Critical care : the official journal of the Critical Care Forum
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The design of clinical trials of interventions aimed at reducing mortality in patients with severe sepsis assumes that the relative treatment effect of the intervention is independent of the patients' risk for death. We reviewed published data from phase III clinical studies of severe sepsis to determine whether a relationship exists between risk for death and the relative benefit of the investigational agent. Such an interaction might warrant a change in the assumptions that underlie current trial designs. ⋯ Our review of published clinical data does not support the hypothesis that mortality risk of the population studied alters the relative treatment effect associated with anti-inflammatory or other agents used to treat severe sepsis. Clinical studies in severe sepsis should continue to enroll patients over a wide range of disease severity, as long as patients enrolled have evidence of sepsis-induced organ dysfunction(s), patients are at an appreciable risk for death (e.g. as evidenced by admission to an intensive care unit), and the potential for benefit outweighs the potential for harm.
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It has been hypothesized that the protein C pathway is a pivotal link between the inflammation and coagulation cascades. The demonstration that a survival benefit is associated with administration of drotrecogin alfa (activated) (recombinant human activated protein C [APC]) in severe sepsis patients has provided new insights into the protein C pathway. APC was originally identified based on its antithrombotic properties, which result from the inhibition of activated Factors V and VIII. ⋯ Based mostly on in vitro studies, binding of APC to its receptor on endothelial cells leads to a decrease in thrombin-induced endothelial permeability injury, while such binding on blood cells, epithelial cells, and neurons has been shown to inhibit chemotaxis, be anti-apoptotic, and be neuroprotective, respectively. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, drotrecogin alfa (activated) was associated with improved cardiovascular function, respiratory function, and a prevention of hematologic dysfunction. This article discusses the way in which the interactions of APC may alter the microcirculation.
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Multicenter Study Comparative Study
Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study.
Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. ⋯ Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients.
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Independent lung ventilation (ILV) can be classified into anatomical and physiological lung separation. It requires either endobronchial blockade or double-lumen endotracheal tube intubation. Endobronchial blockade or selective double-lumen tube ventilation may necessitate temporary one lung ventilation. ⋯ There are some clear indications for ILV as a primary intervention and as a rescue ventilator strategy in both anatomical and physiological lung separation. Potential pitfalls are related to establishing and maintaining lung isolation. Nevertheless, ILV can be used in the intensive care setting safely with a good understanding of its limitations and potential complications.
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The use of epinephrine in septic shock remains controversial. Nevertheless, epinephrine is widely used around the world and the reported morbidity and mortality rates with it are no different from those observed with other vasopressors. In volunteers, epinephrine increases heart rate, mean arterial pressure and cardiac output. ⋯ In conclusion, epinephrine has predictable effects on systemic hemodynamics and is as efficient as norepinephrine in correcting hemodynamic disturbances of septic shock. Moreover, epinephrine is cheaper than other commonly used catecholamine regimens in septic shock. The clinical impact of the transient hyperlactatemia and of the splanchnic effects are not established.