Effects of a New Interface for NIV on Respiratory Drive

Acute Respiratory Failure Clinical Trial

Official title:

Physiological Effects on Respiratory Drive and Transpulmonary Pressure of a New Interface Combining High-flow Nasal Cannula and Cpap in Patients With Mild-to-moderate Acute Respiratory Distress Syndrome: a Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04619667
• Other study ID #: OptiPAP Pes
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 1, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: November 2020
• Source: University Magna Graecia
• Contact: Federico Longhini, MD
• Phone: 00393475395967
• Email: longhini.federico[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot physiologic randomized cross-over study was designed to investigate if, in patients with hARF, a new device combining high-flow oxygen through nasal cannula (HFNC) and continuous positive airway pressure (CPAP) reduces the respiratory effort, as compared to HFNC and CPAP alone (first outcome). Furthermore, the diaphragm activation, as assessed with ultrasound, gas exchange and patient's comfort among different settings will be assessed (secondary outcomes).

Description:

Around 30% of patients admitted to the Intensive Care Unit (ICU) are affected by hypoxemic Acute Respiratory Failure (hARF). The primary supportive treatment in hypoxemic patients is oxygen therapy, which is commonly delivered through nasal prongs or masks. New devices, able to deliver high-flow gas through a nasal cannula (HFNC), have been recently made available. HFNC delivers heated and humidified gas up to 60 L/min, with a fraction of inspired oxygen (FiO2) ranging from 0.21 to 1, via a wide bore soft nasal prong. Warming and humidification of the inspired gas prevent the adverse effects of cool dry gases on the airway epithelium and facilitate expectoration. HFNC also washes out exhaled carbon dioxide (CO2) from the pharyngeal dead space. HFNC has been shown an effective means to deliver oxygen therapy in many clinical conditions.

In healthy subject during spontaneous unassisted breathing, end-expiratory pharyngeal pressure is about 0.3 and 0.8 cmH2O, with open and closed mouth, respectively. Compared to unassisted spontaneous breathing, HFNC generates greater pharyngeal pressure during expiration, while in the course of inspiration it drops to zero, which limits the effectiveness of HFNC in patients with lung edema and/or collapse. By recruiting lung atelectatic regions, reducing venous admixture and decreasing the inspiratory effort, continuous positive airway pressure (CPAP) is likely more effective in these instances. Compared to noninvasive ventilation by application of an inspiratory pressure support, CPAP offers several advantages, which include ease of use and lack of patient-ventilator asynchrony.

CPAP may be applied either through mask or helmet. This latter is better tolerated than facial masks and allows more prolonged continuous CPAP application. When applying CPAP by helmet, however, heating and humidification of the inhaled gas is problematic because of condensation of water inside the interface, so called "fog effect". Moreover, in patients receiving CPAP by helmet some re-breathing occurs.

To overcome these limitations and combine the beneficial effects of HFNC and CPAP, the investigators designed a new device combining HFNC and helmet CPAP.

Recently, this combination was shown to be capable to provide a stable CPAP and effective CO2 washout from the upper airways with negligible CO2 re-breathing. Nonetheless, because of the complex interplay between CPAP and HFNC, the amount of truly applied airway pressure, diaphragm function and temperature inside the helmet might be affected to some extent. In 14 adult healthy volunteers, we found that adding HFNC to CPAP (as referenced to CPAP), 1) did not importantly alter either the pre-set airway pressure during inspiration or temperature inside the helmet; 2) increased expiratory airway pressure proportionally to the flow administered by HFNC, but to a lower extent than HFNC alone (as referenced to spontaneous breathing); 3) determined only slight modifications of the respiratory drive (as assessed through diaphragm ultrasound), compared to CPAP alone, 4) did not cause "fog effect" inside the helmet and 5) did not worsen comfort. We therefore suggested that adding heated humidified air through nasal cannula at a flow of 30 L/min during CPAP would probably be the best setting to be applied in patients with hypoxemic acute respiratory failure.

In patients with hARF, the use of noninvasive respiratory support (CPAP and non-invasive ventilation) is still debated. Patients receiving oxygen therapy, HFNC or CPAP/NIV maintain spontaneous breathing, which allows avoidance of sedation, thus limiting diaphragm dysfunction and delirium, permits easier mobilisation and prevents infections and ICU-acquired weakness. However, the maintenance of spontaneous breathing in patients with damaged lungs and high respiratory drive may result in global/regional pressure/volume changes possibly aggravating initial lung injury. This condition has been defined as patient self-inflicted lung injury (P-SILI). Indeed, respiratory drive is increased in patients with hARF. The high respiratory effort is one of the major determinants of increased transpulmonary pressure (Pl), which is the pressure acting across the lung. Pl represents the pressure alveoli are exposed to, and is considered among the most important determinants of P-SILI. Therefore, the reduction of Pl, across a decrease of the respiratory effort, might be advantageous in patients with hARF.

Investigators have therefore designed this pilot physiologic randomized cross-over study to investigate if, in patients with hARF, HFNC+CPAP reduces the respiratory effort, as compared to HFNC and CPAP (first outcome). Furthermore, we will assess the diaphragm activation, as assessed with ultrasound, gas exchange and patient's comfort among different settings (secondary outcomes).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• presence of hypoxemic Acute Respiratory Failure, as defined by a respiratory rate greater than 25 breaths/min, an acute onset (within 1 week) of respiratory distress, an arterial oxygen tension (PaO2) and inspiratory oxygen fraction (FiO2) ratio (PaO2/FiO2) lower than 200 mmHg during HFNC, an evidence of bilateral pulmonary infiltrates in the chest X-ray or computed tomography scan, and an absence of history of chronic respiratory failure or moderate-to-severe cardiac insufficiency (New York Heart Association greater than grade 2 or left ventricular ejection fraction <50%).

Exclusion Criteria:

• reduced level of consciousness, as indicated by a Glasgow Coma Scale < 12

• severe respiratory distress (i.e. respiratory rate > 35 breaths/min)

• hemodynamic instability, (i.e. systolic arterial pressure <90 mmHg or mean systolic pressure <65 mmHg despite fluid repletion)

• need for vasoactive agents, i.e. vasopressin or epinephrine at any dosage, or norepinephrine >0.3 mcg/kg/min or dobutamine>5 mcg/kg/min

• life-threatening arrhythmias or electrocardiographic signs of ischemia

• acute respiratory failure secondary to neurological disorders, status asthmaticus, chronic obstructive pulmonary disease (COPD), cardiogenic pulmonary oedema

• presence of tracheotomy

• uncontrolled vomiting

• more than 2 acute organ failures

• body mass index >30 kg/m2

• documented history or suspicion of obstructive sleep apnoea

• contraindications to placement of a nasal-gastric feeding tube

• facial anatomy contraindicating helmet or nasal cannula application

• inclusion in other research protocols.

Related Conditions & MeSH terms

• Acute Respiratory Failure
• Respiratory Insufficiency

Intervention

Device:
• High Flow Nasal Cannula (HFNC)
HFNC will be set at 30 L/min, with a temperature at 31° C and 100% of relative humidity
• Continuous Positive Airway Pressure (CPAP)
CPAP will be delivered through a helmet (Castar Next, Intersurgical S.p.A., Mirandola, Italy), with an adjustable Positive End-Expiratory Pressure (PEEP) valve (2.5-20 cmH2O) set at 10 cmH2O (Intersurgical S.p.A., Mirandola, Italy). The helmet will be connected to a turbine-driven ventilator (Monnal T60, Air Liquide Medical Systems, Antony, France) set to deliver oxygen-air admixture at a continuous flow rate of 60 L/min, in order to improve CO2 wash out. No heated humidification will be applied to avoid the "fog effect" in the helmet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

References & Publications (3)

Garofalo E, Bruni A, Pelaia C, Cammarota G, Murabito P, Biamonte E, Abdalla K, Longhini F, Navalesi P. Evaluation of a New Interface Combining High-Flow Nasal Cannula and CPAP. Respir Care. 2019 Oct;64(10):1231-1239. doi: 10.4187/respcare.06871. Epub 2019 — View Citation

Grieco DL, Menga LS, Raggi V, Bongiovanni F, Anzellotti GM, Tanzarella ES, Bocci MG, Mercurio G, Dell'Anna AM, Eleuteri D, Bello G, Maviglia R, Conti G, Maggiore SM, Antonelli M. Physiological Comparison of High-Flow Nasal Cannula and Helmet Noninvasive V — View Citation

Mauri T, Spinelli E, Mariani M, Guzzardella A, Del Prete C, Carlesso E, Tortolani D, Tagliabue P, Pesenti A, Grasselli G. Nasal High Flow Delivered within the Helmet: A New Noninvasive Respiratory Support. Am J Respir Crit Care Med. 2019 Jan 1;199(1):115- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory effort	Inspiratory effort will be assessed as the negative inspiratory swing of the esophageal pressure	After 30 minutes of treatment application
Secondary	Dynamic end-expiratory transpulmonary pressure	Difference between airway pressure and end-expiratory esophageal pressure	After 30 minutes of treatment application
Secondary	Dynamic end-inspiratory transpulmonary pressure	Difference between airway pressure and end-inspiratory esophageal pressure	After 30 minutes of treatment application
Secondary	Dynamic transpulmonary driving pressure	Maximal positive swing in transpulmonary pressure during inspiration	After 30 minutes of treatment application
Secondary	Diaphragm displacement	Diaphragm displacement will be assessed with ultrasound to display the cranio-caudal motion of the diaphragm	After 30 minutes of treatment application
Secondary	Diaphragm thickening fraction	Thickening fraction will be determined with ultrasound in M-mode at end-expiration (Thickexp) and peak inspiration (Thickinsp) as the distance between the diaphragmatic pleura and the peritoneum	After 30 minutes of treatment application
Secondary	Arterial partial pressure of oxygen (PaO2)	Analysis of arterial blood gases	After 30 minutes of treatment application
Secondary	Arterial partial pressure of carbon dioxide (PaCO2)	Analysis of arterial blood gases	After 30 minutes of treatment application
Secondary	Patient's comfort	It will be measured using an 11-point Numeric Rating Scale. Briefly, after detailed explanation before initiating the protocol, patients will be asked to indicate a number between 0 (worst possible comfort) and 10 (no discomfort) on an adapted printed scale.	After 30 minutes of treatment application
Secondary	Patient's Dyspnea	It will be measured using an 11-point Numeric Rating Scale. Briefly, after detailed explanation before initiating the protocol, patients will be asked to indicate a number between 0 (no dyspnoea) and 10 (worst possible dyspnoea) on an adapted printed scale.	After 30 minutes of treatment application