Aerosales en Vm 2015

7/21/2019 Aerosales en Vm 2015

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Aerosol Drug Delivery During MechanicalVentilation: Devices, Selection, Delivery Technique, and

Evaluation of Clinical Response to TherapyArzu Ari, PhD, RRT, PT, CPFT, FAARC,

and James B. Fink, PhD, RRT, FAARC, FCCP

Abstract: Aerosolized medications are increasingly being used inventilator-dependent patients. There are many issues with selection anduse of aerosol delivery devices in patients receiving ventilator support.The purpose of this paper is to explain potential problems associatedwith aerosol devices, delivery technique, and clinical response totherapy to assure patient well-being and safety during inhalation

therapy.

Key Words: nebulizers, metered-dose inhalers, aerosols, drug deliv-

ery, optimum technique, mechanical ventilation

(Clin Pulm Med 2015;22:7986)

Many formulations, both solutions and suspension, such asshort-acting bronchodilators, anticholinergics, cortico-steroids, mucokinetics, antibiotics, antivirals, prostanoids,surfactants, diuretics, anticoagulants, proteins, and peptides,have been used for the treatment of mechanically ventilated

patients.1 Drug delivery to patients receiving ventilator support

has been associated with low delivery efficiency and highvariability in dosing. There are many issues with deviceselection and use of each aerosol device during mechanicalventilation. Standard of practice is still far away from anoptimum technique that should be utilized during inhalationtherapy to mechanically ventilated patients. Therefore, the

purpose of this paper is to identify and explain potentialproblems associated with aerosol devices, delivery technique,

and clinical response to therapy to assure optimal patientbenefit, well-being, and safety during inhalation therapy.

AEROSOL DEVICESTwo types of aerosol devices are used for aerosol drug

delivery to ventilator-dependent patients: (1) nebulizers and (2)pressurized metered dose inhalers (pMDIs). Types of nebu-lizers used for the treatment of intubated and mechanicallyventilated patients are jet nebulizers (JNs), ultrasonic nebu-lizers (UNs), and vibrating mesh nebulizers (VMNs).Figure 1shows illustrations of aerosol devices used for the treatment ofventilator-dependent patients.

NebulizersJNs have been commonly used for aerosol drug delivery

during mechanical ventilation since the advent of modernmechanical ventilation in the mid-1950s. These relativelyinexpensive nebulizers are operated using 2 to 10 L/min ofcompressed gas and cause entrainment often resulting in the

injection of additional gas into the ventilator circuit. This canlead to an increase in volumes and pressures delivered duringmechanical ventilation, especially in smaller patients, if theventilator does not compensate for nebulizer gas flow enteringthe circuit. Therefore, clinicians may be well advised to adjustventilator parameters during aerosol administration and returnthe ventilator to pretreatment levels after the completion oftherapy. During operation of JNs, larger particles tend todeposit on the baffles and walls of the nebulizer. Then, theyreturn to the reservoir to be renebulized causing an evaporativeeffect that increases concentration of medication over time,especially with continuous nebulization. Contamination is arisk associated with the use of JNs during mechanical ven-tilation because the JN reservoir is in a dependent position to

and in direct contact with the ventilator circuit. This allowsfluids, secretions, and pathogens in condensate that forms inthe circuit to drain into the reservoir of the nebulizer where itcontaminates the medication, resulting in the production ofcontaminated aerosol which is then delivered to the patient.

Unfortunately these least expensive aerosol generatorstend to be the least efficient for aerosol delivery duringmechanical ventilation. As JNs have large residual volumes ofup to 2 mL, a substantial portion of drugs placed in the neb-ulizer stays in the reservoir and cannot be delivered to ven-tilator-dependent patients. Consequently, with typical dosevolumes of 3 mL, the efficiency of JNs is much less than otheraerosol device options, which have lower residual drugremaining in the nebulizer at the conclusion of dosing.

Whereas aerosol delivery of JNs ranges from 2% to 5.4%during mechanical ventilation, delivery efficiency of VMNs,UNs, and pMDIs are 8.7% to 33.3%, 8.7% to 17% and 2.5% to

From the Division of Respiratory Therapy, College of Health and HumanSciences, Georgia State University, Atlanta, GA.

The study was conducted in the Aerosol Research Lab at Georgia StateUniversity.

Disclosure: J.B.F. serves as a consultant to the biotech industry. His clientsinclude Aerogen, Ansun, Aridis, Bayer, Dance Biopharm, Parion,

Quark, and WHO. He currently serves as Chief Clinical Officer forAerogen, and Senior Fellow, Aerosol Device Development for DanceBiopharm. He is an adjunct Professor to the Respiratory Care Programsat Georgia State in Atlanta, and Rush Medical School in Chicago. Inaddition, he has a grant from the Brazilian government to serve as aScholar without Borders working with the Cardiopulmonary Physi-otherapy Department at Federale University of Pernumbuco in Recife,Brazil. In all 3 academic programs he supervises graduate students inAerosol Research. He has involvement with the following products:Aeroneb Pro, Solo, Go and Lab (Aerogen), PPDS system for Amikacin(Bayer), Dance 501 Inhaler for insulin (Dance Biopharm), Prototypenasal delivery system (Parion), and Measles vaccine delivery systemfor mass campaigns in third world (WHO). A.A. declares that there areno conflicts of interest.

Address correspondence to: Arzu Ari, PhD, RRT, PT, CPFT, FAARC,Division of Respiratory Therapy, College of Health and Human Sci-ences, Georgia State University, P.O. Box 4019, Atlanta, GA 30302-

4019. E-mail: [email protected] r 2015 Wolters Kluwer Health, Inc. All rights reserved.ISSN: 1068-0640/15/2202-0079DOI: 10.1097/CPM.0000000000000085

CRITICAL CARE/RESPIRATORY CARE

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mailto:[email protected]:[email protected]


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17%, respectively, in a heated humidified ventilator circuit,dependent on position of the aerosol generator.

The insertion and removal of nebulizers from the ven-tilator circuit during mechanical ventilation is often associatedwith a break in the circuit with an interruption of airway

pressure and ventilation, which may cause derecruitment ofthe lung resulting in lower lung volumes for an hour or longer.In addition, breaking the circuit to insert or remove a JN,allows contaminated fluids and secretion to be released into theatmosphere, posing a risk to the environment, health care

providers, and other patients in the vicinity. Spring-loadedvalved T adapters may be used for the attachment of JNs to theventilator circuit to reduce interruption of ventilation when theJN is attached or removed. Thus, they can reduce or eliminateloss of pressure in the ventilator circuit during placement orremoval of a JN while eliminating nebulizer contaminationfrom the fluids and secretions retained in the circuit. However,the valve system in these devices act as an additional baffle foraerosol leaving the nebulizer and have been associated with

reduction of available aerosol to the patient by as much as 30%compared with the standard open T adapter. In a situationwhere deposition from a JN is as low as 3% of total dose, this30% reduction is substantial.

UNs are available for use during mechanical ventilation,but are not widely used. They tend to be expensive, bulky, andgenerate more heat than other aerosol generators, which maycause degradation of heat-sensitive materials such as proteins.UNs may produce particles smaller than suspension, reducingactual drug output, which may not be detectable by observingthe output of the nebulizer. Therefore, UNs are not recom-mended for administration of suspension. The residual volumeof UNs ranges from 0.8 to 1.2 mL. Despite their relativelylarge residual drug volumes, UNs tend to be more efficient

than JNs, perhaps because they do not introduce a secondarygas flow into the ventilator circuits. Like JNs, UN drug res-ervoirs and aerosol generators are position dependent to theventilator circuit, allowing contaminated condensate to drainfrom the circuit into the reservoir.

VMNs have been associated with 3- to 5-fold higher drugdelivery efficiency than JNs with similar to greater efficiencythan UNs. This may be due in part to the smaller residualvolumes (< 0.2mL) than other nebulizers and the lack ofadditional gas added to the circuit of ventilator-dependent

patients. VMNs are the delivery of choice when clinicians needto deliver expensive formulations and precise dosing is needed.Contamination with pathogens and condensation in the circuitis less of an issue with VMNs because they are positioned

superior to the ventilator circuit during therapy and theirmedication reservoir is separated from the ventilator circuit bythe physical barrier of the mesh membrane. While VMNs are

powered by battery or electricity, they tend to be small and lessnoisy than JNs. As VMNs do not add heat to the medication,risk of denaturation of proteins is minimal. With only a single

pass of medication through the aerosol generating mesh, drugconcentration is not altered over time. More viscous drugs may

reduce the rate of aerosol output, requiring longer treatmenttimes. Theoretically, large suspensions may clog the pores ofVMNs over time, but such incidents have not been reported.Despite many advantages compared with other nebulizers, thecost of VMN is an issue, being 20-fold greater than JNs.VMNs are available as a single patient multidose disposablenebulizer and as a more expensive multipatient, autoclavabledevice. For the reusable VMNs cleaning should be gentle withno direct contact to the mesh, to prevent damage.

Pressurized Metered Dose InhalersFor the past 2 decades, pMDIs have been widely used for

aerosol drug delivery to mechanically ventilated patients.pMDIs are small, single patient, multiple dose, disposable

devices that provide easy operation, short treatment time, andconsistent dosing. The pMDI consists of a canister containing

propellants, drugs, and excipients with a metering valve thatreleases a precise quantity of drug and propellant with eachactuation (manually compressing the nozzle of the canister intothe seat of the actuator to release a metered dose of drug and

propellant). Virtually all pMDIs are designed for use withambulatory patients, with an actuator mouthpiece that is opento atmosphere. Consequently, for use in a closed ventilatorcircuit, a third-party designed spacer or low-volume adapterwith a port to accept the nozzle of the canister and spray nozzleto disperse the emitted aerosol within the circuit must be used.Aerosol delivery efficiency varies widely with the shape, size,and design of these adapters. The type of adapter or spacer used

with pMDI affects aerosol drug delivery during mechanicalventilation. Researchers report that bidirectional low-volumeadapters are more efficient than unidirectional adapters,whereas cylindrical/chamber spacers provide 2 to 6 timesmore drug delivery than unidirectional and bidirectional low-volume adapters.24 Collapsible chamber-type spacers reduce

both the volume of the circuit and the formation of condensatein the spacer chamber between treatments. In addition, col-lapsible chamber-type spacers prevent circuit disconnection andminimize the risk of ventilator-associated pneumonia.

For effective drug delivery, the pMDI should be placedproximal to the patient airway and must be actuated manually atthe beginning of inspiration from the ventilator. Microbial con-tamination of canister contents has not been reported with pMDI

use during mechanical ventilation; however, contamination ofthe external surfaces of the canister may provide a vector forcommunication of bacteria from care providers and other

Jet Nebulizer (JN)(Mistyneb)

Vibrating Mesh (VM)(Aeroneb Pro)

Aeroneb

Ultrasonic Nebulizer (UN)(PB Easyneb)

Metered-dose Inhaler (pMDI)and Spacer (AeroVent)

FIGURE 1. Variety of aerosol devices used for drug delivery to ventilator-dependent patients. From left to right: jet nebulizers, vibratingmesh nebulizers, ultrasonic nebulizers, and pressurized metered dose inhalers.

Ari and Fink Clinical Pulmonary Medicine Volume 22, Number 2, March 2015

80 |www.clinpulm.com Copyrightr 2015 Wolters Kluwer Health, Inc. All rights reserved.


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patients, especially when the pMDI is used across multiplepatients. For many years, pMDIs were considered the most cost-effective drug delivery options in critical care. However, with theintroduction of hydrofluoroalkane (HFA) propellants, the highercosts of pMDIs have made use of other types of aerosol gen-erators using unit doses of liquid medications to appear more

cost effective. Nebulizers in general require more preparationtime to set up, cleaning, and maintenance than pMDIs. Treat-ment time with pMDIs is shorter than nebulizers and pMDIs

provide consistent and convenient dosing with each treatmentwith reduced chances of bacterial contamination.57 Therefore,utilization of pMDIs during mechanical ventilation has greatlyincreased over the past 25 years.8,9

It is essential to track the number of doses remaining in apMDI either manually or with the use of a dose counter.Otherwise, it will be impossible to determine the remainingdose in pMDIs with potential for use of pMDIs beyond theircapacity to administer medication. Although newer pMDIshave built-in dose counters, they may not allow removal of thecanister from the actuator or fit in standard commercial

adapter/spacers. Thus, an adapter that fits the specific pMDIshould be used.

DEVICE SELECTIONPrevious evidence confirms similar therapeutic effects of

nebulizers and pMDIs with in-line adapter/spacers in ven-tilator-dependent patients when the drug is available in bothformats.1015 Such studies are largely based on bronchodila-tors. However, not all aerosol devices and interfaces providethe same level of efficiency under all conditions. So the keyquestion is which device to use with which medication for anyspecific ventilator circuit.

Drug AvailabilityThe variety of drugs available with pMDIs is largely lim-ited to bronchodilators and corticosteroids. In addition, the dosevolume of pMDIs (30 to 100 mL/actuation) is much smaller thanthe 2 to 6 mL delivered with nebulizers. Nebulizers present theopportunity for delivery of larger payloads of drugs to the lungswith a broader range of inhaled medication including mucolytics,mucokinetics, antivirals, antibiotics, diuretics, prostanoids, andothers. Consequently, the selection of aerosol devices for aerosoladministration during mechanical ventilation rests with the needsof the patient, the intent of the clinician, and the desired ther-apeutic outcomes. In addition, if the drug is not available in a

pMDI, the nebulizer becomes the default aerosol generatoroption. The need for efficient aerosol delivery increases with the

cost of any specific medication.

Target Payload and Delivery EfficiencyAn expensive drug such as an antibiotic is approved for

inhalation in ambulatory CF patients using a vented breathenhanced JN that delivers approximately 12% of the antibioticdose to the patients lungs. As that nebulizer cannot be usedduring mechanical ventilation, the alternative aerosol deviceselected for use with the ventilator should match or exceed thelung dose achieved in ambulatory patients. Use of standard JNwith 3% efficiency might require up to 4 doses to achieve thetarget 12% lung dose. In contrast, either a UN or VMN, withefficiency of 12% to 17% during mechanical ventilation,would provide a comparable lung dose with a single admin-

istration. In contrast, a pMDI despite 17% delivery efficiencyis not available with many formulation besides bronchodilatorsand inhaled corticosteroids.

Risk and BenefitsAlthough the pMDI is associated with less exhaled aerosol

than a nebulizer, all aerosol generators used in ventilator-dependent patients may lead to escape of aerosol to the envi-ronment, which creates health risks to health care professionals,caregivers, and other patients. However, the aerosols generated

by patients themselves may be the greater risk for transmissionof airborne diseases from swine flu (H1N1) and severe acuterespiratory syndrome to tuberculosis. Consequently, ventilatorsshould be equipped with some form of high-efficiency partic-ulate air filter in the expiratory limb to mechanically reduceescape of aerosol (whether generated by the patient or a nebu-lizer) from the ventilator circuit to the environment.

Risks such as infection with JN and an increase in drugconcentration with JN and UN should be considered duringdevice selection for inhalation therapy in ventilator-dependent

patients.

Cost (Both Drug and Technology)With the transition of pMDIs from chlorofluorocarbon to

the more environmentally friendly HFA propellants, the priceof some pMDIs has increased as much as 5-fold. As the priceof a pMDI increases, the cost advantage can shift to the moreinherently expensive UN and VM technologies using lessexpensive liquid formulations. The cost of pMDIs range from$45 to $375. For instance, the ProAir HFA costs $45 for 200

puffs, whereas the price of the Advair HFA including 120 puffsis $375 in the United States. A unit dose of albuterol/ipra-tropium formulation is


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DELIVERY TECHNIQUESeveral categories of factors affecting aerosol drug

delivery to critically ill patients receiving mechanical ven-tilation include: (1) ventilator-related factors, (2) circuit-relatedfactors, and (3) device-related factors.16 Ventilator-relatedfactors include mode of ventilation, tidal volume, inspiratorytime and duty cycle, flow, bias flow (breath-triggering mecha-nism), and inspiratory waveform. Circuit-related factors includeheat and humidity, artificial airways, and right-angle elbowadapter. Device-related factors include placement of aerosoldevice in the circuit, type of nebulizer, nature of nebulization(intermittent vs. continuous), amount of residual drug (dead)

volume, amount of gas flow, type of adapter/spacer, as well asshaking and actuation of pMDI. Tables 24 explain effects ofventilator-related, circuit-related, and device-related factors,

respectively, while providing recommendations to optimizeaerosol delivery in mechanically ventilated adults.

Successful delivery of medical aerosols to mechanicallyventilated patients can be best achieved with adequate drugdeposition at the intended site of action in the lung. As opti-mum drug delivery in mechanically ventilated patients istechnique dependent, careful attention to delivery techniqueduring mechanical ventilation is essential. Figure 2 shows analgorithm describing steps for optimal drug administration

technique by each aerosol device.According to previous research, placing patients in a semi-

Fowler or seated position increases drug delivery during aerosol

TABLE 2. Ventilator-related Factors, Their Effects, andRecommendations to Optimize Bronchodilator Delivery inMechanically Ventilated Adults

Factors Effects Recommendations

Mode of

ventilation

The efficiency of

nebulizer is lower inpressure-controlledventilation than involume-controlledventilation

Spontaneous modes suchas CPAP increaseaerosol drug deliveryup to 23%

Prefer volume-controlled

ventilation when usinga nebulizer, if possible

Use spontaneous modes,if tolerated by patients

Tidal volume Low-tidal volumedecreases aerosol drugdelivery to the lowerrespiratory tract

Set tidal volume greaterthan the volume oftubing and ETTbetween the nebulizerand the patient. Foradults it should be set to

>500mL, if appropriatefor the patientInspiratory

time andduty cycle

Inspiratory time and dutycycle are directlyrelated to aerosoldelivery duringmechanical ventilation.As inspiratory time orduty cycle increases,more aerosol will bedelivered to the patient

Increase inspiratory timewhile minimizing thedegree of intrinsicPEEP. Duty cycle ofZ0.3 is recommended

Flow Higher inspiratory flowincreases turbulence,transitional flow, andinertial impaction,thereby reducing

aerosol delivery

Use an inspiratory flowof 30 to 50 L/min, iftolerated, duringnebulization

Bias flow(breath-triggeringmechanism)

Bias flow dilutes aerosolgenerated proximal tothe patient but lowflows may improveaerosol from VMNs andUNs placed proximal tothe patient

Use lower bias flowr2 L/min withnebulizers whenpossible

Synchronize actuations ofpMDIs with inspiration

Inspiratorywaveform

Square waveform deliversless aerosol thandecreasing ramp orsinusoidal waveforms

Choose sinusoidal ordecreasing rampwaveforms

Reproduced with permission from Ari and Fink.16

TABLE 3. Circuit-related Factors, Their Effects, andRecommendations to Optimize Bronchodilator Delivery inMechanically Ventilated Adults


Endotracheal

tube (ETT)

Drug delivery decreases

with the reduction of theinner diameter of theETT

Place the largest diameter

ETT that the patient cansafely tolerate. KeepETT clear of secretions

Heat andhumidity

The filter of the heatmoisture exchanger(HME) acts as a barrierto aerosol delivery

Placement of nebulizersbetween the HME andpatient airway mayoverload the HME withexhaled aerosol andincrease work ofbreathing over time

Heated humidifiers may

reduce aerosoldeposition; however,cold dry air is a greaterproblem

Turning off the humidifierfor up to 30 min does notincrease aerosoldeposition

Remove the HME beforeaerosol drugadministration and placeit back into the circuitafter the treatment

Do not place nebulizersbetween the HME andpatient airway

Do not turn off or removethe heated humidifierfrom the circuit.Increase the dose, as

needed for clinicalresponse

Density ofinhaled gas

Heliox creates thepersistence of laminarflows in the ventilatorcircuit and airwaysimproving aerosoldeposition by decreasingparticle impaction losses

The lower density of

heliox is not as effectivein generating aerosolwith jet nebs, requiring2-fold higher flows,which may alterventilator parameters

Vibrating mesh, ultrasonicnebs, and pMDIsgenerate aerosol withoutbeing affected by heliox

Use heliox 80:20 or 70:30for optimal delivery ofaerosols through theventilator circuit. Do notdilute


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therapy.1721 Therefore, when possible, clinicians should utilizethese positions to increase the efficiency and distribution ofaerosol delivery. In patients who cannot sit in the bed duringaerosol administration, the head of the bed should be elevated

between 20 and 30 degrees above horizontal.JNs are commonly operated continuously using an external

gas source and method to meter flow and pressure (often at 50 psi).

Some ventilators offer integrated nebulization options usinginternal compressors or flow diverters to drive JNs. When inte-grated with the software of the ventilator, these units can eliminatethe need for adjustment of ventilator parameters and activation ofventilator alarms during aerosol drug delivery. Most compressorsoperate JNs at a lower driving pressure (< 15 psi) than when using

pressurized gas (Z50 psi), which may produce larger particles andcause a reduction in the efficiency of the JN.22,23

Historically, ventilators with integrated nebulizer outletssynchronized nebulization with inspiration. More recently,ventilators may offer nebulization during inspiration, expira-tion, or continuously through the breathing cycle. It was ini-tially reported that nebulization during inspiration wouldincrease deposition compared with continuous delivery2426

with the nebulizer placed near the patient airway, with lessdifference when placement was more distal from the patient.However, more recent studies report that intermittent

inspiratory nebulization was less efficient than either con-tinuous or intermittent expiratory aerosol generation. Inter-mittent inspiratory mode did not increase lung delivery but diddramatically increased treatment time.27,28 Ventilators withintegrated nebulizer controls often compensate for the addedflow to the nebulizer to maintain tidal volume, inspiratory

pressures, and minute ventilation during aerosol delivery,

reducing the need to adjust parameters or alarms, during andafter nebulization.

It is important to prime the pMDI before first use andwhen the canister has not been used for >24 hours to avoidseparation of drug from the propellants. Similarly, the pMDIshould be shaken before first actuation for each treatment.Otherwise, this simple mistake in delivery technique will leadto a decrease in aerosol deposition to ventilator-dependent

patients.29 Synchronizing pMDI with the beginning of inspi-ration, using a chamber spacer, and placing the spacer 6 inchesfrom the Y adapter in the ventilator circuit increases aerosoldrug delivery during mechanical ventilation.17,30,31

Previous studies show that mistakes in delivery techniqueinfluence aerosol drug delivery in ventilated patients.22,3240 These

mistakes in technique are specific to the delivery device usedduring treatment. For instance, when nebulizers are used for aer-osol delivery during mechanical ventilation, clinicians may set gas

TABLE 4. Device-related Factors, Their Effects, and Recommendations to Optimize Bronchodilator Delivery in Mechanically VentilatedAdults


Position of aerosoldevice in circuit

The location of the aerosol device in the ventilator circuitsignificantly affects aerosol drug delivery

Place the jet nebulizer close to the ventilator. Position thepMDI proximal to the patient. Vibrating mesh and

ultrasonic nebulizers in inspiratory limb near the Yadapter, or proximal to the ventilator when using biasflow

Nebulizer-relatedfactors

Nebulizer type: jet nebulizers are less efficient thanvibrating mesh nebulizers, ultrasonic nebulizers, andpMDIs with spacer

Choose the vibrating mesh nebulizer, USN, or pMDI withspacer for aerosol delivery in mechanically ventilatedpatients

Intermittent and continuous nebulization: intermittentnebulization synchronized with expiration is moreefficient for aerosol delivery than continuous nebulization

Run the jet nebulizer intermittently, if ventilator has thatoption

For continuous jet nebulizer, set the flow rate at 6 to 8 lpmor as recommended by manufacturer and adjust theventilator parameters (Vt, pressure, and alarms)

Residual dead volume: the greater the dead volume, the lessamount of drug is nebulized. Jet nebulizers do notaerosolize below dead volume of 1 to 2.5 mL. Vibratingmesh nebulizers have smaller residual volumes than jet or

ultrasonic nebulizers

Use the vibrating mesh nebulizer when possibleIn the absence of the vibrating mesh nebulizer, increase fill

volume to 4 to 5 mL unless the jet nebulizer isspecifically designed for a smaller fill volume

Gas flow: the ultrasonic and vibrating nebulizers are notinfluenced by gas flow as they are electrically powered.Particle size minimally affected with heliox

Operating the jet nebulizer at a lower flow or pressure thanthe design will increase particle size and reduce delivery.Gas flow inversely related to nebulization time with thejet nebulizer

Use the ultrasonic or vibrating mesh nebulizers for aerosoldelivery with heliox

Set the flow rate at 6 to 8 lpm or as recommended bymanufacturer and adjust the ventilator parameters (Vt andpressure), if you run the jet nebulizer continuously

pMDI-related factors pMDI actuation: synchronized pMDI actuations withinspiration increase aerosol delivery

Synchronize pMDI actuations with inspiration. Actuate atZ15 s intervals

Spacer: using a chamber spacer with the pMDI reduceslosses in the circuit and increases drug delivery up to 6-fold

The efficiency of a bidirectional inline adapter was higherthan the efficiency of an unidirectional inline adapter andachieved efficiency marginally less than chamber spacers

Use chamber spacers with the pMDIs for aerosoladministration to mechanically ventilated patients

Bidirectional inline adapters are a better option thanunidirectional low-volume inline adapters

Shaking the canister: the drug in the pMDI formulations areseparated when standing. Therefore, not shaking a pMDIcanister reduces total and respirable dose up to 35%

Shake the pMDI before the first actuation of each dose(up to 8 puffs) administered

Reproduced with permission from Ari and Fink.16

Clinical Pulmonary Medicine Volume 22, Number 2, March 2015 Aerosol Drug Delivery During Mechanical Ventilation

Copyrightr 2015 Wolters Kluwer Health, Inc. All rights reserved. www.clinpulm.com |83


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flow improperly. Not shaking pMDI before treatment, not syn-chronizing pMDI actuations with the beginning of inspiration, ornot using the right type of spacer with pMDI will significantlyreduce aerosol drug delivery to ventilator-dependent patients. In

addition, improper positioning of the aerosol device in the ven-tilator circuit will influence efficiency of treatment during mech-anical ventilation.33,34

EVALUATION OF CLINICAL RESPONSE TOTHERAPY

There are many factors affecting the patients response tobronchodilator delivery during mechanical ventilation. These

factors include patient airway geometry, degree of airwayresponsiveness, severity of disease, quantity and nature ofsecretions, and degree of airway inflammation.

Review order identify patient and assess need for bronchodilator.Clear the airways by suctioning, if needed.If using an HME, remove it from the circuit.

If using a heated humidifier, do not turn off or disconnect during thetreatment.

JN:

Correctly assemble the nebulizer.Fill the nebulizer with volume on drug

label. You may increase volume to 4-6 mLto increase delivery.

Place the JN in the inspiratory line nearthe Y adapter or proximal to the

ventilator.

VMN:

Correctly assemble the nebulizer.Pour recommended drug volume into

the nebulizer.Place the VMN in the inspiratory line

near the Y adapter or proximal to theventilator.

pMDI:

JN: VMN: pMDI:

Shake and prime the pMDI.Warm the pMDI canister to hand or

body temperature.Place the pMDI spacer/adapter in theinspiratory line near the Y adapter.

Correctly assemble the pMDI canisterwith spacer/adapter.

Ensure that there is no leak in the circuit.Position the patient in an upright position, if possible.

Connect the nebulizer to a gas source.If available, use gas source on theventilator in order to synchronize

nebulization with inspirationOtherwise set gas flow to the JN at 6 to 8

l/min (or flow recommended on label).Adjust ventilator volume or pressure limit

to compensate for added flow.

Connect the nebulizer to a power source.Turn on the power.

Coordinate actuations with beginning ofinspiration.

Do not remove or shake the pMDIbetween actuations.

Wait 15 seconds between actuations.

Observe aerosol cloud for adequate aerosol generation during treatment.

At the completion of treatment, remove device from the ventilator circuit.Clean as recommended by manufacturer or institution.

Reconnect the HME.Return ventilator settings and alarms to previous values. Ensure there

is no leak in the ventilator circuit.

Monitor vital signs, oxygen saturation and patent-ventilatorsynchronization.

Monitor for adverse response.Assess outcome and document findings.

FIGURE 2. An algorithm describing steps for optimal drug administration technique by each aerosol generator. Reproduced withpermission from Ari and Fink.16




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Evaluation of response to therapy should include heartrate, respiratory rate, oxygen saturation, blood pressure,

patient-ventilator asynchronization, and airway resistance.Administration of high doses ofb-adrenergic bronchodilatorsmay result in tachycardia, atrial arrhythmias, or ventriculararrhythmias.41 Comparisons of airway resistance and auto-

positive end expiratory pressure (auto-PEEP) before and afterbronchodilator administration are useful for the evaluation ofpatient response to bronchodilator delivery during mechanicalventilation.42,43 Several studies conducted on patients withchronic obstructive pulmonary disease showed a decreasein airway resistance and auto-PEEP after bronchodilatoradministration.14,17,44

Clinicians should monitor patients before, during, andafter the administration of aerosolized bronchodilator duringmechanical ventilation. It is also important for clinicians tostay with patients during inhalation therapy through nebulizers.This will enable them to assure uninterrupted administration ofaerosol therapy for ventilator-dependent patients and enhance

patient safety by rapid response to complications caused by

aerosol drug delivery during mechanical ventilation.In summary, successful aerosol delivery with metered-

dose inhalers and nebulizers in intubated, mechanically venti-lated patients requires efficient delivery to the lower respiratorytract. There are many issues with selection and use of aerosoldevices in ventilator-dependent patients. Once cliniciansunderstand potential problems and opportunities associatedwith aerosol devices, delivery technique, and clinical responseto therapy, they will be able to optimize aerosol drug deliveryto patients receiving ventilator support while assuring patientsafety and well-being during inhalation therapy.

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