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      Inflammation, Myocardial Dysfunction, and Mortality in Children With Septic Shock: An Observational Study

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          Abstract

          We aimed to investigate whether nuclear factor kappa-B activation, as evaluated by gene expression of its inhibitor (I-κBα) and cytokine serum levels, was associated with myocardial dysfunction and mortality in children with septic shock. Twenty children with septic shock were prospectively enrolled and grouped according to ejection fraction (EF) <45 % (group 1) or EF ≥45 % (group 2) on the first day after admission to the pediatric intensive care unit. No interventions were made. In the first day, patients from group 1 ( n = 6) exhibited significantly greater tumor necrosis factor- alpha (TNF-α) and interleukin (IL)-10 plasma levels. However, I-κBα gene expression was not different in both groups. Mortality and number of complications were significantly greater in group 1. Patients who died had greater plasma concentrations of TNF-α. In conclusion, TNF-α and IL-10 are involved in myocardial dysfunction accompanying septic shock in children, and TNF-α is associated with mortality.

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          Pathogenetic mechanisms of septic shock.

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            Hemodynamic support in fluid-refractory pediatric septic shock.

            Assess outcome in children treated with inotrope, vasopressor, and/or vasodilator therapy for reversal of fluid-refractory and persistent septic shock. Survey; case series. Three pediatric hospitals. Fifty consecutive patients with fluid-refractory septic shock with a pulmonary artery catheter within 6 hours of resuscitation. Patients were categorized according to hemodynamic state and use of inotrope, vasopressor, and/or vasodilator therapy to maintain cardiac index (CI) >3.3 L/min/m2 and systemic vascular resistance >800 dyne-sec/cm/m to reverse shock. Hemodynamic state, response to class of cardiovascular therapy, and mortality. After fluid resuscitation, 58% of the children had a low CI and responded to inotropic therapy with or without a vasodilator (group I), 20% had a high CI and low systemic vascular resistance and responded to vasopressor therapy alone (group II), and 22% had both vascular and cardiac dysfunction and responded to combined vasopressor and inotropic therapy (group III). Shock persisted in 36% of the children. Of the children in group I, 50% needed the addition of a vasodilator, and in group II, 50% of children needed the addition of an inotrope for evolving myocardial dysfunction. Four children showed a complete change in hemodynamic state and responded to a switch from inotrope to vasopressor therapy or vice versa. The overall 28-day survival rate was 80% (group I, 72%; group II, 90%; group III, 91%). Unlike adults, children with fluid-refractory shock are frequently hypodynamic and respond to inotrope and vasodilator therapy. Because hemodynamic states are heterogeneous and change with time, an incorrect cardiovascular therapeutic regimen should be suspected in any child with persistent shock. Outcome can be improved compared with historical literature.
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              Predictive value of nuclear factor kappaB activity and plasma cytokine levels in patients with sepsis.

              The relationship between fluctuating cytokine concentrations in plasma and the outcome of sepsis is complex. We postulated that early measurement of the activation of nuclear factor kappaB (NF-kappaB), a transcriptional regulatory protein involved in proinflammatory cytokine expression, may help to predict the outcome of sepsis. We determined NF-kappaB activation in peripheral blood mononuclear cells of 34 patients with severe sepsis (23 survivors and 11 nonsurvivors) and serial concentrations of inflammatory cytokines (interleukin-6, interleukin-1, and tumor necrosis factor) and various endogenous antagonists in plasma. NF-kappaB activity was significantly higher in nonsurvivors and correlated strongly with the severity of illness (APACHE II score), although neither was related to the cytokine levels. Apart from NF-kappaB activity, the interleukin-1 receptor antagonist was the only cytokine tested whose level in plasma was of value in predicting mortality by logistic regression analysis. These results underscore the prognostic value of early measurement of NF-kappaB activity in patients with severe sepsis.
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                Author and article information

                Contributors
                +5516-3602-2477 , +5516-3602-2700 , carmona@fmrp.usp.br
                Journal
                Pediatr Cardiol
                Pediatr Cardiol
                Pediatric Cardiology
                Springer US (New York )
                0172-0643
                1432-1971
                4 October 2013
                2014
                : 35
                : 3
                : 463-470
                Affiliations
                GRID grid.11899.38, ISNI 0000000419370722, Ribeirao Preto Medical School, , University of Sao Paulo, ; Avenida dos Bandeirantes 3900, Ribeirao Preto, SP 14049-900 Brazil
                Article
                801
                10.1007/s00246-013-0801-6
                7100657
                24091885
                480c036f-57e7-4f25-9f5b-79ac8faecd48
                © Springer Science+Business Media New York 2013

                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
                : 24 June 2013
                : 14 September 2013
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media New York 2014

                Cardiovascular Medicine
                sepsis,echocardiography,nuclear factor kappa-b,pediatric critical care
                Cardiovascular Medicine
                sepsis, echocardiography, nuclear factor kappa-b, pediatric critical care

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