DTIC ADA627786: Inhalation Injury: Pathophysiology and Clinical Care. Proceedings of a Symposium Conducted at the Trauma Institute of San Antonio, San Antonio, TX, USA on 28 March 2006

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burns 33 (2007) 681–692
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Review
Inhalation injury: Pathophysiology and clinical care
Proceedings of a Symposium Conducted at the Trauma
Institute of San Antonio, San Antonio, TX, USA on
28 March 2006
Leopoldo C. Cancioa,*, Andriy I. Batchinskya, Michael A. Dubicka, Myung S. Parka,
Ian H. Blacka, Rube´n Go´meza, Jeffrey A. Faulknerb, Travis J. Pfannenstielb, Steven E. Wolfa
aU.S.ArmyInstituteofSurgicalResearch,FortSamHouston,TX78234-6315,USA
bBrookeArmyMedicalCenter,FortSamHouston,TX,USA
article info
Articlehistory:
Accepted15November2006
Keywords:
Inhalationinjury
Mechanicalventilation
Acuterespiratorydistresssyndrome
Contents
1. Introduction.................................................................................. 682
2. Ventilation–perfusionchangesfollowinglunginjury(AndriyBatchinsky,MD).............................. 682
2.1. Ventilation–perfusion(V/Q)heterogeneity ..................................................... 682
2.2. MultipleInertGasEliminationTechnique(MIGET)............................................... 682
2.3. Acutelunginjury(ALI):V/Qmismatchorshunt?................................................ 682
2.4. MIGETforV/Qrelationshipsinacuterespiratorydistresssyndrome(ARDS)........................... 683
2.5. TheetiologyofhypoxiainARDSvarieswithmechanismofinjury.................................. 683
3. Smokeinhalationinjuryofthelungandairways:roleofoxidants(MichaelA.Dubick,PhD) .................. 683
3.1. Oxidantsaffecttheliningfluidoftherespiratorytractwhereantioxidantconcentrationsvary ........... 683
3.2. Antioxidantsfunctionasreducingagents ..................................................... 683
3.3. Woodsmokeisacomplexmixtureofgasesandparticulates...................................... 684
3.4. Theeffectsofwoodsmokeinhalationonantioxidantsinthelung.................................. 684
3.5. ReactiveoxygenspeciesareamajorfactorinthedevelopmentofALIaftersmokeexposure............. 684
3.6. Nitrogenspeciesandnitricoxideintissuefollowinginhalationinjury............................... 684
3.7. Ininhalationinjurytheroleofoxidantsisnotfullyunderstood.................................... 685
4. AssessmentoftheseverityofinhalationinjurybyCTscan(MyungS.Park,MD)............................ 685
* Correspondingauthor.Tel.:[phone].
E-mailaddress:[email protected](L.C.Cancio).
0305-4179/$32.00#2006ElsevierLtdandISBI.Allrightsreserved.
doi:10.1016/j.burns.2006.11.009
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4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER
Inhalation injury: pathophysiology and clinical care proceedings of a
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symposium conducted at the Trauma Institute of San Antonio, San
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6. AUTHOR(S) 5d. PROJECT NUMBER
Cancio L. C., Batchinsky A. I., Dubick M. A., Park M. S., Black I. H.,
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Gomez R., Faulkner J. A., Pfannenstiel T. J., Wolf S. E.,
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682 burns 33 (2007) 681–692
4.1. EvaluationofCTscanininhalationinjuryinananimalmodel..................................... 685
4.2. CTscanispotentiallyusefulingaugingtheseverityofinhalationinjurynon-invasively ................ 685
5. Emergencyventilationwithinsufflatedoxygen(IanH.Black,MD) ....................................... 685
5.1. Deliveringairviatracheotomyisnotanewidea................................................ 685
5.2. Trachealgasinsufflation(TGI) .............................................................. 686
5.2.1. Questions ........................................................................ 686
6. Clinicalcareofpatientswithinhalationinjury(Rube´nGo´mez,MD,PhD).................................. 686
6.1. Fiberopticbronchoscopy(FOB)fordiagnosisandtreatment ....................................... 686
6.2. Negativeeffectsoffluidrestriction........................................................... 687
6.3. Bronchodilatorsandinhaledheparinmaybehelpfulininhalationinjury ............................ 687
6.4. Lung-protectivestrategiesformechanicalventilation............................................ 687
6.5. Patientswithinhalationinjuryareathighriskforbronchopneumonia.............................. 687
6.6. Tracheostomy ........................................................................... 687
7. Laryngealandupperairwaysequelaeofinhalationinjury(JeffreyA.Faulkner,MD,andTravisA.Pfannenstiel,MD) 687
7.1. Vocalcordparesisinlunginjury ............................................................ 687
7.2. Etiologyofvocalcordparesis ............................................................... 687
7.2.1. Question......................................................................... 688
8. Artificiallungtechnology(LeopoldoC.Cancio,MD)................................................... 688
8.1. Extracorporealmembraneoxygenation(ECMO)................................................. 688
8.2. Theefficiencyofgasexchangeinartificiallungdevices .......................................... 688
8.3. Designconsiderations..................................................................... 688
8.4. EfficientratesofoxygenconsumptionandCO removal.......................................... 689
2
8.5. Intravenousvenousoxygenator(IVOX)........................................................ 689
8.6. Hattlercatheterorintravenousmembraneoxygenator(IMO)...................................... 689
8.7. ArteriovenousCO removal(AVCO R)......................................................... 689
2 2
8.8. Paracorporealrespiratoryassistlung(PRAL).................................................... 689
8.8.1. Questions ........................................................................ 689
9. Inhalationinjury:summaryandconclusions(StevenE.Wolf,MD)....................................... 690
Acknowledgements............................................................................ 690
References................................................................................... 690
1. Introduction basedoncalculationsofthepulmonaryvenousadmixture[1]
and dead space ventilation [2], and assessment of regional
Despiteadvancesincriticalcareingeneralandinmechanical distributionofbloodflowandventilationbyradioactivetracer
ventilationinparticular,inhalationinjurycontinuestoimpose techniques[3,4].Thesemethodsunveiledconsiderableinfor-
an unacceptable burden of morbidity and mortality on burn mation on V/Q relationships, but were limited in resolution
patients.TherecentconflictinIraqhasproducedanincreasein bothatthelowerandupperscalesoftheV/Qratios[5].
thenumberofpatientswithinhalationinjurytreatedhereatthe
U.S. Army Burn Center, and has led to new observations 2.2. MultipleInertGasEliminationTechnique(MIGET)
concerningthemanycomplicationsofinhalationinjurysuchas
theriskoflaryngealsequelae.Meanwhile,ongoingresearchhas With the introduction of the Multiple Inert Gas Elimination
continuedtoexpandourunderstandingofthepathophysiology Technique(MIGET)in1974byPeterWagner[6],acomprehen-
of inhalation injury. In March 2006, we conducted a multi- sive tool in respiratory physiology emerged that became the
disciplinary conference under the auspices of the Trauma goldstandardindistinguishingamongthedifferentintrapul-
InstituteofSan Antonio(TRISAT)whichwasbroadcastfrom monary causes of hypoxia, i.e. true shunt, V/Q mismatch,
thiscenterattheU.S.ArmyInstituteofSurgicalResearch,via alveolarhypoventilationanddiffusionlimitation.Fordetailson
videoteleconference, to our sister institutions, Wilford Hall MIGET,pleaseseeAppendixA.Inanormallungthebloodflowis
Medical Center and the University of Texas Health Science fully contained within the range of V/Q=0.1 and V/Q=10.
CenteratSanAntonio.Ourpurposewastoreviewbothcurrent AbnormallylowV/Qis<0.1andabnormallyhighisV/Q>10.
clinicalpracticeandrecentlaboratoryinvestigations. ShuntisspecifiedasbloodflowinunitswithV/Q<0.005and
deadspaceasventilationinunitswithV/Q>100.
2. Ventilation–perfusion changes following 2.3. Acutelunginjury(ALI):V/Qmismatchorshunt?
lung injury (Andriy Batchinsky, MD)
EarlyMIGETfindingssuggestedthatthepredominantcauseof
2.1. Ventilation–perfusion(V/Q)heterogeneity hypoxiainchronicdiseasesisV/Qmismatch,whereasinacute
lung injury (ALI) it is shunt [7]. However, recent evidence
Attempts to investigate ventilation–perfusion (V/Q) hetero- suggests that subtle differences in pathophysiologic distinc-
geneityhavebeenmadeforabout100yearsandinitiallywere tionamongvariousformsofALImayalsobemadebasedon
burns 33 (2007) 681–692 683
MIGETanalysis.Shimazuet al.at theU.S.Army Institute of
Surgical Research used MIGET to investigate of smoke
inhalation [8]. MIGET sampling was performed before and
24h after smoke exposure. They concluded that 24h post-
exposure,smokeinhalationcausessmallairwaysinjuryand
hypoxia, instigated predominantly by V/Q mismatch rather
than shunt. Histologically, smoke inhalation caused small-
airway injury [8] as well as large-airway injury with ciliary
disorientationandcastformation[9].
2.4. MIGETforV/Qrelationshipsinacuterespiratory Fig.1–SpectrumofARDS.Smokeinhalationinjuryis
distresssyndrome(ARDS) causedbysmallairwayinjury,primarilyfeaturingV/Q
mismatchbyMIGET.Ontheotherendofthespectrumis
In a recent study, we applied MIGET to investigate V/Q pulmonarycontusioncausedbydisruptionofthealveolar
relationshipsinARDSsecondarytoinhalationofchlorinegas capillarymembraneandfeaturingshunt.Chlorine
in sheep and implicated both shunt and transient V/Q inhalationinjuryoccupiesamiddlegroundbetweenthe
mismatch as causative factors for development of hypoxia two,featuringbothV/Qmismatchandanincreasein
in the first 2–24h after inhalation injury [10]. On histology, shunt.
bothsmall-airwayandalveolar–capillarymembraneinjuries
wereidentified.WealsoinvestigatedtheV/Qrelationships6h
after right-sided pulmonary contusion (PC) followed by unstable and partially atelectatic or flooded alveoli can be
12cm3/kghemorrhageandresuscitationinswine.Wefound inferred, moderate PEEP [15] or other lung-recruitment
that shunt and increased dead space ventilation caused the maneuvers may be indicated in an effort to minimize
depressedP O values6hafterpulmonarycontusion.Histo- expansion of the shunt compartment and prevent further
a 2
logically, PC was characterized by evidence of alveolar– atelectasis.
capillary membrane injury. In addition, when dynamic
assessmentofV/Qchangeswasconductedintwoadditional
animals,minutestohoursafterPC,wefoundatransientshift 3. Smoke inhalation injury of the lung and
in blood flow to low but non-zero V/Q compartments airways:roleofoxidants(MichaelA.Dubick,PhD)
(unpublisheddata).SimilarMIGETfindingshavebeenimpli-
cated in other animal [11] and human ARDS studies [12,13]. 3.1. Oxidantsaffecttheliningfluidoftherespiratorytract
These investigators interpreted the transient channeling of whereantioxidantconcentrationsvary
bloodflowtolowV/Qbutother-than-shuntcompartmentsas
MIGET evidence for existence of partially flooded but As it is currently understood, oxidants, such as inhaled
oxygenating alveoli. Furthermore, it is possible that these components of smoke, gaseous air pollutants, particulate
unitsmaythenbecomefullyengagedingasexchangeor,with matter,orothertoxicants,reactfirstwiththeliningfluidthat
diseaseprogression,belosttotheshuntfraction. covers the surfacesof the respiratory tract. This lining fluid
containsanumberofcompoundswithantioxidantproperties,
2.5. TheetiologyofhypoxiainARDSvarieswith bothenzymaticandnon-enzymatic,thatserveasamajorline
mechanismofinjury of defense against oxidative injury [16]. However, the
concentrationsoftheseantioxidantsvaryalongtherespira-
Inconclusion,accumulatingdatasuggeststhatthepercep- tory tract such that they are not distributed uniformly
tionofALIandARDSasapurely‘‘shunt’’phenomenonmay throughout the respiratory system. In addition, compounds
be erroneous. Together with the other lung-injury studies withantioxidantactivitiesarefoundincellsoftherespiratory
employing MIGET, the studies presented here suggest that tract and lung parenchyma, as well as in the blood that
the etiology of hypoxia in different forms of ARDS varies perfusesthesetissues.
with mechanism of injury (Fig. 1). An improved under-
standingofthedifferencesamongvarioustypesofARDS,as 3.2. Antioxidantsfunctionasreducingagents
revealed byMIGET, maybetter our clinical managementof
these patients. For example, those forms of ARDS which Thesecompoundsarelabeledasantioxidantsbasedontheir
feature V/Q mismatch and small-airway injury may be function as reducing agents, chelating agents, detoxifying
amenable to interventions that maintain airway patency, enzymes or cofactors to enzymes. As examples, reducing
such as high-frequency percussive ventilation and nebu- agentssuchasglutathione(reducedform)anduricacidare
lizedanticoagulants[14].Ontheotherhand,formsofARDS considered important water-soluble antioxidants. In addi-
that feature disruption of the alveolar–capillary membrane tion, a number of metalloenzymes such as superoxide
maybeparticularlyvulnerabletooverzealousfluidresusci- dismutase, glutathione peroxidase and catalase have well-
tation. The latter was observed by us in the pulmonary described antioxidant function, as do dietary components
contusionstudyaswellasinthechlorineinhalationstudy. such as Vitamin C, Vitamin E, carotenoids and various
Inbothcases,vigorousfluidloadingworsenedthehypoxia. polyphenolic substances. Certain B Vitamins have also
Finally, in those models of ARDS in which the existence of been included as dietary antioxidants. It should also be
684 burns 33 (2007) 681–692
mentioned that the ability of the cell to compartmentalize 3.4. Theeffectsofwoodsmokeinhalationonantioxidants
function is an important component of its antioxidant inthelung
defense system. The various antioxidants are distributed
differentlyindifferentcompartmentsofthecellsuchasin In other studies we investigated the effects of wood smoke
thecytoplasm,incorporatedintothemembranesandinthe inhalationonantioxidantsinthelung.Ratswereexposedto
sub-cellular organelles. Many antioxidants are found in wood smoke for 16min. Other animals received a 20% total
multiple cellular compartments, but their concentrations bodysurfaceareascaldburnorweresubjectedtoacombined
maydifferwithlocationandfunction.Forexample,itiswell burn injury and smoke inhalation. Evaluation of bronchoal-
established that with exercise, injury or other stress, veolar lavage fluid (BALF) collected 24h after initial injury
mitochondria can generate 10 times the amount of oxygen foundthatascorbicacidandglutathioneconcentrationswere
radicalsthatitgeneratesunderrestingconditions.Thus,the markedly reduced in the smoke-exposed animals compared
cell must have sufficient antioxidants in the appropriate with controls [19]. Concentrations of these antioxidants in
compartmenttohandlethisoxidantburden.Thekeyisfor BALF from the combined injury group were intermediate
cells to maintain their oxidant and antioxidant balance in between these levels. These changes were accompanied by
favor of antioxidants. When this balance shifts in favor of elevatedthiobarbituricacidreactivesubstances(TBARS)levels
oxidants,theantioxidantdefensesystemgetsoverwhelmed in lungs from animals subjected to smoke inhalation or
and oxidant-induced injury can occur. combinedburnandsmokecomparedwithcontrols,suggest-
ingincreasedlipidperoxidationinthesegroups[20].Elevated
3.3. Woodsmokeisacomplexmixtureofgasesand TBARS were also seen in lung tissue from sheep that were
particulates exposed to wood smoke. A dose-dependent effect was
observed in all the lung lobes evaluated [21]. In this study
Evidencesuggeststhatwoodsmokeisacomplexmixtureof sheep were subjected to mild, moderate or severe smoke
chemical substances that exist as gases and particulates injury,definedasexposureto5,10or16unitsofwoodsmoke,
with various chemical and physical properties. Previous respectively, and lung tissues were analyzed 48h after
studies reported that smoke contains oxidants in both the exposure. To determine the possible role of neutrophils in
gaseousandparticlephases,inadditiontoothertoxicants, inducing oxidative injury in this study, we determined
and smoke inhalation generates an inflammatory process myeloperoxidase activity in lung as an index of neutrophil
associated with the development and progression of infiltration [21]. A dose-dependent effect of wood smoke
hypoxia.Traberetal.hypothesizedthatchemicalsinsmoke, inhalation on the elevation of myeloperoxidase activity in
such as aldehydes, damage epithelial cells, releasing most lung lobes was observed, with a marked increase in
chemotacticfactorsandinflammatorymediators,andprime activityafterthe16unitsofsmokedose[21].
neutrophils[17].Theypostulatedthatneutrophil-generated
oxygen radicals and inflammatory mediators initiate bron- 3.5. Reactiveoxygenspeciesareamajorfactorinthe
chial constriction, formation of exudate, and airway casts developmentofALIaftersmokeexposure
thatarecommoninsmokeinhalationinjury[17].Insupport
of this hypothesis, we demonstrated that the wood smoke Thus, the generation of reactive oxygen species has been
itselfcontainsoxidants.Inastudydoneincollaborationwith considered a major factor in the development of acute lung
colleagues at NIOSH in West Virginia, pine or fir smoke injury after smoke exposure. As mentioned, the long-lived
extract incubated with hydrogen peroxide for 3min gener- carbon-centered radicals generated by wood smoke can be
ated hydroxyl radicals as determined by conventional depositedintheairwaysandlung,andhavesufficienttimeto
electron spin resonance [18]. Further analysis determined migrate to critical sites and decompose into free radicals,
that the wood itself contained iron. Iron is known to react initiating tissue damage at multiple sites. To illustrate the
with hydrogen peroxide to form hydroxyl radicals through evidencethatoxidantgenerationandlipidperoxidationinthe
theFentonreaction.Incubatingthesmokeextractlonger(30 lungwererelatedtothedegreeofinjury,tissuesfromsmoke-
or90min)resultedinthedetectionofstablecarbon-centered exposed sheep were analyzed histologically. We observed a
radicalsthatarelong-lived[18].Weobservedsimilarresults dose-dependenteffectofwoodsmokeinhalationontheinjury
withsmokegeneratedfromthethermolysisofDouglasfir.In profile in both the airways and the lung parenchyma [21].
general, most oxygen radicals are very reactive and have Injury in the airway was associated with loss of cilia,
half-lives determined in fractions of a second. In contrast, ulceration of the respiratory mucosa and cast formation.
theselong-livedradicalshavethepotentialtopropagatethe The predominant effects of wood smoke inhalation on lung
injuryprocessafterinhalationofwoodsmoke.Inaddition, parenchyma were edema and infiltration of inflammatory
we observed that the smoke extract activated NFkB, and cells[20,21].
induced lipid peroxidation and TNF-a release by macro-
phages,invitro[18].Takentogether,thesedatasupportthe 3.6. Nitrogenspeciesandnitricoxideintissuefollowing
hypothesis [17] that wood smoke induces a direct oxidant inhalationinjury
effect based on its components, as well as generate a
secondaryoxidanteffectrelatedtoactivationofinflamma- Most recently, we began to investigate reactive nitrogen
tory cells and processes. It is likely that this may be a species and nitric oxide as part of our assessment of
commonmechanismrelatedtoinhalationinjuryofthelung antioxidant status of tissue following inhalation injury. In
andairways. preliminarydatafromsheepexposedtochlorinegas,wedid
burns 33 (2007) 681–692 685
not see a significant change in nitric oxide levels in lung in aeratedandnon-aeratedlung.Themeangrayscaledensityof
response to any dose of chlorine. In contrast, chlorine gas thelungswasalsocalculated.
exposure resulted in elevated TBARS and myeloperoxidase
activity, and reduced levels of antioxidant enzymes at the 4.2. CTscanispotentiallyusefulingaugingtheseverityof
higherlevelsofexposure. inhalationinjurynon-invasively
3.7. Ininhalationinjurytheroleofoxidantsisnotfully Blood-gasdatainthisstudyweresignificantinthatonlyinthe
understood severe group did the alveolar-arterial gradient differ signifi-
cantly from controls. This phenomenon suggests that the
In summary, reactive oxygen, nitrogen, and halogenated lungs are able to compensate for mild to moderate injuries,
species are well documented as actors in lung injury establishing a threshold effect in oxygenation [24]. The
associated with inhalation of wood smoke or other air radiologist’s score was linearly related to severity of injury
pollutantsandtoxicantgases.However,theroleofoxidants at 24h and it outperformed computerized analysis with
in the initiation or progression of the disease is not fully respect to detecting abnormalities, particularly in the mild
understood. There are a number of antioxidants that are andmoderatelyinjuredgroups.Byordinallogisticregression,
distributed throughout the airway and lung parenchyma as the radiologist’s score at 24h was retained in a model for
protectivemechanisms,butasmentioned,theyarenotevenly severity of injury, whereas the FALT and mean gray scale
distributedthroughouttherespiratorysystem,andtheyhave density scores were rejected. Thus, CT scan is potentially
different roles related to their location within the cellular useful in gauging the severity of inhalation injury non-
compartments. At present, evidence is scant that current invasively. Failure of computerized indices based on the
strategiestocounteracttheseoxidantsdirectlyareclinically gray-scale density to detect more subtle injury features
beneficial.Forexample,short-termstudieswithantioxidant indicates the role of small airway injury, as opposed to
supplements,suchasVitaminsCandEinhealthyindividuals, alveolar–capillarymembranedisruptionandalveolarflooding,
did not raise the levels of these antioxidants within the in the pathophysiology of this model of smoke inhalation
respiratorytractandtheclinicalbenefitofsuchsupplementa- injury [8]. Human trials are needed to establish the clinical
tion has been controversial. As we better understand utility of the method, as well as to determine the effect of
mechanismsofoxidant-inducedlunginjuryandthatnotall various modes of mechanical ventilation on the pulmonary
cellularcompartmentsareresponsivetostandardantioxidant parenchyma.
supplementation practices, the future should see more
attempts at targeted delivery of antioxidants (e.g., aerosols)
aspartofmorecomprehensivetreatmentstrategies. 5. Emergency ventilation with insufflated
oxygen (Ian H. Black, MD)
4. Assessment of the severity of inhalation Insufflationofoxygenhasbeenusedasarescuetechniquefor
injury by CT scan (Myung S. Park, MD) airwayobstructionandasanadjunctivetechniqueforacute
lung injury (ALI). What is the rationale for tracheal gas
4.1. EvaluationofCTscanininhalationinjuryinan insufflation,theefficacyoftrachealgasinsufflation,andsome
animalmodel ofitsproblemsinaclinicalsetting?Beforeaddressingthese
questionsitisimportanttoclarifysomenomenclature.Apneic
The presence of inhalation injury is currently diagnosed by oxygenation(AO)usuallyreferstosupraglotticairwaydelivery.
bronchoscopyorbyxenonlungscan.Nomethod,however,is Tracheal insufflation of oxygen (TRIO) is either supra- or
available for grading the severity of injury. The objective of infraglottic insufflation. Tracheal gas insufflation (TGI) com-
this study [22] was to evaluate the utility of CT scan in monly refers to infraglottic insufflation [25]. There is also
assessing the severity of injury. Twenty anesthetized sheep expiratory washout. Investigators have also explored reverse-
evenly divided into 4 groups, consisting of controls, mild, thrustcathetersandcatheterinsufflationduringtheexpira-
moderate,andsevereinjuries,underwentinhalationofwood toryphasetoprovideventilatorybenefit[26,27].
bark smoke. After injury, the sheep were mechanically
ventilatedfor 48h in the animal ICU. The sheep underwent 5.1. Deliveringairviatracheotomyisnotanewidea
CTscansat6,12and24hafterinjury.CTscanswereanalyzed
bytwomethods.First,athoracicradiologist,blindedtogroup Deliveringairviatracheotomyisnotanewidea.Tracheot-
andtimepoint,gradedeachquadrantineachslice,asfollows: omyisoneoftheoldestsurgicalproceduresonrecordand
0=normal, 1=increased interstitial markings, 2=ground- was found in Egyptian hieroglyphics. In 1956, Jacoby
glassappearanceand3=consolidation.Second,commercially published a fascinating article in JAMA [28]. He induced
available vector-based software (3D Doctor, Lexington, MA) patientswhohethoughtweregoingtobecomeobstructed.
was used to perform semi-automated three-dimensional Thesepatientshadlargetrachealororaltumors,andwhen
reconstruction and analysis. Each scan was segmented into they became cyanotic, Jacoby inserted tracheal catheters.
objects based on the Hounsfield-unit ranges established by Interestingly, it worked. Boyce has successfully used pre-
Gattinonietal.[23](air:hyperinflated,normal,poorlyaerated, emptivevesseldilatorcricothyrotomyforover20years[29].
and non-aerated lung). The fraction of the abnormal lung Fruminin1959observedasimilarbenefitusingpureapneic
tissue(FALT)wasthencalculatedfromthevolumesofpoorly oxygenation instead of a tracheal catheter [30]. These
686 burns 33 (2007) 681–692
patientstolerated30–40minofapneicoxygenationwithout 5.2.1. Questions
anyventilation.ThearterialpHreachednadirsof6.8before
theywereventilatedandnonesufferedanynegativeeffects. (cid:2) Dr. Cancio: Can TGI be delivered effectively through any
Inthe1980sSlutskydidstudiesindogsthatshowedthatas plasticcannulainsertedpercutaneouslyintothetrachea?
littleas91mlofoxygenperminutecouldkeepthemalivefor (cid:2) Dr.Black:Yes.
atleast5h[31]. (cid:2) Dr.Cancio:Itakeityoudon’tneedahigh-pressureoxygen-
powereddevice.
5.2. Trachealgasinsufflation(TGI) (cid:2) Dr. Black: Absolutely not. In fact, that is one of the
misconceptions—that you need a special high-pressure
Currently we use tracheal gas insufflation (TGI). Scoop deliverysystem.Youneedahigh-pressuredeliverysystem
catheterscanbeplacedintratracheallyforoxygenconserva- inordertoventilateeffectively.ButyoustillgetsomeCO
2
tion and to reduce the work of breathing in patients with eliminationwithlow-pressureflow.
chronic obstructive pulmonary disease (COPD). There have (cid:2) Dr.Cancio:Operationally,howeasyisittoplacethecatheter
also been some studies of cardiopulmonary resuscitation into the trachea under emergency conditions? It sounds
(CPR)usingTGI,inwhichpositive-pressureventilationisnot simple,butisitsimple?
performed,producingsimilaroutcomes[32]. (cid:2) Dr. Black: It is as easy as it is performing a cricothyroi-
We recently performed a study in uninjured swine, in dotomy, and we expect medics to perform cricothyroido-
which we allowed the animals to desaturate to an SpO of tomiesinemergencysituations.
2
50% or lower [33]. We then initiated TGI via a tracheal
catheter at 2l/min, without jet ventilation. Within 25s the
vastmajorityoftheseanimalsattainedanSpO above90%. 6. Clinical care of patients with inhalation
2
Noanimalstookmorethan50stogetabove90%.Wethen injury (Rube´n Go´mez, MD, PhD)
kepttheseanimalsalivefor1hwithTGIat2l/min,without
ventilation. TGI can produce an auto-PEEP (positive end- This section reviews the clinical care of patients with
expiratory pressure) phenomenon, which may explain the inhalationinjury.Whereappropriate,aratingforthequality
decreasedlevelsofatelectasisobservedinCTscansofthese ofevidenceisprovided.Inhalationinjuryispresentin8–15%of
animals. burn-center admissions [37], was associated with a mean
TodeterminewhetherTGImaybefeasibleinpatientswith mortality of 56% in two large series [37,38], and, when
acute lung injury (ALI), airway pressure release ventilation suspected, is considered one of the major criteria for burn-
(APRV), TGI, or both were performed in an oleic-acid-injury center referral according to the American Burn Association
model.VentilatoryPEEPwasadjustedtoaccountforanyauto- andtheAmericanCollegeofSurgeons[39].Inhalationinjury
PEEP. With TGI, peak inspiratory pressures were reduced below the glottis is what is meant by ‘‘inhalation injury’’ in
dramaticallybyover18cmH O.Themeanairwaypressures reportsfromthisandmanyotherburncenters[40].Mostof
2
werethesame[34].Thoughtherearepracticaldifficultiesin these injuries are actually chemical injuries caused by
executingthisconcept,wethinktheremaybearoleforTGI productsofcombustion,whichareoftenadherenttosmoke
when it is combined with best mechanical ventilation particles. These chemicals cause direct damage to the
practices. TGI in combination with mechanical ventilation epitheliumoftheairways.Thesmallerthesizeofthesmoke
improves ventilation by reducing the dead space, subse- particle,thedeeperitspenetrationintothelung.
quentlyreducingtheP CO .Thus,theminutevolumeandthe
a 2
workofbreathingareactuallydecreased.Additionally,peak 6.1. Fiberopticbronchoscopy(FOB)fordiagnosisand
airway pressure is reduced, and there is evidence of less treatment
inflammation.
TGIdisadvantages[35]includedryingofsecretions.Auto- Thethresholdforintubationshouldbelowwheninhalation
PEEP has to be accounted for. We do not have a good, injury is suspected. Fiberoptic bronchoscopy (FOB) is
commerciallyavailablemechanismfordelivery.Neitherdo performed for diagnosis and treatment. Mild injury gives
wehaveafail-safepressure-reliefvalve.IntheAPRVstudy rise to erythema and edema of the mucosa. In severe
therewasapressure-reliefvalvethatincaseofobstruction inhalation injury FOB may show gray-colored mucosa,
would help prevent pneumothorax. Right now there is a erosions, ulcerations, and/or desquamation. What on the
commercial FDA-approved endotracheal tube, the Bous- firstFOBlookslikemildinhalationinjury,onrepeatedFOB
signactube(VygonSA,Encouen,France),thathasaseparate mayrevealamoresevereinjury.Therefore,itisoftenuseful
port for insufflation. A tube designed for continuous to repeat FOB 1–2 days after burn. Inhalation injury is a
aspirationofsubglotticsecretionscanalsobeusedforthis dynamicdisease[14].FOBisessentialtofollowthedisease
purpose. The Boussignac tube has 6 different micro- andtoremovedebrisandcastsoflargesizeastheyform.The
channels that can be used to deliver oxygen at the carina moreseveretheinhalationinjury,themorefrequentlyFOB
[36]. may be necessary. The presence of an on-site, dedicated
In summary, TGI does work as an emergency rescue respiratorytherapy(RT)teamisanessentialcomponentof
method. It seems to improve CO elimination and to have this burn center’s multidisciplinary approach. RTs provide
2
added benefit over conventional ventilation alone in an ALI thetreatingphysicianswiththeabilitytoperformemergent
model.Improvedmethodsforaccessingthetrachea,however, FOB,aswellastoemployadvancedventilatorssuchasthe
areneeded. VDR-41(seebelow).
burns 33 (2007) 681–692 687
6.2. Negativeeffectsoffluidrestriction 6.6. Tracheostomy
Fluid restriction will not prevent pulmonary edema [41]. In Theroleoftracheostomyisfarfromunequivocallyestablished
fact, under-resuscitation leads to polymorphonuclear cell [51].Atthiscenter,atracheostomyiscustomarilyperformed
sequestration inthelungs,thusmakingpulmonarydamage after14daysoftrachealintubation,orearlierifnecessaryto
worse[42].Atthisburncenter,themodifiedBrookeformulais facilitate pulmonary toilet. More importantly, the fact that
utilizedasforpatientswithoutinhalationinjury,recognizing ventilator days and sepsis, to include pneumonia, indepen-
thatpatientswithinhalationinjuryusuallyrequiremorefluid dentlypredictmortalityinburnpatients[52]underscoresthe
thanpredicted[43]. importanceofaggressiveweaningofthesepatientsfromthe
ventilator.
6.3. Bronchodilatorsandinhaledheparinmaybehelpfulin Inbrief,high-frequencypercussive ventilation,nebulized
inhalationinjury heparin and bronchodilators, thorough pulmonary toilet,
timely diagnosis and treatment of pneumonia, and early
Bronchodilators may be helpful in the treatment of bronch- liberationfromtheventilatorarethemainstaysoftreatment
ospasm following inhalation injury. In animal models, for inhalation injury. More work, to include prospective,
intravenous heparinwas showntodecrease castformation, randomized, controlled trials, is required to optimize the
minute ventilation and peak inspiratory pressures [44]. treatment of these patients, particularly with respect to
Nebulizedn-acetyl-cysteineandheparindecreasedreintuba- mechanicalventilationstrategies.
tionratesandmortalityinchildrenwithinhalationinjury[45]
(ClassIIIevidence).Inviewofthis,nebulizedporcineheparin
(5000–10,000unitsevery4–6h)iscurrentlyusedinthisburn 7. Laryngeal and upper airway sequelae of
centertodecreasecastformation[46]. inhalation injury (Jeffrey A. Faulkner, MD, and
Travis A. Pfannenstiel, MD)
6.4. Lung-protectivestrategiesformechanicalventilation
7.1. Vocalcordparesisinlunginjury
As with other forms of ARDS, a lung-protective strategy
should be employed when mechanically ventilating We present results of a recent evaluation of the laryngeal
patients with inhalation injury [47] (Class II evidence). At sequelaeseeninburnpatients.Uponrequestbyburn-center
this time, no specific ventilator or method has rigorously surgeons, a total of 52 patients underwent evaluation by a
been shown superior to any other. At the U.S. Army Burn speechpathologistattheU.S.ArmyBurnCenter.Twenty-five
Center, a high-frequency percussive ventilator, Volumetric ofthesewerediagnosedwithvocal-cordparesis.Patientswho
Diffusive Respiration (VDR 41, Percussionaire, Sandpoint, were intubated overseas (mostly patients from the current
ID),isusedforpatientswithinhalationinjury.Inadditionto conflict in Iraq) had a 4.5-fold increase in the incidence of
providing improved oxygenation and ventilation at lower vocal-cordparesis.Inaddition,theriskofvocal-cordparesis
pressures than conventional ventilators, the VDR-41 is increasedwithincreasingburnsize.Thus,adjustingfortotal
highly effective at secretion clearance and reversal of body surface area burned, this risk increased to 9.8. Factors
inhalation-injury-induced small airway obstruction and unrelated to the occurrence of paresis included central-line
atelectasis [42,48,49] (Class III evidence). Like airway- placementandtheuseofvasopressors.
pressure release ventilation (APRV), the VDR-41 also
permits spontaneous negative-pressure breathing by the 7.2. Etiologyofvocalcordparesis
patient throughout the respiratory cycle, potentially
improving gas distribution, maintaining diaphragmatic The etiology of these findings is uncertain. However, it is
function, and reducing sedation requirements. Another knownthatanair-filledendotrachealtubeballoonwillexpand
deviceusedatthisburn center primarilyfor thetreatment during flight. This could cause pressure at the cricothyroid
of intubated patients with pneumonia, atelectasis, or joint, causing injury to the recurrent laryngeal nerve as it
copioussecretionsisIntrapulmonaryPercussiveVentilation entersthelarynx.TwoapproachesarecurrentlyusedbyU.S.
(IPV1, Percussionaire, Sandpoint, ID), which provides addi- militaryaeromedicalevacuationteamstopreventthis.
tional capabilities for removal of secretions following U.S. Air Force teams (who transport non-burn patients)
inhalation injury. replacetheairintheballoonwithsalinesolution;U.S.Army
teams(whotransportthemajorityofintubatedburnpatients)
6.5. Patientswithinhalationinjuryareathighriskfor monitor the balloon pressure and reduce the air content as
bronchopneumonia needed.Thismayexplain,inpart,theobservedrelationship
betweenburnandparesis,althoughnocausalrelationshiphas
Patients with inhalation injury are at high risk for bronch- been proven. Further studies in an altitude chamber are
opneumoniabeginning3–10daysafterburn.Inthefirstweek, planned.Electromyographywouldbeusefulinthediagnosis
the causative agents of bronchopneumonia are predomi- ofnerveinjury.
nantlyGram-positiveorganisms.Afterthefirstweek,Gram- Otherpossibleetiologiesincludetraumaticintubation.This
negativeorganismscometothefore.Prophylacticantibiotics can cause cord avulsion, arytenoid dislocation, or mucosal
have not been shown to prevent the development of injuryleadingtoanteriorwebbingorposteriorstenosis.Fig.2
pneumonia[50]. shows an arytenoid dislocation. Long-term intubation can
688 burns 33 (2007) 681–692
be nerve injury, joint fixation, or soft-tissue injury, and the
etiology may be cuff pressures, prolonged intubation, or
intubationtrauma.Prospectiveevaluationofallburnandnon-
burntraumapatientswhohaveundergonefieldintubationis
warranted. Vocal physical therapy is indicated for many of
thesepatients,andhelpspreventarytenoidarthritisresistant
to therapy. In addition, mobilization of the arytenoid, with
concomitantsteroidinjection,maybetherapeutic.
7.2.1. Question
(cid:2) Aphysician:Doyouknowtheincidenceofemergencyre-
intubation during transport that might lend itself to this
kindofinjury?
(cid:2) Dr.Faulkner:Zerointhesepatients.
Fig.2–Arytenoiddislocation,manifestedbyhematoma
aroundthearytenoid(arrow),andmedialdisplacementof
thearytenoid.Thisresolvedafterresolutionofthe 8. Artificial lung technology (Leopoldo C.
hematoma. Cancio, MD)
8.1. Extracorporealmembraneoxygenation(ECMO)
Extracorporeal membrane oxygenation (ECMO) has been
available for many years, but is costly and cumbersome.
ECMO has a significant complication rate, and is labor- and
equipment-intensive. Increasingly, instead of ECMO for the
treatment of patients with ARDS, simpler technologies are
beingproposed.Theseincludeintravenousdevicessuchasthe
Hattlercatheter,andextracorporealdevicessuchasthosefor
arteriovenous CO removal (AVCO R) and the venovenous
2 2
ParacorporealRespiratoryAssistLung(PRAL).
8.2. Theefficiencyofgasexchangeinartificiallungdevices
Theefficiencyofgasexchangeinthesedevicesisaffectedby
severalfactors.First,thepartialpressuresofoxygen(PO )and
2
Fig.3–Vocal-cordfixationsecondarytoarytenoid
ofcarbondioxide(PCO )intheinflowbloodareimportant.For
2
dislocation.Thecorditselfisunscarredinappearance,but
example,ifthePO islowintheinflowbloodthentheamount
2
itisfixedsuchthataspatula(arrow)cannotmoveit.
ofoxygenthatwillbetransferredintothatbloodwillbehigh
becauseofahighgradient.Similarly,ifthePCO ishighinthe
2
inflowblood,thenmoreCO willcomeoutofthebloodand
2
cause subglottic stenosis (hence our practice of performing intothedevice.Thesefactsaffectdeviceplacement,i.e.onthe
tracheostomyafterabout2weeksofendotrachealintubation), venousorarterialside,anddecisionsaboutpatientmanage-
tracheal stenosis, or vocal-cord paresis. In a recent review, ment, such as permissive hypercapnia. Second, the mem-
intubationwasthecauseofupto11%ofcasesofunilateral brane surface area affects the efficiency of gas exchange.
recurrent-nerveparalysis[53]. Finally,thebloodflowrateinfluencesgasexchange.
Three patients at our center have been seen with vocal-
cord fixation secondary to cricoarytenoid joint dislocation 8.3. Designconsiderations
ratherthanparesis.Fig.3showsonesuchpatient.Theetiology
ofcricoarytenoidarthritisisunknownduetoinsufficientdata, Whatarethedesignconsiderations?First,ifanextracorporeal
butpossiblecausesincludeprolongedintubation,theeffectof deviceisplacedonthearterialside,thearterialbloodpressure
inhalationinjury,orasystemicinflammatoryresponse. canbeusedtodrivebloodthroughthesystem.Givenalow-
Recently, Casper et al. reported follow up at 16–25 years resistance circuit, a pump can be avoided and with it the
postburnof10patients[54].Seventypercenthaddysphonia potentialdamagedonetothebloodbythepump.Ontheother
and100%hadabnormallaryngealfindings.Earlieridentifica- hand, if the device is placed on the venous side, there are
tionoftheseabnormalities,forexamplebystroboscopicexam, advantages with respect to PCO and PO gradients. Next,
2 2
may make surgical or behavioral treatment possible. In muchefforthasgoneintodevelopinglow-resistanceexternal
conclusion,weseemtohaveahigherthanexpectedincidence devices. The earlier ECMO devices had relatively high
ofvocal-cordimmobilityafterburn.Thepathophysiologymay resistances; thus, a pump was mandatory. The newer
burns 33 (2007) 681–692 689
low-resistancesystems,liketheNovalung1andtheAVCO R, indicates the utility of such devices in allowing gentle
2
can simply rely on arterial blood pressure to drive blood mechanicalventilationinpatientswhootherwisemightbe
throughthecircuit. difficult to ventilate adequately. The AVCO R system is
2
currentlyinclinicaltrials.
8.4. EfficientratesofoxygenconsumptionandCO The Novalung1 iLA (Novalung GmbH, Hechingen, Ger-
2
removal many)isanAVCO Rdevicewhichiscommerciallyavailablein
2
Europe[58].TheEuropeandataarecurrentlybeingreviewed
Intracorporeal and extracorporeal systems provide different by the U.S. Food and Drug Administration (FDA). The
levels of efficiency with respect to the rates of oxygen Novalung1isanarteriovenoussystem,whichispoweredby
consumption(VO )andCO removal(VCO ).Ahyperdynamic thepatient’sownbloodpressure.
2 2 2
septicpatientmayrequireaVO of315ml/min(i.e., 170ml/
2
min/m2),whereasanormalrestinghumanhasaVO ofabout 8.8. Paracorporealrespiratoryassistlung(PRAL)
2
210–280ml/min.Assumingarespiratory quotientof1, VCO
2
rates are about the same. Thus, a reasonable target for The PRAL is currently in development at the University of
artificiallungtechnologiesisalittleover200ml/minforVO Pittsburgh[59].Thisvenovenousdeviceusesonedual-lumen
2
and VCO . At present, no extracorporeal or intravenous catheter,althoughtwocathetersindifferentveinscanalsobe
2
systems achieve these targets, but substantialreductions in employed.Ithasarotatinghollow-fiberbundle,whichserves
thelevelofmechanicalventilatorysupportarepossible. both to increase gas exchange and to pump the blood. At a
rotationrateof1500rpm,thisdevicedrawsabout750ml/min,
8.5. Intravenousvenousoxygenator(IVOX) i.e.halfthebloodflowofatypicalAVCO Rdevice.Hemolysisis
2
reportedlynegligible.Thisdevicewillbetestedinouranimal
Artificiallungdevicesmaybeintravenousorextracorporeal. labthisyear.
One of the early intravenous devices was the intravenous AVCO R operates ideally at blood flow rates of about
2
oxygenator(IVOX)[55].ItprovidedaVO andVCO ofabout40– 1500ml/min,asdoestheNovalung1.ThePRALrequiresabout
2 2
70ml/min.TheIVOXwenttophaseIIclinicaltrialsinARDS half that. CO removal for the extracorporeal devices is
2
patients. It improved oxygenation in these patients but it currently about 100ml/min. None of these devices are
failedtocauseanimprovementinmortality;therehasbeenno designed primarily to oxygenate, with VO rates of about
2
furtherdevelopmentdoneontheIVOX. 30–60ml/min. We believe, however, that we will be able to
oxygenate casualties by an apneic technique such as that
8.6. Hattlercatheterorintravenousmembrane describedabovebyDr.Black.
oxygenator(IMO) In conclusion, artificial lung technologies continue to
advance,andmayrevolutionizehowwecareforoursickest
The Hattler catheter or intravenous membrane oxygenator casualtieswithARDSsecondarytoinhalationinjuryorother
(IMO)isanintravenousdevicecurrentlyindevelopmentatthe causes.
UniversityofPittsburgh[56].TheIMOfibersarearrangedina
constrained bundle around a helium-powered balloon. The 8.8.1. Questions
balloon inflates and deflates at up to 300beats/min. This
improves blood flow across the fibers, thus improving gas (cid:2) Aphysician:Doallofthesedevicesrequireanticoagulation?
exchange.Gasexchangeplateausatabout250–300beats/min. (cid:2) Dr. Cancio: All of the systems require some degree of
Itisinsertedviatheinternaljugularvein(externaljugularvein anticoagulation. A lot of work has gone into developing
inthesheep)andliesacrosstherightatrium.Thisdeviceis coatingsforthefibersthatwouldhelpreducetheactivated
currently in trials in our animal lab in an ovine model of clotting time required. Clearly, the continued need for
inhalationinjury. anticoagulationisadisadvantageinourcombatcasualties.
(cid:2) Aphysician:Therehasbeensomerecentre-examinationof
8.7. ArteriovenousCO removal(AVCO R) someacuterespiratorydistresssyndrome(ARDS)datathat
2 2
saysthatthehypercapniaiswhatgivesasurvivalbenefit,
Zwischenberger in Galveston has developed a method of and not the low-volume strategy. Are you concerned that
AVCO R using a low-resistance Affinity1 oxygenator (Med- you may be missing the boat taking away that survival
2
tronic, Inc., Minneapolis, MN) [57]. This device primarily benefitbyusingthistechnology?
removesCO ratherthandeliversO .Apumpisnotused,and (cid:2) Dr.Cancio:Ifrankly,findithardtobelievethathypercapnia
2 2
theinflowcannulaisplacedinthefemoralartery.Moderate is truly beneficial and I recall data that suggest that
systemicanticoagulationisrequired.Thesystemisdepen- respiratoryacidosisisnotbeneficial.Inanyevent,Ibelieve
dent on blood flow through the device in order to remove that injurious levels of mechanical ventilation cause
CO , so that hypotension and low cardiac output will inflammation and secondary lung injury, if not overt
2
decreasedeviceperformance.Intheovinestudies,asmoke barotrauma. I thinkthat sometimes it isdifficultforus to
inhalationinjuryandburnmodelisused.AVCO Rmakesit perform lung-protective ventilation under actual clinical
2
possible to dramatically decrease minute ventilation while conditions, and that devices like this might help that
maintainingareasonablePCO .Interestingly,thePO tends minorityofpatientswhotrulyareverydifficulttoventilate.
2 2
toincreaseinAVCO R-treatedanimals,probablybecauseof We also don’t know whether 2ml/kg tidal volume or no
2
a decrease in secondary lung injury. This experience ventilationatallmightbeevenmorebeneficial.