Adaptive Non-invasive Ventilation to Abolish Tidal Flow Limitation

Non-invasive Ventilation With Automatic Expiratory Positive Airway Pressure Titration to Abolish Tidal Expiratory Flow Limitation in COPD Patients With Chronic Hypercapnia

This study aimed to evaluate the effects of a novel automatic non-invasive ventilation (NIV) mode that continuously adjusts expiratory positive airway pressure (EPAP) to the lowest value that abolishes tidal expiratory flow limitation. The investigators conducted a prospective, randomized, cross-over study on stable chronic obstructive pulmonary disease (COPD) patients. Patients were studied in the hospital during two non-consecutive nights while using either fixed or adaptive EPAP. The primary outcome was the transcutaneous partial pressure of carbon dioxide. Secondary outcomes were: oxygen saturation, breathing pattern, oscillatory mechanics, patient-ventilation asynchronies, sleep quality and sleep-related respiratory events.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive; Ventilator Lung; Hypercapnia
• Intervention / Treatment: Device: fixed-EPAP; Device: auto-EPAP

Detailed Description

Study design: prospective, randomized, cross-over study. Study population: moderate to severe COPD patients, long-term users of nocturnal non-invasive ventilation for chronic hypercapnic respiratory failure. Inclusion criteria: age<85 years; presence of tidal expiratory flow limitation in the supine position at an expiratory positive airway pressure of 4 cmH2O. Exclusion criteria: COPD exacerbation within the past two months; acute illness; clinical instability.

Study protocol: Patients were studied in the hospital over 2 non-consecutive nights while using either fixed or automatic EPAP.

Ventilation strategy: pressure-controlled NIV was delivered using a non-commercial version of BiPAP Synchrony Ventilator (Philips-Respironics) via an unvented facial mask (AMARA, Philips-Respironics). The ventilator evaluated the presence of tidal expiratory flow limitation by the forced oscillation technique. In the automatic-EPAP mode, the ventilator continuously adjusted EPAP to the minimum level able to abolish tidal expiratory flow limitation, with a minimum EPAP of 4 cmH2O and keeping the pressure support constant.

Measurements: During each study night, the investigators recorded transcutaneous partial pressure of carbon dioxide and oxygen saturation (TOSCA, Radiometer) continuously. Airway opening pressure, flow and volume tracings were exported from the ventilator. Full laboratory polysomnography (Alice5, Philips-Respironics) was performed according to the American Academy of Sleep Medicine recommendations.

Data analysis: the investigators compared parameters from the two nights using Wilcoxon signed-rank test. P-values <0.05 were considered statistically significant.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BS
    • Lumezzane, BS, Italy
      • Divisione di Pneumologia, Fondazione S. Maugeri, IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• moderate to severe COPD (GOLD 2017);
• long-term users of nocturnal non-invasive ventilation for chronic hypercapnic respiratory failure;
• presence of tidal expiratory flow limitation in the supine position at an expiratory positive airway pressure of 4 cmH2O.

Exclusion Criteria:

• COPD exacerbation within the past two months;
• acute illness;
• clinical instability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fixed-EPAP; EPAP was kept fixed at the prescribed level throughout the night	Device: fixed-EPAP; In the fixed-EPAP mode, the device kept EPAP fixed at the prescribed value
Experimental: Auto-EPAP; EPAP was continuously adjusted using the experimental approach aimed at abolishing tidal expiratory flow limitation	Device: auto-EPAP; In the Auto-EPAP mode, the device automatically adjusted EPAP to the minimum level able to abolish tidal expiratory flow limitation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean transcutaneous partial pressure of carbon dioxide (PtcCO2)	The partial pressure of carbon dioxide measures the efficacy of ventilation. Reducing PCO2 is the aim of nocturnal non-invasive ventilation in stable COPD patients with chronic hypercapnia. PCO2 is normally measured non-invasively using a transcutaneous probe during overnight studies.	Overnight (about 8 hours)
Percent of night time spent in hypercapnia	Hypercapnia is defined as PtcCO2 > 45 mm Hg. The aim of non-invasive ventilation in stable COPD patients is to reduce the time spent with PCO2 levels above the physiological range.	Overnight (about 8 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean peripheral oxygen saturation (SpO2)	Peripheral oxygen saturation in a non-invasive measure of oxygenation, which is routinely evaluated in sleep and ventilation trials.	Through study completion, an average of 8 hours
Desaturation	Desaturations are common complications in respiratory disorders. A desaturation is commonly defined by a reduction in SpO2 < 90%. The investigators computed the percent of night time in which SpO2 was < 90% and the Oxygen Desaturation Index (number of desaturations per hour).	Through study completion, an average of 8 hours
Number of ineffective efforts per hour (IE)	Ineffective efforts are defined as inspiratory efforts that are not supported by the ventilator. They are indicative of patient-ventilator asynchrony, they may be associated with tidal expiratory flow limitation and they increase work of breathing and cause discomfort.	Through study completion, an average of 8 hours
Sleep quality	Sleep quality is a key outcome during overnight studies. Nocturnal non-invasive ventilation may affect sleep quality in two ways: 1) it may improve it by reducing sleep-related respiratory problems; 2) it may worsen it if the ventilation mode causes discomfort to the patient. Sleep quality was evaluated by full laboratory polysomnography. Sleep stages were identified on epochs lasting 30 seconds by a trained operator blind to the study arms. Sleep quality was quantified using the following parameters: Sleep efficiency (percent of night time asleep), percentage of sleep time spent in phase 3 sleep and in REM sleep, number of awakenings per hour.	Through study completion, an average of 8 hours
EPAP	The expiratory positive airway pressure (EPAP) is the parameter that is adjusted in the experimental arm. The ventilator automatically titrates EPAP to the minimum value able to abolish expiratory flow limitation.	Through study completion, an average of 8 hours
Breathing pattern	Tidal volume, respiratory rate, minute ventilation, and inspiratory to expiratory time ratio are the breathing pattern parameters that the respiratory control system adjusts to achieve an adequate gas exchange while minimizing work of breathing. Non-invasive ventilation interacts with and supports breathing pattern.	Through study completion, an average of 8 hours
Difference between mean inspiratory and expiatory reactance	The difference between mean inspiratory and expiatory reactance is measured using the forced oscillation technique. The difference between mean inspiratory and expiratory reactance is an index of tidal expiratory flow limitation. Values > 2.8 cmH2O*s/L are indicative of tidal expiratory flow limitation.	Through study completion, an average of 8 hours
Mean inspiratory resistance	Mean inspiratory resistance is measured using the forced oscillation technique. Inspiratory resistance is an index of airway obstruction, which increases work of breathing and contributes to the development of flow limitation.	Through study completion, an average of 8 hours
Mean inspiratory reactance	Mean inspiratory reactance is measured using the forced oscillation technique.	Through study completion, an average of 8 hours
Sleep related respiratory event	During full laboratory polysomnography the respiratory activity is monitored and sleep related respiratory events are analysed, such as apneas, hypopnea, with a breakdown into central, peripheral or mixed events.	Through study completion, an average of 8 hours

Collaborators and Investigators

• Sponsor: Politecnico di Milano
• Collaborators: Philips Healthcare; Istituti Clinici Scientifici Maugeri SpA
• Investigators: Principal Investigator: Raffaele L Dellacà, Prof., Politecnico di Milano

Publications and helpful links

General Publications

• Milesi I, Porta R, Barbano L, Cacciatore S, Vitacca M, Dellaca RL. Automatic tailoring of the lowest PEEP to abolish tidal expiratory flow limitation in seated and supine COPD patients. Respir Med. 2019 Aug;155:13-18. doi: 10.1016/j.rmed.2019.06.022. Epub 2019 Jun 23.
• Zannin E, Milesi I, Porta R, Cacciatore S, Barbano L, Trentin R, Fanfulla F, Vitacca M, Dellaca RL. Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study. Respir Res. 2020 Nov 18;21(1):301. doi: 10.1186/s12931-020-01567-x.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2014
• Primary Completion (Actual): May 15, 2018
• Study Completion (Actual): May 15, 2018

Study Registration Dates

• First Submitted: July 25, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 4, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypercapnia
• Other Study ID Numbers: Polimi

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No