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
Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study.
We assessed the short-term effects of hypertonic fluid versus isotonic fluid administration in patients with septic shock. This was a double-blind, prospective randomized controlled trial in a 15-bed intensive care unit. Twenty-four patients with septic shock were randomized to receive 250 mL 7.2% NaCl/6% hydroxyethyl starch (HT group) or 500 mL 6% hydroxyethyl starch (IT group). ⋯ In patients with septic shock, hypertonic fluid administration did not promote gastrointestinal mucosal perfusion or sublingual microcirculatory blood flow in comparison to isotonic fluid. Independent of changes in preload or afterload, hypertonic fluid administration improved the cardiac contractility and vascular tone compared with isotonic fluid. The need for ongoing fluid resuscitation was also reduced.
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Trauma patients are often transfused allogeneic red blood cells (RBCs) in an effort to augment tissue oxygen delivery. However, the effect of RBC transfusion on microvascular perfusion in this patient population is not well understood. To this end, we investigated the effect of RBC transfusion on sublingual microvascular perfusion in trauma patients. ⋯ Pretransfusion PPC may be selectively deranged in otherwise stable trauma patients. Patients with relatively altered baseline PPC tend to demonstrate improvement in perfusion following transfusion, whereas those with relatively normal perfusion at baseline tend to demonstrate either no change or, in fact, a decline in PPC. Bedside sublingual imaging may have the potential to detect subtle perfusion defects and ultimately inform clinical decision making with respect to transfusion.
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Exocytosis of granules containing the cytolytic effector (CE) molecules granzyme A (GzmA), granzyme B (GzmB), and perforin is one major pathway of lymphocyte-mediated cytotoxicity. Studies in murine models and the finding of elevated granzyme levels in the plasma of septic patients have implicated cytotoxic lymphocytes in the pathogenesis of sepsis. We sought to evaluate the role of cytotoxic cells and CE in sepsis and determine if intracellular levels of CE in cytotoxic cells correlate with disease severity. ⋯ The GMFI of each GzmA and GzmB in CTLs were associated with the Acute Physiology and Chronic Health Evaluation II score (P = 0.01). A significant increase in the number of granulocytes in the peripheral blood mononuclear cells of SS patients consisted primarily of low-density neutrophils, which expressed increased levels of GzmA (P < 0.01). The results suggest that CTLs are activated in SS and express significantly higher intracellular levels of GzmB and that GzmA and B levels correlate with disease severity.
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Serum micro-RNAs (miRNAs) can be used for the diagnosis and prognosis of various diseases. Using genome-wide scans, we sought to identify serum miRNAs that could be used as prognostic predictors for sepsis patients. We used microarray screens to identify differentially expressed serum miRNAs by comparing samples from 12 surviving and 12 nonsurviving sepsis patients. ⋯ When the cutoff point was set at 0.288, these three combined variables provided 78.13% sensitivity and 91.84% specificity. Our results showed that serum miR-574-5p was correlated with the death of sepsis patients. The combined predictive capability of sepsis stage, Sepsis-Related Organ Failure Assessment scores, and serum miR-574-5p for the death of sepsis patients was better than any single indicator.
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Excessive neutrophil infiltration is a major component in septic lung injury, although the signaling mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. Herein, we hypothesized that Rho-kinase activity may play a significant role in pulmonary neutrophil recruitment and tissue damage in abdominal sepsis. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (0.5 or 5 mg/kg) before cecal ligation and puncture (CLP). ⋯ Moreover, Rho-kinase inhibition significantly reduced sepsis-provoked gene expression of CXC chemokines in alveolar macrophages. In contrast, Rho-kinase inhibition had no effect on platelet shedding of CD40L or plasma levels of MMP-9 in septic mice. In conclusion, these data demonstrate that the Rho-kinase signaling pathway plays a key role in regulating pulmonary infiltration of neutrophils and tissue injury via regulation of CXC chemokine production in the lung and Mac-1 expression on neutrophils in abdominal sepsis.