Preoperative Infusion of Levosimendan in Patients Undergoing Cardiac Surgery

Preoperative Infusion of Levosimendan in High Risk Cardiac Surgery Patients: A Retrospective Study

The aim of this retrospective study will be to investigate the effect of the preoperative administration of levosimendan on the outcome of patients with compromised cardiac function undergoing cardiac surgery

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Cardiac Disease; Cardiac Failure; Inotropes; Ejection Fraction
• Intervention / Treatment: Procedure: preoperative infusion of levosimendan; Procedure: no preoperative infusion of levosimendan

Detailed Description

Patients with severely reduced left ventricular ejection fraction (LVEF) face a high risk of morbidity and mortality after cardiac surgery. Impaired cardiac function preoperatively predisposes patients to low cardiac output syndrome. Levosimendan acts by a different mechanism than traditional inotropes and its preoperative use could improve the outcome of patients with cardiac failure. Specifically, it promotes vasodilation of coronary, pulmonary and systemic vessels, has an anti-inflammatory and anti-oxidant effect and enhances cardiac contractility by improving the response of the myofilaments to intracellular calcium.

The aim of this retrospective study will be to investigate the effect of the preoperative administration of levosimendan on the outcome of patients with compromised cardiac function undergoing cardiac surgery.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 17674
    • Onassis Cardiac Surgery Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• elective cardiac surgery
• cardiac surgery under cardiopulmonary bypass
• low ejection fraction (<40%)

Exclusion Criteria:

• age <18 years old
• urgent operation
• glomerular filtration rate<30 ml/min
• hepatic dysfunction preoperatively
• side effects (hypotension, tachycardia, ST segment abnormalities during levosimendan administration
• redo surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: patients who were administered levosimendan at a dose of 0.1µg/Kg/min for 24 hours prior to surgery	Procedure: preoperative infusion of levosimendan; the study group will consist of patients who have received a continuous infusion of levosimendan 0.1 μg/kg/min for 24 hours before cardiac surgery
Placebo Comparator: patients who were not administered levosimendan prior to surgery	Procedure: no preoperative infusion of levosimendan; the control group will consist of patients who proceeded to the cardiac operation without any infusion for 24 hours preoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hours of mechanical ventilation	hours of mechanical ventilation during patient stay in Intensive Care Unit (ICU)	during stay in ICU, approximately 48 hours postoperatively
vasopressor use in operating room	need for vasopressor use, yes or no	intraoperatively, from induction to end of anesthesia, an average period of 3 hours
vasopressor use in ICU	need for vasopressor use, yes or no	during stay in ICU, approximately 48 hours postoperatively
inotrope use in operating room	need for inotrope use, yes or no	intraoperatively, from induction to end of anesthesia, an average period of 3 hours
inotrope use in ICU	need for inotrope use, yes or no	during stay in ICU, approximately 48 hours postoperatively
incidence of arrhythmias	development of new-onset arrhythmias, yes or no	postoperatively, an average period of 7-10 days
incidence of renal dysfunction	development of new-onset renal dysfunction, defined as an increase in creatinine levels over 0.3 mg/dL from the initial values	postoperatively, an average period of 7-10 days
length of ICU stay	duration of patient stay in ICU in days	postoperatively, an average period of 7-10 days
hospitalization time	duration of hospital stay after surgery in days	postoperatively, up to 20 days after the operation
incidence of death within the first 30 days after surgery	patient survival within the first 30 days after surgery, yes or no	30 days after surgery
need of mechanical assist devices intraoperatively	need for mechanical assist devices, yes or no	intraoperatively, from induction to end of anesthesia, an average period of 3 hours and postoperatively, an average period of 7-10 days
need of mechanical assist devices postoperatively	need for mechanical assist devices, yes or no	postoperatively, an average period of 7-10 days
change from baseline in cardiac output (CO)	a Swan-Ganz catheter will be used for hemodynamic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery), 12 hours after ICU admittance, 24 hours after ICU admittance,
change from baseline in mean arterial pressure (MAP)	a Swan-Ganz catheter will be used for hemodynamic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery), 12 hours after ICU admittance, 24 hours after ICU admittance,
change from baseline in mean pulmonary arterial pressure (MPAP)	a Swan-Ganz catheter will be used for hemodynamic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery), 12 hours after ICU admittance, 24 hours after ICU admittance,
change from baseline in systemic vascular resistance (SVR)	a Swan-Ganz catheter will be used for hemodynamic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery), 12 hours after ICU admittance, 24 hours after ICU admittance,
change from baseline in pulmonary vascular resistance (PVR)	a Swan-Ganz catheter will be used for hemodynamic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery), 12 hours after ICU admittance, 24 hours after ICU admittance,
change from baseline in pulmonary capillary wedge pressure (PCWP)	a Swan-Ganz catheter will be used for hemodynamic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery),12 hours after ICU admittance, 24 hours after ICU admittance,
change from baseline in cardiac function	transesophageal echocardiography will be used for echocardiographic measurements	10 minutes after anesthesia induction, 10 minutes after bypass discontinuation, end of operation (an average period of 3 hours after start of surgery)

Collaborators and Investigators

• Sponsor: Aretaieion University Hospital

Publications and helpful links

General Publications

• Tasouli A, Papadopoulos K, Antoniou T, Kriaras I, Stavridis G, Degiannis D, Geroulanos S. Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Eur J Cardiothorac Surg. 2007 Oct;32(4):629-33. doi: 10.1016/j.ejcts.2007.07.010. Epub 2007 Aug 15. Erratum In: Eur J Cardiothorac Surg. 2008 Mar;33(3):521.
• Landoni G, Biondi-Zoccai G, Greco M, Greco T, Bignami E, Morelli A, Guarracino F, Zangrillo A. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med. 2012 Feb;40(2):634-46. doi: 10.1097/CCM.0b013e318232962a.
• Tritapepe L, De Santis V, Vitale D, Guarracino F, Pellegrini F, Pietropaoli P, Singer M. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery. Br J Anaesth. 2009 Feb;102(2):198-204. doi: 10.1093/bja/aen367.
• De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg. 2007 Apr;104(4):766-73. doi: 10.1213/01.ane.0000256863.92050.d3. Erratum In: Anesth Analg. 2007 Jun;104(6):1544. Dosage error in article text.
• Kivikko M, Lehtonen L. Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Curr Pharm Des. 2005;11(4):435-55. doi: 10.2174/1381612053382043.
• Mehta RH, Leimberger JD, van Diepen S, Meza J, Wang A, Jankowich R, Harrison RW, Hay D, Fremes S, Duncan A, Soltesz EG, Luber J, Park S, Argenziano M, Murphy E, Marcel R, Kalavrouziotis D, Nagpal D, Bozinovski J, Toller W, Heringlake M, Goodman SG, Levy JH, Harrington RA, Anstrom KJ, Alexander JH; LEVO-CTS Investigators. Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery. N Engl J Med. 2017 May 25;376(21):2032-2042. doi: 10.1056/NEJMoa1616218. Epub 2017 Mar 19.
• Cholley B, Caruba T, Grosjean S, Amour J, Ouattara A, Villacorta J, Miguet B, Guinet P, Levy F, Squara P, Ait Hamou N, Carillion A, Boyer J, Boughenou MF, Rosier S, Robin E, Radutoiu M, Durand M, Guidon C, Desebbe O, Charles-Nelson A, Menasche P, Rozec B, Girard C, Fellahi JL, Pirracchio R, Chatellier G; -. Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):548-556. doi: 10.1001/jama.2017.9973.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): November 9, 2020
• Study Completion (Actual): November 9, 2020

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 19, 2020
• Last Update Submitted That Met QC Criteria: November 12, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: levosimendan; low output syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Failure; Heart Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: 667/24.02.2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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