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      Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care

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      , , , , for the Alberta Sepsis Network
      Critical Care
      BioMed Central

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          Abstract

          Introduction

          Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited.

          Methods

          The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate ( t-test and Fisher’s Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days.

          Results

          Seventy-nine children, age median 60 (IQR 22–133) months, 40 (51 %) female, 39 (49 %) with severe underlying co-morbidity, 44 (56 %) with septic shock, and median PRISM-III 10.5 [IQR 6.0-17.0] were enrolled. Most patients presented in an ED: 36 (46 %) at an outlying hospital ED, and 21 (27 %) at the Children’s Hospital ED. Most infections were pneumonia with/without empyema (42, 53 %), meningitis (11, 14 %), or bacteremia (10, 13 %). The time from presentation to acceptable antibiotic administration was a median of 115.0 [IQR 59.0-323.0] minutes; 20 (25 %) of patients received their antibiotics in the first hour from presentation. Independent predictors of PICU LOS were PRISM-III, and severe underlying co-morbidity, but not time to antibiotics. In the septic shock subgroup, the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS (effect size 0.22 days; 95 % CI 0.5, 0.38; per ml/kg). Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity. In the septic shock subgroup, volume of fluid boluses in the first 2 hours was independently associated with more ventilator days (effect size 0.09 days; 95 % CI 0.02, 0.15; per ml/kg).

          Conclusion

          Higher volume of early fluid boluses in children with sepsis and septic shock was independently associated with longer PICU LOS and ventilator days. More study on the benefits and harms of fluid bolus therapy in children are needed.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13054-015-1010-x) contains supplementary material, which is available to authorized users.

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          Most cited references22

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          Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003.

          To determine recent trends in rates of hospitalization, mortality, and hospital case fatality for severe sepsis in the United States. Trend analysis for the period from 1993 to 2003. U.S. community hospitals from the Nationwide Inpatient Sample that is a 20% stratified sample of all U.S. community hospitals. Subjects of any age with sepsis including severe sepsis who were hospitalized in the United States during the study period. None. Utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for septicemia and major organ dysfunction, we identified 8,403,766 patients with sepsis, including 2,857,476 patients with severe sepsis, who were hospitalized in the United States from 1993 to 2003. The percentage of severe sepsis cases among all sepsis cases increased continuously from 25.6% in 1993 to 43.8% in 2003 (p < .001). Age-adjusted rate of hospitalization for severe sepsis grew from 66.8 +/- 0.16 to 132.0 +/- 0.21 per 100,000 population (p < .001). Age-adjusted, population-based mortality rate within these years increased from 30.3 +/- 0.11 to 49.7 +/- 0.13 per 100,000 population (p < .001), whereas hospital case fatality rate fell from 45.8% +/- 0.17% to 37.8% +/- 0.10% (p < .001). During each study year, the rates of hospitalization, mortality, and case fatality increased with age. Hospitalization and mortality rates in males exceeded those in females, but case fatality rate was greater in females. From 1993 to 2003, age-adjusted rates for severe sepsis hospitalization and mortality increased annually by 8.2% (p < .001) and 5.6% (p < .001), respectively, whereas case fatality rate decreased by 1.4% (p < .001). The rate of severe sepsis hospitalization almost doubled during the 11-yr period studied and is considerably greater than has been previously predicted. Mortality from severe sepsis also increased significantly. However, case fatality rates decreased during the same study period.
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            Internacional pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics

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              Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome.

              Experimental and clinical studies of septic shock support the concept that early resuscitation with fluid and inotropic therapies improves survival in a time-dependent manner. The new American College of Critical Care Medicine-Pediatric Advanced Life Support (ACCM-PALS) Guidelines for hemodynamic support of newborns and children in septic shock recommend this therapeutic approach. The objective of this study was to determine whether early septic shock reversal and use of resuscitation practice consistent with the new ACCM-PALS Guidelines by community physicians is associated with improved outcome. A 9-year (January 1993-December 2001) retrospective cohort study was conducted of 91 infants and children who presented to local community hospitals with septic shock and required transport to Children's Hospital of Pittsburgh. Shock reversal (defined by return of normal systolic blood pressure and capillary refill time), resuscitation practice concurrence with ACCM-PALS Guidelines, and hospital mortality were measured. Overall, 26 (29%) patients died. Community physicians successfully achieved shock reversal in 24 (26%) patients at a median time of 75 minutes (when the transport team arrived at the patient's bedside), which was associated with 96% survival and >9-fold increased odds of survival (9.49 [1.07-83.89]). Each additional hour of persistent shock was associated with >2-fold increased odds of mortality (2.29 [1.19-4.44]). Nonsurvivors, compared with survivors, were treated with more inotropic therapies (dopamine/dobutamine [42% vs 20%] and epinephrine/norepinephrine [42% vs 6%]) but not increased fluid therapy (median volume; 32.9 mL/kg vs 20.0 mL/kg). Resuscitation practice was consistent with ACCM-PALS Guidelines in only 27 (30%) patients; however, when practice was in agreement with guideline recommendations, a lower mortality was observed (8% vs 38%). Early recognition and aggressive resuscitation of pediatric-neonatal septic shock by community physicians can save lives. Educational programs that promote ACCM-PALS recommended rapid, stepwise escalations in fluid as well as inotropic therapies may have value in improving outcomes in these children.
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                Author and article information

                Contributors
                bmvanparidon@gmail.com
                cathy.sheppard@albertahealthservices.ca
                gonzalo.guerra@albertahealthservices.ca
                780 2485435 , ari.joffe@albertahealthservices.ca
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                17 August 2015
                17 August 2015
                2015
                : 19
                : 1
                : 293
                Affiliations
                [ ]Department of Pediatrics, Sophia Childrens Hospital Erasmus University Medical Centre, Rotterdam, The Netherlands
                [ ]Faculty of Nursing, University of Alberta, Edmonton, AB Canada
                [ ]Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Alberta, Edmonton, AB Canada
                [ ]4-546 Edmonton Clinic Health Academy, 11405 87 Ave, Edmonton, AB T6G 1C9 Canada
                Article
                1010
                10.1186/s13054-015-1010-x
                4539944
                26283545
                41feeb46-b25c-47f8-830f-6ca662ce5a85
                © van Paridon et al. 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 April 2015
                : 23 July 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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