Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The aim of the study is to examine the pharmacokinetics and pharmacodynamic properties of Levosimendan in cardiac surgery patients with pulmonary hypertension and impaired right ventricular function.
Pulmonary hypertension (PH) is a pathophysiological disorder hemodynamically characterized by increased pulmonary vascular resistance and pressure. This can lead to right ventricle pressure overload and failure which is worsened by cardiopulmonary bypass (CPB) and extracorporeal circulation and is accompanied by high rates of morbidity and mortality in cardiac surgery patients. Pharmacological agents used to decrease pulmonary vascular resistance and right ventricle afterload are prostaglandins, iloprost, milrinone, nitric oxide (NO) and recently Levosimendan. These agents can be administered intravenously or via inhalation.
In this study, Levosimendan will be administered in patients with pulmonary hypertension undergoing cardiac surgery. The aim of the study is to examine the pharmacokinetics and pharmacodynamic properties of Levosimendan in cardiac surgery patients with pulmonary hypertension and impaired right ventricular function. The drug will be administered in different doses to define the dose at which Levosimendan administration reduces pulmonary vascular resistance and pressure without causing significant reduction of systemic vascular resistance and pressure. The anti-inflammatory effect of the perioperative use of Levosimendan in cardiac surgery will also be studied.
In this setting, 45 patients with PH caused by left sided heart disease, will be assigned into three groups:
GROUP A: Administration of Levosimendan at a dosage of 3mcg/kg after anesthesia induction.
GROUP B: Administration of Levosimendan at a dosage of 6mcg/kg after anesthesia induction.
GROUP C: Administration of Levosimendan at a dosage of 12mcg/kg after anesthesia induction.
Before and after the administration of the drug, heart function will be evaluated by hemodynamic measurements obtained by the Swan-Ganz catheter. These parameters will be heart rate (HR), blood pressure (BP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR). Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) will also be used. The anti-inflammatory action of Levosimendan will also be evaluated by interleukin-6 (IL-6) measurements.
This study will lead to conclusions regarding the effectiveness of Levosimendan administration in the treatment of right heart failure and PH in cardiac surgery patients.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| levosimendan administration at a dose of 3 mcg/kg after anesthesia induction | Active Comparator | levosimendan will be administered at a dose of 3 mcg/kg after anesthesia induction |
|
| levosimendan administration at a dose of 6 mcg/kg after anesthesia induction | Active Comparator | levosimendan will be administered at a dose of 6 mcg/kg after anesthesia induction |
|
| levosimendan administration at a dose of 12 mcg/kg after anesthesia induction | Active Comparator | levosimendan will be administered at a dose of 12 mcg/kg after anesthesia induction |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| levosimendan at a dose of 3 mcg/kg | Drug | levosimendan will be administered intravenously at a dose of 3 mcg/kg after anesthesia induction |
|
| Measure | Description | Time Frame |
|---|---|---|
| change from baseline in mean pulmonary arterial pressure (MPAP) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission |
| Measure | Description | Time Frame |
|---|---|---|
| change from baseline in pulmonary vascular resistance (PVR) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission |
| change from baseline in mean arterial pressure (MAP) |
| Measure | Description | Time Frame |
|---|---|---|
| change from baseline in blood levels of levosimendan | blood levels will be measured with liquid chromatography | 20 minutes, 6 hours, 12 hours, 24 hours and 80 hours after administration |
| change from baseline in blood levels of interleukin-6 (IL-6) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kassiani Theodoraki, PhD, DESA | Aretaieion University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Onassis Cardiac Surgery Center | Athens | 17674 | Greece |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12419726 | Background | Theodoraki K, Rellia P, Thanopoulos A, Tsourelis L, Zarkalis D, Sfyrakis P, Antoniou T. Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass. Can J Anaesth. 2002 Nov;49(9):963-7. doi: 10.1007/BF03016884. | |
| 28717881 | Background | Theodoraki K, Thanopoulos A, Rellia P, Leontiadis E, Zarkalis D, Perreas K, Antoniou T. A retrospective comparison of inhaled milrinone and iloprost in post-bypass pulmonary hypertension. Heart Vessels. 2017 Dec;32(12):1488-1497. doi: 10.1007/s00380-017-1023-2. Epub 2017 Jul 17. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| levosimendan at a dose of 6 mcg/kg | Drug | levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction |
|
| levosimendan at a dose of 12 mcg/kg | Drug | levosimendan will be administered intravenously at a dose of 12 mcg/kg after anesthesia induction |
|
a Swan-Ganz catheter will be used for hemodynamic measurements |
| 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission |
| change from baseline in systemic vascular resistance (SVR) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission |
| change from baseline in pulmonary capillary wedge pressure (PCWP) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission |
| change from baseline in cardiac output (CO) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission |
| change from baseline in tricuspid annular plane systolic excursion (TAPSE) | transthoracic and transesophageal echocardiography will be used for echocardiographic measurements | 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration |
| change from baseline in fractional area change | transthoracic and transesophageal echocardiography will be used for echocardiographic measurements | 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration |
blood levels will be measured with the enzyme linked immunosorbent assay (ELISA)
| end of surgery, 6 hours, 12 hours and 24 hours after Intensive Care Unit (ICU) admission |
| 19151265 | Background | Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009 Feb;108(2):422-33. doi: 10.1213/ane.0b013e31818d8b92. |
| 29979110 | Background | Hansen MS, Andersen A, Nielsen-Kudsk JE. Levosimendan in pulmonary hypertension and right heart failure. Pulm Circ. 2018 Jul-Sep;8(3):2045894018790905. doi: 10.1177/2045894018790905. Epub 2018 Jul 6. |
| 18496375 | Background | Boost KA, Hoegl S, Dolfen A, Czerwonka H, Scheiermann P, Zwissler B, Hofstetter C. Inhaled levosimendan reduces mortality and release of proinflammatory mediators in a rat model of experimental ventilator-induced lung injury. Crit Care Med. 2008 Jun;36(6):1873-9. doi: 10.1097/CCM.0b013e3181743e63. |
| 30052230 | Background | Kundra TS, Nagaraja PS, Bharathi KS, Kaur P, Manjunatha N. Inhaled levosimendan versus intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Ann Card Anaesth. 2018 Jul-Sep;21(3):328-332. doi: 10.4103/aca.ACA_19_18. |
| 30612930 | Background | Elhassan A, Essandoh M. Inhaled Levosimendan for Pulmonary Hypertension Treatment During Cardiac Surgery: A Novel Application to Avoid Systemic Hypotension. J Cardiothorac Vasc Anesth. 2019 Apr;33(4):1169-1170. doi: 10.1053/j.jvca.2018.11.039. Epub 2018 Nov 28. No abstract available. |
| 17631672 | Background | Zhang J, Gage EM, Ji QC, El-Shourbagy TA. A strategy for high-throughput analysis of levosimendan and its metabolites in human plasma samples using sequential negative and positive ionization liquid chromatography/tandem mass spectrometric detection. Rapid Commun Mass Spectrom. 2007;21(14):2169-76. doi: 10.1002/rcm.3046. |
| D002318 |
| Cardiovascular Diseases |
| D006331 | Heart Diseases |