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
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.
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We examined the modifying effects of a Kunitz trypsin inhibitor (KTI) and a Bowman-Birk trypsin inhibitor (BBI), purified from soybean, as intraperitoneal (i.p.) injection and dietary supplements on bacterial lipopolysaccharide (LPS)-induced lethality in mice. We initially examined the suppressing effects of i.p. injection of KTI (50 mg/kg) and BBI (50 mg/kg) on LPS-induced lethality after i.p. injection of LPS. ⋯ Here, we show that i.p. and daily oral administration of KTI, but not BBI, caused a significant reduction of the LPS-induced lethality; that LPS significantly induced plasma TNF-alpha, IL-1beta, and IL-6 levels in mice after LPS challenge; that concomitant administration of KTI, but not BBI, inhibits the LPS-induced plasma levels of these cytokines; and that KTI, but not BBI, suppressed LPS-induced upregulation of cytokine expression through suppression of phosphorylation of three mitogen-activated protein (MAP) kinase pathways, ERK1/2, JNK, and p38, in peritoneal macrophages. These data allow us to speculate that i.p. injection and dietary supplementation of a soybean KTI may play a role as a potent anti-inflammatory agent by inhibiting activation of MAP kinases, leading to the suppression of cytokine expression.
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Randomized Controlled Trial Clinical Trial
Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery.
The objective of this study was to assess the impact on outcome of adjuvant therapy (high-dose of immunoglobulin [Ig] M-enriched intravenous Ig, IVIG) in intensive care unit (ICU) patients who underwent surgery by abdominal sepsis. This was a prospective, randomized, double-blind, controlled study set in the medical/surgical ICUs of seven teaching hospitals. Patients with severe sepsis and septic shock of intra-abdominal origin admitted to the ICU within 24 h after the onset of symptoms were included in the study. ⋯ IAT was the only variable independently associated with death (odds ratio, 19.4) in a logistic regression model. We conclude that IVIG administration, when used in combination with adequate antibiotics, improved the survival of surgical ICU patients with intra-abdominal sepsis. The initial choice of antibiotic has a dramatic impact on outcome.
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We tested whether nitric oxide (NO) could synergize with hypoxia to induce damage to the aorta isolated from rat. We found that 4 h of mild hypoxia (5% O2) caused substantial necrosis of isolated rat aortae (measured as lactate dehydrogenase release) if inducible NO synthase (iNOS) had previously been induced by endotoxin plus interferon-gamma. Mild hypoxia caused no significant necrosis in the absence of this inflammatory activation, and inflammatory activation caused little damage at a higher oxygen levels (21% oxygen). ⋯ A specific inhibitor of mitochondrial respiration, myxothiazol, caused necrosis of aortae over a similar time course to NO. DETA/NO plus mild hypoxia-induced cell death was substantially reduced by a glycolytic intermediate 3-phosphoglycerate, suggesting that necrosis resulted from energy depletion secondary to respiratory inhibition. This NO-induced sensitization of aorta to mild hypoxia may be important in sepsis and other pathologies where iNOS is expressed.
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After asphyxia, it is standard to resuscitate the newborn with 100% oxygen, which may create a hypoxia-reoxygenation process that may contribute to subsequent myocardial dysfunction. We examined the effects of graded reoxygenation on cardiac function, myocardial glutathione levels, and matrix metalloproteinase (MMP)-2 activity during recovery. Thirty-two piglets (1-3 days old, weighing 1.5-2.1 kg) were anesthetized and instrumented for continuous monitoring of cardiac index, and systemic and pulmonary arterial pressures. ⋯ The hypoxia-reoxygenated (21%-100%) hearts had similarly increased MMP-2 activity and decreased glutathione levels (P < 0.05, 100% vs. controls), which correlated significantly with cardiac index and stroke volume during reoxygenation, and similar features of early myocardial necrosis. In neonatal resuscitation, if used with caution because of a slower resolution of pulmonary hypertension, 21% reoxygenation results in similar cardiac function and early myocardial injury as 50% or 100%. The significance of higher oxidative stress with high oxygen concentration is unknown, at least in the acute recovery period.