Seventynot

ARANDOMIZEDEVALUATIONOFTHEREVERSALOFKETAMINEBYPHYSOSTIGMINEJOHNC.
DRUMMOND,JOHNBREBNER,SAMUELGALLOONANDPATRICIAS.
YOUNGTHEUSEOFKETAMINEHYDROCHLOR[DE(Keta-lar,C1-58)inadultanaestheticpracticehasbeenlimitedbyemergencereactions,~-sKetaminehasseveralusefulclinicalattributesincludingeaseofadministration,rapidonsetofaction,partialpre-servationoflaryngo-pharyngealreflexes,9pro-foundsomaticanalgesia,~~shortdurationofef-fect,suitabilityforasthmaticpatients,=t.
=zmildtomoderatecardiovascularstimulationandin-creaseduterinetone.
t3However,thepost-operativeoccurrenceofdelirium,illusions,hal-lucinationsandvividfrequentlyunpleasantdreamshasreducedtheacceptabilityofketamineanaesthesiaintheeyesofpatients,anaesthetistsandrecoveryroompersonnel.
Therehavebeennumerousattemptstoamelioratetheundesirablepostoperativepsychicphenomena,bothpharmacologically3'5'6'~'~'t7andbycontrolofsensoryinputduringemergenccJsNoregimenhasprovenconspicuouslysuccess-ful.
Theefficacyofthetertiaryamineeholines-teraseinhibitorphysostigminesalicylateinthereversalofthesomnolenceanddeliriumcausedbynumerousdrugshasbeenestablished.
~9Anisolatedreportofthesuccessfulreversalofketaminesedationwithphysostigmineappearedin1976.
Balmer,z~inanapparentlysmallseries,observedrapidawakeningofvolunteersandpa-tientsrenderedunconsciousbyaninfusionofketamine.
Hisstudydidnotinvolveacontrolseriesandthedoseofketamineandthedose.
timeandrouteofadministrationofphysostigminewerenotspecified.
ThisreportofBalmertogetherwithsuggestivedatafromanimalstudies~h'2promptedustoundertakeaprospectivecontrolleddouble-blindtrialofthereversalofketamineeffectswithphysostigmine.
Wehaveevaluatedtheinfluenceofintravenousphysostigmineadministeredpost-operativelyonthetimecourseofrecoveryoforientationandconsciousnessandontheoccur-renceofpsychicsequelaefollowingketamineanaesthesiaforabriefgynaecologicprocedure.
JohnC.
Drummond,M.
D.
,JohnBrebner,M.
D.
,Ph.
D.
,F.
R.
C.
P.
(C),SamuelGalloon,M.
B.
,CH.
B.
,F.
F.
A.
R.
C.
S.
,PatriciaS.
Young,R.
N.
TheDepart-meatofAnaesthesia,UniversityofTorontoandTo-rontoGeneralHospital.
Canad.
Anaesth.
Soc.
J.
,vol.
26,no.
4,July1979METHODSOnehundredandelevenpatientsbetweentheagesof18and35undergoingtherapeuticabortionbydilatationandsuctioncurettage,werestudied.
Patientswhogaveahistoryofaseizuredisorder,cardiovasculardisease,psychiatricillness,re-centingestionofsedative,hypnoticorpsycho-activedrugsandpatientsnotspeakingEnglishorFrenchwereexcluded.
Consentwasobtainedfromallpatientsalthoughnomentionwasmadeofdreamsorotherpsychicphenomena.
Theprotocolwasapprovedbythehumanex-perimentationcommitteeoftheUniversityofToronto.
Eachpatientreceivedweight-adjustedpre-medicationwithPantoponandatropineapproxi-mately90minutespreoperatively(TableI).
In-ductionandmaintenanceofanaesthesiawereachievedbyastandardinitialdoseofketamine,2rag-kg-tadministeredintravenouslyover40to60seconds,andincrementsof0.
5mg-kg-tasrequiredbypatientresponse.
Patientsbreathedroomair.
Ineighty-fourpatients(GroupA),physostigmine(50pg.
kg-a)orasalineboluswasadministeredintravenouslyonarandombasisintheoperatingroomuponconclusionoftheproce-dure.
ThedoseofphysostigmineadministerediswithintherangequotedbyGreene,23althoughitsomewhatexceedsthatnormallyemployedinourhospital.
24Thedosewasestablishedbymeansofapilotstudy.
Immediatelyafterphysostigmineadministrationthepatientwastransportedtotherecoveryroom.
Anobserver(J.
C.
D.
)whowasnotpresentattheconclusionoftheprocedureassessedthepatient'slevelofconsciousnessandorientationuponarrivalintherecoveryroomand5,10,20,30,45and60minutesthereafter.
Forthepurposesofrecordingrecoverystatus,sixstagesoflevelofconsciousnessandfivestagesoforientationweredefined(TableII).
Patientsre-ceivedroutinepostoperativenursingcareandevaluationandnomeasurestoreduceafferentstimuliwereemployed.
Whileintherecoveryroom,patientswereobservedcontinuouslyandanyinstanceofemergencereactionsintheformofapparenthallucinationsorrestlessnessre-quitingnursinginterventionwasrecorded,as288DRUMMOND,etol.
:KETAMINEREVERSALBYPHYSOSTIGMINETABLEIPREMEDICATIONWeight(kg)Pantopon(rag)Atropine(rag)45-54.
9100.
355-64.
9150.
465-74.
920O.
675-250.
6TABLEIICRITERIAFORRECOVERYROOMSTAGINGLevelofConsciousnessStage1Comatose.
Unresponsivetophysicalorverbalstimuli.
StageI[Respondstophysicalstimuli.
Noornon-specificresponsetoverbalstimuli.
Doesnotrespondaccuratelytoquestionsorcom-mands.
StageII[Purposefullyresponsivetoverbalstimuli,butdifficulttorouserequiringrepeatedorloudcommands.
StageIVSleepsifundisturbedbutrousesreadily.
StageVAwake.
Eyesopenmorethan50percentofthetimeand/orspeaksspontaneously.
StageVIFullyawake.
OrientationStageIDisorientedtoperson,placeandtimeand/orbchaviouruncontrollable.
Stage]IAsinStageI,butcanbrsettledwhenreassured.
StagellIOrientedtopersononly.
StageIVOrientedtopersonplusplaceortime.
StageVOrientedtotime,placeandperson.
TABLEIIICRITERIAFORRECOVERYROOMDISCHARGEI.
Minimumof60minutes.
2.
Minimumof30minutesafteranydrugadminis-tration.
3.
Vitalsignswithinpreoperativelimits.
4.
Vitalsignsstablefor:30minutes.
5.
Awakeandorientedtowithinpreoperativelimits.
289administration,z6Accordingly,toassesstheim-portanceofanincreasedintervalbetweentheadministrationofketamineandphysostigmine,afurther27patientswerestudied(GroupB).
GroupBpatientsreceivedphysostigmine/placebo30minutesafterthelastdoseofketamine.
Pre-medication,inductionandmaintenancewereac-complishedinthesamemannerasGroupA.
Uponconclusionoftheprocedure,thepatientwastransportedtotherecoveryroomwhereaninitialassessmentofconsciousnessandorienta-tionwasmade.
Theassessmentwasnextper-formed30minutesafterthelastdoseofketamineandimmediatelypriortoadministeringthephysostigmine/placebo.
Thephysostigmine/placebowasadministeredbytherecoveryroomobserverfromasyringepreparedintheoperatingroomandlabeledwiththepatient'snameonly.
Assessmentswererepeatedat5,10,20,30,45and60minutesfollowingadministration.
Onthemorningofthedayfollowinganaes-thesia,averbalquestionnairewasadministeredbyanurse(P.
Y.
)experiencedwiththeadminis-trationofpostoperative.
questionnairesbutunac-quaintedwiththeoperativeorrecoveryroomcourse.
Seventy-nineof84patientsinGroupAand24of27patientsinGroupBwereaccessiblepostoperatively.
Thequestionnairesoughttoidentifyaspectsofthepost-anaesthesiacoursewhichareknownormightbeexpectedtoaffectpatientacceptanceofananaesthetictechnique.
Specificquestionsconcerningtheoccurrenceandnatureofdreamsandtheoccurrenceofnausea,vomitinganddizzinesswereposed.
LevelofConsciousnessandOrientationscoresweretreatedarithmeticallyingeneratingaveragescoresforthevariouspopulationsatagiventime.
Statisticalanalysisofthesescoreswasdonebyanon-parametrictest(Chisquare).
Allotherstatisticalanalysiswasdonebyanunpairedt-test.
Significanceistakenasprovenwhenpnotdemonstrate290CANADIANANAESTHETISTS"SOCIETYJOURNALTABLEIVPATIENTANDANAESTHETICDATAGroupAGroupBPhysostigmiuePlaceboPhysostigminePlacebon~40n~44n=14n=13Weight(k8)59.
94-13.
257.
5+10.
7n.
s.
62.
5+_8.
358.
6_+9.
2n.
s,*Ase(yr)23.
3___4.
123.
2+4.
1n.
s.
24.
8_+5.
224.
9+4,6n.
s.
No.
ofdoses2.
11.
12.
3__1.
3n.
s.
2.
2_+1.
92.
1+_1.
1n.
s.
Totaldose(mg.
k8-~)2,5_+0.
52.
7+0.
7n.
s.
2.
6+0.
92.
5_+0,5n.
s.
Duration(rain)10.
2~4.
010.
0+3.
3n.
s.
10.
6+4.
710,0+3.
8n.
s.
*n.
s:Differencenotstatisticallysignificant.
TABLEVRECOVERYROOMDATA:GROUPAPhysostigminePlacebon~40n~44L.
O.
C.
onRRarrival1.
9__.
0.
92.
5+0.
8pnotedinfouroftheGroupBpatientswhoreceivedphysostigminesalicyLate.
Thesechangeswerebriefandbeyondthesensitivityofourstaging(TableII).
Thetotalrecoveryroomtimewasgreater,however,forthephysostigminegroup,(116minutes,S.
D.
=35.
5),thanfortheplacebogroup(84.
Iminutes,S.
D.
=24.
3)(pnotshowsignificantdif-DRUMMOND,elal.
:KETAMINEREVERSALBYPHYSOSTIGM[NETABLEVIRECOVERYROOMDATA:GROUPB291PhysostigminePlacebon=14n~-13L.
O.
C.
onRRarrival2.
9+0.
62.
50.
9n.
s.
p~e-drug3.
8_+0.
74.
1_+1.
0n.
s.
at30rain.
4.
5+0.
55.
0_+0.
9n.
s.
Orient.
onRRarrival2.
5_.
+1.
52.
5_+1.
8n.
s.
pre-drug4.
7+0.
64.
4_4-1.
5n.
s.
at30min.
5.
0+0.
05.
0__0.
0n.
s.
RRtime(rain)116.
0_+35.
584.
124.
3pnotstatisticallysignificant.
TABLEVIIEMERGENCEREACTIONS:HALLUCINATIONSAND/ORRESTLESSNESSGroupAGroupBPSPlaceboPSPlaceboCombinedn=40n=44n--14n=13n~IllEmergenceReactionsHallucinations(~)814n.
s.
00n.
s.
8n.
s.
Restlessness(7o)2014n.
s.
2915n.
s.
18n.
s.
Overall(~o)2523n.
s.
2915n.
s.
23n.
s.
PS:PhysostigmineSalicy[ate.
il.
s.
:Differencenotstatisticallysignificant.
TABLEVIIIDATAFROMPOSTOPERATIVEQUESTIONNAIREGroupAGroupBPSPlaceboPSPlaceboCombinedn----37n=42n=13n=12n=104Dreams(~o)6264n.
s.
6775n.
s.
65n.
s.
UnpleasantDreams(7o)3829n.
s.
5017n,s,33n,s,Nausea(7o)8679n.
s,9275n.
s.
83n.
s.
Vomiting(7o)8974n.
s.
8373n.
s.
82n.
s.
Dizziness(7o)7060n.
s.
5883n.
s.
66n.
s.
PS:PhysostigmineSalicylate.
n.
s.
:Differencenotstatisticallysignificant.
ferencesintheoccurrenceofemergencereac-tionsintheformofhallucinationsorrestlessness(TableVII).
InGroupA,apparenthallucinationswereobservedin8percent(3/40)ofpatientswhoreceivedphysostigmineandin14percent(6/44)ofthosewhoreceivedplacebo.
NohallucinationswereobservedinGroupBpatients.
Restlessnessrequiringinterventionintheformofrestraintorreassuranceoccurredin20percent(8/40)ofGroupApatientswhoreceivedphysostigmineandin14percent(6/44)ofcontrols.
ThepatternwassimilarinGroupB.
Restlessnesswasob-servedin29percent(4/14)ofGroupBpatientswhoreceivedphysostigmineandin15percent(2/I3)ofcontrols.
AsummaryofdatacollectedbyquestionnaireonthedayfollowinganaesthesiaispresentedinTableViii.
Dreams.
Physostigminedidnotproducesignificantdifferencesintheincidenceofdream-292CANADIANANAESTHETISTS'SOCIETYJOURNALingduringanaesthesiaandrecovery.
InGroupA,62percent(23137)ofpatientswhoreceivedphysostigmineexperienceddreams.
Sixty-onepercentofthese(14/23),i.
e.
38percentofthetotalpopulation,describedtheirdreamsasun-pleasant.
Sixty-fourpercent(27142)ofGroupAcontrolsexperienceddreams.
Forty-fourpercent(12/27)or29percentofthepopulationdescribedtheirdreamsasunpleasant.
ThepatternwassimilarinGroupB.
Sixty-sevenpercent(8[12)ofthephysostigminegroupdreamed.
In75percent(618,50percentofthepopulation)thedreamswereunpleasant.
Seventy-fivepercent(9/12)ofGroupBcontrolsexperienceddreamsofwhich22percent(2/9,17percentofthepopulation)wereunpleasant.
Theincidenceofnausea,vomitinganddizzi-nessexperiencedafteranaesthesiawashighinbothgroupsandcomparableincontrolandex-perimentalpopulations(TableVIII).
Subjectswerenotobservedsystematicallyforsignsofincreasedcholinergicactivitywiththeexceptionofthecardiovascularsystem.
Onepa-tientinGroupBdevelopedatransientbrady-cardia,rate44,2to3minutesafterphysostig-mine.
Notreatmentwasrequired.
Excessivesweatingandsalivationwerenotedinasmallnumberofpatients.
Thelatterwasnotofconse-quenceintermsofthepatients'spontaneousmaintenanceofaclearairway.
DISCUSSIONOpiateoropiate-hyoscinecombinationshavebeenfoundbysometobeoptimumpre-medicationforketamineanaesthesia.
2"~4Wead-ministeredPantoponbutexcludedhyoscinebe-causeoftheestablishedeffectofphysostigmineonthepostoperativesomnolencecausedbyhyoscine.
2~'24Atropinewasincluded,however,becauseexcesssalivationhasbeenfoundbysometobetroublesomeduringketamineanaes-thesiaandbecausebradycardiahasbeenob-servedduringdilatationofthecervixinpatientswhodidnotreceiveanli-cholinergicsbeforedi-latationandcurettageunderketamineanaes-thesia.
~sInthedoseemployed,atropineshouldrarelyproducesomnolenceorbehaviouralab-normality,zsMyriadcombinationsofopiates,hypnotics,tranquillizersandanti-cholinergiesadministeredbeforeorafterketaminehavebeenevaluatedinattemptstoreduceoreliminatethevariouspsy-chicsequelaeofketamineanaesthesia)"5"6"t~1~Becausenoregimenhasconsistentlyreducedsequelaeinadultstolevelsacceptabletopatientsandphysicians,theuseofketaminehasbeenrestrictedingeneraltopaediatricpracticeandtospecialcircumstancesinadultanaesthesiawheretheadvantagesjustifythedisadvantages.
ThebriefreportbyBalmer20appearedtopro-videameansofbroadeningtheusefulnessofketamine.
Itseemedpossiblethatphysostigminemightantagonizeketamine.
Whileketaminelackstheanti-cholinergicpropertiescommontothemajorityofagentsantagonizedbyphysostig-mine,theeffectivenessofphysostigmineasanantidotetodrugswithoutknownanti-cholinergicactivity,suchasdiazepam,~9ethclorvinyl(Placidyl),methyprylon(Noludar)2vandhalo-thanezshasbeendemonstrated.
Animalstudieshaveprovidedadditionalinformationsuggestiveofaroleforphysostigmineasaketaminean-tagonist.
AIbin,etal.
2~notedtheattenuationofpostoperativedeliriumandadecreasedrecoverytimeindogsgivenapotentcholinesterasein-hibitoreitherbeforeorafterananaestheticdoseofketamine.
WintersandKott22demon-stratedthatthebehaviouralandelectro-encephalographicmanifestationsofketamineanaesthesiaincatscouldbepreventedbypre-treatmentwithphysostigmine.
Accordingly,westudiedII1patientswhohadundergoneketamineanaesthesiafortherapeuticabortionbydilatationandsuctioncurettage.
Theresultsofthisstudy,however,donotdemon-strateimprovementofanyaspectofthepost-operativecourseofpatientswhoreceivedphysostigmineafterketamineanaesthesia,Infact,patientswhoreceivedphysostigmineim-mediatelyuponconclusionoftheoperativepro-cedurehaddelayedrecoveryofconsciousnessandorientationandspentLongerperiodsintherecoveryroomthancontrols.
Bycontrast,pa-tientsinwhomadministrationofphysostigminewasdelayeduntil30minutesafterthelastketaminedose(GroupB)didnotdemonstratedelayedrecoveryasmeasuredbyourcriteria.
Itseemsunlikelythatprolongationofrecoveryofconsciousnessandorientationwastheeffectofphysostigminepersebecausecomparablein-creaseswerenotseeninGroupBpatientswhowereinadvancedstagesofrecovery(SeeTableV)whenphysostigminewasadministered.
Theprolongedrecoveryoforientationandcon-sciousnessinGroupApatientswhoreceivedphysostigmineraisesthepossibilityofasyner-gismofeffectbetweenketamineandphysostig-mine.
CurrentknowledgeofthepharmacologyofketamineandphysostigminedoesnotprovideanDRUMMOND,eta[.
:KETAMINEREVERSALBYPHYSOSTIGM1NE293explanationforsuchaneffect,Asacholin-esteraseinhibitorphysostigminemightbeex-pectedtoenhancetheeffectofdrugsactingthroughcholinergicmechanisms;butcholinergicactivityhasnotbeenattributedtoketamine.
Ourresultssuggestthepossibilitythattheneuro-transmitteracetylcho]inrmayprovetobeamediatoroftheactivityofketamine.
Theexplanationofthesynergismwhichtheseresultsimplymight,ontheotherhand,liewithhithertounidentifiedeffectsofphysostigmine.
Physostigmineisviewedasacholinergicdrug.
However,itseffectivenessasanantidotetoagentswithoutestablishedanti-cholinergicac-tivity*9.
27.
28haspromptedsuggestionsthatithasnon-specificanalepticactivity,zlItdoesappearlikelythatketamineproducesits"dissociative'"anaestheticeffectbycentralnervoussystemex-citationatsubcorticallevelsratherthanbyde-pression.
29"3~Inthislight,theapparentpotentia-tionofketaminebyphysostigminemaybemorereadilyunderstandable.
OurresultscontradictthoseofBalmer2~whofoundphysostigmineeffectiveinreversingketamine-inducedsomnolence.
Hisstudiesevolvedfromexperienceinasomnolentpatientwhohadreceiveddiazepam,droperidolandketamine.
Thepatientawakenedpromptlyafterphysostigmineadministration.
Residualanal-gesiawasnotedand,sincenoagentwithanal-gesiceffectsotherthanketaminehadbeengiven,heconcludedthatthesedativeeffectsofketaminehadbeenreversed.
Ithasbeenestab-lishedthattheanalgesicactionofketamineismoreprolongedthanthesoporificeffects31anditseemslikelythathispatientawakenedbecauseofthereversalofthesedativeeffectsofdiazepamanddroperidolratherthanofketamine.
Physostigminesalicylatewasofnobenefitinreducingemergencereactionsdefinedhereasrestlessnessorhallucinatorybehaviourapparenttorecoveryroomobservers,Theincidencewas26percentamongphysostigmine-treatedpa-tientsand21percentamongcontrols.
The23percentrateforthetotalpopulation(26/111)isremarkablysimilartothe24percentincidenceofemergencereactionsnotedbySussmansinamoreheterogenouspopulationofpatientsover16yearsofage.
TheabsenceofhallucinationsinGroupBpatientsisnoteworthy.
Thesepatientswerenotundergoingrepeatedassessmentduringtheearlyportionoftherecoveryroomstayandtheapparentreductionofhallucinationsmaybetheresultofdecreasedafferentstimuliduringearlyawakening.
Theimplicationforrecoveryroommanagementofketaminepatientsisobvi-ousandhasbeensuggestedpreviously)zHow-ever,thelimitationscreatedbythenatureoftherecoveryroomenvironmentandthenecessitytomonitorvitalsignsmakeseffectivereductionofafferentstimulidifficultandimpractical.
Similarly,physostigminedidnotdecreasetheincidenceofdreams(TableVII).
Sixty-threepercent(31/49)ofpatientstreatedwithphysostig-mineand67percent(36/54)ofcontrolsdreamed.
Theoverallincidenceofdreams,65percent,parallelsthe60percentratenotedbyKrestow7inastudyofdreamsafterketamineanaesthesiafortherapeuticabortion.
The33percentincidenceofunpleasantdreamsinthetotalpopulationisalsosimilartotheobserved38percentrateinKrestow'sstudy.
Unpleasantdreamsweresomewhat,thoughnotsignificantly,morefre-quentinthegroupstreatedwithphysostigmine(41percent)thanincontrols(26percent).
Nauseaandvomitingoccurredin75to90percentofpatientsinthevariousexperimentalgroups,theincidencebeingslightlybutnotsignificantlyhigherinthosewhoreceivedphysostigmine.
Thisfrequencyofnauseaandvomitingisunacceptablyhigh.
Improvementmightbeanticipatedwiththeuseofpremedieantswithanti-emeticactivity,suchashyoscine.
promethazineanddroperidol.
Theresultswehaveobtaineddonotjustifytheuseofphysostigminesalicylateasaketamineantidote,Weconclude,infact,thatwhenad-ministeredintheearlystagesofspontaneousre-coveryfromtheanaestheticeffectsofketamine,physostigmineisinsomewaysynergisticwithketamineandwillprolongrecoveryoforientationandconsciousness.
Inaddition,physostigmineadministeredafterketamineanaesthesiadoesnotdecreasetheincidenceofemergencephenomenameasuredeitherobjectivelyorsubjectively.
Inourhandsketamineremainsanagentwhichisusefulinpaediatricpracticeandinspecialcir-cumstancesinadultanaesthesiawhereitsad-vantagesduringoperationoutweighthedisad-vantagesoftherecoveryphase.
SUMMARYOnehundredandelevenpatientsundergoingketamineanaesthesiafortherapeuticabortionwerestudiedinadouble-blindtrialofthereversalofketaminebyphysostigmineadministeredpostoperatively.
Theresultsdemonstratethatphysostigminedoesnotshortenrecoverytimeorreducetheoccurrenceofketamineemergence294CANADIANANAESTHETISTS'SOCIETYJOURNALphenomenasuchashallucinations,restlessnessanddreams.
Infact,therecoverycoursewasprolongedinpatientsgivenphysostigmineim-mediatelyuponterminationofanaesthesiaascomparedwithcontrols.
Bycontrast,whenphysostigminewasgiven30minutesafterthelastdoseofketamine,therecoverywasnotpro-longedascomparedwiththatoftheplacebo-treatedcontrols.
Thesefindingssuggestsomesynergismbetweentheeffectsofketamineandphysostigmineandshoulddiscouragetheuseofphysostigmineasaketumineantidote.
R~SUM~Cette6tudehdoubleinsuportesurceren-versementdelak6tamineparlaphysostigmineadministr6ependantlap6riodepost-op6ratoire~tcentonzepatientesanesthdsidespourunavorte-meatth6rapeutique.
Lesrdsultatsmontrentquelaphysostigmineneraccourcitpasletempsder6cup6rationninediminueI'incideneedesph~nom/:nesd'dmergenceassoci6shlak,~tamine(hallucinations,agitation,r6ves).
Enr6alit6,lar6cup6rationdespatientesquiavaientre~udelaphysostigmineimmddiatementapr6sranesth6siefurprolongdecomparativementauxcontr61es.
Parcontre,silaphysostigmined/airadministrde30minutesapesladerni6redosedekdtamine,lardcup6rationnes'estpasprolong6eencom-paraisonaveclespatientesquiavaientrequunplacebo.
Cesr6sultatslaissantsupposerrexis-tencedesynergismeentreleseffectsdelak6tamineetdelaphysostigmineetdevraientd6couragerrusagedelaphysostigminecommeantidotedelak6tamine.
ACKNOWLEDGEMENTSTheauthorswishtothankthegynaecologistsofTorontoGeneralHospitalforpermittingtheparticipationoftheirpatients.
Asever,wearegratefultotheRecoveryRoomnursesfortheirpatienceandvigilance.
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