Abstract and Introduction
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.
Infections account for 26.5% of the global burden of disease and 25% of deaths in children worldwide. However, the clinical manifestations of these infections vary from minimal symptoms to multiple organ failure and death. The currently accepted definitions of sepsis, severe sepsis, and septic shock were developed and refined using different criteria to help identify, treat, and study patients with infections who are at higher risk of significant morbidity and mortality.[3,4] However, specific variables identifying children with sepsis and their resulting outcomes have never been rigorously evaluated in a systematic review.
The 2016 sepsis definition update in adult patients (Sepsis-3) included a systematic review of reported criteria used to identify adults with septic shock. This review focused on hemodynamic criteria, was primarily limited to studies from upper middle-income countries (UMICs) and high-income countries (HICs), and specifically excluded pediatric studies. Furthermore, results of adult trials cannot be extrapolated to children because of differences in epidemiology, mortality rates, underlying diseases, disease-specific outcomes,[9,10] and differing responses to therapy.[11,12]
Therefore, the Society of Critical Care Medicine (SCCM) convened the Pediatric Sepsis Definition Taskforce to evaluate, develop, and validate criteria for the identification of sepsis in children. As part of this process, the Taskforce conducted a systematic review with the explicit goal of determining the ability of demographic, clinical, laboratory, organ dysfunction, and illness severity variables to capture children with more severe infections. For this purpose, we assessed association of these variables with: 1) sepsis, severe sepsis, or septic shock in children with suspected or confirmed infection and 2) with new or progressive multiple organ dysfunction (NPMODS) or mortality in children with sepsis, severe sepsis, or septic shock.
Crit Care Med. 2022;50(1):21-36. © 2022 Lippincott Williams & Wilkins