DMSEMINAR

DM SEMINAR
AerosoltherapyinICU
py
Inderpaul Singh Sehgal
InderpaulSinghSehgal
 Aerosol therapy
Aerosoltherapy

Aerosoltherapyreferstothedeliveryofadrugtothe
Aerosol therapy refers to the delivery of a drug to the
bodyviatheairwaysbydeliveringitinanaerosolised
form
form

Anaerosol
An aerosol is astablesuspensionofsolid
a stable suspension of solid orliquid
or liquid
particles dispersed inairasafine mist
Physiological basis for aerosol delivery
Physiologicalbasisforaerosoldelivery
Impaction
Impaction:Particlehavingasize>3depositin
: Particle having a size > 3 deposit in
orophaynx andlargerairways
Diffusion:diffusionbywayofBrownianmotionis
thedominantmechanismforthesmallersized
aerosols(<0.5)
Sedimentation :particlesizeintherangeof13
:particle size in the range of 1 3
aresubjecttogravitationalsedimentationinthe
smallairwaysandtendstobeenhancedbybreath
holding
g
Martonen TB,etal PharmRes1993;10:8718
 Physical Characteristics of Aerosol
PhysicalCharacteristicsofAerosol

Sizeoftheaerosoldropletsisgenerallycharacterised
bymassmedianaerodynamicdiameter(MMAD)
TheMMADofanaerosolreferstotheparticle
diameter that has 50% of the aerosol mass residing
diameterthathas50%oftheaerosolmassresiding
aboveand50%ofitsmassbelowit
AnydropletwithMMADlargerthan5islikelytobe
filteredoutintheupperairwaysandfailtoreach
eventhelargerairways
 Aerosol
Aerosolparticleslessthan5insizereadilyreachthe
particles less than 5 in size readily reach the
distalareasoftherespiratorytract
Aparticlesizelessthan2isidealandisableto
percolaterightuptotheperipheralairways
Aerosolscontainingdrugswithhygroscopicproperties
arelikelytoincreaseinsizeinhumidconditionsthat
y
mayadverselyimpactthedeliveryofthedrug
Aerosols
Aerosolsthataregeneratedataveryhighvelocitytend
that are generated at a very high velocity tend
togetdepositedintheupperairwaysand
consequently the delivery to the lower airways is
consequentlythedeliverytothelowerairwaysis
compromised
 Pros&Cons

HessDRetalL.Aguidetoaerosoldeliverydevicesforrespiratorytherapists2005
FinkJB.:Mosbysrespiratorycareequipment.2010:91140
 Typesofaerosols
yp

Blandaerosol Pharmacologically active

i

Sterilewateror Aerosolswhichdeliverdrugs
hypotonic,normotonic,and tothelungs
hypertonicsaline
deliveredwithorwithout
oxygen
yg
 Blandaerosol

Humidifyinspiredgas,
Hydratedrymucosalsurfacesinpatientswith
Hydrate dry mucosal surfaces in patients with
inflamedupperairways
Enhanceexpectorationoflowerairway
E h i fl i
secretions
Inducesputumexpectorationfordiagnostic
purposes
 Routine
Routineuseofblandaerosolsisusually
use of bland aerosols is usually
discouraged
ineffectiveinliquefyingthesecretionsassufficient
e ect e que y g t e sec et o s as su c e t
volumefailtoreachthelowerairways
GallonAM.Thorax 51:429,1996.
theuseofblandaerosolsinthetreatmentofCOPD
hasnotbeenshowntobeofanybenefit

Blandaerosolsmayprovokebronchospasmandplace
p
patientsatriskfornosocomialpneumonia
p
AmericanThoracicSociety/EuropeanRespiratorySociety:
AmJRespir Crit CareMed152:577,1995
 Pharmacologicallyactiveaerosols
g y
Inhaled
Inhaledtherapyhasbeenusedclinicallysince
therapy has been used clinically since
theearlydaysofmedicalhistory
Drug
Drugisdelivereddirectlytoitstargetedsiteofaction
is delivered directly to its targeted site of action
Fewersideeffects,andtheonsetofactionisgenerallyfaster
Broad rangeofdrugsisavailable
g g asaerosols to treat lungg
diseases
adrenergic agonist
anticholinergics
ti h li i
antiinflammatory agents
antiinfectives
 Potentialhazardsofaerosoldrugtherapy
include
reactiontothedrugbeingadministered
reaction to the drug being administered
riskofinfection
bronchospasm
potential for delivering too much or too little ofthe
drugg

FinkJ:EgansFundamentalsofRespiratoryCare8thed.St.Louis,Mosby,2003,p761
Factorsaffectingdrugdelivery

Dhand R etalClin Chest Med29(2008)277296

 Inhalationtherapyinpatientsreceivinginvasive
mechanical ventilation
mechanicalventilation
Drugsadministeredasaerosolsinmechanically
ventilatedpatients:
til t d ti t
Bronchodilators
bagonists(albuterol,metaproteronol,fenoterol)
g ( p )
anticholinergicagents(ipratropiumbromide);
Prostaglandins
alprostadil, prostacyclin, iloprost, treprostonil
alprostadil,prostacyclin,iloprost,treprostonil
Mucolytics
acetylcysteine
Proteins
Proteins
Pulmozyme,surfactant
Antibiotics
antibacterials
tib t i l (aminoglycosides);antivirals(ribavirin);
( i l id ) ti i l ( ib i i )
antifungals(amphotericin);
Corticosteroids
b l
beclomethasone;budesonide
th b d id
 Bronchodilators
Indications
Indicationsforusingbronchodilatortherapy
for using bronchodilator therapy
inventilatorsupportedpatientsareas
follows
follows
1. asthma
2. COPD
3. acutebronchospasmorwheezing
4. elevatedairwayresistance
5. dynamichyperinflation
6. difficultyinweaning
7. p
chronicventilatordependence
 Goalsofbronchodilatortherapy
py

Reversebronchoconstriction
e e se b o c oco st ct o
Decreasetheworkofbreathing
Relievedyspnea
 Bronchodilators
2 adrenergics Anticholinergics
Shortacting Shortacting
Long acting
Longacting L
Longacting
ti
Bronchodilating
h dil i properties i Appear to have a role in acute asthma when
Appeartohavearoleinacuteasthmawhen
Augmentation ofmucociliary combinedwithsympathomimeticdrugs
clearance Inintubated patients toprevent bradycardia
Metabolicresponses induced bysuctioning
Inhibitionofmediatorreleasefrom Inpatientswithseverebronchorrhea
Mast cells basophils and possiblyothercells
Mastcells,basophils,and possibly other cells
Tremoristheprincipal sideeffectof2agonists
Hyperglycemia ,hypokalemia andhypomagnesemia

firstlinetherapyforthecriticallyillneedingbronchodilatation
 Prostanoids

Administrationofprostacyclinbyinhalation
provides targeted pulmonary vasodilation
providestargetedpulmonaryvasodilation
Aerosolizedvasodilatorsselectivelyincrease
bloodflowtowellventilatedbutpoorly
perfusedlungregions
f dl i

Dhand R.Curr Opin Crit Care2007;13:2738

 InhaledprostacyclinandprostaglandinE1are
aseffectiveasnitricoxideinimproving
ff d
oxygenation and hemodynamics
oxygenationandhemodynamics
Inhalediloprost ortreprostonil couldbe
employedfortreatmentofacutepulmonary
hypertension in mechanically ventilated
hypertensioninmechanicallyventilated
patients

Dhand R.Curr Opin Crit Care2007;13:2738

Respir Care2010;55(2):144157
Care 2010;55(2):144 157
 Review

AlthoughuseofneitheriNO
Although use of neither iNO noriAP
nor iAP hasreducedmortalityinpatients
has reduced mortality in patients
withARDS/ALI,bothcanaffordmodest,shorttermimprovementsin
oxygenation,whichcanbesignificantinpatientswithsevere,
refractoryhypoxemia
f t h i
September2010Volume111Number3
 Surfactant
Surfactantreplacementtherapy(SRT)hasbeen
evaluatedtocorrectdeficiencyoffunctional
surfactant in neonates and adults with acute
surfactantinneonatesandadultswithacute
lunginjury
ExogenoussurfactantsemployedforSRTare
mixturesofsyntheticphospholipidsalone
(Exosurf) or they are modified natural surfac
(Exosurf)ortheyaremodifiednaturalsurfac
tants obtainedfrommincedanimallung
 Theseexogenoussurfactantslacksurfactant
protein A and D and differ from natural
proteinAandDanddifferfromnatural
surfactantswithrespecttotheirfunctional
andmorphologicproperties
Inhaledsurfactantadministeredtoanimals
h l d f d i i d i l
g g j y
withnon homogeneouslunginjuryis
preferentiallydepositedinwellventilated
andlessinjuredlungregions
 Twoprospectivemulticenterrandomized
trials evaluated the efficacy of inhaled
trialsevaluatedtheefficacyofinhaled
surfactant(Exosurf)inpatientswithsepsis
inducedARDS
IInbothtrials,therewerenoimprovementsin
b th t i l th i t i
yg
oxygenation,durationofmechanical
ventilation,lengthofstayintheintensive
careunit,orsurvival
i i l
AmongpatientswithARDScausedbyadirectlunginjury,
those who received surfactant tended to have a higher
thosewhoreceivedsurfactanttendedtohaveahigher
survivalratethanthosewhoreceivedstandardtherapy
N E l JMed2004;351:88492
NEngl J M d 2004 351 884 92
 InhaledAntibiotics
HighmortalityrateassociatedwithVAP
High mortality rate associated with VAP
Limitedpenetrationofantibioticsintothe
p
lungafteri.v administration

Explorationofalternativeroutesofadministration
 Whyinhalationalroute?
y

Deliveryofgreaterantibioticconcentration
to the airways
totheairways
Favorableoutcomesinpatientswithcystic
fibrosis
Lessersystemicsideeffects

Palmer LB.Clin Chest Med32(2011)559574

 Inhaled
Inhaledantibiotictherapyinmechanically
antibiotic therapy in mechanically
ventilatedpatientsiscontroversialandless
welldefined
Recentwork,however,suggeststhat aerosolized
antibioticscanbeusedinmechanicallyventilated
patients
patients
Palmer LB.Clin Chest Med32(2011)559574
 Inhaledantibiotictherapyinthemechanically
py y
ventilatedpatientappearspromising,butmust
stillberegardedasinvestigational
ill b d d i i i l
 Mucolytics
y
Retentionofairwaysecretionsisassociated
withahighriskofpneumonia
Acetylcysteine isoftenemployedtoenhance
is often employed to enhance
secretionclearancebyreducingsputum
viscosity
Increase
Increaseininspiratoryairwayresistanceafter
in inspiratory airway resistance after
administrationofmucolyticagentsbyaerosol
orbolusinstillationisaproblemwiththe
b l i ill i i bl ih h
g
routineuseoftheseagents
 Recombinant
RecombinanthumanDNase
human DNase (Pulmozyme)
(Pulmozyme)
wasshowntoimprovemucusclearancein
ventilatorsupportedpatientswithspinal
cord injury and recurrent atelectasis
cordinjuryandrecurrentatelectasis
refractorytoconventionaltreatment
Duetocostconstraints,Pulmozyme cannot
b
berecommendedforroutineuseinthe
d df i i h
g p
managementoftheventilatordependent
patientswithinspissated secretions
 Corticosteroids
Inhaledcorticosteroidsnotrecommendedfor
thecriticallyillwithacuteexacerbationsof
obstructivelungdisease
When
Whenpatientsarehospitalizedforreasons
patients are hospitalized for reasons
otherthanacuteairwayobstruction,inhaled
corticosteroidsmaybecontinuedifpatients
have been taking these agents for asthma or
havebeentakingtheseagentsforasthmaor
COPDmaintenancetherapy.
 The
Theuseofinhaledcorticosteroidshasbeen
use of inhaled corticosteroids has been
recommendedforuseinneonatesand
infantswithbronchopulmonary dysplasia
IInhaledcorticosteroidsprobablyhaveonlya
h l d ti t id b bl h l
limitedroleinthetreatmentofventilator
supportedprematureinfants.
 Factorsgoverningpulmonarydeposition
g gp y p
Fivemajorvariablesneedtobeconsideredto
j
optimizeaerosoldeliveryduringmechanical
ventilation
1 aerosolgenerator
g
2 aerosolparticlesize
3 conditions in the ventilator circuit
conditionsintheventilatorcircuit
4 artificialairway
5 ventilator parameters
 THEAEROSOLGENERATOR
Devicewhichgeneratesaerosol
g
CFC
pMDIs

HFA

Jetnebulizers

Nebulizers
Nebulizers

Ultrasonic nebulizers
Ultrasonicnebulizers
 Choice of aerosol generator
Choiceofaerosolgenerator
Bettergenerator>bettersize>better
g
deposition
Largerparticlesaretrappedintheventilator
circuit and endotracheal tube
circuitandendotrachealtube
DevicesthatproduceaerosolswithMMAD<2
p
mmaremoreefficientduringmechanical
ventilation
il i
Drug delivery with various devices
Drugdeliverywithvariousdevices

HessDRetalL.Aguidetoaerosoldeliverydevicesforrespiratorytherapists2005
FinkJB.:Mosbysrespiratorycareequipment.2010:91140
HessDRetalL.Aguidetoaerosoldeliverydevicesforrespiratorytherapists2005
FinkJB.:Mosbysrespiratorycareequipment.2010:91140
 p
pMDIs

Inventilatedpatients,pMDIsarechieflyused
todeliverbronchodilators
d li b h dil
pMDIs
pMDIsmorepopularthannebulizersforuse
more popular than nebulizers for use
intheintensivecareunit
StephenP.Respir Care2005;50(9):11771188
Chlorofluorocarbon(CFC)basedMDIshave
( )
beenreplacedbyanewergenerationof
h d fl
hydrofluoroalkane
lk (
(HFA)basedMDIs
)b d
 WasCFCbetter?
Inbenchmodelsofmechanicalventilation,
In bench models of mechanical ventilation,
albuterolHFA pMDIsemployedwithan
Aerovent spacerprovidedrugdeliverythatis
lower than that with CFC pMDIs
lowerthanthatwithCFC pMDIs
Contrarily,beclomethasoneHFA
Contrarily beclomethasone HFA pMDIs
pMDIs
employedwithanAerochamber HCMV
spacerhadahigherefficiencyofdrug
d li
deliverythanthebeclomethasoneCFCpMDI
h h b l h CFC MDI
 Differentformulationsandtypesofspacer
Different formulations and types of spacer
ThebeclomethasoneHFApMDI isasolution
basedwhereasthealbuterolHFA pMDI isa
suspension based
suspensionbased
SolutionbasedpMDI
p produceanextrafine
p
aerosolwithMMADof1.2m
Efficiencyofdrugdeliverydependsonhow
well the canister stem fits into the actuator
wellthecanisterstemfitsintotheactuator
ToimprovedrugdeliverywithHFA
To improve drug delivery with HFApMDIs
pMDIsin
in
thesettingofmechanicalventilation,the
actuatorsrequiredtoconnectthemin
i d h i
ventilatorcircuitsneedtobematchedtothe
sizeofthepMDI canisterstem
 Spaceroradapterdevices
p p
SSeveralcommerciallyavailableadaptersor
l i ll il bl d t
p
spacersareusedtoconnectthepMDIp
canistertotheventilatorcircuit
Thetypesofadaptersavailableforclinical
use include elbow adapters inline devices
useinclude,elbowadapters,inlinedevices
thatmaybeunidirectionalorbidirectional,
andchamberorreservoiradapters

Dhand R.JAEROSOLMED.Vol 21,(1),2008:4560

 AchamberspacerwithapMDI
A chamber spacer with a pMDI inaventilator
in a ventilator
circuitresultsinfour tosixfold greateraerosol
drugdeliverycomparedwitheitheranelbow
adapter or a unidirectional inline spacer
adapteroraunidirectionalinlinespacer
Rauetalfoundthattheefficiencyofa
bidirectionalinlinespacerwashigherthana
unidirectional inline spacer and was
unidirectionalinlinespacer,andwas
comparabletothatachievedwithchamber
spacers;however,theperformanceofthe
p
bidirectionalspacerhasnotbeenestablishedin
clinicalstudies

RauJL etal.Respir Care.1998;43:705712

TheAerochamber
The Aerochamber HCMV
HC MV isanothercommerciallyavailableadapterforaerosol
is another commercially available adapter for aerosol
deliverywithpMDIsinmechanicallyventilatedpatients

ItismoreefficientforaerosoldeliverywithbeclomethasoneHFA
y pMDIs
p
comparedtobeclomethasoneCFC pMDIs
ApMDI andchamberspacerplacedata
distance of approximately 15 cm from the
distanceofapproximately15cmfromthe
endotrachealtubeprovidesefficientaerosol
deliveryandelicitsasignificantbronchodilator
response
response
 Nebulizers
Both
Bothjetandultrasonicnebulizershavebeen
jet and ultrasonic nebulizers have been
employedforaerosoldeliveryduring
mechanicalventilation
h i l til ti
p y y
Nebulizersareemployedtodeliveravariety
ofagentssuchasbronchodilators,
prostanoids,antibiotics,surfactant,mucolytic
t id tibi ti f t t l ti
agents,andcorticosteroidstomechanically
ventilatedpatients

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.2008:21;4560
 Jetnebulizers
Ajetofcompressedairoroxygenunderhigh
pressureisemployedtogenerateanaerosol
Jetnebulizersareconnectedintheinspiratorylimb
Jet nebulizers are connected in the inspiratory limb
oftheventilatorcircuit
Theymaybeoperatedcontinuouslybypressurized
gasfromawallsystemorgascylinder
Intermittentdeliverybytheairflowgeneratedby
Intermittent delivery by the air flow generated by
theventilatorcouldbeemployedtorunthe
nebulizerduringinspiration
 Intermittentoperationismoreefficient
Intermittent operation is more efficient
Therateofaerosolproductionishighly
p g y
variable,notonlyamongbrandsofnebulizers
b
butevenindifferentbatchesofthesame
i diff b h f h
brand
Ventilatorswithinbuiltnebulizersfacilitate
reproducibleandconsistentdosingwitha
variety of agents in ventilated patients
varietyofagentsinventilatedpatients
 Thenatureoftheaerosolproduced,particlesize,differs
amongvariousnebulizer brands
Operational
Operationalefficiencyofanebulizerchangeswiththe
efficiency of a nebulizer changes with the
pressureofthedrivinggasandwithdifferentfill
volumes
volumes
Placingajetnebulizeratadistancefromthe
endotrachealtubeimprovesitsefficiencycompared
withplacingitbetweenthepatientYandendotracheal
tube
Addition
Additionofareservoirbetweenthenebulizerand
of a reservoir between the nebulizer and
endotrachealtubealsomodestlyincreasesefficiencyof
d
drugdelivery
d li
 Ultrasonic nebulizers
Vibrationfrequencyandamplitudeofvibrationof
thepiezoelectriccrystalinfluenceaerosolparticle
size and drug output respectively
sizeanddrugoutput,respectively
Mostultrasonicnebulizershaveahigherrateof
nebulizationandrequireashortertimeof
p j
operationthanjetnebulizers
Aerosolparticlesizeislargerwithultrasonic
nebulizerscomparedtojetnebulizers
b l d b l
 Ul
Ultrasonicnebulizershaveahigherefficiencyfor
i b li h hi h ffi i f
aerosoldeliveryduringmechanicalventilationthanjet
nebulizers
The
Thecostandbulkofultrasonicnebulizersandtheir
cost and bulk of ultrasonic nebulizers and their
relativeinefficiencyinnebulizingdrugsuspensionsare
majorlimitationstotheiruse
Placementofultrasonicnebulizersproximalor
distaltotheYpieceintheventilatorcircuit
does not influence the efficiency of aerosol delivery
doesnotinfluencetheefficiencyofaerosoldelivery

Theefficiencyofaerosoldeliverywithultrasonic
nebulizers can be modestly improved by employing a
nebulizerscanbemodestlyimprovedbyemployinga
longerinspiratorytime,byreducingtheminute
ventilation,andbyemployingalowerrespiratoryrate
il i db l i l i
 Wh
Whenusedoptimally,MDIsandnebulizersare
d ti ll MDI d b li
equallyeffectiveinthetreatmentofpatientswith
obstructivelungdisease
MDIs
MDIsarepreferredinventilatedpatientsover
are preferred in ventilated patients over
nebulizers
Rateofnebulizeraerosolproductionishighly
, y g
variable,notonlyamongbrandsofnebulizers
Natureoftheaerosolproduced,especiallyparticle
size,ishighlyvariableamongdifferentnebulizers
h hl bl d ff b l
 AEROSOLPARTICLESIZE

Duringmechanicalventilation,largerparticles
p
producedbypMDIsandnebulizersaretrappedin
yp pp
theventilatorcircuitandendotrachealtube
D
DevicesthatproduceaerosolswithMMAD2m
i h d l i h MMAD 2
aremoreefficientduringmechanicalventilation
thandevicesthatproduceaerosolswithlarger
particles
particles
CONDITIONSINTHEVENTILATOR
CIRCUIT
CIRCUIT
Humidity

Humidificationleadstoanincreasedloss of
aerosolintheventilatorcircuit
Withcarefulattentiontothetechniqueof
administration,theimpactofhumidityondrugdelivery
canbeovercomebydeliveringasomewhathigherdrug
dose
 Adrycircuitcouldbeemployedfordeliveryof
p g
expensiveorthoseagentsforwhichthe
amountofdrugdepositioniscritical
Whenadrycircuitisemployed,drug
When a dry circuit is employed drug
administrationshouldbeachievedwithina
shortperiod(lessthan10min)tominimize
h (l h )
theeffectsofdrygasontheairwaymucosa

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

ThefilterintheHMEisabarriertoaerosol
delivery and it has to be removed from the
delivery,andithastoberemovedfromthe
circuitduringaerosoldelivery

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

 Gasdensity
y
Inhalationofalessdensegassuchasheliumoxygen
70/30 i t
70/30mixture,improvesdrugdeliveryinboth
i d d li i b th
pediatricandadultmodelsofmechanicalventilation
WithpMDIstheremaybeasmuchas50%increasein
the amount of aerosol delivered to the lower
theamountofaerosoldeliveredtothelower
respiratorytract
Howevernebulizeroperationwithhelium oxygen
reduceddrugoutputandrespirable mass
 Apracticalmethodtoachievemaximumpulmonary
p g
depositionofaerosolfromanebulizerduring
mechanicalventilationistooperatethenebulizer
with oxygen at a flow rate of 6 to 8 L/min and to
withoxygenataflowrateof6to8L/minandto
entraintheaerosolgeneratedintoaventilator
circuitcontainingheliumoxygen

GoodeML,etal. AmJRespir Crit CareMed.2001;163:109114

 ARTIFICIALAIRWAY
Aerosolimpactionontheendotrachealtubeposesa
significantbarriertoeffectivedrugdelivery
Drug
Druglosseswithintheendotrachealtubecouldbe
losses within the endotracheal tube could be
minimizedbyplacingtheaerosolgeneratorata
di
distancefromtheendotrachealtubeinsteadofbeing
f h d h l b i d fb i
directlyconnectedtoit
WhenapMDI andspacerareemployed,thepresence
of humidity in the circuit increased aerosol deposition
ofhumidityinthecircuitincreasedaerosoldeposition
intheendotrachealtubebyapproximatelythreefold

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

 Invitrostudiesshow,significantendotrachealtube
deposition of aerosol with ultrasonic nebulizers but
depositionofaerosolwithultrasonicnebulizers but
notwithjetnebulizers
Aerosoldepositionintracheostomytubeshasnot
been studied in as much detail as endotra cheal
beenstudiedinasmuchdetailasendotra
tubes

HarveyCJetal.Eur Respir J.1997;10:905909

 VENTILATORPARAMETERS

Theactuationofametereddoseinhaler(MDI)
mustbesynchronizedwiththepreciseonsetof
tb h i d ith th i t f
inspiratoryairflowfromtheventilator
Asshortas1to1.5secdelaybetweenMDI
actuationandaventilatorbreathcanprofoundly
reduce the efficiency of drug delivery
reducetheefficiencyofdrugdelivery

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

 Intermittentoperationoftheismoreefficient
p
foraerosoldeliverycomparedwithcontinuous
aerosol generation because it minimizes
aerosolgenerationbecauseitminimizes
aerosolwastageduringtheexhalationphase
of the breathing cycle
ofthebreathingcycle

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

 Lowerdrivingpressureprovidedbythe
( p ) p y
ventilator(<15psi)thanthatprovidedby
pressurizedgas(>50psi)coulddecreasethe
efficiency of some nebulizers
efficiencyofsomenebulizers
Aerosolgeneratedbyanebulizeroperatingat
thelowerpressuremaygenerateparticles
h l l
whosediameterislargerthanthe1to5m
thatisoptimalforaerosoldeposition
Characteristicsoftheventilatorbreath
Thecharacteristicsoftheventilatorbreathhavean
importantinfluenceonaerosoldrugdelivery
A
Atidalvolumeof500mLormore(inanadult)longer
tidal volume of 500 mL or more (in an adult) longer
inspiratorytime,andslowerinspiratoryflowsimprove
aerosol delivery
aerosoldelivery
Drugdeliveryislinearlycorrelatedwithalongerduty
cycle(Ti/Ttot)forbothpMDIsandnebulizers
DrugdeliveryisimprovedwhenapMDI
g y p p issynchronized
y
withasimulatedspontaneousbreathcomparedwitha
controlled ventilator breath of similar tidal volume
controlledventilatorbreathofsimilartidalvolume
HigherdrugdeliverywithhigherTi/Ttot ratioandatlowerflowrates

FinkJBetal.AmJRespir Crit CareMed.1999;159:6368

Linear relationship between drug delivery and inspiratory time
Linearrelationshipbetweendrugdeliveryandinspiratorytime

FinkJBetal.AmJRespir Crit CareMed.1999;159:6368

 UnlikeMDIs,nebulizerefficiencyisnotablylower
duringpressurecontrolledventilationthanduring
volumecontrolledventilation
Use
Useofaflowtriggerwithanebulizercoulddilutethe
of a flow trigger with a nebulizer could dilute the
aerosolandincreasethewashoutoftheaerosolinto
the expiratory limb between breaths
theexpiratorylimbbetweenbreaths
Deliverytobothfiltersatthebronchiwasgreater
withsinusoidal(362.9
ih i id l ( 40.4ug)anddecelerating
) dd l i
flows(392.9 33.9IJ.g) thanwithsquareflow
waveform(327.3 36.8ug)(p<0.01ineachinstance)

FinkJBetal.AMJRESPIRCRITCAREMED1996;154:3827.
Aerosoldeliveryinvolumev/spressurecontrolledmodes

FinkJBetal.AMJRESPIRCRITCAREMED1996;154:3827.
 Operationalefficiencyofanebulizerchanges
with the pressure of the driving gas and with
withthepressureofthedrivinggasandwith
differentfillvolumes
Unlessscrupulouslycleanedanddisinfected,
nebulizerscanbeasourceforaerosolization
ofbacteria
Ventilatormode(Pressurev/sVolume)and
Ventilator mode (Pressure v/s Volume) and
lungmechanicscaninfluencedrugdelivery
fromanebulizer
Nebulizers MDI
Highlyvariableoperationalefficiency provideareliabledose,

p
Dependsonventilator flow easytoadminister
y

sourceforaerosolization ofbacteria donotposeariskofbacterial

contamination
contamination
Expensive Cheaper
Addflowtotheventilatorcircuit Donotaddadditionalflow
 A
Asignificantproportionoftheinhaledmassdepositsin
significant proportion of the inhaled mass deposits in
theendotrachealtubeandasmallerproportionis
exhaled
exhaled
Efficiencyofdrugdepositioninthelowerrespiratory
tract of ventilated patients is lower with nebulizers than
tractofventilatedpatientsislowerwithnebulizersthan
withpMDIs
Higherdrugdosesareemployedwithnebulizersto
h d d l d h b l
offsettheirreducedefficiency
Thetotalamountofdrugdepositinginthelower
respiratorytractwithjetnebulizersisprobably
comparabletothatachievedwithsmallerdrugdoses
employedwithapMDI
Technique of aerosol delivery by pMDI
TechniqueofaerosoldeliverybypMDI

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

Technique for drug delivery by jet nebulizer
Techniquefordrugdeliverybyjetnebulizer

Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560

 Vibratingmeshnebulizers
g
1. Newergenerationofnebulizersemployavibrating
meshorplatewithmultipleaperturestoproduce
anaerosol
2. Thesehighrateofnebulizationanddrugoutputis
two to three times higher than with jet nebulizers
twotothreetimeshigherthanwithjetnebulizers
3. Temperatureofthesolutiondoesnotchange
duringoperationofthevibratingmesh nebulizers,
andproteinsandpeptidescanbenebulizedwith
minimalriskofdenaturation
 Intratracheal catheter
Anoveldevicethatproducesanaerosolinthetrachea
Acentrallumentransmitsthesolutiontobenebulized
andcompressedgasisforcedunderhighpressure(100
psi)atavariableflowrate(0.13.0L/min)through
severaladditionallumensthatsurroundthecentral
lumen
Dropletsofdrugsolutionformatthetipofthecatheter
andaerosolisformedbythepressurizedgasbreaking
uptheliquiddroplets
Theuseoftheintratracheal catheterispresentlyunder
investigation
investigation
Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560
 Inhaledtherapyduringnoninvasive
positivepressureventilation
ii il i
Severalinvestigatorshaveemployedinvitromodels
todeterminetheoptimaltechniquesforaerosol
deliveryinpatientsreceivingNIPPV
Optimum
Optimumsettingsrequiredformaximumdrug
settings required for maximum drug
deliverywithapMDI duringNIPPVhavenotbeen
established
established
Inabenchmodel,10cmH2Ocontinuouspositive
airwaypressure(CPAP)reduceddrugdeliveryfrom
ajetnebulizer
Dhand R.JOURNALOFAEROSOLMEDICINEANDPULMONARYDRUGDELIVERY.Vol 21,(1),2008:4560
 ChartCetalfoundafivefoldvariation(between5
)
and25%ofthenominaldose)intheamountof
albuteroldeliveredbyajetnebulizerinvitro;
D
Deliverywashighest(25%)whenthenebulizerwas
li hi h (25%) h h b li
closetothepatient,inspiratorypressurewashigh
(20cmH2O),andexpiratorypressurewaslow
(5cmH2O)
(5cmH2O)
BothpMDIsandnebulizerscouldbeemployed
during NIPPV but further studies are needed to
duringNIPPV,butfurtherstudiesareneededto
optimizedrugdeliveryfromthesedevices
duringNIPPV
 Conclusion
Aerosoltherapyisanintegralpartof
py g p
managementofpatientsinICU
Aerosolsizeof1to5micronMMADare
A l i f1t 5 i MMAD
betterdepositedinlungs
Humidityintheventilatorcircuitreduces
drug delivery
drugdelivery
Highflowrates,reducedinspiratorytime
andlowtidalvolumeshamperdrugdelivery
dl id l l h d d li
 Spacerimprovesdrugdelivery
pMDI betterthannebulizersfordrugdelivery
better than nebulizers for drug delivery
Distanceof15cms fromETininspiratory
li b i
limbimprovesdrugdelivery
d d li
,
Roleofinhaledantibiotics,surfactant&
vasodilatorsneedsfurthervalidation