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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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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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.
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Hypotensive resuscitation (Hypo) has been considered an alternate resuscitation strategy in clinical settings that prevent the application of standard Advanced Trauma Life Support care. However, validation of this approach when used for prolonged periods of time remains to be demonstrated. The purpose of this study was to evaluate prolonged Hypo as an alternative to standard resuscitation using various currently available resuscitative fluids. ⋯ HEX required significantly less intravenous fluid (0.7x total estimated blood volume [EBV]) compared with HypoLR (1.9x EBV) and StandLR (3.2x EBV) (P < 0.05). Although HBOC required the smallest fluid volume (0.4x EBV), survival was no better than C and it resulted in the most significant acidosis. These results support the decision to use Hextend for Hypo, a strategy currently being applied on the battlefield.
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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.