Pilot Study of High-flow Humidified Nasal Oxygen During Breaks From Noninvasive Ventilation

Background: Noninvasive ventilation (NIV) provides respiratory support to many patients
affected by acute respiratory failure. This treatment, compared to invasive mechanical
ventilation, allows patients to take intermittent breaks during which oxygen therapy is
provided through a nasal cannula or mask. During these breaks, the lack of ventilator
support may predispose to respiratory distress, retention of CO2 and oxygen desaturation.
Optiflow is a nasal humidified (37◦C, 44mg/L H2O) high-flow (up to 60 L/min) therapy which
can provide greater support than standard oxygen therapy during the breaks from NIV.

Aim of the study is to evaluate Optiflow as an alternative to standard oxygen therapy during
breaks from NIV in patients with acute respiratory failure. The investigators hypothesize
tha Optiflow will reduce the total length of stay on NIV, and increase the comfort and
length of the breaks. Also, the investigators anticipate that it will reduce respiratory
rate, accessory muscle use and dyspnea score compared to standard oxygen therapy.

Experimental design Prospective open-label, parallel, randomized (1:1) controlled study,
with a target enrollment of 70.

Study procedures Enrolled patients receiving NIV will be randomized into two arms; a
treatment group which will receive Optiflow during breaks and a control arm which will
receive standard oxygen therapy during breaks. In both cases, FiO2 will be titrated to
maintain oxygen saturation above 90%. The necessity of breaks will be determined together
with the patients (talk, eat, medication, communicate with family, inability to tolerate the
interface), and the need to resume NIV will be based on clinical data, such as dyspnea,
respiratory rate, heart rate, blood pressure, oxygen saturation, transcutaneous carbon
dioxide (CO2) and patients' desire.

Recorded data: The investigators will record demographic baseline data; Glasgow Coma Scale,
respiratory and heart rate, blood pressure, dyspnea score, accessory muscle use, and comfort
score at randomization, at the end of each NIV session and NIV break; the length of each NIV
session and break; the medications administered and all the arterial blood gases (ABG) on a
daily basis. Moreover the investigators will record the NIV parameters and inspired oxygen
fraction (FiO2) at each session and break.

Risks: The investigators don't anticipate any significant risks related to the study
procedures and equipment. Some patients may not tolerate the Optiflow and some patients may
fail NIV and require intubation.

Inclusion Criteria:

- Patients of 18 or more years of age treated with Bipap or CPAP as per hospital
protocol, with an underlying clinical diagnosis of acute respiratory failure.

- Patients that, prior to administration of NIV, had persistent respiratory acidosis
with a pH <7.35 and arterial CO2 > 45 mmHg despite controlled oxygen therapy and
standard medical management i.e. bronchodilators, corticosteroids and antibiotics, or

- Patients with hypoxemic respiratory failure with a PaO2/FiO2 ratio < 300 and
respiratory rate ≥ 24.

- Anticipated duration on NIV of at least 24 hrs

Exclusion criteria:

- Usual contraindications to NIV

- Respiratory arrest

- Unable to fit mask

- Medically unstable or multiple organ failure or unstable coronary disease

- Agitated or uncooperative

- Unable to protect airways

- Swallowing difficulties

- Excessive secretions not managed by clearance techniques

- Recent upper airway or gastro-intestinal surgery

- Facial deformity or previous head and neck surgery

- Undrained pneumothorax

- NIV failure within first 2 hours (either intolerance or requirement for intubation)

- Managed for greater than 48 hours on NIV prior to randomization

- Disorientation, confusion, unable to rate comfort or dyspnea

- Expected to require NIV for fewer than 24 hrs from the time of enrollment

- Patient previously in study

- Patients on CPAP nighttime only due to OSA

Withdrawal/Termination criteria:

- Patients will be withdrawn from the study when NIV fails and/or the patient is
intubated.