Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery

Pulmonary Hypertension Clinical Trial

Official title:

Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05838846
• Other study ID #: 2/2023 ANET 60
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: April 1, 2023
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Menoufia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective double blinded 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.

Description:

Standard preoperative assessment for cardiac surgery will be done for all patients. Premedication will be given according to standard protocol in our university hospitals as follow bromazepam 3mg oral and ranitidine 150 mg orally in the night-before then another dose of ranitidine 150 mg 2 hours before arrival in operating theatre by small sips of clear liquid. On arrival to induction room wide bore IV access will be inserted using local anesthetic then arterial cannula in radial artery will be inserted the same manner using local anesthetic then in operating room routine monitoring including a five-lead electrocardiogram, pulse oximeter and invasive blood pressure will be attached. Anesthesia will be induced with midazolam 0.02 mg/kg and fentanyl 2-5 mcg/kg and muscle relaxation will be achieved by cis-atracurium 0.15 mg/kg. After tracheal intubation, central venous line and transesophageal echocardiography will be inserted, then anesthesia will be maintained throughout the procedure with morphine 20 mcg/kg/min, cis-atracurium 2 mcg/kg/min and sevoflurane 0.4% - 2% MAC. Ventilation will be adjusted to maintain end-tidal carbon dioxide in the range of 30-40 mmHg. During cardiopulmonary bypass, flow of 2.2 l/min/m2 will be achieved, 20 ml/kg cold blood cardioplegia will be given manually and pressure controlled at 20 - 30 min interval along with hot shot at start of weaning from CPB, temperature will be maintained at 32-34℃ and propofol 1% infusion at rate of 8 - 12ml/hr. In initial TEE study, baseline measures will be taken assessing left ventricular ejection fraction, and right ventricular hemodynamics represented by right ventricular function measured by [tricuspid annulus plane systolic excursion, fractional area changes, and right ventricular systolic pressure by doppler] also, pulmonary vascular resistance and systemic vascular resistance will be calculated, plus patients hemodynamics (mean arterial blood pressure, heart rate) and inotropic score all measures will be recorded.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 116
• Est. completion date: March 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 multiple valve diseases -other than mitral valve-.
• 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.

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Mitral Valve Replacement
• Pulmonary Hypertension
• Respiratory Aspiration

Intervention

Drug:
• 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 (21-23), 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.
• IV Milrinone
Patients will receive intravenous milrinone - started after induction of anesthesia - infusion at dosage of 0.5 mcg/kg/min without loading dose (24), Pulmonary vascular resistance and systemic vascular resistance will be calculated at the same corresponding time points to group A.

Locations

Country	Name	City	State
Egypt	Menoufia University Hospitals	Shibin Al Kawm	Menoufia

Sponsors (1)

Lead Sponsor	Collaborator
Menoufia University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pulmonary artery pressure		Intraoperative
Secondary	Incidence of systemic hypotension		Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Hemodynamic affection and need of vasopressors and inotropes.		Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Pulmonary vascular resistance versus systemic vascular resistance	Systemic vascular resistance: (MAP-CVP) x 80 / CO; Pulmonary vascular resistance = (MPAP-LAP) X 80 / CO	Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Right ventricular function	Measured by tricuspid annulus plane systolic excursion, fractional area changes, and right ventricular systolic pressure by doppler	Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Duration of mechanical ventilation		Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Need for mechanical circulatory support devices		Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Urine output		Intraoperative and postoperative in ICU (up to 24 hours)
Secondary	Length of intensive care (ICU) in stay		Intraoperative and postoperative in ICU (up to 24 hours)