Chapter 36 -- Aerosol Drug Therapy

Aerosol

Suspension of solid or liquid particles in gas.

Medical aerosols

Generated with devices that physically disperse matter into small particles and suspend them into gas.

Atomizers

Jet and capillary.

Nebulizers

Jet, capillary, and baffle.

Inhalers

Propellant.

Aerosol output

- Mass of fluid or drug contained in aerosol
- Output rate is mass of aerosol generated per unit of time

Emitted dose

Mass of drug leaving mouthpiece as aerosol.

Gravimetric analysis

Measures aerosol weight.

Assay

Measures quantity of drug.

Particle size

Depends on three factors:
1. Substance being nebulized.
2. Method used.
3. Environmental conditions.

Geometric standard deviation (GSD)

Variability of particle sizes.
- Greater the GSD, wider range of particle sizes and more heterodisperse aerosols

Heterodisperse aerosols

Aerosols with particles of different sizes.

Monodisperse aerosols

Aerosols with particles of similar sizes.

Deposition

- Only fraction of emitted aerosol (emitted dose) will be inhaled
- Only fraction of inhaled aerosol (respirable dose) is deposited in lungs

Inhaled mass

Amount of drug inhaled.

Respirable mass

Portion of inhaled mass that can reach lower airways.

Deposition influences

- Inspiratory flow rate
- Flow pattern
- Respiratory rate
- Inhaled volume
- I:E ratio
- Breath-holding

Deposition key-mechanisms

- Inertial impaction
- Gravimetric sedimentation
- Brownian diffusion

Inertial impaction

- Occurs when aerosol in motion collides with and are deposited on surface
- Primary deposition mechanism for larger particles (>5 um)
- Greater mass and velocity of moving object, then greater inertia and greater tendency of that object to continue movin

Sedimentation

- Occurs when aerosol particles settle out of suspension and are deposited due to gravity
- Represents primary mechanisms for deposition of small particles (1-5 um)
- Greater mass of particle, the faster it settles

Breath-holding after inhalation of aerosol

Increases sedimentation and distribution across lungs.

Brownian diffusion

- Primary deposition mechanism for very small particles (<3 um) deep within lung
- Particles between 1 and 0.5 um have very low mass and are so stable that most remain in suspension and are exhaled back into environment
- Particles >0.5 um have greater re

Aging

Process by which aerosol suspension changes over time.

Aerosol aging

Depends on:
- Composition of aerosol
- Initial size of its particles
- Time in suspension
- Ambient condition

Aerosol therapy hazards

Primary hazard of aerosol drug therapy is adverse reactions to medication.
Other possible hazards include:
- Airway reactivity
- Pulmonary and systemic effects of bland aerosols
- Drug concentration changes during nebulization
- Eye irritation

Pressurized metered-dose inhalers (pMDIs)

Pressurized canister containing prescribed drug in volatile propellant combined with surfactant and dispersing agent.
- Most commonly prescribed method of aerosol therapy
- Portable, compact, and easy to use
- Provide multidose convenience
- Has serious l

Breath-actuated pMDIs

- Incorporates trigger activated during inhalation
- Reduces need for patient/caregiver to coordinate MDI actuation with inhalation

Aerocount inhaler

- Flow-triggered
- Eliminates the need for hand-breath coordination

Easihaler and Tempo

Breath-actuated

Factors affecting pMDI performance

- Temperature
- Nozzle size and cleanliness
- Priming
- Timing of actuation intervals

Aerosol delivery characteristics

- pMDIs can produce particles in respirable range (MMAD 2-6 um)
- 80% of aerosol deposits in oropharynx
- Pulmonary deposition ranges between 10-20% in adults and larger children

pMDI use

- Should be actuated at beginning of inspiration with mouthpiece held 4 cm in front of open mouth

Open-mouth technique

Concerns include:
- Ipratropium bromide administration along with poor coordination can result in drug being sprayed into eyes
- Anticholinergic agents have been associated with increased ocular pressure
- Steroid pMDIs can increase incidence of opportuni

Spacers

- Simple, valveless extension device that adds distance between pMDI outlet and patient's mouth
- Reduces oropharyngeal deposition and need for hand-breath coordination

Holding chambers

- Incorporates one or more valves that prevent aerosol in chamber from being cleared on exhalation
- Provides less oropharyngeal deposition, higher respirable drug dosages, and better protection from poor hand-breath coordination than simple spacers

Dry powder inhalers (DPIs)

- Breath-actuated dosing system
- Patient creates aerosol by drawing air through dose of finely milled drug powder
- Dispersion of powder into respirable particles depends on creation of turbulent flow in inhaler
- Do not use propellants and do not requir

Unit-dose DPI

Aerolizer and handihaler dispense individual doses of drug from punctured gelatin capsules.

Multiple-dose DPI

Diskhaler contains case of four or eight individual blister packets of medication on disk inserted into inhaler.

Multiple dose drug reservoir DPI

Twisthaler, Flexhaler, and Diskus are preloaded with quantity of pure drug sufficient for dispensing 120 doses of medication.

Factors affecting DPI performance and drug delivery

- Intrinsic resistance and inspiratory flow rate
- Exposure to humidity and moisture
- Patient's inspiratory flow ability

DPI use

Should not be used by infants, small children, those who cannot follow instructions, and patients with severe airway obstruction.

Pneumatic (jet) nebulizers

Most nebulizers are powered by high-pressure oxygen or air provided by portable compressor, compressed gas cylinder, or 50-psi gas outlet.

Factors affecting nebulizer performance

- Nebulizer design
- Gas pressure/flow
- Gas density
- Medication characteristics

Small volume nebulizers (SVN)

Four categories:
1. Continuous nebulizer with simple reservoir.
2. Continuous nebulizer with collection reservoir bag.
3. Breath-enhanced (BE).
4. Breath-actuated nebulizer (BAN).

Continuous nebulizer with simple reservoir

May increase inhaled dose by 5-10% or increase inhaled dose from 10-11% with 6" piece of reservoir tube.

Continuous nebulizer with collection reservoir bag

- Bag reservoirs hold aerosol generated during exhalation
- Allows small particles to remain in suspension for inhalation with next breath while larger particles rain out
- Attributed to 30-50% increase in inhaled dose

Breath-enhanced (BE)

Generate aerosol continuously, utilizing system of vents and one-way valves.

Breath-actuated nebulizer (BAN)

Can increase inhaled aerosol mass by 3-4 fold over conventional continuous nebulizers.

SVN technique

- Slow inspiratory flow optimizes SVN aerosol deposition
- Selection of delivery method is based on patient ability, preference, and comfort

Large volume nebulizers

- Particularly useful when traditional dosing strategies for patients with bronchospasm are not affective

Special LVNs

Provide CBT.
- HEART
- Westmed
- HOPE
- Small-particle aerosol generator (SPAG)

Small-particle aerosol generator (SPAG)

- Designed specifically for administration of ribavirin
- Incorporates drying chamber with its own flow control to produce stable aerosol
- Concerns include caregiver exposure to drug and drug precipitation can jam breathing valves in mechanical ventilato

Hand-bulb atomizers and spray pumps

- Used to administer sympathomimetric, anticholinergic, antiinflamatory, and anesthetic aerosols to upper airway
- Deposition with hand-bulb atomizer applied to nose occurs mostly in anterior nasal passages with clearance to nasopharynx
- Spray pump produ

Ultrasonic nebulizers (USNs)

- Uses piezoelectric crystal to produce aerosol
- Crystal converts electrical energy into high-frequency vibrations to produce aerosol
- Capable of higher aerosol outputs (0.2-1.0 ml/min) and higher aerosol densities than are conventional jet nebulizers
-

Large-volume USN

- Incorporates air blowers to carry mist to patient
- Primarily used for deliver of bland aerosol therapy or sputum induction
- Low flow through nebulizer is associated with smaller particles and higher mist density
- Temperature of solution placed in USN

Small-volume USN

- Can be used to deliver bronchodilators, antibiotics, and anti-inflammatory agents
- Can be used to administer undiluted bronchodilator to patient with sever bronchospasm
- Patient's inspiratory flow draws aerosol from nebulizer into lung

Vibrating mesh (VB) nebulizer (Active)

- Utlizes dome-shaped aperture plated containing more than 1000 funnel-shaped apertures
- Exit velocity of aerosol is low (<4 m/sec)
- Particle size can range between 2-3 um (MMAD), varying with exit diameter of apertures
- Can nebulize single drops as sm

Vibrating mesh (VB) nebulizer (Passive)

- Utilizes mesh separated from ultrasonic horn by liquid to be nebulized
- Residual drug volume ranges from 0.1-0.4 ml
- Care should be exercised when transitioning to these devices

Smart nebulizers

Akita (Activaero):
- Controls inspiratory flow to keep it slow (12-15 lpm) and reduce impaction loss of aerosols in upper airways
- Patient pulmonary function is stored on smart card programmed to tell device when to generate aerosol during inhalation

Special medication delivery issues for infants and children

- Smaller airway diameter than adults
- Breathing rate is faster
- Nose breathing filters out large particles
- Lower minute volumes
- Patient cooperation and ability varies with age and developmental ability
- Should never be delivered during crying (red

Blow-by technique

- Used if patient cannot tolerate mask treatment
- Practitioner directs aerosol from nebulizer toward patient's nose and mouth distance of several inches from face

Components of patient assessment

- Patient interviewing
- Observation
- Measurement of vital signs
- Auscultation
- Blood gas analysis
- Oximetry

Conduct dose

Response filtration to determine best dosage for patients with moderate obstruction.

Off-label use

- Use of drugs that have not been approved and viable alternative exists
- Should always be backed up by appropriate departmental or institutional policies and procedures

CBT

- Used to treat severe asthma
- Doses ranging from 5-20 mg/hour have proved to be safe for adult and pediatric patients with severe asthma
- Patient carefully assessed every 30 minutes fro first 2 hours; then hourly
- Positive response indicated by increa

Aerosol administration to mechnically ventilated patients

- SVN
- USN
- VM
- pMDI
- DPI

Assessing response to bronchodilator

- Measure change in difference between peak and plateau pressures
- Drop in peak = bronchodilator is effective
- Drop in plateau = bronchodilator is effective

Non-invasive ventilation

- Administered with standard and bi-level ventilators
- Bi-level ventilators often utlize flow turbine, with fixed valve or leak in circuit which permits excess flow to vent to atmosphere

High-flow nasal oxygen

- Type and location of nebulizer used with high-flow nasal oxygen, cannula size, respiratory pattern, and oxygen flow affect inhaled dose

Intrapulmonary percussive ventilation

- Provides high-frequency oscillation of airway while administering aerosol particles
- Aerosol generator should be placed in circuit as close to patient's airway

High-frequency oscillatory ventilation

Administration of albuterol sulfate via VM placed between ventilator circuit and patient airway delivers.