Critical care : the official journal of the Critical Care Forum
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Because they share one pathognomonic sign (major hyperthermia), classic or environmental heatstroke and malignant hyperthermia have often been confronted from the therapeutic point of view. As expected and according to major physiopathological discrepancies between both syndromes, analysis of published data does not support effectiveness of dantrolene in heatstroke despite its significant reduction in mortality in malignant hyperthermia. If cooling methods still represent the cornerstone of the heatstroke therapeutic approach, the magnitude of heat-related deaths and the morbidity associated with the August 2003 French heatwave have highlighted the need for more ambitious methods of treatment.
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Stridor is one of the most frequent causes of early extubation failure. The cuff-leak test may help to identify patients at risk to develop post-extubation laryngeal edema. However the discrimination power of the cuff-leak test is highly variable and can be use, at best, to detect patients at risk to develop edema but should not be used to postpone extubation as tracheal extubation can still be successful in many patients with a positive test. In this editorial, the author discuss the factors influencing the leak and hence its predictive value.
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The management challenges of patients with nosocomial pneumonia are great because of resistance among the responsible pathogens. In this issue of Critical Care, Argyris Michalopoulos and colleagues describe the use of inhaled colistin in the treatment of multidrug-resistant Gram-negative nosocomial pneumonia in a small group of patients. Although seven of eight patients who received nebulized colistin showed clinical improvement, some patients also received other active antibiotics. ⋯ In addition, although adverse events were not documented in patients receiving colistin, formal assessments for bronchoconstriction and neurological toxicity were not completed in this retrospective study. Although resistance to colistin in Gram-negative organisms has not evolved, the risk of breakthrough infection with Gram-positive and inherently resistant Gram-negative bacteria remains a concern. The results of this limited study do, however, suggest that further studies examining the use of nebulized colistin are merited.
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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.