Methods Study design and setting A randomized crossover clinical trial will be conducted
at the University General Hospital of Larissa and Sotiria Thoracic Diseases Hospital of
Athens. The order of therapy will be allocated using sequentially numbered, sealed
envelopes not prepared by the study staff. It is not possible for the researchers or the
patients to be blinded, due to the research design. Patients presenting to the emergency
medicine department of the aforementioned hospitals with acute exacerbation of COPD will
be screened for suitability. Consent to participate in the trial will be obtained from
the patient or next of kin and the study will be conducted according to ICH-GCP and
clinical trial regulations. The results of the study will be presented based on the
CONSORT 2010 statement for randomized crossover trials.
Hypothesis The investigators hypothesize that patients on DUET asymmetric nasal high flow
interface will generate higher external PEEP and will achieve a better clearance of CO2
compared to conventional NHF interface, leading to less inspiratory effort, less work of
breathing and thus in reduction of pCO2 levels.
Study population and interventions Patients considered eligible for the study will be
those (1) presenting to the emergency department with (2) acute exacerbation of COPD
(defined as any worsening of the patient's respiratory symptoms that is beyond normal
day-to-day variations and leads to change in medication) with (3) mild-to-moderate acute
hypercapnic respiratory failure (defined as 7.35>pH>7.25 and arterial CO2 tension (PaCO2)
>45 mmHg).
Patients will be excluded if they meet one or more of the following criteria: acute on
chronic hypercapnic respiratory failure, severe facial deformity, facial burns, fixed
upper airway obstruction and any of the following criteria for imminent intubation and
invasive mechanical ventilation (i.e. respiratory or cardiac arrest, diminished
consciousness (Glasgow coma score <8), psychomotor agitation inadequately controlled by
sedation, massive aspiration, persistent inability to remove respiratory secretions,
severe haemodynamic instability unresponsive to fluids and vasoactive drugs, severe
ventricular or supraventricular arrhythmias and life threatening hypoxaemia).
Fifty patients with acute exacerbation of COPD and mild to moderate hypercapnic
respiratory failure will receive NHF oxygen therapy. Twenty-five patients will be
randomly assigned to first receive NHF oxygen therapy with the largest DUET asymmetric
NHF interface that fits best to the patients' nostrils, followed by medium size
conventional NHF interface. Twenty-five patients will be randomly assigned to receive NHF
oxygen therapy with medium size conventional NHF interface first, followed by the largest
DUET asymmetric NHF interface that fits best to the patients' nostrils. During the study
period, all patients will be studied in a semi-recumbent position and monitoring
equipment will be applied. All patients will receive NHF therapy with the initial setting
of flow at 60 lt/min, temperature at 37°C and FiO2 adjusted to maintain SpO2 between
88-92%. The NHF device and consumables will be the same for all patients (AIRVO 3, Fisher
& Paykel Healthcare Ltd., Auckland, New Zealand).
Patients will receive the first randomized therapy for 3 hours (NHF therapy with DUET or
conventional NHF interface), followed by a 30 min washout period of conventional oxygen
therapy to control for the carry-over effect, after which they will cross over to the
second therapy for 3 hours (NHF therapy with the largest DUET or conventional medium size
NHF interface).
At any study point, if patient discomfort and/or deterioration or lack of improvement of
the abovementioned physiologic variables occur, the researcher-attending physician will
be free to switch the patient to NIV or invasive mechanical ventilation.
Data collection A case report form will be filled for each study participant. Demographic
data including sex, age, weight, height, most recent pulmonary function testing and any
concomitant health problems will be documented. Arterial blood gases (ABGs), vital signs
(systolic and diastolic arterial pressure, heart rate), respiratory variables
(respiratory rate, accessory muscle use, thoracoabdominal asynchrony), dyspnea score
(with the Borg scale) and any pulmonary or extrapulmonary complications will be assessed.
Researchers will also record patient's comfort by assessing the following: machine noise
levels, mouth dryness and general perception of tolerance using a visual analogue scale
from 0 (no inconvenience due to noise, no dryness, no discomfort) to 10 (maximum
inconvenience due to noise, maximum dryness, maximum discomfort).
Pulse oximetry and calibrated transcutaneous CO2 monitoring will be attached and
monitored continuously during the study period. A bio-impedance surface sensor will be
placed and calibrated to measure noninvasively and continuously respiratory rate, tidal
volume and minute ventilation (ExSpiron 2Xi, Respiratory motion, Inc., Waltham,MA).
The abovementioned measurements including ABGs will be collected at baseline, at the end
of first randomized therapy, at the end of the washout period and at the end of the
second therapy.
The cut-off values of the examined physiologic parameters indicating poor outcome with
NHF are SpO2<88% not corrected with supplemental oxygen, respiratory rate >35
breaths·min-1, thoraco-abdominal asynchrony and auxiliary respiratory muscle use,
worsening of hypercapnia and acidaemia, indicating further respiratory muscle fatigue and
sequential organ failure assessment score >4.
