Critical care : the official journal of the Critical Care Forum
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Comparative Study
Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis.
We performed a study to determine whether an enrollment sequence effect noted in the PROWESS (recombinant human activated Protein C Worldwide Evaluation in Severe Sepsis) trial exists in the ADDRESS (Administration of Drotrecogin Alfa [Activated] [DrotAA] in Early Stage Severe Sepsis) trial. ⋯ Analyses suggest that an enrollment sequence effect was present in the ADDRESS and PROWESS trials. Analysis of this effect on outcomes suggests that it is most apparent in patients at lower risk of death. In PROWESS, this effect appeared to be associated with a reduction of the DrotAA treatment effect for the first patients enrolled at each site. In ADDRESS, this effect may have contributed to early termination of the study. The finding of an enrollment sequence effect in two separate trials suggests that trial designs, site selection and training, data collection and monitoring, and statistical analysis plans may need to be adjusted for these potentially confounding events.
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Resistance rates are increasing among several problematic Gram-negative pathogens that are often responsible for serious nosocomial infections, including Acinetobacter spp., Pseudomonas aeruginosa, and (because of their production of extended-spectrum beta-lactamase) Enterobacteriaceae. The presence of multiresistant strains of these organisms has been associated with prolonged hospital stays, higher health care costs, and increased mortality, particularly when initial antibiotic therapy does not provide coverage of the causative pathogen. ⋯ Taken together, these observations underscore the importance of a 'hit hard and hit fast' approach to treating serious nosocomial infections, particularly when it is suspected that multiresistant pathogens are responsible. They also point to the need for a multidisciplinary effort to combat resistance, which should include improved antimicrobial stewardship, increased resources for infection control, and development of new antimicrobial agents with activity against multiresistant Gram-negative pathogens.
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Sepsis still represents an important clinical and economic challenge for intensive care units. Severe complications like multi-organ failure with high mortality and the lack of specific diagnostic tools continue to hamper the development of improved therapies for sepsis. Fundamental questions regarding the cellular pathogenesis of experimental and clinical sepsis remain unresolved. ⋯ Importantly, the survival rate of RAGE knockout mice was more than fourfold that of wild-type mice in a septic shock model of cecal ligation and puncture (CLP). Additionally, the application of soluble RAGE, an extracellular decoy for RAGE ligands, improves survival in mice after CLP, suggesting that RAGE is a central player in perpetuating the innate immune response. Understanding the basic signal transduction events triggered by this multi-ligand receptor may offer new diagnostic and therapeutic options in patients with sepsis.
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Randomized Controlled Trial Comparative Study
Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension.
Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension. ⋯ In animals with acute pulmonary hypertension, inhaled iloprost improved global haemodynamics primarily via selective pulmonary vasodilatation and restoration of left ventricular preload. The reduction in right ventricular afterload is associated with a paradoxical decrease in right ventricular contractility. Our data suggest that this reflects an indirect mechanism by which ventriculo-vascular coupling is maintained at the lowest possible energetic cost. We found no evidence for a direct negative inotropic effect of iloprost.
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Multicenter Study
Determinants of tracheostomy decannulation: an international survey.
Although tracheostomy is probably the most common surgical procedure performed on critically ill patients, it is unknown when a tracheostomy tube can be safely removed. ⋯ Patient level of consciousness, cough effectiveness, secretions, and oxygenation are important determinants of clinicians' tracheostomy decannulation opinions. Most surveyed clinicians defined decannulation failure as the need to reinsert an artificial airway within 48 to 96 hours of planned tracheostomy removal.