Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents

Study Overview
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Brief Summary
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The aim of this study is to examine and compare the effect of Levosimendan and Milrinone administered intravenously and via inhalation respectively in cardiac surgery patients with pulmonary hypertension and right ventricular dysfunction.

Detailed Description
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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, the intravenous administration of Levosimendan will be compared with the inhalational use of milrinone in patients with pulmonary hypertension undergoing cardiac surgery. In this setting, 40 patients with PH caused by left sided heart disease, will be assigned into two groups: GROUP A: Intravenous administration of Levosimendan in dosage 6mcg/kg after induction of anesthesia. GROUP B: Inhalational administration of milrinone in dosage 50mcg/kg after induction of anesthesia. 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. This study will lead to conclusions regarding the effectiveness of intravenous administration of Levosimendan and inhalational use of Milrinone in the treatment of right heart failure and PH in cardiac surgery patients.

Official Title
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Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension

Conditions
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Hypertension, Pulmonary, Cardiac Failure, Pulmonary Vascular Resistance Abnormality

Intervention / Treatment
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* Drug: levosimendan at a dose of 6 mcg/kg
* Drug: milrinone at a dose of 50 mcg/kg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia<br>in this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass | Drug: levosimendan at a dose of 6 mcg/kg<br>* levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction<br>* Other names: Group Levo;|
| Active Comparator: Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia<br>in this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass | Drug: milrinone at a dose of 50 mcg/kg<br>* milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction<br>* Other names: Group Milri;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | 
| change from baseline in pulmonary vascular resistance (PVR) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | 
| change from baseline in mean arterial pressure (MAP) | a Swan-Ganz catheter will be used for hemodynamic measurements | 20 minutes after vasodilator 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 vasodilator 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 vasodilator 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 vasodilator 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 vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | 
| change from baseline in fractional area change | transthoracic and transesophageal echocardiography will be used for echocardiographic measurements | 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary vascular resistance, pulmonary hypertension, vasodilators, milrinone, levosimendan, cardiopulmonary bypass