MAC (from: Notes on thoracic anaesthesia) - Nickalls.org

22 Pages·2012·0.71 MB·English

Supporting technologies — MAC
©RWDNickalls(retired),
DepartmentofAnaesthesia,
NottinghamUniversityHospitals,
CityHospitalCampus,
Nottingham, UK.
[email protected]
www.nickalls.org
9 Supportingtechnologies 136 9.4.3 Temperature cor-
rectedMAC . . . . . 147
9.4 MAC . . . . . . . . . . . 136
9.4.4 Dosage and MAC
9.4.1 History . . . . . . 136
correction . . . . . 148
9.4.2 Age-correctedMAC 141 9.4.5 References . . . . . 151
FROM:NickallsRWD. Notesonthoracicanaesthesia
http://www.nickalls.org/dick/papers/thoracic/book-thorax.pdf
REVISION:August2011
9
Supporting technologies
9.4 MAC
Ethercontributesotherbenefitsbesidespreventingthepain.
Itkeepspatientsstill,whootherwisewouldnotbe.
JohnSnow
From:Eger(1974),1 p.1
9.4.1 History
JohnSnow
JohnSnow(1813–1858)appearstohavebeenthefirstpersontoappreciatetheimportance
ofcontrollingtheinspiredconcentrationofvolatileanaesthetics,andwithinfiveyearsof
WilliamMorton’setherdemonstration2hehadsingle-handedlyestablishedthescientific
foundationsunderpinningthepharmacokineticsofvolatileanaesthetics.
SnowwasaLondon-basedGPwithhospitalconnections,andhadbeeninterestedfora
longtimeintheuseofinhalationagentsonrespiration. Heinitiallyinvestigatedtheuseof
carbondioxide,andhadbeenexperimentingwithinhaledethersince1843believingitto
beausefulmedicineforimprovingcirculation. In1846hepublishedanarticleentitled
“Pathologicaleffectsofatmospheres”(Maltby2002;Vinten-Johansenetal.2003).
Consequently, following Morton’s demonstration of ether anaesthesia (October 16,
1846)attheMassachusettsGeneralHospital(Boston,USA),andthesubsequentdemon-
strationinLondoninDecember1846byMrJRobinson3,Snowfoundhimselfintheright
placeattherighttime4. Furthermore,withhisinterestinchemistryandrecentresearches
1Thisquotation,whichheadsEger’sownchapteronMAC,isfrom:Snow(1847,p.53).
2WilliamMorton(1819–1868)gavehisdemonstrationonOctober16,1846.Foranexcellentaccountofthe
historyandbackgroundseeMacQuitty(1969).
3RobinsonJ(1847).Correspondence.MedicalTimes,15;273–274.
4Indeed,Robinson(1847)indicatesthatheanaesthetisedapatient“... inthepresenceofmyfriends—Mr.
Stocks,Mr.Snow,andMr.Fenny.”
136
RWDNickalls (August2011) MAC 137
intoinhaledetherhealsofoundhimselftobejusttherightpersontogetinvolvedinthis
newanaesthesiaphenomenon. SincehisGPworkwasnotveryprofitable,Snowdecided
totakeupanaesthesia.
Snowwasextraordinarilyindustriousandproductive. Bymid1847hehad(a)defined
andpublishedthetemperaturecharacteristicsofethervapour(January1947),(b)designeda
temperature-compensatedetherinhaler,(c)definedarangeofclinicalstagesofanaesthesia
(hisfive‘degreesofnarcotism’),and(d)performedmanyanimalexperimentswithaview
todeterminingtheeffectsofdifferentinspiredconcentrationsofbothetherandchloroform.
Snowappreciatedthesignificanceofknowingthesaturatedvapourpressure,andwenton
toshowthattheamountofvolatileagentrequiredtoproduceanaesthesiawasinversely
relatedtoitssolubilityintheblood.
Snowpublishedhisfindingsinaneighteen-partseriesofarticlesinthejournalLondon
MedicalGazette duringtheperiod1848to1851,entitled“Onnarcotismbytheinhalation
ofvapours”. Inthefollowingextracts(allfromPart–Ioftheseries)Snowdescribesthe
effectsonamouseofasequenceofstepincreasesintheinspiredconcentrationofether
(from approximately 12% to 47%).5 Notice the detail of his observations, and how
· ·
hepaysparticularattentiontohowwellthemousebreathes(Ihaveaddedacalculated
concentrationinMACether ateachstagetomakeiteasiertofollowhisexperiments).
mouse
Iconsider,however,thatIhavefoundaplanofdeterminingmoreexactlythe[required]
proportionofetherandofothervolatilesubstancespresentinthebloodinthedifferent
degreesofnarcotism.Itconsistsofascertainingthemostdilutedmixtureofvapourand
ofairthatwillsufficetoproduceanyparticularamountofnarcotism;andisfounded
onthefollowingconsiderations,andcorroboratedbyitsagreeingwiththecomparative
physiologicalstrengthofthevarioussubstances.
... TheplanwhichIadoptedtoascertainthesmallestquantityofvapour,inproportion
totheair,thatwouldproduceagiveneffect,wastoweighasmallquantityofthe
volatileliquidinalittlebottle,andintroduceitintoalargeglassjarcoveredwitha
plateofglass;andhavingtakencarethattheresultingvapourwasequallydiffused
throughtheair,tointroduceananimalsosmall,thatthejarwouldrepresentacapacious
apartmentforit,andwaitforthatperiodwhentheeffectsofthevapournolonger
increased....
Exp.17.—Twograinsofetherwereputintoajarholding200cubicinches[116%,
·
036MAC],andthevapourdiffusedequally,whenatamemousewasintroduced,and
·
allowedtoremainaquarterofanhour,butitwasnotappreciablyaffected.
Exp.18.—Anothermousewasplacedinthesamejar,withthreegrainsofether,being
agrainandahalftoeach100cubicinches[175%,055MAC].Inaminuteanda
· ·
halfitwasunabletostand,butcontinuedtomoveitslimbsoccasionally.Itremained
eightminuteswithoutbecomingfurtheraffected.Whentakenoutitwassensibleto
pinching,butfelloveronitssideinattemptingtowalk. Inaminuteandahalfthe
effectoftheetherappearedtohavegoneoffentirely.
5MACether =32% (Eger1974,p.5).
mouse ·
RWDNickalls (August2011) MAC 138
Exp.19.—Awhitemouseinthesamejar,withfourgrainsofether[233%,072MAC],
· ·
wasunabletostandattheendofaminute,andattheendofanotherminuteceasedto
move,butcontinuedtobreathnaturally,andwastakenoutattheendoffiveminutes.
Itmovedonbeingpinched,begantoattempttowalkattheendofaminute,andintwo
minutesmoreseemedquiterecovered.
Exp.20.—Fivegrainsofether,beingtwoandahalfgrainstoeach100cubicinches
[292%,091MAC],werediffusedthroughoutthesamejar,andamouseputin. It
· ·
becamerathermorequicklyinsensiblethantheoneinthelastexperiment. Itwas
allowedtoremaineightminutes. Itmoveditsfootaverylittlewhenpinched,and
recoveredinthecourseoffourminutes.
Exp.21.—Awhitemousewasplacedinthesamejarwithsixgrainsofether[35%,
·
11MAC].Inaminuteandahalfitwaslyinginsensible.Attheendofthreeminutes
·
thebreathingbecamelaborious,andaccompaniedbyakindofstertor.Itcontinuedin
thisstatetilltakenout,attheendofsevenminutes,whenitwasfoundtobetotally
insensibletopinching. Thebreathingimprovedattheendofaminute;itbeganto
moveattheendofthreeminutes;andfiveminutesafteritsremovalithadrecovered.
Exp.22.—Thesamemousewasputintothisjaronthefollowingday,withseven
grainsofether,being35grstothe100cubicinches[408%,128MAC].Stertorous
· · ·
breathing came on sooner than before; it seemed at the point of death when four
minuteshadelapsed;andbeingthentakenout,waslongerinrecoveringthanafterthe
lastexperiment.
Exp.23.—Twoorthreedaysafterwardsthesamemousewasplacedinthejar,with
eightgrainsofether,being4grainstothe100cubicinches[466%,146MAC].It
· ·
becameinsensibleinhalfaminute.Intwominutesandahalfthebreathingbecame
difficult,andatalittlemorethanthreeminutesitappearedthatthebreathingwasabout
tocease,andthemousewastakenout.Inaminuteortwothebreathingimproved,and
inthecourseoffiveminutesfromitsremovalithadrecovered.
... Wefindfromtheeighteenthexperiment,thatagrainandahalfofetherforeach
100cubicinchesofair,issufficienttoinducetheseconddegreeofnarcotisminthe
mouse;andagrainandahalfofethermake19cubicinchesofvapour,ofsp.gr.2586.
NowtheetherIemployedboiledat96 [F].·6 Atthistemperature,consequently·,its
◦
vapourwouldexcludetheairentirely;andtheethervapourincontactwiththeliquid
giving it off, could only be raised to 100 by such a pressure as would cause the
◦
boilingpointoftheethertorisetothattemperature. Thatpressurewouldbeequal
to324inchesofmercury[1082Atm.],or24inchesabovetheusualbarometrical
· · ·
pressure;andthevapourwouldbecondensedsomewhat,sothatthespaceof100cubic
inches[at1082Atm.]wouldcontain108cubicinchesattheusualpressure[1Atm.].
·
Thisisthequantity,then,withwhichwehavetocompare19cubicinches,inorderto
·
ascertainthedegreeofsaturationofthespaceintheair-cellsofthelungs,andalsoof
696◦F=35·5◦C.(F−932=C5).Purediethyl-etherboilsat34·51◦C(CRCHandbookofchemistryandphysics;
1972).
RWDNickalls (August2011) MAC 139
theblood;andbycalculation,aswhentreatingofchloroform,
19isto108as00175isto1
· ·
Sothatwefind00175[175%],or1/57th,tobetheamountofsaturationoftheblood
· ·
byethernecessarytoproducetheseconddegreeofnarcotism;
Snow(1848a)
NoticetheinterestingwayinwhichSnow calculatesthevapourconcentrationresulting
from15grains7ofliquiddiethyl-ether8in100cubicinches9ofairat100 F10as175%.
◦
· ·
Myowncalculationrunsasfollows. Sincethemolecularweightofdiethyl-etheris7412,
·
thevolumeofpureethervapouratSTPoccupiedby9675mgliquidether(15grains)is
givenby11 · ·
9675
224 · =2924cc
· ×7412 ·
·
Ifwenowcorrectthisvolumeforatemperatureof100 F12(377 C)weobtain2924
◦ ◦
3107/273=333cc. Adding this volume of pure vapour to 10·0 cubic inches of·air1×3
· ·
(alsoat377 C)givesaconcentrationof
◦
·
333
· =001754 175%
333+(100 2543 3107/273) · ≡ ·
· × · × ·
However,wehavemadesomesimplifyingassumptions(e.g.,constantpressureandcom-
pletemixing),andsinceSnowonlyusedaglassjarwithasimplelid,itislikelythatsome
ofthemixtureescapedfromthejarbeforemixingwascomplete.14
ItisclearfromtheseextractsfromSnow’spublications,thatSnowwasseekingthe
inspiredconcentrationassociatedwitheachofhisfive‘degreesofnarcotism’,andthat
hewasguidedbytwokeyprinciples,namely(a)todetermine‘themostdilutedmixture’
whichgavetheseeffects(i.e.,theminimumconcentration),and(b)waitinguntil‘theeffect
nolongerincreased’(i.e.,atequilibrium).
Snow’s pharmacological approach of linking particular inspired concentrations of
vapourtoparticularstatesordepthsofanaesthesia,andthenusingthisinformationtotry
anddeliverasaferformofanaesthesiabycontrollingtheinspiredvapourconcentration
was, therefore, strikingly similar to our modern use of MAC.15 His experiments were
71grain=645mg.
98C1Hcu3bCicHi2nOchC·=H22C5H433;=m1o6le3c8ulcacr.weight=74·12;BP=34·51◦C
10100 F=377 C·. ·
111gm◦molof·v◦apouroccupies224LatSTP.
12Notethatthisisroughlymouseb·odytemperature.
13Wekeepthepressureconstantandassumecompletemixing.
14Pleaseemailmeifyouimproveonthisanalysis.
15ThefirstpaperonMACwasbyMerkelandEger(1963).ThedefinitionofMACisasfollows:–theminimum
alveolarconcentration,atequilibrium,andat1atmospherepressure,whichpreventsmovementin50%of
patientstoastandardsurgicalincision.ForanexcellentearlyoverviewofMACseeChapter1inthetimeless
classicbookbyEger(1974).
RWDNickalls (August2011) MAC 140
carefullyperformed,observed,andwelldocumented—infactsomuchsothattheyeven
allowustomakeareasonablyaccurateestimateofMACforthemouse. Forexample,
Snow’sexperiments20and21suggestthattheinspiredconcentrationofetherassociated
with50%movementwasbetween29%and35%,givinganestimateclosetothemodern
valueofMACether forthemouse16·of32%.·
mouse
·
100 years or so later in the early 1960s Eger and Severinghaus embodied Snow’s
concepts in the form of MAC (Merkel and Eger 1963; Saidman and Eger 1964; Eger,
Saidman,andBrandstater1965a).
EdmondEger
In1960EdmondEgerjoinedtheSanFranciscoDepartmentofAnaesthesia,andbecame
a‘ResearchFellow’toJohnSeveringhaus(Eger2002,Maltby2002). EgerandDrGiles
Merkel(ResearchFellow)weregiventhetaskofdefiningthepropertiesofanewvolatile
anaestheticagentcalledhalopropane. Egerdescribestheearlystepsasfollows.
FromstudiesJohn[Severinghaus]andothershadperformedwithcarbondioxide,we
knew thatmeasuringtheend-tidalconcentrationofagasgave usahandleonthe
arterialpartialpressureforthatgas. Also,theworkofKetyandSchmidtindicated
thatthecerebralpartialpressureofaninertgasshouldrapidlyequilibratewiththe
partialpressureinarterialblood. So,ifwemeasuredtheend-tidalconcentrationof
halopropaneandhelditstableforasufficientperiodoftime,theend-tidalconcentration
wouldgiveusameasureoftheanestheticpartialpressureatitssiteofaction. With
that,wehadthefirstpartofMAC.
Thesecondpartwasnothardtocomeby. ... Movement. Acategoricalresponse,
seemedjustthething... Sowemarriedtheend-tidalconcentrationwithmovement–no
movementasanindexofanesthesia,andMACwasborn.
Everythingexceptthename. John’sgroupmeteveryMondaymorningtodiscuss
thepreviousweek’sworkandwhatmightbedoneinthecomingweek... Atoneof
theseGilesandItoldofourtechniquefordeterminingtheminimalalveolaranesthetic
concentration,andJohnconnectedthistotheratioofthespeedofanairplanerelative
tothespeedofsound(aMAACratio).Johnnowsaysitneverwasclearwhywechose
MACratherthanMAAC.Idon’tremembereither,exceptthatwewantedtoemphasise
theword“alveolar”. Besides,voicing“MAAC”mightmakeussoundlikebleating
sheepratherthananesthesiologists.
ThenextstepwastodetermineMACinhumans. ... Theresultwastheseriesof
articlesthatwerepublishedin1965(Eger,SaidmanandBrandstater1965a,1965b;
Egeretal.1965).
Eger(2002)
16Eger(1974),p.5.
RWDNickalls (August2011) MAC 141
JohnSeveringhaus
Severinghaus(Severinghaus2009,Maltby2002)recalledthisepisodeinarecentjournal
interviewasfollows(Kofke2003).
Dr.Egerwasinterestedintherelativepotencyofanesthetics. Hewantedawayto
comparethemnumericallyintermsoftheiralveolarconcentrationsatthetimeof
establishmentofaminimallevelofanesthesiatopermitsurgery. Itwascleartoall
thatforeachpatientoranimal, therewasacriticalalveolar(andthusarterialand
ultimatelybrain)pressureofanagentthatjustpreventedamotorresponsetopain.He
believedthiswouldbearelativelyinvariantnumberbetweenpatientsThiswouldbe
theminimalalveolaranestheticconcentration. Irecalledthatinaviation,asimilar
index,Mach,wastheratioofanaircraft’sspeedtothespeedofsound.17 Ahypersonic
flightwasdefined,forexample,asMach2,twicethespeedofsound.Isuggestedthe
samesymbolbeusedfortheratioofconcentrationoftheanestheticinthealveoli(as
determinedintheairwayatendexpiration)tothatcriticalno-movementlevel,which
wouldbedefinedas1MAC,originallyMAAC.ItstillshouldbeMAACsincewecan’t
agreeonwhetherthesingle‘A’referstoalveolaroranestheticorboth.
Kofke(2003)
WilliamMapleson
In1979,afar-sightedWilliamMaplesonanticipatedtheincreasinglycentralroleofMAC
withrespecttohowanaesthetistsdeliveredagivendepthofanaesthesia,asfollows(see
alsoMaltby2002).
... Tothisend,theanaesthetistwillbeinvitedtosethisflowsofoxygenandnitrous
oxideinthenormalwayandthentosetthebraintensionofanaestheticherequires,
notinkPaormmHg,butintotalMACunits.
Mapleson(1979).
MorerecentlytheclinicalutilityofMAChasbeenextendedbyestablishingitsvariation
withage(Mapleson,1996),temperature(Eger2001)andhaircolour(Liemetal.2004).
9.4.2 Age-correctedMAC
Although several factors are known to be associated with altered anaesthetic require-
ments,18ageisthemostimportantowingtotheincreasinglylargeage-rangemetwithin
clinicalpractice.
Whileagehaslongbeenknowntoinfluenceanaestheticrequirement(Gregory,Eger
andMunson1969),theexactvariationofMACwithagewasformalisedonlyrecently
byMapleson(1996),followingameta-analysisoftheavailabledata(seeTable9.1). In
17SeveringhausworkedonradartechnologyduringWorldWarII(Kofke2003).
18Thekeyfactorsarenarcotics(seesectiononremifentanilintheappendix),age,temperature,pregnancy,and
haircolour(Liemetal.2004,showedthatpatientswithredhairhada19%increasedMACrequirement).
RWDNickalls (August2011) MAC 142
particular,Maplesonshowedthatsemi-logplotsofMACagainstage(age 1year)forall
≥
inhalationalagentsarelinearandparallel,andhenceitisprobablethatalltheinhalational
agentsachievetheireffectsbyasimilarmechanism. Onthisbasis,therefore,Mapleson
derivedthefollowingrelationshipbetweenageandMACfromthepooleddata,
MACage=MAC40 10−0·00269(age−40)
×
whichexpressesMACforagivenageasafunctionofthatat40years(MAC ).
40
Table9.1:
MACdatabasedonage 1year.The95%confidencelimits(CL)forages1
≥
and80yearsareupto1%greaterthanatMAC (fromMapleson1996). For
40 ∗
theCO valueseeEiseleandEger(1967).
2
Agent 1year 40years 80years 95%CL( %MAC )
40
±
Halothane 095 075 058 6
· · ·
Isoflurane 149 117 091 6
· · ·
Enflurane 208 163 127 17
· · ·
Sevoflurane 229 180 140 6
· · ·
Desflurane 83 66 51 10
· · ·
Carbondioxide — 30 — —
∗
≈
Xenon 92 72 57 16
Nitrousoxide 133 104 81 8
Thecomputedreal-timeMACasdisplayedbytheDatexAS/3andS/5anaesthesia
monitors relates to normothermic patients aged approximately35 years-old. However,
sincemanyofthethoracicpatientsarequiteelderlyitismoreappropriateclinicallyto
useanage-correctedMAC.Areal-timesoftwareversionwhichincorporatesnitrousoxide
isshowninFigure9.5(page149). Printversions19 intheformofgraphswhichallow
fornitrousoxideusehavebeendesigned(NickallsandMapleson2003),aseparatechart
beingusedforeachvolatileagentasshowninFigures9.1–9.3. Theuseofnitrousoxide
isaccommodatedinthechartsbyoffsettingtheright-handN Oscalesverticallybythe
2
amountgivenby
MACage,volatile
FE(cid:48)N2O× MACage,N2O ·
Theprintversionsareavailablefordownload20 andalsoinAllmanandWilson(2006).
AnomogrambyLerou(2004)alsogivesage-correctedMAC.
19Theseallowanyonetoconfidentlyusethecommonvolatileagentswithpatientsofanyagewithoutany
guessworkortheneedforsuperhumanmemory.Themotivationfordevelopingaconvenientgraphicversion
arosefrommywantingapaper-equivalentforusewhenworkingatanotherhospital,sinceIthenhadnoaccessto
myownreal-timecomputerversionbasedinthethoracictheatreattheCityHospital.
20http://www.nickalls.org/dick/xenon/rwdnXenon.html#workstation-mac
RWDNickalls (August2011) MAC 143
ISOFLURANE End-expired (%) in
67% 50%
MAC N O N O
2 2
End-tidal(%)in100%oxygen/air 0011111222··········6802468024 (cid:13)001111c······680246R.........................................W................................................................................................................•.•..•................................................D......................................................................................................................................................................................N................................................................................................................•..•.•...i...............................................c........................................................................k.....................................................................................a...............................................................................l........................................l...........•.•..•...............................s.................................................................................................................2........................................................................................0.................................................................................0..................•.•..•..................................................................3...........................................................................................................................................................................................................................................................................•.•.•.....................................................................................................................................................................................................................................................................................................................................•.•..•..................................................................................................................................................................................................................................................................................................................................•.•..•.....................................................................................................................................................................................................................................................................................................................................•.••...............................................................................................................................................................................................................................................................................................................................•.•..•............................................................................................................................................................................... 00001111········024680246 000011111·········0246802468
0 10 20 30 40 50 60 70 80 90 100
Age (years)
Figure9.1:
Age-relatediso-MACcurvesdrawnusingthedataofMapleson(1996), The
dotsontheiso-MACcurvesaretohelpalignment.Theleft-handordinatescale
indicatestheend-expiredisofluraneconcentrationwhenusinganoxygen/air
mixture.Thetworight-handordinatescalesindicatetheend-expiredisoflurane
concentrationwhenusingnitrousoxide50%and67%inoxygen.Thevertical
shiftsforthenitrousoxide50%and67%scalesare056and075respectively.
· ·
ForagivenageandMACtheassociatedend-expiredisofluraneconcentration
isreadfromtheappropriateordinatescale. Forexample,aMACof12fora
·
60-yearoldpatientusingisofluraneandnitrousoxide67%inoxygenrequires
anend-expiredisofluraneconcentrationofapproximately05%.
·
RWDNickalls (August2011) MAC 144
SEVOFLURANE End-expired (%) in
67% 50%
MAC
3 8 N O N O
2 2
End-tidal(%)in100%oxygen/air 011111222223333···············802468024680246 (cid:13)001111c······680246R................................W.................................................................................................................•.•.•.................................................D.....................................................................................................................................................................................N................................................................................................................••...•..i...............................................c.........................................................................k..................................................................................a..................................................................................l.......................................l...........••...•............................s....................................................................................................................2.........................................................................................0................................................................................0..................••...•....................................................................3........................................................................................................................................................................................................................................................................••..•.....................................................................................................................................................................................................................................................................................................................................••...•...................................................................................................................................................................................................................................................................................................................................••..•.....................................................................................................................................................................................................................................................................................................................................••.•...............................................................................................................................................................................................................................................................................................................................••...•........................................................................................................................................................................................ 000011111222············0246802468024 0000111112222·············02468024680246
·
0 10 20 30 40 50 60 70 80 90 100
Age (years)
Figure9.2: