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NCT Number: NCT05838846

Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery

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.

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Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Menoufia University Hospitals

Shibīn al Kawm, Menoufia, Egypt

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Inhaled Milrinone

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.

IV Milrinone

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.

Primary outcomes

  1. Change in pulmonary artery pressure

    Time frame: Intraoperative

Secondary outcomes

  1. Incidence of systemic hypotension

    Time frame: Intraoperative

  2. Hemodynamic affection and need of vasopressors and inotropes.

    Time frame: Intraoperative

  3. Pulmonary vascular resistance versus systemic vascular resistance

    Time frame: Intraoperative

    Systemic vascular resistance: (MAP-CVP) x 80 / CO

    Pulmonary vascular resistance = (MPAP-PAWP) X 80 / CO

  4. Right ventricular function

    Time frame: Intraoperative

    Measured by tricuspid annulus plane systolic excursion, fractional area changes, and right ventricular systolic pressure by doppler

  5. Duration of mechanical ventilation

    Time frame: Postoperative in ICU (up to 24 hours)

  6. Need for mechanical circulatory support devices

    Time frame: Intraoperative

  7. Urine output

    Time frame: Intraoperative

Sponsors and collaborators

Lead sponsor

Menoufia University

Other

Registry information

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
May 3, 2023
Registry last updated
Feb 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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