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      Prediction of pediatric sepsis mortality within 1 h of intensive care admission

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          Abstract

          The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children.

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          Systemic inflammatory response syndrome criteria in defining severe sepsis.

          Kirsi-Maija Kaukonen, Michael Bailey, David Pilcher … (2015)
          The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach.
          Article 0 comments Cited 340 times – based on 0 reviews     Review now
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            Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial.

            B P Giroir, Eman S H Abd Allah, William L Macias … (2007)
            Drotrecogin alfa (activated) (DrotAA) is used for the treatment of adults with severe sepsis who have a high risk of dying. A phase 1b open-label study has indicated that the pharmacokinetics and pharmacodynamics of DrotAA are similar in children and adults. We initiated the RESOLVE (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE) trial to investigate the efficacy and safety of the drug in children. Children aged between 38 weeks' corrected gestational age and 17 years with sepsis-induced cardiovascular and respiratory failure were randomly assigned to receive placebo or DrotAA (24 microg/kg/h) for 96 h. We used a prospectively defined, novel primary endpoint of Composite Time to Complete Organ Failure Resolution (CTCOFR) score. Secondary endpoints were 28-day mortality, major amputations, and safety. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov, number NCT00049764. 477 patients were enrolled; 237 received placebo, and 240 DrotAA. Our results showed no significant difference between groups in CTCOFR score (p=0.72) or in 28-day mortality (placebo 17.5%; DrotAA, 17.2%; p=0.93). Although there was no difference in overall serious bleeding events during the 28-day study period (placebo 6.8%; DrotAA 6.7%; p=0.97), there were numerically more instances of CNS bleeding in the DrotAA group (11 [4.6%], vs 5 [2.1%] in placebo, p=0.13), particularly in children younger than 60 days. For CTCOFR score days 1-14, correlation coefficient was -0.016 (95% CI -0.106 to 0.74); relative risk for 28-day mortality was 1.06 (95% CI 0.66 to 1.46) for DrotAA compared with placebo. Although we did not record any efficacy of DrotAA in children with severe sepsis, serious bleeding events were similar between groups and the overall safety profile acceptable, except in children younger than 60 days. However, we gained important insights into clinical and laboratory characteristics of childhood severe sepsis, and have identified issues that need to be addressed in future trials in critically ill children.
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              Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock.

              Joseph Carcillo, Patricia I. Fields, (2002)
              The Institute of Medicine has called for the development of clinical guidelines and practice parameters to develop "best practice" and potentially improve patient outcome. To provide American College of Critical Care Medicine clinical guidelines for hemodynamic support of neonates and children with septic shock. Individual members of the Society of Critical Care Medicine with special interest in neonatal and pediatric septic shock were identified from literature review and general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (1998-2001). The MEDLINE literature database was searched with the following age-specific keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, and extracorporeal membrane oxygenation. More than 30 experts graded literature and drafted specific recommendations by using a modified Delphi method. More than 30 more experts then reviewed the compiled recommendations. The task-force chairman modified the document until <10% of experts disagreed with the recommendations. Only four randomized controlled trials in children with septic shock could be identified. None of these randomized trials led to a change in practice. Clinical practice has been based, for the most part, on physiologic experiments, case series, and cohort studies. Despite relatively low American College of Critical Care Medicine-graded evidence in the pediatric literature, outcomes in children have improved from 97% mortality in the 1960s to 60% in the 1980s and 9% mortality in 1999. U.S. hospital survival was three-fold better in children compared with adults (9% vs. 27% mortality) in 1999. Shock pathophysiology and response to therapies is age specific. For example, cardiac failure is a predominant cause of death in neonates and children, but vascular failure is a predominant cause of death in adults. Inotropes, vasodilators (children), inhaled nitric oxide (neonates), and extracorporeal membrane oxygenation can be more important contributors to survival in the pediatric populations, whereas vasopressors can be more important contributors to adult survival. American College of Critical Care Medicine adult guidelines for hemodynamic support of septic shock have little application to the management of pediatric or neonatal septic shock. Studies are required to determine whether American College of Critical Care Medicine guidelines for hemodynamic support of pediatric and neonatal septic shock will be implemented and associated with improved outcome.
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                Author and article information

                Journal
                Title: Intensive Care Medicine
                Abbreviated Title: Intensive Care Med
                Publisher: Springer Nature
                ISSN (Print): 0342-4642
                ISSN (Electronic): 1432-1238
                Publication date Created: August 2017
                Publication date (Print): February 20 2017
                Volume: 43
                Issue: 8
                Pages: 1085-1096
                Affiliations
                [1 ]On behalf of the Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group
                Article
                DOI: 10.1007/s00134-017-4701-8
                PubMed ID: 28220227
                SO-VID: 1629b6f9-eda8-4879-bad9-c79a2cb9cac1
                Copyright © © 2017
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                http://www.springer.com/tdm

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