Inhaled Milrinone and Epoprostenol for the Prevention of Difficult Cardiac Pulmonary Bypass Separation

Summary

In cardiac surgery, the presence of pulmonary hypertension (PH) is a prognostic factor associated with increased mortality and morbidity. In this context, one of the main causes of PH is related to reperfusion ischemia during weaning from extracorporeal circulation (CPB). One of the consequences of PH is right ventricular dysfunction. During weaning from CPB, the development of a right ventricular dysfunction is associated with increased requirements for vasopressor and inotropic agents, duration of mechanical ventilation, prolonged intensive care and hospital stay, and increased mortality compared with patients with left ventricular (LV) dysfunction. The management of patients with PH with or without right ventricular (RV) dysfunction relies on several strategies such as the administration of intravenous and inhaled agents, or mechanical ventricular support. Among those agents, the administration of inotropes or pulmonary vasodilators such as epoprostenol, milrinone and nitric oxide are among the most widely used treatments recommended by the Canadian Cardiovascular Society. At the Montreal Heart Institute, inhaled epoprostenol and milrinone are routinely administered to patients with PH or LV dysfunction in the perioperative setting. Despite the frequent use of inhaled epoprostenol and milrinone, Health Canada has not yet approved the use of these molecules.

The primary objective of this multicenter, double-blind, randomized clinical trial is to evaluate the clinical efficacy of the combined administration of inhaled epoprostenol and milrinone in a cardiac surgery setting. This trial will compare the clinical outcome of 71 patients who will receive inhaled epoprostenol and milrinone before the start of bypass surgery to 71 patients who will receive a placebo before the start of the CPB. The primary clinical outcome is the proportion of patients with an "unsuccessful" CPB weaning defined by the use of an inotrope +/- vasopressor agent or the use of mechanical circulatory support or a return to bypass grafting for hemodynamic reasons.

This clinical trial will evaluate the clinical efficacy of the combination of inhaled agents in a cardiac surgery setting. Therefore, if the results of this study are positive, the combination of inhaled epoprostenol and milrinone will optimize the management of patients with pulmonary hypertension with or without a right ventricular dysfunction.

Conditions

• Right Heart Failure
• Right Ventricular Dysfunction

Interventions

DRUG

Combined Epoprostenol Sodium & Milrinone

One syringe containing 4mg of milrinone (1mg/mL, 4mL) and one syringe containing 60 mcg of epoprostenol (15 mcg/mL, 4mL). The drugs will be administered via an ultrasonic nebulizer (Aeroneb Professional Nebulizer System, Aerogen Ltd, Galway, Ireland, registration number: 66728) over a period of 20 minutes. This type of nebulizer is used routinely at the Montreal Heart Institute and can hold a maximum of 8 mL of solutions.

DRUG

Normal saline

The control group will receive two syringes of 4mL of Normal Saline, before CPB start. The placebo will be administered via an ultrasonic nebulizer (Aeroneb Professional Nebulizer System, Aerogen Ltd, Galway, Ireland, registration number: 66728) over a period of 20 minutes. This type of nebulizer is used routinely at the Montreal Heart Institute and can hold a maximum of 8 mL of solutions.

Sponsors & Collaborators

• Montreal Heart Institute

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-11-01

Primary Completion

2026-11-01

Completion

2027-01-01