Role of the Nitric Oxide (NO) in Pre-oxygenation Before Anesthetic Induction in Patients With a Pulmonary Hypertension in Cardiac Surgery. Pilot Study of Feasibility (NOCaPH)

The pulmonary hypertension (HTP) due to a left heart disease or a hypoxemiant lung disease is frequent in cardiac surgery. The HTP represents an independent risk factor of morbidity and mortality in cardiac surgery, entering to the criteria of Euroscore evaluation (European System for Cardiac Operative Risk Evaluation).

An acute perioperative hemodynamic decompensation of these patients is frequent. Perioperative hemodynamic modifications, hypoxemia, hypercapnia, sympathetic stimulation, increase pulmonary vascular resistances (RVP) and might provoke right ventricular failure.

The anesthetic induction and the beginning of mechanical ventilation are the most sensible times due to the risk of hemodynamic decompensation. The suppression of the sympathetic tonus which is consequence of the anesthetic induction, decrease the systemic vascular resistances and lead to decrease of blood pressure. In return, the anesthetic induction is associated with an increase of pulmonary vascular resistances, resulting in increase of the postcharge and the work of the right ventricle (VD). These systemic and pulmonary hemodynamic modifications can lead to equalization, or even an inversion of the systemic and pulmonary pressures. As consequence, a hemodynamic collapse or even a heart arrest can arise.

The patients suffering from HTP are hypoxemic. They have very limited oxygen reserves due to decrease of the functional residual capacity (CRF). The apnea period, which follows the anesthetic induction, is often associated with a fast desaturation, even if a good pre-oxygenation was performed before. This desaturation causes an increase of the pulmonary vascular resistances with the hemodynamic consequences previously mentioned. A risk of hypoxic heart arrest is also present.

Nitric Oxide (NO) is an endogenous mediator produced from the vascular endothelium. The NO is a powerful vasodilator and is used in intensive care in inhaled way as selective pulmonary vasodilator (iNO). NO decreases the RVP, the shunt effect and improves the oxygenation by optimization of ventilation-perfusion ratio. The short lifetime of iNO (6sec approximately) allows a fast metabolism without inducing any undesirable effects such as the systemic hypotension.

No studies, until now, have investigated the use of iNO in pre-oxygenation before anesthetic induction in cardiac surgery.

We hope to demonstrate that iNO used in oxygenation before anesthetic induction will have a beneficial effect on the respiratory and cardiovascular parameters.

Our objective is to estimate the feasibility and the tolerance of iNO before anesthetic induction of the patients with a moderate or severe HTP programmed for cardiac surgery with extracorporeal circulation. The effect will be estimated in terms of efficiency (hemodynamic and respiratory optimization).

Study Overview

• Status: Unknown
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Nitric oxide

Detailed Description

Before the anesthetic induction every included patient will follow these protocol:

• Standard monitoring (ECG Electrocardiogram, SpO2 Pulsed oxygen saturation)
• Insertion of radial arterial line and periferic IV line under local anesthesia,
• Insertion of a internal jugular central line and Swan Ganz catheter under local anesthesia
• Preoxygenation in 100% oxygen for 10 min
• Further preoxygenation with a mixture of 100% oxygen associated with the iNO in a dose of 1,2 L / mn.
• Anesthesia induction and initiation of mechanical ventilation.
• Progressive decrease of iNO dose and stop of iNO administration.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • CHU de Clermont-Ferrand
    • Sub-Investigator: Henri BOBY
    • Principal Investigator: Vedat ELJEZI

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Age > 18 years old

• Open-heart cardiac surgery
• HTP Pulmonary hypertension (class 2 or 3) with PAPs (Systolic pulmonary artery pressure) > 40 mmHg diagnosed by preoperative righ cardiac catheterization or by transthoracic echocardiography.
• Patient have signed their consent according to the modalities described by the Code of Public health system.
• Patients affiliated to a national insurance (social security) system.

Exclusion Criteria:

• Heart transplant
• HTP of type 1, 4, 5 according to the classification of Dana Point(2008)
• Deficit in methemoglobin reductase
• Protocole refuse from patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nitric oxyde	Drug: Nitric oxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary arterial systolic, diastolic and mean pressure	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
Pulmonary arterial mean/arterial mean ratio	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
SpO2 (Pulsed oxygen saturation)	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
FeO2 (Fraction expired oxygen) (data not available just during intubation phase)	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
Cardiac index	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
Systemic vascular resistances	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
SVO2 (Central Venous Saturation)	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
Sat O2 (Blood oxygen saturation)	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
PaO2 (Partial pressure of arterial oxygen)	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1
MetHb (methemoglobin)	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 (Fraction of inspired oxygen) will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic, diastolic and mean arterial pressure	These measures will be taken each minute between t0 (conditioning of the patient's arrival in the operating room) and the time when FiO2 will be 60% (when the endotracheal tube is in place, between 30 and 40 minutes after t0)	at day 1

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: ARAMU Association

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 20, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): February 4, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Pulmonary hypertension; Nitric oxide; Cardiac surgery; Induction anesthesia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; 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: CHU-0221; 2014-003338-15 (EudraCT Number)