Injection therapy for nonvariceal gastrointestinal...
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NONV AR ICEAL HEMORRHAGE Injection therapy for nonvariceal gastrointestinal bleeding PAUL KORTAN, MD, FRCPC ABSTRACT: Gastrointestinal hemor rhage is a common and serious problem - its average mo rtality of 1 0% has changed little over the past 40 years. In 80% of patients the bleeding stops spo ntaneously. In patients with continu ous or recur- re nt bl eedmg (20%), mo rtality and morbidity are high, a nd emergency surgery is often required, which has a high er mo rtality than the same ope ration perf ormed el ectively. Succes.sful therapeutic end oscopic mt erve nuon in this h ig h nsk group is necessary to improve o utcome. For inj ec tion treat me nt of nonvariceal bleeding lesion s, the author has bee n usmg th e Soehendra me th od (l : I 0, 000 adrenaline a nd poltdoca nol) with success m 90 1 '10 of actively bleeding patie nts. T h ree controllt·d trials of end oscopic sclerosis in bl eeding pept ic ulcer disease showed decreased bl ood transfusion s, surgery a nd hospital stay, but did n ot fi nd any sign ifi cant differen ce m morta li ty. The i dea l solution and the usef ulness of additional therapy are questions which mu st be addressed v ia prospec tive con- trolled trialsofa large numberof pat ie nts. CanJ Gastroenterol 1990;4(9):650- 652 Key Wo rds: Adrenalin e, Gastrointestinal bleeding, Hemostasis, Inj ection chera/ JY Traitement par injection des hemorragies gastrointestinales non variqueus.es RESU ME: L'hemorrag1e gastro-incestmale est un probleme courant serieux qu i s'accompagne d' une morra lice moyenn e de 10 %, chiffre qui a peu change au cours des quarante dernieres annees. Chez 80 % des patients, l'hemorragie cesse spontanement. Chez Jes pat i ents qui saignent consrnmment ou do ne les sa 1gne- ments recidivent (20 %), la mortalite et la morbidite sont elevces et une inte rvention d'urgence s'impose souvent, laque ll e est assort1e <l' un taux de mo rta li te supcrieure a ce lle des memes operat ions a froid. Da ns cc groupe a ri sque el eve, ii est n ccessa ire de r ecou rir aux in t erve nti ons en doscop iques therape uttqucs afin d'ame liorcr les resultats. L'auteur a recours au tra1tement par inject i on des lesions non variqueuses qui saigne nt ; ii utilise la me thode de Soe hendra (1: IO 000 adrenaline et po li docanol) avec succes chez 90 % des pat i ents qui sai gnent acttvemcnt. Trois essais controles unit s.mt des injections sclerosa ntes effectuees sous endoscopic dans le tra itement des ulceres gastro- duode naux hemorragiques rappo rtent une diminut i on des transfusions, des gestes D1111swn of Gas t roent erolo,a, Universi ty of Tcmmw, T he WI ell esl ey / los p, ral, Toronw, Onrano Corresponden ce and reprmrs. Dr P Korum , Assrsran r P rofessm, Dit•1s1cm of Gastroenwrol oJ:Y, Univers ity of Toronto, The Wlellesle"I I lo sp1 tal, 1 60 Wlellesley Street Ea..11, Swte 41 9, Jones Buildi ng, Toronw, Onrano M4 Y I) 3 G ASTROINTESTINAL IIEM ORRHAGE 1s a co mmon and serious problem with an average mo rta li ty of I 0% (I). It is often assumed that early correct Jrag· nosis will re<lu ce mortality rate,; how- ev er, several co ntrolled studies hal'e shown no such advantage, anJ there has been little change in morrnlicyover th e p as t 40 ye ars. Since the va11 mai or rty of upp er gastrointcmnal bleeding episo des arc scl f- lim1ceJ , it ha, been c~ timated that more than SOOJ patie nts would ha ve to be ranJorn 1: eJ be fo re a trial could demonstrate t hat end oscopy decreases mo rta li ty. More importantl y, th e maiority of endoscopic trials were ca rried our before the cvolu- tton of th erapeutic technique~ that cm po tentia lly co n t rol gastrointc~tmal bleeding ( 2,3 ). In 80% of patients, the hlecdmg stops spon taneously and the hospital cour e 1s usually benign. However, m patie nts wi th continuous or r ecu rrent bleeding ( 20% ) , mortality and rnor- b 1d1ty are high and emerge ncy sur gcr, is often needed ( 4). Emergency su r gery for upper gastro intestinal bleeding isa1- sociate<l with a higher mortality than for the same operauon perfo rmed elec, t 1vel y. Successful therapeutic endo- scopic intervention in t hb high ri s~ group 1s necessa ry to 11nprove the o ut· co m e. A numb e r o f e ndosco pic th erapeutic m0Ja li t1e~ are now a vail, abl e to tre at upper gast ro mtesnnal 650 CAN J UA~TROENTEROL VOL 4 No 9 DECEMBER 1990
Transcript of Injection therapy for nonvariceal gastrointestinal...
NON V ARICEAL HEMORRHAGE
Injection therapy for nonvariceal gastrointestinal
bleeding
PAUL KORTAN, MD, FRCPC
ABSTRACT: G astrointestinal hemorrhage is a common and serious problem -its average mortality of 10% has changed little over the past 40 years. In 80% of patients the bleeding stops spontaneously. In patients with continuous or recurrent bleedmg (20%), mortality and morbidity are high , and emergency surgery is often required, which has a higher mortality than the same operation performed e lectively. Succes.sful the rapeutic endoscopic mtervenuon in this h igh nsk group is necessary to improve outcome. For injection treatment of no nvariceal bleeding lesions, the autho r has been usmg the Soehendra method (l : I 0,000 adrenaline and poltdocanol) with success m 901
'10 of actively bleeding patients. T h ree con t rollt·d tria ls of endoscopic sclerosis in bleeding peptic ulcer disease showed decreased blood transfusions, surgery and hospita l stay, but did not find any significant difference m mortali ty. The ideal solution and the usefulness of addit ional therapy are questions which must be addressed v ia prospective controlled trialsofa large numberof pat ients. CanJ Gastroenterol 1990;4(9):650-652
Key W ords: Adrenaline, Gastrointestinal bleeding, Hemostasis, Injection chera/JY
Traitement par injection des hemorragies gastrointestinales non variqueus.es
RESUME: L'hemorrag1e gastro-incestmale est un probleme courant serieux qui s'accompagne d'une morra lice moyenne de 10 %, chiffre qui a peu change au co urs des quarante dernieres annees. Chez 80 % des patients, l'hemorragie cesse spontanemen t. Chez Jes patients qui saignent consrnmment ou done les sa1gnemen ts recidivent (20 %), la morta lite e t la morbid ite sont elevces et une intervention d 'urgence s'impose souvent, laquelle est assort1e <l'un taux de morta lite supcrieure a celle des memes operations a froid. Dans cc groupe a risque e leve, ii est n ccessaire de recou ri r aux interve n t ions en doscopiq ues therapeuttqucs afin d'ameliorcr les resultats. L'auteur a recours au t ra1tement par injection des lesions non variqueuses qui saignent; ii ut ilise la methode de Soehendra (1 : IO 000 adrenaline et polidocanol) avec succes chez 90 % des patients qui sa ignent acttvemcnt. Trois essa is controles units.mt des injections sclerosantes effectuees sous endoscopic dans le traitement des ulceres gastro duodenaux hemorragiq ues rapporten t une diminution des transfusions, des gestes
D1111swn of Gastroenterolo,a, University of Tcmmw, T he WI ellesley / losp,ral , Toronw, Onrano
Correspondence and reprmrs. Dr P Korum , Assrsranr Professm, Dit•1s1cm of GastroenwroloJ:Y, University of Toronto, The Wlellesle"I I losp1tal, 160 Wlellesley Street Ea..11, Swte 41 9, Jones Building, Toronw, Onrano M4Y I) 3
GASTROINTESTINAL I IEMORRHAGE 1s a common and serious problem
with an average mortality of I 0% (I). It is often assumed that early correct Jrag· nosis will re<luce mortality rate,; however, several control led studies hal'e shown no such advantage, anJ there has been little change in morrnlicyover the past 40 years. S ince the va11 maiorr t y o f uppe r gas trointcmnal bleeding episodes arc sclf-lim1ceJ, it ha, been c~timated tha t more than SOOJ patients would have to be ranJorn1:eJ before a tria l could demonstrate that endoscopy decreases mortality. More impo rtan tly, the maiority of endoscopic tria ls were carried our before the cvolutton of therapeutic technique~ that cm po tentia lly con t rol gastrointc~tmal bleeding (2,3 ).
In 80% of patients, the hlecdmg stops spo ntaneously and the hospital cour e 1s usually benign. However, m
patients with continuous or recurrent bleeding ( 20%), mortality and rnorb1d1ty are high and emergency surgcr, is often needed ( 4) . Emergency surgery for upper gastrointest inal bleeding isa1-sociate<l with a higher mortality than for the same operauon performed elec, t 1vely. S uccessfu l the rapeutic endoscopic intervention in thb high ris~ group 1s necessary to 11nprove the out·
come. A numbe r o f endoscopic therapeutic m0Jalit1e~ are now avail, able to t reat upper gastromtesnnal
650 CAN J UA~TROENTEROL VOL 4 No 9 DECEMBER 1990
chirurgicaux et des hospitalisations, mais ne montrent aucune difference significative quanc a la mortalite. ll faudrait examiner quelles seraient la solution idfale et l'utilite d'un traitemcnc additionnel a l'aide d'essais prospectifs controles portant sur un grand nombre de patients.
bleeding. These include yttriumaluminum-garnet (Y AG) laser, monopolar and bipolar coagulation, heater probe and injection therapy. None of these modalities has been sufficiently well studied to permit definitive recommendations.
The ideal hemostatic technique should be simple, safe, portable, inexpensive and effective. These criteria are best fulfilled by injection therapy. Injection sclerotherapy has hcen used extensively in the control of bleeding esophageal vances and over the past few years has gained popularity for nonvariceal bleeding. The technique has been practised in Japan and West Germany since the mid 1970s (5). A number of different substances have been injected, most of which are vasoconstrictors or sclcrosancs. Table 1 lists the injectable agents that have been u~ for treatment of upper gastrointestinal bleeding.
TECHNIQUE Once an active or potential bleeding
site has been accurately located, injection therapy can be attempted. The injection is performed using a variceal injecwr. A large single or double channel endoscope is preferred to allow for adequate suctionin g of blood . Sclerosant or vasoconstrictor is injected at three or four sites surrounding an exposed bleeding vessel or nonbleeding visible vessel. The volume of agent injected depends on the type and should be minimized to avoid extension of ulcer and transmural injury.
MECHANISMS OF ACTION The hemostatic mechanism of injec
table agents is based on vasoconstricting or sclerosing effect.
Adrenaline in animal experiments has been shown co cause a prolonged decrease in local gastric bloodflow (6-8). The decrease in flow is felt co be secondary to the vasoconstrictive effect
of adrenaline rather than to a mechanical effect of the injected volume.
Injection of absolute ethanol has been shown to cause degeneration and necrosis of the blood vessel wall with consequent thrombosis (9,10). This is accomplished by the fixative effect of ethanol. Part of the hemostasis may be supported by mechanical compression of vessels.
Hypcrtonic saline was shown to
cause tissue edema, degeneration of vascular wall and consequent thrombosis in the vascular lumen ( I l).
Rutgeerts (12) examined the tissue effects of adrenaline 1: 10,000, absolute alcohol and 1 % polidocanol, anti compared them with Y AG laser and BICAP
in dogs. Adrenaline caused focal damage without thrombosis of submucosal vessels and without serositis. Ethanol caused dehydration and fixation of the tissue with extensive suhmucosal and muscular necrosis and vessel thrombosis. Serositis was frequently observed. There was a linear relationship between the extent of damage and the volume of solution injected. Injection of I% polidocanol cause<l lesions characterized by mucosa I necrosis, partial necrosis of submucosa and submucosa l edema. There was partial thrombosis of the vessels. The extent of damage from l % polidocanol was related to the volume injected.
CLINICAL EXPERIENCE Uncontrolled studies have been re
ported on the use of injection treatment with a number of <lifferent hemostatic agents, with successful treatment ranging from 84 to 100%. Asaki (9) injected absolute alcohol and obtained hemostasis in 10096 of patients with I 0% reblee<ling. Sugawa ( 13) also using alcohol obtained permanent hemostasis in 88% of patients. Soehendra ( 14) has been injecting adrenaline 1: 10,000 combined with l % polidocanol and obtained hemostasis m 84% of pulsatile
CAN J GASTROENTEROL VOL 4 No 9 DECEMBER 1990
Injection therapy for nonvariceal GI bleeding
TABLE 1 Injectable agents used for treatment of upper gastrointestinal bleeding Adrenaline l: 10,000 Adrenaline and hypertonic saline
solution Adrenaline l : 10,000 followed by
polldocanol Absolute ethanol Thrombln Ethanolamine
bleeders. Leung ( 15) used adrenaline alone with permanent hemostasis in 92% of patients.
Rutgeerts anc..l colleagues ( 16) randomized 140 patients with ulcers cont a in ing an actively hleeding or nonhleeding visible vessel to sham treatment or to one of three endo~copic methods of hemostasis: adrenaline l:10,000 alone, adrenaline 1:10,000 plus I 'Xi polidocanol, and adrenaline followed by YAG laser treatment. In patients with a nonbleeding visible vessel. the sham treatment was significantly less effective than adrenal ine plus polidocanol or adrenaline plus laser in achieving hemostasis. All three treatmen rs reduced total transfusion requirement sign ificantly compared with sham treatment. Adrenaline plus polidocanol was significantly more effective than adrenaline alone in achieving permanent hemosrnsis. Adrenaline plus laser was also more effective than adrenaline alone, but this difference was not statistically significant. The authors concluded that injection therapy with adrenaline plus poli<locanol should be the treatment of choice hascd on cost, ease of use and safety.
A recent report from Spain documents the efficacy of this technique in a controlled trial (l 7). One hundred an<l thirteen patients with hemorrhage were randomized to endoscopic injection therapy and Hz blockers, or to 112 blockers alone. Each group had an equal number of patients with hleeding and nonhlee<lmg visible vessels. All les,ons were injected with 3 rn 10 mL of adrenaline I : 10,000 and 6 to 12 mL of I% polidocanol. Major recurrent hlceding occurre<l in 5% of injected patients :md in 23% of patients randomized to
651
KORT AN
treatment wah I lz blockers alone (P<0.001 ). The neeJ for emergency surgery was reduccJ from 34 to 5% ( P<0.00 I) and there was n significantly reduccJ requirement for blood transfusions and a reduction in the length of hospital stay.
A scconJ randomized stutly by Chung et al ( 18) compared iniection of aJrenaline into blcetling ulcers with no endoscopic treatment. There was a significant difference in the two groups with respect to requirement for emergency surgery, requirement of bkxxl transfusion anti median hospital stay.
The th1rJ prmpect1ve randomized trial was carried out by Balanzo ct al (l 9). They stutlied 72 patients with
REFERENCES l. Silvemem FE, Gilbert DA, TeJe~w
FJ, Buenger NK, Persing J. The Nation-,11 ASGE survey on upper gasrromtes-rmal hleedmg. I. StuJy Jcsign and baseline data. Gastromrcst EnJosc 1981;27:73-9.
2. Silver.,cem FE, Gilbert [)A, Tedesco FD, Buenger NK, Pen,mg J. The Nanonal ASGE survey on upper g,1stro-intestinal hleedmg. IL Clmical pmg-nosttc fa<; )rs. Gasrromtesr EnJosc.. 1981;27:80-93.
3. Mor,::an AG, Clamp SE. OMGE inter-nat10nal upper gastrointestinal bleed-mg survey 1978-1982. Scand J Gastrocnceml ! 984;19(Suppl 95):41-58.
4. Fleischer D. Ecidogy anJ prevalence of severe pers1srenr upper gasmimtestinal hlceJmg. Gastrocnternlogy 1983;84:5 38-43.
5. Soehendra N, Werner BL. New tech-nique for endoscopic treatment of hleedmg gam1c ulcer. Endosrnpy 1976;8:85-7
6. Leung FW, Sung JY, Chung SCS, Leung JWC. Endoscopic assessment of mucosa! hemoJynamic c..hangcs ma canine model of gastric ulcer. Gastromtest Endosc 1989; 3 5: 186.
7. Chung SCS, Leung FW, LeungJWC. Is va~oconstnct11m the mechani,m of hemosrasis in blee<lmg ulcers injected
652
bleeding ulcers. Half were rantlomized to inJection treatment with adrenaline plus poli<locanol and half were managed medically. The study again confirmed the benefit of inject10n therapy comparing the requirement for emergency surgery and blooJ transfusions. None of these studies was able to show a significant difference m mortality.
COMPLICATIONS The use of polidocanol has been as,
soc.iatcJ with the appearance of large ulcers when more than 20 mL have been iniccted. The perforation rate is l % (20). ln1cction ot absolute alcohol has been associated with a less than I 'X, perforation rate ( 13 ).
with cpinephnnc? A study usmg reflec-ranee spectrophotometry. Gastmmresr EnJosc 1988;34: 174.
8. ChungSCS, Suen MWM, Galvma M, Lee TW, Leung JWC. The effect of submucosal epmephrme on blood losi. from stand.ml bleeding ukt·rs. Gamointest Endosc 1988; H: 189-90.
9. Asak1 S, Nishimum T, Saroh A, Goto Y. EnJo,cop1c control of gastromtes-tinal hemorrhage by local mjection of absolute ethanol: A hasic assessment of the proceJun:. Tohuku J Exp Ml•d 1983; 140: 3 39-52.
10. Sugawa C, Fujita Y, Lucas CE, Raval M, Masuyama 11. Hemostat1c effect of local intramural mJection of dehydrated ethanol m the canme gastrointestinal tract. Gastromtesl Endnse 1989; 35:28 32.
11. Hir..10 M, Kobayashi T, Masuda K, ct al Emlnscopic.. h:al mJcct1on of hy-pcrtontc.. saline-epinephrine solution to arrest hemorrhage tr<lm the upper gastromtestinal tract. Gastmintest EnJnsc 1985;,UI 3-7.
12. Rutgeerts P, Gehocs K, Vantrappcn G. Experimental studies of 111Ject1on therapy for severe nonvanceal bleeding 111 Jogs. Gastmenterology 1989;97 :610-21.
13. Sugawa C, Fujita Y, Ikeda T, Wale AJ. Endoscopic hcmrn,tas1s ot ninety eight percent dehydrated ethan11I. Surg
CONCLUSIONS ln1ection sclerotherapy h
nonvariceal gastro111tcstmal hleeJ1r 1s the least expensive anJ most wide available form of endosc1)p1c thtr,1p The technique of ll1JCttllln treatmcr is easy w learn, ,md most endoscor1 who pracuce sclerotherapy esophageal vances are ,1ble to pi:rfoq this procedure. The controlled stuJ1~ up to the present time have shown reduction 111 rhe requirement t blood trnnsfus1ons, decreased need (o
surger), shorter hospital st,1y ,tn
therefore a lower overall cost. H,)pe fully larger umtrnllcd stuJ1es 1111 show a significant impact on mo talll y.
Gynccol Ohstct 1986; 162.161 3. 14. SoehcnJrn N, Grimm 11, Stenzel M
lnjecti11n of non-varic~.11 blccJin~ lesions of the gasrmmte.,unal traci. Endoscopy 1985; l 7: 129 32
15. Leung JWC, Chung SCS. Endoswr1C mJecttt•n of aJren.ilm in bleeding pep-tic uker. Ga,tromtt·,t Fndosc 1987;33:7"3-5.
16. Rutgeerts P, Vancrappt·n G, Brnt'Ckatn L, Coremans G, Janssens J, Hide M ( :nmp,mson ot endt1.cop1c pohdoc,mol lllJCCt 10n and Y AG laser rhcr.1py t~,r blcedmg pl'ptlc ulc..cn,. !..meet 1989;1:l 164•7.
17 Panes J, Vivcr J, fomc M, Garcia• Olivares E, Mnrco C, Garau J. Con-trollcJ mal 11f cnJosc\lpK ,clcro<1s m hlcedmg pepuc ukcn,. L meet 1987 ;11: 1292 4.
18. Chung SCS, Leung JWC. St<·clc RJC, Crofts TJ, I I AKC. EndoseopK mj<'C mm of adrenaline tnr actively hlecJmg ulcers: A rnndonmeJ mal. Br Med J 1988;296: 16 31 -3
19. Balanw J, Samz S, Sud, J, ct al. End()-scoptl hemoscas1s by loul mJcction uf epmephrine ,mJ poliJocrnnl m hlceJ· mg ulcer. A prospective random1zcJ mal. Endoscopy I 988;20:289-91
20. W orJehoff D, Ci ros 11. EnJoscop1, huno,tas1s hy inJe<.tion thcr 1py in
high risk patients. Endoscopy 1982;14:!96 9
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