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
-
Comparative Study
Comparison of hypertonic with isotonic saline hydroxyethyl starch solution on oxygen extraction capabilities during endotoxic shock.
Hypertonic colloid solutions reportedly exert protective effects on the microcirculation. The present study investigated the effects of a hypertonic saline hydroxyethyl starch (HES) solution on the oxygen extraction capabilities in an endotoxic shock model in the dog. Fourteen anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin before being randomly divided into two groups to receive a 4 mLkg infusion in 10 min of either hypertonic (7.5%, n = 7), or isotonic (.9%, n = 7) HES solution. ⋯ There were no significant differences in blood gases or lactate concentrations between the groups. When cardiac tamponade was induced to study the tissue oxygen extraction capabilities, hypertonic saline HES-treated dogs had a slightly lower critical oxygen delivery (11.1+/-1.6 vs. 14.2+/-3.3 mL/kg x min, p = NS), and a significantly higher critical oxygen extraction ratio (61.9+/-17.1 vs. 44.0+/-11.5%, p < .05) than the isotonic group. We conclude that during endotoxic shock in dogs, hypertonic saline HES solution can increase whole body oxygen extraction capabilities, probably by an improvement in microvascular perfusion in septic conditions.
-
Randomized Controlled Trial Clinical Trial
Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary artery bypass surgery and its modulation by pentoxifylline.
The influence of coronary artery bypass grafting (CABG) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 as well as its modulation by pentoxifylline (PTF) were studied in a prospective, randomized, double-blinded study. 12 patients undergoing elective CABG were randomly assigned to receive either saline or PTF (1 mg/kg as a loading dose followed by 1 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after CABG, and (C) 24 h after CABG. Cytokine plasma levels as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA expression in peripheral blood mononuclear cells. ⋯ However, application of PTF during CABG neither inhibited the spontaneous production of IL-10 nor modulated cytokine production ex vivo. These results suggest a biphasic response of stimulated peripheral blood mononuclear cell cytokine gene expression during CABG with an initial tolerance to LPS stimulation. The application of PTF during CABG in doses that are primarily based on its use in occlusive arterial disease do not seem to modulate the release of the cytokines studied.
-
Over the past decade, the biotechnology/pharmaceutical industry has been diligently working on the development of immunomodulatory agents for the treatment of shock and sepsis, and the literature is rife with descriptions of novel and innovative molecules that promise to become the panacea for these conditions. Unfortunately, despite promising preclinical evidence, dozens of these new agents have failed to demonstrate clinical efficacy in controlled, randomized clinical trials, abandoning the bedside physician to the traditional armamentarium of drugs and therapeutics for the treatment of patients with these complex, progressive, and life-threatening conditions. The reasons for this quandary are controversial, complex, and multifactorial. ⋯ As a result, it is not surprising that clinical trials of agents based on clinically flawed models failed to demonstrate clinical efficacy. The lack of clinical insight during preclinical development of these agents has contributed to the current impasse of the development of safe, efficacious, and potentially lifesaving agents for the treatment of shock and sepsis. Thus, the goal of this review article is to review the advantages and disadvantages of commonly used sepsis and shock models in light of lessons learned from these clinical trials.
-
Diaspirin cross-linked hemoglobin (DCLHb), a hemoglobin-based blood substitute, has been found to improve systemic hemodynamics, cutaneous oxygen tension, and normalization of blood lactate levels and acid-base equilibrium after hemorrhage in animals. The present study was conducted to determine the dose-dependent effect of a 10% solution of DCLHb (20, 50, and 100% of shed blood volume; SBV) on regional blood circulation in hemorrhaged rats. Hemorrhage was induced in urethane-anesthetized rats by bleeding them at a rate of approximately .5 to 1 mL/min until a mean arterial pressure of 35-40 mmHg was achieved. ⋯ Resuscitation with the RL did not produce any improvement in renal cortical perfusion. However, resuscitation with DCLHb significantly increased renal cortical perfusion (364.7%) due to an increase in both CMBC (123.4%) and their velocity (109.9%). It is concluded that DCLHb in a dose of 50% of SBV produces maximal improvement in regional blood circulation of hemorrhaged rats.