Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery

NCT ID: NCT05838846

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2025-01-01

Brief Summary

This prospective open-label randomized study aims to compare the effect of inhaled versus intravenous milrinone on the pulmonary vascular resistance in patients undergoing mitral valve replacement surgery.

The primary outcome is to determine change in pulmonary artery pressure. The secondary outcomes include,

• Incidence of systemic hypotension.
• Hemodynamic affection and need of vasopressors and inotropes.
• Change in pulmonary vascular resistance versus systemic vascular resistance.
• Right ventricular function.
• Duration of mechanical ventilation.
• Need for mechanical circulatory support devices.
• Urine output
• Length of intensive care (ICU) in stay.

As the investigators hypothesize that inhaled milrinone has a selective pulmonary vasodilator effect devoid of the systemic hypotension with the intravenous administration.

Detailed Description

All patients underwent standard preoperative cardiac surgery assessment. Premedication included bromazepam and ranitidine, given the night before and 2 hours prior to arrival to OT. On arrival, IV access and arterial cannula were inserted under local anesthesia, along with routine monitoring electrocardiogram (ECG), pulse oximetery (SpO2), and IBP.

Anesthesia was induced with midazolam, fentanyl, and cis-atracurium. After tracheal intubation, ultrasound (US) guided- central venous catheter (CVC) was inserted and TEE also applied and then anesthesia maintained with morphine, cis-atracurium infusions, and sevoflurane. Mechanical ventilation was set to maintain end-tidal carbon dioxide (etco2) in the range of 30-40 mmHg using lung protective ventilation strategies.

During CPB, flow of 2.2 L.min-1.m-2, a custodiol cardioplegia was given, temperature kept at 28-32℃ and anesthesia maintained by sevoflurane- through a vaporizer mounted on CPB machine-.

A senior consultant certified cardiac anesthetist conducted a baseline TEE using Philips EPIQ CVxi echocardiography machine. Baseline measures included left ventricular ejection fraction (LVEF), and RV function represented by tricuspid annulus plane systolic excursion (TAPSE), fractional area changes (FAC), and right ventricular systolic pressure (RVSP) by doppler also, PVR and systemic vascular resistance (SVR) was calculated, plus patients hemodynamics (mean arterial blood pressure (MAP), heart rate (HR)), all measures were recorded.

Conditions

Mitral Valve Replacement; Pulmonary Hypertension; Inhaled Milrinone; Intravenous Milrinone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group A (iMil)

Patients will receive 2 doses of inhaled milrinone at the following time points (after sternotomy and after aortic cross clamp off) at dosage of 50 mcg/kg by nebulization, inhaled milrinone will be administered through Aerogen solo with Pro-X controller - continuous mode- attached to ventilator circuit distal to viral/ bacterial heat and moisture exchange filter.

Then pulmonary vascular resistance and systemic vascular resistance will be calculated after first dose ended by 2 minutes and after second dose ended by 15 minutes till stabilization of post CPB other variables like temperature and acid-base status, both measurements will be done while using inspired oxygen of 0.80.

Group Type: EXPERIMENTAL

Inhaled Milrinone

Intervention Type: DRUG

Patients will receive 2 doses of inhaled milrinone at the following time points (after sternotomy and after aortic cross clamp off) at dosage of 50 mcg/kg by nebulization, inhaled milrinone will be administered through Aerogen solo with Pro-X controller - continuous mode- attached to ventilator circuit distal to viral/ bacterial heat and moisture exchange filter.

Group B (IvMil)

Patients will receive intravenous milrinone - started after induction of anesthesia - infusion at dosage of 0.3 - 0.75 mcg/kg/min after loading dose of 50 mic/kg over 10 min. After cross clamp off and temperature of 32 degree, Pulmonary vascular resistance and systemic vascular resistance will be calculated at the same corresponding time points to group A.

Group Type: ACTIVE_COMPARATOR

IV Milrinone

Intervention Type: DRUG

Patients will receive intravenous milrinone infusion at dosage of 0.3 - 0.75 mcg/kg/min with loading dose of 50 mcg/kg over 10 min. After cross clamp off and temperature of 32 degree, Pulmonary vascular resistance and systemic vascular resistance will be calculated at the same corresponding time points to group A.

Interventions

Inhaled Milrinone

Patients will receive 2 doses of inhaled milrinone at the following time points (after sternotomy and after aortic cross clamp off) at dosage of 50 mcg/kg by nebulization, inhaled milrinone will be administered through Aerogen solo with Pro-X controller - continuous mode- attached to ventilator circuit distal to viral/ bacterial heat and moisture exchange filter.

Intervention Type: DRUG

IV Milrinone

Patients will receive intravenous milrinone infusion at dosage of 0.3 - 0.75 mcg/kg/min with loading dose of 50 mcg/kg over 10 min. After cross clamp off and temperature of 32 degree, Pulmonary vascular resistance and systemic vascular resistance will be calculated at the same corresponding time points to group A.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Severe mitral regurgitation and moderate or severe pulmonary hypertension
• Scheduled for mitral valve replacement surgery

# Criteria of severe mitral regurgitation:

• Central jet MR >40% LA or holosystolic eccentric jet MR
• Vena contracta ≥ 0.7 cm
• Regurgitant volume ≥60 ml
• Regurgitant fraction ≥50%
• EROA ≥0.40 cm2

# Criteria of moderate and severe pulmonary hypertension:

• Moderate pulmonary hypertension; mean pulmonary artery pressure > 41 mmHg while, severe pulmonary hypertension; mean pulmonary artery pressure > 55 mmHg
• Mean pulmonary artery pressure > 40% of mean systemic blood pressure.
• Mean pulmonary artery pressure approximated from estimated systolic pulmonary artery pressure as following; mPAP= (estimated sPAP X 0.61) ± 2

Exclusion Criteria

• Patients with aortic valvular lesions or pulmonary stenosis.
• Hemodynamic instability in the preoperative time (defined as acute requirement for vasoactive support or mechanical device).
• Contraindication to transesophageal echocardiography; esophageal stricture, tumor or diverticulum or active upper gastrointestinal bleeding
• Patients with hepatic or renal dysfunction.
• Patients with coagulopathy.
• Emergency surgeries.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Menoufia University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Ashraf Nasr

Assisstant Lecturer Anesthesia, Intensive care and Pain management - Faculty of Medicie - Menoufia University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ghada A Hassan, Professor

Role: STUDY_CHAIR

Faculty of Medicine - Menoufia University

Mohamed A Salem, A. Professor

Role: STUDY_CHAIR

Faculty of Medicine - Menoufia University

Khaled M Gaballah, A. Professor

Role: STUDY_CHAIR

Faculty of Medicine - Menoufia University

Mohammed O El Gouhary, Lecturer

Role: STUDY_DIRECTOR

Faculty of Medicine - Ain Shams University

Locations

Menoufia University Hospitals

Shibīn al Kawm, Menoufia, Egypt

Countries

Egypt

Other Identifiers

2/2023 ANET 60

Identifier Type: -

Identifier Source: org_study_id