Efficacy and safety of levosimendan in elderly patients with severe heart failure / 中华内科杂志

Objective:To investigate the efficacy and safety of different dosage regimens of levosimendan in elderly patients with severe heart failure.Methods:Thirty-two patients 75 years or older were randomly divided into a loading dose group (16 cases) in which levosimendan was maintained at 0.1 μg·kg -1·min -1 for 24 h after loaded with 6 μg/kg, and a maintenance dose group (16 cases) with same schedule without loading dose. The amino-terminal brain natriuretic peptide (NT-proBNP) before and after treatment was detected. Left ventricular ejection fraction (LVEF), stroke volume (SV), stroke volume index (SVI) by echocardiograph were monitored. Adverse events, the length of stay in ICU and 28-day mortality were recorded. Results:The NT-proBNP level in loading group after treatment was 1 950 (922,6 481)ng/L, which was improved than that before treatment [4 018(2 716,9 637)ng/L, P<0.05]. The result was similar in maintenance group [1 390 (599,3 297)ng/L vs. 4 576 (2 681,10 682)ng/L, P<0.05]. LVEF in loading group before and after treatment was (39.4±8.8) % vs. (48.9±9.2) % respectively, while in maintenance group it was (40.4±8.8) % vs. (48.7±12.0) % (both P<0.05). SV were also improved after treatment in both groups compared with baseline levels ( P<0.05). NT-proBNP started to decline on day 3 in the loading group, while on day 7 in the maintenance group. SVI recovered on day 14 in the loading group [ (29.4±6.5) ml/m 2 vs. (27.3±6.7) ml/m 2, P<0.05], while it did not change much in the maintenance group. There was no significant differences as to the length of stay in ICU [ (11.1±4.4) d in loading group vs. (9.6±3.5) d in maintenance group] and 28-day mortality rates were comparable (2/16 in loading group vs. 1/16 in maintenance group) . The adverse events were 7 vs. 2 cases in loading group and maintenance group respectively, which were mild and all alleviated. Conclusion:The application of levosimendan only with maintenance dose improves cardiac function in very elderly patients with severe heart failure. Adverse events are mild and manageable.

The effects of levosimendan on the cardiac function and prognosis in elderly patients with septic shock and myocardial contractility impairment / 中华内科杂志

Objective To investigate the effect of levosimendan on cardiac function and prognosis in elderly patients with septic myocardial contractility impairment.Methods A prospective,randomized,controlled study was conducted.The elderly patients with septic myocardial contractility impairment who were admitted to Intensive Care Unit in Zhejiang Hospital were consecutively enrolled from January 2017 to September 2017.The key inclusive criterion was left ventricular ejection fraction (LVEF) ≤ 50％ after fluid resuscitation.A total of 30 patients were randomly assigned to levosimendan group (n=15) and dobutamine group (n=15).Based onconventional treatment,intravenous dobutamine (5 μg per kilogram of body weight per minute) or levosimendan (0.2 μg per kilogram of body weight per minute)were continuously administrated for 24 hours in two groups.At 0 h,24 h,48 h,72 h after injection,the following parameters or values were recorded including serum lactic acid (Lac),and echocardiographic parameters such as LVEF,stroke volume (SV).The time of mechanical ventilation,length of stay in ICU and 28-day mortality were compared in two groups.Results Compared with dobutamine group,blood Lac at 24 h [(1.97±1.10)mmol/L vs.(2.73 ± 2.06) mmol/L,P=0.002] decreased significantlyin levosimendan group.LVEF and SV were significantly higher in levosimendan group at 24 h [LVEF:(47.93±5.01)％ vs.(45.60±5.47)％,P=0.004;SV:(47.73 ± 14.01) ml vs.(44.80±16.89) ml,P=0.035;respectively],48 h [LVEF:(51.07 ± 5.05)％ vs.(46.73 ± 6.34)％,P=0.004;SV:(49.87 ± 14.15) ml vs.(45.07± 16.94) ml,P=0.005;respectively] and 72 h [LVEF:(53.20±5.92)％ vs.(47.70±6.71)％,P=0.002;SV:(51.27±14.98) ml vs.(45.73±17.34) ml,P=0.010].The time of mechanical ventilation,length of stay in ICU and 28-day mortality were comparable between two groups (P＞0.05).Conclusions Levosimendan improves cardiac systolic function and tissue perfusion in elderly patients with septic myocardial contractility impairment.However,cardiac diastolic function,liver and kidney function are not further improved by levosimendan compare with dubutamine.Time of mechanical ventilation,length of stay in ICU and 28-day mortality in two groups are similar.

The influence of left ventricular-arterial coupling on the prognosis of elderly patients with septic shock / 中华内科杂志

Objective To investigate the influence of left ventricular-arterial coupling(VAC) on clinical prognosis of elderly patients with septic shock.Methods A total of 56 elderly septic shoek patients were enrolled in this study,all of whom were admitted to Department of Intensive Care Unit in Zhejiang Hospital from August 2014 to October 2015.The patients were divided into two groups according to the status of left ventricular-arterial coupling when septic shock was diagnosed,which were left ventricular-arterial uncoupling group(UC group) and left ventricular-arterial coupling group(C group).Various parameters were recorded,including blood lactate level,central venous oxygen saturation(ScvO2),serum level of N-terminal pro-brain natriuretic peptide(NT-proBNP) and cardiac troponin Ⅰ (cTN Ⅰ),dose of vasoactive drugs,the total fluid volume and urine volume per hour within 24 hours.The 28-day survival rate was a key index of prognosis.Multivariate logistic regression was taken to analyze risk factors related to death within 28 day.Results Compared with C group,UC group had lower values of left ventricular ejection fraction[(42.43 ±4.76)％ vs (53.17±3.01)％;P＜0.01] and cardiac index[(2.36±0.68) L· min-1 · m 2vs (2.93±0.45)L · min-1 · m-2;P ＜0.01].Yet serum levels of NT-proBNP[lg NT-proBNP 3.93 ±0.53 vs 3.40 ±0.63;P =0.004] and cTN Ⅰ [lg cTN Ⅰ-0.16 ± 0.68 vs-1.03 ± 0.69;P ＜ 0.001] in UC group were higher than those in C group.Moreover,the total fluid volume within 24 hours [(3 806.3 ± 831.4) ml vs (3 142.0±770.0) ml;P =0.016],blood lactate level[(5.61 ±2.68) mmol/L vs (3.93 ± 1.59)mmol/L;P =0.043] and dose of norepinephrine[(0.630 ±0.300) μg · kg-1 · min-1 vs (0.292 ±0.234)μg · kg-1 · min-1;P =0.001] in UC group were greater than those in C group,while ScvO2 [(60.75 ±2.91)％ vs (64.42 ±2.19)％;P＜0.001] and urine volume per hour[(0.518 ±0.358) ml vs (0.926 ±0.678) ml;P =0.007] were less than those in C group.Compared with C group,UC group had a lower 28-day survival rate [43.2％ (19/44) vs 9/12;P =0.049].Ea/Ees ratio was negatively correlated with LVEF,ScvO2 (r =-0.686,P ＜ 0.001;r =-0.411,P =0.002),positively correlated with NT-proBNP,cTN Ⅰ (r =0.294,P =0.028;r =0.363,P =0.006),yet no obvious correlation was noticed with blood lactate level (r =0.170,P =0.21).Multiple logistic regression analysis showed that VAC(OR =11.187,95％ CI 2.489-50.285;P =0.002),lactate level (OR =1.727,95 ％ CI 1.164-2.563;P =0.007) and lg cTN Ⅰ (OR =0.247,95 ％ CI 0.079-0.779;P =0.017) were independent risk factors affecting 28-day mortality.Conclutions In elderly patients with septic shock,left ventricular-arterial uncoupling indicates a lower 28-day survival rate,worse cardiac function and tissue perfusion.Ea/Ees ratio might sever as a predictive indicator of 28-day mortality.

Association of poly(ADP-ribose) polymerase activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Severe sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients. This study aimed to investigate the association of poly (ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.</p><p><b>METHODS</b>A total of 64 patients with septic shock were divided into the survival group (n = 41) and the nonsurvival group (n = 23) according to mortality at 28 days after enrollments. PARP-1 activity in circulating mononuclear cells, brain natriuretic peptide, Acute Physiology and Chronic Health Evaluation II score, the cardiac index (CI), the cardiac function index (CFI), global ejection fraction (GEF), and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit.</p><p><b>RESULTS</b>PARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients. PARP-1 activity in circulating mononuclear cells was strongly, negatively correlated with the CI, the CFI, GEF, and dp/dt max. Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction. The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.</p><p><b>CONCLUSION</b>PARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.</p>

Value of stroke volume variation in guiding fluid resuscitation therapy in the elderly septic patients / 中华老年医学杂志

Objective To investigate the clinical values of central venous pressure (CVP) versus stroke volume variation (SVV) in patients with severe sepsis after early goal-directed therapy (EGDT).Methods Totally 30 mechanically ventilated patients with severe sepsis who underwent goal-achieved EGDT were enrolled and randomly divided into CVP group (study group) and SVV group (control group) according to the data detected by pulse contour continuous cardiac output (PiCCO) analysis device.The differences in 28-day survival,3-day APACHE Ⅱ score,time of ICU stay,duration of mechanical ventilation,number that need CRRT,entral venous pressure (CVP),heart end-diastolic volume index (GEDVI),intrathoracic blood volume index (ITBVI),extravascular lung water index (EVLWI),cardiac index (CI),central venous oxygen saturation (ScvO2),lactate clearance rate and APACHE Ⅱ score were compared between the 2 groups.Results The death rate had no difference between the 2 groups(x2=0.240,P=0.624).Among survival patients in the CVP group,the time of ICU stay and duration of mechanical ventilation were shorter in study group than in control group(t=2.166,P=0.041;t=2.104,P=0.046),APACHE Ⅱ score at 3th day was decreased(t=2.20,P =0.038).The values of ITBVI,GEDVI,CI,lactate clearance rate were higher in study group than in control group (t=2.759,2.146,2.199,2.654,3.362,P=0.011,0.043,0.038,0.014,0.003).EVLWI and APACHE Ⅱ score were not different (P＞0.05) between the two groups.Conclusions SVV as a recovery target for fluid resuscitation can reach a better recovery results and improvement of prognosis than CVP goal-achieved EGDT.

Role of damaged mitochondria in cardiocyte apoptosis in septic rats / 中华急诊医学杂志

Objective To investigate the role of damaged mitochondria in cardiac cell apoptosis in septic rats and the possible mechanism involved.Methods Seventy-two Sprague-Dawley rats were randomly (random number) divided into negative control group (n =18) and septic group (further divided into three groups as per rats sacrificed 6 h,12 h,and 24 h after endotoxin injection intra-peritoneally,n =18).The hearts of rats were taken.The changes of cardiac morphology were observed under light microscope and scanning electron microscope.Cell apoptosis in situ were examined by using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B (NF-κB) activation in myocardium was detected by using Western blotting to estimate myocardial cell apoptosis.Mitochondrial lipid and protein oxidation were measured to assess oxidative stress,and mitochondrial superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined to estimate antioxidant defense.Results Septic induced inflammatory cells infiltration,myocardium degeneration and effusion in a time-dependent manner.A remarkable expansion of capillaries could be observed in the hearts of infected rats at post-challenge of 24 h.Compared with sham-treated rats,the percentage of apoptosis increased in a time-dependent manner in the hearts of infected rats at 6 h,12 h,24 h of post-injection (P ＜0.05).The concentration of NF-κB p65 in the cytosol decreased gradually and increased in the nucleus during sepsis in a time-dependent manner (P ＜0.05),indicating that septic challenge provoked progressive activation of NF-κB.Mitochondrial cristae disappeared in 6 h of challenge,and significant mitochondrial cristae disappearance,vacuolization,and rupture of mitochondria membrane became markedly obvious 12 and 24 h later.Both SOD and GPx activities decreased,while mitochondrial lipid and protein oxidation increased in a time-dependent manner after 6-24 h of challenge (P ＜ 0.05).Conclusions Septic challenge induced myocardial apoptosis and mitochondrial damage.Further,damaged mitochondria might play an important role by means of alteration of defenses against reactive oxygen species in myocardial cell apoptosis during sepsis.

Prognostic value of stroke volume variation in septic patients / 中华急诊医学杂志

Objective To investigate the prognostic value of stroke volume variation (SVV) in patients with severe sepsis after early goal-directed therapy (EGDT). Method Thirty-eight mechanically ventilated patients with severe sepsis underwent EGTD were divided into high SVV (≥10%) group and low SW (< 10%) group according to the data obtained from pulse contour continuous cardiac output (PiCCO) analysis device. The differ-enees in the rate of 28-day survival, length of ICU stay, duration of meehanical ventilation and eomplieation of in-fection between two groups of patients were compared. The rate of 28-day survival of patients was analyzed by using Kaplain-Meier survival analysis, and the relationship between SVV and mortality within 28 days was analyzed by using logistic regression model. Results In comparison with low SVV group, the rate of 28-day survival of high SVV group was signifieantly increased (87.5 % vs. 57.1%, P = 0.032), the length of ICU stay was significantly shortened (27.1±9.2) vs. (41.6±10.0) (P = 0. 004) and duration of mechanical ventilation was significantly more brief (20.4±7.3) vs. (28.5±8.3) (P = 0.038). The rate of cumulative survival of patients in high SVV group was higher than that in low SVV group. In addition, logistie analysis showed SW < 10% increased the risk of 28-day mortality (OR = 3.97; 95% CI 1.63 - 9.21, P = 0. 014). Conclusions The SVV can be served as a prognostic indicator in patients with severe sepsis after EGDT.

Significance of procalcitonin test for directing antibiotic therapy in elderly patients with ventilator associated pneumonia / 中华老年医学杂志

Objective To explore the significance of the plasma procalcitonin (PCT) level for directing antibiotic therapy in elderly patients with ventilator-associated pneumonia (VAP).Methods The 50 elderly patients with VAP were randomly separated into the regular therapy group and the PCT-directed therapy group. The regular therapy group was given regular antibiotic therapy, while the antibiotic therapy was decided according to the plasma level of PCT in the PCT-directed therapy group. The used time and utilization rate of antibiotics, as well as inflammatory indicators including white blood cells, neutrophils, C-reactive protein (CRP) and clinical pulmonary infection score (CPIS) were compared between the two groups. Results After treatment, there were no significant differences in white blood cells, neutrophils and CRP between the PCT-directed therapy group and regular therapy group [(8.9 ± 3.5 ) × 109/L vs. (9.4 ± 3.7) × 109/L, 0.62 ± 0.04 vs.0.60±0.04, (18.7±8.5) mg/Lvs. (21.6±6.0) mg/L, t=0.47, 1.84 and 1.37, allP＞0.05],but the CPIS was markedly lower in PCT-directed therapy group than in regular therapy group [(4.0± 1.4) scores vs. (4.7± 1.0) scores, t= 2. 18, P＜0.05]. The neutrophils, CRP and CPIS were significantly lower after treatment than before in the both groups. The concentration of PCT was decreased after treatment than before [(0.5 ± 0.9) mg/L vs. (1.7 ± 0.7) mg/L]. Meanwhile, the time using antibiotics was longer in regular treatment group than in PCT-directed therapy group [(8.72±1.32) d vs. (5.17±0.72) d, t=11.96, P＜0.01], the utilization rate of antibiotics was higher (95.2 % vs. 55.2 %, χ2 = 12.41, P＜0.01) in regular treatment group. Conclusions Using PCT levels for directing treatment in elderly patients with VAP can achieve better curative effect and reduce the use of antibiotics.

The metabolite features of chronic pancreatitis in rats / 中华胰腺病杂志

Objective To investigate the metabolite features of chronic pancreatitis in rats in vitro by high resolution magic angle spinning nuclear magnetic resonance spectroscopy. Methods A total of 30 Spraque-Dawley rats were randomized into experimental group (n =20) and control group (n = 10). All the animals in experimental group were intravenously injected with 8 mg/kg body weight DBTC, and the animals in the control group received same amount of solvent. Pancreatic tissues were examined by histology and Van Gieson staining. Metabolic changes of chronic pancreatitis in vitro in rats were studied by high resolution magic angle spinning nuclear magnetic resonance spectroscopy. Results 60 days after DBTC application, the pancreatic tissue was characterized by an extended interstitial fibrosis with infiltrating mononuclear cells. Compared with the control group, the signal intensities of phosphocholine (Pc) and glycerophosphocholine (Gpc), taurine (Tau), lactate (Lac) of chronic pancreatitis group increased. Oppositely, the signal intensities of betine (Bet), glutamic acid ( Glu ), alanine (Ala), ileucine (He), leucine ( Leu ) and valine (Val) decreased. The signal intensities of acetic acid (Ace) and choline (Cho) were not changed. Conclusions There were obvious metabolic features of chronic pancreatitis in rats, and it is helpful for the application of magnetic resonance spectroscopy in chronic pancreatitis in human studies.

Effects of plasma brain natriuretic peptide on prognosis of elderly patients with severe sepsis / 中华急诊医学杂志

Objective To evaluate the predictive value of brain natriuretic peptide (BNP) on mortality in elderly patient with severe sepsis or septic shock. Method Eighty-three elderly patients meeting with criteria of severe sepsis or septic shock by the American College of Chest Physicians and the Society of Critical Care Medicine (ACCP/SCCM) in 2001, admitted in Intensive Care Unit (ICU) of Zhejiang Hospital during May 2004 to June 2007, were enrolled, and patients with chronic renal failure were excluded. The patients were divided into survivor and non - survivor group according to whether they survived within 28 days staying in ICU, the difference of plasma BNP level,serum C-creative protein (CRP) concentration, APACHE II and SOFA scores on admission day and BNP level on the third day between the two groups were compared; thereafter, the relationship between muhiple variables including age, admission day, BNP, CRP, APACHE 11 and SOFA scores, the 3rd day BNP level and 28-day mortality were analyzed by Logistic regression, and meanwhile the independent predictors for ICU moaality among which were determined. Results BNP levels on both admission day and the 3rd day were significantly higher in nomurvivor group than those in survivor group[ ( 1056.38±676.34) pg/ml vs. (611.59±610.02) pg/ml,p =0.002 and (1448.48+891.11) pg/ml vs. (522.41±575.20) pg/ml, P<0.001, respectively]. By Logistic regression analysis, BNP level on the 3rd day and SOFA score on admission day were independent predictors of ICU mortality, The receiver operating characteristic (ROC) curves indicated that values of areas under the curve of the admission day and the 3rd day BNP levels for 28-days mortality were 0.735 (95% CI,0. 621～0. 848, P <0.001) andO.836 (95% CI, 0.746～0,926,P<0.001), respectively. Conclusions Plasma BNP inereaseds in majority of eldedy patients with severe sepsis or septic shock, which may serve as irdex for prognosis in elderly severe septic paients.

Effects of high volume hemofiltration(HVHF) on cytokines in elderly patients with septic shock and MODS / 中华急诊医学杂志

Objective To study the effects of HVHF on cytokines in elderly patients with septic shock and MODS. Methods 22 elderly patients with septic shock and MODS were included in this prospective and interventional study. Before HVHF and 1,3,6,9,12,18 and 24 hour after HVHF, blood sample and ultrafiltration fluid were collected for cytokines analysis(radioimmunoassay). Results All patients finished HVHF. No severe side effects were observed,and the APACHEⅡ and MODS scores were decreased during HVHF(P

Role of antibody chin in analysis of inflammatory cytokine expression in severe sepsis / 中华急诊医学杂志

Objective To investigate the expression of inflammatory cytokines in patients with severe sepsis by using an antibody chip.Methods Twelve patients with severe sepsis and other 10 patients whose age and gender were matehed were enrolled in this study.Proteins from patients were labeled with biotin.The biotin-labeled proteins reaeted with antibody chips,on which there were antibodies of 40 major inflammatory cytokines.The target proteins were conjugated with streptomycin antibody labeled by horseradish peroxidase(HRP),and signals were imaged by laser scanner.Results In comparison with control group,the serum levels of inflammatory eytokines ineluding pro-and anti-inflammatory cytokines,ehemokines and certain eytokines receptors were notably increased,while expression of anti-inflammatory interleukin(IL)-2,-4,-13,-15 was remarkably decreased in sepsis group.Conclusions Excess inflammatory response and imbalance of pro-and anti-inflammatory eytokines were presented in the eourse of severe sepsis.

Effect of early goal-directed therapy on myocardial protection in severe sepsis/septic shock patients / 解放军医学杂志

0.05) between two groups.After EGDT,the level of cTnI in EGDT group was obviously dowered on the 7th day (0.16?0.22?g/L) and 14th day (0.09?0.13?g/L) compared with those in control group (0.39?0.43,0.29?0.29?g/L,P

Assessment of fluid treatment in elderly patients with severe sepsis guided by monitoring the variation of stroke volume / 解放军医学杂志

0.05).Conclusions Fluid therapy guided by functional hemodynamic index SVV in elderly patients with severe sepsis under MV is safe and more effective than that guided by CVP.SVV is valuable in prodicting the response to fluid treatment in elderly patients with severe sepsis.