High-Frequency Oscillatory Ventilation Associated With Inhaled Nitric Oxide in Children
Condition: Acute Hypoxemic Respiratory Failure
MeSH terms: Respiratory Insufficiency
Study type: Interventional
Phase: Phase 3

Summary: 
      Background/Objectives: Acute hypoxemic respiratory failure (AHRF) is a frequent cause of
      pediatric ICU admission. Early treatment with inhaled nitric oxide (iNO) plus conventional
      mechanical ventilation (CMV) improves oxygenation, responsiveness being significantly
      influenced by alveolar recruitment level. High-frequency oscillatory ventilation (HFV) is
      conceptually very attractive as constant mean airway pressure optimizes lung recruitment;
      this could maximize iNO effects.

      Aims: To analyze the effects of HFV on oxygenation indexes in AHRF children under CMV and
      iNO.

      Methods: Children with AHRF (oxygenation index ≥10) aged between one month and 14 years under
      CMV with PEEP≥10cmH2O and 5ppm iNO for 1h were randomly assigned to CMV (CMVG, n=12) or HFV
      (HFVG, n=12) in a crossover design. Children with chronic cardiac or pulmonary diseases were
      excluded. Patients were kept under one of the two ventilation modes for 8h, crossing to the
      other for 8h, and then back again to complete 24h observation. Blood gas analysis,
      oxygenation indexes, and hemodynamic variables were recorded at enrollment (Tind), 1h after
      iNO start and then every 4h (T4h etc). The Mann-Whitney U test compared group ages and PRISM
      scores, and the Fisher test genders. Moments and groups were compared by repeated measure
      analysis for independent groups. Significance was considered at p<0.05.
    

Detailed description: 
      Acute hypoxemic respiratory failure (AHRF) is a frequent cause of admission and complicates
      evolution of critically ill children. Mortality rate is still high, mainly when acute
      respiratory distress syndrome (ARDS) evolves.

      Clinical management of AHRF is essentially supportive and includes control of underlying
      infections, fluid balance and hemodynamic status, nutritional support, and optimized
      protective mechanical ventilation4,5,6. Ventilatory strategies should be directed at
      minimizing ventilator-induced lung injury (VILI), eliminating oxygen toxicity, and
      controlling lung inflammation. Also, when hypoxemia persists, additional treatments may be
      implemented, such as inhaled nitric oxide (iNO)and high-frequency oscillatory ventilation
      (HFOV).

      Recently, we have demonstrated that early treatment with iNO associated with protective
      conventional mechanical ventilation (CMV) causes acute and sustained improvement in
      oxygenation, with earlier reduction in ventilator settings that are associated with a high
      risk of VILI and oxygen toxicity; this might contribute to reducing the mortality rate in
      children with ARDS.

      However, many studies have given no value to iNO therapy because of a lack of impact on
      mortality rate. Despite this, it should be considered that the improvement in oxygenation
      promoted by NO inhalation may be useful as rescue therapy. Also, it is known that
      responsiveness to iNO can be significantly influenced by applying sufficient positive and
      expiratory pressure (PEEP), as this seems to recruit additional alveoli for gas exchange. In
      this sense, HFOV is very attractive as the application of a constant mean airway pressure
      maintains an "open lung" and optimizes lung recruitment; this could maximize iNO effects.

      Two experimental studies have shown increased iNO effects when the gas was used together with
      HFOV. In ARDS adults, Authors studied this association and demonstrated improvement in
      oxygenation with significant reduction in FiO2, probably due to the degree of alveolar
      recruitment during HFOV which may increase the amount of alveolar/capillary interface
      available for iNO to act upon.

      In pediatrics, there is one study combining iNO and HFOV in newborn babies with severe
      persistent pulmonary hypertension which concluded that the association is often more
      successful than each treatment alone23. After neonatal period, a retrospective (post hoc)
      data analysis from a multicenter, randomized controlled trial on the effects of iNO in the
      treatment of AHRF concluded that the combination of HFOV with iNO causes greater improvement
      in oxygenation than either treatment strategy alone.

      Therefore, the question about the potential role of the association between iNO therapy and
      HFOV in AHRF children is still open and remains to be defined. Our hypothesis is the
      association between early iNO treatment and HFOV improves oxygenation more consistently and
      for longer time than the association of the gas with protective conventional mechanical
      ventilation.

      The aim of this study was to analyze the effects of HFOV on oxygenation indexes in AHRF
      children under CMV and iNO therapy.
    

Intervention name(s): High frequency oscillatory ventilation
Intervention type(s): Procedure
Intervention description(s): Mechanical ventilation as high frequency oscillatory ventilation for 8h periods
Other intervention name(s): HFOV
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: high frequency oscillatory ventilation; respiratory failure; children; inhaled nitric oxide