Control ofBleeding Varices byVasopressin: [601454]

Control ofBleeding Varices byVasopressin:
AProspective Randomized Study
WILLARD C.JOHNSON, M.D.,WARREN C.WIDRICH, M.D.,JACKE.ANSELL, M.D.,ALANH.ROBBINS, M.D.,
DONALD C.NABSETH, M.D.
FromJuly1975toNovember 197625patients withbleeding
esophagogastric varicesdocumented byendoscopy whofailed
torespond toconservative medicaltreatment weretransferred
totheSurgical Service. Thesepatients, whoweremainly
Child'sClass"C"alcoholic cirrhotic patients, weretreated
withvasopressin infusedcontinuously usingastandardized
doseintoeitheraperipheral veinorthesuperior mesenteric
artery(SMA)according toapredetermined randomization.
Nosignificant difference inefficacy forcontrolofbleeding
(average rate=56%)relatedtorouteofadministration was
found.Because catheter-related complications intheSMA
groupweresignificantly greater, weconcluded thatthemethod
ofchoiceinvasopressin treatment ofesophagogastric variceal
bleeding isacontinuous infusionbywayofaperipheral vein.
CONTROL OFACUTE GASTRO-ESOPHAGEAL variceal
hemorrhage inpatients withportalhypertension
isadifficult problem forwhichthereisnodefinitive
solution. Currentrecommendations includeemergency
porto-caval shuntsurgery,22 Sengstaken-Blakemore
(S-B)tubeinsertion,3 bloodandcoagulation factor
replacement, andvasopressin administration.19 The
vasopressor effectofpituitary extracts wasnotedby
Oliver21 in1895andtheeffectofdecreased portal
pressure wasobserved byClarkin1928.5Successful
controlofvariceal bleeding intwopatients witha
bolusintravenous injection of20uofvasopressin
wasreported byKehneetal.16in1956.Bolusin-
travenous vasopressin subsequently received wide-
spreadclinicalapplication.7'24'25 Theproblems of
severesystemic effectsand,frequently, atendency
torebleedafterinitialcontrolwasachieved prompted
Nusbaum etal.19in1968torecommend thetech-
niqueofcontinuous infusion ofvasopressin intothe
superior mesenteric artery.Morerecently Thomford
etal.30andBarretal.2havenotedthatcontinuous
Presented attheAnnualMeeting oftheAmerican Surgical
Association. BocaRaton,Florida, March23-25,1977.
Reprint requests: Willard C.Johnson, M.D.,Department of
Surgery, Boston V.A.Hospital, 150SouthHuntington Avenue,
Boston,Massachusetts 02130.FromtheDepartments ofSurgery, Radiology and
Medicine, BostonVeterans Administration Hospital
andTuftsUniversity SchoolofMedicine,
Boston, Massachusetts
peripheral intravenous infusion ofvasopressin appears
toaffectportalpressure tothesameextentasinfu-
sionthrough thesuperior mesenteric artery.Their
findings werealsoconsistent withobservations of
otherinvestigators9 15thatthesystemic effectof
vasopressin oncoronary arteryflowandcardiac
outputwassimilarregardless ofsiteofadministration.
In1975Sirineketal.27suggested that,sinceselec-
tiveinfusion ofvasopressin intotheSMArequires
specialequipment andpersonnel, delaysadministra-
tionofthedrug,introduces thehazards ofarterial
catheterization, andmaynotavoidpotentially unde-
sirablesideeffects,thecontinuous administration of
vasopressin through aperipheral veinmaybeprefer-
able.Thepurpose ofthisprospective randomized
studywastoevaluate thetworoutesofvasopressin
administration inpatients withsevereliverdisease
andlife-threatening hemorrhage withregardtoefficacy
ofbleeding controlandoccurrence ofundesirable side
effects.
PatientSelection andMethods
FromJuly1975toNovember 1976patients with
bleeding gastricand/oresophageal varicesdocumented
byendoscopy whofailedtorespond tolavage,ant-
acidtherapy, andbloodandcoagulation factorreplace-
mentweretransferred fromtheMedical Service
totheSurgical Intensive CareUnit.Eachpatientwas
treatedwithcontinuous vasopressin andtherouteof
administration wasdetermined byarandom number
table.6Nopatientwithbleeding variceswasexcluded
asbeingtoosickorbecause ofcoagulopathy orcon-
currentgastritis.
369

JOHNSON ANDOTHERS
FIG.1.Schematic representation ofthetreatment ofvariceal
hemorrhage bycontinuous vasopressin infusion: Group1,byperiph-
eralvein;Group2,bySMAcatheter.
Vasopressin wasadministered withanIVAC500
infusion pump(IVACCorp.,SanDiego,Ca.)(Fig.1).
Thedoseofvasopressin wasstandardized andgiven
atacontinuous rateof0.4u/minuntilbleeding stopped
orfor24hours.Aftercontrol, vasopressin was
reduced toarateof0.2u/minfor24hours,then0.1
u/minforthenext24hours.Saline wasinfusedfora
further24hoursbeforediscontinuation oftreatment.
Ifre-bleeding occurred whilethecatheter wasin
place,theinitialdosewasreinstituted andthewean-
ingprocess wasbegunagain.Itwasnotedthatareduc-
tionoftheinitialdosage to0.2u/min wasrequired
beforebleeding wascontrolled because ofcardiac
defects. Catheterization fordirectarterial infusion
wasaccomplished inthefollowing manner. Arteriog-
raphyoftheceliacandsuperior mesenteric arteries
wasperformed. Asteam-shaped Becton-Dickenson
RPXcatheter (I.D.,0.054inchtapered overa0.045
inchguide-wire) wasinserted through afemoral artery
andpositioned intothesuperior mesenteric artery
underfluoroscopic control.Toenhance visualization of
themesenteric venous system, portalveinandgastro-
esophageal varices, papaverine hydrochloride, 45mg,
wasgivenintra-arterially immediately priortomethyl-
glucamine iothalamate, 80ml,forarteriography. Four-
teenfilmswereexposed during a24-second period
andafifteenth filmwasexposed 30seconds later.Iftherewasnoextravasation ofcontrast medium
andifgastro-esophageal varicesaloneweredemon-
strated, thecatheter wasleftinposition. Iftheright
hepaticarteryoriginated fromtheSMA,thecatheter
wasrepositioned toamoreperipheral location toavoid
vasopressin perfusion oftheliver.Thearterialpunc-
turesitewastreatedby"defatting" withalcohol,
application ofbetadine ointment tothecatheter and
anocclusive dressing. Thedressing waschanged every
24hoursandcatheter carewasrepeated.
Duringvasopressin therapy, patients werefollowed
withcontinuous cardiacmonitoring andserialEKGs.
Liverfunction testsandcoagulation studieswerealso
performed. Bloodwascollected in3.8%sodium
citrate(1:10dilution) forcoagulation studiesandin
EDTAforplatelet counts.Platelet-poor plasmawas
separated bycentrifugation at2000gx15minutes at
40andthesamples weretestedimmediately. The
following hematological studiesweredone;prothrom-
bintime,activated partialthromboplastin time,throm-
bintime,fibrinogen concentration, fibrinogen degrada-
tionproducts, platelet countsandbleeding time.A
clinically important coagulation deficitwasdefined
asaprothrombin timegreater thanfiveseconds
abovecontrol, apartialthromboplastin timegreater
than15seconds abovecontrol oraplatelet count
orlessthan50,000. Vitamin K,fresh-frozen
plasmaandplatelettransfusions weregivenasindi-
cated.Allpatients weretreatedwithantacids, via
nasogastric tubewhileactivelybleeding, andthenwith
oraladministration of30ccMylanta IT®(StuartPhar-
maceuticals, Wilmington, De.)Control ofbleed-
ingwasdefined asnotrequiring morethan1000cc
ofbloodreplacement duringvasopression infusion and
for15daysthereafter. Temporary controlofbleeding
wasdefinedasnotrequiring morethan1000ccofblood
replacement duringvasopressin infusion, butblood
replacement totalling morethan1000ccwasrequired
duetorebleeding inthe15daysfollowing dis-
continuation ofvasopressin. Combined control of
bleeding wasdefined ascontrol ofbleeding ac-
complished, afterinitialfailureofvasopressin alone,
withtheaddition ofaSengstaken-Blakemore tube;
transfusion requirements for15daysthereafter were
lessthan1000cc.
Results
Because ofthedevelopment oftwomajorcatheter
complications intheSMAgroup,resultsweretabulated
when25patients hadbeenstudied. Thegroupswere
comparable inseverity ofillness.Allpatients had
ahistoryofheavyalcoholic intakeandmorethan85%
ofpatients ineachgrouphadClass"C"liverdisease
byChild'sClassification. Theaveragebloodlossbefore370 Ann.Surg. oSeptember 1977

CONTROL OFBLEEDING VARICES BYVASOPRESSIN
introduction intothestudywasseventoeightunits
foreachgroup.About40oofpatients ineachgroup
hadevidence ofaclinically important coagulopathy.
Afewpatients ineachgrouphadbothbleeding
varicesandgastritis (Table1).
ControlofBleeding
Bleeding wascontrolled duringinfusion andfor15
daysaftervasopressin administration in50%(7/14)of
theSMAgroupandin64%(7/11)oftheperipheral
veingroup(Table2).Thisdifference isnotstatistically
significant. Eightpatients (fourineachgroup)failed
torespond tov1asopressin therapy. Sengstaken-Blake-
moretubeswereinserted intothesepatients andthis
combined therapy wassuccessful intwopatients in
eachgroup.Fourpatients, eachofwhomhadsevere
coagulopathy, exsanguinated; twoofthesepatients
wereintheSMAgroupandtwowereintheperipheral
veingroup.Threepatients intheSMAgrouprebled
duringthe15-dayperiodfollowing discontinuation of
infusion. Bleeding wassubsequently controlled inthese
patientsbyeitherperipheral veinvasopressin oranS-B
tube.
TABLE1.PatientDataProfile
Vasopressin Infusion via
SMA Peripheral
Catheter Vein
No.patientsentered 14 11
HistoryandPhysical Examination
Heavyalcoholconsumption 14 11
Average no.unitsbloodbefore
randomization incurrent
hospitalization 8.0u 7.3u
Diagnosis:Bleeding varices 12 9
Bleeding varicesandgastritis 2 2
Child's"C"classification 12 10
Encephalopathy(moderate) 2 1
(mild) 5 4
(absent) 7 6
Ascites
(tense) 5 5
(present) 5 4
(absent) 4 2
Laboratory Data
Average totalbilirubin(mgo) 3.5 5.0
Average serumalbumin(g%) 2.68 2.60
Average no.secPTabovecontrol 4.2 4.8
Average no.secPTTabovecontrol 10 12
Average plateletcount 115,000 107,000
Presence ofclinically important coag-
ulationdeficits 6pts 5ptsTABLE2.ControlofBleeding
Vasopressin Infusion
Via
SMA Peripheral
Catheter Vein
Control-during andaftervasopressin 7 7
Temporary control-during vasopressin
only 3 0
Combined control-vasopressin andS-B
tube 2 2
Exsanguination 2 2
Totalno.patients 14 11
Catheter Related Complications
Twopatients intheSMAgroupsustained significant
catheter-related complications (Table3).Subintimal
dissection leading toocclusion oftheSMAorifice
occurred inonepatient.Bleeding wascontrolled for
11dayswithacombination ofSengstaken-Blakemore
tubeinsertion for24hours,followed byintravenous
vasopressin andleftgastricveinocclusion, butthis
patientdiedwithmultiple organfailure. Atautopsy
therewasnoevidence ofischemic boweldisease.
Thesecondpatientdeveloped asepticfemoralpseudo-
aneurysm whichruptured andrequired proximal liga-
tionoftheexternal iliacarteryanddistalligationof
thesuperficial femoral artery.Thispatientsurvived
andnowhasclaudication at100yardsafterbrisk
walking.
Fivepatients hadminorcatheter-related complica-
tions.IntheSMAgroup,twopatients developed
smallhematomas attheinsertion site,onepatienthad
groinbleeding ofadegreetorequirecatheterization
oftheothergroin,andonepatienthadasuperficial
sepsisatthegroinpuncture site.Intheperipheral
veingroup,onepatientdeveloped forearm phlebitis.
Withregardtocatheter-related complications, the
groupsaresignificantly different (p=0.065).
CardiacEffects
Nopatientineithergroupsustained myocardial
infarction asevidenced byserialEKGs.Arrythmias
TABLE3.Complications ofVasopressin Infusion
Vasopressin Infusion Via
SMA Peripheral
Catheter Vein
No.patientsentered 14 11
Majorcathetercomplications 2 0
Minorcathetercomplications 4 1
Cardiacarrhythmias 6 1
30-daymortality 4 5Vol.186.oNO.3371

Ann.Surg.*September 1977
werenotedin6patients intheSMAgroup(three
bradycardias, twoPVCsandoneWenckebach phe-
nomenon). Onepatientintheperipheral veingroup
developed Wenckebach phenomenon. Arrhythmias re-
sponded toreduction ofthevasopressin dosefrom
0.4u/minto0.2u/mininallbutonepatientwhore-
quiredtheaddition ofaslowdriplidocaine infusion
tocontrol persistent PVCs.Isuprel (isoprotorenol
hydrochloride) wasnotadministered.
PatientSurvival
The30-daysurvival ratefortheentireserieswas
64%(16/25),andcurrently 48%(12/25)ofthepatients
arealive6to21monthsfollowing entryintothestudy.
Ofthepatientswithclinically important coagulopathy,
45%survived for30days,whereas 79oofthepatients
withoutcoagulation deficitssurvived. Thisdifference
isnotstatistically significant. Insurviving patients,
theaveragemaximum serumbilirubin increase during
vasopressin infusion was2.7mg%intheperipheral
veingroupand2.5mgointheSMAgroup.Thirty
dayslatertheaverage serumbilirubin levelwas2.1
mg%ointheSMAgroupand2.2mgointheperipheral
veingroup.Ingeneral, wewereunabletostatistically
correlate survival withserumbilirubin.
Thebestprognostic factoroflong-term survival
wastheinitialresponse tovasopressin therapy. Ofthe
14patients whosebleeding wascontrolled during
andaftervasopressin therapy(Table2),11patients
survived. Ofthe11patients whowereclassified as
Temporary Control,Combined ControlorExsanguina-
tion,onlyonepatientisaliveinthe6to21month
follow-up period.Thisobservation ishighlysignificant
(p<0.01).
Statistical Analysis
ByStudent's "t"testforunpaired data,wefound
nodifference intheefficacyofvasopressin incontrol
ofacutegastro-esophageal varicealbleeding relatedto
routeofadministration.6 Whenthegroupswerecom-
paredwithregardtocatheter-related andcardiaccom-
plications aswellasabilitytocontrolbleeding, itwas
notedthatadifference wassignificant (p<0.04)by
Fischer's ExactTest6andthattheperipheral vein
groupappeared tofarebetter.It,therefore, was
evident thattheonlyclinicaljustification forcon-
tinuation ofthestudywouldbewiththehypothesis
thatSMAinfusion ofvasopressin wasmoreeffec-
tiveinthecontrolofhemorrhage thanperipheral vein
infusion. Itwascalculated thatwithanassigned beta-
errorof20%oandalphaerror5%,asamplesizeof
336patientswouldberequired tostatistically validatea15%therapeutic benefit.6 Sincetheresultsofour
studyof25patients showed acontrolrateof64%for
peripheral veinvasopressin andacontrolrateof50%
forSMAvasopressin, itseemedveryunlikely thatthe
SMAroutecouldbe15%moreeffective thanthe
peripheral vein.Bylowering ourexpectations to
demonstrate a10%difference intherapeutic efficacy,
itwouldbenecessary toevaluate asamplesizeof
nearly600patients. Weighing ourexperience with
catheter complications aswellasotherreportsinthe
literature,4 14'19'23itcanbeexpected that15majorand
45minorcomplications wouldbelikelytooccurduring
astudyofthisscope.
Discussion
Nusbaum etal.19reported a98%success ratein
bleeding controlwithsuperior mesenteric arterialinfu-
sionofvasopressin. In1975wereviewed ourexperi-
encewith49patients andthoseofotherinvestiga-
tors.14Whilevariceal hemorrhage wasinitially con-
trolledbySMAvasopressin infusion in80oofthe
reported 181cases,complete controlwasobtained in
50%.Sincepatients withuppergastrointestinal bleed-
ingarefrequently treatedconservatively beforevaso-
pressininfusion isinstituted, a"selection process"
mayexplainthedifference insuccessratethatweand
othershavefoundwithSMAvasopressin therapy.
Oursuccess ratewithintravenous vasopressin inun-
controllable bleeders inthepresent studyiscom-
parable totheexperience wereported in1975with
SMAinfusion inasimilarpatientpopulation.
Vasopressin isknowntoexertanintensevasocon-
strictoractionontheprehepatic splanchnic viscera
andthiseffectisgenerally believed tobethecause
ofthereduced portalpressure whichusuallyfollows.
Texterandco-workers29 haveconcluded thatthein-
creaseinresistance occurslargelyinthesmallvessel
segmentfromsmallarterytosmallvein.Eiseman etal.8
andJohnson etal.'3havesuggested thattheincreased
resistance inresponse tovasopressin occursinsub-
mucosal arteriovenous shunts.Theobservation by
Erwald etal.10thatprehepatic splanchnic oxygen
uptakeisunchanged duringvasopressin administration
wouldtendtosupport thelattertheory. Shepherd
etal.26havereported acloserelationship between
86Rbextraction andoxygenuptakeinperfused gut
loopsandhavesuggested thatoxygenuptakemaybe
areliable meansofmeasuring thedegreeofcapillary
perfusion. Theobservation byErwald etal.10that
mesenteric oxygenuptakeisunchanged duringvaso-
pressininfusionismoreconsistent withadirecteffect
ofvasopressin uponsubmucosal arteriovenous com-372 JOHNSON ANDOTHERS

CONTROL OFBLEEDING VARICES BYVASOPRESSIN
munications thanwithamajoreffectofvasopressin
onthesmallvessel segment, since areduction in
capillary perfusion wouldpresumably bereflected in
decreased mesenteric oxygenuptake.Thesuppression
ofportal venousPo2inresponse tovasopressin noted
byMillette etal.18isalsoconsistent withaneffectof
vasopressin tocloseoffsubmucosal arteriovenous
communications.
Regardless ofthemajorsiteofaction,itisclear
thattheeffectofvasopressin ontheprehepatic splanch-
nicvasculature resultsinadiminution ofbloodflow-
ingthrough theportalvein.Thatadecrease inportal
bloodflowisnotalwaysaccompanied byapropor-
tionaldecrease inportal pressure hasbeennotedby
Millette etal.18Ourfindings (unpublished) andthose
ofNusbaum etal.20andBarretal.2alsosuggest that
manycirrhotic patients donotrespond tovasopressin
infusion withnotable reductions ofportal venous
pressure. Thisobservation isnotsurprising inthe
cirrhotic patientwheredirecttransmission ofhepatic
arterial pressure totheportal venous system mayoccur
asaresultofseveredistortion ofthehepaticarchi-
tectureandofanincreased number ofpresinusoidal
hepatic arterytoportalveincommunications.28
Theintenseandsustained vasoconstrictive effects
ofvasopressin ontheprehepatic vasculature arecon-
finedtothesplanchnic vessels. Theeffectofvaso-
pressin onhepaticarterialvesselsistransient, lasting
lessthanfiveminutes, andisfrequently followed by
increased arterialflow.11Erwaldhasdemonstrated that
inconscious alcoholic patients thereisacompensatory
increase inhepatic arterialflowwhenportalblood
flowisreduced duringvasopressin administration.
Hepatic oxygenuptakeremains thesame.10
Vasopressin hasbeeneffective incontrolling bleed-
ingfromgastro-esophageal varicesdespite minimal
reductions inportal pressure. Themechanism forthis
isunclear. Itmaybethatwithreduced bloodflow
intheportalvein,thekinetic energyofportalblood
isdissipated inthehepatofugal flowtowardthevarices
andthatthepressure withinthevarixisnotnecessarily
thatwithintheportalvein.Inanangiographic study
inthedog,Aronsen andNylander1 haveobserved
theradiographic disappearance ofsubmucosal esoph-
agealvaricesduringvasopressin infusion. Ourimpres-
sionthatadirect response ofvasopressin toshutoff
submucosal arteriovenous communications maybere-
latedtothisobservation is,ofcourse, conjectural.
Thetheoryproposed byAronsen andNylander1 and
others20 thatthesubmucosal varices arecompressed
byvasopressin-induced contracture ofthemusclelayer
oftheesophageal wallisdifficult toreconcile with
theexperimental evidence thatsuggests thatstimu-373
latoryeffectsofvasopressin onthegastrointestinal
tractarelimitedtopropulsive wavesandthatintes-
tinaltoneinmananddogisdepressed byvaso-
pressin.12 Themechanism bywhichvariceal bleeding
controlissustained aftervasopressin isdiscontinued
isalsonotclearlyunderstood. Possible reduction in
intra-variceal pressure wouldnotbesustained after
discontinuation ofthedrug,however, vasopressin may
inducethrombosis inthevessel.Healing ofanarea
traumatized byheavyalcoholintakeorrefluxesoph-
agitismayalsooccurduringtheperiodofvasopressin
controlasaresultofantacidtherapy. Duringthistime
correction ofcoagulation deficitsmaycontribute to
bleeding controlwhenvasopressin isdiscontinued.
Wehavefoundthecontinuous infusion ofvaso-
pressintobeusefulinthetreatment ofmassive gas-
troesophageal variceal bleeding. Itisourimpression
thattheintravenous routeisaseffective asthedirect
intra-arterial routeandwenowemployitalmostex-
clusively. Cardiacarrythmias appeartobedose-related
andproblems rarelyoccurwithvasopressin dosesof
0.2u/minorless.SirinekandThomford27 havesug-
gestedthatIsuprelmaybeusefulincounteracting
vasopressin-induced bradycardia andcardiacoutput
reduction. Although noneofthepatients inourstudy
sustained evidence ofmyocardial infarction, theknown
constrictive effectofvasopressin oncoronary arteries
hasmadeusreluctant touseadrugwhichincreases
oxygendemand oftheheart.
Ourcurrent method oftreatment ofthecirrhotic
patientpresenting withmassive variceal bleeding
is,briefly, asfollows: 1)Thepatient istreated
withcontinuous intravenous vasopressin inastand-
ardized dosage described inthisstudy, and
receives overallsupport, antacid therapy andcor-
rection ofcoagulation deficits. 2)Ifbleeding is
notcontrolled byvasopressin infusion, theSengs-
taken-Blakemore tubeisinserted tomanagetheacute
bleeding episode, followed bytranshepatic obliteration
oftheleftgastricveinformorepermanent control.17'31
3)Ifcontrolofbleeding isstillnotattained, anemer-
gencyshuntprocedure isperformed. Inourexperience,
failuretocontrolbleeding israreinpatients without
severecoagulopathy. 4)Whenbleeding iscontrolled,
fourtosixweeksofhospitalization isrecommended
toprovidenutritional support, toimprove liverfunc-
tion,andtoinstitute diuretic therapy forascites.
Percutaneous transhepatic portography isperformed
todetermine thespecific flowcharacteristics ofthe
portalandsplanchnic venoussystems.31 5)Finally,
selective spleno-renal shunting procedures areper-
formed, whenpossible, inanefforttoobviate recur-
rentbleeding episodes andthehighincidence ofVol.186.No.3

374 JOHNSON ANDOTHERS Ann.Surg.*September 1977
encephalopathy observed afterstandard porto-caval
shuntprocedures.
Acknowledgment
Theauthors wishtothankDr.Shigeru Ochi,biostatistician,
V.A.HinesCooperative Studies Program Coordinating Center,
forassistance withthestatistical analysis.
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DISCUSSION
DR.WILLIAM S.BLAKEMORE (Toledo, Ohio):Firstofall,there
isagrowing weightofevidence fromsmallseriesthatintravenous
Pituitrin iseffective, andmaybejustaseffective, asintraarterial.
However, thereareseveralaspectsofthesearguments whichremain
lessthanfullyconvincing.
First,thecomplication rateinthisseriesis20to100times
greaterthanthoseinthehandsofexperienced angiographers. There
hasbeenacontinued emphasis sinceintroducing thetechnique that
thosepeoplewhoknowhowtodoitshoulddoit,andthatthose
peoplewhoarelearning shoulddoitonlyunderclosesupervision.
Secondly, thecardiacarrhythmias areontwicetherecommended
dose,anditwasrecommended, andhasalwaysbeen,thatthedosageintra-arterially bemonitored byrepeatangiography afterashort
intervalofinitiating treatment.
Thirdly, thearguments relatedtotheuseofthisinportalhyper-
tensionshouldnotbeconfused withtherationale foruseofthisfor
othermodalities, suchasdruginfusion, superselective catheteriza-
tion,ofvarices, forarterialbleeding, andselective embolectomy,
allofwhicharestillundertrial,andmayalsocomeundersuch
criticalreview.
We'rethankful toStephen Wangensteen andastudentfrom
Charlottesville, asamatteroffact,forpointing outthesideeffects
ofequaldosageofintraarterial andintravenous Pituitrin inpatients
withcardiaclesions.
Therefore, Ithinkthattheanswers arenothere;thatyoucould
equallytakefromthedatathatwehaveintheabstract that,be-