Treatment of Hemorrhagic Gastritis by Antacid

SIMON J. SIMONIAN, Sc. D., M.D., LON E. CURTIS, M.D.

A simple and safe method of nonsurgical treatment for the con-trol of massive acute gastric mucosal hemorrhage is described.The procedure was developed from experimental and clinicalobservations that the presence of gastric hydrochloric acid playedan important part in the development and perpetuation of theentity. The treatment consists of complete neutralization ofgastric acid with antacid to a pH of 7. The antacid is intermit-tently added and aspirated through a nasogastric tube to maintainthe pH of the aspirate at 7. In a retrospective analysis, the hemor-rhage was controlled in 44 of 49 patients (89%). Five patients whocontinued to bleed underwent surgery (10%). Three patientshad vagotomy and pyloroplasty and their bleeding ceasedwithout recurrence. Two patients underwent partial gastrectomy,but they developed recurrent bleeding and died. One patient whosebleeding has been controlled by vagotomy and pyloroplastydied without hemorrhage 10 days after operation. Of the 44 pa-tients whose bleediung had been controlled by antacid, 11 patientsdied without hemorrhage one or more weeks later. These resultsof 89o control of hemorrhage compare favorably with thosein the literature.

TrHE THERAPY of massive acute gastric mucosal hemor-rhage remains an unsolved problem."130'35 All experi-

mental studies on the restrained animal model for theproduction of stress ulcers have shown that gastric ero-sions occur only when acid is present in the stomach. Instressed animqls, pretreatment with antacid to raise thegastric pH, vagotomy or anticholinergics significantly re-duces the incidence of these lesions.3'4'17'23 In patientswhose bleeding from gastric erosions has been controlledby vagotomy, the nasogastric aspirate was found to have apH of 7.3The frequency of bleeding secondary to stress-induced

ulceration of the gastric mucosa has increased because ofintensive care which can prolong the lives of critically illand injured patients. Most recpnt reports of combined

From the Departments of Surgery,University of Chicago Pritzker School of Medicine,

Chicago, Illinoisand Tufts University School of Medicine,

Boston, Massachusetts

medical and surgical treatment of such patients haveshown a high frequency of uncontrolled gastric bleedingand a high mortality. 15,30,35The purpose of this report is to analyze the results of

pH-controlled neutralizations of gastric hydrochloric acidwith antacid in the treatment of a group of patients withmassive acute gastric mucosal hemorrhage.

Materials and Methods

The study consisted of 49 patients with documentedacute gastric mucosal hemorrhage, hospitalized at theBoston City Hospital between October 1971 and June1974; the Tufts-New England Medical Center Hospitalsbetween July 1973 and November 1975; and at the Uni-versity of Chicago Hospitals between July 1974 and No-vember 1975. The diagnosis was based on endoscopicfindings in all patients and it was confirmed at surgery infive. There were 35 men and 14 women, ranging in agefrom 21 to 73 years, with a mean of 56 years. The totalblood transfusion requirements per patient were 1500 mlto 7500 ml, with a mean of 4200 ml. Excluded are patientswith less that 1500 ml blood transfusion requirement.The bleeding was associated with surgery, trauma,

sepsis, and excess intake of alcohol. Patients whosebleeding was secondary to peptic gastric or duodenalulcers or to esophageal varices, or to associated coagulo-pathy, were excluded. Table 1 summarizes the stressfulfactors related to this group of patients.

Treatment consisted of removal of blood clots from thestomach, iced saline lavage, followed by instillation ofantacid-buffer (magaldrate, Riopan) into a nasogastric

429

Presented at the Annual Meeting of the American Surgical Associa-tion, New Orleans, Louisiana, April 7-9, 1976.

Reprint requests: Simon J. Sinlonian, M.D., 950 East 59th Street,Department of Surgery, Box 402, Chicago Illinois 60637.

SIMONIAN AND CURTIS

TABLE 1. Associated Factors in 49 Patients With MassiveGastric Musocal Hemorrhage

Associated Factor No. Patients

Surgery-sepsis 26Ethanol 16Trauma-sepsis 7

tube until the pH of the nasogastric aspirate was returnedto 7. In each patient, the amount of buffer required perhour to raise and maintain the intragastric pH at 7 wastitrated as follows: a nasogastric tube was passed intothe stomach; the gastric contents were aspirated as com-pletely as possible and emptied into a basin by the bedside;using phenaphthazine pH paper (Nitrazine), the pH of theintragastric contents was measured and recorded. In mostpatients, the pH was 5 or below 5. Sixty ml of antacid wasinstilled into the stomach by gravity drainage and wasallowed to mix for 15 minutes with the nasogastric tubeclamped. At the end of 15 minutes, the stomach was re-aspirated. If the pH was below 7, an additional incrementof 30 ml of antacid (total volume of antacid, 90 ml) wasinstilled. Again, 15 minutes was allowed for mixing beforethe next pH measurement was taken. This procedure wascontinued until the amount of antacid required per 15minutes to raise and maintain the intragastric pH at 7 wasdetermined, usually in less than an hour. Thereafter,clamping of the nasogastric tube was prolonged to hourlyintervals and the predetermined volume of antacid wasinstilled and reaspirated from the stomach to return thepH to 7. Titration was carried out by a nurse in the inten-sive care unit, and the measured volumes of antacidand pH value taken at the end of each hour were recordedon the bedside chart. In the majority of patients, thevolume of antacid required to completely inactivate thegastric hydrochloric acid at a pH of 7 was 60 to 180 mlper hour.

Control of bleeding was usually achieved 4 to 24 hoursafter neutralizing gastric hydrochloric acid. If at the endof 24 hours there was clinical evidence that the bleedinghad stopped (as indicated by blood-free nasogastricaspirate; cessation in blood transfusion requirements;and stabilization of hematocrit and vital signs), the fre-quency of antacid instillation and nasogastric tube clamp-ing was reduced to 2 hourly intervals and continuedfor another 24 hours. If after 24 hours there was no furtherevidence of bleeding, the frequency of instillation andclamping was further decreased to every 4 hours for an-

TABLE 2. Results of Surgical Treatment

Procedure No. Patient Rebled Died

Two-thirds gastrectomy 2 2 2 (100%o)Vagotomy and pyloroplasty 3 0 1 (33%)

other 12 to 24 hours. The nasogastric tube was removedon the fourth day.The intermittent addition and removal of the antacid

solution (rather than the continuous infusion of antacid)reduced the likelihood of the antacid solution beingaspirated into the lungs or absorbed in the intestines.

Results

Definition of Control ofHemorrhageThe therapy was considered successful when the fol-

lowing conditions were met for at least 6 days after thediscontinuation of the gastric acid neutralization: clearnasogastric aspirate; no blood transfusion requirements;stable hematocrit, blood pressure and pulse.

Patients Treated with pH-Controlled Neutralizationsof Gastric Acid with Antacid

In 44 of 49 patients (89o) treated with antacid with acontrolled pH of 7, the hemorrhage was arrested and nofurther therapy for gastric mucosal hemorrhage was re-quired. Five patients continued to bleed. In two of thesepatients, the nasogastric tube was found, during surgery,to be curled up in the distal position of the stomach.Although the nasogastric returns had a pH of 7 beforesurgery, the erosions of the mucosa of the fundus werebleeding, probably because the proximal stomach wasnot in constant contact with sufficient antacid to neu-tralize the hydrochloric acid secreted. A two-thirdsgastric resection was performed in these two patients.Both patients rebled in the immediate postoperativeperiod and died within 6 days of the operation.

In another 2 of these 5 patients, organized clot wasattached to the fundus at surgery. Prior to operation,the bleeding had ceased with antacid, but there was re-bleeding on three occasions within 6 days in one of thesepatients. On repeat endoscopy, the clots were seen in thestomach, but the hematoma could not be removed exceptat operation. In the second patient, there was rebleedingwithin 6 days on two instances, again because of inade-quate removal of clots from the stomach. At operation,both patients underwent vagotomy and pyloroplasty,after removing the blood clots. There was immediateblanching of the gastric mucosa with cessation of thehemorrhage in both patients. The phenomenon of postvagotomy blanching has been reported by others.33The pH of the nasogastric aspirate rose to 7 in the intra-

operative period following vagotomy. The pH of the naso-gastric aspirate remained at 7, without the addition of anyantacid, when it was measured in the immediate post-operative period. There was no further bleeding in eitherof these patients, but one of them died 10 days later of anundetermined cause.

In the fifth patient, the pH could not be maintained at 7.

430 Ann. Surg. o October 1976

HEMORRHAGIC GASTRITIS

It fluctuated between pH 5 and 7, despite instillation of150 to 180 ml of antacid every hour, and bleeding con-tinued. He underwent vagotomy and pyloroplasty. Thebleeding was controlled and he survived. For the last threepatients in whom surgery was performed, there was con-trol of bleeding in all, but one died. The results ofsurgery are summarized in Table 2.The overall incidence of surgical intervention to control

massive gastric mucosal hemorrhage was reduced to 10%o,which compares favorably with reports in the literature.35

Complications Related to Neutralizationof Gastric Acid with Antacid

It was not necessary in any of these patients treatedwith antacid at pH 7 to discontinue the therapy becauseof local or systemic complications. In a few patients,antacid administration caused diarrhea with water andelectrolyte loss. This complication was controlled bycareful management of fluid and electrolyte balance intra-venously. In a small number of patients, the antacid hada mild alkalemic effect with elevation of the arterial pHto between 7.5 and 7.6. This was handled by preventingthe elevation ofthe intragastric pH above 7. A few patientshad mild and transient elevation of serum magnesiumconcentration without apparent ill effect.

Rebleeding after Therapy

Of the 44 patients treated and controlled by inactivationof gastric acid with antacid, three had rebleeding within7 days after neutralization was discontinued. They re-quired a second series of instillations of antacid andneutralization for control of the hemorrhage.

Mortality During Short Term Followup

Of the 44 patients in whom the bleeding was controlledby antacid, only 33 survived. Eleven patients died with-out hemorrhage one or more weeks later. The causes ofthese deaths are listed in Table 3.

Discussion

In most patients, bleeding from the gastric mucosa ismild to moderate in amount and is self-limited. In con-trast, for some patients, hemorrhage is massive andcontinues in spite of gastric lavage with iced saline andreplacement of blood; surgical intervention becomesnecessary. The operation ofchoice to control bleeding andprevent recurrence is still controversial. A literaturesurvey15 confirms that subtotal gastrectomy alone wasfollowed by a high incidence of rebleeding (52%) andmortality (30o). The addition of vagotomy significantlyreduced the recurrence ofbleeding and mortality. Controlof rebleeding was greater with vagotomy and partial

431TABLE 3. Cause of Death in Eleven of Forty-four Patients

Cause of Death No. Patients

Sepsis 4Cardiac failure 2Pulmonary failure 1Hepatic failure 1Metastatic carcinoma 1Undetermined 2

gastrectomy (15%) than with vagotomy and pyloroplasty(29%). Total gastrectomy offers complete protectionagainst rebleeding, but it is associated with a high inci-dence of death and cannot be recommended at the presenttime as a primary procedure. Any kind of surgery addsfurther stress to these critically ill patients. The need fornon-surgical methods that can control massive gastricstress bleeding is obvious.Many ingenious methods of non-surgical therapy have

been reported for the treatment of this syndrome, suchas gastric cooling,25 intragastric or intraperitoneal instilla-tion of levarterenol,1420'21 endoscopic application of acrylicpolymer,19 endoscopic electrocoagulation,2'26 laser-in-duced hemostasis through a fiberoptic carrier,16 24and em-bolic arterial occlusion.28 Further data are required to eval-uate the effectiveness of these non-surgical treatments. Anadditional method consists of selective intra-arterial in-fusion of posterior pituitary extract or other vasoconstric-tor.1'29 Intra-arterial vasopressin has controlled the massivebleeding in 31 of 45 patients (69o).1 The method requiresspecialist personnel and selective catheterization usuallyof the left gastric artery. The latter has not been possibleto carry out technically 16 to 28% of the time.

Titration of gastric acid with antacid to a pH of 7 seemsto provide an alternative to intra-arterial infusion of vaso-pressor and to surgery. Our present results comparefavorably with those obtained by operative proceduresand other nonsurgical methods, the hemorrhage havingbeen controlled in 44 of 49 patients treated (89o). Ourobservations are a retrospective analysis of a group ofselected patients. A prospective, randomized clinical trialis required to confirm or refute the validity of these ob-servations. We recommend such a study.The method of neutralization of gastric HCl described

was developed from the physiological concept that a majordeterminant ofthe pathogenesis ofgastric mucosal ulcera-tion is the presence of gastric HCl. The presence ofacid seems to be necessary for the production of gastricmucosal ulcers in restrained animals. Rats stressed byrestraint and pretreated with antacid to raise the gastricpH above 3.5 had a reduced incidence of gastric ulcera-tions from 61% in the control group, to 18% in the antacid-treated group. Vagotomy and anticholinergics also signifi-cantly reduced the incidence ofrestraint ulcers.3'4'17'23 Hem-orrhagic shock caused mucosal gastric ulcers in rats.27 By

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432 SIMONIAN AND CURTIS Ann. Surg. * October 1976

bathing the mucosa with increasingly stronger but stillphysiological acid solutions, the incidence of ulcers wasincreased. Interest in back diffusion of acid across themucosal barrier as a possible cause of ulceration hasbeen generated by gastric pouch studies using variouschemicals including acetylsalicylic acid,10 alcohol,1' andbile salts.'2 Back diffusion would also explain the low levelsof gastric acid on routine gastric analysis frequently pres-ent in these patients. A short period of hemorrhagic shockin the rabbit was shown to have a disruptive effect onthe gastric mucosal barrier to hydrogen ions similar tothat produced by the above chemicals.31 Back diffusionand gastric ulceration were inhibited by antacids. In aseries of critically ill hospitalized patients approximatelyhalf demonstrated an increased rate of back diffusion.3'Patients with stress ulcers were helped by antacids. Toexplain the clinical occurrence of neurogenic stressulcers, a hypothalamic pituitary and an autonomic path-way have been proposed.22 In a series of comatosepatients, almost all bled from the gastrointestinal tract.33No patient treated with antacids and anticholinergicsrequired gastric surgery to control the bleeding. In anothersimilar series by the same authors, gastric hemorrhagewas prevented by the prophylactic use of anticholiner-gics.34 Neutralizing intragastric acidity with antacid astherapy for hemorrhagic gastritis has been proposed withcontinuous intragastric infusion of sodium bicarbonatesolution.'8 Massive gastrointestinal hemorrhage from avariety of sources was arrested in 23 of 25 patients whenintragastric pH of 7 was constantly maintained by hourlyadministration of antacid.7 Apparently a pH of 7 is neces-sary to control the hemorrhage, because two patients inwhom the bleeding stopped at that pH had rebleedingwhen the pH was allowed to drift to 5. When the intra-gastric pH in these patients was raised back to 7 with addi-tional antacid, hemorrhage ceased.7 The pH of the naso-gastric aspirate was measured in two patients of the pres-ent group following vagotomy and pyloroplasty. The pHwas 7 and remained 7 for several days. The hemorrhage inthese two patients ceased and there was no rebleeding.

Since the earlier descriptions of variants ofthese lesionsby Curling,6 Dieulafoy13 and Cushing,9 considerable expeni-mental and clinical data indicate that the mechanism ofstress ulcers appears to be an interaction among severalfactors.5 Many of these factors appear to act in thepresence of acid. However, in rats, vagotomy was inef-fective in reducing the ulcer rate when hemorrhagewas superimposed upon restraint.27 The last evidence indi-cates there is a pathway for the production of gastricmucosal ulcers in the absence of acid.

In the present group of patients, the failure to controlthe hemorrhage in 5 patients was partly due to technique:completely neutralizing the intragastric acid at the bleed-ing site was not possible.The mechanism of action of controlled intragastric pH

of 7 in the treatment of acute mucosal hemorrhage ap-

pears to involve: complete neutralization of gastric HCI;inhibition of back diffusion of hydrogen ions; inhibition ofpepsin action and, as a result of recent experiments, en-hancement of normal coagulation.8

AcknowledgmentsFor the endoscopic studies we thank Dr. Norman Zamchek, Boston

City Hospital; Dr. Richard Norton, Tufts-New England MedicalCenter Hospitals, and Dr. Michael 0. Blackstone, University ofChicago Hospitals.

References1. Athanasoulis, C. A., Blum, S., Waltman, A. C., et al.: Control of

Acute Gastric Mucosal Hemorrhage. N. Engl. J. Med., 290:597,1974.

2. Blackwood, W. D. and Silvis, S. E.: Gastroscopic Electrosurgery.Gastroenterology, 61:305, 1971.

3. Bonfils, S. G., Rossi, G., Liefooghe, G., and Lambling, A.:"Ulcer" Experimental de Constrainte du Rat Blanc. I. Methods.Frequence des Lesions. Modification par Certain ProcedesTechnique et Pharmacodynamiques. Rev. Fr. Etud. Clin. Biol.,4:146, 1959.

4. Brodie, D. A. and Hanson, H. M.: A Study of Factors Involved inthe Production of Gastric Ulcers by the Restraint Technique.Gastroenterology, 38:353, 1960.

5. Bufferfield, W. C.: Experimental Stress Ulcers: A Review. Surg.Annual, 7: 261, 1975.

6. Curling, T. B.: On Acute Ulceration of the Duodenum, in Casesof Bums. Med. Chir. Trans., 25: 260, 1842.

7. Curtis, L. E., Simonian, S. J., Buerk, C. A., et al.: Evaluation ofthe Effectiveness of Controlled pH in Management of MassiveUpper Gastrointestinal Bleeding. Am. J. Surg., 125:474, 1973.

8. Curtis, L. E.: Unpublished observations, 1975.9. Cushing, H.: Peptic Ulcers and the Interbrain. Surg. Gynecol.

Obstet., 55:1, 1932.10. Davenport, H. W.: Gastric Mucosal Injury by Fatty and Acetyl-

salicylic Acids. Gastroenterology, 46:245, 1964.11. Davenport, H. W.: Ethanol Damage to Canine Oxyntic Glandular

Mucosa. Proc. Soc. Exp. Biol. Med., 26:657, 1967.12. Davenport, H. W.: Destruction of Gastric Mucosal Barrier by De-

tergents and Urea. Gastroenterology, 54:175, 1968.13. Dieulafoy, G.: Exulteratis Simplex: L'Intervention Chirurgicale

dans les Hematemeses Foudroyantes Consecutives. Bull. Acad.Med., 39:49, 1898.

14. Douglass, H. O., Jr.: Levarterenol Irrigation: Control of MassiveGastrointestinal Bleeding in Poor-Risk Patients. JAMA, 230:1653, 1974.

15. Drapanas, T., Woolverton, W. C., Reeder, J. W., et al.: Ex-periences with Surgical Management of Acute Gastric MucosalHemorrhage: A Unified Concept in the Pathophysiology. Ann.Surg., 173:628, 1971.

16. Dwyer, R. M., Haverback, B. F., Bass, M., et al.: Laser-InducedHemostasis in the Canine Stomach: Use of a Flexible Fiber-optic Delivery System. JAMA, 231:486, 1975.

17. Hanson, H. M. and Brodie, D. A.: Use of the Restraint RatTechnique for Study of the Anti-Ulcer Effect of Drugs. J. Appl.Physiol., 15:291, 1960.

18. Ivey, K. J.: Acute Hemorrhagic Gastritis: Modem Concepts Basedon Pathogenesis. Gut, 12:750, 1971.

19. Keller, R. T. and Logan, G. M.: Treatment of HemorrhagicGastritis by the Endoscopic Application of Acrylic Polymer.Gastroint. Endosc., 21:75, 1974.

20. Kiselow, M. C. and Wagner, M.: Intragastric Instillation ofLevarterenol: Method for Control of Upper GastrointestinalHemorrhage. Arch. Surg., 107:387, 1973.

21. LeVeen, H. H., Falk, G., Diaz, C., et al.: Control ofGastrointestinalBleeding. Am. J. Surg., 123:154, 1972.

22. Leonard, A. S., Long, D., French, L., et al.: Pendular Pattern inGastric Secretion and Blood Flow Following HypothalamicStimulation-Origin of Stress Ulcer. Surgery, 56:109, 1964.

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23. Levine. R. J. and Senay, E. C.: Studies on the Role of Acid in thePathogenesis of Experimental Stress Ulcers. Psychosom. Med.,32:61, 1970.

24. Nath, G., Gorisch, W. and Kiefhaber, P.: First Laser Endoscopyvia a Fiberoptic Transmission System. Endoscopy, 5:208, 1973.

25. Palmer, E. D.: Hemorrhage from Erosive Gastritis and its SurgicalImplications. Gastroenterology, 36:856, 1959.

26. Papp, J. P.: Endoscopic Electrocoagulation in Upper Gastro-intestinal Hemorrhage: A Preliminary Report. JAMA, 230:1172,1974.

27. Ritchie, W. P., Jr., Roth, R. R. and Fischer, R. P.: Studies on thePathogenesis of Stress Ulcer": Effect of Hemorrhage, Trans-fusion and Vagotomy in the Restrained Rat. Surgery, 71:445,1972.

28. Rosch, J., Dotter, C. T. and Brown, M. J.: Selective ArterialEmbolization. Radiology, 102:303, 1972.

29. Rosch, J., Dotter, C. T., and Antonovic, R.: Selective Vasocon-strictor Infusion in the Management of Arterio-Capillary Gastro-intestinal Hemorrhage. Am. J. Roentgenol. Radium Ther. Nucl.Med., 116:279, 1972.

30. Simonian, S. J., Stratoudakis, A., Lawrence, M., et al.: Non-surgical Control of Massive Acute Gastric Mucosal Hemorrhagewith Antacid Neutralization of Gastric Content. Surg. Clin.North Am., 56:21, 1976.

31. Skillman, J., Gould, S., Chung, R., and Silen, W.: The GastricMucosal Barrier: Clinical and Experimental Studies in theCritically III and Normal Man, and in the Rabbit. Ann. Surg.,172:564, 1970.

32. Sullivan, R. C., Rutherford, R. B. and Waddall, W. R.: SurgicalManagement of Hemorrhagic Gastritis by Vagotomy and Pyloro-plasty. Ann. Surg., 159:554, 1964.

33. Watts, C. C. and Clark, K.: Gastric Acidity in the ComatosePatient. J. Neurosurg., 30:107, 1969.

34. Watts, C. C. and Clark, K.: Effects of an Anticholinergic Drug onAcid Secretion in the Comatose Patient. Surg. Gynecol. Obstet.,130:61, 1970.

35. Welch, C. E. and Hedberg, S.: Gastrointestinal Hemorrhage. Adv.Surg., 7:95, 1973.

DiscUSSION

DR. WILLIAM M. STAHL, JR. (New York, New York): Dr. Simonianhas brought to us a simple but effective and important treatmentmodality in these very difficult patients who are threatening to die ofbleeding, in addition to the many other underlying conditions fromwhich they suffer.Our interest in the antacid control of the gastric content began

several years ago, when my colleagues, Drs. Robbins and Idjadi,and I studied prospectively 50 patients admitted to our intensive careunit, and measured acid, pepsin, and various glycosaminoglycancomponents of the gastric contents. We found, in contrast to some ofthe measurements in the literature, that in all of these patients who werehighly stressed from a variety of causes, the gastric acidity was sig-nificantly higher than in a series of normal patients measured in thesame way, and that in the 30%o of these patients who went on to bleedmassively, requiring transfusion-essentially the same group asmentioned here-the acid studies were significantly higher than in thestressed patients who did not bleed.

Following this, we instituted prophylactic antacid therapy, with areduction in the amount of massive bleeding in the next 50 patients.

I have two questions for Dr. Simonian. One is, there are 16 patientsin his group from alcoholic gastritis, whereas the rest are posttraumaticsepsis, either scheduled trauma or accidental trauma, and I wonder ifhe feels that these are the same lesion. We tend to feel that thealcoholic gastritic will stop, usually, with medical therapy, whereasthe stress ulcer patient may not.The second is: Has his group had any experience with the prophylac-

tic, or preventative use of antacid to maintain the pH at seven? Andif so, has there been a reduction in a prospective sense in the incidence ofbleeding in the stressed patient?

DR. JOHN J. SKILLMAN (Boston, Massachusetts): Dr. Simonianhas presented some evidence to suggest that neutralization of gastricacid is important in the therapy of patients who are bleeding fromacute hemorrhagic gastritis. However, as pointed out in the manuscript,these are uncontrolled observations, which nevertheless are impres-sive, in that 80%o to 90%o of the patients who were treated for significantbleeding, in fact, stopped bleeding.The importance of acid in the initiation of gastric mucosal bleeding

has been well demonstrated in a number of clinical and experimentalstudies. The results of a non-randomized clinical trial have been pub-lished recently in The Lancet in which cimetidine, and an H2 receptorantagonist, was used to treat patients who were bleeding from acutehemorrhagic gastritis. Considerable success in the arrest of hemorrhagewas also achieved in this study, although it must again be emphasizedthat this was also a non-randomized trial.The etiologic role of back diffusion of hydrogen ion has been a sub-

ject of considerable controversy in this area. People who have lookedat this, including ourselves, have tended to focus in the past on the

absolute amount of hydrogen ion which disappears through the gastricmucosa in patients who are likely to develop this problem. Recent experi-ments in Dr. Silen's laboratory would suggest that the absolute amountof acid which is back diffusing may be less important than the relation-ship between the state of energy metabolism of the mucosa and therelative amount of hydrogen ion which may be available to causemucosal damage. In other words, the process of acid secretiongenerates an alkaline tide in the oxyntic cell which may act as a bufferfor those cells which are normally perfused, and, by this mechanism,the cell may be capable of absorbing more hydrogen ion without under-going disruption. Mucosal hypoperfusion might limit the bufferingcapability of the mucosal cells.We believe that patients who bleed after ethanol or aspirin ingestion

may be somewhat different than the patients with trauma and sepsis.Our own studies and those of Basil Pruitt would suggest that the pa-tients who develop bleeding after trauma and sepsis are more like thepatients who develop this problem after major bums. I would like toknow if the five patients who required operation in this study werefrom the patient group with ethanol or aspirin ingestion since these arethe ones, in our experience, who are most likely to stop bleeding?

Secondly, in our own patient population, we identified a group ofclinical abnormalities: respiratory and renal failure, sepsis, jaundiceand hypotension-in other words, a constellation of clinical prob-lems which almost always accompany bleeding in these patients. I wouldlike to know how often these abnormalities were found in the sepsisreported today.

Thirdly, it would be of interest to know the distribution of thelesions which were seen on endoscopy. In our experience, these havebeen largely confined to the fundic portion of the stomach, sometimesin the antrum, and infrequently duodenal.

Finally, the best type of operation to perform on patients whose bleed-ing from this problem requires surgical control is still uncertain.However, it would appear from the collected data in the literature thata vagotomy is definitely important. Our own feeling is that for those pa-tients who bleed in association with drug ingestion-a pyloroplastyand vagotomy may be adequate treatment, if operation is needed. Inpatiens who have sepsis or trauma as a major factor, a generous resec-tion plus vagotomy is usually necessary.

DR. WILLIAM V. MCDERMOTT, JR. (Boston, Massachusetts): Dis-cussing this excellent, straightforward, and apparently simplistic re-port by Drs. Simonian and Curtis, I have no intention in reporting inany detail our corroborating experience, but only to point out the ob-vious analogy to the famous story of Edgar Allan Poe, The PurloinedLetter; namely, that what is most obvious often escapes us in life, andit is true in surgery as well. Among the innumerable noninvasive pro-grams designed over decades to control upper gastrointestinal hemor-rhage, treatment with antacids has always been a tenet of orthodoxy insurgical teaching. What did escape us, however, was the fact that inmost instances we were not accomplishing any effective neutralization.