delivery of inhaled medication in adults

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Delivery of inhaled medication in adults

Dean Hess, RRT, PhD

UpToDate performs a continuous review of over 375 journals and other resources. Updates areadded as important new information is published. The literature review for version 15.1 is current

through December 2!" this topic was last changed on #anuar$ %& 27. The ne't version ofUpToDate (15.2) will be released in #une 27.

INTRODUCTION The inhalation of therapeutic aerosols is an effective method of drug deliveryfrequently applied to the management of respiratory disease. Inhalation (or aerosol therapy can !e

employed "ith a range of medications using a num!er of different techniques. #$amples include%

Inhaled !eta agonists and anticholinergic !ronchodilators are used to treat chronic o!structive

lung diseases

Inhaled steroids have a central role in the management of asthma

Inhaled anti!iotics and muco&inetic agents are therapies for cystic fi!rosis and !ronchiectasis

Inhaled pulmonary vasodilators are used to manage pulmonary hypertension ')

In the future, patients "ith nonrespiratory disease may !enefit from aerosol delivery of

drugs, including insulin and opiates '*)

OVERVIEW Three principal types of devices are used to generate therapeutic aerosols% ne!uli+ers,metered dose inhalers, and dry po"der inhalers. ll three generate aerosols using different

mechanisms. In many cases, clinicians must choose the most appropriate device for drug delivery as"ell as the appropriate therapeutic agent '-).

In addition, the patient technique for proper use differs among these devices. The patientaerosol

generator interface is an important, !ut often overloo&ed, component of patient compliance andtherapeutic response. Ineffective use of any of these devices "ill result in su!optimal drugdeposition. s a result, patient instruction and compliance are crucial aspects of prescription and use

of these devices.

ll three types of devices can !e used to efficiently deliver medication to spontaneously !reathing

patients. /nly ne!uli+er systems and metered dose inhalers can !e used in intu!ated patients0 drypo"der inhalers should not !e used in intu!ated patients.

NEBULIER! The !asic design and performance of pneumatic (or 1et ne!uli+ers have changedlittle over the past *2 years (sho" figure . 3e!uli+er performance is affected !y !oth technical and

patientrelated factors (sho" ta!le '4,2). 5et ne!uli+ers are often considered interchangea!le.Ho"ever, differences in performance among ne!uli+ers produced !y various manufacturers have

!een reported, some of "hich have clinical implications '6,7). This may !e less important for inhaled!ronchodilators, although ne"er ne!uli+er designs should !e considered for more e$pensive

formulations "here precise dosing is required. (8ee 93e" ne!uli+er designs9 !elo".

In addition to differences in design, the performance of ne!uli+ers is influenced !y several common

factors, including mechanism, use of mouthpiece or facemas&, and drug formulation.

"echanism The operation of a pneumatic ne!uli+er requires a pressuri+ed gas supply, "hich acts

as the driving force for liquid atomi+ation. :ompressed gas is delivered as a 1et through a smallorifice, generating a region of negative pressure a!ove the medication reservoir. The solution to !e
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aerosoli+ed is first entrained, or pulled into the gas stream and then sheared into a liquid film. Thisfilm is unsta!le, and rapidly !rea&s into droplets due to surface tension forces.

!affle placed in the aerosol stream allo"s formation of smaller particles and recycling of largerdroplets into the liquid reservoir. The aerosol is entrained into the inspiratory gas stream inhaled !y

the patient.

The correct technique for use of a ne!uli+er is important (sho" ta!le * ';,


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2? percent if it is po"ered "ith helio$ '4). Helio$ may improve aerosol delivery to the lo"errespiratory tract, !ecause the decrease in density results in the creation of smaller particles0

ho"ever, the clinical !enefit of this approach is unclear '2*?). (8ee 9Physiology and clinical use ofhelio$9.

"outh#ieces and facemas$s Inhaled aerosols can !e administered using a mouthpiece or afacemas&. Eronchodilator response appears similar "ith either interface, and some have argued that

the selection of patient interface should !e !ased upon patient preference. 8ignificant facial and eye

deposition of aerosol can occur "hen a face mas& is used, especially in young children '*). #yedeposition is of particular concern "hen aerosoli+ed anticholinergic agents are administered, as this

can result in !lurring of vision, pupil dilation, and "orsening of narro" angle glaucoma. Fhen a

facemas& is used, it is important to instruct the patient to inhale through the mouth to minimi+enasopharyngeal deposition of medication. Fe generally favor use of a mouthpiece, rather than a face

mas&, for aerosol administration.

Breathin% #attern The !reathing pattern of the patient affects the amount of aerosol deposited in

the lo"er respiratory tract. irflo" o!struction increases the need for inhaled !ronchodilator therapy,!ut can decrease the effectiveness of that treatment. To improve aerosol penetration and deposition

in the lungs, the patient should !e encouraged to use a slo" !reathing pattern "ith an occasionaldeep !reath.

Dru% formulation Drug formulation can affect ne!uli+er performance '***4). >etered doseinhalers and dry po"der inhalers have al"ays !een tested and approved as a drugdelivery system

com!ination. 8ome drug solutions are only approved for delivery "ith specific ne!uli+ers '*2).#$amples of medications that should !e delivered only !y approved ne!uli+er include pentamidine,

ri!avirin, rhD3ase, and to!ramycin.

Ne&uli'ers for s#ecific medications 8pecially constructed smallvolume ne!uli+ers, such as the

Respirgard II for aerosoli+ed pentamidine, should !e used "hen contamination of the am!ientenvironment "ith the aerosoli+ed drug needs to !e avoided '4). The Respirgard II is fitted "ith one

"ay valves and filters to minimi+e gross contamination of the environment.

separate device "as developed to allo" the safe delivery of aerosoli+ed ri!avirin, "hich ispotentially teratogenic. The 8mallParticle erosol Cenerator (8PC "as designed specifically toaerosoli+e ri!avirin. It consists of a ne!uli+er and drying cham!er that reduce the >>D to a!out .-

=m, "hich optimi+es drug delivery to distal airspaces. The 8PC is used "ith a scavenging system tominimi+e contamination of the am!ient environment.

Ne( ne&uli'er desi%ns Fith the traditional ne!uli+er design, an aerosol is generated throughoutthe patientGs respiratory cycle. This results in considera!le "aste of aerosol during e$halation. 3e"er

designs reduce aerosol "aste during the e$halation phase .

Ereathenhanced ne!uli+ers, such as the Pari @:, are designed to allo" release of more

aerosol during inhalation. Fith this design, e$haled gas is routed out the e$piratory valve in themouthpiece and aerosol is contained in the ne!uli+er cham!er during the e$piratory phase.

The :irculaire ne!uli+er reduces "aste from a constantoutput ne!uli+er !y attachment of a

storage !ag "ith a one"ay valve in the mouthpiece connector. During the e$piratory phase, aerosol

is collected in the !ag and delivered to the patient on the su!sequent inhalation.

The ero#clipse ne!uli+er has a !reathactuated valve that triggers aerosol generation only

during inhalation, eliminating the need for a storage !ag or reservoir '*6).

Ultrasonic ne&uli'ers ltrasonic ne!uli+ers consist of a po"er unit and transducer, "ith or "ithout

an electric fan '4). The po"er unit converts electrical energy to highfrequency ultrasonic "aves "ith
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a frequency of .6- megahert+. pie+oelectric element in the transducer vi!rates at the samefrequency as the applied "ave. ltrasonic "aves are transmitted to the surface of the solution to

create an aerosol. fan is used to deliver the aerosol to the patient, or the aerosol is evacuatedfrom the ne!uli+ation cham!er !y the inspiratory flo" of the patient.

8mall volume ultrasonic ne!uli+ers are commercially availa!le for delivery of inhaled !ronchodilators0large volume ultrasonic ne!uli+ers are used for sputum induction. potential issue "ith the use of

ultrasonic ne!uli+ers is drug inactivation !y ultrasonic "aves0 ho"ever, to date this has not !een

sho"n to occur "ith medications commonly delivered using this system.

Vi&ratin% mesh ne&uli'ers 8everal manufacturers have developed aerosol devices that use avi!rating mesh or plate "ith multiple apertures to produce a liquid aerosol (sho" figure - '*7).

common feature of these devices is their a!ility to generate aerosols "ith a high fineparticlefraction, "hich results in more efficient drug delivery compared to conventional ne!uli+ers. The

aerosol is generated as a fine mist, and no internal !affling system is required. These ne!uli+ers areporta!le, !atteryoperated, and they have minimal residual medication volume0 some are !reath

actuated '*7). They are !eing developed in cooperation "ith pharmaceutical companies to delivere$pensive formulations "ith "hich precise dosing is needed.

The i3e! ne!uli+er uses vi!rating mesh technology "ith adaptive aerosol delivery (DD. DD

monitors the patientGs !reathing pattern and in1ects the aerosol at the !eginning of inhalation. Thisimproves the li&elihood of the aerosol penetrating deep into the respiratory tract. This ne!uli+er isused specifically for the administration of entavisJ (iloprost Inhalation 8olution (:oTheri$, Inc for

the treatment of pulmonary arterial hypertension (sho" figure 4.

"ETERED DO!E IN)*LER! metered dose inhaler (>DI consists of a pressuri+ed canister, ametering valve and stem, and a mouthpiece actuator (sho" figure 2 '*;). The canister contains the

drug suspended in a mi$ture of propellants, surfactants, preservatives, flavoring agents, and

dispersal agents. The propellant has traditionally !een a chlorofluorocar!on (::. ollo"ingadoption of the >ontreal protocol, an international agreement to !an ::s, ::free propellants

such as hydrofluoroal&ane (H --a have !ecome availa!le '*DI is "armer and softer than the :: plume. Fithout this

information, the patient may interpret the difference in sensation as the aerosol passes through theupper respiratory tract as an ineffectively delivered dose.

The mi$ture is released from the >DI canister through a metering valve and stem into an actuator!oot. fter volatili+ation of the propellant, the final volume emitted from the >DI is 2 to *? m@ per

dose '44). The >DI can !e actuated as frequently as every 2 seconds '42). @ung deposition ranges!et"een ? percent and *2 percent of the nominal dose in adults. The correct technique for using a

>DI is sho"n in the ta!le (sho" ta!le - ';, :orporation, designed for patients"ith poor hand!reath coordination, is an e$ample of a flo"triggered >DI that actuates in response

to the patientGs inspiratory effort '462?).

+atient teachin% Important patient teaching issues related to the use of an >DI include priming,creaming (separation of drug from other ingredients in the canister, and determining "hen the

canister is empty. Fhen an >DI is ne", or if it has not !een used for several days (eg, a patientusing inhaled !etaagonists on an asneeded !asis, the first several actuations deliver an

inconsistent dose until the metering cham!er is primed '22-). The clinical effects of this can !e

avoided !y "asting several actuations from the >DI. :reaming is reversed !y sha&ing the canister!efore use '24,22).

Determinin% (hen an "DI is em#ty It is important for the patient to have a means to determine"hen the canister is empty. fe" >DIs are no" !eing manufactured "ith integrated dose counters,

including entolinHJ, availa!le in the nited 8tates as of 5une *??6 (sho" figure 6 '26). nothermethod is to have the patient maintain a log of the num!er of actuations, and to dispose of the
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device "hen the designated num!er of actuations has !een reached. The technique of dropping thecanister into a pan of "ater and o!serving ho" it floats has !een sho"n to !e unrelia!le and is no

longer recommended '27,2;). (8ee 9>etered dose inhaler techniques in adults9and see 9Patientinformation% >etered dose inhaler techniques9.

!#acers and holdin% cham&ers 8pacers and valved holding cham!ers are accessory devices thatreduce oropharyngeal deposition of drug, improve distal delivery, and minimi+e the importance of

hand!reath coordination. spacer device is an openended tu!e or !ag that allo"s the >DI plume

to e$pand and the propellant to evaporate. valved holding cham!er incorporates a one"ay valvethat permits aerosol delivery from the cham!er only during the inspiratory phase.

ccessory devices either use the !oot that comes "ith the >DI or incorporate a universal canister

adapter to actuate the >DI (sho" figure 7. valved holding cham!er can incorporate a mas& forpatients "ho are una!le to use a mouthpiece due to age, poor coordination, or impaired mental

status. The technique for use of a spacer or valved holding cham!er is provided (sho" ta!le 4 ';,DI has !een actuated '6466).

DR, +OWDER IN)*LER! Dry po"der inhalers (DPIs create aerosols !y dra"ing air through a

dose of po"dered medication (sho" figure ;and sho" figure


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'7*7;). ccordingly, the selection of an aerosol delivery device is not !ased on a clear superiority ofone device over another '-).

The selection of an aerosol delivery device is usually !ased upon the preference and convenience ofthe clinician and patient, the a!ility of the patient to use the device correctly, and the cost of

therapy. The selection of device is also limited !y drug formulation, as some formulations are onlyavaila!le for one delivery device. The ne!uli+er is often considered the most e$pensive aerosol

delivery device. The prescription of multiple delivery devices can !e confusing, and may impair

compliance "ith therapy, particularly in patients "ith complicated regimens '7DI or a ne!uli+er. DPI cannot !e used to deliver

dry po"der during mechanical ventilation !ecause ventilator circuit humidification impairs aerosolformation.

num!er of factors affect aerosol delivery during mechanical ventilation (sho" ta!le 7 ';;7). /nema1or factor is that humidification of inhaled gas decreases aerosol deposition !y appro$imately 4?

percent due to increased particle drug deposition in the ventilator circuit. or this reason, increaseddosage of medication is often required to achieve a therapeutic effect in mechanically ventilated

patients.

"etered dose inhaler special actuator is needed to adapt the >DI into the ventilator circuit

(sho" figure . The si+e, shape, and design of these actuators have a ma1or impact on drug deliveryto the patient. n >DI "ith a cham!er results in a four to si$fold greater delivery of aerosol than

>DI actuation into a connector attached directly to the endotracheal tu!e, or into an inline devicethat lac&s a cham!er. Fhen using an >DI during mechanical ventilation, it is important to

synchroni+e actuation "ith inspiratory airflo" to optimi+e drug delivery.

Heliumo$ygen mi$tures also affect aerosol deposition, and in vitro modeling has reported a 2?

percent increase in deposition of al!uterolfrom an >DI during mechanical ventilation "hen helio$"as used as the driving gas ';;). Ho"ever, helio$ can dramatically interfere "ith the functioning of

flo" sensors and o$ygen levels "hen delivered through a mechanical ventilator, and care must !e

ta&en if this approach is employed ';


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Choice of device lthough the ne!uli+er is less efficient than the metered dose inhaler duringmechanical ventilation, the ne!uli+er can deliver a greater cumulative dose to the lo"er respiratory

tract 'DIs produce similar therapeutic effects in mechanically ventilatedpatients 'DI for routine !ronchodilator therapy in ventilatorsupported patients

is preferred !ecause of the pro!lems associated "ith the use of ne!uli+ers, including contaminationand triggering difficulty, as "ell as increased pressure and volume delivery.

erosol delivery !y >DI is easy to administer, involves less personnel time, provides a relia!le dose

of the drug, and is free from the ris& of !acterial contamination. Fhen an >DI is used "ith an inlinespacer, the ventilator circuit does not need to !e disconnected "ith each treatment0 this may reduce

the ris& of ventilatorassociated pneumonia. This also prevents the loss of positive ende$piratory

pressure (P##P in patients "ith acute respiratory distress syndrome (RD8. (8ee 9entilator circuitchange and ventilatorassociated pneumonia9, and see 9>echanical ventilation in acute respiratory distress

syndrome9.

erosol therapy can also !e administered during noninvasive positive pressure ventilation (3PP

(sho" figure * 'etered dose inhaler techniques9, and see 9Patient information% Ho" to use a pea&

flo" meter9. Fe encourage you to print or email these topics, or to refer patients to our pu!lic "e!site """.patients.uptodate.com, "hich includes these and other topics.

!U""*R, #ffective delivery of inhaled medications requires selection of the appropriate drug,proper use of the delivery device, education of the patient in the correct use of the device, and

patient compliance. requent revie" of the proper use of the device is crucial. ll health careprofessionals interacting "ith the patient share responsi!ility for this teaching and should personally

understand the correct use of the various devices.

*vaila&le devices

Three principal types of devices are used to deliver inhaled medications% ne!uli+ers, metered

dose inhalers (>DIs, and dry po"der inhalers (DPIs. The ne!uli+er is often considered the most

e$pensive aerosol delivery device. (8ee 9/vervie"9 a!ove

The most commonlyused type of ne!uli+er is the pneumatic (or 1et ne!uli+ers (sho" figure

. 3e!uli+er performance is affected !y !oth technical factors, such as mechanism of aerosolgeneration and drug formulation (not all medications can !e used "ith all ne!uli+ers, as "ell as

patientrelated factors (sho" ta!le . (8ee 93e!uli+ers9 a!ove.

Fith all of the standard ne!uli+ers, patients should !e encouraged to use a slo" !reathing

pattern "ith an occasional deep !reath. Fe generally favor the use of mouthpieces over face mas&s,as the latter are associated "ith some facial and eye deposition of aerosol. (8ee 9>outhpieces and

facemas&s9 a!ove.

3e"er ne!uli+er designs include !reathactuated devices that deliver the ma1ority of the

medication during inhalation, and vi!rating mesh ne!uli+ers that produce a very fine mist ofaerosoli+ed medication and deliver more of the dose to the patient. (8ee 93e" ne!uli+er designs9a!ove.
http://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=92http://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=93http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/9368http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/9368http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/8698http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/8698http://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/neb_or_m.htmhttp://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=94,95http://www.utdol.com/utd/content/topic.do?topicKey=drug_a_k/8957&drug=truehttp://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=96http://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=97http://www.utdol.com/utd/content/topic.do?topicKey=asthma/12318http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/28526http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/28526http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/5532http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/5532http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/6024http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/5100http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/2888http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/2888http://www.patients.uptodate.com/http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#2%232http://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/pneuma5.htmhttp://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/pneuma5.htmhttp://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/nebulize.htmhttp://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#3%233http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#5%235http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#5%235http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#9%239http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#9%239http://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=92http://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=93http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/9368http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/9368http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/8698http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/8698http://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/neb_or_m.htmhttp://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=94,95http://www.utdol.com/utd/content/topic.do?topicKey=drug_a_k/8957&drug=truehttp://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=96http://www.utdol.com/utd/content/abstract.do?topicKey=asthma/4562&refNum=97http://www.utdol.com/utd/content/topic.do?topicKey=asthma/12318http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/28526http://www.utdol.com/utd/content/topic.do?topicKey=cc_medi/28526http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/5532http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/5532http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/6024http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/5100http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/2888http://www.utdol.com/utd/content/topic.do?topicKey=al_asthm/2888http://www.patients.uptodate.com/http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#2%232http://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/pneuma5.htmhttp://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/pneuma5.htmhttp://www.utdol.com/utd/content/image.do?imageKey=pulm_pix/nebulize.htmhttp://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#3%233http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#5%235http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#5%235http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#9%239http://www.utdol.com/utd/content/topic.do?topicKey=asthma/4562&view=print#9%239


8/25

>DI consists of a pressuri+ed canister, a metering valve and stem, and a mouthpiece

actuator (sho" figure 2 '*;). :: propellants are gradually !eing replaced "ith non:: agents, such

as hydrofluoroal&ane (H. @ung deposition ranges !et"een ? and *2 percent of the nominal dosein adults. (8ee 9>etered dose inhalers9 a!ove.

The correct technique for using a >DI is sho"n in the ta!le (sho" ta!le -. The utohaler is an

e$ample of a flo"triggered >DI that actuates in response to the patientGs inspiratory effort and can

!e useful to patients "ho have trou!le coordinating !reathing and actuation. Patients should also !etaught a!out the importance of priming and sha&ing the canister !efore use, and ho" to determine

"hen the canister is empty. (8ee 9>etered dose inhalers9 a!ove.

>DIs can !e used "ith spacers and valved holding cham!ers, accessory devices that reduce

oropharyngeal deposition of drug, improve distal delivery, and minimi+e the importance of hand!reath coordination. (8ee 98pacers and holding cham!ers9 a!ove.

DPIs create aerosols !y dra"ing air through a dose of po"dered medication (sho" figure ;and

sho" figure DIs, or DPIs are all effective "hen used

correctly. Thus, "e recommend selecting a delivery device !ased upon convenience, cost, and thepatientGs preferences and a!ility to use the device correctly (-rade /B. (8ee 98pontaneously !reathing

patients9 a!ove.

Techniques have also !een descri!ed for the delivery of aerosols !y ne!uli+er or >DI in a

spontaneously !reathing patient "ith a tracheostomy tu!e (sho" figure ?. (8ee 9Patients "ith

tracheostomies9 a!ove.

In mechanicallyventilated patients, !oth >DIs and ne!uli+ers are equivalently effective. Fe

suggest the use of >DIs, !ecause this method is technically easier, involves less personnel time,

provides a relia!le dose of the drug, and is free from the ris& of !acterial contamination that canoccur "ith a ne!uli+er (-rade 0B. Patients can also receive inhaled therapies during 3PP. (8ee9>echanically ventilated patients9 a!ove.

se of UpToDateis su!1ect to the 8u!scription and @icense greement.

RE.ERENCE!. /lsche"s&i, H, 8imonneau, C, Calie, 3, et al. Inhaled iloprost for severe pulmonary hypertension. 3

#ngl 5 >ed *??*0 -47%-**.

*. Henry, RR, >udaliar, 8R, Ho"land III, F:, et al. Inhaled insulin using the #R$ insulin dia!etesmanagement system in healthy and asthmatic su!1ects. Dia!etes :are *??-0 *6%764.

-. Dolovich, >E, hrens, R:, Hess, DR, et al. Device selection and outcomes of aerosol therapy%

evidence!ased guidelines% merican :ollege of :hest PhysiciansAmerican :ollege of sthma,

llergy, and Immunology. :hest *??20 *7%--2.

4. Hess, DR. 3e!uli+ers% principles and performance. Respir :are *???0 42%6?


9/25

ne!uli+er flo", and ne!uli+er !rand. :hest ed *??*0 62%-7.

6. Henderson, 8/, charya, P, Lilagh!ian, T, et al. se of helio$driven ne!uli+er therapy in the

treatment of acute asthma. nn #merg >ed


10/25

ed *???0 24%*


11/25

6*. Fildha!er, 5H, 5anssens, H>, Pierart, , et al. Highpercentage lung delivery in children from

detergenttreated spacers. Pediatr Pulmonol *???0 *5 *??0 -*-%;ed 5 *??0 -*-%


12/25

minute volume measurement and ventilator volumes delivered. :rit :are >ed ed


13/25

Ne&uli'er #erformance

actors affecting aerosol delivery !y ne!uli+erTechnical actors

>echanism and manufacturer

lo" rate

ill volume

8olution characteristics

:haracteristics of driving gas

Designs to enhance output

:ontinuous vs. intermittent delivery

Patient actorsEreathing pattern

3ose vs mouth !reathing

rtificial air"ay

ir"ay o!struction

Positive pressure level

Ne&uli'er techni1ue

Technique for use of medication ne!uli+er

ssem!le apparatus

dd medication to ne!uli+er

se a fill volume of 4 to 6 m@

ttach a gas source "ith a flo" of ; @Amin

Place patient in a comforta!le position

Instruct patient to !reathe through the mouth

Periodically tap ne!uli+er to return impacted particles to reservoir.

#ncourage patient to !reathe "ith a slo" inspiratory flo" and an occasional deep !reath

ssess patient for comfort, adverse effects, and response throughout treatment

Terminate treatment "hen ne!uli+er !egins to sputter

Ne&uli'ers vi&ratin% mesh

i!rating mesh ne!uli+ers


14/25

i!rating mesh ne!uli+ers generate fine mists "ith more efficient dry delivery and minimalresidual medication volume compared to conventional ne!uli+ers.

Ne&uli'er iNe&

i3e! ne!uli+er sho"ing device and principle of operation

The i3e! ne!uli+er monitors the patientGs !reathing pattern and in1ects the aerosoli+ed

medication at the start of each inhalation. It is used for the administration of iloprost.

"etered dose inhaler


15/25

>etered dose inhaler

>edication is stored under pressure in the canister and released in fi$ed volumes from the

dosing cham!er follo"ing actuation.

"etered dose inhaler techni1ue

Technique for use of a >DI

Farm the >DI canister to !ody temperature

8ha&e vigorously

ncap mouthpiece and chec& for loose o!1ects in the device

/pen mouth and &eep tongue from o!structing the mouthpiece

Hold the >DI in a vertical position, "ith the outlet aimed at the mouth

Place canister outlet !et"een lips or position it a!out 4 cm from the mouth

Ereathe out normally

Ereathe in slo"ly0 actuate the >DI at !eginning of inspiration

:ontinue to inhale to total lung capacity

Hold !reath for 4 to ? seconds

Fait at least 2 seconds !et"een actuations

Recap mouthpiece

"DI (ith counter

>DI "ith counter


16/25

8ome >DIs are no" manufactured "ith !uiltin dose counters.

"DI s#acers

ccessory devices used "ith metered dose inhalers


17/25

( ero:ham!er, (E ero:ham!er "ith mas&, and (: Inspir#ase. These devices canfacilitate the use of metered dose inhalers and decrease the amount of drug deposited on

the upper air"ay.

"DI (ith s#acer techni1ue

Technique for use of >DI "ith spacer or valved holding cham!erFarm >DI canister to !ody temperature

ssem!le apparatus and chec& for loose o!1ects in the device

8ha&e canister vigorously

Hold canister in vertical position

Ereathe out normally

Place holding cham!er in mouth, or place mas& completely over nose and mouth

#ncourage patient to !reathe through mouth

Ereathe in slo"ly and actuate >DI once at the !eginning of inspiration

llo" 2 seconds !et"een actuations

Dry #o(der inhalers

#$amples of various dry po"der inhalers

Fith these devices, the patient inhales the medication in the form of a fine po"der ratherthan an aerosol. ( eroli+er, (E Tur!uhaler, (: Dis&us, (D Dis&haler, (# HandiHaler.

:ourtesy of Dean Hess, RRT, PhD.


18/25

D+I t(isthaler

The t"isthaler device

Dry #o(der inhaler techni1ue I

Technique for use of various dry po"der inhalers Ieroli+er

Remove cover and hold the !ase of inhaler.

T"ist mouthpiece in countercloc&"ise direction.

Remove capsule from foil !lister immediately !efore use and place capsule in the !ase of the

inhaler.

Hold the !ase of the inhaler and turn cloc&"ise to close.

8imultaneously press !oth !uttons once to pierce the capsule.

#$hale normally do not e$hale into the mouthpiece.

Tilt head !ac& slightly, hold device hori+ontal "ith the !uttons on the left and right, place

mouthpiece into the mouth, and close lips around mouthpiece.

Ereathe in rapidly and steadily, as deeply as possi!le0 hold !reath.

Remove device from mouth and e$hale outside device.

/pen cham!er and e$amine capsule0 if po"der remains, repeat inhalation process.

fter use, remove and discard capsule, and cover mouthpiece0 store device in cool, dry place.

Dis&haler


19/25

Remove mouthpiece cover and pull tray out from device.

Place dis& on "heel "ith num!ers facing up.

Rotate dis& !y sliding tray out and in.

@ift !ac& of lid until fully upright so that needle pierces !oth sides of !lister.

Leep device level "hile inhaling dose "ith a rapid and steady flo".



Erush off any po"der remaining "ithin device once every "ee&0 store device in cool, dry place.

Dis&us

/pen the device and slide the lever until it clic&s.

Leep device level "hile inhaling dose.


Remove device from mouth and e$hale outside device0 store device in cool, dry place.

Dry #o(der inhaler techni1ue II

Technique for use of various dry po"der inhalers IIHandiHaler

:apsules should !e stored in sealed !listers and only removed immediately !efore use.

Peel !ac& the foil using the ta! until one capsule is fully visi!le.

/pen the dust cap !y pulling it up"ards, then open the mouthpiece.

Place the capsule in the center cham!er (it does not matter "hich end of the capsule is placed in

the cham!er.

:lose the mouthpiece firmly until you hear a clic&, leaving the dust cap open.

Hold the HandiHaler "ith the mouthpiece up"ards and press the piercing !utton completely in

once and release.

Ereathe out completely. Do not !reathe into the mouthpiece at any time.

:lose your lips tightly around the mouthpiece.


To ensure you get the full dose, repeat the inhalation from the HandiHaler as descri!ed.

fter the dose, open the mouthpiece, tip out the used capsule, and dispose. Do not handle used


20/25

capsules.

:lose the mouthpiece and dust cap for storage0 store device in cool, dry place.

Tur!uhaler

T"ist and remove cover.

Hold inhaler upright "ith mouthpiece facing up.

Turn grip right then left until it clic&s.

Inhaler may !e held upright or hori+ontal.



Replace cover and t"ist to close0 store device in cool, dry place.

T"isthaler

Hold the inhaler straight up "ith the pin& portion (the !ase on the !ottom.

Remove the cap "hile it is in the upright position to ma&e sure you get the right amount ofmedicine "ith each dose.

Hold the pin& !ase and t"ist the cap in a countercloc&"ise direction to remove it.

s you lift off the cap, the dose counter on the !ase "ill count do"n !y . This action loads the

medicine that you are no" ready to inhale.

>a&e sure the indented arro" located on the "hite portion (directly a!ove the pin& !ase is

pointing to the dose counter.

Ereathe out normally do not e$hale into the device.

Place the mouthpiece into your mouth, "ith the mouthpiece facing to"ards you, and close yourlips tightly around it.

Inhale dose "ith a rapid and steady flo" "hile holding the T"isthaler hori+ontal.

Remove the mouthpiece from your mouth and hold your !reath for 2 to ? seconds (or as long as

you comforta!ly can.

Fhen you e$hale, !e sure that you are not e$haling into the device

Immediately replace the cap and turn in a cloc&"ise direction as you gently press do"n until youhear a clic&.

irmly close the T"isthaler to assure that your ne$t dose is properly loaded.

Ee sure that the arro" is in line "ith the dosecounter "indo".

8tore device in cool dry place.

The dose counter displays the num!er of doses remaining. Fhen the unit reads ?, this indicates


21/25

the last remaining dose. Fhen the counter reads ??, the unit must then !e discarded.

*erosol device com#arison

dvantages and disadvantages of various aerosol devices

Type dvantages Disadvantages5et ne!uli+er Patient coordination not

required

High doses possi!le

3o :: release

#$pensive

3ot porta!le pressuri+ed gas sourcerequired

>ore time required

:ontamination possi!le

Device preparation required !eforetreatment

3ot all medications availa!le

@ess efficient than other devices (deadvolume loss

ltrasonic ne!uli+er Patient coordination notrequired

High doses possi!le

3o :: release

8mall dead volume

Nuiet

3o drug loss duringe$halation

aster delivery than 1etne!uli+er

#$pensive

:ontamination possi!le

Prone to malfunction

3ot all medication availa!le

Device preparation required !eforetreatment

>etereddose inhaler :onvenient

@ess e$pensive than ne!uli+er

Porta!le

>ore efficient than ne!uli+er

3o drug preparation required

Difficult to contaminate

Patient coordination essential

Patient actuation required

@arge pharyngeal deposition

Difficult to deliver high doses

>any use :: propellants


>etereddose inhaler "ith @ess patient coordination >ore comple$ for some patients


22/25

holding cham!er required

@ess pharyngeal deposition >ore e$pensive than >DI alone

@ess porta!le than >DI alone

Dry po"der inhaler @ess patient coordinationrequired

:onvenient

Ereathhold not required

Propellant not required

Porta!le

Ereathactuated

Requires moderate to high inspiratory flo"

8ome units are single dose

:an result in high pharyngeal deposition


Difficult to deliver high doses

::% chlorofluorocar!on0 >DI% metereddose inhaler.

rom :onsensus 8tatement% erosols and Delivery Devices. Respir :are *???0 42%2;


23/25

*erosol delivery ventilator

actors affecting aerosol delivery during mechanical ventilation3e!uli+er

Position of ne!uli+er placement in the circuit

Type of ne!uli+er and fill volume

Treatment time

Duty cycle (I%# ratio

entilator !rand

>DI

Type of actuator

Timing of actuation

3e!uli+er and >DI

#ndotracheal tu!e si+e

Humidification of the inspired gas

"DI in2line s#acer

Inline metered dose inhaler spacing device

sing a cham!er results in a four to si$fold greater delivery of aerosol than actuation intoa connector attached directly to the endotracheal tu!e, or into an inline device that lac&s a

cham!er.

Ne& or "DI use (ith N++V


24/25

erosoli+ed medications, either !y ne!uli+er or >DI, can !e administered during 3PP

-rade /B

Crade E recommendation Crade E recommendation is a strong recommendation, and applies to most patients. :linicians

should follo" a strong recommendation unless a clear and compelling rationale for an alternativeapproach is present.

#$planation% Crade recommendation is a strong recommendation. It means that "e !elieve that if you follo"

the recommendation, you "ill !e doing more good than harm for most, if not all of your patients.Crade E means that the !est estimates of the critical !enefits and ris&s come from randomi+ed,

controlled trials "ith important limitations (eg, inconsistent results, methodologic fla"s, impreciseresults, e$trapolation from a different population or setting or very strong evidence of some other

form. urther research (if performed is li&ely to have an impact on our confidence in the estimatesof !enefit and ris&, and may change the estimates.

Recommendation %rades. 8trong recommendation% Eenefits clearly out"eigh the ris&s and !urdens (or vice versa

for most, if not all, patients

*. Fea& recommendation% Eenefits and ris&s closely !alanced andAor uncertain

Evidence %rades

. Highquality evidence% :onsistent evidence from randomi+ed trials, or over"helming

evidence of some other form

E. >oderatequality evidence% #vidence from randomi+ed trials "ith important limitations,or very strong evidence of some other form


25/25

:. @o"quality evidence% #vidence from o!servational studies, unsystematic clinicalo!servations, or from randomi+ed trials "ith serious fla"s

or a complete description of our grading system, please see the pToDate editorial policy

that can !e found !y clic&ing on Help, and then !out pToDate

-rade 0B

Crade *E recommendation Crade *E recommendation is a "ea& recommendation0 alternative approaches may !e !etter forsome patients under some circumstances.

#$planation% Crade * recommendation is a "ea& recommendation. It means 9this is our suggestion, !ut you

may "ant to thin& a!out it.9 It is unli&ely that you should follo" the suggested approach in all yourpatients, and you might reasona!ly choose an alternative approach. or Crade * recommendations,

!enefits and ris&s may !e finely !alanced, or the !enefits and ris&s may !e uncertain. In deciding

"hether to follo" a Crade * recommendation in an individual patient, you may "ant to thin& a!outyour patientGs values and preferences or a!out your patientGs ris& aversion.

Crade E means that the !est estimates of the critical !enefits and ris&s come from randomi+ed,

controlled trials "ith important limitations (eg, inconsistent results, methodologic fla"s, impreciseresults, e$trapolation from a different population or setting or very strong evidence of some other

form. urther research (if performed is li&ely to have an impact on our confidence in the estimatesof !enefit and ris&, and may change the estimates.

Recommendation %rades

. 8trong recommendation% Eenefits clearly out"eigh the ris&s and !urdens (or vice versa

for most, if not all, patients

*. Fea& recommendation% Eenefits and ris&s closely !alanced andAor uncertain

Evidence %rades

. Highquality evidence% :onsistent evidence from randomi+ed trials, or over"helming

evidence of some other formE. >oderatequality evidence% #vidence from randomi+ed trials "ith important limitations,

or very strong evidence of some other form

:. @o"quality evidence% #vidence from o!servational studies, unsystematic clinical

o!servations, or from randomi+ed trials "ith serious fla"s

or a complete description of our grading system, please see the pToDate editorial policy

that can !e found !y clic&ing on Help, and then !out pToDate.

delivery of inhaled medication in adults

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