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Long-term mortality in pediatric sepsis: a systematic review and meta-analysis.

BACKGROUND: Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols. METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software. RESULTS: A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I2 = 98.2%, p&#x2009;<&#x2009;0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited. CONCLUSION: Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.

Humans↗

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

OBJECTIVE: Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. DESIGN: Consensus conference. METHODS: This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. RESULTS: Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. CONCLUSION: We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.

Adolescent↗

Advances in the emergency management of pediatric sepsis.

PURPOSE OF REVIEW: Sepsis requires prompt recognition and aggressive therapy; early goal-directed therapy decreases morbidity and mortality. Recommendations on the specific management of pediatric sepsis have historically been extrapolated from adult literature and from expert/consensus opinion. This review serves to appraise recent recommendations and determine the applicability of newly promoted adult guidelines for pediatric sepsis. RECENT FINDINGS: The first and most recent recommendations on the management of pediatric sepsis were published in 2002 by expert consensus with the recognition that there were few data from randomized controlled trials or meta-analysis. Previous to this, adult guidelines were used in the management of pediatric sepsis. New definitions for pediatric sepsis provided by expert consensus take into account the specific physiologic changes. Prompt correction of hemodynamic derangements has been shown to improve outcome through aggressive volume resuscitation and early initiation of vasopressor therapy. Frequent reassessment has been emphasized to ensure appropriate management. SUMMARY: Prompt recognition, institution of appropriate therapy, and continual assessment for children with sepsis and shock are essential for improved outcomes. The emerging new literature on early goal-directed therapy is most applicable to care in the emergency department.

Anti-Bacterial Agents↗

Scope and epidemiology of pediatric sepsis.

OBJECTIVE: To summarize the scope and epidemiology of pediatric sepsis. DESIGN: Review of published literature. RESULTS: Sepsis is a leading cause of death in infants and children, with >42,000 cases of severe sepsis annually in the United States and millions worldwide. Half of the children with severe sepsis in the United States are infants, and half of infants are low- or very low-birth-weight babies. Underlying disease occurs in 49% of U.S. children with severe sepsis. National hospital costs associated with severe sepsis in the United States were $2.3 billion in 1999. Relatively simple strategies to identify and treat children with sepsis in the developing world have shown remarkable success. These strategies have included empirical antibiotics in babies at high risk of sepsis and aggressive fluid resuscitation in Dengue hemorrhagic fever. CONCLUSIONS: Sepsis is a major health problem among children in both developing and industrialized countries. However, sepsis is both preventable and treatable. Improved prevention and treatment of sepsis could have a substantial effect on survival and quality of life of all children, both those who are otherwise healthy and those who are chronically ill. The variations in the epidemiology of pediatric sepsis underscore the need for a multidisciplinary approach and consistently applied definitions.

Adolescent↗

Inflammatory cytokine and nitric oxide responses in pediatric sepsis and organ failure.

OBJECTIVE: To examine the relationship of circulating proinflammatory and anti-inflammatory cytokine concentrations to nitric oxide and organ failure in pediatric sepsis. DESIGN: Prospective study. SETTING: Pediatric intensive care unit (ICU), children's Hospital of Pittsburgh, University of Pittsburgh. PATIENTS: Nineteen patients with a diagnosis of sepsis admitted to the pediatric ICU. Twelve uninfected critically iII patients served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin (IL)-10, IL-6, and nitrite/nitrate concentrations were measured and compared with an index of organ failure daily for 3 days after presentation with the sepsis syndrome. Children with increased plasma IL-6 concentrations (n = 6) had increased plasma nitrite/nitrate concentrations (p < 0.01 on each day), increased organ failure scores (p < .05 on days 1 and 3), and the highest plasma IL-10 concentrations (p < .05 on days 1 and 3, p = .054 on day 2) when compared with children with sepsis and undetectable IL-6 concentrations. Children with sepsis and detectable IL-6 concentrations, and children with undetectable IL-6 concentrations, both had increased nitrite/nitrate concentrations (p < .005 on days 1 through 3) and increased IL-10 concentrations (p < .05 on days 1 and 2) compared with controls. Children with increased IL-6 concentrations had higher organ failure on each day (p < .01), and children with undetectable IL-6 concentrations had higher organ failure on days 1 and 2 only (p < .005) when compared with controls. Organ failure improved over time in the children with undetectable IL-6 concentrations (p < .005). CONCLUSIONS: Increased plasma nitrite/nitrates and increased organ failure scores occurred in the children with sepsis who had an exaggerated proinflammatory state, despite a pronounced anti-inflammatory response. When the anti-inflammatory response predominated and the proinflammatory state was dampened, organ failure status improved.

Adolescent↗

Pediatric sepsis definitions: past, present, and future.

OBJECTIVE: To review the past, present, and future definitions of sepsis and the systemic inflammatory response syndrome in children. METHODS: Review of the literature. RESULTS: The history and development of the adult-derived sepsis syndrome and its application to pediatric-specific sepsis definitions is provided. Initially, only adult definitions were applied to pediatric studies. Recently, pediatric-specific definitions have been published. The pediatric consensus conference-derived definitions for systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock are summarized, and their limitations are discussed. CONCLUSIONS: The potential value and inconsistencies of the current pediatric-specific sepsis definitions are discussed. Future direction of the definitions and their applications are presented.

Child↗

Plasma nitrite and nitrate concentrations and multiple organ failure in pediatric sepsis.

OBJECTIVE: To determine whether plasma nitrite and nitrate concentrations are associated with the development of sepsis-induced multiple organ failure. DESIGN: Prospective study. SETTING: University children's hospital. PATIENTS: Fifty-three consecutive children meeting criteria for sepsis and not receiving exogenous sources of nitric oxide. INTERVENTIONS: Plasma nitrite and nitrate concentrations were measured, and the number of organs failing was scored using an organ failure index on the first 3 days of sepsis. MEASUREMENTS AND MAIN RESULTS: Children with three or more organs failing on day 3 of sepsis had higher plasma nitrite and nitrate concentrations than children who had resolution of failure of three or more organs by day 3 of sepsis (days 2 and 3) and children who never had three organs failing in the first 3 days of sepsis (days 1, 2, and 3). Children who developed sequential pulmonary/hepatic/renal organ failure had significantly higher plasma nitrite and nitrate concentrations (days 1, 2, and 3). Nonsurvivors had significantly higher plasma nitrite and nitrate concentrations (days 2 and 3) than survivors. Plasma nitrite and nitrate concentrations on day 1 predicted the development of persistent failure of three of more organs and sequential multiple organ failure but not mortality. CONCLUSION: Increased plasma nitrite and nitrate concentrations are associated with the development of multiple organ failure in pediatric sepsis.

Adolescent↗

Elevated interleukin-1 receptor antagonist levels in pediatric sepsis syndrome.

OBJECTIVE: To measure plasma levels of interleukin-1 beta, interleukin-1 receptor antagonist (IL-Ira), and tumor necrosis factor alpha in children with sepsis syndrome. STUDY DESIGN: A prospective, observational study of 14 patients aged 5 months to 13 years with sepsis syndrome admitted to a pediatric intensive care unit. Cytokine levels were measured by enzyme-linked immunosorbent assay at baseline and at a 12, 24, and 48 hours and compared with the levels of 21 age-matched control subjects. RESULTS: The mean pediatric risk of mortality score was 16.1. Bacterial and viral sepsis was confirmed in five and three patients, respectively. Compared with the levels in the control subjects (mean level of IL-Ira: 654 pg/ml), the IL-Ira levels were elevated in the septic patients, with mean values of 17855 (p < 0.001), 12771 (p < 0.001), 9182 (p < 0.01), and 2296 pg/ml (p = not significant) at baseline and at 12, 24, and 48 hours, respectively. The IL-Ira level was greater than 1000-fold higher than the IL-1 beta level at all time points in 13 of 14 septic patients. CONCLUSIONS: At the time of hospital admission, circulating IL-Ira levels in a cohort of children with sepsis syndrome were at concentrations known to block IL-1 receptors. Thus additional benefit from exogenous IL-Ira therapy would be questionable. Further studies are indicated to determine whether there is a population of patients with sepsis who could benefit from administration of exogenous IL-Ira.

Adenoviridae↗

Pediatric sepsis: the infection unto death.

A significant percentage of pediatric patients admitted to an ICU have an infectious disease process. Many infants and children go on to develop sepsis, a major cause of death in the intensive care unit. Caring for these children presents a collaborative challenge because of the multifactorial etiology and the complicated pathophysiology. This article focuses on the specific implications of sepsis for infants and children.

Blood Gas Analysis↗

Pediatric sepsis and multiple organ dysfunction syndrome.

Systemic inflammatory response syndrome may be viewed as the systemic expression of cytokine signals that normally function on an autocrine or paracrine level. Sepsis is defined as systemic inflammatory response syndrome caused by an infection. Multiple organ dysfunction syndrome may represent the end stage of severe systemic inflammatory response syndrome or sepsis. Many cells are involved, including endothelial cells and leukocytes and multiple proinflammatory and antiinflammatory mediators (cytokines, oxygen free radicals, coagulation factors, and so forth). Various pathophysiologic mechanisms have been postulated. The most popular theory is that the inflammatory process loses its autoregulatory capacity; however, microcirculatory dysregulation and apoptosis may also be important, and a new paradigm posits a complex nonlinear system. Many new treatments have been studied recently. The usefulness of immune modulating diets remains to be evaluated. Molecular immunomodulation is still of unclear value. The therapy of sepsis and multiple organ dysfunction syndrome remains mainly supportive.

Adjuvants, Immunologic↗

False negative bone scans in pediatric sepsis of the axial skeleton.

The early diagnosis of disk space infections and sacroiliitis in children can be difficult because of protean presenting symptoms, nonspecific laboratory studies, and normal plain films. Technetium phosphate scintigraphy has been reported as a diagnostic method with an accuracy of up to 100% in some series. In this case report we present two patients with negative technetium bone scans in the face of active infection, illustrating the need to pursue the diagnosis using other modalities.

Discitis↗