Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents

NCT04718350 | Completed

• 1 other identifier: levo-milri
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to examine and compare the effect of Levosimendan and Milrinone administered intravenously and via inhalation respectively in cardiac surgery patients with pulmonary hypertension and right ventricular dysfunction.

Conditions

Hypertension, Pulmonary; Cardiac Failure; Pulmonary Vascular Resistance Abnormality

Keywords

pulmonary vascular resistance; pulmonary hypertension; vasodilators; milrinone; levosimendan; cardiopulmonary bypass

Outcome Measures

Primary Outcomes (10)

• change from baseline in mean pulmonary arterial pressure (MPAP)

  a Swan-Ganz catheter will be used for hemodynamic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in pulmonary vascular resistance (PVR)

  a Swan-Ganz catheter will be used for hemodynamic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in mean arterial pressure (MAP)

  a Swan-Ganz catheter will be used for hemodynamic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in systemic vascular resistance (SVR)

  a Swan-Ganz catheter will be used for hemodynamic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in pulmonary capillary wedge pressure (PCWP)

  a Swan-Ganz catheter will be used for hemodynamic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in cardiac output (CO)

  a Swan-Ganz catheter will be used for hemodynamic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in tricuspid annular plane systolic excursion (TAPSE)

  transthoracic and transesophageal echocardiography will be used for echocardiographic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• change from baseline in fractional area change

  transthoracic and transesophageal echocardiography will be used for echocardiographic measurements

  20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission

• length of ICU stay

  duration of patient stay in ICU in days

  postoperatively, an average period of 7-10 days

• hospitalization time

  duration of hospital stay after surgery in days

  postoperatively, up to 20 days after the operation

Study Arms (2)

Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia

ACTIVE COMPARATOR

in this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass

Drug: levosimendan at a dose of 6 mcg/kg

Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia

ACTIVE COMPARATOR

in this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass

Drug: milrinone at a dose of 50 mcg/kg

Interventions

levosimendan at a dose of 6 mcg/kg DRUG

levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction

Also known as: Group Levo

Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia

milrinone at a dose of 50 mcg/kg DRUG

milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction

Also known as: Group Milri

Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with pulmonary hypertension due to left ventricular dysfunction based on echocardiographic diagnosis preoperatively
• elective cardiac surgery

You may not qualify if:

• primary pulmonary hypertension
• thromboembolic disease
• chronic obstructive pulmonary disease
• emergency surgery
• redo surgery
• inability to consent to the study

Sponsors & Collaborators

• Aretaieion University Hospital: lead

Study Sites (1)

Onassis Cardiac Surgery Center

Athens, 17674, Greece

Location

Related Publications (5)

• Theodoraki K, Thanopoulos A, Rellia P, Leontiadis E, Zarkalis D, Perreas K, Antoniou T. A retrospective comparison of inhaled milrinone and iloprost in post-bypass pulmonary hypertension. Heart Vessels. 2017 Dec;32(12):1488-1497. doi: 10.1007/s00380-017-1023-2. Epub 2017 Jul 17.

  PMID: 28717881 BACKGROUND

• Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009 Feb;108(2):422-33. doi: 10.1213/ane.0b013e31818d8b92.

  PMID: 19151265 BACKGROUND

• Hansen MS, Andersen A, Nielsen-Kudsk JE. Levosimendan in pulmonary hypertension and right heart failure. Pulm Circ. 2018 Jul-Sep;8(3):2045894018790905. doi: 10.1177/2045894018790905. Epub 2018 Jul 6.

  PMID: 29979110 BACKGROUND

• Kundra TS, Nagaraja PS, Bharathi KS, Kaur P, Manjunatha N. Inhaled levosimendan versus intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Ann Card Anaesth. 2018 Jul-Sep;21(3):328-332. doi: 10.4103/aca.ACA_19_18.

  PMID: 30052230 BACKGROUND

• Elhassan A, Essandoh M. Inhaled Levosimendan for Pulmonary Hypertension Treatment During Cardiac Surgery: A Novel Application to Avoid Systemic Hypotension. J Cardiothorac Vasc Anesth. 2019 Apr;33(4):1169-1170. doi: 10.1053/j.jvca.2018.11.039. Epub 2018 Nov 28. No abstract available.

  PMID: 30612930 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Study Officials

• Kassiani Theodoraki, PhD, DESA

  Aretaieion University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: January 16, 2021
• First Posted: January 22, 2021
• Study Start: January 27, 2021
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)