Critical care : the official journal of the Critical Care Forum
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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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Microcirculatory dysfunction plays a pivotal role in the development of the clinical manifestations of severe sepsis. Prior to the advent of new imaging technologies, clinicians had been limited in their ability to assess the microcirculation at the bedside. Clinical evidence of microcirculatory perfusion has historically been limited to physical examination findings or surrogates that could be derived from global parameters of oxygen transport. ⋯ Although the study of the microcirculation has long been the domain of basic science, newly developed imaging technologies, such as orthogonal polarization spectral imaging, have now given us the ability to directly visualize and analyze microcirculatory blood flow at the bedside, and see the microcirculatory response to therapeutic interventions. Disordered microcirculatory flow can now be associated with systemic inflammation, acute organ dysfunction, and increased mortality. Using new technologies to directly image microcirculatory blood flow will help define the role of microcirculatory dysfunction in oxygen transport and circulatory support in severe sepsis.
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The authors of a recent paper have described an updated simplified acute physiology score (SAPS) II mortality model developed on patient data from 1998 to 1999. Hospital mortality models have a limited range of applicability. SAPS II, Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III, and mortality probability model (MPM)-II, which were developed in the early 1990s, have shown a decline in predictive accuracy as the models age. ⋯ In particular, mortality tends to get over predicted when older models are applied to more contemporary data, which in turn leads to 'grade inflation' when benchmarking intensive care unit (ICU) performance. Although the authors claim that their updated SAPS II can be used for benchmarking ICU performance, it seems likely that this model might already be out of calibration for patient data collected in 2005 and beyond. Thus, the updated SAPS II model may be interesting for historical purposes, but it is doubtful that it can be an accurate tool for benchmarking data from contemporary populations.
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This study was performed to determine whether surfactant application during extracorporeal membrane oxygenation (ECMO) improves lung volume, pulmonary mechanics, and chest radiographic findings in children with respiratory failure or after cardiac surgery. ⋯ Surfactant application may be of benefit in children with respiratory failure treated with ECMO, but these findings need confirmation from prospective studies.
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Intensive monitoring and aggressive management of perioperative haemodynamics (goal directed therapy) have repeatedly been reported to reduce the significant morbidity and mortality associated with high risk surgery. It may not matter what particular monitor is used to assess cardiac output but it is essential to ensure adequate oxygen delivery. If this management cannot begin preoperatively, it is still worth beginning goal directed therapy in the immediate postoperative period.