Comparison Between Levosimendan and Adrenaline in CABG Patients

Levosimendan Versus Adrenaline in Patients With Low Left Ventricular Function Undergoing Elective On-Pump Coronary Artery Bypass Graft Surgery. A Randomized Controlled Study

The aim of this study is to compare between levosimendan and adrenaline in patients with pre-existing impaired systolic function (EF 30-40%), undergoing elective on-pump CABG, as regards hemodynamics and echocardiographic parameters.

Study Overview

• Status: Not yet recruiting
• Conditions: Open Heart Surgery
• Intervention / Treatment: Drug: Levosimendan; Drug: Adrenaline

Detailed Description

Patients undergoing cardiac surgery are at risk of post-cardiotomy myocardial dysfunction. This condition causes delayed recovery, organ failure, prolonged intensive care unit and hospital stays, and an increased risk of mortality. These patients often require inotropic support, which has been associated with an increased risk of cardiovascular complications. Treatment of myocardial dysfunction includes optimization of myocardial contractility through appropriate fluid and pharmacologic management and mechanical support . Extensive use of inotropes in this situation is needed, but the optimal pharmacologic management of myocardial dysfunction in cardiac surgery is a matter of ongoing debate .Available inotropes including adrenaline may increase myocardial oxygen consumption, heart rate and risk of arrhythmia. An increase in myocardial oxygen consumption by inotropes in a state of inadequate oxygen delivery may further deteriorate underlying cardiac dysfunction and even lead to increased mortality . There are questions regarding the ideal inotrope to use during the post cardiopulmonary bypass (CPB) period in patients undergoing on-pump CABG surgery. The occurrence of myocardial dysfunction after cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with a unique mechanism of action. By binding to cardiac troponin C, it enhances myofilament responsiveness to calcium, thereby increasing myocardial contraction without increasing myocardial oxygen consumption. In addition, levosimendan activates adenosine triphosphate-dependent potassium channels, which are important mediators of ischemic and anesthetic cardioprotection. Levosimendan might thus have a potential benefit for patients with myocardial oxygen imbalance requiring inotropic drug support . The hypothesis of the present study is that levosimendan without loading dose can improve myocardial function and provide better hemodynamics as well as echocardiographic parameters compared with adrenaline in patients with low ejection fraction undergoing op-pump CABG

• Study Type: Interventional
• Enrollment (Anticipated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Abdelrahman Mohamed Abdelhafeez; Phone Number: 00201112272212; Email: feezoo15@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ischemic hear disease
• age 18 and 65 years
• low left ventricular function (ejection fraction 30 - 40%),
• elective coronary artery bypass grafting (CABG) surgery

Exclusion Criteria:

• Age over 65 years
• Patients with end organ failure (renal, liver)
• Associated significant valve lesions
• Uncontrolled diabetes mellitus
• Emergency surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group (L) levosimendan group; Patients in this group will receive levosimendan (0.1 μg/kg/min) during re-warming of the patients.	Drug: Levosimendan; Patients in this group will receive levosimendan
Active Comparator: Group (A) Adrenaline group; Patients in this group will receive Adrenaline (0.05 μg /kg/min) during re-warming of the patients.	Drug: Adrenaline; Patients in this group will receive Adrenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic function (EF) will be measured in both groups Levosemindan and Adrenaline in patients with low ejection fraction (30-40%), undergoing elective on pump Coronary Artery Bypass Graft (CABG).	transesophageal echo (TEE) will be continuously used to monitor LV systolic and diastolic function during surgery and recordings will be made simultaneously with hemodynamic measurements. LV Ejection Fraction In the transgastric mid-papillary view, the echo machine will be switched to M-mode and the following measurements will be taken: o LV end-diastolic diameter o LV end-systolic diameter The machine will then calculate the LV ejection fraction according to Teich's method	24 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LV Myocardial Performance (Tei) Index will be measured in both groups	The left ventricle myocardial performance index will be calculated by placing pulsed Doppler sample volume between the anterior leaflet of the mitral valve and the left ventricle outflow tract (LVOT) in the deep transgastric view. Tei index = (a-b)/b, where (a) = distance between the mitral A wave and E wave, and (b) = distance between the start and end of the LVOT flow)	24 hour
LV Stroke Volume and Cardiac Output will be measured in both groups	The LVOT diameter will be measured in the mid-esophagus long-axis view. Assuming that the LVOT is circular in shape, the LVOT cross-sectional area will be calculated . The velocity time integral (VTI) of LVOT will be determined by pulsed Doppler imaging in the deep transgastric view by tracing the LVOT ejection curve. The stroke volume (SV) will then be calculated as: Stroke volume (cm3) = LVOT cross sectional area x LVOT VTI Cardiac output (CO) will then be calculated as CO = SV x heart rate, and cardiac index (CI) will be calculated as CI = CO/body surface area.	24 hour
LV diastolic function will be measured in both groups	In the mid-esophageal four-chamber view, E-wave velocity, A-wave velocity and E/A ratio will be determined by placing the sample volume of pulsed-wave Doppler at the tips of the mitral leaflets. Using tissue Doppler imaging, e'-wave velocity will be measured at both the lateral and septal mitral annulus, and the average of both measurements will be reported and used in subsequent calculations. The E/e' index will be calculated	24 hour

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 6, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Phosphodiesterase 3 Inhibitors; Epinephrine; Racepinephrine; Epinephryl borate; Simendan
• Other Study ID Numbers: Tee in open heart surgery

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No