Please select the eligibility criteria that correspond to the clinical trial below.
Title: Use of Bubble CPAP Compared to Nasal Prong Oxygen or Humidified High Flow in Children Under Five With Severe Pneumonia and Hypoxaemia: a Randomized Trial
Brief Summary: Continuous Positive Airway Pressure (CPAP) is a common form of support for patients admitted to Intensive Care Units (ICUs) of industrialized countries with respiratory distress (1). Nasal CPAP (NCPAP) is effective in correcting hypoxemia and contributes to reducing the number of children requiring endo-tracheal intubation and mechanical ventilation (2). CPAP is most frequently delivered to neonates using conventional mechanical ventilators, and thus there is minimal or no cost saving. There are other ways of delivering CPAP, such as Bubble-CPAP, which requires a source of gas flow (typically 6-8 L/ minute in a neonate), an air-oxygen blender, a humidifier and a T-piece.(3). The expiratory arm is inserted in a bottle of water and the level of CPAP delivered is equivalent to the length of the expiratory tubing that remains under water. Robust equipment is now available at a fraction of the cost of mechanical ventilators. Bubble-CPAP has potential advantages over the mechanical ventilation, such as lower cost, ease of application by nursing staff, lower risk of complications, and has been proposed as an inexpensive method of delivering CPAP in developing countries (3).

High flow air/oxygen mix is useful in reducing the indication of mechanical ventilation (4); however, there is a lack of randomized studies comparing it with bubble CPAP or with standard flow O2 supplementation by nasal prongs. High flow air/oxygen mix uses flows of 2 litre per kg per minute of blended air/oxygen mix, usually with a low fraction of inspired oxygen (say 25-40%). It is easy to apply, but requires additional equipment to standard oxygen therapy, and closer monitoring. "High flow" delivers uncertain levels of CPAP, so it is not clearly superior to bubble-CPAP, and there have been no controlled comparative trials of these two techniques.

Pneumonia and malnutrition are two of the most common co-morbidities in children in developing countries (5). In hospitals in resource-poor settings, children with severe malnutrition and pneumonia often present with respiratory distress with or without severe hypoxaemia and impending respiratory failure (6). They initially receive O2 supplementation through nasal prong or face mask. Support from bubble CPAP might help to effectively treat hypoxaemia, improve respiratory function, avoid the need for mechanical ventilation and its complications, and reduce mortality.

Almost half of the patients admitted in the intensive care unit of the Dhaka hospital of ICDDR,B present with hypoxaemia, many with impending respiratory failure. Children with pneumonia also invariably have severe malnutrition with or without diarrhoea (Chisti MJ, MMed thesis, unpublished data). They often need mechanical ventilation, with attendant costs, complications and high mortality rates. However, no published data are available about the use of bubble-CPAP in children with pneumonia and malnutrition and there have been no controlled trials of CPAP in developing countries.

The Hypothesis is:

In children with severe pneumonia and hypoxaemia the probability of treatment failure (see definition below) will be significantly lower when respiratory support is initially provided by bubble-CPAP or high-flow, humidified air/O2 mix by nasal prongs, compared to standard oxygen flow.


Options:
A: Inclusion Criteria:

* Children aged 6 months or less
* Moderate (Respiratory Distress Assessment Instrument score of 4 or greater) viral bronchiolitis (as defined by McConnockie)
* Meeting Admission criteria

Exclusion Criteria:

* History of prematurity
* Chronic lung disease
* Cystic fibrosis
* Congenital heart disease
* Neuromuscular disease
* Airway anomalies
* Immunodeficiency
* Those requiring immediate intubation and ventilation.
B: Inclusion Criteria:

Children of either sex, aged 0-4 years, with severe/very severe pneumonia (per WHO guidelines) and hypoxaemia (SpO2 \< 90%) will be included in our study in the ARI Unit of the Longer Stay Ward (LSW), High Dependency Unit HDU, and ICU unit of Dhaka Hospital of ICDDR,B.

Exclusion Criteria:

Children with uncorrected cyanotic CHD, hypercapnoea (PCO2 \> 65 mm of Hg), status asthmaticus and upper-airway obstruction, and those for whom inform consent can't be secured from their parents/ care-givers. Children with features (any two of three criteria given below) of "treatment failure" on admission (before enrollment into the study) will also be excluded from the study. Arterial blood gas analysis will be performed to check the exclusion criteria
C: Inclusion Criteria:

Eligible patients will fall into one of two groups:

Group A (Step-up)

1. Age \>36 weeks corrected gestational age and \<16 years, AND
2. Deemed to require non-invasive respiratory support by the treating clinician for an acute illness, AND
3. Satisfies one or more of the following criteria:

   * Hypoxia (oxygen saturation \<92% in fraction of inspired oxygen (FiO2) \>0.40, or equivalent). FiO2 of 0.40 roughly equates to standard unhumidified nasal cannula oxygen delivered at 6 L/min or oxygen delivered via facemask without a rebreather bag at 6-10 L/min.
   * Acute respiratory acidosis (pH \<7.3 with a concomitant pCO2 \>6.5 kPa)
   * Moderate respiratory distress (use of accessory muscles, subcostal and intercostal recession, tachypnoea for age, grunting)

Group B (Step-down)

1. Age \>36 weeks corrected for gestation and \<16 years, AND
2. Deemed to require non-invasive respiratory support by the treating clinician after extubation, following a spell of invasive ventilation

   * Either immediately after extubation as a 'planned' procedure, irrespective of clinical condition ('planned') OR
   * Prompted by deterioration in clinical condition within 72 hours after extubation ('rescue'). Clinical parameters to assess the need for NRS in this situation will be similar to point 3 in Group A.

Exclusion Criteria:

1. Deemed by the treating clinician to require immediate intubation/invasive ventilation due to severe hypoxia, acidosis and/or respiratory distress, upper airway obstruction or recurrent apnoeas
2. Tracheostomy in place
3. Pre-existing air-leak syndrome (pneumothorax/pneumomediastinum)
4. Midfacial/craniofacial anomalies (unrepaired cleft palate, choanal atresia) or had recent craniofacial surgery
5. Agreed limitation of intensive care treatment plan in place ('not for intubation')
6. On domiciliary non-invasive ventilation prior to PICU admission
7. Managed on either HFNC and/or CPAP (or other form of non-invasive ventilation such as BiPAP) in the preceding 24 hours
8. Previously recruited to this study during the same PICU admission
9. Cannot be treated with HFNC

   * Unavailability of appropriate sized nasal prongs
   * Unavailability of HFNC device
10. Cannot be treated with CPAP

    * Unavailability of right size of face mask, prong or other patient interface
    * Unavailability of CPAP device
D: Inclusion Criteria:

* Clinical diagnosis of bronchiolitis defined as the first viral episode of respiratory distress before 2 years of aging, presenting with rhinitis, tachypnea, cough, wheezing, prolonged expiratory time, crackles and use of accessory muscles, with or without fever, with or without infiltrate on the chest X ray
* bronchiolitis severity Wang modified score ≥ 10

Exclusion Criteria:

* recurrent wheezing
* heart disease
* chronic lung disease
* neuromuscular disease
* primary diagnosis was not bronchiolitis (pneumonia, pertussis)
* critically ill infants who had an immediate need of intubation

Answer: B