ABSTRACT
There are limited pharmacokinetic (PK) studies on vancomycin in patients treated with continuous renal replacement therapy (CRRT), and the results have been inconsistent. Because of individual differences, proposing a definite recommendation for the clinical regimen is not possible. Rapidly reaching target vancomycin concentrations will facilitate effective treatment for critically ill patients treated with CRRT. In this study, to understand the dynamic change in drug clearance rates in vivo, analyze the effect of PK changes on drug concentrations, and recommend loading and maintenance dosage regimens, we monitored the blood concentrations of vancomycin and calculated the area under the curve in two critically ill patients treated with vancomycin and continuous veno-venous hemofiltration (CVVH). On the basis of real-time therapeutic drug monitoring results and PK parameters, an individualized vancomycin regimen was developed for patients with CVVH. Good clinical efficacy was achieved, which provided support and reference for empirical vancomycin therapy in these patients.
ABSTRACT
The incidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common health problem in the clinic and is projected to increase in prevalence in the future. Mechanical ventilation is commonly used to provide respiratory support and has become indispensable in emergency and critical medicine. However, ventilator use can result in lung tissue damage, collectively termed ventilator-induced lung injury (VILI). In the present study, phosphoprotein profiling of blood and tissue samples from ventilated and non-ventilated mice was performed and key changes in protein levels and cell signaling during VILI were identified. Activation of the PI3K/AKT and mitogen activated protein kinase signaling pathways, in addition to changes in expression of cancer, inflammatory and cell-death related proteins were detected in response to mechanical ventilation. Focal adhesion-related protein levels and signaling pathways were also significantly altered in an injury model compared with control. VILI can affect patient mortality in ALI and ARDS cases, and no targeted treatment options currently exist. Identifying biomarkers and understanding the signaling pathways associated with VILI is critical for the development of future therapies.
ABSTRACT
Ventilator-induced lung injury (VILI) has implications for mortality from acute lung injury (ALI) and for acute respiratory distress syndrome (ARDS) patients; the complicated mechanisms of VILI have not been well defined. To discover new biomarkers and mechanisms of VILI, isobaric Tag for Relative and Absolute Quantitation (iTRAQ)-based quantitative proteomics were applied to identify differentially expressed proteins in mice treated with high tidal volume ventilation (HV), low tidal volume ventilation (LV) and lipopolysaccharide (LPS). A total of 14 dysregulated proteins showed the same change trend both in the LV and HV group and no change in the LPS group, and most importantly, the fold change of these proteins increased with the increase of volume ventilation, which indicates these proteins may be considered as potential markers specific for VILI. Ingenuity pathway analysis (IPA) canonical pathways analysis identified the top 4 canonical pathways, including the extrinsic prothrombin activation pathway, coagulation systems, the intrinsic prothrombin activation pathway and the acute phase response, suggesting that these pathways, as associated with these proteins' expression, may be important therapeutic targets for reducing VILI. These findings will provide a new perspective for understanding the pathogenesis of VILI in the future.
