Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis

Tonial, Cristian Tedesco; García, Pedro Celiny Ramos; Schweitzer, Louise Cardoso; Costa, Caroline Abud Drumond; Bruno, Francisco; Fiori, Humberto Holmer; Einloft, Paulo Roberto; Garcia, Ricardo Branco; Piva, Jefferson Pedro

doi:10.1016/j.jpedp.2017.02.002

Cited by 11 publications

(15 citation statements)

References 22 publications

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“…5 In a separate cohort of children with sepsis, hyperferritinemia was associated with disease severity, including longer hospital LOS, longer intensive care unit LOS, fewer mechanical ventilation-free hours, higher inotrope score, and higher Pediatric Index of Mortality 2 score. 10 Bennett et al demonstrated that children with ferritin greater than 3000 ng/mL were significantly more likely to receive critical care and suffer mortality during hospitalization compared with children with ferritin between 1000 and 3000 ng/mL. 6 Though the mechanistic underpinnings of ferritin's role in severe disease have not been entirely elucidated, a "Hyperferritinemic Syndrome" has been proposed, implicating ferritin as part of the pathogenic mechanisms underlying systemic inflammatory response triggered by a number of pathways.…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein and Ferritin Are Associated With Organ Dysfunction and Mortality in Hospitalized Children

Horvat

Bell

Kantawala

et al. 2019

Clin Pediatr (Phila)

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Our objective was to determine if C-reactive protein (CRP) and ferritin values alone and in combination are associated with mortality among hospitalized children. All hospitalized patients at our institution with a CRP or ferritin assay in 2015 and 2016 were included. Area under the receiver operating curves (AUROC) were examined, optimal cut-points determined, and patients were stratified into low-, intermediate-, or high-risk groups based on elevation of zero, one, or both biomarkers. A total of 14 928 CRP and 653 ferritin values were obtained, with both obtained for 172 patients. AUROC for maximum CRP value was 0.76 (0.68-0.85) with a cut-point of 7.1 mg/dL for in-hospital mortality and 0.90 (0.83-0.98) for maximum ferritin with a cut-point of 373 ng/mL. Elevation of both ferritin and CRP was associated with the highest inpatient mortality (21.7%) and greatest organ dysfunction, followed by either biomarker alone. Additional prospective study of these biomarkers in combination is warranted.

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Section: Discussionmentioning

confidence: 99%

C-Reactive Protein and Ferritin Are Associated With Organ Dysfunction and Mortality in Hospitalized Children

Horvat

Bell

Kantawala

et al. 2019

Clin Pediatr (Phila)

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“…Hyperferritinemia, regardless of the underlying pathology, is associated with high mortality (74)(75)(76). As a marker of significant macrophage activation, individuals manifesting a hyperferritinemic phenotype show a typical pattern of reticuloendothelial system activation and multiple organ dysfunction (74)(75)(76)(77)(78)(79)(80). This phenotype is classically described in primary or familial hemophagocytic lymphohistiocytosis (FHLH), a recessive genetic disorder of excessive macrophage activation driven by IFN-γ that results from an inability to clear pathogen subsequent to inherited defects of CTL and NK cell-mediated cytolytic killing.…”

Section: Ferritin In Inflammatory Human Diseasementioning

confidence: 99%

Hyperferritinemia and inflammation

Kernan

Carcillo

2017

International Immunology

498

407

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Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an 'innocent bystander' biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.

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“…Since the first description by Garcia et al (12), association between ferritin and poor outcome in children with septic shock has generated great interest among intensivists and clinicians. Studies relating ferritin to various aspects of pediatric sepsis have been published (13)(14)(15)(16). Though many centers have now routinely started using ferritin as a marker of severity of illness and in diagnosing infection associated hemophagocytic lymphohistiocytosis (Ia-HLH), there is scarcity of information on this topic in children with tropical infections.…”

Section: Introductionmentioning

confidence: 99%

Serum Ferritin Predicts Neither Organ Dysfunction Nor Mortality in Pediatric Sepsis Due to Tropical Infections

et al. 2020

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Objective: To evaluate serial ferritin levels measured in the initial 72 h of admission as a biomarker for new and progressive multi organ dysfunction syndrome (NPMODS) and mortality (unfavorable outcomes) in critically ill children with sepsis due to tropical infections.Material and Methods: In this prospective observational study from a tertiary care teaching hospital in India, children 3 month to 12 years with a diagnosis of acute febrile illness and any two features suggesting tropical infections [cytopenia (platelet count <1,00,000/cu.mm, total leucocyte count <4,000/cu.mm), hepatomegaly and/or splenomegaly, lymphadenopathy, systemic signs (rash, edema), respiratory distress, and encephalopathy not accounted by localized infection] were eligible for inclusion. Children with known or suspected disorder of iron metabolism were excluded. Primary outcome was to determine the association of serial ferritin levels with mortality and NPMODS. Secondary outcomes included estimation of the prevalence of hyperferritinemia and comparison of risk prediction scores with serial ferritin measurement in predicting unfavorable outcomes.Measurements and Main Results: In the 202 children enrolled, diagnosis could be established in 133 (65.8%) children. Scrub typhus and dengue were the most common infections. Median (IQR) ferritin measured at admission (n = 183) and on day 3 (n = 120) of hospital stay were 798 (378, 3,205) μg/L and 429 (213,680) μg/L, respectively. Majority (n = 180, 89.1%) had MODS at admission defined as per International pediatric sepsis consensus conference. NPMODS occurred in 47 (23.3%) children of whom 37 (18.3%) died. Children with three or less organ dysfunctions had lower mortality. Neither admission ferritin values nor the percentage change over 72 h was different between children with favorable and unfavorable outcomes. Pediatric Risk of Mortality (PRISM-III) and daily Pediatric Logistic Organ Dysfunction score (dPELOD2 score) were significantly different in those with unfavorable outcomes. Admission ferritin levels and percentage change in 72 h had poor discriminatory power for mortality with AUC of 0.53 (0.53, 0.67) and 0.50 (0.50, 0.64), respectively. dPELOD2 had the best discriminatory power for mortality with AUC of 0.89 (0.89, 0.95).Conclusions: Serial ferritin estimation predicted neither organ dysfunction nor mortality in pediatric sepsis with tropical infections. dPELOD-2 and PRISM-III predicted unfavorable outcomes better than ferritin. The current diagnostic criteria for MODS overestimated organ dysfunctions in tropical infections and hence may need modification with further validation in this epidemiological cohort.

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Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis

Cited by 11 publications

References 22 publications

C-Reactive Protein and Ferritin Are Associated With Organ Dysfunction and Mortality in Hospitalized Children

C-Reactive Protein and Ferritin Are Associated With Organ Dysfunction and Mortality in Hospitalized Children

Hyperferritinemia and inflammation

Serum Ferritin Predicts Neither Organ Dysfunction Nor Mortality in Pediatric Sepsis Due to Tropical Infections

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