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
Efficacy and safety of dopamine versus norepinephrine in the management of septic shock.
The optimum septic shock vasopressor support strategy is currently debated. This study was performed to evaluate the efficacy and safety of norepinephrine (NE) and dopamine (DA) as the initial vasopressor in septic shock patients who were managed with a specific treatment protocol. A prospective, randomized, open-label, clinical trial was used in a medical intensive care unit comparing DA with NE as the initial vasopressor in fluid-resuscitated 252 adult patients with septic shock. ⋯ In this protocol-directed vasopressor support strategy for septic shock, DA and NE were equally effective as initial agents as judged by 28-day mortality rates. However, there were significantly more cardiac arrhythmias with DA treatment. Patients receiving DA should be monitored for the development of cardiac arrhythmias (NCT00604019).
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Randomized Controlled Trial
Effects of the pan-selectin antagonist bimosiamose (TBC1269) in experimental human endotoxemia.
Selectins mediate the adhesion of leukocytes to activated endothelial cells and activated platelets. In addition to these cell-to-cell interactions, they influence the fibrin content and size of venous thrombi in different animal models. However, the exact role of selectins in human endotoxemia still remains unclear. ⋯ The pan-selectin antagonist bimosiamose does not attenuate TF-triggered coagulation or inflammation in human endotoxemia. This indicates a minor influence of this selectin antagonist in this model. In addition, infusion of bimosiamose was safe and well tolerated in human endotoxemia.
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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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Randomized Controlled Trial
Preoperative methylprednisolone administration maintains coagulation homeostasis in patients undergoing liver resection: importance of inflammatory cytokine modulation.
Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. ⋯ Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.
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Randomized Controlled Trial
A prospective randomized trial comparing oxygen delivery versus transcutaneous pressure of oxygen values as resuscitative goals.
Transcutaneous pressure of oxygen (PtcO2) correlates with arterial pressure of oxygen (PaO2) in nonshock states, but in shock states, PtcO2 approximates cardiac output with no response to increasing fraction of inspired oxygen (FiO2) and PaO2. An incremental change of more than 21 mmHg in PtcO2 in response to an FiO2 of 1.0 (identified as the oxygen challenge test [OCT]) implies adequate tissue perfusion, and lack of response has been associated with mortality. Patients with severe sepsis and septic shock requiring pulmonary artery catheters were randomized to two groups: the oxygen delivery (DO2) group was treated to a DO2 and mixed venous oxygen saturation goals, and the PtcO2 group was treated to achieve an OCT value of 40 mmHg or more. ⋯ The area under the receiver operating curve was 0.824 for the OCT at T24. The best OCT value was 25 mmHg at T24 with positive and negative predictive values of 87% and 90%, respectively. Treating patients with severe sepsis/septic shock to an OCT value of 25 mmHg or more may provide a specific end point of resuscitation that may be associated with better survival than resuscitating to the central hemodynamic parameters of DO2 and mixed venous oxygen saturation.