Critical care : the official journal of the Critical Care Forum
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Venous thromboembolism is a relatively frequently occurring complication in critically ill patients admitted to the ICU despite prophylactic treatment with subcutaneous low molecular weight heparin. Several studies show that critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared to control patients after administration of subcutaneous heparin. Robinson and colleagues show in this issue of Critical Care dose-dependent but relatively low levels of anti-factor Xa activity at increasing doses of enoxaparin. Anti-factor Xa levels thought to be required for adequate thromboprophylaxis are observed only at doses of enoxaparin that are one and a half times higher than the conventional dose (40 mg).
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There is an increasing interest in biphasic positive airway pressure with spontaneous breathing (BIPAP+SBmean), which is a combination of time-cycled controlled breaths at two levels of continuous positive airway pressure (BIPAP+SBcontrolled) and non-assisted spontaneous breathing (BIPAP+SBspont), in the early phase of acute lung injury (ALI). However, pressure support ventilation (PSV) remains the most commonly used mode of assisted ventilation. To date, the effects of BIPAP+SBmean and PSV on regional lung aeration and ventilation during ALI are only poorly defined. ⋯ In this model of ALI, the reduction of tidal re-aeration and hyperaeration during BIPAP+SBmean compared to PSV is not due to decreased nonaerated areas at end-expiration or different distribution of ventilation, but to lower tidal volumes during BIPAP+SBspont. The ratio between spontaneous to controlled breaths seems to play a pivotal role in reducing tidal re-aeration and hyperaeration during BIPAP+SBmean.
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Activated Protein C (APC), an endogenous anticoagulant, improves tissue microperfusion and endothelial cell survival in systemic inflammatory states such as sepsis, but intravenous administration may cause severe bleeding. We have thus addressed the role of APC delivered locally by inhalation in preventing acute lung injury from alveolar overdistention and the subsequent ventilator-induced lung injury (VILI). We also assessed the effects of APC on the activation status of Extracellular- Regulated Kinase 1/2 (ERK) pathway, which has been shown to be involved in regulating pulmonary responses to mechanical stretch. ⋯ Topical application of APC by inhalation may effectively reduce lung injury induced by mechanical ventilation in mice.
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Gas6, the protein product of the growth arrest specific gene 6, is present in human circulation at subnanomolar concentrations. It is secreted by endothelial cells and is important for the activation of endothelium during inflammation. Axl, the tyrosine kinase receptor for Gas6, is also present in endothelium and can be cleaved and released into the circulation. The soluble of form Axl (sAxl), which is present in plasma, can bind Gas6 and inhibit Axl-mediated cell signalling. ⋯ We can confirm results of earlier studies showing that circulating Gas6 is increased in sepsis and related syndromes. sAxl is increased, but less pronounced than Gas6. The concentrations of Gas6 and sAxl correlate with a number of inflammatory markers, suggesting a role in systemic inflammation.
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Certain noble gases, though inert, exhibit remarkable biological properties. Notably, xenon and argon provide neuroprotection in animal models of central nervous system injury. ⋯ Their data are of interest as argon is more abundant, and therefore cheaper, than xenon (the latter of which is currently in clinical trials for perinatal hypoxic-ischemic brain injury; TOBYXe; NCT00934700). We eagerly await in vivo data to complement the promising in vitro data hailing argon neuroprotection.