Transcript Chapter_036 (2)

Chapter 36
Aerosol Drug Therapy
Copyright © 2013, 2009, 2003, 1999, 1995, 1990, 1982, 1977, 1973, 1969 by Mosby, an imprint of Elsevier Inc.
Learning Objectives





Define the term “aerosol.”
Describe how particle size, motion, and
airway characteristics affect aerosol
deposition.
Describe how aerosols are generated.
List the hazards associated with aerosol drug
therapy.
Describe how to select the best aerosol drug
delivery system for a given patient.
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Learning Objectives (cont.)



Describe how to initiate and modify aerosol
drug therapy.
State the information patients need to know to
properly self-administer drug aerosol therapy.
Describe how to assess patient response to
bronchodilator therapy at the point of care.
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Learning Objectives (cont.)


Describe how to apply aerosol therapy in
special circumstances.
Describe how to protect patients and
caregivers from exposure to aerosolized
drugs.
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Introduction
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
Aerosol is suspension of solid or liquid
particles in gas
In clinical setting, medical aerosols are
generated with devices that physically
disperse matter into small particles &
suspend them into gas

Atomizers
 Nebulizers
 Inhalers
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Introduction (cont.)

Medication aerosol provides higher
therapeutic index


Higher local drug concentration in lung
Lower systemic effects
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Characteristics of Therapeutic
Aerosols

Aerosol Output

Mass of fluid or drug contained in aerosol
 Output rate is mass of aerosol generated per unit
of time
• Varies depending on different nebulizers & inhalers used
 Emitted dose describes mass of drug leaving
mouthpiece as aerosol
 Measured by collecting aerosol that leaves
nebulizer on filters
• Gravimetric analysis measures aerosol weight
• Assay measures quantity of drug
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Characteristics of Therapeutic
Aerosols (cont.)

Particle size


Depends on 3 factors
1. Substance being nebulized
2. Method used
3. Environmental conditions
Methods to measure medical aerosol particle
distribution include:
• Cascade impaction
• Laser diffraction
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Characteristics of Therapeutic
Aerosols (cont.)

Particle size (cont.)

Geometric standard deviation (GSD) describes
variability of particle sizes
• Heterodisperse aerosols are aerosols with particles of
different sizes
• Monodisperse aerosols are aerosols with particles of
similar sizes
• Greater the GSD, wider range of particle sizes & more
heterodisperse aerosols
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Characteristics of Therapeutic
Aerosols (cont.)
● Deposition

Only fraction of emitted aerosol (emitted dose) will
be inhaled
 Only fraction of inhaled (respirable dose) is
deposited in lungs
 Amount of drug inhaled called “inhaled mass.”
 Portion of inhaled mass that can reach lower
airways is “respirable mass”
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Characteristics of Therapeutic
Aerosols (cont.)

Deposition (cont.)
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
Influenced by
• Inspiratory flow rate
• Flow pattern
• Respiratory rate
• Inhaled volume
• I:E ratio
• Breath-holding
Key mechanisms of aerosol deposition include:
• Inertial impaction
• Gravimetric sedimentation
• Brownian diffusion
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Key mechanisms causing aerosol deposition
include all of the following, except:
A.
B.
C.
D.
Sedimentation
inertial impaction
Brownian diffusion
osmosis
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Characteristics of Therapeutic
Aerosols (cont.)

Deposition (cont.)

Inertial impaction
• Occurs when aerosol in motion collides with & are
deposited on surface
• Primary deposition mechanism for larger particles
(>5 µm).
• Greater mass & velocity of moving object, then greater
inertia & greater tendency of that object to continue
moving along its set path
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Characteristics of Therapeutic
Aerosols (cont.)
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Characteristics of Therapeutic
Aerosols (cont.)
● Deposition (cont.)

Sedimentation
• Occurs when aerosol particles settle out of suspension &
are deposited due to gravity
• Represents primary mechanism for deposition of small
particles (1-5 µm)
• Breath-holding after inhalation of aerosol increases
sedimentation & distribution across lungs
• Greater mass of particle, the faster it settles
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Characteristics of Therapeutic
Aerosols (cont.)
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Characteristics of Therapeutic
Aerosols (cont.)

Deposition (cont.)

Brownian diffusion
• Primary deposition mechanism for very small particles
(<3 µm) deep within lung
• Particles between 1 & 0.5 µm have very low mass & are
so stable that most remain in suspension & are exhaled
back into environment
• Particles <0.5 µm have greater retention rate in lungs
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Characteristics of Therapeutic
Aerosols (cont.)
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Characteristics of Therapeutic
Aerosols (cont.)
● Aging


Process by which aerosol suspension changes
over time
How aerosol ages depends on:
• Composition of aerosol
• Initial size of its particles

Particle size can change due to evaporation or hygroscopic
water absorption
• Time in suspension
• Ambient condition
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Characteristics of Therapeutic
Aerosols (cont.)
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Hazards of Aerosol Therapy


Primary hazard of aerosol drug therapy is
adverse reaction to medication
Other possible hazards:

Infection
 Airway reactivity
 Pulmonary & systemic effects of bland aerosols
 Drug concentration changes during nebulization
 Eye irritation
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Hazards of aerosol drug therapy include all of the
following, except:
A.
B.
C.
D.
Infection
Hyperinflation
systemic effects
eye irritation
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Aerosol Drug Delivery Systems
● Pressurized metered-dose inhalers (pMDIs)


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Pressurized canister containing prescribed drug in
volatile propellant combined with surfactant &
dispersing agent
Most commonly prescribed method of aerosol
therapy
Portable, compact, & easy to use
Provides multidose convenience
Has serious limitation
• Lacks counter to indicate number of doses remaining in
canister
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Aerosol Drug Delivery Systems
(cont.)
● Pressurized metered-dose inhalers (cont.)


Most pMDIs are “press and breathe”
Variations of pMDIs
• Breath-actuated pMDIs


Incorporates trigger activated during inhalation
Reduces need for patient/caregiver to coordinate metered
dose inhaler actuation with inhalation
• Aerocount Autohaler


Flow-triggered
Eliminates need for hand-breath coordination
• Easihaler & Tempo

Breath-actuated
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)
● Factors affecting pMDI performance & drug
delivery

Temperature
• Decreased temperature (<10º C) decrease output of CFC
pMDIs

Nozzle size & cleanliness
• As debris builds up on nozzle or actuator orifice, emitted
dose is reduced
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Aerosol Drug Delivery Systems
(cont.)

Factors affecting pMDI performance & drug
delivery (cont.)

Priming
• Shaking device & releasing one or more sprays into air
when pMDI is new or has not been used for awhile
• Mixes drug & propellant
• Required to provide adequate dose

Timing of actuation intervals
• When propellants are released, device cools & changes
aerosol output
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Aerosol Drug Delivery Systems
(cont.)
● Aerosol delivery characteristics
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

pMDIs can produce particles in respirable range
(MMAD 2-6 µm)
~80% of aerosol deposits in oropharynx
Pulmonary deposition ranges between 10% &
20% in adults & larger children
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Aerosol Drug Delivery Systems
(cont.)

Technique for use of pMDI



Most patients do not use proper technique
Thorough education of patient can take up to 30
minutes
MDI should be actuated at beginning of inspiration
with mouthpiece held 4 cm in front of open mouth
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Aerosol Drug Delivery Systems
(cont.)

Technique for use of pMDI (cont.)

Concerns with open-mouth technique
• 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 opportunistic
oral yeast infection & dysphonia
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Aerosol Drug Delivery Systems
(cont.)

pMDI accessory devices

Breath-actuated pMDIs
• Trigger actuation when patient inhales
• Useful when patient cannot coordinate inhalation with
actuation

Spacers
• Simple valveless extension device that adds distance
between pMDI outlet & patient’s mouth
• Reduces oropharyngeal deposition & need for handbreath coordination
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Aerosol Drug Delivery Systems
(cont.)

pMDI accessory devices (cont.)

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, & better protection from poor
hand-breath coordination than simple spacers
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Dry powder inhalers
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

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
• Flow is function of ability of patient to inhale powder with
sufficiently high inspiratory flow rate

Do not use propellants & do not require handbreath coordination needed for pMDIs
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Dry powder inhalers (cont.)

Categorized based on design of their dose
containers
• Unit-dose DPI

Aerolizer & Handihaler dispense individual doses of drug
from punctured gelatin capsules
• Multiple-unit 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, & Diskus are preloaded with quantity
of pure drug sufficient for dispensing 120 doses of
medication
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Dry powder inhalers (cont.)


Factors affecting DPI performance & drug delivery
include
• Intrinsic resistance & inspiratory flow rate
• Exposure to humidity & moisture
• Patient’s inspiratory flow ability
Technique for use of DPI
• Patients must generate inspiratory flow rate of at least
40-60 L/min to produce respirable powder aerosol
• DPIs should not be used by infants, small children, those
who cannot follow instructions, & patients with severe
airway obstruction
• Requires cleaning in accordance with product label
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What is a disadvantage of using a pressurized
metered-dose inhaler versus a dry-powder
inhaler?
A.
B.
C.
D.
requires high inspiratory flow
most units are single dose
determining the amount of drug remaining
contamination
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Aerosol Drug Delivery Systems
(cont.)
Dry powder inhalers
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Aerosol Drug Delivery Systems
(cont.)

Pneumatic (jet) nebulizers


Most nebulizers are powered by high-pressure
oxygen or air provided by portable compressor,
compressed gas cylinder, or 50-psi wall outlet
Factors affecting nebulizer performance
• nebulizer design
• gas pressure
• gas density
• medication characteristics
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Aerosol Drug Delivery Systems
(cont.)
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The main factors the affect the performance of a
pneumatic jet nebulizer include all of the following,
except:
A.
B.
C.
D.
nebulizer design
gas pressure
medication characteristics
ambient relative humidity
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Aerosol Drug Delivery Systems
(cont.)

Small volume nebulizers (SVN)

Four categories
1. Continuous nebulizer with simple reservoir

May increase inhaled dose by 5-10%, or increase inhaled dose
from 10 to 11% with 6-inch piece of reservoir tube
2. 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
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Aerosol Drug Delivery Systems
(cont.)

Small volume nebulizers (SVN) (cont.)

Four categories
3. Breath enhanced (BE)

Generate aerosol continuously, utilizing system of vents &
one-way valves
4. Breath actuated nebulizer (BAN)

Can increase inhaled aerosol mass by 3-4 fold over
conventional continuous nebulization
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Small volume nebulizers (SVN) (cont.)

Technique
• Slow inspiratory flow optimize SVN aerosol deposition
• Selection of delivery method (mask or mouthpiece) is
based on patient ability, preference, & comfort

Infection control issues
• Nebulizers should be cleaned & disinfected, or rinsed
with sterile water, & air dried between uses
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Large-volume jet nebulizers


Also used to deliver aerosolized drugs to lungs
Particularly useful when traditional dosing
strategies for patients with bronchospasm are not
effective
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Aerosol Drug Delivery Systems
(cont.)

Large-volume jet nebulizers (cont.)

Special large-volume nebulizers provide CBT
• HEART
• Westmed
• HOPE
• 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 & drug
precipitation can jam breathing valves in mechanical
ventilator circuit
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)
● Hand-bulb atomizers & spray pumps



Used to administer sympathomimetic,
anticholinergic, antiinflamatory, & 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 produces aerosol suspension with
large particle size, which are ideal for upper
airway deposition
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Aerosol Drug Delivery Systems
(cont.)
● Ultrasonic nebulizers (USNs)





Uses piezoelectric crystal to produce aerosol
Crystal converts electrical energy into highfrequency vibrations to produce aerosol
Capable of higher aerosol outputs (0.2-1.0 ml/min)
& higher aerosol densities than are conventional
jet nebulizers
Output is directly affected by amplitude setting
Particle size is inversely proportional to frequency
of vibrations
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Aerosol Drug Delivery Systems
(cont.)

Ultrasonic nebulizers (cont.)

Large-volume USN
• Incorporates air blowers to carry mist to patient
• Primarily used for delivery of bland aerosol therapy or
sputum induction
• Low flow through nebulizer is associated with smaller
particles & higher mist density
• Temperature of solution placed in USN increases during
use
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Aerosol Drug Delivery Systems
(cont.)

Ultrasonic nebulizers (cont.)

Small-volume USNs
• Used to deliver aerosolized medications


Can be used to deliver bronchodilators, antibiotics, & antiinflammatory agents
Can be used to administer undiluted bronchodilator to
patient with severe bronchospasm
• Patient’s inspiratory flow draws aerosol from nebulizer
into lung
• Does not add extra gas flow to ventilator circuit, reducing
need to change & reset ventilator & alarm settings during
aerosol administration
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Vibrating mesh (VM) nebulizers

Types
• Active





Utilizes dome-shaped aperture plate (attached to piezo
ceramic element), containing more than 1000 funnelshaped apertures
Exit velocity of aerosol is low (<4 m/sec)
Particle size can range between 2-3 µm (MMAD), varying
with exit diameter of apertures
Can nebulize single drops as small as 15 µL of
formulations containing small & large molecules,
suspensions, microsuspensions, & liposomes
Includes Aeroneb Go pro, Solo, & eFlow (Pari)
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Aerosol Drug Delivery Systems
(cont.)

Vibrating mesh (VM) nebulizers (cont.)

Types
• Passive


Utilizes mesh separated from ultrasonic horn by liquid to
be nebulized
Includes NEU-22 (Omron) & I-neb (respironics)

Residual drug volume range from 0.1-0.4 mL
 Care should be exercised when transitioning to
these devices
• Greater percentage of standard unit doses are emitted as
aerosol
• Higher doses may create adverse effects
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

New nebulizer designs for liquids

AERs
• Has built-in electronic monitoring capabilities for
measuring inspiratory flow rate (IFR)

Dose administered is logged to provide record of
treatments
• Uses drug solution in unit-dose, sterile, preservative-free
blister pack containing 25-50 µL of fluid
• Emitted dose is more than 70% of dose contained in
blister with inspiratory flow rate ranging from 30-85 L/min
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Aerosol Drug Delivery Systems
(cont.)

New nebulizer designs for liquids (cont.)

Respimat
• Small hand held inhaler
• Uses mechanical energy to create aerosol from liquid
solutions to produce low-velocity spray (10 mm/sec) that
delivers unit dose in single actuation
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Aerosol Drug Delivery Systems
(cont.)

Smart nebulizers

I-neb (Phillips respironics)
• Breath-actuated passive vibrating mesh nebulizer
• Has adaptive aerosol delivery that monitors pressure
changes & inspiratory time for patient’s first three
consecutive breaths
• Drug is aerosolized over 50% of inspiratory maneuver
during fourth & subsequent breaths
• Has been released for delivery of prostacyclin
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Smart nebulizers (cont.)

Akita (Activaero)
• Controls inspiratory flow to keep it slow (12-15 lpm) &
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
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Aerosol Drug Delivery Systems
(cont.)

Special medication delivery issues for infants
& children

Smaller airway diameter than adults
 Breathing rate is faster
 Nose breathing filters out large particles
 Lower minute volumes
 Patient cooperation & ability varies with age &
developmental ability
• Aerosols should never be administered to crying child
• Crying reduces lower airway deposition of aerosol
medication
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Aerosol Drug Delivery Systems
(cont.)
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Aerosol Drug Delivery Systems
(cont.)

Blow-by technique


Used if patient cannot tolerate mask treatment
Practitioner directs aerosol from nebulizer toward
patient’s nose & mouth distance of several inches
from face
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Aerosol Drug Delivery Systems
(cont.) 36-29
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Assessment-Based Bronchodilator
Therapy Protocols
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Assessment-Based Bronchodilator
Therapy Protocols (cont.)

Role of RT

Assess patient response
• Ongoing patient assessment is key to effective
bronchodilator therapy protocol
• Peak flow measurement can provide trends if same
device is used from one treatment to next
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Assessment-Based Bronchodilator
Therapy Protocols (cont.)

Role of RT(cont.)

Assess patient response
• Components of patient assessment






Patient interviewing
Observation
Measurement of vital signs
Auscultation
Blood gas analysis
Oximetry
• Conduct dose-response titration to determine best
dosage for patients with moderate obstruction

Patient education
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Special Considerations

Acute care & “off label” use

Off-label use
• Clinicians may explore & consider nonstandard methods
(doses, frequency, & devices) for administration of
approved inhaled drugs to patients in acute care
environment
• Use of drugs that have not been approved for inhalation,
ranging from heparin to certain antibiotics
• Should be avoided when approved & viable alternative
exists
• Off-label administration should always be backed by
appropriate departmental or institutional policies &
procedures
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Special Considerations (cont.)

Continuous nebulization for refractory
bronchospasm



CBT with nebulized albuterol doses ranging from
5-20 mg/hour have proved to be safe for adult &
pediatric patients with severe asthma
Patient carefully assessed every 30 minutes for
first 2 hours; then hourly
• Patient must be observed for adverse drug responses
Positive response indicated by increase in PEFR
of at least 10% after first hour of therapy
• Goal is at least 50% of predicted value
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Special Considerations (cont.)
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Which of the following is NOT true regarding
continuous bronchodilator therapy?
A. CBT has proved to be safe for adult and
pediatric patients with severe asthma.
B. An increase in PEFR of at least 10-15% after
the first hour of therapy indicates a positive
response.
C. Once CBT is started, the patient need not be
assessed throughout the therapy.
D. The goal for PEFR is at least 50% of predicted
value.
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Special Considerations (cont.)

Aerosol administration to mechanically
ventilated patients

4 primary forms of aerosol generator used to
deliver aerosols during mechanical ventilation
1. SVN
2. USN
3. VM
4. pMDI with third part adapter
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Special Considerations (cont.)

Aerosol administration to mechanically
ventilated patients (cont.)

Techniques used for assessing response to
bronchodilator
• Measure change in difference between peak & plateau
pressures

Drop in peak pressure during mechanical ventilation
suggests effective bronchodilation
• Automatic positive end-expiratory pressure levels may
decrease in response to bronchodilators
• Breath-to-breath variations
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Special Considerations (cont.)
● Non-invasive ventilation


Administered with standard & bi-level ventilators
Bi-level ventilators often utilize flow turbine, with
fixed valve or leak in circuit which permits excess
flow to vent to atmosphere
● High-flow nasal oxygen


Type & location of nebulizer used with high-flow
nasal oxygen, cannula size, respiratory pattern, &
oxygen flow affect inhaled dose
Heliox (80:20) improve aerosol delivery at higher
flow rates
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Special Considerations (cont.)
● 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 & patient airway delivers
>10% of dose to infants & adults
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Controlling Environmental
Contamination



Nebulized drugs may enter room directly from
nebulizer or during patient exhalation
Pentamidine & ribavirin were associated with
health risks to caregivers
Continuous pneumatic nebulizers produce
greatest amount of second-hand aerosol
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Controlling Environmental
Contamination



Use of one-way valves & filters can help
Negative-pressure rooms & treatment booths
are useful strategies
Personal protective equipment is
recommended when caring for patient with
disease that can be spread by airborne route
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Controlling Environmental
Contamination
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