Pediatric Sepsis: What’s New?

The impact of pediatric sepsis on pediatric mortality is enormous with sepsis accounting for 35%-42% of deaths, and nearly two-thirds of pediatric intensive care unit (PICU) admissions. Sepsis was clearly conceptualized in the year 1992 for the first time, marking a significant milestone in understanding its impact. It was described as systemic inflammatory response syndrome (SIRS), and not specifically for children.[1] In 2005, the first pediatric sepsis guidelines (Sepsis 2) introduced terms like SIRS, sepsis, and septic shock for children.[2] The 2016 “Sepsis 3 update” revised the adult criteria, narrowing the definition of sepsis and defining septic shock, where they focused on organ dysfunction. But this was not directly applicable to children due to age-related differences in vital signs, responses, and outcomes.[3] The 2020 Surviving Sepsis Campaign (SSC) Guideline provided a new operational definition of sepsis as a suspected or confirmed infection with organ dysfunction. This replaced terms like SIRS and severe sepsis, as SIRS variables were found to have poor predictive values. However, the guidelines’ applicability across countries and organ-system predictability remain uncertain.[4] Pediatric sepsis, characterized by life-threatening organ dysfunction due to an uncontrolled infection response, prompted the development of the Phoenix score. It evaluates four major systems - respiratory, cardiovascular, hematological, and neurological with a score ≥2 indicating sepsis, and ≥3 with one cardiovascular point indicating septic shock.[5] Fluid resuscitation strategies in sepsis differ by setting. In resource-limited settings, up to 40 mL/kg for hypotensive patients, and only maintenance fluids for those with poor peripheral perfusion with normal blood pressure is recommended. But if ICU facility is available, up to 60 mL/kg can be given with cautious administration if hypotension persists with monitoring for fluid overload. For obese patients, fluid is tailored to ideal body weight to prevent overdose. Crystalloids are always preferred and recently there is a trend towards using balanced salt solutions (BSS) to prevent hyperchloremia induced renal injury.[4] While dopamine was once the first-line agent, the 2020 SSC guideline recommend epinephrine or norepinephrine as initial vasoactive agent, depending on the patient need and clinical judgment. While choosing between epinephrine and norepinephrine; the clinical judgement plays a major role.[4] The role of intravenous steroids in inotrope-resistant shock remains unclear; the RESOLVE study found no significant difference in mortality or ventilator support between steroid and control groups.[4-6] For sepsis without shock, antibiotics should be given within 3 hour to minimize harm, though a 2020 study found no correlation between timely antibiotic administration and outcomes like mortality or PICU stay length. In case of septic shock, antibiotics are to be started within 1 hour.[4] Emerging biomarkers, such as presepsin, interleukin-6, and pro-adrenomedullin show promise for earlier and more accurate sepsis diagnosis compared to traditional markers like C- reactive protein (CRP) and procalcitonin. Additionally, rapid molecular diagnostics (e.g., polymerase chain reaction [PCR], Matrix-Assisted Laser Desorption/Ionization Time-of-Flight [MALDI-TOF] are becoming popular, emphasizing early pathogen detection and reducing unnecessary antibiotic use.[4] New therapies, including immunoglobulin therapy, cytokine adsorption, and precision immunotherapy (e.g., anakinra for hyperinflammation), are being explored to address immune dysregulation in pediatric sepsis.[4] Financial support and sponsorship Nil. Conflict of interest There are no conflict of interest.