

Data Extraction and Management

Data were extracted from full-text articles using a Research Electronic Data Capture (REDCap) platform[15] hosted at the Children's Hospital of Eastern Ontario Clinical Research Unit. Corresponding authors were contacted twice for missing data. The quality of selected articles was determined using the first four domains of the Quality in Prognostics Studies tool for assessment of risk of bias in observational studies.[16] The last two domains pertain to confounding and statistical analysis that were not applicable to the unadjusted data used in our meta-analysis. The overall risk of bias was determined as the highest risk of bias attributed to any criterion. Unadjusted data were extracted since many studies did not report adjusted data and others did not specify the variables they adjusted for or adjusted for different variables.[17] Studies were categorized as being conducted in low-income countries (LICs), low-middle-income countries (LMICs), UMICs, and HICs according to the World Bank classification of 2019–2020.[18]

Outcomes

The primary outcome for the meta-analysis of articles describing children with infection was the presence of sepsis, severe sepsis, or septic shock as defined in each individual study. The primary outcome for the meta-analysis of articles describing children with sepsis, severe sepsis, or septic shock was the development of NPMODS and/or death. Mortality was defined as at or prior to hospital discharge.

Data Synthesis and Analysis

Frequencies and descriptive statistics are reported for study demographics and patient characteristics from included studies. We pooled outcomes reported by two or more studies. We calculated unadjusted prognostic odds ratios (ORs) and 95% CIs for dichotomous variables and calculated the mean difference with 95% CIs for continuous variables. We imputed the mean and SD when median, interquartile range, or range and sample size were reported.[19,20] Statistical heterogeneity was assessed using I2 statistic and visual inspection of the forest plots, and DerSimonian-Laird random-effects model was employed for all comparisons. All analyses were conducted using Stata (StataCorp, Release 16.1. College Station, TX).[21] Baseline sepsis, severe sepsis, and septic shock rates among HIC, UMIC, and LMIC were compared using Kruskal-Wallis tests weighted for study sample sizes.

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