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