Effect of Intraoperative Iloprost Inhalant on Hemodynamic Stability in Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery

Study Overview
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Brief Summary
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Considering that the cause of hemodynamic instability during OPCAB is closely related to right ventricular dysfunction with pulmonary artery hypertension, the use of inhaled iloprost (a selective pulmonary vasodilator) in patients undergoing OPCAB maybe beneficial for hemodynamic management. Previous research has showed that inhaled iloprost reduce pulmonary arterial pressure and pulmonary vascular resistance. Therefore, by administering inhaled iloprost before the graft anastomosis might improve cardiac output, mixed venous blood oxygen saturation, and pulmonary oxygenation during the surgery especially during the graft anastomosis. The objective of our study is to evaluate the effect of inhaled Iloprost on hemodynamic stability in patients undergoing off-pump coronary artery bypass graft surgery.

Official Title
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Effect of Intraoperative Iloprost Inhalant on Hemodynamic Stability in Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery: a Randomized, Blinded Clinical Trial

Conditions
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Coronary Artery Occlusive Disease

Intervention / Treatment
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* Drug: Iloprost
* Drug: Control (Normal saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 20 years and undergoing off-pump coronary artery bypass graft surgery with any of the following condition: High risk of hemodynamically unstable (patient in NYHA functional class III-IV, or mean pulmonary-artery pressure ≥ 25 mm Hg or right ventricular systolic pressure ≥ 50mmHg in preoperative echo findings, preoperative left ventricular ejection fraction < 50%, acute myocardial infarction within 1 month of surgery, ventricular fibrillation) History of previous cardiac operation (redo) Left main coronary artery disease Lesion at all three major coronary arteries Exclusion Criteria: Emergency operation Patients undergoing minimally Invasive Direct Coronary Artery Bypass Patients with cardiogenic shock or ventricular-assist device (eg. ECMO, IABP) Patients with pre-existing infections prior to surgery (eg. sepsis) Patients with liver cirrhosis Patients with hemorrhagic disease / bleeding risk (history of active peptic ulcer, intracranial hemorrhage, congenital hemorrhagic disease etc.) Patients with cerebrovascular event (TIA, stroke) within 3 months Patients with symptomatic asthma/chronic obstructive pulmonary disease who are receiving treatment such as inhaler or steroid Patient with severe chronic kidney disease (GFR(CKD-EPI) <30ml/min/1.73m2) Patient with acute kidney injury Patients who have participated in other clinical studies that may affect prognosis Patients who cannot understand the informed consent (eg. Foreigner)

Ages Eligible for Study
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Minimum Age: 20 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
Interventional Model Description: Patients are divided into 2 groups, who are administered aerosolized iloprost through a nebulizer connected to the inspiratory limb of the respiratory system, or who are administered same volume of normal saline at the same time and in the same manner.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Participants in this group are administered inhaled normal saline. | Drug: Control (Normal saline)<br>* Participants in Control group will be administered aerosolized 5 ml of normal saline in 15 min through a nebulizer connected to the inspiratory limb of the respiratory system when the internal mammary artery harvesting is done.<br>|
| Experimental: iloprost group<br>Participants in this group are administered inhaled iloprost. | Drug: Iloprost<br>* Participants in Iloprost group will be administered aerosolized 20 μg iloprost in 15 min through a nebulizer connected to the inspiratory limb of the respiratory system when the internal mammary artery harvesting is done.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative cardiac index | Compare the lowest intraoperative cardiac index between the Iloprost group and the control group during surgery, especially during the graft anastomosis. | 5 minutes before iloprost administration | 
| Intraoperative cardiac index | Compare the lowest intraoperative cardiac index between the Iloprost group and the control group during surgery, especially during the graft anastomosis. | 30 minutes after Iloprost administration | 
| Intraoperative cardiac index | Compare the lowest intraoperative cardiac index between the Iloprost group and the control group during surgery, especially during the graft anastomosis. | 5 minutes after the start of graft anastomosis | 
| Intraoperative cardiac index | Compare the lowest intraoperative cardiac index between the Iloprost group and the control group during surgery, especially during the graft anastomosis. | 5 minutes after pericardial closure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| systemic arterial blood pressure for the intraoperative hemodynamic parameters |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| central venous pressure(CVP in mmhg) for the intraoperative hemodynamic parameters |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| pulmonary artery pressure for the intraoperative hemodynamic parameters |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| heart rate for the intraoperative hemodynamic parameters |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| EKG rhythm for the intraoperative hemodynamic parameters |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| mixed venous oxygen saturation for the intraoperative hemodynamic parameters |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| PaO2/FiO2 ratio for the ventilation and oxygenation parameter |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| oxygen saturation in arterial blood for the ventilation and oxygenation parameter |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| arterial blood gas (ABG) test for oxygenation parameter |  | 15 minutes after induction of anesthesia (baseline), 30 minutes after Iloprost administration, 5 minutes after pericardial closure | 
| airway pressure (peak, plateau, PEEP) for the lung mechanics |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| dynamic compliance for the lung mechanics |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure | 
| driving pressure for the lung mechanics |  | 15 minutes after induction of anesthesia (baseline), 5 minutes before iloprost administration, 30 minutes after Iloprost administration, 5 minutes after the start of graft anastomosis, 5 minutes after pericardial closure |