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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Therapeutic goals for hemorrhagic shock resuscitation are the increase of cardiac output and oxygen delivery. The possibility exists that because of microcirculatory effects, different volume expanders result in different tissue oxygen delivery and oxygen use. In a rabbit model of resuscitation from hemorrhagic shock (50% blood loss), we compared the effects of an hemoglobin-based O2-carrying solution (HbOC) with those elicited by albumin, hydroxyethyl starch (HES), or saline on systemic hemodynamics, skeletal muscle O2 pressure (PtiO2), and interstitial concentration of lactate (LACi) through the combined implantation of a microdialysis probe and a sensitive O2 electrode into the hind limb. ⋯ Tissue oxygen use as estimated by LACi increased transiently at the beginning of volume expansion with similar maximum values. Animals resuscitated with saline had significantly higher LACi concentrations after the onset of volume expansion as compared with HbOC but not with colloids. Our results demonstrate that there are measurable differences in MAP and BF upon resuscitation with the four different solutions and there is a slower increase in tissue PtiO2 with saline than with colloids associated with significantly increased LACi consistent with delayed reoxygenation upon resuscitation with saline.
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It has been demonstrated that lipopolysaccharide (LPS)-induced cytokine response in patients with sepsis differ from the normal host, yet this has not been controlled for the presence of underlying disease. We studied the ability of LPS and killed gram-negative bacteria (GNB) to induce tumor necrosis factor (TNF)-alpha and interleukin (IL) 10, and of phytohemagglutinin (PHA) to induce interferon (IFN)-gamma, in whole blood from patients with sepsis (SP, n = 20), patients with matched underlying disease and without sepsis (control patients, n = 20), and healthy volunteers (HV, n = 20). LPS-induced TNF-alpha production was lower in SP (median = 638 pg/mL) compared with control patients (4060 pg/mL; P= 0.003), and control patients production was lower compared with HV (5329 pg/mL; P < 0.001). ⋯ IL-10 production was not different among the three groups. Down-regulation of TNF-alpha production in patients with sepsis, although not restricted to them, was more pronounced with LPS than with GNB. Although the presence of underlying disease may be involved in the regulatory mechanisms of host response, the use of controls with matched underlying diseases provides strong evidence for the septic condition in the down-regulation of inflammatory response in patients with sepsis.
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Previous studies have demonstrated sepsis-specific changes in the transcription of key hepatic genes. However, the role of hepatic transcription factors in sepsis-associated organ dysfunction has not been well established. We hypothesize that the binding activities of C/EBPalpha and beta, HNF-1alpha, and HNF-3 transiently decrease during mild sepsis but persistently decrease after fulminant sepsis, and that the decrease in this binding activity correlates in time and severity with previously described decreases in the transcription of key hepatic genes. ⋯ Furthermore, the loss of activity after 2CLP correlated in time with outcome. Sepsis decreases DNA binding activities of C/EBPalpha and HNF-1alpha, two key hepatocyte transcription factors, in a time course consistent with down-regulation of their target hepatic genes. Therefore, alterations in transcription factor binding are likely important in the transcriptional modulation that is characteristic of hepatic dysfunction in sepsis.
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The prognostic value of basal and corticotropin-stimulated cortisol concentration in patients with sepsis remains a controversial issue. In a retrospective cohort study, 82 consecutive patients with septic shock underwent a short corticotropin test performed more than 24 h after the onset of vasopressor therapy. Forty-one (50%) patients died within 28 days after the onset of septic shock. ⋯ On multivariate analysis, a cortisol level >20 microg/dL (P = 0.0002), a maximal response to corticotropin <9 microg/dL (P = 0.044), abnormal lactate values (P = 0.0098), and positive blood cultures (P = 0.004) were independent predictors of 28-day mortality. In conclusion, high basal cortisol and low increase on corticotropin stimulation are predictors of a poor outcome in late septic shock. The underlying mechanisms of these prognostic patterns remain to be elucidated.