Effects of Vibrating Mesh Nebulisation in Patients on Long-term Tracheostomy Ventilation: a Pilot Randomised Crossover Trial (EVOLVE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Long-term tracheostomy ventilation (LTTV) is frequently complicated by high secretion burden, arising from accumulation of oronasal and bronchial secretions due to impaired bulbar or cough function. Patients are therefore at an increased risk of sputum plugging and respiratory infection, leading to potentially life-threatening deterioration. In patients undergoing weaning from prolonged mechanical ventilation, liberation from invasive mechanical ventilation can be delayed by excessive secretion burden, detrimentally affecting quality of life and escalating healthcare costs.
The principal treatment strategies for secretion retention are oral and tracheal suction, mucolytic therapy (enteral or nebulised) and mechanical insufflation-exsufflation (MIE). There are few robust data to support the use of these treatment modalities, although they are routinely used in clinical practice on an empirical basis. The use of nebulised hypertonic saline is well-established in the management of non-cystic fibrosis bronchiectasis and is frequently used to aid airway clearance in LTTV patients. Nebulised salbutamol is widely used as a bronchodilator in tracheostomised patients with a tendency to develop bronchospasm, whether due to established obstructive airways disease or airways inflammation from secretion retention or ventilator-associated pneumonia.
Vibrating mesh nebulisation (VMN) is increasingly used for aerosol delivery in mechanically ventilated patients, with advantages including reduced residual volume, quieter operation and higher levels of drug deposition. However, its superiority in improving secretion clearance and bronchodilation compared with jet nebulisation (JN) is yet to be established. Both VMN and JN are currently utilised within clinical practice as standards of care.
This pilot randomised crossover trial seeks to recruit 12 patients to establish whether VMN of hypertonic saline and salbutamol has a greater effect than standard JN in improving:
Neural respiratory drive (measured by assessment of the electrical activity of breathing muscles via parasternal EMG) Secretion burden Breathlessness
Participants will be recruited as inpatients within the Lane Fox Unit. Following consent for trial involvement, there will be a 24-hour washout period receiving normal saline nebulisers. Baseline data including ventilator settings, anthropometrics and clinical observations will be recorded before participants are randomly allocated to receive salbutamol and hypertonic (3%) saline via either VMN or JN four times per day for 30 hours. During this period, measurements will include:
Neural respiratory drive (via parasternal EMG) Carbon dioxide levels (via forehead probe) Breathlessness and sputum burden (using numerical scales) 24-hour sputum volume with samples for bacterial/viral analyses
Following a 24-hour washout period, participants will receive salbutamol and hypertonic saline via the alternative nebuliser type for 30 hours, with identical data collection.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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London
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London, London, United Kingdom, SE1 7EH
- Lane Fox Unit, St Thomas' Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients receiving long-term tracheostomy ventilation as inpatients of the Lane Fox Respiratory Service at Guy's and St Thomas' NHS Foundation Trust
- Requiring prolonged mechanical ventilation for at least 6 hours per day for at least 21 days
- Has a cuffed tracheostomy in situ
- Aged 18-80 years old
- Receiving normal (0.9%) saline or hypertonic saline nebulisation at the time of enrolment into the study
- Requiring and tolerating tracheal suctioning for secretion management
- Able to communicate symptom burden to the research team
- Able to give informed consent for participation in the study
- Clinical stability, with no requirement for changes in ventilatory support, as assessed by the responsible clinician for at least 48 hours prior to enrolment in study
Exclusion Criteria:
Severe, non-respiratory organ dysfunction including, but not limited to:
- Congestive cardiac failure
- Cardiac arrhythmia
- End-stage malignancy
- End-stage renal failure
Acute pulmonary pathology requiring emergency treatment including, but not limited to:
- Ventilator associated pneumonia at the time of screening
- Pneumothorax
- Pulmonary embolism
- Severe cognitive impairment
- Psychosocial factors that would preclude completion of the study protocol
- Previous intolerance of aerosolised hypertonic 3% saline or nebulised salbutamol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Vibrating mesh nebulisation then jet nebulisation
Participants will receive hypertonic saline and salbutamol via vibrating mesh nebulisation for the first 30 hours.
After a 24-hour washout period, they will receive the same medications via jet nebulisation.
|
Vibrating mesh nebulisation (VMN) uses a mesh membrane that oscillates at high frequency (typically 128 kHz) to produce a stream of drug-carrying droplets of pre-determined size to be inhaled.
Jet nebulisers use the flow of a gas (air or oxygen) to draw medication up through a capillary tube to generate small particles to be inhaled.
|
|
Experimental: Jet nebulisation then vibrating mesh nebulisation
Participants will receive hypertonic saline and salbutamol via jet nebulisation for the first 30 hours.
After a 24-hour washout period, they will receive the same medications via vibrating mesh nebulisation.
|
Vibrating mesh nebulisation (VMN) uses a mesh membrane that oscillates at high frequency (typically 128 kHz) to produce a stream of drug-carrying droplets of pre-determined size to be inhaled.
Jet nebulisers use the flow of a gas (air or oxygen) to draw medication up through a capillary tube to generate small particles to be inhaled.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Neural Respiratory Drive
Time Frame: At baseline and during both 30 hour nebuliser allocations. Following nebulisation measurements to be made at 15 and 30 minutes
|
Parasternal electromyography, which reflects the load-capacity relationship of the respiratory system, will likely decrease with more effective bronchodilation and secretion clearance.
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At baseline and during both 30 hour nebuliser allocations. Following nebulisation measurements to be made at 15 and 30 minutes
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Sputum viscosity
Time Frame: Daily during both 30 hour periods
|
Sputum viscosity will be measured by a single assessor using the Qualitative Sputum Analysis Tool (QSAT) score daily during both 30-hour periods.
The QSAT score includes sputum volume, type (mucoid, mucopurulent and purulent) and grades viscosity from 1 (adherent) to 4 (easily pourable) in 0.5 increments.
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Daily during both 30 hour periods
|
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Sputum weight
Time Frame: At baseline and during both 30 hour nebuliser periods
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24 hour cumulative wet sputum weight will be measured at baseline and during each nebuliser phase
|
At baseline and during both 30 hour nebuliser periods
|
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Respiratory Flow
Time Frame: At baseline and during each 30 hour time period
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Assessment of respiratory flow via pneumotach within both 30 hour time periods
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At baseline and during each 30 hour time period
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Symptoms of breathlessness (modified Borg dyspnea scale)
Time Frame: At baseline and during both 30 hour nebulisation periods
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Patient perception of breathlessness will be assessed using the modified Borg dyspnoea scale (mBorg).
The scale ranges from 0 to 10 (whole numbers plus 0.5), where 0 indicates no breathing difficulty and 10 represents maximal breathing difficulty.
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At baseline and during both 30 hour nebulisation periods
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Symptoms of breathlessness (numerical rating scale)
Time Frame: At baseline and during both 30 hour nebulisation periods
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Patient perception of breathlessness will be assessed using a numerical rating scale from 0 to 10, where 0 represents no breathlessness and 10 represents the worst breathlessness imaginable.
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At baseline and during both 30 hour nebulisation periods
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Symptoms of sputum burden
Time Frame: At baseline and during both 30 hour nebulization periods
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Patient perception of secretion burden will be assessed using a numerical rating scale rated from 0 to 10, where 0 represents no burdensome secretions and 10 represents secretions being the worst imaginable.
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At baseline and during both 30 hour nebulization periods
|
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Heart Rhythm
Time Frame: At baseline and during the 2 x 30 hour periods
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Changes in heart rhythm will be assessed by ECG monitoring to detect variations following administration of salbutamol and hypertonic saline by VMN versus JN.
Any changes in heart rhythm or arrhythmias will be documented.
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At baseline and during the 2 x 30 hour periods
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Heart rate
Time Frame: At baseline and during 2 x 30 hour periods
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Heart rate will be assessed by continuous ECG monitoring to detect changes following administration of salbutamol and hypertonic saline by VMN versus JN.
Heart rate will be measured in beats per minute.
|
At baseline and during 2 x 30 hour periods
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Collaborators and Investigators
Investigators
- Principal Investigator: Eui Sik Suh, MBBS MChem(Oxon) PhD FRCP, Guy's and St Thomas' NHS Foundation Trust
Publications and helpful links
General Publications
- Tarrant BJ, Le Maitre C, Romero L, Steward R, Button BM, Thompson BR, Holland AE. Mucoactive agents for chronic, non-cystic fibrosis lung disease: A systematic review and meta-analysis. Respirology. 2017 Aug;22(6):1084-1092. doi: 10.1111/resp.13047. Epub 2017 Apr 11.
- Kellett F, Redfern J, Niven RM. Evaluation of nebulised hypertonic saline (7%) as an adjunct to physiotherapy in patients with stable bronchiectasis. Respir Med. 2005 Jan;99(1):27-31. doi: 10.1016/j.rmed.2004.05.006.
- Mifsud Bonnici D, Sanctuary T, Warren A, Murphy PB, Steier J, Marino P, Pattani H, Creagh-Brown BC, Hart N. Prospective observational cohort study of patients with weaning failure admitted to a specialist weaning, rehabilitation and home mechanical ventilation centre. BMJ Open. 2016 Mar 8;6(3):e010025. doi: 10.1136/bmjopen-2015-010025.
- Arnott A, Hart R, McQueen S, Watson M, Sim M. Prospective randomised unblinded comparison of sputum viscosity for three methods of saline nebulisation in mechanically ventilated patients: A pilot study protocol. PLoS One. 2023 Aug 17;18(8):e0290033. doi: 10.1371/journal.pone.0290033. eCollection 2023.
- Anand R, McAuley DF, Blackwood B, Yap C, ONeill B, Connolly B, Borthwick M, Shyamsundar M, Warburton J, Meenen DV, Paulus F, Schultz MJ, Dark P, Bradley JM. Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis. Thorax. 2020 Aug;75(8):623-631. doi: 10.1136/thoraxjnl-2019-214355. Epub 2020 Jun 8.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 348268
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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