Changes in Regional Lung Ventilation Following Mechanical Insufflation-Exsufflation
Condition: Neuromuscular Diseases
MeSH terms: Neuromuscular Diseases
Study type: Interventional

Summary: 
      Patients with NMD can suffer from a range of respiratory problems due to respiratory muscle
      weakness. Cough muscle weakness worsens secretion clearance from the airways, and increases
      the risk of infection. As a result, these patients often require chest physiotherapy or are
      supported with devices to aid clearance (such as mechanical insufflation-exsufflation) to
      reduce the risk of infection. Although evidence supports the use of these devices, the
      optimal technique or settings on the device are not clear.

      Electrical impedance tomography (EIT) is a new technology that involves wearing a belt of
      sensors around the chest that provides information on how well the lungs are being filled
      with air. It allows a non-invasive assessment of the effect of each secretion clearance
      technique on lung ventilation in real-time.

      This study aims to compare how well the lung is filled with air between three different
      techniques for secretion clearance (clearing mucus and phlegm from the airways), in order to
      determine which of the techniques is the most effective, in patients with NMD.
    

Detailed description: 
      Electrical Impedance Tomography (EIT) is a non-invasive, bedside monitoring technique that
      provides semi-continuous, real-time information about the regional distribution of the
      changes in electrical resistivity of the lung tissue due to variations in ventilation in
      relation to a reference state.

      Information is gained by repeatedly injecting small alternating electric currents (usually 5
      mA) at high frequency of 50 - 80 kHz through a system of skin electrodes (usually 16) applied
      circumferentially around the thorax in a single plane between the 4th and 6th intercostal
      space. While an adjacent pair of electrodes 'injects' the current ('adjacent drive
      configuration'), all the remaining adjacent passive electrode pairs measure the differences
      in electric potential. A resistivity (impedance) image is reconstructed from this data by a
      mathematical algorithm using a two dimensional model and a simplified shape to represent the
      thoracic cross-section.

      The resulting image possesses a high temporal and functional resolution making it possible to
      monitor dynamic physiological phenomena (e.g., delay in regional inflation or recruitment) on
      a breath by breath basis. It is important to realize that the EIT images are based on image
      reconstruction techniques that require at least one measurement on a well-defined reference
      state. All quantitative data are related to this reference and can only indirectly quantify
      (relative) changes in local lung impedance (but not absolute).

      Patients with respiratory muscle weakness have reduced cough strength and this can cause
      difficulties with clearing respiratory secretions. This impaired secretion clearance can lead
      to respiratory infections and acutely can causing small airway occlusion with subsequent
      ventilation-perfusion mismatch adversely effecting pulmonary mechanics. The use of cough
      assist devices, such as mechanical insufflation-exsufflation (MIE) can improve secretion
      clearance. Although there is evidence that these devices can improve secretion clearance the
      optimal pressures or technique required to provide effective secretion clearance is not
      known. Furthermore the use of high pressure swings that are now frequently used in clinical
      practice could lead to lung derecruitment. The use of EIT would allow a novel and effective
      method of assessing the ability to clear secretions and optimise ventilated lung in
      neuromuscular patients with poor cough and assess post procedure derecruitment.

      MIE: A pilot physiological study will be performed in patients with neuromuscular disease
      with acute (10 patients) and chronic (10 patients) secretion management issues that require
      clinical use of MIE. These patients will be studied using 3 different clearance strategies
      low pressure MIE, higher pressure MIE and standard airway techniques. The project will assess
      differences in regional ventilation following augmented airway clearance and inform potential
      endpoints and feasibility for a larger trial regarding speed of recovery from respiratory
      infections in patients with neuromuscular disease.

      There is a paucity of data regarding the physiological efficacy of MIE devices and although
      clinical consensus regards them as a beneficial adjunct to the management of patients with
      respiratory muscle weakness causing a reduction in effective secretion clearance it is less
      clear the optimum protocol to achieve secretion clearance. The aim of chest physiotherapy is
      to achieve clearance of airway secretions and allow improved gas exchange by enhancing
      ventilation and perfusion matching within the lung. The data suggesting optimum pressures for
      MIE are based around early work on achieving enhanced cough peak expiratory flow. More
      recently higher pressures have been suggested to achieve enhanced airway clearance. There may
      be potential beneficial effects with high pressure MIE by enhancing airway opening during the
      insufflation pressure achieving a degree of lung volume recruitment. Conversely, high
      insufflation pressures may adversely affect both pulmonary and cardiac physiology which may
      be further impacted by the large pressure swing during exsufflation. This is particularly
      relevant given the increasing co-morbid cardiomyopathy that occurs in many congenital
      neuromuscular diseases.

      The initial phase of the project would be to generate pilot data with a comprehensive
      physiological evaluation of patients with neuromuscular disease and requirement of cough
      augmentation with MIE devices. The patients will undergo a randomised protocol of chest
      clearance with standard physio, low pressure and high pressure MIE. Data from this trial will
      allow an optimal treatment strategy to be developed and if data suggested would provide
      sufficient data to power an interventional trial to examine important clinical outcomes.
    

Intervention name(s): Acute Intervention; Stable Intervention
Intervention type(s): Other; Other
Intervention description(s): Patients will be set up onto their Non Invasive Ventilator and assessed for an hour prior to, during and following secretion clearance and will have the following assessed:
Electrical impedance tomography (EIT)
EMGpara
SpO2
tcCO2
Respiratory inductance plethysmography
EIT will be performed as 2 to 10-minutes recording of quiet breathing before and after each intervention
Interventions will be set as follows with a 30 minute washout period between modes:
Manual techniques only
MIE at low pressure (+30 to -30)
MIE at high pressure (+60 to -60); Patients will be set up onto their Non Invasive Ventilator and assessed for an hour prior to, during and following secretion clearance and will have the following assessed:
Electrical impedance tomography (EIT)
EMGpara
SpO2
tcCO2
Respiratory inductance plethysmography
EIT will be performed as 2 to 10-minutes recording of quiet breathing before and after each intervention
Interventions will be set as follows with a 30 minute washout period between modes:
Manual techniques only
MIE at low pressure (+30 to -30)
MIE at high pressure (+60 to -60)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other