Noninvasive Continuous Positive Airway Pressure (NCPAP) in Children
Condition: Acute Respiratory Failure
MeSH terms: Respiratory Insufficiency
Study type: Interventional
Phase: Phase 3

Summary: 
      In critically ill pediatric patients with Acute Respiratory Failure (ARF), Noninvasive
      Continuous Positive Airway Pressure (NCPAP) is applied to avoid intubation and all related
      complications such as tracheal injury and predisposition to nosocomial pulmonary infections.
      The choice of the interface is one of the crucial issues affecting treatment outcome in
      pediatric age and in particular in preschool children in whom intolerance frequently
      compromise noninvasive respiratory treatment. NCPAP is applied either through nasal or facial
      tight fitting masks and the most important principle in guiding the selection of an interface
      is that it should fit comfortably. However, while nasal mask can leak gas when the infant
      opens his/her mouth, facial mask can cause significant gastric distension and vomiting, with
      risk of aspirating gastric contents. Moreover, complications such as air leaks, skin
      irritation on the bridge of the nose, and discomfort reported with nasal or facial masks in
      children frequently lead to interruption of the respiratory treatment. Thus, improving the
      interface between the patient and the ventilator would be expected to facilitate longer and
      more effective application of NCPAP.

      A new small helmet specifically designed for young infants has been recently introduced to
      administer NCPAP. In a recent short term crossover physiological randomized controlled trial,
      the investigators found that NCPAP by helmet was associated with enhanced feasibility, less
      need of sedation and prolonged application time (see references below). The purpose of this
      prospective randomized multicenter study is to compare the efficacy and feasibility of NCPAP
      delivered either by helmet or by facial mask to treat acute respiratory failure in infants
      admitted to Pediatric Intensive Care Unit (PICU).
    

Detailed description: 
      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.
    

Intervention name(s): NCPAP by helmet; NCPAP by facial mask
Intervention type(s): Device; Device
Intervention description(s): The infant helmet (Castar Starmed© Mirandola, Italy) is secured to a soft collar that adheres to the child's neck and is connected to a high flow NCPAP circuit (high fresh gas flow >40 L/min to avoid carbon dioxide rebreathing). To facilitate tolerance up to a maximum of 2 boluses of midazolam 0.1 mg/kg i.v. can be administered eventually followed by an i.v. continuous infusion rate according to OPS scale. Once the interface is positioned, a baseline Continuous Positive Airway Pressure (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. FiO2 is set to achieve a SpO2 ≥ 92%. If intolerance persisted despite sedative administration, the alternate interface can be used before considering tracheal intubation. All patients are kept in semirecumbent position.; The size of NCPAP full face or nasal masks are chosen to be more comfortable for the infants (Respironics, Murrysville). The masks are secured by head straps while avoiding a tight fit and air leaks. A protective hydrocolloid sheet was applied over the nasal bridge (DuoDERM, ConvaTec, Deeside, UK). After a short adaptation period, it is firmly applied on the face by a pediatric head cap (Respironics, Murrysville ) to minimize air leaks. The mask is then connected to the same circuit previously described for helmet NCPAP.
Other intervention name(s): Noninvasive Continuous Positive Airway Pressure by helmet; Noninvasive Continuous Positive Airway Pressure by mask
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Acute Respiratory Failure; Continuous Positive Airway Pressure; Infants; Helmet