Daily Sepsis Research Analysis
Three studies advance sepsis-related science across systems, clinical care, and mechanisms. A multinational cohort quantifies pediatric acute critical illness in resource-constrained hospitals and highlights early deaths and sepsis as a key contributor. A meta-analysis informs fluid choice in pediatric septic shock, and a murine study of leptospirosis challenges the cytokine-storm paradigm by implicating neutrophil-driven vascular leakage and myocarditis.
Summary
Three studies advance sepsis-related science across systems, clinical care, and mechanisms. A multinational cohort quantifies pediatric acute critical illness in resource-constrained hospitals and highlights early deaths and sepsis as a key contributor. A meta-analysis informs fluid choice in pediatric septic shock, and a murine study of leptospirosis challenges the cytokine-storm paradigm by implicating neutrophil-driven vascular leakage and myocarditis.
Research Themes
- Global pediatric critical illness burden and early mortality in resource-constrained settings
- Fluid resuscitation strategy for pediatric septic shock (balanced crystalloids vs saline)
- Immunopathology challenging the cytokine-storm paradigm in sepsis-like infections
Selected Articles
1. Prevalence, aetiology, and hospital outcomes of paediatric acute critical illness in resource-constrained settings (Global PARITY): a multicentre, international, point prevalence and prospective cohort study.
In 7,538 children across 19 countries, 13.1% met criteria for paediatric acute critical illness, with the highest prevalence (28.0%) in low-SDI countries. Sepsis/septic shock accounted for 10.4% of P-ACI, and 59% of all deaths occurred within 48 hours, underscoring the need for basic critical care capacity.
Impact: Provides the most comprehensive, multicountry estimate of pediatric critical illness burden in resource-constrained hospitals and identifies early mortality windows and sepsis as major targets.
Clinical Implications: Health systems in low-resource settings should prioritize early triage and delivery of basic critical care (oxygen, fluids, antibiotics, organ support), with focus on the first 48 hours. Data inform resource allocation and capacity building targeting sepsis and pneumonia.
Key Findings
- Overall P-ACI prevalence was 13.1% (985/7,538), highest in low-SDI countries at 28.0%.
- Sepsis/septic shock accounted for 10.4% of P-ACI; pneumonia was 15.4% and malaria 9.6%.
- Among P-ACI patients, mortality was 6.3%, and 59% of all deaths occurred within 48 hours of presentation.
- Country SDI category was not independently associated with P-ACI frequency after adjustment.
Methodological Strengths
- Multinational, multicentre design across 46 sites in 19 countries
- Standardised case definition using DEFCRIT with prospective in-hospital outcome follow-up and multivariable adjustment
Limitations
- Point-prevalence design across four discrete days may not capture temporal variability
- In-hospital follow-up only; long-term outcomes not assessed
Future Directions: Implementation research to scale basic critical care in low-SDI settings, targeted interventions within the first 48 hours, and prospective evaluation of sepsis care bundles.
2. Myocarditis and neutrophil-mediated vascular leakage but not cytokine storm associated with fatal murine leptospirosis.
Fatal murine leptospirosis was characterized by elevated IL-10, neutrophilia, and neutrophil-driven vascular leakage, with myocarditis as the principal cause of death. Contrary to assumptions from sepsis, a cytokine storm was not observed, reframing immunopathology and therapeutic targets.
Impact: Challenges the prevailing cytokine-storm narrative in sepsis-like bacterial infections and identifies myocarditis and neutrophil-mediated vascular leakage as key lethal mechanisms.
Clinical Implications: Clinicians should consider myocarditis in severe leptospirosis and the potential benefit of strategies that modulate neutrophil-driven vascular permeability, beyond anti-cytokine approaches.
Key Findings
- No cytokine storm or massive necroptosis; instead, elevated IL-10 and RANTES were detected.
- Severe disease associated with neutrophilia and neutrophil-mediated vascular permeability.
- Myocarditis was identified as the main cause of death in the murine model.
Methodological Strengths
- In vivo mechanistic analysis with cytokine profiling and histopathology across organs
- Alignment of murine findings with clinical features observed in human leptospirosis
Limitations
- Translation from murine intraperitoneal infection to human disease may be limited
- Sample sizes and detailed statistical parameters are not specified in the abstract
Future Directions: Validate myocarditis and neutrophil-targeted interventions in human leptospirosis and explore biomarkers predicting vascular leakage.
3. Balanced crystalloid versus saline for resuscitation in pediatric septic shock: a systematic review and meta-analysis.
Across 12,231 pediatric patients (4 RCTs), balanced crystalloids reduced hyperchloremia and, in RCTs, reduced renal replacement therapy versus saline, with no differences in AKI or mortality. Hospital length of stay was longer with balanced solutions, highlighting trade-offs in fluid selection.
Impact: Synthesizes the best available evidence on fluid choice for pediatric septic shock, informing practice where guidance is inconsistent.
Clinical Implications: Balanced crystalloids may be preferred to reduce hyperchloremia and potentially renal replacement therapy needs, but clinicians should weigh the association with longer hospital stay and patient context.
Key Findings
- Meta-analysis of 8 studies (12,231 patients; 4 RCTs) found no differences in AKI, mortality, mechanical ventilation, or PICU length of stay between balanced solutions and saline.
- Balanced solutions reduced hyperchloremia (RR 0.70) and, in RCT-only subgroup, reduced need for renal replacement therapy (RR 0.58).
- Hospital length of stay was longer with balanced solutions (MD 3.38 days; I² = 0%).
Methodological Strengths
- Inclusion of randomized trials with subgroup analysis and low heterogeneity for key outcomes
- Comprehensive database search and prespecified clinical endpoints
Limitations
- Mix of RCTs and observational studies introduces potential bias and confounding
- Variation in follow-up duration (3–90 days) and fluid protocols across studies
Future Directions: Large, pragmatic pediatric RCTs comparing balanced solutions versus saline with standardized protocols and patient-centered outcomes (kidney recovery, function) are warranted.