Cardiac Failure, Hypertension, Pulmonary, Pulmonary Vascular Resistance Abnormality
Conditions
Keywords
pulmonary vascular resistance, pulmonary hypertension, vasodilators, cardiopulmonary bypass
Brief summary
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.
Detailed description
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.
Interventions
DRUGlevosimendan at a dose of 3 mcg/kg
levosimendan will be administered intravenously at a dose of 3 mcg/kg after anesthesia induction
levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction
DRUGlevosimendan at a dose of 12 mcg/kg
levosimendan will be administered intravenously at a dose of 12 mcg/kg after anesthesia induction
Sponsors
Aretaieion University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* patients with pulmonary hypertension due to left ventricular dysfunction based on echocardiographic diagnosis preoperatively * elective cardiac surgery
Exclusion criteria
* primary pulmonary hypertension * thromboembolic disease * chronic obstructive pulmonary disease * emergency surgery * redo surgery * inability to consent to the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change from baseline in mean pulmonary arterial pressure (MPAP) | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | a Swan-Ganz catheter will be used for hemodynamic measurements |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change from baseline in mean arterial pressure (MAP) | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | a Swan-Ganz catheter will be used for hemodynamic measurements |
| change from baseline in systemic vascular resistance (SVR) | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | a Swan-Ganz catheter will be used for hemodynamic measurements |
| change from baseline in pulmonary vascular resistance (PVR) | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | a Swan-Ganz catheter will be used for hemodynamic measurements |
| change from baseline in pulmonary capillary wedge pressure (PCWP) | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | a Swan-Ganz catheter will be used for hemodynamic measurements |
| change from baseline in tricuspid annular plane systolic excursion (TAPSE) | 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration | transthoracic and transesophageal echocardiography will be used for echocardiographic measurements |
| change from baseline in fractional area change | 20 minutes after levosimendan administration, at the end of surgery, 2 hours after Intensive Care Unit (ICU) admission and 80 hours after levosimendan administration | transthoracic and transesophageal echocardiography will be used for echocardiographic measurements |
| change from baseline in cardiac output (CO) | 20 minutes after levosimendan administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | a Swan-Ganz catheter will be used for hemodynamic measurements |
Other
| Measure | Time frame | Description |
|---|---|---|
| change from baseline in blood levels of levosimendan | 20 minutes, 6 hours, 12 hours, 24 hours and 80 hours after administration | blood levels will be measured with liquid chromatography |
| change from baseline in blood levels of interleukin-6 (IL-6) | end of surgery, 6 hours, 12 hours and 24 hours after Intensive Care Unit (ICU) admission | blood levels will be measured with the enzyme linked immunosorbent assay (ELISA) |
Countries
Greece
Outcome results
None listed