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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Previous animal and human studies have suggested that total plasma sulfide plays a role in the pathophysiology of shock. This study's aim was to determine the value of total plasma sulfide as a marker of shock severity in nonsurgical adult patients admitted to the ICU. Forty-one patients, with various types of shock (septic, cardiogenic, obstructive, and hypovolemic), were included in the study, with an average total plasma sulfide concentration of 23.2 ± 26.3 µM. ⋯ Area under the receiver operating characteristic for total plasma sulfide as a predictor of ICU mortality was 0.739 (confidence interval, 0.587-0.892; P = 0.009). Even after correcting for APACHE II score and lactate values, total plasma sulfide correlated with mortality (odds ratio, 1.058; 95% confidence interval, 1.001-1.118; P = 0.045). The study provides evidence that, in nonsurgical adult ICU patients admitted because of any type of shock, total plasma sulfide correlates with administered norepinephrine dose at admission, severity of disease (APACHE II score ≥30 points), and survival outcome.
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Sepsis is characterized by systemic inflammation with release of a large amount of inflammatory mediators. If sustained, this inflammatory response can lead to multiple organ failure and/or immunoparalysis. In the latter condition, the host may be susceptible to opportunistic infections or be unable to clear existing infections. ⋯ It also suggests that LXA4 reduced systemic inflammation and NF-κB activation without compromising host defense. Increased macrophage recruitment was in part due to a direct effect of LXA4 as LXA4 increased peritoneal macrophage recruitment in sham controls and partly due to reduced production of IL-10 as LXA4 decreased macrophage IL-10 release (a known inhibitor of macrophage migration) after CLP. The results suggest that LXA4 increased survival in sepsis by simultaneously reducing systemic inflammation as well as bacterial spread.
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Toll-like receptor 2 (TLR2) has been implicated in neutrophil and cardiac dysfunction during sepsis. Here we tested the hypothesis that nonhematopoietic (parenchymal) and hematopoietic TLR2 play distinct roles in sepsis pathogenesis. To achieve this, we generated two groups of chimeric mice with TLR2 deletions either in nonhematopoietic cells (knockout [KO] mice with wild-type [WT] bone marrow [BM]) or in BM cells (WT mice with KO-BM). ⋯ Moreover, CLP induced a robust ROS production in the peritoneal leukocytes isolated from WT mice but not from TLR2 KO mice. Taken together, these data indicate that TLR2, particularly that of nonhematopoietic cells, plays a major role in sepsis pathogenesis by impairing neutrophil migratory and phagocytic function, promoting cytokine production, and mediating cardiac contractile dysfunction during polymicrobial sepsis. Toll-like receptor 2 also mediates critical ROS production during polymicrobial sepsis.
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The purpose of this study was to evaluate the prognostic significance of classification of patients with septic shock into different critical illness-related corticosteroid insufficiency subgroups. A retrospective observational study was conducted in patients with septic shock who underwent a short corticotropin stimulation test within 72 h of the onset of shock. Patients were classified into normal adrenal function (NOM), low basal cortisol (LBC) (basal cortisol, <10 μg/dL), or low Δ cortisol (LDC) (basal cortisol, ≥10 μg/dL; cortisol, <9 μg/dL) groups. ⋯ The 28-day mortalities of the NOM, LBC, and LDC groups were 40.5%, 38.5%, and 63.2%, respectively (P = 0.007). Classification into the LDC group significantly increased the odds of 28-day mortality (odds ratio, 2.717; 95% confidence interval, 1.452-5.082; P = 0.002) and remained an independent risk factor for mortality even after controlling for all the other potential risk factors identified (odds ratio, 3.638; 95% confidence interval, 1.418-9.028; P = 0.006). Classification into the LDC group is an independent risk factor for mortality in hydrocortisone-treated septic shock patients.