|Year : 2020 | Volume
| Issue : 4 | Page : 1388-1392
Levosimendan vs intra-aortic balloon pump in low ejection fraction coronary artery bypass grafting patients
Amr M Allama, Ahmed L Dokhan, Ahmed H Onsi, Mohamed G Hagag
Department of Cardiothoracic Surgery, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||29-Mar-2020|
|Date of Decision||15-Apr-2020|
|Date of Acceptance||06-May-2020|
|Date of Web Publication||24-Dec-2020|
Ahmed H Onsi
Department of Cardiothoracic Surgery, Menoufia Faculty of Medicine, Yassin Abdel Ghaffar Street from Gamal Abdel Naser Street, Shebin ElKom, Menoufia
Source of Support: None, Conflict of Interest: None
Coronary artery bypass grafting (CABG) surgery in poor left ventricular function patients is still risky with much postoperative comorbidity that mandates trials to find the best management protocol to cure those patients safely. The authors aimed at evaluating the postoperative outcome of preoperative prophylactic use of levosimendan vs intra-aortic balloon pump (IABP) in those patients.
Patients and methods
In all, 90 patients presented with coronary insufficiency with an ejection fraction of less than 35% and underwent CABG. They were divided into three groups: group A (30 patients) who did not receive preoperative prophylactic support with neither IABP nor levosimendan; in group B (30 patients) IABP was inserted with induction of anesthesia; and in group C (30 patients) levosimendan was administered intravenously through the central line after induction of anesthesia. The authors followed postoperative hemodynamics and morbidities during hospital stay till discharge.
Group C had significantly lesser ICU stay than other groups. Groups B and C had significantly lower needs of postoperative inotropic supports than group A. However, mortality and other major morbidities were similar among the three groups.
Patients with prophylactic preoperative support with IABP or levosimendan had the same postoperative outcome as patients without preoperative support in a situation of CABG with low ejection fraction. However, this prophylactic use add a value of lower needs of postoperative inotropes and moreover levosimendan is associated with lesser ICU stay.
Keywords: coronary artery bypass grafting, ejection, fraction, intra-aortic balloon pump, levosimendan
|How to cite this article:|
Allama AM, Dokhan AL, Onsi AH, Hagag MG. Levosimendan vs intra-aortic balloon pump in low ejection fraction coronary artery bypass grafting patients. Menoufia Med J 2020;33:1388-92
|How to cite this URL:|
Allama AM, Dokhan AL, Onsi AH, Hagag MG. Levosimendan vs intra-aortic balloon pump in low ejection fraction coronary artery bypass grafting patients. Menoufia Med J [serial online] 2020 [cited 2021 Apr 19];33:1388-92. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1388/304516
| Introduction|| |
Low preoperative left ventricular ejection fraction (LVEF), defined as an LVEF of less than 35%, is common in patients undergoing cardiac surgery, especially those scheduled for coronary artery bypass grafting (CABG). As known, those patients are at a higher risk for postoperative complications and mortality after cardiac surgery; therefore, an early recognition of patients at risk for a worse outcome plays a pivotal role in the decision-making process, allowing prompt institution of an adequate support.
Intra-aortic balloon pump (IABP) after 40 years since its first-in-man description, the situations and strategies in which to utilize its attractive physiological properties are still open to debate. Also, in the last decade, levosimendan has been studied in numerous clinical trials in cardiac surgery settings in which the drug has shown beneficial hemodynamic and cardioprotective effects and a favorable outcome effect.
Despite all the improvements in medical therapy and surgical techniques for management of those patients, there are still challenges. We aimed at evaluating the postoperative outcome of preoperative prophylactic use of levosimendan vs IABP in those patients.
| Patients and Methods|| |
This prospective, randomized study was performed at the Cardiothoracic Surgery Departments of Menoufia University Hospital and Nasser Institute Hospital from January 2017 to July 2019. The study was previously approved by the Ethics Committee for Clinical Research of the institutions. Consent was taken from each patient to share in the study. All patients presented with coronary insufficiency confirmed by coronary angiographic studies and preoperative echocardiography revealed poor left ventricular function (defined as an ejection fraction of less than 35%). The patients were allocated randomly into three groups as every patient selected a ball labeled either A B, or C from a jar filled with many balls. Group A (30 patients, the control group) patients did not receive preoperative prophylactic support with neither IABP nor levosimendan. In group B (30 patients) IABP was inserted with induction of anesthesia and kept for at least 24 h postoperatively till the patient's hemodynamics and parameters show no clinical or laboratory findings of low cardiac output. In group C (30 patients), levosimendan was administered intravenously through the central line after induction of anesthesia.
Patients presented with multivessel disease for CABG confirmed by coronary angiographic studies, with preoperative echocardiography that revealed poor left ventricular function with an ejection fraction of less than 35%.
Emergency cases, redo cases, off-pump cases, other associated cardiac procedures including associated valve surgery, patients with peripheral vascular disease, severe form of chronic obstructive pulmonary disease, severe liver or kidney diseases, patients with previous stroke, and the use of platelet alternating medications within 1 week of operation.
All patients in this study had full comprehensive clinical history. Complete clinical examination was performed for all patients. Laboratory investigations such as resting 12-lead ECG, plain chest radiography, echocardiography, and coronary angiography were done.
The CABG was performed using the on-pump technique through median sternotomy, using the conduits as left internal mammary artery, complemented with additional saphenous vein grafts.
In group B, an IABP was inserted percutaneously, without a sheath in all patients. In group C, levosimendan was administered for ∼24 h at a continuous infusion of 0.1 μg/kg/min diluted in 5% glucose with a 0.25 mg/ml concentration, without boluses, through a central venous catheter.
Outcomes of interest
The outcomes of interest were cardiopulmonary bypass time and ischemic time, the use of inotropic drug and number of grafts, duration of mechanical ventilation (in hours), duration of ICU stay (in hours), postoperative blood loss, blood transfusion and number of blood units used, reoperation for bleeding, low cardiac output syndrome (LCOS) which includes decreases in the cardiac index to less than 2.0 l/min/m2 and a systolic blood pressure of less than 90 mmHg, in conjunction with signs of tissue hypoperfusion (cold periphery, clammy skin, confusion, and oliguria elevated lactate level) in the absence of hypovolemia and the need for inotropic support, new ECG evidence of ischemia or infarction, incidence of postoperative arrhythmias, and readmission to the ICU. Pulmonary, infective, neurological, and renal complications, postoperative echocardiography, postoperative hospital stays (in days), and postoperative in-hospital mortality were assessed.
Results were collected, tabulated, and statistically analyzed by an IBM compatible personal computer with the Statistical Package for the Social Sciences, version 20 (SPSS Inc. released 2011, IBM SPSS statistics for windows, version 20.0; IBM Corp., Armonk, New York, USA). Data were expressed as mean, SD or median and range for continuous variables, and as frequencies (percentages) for categorical variables. Student's t-test was used for normally distributed quantitative variables. Mann–Whitney test (U) was used for non-normally distributed quantitative variables.
| Results|| |
Demographics of the studied groups are demonstrated in [Table 1] with no statistical significance between the three groups. The operative data is illustrated in [Table 2] with no statistical significance between the three groups in the time on bypass. Postoperatively, the need of inotropic supports showed that in group A: three (10.7%) patients needed minimal support (≤50 ng of adrenaline and/or noradrenaline), eight (27.5%) patients needed moderate support (50–100 ng of adrenaline and/or noradrenaline), six (21.4%) patients needed high inotropic support (≥100 ng of adrenaline and/or noradrenaline), and 11 (39.2%) patients needed to insert an IABP with high support. In group B, 10 (34.4%) patients needed minimal support, 10 (34.4%) patients needed moderate support, and nine (31.03%) patients needed high inotropic support with the IABP which has already been inserted in this group. In group C: nine (31.03%) patients needed minimal support, 13 (44.8%) patients needed moderate support), four (13.7%) patients needed high inotropic support, and three (10.3%) patients needed to insert an IABP with the high support. There is significant decrease in the amount of support when levosimendan is used [Table 3].
The mean ICU stay in group A was 7.3 ± 0.85 days, while in group B it was 5.2 ± 0.85 days, in group C it was 4.4 ± 0.77 days. There was statistical significance between the three groups [Figure 1].
In group A, six patients had postoperative arrhythmia in the form of rapid AF amiodarone infusion, while in group B, four patients had postoperative arrhythmia in the form of rapid AF, premature ventricular contractions, while in group C, seven patients had postoperative arrhythmias. There was no statistical significance between the three groups [Figure 1].
In group A, one patient had reopening, while in group B three patients had reopening, and in group C two patients had reopening. There was no statistical significance between the two groups [Figure 1].
With respect to in-hospital mortality, in group A, four patients died, two of them failed to come off bypass and two died from multiorgan failure due to LCOS. One patient died at postoperative day 4 and the other at postoperative day 6, while in group B three patients died, one patient failed to come off bypass and among the other patients one developed acute renal failure and died at the fifth postoperative day. The third patient died from septicemia and died after 2 weeks. While in group C, two patients died, one of them failed to come off bypass and the other died on the first day postoperatively due to hemodynamic instability. There was no statistical significance between the three groups [Figure 1].
| Discussion|| |
Patients with an ejection fraction of less than 35% are at high risk of developing postoperative LCOS, following cardiac surgery. Preventing LCOS is therefore a priority for the cardiac surgery team working with cardiac surgical patients. The incidence of LCOS following CABG surgery varies from 3 to 14%. In the last decade, patients referred for cardiac surgery are different than before. Comorbidities and the risk score of the patients are getting higher.
In our study, the need for postoperative high inotropic supports (≥100 ng adrenaline or noradrenaline according to the pharmacological agents to optimize cardiac output and blood pressure of the advanced cardiovascular life support) was in group A 17 (56.6%) patients, while in group B it was nine (30%) patients while in group C seven (23.3%) patients showed a significant decrease in the amount of support when prophylactic IABP or levosimendan was used. However, the use of levosimendan showed a significant decrease in arterial blood pressure in the early postoperative period, so, the main support was noradrenaline in most of the patients who received levosimendan. Lomivorotov et al. reported the same results. Ranucci et al. also reported that primary circulatory support with IABP showed a significant increase in improved organ perfusion assessed by mixed venous oxygen saturation with secondary increase in cardiac output. According to the clinical data of REVIVE II and SURVIVE trials, moderate hypotension was the most frequent observed after a bolus infusion of levosimendan. However, based on this finding we would not administer any bolus of levosimendan in our patients in order to reduce the risk of intraoperative hypotension. Previous authors using a continuous infusion of levosimendan without a loading dose observed beneficial effects without hypotension. Moreover, 2012 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure recommended the use of levosimendan without loading dose,.
In our study, group A ICU stay ranged from 4 to 8 days with a mean of 7.3 ± 0.85 day, while group B had ICU stay ranging from 3 to 6 days with a mean of 5.2 ± 0.85 day. Group C had ICU stay ranging from 2 to 5 days with a mean of 4.4 ± 0.77; there was statistical significance between the three groups. The longer postoperative ICU stay in group A was due to gradual weaning of the high doses of inotropes and hemodynamic instability that occurred with the rapid withdrawal. While in group B, the rate of reopening was higher and one patient required hemodialysis which prolonged the ICU stay. Although seven patients in group C developed arrhythmia in the form of rapid atrial fibrillation, they responded rapidly to increasing intravenous fluids, correction of hypokalemia, and amiodarone bolus infusion which was continued later on with oral amiodarone. There was no statistical significance between the groups as regards postoperative arrhythmia. The incidence of arrhythmia being higher with levosimendan in our study can be explained by the main action of levosimendan as a calcium sensitizer which enhances cardiac contractility without increasing oxygen consumption, and induces vasodilation but this arrhythmia is controlled rapidly by correction of electrolytes, increased filling pressure, and responded rapidly to amiodarone without needing direct current cardioversion defibrillation. LICORN study concluded that levosimendan administration has been associated with higher incidence of atrial fibrillation in comparison to placebo. In contrast, meta-analysis of studies involving surgical patients suggested a reduced incidence of atrial fibrillation in the group of patients treated with levosimendan.
There was no statistical significance between the three groups in the number of reopened cases. Although it was slightly higher in group B with IABP mostly due to the concomitant heparin infusion or due to associated platelet dysfunction and coagulopathy. Lavana et al. showed in a retrospective analysis that starting IABP before surgery reduced hospital mortality, despite a higher predicted mortality. The main disadvantages of IABP include the development of limb ischemia, vessel damage, or bleeding (both local and mediastinal).
In our study in group A, four patients died, two of them failed to come off bypass and two died from multiorgan failure due to the LCOS, one patient died at postoperative day 4 and the other at postoperative day 6, while in group B three patients died, one patient failed to come off bypass and of the other patients one developed acute renal failure and died at the fifth postoperative day, the third patient died from septicemia and died after 2 weeks. While in group C, two patients died, one of them failed to come off bypass and the other died on the first day postoperatively due to hemodynamic instability. There was no statistical significance between the three groups. Levin and colleagues showed a significant reduction of mortality with the use of levosimendan in high-risk cardiac patients,. The results of our research suggest starting levosimendan infusion after induction of anesthesia as a good alternative to IABP in high-risk cardiac patients.
Our limitations were the high cost of the set of the IABP and short-term follow-up to detect post-hospital discharge morbidities and mortalities. So, we recommend further studies with a large number of patients and long-term follow-up to confirm the results.
| Conclusion|| |
Patients with prophylactic preoperative support with IABP or levosimendan has the same postoperative outcome as patients without preoperative support in a situation of CABG with low ejection fraction. However, this prophylactic use adds a value of lower needs of postoperative inotropes and moreover levosimendan is associated with lesser ICU stay.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sandhu A, McCoy LA, Negi SI, Hameed I, Atri P, Al'Aref SJ, et al
. Use of mechanical circulatory support in patients undergoing percutaneous coronary intervention: insights from the National Cardiovascular Data Registry. Circulation 2015; 132
Unverzagt S, Buerke M, de Waha A, Haerting J, Pietzner D, Seyfarth M, et al
. Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock. Cochrane Database Syst Rev 2015; 27
Krishna M, Zacharowski K. Principles of intra-aortic balloon pump counterpulsation. Contin Educ Anaesth Crit Care Pain 2009; 9
Maharaj R, Metaxa V. Levosimendan and mortality after coronary revascularisation: a metaanalysis of randomised controlled trials. Crit Care 2011; 15
Elahi MM, Matata BM. Myocardial protection against ischemia reperfusion injury: novel approaches in maintaining homeostatic stability in blood. Rec Pat Cardiovasc Drug Discov 2006; 1
Lomivorotov VV, Cherniavskiy AM, Boboshko VA, Kornilov IA, Lomivorotov VN, Karaskov AM. Levosimendan vs. intra-aortic balloon pump in high-risk cardiac surgery. Asian Cardiovas Thorac 2011; 19
Ranucci M, Castelvecchio S, Biondi A. Surgical and Clinical Outcome Research (SCORE) Group A randomized controlled trial of preoperative intra-aortic balloon pump in coronary patients with poor left ventricular function undergoing coronary artery bypass surgery. Crit Care Med 2013; 41
Packer M. REVIVE II: multicenter placebo-controlled trial of levosimendan on clinical status in acutely decompensated heart failure. Program and abstracts from the American Heart Association Scientific Sessions 2005; November 13–16, 2005; Dallas, Texas. Late Breaking Clinical Trials II.
Mebazaa A. The SURVIVE-W Trial: comparison of dobutamine and levosimendan on survival in acute decompensated heart failure. Program and abstracts from the American Heart Association Scientific Sessions 2005; November 13–16, 2005; Dallas, Texas. Late Breaking Clinical Trials IV.
Caruba T, Hourton D, Sabatier B, cholley B. Effect of levosimendan on low cardiac output syndrome in patients with low ejection fraction undergoing coronary artery bypass grafting with cardiopulmonary bypass (LICORN study). JAMA 2017; 318
Lavana JD, Fraser JF, Smith SE, Drake L, Tesar P, Mullany DV. Influence of timing of intra-aortic balloon placement in cardiac surgical patients. J Thorac Cardiovasc Surg 2010; 140
Levin R, Degrange MA, Porcile R, Salvagio F, Blanco N, Botbol AL, et al
. The calcium sensitizer levosimendan gives superior results to dobutamine in postoperative low cardiac output syndrome. Rev Esp Cardiol 2008; 61
Landoni G, Rodseth RN, Santini F, Ponschab M, Ruggeri L, Székely A, et al
. Randomized evidence for reduction of perioperative mortality. J Cardiothorac Vasc Anesth 2012; 26
[Table 1], [Table 2], [Table 3]