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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The reduction of neutrophil migration to an infectious focus is associated with a high mortality in severe sepsis. Previously, we showed that heme oxygenase (HO) products downregulate neutrophil recruitment in a noninfectious inflammatory model. The present study was designed to determine the role of HO in sepsis induced by cecal ligation and puncture (CLP) model. ⋯ Furthermore, hemin resulted in a reduction of neutrophil migration both in vivo and in vitro. Altogether, our results demonstrated that pretreatment with the HO inhibitor prevents the pathological findings in severe CLP. However, the combination of pretreatment plus posttreatment with ZnPP IX enhances sepsis severity because of an increase in circulating levels of heme, which is deleterious to the host tissues and also inhibits neutrophil migration.
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This prospective study was aimed to test the hypothesis that tissue hemoglobin oxygen saturation (StO₂) measured noninvasively using near-infrared spectroscopy is a reliable indicator of global oxygen delivery (DO₂) measured invasively using a pulmonary artery catheter (PAC) in patients with septic shock. The study setting was a 26-bed medical-surgical intensive care unit at a university hospital. Subjects were adult patients in septic shock who required PAC hemodynamic monitoring for resuscitation. ⋯ A StO₂ cutoff value of 75% predicted iDO₂ below 450, with a sensitivity of 0.9 and a specificity of 0.9. In patients in septic shock and normalized MAP, low StO₂ reflects extremely low iDO₂. Steady-state StO₂ does not correlate with moderately low iDO₂, indicating poor sensitivity of StO₂ to rule out hypoperfusion.
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Oxidative stress, a situation with increased reactive oxygen species production and/or decreased antioxidant defense mechanisms, is evident in the pathogenesis of sepsis. Peroxiredoxin 4 (Prx4) is a hydrogen peroxide degrading peroxidase recently found circulating in blood of septic patients and potentially reflecting an antioxidant system in imbalance. We studied Prx4 serum levels of 79 consecutively enrolled medical intensive care unit patients. ⋯ In this study, elevated serum levels of the antioxidant Prx4 were associated with an increased disease severity and adverse outcome of critically ill patients with sepsis. Peroxiredoxin 4 may therefore be a helpful new biomarker for diagnosing, monitoring, and risk assessing these patients. The pathophysiological mechanisms behind the observed increase remain to be elucidated.
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Midkine, a multifunctional cytokine, in patients with severe sepsis and septic shock: a pilot study.
The objective of the study was to evaluate whether severe sepsis and septic shock are related to alterations in midkine concentrations, to identify disease-related factors associated with these alterations, and to initially appraise whether midkine might serve as a biomarker in sepsis. Prospective observational cross-sectional study with 5-day follow-up. Circulating midkine was measured (enzyme-linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory response syndrome [SIRS]) patients, and 87 healthy subjects. ⋯ In conclusion, sepsis and septic shock are associated with midkine elevation, substantially more pronounced than in inflammation, even systemic, revealing a new potential mediator of deregulation of neutrophil migration. Sepsis-related global hypoxia seems to contribute to midkine elevation. Our results substantiate further research on possible midkine application as a sepsis biomarker: in differentiating SIRS from sepsis and identifying gram-positive sepsis and septic patients at risk of CVI and shock.