Asymmetric (DUET) Versus Conventional Nasal High Flow Interface for Management of Hypercapnic Patients With Mild to Moderate Acute Exacerbation of COPD: A Randomized, Crossover Clinical Trial

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).