Objective:To investigate the effect of levosimendan on 28-day mortality in patients with sepsis.Methods:The English databases including Embase,PubMed,Web of Science,Cochrane Library and Chinese databasesincluding Chin...Objective:To investigate the effect of levosimendan on 28-day mortality in patients with sepsis.Methods:The English databases including Embase,PubMed,Web of Science,Cochrane Library and Chinese databasesincluding China National Knowledge Infrastructure(NKI),Wan fang Data,VIP,CBM were searched with levosimendan,sepsis and septic shock is as search terms.The published clinical randomized controlled trials of levosimendan injection were searched and the primary outcome measures of 28-day and 30-day mortality were included.Secondary outcome measures were left ventricular ejection fraction,left ventricular work index,cardiac index,and lactic acid.The literature retrieved is from the establishment of the database to October 2022.Stata 14.0 software was used for all data consolidation,publication bias monitoring and sensitivity analysis.Results:A total of 15 studies with 1337 patients were included in this meta-analysis.The results showed that at the 28-day mortality of patients with sepsis in the levosimendan group was not statistically superior to the 28-day mortality in the control group[RR=0.91,95%CI(0.78~1.06),Z=1.24,P=0.22].However,levosimendan can increase left ventricular ejection fraction,decrease left ventricular function index,increase cardiac index and decrease lactic acid in patients with sepsis.Conclusion:There is insufficient evidence to support a reduction in 28-day mortality in sepsis patients with levosimendan.However,levosimendan showed positive results on hemodynamic parameters,and more clinical trials are needed to verify the application of levosimendan in hemodynamic parameters of sepsis.展开更多
[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medici...[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medicine-cardiovascular department in The First People s Hospital of Yulin from January 2019 to February 2020 were randomly divided into two groups, 50 cases in each group. Both groups were treated with conventional anti-heart failure drugs. The control group was given levosimendan once, and the observation group was given levosimendan three times, with an interval of one month. The creatinine (Cr) level, serum NT proBNP, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were observed at 48 h before and after treatment and one month and two months after treatment in both groups. [Results] Compared with before treatment, the levels of NT-proBNP decreased in the two groups at 48 h after treatment, and the difference was statistically significant ( P <0.05). The Cr level of the control group did not change significantly before and after treatment, and the Cr level of the observation group decreased at one and two months after treatment compared with before treatment, with statistically significant differences ( P <0.05). Compared with before treatment, NT-proBNP and LVEDD decreased and LVEF increased at one and two months after treatment, and the differences were statistically significant ( P <0.05). There were no obvious adverse reactions in the two groups of patients during the treatment. [Conclusions] Repetitive use of levosimendan in the treatment of acute heart failure could significantly improve the renal function, cardiac contractility and cardiac function of patients, and with the passage of time, the treatment effect was improved, which is worthy of clinical promotion.展开更多
Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1...Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.展开更多
Background: Left ventricular ejection fraction is an independent determinant of the outcome of coronary artery bypass surgery. Low preoperative ejection fraction requires special care in terms of pharmacological and m...Background: Left ventricular ejection fraction is an independent determinant of the outcome of coronary artery bypass surgery. Low preoperative ejection fraction requires special care in terms of pharmacological and mechanical inotropic support. Adrenaline is the most widely used inotropic drug, while levosimendan is a relatively new inotropic drug in the field of cardiac surgery. In this study, we aimed to evaluate the relative efficacy of levosimendan in low ejection fraction patients undergoing coronary artery bypass grafting (CABG). Methods: A retrospective comparative study was performed with 63 patients who underwent isolated on-pump elective CABG with a preoperative ejection fraction below 40%. Patients were allocated to the adrenaline group (n = 35) and levosimendan group (n = 28). Patients were further stratified according to ejection fraction above 30% and below or equal to 30%. The primary outcome was cardiac-related mortality, while other parameters were considered secondary endpoints. Results: EuroSCORE of the adrenaline group was 3.34 ± 1.26 and for the levosimendan group 3.15 ± 1.42 (p value 0.576). Nine patients of the adrenaline group had new postoperative atrial fibrillation compared to seven patients in the levosimendan group (p value 0.948). Two patients of the adrenaline group had postoperative ventricular arrhythmia compared to only one patient in the other group (p value 0.691). The adrenaline group had higher doses of inotropic support compared to the levosimendan group 210.84 ± 23.74 and 157.4 ± 22.69 ng/kg/min respectively (p value Conclusions: The levosimendan-based protocol failed to improve overall mortality in low ejection fraction patients undergoing CABG. However, this protocol significantly reduced the dose of inotropic and vasoconstrictor support needed, ventilation hours and duration of ICU stay.展开更多
Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress...Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H2O2 in human saphenous vein (HSV) segments. Methods: We studied H2O2 induced contractions of isolated HSV mounted in standard tissue baths. H2O2 (10-6 – 10-3 M) was added cumulatively to the organ bath. Concentration-response curves to H2O2 were repeated in the presence of levosimendan (10–8 M). In the second series of experiments, strips were contracted with 5-HT (10–5 M). When the contraction reached a stable plateau, H2O2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H2O2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H2O2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H2O2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.展开更多
Introduction: In this study we explicated early results of patients (the patients in whom levosimendan was used) who underwent coronary artery bypass graft surgery with ejection fraction 35% or less. We compared this ...Introduction: In this study we explicated early results of patients (the patients in whom levosimendan was used) who underwent coronary artery bypass graft surgery with ejection fraction 35% or less. We compared this group with the patients in whom levo-simendan was not used. Material and Methods: 97 patients who have 35% ejection fraction or less taken to isolated coronary artery bypass surgery between January 2009 and December 2011 in our clinic are chosen for this study retrospectively. We compared the patients in whom levosimendan was used with the patients in whom levosimendan was not used. Levo- simendan (Simdax, Abbott) has been used according to surgeon’s decision in patients. Results: The mean age of group 1 was 62.3 ± 7.6, and the mean age of group 2 was 59.3 ± 10.5 (p > 0.05). It was detected that the average ejection fraction was less in group 1 (p 0.05). It was found that need for blood transfusion were less in group 1 than group 2 (p 0.05). Conclusion: We consider levosimendan reduces need for blood transfusion in coronary artery bypass graft surgery. This results may change with increasing number of patients so we consider that multicenter larger study is needed.展开更多
Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart fa...Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group;serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group;serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group;serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.展开更多
Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery. The study tried to evalu...Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery. The study tried to evaluate the effects of levosimendan and ulinastain for protecting myocardium from ischemia-reperfusion (I / R) injury to展开更多
基金This study was supported by National Natural Foundation Project of China(No81760341)。
文摘Objective:To investigate the effect of levosimendan on 28-day mortality in patients with sepsis.Methods:The English databases including Embase,PubMed,Web of Science,Cochrane Library and Chinese databasesincluding China National Knowledge Infrastructure(NKI),Wan fang Data,VIP,CBM were searched with levosimendan,sepsis and septic shock is as search terms.The published clinical randomized controlled trials of levosimendan injection were searched and the primary outcome measures of 28-day and 30-day mortality were included.Secondary outcome measures were left ventricular ejection fraction,left ventricular work index,cardiac index,and lactic acid.The literature retrieved is from the establishment of the database to October 2022.Stata 14.0 software was used for all data consolidation,publication bias monitoring and sensitivity analysis.Results:A total of 15 studies with 1337 patients were included in this meta-analysis.The results showed that at the 28-day mortality of patients with sepsis in the levosimendan group was not statistically superior to the 28-day mortality in the control group[RR=0.91,95%CI(0.78~1.06),Z=1.24,P=0.22].However,levosimendan can increase left ventricular ejection fraction,decrease left ventricular function index,increase cardiac index and decrease lactic acid in patients with sepsis.Conclusion:There is insufficient evidence to support a reduction in 28-day mortality in sepsis patients with levosimendan.However,levosimendan showed positive results on hemodynamic parameters,and more clinical trials are needed to verify the application of levosimendan in hemodynamic parameters of sepsis.
基金Supported by Scientific Research and Technology Development Program of Yulin City(20204031).
文摘[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medicine-cardiovascular department in The First People s Hospital of Yulin from January 2019 to February 2020 were randomly divided into two groups, 50 cases in each group. Both groups were treated with conventional anti-heart failure drugs. The control group was given levosimendan once, and the observation group was given levosimendan three times, with an interval of one month. The creatinine (Cr) level, serum NT proBNP, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were observed at 48 h before and after treatment and one month and two months after treatment in both groups. [Results] Compared with before treatment, the levels of NT-proBNP decreased in the two groups at 48 h after treatment, and the difference was statistically significant ( P <0.05). The Cr level of the control group did not change significantly before and after treatment, and the Cr level of the observation group decreased at one and two months after treatment compared with before treatment, with statistically significant differences ( P <0.05). Compared with before treatment, NT-proBNP and LVEDD decreased and LVEF increased at one and two months after treatment, and the differences were statistically significant ( P <0.05). There were no obvious adverse reactions in the two groups of patients during the treatment. [Conclusions] Repetitive use of levosimendan in the treatment of acute heart failure could significantly improve the renal function, cardiac contractility and cardiac function of patients, and with the passage of time, the treatment effect was improved, which is worthy of clinical promotion.
文摘Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.
文摘Background: Left ventricular ejection fraction is an independent determinant of the outcome of coronary artery bypass surgery. Low preoperative ejection fraction requires special care in terms of pharmacological and mechanical inotropic support. Adrenaline is the most widely used inotropic drug, while levosimendan is a relatively new inotropic drug in the field of cardiac surgery. In this study, we aimed to evaluate the relative efficacy of levosimendan in low ejection fraction patients undergoing coronary artery bypass grafting (CABG). Methods: A retrospective comparative study was performed with 63 patients who underwent isolated on-pump elective CABG with a preoperative ejection fraction below 40%. Patients were allocated to the adrenaline group (n = 35) and levosimendan group (n = 28). Patients were further stratified according to ejection fraction above 30% and below or equal to 30%. The primary outcome was cardiac-related mortality, while other parameters were considered secondary endpoints. Results: EuroSCORE of the adrenaline group was 3.34 ± 1.26 and for the levosimendan group 3.15 ± 1.42 (p value 0.576). Nine patients of the adrenaline group had new postoperative atrial fibrillation compared to seven patients in the levosimendan group (p value 0.948). Two patients of the adrenaline group had postoperative ventricular arrhythmia compared to only one patient in the other group (p value 0.691). The adrenaline group had higher doses of inotropic support compared to the levosimendan group 210.84 ± 23.74 and 157.4 ± 22.69 ng/kg/min respectively (p value Conclusions: The levosimendan-based protocol failed to improve overall mortality in low ejection fraction patients undergoing CABG. However, this protocol significantly reduced the dose of inotropic and vasoconstrictor support needed, ventilation hours and duration of ICU stay.
文摘Aim: Increased oxidative stress plays important roles in vascular dysfunction in patients undergoing coronary artery bypass graft surgery. Hydrogen peroxide (H2O2) is used as an experimental model for oxidative stress. The present study was designed to assess the effects of levosimendan pretreatment on the contractile effects induced by H2O2 in human saphenous vein (HSV) segments. Methods: We studied H2O2 induced contractions of isolated HSV mounted in standard tissue baths. H2O2 (10-6 – 10-3 M) was added cumulatively to the organ bath. Concentration-response curves to H2O2 were repeated in the presence of levosimendan (10–8 M). In the second series of experiments, strips were contracted with 5-HT (10–5 M). When the contraction reached a stable plateau, H2O2 was administrated cumulatively into the organ bath. The same procedure was conducted in the presence of levosimendan. Results: Pretreatment of the SV strips with levosimendan significantly reduced the contractile response to each concentration of H2O2 . 5-HT produced contractions in SV strips. Further treatment of these strips with H2O2 resulted in statistically significant concentration-dependent increases in tension. Preincubation of the tissues with levosimendan did not significantly influence the maximum amplitude of the 5-HT-induced tone but inhibited the contractile effect of H2O2 on the 5-HT-induced contraction. Conclusion: Pretreatment of HSV with clinical concentrations of levosimendan inhibits the vasoconstriction caused by oxidative stress, indicating its potential preventive effect against oxidative stress induced graft spasm.
文摘Introduction: In this study we explicated early results of patients (the patients in whom levosimendan was used) who underwent coronary artery bypass graft surgery with ejection fraction 35% or less. We compared this group with the patients in whom levo-simendan was not used. Material and Methods: 97 patients who have 35% ejection fraction or less taken to isolated coronary artery bypass surgery between January 2009 and December 2011 in our clinic are chosen for this study retrospectively. We compared the patients in whom levosimendan was used with the patients in whom levosimendan was not used. Levo- simendan (Simdax, Abbott) has been used according to surgeon’s decision in patients. Results: The mean age of group 1 was 62.3 ± 7.6, and the mean age of group 2 was 59.3 ± 10.5 (p > 0.05). It was detected that the average ejection fraction was less in group 1 (p 0.05). It was found that need for blood transfusion were less in group 1 than group 2 (p 0.05). Conclusion: We consider levosimendan reduces need for blood transfusion in coronary artery bypass graft surgery. This results may change with increasing number of patients so we consider that multicenter larger study is needed.
文摘Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group;serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group;serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group;serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.
文摘Objective Levosimendan,a new calcium ion sensitizer,is currently used in the treatment of heart failure and as an option for patients with injury to the left heart or at high risk for surgery. The study tried to evaluate the effects of levosimendan and ulinastain for protecting myocardium from ischemia-reperfusion (I / R) injury to
