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.
