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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Victims of fire accidents who sustain both thermal injury to the skin and smoke inhalation have gross evidence of oxidant injury. Therefore, we hypothesized that delivery of vitamin E, an oxygen superoxide scavenger, directly into the airway would attenuate acute lung injury postburn and smoke inhalation. Sheep (N = 17 female, 35 +/- 5 kg) were divided into 3 groups: (1) injured, then nebulized with vitamin E (B&S, Vitamin E, n = 6); (2) injured, nebulized with saline (B&S, Saline, n = 6); and (3) not injured, not treated (Sham, n = 5). ⋯ B&S injury decreased pulmonary gas exchange (PaO2/FiO2 ratios) from 517 +/- 15 at baseline to 329 +/- 49 at 24 h and to 149 +/- 32 at 48 h compared with sham ratios of 477 +/- 14, 536 +/- 48, and 609 +/- 49, respectively. Vitamin E treatment resulted in a significant improvement of pulmonary gas exchange; ratios were 415 +/- 34 and 283 +/- 42 at 24 and 48 h, respectively. Vitamin E nebulization therapy improved the clinical responses to burn and smoke inhalation-induced acute lung injury.
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Recently, we demonstrated that mice under lethal sepsis present failure of neutrophil migration (FNM) to infectious focus, which is mediated by nitric oxide. The aims of the present study were to investigate whether FNM is also observed in severe sepsis induced by cecal ligation and puncture in rats and the effects of the prevention of nitric oxide production and of the elimination of the infectious focus through peritoneal lavage or by antimicrobial treatment on FNM and disease outcome. Rats were submitted to several septic stimuli (low, moderate, and severe) by cecal ligation and puncture. ⋯ In contrast, the antimicrobial treatment of severe septic stimulus animals with sulfamethoxazole and trimethoprim significantly improved the survival rate of the severe septic stimulus but did not re-establish neutrophil migration. However, the association of aminoguanidine plus sulfamethoxazole and trimethoprim brought about a significant increase in the survival rate and re-established neutrophil migration to infectious focus; reduced the colony-forming units in the peritoneal cavity, blood, and lung tissues; and caused an improvement in the cardiovascular performance. The results showed, for the first time, that the pharmacological prevention of FNM to the infectious focus associated with the antimicrobial therapy could be a new beneficial strategy for the treatment of sepsis syndrome.
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No pharmacologic agent has shown benefit in treating heatstroke. Previous data indicate that enhanced heat shock protein 70 (HSP-70) expression can improve survival postexperimental heatstroke. Glutamine (GLN) can enhance HSP-70 expression in other injury models. ⋯ These results also indicate that enhanced HSP-70 may have functional significance as GLN-treated animals had decreased gut permeability, plasma endotoxin, and improve survival following lethal hyperthermia. Enhanced expression of HSP-70 may be an important mechanism leading to enhanced survival via GLN. These data indicate that oral GLN may useful in prevention of mortality from heatstroke in at risk populations.
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Multiple trauma patients have an impaired immune system and thus frequently develop life-threatening septic complications. Because there is an ongoing debate on which are the most predictive immunologic parameters of clinical outcome, we prospectively studied 19 multiple trauma patients with sepsis (mean age, 38.7 +/- 15.8 years; mean Injury Severity Score, 40.6 +/- 11.6) over a period of 14 days. The following parameters were measured daily after admission to the intensive care unit: ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production, monocyte human leukocyte antigen (HLA)-DR expression, constitutive interleukin (IL) 6 secretion, white blood cell count, and C-reactive protein. ⋯ Immediately after trauma, all patients had significantly lower levels of HLA-DR and ex vivo LPS-stimulated TNF-alpha secretion than healthy controls (n = 7; P < 0.001). On the day after clinical diagnosis of sepsis, before any other parameter differed between survivors (n = 13) and nonsurvivors (n = 6), ex vivo LPS-induced TNF-alpha secretion was significantly lower (P < 0.05) in nonsurvivors than in survivors. We conclude that ex vivo LPS-induced TNF-alpha production is an earlier predictor of clinical outcome in multiple trauma patients with sepsis than monocyte HLA-DR expression, constitutive IL-6 secretion, or any other parameter assessed.
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The best strategy for volume therapy has been the focus of debate and there are still no unique accepted guidelines. There is increasing evidence that some plasma substitutes possess additional effects on organ perfusion, microcirculation, tissue oxygenation, inflammation, endothelial activation, capillary leakage, and tissue edema that are beyond their volume replacing properties. Whether the different plasma substitutes differ with regard this additional effects was reviewed. ⋯ Some important results from the literature are not reflected in the actual recommendations for treating volume deficits in the critically ill: although crystalloids have been shown to have considerable negative effects on microcirculation, organ perfusion, tissue oxygenation, and endothelial integrity, they are still often recommended as first choice volume replacement strategy. In several experimental studies hypertonic solutions have been shown to have various beneficial effects, they have not been, however, translated into humans. In future, the choice of the ideal volume replacement regimen should not only be focused on its volume restoring properties, but additional effects (e.g. on organ perfusion on, tissue oxygenation, inflammation, endothelial activation, capillary leakage) should also be taken into account when treating hypovolemia in the critically ill.