Role of Inhaled Nitric Oxide in Vascular Mechanics and Right Ventricular Function

Role of Inhaled Nitric Oxide in Vascular Mechanics and Right Ventricular Function Following Cardiac Surgery

The aim of this study is to evaluate the role of nitric oxide on pulmonary vasculature and right ventricular function in postoperative cardiac surgery patients.

Study Overview

• Status: Recruiting
• Conditions: Hemodynamic Stability; Collapsed Lung
• Intervention / Treatment: Drug: Nitric Oxide; Procedure: Alveolar recruitment maneuver

Detailed Description

This study will evaluate modifiable pathophysiological treatments for postoperative pulmonary hypertension and right ventricular dysfunction.

One pharmacological, inhaled nitric oxide, and one non-pharmacological, the OLA strategy combining lung recruitment and stabilization with individually optimized positive end-expiratory pressure (PEEP) and the possible synergistic effects of both interventions on right ventricular performance. Apart from acting specifically on the pathophysiological mechanisms described, the combination of an OLA strategy and iNO may be particularly beneficial, as modification of pulmonary status by OLA may, in theory, enhance the effects of iNO by significantly increasing gas exchange area and thus alveolar ventilation.

A number of closely related physiological variables will also be studied to better characterize the effects of both strategies and their combination. This may help to better establish the indication for iNO in cardiac surgery patients and improve our understanding of mechanisms that are also present in ARDS patients, albeit on a different scale.

This is a prospective randomized controlled physiological prospective study to be performed in two hospitals. The intervention period is limited to the first 2 -3 hours postoperatively. A total of 54 patients will be recruited.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fernando Suarez Sipmann, MD PhD; Phone Number: +34 915202200; Email: fsuarezsipmann@gmail.com
• Study Contact Backup: Name: Isabel Magana Bru, MD; Phone Number: +34 915202200; Email: isabelmgbru@gmail.com

Study Locations

• Spain
  • Madrid, Spain, 28006
    • Recruiting
    • Fernando Suárez Sipmann
    • Contact: Fernando Suarez Sipman; Phone Number: 915 20 22 00; Email: fsuarezsipmann@gmail.com
    • Contact: Isabel Magana Bru; Phone Number: 915 20 22 00; Email: isabelmgbru@gmail.com
    • Sub-Investigator: Isabel Magana Bru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• Age > 18 years
• Under controlled mechanical ventilation in passive conditions
• Presence of postoperative lung collapse (confirmed by pulmonary echocardiography and Air test)
• Preoperative left ventricular ejection fraction (LVEF) ≥ 30%.
• Absence of hypovolemia: absence of "kissing" ventricles and/or collapsibility index of the superior vena cava < 20%.
• Stable spontaneous heart rhythm
• Postoperative hemodynamic stability:
• Mean arterial pressure (MAP) ≥ 60 mmHg
• Central venous pressure (CVP) ≥ 10 mmHg
• Heart rate (HR) ≤ 100 bpm without tachyarrhythmias
• Lactic acid ≤ 3 mmol/L
• Single vasopressor treatment
• Norepinephrine dose ≤ 0.2 μg/kg/min, without an increase ≥ 15% in the last 30 -minutes.

Obtained informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment (CONT); The patient will be managed according to the routine clinical protocol, homogenizing the interventions in both participating centers.
Experimental: iNO 20-40 ppm; In this arm, inhaled nitric oxide therapy will be initiated at 20 ppm immediately after randomization and after initial data collection. The dose will be reassessed after the first 30 min and may be increased to a maximum of 40 ppm depending on the response observed in ventricular function.	Drug: Nitric Oxide; Administer nitric oxide upon arrival from cardiac surgery and assess cardiac and pulmonary function afterwards.
Experimental: iNO 20 - 40 ppm + Lung recruitment (iNO-RM); After 30 min after initiation of nitric oxide therapy following randomization, once patient stability has been confirmed, a brief recruitment maneuver will be performed and the subsequent PEEP level will be individualized according to the best lung compliance. Ventilation will then continue with the standard baseline ventilator settings, but with the PEEP level individually optimized.	Drug: Nitric Oxide; Administer nitric oxide upon arrival from cardiac surgery and assess cardiac and pulmonary function afterwards.; Procedure: Alveolar recruitment maneuver; Progressive pressure increase on the ventilator to recruit collapsed alveoli and improve pulmonary ventilation.; Other Names: Alveolar recruitment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right ventricular cardiac function specifically those directly related to the estimation ofright ventricular-vascular coupling	The parameters will be evaluated by TEE. Right ventricular function parameters will be assessed by the ratio of right ventricular end-diastolic to left ventricular end-diastolic diameters, right ventricular shortening fraction, tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI). estimation of systolic pulmonary artery pressure (PAPs), estimation of pulmonary vascular resistance by Doppler, Right ventricular outflow tract notch pattern, right ventricular outflow tract acceleration time (RVOT-AT).	A first TTE baseline measurement (T1) will be taken after arrival in the ICU after cardiac surgery, then another measurement will be taken 30 minutes after the first intervention (at iNO) (T2), and a new measurement will be taken 30 minutes later (T3).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrical impedance tomography (EIT) derived variables	With electrical impedance tomography (EIT), investigators will analyze the regional distribution of lung ventilation and percussion, the relative distribution of ventilation and percussion in predefined regions of interest, changes in lung aeration (end-expiratory lung volume difference) and pulmonary artery pulsatility.	A first baseline measurement (T1) will be taken after arrival at the ICU after cardiac surgery, then another measurement will be taken 30 minutes after the first intervention (in iNO) (T2), and a new measurement will be taken 30 minutes later (T3).

Collaborators and Investigators

• Sponsor: Fernando Suarez Sipmann
• Collaborators: Air Liquide SA

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: October 20, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pleural Diseases; Pneumothorax; Pulmonary Atelectasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: RONNIN- CCV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No