Luregn Schlapbach

Objectives: – Evaluate the predictive and prognostic performance of the Phoenix Sepsis Criteria (PSC) and Phoenix Sepsis Score (PSS) compared with International Pediatric Sepsis Consensus Conference (IPSCC) criteria and other organ dysfunction scores in children admitted to the PICU with suspected infection. Design: – Multicenter, prospective cohort study. Setting: – Eight PICUs within the Italian Network of PICU Study Group (TIPNet). Patients: – Patients younger than 18 years admitted with suspected infection (from February 2022 to April 2024). Interventions: – None. Measurements and Main Results: – Vital signs, organ dysfunction markers, and organ support requirements were collected during day 1 and day 2 of PICU admission. Sepsis was assessed using IPSCC criteria and PSC. IPSCC Severe Sepsis, PSS, Phoenix-8, Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment, and Pediatric Multiple Organ Dysfunction Score were calculated as organ dysfunction scores. Sepsis criteria predictive performance was assessed using sensitivity and positive predictive value (PPV). Organ dysfunction scores prognostic performance was assessed using the area under the precision-recall curve (AUPRC). Primary outcome was PICU mortality. Among 687 patients, PSC showed higher predictive performance than IPSCC sepsis criteria, with improved sensitivity and PPV for mortality on day 1 (PSC: sensitivity, 96.4%; 95% CI, 95.0–97.8%; PPV, 7.6%; 95% CI, 5.6–9.6% and IPSCC: sensitivity, 82.1%; 95% CI, 79.3–85.0%; PPV, 6.2%; 95% CI, 4.4–8.0%) and day 2 (PSC: sensitivity, 100.0%; 95% CI, 100.0–100.0%; PPV, 10.0%; 95% CI, 7.6–12.5% and IPSCC: sensitivity, 75.0%; 95% CI, 71.5–78.5%; PPV, 9.0%; 95% CI, 6.7–11.3%). PELOD-2 exhibited the highest AUPRC for mortality (day 1, 0.45; 95% CI, 0.26–0.63 and day 2, 0.59; 95% CI, 0.38–0.77). IPSCC Severe Sepsis score was outperformed by all other organ dysfunction scores, including PSS and Phoenix-8. All prognostic performances improved from day 1 to day 2. Conclusions: – PSC and PSS performed superior to IPSCC criteria in diagnosing and prognosticating pediatric sepsis, with improved performance at day 2 of PICU admission. This study first validated PSC and PSS in a European cohort.

Purpose

Sepsis is a leading cause of pediatric morbidity and mortality worldwide. Current guidelines recommend fluid bolus administration of 40–60 mL/kg as part of initial resuscitation, despite limited evidence and concerns about potential harm from high fluid volumes. The ANDES-CHILD pilot study hypothesizes that early initiation of inotropes is feasible and reduces fluid use compared to standard resuscitation.

Methods

Multicenter open label randomized controlled pilot trial conducted in three Pediatric Emergency Departments in Latin America. Children aged 28 days to 18 years with presumed septic shock will be randomized in a 1:1 ratio to receive either early adrenaline infusion after 20 mL/kg fluid bolus versus standard resuscitation with 40–60 mL/kg fluid bolus prior to initiating inotropes. The primary outcome is feasibility, with survival free of organ support censored at 28 days as the exploratory primary clinical outcome. The study will enroll 40 patients, representing approximately 10% of a full trial, with follow-up at 28 days. Baseline characteristics, adverse events and protocol violations will be summarized descriptively. Outcomes will be analyzed using difference estimates with 95% confidence intervals. An intention-to-treat approach will be used for statistical analysis.

Discussion

This pragmatic pilot study will generate essential data to evaluate the feasibility and guide the design of a full trial aimed to assessing the benefits of early inotrope use in pediatric septic shock. The study was registered on ClinicalTrials.gov prior to the start of recruitment (NCT06478797). Recruitment started on July 18, 2024.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations.