Effects of Inhaled Nitric Oxide on Sublingual Microcirculation in Patients With Right Ventricular Dysfunction After Cardiac Surgery

Effects of Inhaled Nitric Oxide on Sublingual Microcirculation in Patients With Right Ventricular Dysfunction After Cardiac Surgery: a Prospective Interventional Study

Right ventricular (RV) dysfunction complicates 0.1-3% of cardiac surgical procedures and is strongly associated with elevated postoperative mortality. Pulmonary hypertension is a key determinant of perioperative RV failure. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that reduces pulmonary arterial pressure and has been widely used as adjunctive therapy in this setting. However, whether iNO influences systemic microcirculatory perfusion in these patients remains undefined.

We conducted a single-centre, prospective, interventional study. Adult patients with post-cardiotomy RV dysfunction - defined as central venous pressure (CVP) ≥ 15 mmHg combined with a pulmonary artery systolic pressure (PASP) > 35 mmHg on transthoracic echocardiography - were eligible. On top of standard postoperative care, patients received inhaled NO at 10-20 ppm for 2 hours without any concomitant change in vasoactive support. General characteristics, haemodynamic variables and sublingual microcirculatory parameters were recorded at baseline and again after 2 hours of iNO. The primary endpoint was the change in sublingual perfused vessel density (PVD). Secondary endpoints included mean arterial pressure (MAP), CVP, transthoracic echocardiographic indices, oxygenation index (OI), other sublingual microcirculatory parameters, capillary refill time (CRT), duration of mechanical ventilation and ICU length of stay.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension; Cardiac Surgery Intensive Care Treatment; Right Ventricular (RV) Dysfunction
• Intervention / Treatment: Drug: Inhaled Nitric Oxide (iNO) use

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital, School of Medicine, Southeast University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Adult patients (≥ 18 years) admitted to the ICU after cardiac surgery;
• Receiving mechanical ventilation;
• Central venous pressure (CVP) ≥ 15 mmHg plus a pulmonary artery systolic pressure (PASP) > 35 mmHg on transthoracic echocardiography;

Exclusion criteria :

• Contraindications to inhaled nitric oxide therapy, such as lethal congenital cardiac defects (including left-to-right shunts) and congenital methaemoglobinaemia;
• Known allergy or hypersensitivity to nitric oxide;
• Inability to obtain or adequately analyse sublingual microcirculatory images (e.g., due to poor image quality, motion artefact, or inability to cooperate with the acquisition protocol);
• Use of mechanical circulatory support devices that significantly influence haemodynamics, including extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), or left ventricular assist device (LVAD);
• Age > 80 years;
• Any condition judged unsuitable for inhaled nitric oxide therapy by the treating investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Inhaled Nitric Oxide; On top of standard postoperative management (including conventional mechanical ventilation, sedation, vasoactive and inotropic support, fluid management and renal replacement therapy as clinically indicated), patients received inhaled nitric oxide at a concentration of 10-20 ppm delivered through the inspiratory limb of the ventilator circuit using a validated NO delivery system with continuous monitoring of NO, NO2 and O2 concentrations.

Drug: Inhaled Nitric Oxide (iNO) use; On top of standard postoperative management (including conventional mechanical ventilation, sedation, vasoactive and inotropic support, fluid management and renal replacement therapy as clinically indicated), patients received inhaled nitric oxide at a concentration of 10-20 ppm delivered through the inspiratory limb of the ventilator circuit using a validated NO delivery system with continuous monitoring of NO, NO2 and O2 concentrations. The dose was titrated within this range by the treating intensivist according to the haemodynamic response. No changes to vasoactive, inotropic or vasopressor therapy, sedation or ventilator settings were made during the 2-hour study window unless clinically mandated, in which case the patient was withdrawn from analysis. Haemodynamic, echocardiographic and microcirculatory measurements were performed immediately before iNO initiation (0 h) and after 2 hours of continuous administration (2 h).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
perfused vessel density (PVD)	Perfused vessel density (PVD) is defined as the density of small vessels with actual blood flow per unit tissue area (usually capillaries and small vessels with diameter <20 μm), obtained noninvasively at the sublingual mucosa using a handheld vital microscope (sidestream dark field, SDF, or incident dark field, IDF) probe.	At enrollment and 2 hours after study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate		At enrollment and 2 hours after study drug administration
Mean arterial pressure		At enrollment and 2 hours after study drug administration
Central venous pressure		At enrollment and 2 hours after study drug administration
Urine output		At enrollment and 2 hours after study drug administration
Duration of mechanical ventilation, ICU length of stay and 28-day mortality.		At enrollment and 28 days after study drug administration
Tricuspid annular plane systolic excursion (TAPSE)	Measures the longitudinal displacement of the tricuspid annulus toward the cardiac apex during systole, obtained by M-mode in the apical 4-chamber view.	At enrollment and 28 days after study drug administration
Right ventricular fractional area change (RVFAC)	Calculated as: (RV end-diastolic area - RV end-systolic area) / RV end-diastolic area × 100%, by tracing the RV area in the apical 4-chamber view.	At enrollment and 28 days after study drug administration
E/e' ratio	This ratio is used to estimate left ventricular filling pressure (LVFP/LVEDP) and grade diastolic dysfunction.	At enrollment and 2 hours after study drug administration
Pulmonary artery systolic pressure (PASP)	Noninvasively estimated from the peak tricuspid regurgitation (TR) jet velocity: PASP = 4 × (TR velocity)² + estimated right atrial pressure.	At enrollment and 2 hours after study drug administration
PaO₂/FiO₂ ratio	Arterial oxygen partial pressure divided by the fraction of inspired oxygen	At enrollment and 2 hours after study drug administration
Lactate		At enrollment and 2 hours after study drug administration
Central venous-to-arterial PCO₂ difference (Pcv-aCO₂)	Reflects the adequacy of blood flow (cardiac output) to clear CO₂ produced by tissues-a "flow" marker rather than an oxygenation marker.	At enrollment and 2 hours after study drug administration
Central venous oxygen saturation (ScvO₂)	Oxygen saturation of blood sampled from the superior vena cava (central venous catheter), reflecting the balance between systemic oxygen delivery (DO₂) and consumption (VO₂).	At enrollment and 2 hours after study drug administration
Capillary refill time (CRT)	Time for distal capillary bed (e.g., fingertip/knee) to return to baseline color after standardized compression (5 s) - a bedside peripheral/ microcirculatory perfusion marker.	At enrollment and 2 hours after study drug administration
microvascular flow index (MFI)	A semi-quantitative flow velocity score: the image is divided into 4 quadrants, and the predominant flow type in each quadrant is scored: 0 = no flow; = intermittent flow; = slow flow; = continuous normal flow The final MFI is the mean of the 4 quadrant scores;	At enrollment and 2 hours after study drug administration
proportion of perfused vessels (PPV)	The percentage of vessels with blood flow out of all vessels: PPV = (number of perfused vessels ÷ total number of vessels) × 100%	At enrollment and 2 hours after study drug administration

Collaborators and Investigators

• Sponsor: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): September 30, 2026
• Study Completion (Actual): September 30, 2026

Study Registration Dates

• First Submitted: October 22, 2026
• First Submitted That Met QC Criteria: October 31, 2026
• First Posted (Actual): November 5, 2026

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: October 31, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary hypertension; Cardiac surgery; Microcirculation; Inhaled nitric oxide; Right ventricular dysfunction; Perfusion vessel density
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Respiratory Tract Diseases; Lung Diseases; Ventricular Dysfunction; Hypertension; Hypertension, Pulmonary; Ventricular Dysfunction, Right; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Nucleosides; Ribonucleosides; Purine Nucleosides; Inosine
• Other Study ID Numbers: 2025ZDSYLL092-P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: CSR

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