Use Of Levosimendan Research Articles

Levosimendan Reduces Mortality and Low Cardiac Output Syndrome in Cardiac Surgery.

There has been conflicting evidence concerning the effect of levosimendan on clinical outcomes in patients undergoing cardiac surgery. Therefore, we performed a systematic review and conducted this meta-analysis to provide evidence for/against the administration of levosimendan in cardiac surgery patients. We performed a meta-analysis from literature search in PubMed, EMBASE, and Cochrane Library. Only randomized controlled trials comparing the administration of levosimendan in cardiac surgery patients with a control group (other inotrope, standard therapy/placebo, or an intra-aortic balloon pump) were included. In addition, at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome (LCOS), acute kidney injury, renal replacement therapy, atrial fibrillation, prolonged inotropic support, length of intensive care unit, and hospital stay. The pooled treatment effects (odds ratio [OR], 95% confidence intervals [CI]) were assessed using a fixed or random effects model. The literature search retrieved 27 randomized, controlled trials involving a total of 3,198 patients. Levosimendan led to a significant reduction in mortality (OR: 0.67; 95% CI: 0.49-0.91; p = 0.0087). Furthermore, the incidence of LCOS (OR: 0.56, 95% CI: 0.42-0.75; p < 0.0001), acute kidney injury (OR: 0.63; 95% CI: 0.46-0.86; p = 0.0039), and renal replacement therapy (OR: 0.70; 95% CI: 0.50-0.98; p = 0.0332) was significantly decreased in the levosimendan group. Our meta-analysis suggests beneficial effects for the prophylactic use of levosimendan in patients with severely impaired left ventricular function undergoing cardiac surgery. The administration of levosimendan was associated with a reduced mortality, less LCOS, and restored adequate organ perfusion reflected in less acute kidney injury.

Rationale, experimental data, and emerging clinical evidence on early and preventive use of levosimendan in patients with ventricular dysfunction.

Acute ventricular dysfunction (AVD) is a complex condition with substantial morbidity and mortality, still featuring unique therapeutic challenges. Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener that was developed as an inodilating drug for the treatment of acute heart failure and cardiogenic shock. Differently from other more widely used inotropic agents, levosimendan has some exclusive characteristics, in terms of mechanisms of action, pharmacodynamic profile, and haemodynamic effects. This may have important clinical implications. In particular, in patients with AVD or in patients with pre-existing severe ventricular impairment undergoing planned myocardial stress, the administration of levosimendan before the onset of overt symptoms or before cardiovascular therapeutic procedures may have the potential to bridge the patient through the critical phase. In this review, we will focus on the rationale, the existing experimental data, and the emerging clinical experience supporting an early, even preventive use of levosimendan in severe ventricular dysfunction, beyond its recognized indications.

Impact of Perioperative Levosimendan Administration on Risk of Bleeding After Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

Levosimendan, a calcium sensitizer and potassium channel opener, has been demonstrated to improve myocardial function without increasing oxygen consumption and to show protective effects in other organs. Recently, a prospective, randomized controlled trial (RCT) revealed an association between levosimendan use and a possible increased risk of bleeding postoperatively. Levosimendan's anti-platelet effects have been shown in in vitro studies. Current studies do not provide sufficient data to support a relation between perioperative levosimendan administration and increased bleeding risk. Our goal was to investigate the relation between perioperative levosimendan administration and increased bleeding risk using a meta-analysis study design. The PubMed, Ovid, EMBASE and Cochrane Library databases were searched for relevant RCTs before July 1, 2019. The outcome parameters included reoperation secondary to increased bleeding in the postoperative period, the amount of postoperative recorded blood loss, and the need for transfusion of packed red blood cells (RBCs) and other blood products. A total of 1160 patients in nine RCTs (576 in the levosimendan group and 584 in the control group) were included according to our inclusion criteria. Analysis showed that perioperative levosimendan administration neither increased the rate of reoperation secondary to bleeding nor increased the amount of postoperative chest tube drainage when compared with the control group. In terms of blood product transfusion, levosimendan did not influence the requirement for RBC transfusion, platelet transfusion nor fresh frozen plasma (FFP) transfusion. Levosimendan also did not shorten or prolong the aortic cross-clamp time or the cardiopulmonary bypass time. The analyzed parameters, including reoperations due to bleeding, postoperative chest drainage and the requirement for blood products, revealed that levosimendan did not increase postoperative bleeding risk. More studies with a larger sample size are needed to address a more reliable conclusion due to study limitations.

Use of Levosimendan as a Strategy to Wean off Veno-Arterial ECMO in Cardiogenic Shock; A Systematic Review and Metanalysis

Background VA ECMO is commonly used to support patients suffering profound cardiogenic shock. However, the ideal strategy to wean patients of VA ECMO remains unknown. Methods A systematic search including Pubmed, Cochrane Library and EMBASE was performed to evaluate studies comparing Levosimendan vs. other weaning strategies in patients with cardiogenic shock on VA-ECMO. Evaluated end-point was successful discontinuation on VA-ECMO support. Results Four studies met inclusion criteria for a total of 471 patients, . Mean age was 61, 292 (70%) of the patients were male. Hypertension, CAD and Diabetes were present in 282 patients (60%), 216 (46%) and 136 (29%) respectively, with no significant difference in between groups. The majority of patients required ECMO due to acute myocardial infarction or post cardiotomy shock (up to 50%). 262 received Levosimendan and 209 recieved other interventions. Out of the group who received the calcium sensitizer 215 patients (82%) were successfully weaned vs 135 patients (65%) on the control group, OR 1.27 (CI 95% 1.13-1.4) P Conclusions This metanalysis suggests that the use of Levosimendan on patients while on VA ECMO support for cardiogenic shock improves weaning success

On the possibility to increase sensitivity of diagnostic tests for fixed pulmonary hypertension in heart transplant candidates

Background: Fixed pulmonary hypertension (PH) in heart transplant candidates is a risk factor for right ventricular failure in the postoperative period and early mortality. Patients with fixed PH are not included in the waiting list. Thus, the correct assessment of the pulmonary circulation before the operation affects both clinical management and prognosis. Aim: To reduce the risk of incorrect patient non-inclusion to the waiting list by reduction of false negative test results for PH reversibility.Materials and methods: Fourteen heart transplant candidates were included in this retrospective cohort single center study. Fixed PH with pulmonary vascular resistance (PVR) exceeding 3.5 Wood's units was found in all these patients using right heart catheterization and pulmonary vasoreactivity tests. Initially, these patients had not been put into the waiting list. Pulmonary catheterization was performed in the intensive care unit with a Swan-Ganz catheter and pre-pulmonary thermodilution technique. To perform pulmonary vasoreactivity tests, inhaled iloprost (n = 12) or nitric oxide (n = 2) were used. Subsequently all patients received levosimendan infusion at a dose of 12.5 (0.05–0.2) mg/kg/min, with repeated pulmonary artery catheterization and pulmonary vasoreactivity tests at 72 hours after the infusion. Pulmonary vasoreactivity tests results allowed 13 patients to be included into the waiting list. Heart transplantation was performed in 8 recipients, with postoperative assessment of their hemodynamic and clinical parameters. Data are presented as median [25th percentile; 75th percentile].Results: After the levosimendan infusion, there was a decrease in the pulmonary artery mean pressure from 45 [36; 47] to 29.5 [23; 37] mm Hg (p &lt; 0.01), and in PVR from 6.9 [4.9; 8.9] to 3.6 [2.9; 5.9] Wood's units (p &lt;0.01). In 7 patients, PVR decreased to less than 3.5 Wood's units: the rest of the patients underwent pulmonary vasoreactivity tests. As a result, 13 of 14 patients showed reversible PH and were included into the waiting list. By the date of the manuscript submission, heart transplantation has been performed in 8 patients. Their PVR 6 hours after surgery was 2.2 [2; 3.1] Wood's units; there were no cases of fixed PH and right heart failure. There was a single death associated to a hemorrhagic stroke at day 6 after heart transplantation. The sensitivity of pre-operative pulmonary vasoreactivity tests with the use of levosimendan was 87.5%.Conclusion: Levosimendan infusion may increase the sensitivity of the pulmonary vasoreactivity tests before patients' inclusion into the waiting list for heart transplantation.

Levosimendan: What Have We Learned So Far?

Vasoactive therapy represents a pivotal yet debated topic in critically ill patients and in those with chronic heart failure. Levosimendan, a calcium sensitizer agent with inodilating properties, has been in the market for 27 years and new indications came out over time. The aim of the present review is to highlight what is actually proven and what is debated on the use of levosimendan in light of its pharmacologic features and the pathophysiological evidence. Levosimendan was firstly seen as an inodilator acting through calcium sensitization in myocytes both in the myocardium and in vascular smooth muscle. Over the years, its anti-inflammatory properties became clearer and a role in preconditioning and weaning from mechanical circulatory support was postulated. More recently, a possible action on other muscular fibers, namely, diaphragmatic myocytes, was observed, leading to a possible application in mechanical ventilation-related diaphragmatic dysfunction. Preliminary data showed promising effects of levosimendan in patients with sepsis-related and stress-related (Takotsubo) myocardial dysfunction, in those difficult-to-wean from mechanical circulatory support and in ventilator-associated diaphragmatic dysfunction. Moreover, its vasodilating, anti-oxidant, and neuroendocrine properties pave the way to a number of additional possible applications. Larger studies yielding to more conclusive results on these indications are under way or need to be planned in the future.

Perioperative Use of Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery on Cardiopulmonary Bypass

Perioperative Use of Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery on Cardiopulmonary Bypass

Perioperative Use of Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery on Cardiopulmonary Bypass

Background: Patients undergoing cardiac surgery are becoming older and with greater comorbidities, carrying an increased risk for perioperative complications, which result in higher mortality and higher costs for the health care service. Objective: Our study is randomized, double-blind, placebo-controlled, multicenter clinical study to evaluate the efficacy of levosimendan given preoperatively in high-risk patients with Left ventricular ejection fraction (LVEF) ≤35% undergoing cardiac surgery on cardiopulmonary bypass (CPB). Patients and methods: This study was carried out in Cardiothoracic Department, Natinaol Heart Institute, Al Hussin hospital, Air Forced Specialized Hospital, and Saudi German Hospital. 60 patients treated with study drug were enrolled, the study population was drawn from patients with an LVEF ≤35% scheduled to undergo cardiac surgery with planned CPB. Results: Our results showed that the relative risk for postoperative mortality at 60 days was reduced by 10% in the levosimendan group when compared with the control group [4 of 30 (13%) in the levosimendan group vs 7 of 30 (23%) in the control group] with p value =0.5, however the incidence of 30-day out-of-hospital complications was not statistically different between the two groups. In the levosimendan group, no significant reduction in the rate of renal replacement therapy was observed [7 of 30 (23.3%) in the levosimendan group vs 8 of 30 (26.7%) in the control group]. Conclusion: Levosimendan is safe and well tolerated in patients undergoing cardiac surgery with cardiopulmonary bypass who have low LVEF and are at risk of the development of postoperative low cardiac output syndrome (LCOS).

The efficacy and safety of prophylactic use of levosimendan on patients undergoing coronary artery bypass graft: a systematic review and meta-analysis.

Prophylactic use of levosimendan in cardiac surgery remains controversial and no meta-analysis has been done exclusively about that in patients undergoing coronary artery bypass graft (CABG) surgery. We conducted this systematic review and meta-analysis of levosimendan in CABG using PubMed, Embase, Scopus, and Cochrane Library (till April 20, 2018). Two-hundred and forty manuscripts were identified and 21 randomized trials (1727 patients in total) investigating the effect of levosimendan on the patients undergoing CABG surgery were finally included in this analysis. We found that levosimendan was an effective, well-tolerated inotropic agent in CABG, which was associated with a significantly reduced mortality rate [odds ratio (OR) 0.43, 95% confidence interval (CI) (0.26, 0.71), p = 0.001, I2 = 0%] and postoperative atrial fibrillation [OR 0.50, 95% CI (0.26, 0.97), p = 0.04, I2 = 76%], but a higher incidence of hypotension [OR 2.26, 95% CI (1.05, 4.85), p = 0.04, I2 = 79%]. Subgroup analyses revealed that such a benefit was mainly observed in the isolated CABG, the preoperative administration, with-bolus and on-pump subgroups. More high-quality and well-designed prospective studies are needed to confirm or disprove our findings in future.

Evaluation of ventriculo-arterial coupling in ST elevation myocardial infarction with left ventricular dysfunction treated with levosimendan

BackgroundAcute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) is usually treated with inotropic support or vasoactive medications.In this study, we aimed at investigating the role of levosimendan on cardiovascular determinants of contractility and afterload in patients with AHF following STEMI treated with percutaneous coronary intervention (PCI). MethodsForty-eight consecutive STEMI patients were retrospectively enrolled. Non-invasive assessment of left ventricular elastance (Ees) and arterial elastance (Ea) and their relationship, ventriculo-arterial coupling (VAC) was performed before and after levosimendan infusion. ResultsAfter infusion of levosimendan a significant increase in SV was detected in all patients (from 48 ± 17 to 60 ± 21 ml, p < 0.001). VAC slightly decreased from 1.74 ± 0.8 to 1.66 ± 0.7 (p = NS) as a result of a profound reduction in arterial elastance (Ea 2.34 ± 1.09 to 1.74 ± 0.5 mm Hg/ml, p < 0.001) and in ventricular elastance (Ees 1.57 ± 0.12 to 1.24 ± 0.09 mm Hg/ml, p = 0.021). Ejection fraction (EF) (from 0.29 ± 0.1 to 0.32 ± 0.1, p < 0.01) and WMSI, (from 2.16 ± 0.47 to 2.05 ± 0.54, p < 0.05) also, significantly improved.Finally, baseline VAC was able to predict the use of norepinephrine (NE) and early and one-year mortality of patients treated. ConclusionIn STEMI patients with AHF the use of levosimendan significantly increases stroke volume after 24-hour treatment through Ea reduction. Baseline VAC seemed to predict early and late mortality and early and prolonged use of NE, however, this needs to be tested in larger series of patients and multivariate adjustments for other prognostic predictors.

Levosimendan as a new force in the treatment of sepsis-induced cardiomyopathy: mechanism and clinical application.

The heart is one of the organs most vulnerable to sepsis. This review describes the general characteristics of sepsis-induced cardiomyopathy and the main pathogenesis of myocardial dysfunction in sepsis. Levosimendan is a novel drug for treatment of sepsis-induced myocardial dysfunction. This review also elaborates on the pathogenesis of levosimendan, including the mechanisms of its anti-inflammatory effects, improvement of myocardial ischaemia, increased synthesis of nitric oxide, vascular endothelial cell protection, increased myocardial contractility, improved diastolic function, and inhibition of hypoxia-inducible factor-1α expression. Many clinical studies have proven that levosimendan effectively prevents myocardial dysfunction in sepsis. In addition to the widespread use of levosimendan in patients with heart failure, the role of levosimendan in the treatment of patients with sepsis-induced cardiomyopathy will be increasingly studied and applied in the future.

Levosimendan treatment in a child with treatment-resistant left ventricular systolic dysfunction after scorpion sting

Background: Scorpion stings are common in countries dominated by rural and coastal settlements with temperate climate. Scorpion stings are usually harmless and can be seen in local findings, but in some cases, systemic, neurotoxic, and cardiotoxic findings can be seen. Case report: A 3 year 7 month old girl was referred to pediatric emergency care 2 h after yellow scorpion (species of Leiurus abdullahbayrami) sting. In our case, cardiac function insufficiently progressed in spite of the standard inotropic and milrinone treatment. On the third day of hospitalization, levosimendan was initiated with good clinical effect. Conclusion: In the literature, the use of levosimendan in pediatric patients has been limited to those with low cardiac output syndrome after cardiovascular surgery. The use of levosimendan in children with scorpion sting has been previously reported only in Banille et al.’s study. Scorpion antivenom should be administered intravenously as soon as possible in cases of systemic findings that develop after scorpion stings. This report suggests that levosimendan is temporally associated with improvement in patients who have severe cardiac dysfunction due to scorpion sting and refractory to current treatment.

What's New in Cardiopulmonary Bypass

This is a narrative review of recent articles (mainly published in 2017 and 2018) related to the conduct of cardiopulmonary bypass (CPB) that should be of interest to the cardiac anesthesiologist. Some of the topics covered include recent guidelines on temperature management, anticoagulation, perfusion practice, use of transesophageal echocardiography during CPB, optimal mean arterial pressure, vasoplegia, bleeding, perioperative anemia, post-cardiac surgery transfusion, acute kidney injury, delirium and cognitive decline, CPB during pregnancy, lung management, radial-to-femoral artery pressure gradients during CPB, prophylactic perioperative intra-aortic balloon pump, del Nido cardioplegia, antibiotic prophylaxis, and use of levosimendan in cardiac surgery. The review concludes with a perspective on the effect of these development on the practice of cardiac anesthesia.

The effects of levosimendan use on high-sensitivity C-reactive protein in patients with decompensated heart failure.

IntroductionThe present study was intended to investigate the effect of levosimendan on high-sensitivity C-reactive protein (hsCRP) levels in hospitalized patients with decompensated heart failure.Material and methodsThe present study was designed as a prospective controlled clinical trial. A total of 50 patients with decompensated heart failure who were admitted to our hospital were included in the present study. Patients with stage III–IV heart failure based on the New York Heart Association, with systolic blood pressure > 100 mm Hg and with left ventricular ejection fraction of < 35%, were selected for the study population. The selected patients were divided into groups, levosimendan and furosemide.ResultsThere was no significant difference between the groups based on demographics, basal echocardiographic and basal laboratory data. No difference was determined in basal hsCRP (mg/l) levels between the group admitted levosimendan infusion and the furosemide group (9.99 ±6.2, 9.23 ±6.4, p = 0.66). However, the hsCRP levels measured at the 24th h (38.34 ±32.1 vs. 12.97 ±12.3, p < 0.001), the 48th h (31.13 ±29.9 vs. 12.44 ±10.1, p = 0.003) and the 72nd h (27.41 ±26.9 vs. 9.89 ±8.4, p = 0.002) were significantly higher in the levosimendan infusion group than the furosemide group.ConclusionsIt was found that hsCRP levels were significantly higher in the levosimendan infusion group than the furosemide group. Such an outcome could be related to myocyte injury and/or the amplification of the inflammatory response due to levosimendan.

Use of levosimendan in acute heart failure.

As a calcium sensitizer and inodilator that augments cardiac contractility without increasing myocardial oxygen demand or exacerbating ischaemia, levosimendan may be well configured to deliver inotropic support in cases of acute heart failure (AHF). Other factors favouring levosimendan in this setting include its extended duration of action due to the formation of an active metabolite and the lack of any attenuation of effect in patients treated with beta-blockers. Effects of levosimendan on systemic haemodynamics include its significant, dose-dependent increases in cardiac output, stroke volume and heart rate, and decreases in right and left ventricular filling and total peripheral resistance. Rapid and sustained reduction in levels of natriuretic peptides is a consistent effect of levosimendan use and potentially favourable effects on other neurohormonal indicators of cardiac distress are also observed. Levosimendan has repeatedly been shown to be effective in relief of symptoms of AHF, notably dyspnoea and fatigue, while mortality data from clinical trials and registries suggest that levosimendan is markedly less likely than catecholaminergic inotropes to worsen prognosis. The vasodilator pharmacology of levosimendan is also pertinent to the drug’s use in AHF, in which setting organ under-perfusion is often a key pathology. These considerations suggest that levosimendan may have a more favourable impact on the circumstances of the majority of AHF patients than adrenergic agents that act only or primarily as cardiac stimulants. They also suggest that levosimendan may advantageously be integrated into a comprehensive strategy of early intervention designed and intended to prevent cardiac destabilization worsening to the point where hospitalization is necessary. Levosimendan should be used with caution and with tightened haemodynamic monitoring in patients who have low baseline blood pressure (systolic blood pressure <100 mmHg; diastolic blood pressure <60 mmHg), or who are at risk of a hypotensive episode.

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper.

:Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate–sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

Levosimendan for Perioperative Cardioprotection: Myth or Reality?

Background: Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. It is mainly used for the therapy of acute decompensated heart failure. Several studies on animals and humans provided evidence of the cardioprotective properties of levosimendan including preconditioning and anti-apoptotic. In view of these favorable effects, levosimendan has been tested in patients undergoing cardiac surgery for the prevention or treatment of low cardiac output syndrome. However, initial positive results from small studies have not been confirmed in three recent large trials.Aim: To summarize levosimendan mechanisms of action and clinical use and to review available evidence on its perioperative use in a cardiac surgery setting.Methods: We searched two electronic medical databases for randomized controlled trials studying levosimendan in cardiac surgery patients, ranging from January 2000 to August 2017. Meta-analyses, consensus documents and retrospective studies were also reviewed.Results: In the selected interval of time, 54 studies on the use of levosimendan in heart surgery have been performed. Early small size studies and meta-analyses have suggested that perioperative levosimendan infusion could diminish mortality and other adverse outcomes (i.e. intensive care unit stay and need for inotropic support). Instead, three recent large randomized controlled trials (LEVO-CTS, CHEETAH and LICORN) showed no significant survival benefits from levosimendan. However, in LEVO-CTS trial, prophylactic levosimendan administration significantly reduced the incidence of low cardiac output syndrome.Conclusions: Based on most recent randomized controlled trials, levosimendan, although effective for the treatment of acute heart failure, can't be recommended as standard therapy for the management of heart surgery patients. Further studies are needed to clarify whether selected subgroups of heart surgery patients may benefit from perioperative levosimendan infusion.

Perioperative Use of Levosimendan Improves Clinical Outcomes in Patients After Cardiac Surgery: A Systematic Review and Meta-Analysis.

Severe postoperative complications can affect cardiac surgery patients. Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery. However, the patient benefits are controversial. PubMed, Embase, and the Cochrane library were systematically searched for randomized controlled trials comparing levosimendan with control in adult cardiac surgery patients. Twenty-five studies (3247 patients) were included. Pooled data indicated that levosimendan reduced mortality after cardiac surgery [odds ratio (OR) 0.63, 95% confidence interval (CI): 0.47-0.84, P = 0.001]. However, this reduction was restricted to patients with low (<50%) left ventricular ejection fraction (OR 0.49, 95% CI: 0.35-0.70, P = 0.0001). It significantly reduced the incidence of postoperative acute kidney injury (OR 0.55, 95% CI: 0.41-0.74, P < 0.0001) and renal replacement therapy use (OR 0.56, 95% CI: 0.39-0.80, P = 0.002). Moreover, levosimendan significantly shortened the duration of the intensive care unit stay (weighted mean differences -0.49 day, 95% CI: -0.75 to -0.24, P = 0.0002) and mechanical ventilation use (weighted mean differences -2.30 hours, 95% CI: -3.76 to -0.84, P = 0.002). In conclusion, levosimendan reduced the mortality in patients with low left ventricular ejection fraction and decreased the incidence of acute renal injury and renal replacement therapy use. In addition, it shortened the duration of the intensive care unit stay and mechanical ventilation use.

Perioperative use of levosimendan in cardiac surgery. Hungarian recommendation

Low output syndrome significantly increases morbidity and mortality of cardiac surgery and lengthens the durations of intensive care unit and hospital stays. Its treatment by catecholamines can lead to undesirable systemic and cardiac complications. Levosimendan is a calcium sensitiser and adenosine triphosphate (ATP)-sensitive potassium channel (IK,ATP) opener agent. Due to these effects, it improves myocardium performance, does not influence adversely the balance between O2 supply and demand, and possesses cardioprotective and organ protective properties as well. Based on the scientific literature and experts' opinions, a European recommendation was published on the perioperative use of levosimendan in cardiac surgery in 2015. Along this line, and also taking into consideration cardiac surgeon, anaesthesiologist and cardiologist representatives of the seven Hungarian heart centres and the children heart centre, the Hungarian recommendation has been formulated that is based on two pillars: literature evidence and Hungarian expert opinions. The reviewed fields are: coronary and valvular surgery, assist device implantation, heart transplantation both in adult and pediatric cardiologic practice. Orv Hetil. 2018; 159(22): 870-877.

Levosimendan in patients with left ventricular dysfunction undergoing cardiac surgery: a meta-analysis and trial sequential analysis of randomized trials

Patients with left ventricular dysfunction (LVD) undergoing cardiac surgery have a high mortality rate. Levosimendan, a calcium sensitizer, improves myocardial contractility without increasing myocardial oxygen demand. It is not clear whether levosimendan can reduce mortality in cardiac surgery patients with LVD. The PubMed, Embase, and Cochrane Central databases were searched to identify randomized trials comparing levosimendan with conventional treatment in cardiac surgery patients with LVD. We derived pooled risk ratios (RRs) with random effects models. The primary endpoint was perioperative mortality. Secondary endpoints were renal replacement treatment, atrial fibrillation, myocardial infarction, ventricular arrhythmia, and hypotension. Fifteen studies enrolling 2606 patients were included. Levosimendan reduced the incidence of perioperative mortality (RR: 0.64, 95%CI: 0.45–0.91) and renal replacement treatment (RR:0.71, 95%CI:0.52–0.95). However, sensitivity analysis, subgroup analysis and Trial Sequential Analysis (TSA) indicated that more evidence was needed. Furthermore, levosimendan did not reduce the incidence of atrial fibrillation (RR:0.82, 95%CI:0.64–1.07), myocardial infarction (RR:0.56, 95%CI:0.26–1.23), or ventricular arrhythmia (RR:0.74, 95%CI:0.49–1.11), but it increased the incidence of hypotension (RR:1.11,95%CI:1.00–1.23). There was not enough high-quality evidence to either support or contraindicate the use of levosimendan in cardiac surgery patients with LVD.