Critical care : the official journal of the Critical Care Forum
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The article by Van Herpe and colleagues in the previous issue of Critical Care describes the glycemic penalty index (GPI), which weights both hyperglycemic and hypoglycemic blood glucose measurements commensurate to their clinically significant difference from target. Although certain adverse consequences result from isolated severe hyperglycemic episodes, several specific outcomes depend upon overall hyperglycemia. In contrast, although mortality has been related epidemiologically to overall low blood glucose, specific negative outcomes may depend upon isolated episodes. Capturing both hypoglycemia and hyperglycemia in a single index will be shown to be useful if the GPI enables us to better define insulin strategies, outcomes, and targets.
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Stimulation of beta2-adrenergic receptors (beta2-ARs) inhibits tumor necrosis factor-alpha (TNF-alpha) release in monocytes. In septic shock, endogenous catecholamines induce beta2-AR downregulation, leading to an increased TNF-alpha release. The aims of this study were to analyze the molecular mechanisms of beta-adrenergic downregulation and to explore therapeutic interventions with maintained anti-inflammatory efficacy in septic shock using the inhibition of phosphodiesterase 4 (PDE4). ⋯ In septic shock, the anti-inflammatory effects of catecholamines are blunted by downregulation of beta2-ARs and upregulation of the inhibitory G protein in CD14+ monocytes. Beta-adrenergic downregulation is overcome by inhibitors of PDE4. These results provide a mechanistic rationale for the therapeutic use of selective PDE4 inhibitors in the treatment of septic shock.
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The pathogenesis of septic acute kidney injury (AKI) is not well understood. In the present issue of Critical Care, the combined clinical and experimental study from Mariano's group provides new insight into the disease. The study shows that plasma from septic burn patients with acute renal failure initiated pro-apoptotic effects and functional alterations in renal tubular cells and podocytes in vitro that correlated with the degree of proteinuria and renal dysfunction. ⋯ Sepsis and burn had additive effects. Apart from increasing our understanding of the pathogenesis of septic AKI, the study justifies further research on therapeutic interventions in several directions. These include the binding and elimination of the source of endotoxin by selective decontamination of the digestive tract, the blocking of apoptotic pathways, or the extracorporeal removal of circulating toxic mediators using high permeability hemofiltration or coupled plasma filtration and absorption.
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Acute lung injury (ALI) can result from various insults to the pulmonary tissue. Experimental and clinical data suggest that spontaneous breathing (SB) during pressure-controlled ventilation (PCV) in ALI results in better lung aeration and improved oxygenation. Our objective was to evaluate whether the addition of SB has different effects in two different models of ALI. ⋯ SB improves oxygenation, reduces shunt fraction, and increases EELV in both models of ALI.
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The current gold standard for the diagnosis of elevated intracranial pressure (ICP) remains invasive monitoring. Given that invasive monitoring is not always available or clinically feasible, there is growing interest in non-invasive methods of assessing ICP using diagnostic modalities such as ultrasound or magnetic resonance imaging (MRI). ⋯ They report a positive correlation between measurements of the ONSD on MRI and invasive ICP measurements. If the findings of this study can be replicated in larger populations, this technique may be a useful non-invasive screening test for elevated ICP in select populations.