Inotropes

Inotropes increase the force of contraction of cardiac muscle and thereby increase cardiac output. In general, they are used to prevent anaerobic metabolism by improving oxygen delivery to the tissues. Inotropic agents have varying pharmacological profiles; drug selection according to the clinical circumstance enables benefits to be maximized while minimizing side effects. Most inotropes act to increase intracellular calcium levels. Adrenoceptor agonists (e.g. epinephrine) achieve this by activating adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) levels and protein kinase activity, which potentiates the opening of voltage-gated calcium channels and increases the amount of calcium released from the sarcoplasmic reticulum. Phosphodiesterase inhibitors (e.g. milrinone) block the degradation of cAMP, thereby increasing protein kinase activity and calcium levels. Raised intracellular calcium is, however, associated with arrhythmias and cell death, leading to the development of newer agents that act by different mechanisms. Levosimendan improves the sensitivity of the contractile apparatus to calcium, thereby increasing inotropy. Epinephrine remains the drug of choice in emergencies (cardiac arrest, anaphylaxis). Inotropes are commonly administered by controlled infusion in the critical care environment, to allow close monitoring and careful titration. The combined use of several inotropes in lower doses may confer a benefit over single agents used at high doses.     

注射用益气复脉（冻干）联合左西孟旦对慢性心力衰竭患者心功能、血流动力学和炎性因子的影响

目的 注射用益气复脉（冻干）联合左西孟旦对慢性心力衰竭患者心功能、血流动力学和炎性因子的影响。方法 选取2018年10月-2019年10月聊城市中医医院收治的慢性心力衰竭住院患者100例为研究对象,将患者按入组顺序进行编号分为对照组和观察组,每组各50例。对照组给予左西孟旦注射液治疗,设定初始负荷剂量为12 μg/kg,持续注射10 min;之后以0.1 μg/（kg·min）剂量静脉滴注,1 h后将滴注剂量增至0.2 μg/（kg·min）并持续滴注23 h。观察组在对照组治疗基础上静脉滴注注射用益气复脉（冻干）,1.3 g药液溶至5%葡萄糖注射液250 mL中,1次/d,连续治疗14 d。比较两组患者治疗前后的心功能指标、血流动力学和炎性因子水平。结果 治疗后,两组脑钠肽（BNP）水平均显著降低,每搏心输出量（SV）、左室射血分数（LVEF）及6 min步行试验距离均显著升高（P<0.05）;且观察组患者BNP显著低于对照组,SV、LVEF及6 min步行试验距离显高于对照组（P<0.05）。治疗后,两组心率（HR）、收缩压（SBP）及舒张压（DBP）均显著降低（P<0.05）;观察组患者HR显著低于对照组,SBP、DBP显著高于对照组（P<0.05）。治疗后,两组血浆超敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）及白介素-6（IL-6）水平均显著降低（P<0.05）;观察组患者血浆hsCRP、TNF-α及IL-6水平显著低于对照组（P<0.05）。结论 采用注射用益气复脉（冻干）联合左西孟旦治疗慢性心力衰竭,可显著改善心功能和血流动力学指标,抑制全身炎症反应,其效果优于单纯左西孟旦治疗。     

左西孟旦治疗急性失代偿性心力衰竭的效果评价

目的:评价左西孟旦治疗急性失代偿性心力衰竭的临床效果。方法:将60例常规治疗不能缓解的急性失代偿性心力衰竭患者随机分为两组。研究组给予左西孟旦治疗,以0.1μg/(kg·min)持续输注24 h;对照组给予多巴酚丁胺5~10μg/(kg·min)持续输注24 h。治疗前后评估患者全身状况、生命体征并检测24 h尿量、脑钠肽(BNP)、左室射血分数(LVEF)、每搏输出量(SV)等相关指标的变化。结果:与对照组相比,研究组在改善全身状况、增加24 h尿量、降低BNP、改善LVEF、增加SV方面均表现显著优势(P<0.05)。结论:左西孟旦对于急性左心衰患者疗效优于多巴酚丁胺,能明显改善患者心功能及心力衰竭症状。     

左西孟旦治疗60例重度心力衰竭患者疗效观察

目的：研究静脉注射左西孟旦治疗心力衰竭患者的疗效。方法选取我科2012年1月至2014年1月收治的心力衰竭患者60例,其中缺血性心肌病30例,扩张型心肌病30例。常规药物治疗效果不佳,加用左西孟旦注射液治疗,使用方法按说明书：治疗的初始负荷剂量为12μg／kg,注射时间10 min,之后持续输注0．1μg·kg-1·min-1。应用左西孟旦治疗48 h后,比较左心室射血分数（left ventricular ejection fraction,LVEF）、每搏心输出量（stroke volume, SV）和N末端脑钠肽（N-terminal brain natriuretic peptide,NT-BNP）较治疗前的改善情况,以综合评价左西孟旦治疗心力衰竭的疗效。结果治疗48 h后,LVEF上升均值6．41％,与用药前比较差异有统计学意义（P＜0．05）;其中缺血性心肌病组（8．32％）比扩张型心肌病组（4．5％）升高,两组比较差异有统计学意义（P＜0．05）。SV上升均值为13．91 mL,与用药前比较差异有统计学意义（P＜0．05）;缺血性心肌病组SV上升均值（17．56 mL）比扩张型心肌病组（10．26 mL）高,两组比较差异有统计学意义（P＜0．05）。NT-BNP下降均值为4051 pg／mL,与用药前比较差异有统计学意义（P＜0．05）;用药后患者呼吸困难和全身临床状况显著改善。结论与常规治疗比较,左西孟旦注射液治疗重度失代偿性心力衰竭疗效确切;左西孟旦注射液对缺血性心肌病患者血流动力学的改善优于扩张型心肌病。     

左西孟旦在老年急性左心衰竭患者中的应用

目的评价左西孟旦治疗老年急性左心衰竭的临床疗效。方法选取2011年6月至2013年6月在第四军医大学西京医院老年病科住院的急性左心衰竭患者72例,其中男49例、女23例,年龄65～87（75.1±9.8）岁。将其随机分为对照组和左西孟旦组（n＝36）,对照组给予常规抗心力衰竭治疗,左西孟旦组在常规抗心力衰竭治疗的基础上加用左西孟旦。观察两组患者的临床疗效、每搏心输出量（SV）、左室射血分数（LVEF）及N-末端脑钠肽前体（NT-pro-BNP）的改善情况。结果治疗后两组患者的心力衰竭症状和体征均有显著改善。SV及LVEF明显提高（P＜0.05）,NT-pro-BNP下降明显（P＜0.05）。左西孟旦组的总有效率显著高于对照组（94.4% vs 69.4%,P＜0.05）。与对照组比较,左西孟旦治疗组SV及LVEF显著提高（P＜0.05）,NT-pro-BNP下降更明显（P＜0.05）。结论左西孟旦注射液治疗老年急性左心衰竭患者疗效确切,安全性好。     

左西孟旦和肾上腺素对心脏术后低心排综合征治疗作用的比较

目的比较左西孟旦和肾上腺素对心脏术后低心排综合征（LCOS）的作用。方法将48例心脏术后LCOS患者随机分为两组,左西孟旦组（A组,n＝23）按0.05～0.2μg/（kg·min）持续24h,肾上腺素组（B组,n＝25）按0.01～0.04μg/（kg·min）持续1周,维持平均动脉压≥65mmHg。监测心率、平均动脉压、肺毛细血管楔压、中心静脉压、心输出量、心指数、全身血管阻力;用心脏超声分别评价用药前和用药后3和7d的心功能;监测用药前和用药后24和48h的血乳酸值、血肌酐、尿素氮、尿量。观察术后并发症及预后情况。结果两种药物均能显著增加心输出量和心指数（P＜0.05）。A组用药后各时间点全身血管阻力均较B组明显下降（P＜0.05）,且均较用药前明显下降（P＜0.05）。A组用药后24,48h平均动脉压与用药前相比均有显著下降（P＜0.05）。心脏超声结果显示两种药均能改善心功能（P＜0.05）。用药后血乳酸值均显著降低（P＜0.05）。A组用药后48h,尿素氮、血肌酐及尿量均较用药前变化显著（P＜0.05）,且该时间点尿素氮较B组显著降低（P＜0.05）。与B组相比,A组房颤发生率显著减少（P＜0.05）,术后并发症也有减少的趋势。结论两种药物均能明显提高心脏术后LCOS患者血流动力学及心功能指标,改善组织灌注,而左西孟旦对患者肾功能更有益。     

Effectiveness of prophylactic levosimendan in high-risk valve surgery patients

Background

Levosimendan has anti-ischaemic effects, improves myocardial contractility and increases systemic, pulmonary and coronary vasodilatation. These properties suggest potential advantages in high-risk cardiac valve surgery patients where cardioprotection would be valuable. The present study investigated the peri-operative haemodynamic effects of prophylactic levosimendan infusion in cardiac valve surgery patients with low ejection fraction and/or severe pulmonary arterial hypertension.

Methods

Between May 2006 and July 2007, 20 consecutive patients with severe pulmonary arterial hypertension (systolic pulmonary artery pressure ≥ 60 mmHg) and/or low ejection fraction (< 50%) who underwent valve surgery in our clinic were included in the study and randomised into two groups. Levosimendan was administered to 10 patients in group I and not to the 10 patients in the control group. Cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) were recorded for each patient preoperatively and for 24 hours following the operation.

Results

CO and CI values were higher in the levosimendan group during the study period (p < 0.05). MPAP and PVR values were significantly lower in the levosimendan group for the 24-hour period (p < 0.05) and SVR values were significantly lower after 24 hours in both groups. When clinical results were considered, no difference in favour of levosimendan was detected regarding the mortality and morbidity rates between the groups.

Conclusion

Levosimendan improved the haemodynamics in cardiac valve surgery patients with low ejection fraction and/or severe pulmonary arterial hypertension, and facilitated weaning from cardiopulmonary bypass in such high-risk patients when started as a prophylactic agent.     

Acute heart failure: inotropic agents and their clinical uses

Inotropic agents are indispensable for the improvement of cardiac contractile dysfunction in acute or decompensated heart failure. Clinically available agents, including sympathomimetic amines (dopamine, dobutamine, noradrenaline) and selective phosphodiesterase-3 inhibitors (amrinone, milrinone, olprinone and enoximone) act via cAMP/protein kinase A (PKA)-mediated facilitation of intracellular Ca²⁺ mobilisation. Phosphodiesterase-3 inhibitors also have a vasodilatory action, which plays a role in improving haemodynamic parameters in certain patients, and are termed inodilators. The available inotropic agents suffer from risks of Ca²⁺ overload leading to arrhythmias, myocardial cell injury and ultimately, cell death. In addition, they are energetically disadvantageous because of an increase in activation energy and cellular metabolism. Furthermore, they lose their effectiveness under pathophysiological conditions, such as acidosis, stunned myocardium and heart failure. Pimobendan and levosimendan (that act by a combination of an increase in Ca²⁺ sensitivity and phosphodiesterase-3 inhibition) appear to be more beneficial among existing agents. Novel Ca²⁺ sensitisers that are under basic research warrant clinical trials to replace available inotropic agents.