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      Serum Ferritin for Predicting Outcome in Children With Severe Sepsis in the Pediatric Intensive Care Unit

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          Abstract

          Objectives

          To evaluate the prognostic ability of serum ferritin when estimated within 5 days of onset of illness in children with severe sepsis admitted to a pediatric intensive care unit.

          Methods

          This observational study enrolled children aged 1 month to 12 years with severe sepsis. Hemoglobin, serum ferritin and C-reactive protein levels were measured within five days of illness. Final outcomes were recorded in all enrolled children.

          Results

          70 children with median (IQR) age of 27 (8,108) months were enrolled during the study period (July, 2019 to August, 2021). 28 (40%) of these had poor outcome (nonsurvival). The median (IQR) level of serum ferritin was 1369 (558–5607) ng/mL in non-survivors and 282 (129–680) ng/mL in survivors ( P<0.05). A significant correlation was seen between serum ferritin and Pediatric Risk of Mortality III (PRISM III) score ( r=0.364 P=0.002) and pediatric Sequential Organ Failure Assessment (pSOFA) score ( r=0.246 P=0.04) at 48 hours of admission. 54 (77.1%) children were anemic. Serum ferritin levels in children with anemia also had a good predictive ability for poor outcome [AUC: 0.764, 95% CI: 0.634, 0.894].

          Conclusions

          Serum ferritin levels, within five days of onset of illness, predicted poor outcome in critically ill children with severe sepsis and in children with microcytic anemia.

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          Most cited references17

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          Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

          Jane C. Burns, Elfriede Pahl, Tsutomu T. Saji … (2017)
          Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries.
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            International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

            Brahm Goldstein, Brett Giroir, Adrienne G Randolph (2005)
            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. Consensus conference. 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. 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. 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.
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              Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children

              L. Nelson Sanchez-Pinto, Travis J. Matics (2017)
              This cohort study assesses the validity of a pediatric version of the Sequential Organ Failure Assessment (SOFA) scoring system compared with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) to examine the in-hospital mortality of critically ill children with confirmed or suspected infection and sepsis. Questions Is a pediatric version of the Sequential Organ Failure Assessment score valid, and can it be used to evaluate the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) in critically ill children? Findings In this large cohort study of 8711 pediatric intensive care unit encounters, the pediatric Sequential Organ Failure Assessment score demonstrated excellent discrimination for in-hospital mortality, and the Sepsis-3 definitions identified a cohort of patients with high mortality and microbiological characteristics associated with severe sepsis in prior studies. Meaning The evaluation of the Sepsis-3 definitions in children using the pediatric Sequential Organ Failure Assessment score shows promising results. Importance The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children. Objectives To adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection. Design, Setting, and Participants This retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison. Exposures Organ dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions. Main Outcomes and Measures The primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection. Results In all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range [IQR]) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course. Conclusions and Relevance The pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.
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                Author and article information

                Contributors
                Jaikumar Govindaswamy Ramamoorthy: gr_jaikumar@yahoo.in
                Journal
                Journal ID (nlm-ta): Indian Pediatr
                Journal ID (iso-abbrev): Indian Pediatr
                Title: Indian Pediatrics
                Publisher: Springer India (New Delhi )
                ISSN (Print): 0019-6061
                ISSN (Electronic): 0974-7559
                Publication date (Electronic): 29 December 2022
                Publication date (Print): 2022
                Volume: 59
                Issue: 12
                Pages: 939-942
                Affiliations
                [1 ]GRID grid.414953.e, ISNI 0000000417678301, Department of Pediatrics, , Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), ; Puducherry, India 605 006
                [2 ]GRID grid.414953.e, ISNI 0000000417678301, Department of Biochemistry, , Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), ; Puducherry, India
                Article
                Publisher ID: 2668
                DOI: 10.1007/s13312-022-2668-1
                PMC ID: 9798957
                PubMed ID: 36511209
                SO-VID: 94d6697f-2deb-453d-85df-1f3ea9bec8a9
                Copyright © © Indian Academy of Pediatrics 2022
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 31 May 2022
                Date revision received : 10 July 2022
                Date accepted : 12 November 2022
                Categories
                Subject: Research Paper
                Custom metadata
                issue-copyright-statement © Indian Academy of Pediatrics 2022

                Keywords: anemia,c-reactive protein,infection,mortality
                Data availability:
                Keywords: anemia, c-reactive protein, infection, mortality

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