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
Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport.
Adenosine triphosphate-sensitive potassium channels are important regulators of arterial vascular smooth muscle tone and are implicated in the pathophysiology of catecholamine tachyphylaxis in septic shock. The present study was designed as a prospective, randomized, double-blinded, clinical pilot study to determine whether different doses of glibenclamide have any effects on norepinephrine requirements, cardiopulmonary hemodynamics, and global oxygen transport in patients with septic shock. We enrolled 30 patients with septic shock requiring invasive hemodynamic monitoring and norepinephrine infusion of 0.5 microg.kg-1.min-1 or greater to maintain MAP between 65 and 75 mmHg. ⋯ Glibenclamide decreased plasma glucose concentrations in a dose-dependent manner but failed to reduce norepinephrine requirements. None of the doses had any effects on cardiopulmonary hemodynamics, global oxygen transport, gas exchange, or electrolytes. These data suggest that oral glibenclamide in doses from 10 to 30 mg fails to counteract arterial hypotension and thus to reduce norepinephrine requirements in catecholamine-dependent human septic shock.
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Multicenter Study
Daily variation in endotoxin levels is associated with increased organ failure in critically ill patients.
High blood levels of endotoxin on admission to the intensive care unit are predictive of adverse outcomes, including organ failure and death. However, the significance of changes in endotoxin levels over time has not been evaluated. We examined whether dynamic daily changes in endotoxin levels resulted in the development of greater organ dysfunction over time in critically ill patients. ⋯ Endotoxin activity assay variability was found to be independent of infection status (P = 0.52). Daily dynamic variation in endotoxin levels is a marker of increased severity of illness as measured by burden of total organ dysfunction over time. Further studies are warranted to assess the role of daily variation in endotoxin levels in the pathogenesis and potential therapy of organ failure in the critically ill.
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Comparative Study
Continuous versus bolus infusion of terlipressin in ovine endotoxemia.
In patients with sepsis, hemodynamic support is often complicated by a tachyphylaxis against conventional vasopressor agents. Bolus infusion of terlipressin, a vasopressin analog, has been reported to increase mean arterial pressure in patients with catecholamine-resistant septic shock. However, bolus infusion of terlipressin may be associated with severe side effects, including pulmonary vasoconstriction and impairment of oxygen delivery. ⋯ These unwanted side effects were prevented by continuous low-dose infusion of the drug. In conclusion, continuous infusion of terlipressin stabilized hemodynamics and improved myocardial performance in endotoxemic ewes without obvious side effects. Continuous low-dose terlipressin infusion may represent a useful alternative treatment of arterial hypotension related to sepsis and systemic inflammatory response syndrome.
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Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. ⋯ Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.
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Lung ischemia-reperfusion (I/R) injury plays an important role in many clinical issues. A series of mechanisms after I/R has been uncovered after numerous related studies. Organ preconditioning (PC) is a process whereby a brief antecedent event, such as transient ischemia, oxidative stress, temperature change, or drug administration, bestows on an organ an early or delayed tolerance to further insults by the same or different stressors. ⋯ Less prominent and transient increase in expression of HSP-70 was found in the PC group. We concluded that the intratracheal thermal PC can effectively attenuate I/R-induced lung injury through various mechanisms, including the decrease of various proinflammatory cytokines. The mechanism of its protective effect might be related to the increased expression of HSP-70.