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Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery

Phase 2
Completed
Conditions
Pulmonary Hypertension
Intravenous Milrinone
Mitral Valve Replacement
Inhaled Milrinone
Interventions
Registration Number
NCT05838846
Lead Sponsor
Menoufia University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group A (iMil)Inhaled MilrinonePatients 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 B (IvMil)IV MilrinonePatients 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.
Primary Outcome Measures
NameTimeMethod
Change in pulmonary artery pressureIntraoperative
Secondary Outcome Measures
NameTimeMethod
Incidence of systemic hypotensionIntraoperative
Hemodynamic affection and need of vasopressors and inotropes.Intraoperative
Right ventricular functionIntraoperative

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

Duration of mechanical ventilationPostoperative in ICU (up to 24 hours)
Need for mechanical circulatory support devicesIntraoperative
Urine outputIntraoperative
Pulmonary vascular resistance versus systemic vascular resistanceIntraoperative

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

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

Trial Locations

Locations (1)

Menoufia University Hospitals

🇪🇬

Shibīn Al Kawm, Menoufia, Egypt

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