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Perioperative right ventricular (RV) function is an important determinant of postoperative outcomes after cardiac surgery. Perioperative RV dysfunction increases the need for perioperative inotropic support, prolongs intensive care unit stay and increases in-hospital mortality, in this study, we aim to investigate the effect of the preoperative administration of levosimendan on the outcome of patients with compromised right ventricular function undergoing cardiac surgery
Perioperative right ventricular (RV) function is an important determinant of postoperative outcomes following cardiac surgery. Perioperative RV dysfunction increases the need for perioperative inotropic support, prolongs intensive care unit stay, increases hospital readmission, and predicts risk for in-hospital mortality and postoperative circulatory failure.
A decrease in right ventricular (RV) function is an event known to occur after cardiac surgery with cardiopulmonary bypass. Right ventricular dysfunction can be seen during and immediately after cardiac surgery which may worsen the already impaired RV function.
Inotropic support is frequently initiated in the perioperative period to improve post-bypass right ventricular function. However, inotropes include the potential risk of increased myocardial oxygen consumption, which can result in cardiac ischemia, with subsequent damage to hibernating but viable myocardium, and arrhythmias. This has prompted an ongoing debate on the potential harm associated with inotropic therapy in cardiac surgery. Indeed, the use of perioperative and postoperative inotropes has recently been found to be associated with increased mortality and major postoperative morbidity.
Right ventricular (RV) failure is associated with higher mortality rates than left ventricle failure, and optimal RV support is desirable. Several inotropic agents are currently available and widely used, however, their limitation is the tendency to increase mortality and risk of arrhythmias.
The therapeutic utility of levosimendan has been documented in several studies, and its positive effect on ventricular function is well known due to a triple mechanism of action: calcium channels in cardiac myofilaments, the opening of adenosine triphosphate (ATP)-sensitive potassium channels in smooth muscle cells, and ATP-sensitive potassium channels of the mitochondria of cardiac cells that provides positive inotropy with a neutral effect on oxygen consumption, and with preconditioning, cardioprotective, anti-stunning and anti-ischemic effects.
However, only a few studies have evaluated the effects of levosimendan on RV function. In this study, we aimed to investigate the effects of levosimendan on RV function in patients during open-heart surgery with cardiopulmonary bypass.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Levosimendan group | Active Comparator | Patients will be admitted to ICU preoperatively and Levosimendan infusion will be started after insertion of an arterial line 12 hours before surgery in the ICU at a dose of 0.2 μg kg/min for the first hour and then reduced to 0.1 μg kg/ min to be continued in the operating room and then in the ICU (total infusion time of 24 hours). |
|
| Standard group | Other | Patients will not receive Levosimendan perioperatively and will be managed with standard care according to our institutional protocol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levosimendan | Drug | Patients will receive Levosimendan infusion 12 hours before surgery in the ICU at a dose of 0.2 μg kg/min for the first hour and then reduced to 0.1 μg kg/ min to be continued in the operating room and then in the ICU (total infusion time of 24 hours). |
| Measure | Description | Time Frame |
|---|---|---|
| Right ventricular function | Assessed by measuring Tricuspid annular plane systolic excursion (TAPSE) in millimeter will be measured intraoperatively by trans-esophageal echocardiography (TEE) and on day 1, 3 and 7 postoperatively by transthoracic echocardiography. | 7days |
| Right ventricular systolic pressure (RVSP) | Measured in mmhg intraoperatively by trans-esophageal echocardiography (TEE) on day 1, 3 and 7 postoperatively by transthoracic echocardiography . | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of mechanical ventilation | During ICU Stay in Hours | 2 Days |
| Vasoactive-Inotrope score (VIS) | will be recorded using the following calculation: dopamine dose (ug/kg/min) + dobutamine dose (ug/kg/min) + [10 × milrinone dose (ug/kg/min)] + [100 × epinephrine dose (ug/kg/min)] + [10,000 × vasopressin dose (U/kg/min)] + [100 × norepinephrine dose (ug/kg/min)].at admission, 12 hours, 24 hours and 48 hours. |
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Inclusion Criteria:
Exclusion Criteria:
Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent on venous return.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cardiothoracic Academy, Ain Shams University Hospitals | Cairo | 11566 | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24614322 | Result | Nielsen DV, Hansen MK, Johnsen SP, Hansen M, Hindsholm K, Jakobsen CJ. Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis. Anesthesiology. 2014 May;120(5):1098-108. doi: 10.1097/ALN.0000000000000224. | |
| 28416392 | Result | Bootsma IT, de Lange F, Koopmans M, Haenen J, Boonstra PW, Symersky T, Boerma EC. Right Ventricular Function After Cardiac Surgery Is a Strong Independent Predictor for Long-Term Mortality. J Cardiothorac Vasc Anesth. 2017 Oct;31(5):1656-1662. doi: 10.1053/j.jvca.2017.02.008. Epub 2017 Feb 5. |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077464 | Simendan |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D006835 | Hydrazones |
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D011724 | Pyridazines |
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| Standard Care | Drug | Patients will not receive Levosimendan and will receive standard care according to the institution protocol |
|
| 2 Days |
| Occurrence of arrhythmias | Present or no and type of arrhythmias During Hospital Stay | 7 to 10 Days |
| length of ICU stay | In Days | 7 to 10 Days |
| Length of Hospital Stay | In Days | 14 Days |
| 18297097 | Result | du Toit EF, Genis A, Opie LH, Pollesello P, Lochner A. A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart. Br J Pharmacol. 2008 May;154(1):41-50. doi: 10.1038/bjp.2008.52. Epub 2008 Feb 25. |
| 17566702 | Result | Haddad F, Denault AY, Couture P, Cartier R, Pellerin M, Levesque S, Lambert J, Tardif JC. Right ventricular myocardial performance index predicts perioperative mortality or circulatory failure in high-risk valvular surgery. J Am Soc Echocardiogr. 2007 Sep;20(9):1065-72. doi: 10.1016/j.echo.2007.02.017. Epub 2007 Jun 12. |
| 17086092 | Result | Lepran I, Pollesello P, Vajda S, Varro A, Papp JG. Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model. J Cardiovasc Pharmacol. 2006 Oct;48(4):148-52. doi: 10.1097/01.fjc.0000246151.39758.2a. |
| 15475828 | Result | Eriksson O, Pollesello P, Haikala H. Effect of levosimendan on balance between ATP production and consumption in isolated perfused guinea-pig heart before ischemia or after reperfusion. J Cardiovasc Pharmacol. 2004 Sep;44(3):316-21. doi: 10.1097/01.fjc.0000137163.22359.17. |
| 21784540 | Result | Papp Z, Edes I, Fruhwald S, De Hert SG, Salmenpera M, Leppikangas H, Mebazaa A, Landoni G, Grossini E, Caimmi P, Morelli A, Guarracino F, Schwinger RH, Meyer S, Algotsson L, Wikstrom BG, Jorgensen K, Filippatos G, Parissis JT, Gonzalez MJ, Parkhomenko A, Yilmaz MB, Kivikko M, Pollesello P, Follath F. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012 Aug 23;159(2):82-7. doi: 10.1016/j.ijcard.2011.07.022. Epub 2011 Jul 23. |
| 16181823 | Result | Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005 Sep 19;96(6A):47G-58G. doi: 10.1016/j.amjcard.2005.07.021. |
| 12947373 | Result | Alam M, Hedman A, Nordlander R, Samad B. Right ventricular function before and after an uncomplicated coronary artery bypass graft as assessed by pulsed wave Doppler tissue imaging of the tricuspid annulus. Am Heart J. 2003 Sep;146(3):520-6. doi: 10.1016/S0002-8703(03)00313-2. |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |