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 insult from severe hemorrhage is a multifactorial injury involving ischemia/reperfusion with inflammatory dysfunction. Our laboratories and others have demonstrated that the administration of exogenous carbon monoxide (CO) at low concentrations provides cytoprotection in vivo and in vitro. The purpose of these investigations was to test the hypothesis that CO protects against hemorrhagic shock- and resuscitation-induced systemic inflammation and end-organ damage. ⋯ CO protects against systemic effects of hemorrhagic shock and resuscitation. The precise cellular mechanisms involved require further elucidation. CO may prove to be an adjunctive therapy that could be instituted rapidly and with ease as an out-of-hospital therapeutic modality for severe blood loss after trauma.
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The beneficial effects of interventions to control fever in sepsis are controversial. We investigated whether the use of acetaminophen and external cooling is beneficial to control fever in septic shock. We studied 24 fasted, anesthetized, invasively monitored, mechanically ventilated female sheep (27.0 +/- 4.6 kg) that received 0.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. ⋯ In this clinically relevant septic shock model, the febrile response thus resulted in better respiratory function, lower blood lactate concentration, and prolonged survival time. Antipyretic interventions including acetaminophen and external cooling were associated with lower circulating HSP70 levels. These data challenge the temperature control practices often used routinely in acutely ill patients.
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It has been proposed that factors originating from the gut after severe trauma/shock are introduced into the systemic circulation through the mesenteric lymphatics and are responsible for the cellular injury and inflammation that culminates in acute multiple organ dysfunction syndrome (MODS). Indeed, it has been shown that lymph collected from shocked but not sham-shocked animals causes endothelial cell death, neutrophil activation, and bone marrow (BM) colony growth suppression in vitro. In an attempt to isolate the factor(s) in lymph responsible for endothelial cell toxicity, lymph from shock and sham animals was fractionated by solid phase extraction (SPE) and ion exchange chromatography (IEX). ⋯ Subsequent analysis of each SPE toxic fraction by gel electrophoresis and mass spectrometry suggests the toxicity is associated with a modified form of rat serum albumin (mod-RSA) and multiple lipid-based factors. Therefore, we have been able to demonstrate by two different separation techniques that shock lymph contains two or more factors that may account for the toxicity to endothelial cells. Further investigations are needed to determine the type of RSA modification and the identity of the lipid factors and their role in MODS.
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Randomized Controlled Trial Multicenter Study Clinical Trial
A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection.
Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). ⋯ There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.