Effects of Levosimendan on Diaphragmatic Dysfunction in Patients with Sepsis.

OBJECTIVE: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. METHODS: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBT) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 µg/kg for 10 minutes, followed by a continuous infusion at 0.2 µg/kg/min. The control group received an equivalent dose of a placebo. The pre- and post-administration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). RESULTS: Forty-four patients were enrolled in the study. We found that post-administration of levosimendan, the patients' tidal volume (GCSMV) increased, while the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO 2 ) decreased when compared to the pre-administration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively), and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant ( P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the post-administration levels of DE, TFdi, and D-RSBI as compared to the pre-administration period ( P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning ( P = 0.545). CONCLUSION: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.

Prediction of fluid responsiveness for patients in shock using a ventilator disconnection test combined with the pulse contour-derived cardiac index.

BACKGROUND: Finding a simple and reliable method to predict and assess fluid responsiveness has long been of clinical interest. OBJECTIVE: To investigate the predictive value of a ventilator disconnection (DV) test combined with the pulse contour-derived cardiac output (PiCCO) index on fluid responsiveness for patients in shock. METHODS: Thirty-two patients were chosen for the study. Patients who were in shock, received mechanical ventilation, and met the inclusion criteria were selected. Patients were divided into a fluid-responsive group (14 patients) and fluid-unresponsive group (18 patients) based on whether the increase in cardiac index (Δ CI) was > 10% or not, respectively, following the fluid challenge test. Changes in heart rate, pulse oximeter-measured oxygen saturation, mean arterial pressure (MAP), and CI before and after passive leg raising (PLR), DV, and fluid challenge tests were observed. We used Pearson's correlation coefficient to analyze an increase in the MAP (Δ MAP) and Δ CI before and after the PLR, DV, and fluid challenge tests; the sensitivity and specificity of the Δ MAP and Δ CI in the PLR and DV tests for predicting fluid response were also analyzed by plotting the receiver operating characteristic (ROC) curves. RESULTS: CI results in the PLR and DV tests, as well as the fluid challenge test, were significantly higher in the fluid-responsive group compared with before the test (P< 0.05). The Δ CI before and after the PLR, DV, and fluid challenge tests were positively correlated among patients in the fluid-responsive group. The area under the ROC curve for the post-PLR test CI and the post-DV CI for predicting fluid responsiveness was 0.869 (95% confidence interval (CI) [0.735-1.000, P= 0.000]) and 0.937 (95% CI [0.829-1.000, P= 0.000]), respectively, in patients in the fluid-responsive group. The sensitivity and specificity of the post-DV CI for predicting fluid responsiveness in all patients was 100.0% and 88.9%, respectively, using a 5% increase as the cut-off value. CONCLUSION: Application of DV, combined with PiCCO, has a high predictive value for fluid responsiveness among patients in shock.

Efficacy of Levosimendan in the Treatment of Patients With Severe Septic Cardiomyopathy.

OBJECTIVE: This study was designed to compare the effects of levosimendan and dobutamine on hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤35%). DESIGN: A prospective, single-blind, randomized controlled study. SETTING: In Baoding, China. PARTICIPANTS: Thirty patients with severe septic cardiomyopathy treated in the authors' hospital's Department of Critical Medicine from September 2018 to September 2021 were enrolled in this study. INTERVENTIONS: These patients were divided randomly into the levosimendan group and dobutamine group. The LVEF, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index, heart rate, norepinephrine dose, and lactate at the time of enrollment and the 24th hour were compared, along with myocardial injury markers on the third day, C-reactive protein, mechanical ventilation time, length of intensive care unit (ICU) stay, cost, and 28-day mortality. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: At the 24th hour after treatment, CI, LVEF, SVI, and fluid volume were found to be higher in the levosimendan group than in the dobutamine group, whereas the dose of norepinephrine was lower in the former rather than the latter group. On the third day of treatment, cardiac troponin I in the levosimendan group was lower than that in the dobutamine group. Although the differences in 28-day mortality, ICU stay, and ICU treatment cost between the groups were not statistically significant, the ventilator application time of the levosimendan group was significantly shorter than that of the dobutamine group. CONCLUSIONS: Compared with dobutamine, levosimendan was more effective at improving cardiac function, reducing myocardial injury, and reducing mechanical ventilation time in patients with severe septic cardiomyopathy.

[Effect of diallyl trisulfide on tumor necrosis factor-alpha expression and nuclear factor-KappaB activity in mice with acute lung injury induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor-alpha (TNF-alpha) expression and nuclear factor-KappaB (NF-KappaB) activity in mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: ALI murine model was reproduced by injection of LPS intraperitoneally. Mice were randomly divided into normal saline control group, ALI group, DATS prevention group, DATS treatment group, and DATS control group. The TNF-alpha levels in the serum and in the supernatant of lung homogenates were measured with enzyme linked immunoadsorbent assay (ELISA). The expression of TNF-alpha mRNA in the lung tissues was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-KappaB activity in the lung tissues was detected by electrophoresis mobility shift assay (EMSA). RESULTS: The levels of TNF-alpha induced by LPS in the serum and the supernatant of lung homogenates were increased markedly at 2 hours in ALI group (both P<0.01), and decreased at 6 hours, but they were still higher than those of the control groups (all P<0.01). They were reduced in DATS prevention group at 2 and 6 hours compared with those of ALI group (P<0.05 or P<0.01), but no change was noted in DATS treatment group (all P>0.05). The expression of TNF-alpha mRNA in the lung tissues of ALI group increased markedly at 2 hours compared with those of control groups (both P<0.01), and it could be down-regulated by pretreatment with DATS (P<0.05). No change in DATS was found in treatment group. NF-KappaB activity in the lung tissue increased in ALI group compared with that of control groups (both P<0.05), and it was markedly reduced in DATS prevention group (P<0.05), but no change was found in DATS treatment group. CONCLUSION: Pretreatment of DATS for ALI in mice could inhibit NF-KappaB activity, TNF-alpha mRNA expression in lung tissues, and decrease the release of TNF-alpha in the serum and the lung homogenates, and they might be the underlying mechanisms of prevention of the occurrence of ALI by DATS.