ObjectiveTo evaluate the predictive value of the diaphragm ultrasound for weaning from mechanical ventilation.MethodsThe patients who received mechanical ventilation in Fujian Provincial Hospital between February 2016 to December 2017 and met the criteria for a T-tube spontaneous breathing trial were included in the study. Then right diaphragmatic displacement (DD) and diaphragmatic thickening fraction (DTF) were evaluated using M-mode ultrasonography as well as the rapid shallow breathing index (RSBI, the ratio of respiratory rate to tidal volume). A new index was named as the diaphragmatic-RSBI (D-RSBI, the ratio of respiratory rate to DD). The patients were classified into a success group or a failure group according to the weaning outcomes. The receiver operating characteristic (ROC) curves were calculated to evaluate the predictive performance of each index.ResultsFifty-nine patients were weaned successfully and failure of weaning was found in 29 patients. There were no statistically significant differences in pre-weaning parameters including age, sex, systolic blood pressure, diastolic blood pressure, blood lipid index (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride), or fast blood glucose between the weaning success group and the weaning failure group (P>0.05), but there were statistically significant differences in body mass index and acute physiology and chronic health condition Ⅱ score between two groups (P<0.05). DD [(13.44±3.23)mm vs. (10.28±2.82)mm, DTF [(32.43±12.35)% vs. (27.64±5.77)%, P<0.05] and D-RSBI [(1.49±0.47) breaths·min–1·mm–1 vs. (2.55±0.87) breaths·min–1·mm–1, P<0.05] differed significantly between the weaning success group and the weaning failure group. A cutoff of DTF≥27.9% yielded a sensitivity of 98.3%, a specificity of 62.1%, and an area under the ROC curve (AUC) of 0.873. A cutoff of D-RSBI≤1.73 breaths·min–1·mm–1 yielded a sensitivity of 76.3%, a specificity of 93.1%, and an AUC of 0.887. By comparison, when RSBI was ≤50.9 breaths·min–1·mm–1, there was a sensitivity of 91.5%, a specificity of 86.2%, and an AUC of 0.927. There was no statistically significant difference in AUC between D-RSBI and RSBI (P>0.05).ConclusionsDiaphragm ultrasound is feasible to predict the outcome of weaning. DTF and D-RSBI are as same accurate as the traditional RSBI in predicting the weaning outcome, but more objective and suitable for clinical application.
Objective To investigate the role and mechanisms of trimetazidine (TMZ) in intensive care unit-acquired weakness (ICU-AW). Methods Seventy wild-type male C57BL/6 mice were selected and the ICU-AW mouse model was constructed by intraperitoneal injection of different concentrations of lipopolysaccharide (LPS). The body weights, grip strengths, and 96-hour survival rates of each group were observed, and the optimal concentration of LPS and time of sampling were screened out, the mRNA and protein expression of the gastrocnemius muscle atrophic proteins Atrogin-1 and muscle-specific RING finger protein 1 (MuRF1) were further detected to verify the success of modelling, and LPS (12 mg/kg) was used as the subsequent modelling concentration according to the preliminary results. After successful modelling, another 70 mice were randomly divided into normal control group (Normal group), LPS solvent (Vehicle) group, LPS group, LPS+TMZ solvent group, LPS+TMZ group, LPS+TMZ+AC-YVAD-CMK (AC) solvent group, and LPS+TMZ+AC group, with 10 mice in each group. The Normal group did not have any intervention; the Vehicle group was injected intraperitoneally with an equal volume of saline with LPS; the remaining groups were injected intraperitoneally with LPS (12 mg/kg); after the completion of the LPS injection, the LPS+TMZ group, the LPS+TMZ+AC solvent group, and the LPS+TMZ+AC group were given TMZ (5 mg/kg) by gastric gavage once a day for 4 days. The LPS+TMZ solvent group was given TMZ equivalent saline gavage once a day for 4 days. The LPS+TMZ+AC group was injected intraperitoneally with the cysteinyl aspartate specific proteinase 1 (Caspase-1) inhibitor AC-YVAD-CMK (AC, 6.5 mg/kg) 1 h before LPS injection, and the LPS+TMZ+AC solvent group was injected with an equal amount of AC solvent phosphate buffer. At the end of TMZ treatment, body weight, grip strength, 96-hour survival rate, mRNA and protein expression of MuRF1, Atrogin-1, Caspase-1, and gasdermin D (GSDMD) in gastrocnemius muscle, as well as serum IL-1β and IL-18 concentrations in mice were detected in each group, and the gastrocnemius muscle was stained with HE to observe histopathological changes. Results Compared with the Normal group, mice in the LPS (12 mg/kg) and LPS (14 mg/kg) groups showed significant decreases in body weight and grasping strength and the weakening was most obvious at 3 - 5 d (P<0.05), but the survival rate of the LPS (12 mg/kg) group was higher than that of the LPS (14 mg/kg) group (P<0.05), the HE staining of gastrocnemius muscle showed that the mice in the LPS (12 mg/kg) group was significantly atrophied compared with that of the Normal group, and the gene and protein expression of MuRF1 and Atrogin-1 were significantly elevated (P<0.05), and the mice injected with LPS (12 mg/kg) for 4 days (96 h) were finally selected as the conditions for subsequent experimental modelling and sampling.The mRNA and protein expression of Caspase-1 and GSDMD in skeletal muscle was significantly higher in the LPS group compared with the Normal and Vehicle groups (P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly higher(P<0.01). Mice in the TMZ group showed significant improvement in body weight, grip strength, survival rate, and degree of muscle atrophy compared with the LPS and TMZ solvent groups (P<0.05); gene and protein levels of MuRF1, Atrogin-1, Caspase-1, and GSDMD in the gastrocnemius muscle were significantly reduced (P<0.05); and levels of serum IL-1β and IL-18 were significantly reduced (P<0.05) ); the mice in the LPS+TMZ+AC group had significantly improved body weight, grip strength, survival rate, and muscle atrophy compared with the LPS+TMZ group and the LPS+TMZ+AC solvent group (P<0.05), and the gene and protein contents of MuRF1, Atrogin-1, Caspase-1, and GSDMD in the gastrocnemius muscle were reduced (P<0.05), and the serum IL-1β and IL -18 concentrations were reduced (P<0.05). Conclusion TMZ is able to exert a skeletal muscle protective effect by inhibiting Caspase-1/GSDMD-mediated pyroptosis, which is an important reference for the prevention and treatment of ICU-AW.