Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Resuscitation from hemorrhagic shock (50% of blood volume, BV) followed by continuous bleeding (20% of BV per hour, over the entire observation time, 90 min) was studied in the unanesthetized hamster chamber window model. Blood losses equaled 100% of total BV. A single volume infusion (resuscitation) was performed 60 min after hemorrhage using 25% of the BV with 10% hydroxyethyl starch (HES 200, group HES4), or a mixture of HES 200 with 0.3% or 0.6% (w/v) alginate (groups HES7 and HES10, respectively) leading to solutions with a uniform colloidal oncotic pressure (84-87 mmHg) and viscosities ranging from 3.8 to 9.8 cp. ⋯ All microvascular parameters 90 min after resuscitation with low viscosity fell back to the shock level. Improved recovery obtained with a hyperviscous plasma expander was related to microcirculation shear stress preservation, leading to improve blood flow by lowering peripheral vascular resistance when compared with low viscosity resuscitation. These findings suggest the possibility of using hyperviscous plasma expanders to prolong the period for initial treatment of blood losses and definitive institution therapy.
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Patients with septic shock often display features of T cell hyporesponsiveness and immune suppression, which, if persistent, are associated with increased mortality. In the murine cecal ligation and puncture (CLP) model of sepsis, we previously reported that early treatment with the anti-inflammatory cytokine interleukin 10 (IL-10) delays the onset of irreversible shock, defined as the time at which rescue surgery to remove the necrotic cecum is no longer effective. Because IL-10 can be immunostimulatory for T cells, we hypothesized that in the CLP model, late IL-10 treatment after removal of the infectious nidus at the onset of irreversible shock would restore T cell responsiveness and increase survival. ⋯ By 25 h after intervention, only the dual treatment group of cecal removal and IL-10 exhibited T cell responsiveness that was similar to pre-CLP levels (P = 0.26) and had a 7-day survival of 90% (P < or = 0.002 compared with all other groups). Thus, even in the advanced stages of septic shock when standard therapies fail, treatment with IL-10 extends the therapeutic window. For an individual mouse, the efficacy of such treatment may be predicted by an early postintervention IL-6 level.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis.
Despite recent advances in the prospective identification of the patient with sepsis who may benefit from anti-inflammatory or antithrombotic therapies, successful treatment regimens have been fairly modest. We have explored whether determination of several proinflammatory cytokine or mediator concentrations can complement physiologic scoring systems to identify patients with severe sepsis who will survive or expire within 28 days. The design of the study included an exploratory analysis performed in conjunction with a prospective, randomized, double-blind, placebo-controlled, multicenter, clinical trial and involved 33 academic institutions in the United States. ⋯ Selected baseline proinflammatory cytokine concentrations and APACHE II score were correlated (P < 0.01). IL-6 concentration is a strong candidate for predicting clinical outcome in patients with severe sepsis alone, or when combined with the APACHE II or MOD scores. The potential usefulness of the combination of cytokine measurements and prognostic scores to identify patients who may benefit from treatment with anti-inflammatory or antithrombotic therapies should be further evaluated.
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Randomized Controlled Trial Clinical Trial
Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.
We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). ⋯ After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This strategy also significantly reduced the extent of third space fluid losses while also having a favorable impact on the intravascular volume status as evidenced by the improved urine output.
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Several studies have noted gender differences in adult mortality related to thermal injury, however, little is published on gender-related outcomes of burn patients 17 years of age or less. The aim of this study was to evaluate the relationships between mortality, gender, prepubertal and during puberty, ethnic origin, and age, with or without identified sepsis in severely burned children. Seven hundred forty-seven children admitted to our burn hospital from March 1985 to January 2005 with burns greater than 40% total body surface area were studied. ⋯ Nearly 60% of the male nonsurvivors and 48% of the female nonsurvivors in this study had identifiable sepsis at postmortem. The mortality rate was higher in infants and toddlers, age 0 to 2.9 years, compared with children and adolescents, age 3 to 17 years; however, there was no significant difference in rate of mortality between genders, prepuberty versus puberty, those with septic episodes, or ethnic origin. Burn mortality among infants and toddlers, children, and adolescents with greater than 40% total body surface area burns with or without identified sepsis could not be shown to be gender or ethnic origin dependent.