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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We postulated that hypertonic solutions could minimize the accumulation of lung water and subsequent respiratory derangements that occur after pulmonary contusion. Anesthetized pigs underwent contusion of the right chest at baseline and then were hemorrhaged (30 cc/kg) over 20 min. They were resuscitated with either 7.5% NaCl (4 cc/kg) or .9% saline (90 cc/kg) for 20 min and observed for 4 h. ⋯ Static compliance measurements were significantly decreased from baseline in both groups following pulmonary contusion. There were no differences in wet to dry lung weights or computed tomography scan injury volume between groups. We conclude that small volume hypertonic saline resuscitation does not reduce the magnitude of lung injury or provide substantial physiologic benefit over isotonic solutions following pulmonary contusion.
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To determine the contribution of xanthine oxidase-mediated reperfusion injury to the blood flow deficits seen in the intestinal microcirculation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol after shock but before standard resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group served as control. ⋯ Blood flow in first order arterioles 120 min postresuscitation was 41% of baseline in the standard resuscitation group and 77% of baseline in the allopurinol-treated group. A1 arteriolar diameter was not significantly different between the two groups, being 73 and 82% of baseline, respectively. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to blood flow deficits in the small intestinal microcirculation after resuscitated hemorrhagic shock and that the improvement in blood flow seen with allopurinol is not due to vasodilation within the microvasculature.
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Up-regulation of the leukocyte beta 2 integrin, CD18, is a key event in neutrophil-endothelial adhesion and neutrophil-mediated organ injury. Inhibition of CD18 with monoclonal antibodies reduces lung and liver neutrophil sequestration in animal models of Gram-negative bacteremia or endotoxemia. However, with a persistent septic challenge, interference with host leukocyte phagocytic defense could adversely affect outcome. ⋯ Our data demonstrate that peritoneal neutrophil migration in response to an endogenous fecal challenge is CD18-dependent, and that this mechanism forms a vital part of host defense. Inhibition of CD18 increased neutrophil sequestration in the liver and lung and increased liver injury. This study demonstrates a paradoxical increase in organ neutrophil sequestration using a leukocyte anti-adhesion therapy during sepsis and suggests that anti-adhesion therapies targeted towards neutrophil may worsen outcome if given during an ongoing, localized infection.
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Randomized Controlled Trial Clinical Trial
Multivariate regression modeling for the prediction of inflammation, systemic pressure, and end-organ function in severe sepsis.
The purpose of this study was to evaluate the feasibility of developing multivariate equations that predicted blood pressure and measured levels of end-organ function indicators quantitatively up to 72 h in advance in critically ill patients with severe sepsis. Data collected prospectively from 59 patients entered into two sequential placebo-controlled clinical trials of recombinant interleukin-1 receptor antagonist in severe sepsis and septic shock was analyzed retrospectively. A series of multivariate equations were developed to predict systemic pressure, coagulation, and vital organ function indicators quantitatively at 24, 48, and 72 h after the onset of severe sepsis. ⋯ Resolution of organ failure indicators present at baseline was predicted successfully in individual patients, with 20/27 (74%) specificities > or = 76%. In critically ill patients with severe sepsis, multivariate analysis of interactions among clinical observations, standard laboratory tests, and inflammatory response mediators produced equations that predicted systemic blood pressure and inflammatory and end-organ function indicators quantitatively up to 72 h in advance. Whether or not this methodology might be developed further to predict subclinically the onset and resolution of acute organ failure and shock in critically ill patients, and if it can be validated in a prospective trial will require further studies.
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Platelet-activating factor (PAF) is a potent vasoactive and inflammatory lipid mediator which has been implicated in the hemodynamic alterations of endotoxemia and sepsis. Different PAF receptor antagonists have been shown to attenuate the systemic and pulmonary disturbances of sepsis, but they were generally administered before the injection of endotoxin and their effects have not been consistent. To examine the effects of BB-882, a novel potent PAF receptor antagonist, on general hemodynamics and regional flow distribution in a canine endotoxic shock model, 14 anesthetized and ventilated dogs received 2 mg/kg of Escherichia coli endotoxin intravenously (i.v.) followed by generous fluid resuscitation. ⋯ This study demonstrates that the administration of a PAF receptor antagonist following endotoxic shock in fluid resuscitated dogs does not offer significant hemodynamic benefit. Pretreatment with BB-882 at the dose used only enhanced mesenteric perfusion. These findings do not support beneficial effects of PAF receptor antagonists in septic shock.