Pilot Study of Physiological Effect of High-Flow Nasal Cannula on Respiratory Pattern and Work of Breathing

NCT02514798 | Completed

• 1 other identifier: IRB-11570
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Patients affected with severe parenchymal pulmonary diseases, such as Chronic Obstructive Pulmonary Disease (COPD ), may experience dyspnea at rest due to increased work of breathing and reduced oxygenation. The delivery of high-flow humidified nasal oxygen (HFNC) has been shown to have a positive-end-expiratory pressure (PEEP) effect and is able to flush out CO2 from the upper airways, reducing dead space ventilation. Furthermore it has been proven to reduce the respiratory rate shortly after its initiation. These multiple actions offer the potential of changing the respiratory pattern and reducing work of breathing, improving the efficiency of breathing. In this short-term, physiological, open, randomized, cross-over pilot study the investigator swill describe the effects of varying settings of high-flow nasal oxygen on respiratory rate, tidal volume, and diaphragmatic work of breathing in patients with severe COPD. The investigators will also describe changes in gas exchange and effects on the subjects' comfort and dyspnea and the breathing responses to varying setting of CPAP in the subject population.

Conditions

COPD

Keywords

COPD; HFNC; work of breathing

Outcome Measures

Primary Outcomes (3)

• respiratory rate

  respiratory rate (RR) will be determined using a Respiratory Inductive Plethysmography (RIP) system. This will measure the thoracic and abdominal excursion of the subjects via two inductive wires which are sewn into the elastic bands that encircle the thorax and abdomen. The acquired signals represent changes in cross-sectional area and, following calibration to determine the relative contribution of each signal, and volume calibration using spirometry, their weighted sum will reflect VTi. The RIP companion software will be used to derive RR. It will be expressed as breaths per minute

  90 minutes

• tidal volume

  Inspiratory tidal volume (VTi) will be determined using a Respiratory Inductive Plethysmography (RIP) system. This will measure the thoracic and abdominal excursion of the subjects via two inductive wires which are sewn into the elastic bands that encircle the thorax and abdomen. The acquired signals represent changes in cross-sectional area and, following calibration to determine the relative contribution of each signal, and volume calibration using spirometry, their weighted sum will reflect VTi (mL).

  90 minutes

• diaphragmatic work of breathing

  Esophageal and gastric pressures will be measured with an esophageal ballon positioned at the lower third of the esophagus, filled with 0.5 mL of air and a gastric balloon filled with 1 mL of air. Transdiaphragmatic pressure (Pdi) is calculated as the difference between gastric (Pga) and esophageal (Pes) pressure. The pressure time integrals of the diaphragm and the other inspiratory muscles are calculated per breath (PTPdi/b and PTPes/b, respectively) and per minute (PTPdi/min and PTPes/min). Measurements will be collected at baseline, at each randomized HFNC and CPAP settings during the last 4 minutes of each 10 minutes session.

  90 minutes

Secondary Outcomes (3)

• changes in gas exchange

  90 minutes

• effects on the subjects' comfort

  90 minutes

• effects on the subjects' dyspnea

  90 minutes

Study Arms (2)

High-flow humidified nasal oxygen delivery system

EXPERIMENTAL

We will describe effects of varying settings of high-flow nasal oxygen (10-30-45-60 L/min) on respiratory rate, tidal volume, and diaphragmatic work of breathing in patients with severe COPD. We will also describe changes in gas exchange and effects on the subjects' comfort and dyspnea. This will be measured using, esophageal and gastric balloons, respiratory inductance plethysmography (RIP) system, and Sentec transcutaneous monitoring system.

Other: Esophageal and gastric balloons; Other: Respiratory Inductance Plethysmography (RIP) system; Other: Sentec transcutaneous monitoring system; Device: High-flow humidified nasal oxygen delivery system

CPAP (Positive Control)

ACTIVE COMPARATOR

We want to describe the breathing responses to varying setting of CPAP in the subject population. We plan to use the CPAP response as a "positive control", to determine if our population responds as described by CPAP studies in the literature. This will be measured using, esophageal and gastric balloons, respiratory inductance plethysmography (RIP) system, and Sentec transcutaneous monitoring system.

Other: Esophageal and gastric balloons; Other: Respiratory Inductance Plethysmography (RIP) system; Other: Sentec transcutaneous monitoring system; Device: CPAP (Positive Control)

Interventions

Esophageal and gastric balloons OTHER

Esophageal and gastric pressures will be measured with an esophageal ballon positioned at the lower third of the esophagus, filled with 0.5 mL of air and a gastric balloon filled with 1 mL of air. The proper position of balloons will be verified using the occlusion test as previously described. Transdiaphragmatic pressure (Pdi) is calculated as the difference between gastric (Pga) and esophageal (Pes) pressure. The pressure time integrals of the diaphragm and the other inspiratory muscles are calculated per breath (PTPdi/b and PTPes/b, respectively) and per minute (PTPdi/min and PTPes/min). Measurements will be collected at baseline, at each randomized HFNC and CPAP settings during the last 4 minutes of each 10 minutes session.

CPAP (Positive Control); High-flow humidified nasal oxygen delivery system

Respiratory Inductance Plethysmography (RIP) system OTHER

Inspiratory tidal volume (VTi), respiratory rate (RR), breath duration (Ttot), inspiratory time (Ti) and fractional inspiratory time (Ti/Ttot) will be determined using a Respiratory Inductive Plethysmography (RIP) system. This will measure the thoracic and abdominal excursion of the subjects via two inductive wires which are sewn into the elastic bands that encircle the thorax and abdomen. The acquired signals represent changes in cross-sectional area and, following calibration to determine the relative contribution of each signal, and volume calibration using spirometry, their weighted sum will reflect VTi. The RIP companion software will be used to derive RR, Ttot, Ti and Ti/Ttot on a breath by breath basis.

CPAP (Positive Control); High-flow humidified nasal oxygen delivery system

Sentec transcutaneous monitoring system OTHER

The oxygenation, the level of carbon dioxide, and the heart rate will be recorded using the Sentec transcutaneous monitoring system: a probe will be placed at the earlobe or on the forehead, and it will measure in a noninvasive way these parameters.

CPAP (Positive Control); High-flow humidified nasal oxygen delivery system

High-flow humidified nasal oxygen delivery system DEVICE

High-flow humidified nasal oxygen delivery system

CPAP (Positive Control) DEVICE

Also known as: Continuous Positive Airway Pressure

CPAP (Positive Control)

Eligibility Criteria

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

You may qualify if:

• Subjects are 18 or more years of age
• Chronic respiratory failure, defined as indication for long-term oxygen therapy
• Underlying diagnosis of severe COPD (GOLD stage III or IV)

You may not qualify if:

• Recent (\<1 month) exacerbation Acute exacerbation is defined as a sudden worsening of COPD symptoms (shortness of breath, quantity and color of phlegm) requiring a change in the baseline therapy.
• Respiratory rate at rest \>28/min
• Subject requires \> 6 L/min nasal O2 to maintain SpO2 \>88% at rest
• Subject has severe dyspnea at rest
• Subject has swallowing disorder or chronic aspiration
• Prior esophageal surgery, known esophageal stricture or any other condition that would place the subject at risk during balloon placement
• Recent (\< 1 month) abdominal and thoracic surgery
• Severe coagulopathy (defined as platelet count \<5000/μL or international normalised ratio \>4)
• Subject is too cognitively impaired to give subjective ratings for visual analogue scale.The PI and the Co-Investigators will assess the patient cognition using the Mini Mental State Examination (MMSE)
• Allergy or sensitivity to lidocaine
• Inability to obtain informed consent
• Pregnancy and breastfeeding

Sponsors & Collaborators

• Tufts Medical Center: lead
• Fisher and Paykel Healthcare: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02116, United States

Location

Related Publications (10)

• Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir Med. 2009 Oct;103(10):1400-5. doi: 10.1016/j.rmed.2009.04.007. Epub 2009 May 21.

  PMID: 19467849 BACKGROUND

• Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive airway pressure. Br J Anaesth. 2009 Dec;103(6):886-90. doi: 10.1093/bja/aep280. Epub 2009 Oct 20.

  PMID: 19846404 BACKGROUND

• Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011 Dec;107(6):998-1004. doi: 10.1093/bja/aer265. Epub 2011 Sep 9.

  PMID: 21908497 BACKGROUND

• El-Khatib MF. High-flow nasal cannula oxygen therapy during hypoxemic respiratory failure. Respir Care. 2012 Oct;57(10):1696-8. doi: 10.4187/respcare.02072. No abstract available.

  PMID: 23013907 BACKGROUND

• Sztrymf B, Messika J, Bertrand F, Hurel D, Leon R, Dreyfuss D, Ricard JD. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011 Nov;37(11):1780-6. doi: 10.1007/s00134-011-2354-6. Epub 2011 Sep 27.

  PMID: 21946925 BACKGROUND

• Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010 Apr;55(4):408-13.

  PMID: 20406507 BACKGROUND

• Mundel T, Feng S, Tatkov S, Schneider H. Mechanisms of nasal high flow on ventilation during wakefulness and sleep. J Appl Physiol (1985). 2013 Apr;114(8):1058-65. doi: 10.1152/japplphysiol.01308.2012. Epub 2013 Feb 14.

  PMID: 23412897 BACKGROUND

• Braunlich J, Beyer D, Mai D, Hammerschmidt S, Seyfarth HJ, Wirtz H. Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients. Respiration. 2013;85(4):319-25. doi: 10.1159/000342027. Epub 2012 Nov 1.

  PMID: 23128844 BACKGROUND

• Prinianakis G, Delmastro M, Carlucci A, Ceriana P, Nava S. Effect of varying the pressurisation rate during noninvasive pressure support ventilation. Eur Respir J. 2004 Feb;23(2):314-20. doi: 10.1183/09031936.03.00010203.

  PMID: 14979510 BACKGROUND

• Vitacca M, Ambrosino N, Clini E, Porta R, Rampulla C, Lanini B, Nava S. Physiological response to pressure support ventilation delivered before and after extubation in patients not capable of totally spontaneous autonomous breathing. Am J Respir Crit Care Med. 2001 Aug 15;164(4):638-41. doi: 10.1164/ajrccm.164.4.2010046.

  PMID: 11520729 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Gastric Balloon; Drug Delivery Systems; Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Equipment and Supplies; Drug Therapy; Therapeutics; Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Respiratory Therapy

Study Officials

• Nicholas S Hill, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 4, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: April 1, 2018
• Last Updated: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)