Prospective, randomized, multicenter clinical study on parallel groups involving all
consecutive infants ageing >1 month <2 yrs, admitted to PICU at Fondazione IRCCS Ca'Granda
Ospedale Maggiore Policlinico, Children Hospital V. Buzzi Milan, and at Gemelli Università
Cattolica del Sacro Cuore Rome, for mild to severe acute respiratory failure (ARF). For
screening purposes ARF is defined as the presence of all the following: respiratory rate >50
breaths/min; Partial arterial Oxygen tension/Inspired Oxygen Fraction ratio (PaO2/FiO2) <300,
chest x-ray compatible with clinical diagnosis, no significant clinical improvement after
breathing oxygen at 8 l/min or more for at least 15 min.
Before enrollment patients receive standard medical therapy consisting of oxygen
administration via Venturi mask to achieve a peripheral oxygen saturation (SpO2)> 92% and
medications including aerosolized salbutamol or adrenaline, anticholinergic, steroids,
intravenous antibiotics, correction of electrolytes, and intravascular volume abnormalities
as clinically indicated. Heart rate, systemic arterial blood pressure, respiratory rate, and
SpO2 are continuously monitored. Patients are defined as requiring NCPAP if they deteriorate
despite medical treatment and meet at least one of the following criteria: SpO2<90% with FiO2
> 40%, arterial pH < 7.25, respiratory rate > 50 breaths/min, severe deterioration in mental
status (Glasgow Coma Scale < 10). Eligible patients meeting two or more of the above criteria
are randomly assigned to receive NCPAP either by full-face mask or by helmet. Random
assignment is made by sealed envelopes. Informed consent is obtained from at least one parent
or a legal guardian before the enrollment in the study.
To facilitate tolerance up to a maximum of 2 boluses of midazolam 0.1 mg/kg intravenous can
be administered eventually followed by an intravenous continuous infusion rate, according to
the attending physician's discretion. Once the interface is positioned, a baseline CPAP level
is set at 4 cm H2O and then raised in increments of 2 cm H2O every 20 min up to a maximum of
10 cm H2O to improve respiratory performance as evidenced by oxygen need, respiratory rate
decrease and the reduction of accessory muscles activity. Inspired Oxygen Fraction (FiO2) is
set to achieve a SpO2≥ 92%. NCPAP is administered intermittently for at least 8 hours a day
for the first 48 hours after enrollment, but the daily administration can last longer if well
tolerated or less if either weaning or intubation criteria are achieved. In case of
persistent intolerance to the interface despite sedative administration, the alternate
interface can be used before considering tracheal intubation. For patients with a nasogastric
tube a seal connector in the lower rigid part of the helmet or in the dome of the mask are
used to avoid air leaks. All patients are kept in semirecumbent position.
Criteria for weaning NCPAP can be discontinued if infants show normal mental status, stable
haemodynamics, SpO2>94% in room air and no activation of accessory muscles or paradoxical
abdominal motion.
Criteria for endotracheal intubation The predetermined criteria for endotracheal intubation
NCPAP administration, despite the use of NCPAP, any hemodynamic or electrocardiographic
instability; inability to improve dyspnea, conditions requiring intubation either to protect
the airways or to manage copious tracheal secretions.
End points and definitions The primary outcome variable is the rate of treatment failure in
each group. Treatment failure is defined as infants either shifted to the alternate interface
because of intolerance or tracheally intubated because of gas exchange deterioration. A
successful treatment is defined as the ability to administer NCPAP for at least 8 hours a day
for the first 24 hours and to avoid tracheal intubation in the first 48 hours. Secondary
end-points included: gas exchange improvement, complications not present on admission, length
of the stay and mortality in PICU.
Arterial partial oxygen and carbon dioxide tension, arterial pH, respiratory rate, heart rate
and systolic arterial blood pressure are evaluated at 2, 24 and 48 hours after enrollment.
Early improvement in oxygenation is defined as an increase in PaO2/FiO2 > 20% above baseline;
sustained improvement is defined as the ability to maintain increase in oxygenation at 24
hours after enrollment.
At the same time intervals Objective Pain Scale (OPS), an index of patient intolerance to the
interface and Respiratory Effort Score (RES), an index of respiratory muscles activity, are
recorded. Intolerance to the NCPAP treatments defined as an increment in OPS>4. In the first
24 hours the total amount of sedation and the total duration of NCPAP administration are also
recorded.