AEROSOL THERAPY
INTRODUCTION
An aerosol is defined as a suspension of liquid or solid in a gaseous medium
The aim of aerosol therapy is to deliver a therapeutic dose of the drug to the desired
site of action
ADVANTAGES OF PULMONARY DELIVERY OF DRUG
• Deliver high drug concentrations directly to the disease site
• Minimizes risk of systemic side-effects
• Rapid clinical response
• Bypass barriers to therapeutic efficacy, such as poor gastrointestinal absorption and
first-pass metabolism in liver
• Achieve a similar or superior therapeutic effect at a fraction of the systemic dose
AEROSOL SYSTEM INCLUDES
• The drug
• The aerosol device
• The patient’s respiratory system
• The ventilator system
EFFICIENCY OF THE AEROSOL SYSTEM
• The aim of aerosol system is to produce aerosols with characteristics suitable for
drug delivery to the lungs
• Aerosol system performance
• Emitted dose (ED)—the amount of drug exiting the delivery device
• Fine particle fraction (FPF)—the mass of particles below a cut-off diameter
• The overall efficiency of the aerosol system is a composite of the ED, the dose
delivered to the lung (FPF as a surrogate marker) and lung bioavailability
CHARACTERISTICS OF THERAPEUTIC AEROSOLS
• Aerosol output
• Particle size
• Deposition
• Changes in the aerosol over time (aging)
MECHANISM OF AEROSOL DEPOSITION
Impaction
• Turbulence and high air velocity associated with aerosolization, is predominant in
the first 10 branching's of the airway
Sedimentation
• In the distal five to six airway generations, however, predominates due to lower air
velocity
Diffusion
• Diffusion is the predominant mechanism for lung deposition
• 2–5 μm
General factors affecting aerosolized drug delivery
• Airway anatomy and physiology
• Abnormal airways and impaired mucociliary clearance serve as a barrier to effective
aerosolized drug therapy
• Regional lung aeration
• Airflow is not homogeneous throughout the lungs
• Lung diseases are regional which adds to the heterogeneity to regional airflow
Aerosol Device
• Nebulizers
• Jet nebulizers
• Ultrasonic nebulizers
• Mesh nebulizers
• Pressurized metered dose inhalers (pMDIs)
Jet Nebulizers
• Aerosols are generated by passing pressurized gas at a high velocity through a small
“jet” orifice
• Pressurized gas shear liquid into droplets due to surface tension
• Designed for delivery of drugs such as SABAs and corticosteroids
• Only about 5% of the aerosol is respirable, the remainder is removed by impaction
and returned to the reservoir
• Cleaning is typically to rinse after each use and boil wash weekly
• Nebulizer replacement typically after 30 days (disposable) or 6 months (durable)
Ultrasonic nebulizer
• Ultrasonic nebulizer uses a piezoelectric transducer that produces ultrasonic waves
• The frequency of ultrasonic waves is inversely related to the particle size of aerosols
whereas the amplitude of crystal vibration is directly related to drug output delivered
by the nebulizer
• Factors affecting output from ultrasonic nebulizers:
• Characteristics of the liquid solution (viscosity, density, surface tension)
• The piezoelectric transducer (vibration frequency, vibration amplitude)
• Medication chamber (size and baffles)
• Problem with ultrasonic nebulizers is that the drug solution becomes more
concentrated during operation, and the solution temperature increases by 10°C to
15°C after a few minutes of ultrasonic nebulization
• The increase in temperature has the potential to denature some drug formulations
Vibrating Mesh Nebulizer
• Piezo element vibrates the mesh, this vibration pumps liquid drug through the mesh,
the liquid is emitted from the mesh in droplets generating the aerosol
• 100% of the aerosol produced by the mesh is respirable
• Cleaning: rinse after every use, wash daily and boil weekly, often using distilled
water
• Mesh replacement typically after 6 or 12 months
Pressurized Metered-Dose Inhalers (pMDIs)
• pMDIs are small, portable, convenient, multi-dose devices that use a propellant
under pressure to deliver a metered dose of an aerosol
• Propellants
• Chlorofluorocarbon or
• Hydrofluoroalkane
Pressurized Metered-Dose Inhaler-Related
Factors
Priming and Shaking pMDIs
• Priming the pMDIs before first treatment and every time when it has not been used
for 24 hrs
• Total and respirable doses with pMDIs are reduced by 26% and 36%, respectively,
if the pMDIs is not shaken before use
• 2 or more rapid actuations of a pMDIs may lead to a decrease in drug delivery due
to turbulence and coalescence
• Timing of pMDIs Actuation
• Delay between a pMDIs actuation and inspiration decreases aerosol deposition due
to sedimentation and electrostatic charge
• Failure to synchronize pMDIs actuation with inspiration decreases aerosol delivery
by 35%
Spacer
• The types of spacers - Unidirectional Adapters Bidirectional adapters, and Chamber
spacers
• Large-volume spacers retain more of the aerosols delivered by pMDIs compared
with small-volume spacers, decreasing the amount of aerosol available from the
pMDIs
• Non-electrostatic material, aerosols remain suspended for longer periods within the
space
Type of spacer
Placement of pMDIs in the Ventilator Circuit
• 15 cm from the Y-adapter achieve deposition efficiencies of 17% as compared to
7.6% between the ETT and Y-adapter
• The Aero chamber HC MV is designed for use during mechanical ventilation
CHARACTERISTICS OF AEROSOL DEVICES USED IN
Critical Care
Nebulizer-Related Factors
Fill Volume
• Aerosol output from jet nebulizers are directly related
• Treatment time increases with a greater fill volume
• Fill volume of 4 –5 mL is recommended to increase output from jet nebulizers
Residual volume
• Amount of drug that remains in nebulizer at the end of aerosol therapy
• Residual volume ranges from 0.5 to 2.5 mL depending on type of nebulizer used
• This is a major factor associated with the lower aerosol delivery efficiency of jet
nebulizer
Position of the aerosol generator
• Jet nebulizer deliver maximum aerosol - at position 3
• It has been hypothesized that the continuous gas flow driving the jet nebulizer
allows aerosol to charge (fill) the inspiratory limb of the ventilator circuit and
function as a reservoir., so improves the aerosol delivery
• In contrast, aerosol from the ultrasonic and vibratingmesh nebulizers at position
tends to collect at the aerosol generator and not to be transported to the patient until
gas from the ventilator flows from the ventilator.
Nebulizer-Related Factors
Intermittent or Continuous Nebulization
• Intermittent nebulization during mechanical ventilation provides as much as 4-fold
greater inhaled dose compared with continuous nebulization
Circuit Related Factors
Gas Density
• The delivery efficiency of aerosol devices during mechanical ventilation and the gas
density in the ventilator circuit are inversely related
Heliox
• has lower density
• is not effective in generating aerosols with jet nebulizers
• Therefore, it should not be used to power jet nebulizers
Circuit Related Factors
Endotracheal tube
• Aerosol deposition has been found to be significantly lower with smaller ETT
• Delivery efficiency of a jet nebulizer with a 7-mm inner diameter ETT was similar
compared with a 9-mm inner diameter ETT in ventilator dependent subjects
Tracheostomy
• Patients who are not mechanically ventilated, a T-piece interface between the
tracheostomy tube and the nebulizer has been demonstrated to be more effective than
a tracheostomy mask
• Tracheostomy tube was not a barrier to lung deposition because 3% of aerosols
deposited on the tracheostomy tube
• Aerosol delivery through a tracheostomy tube was greater than that through an ETT
due to the shorter length of the tracheostomy tube
Ventilation Mode
• Aerosol deposition within the lower respiratory tract more with CPAP than with
controlled mechanical ventilation
• The use of PEEP during aerosol therapy improved lung function in spontaneously
breathing adults more than administering therapy without PEEP
Ventilator Parameters
Tidal volume (VT)
• VT is not directly proportional to aerosol drug delivery during mechanical
ventilation as long as the VT is greater than the internal volume of the ventilator
tubing and artificial airways
• VT of 8 –10 mL/kg can result in volutrauma and should not be used to improve
the delivery efficiency of aerosol devices during mechanical ventilation.
Inspiratory time
• Directly related to aerosol deposition in ventilator-dependent patients
• Use of a duty cycle 0.3 is suggested for aerosol therapy during mechanical
ventilation
• Monitor the degree of intrinsic PEEP
• Because it may worsen dynamic hyperinflation in patients with air-flow limitation
Inspiratory flow
• Lower inspiratory flows increase aerosol delivery to ventilator-dependent
patients
• Peak inspiratory flows should be decreased as much as possible if this is tolerated by
the patient
• Decreasing inspiratory flow from 80 to 40 L/min improved aerosol deposition by
2- fold in subjects receiving ventilator support
• Although low inspiratory flow rates improve the aerosol delivery but also increases
the intrinsic PEEP
• Square wave airflow pattern enable generation of laminar airflow to improve drug
deposition in the lungs
Heat and Humidity
• Heated and humidified ventilator circuit leads to decrease in aerosol deposition by
changes in aerosol particle size during mechanical ventilation.
• Humidity during aerosol therapy in ventilator-dependent subjects increased particle
size from 1.5 to 2.3
• 40% less aerosol deposition with heated and humidified gas compared with
unheated and non-humidified ventilator circuit
Heat and Humidity
• Dry circuit use may be cost-effective with expensive drugs such as antibiotics, to
complete aerosol therapy in 10 min to minimize the effect of dry gas on the airway
mucosa
Heat-and-moisture exchangers (HMEs)
• HME filter acts as a barrier to drug delivery, HMEs should not be placed between
the artificial airway of the patient and the aerosol device
Effect of high-flow nasal cannula
• RE´ MINIAC ET AL. assessed the mass and the particle size distribution of the
aerosol emitted from the nasal cannula using nebulizers placed at three positions in
the HFNC circuit
(1) before the humidification
chamber
(2) after the chamber
(3) immediately upstream from the nasal cannula
Effect of high-flow nasal cannula
• Position of the nebulizer
• A position closer to the patient improved delivery of the drug upstream
• Nebulizer type
• VMNs demonstrated improved delivery as compared with jet nebulizers
• Airflow
• The delivery of respirable mass is lower with higher airflow and improves at a lower
airflow. Drugs used in inhalation route in critical care Anti-infective
agents
