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Aerosol

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A suspension of a solid or liquid particles in gas

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Aerosols occur in nature as:

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-pollens -Spores -Dust -Smoke -Fog -Mist

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Medical Aerosols are generated with

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-atomizers -nebulizers -inhalers (all are items that disperse matter into small particles & suspend them into a gas)

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The aim of medical aerosol therapy is to:

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Deliver a therapeutic dose of the selected agent (drug) to the desired site of action.

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Key characteristics of aerosols

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-aerosol output -particle size -desposition -aging

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Aerosol Output

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-the mass of fluid or drug contained in aerosol product by a nebulizer. -the mass of aerosol generated per unit of time

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Emitted Dose

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The mass of drug leaving the mouthpiece of a nebulizer or inhaler as aerosol

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Aerosol particle size depends on:

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-the substance for nebulization - method used to generate the aerosol -The environmental conditions surrounding the particle

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The only reliable way to determine the characteristics of an aerosol suspension is:

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Laboratory measurement

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2 most common laboratory methods used to measure medical aerosol particle size distribution are:

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-cascade impaction - laser diffraction

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Cascade impactors

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are designed to collect aerosols of different sizes ranges on a series of stages ot plates

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Laser Diffraction

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A computer is used to estimate the range and frequency of droplet volumes crossing the laser beam.

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Mass Median Aerodynamic Diameter (MMAD)

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measure of central tendency that describes the particle diameter in micrometers in medical aerosols and pertains to cascade impaction.

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Volume Mean Diameter (VMD)

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the median diameter of an aerosol particle measured in units of volume.

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Geometric Standard Deviation (GSD)

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describes the variability of particle sizes in an aerosol distribution set at 1 standard deviation above or below the median (15.8% & 84.13)

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The Greater the GSD

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the wider the range of particle sizes, and the more heterodisperse the aerosol

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Monodisperse

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Aerosols consisting of particles of similar size (GSD less than or equal to 1.2)

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Inhaled Mass

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- AKA inhaled dose - the amount of drug inhaled

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Fine-Particle Fraction

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...

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Respirable Mass

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proportion of aerosolized drug of the proper particle size to reach the lower respiratory tract

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Whether aerosol particles that are inhaled into the lungs are deposited into the respiratory tract depends on:

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-size -shape -motion of the particled and on the physical characteristics of the airways and breathing pattern.

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Deposition

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estimony of a witness taken on interrogatories, either oral or in writing.

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Key Mechanisms of aerosol desposition include:

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-inertial impaction -gavimetric sedimentation -Brownian Diffusion

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Inertial Impaction

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occurs when suspended particles in motion collide with and are deposited on a surface -this is the primary deposition mechanism for particles larger than 5um

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Sedimentation

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Occurs when aerosol particles settle out of suspension & are deposited owing to gravity. -The greater mass of the particle the faster it settles.

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Breath holding after inhalation of an aerosol increases.....

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The residence time for the particles in the lung and enhances distribution across the lungs and sedimentaiton

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Brownian Diffusion

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The primary mechanism for desposition of small particles (< 3um), mainly in the respiratory region where bulk gas flow ceases

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Large Paticles

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- are more susceptible to the force of gravity than smaller particles. -are more affected by the bombardment of molecules deposited by diffusion.

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Depth & Penetration & desposition of a particle in the respiratory tract vary...

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with size and tidal volume. - with this knowledge it may be possible to target aerosol deposition to specific areas of the lunh by using the proper particle size and breathing pattern.

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Aging

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-The process by which an aerosol suspension changes over time.

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How aerosol ages depends on:

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-composition of the aerosol -initial size of its particles -time in suspension -the ambient conditions to which it is exposed.

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Aersol particle can change size as a result of

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-evaporation or -hygroscopic water absorption.

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Determinant of Desposition (where a particle of any specific size is deposited)

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-particle size -inspiratory flow rate -flow pattern -respiratory rate -inhaled volume -ratio of inspiraton time to expiratory time. -breath holding.

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precise amount of drug delivered to the patient's airways can be measured in terms of:

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-patient's clinical response to aerosol drug therapy including the desired therapeutic effects and any unwanted adverse effects.

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Scintigraphy

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photograph showing the distribution and intensity of radioactivity in various tissues and organs after administration of a radiopharmaceutical.

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Hazards of aerosol drug therapy

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-(PRIMARY HAZARD) adverse reaction to the medication being adminitered. -infection -airway reactivity -systemic effects of bland aerosols -drug concentration -eye irritation.

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Risk for Caregivers and Bystanders

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risk the above hazards as a result of exposure to secondhand aerosol drugs.

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Infections from aerosol generators

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-nosicomial infections occur by spreading bacteria by the airborne route.

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The most common sources of bacteria are

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-patient secretions -contaminated solutions -caregiver's hands.

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procedures to help reduce contamination and infection associated with respiratory care equipment

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-nebulizers should be sterilized between patients -nebulizers should frequently be replaced with disinfected or sterile units or rinsed with sterile water (not tap water) and ait dried every 24 hours.

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Cold air and high-density aerosols can cause:

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Reactive bronchospasm and increased airway resistance.

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Monitoring for reactive bronchospasm should include:

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-peak flow measuremenrs or percentage forced expiratory volume in 1 second before and after therapy. -auscultation for for adventitious breath sounds -observation of the patient's breathing pattern and overall appearance. - most essential: communicating with the patient during therpay to determine the perceived work of breathing.

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Pulmonary and Systemic Effects Excess water can cause:

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overhydration

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oulmonary and systemic effects excess saline solution can cause

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hypernatremia

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Preliminary assessment should balance

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the need versus the risk of aerosol therapy

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appropriate airway clearance techniques should accompany

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any aerosol therapy designed to help mobilize secretions.

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Drug Concentration: what increases solute concentrations during nebulization

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eveporation heating baffling recycling of drug solutions

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Continuous Drug Delivery

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when nebulization occurs over extended periods this is the greatest effect.

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Eye irritation is caused by:

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aerosol asministered via face mask which causes the drug to be deposited in the eyes.

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Workplace exposure to aerosol may be detectable in

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-the plasma of bystanders & health care providers.

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Implementation of an occupational health and safety policy could include:

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-using systems that introduce less aerosol to the atmosphere -dry powder inhalers - filtering exhalation to contain aerosol -using environmental controls.

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Aerosol generators include

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-pMDIs (w/ or w/o spacers & holding chambers) -DPIs - Small and Large Volume (jet) nebulizers - Hand-Bulb atomizers -Ultrasonic Nebulizers -Vibrating Mesh Nebulizers

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Most commonly prescribed method of aerosol delivery in the US

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pMDI

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pMDI

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-used to administer bronchodilators, anticholinergics, & steroids - Are easy to use but commonly misused.

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Propellant

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something that propels or provides thrust, as the propellant in a metered dose inhaler

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pMDI is

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- a pressurized canister that contains the prescribed drug in a volatile propellant combined with a surfactant and dispersing agent.

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How pMDI works

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When the canister is inverted (nozzle down) and placed in its actuator, or "boot," the volatile suspension fills a metering chamber that controls the amount of drug delivered. Pressing down on the canister aligns a hole in the metering valve with the metering chamber. The high propellant vapor pressure quickly forces the metered dose out through this hole and through the actuator nozzle.

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The output volume of pMDIs range

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from 30-100mcl

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Chlorofluorocarbons (CFCs)

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gaseous chemical compounds that were originally used to power metered dose inmhalers but currently phased out of use

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Components of pMDI, including function of the metering valve

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...

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hydrofluoroalkane (HFA)

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the current gaseous chemical compound used to power metered dose inhalers.

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Before initial use and after storage, every pMDI should be

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-primed by shaking and actuating the device to atmosphere one to four times. -without the priming, the initial dose actuated from a new pMDI cansiter contains less active substance than subsequent acutations. - waste a single does when it has not been used for 4-6 hours

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Breath-Actuated Pressurized Metered Dose Inhaler

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-variation of a pMDI -incorporates a trigger that is activated during inhalation. -This trigger reduces the need for the patient or caregiver to coordinate MDI acutation with inhalaiton.

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Aerocount Autohaler

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-flow triggered pMDI designed to eliminate the need for hand-breath coordination by automatically triggering in response to the patient's inspiratory effort.24 To use the Autohaler, the patient cocks a lever on the top of the unit, which sets in motion a downward spring force. Using the closed-mouth technique, the patient draws through the mouthpiece. When the patient's flow rate exceeds 30 L/min, a vane releases the spring, which forces the canister down and triggers the pMDI. In the United States, the Autohaler is available only with pirbuterol, a bronchodilator similar to albuterol.

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Dose Counters

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- a serious limitation of pMDIs is the lack of a "counter" to indicate the number of doses remaining in the canister.

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Tail-off effect

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refers to variability in the amount of drug dispensed toward the end of the life of the canister.

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without a dose counter

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there is no viable method to determine remaining drug in a pMDI other manually keeping a log of every dose taken.

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Factors Affecting Pressurized Metered Dose Inhaler Performance & Drug Delivery

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-Temperature - Nozzle Size and Cleanliness - Priming - Timing od Actuation Intervals

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temperature

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Decreased temperature (<10° C) has been shown to decrease the output of CFC pMDIs.

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Nozzle Size and Cleanliness

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-as debris builds up on the nozzle or actuator orifice, the emitted dose is reduced.

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Priming

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-Shaking the device and releasing one or more sprays into the air when the pMDI is new or has not been used for a while. -done to mix the drug and the propellant -required to provide an adequate dose.

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Timing of Actuation Intervals

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-Manufacturers recommended 30 sec to 1 min between actuations. -Very rapid acutation of multiple puffs per breath reduces inhaled drug per puff

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Optimal Technique for use of MDI steps 1-5

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1.Warm the pMDI canister to hand or body temperature, and shake it vigorously. 2.Before first use of a new pMDI and when the pMDI has not been used for several days, prime the pMDI by pointing it into the air (away from people) and actuating. 3.Assemble the apparatus and uncap the mouthpiece, ensuring there are no loose objects in the device. 4. Open mouth technique*: Open your mouth wide, keeping tongue down. Hold the pMDI with the canister oriented downward and the outlet aimed at your mouth. Position the pMDI approximately 4 cm (two fingerbreadths) away from your mouth. 5.Closed mouth technique†: Place mouthpiece between lips, with tongue out of the path of the outlet.

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Optimal Technique for use of MDI steps 6-11

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6.Breathe out normally. 7.As you slowly begin to breathe in (<0.5 L/sec), actuate the pMDI. 8.Continue inspiration to total lung capacity. 9.Hold your breath for up to 10 seconds. Then relax and breathe normally. 10.Wait 1 minute between puffs. 11.Disassemble the apparatus, and recap the mouthpiece.

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Through preliminary patient instuction

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-can last 10-30 min -should include: - demonstration - Practice - Confirmation of patient performance

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Cold Freon Effect

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-occurs when the cold aerosol plume reaches the back of the mouth and the pati ent stops inhaling. -can be reduced by using a spacer or holding chamber.

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with ipatropium use

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the closed-mouth technique to avoiid spraying in the eyes.

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To avoid opportunistic oral yeast infection:

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rinse the mouth after steriod use.

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pMDI steroid aerosol impaction occurs deep in the hypopharynx, which cannot be easily rinsed with gargling for this reason...

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steroid pMDIs should not be used alone but always in combination with a spacer or valved holding chamber.

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Spacers and Valved holding Chambers

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-are pMDI accessory devices designed to reduce both oropharyngeal deposition and the need for hand-breath coordination. -all spacers add distance between the pMDI and the mouth, reducing the initial forward velocity of the pMDI droplets. -reduces foul taste.

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Determine Dose Left in Pressurized MDI with dose counters

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The user should29: 1.Determine how many puffs of drug the pMDI has when full. 2.Learn to read the counter display because each dose counter has a different way of displaying doses left in the canister. 3.Check the counter display to track the pMDI actuations remaining in the canister. 4.Reorder the pMDI when there are a few days of drug remaining. 5.Dispose of the pMDI properly, after the last dose is dispensed.

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Determine Dose Left in Pressurized MDI without dose counters

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The user should29: 1.Read the label to determine how many puffs of drug the pMDI has when full. 2.Calculate how long the pMDI will last by dividing the total number of puffs in the pMDI by the total puffs used per day. If the pMDI is used more often than planned, it will run out sooner. 3.Identify the date that the medication will run out, and mark it on the canister or on a calendar. 4.For drugs that are prescribed to be taken as needed, track the number of puffs of drug administered on a daily log sheet and subtract them from the remaining puffs to determine the amount of medication left in the pMDI. 5.Keep the daily log sheet in a convenient place, such as taped to the bathroom mirror. 6. Refill the pMDI prescription when there are a few days of use remaining in the pMDI. 7.Dispose of the pMDI properly when the last dose is dispensed.

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Valved holding chambers

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- protect the patient from poor hand-breath coordination, with exhaled gas venting to the atmosphere, allowing aerosol to remain in the chamber available to be inhaled with the next breath. -allow infants, small children, and adults who cannot control their breathing pattern to be treated effectively with pMDIs.

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Basic Concepts for spacer devices include:

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1. Small volume adapters 2. Open Tube Designs 3. Bag reservoirs 4. Valved holding chambers.

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Spacer

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-A spacer is a simple valveless extension device that adds distance between the pMDI outlet and the patient's mouth. -This distance allows the aerosol plume to expand and the propellants to evaporate before the medication reaches the oropharynx.

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Holding Chambers

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- allow the aerosol plume to develop and reduce oropharyngeal deposition. A holding chamber also incorporates one or more valves that prevent aerosol in the chamber from being cleared on exhalation. - provide less oropharyngeal deposition, higher respirable drug dosages, and better protection from poor hand-breath coordination than simple spacers.

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Holding Chambers vs Spacers

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holding chambers produce a finer, slower moving, more "respirable" aerosol with less impaction of drug in the oropharyngeal area (1% of dose) than simple spacers

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Optimal Technique for Use of Metered Dose Inhaler With A Valved Holding Chamber

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1.Warm the pMDI to hand or body temperature. 2.Assemble the apparatus, ensuring there are no objects or coins in the chamber that could be aspirated or obstruct outflow. 3.Hold the canister vertically, and shake it vigorously. Prime if necessary. 4.Place the pMDI in the holding chamber inlet, position chamber outlet in the mouth (or place the mask over nose and mouth), and encourage the patient to breathe through the mouth. Visually inspect for proper valve function. 5.With normal breathing, actuate the pMDI once and have the patient breathe through the device for three to seven breaths (three breaths for adults and seven breaths for infants).* 6.Allow 30 to 60 seconds between actuations.

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Holding chambers with masks are available for use in the care of infants, children, and adults.

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- allow effective administration of aerosol from a pMDI to patients who are unable to use a mouthpiece device (because of their size, age, coordination, or mentation). - Holding chambers are helpful in administration of pMDI steroids because deposition of the drug in the mouth is largely eliminated, and systemic side effects can be minimized.

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Cleaning of holding chambers and spacers

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should be cleaned regularly, typically monthly, as recommended by the manufacturer. Use of dilute liquid dishwashing soap, with or without rinsing, and allowing to air dry are recommended.

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Dry Powder Inhaler (DPI)

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- typically a breath-actuated dosing system. - patient creates the aerosol by drawing air though a dose of finely milled drug powder with sufficient force to disperse and suspend the powder in the air. - dispersion of the powder into respirable particles depends on the creation of turbulent flow in the inhaler. Turbulent flow is a function of the ability of the patient to inhale the powder with a sufficiently high inspiratory flow rate

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3 Categories of DPIs

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1. Unit-Dose DPI 2. Multiple unit-dose DPI 3. Multiple Dose Drug Reservoir DPI

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Unit-Dose DPIs

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dispense individual doses of drug from punctured gelatin capsules.

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Multiple Unit-Dose DPIs

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contain a case of four or eight individual blister packets of medication on a disk inserted into the inhaler.

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Optimal performance for each DPI occurs at

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- a specific inspiratory flow rate. - The fine-particle fraction of respirable drug from existing DPIs ranges from 10% to 60% of the nominal dose. - The higher the resistance or the greater the flow requirement of a DPI device, the more difficult it is for a compromised or young patient to generate inspiratory flow sufficient to obtain the maximum dose of drug from the device.

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In a humid Environment the emitted dose

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decreases

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If inhalation is not performed at the optimal inspiratory flow rate for a particular device,

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delivery to the lung decreases as the dose of drug dispensed decreases and the particle size of the powder aerosol increases

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Passive, or patient-driven, DPIs rely on

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the patient's inspiratory effort to dispense the dose.

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The most critical factor in using a passive DPI is the need for high inspiratory flow.

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- Patients must generate an inspiratory flow rate of at least 40 to 60 L/min to produce a respirable powder aerosol.

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DPIs SHOULD NOT BE USED FOR

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the management of acute bronchospasm.

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exhalation into the device before inspiration can result in

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- loss of drug delivery to the lung

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Optimal Technique for Use of a Dry Powder Inhaler

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1.Assemble the apparatus. 2.Load dose, keeping device upright. 3.Exhale slowly to functional residual capacity. 4.Seal lips around the mouthpiece. 5.Inhale deeply and forcefully (>60 L/min). A breath hold should be encouraged but is not essential. 6.Repeat the process until dose is completed. 7.Monitor adverse reactions. 8.Assess beneficial effects.

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Nebulizers

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generate aerosols from solutions and suspensions.

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three categories of nebulizers include

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(1) pneumatic jet nebulizers, (2) USNs, and (3) VM nebulizers.

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Small volume nebulizers (SVNs)

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most commonly used for medical aerosol therapy hold 5 to 20 ml of medication.

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Large volume nebulizers

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-also known as jet nebulizers, -hold up to 200 ml and may be used for either bland aerosol therapy or continuous drug administration.

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Most modern jet nebulizers are powered by

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-high-pressure air or oxygen (O2) provided by a portable compressor -compressed gas cylinder, - 50-psi wall outlet.

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a typical SVN is powered by

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a high-pressure stream of gas directed through a restricted orifice (the jet). The gas stream leaving the jet passes by the opening of a capillary tube immersed in solution. Because it produces low lateral pressure at the outlet, the high jet velocity draws the liquid up the capillary tube and into the gas stream, where it is sheared into filaments of liquid that break up into droplets. This primary spray produces a heterodisperse aerosol with droplets ranging from 0.1 to 500 µm.

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Determining Doses Left in the Dry Powder Inhaler

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...

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Factors Affecting Performance of SVN

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-Nebulizer Design -Gas Source: Wall, Cylinder, Compressor - Characteristics of Drug Formulation

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Nebulizer Design

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•Baffles •Fill volume •Residual drug volume •Nebulizer position •Continuous vs. intermittent nebulization •Reservoirs and extensions •Vents, valves, and gas entrainment •Tolerances in manufacturing within lots

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Gas Source: Wall, Cylinder, Compressor

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•Pressure •Flow through nebulizer •Gas density •Humidity •Temperature

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Characteristics of Drug Fomulation

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•Viscosity •Surface tension •Homogeneity

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Baffle

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is a surface on which large particles impact and fall out of suspension, whereas smaller particles remain in suspension, reducing the size of particles remaining in the aerosol.

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well-designed baffling systems decrease both

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the MMAD (size) and the GSD (range of sizes) of the generated aerosol.

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Residual Drug Volume

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-or dead volume, is the medication that remains in the SVN after the device stops generating aerosol and "runs dry."37 -The residual volume of a 3-ml dose can range from 0.5 to more than 2.2 ml, which can be more than two-thirds of the total dose. -Residual volume also depends on the position of the SVN.

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Droplet size and nebulization time are inversely proportional to gas flow through the jet.

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higher the flow of gas to the nebulizer, the smaller the particle size generated, and the shorter is the time required for nebulization of the full dose.

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Gas pressure and flow through the nebulizer affect particle size distribution and output.

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-the higher the pressure or flow, the smaller the particle size, the greater the output, and the shorter the treatment time. -Too low a gas pressure or flow can result in negligible nebulizer output.

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Concerns in the use of disposable nebulizers with compressors at home involve

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possible degradation of performance of the plastic device over multiple uses

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Failure to clean the nebulizer properly resulted in

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degradation of performance because of clogging of the Venturi orifice, reducing the output flow, and buildup of electrostatic charge in the device.

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Gas density affects both aerosol generation and delivery to the lungs.

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-The lower the density of a carrier gas, the less turbulent the flow (i.e., the lower the Reynolds number), resulting in less aerosol impaction. -The lower the density of a carrier gas, the less aerosol impaction occurs as gas passes through the airways, and the greater the deposition of aerosol in the lungs.

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Humidity and temperature can affect particle size and the concentration of drug remaining in the nebulizer.

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-evaporation of water and adiabatic expansion of gas can reduce the temperature of the aerosol to 10° C less than ambient temperature. -This cooling may increase solution viscosity and reduce the nebulizer output, while decreasing particle MMAD.40 -Aerosol particles entrained into a warm and fully saturated gas stream increase in size.

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Four categories of jet SVNs include

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(1) continuous nebulizer with simple reservoir, (2) continuous nebulizer with collection reservoir bag, (3) breath-enhanced nebulizer, and (4) breath-actuated nebulizer

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Most Commonly Used SVN

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Constant output design

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In neonates and infants,

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given the small minute volumes and small airways with increased impaction and reduced sedimentation, deposition can be only 0.5%.

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A reservoir on the expiratory limb of the nebulizer

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conserves drug aerosol

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Many types of disposable SVNs are packaged with a 6-inch (15-cm) piece of aerosol tubing to be used as a reservoir

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This may increase inhaled dose by 5% to 10% or increase the inhaled dose from 10% to approximately 11% with the reservoir tube.

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Continuous Small Colume Nebulizers with Collection Bags

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- hold the aerosol generated during exhalation and allow the small particles to remain in suspension for inhalation with the next breath, while larger particles rain out, attributed to a 30% to 50% increase in inhaled dose

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Breath-Enhanced Nebulizers

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-nebulizers that entrain room air in direct relationship to the inspiratory flow of the patient -generate aerosol continuously, using a system of vents and one-way valves to minimize aerosol waste

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Breath-Actuated Nebulizers

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-aerosol device that is responsive to the patient's inspiratory effort and reduces or eliminates aerosol generation during exhalation -generate aerosol only during inspiration. -eliminates waste of aerosol during exhalation and increases the delivered dose threefold or more over continuous and breath-enhanced nebulizers.

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AeroEclipse

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-A unique, spring-loaded, one-way valve design draws the jet to the capillary tube during inspiration and causes nebulization to cease when the patient's inspiratory flow decreases below the threshold or the patient exhales into the device. -Expiratory pressure on the valve at the initiation of exhalation moves the nebulizer baffle away from its position directly above the jet orifice, reduces the pressure, and stops aerosolization

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Technique for using a SVN

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-Slow inspiratory flow optimizes SVN aerosol deposition. -deep breathing and breath holding during SVN therapy do little to enhance deposition over normal tidal breathing. -As long as the patient is mouth breathing, there is little difference in clinical response between therapy given by mouthpiece and therapy given by mask

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The CDC recommends that nebulizers

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be cleaned and disinfected, or rinsed with sterile water, and air dried between uses.

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Large volume jet nebulizers

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- used to deliver aerosolized drugs to the lung. - particularly useful when traditional dosing strategies are ineffective in the management of severe bronchospasm.

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A potential problem with continuous bronchodilator therapy (CBT)

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is increase in drug concentration. Patients receiving CBT need close monitoring for signs of drug toxicity (e.g., tachycardia and tremor).

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Another special-purpose large volume nebulizer

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-a small particle aerosol generator (SPAG) - The SPAG was manufactured by ICN Pharmaceuticals specifically for administration of ribavirin (Virazole) to infants with respiratory syncytial virus infection. -incorporates a drying chamber with its own flow control to produce a stable aerosol.

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SPAG

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duces medical gas source from the normal 50 pounds per square inch gauge (psig) line pressure to 26 psig with an adjustable regulator. The regulator is connected to two flowmeters that separately control flow to the nebulizer and drying chamber. The nebulizer is located within the glass medication reservoir, the fluid surface and wall of which serve as primary baffles. As it leaves the medication reservoir, the aerosol enters a long, cylindrical drying chamber. Here the second (separate) flow of dry gas is entrained, reducing particle size by evaporation, creating a monodisperse aerosol with an MMAD of 1.2 to 1.4 µm. Nebulizer flow should be maintained at approximately 7 L/min with total flow from both flowmeters not less than 15 L/min. The latest model operates consistently even with back pressure and can be used with masks, hoods, tents, or ventilator circuits.

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Optimal Technique for Using a SVN 1-5

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1.Assess the patient for need (clinical signs and symptoms, breath sounds, peak flow, %FEV1) 2.Select mask or mouthpiece delivery (nose clips may be needed with mouthpiece). 3.Use conserving system (thumb port, breath actuator or reservoir) if indicated. 4.Place drug in the nebulizer. If using a multidose vial, add saline to approved dose volume (per drug label). 5.Set gas flow to nebulizer at 6 to 10 L/min (per manufacturer label).

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Optimal Technique for Using a SVN 6-10

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6.Coach patient to breathe slowly through the mouth at normal VT. 7.Continue treatment until nebulizer begins to sputter. 8.Rinse the nebulizer with sterile water and air dry, or discard, between treatments. 9.Monitor patient for adverse response. 10.Assess outcome (change in peak flow, %FEV1).

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Two specific problems are associated with SPAG use to deliver ribavirin.

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1. Caregiver exposure to the drug aerosol. 2.Drug precipitation can jam breathing valves or occlude the ventilator circuit.

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The Problem of Drug precipitation can jam breathing valves or occlude the ventilator circuit cn be overcome by:

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(1) placing a one-way valve between the SPAG and the circuit and (2) filtering out the excess aerosol particles before they reach the exhalation valve, changing filters frequently to avoid increasing expiratory resistance.

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Guidelines for Use of Aerosol Devices in the Care of Infants and Children

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Device Age Group SVN Neonate to all ages Valved chamber with mask Neonate/infant/toddler Valved chamber with mouthpiece >3 years pMDI alone >4 years Breath-actuated Neb >4 years DPI ?4 years

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Spontaneous breathing in all patients, including pediatric and neonatal patients, results in

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greater deposition of aerosol from an SVN than occurs with positive pressure breaths (e.g., intermittent positive pressure ventilation). This mode of ventilation reduces aerosol deposition more than 30% compared with the effect of spontaneously inhaled aerosols

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Regardless of the device used, the clinician must be aware of

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the limitations of aerosol drug therapy. First, depending on the device and patient, 10% or less of drug emitted from an aerosol device may be deposited in the lungs (Figure 36-30). As indicated in Box 36-7, additional reductions in lung deposition can occur in many clinical situations that sometimes necessitate the use of higher dosages.

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Clinical efficacy varies according to

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both patient technique and device design. For these reasons, the best approach to aerosol drug therapy is to use an assessment-based protocol that emphasizes individually tailored therapy modified according to patient response.

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Factors Associated With Reduced Aerosol Drug Deposition in the Lung

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Mechanical ventilation • Artificial airways • Reduced airway caliber (e.g., infants and children) • Severe airway obstruction • High gas flows • Low minute volumes • Poor patient compliance or technique • Limitation of specific delivery device

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Careful, ongoing patient assessment is

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is key to an effective bronchodilator therapy protocol. To guide practitioners in implementing effective bedside assessment, the AARC has published Clinical Practice Guideline: Assessing Response to Bronchodilator Therapy at Point of Care.

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conventional spirometry

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remains the standard for determining bronchodilator response.

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the AARC recommends that when monitoring trends,

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the same unit be used for a given patient and that the patient's range be reestablished if a different flowmeter is used

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Sole dependence on tests of expiratory airflow for assessing patient response to therapy is

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unwise because not all patients can perform these maneuvers. Other components of patient assessment useful in evaluating bronchodilator therapy include patient interviewing and observation, measurement of vital signs, auscultation, blood gas analysis, and oximetry.

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Restlessness, diaphoresis, and tachycardia also may indicate

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severity of airway obstruction but must not be confused with bronchodilator overdose

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In terms of breath sounds, a decrease in wheezing accompanied by an overall decrease in the intensity of breath sounds indicates

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worsening airway obstruction or patient fatigue. Improvement is indicated when wheezing decreases and the overall intensity of breath sounds increases.

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All patients with acute airway obstruction should be monitored for oxygenation status with

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pulse oximetry. This value can be used in conjunction with observational assessment to titrate the level of inspired O2 given to the patient (see Chapter 35). Arterial blood gases are not essential for determining patient response to bronchodilator therapy but may be needed for patients in severe distress to assess for hypercapnic respiratory failure

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Poor patient response to bronchodilator therapy often occurs because

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an inadequate amount of drug reaches the airway. To determine the "best" dose for patients with moderate obstruction, the respiratory therapist (RT) should conduct a dose-response titration.

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A simple albuterol dose-response titration involves

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giving an initial 4 puffs (90 mcg/puff) at 1-minute intervals through a pMDI with a holding chamber. After 5 minutes, if airway obstruction is not relieved, the RT gives 1 puff per minute until symptoms are relieved, heart rate increases to more than 20 beats/min, tremors increase, or 12 puffs are delivered. The best dose is the dose that provides maximum relief of symptoms and the highest PEFR without side effects.

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Frequency of Assessment of Bronchodilator Therapy For Patient with an Acute Disorder Who is in Unstable Condition

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• Whenever possible, perform a full assessment and obtain a pretreatment baseline. • Assess and document all appropriate variables before and after each treatment (breath sounds, vital signs, side effects during therapy, and PEFR or FEV1). • The frequency with which physical examination and PEFR or FEV1 are repeated should be based on the acuteness of the disorder and the severity of the patient's condition. • SpO2 should be monitored continuously, if possible. • Assessment should continue as dosages are changed to optimize patient response (e.g., if an asthmatic patient achieves 70% to 90% of predicted or "personal best" or becomes symptom-free).

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Frequency of Assessment of Bronchodilator Therapy For Stable Patient

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• In the hospital, PEFR should be measured initially before and after each bronchodilator administration. Thereafter, twice-daily determinations may be adequate. • In the home, PEFR ideally should be measured three or four times a day: on rising, at noon, between 4 PM and 7 PM, and at bedtime. • For a stable COPD patient at home, measuring PEFR twice a day may be adequate. • Patients with asthma should adjust the frequency of PEFR measurement according to the severity of symptoms. • PEFR levels before and after bronchodilator use, medication dose, date and time, and dyspnea score should be documented. • The patient should be reevaluated periodically for response to therapy

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Practitioner demonstration followed by repeated patient return demonstration is a

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must and should be done frequently, such as with each office or clinic visit.

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Every drug approved for inhalation to date has been designed for and tested in

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populations of ambulatory patients with moderate disease. As patients with lung disease become acutely and critically ill, the approved label doses, frequency of administration, and devices may not be practical or effective, especially for treatment of patients requiring ventilatory support. In such cases, clinicians may explore and consider nonstandard methods (doses, frequency, and devices) for administration of approved inhaled drugs to patients in the acute care environment, known as off-label use

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Another type of off-label use involves drugs that

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have not been approved for inhalation, ranging from heparin to certain antibiotics. Although physicians may order such drugs via inhalation, the risk to the patient and institution is greater when the administration of such drugs via inhalation has not been thoroughly studied. All forms of off-label use should be avoided when approved and viable alternatives exist. Likewise, off-label administration should always be backed by appropriate departmental or institutional policies and procedures.

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Patients in the emergency department with severe exacerbation of asthma or acute bronchospasm often have been taking standard doses of their bronchodilators for

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24 to 36 hours before admission without response. Giving nebulizer treatments with standard bronchodilator doses and repeating the treatments until the symptoms are relieved can require hours of staff time. Administering higher doses of albuterol in short time frames can be accomplished by nebulization of undiluted albuterol (8 to 20 breaths) or by protocol titration with a pMDI and holding chamber (up to 12 puffs).

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Pediatric Asthma Score

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SCORE Indicator 0 1 2 PaO2 >70 mm Hg (air) <70 mm Hg (air) 94% (air) <94% (air) <94% (40% O2) Cyanosis No Yes Yes Breath sounds Equal Unequal Absent Wheezing None Moderate Marked Accessory muscle use None Moderate Marked Level of consciousness Alert Agitated or depressed Comatose

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After CBT is started, the patient is carefully assessed every

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30 minutes for the first 2 hours and thereafter every hour. A positive response is indicated by an increase in PEFR of at least 10% after the first hour of therapy. The goal is at least 50% of the predicted value. For small children, improved oxygenation (oxygen saturation by pulse oximeter [SpO2] >92% on room air) with evidence of decreased work of breathing indicates a favorable response. Once the patient "opens up," intermittent SVN administration is resumed, or a pMDI dose-response assessment is conducted.

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Four primary forms of aerosol generator are used to deliver aerosols during mechanical ventilation

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SVN, USN, VM nebulizer, and pMDI with third-party adapter

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Factors Affecting Aerosol Drug Delivery During Mechanical Ventilation

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Category Factor Ventilator-related Mode of ventilation VT Respiratory rate Duty cycle Inspiratory waveform Breath-triggering mechanism Circuit-related Size of endotracheal tube Type of humidifier Relative humidity Density and viscosity of inhaled gas Device-related MDI Type of spacer or adapter used Position of spacer in circuit Timing of MDI actuation SVN Type of nebulizer used Fill volume Gas flow Cycling: inspiration vs. continuous Duration of nebulization Position in circuit Patient-related Severity of airway obstruction Mechanism of airway obstruction Presence of dynamic hyperinflation Spontaneous ventilation Disease process Drug-related Dose Aerosol particle size Targeted site for delivery Duration of action

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Additional techniques can be used for mechanically ventilated patients because

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(1) a change in the differences between peak and plateau pressures (the most reliable indicator of a change in airway resistance during continuous mechanical ventilation) can be measured, (2) automatic positive end expiratory pressure levels may decrease in response to bronchodilators (see Chapter 41), and (3) breath-to-breath variations make measurements more reliable when the patient is not actively breathing with the ventilator.70

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Optimal Technique for Aerosolized Drug Delivery to Mechanically Ventilated Patients

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1 Review order, identify the patient, gather equipment, and assess the need for bronchodilators. 2 Clear the airways as needed, by suctioning the patient as needed. 3 If using a circuit with heat and moisture exchanger (HME), remove HME from between the aerosol generator and the patient. 4 If using heated humidifier, do not turn off or disconnect before or during treatment. 5 Assemble equipment (tubing, nebulizer, circuit adapter). 6 Fill the nebulizer with recommended volume and medication per physician order and label. 7 Place adapter in the inspiratory limb, 6 inches from the "wye," and connect aerosol generator. 8 Turn off or minimize bias flow during treatment. 9 Connect the nebulizer to a gas or power source, as appropriate. 10a For jet nebulizer (including SVN): Use gas source on ventilator to synchronize nebulization with inspiration, if available; otherwise, set gas flow 2 to 10 L/min as recommended on nebulizer label, and adjust ventilator volume or pressure limit and alarms to compensate for added flow and volume. 10b For USN and VM nebulizer: Attach power source and cable from controller. 10c For pMDI: Shake canister and connect to spacer or adapter; actuate at beginning of inspiration. 11 Observe aerosol cloud for adequate aerosol generation during nebulization. 12 After appropriate dose is administered, remove aerosol generator from the ventilator circuit. 13 Reconnect HME, as appropriate. 14 Return ventilator settings and alarms to previous values. 15 Ensure there is no leak in the ventilator circuit. 16 Rinse the nebulizer with sterile or distilled water, shake off excess water, and allow to air dry. 17 Store aerosol device in a clean, dry place. 18 Monitor heart rate, SpO2, blood pressure, and patient-ventilator synchronization. 19 Monitor the patient for adverse response. 20 Assess the airway, and suction as needed; document findings.

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Aerosol administration by a VM nebulizer has been estimated to deliver greater than

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10% deposition in adults and infants without the addition of gas into the ventilator circuit. The low residual drug volume and small particle size are associated with higher efficiency. Similar to the USN, the VM nebulizer does not add gas flow into the ventilator circuit, so ventilator parameters and alarms do not need to be adjusted before, during, or after nebulization. In contrast to jet SVNs and USNs, the medication reservoir of the VM nebulizer is above the circuit and separated from the ventilator tubing by the mesh, reducing the risk of retrograde contamination of medication in the reservoir from the ventilator circuit. Because of the nature of the mesh, the reservoir can be opened and medication can be added to the nebulizer without creating a perceptible leak during ventilation.

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Direct pMDI actuation by simple elbow adapters typically results in the least

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pulmonary deposition, with most of the aerosol impacting in either the ventilator circuit or the tracheal airway. Higher aerosol delivery percentages occur only when an actuator or spacer is placed in-line in the ventilator circuit. These spacers allow an aerosol "plume" to develop before the bulk of the particles impact on the surface of the circuit or endotracheal tube. The result is a more stable aerosol mass that can penetrate beyond the artificial airway and be deposited mainly in the lung. This situation leads to a better clinical response at lower doses

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With continuous or bias flow through the ventilator circuit, the delivery is reduced

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as flow increases, whereas placement of a VM nebulizer near the ventilator increases delivery

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Noninvasive ventilation may be administered with

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standard and bilevel ventilators. Bilevel ventilators often use a flow turbine, with a fixed valve or leak in the circuit that permits excess flow to vent to atmosphere. Placement of the aerosol generator between the leak and the patient's airway seems to provide the highest aerosol delivery efficiency.74 A VM nebulizer delivers a greater fine-particle dose than an SVN during noninvasive ventilation presumably because of the lower residual drug volume and lower total flow in the circuit.

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Intrapulmonary percussive ventilation provides

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high-frequency oscillation of the airway while administering aerosol particles. During intrapulmonary percussive ventilation, the aerosol generator should be placed in the circuit as close to the patient's airway as practical.

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When used in conjunction with high-frequency oscillatory ventilation, administration of albuterol sulfate via a VM nebulizer placed between the ventilator circuit and the patient airway has been reported to

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deliver greater than 10% of dose to both infants and adults.79,80 A pMDI with adapter placed immediately proximal to the endotracheal tube achieved similar results in adult patients ventilated via high-frequency oscillatory ventilation.81

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Drugs for nebulization that escape from the nebulizer into the atmosphere or are exhaled by the patient can be inhaled by

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anyone in the vicinity of the treatment. The risk imposed by this environmental exposure is clear and is associated with a range of drugs and patients with infectious disease. Pentamidine and ribavirin were associated with health risks to health care providers even when used in conjunction with filters on exhalation ports of nebulizers, containment and scavenger systems, and high-efficiency particulate air (HEPA) filter hoods and ventilation systems (Figure 36-36).

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Continuous pneumatic nebulizers produce the greatest amount of

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secondhand aerosol, with most (60%) of the aerosol produced passing directly into the environment. The Respirgard II (Vital Signs, Totowa, NJ) nebulizer was developed for administration of pentamidine, adding one-way valves and an expiratory filter to contain aerosol that is exhaled and not inhaled. Breath-actuated nebulizers, DPIs, and pMDIs tend to generate less secondhand aerosol.

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The greatest occupational risk for RTs has been associated with

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the administration of ribavirin and pentamidine. Conjunctivitis, headaches, bronchospasm, shortness of breath, and rashes have been reported among individuals administering these drugs.83 Patients given aerosolized ribavirin or pentamidine must be treated in a private room, booth, or tent or at a special station designed to minimize environmental contamination.

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When ribavirin or pentamidine is given, the treatment is provided in a

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a private room. The room should be equipped for negative pressure ventilation with adequate air exchanges (at least six per hour) to clear the room of residual aerosols before the next treatment. HEPA filters should be used to filter room or tent exhaust, or the aerosol should be scavenged to the outside.

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Booths or stations should be used for

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sputum induction and aerosolized medication treatments given in any area where more than one patient is treated. The area should be designed to provide adequate airflow to draw aerosol and droplet nuclei from the patient into an appropriate filtration system or an exhaust system directly to the outside. Booths and stations should be adequately cleaned between patients

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A variety of booths and specially designed stations are available for delivery of pentamidine or ribavirin

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The Emerson containment booth (Figure 36-37) is an example of a system that completely isolates the patient during aerosol administration. The AeroStar Aerosol Protection Cart (Respiratory Safety Systems, San Diego, CA) is a portable patient isolation station for administration of hazardous aerosolized medication. It has been used during sputum induction and for pentamidine treatment. The patient compartment is collapsible with a swing-out counter and three polycarbonate walls. Captured aerosols are removed with a HEPA filter. A prefilter is used to retain larger dust particles and to prevent early loading of the more expensive HEPA filter.

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Filters and nebulizers used in treatments with pentamidine and ribavirin should be treated as

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hazardous wastes and disposed of accordingly. Goggles, gloves, and gowns should be used as splatter shields and to reduce exposure to medication residues and body substances. Staff members should be screened for adverse effects of exposure to the aerosol medication. The risks and safety procedures should be reviewed regularly.

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Personal protective equipment is recommended when

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caring for any patient with a disease that can be spread by the airborne route.84 The greatest risk is communication of tuberculosis or chickenpox.

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The primary hazard of aerosol drug therapy is

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an adverse reaction to the medication being administered. Other hazards include infection, airway reactivity, systemic effects of bland aerosols, and drug reconcentration

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For targeting aerosols for delivery to the upper airway (nose, larynx, trachea), particles in the 5- to 20-µm MMAD range are used; for the lower airways,

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2- to 5-µm particles are used; and for the lung parenchyma (alveolar region), 1- to 3-µm particles are used.

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Where aerosol particles are deposited in the respiratory tract depends on their

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size, shape, and motion and on the physical characteristics of the airways. Key mechanisms causing aerosol deposition include inertial impaction, sedimentation, and brownian diffusion.

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Hand-bulb atomizers and nasal spray pumps are used to

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administer sympathomimetic, anticholinergic, antiinflammatory, and anesthetic aerosols to the upper airway, including nasal passages, pharynx, and larynx (see also Chapter 32). These agents are used to manage upper airway inflammation and rhinitis, to provide local anesthesia, and to achieve systemic effects.

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The USN uses a piezoelectric crystal to

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generate an aerosol. The crystal transducer converts an electrical signal into high-frequency (1.2- to 2.4-MHz) acoustic vibrations. These vibrations are focused in the liquid above the transducer, where they disrupt the surface and create oscillation waves (Figure 36-25). If the frequency of the signal is high enough and its amplitude strong enough, the oscillation waves form a standing wave that generates a geyser of droplets that break free as fine aerosol particles.

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Large volume USNs (used mainly for bland aerosol therapy or sputum induction) incorporate

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air blowers to carry the mist to the patient (see Chapter 35). Low flow through the USN is associated with smaller particles and higher mist density. High flow yields larger particles and less density. In contrast to jet nebulizers, the temperature of the solution placed in a USN increases during use. As the temperature increases, the drug concentration increases, as does the likelihood of undesired side effects.

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Small volume USNs have been promoted for administration of a wide variety of formulations ranging from

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bronchodilators to antiinflammatory agents and antibiotics

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Two types of VM nebulizers, active and passive, are available commercially.

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Active VM nebulizers use a dome-shaped aperture plate, containing more than 1000 funnel-shaped apertures. This dome is attached to a plate that is also attached to a piezoceramic element that surrounds the aperture plate. Electricity applied to the piezoceramic element causes the aperture plate to be vibrated at a frequency of approximately 130 kHz (or one-tenth that of a USN), moving the aperture plate up and down by 1 µm or 2 µm, creating an electronic micropump. The plate actively pumps the liquid through the apertures, where it is broken into fine droplets. The exit velocity of the aerosol is low (<4 m/sec), and the particle size can range from 2 to 3 µm (MMAD), varying with the exit diameter of the apertures (Figure 36-26). Examples of an active VM nebulizer include the Aeroneb Go, Pro, and Solo nebulizers (Aerogen, Inc, Galway, Ireland) and the eFlow (Pari, Midlothian, VA). An active VM nebulizer can provide nebulization with single drops 15 mcl of formulations containing small and large molecules, suspensions, microsuspensions, and liposomes. Passive VM nebulizers use a mesh separated from an ultrasonic horn by the liquid for nebulization. A piezoelectric transducer vibrates the ultrasonic horn, which pushes fluid through the mesh. Passive VM nebulizers include the NEU-22 (Omron, Kyoto, Japan) and the I-Neb (Philips Respironics, Murraysville, PA).

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The Respimat soft mist inhaler (Boehringer, Ingelheim am Rhein, Germany) is a

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small hand-held inhaler that uses mechanical energy to create an aerosol from liquid solutions to produce a low-velocity spray (10 mm/sec) that delivers a unit dose of drug in a single actuation. To operate the device, patients twist the body of the device to load an internal spring, place the mouthpiece of the Respimat between the lips, and press a button to release the drug through a uniblock to create spray, which is released over 1.1 to 1.4 seconds, depending on the formulation configuration. The Respimat device requires hand-breath coordination on the part of the patient, as does a pMDI, but because of the longer spray time, it seems more likely to get a greater percent of emitted dose despite coordination issues. Because of the small particle size and low-velocity spray, pulmonary deposition of 40% is independent of inspiratory flows with oral deposition (40%) half the oral dose used with most pMDIs and DPIs (80%). The Respimat is currently available with several drugs in Europe and is slated for introduction with tiotropium in the United States.54

Egan’s Chapter 36 Aerosol Therapy – Flashcards

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