NAVA in Infants With Acute Viral Bronchiolitis: A Feasibility Study
Condition: Acute Viral Bronchiolitis
MeSH terms: Bronchiolitis; Bronchiolitis, Viral
Study type: Interventional

Summary: 
      This exploratory intervention feasibility study aims to evaluate the use of a novel mode of
      ventilation known as Neurally adjusted ventilatory assist (NAVA) in infants with acute viral
      bronchiolitis.

      The main aims are:

        1. To determine whether an optimal combination of NAVA support level and Positive End
           Expiratory Pressure (PEEP) exists that can:

             1. maximise aspects of respiratory muscle unloading and

             2. minimize air trapping

        2. To evaluate the impact of two morphine infusion doses on comfort levels and respiratory
           drive (standard = 20mcg/kg/hr, low = 5mcg/kg/hr) during ventilation titration.

      Patients will act as their own control and will be randomly allocated to receive either
      standard or low dose morphine. They will receive the alternate dose on day 2. During each
      period of morphine dosing ventilation levels will be titrated and vital signs, respiratory
      parameters and comfort b scales will be recorded.
    

Detailed description: 
      This study is a Randomised, non-blinded, crossover (morphine dose), mode of ventilation
      feasibility study to evaluate the use of NAVA in infants with acute viral bronchiolitis.

      Background and study aims:

      This study aims to evaluate a novel mode of mechanical ventilation (breathing machine),
      Neurally Adjusted Ventilatory Assist (NAVA), in infants admitted to the paediatric intensive
      care unit (PICU) with acute viral bronchiolitis. This respiratory illness accounts for 12% of
      PICU admissions nationally. Current modes of ventilation are inefficient, often requiring
      prolonged use of sedative drugs for comfort and to improve ease of ventilation
      (synchronicity). Consequences of prolonged sedative use are muscle wastage including the
      respiratory muscles, increased risk of developing secondary infections and the potential for
      withdrawal from medication symptoms.

      NAVA is a mode of ventilation that is delivered using our current ventilators (breathing
      machines). However, it differs from current modes by providing respiratory support in
      proportion to the signal from the brain to move the diaphragm, this is achieved via
      measurement of electrical activity of the diaphragm (the main muscle used to initiate a
      breath). This is measured by using a modified version of the patients' feeding tube (which is
      used in PICU to feed patients whilst on a ventilator).

      Research in children to date has demonstrated that NAVA, compared to other ventilatory modes,
      allows for improved ventilator synchrony, reduced work of breathing and potentially less
      sedative use. This is consistent with our clinical impression (we have been using NAVA in an
      ad hoc way for >5 years). Although some of these studies included infants with bronchiolitis,
      the findings were not specific to this patient group. Of note, we do not yet know how to
      optimise NAVA settings in bronchiolitis, and whether current common sedative drugs (e.g.
      morphine) affect this, by decreasing respiratory drive excessively (potentially compromising
      NAVA utility).

      We will evaluate how to optimise NAVA settings when compared to conventional ventilation in
      infants with acute viral bronchiolitis admitted to PICU. A range of NAVA settings will be
      systematically evaluated over two periods on consecutive days (maximum 4 hours per period per
      day). Observation of the effects of different levels of NAVA support on synchronicity, work
      of breathing and changes in physiological parameters will take place. Patients will also
      receive 2 different adjustments to their morphine infusions in random order on the
      consecutive days: standard dose morphine (20mcg/kg/hr) and low dose morphine (5mcg/kg/hr).
      Both morphine doses are within the range currently used clinically. Patient comfort will be
      assessed frequently throughout, and the effects of morphine on diaphragmatic neural activity
      will be recorded.

      Who can participate:

        -  Infants aged > 36 weeks corrected gestation and < 1 year of age

        -  Admitted to PICU with acute viral bronchiolitis within 48 hours of admission

        -  Likely to require mechanical ventilation for > 24 hours after enrolment

        -  Able to pass a nasogastric tube

      What does the study involve:

      Within 48 hours parents/carers of patients admitted with a primary diagnosis of acute viral
      bronchiolitis who meet the inclusion criteria will be approached by a member of the direct
      healthcare team and invited to take part in the study. The pre-existing feeding tubes will be
      replaced with NAVA catheters by the bedside nurse or research team. Ventilation modes will be
      titrated on 2 consecutive days accompanied by two different Morphine doses delivered to the
      participant in random order. Participants will be randomised to receive either standard dose
      morphine (20mcg/kg/hr) or low dose morphine (5 mcg/kg/hr). These doses have been chosen to
      reflect current clinical practice and also using knowledge of morphine kinetics/dynamics on
      infant respiratory drive.

      Ventilation titration involves changes in NAVA level which increase over time and changes in
      PEEP which decrease over time to assess the ventilator setting that the patient responds to
      in terms of the outcome measures. This will enable identification of the optimum ventilation
      strategy for that participant. Titration will occur over time on 2 consecutive days as
      outlined above. There will be a wash in period of 5-10 minutes for each change in ventilator
      setting and a period of 5 minutes when the recordings of the outcome measures will take
      place.

      Baseline recordings will be taken for current ventilator settings, vital signs and
      respiratory measures and COMFORT-behavioral scale (comfort/pain scale). Study procedures will
      be timed to accommodate routine care such as daily physiotherapy sessions.

      Benefits and risks:

      Due to changes in ventilation settings during the two NAVA/PEEP titration periods (one per
      day) there is the potential for the child to experience changes in their comfort levels
      and/or physiological parameters. These will be continuously monitored by the researchers and
      the clinical bedside team. If the patient experiences discomfort during the study period as
      expressed by a COMFORT-b the patient will be returned to the previous ventilator settings and
      the reasons for discomfort will be assessed. Pain and sedation guidance will be adhered to as
      per usual care.
    

Intervention name(s): Neurally Adjusted Ventilatory Assist
Intervention type(s): Device
Intervention description(s): NAVA mode will be titrated as per protocol alongside titration of PEEP levels. Peep will be titrated for all NAVA levels in a descending order 10,5,0 NAVA level will be titrated in an ascending order 0.5, 1.0, 1.5, 2.0 at each PEEP level
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Patients will act as their own control. They will be randomised on day 1 to receive either standard dose or low dose morphine and on day two they will receive the alternate dose. Ventilation levels will be titrated as per a titration protocol.
Masking: None (Open Label)
Primary purpose: Other