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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Randomized Controlled Trial Multicenter Study Clinical Trial
Prospectively validated prediction of organ failure and hypotension in patients with septic shock: the Systemic Mediator Associated Response Test (SMART).
Conventional outcomes research provides only percentage risk categories that are not applicable to individual patients, and it predicts only mortality, utilization of resources and/or broad groupings of multiple organ system dysfunction. The purpose of the present study was to determine whether or not the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic parameters, standard hospital laboratory tests, and circulating cytokine concentrations to predict continuous and dichotomous dependent clinical variables, in advance, in individual patients with septic shock and to integrate these into prospectively validated models. Two hundred forty (240) patients with septic shock who were entered into the placebo arm of a multi-institutional clinical trial were randomly separated into a model building training cohort (n = 154) and a predictive cohort (n = 86), which was used to prospectively validate the prognostic models built upon the training cohort database. ⋯ For hematologic/coagulation models, 37/56 (66%) up to seven days had r > 0.900. Among dichotomous models, ROC AUC > 0.700 was achieved in 30/49 (61%) during the first week. SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with septic shock.
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To test the effects of prostaglandin E1 on 2.5 h of ischemia followed by 2 h of reperfusion, continuous nitric oxide measurements (electrochemical) were correlated with intermittent assays of superoxide and peroxynitrite levels (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus muscle. Administering prostaglandin E1 (1 microg/kg) before or during ischemia/reperfusion caused normalization of the release of nitric oxide, superoxide, and peroxynitrite to slightly above preischemic levels. This pattern was dramatically different from that observed during ischemia/reperfusion alone, where nitric oxide concentration increased three times above its basal level. ⋯ Prostaglandin E1 treatment does not directly inhibit constitutive nitric oxide synthase, like the inhibitor N(omega)-monomethyl-L-arginine. Some phenomenon associated with ischemia turns on endothelial constitutive nitric oxide synthase to start transforming L-arginine and oxygen into nitric oxide, but prostaglandin E1 seems to inhibit this phenomenon. Thus, essential local L-arginine pools are not depleted, and normal basal levels of essential nitric oxide are maintained, whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient constitutive nitric oxide synthase is prevented.
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This study was undertaken to examine the role of lactate on cardiac function and metabolism after severe acute hemorrhagic shock. Anesthetized, nonheparinized rats were bled to a mean arterial pressure of 25-30 mm Hg for 1 h; controls were not bled. Their hearts were removed, and cardiac work and efficiency (work/oxygen consumption) were measured in the isolated working heart mode for 60 min. ⋯ Compared to control hearts, shocked hearts exhibited a 20-30% decrease in PDH activity. Shocked hearts perfused with lactate demonstrated no increase in acetyl CoA content but did have a significant increase in tissue succinyl CoA compared to control hearts perfused with lactate or shocked hearts perfused without lactate. In the heart recovering from severe hemorrhagic shock, lactate improves cardiac efficiency in the presence of free fatty acids, possibly by a anaplerosis of the tricarboxylic acid cycle.
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We have demonstrated previously that dichloroacetate (DCA) treatment in rodents ameliorates, via activation of the pyruvate dehydrogenase complex, the cardiovascular depression observed after hemorrhagic shock. To explore the mechanism of this effect, we administered DCA in a large animal model of hemorrhagic shock. Mongrel hounds were anesthetized with 1.5% isoflurane and were measured for hemodynamics, myocardial contractility, and myocardial substrate utilization. ⋯ However, DCA treatment was associated with a decreased stroke volume index (0.56 +/- 0.06 vs. 0.82 +/- 0.08 mL/kg/beat) and a decreased myocardial efficiency (19 vs. 41 L x mm Hg/mL/100 g tissue). During resuscitation by DCA, myocardial lactate consumption was reduced (21.4 +/- 3.7 vs. 70.7 +/- 16.3 micromole/min/100 g tissue) despite a three-fold increase in myocardial pyruvate dehydrogenase activity, while free fatty acid levels actually began to rise. Although increased lactate oxidation should be beneficial during resuscitation, we propose that DCA treatment led to a deprivation of myocardial lactate supply, which reduced net myocardial lactate oxidation, thus compromising myocardial function during resuscitation from hemorrhagic shock.