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 control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrochloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirated through a nasogastric tube to maintain the pH of the aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleediung had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89o control of hemorrhage compare favorably with those in the literature.
TrHE THERAPY of massive acute gastric mucosal hemorrhage remains an unsolved problem."130'35 All experimental studies on the restrained animal model for the production of stress ulcers have shown that gastric erosions occur only when acid is present in the stomach. In stressed animqls, pretreatment with antacid to raise the gastric pH, vagotomy or anticholinergics significantly reduces the incidence of these lesions.3'4'17'23 In patients whose bleeding from gastric erosions has been controlled by vagotomy, the nasogastric aspirate was found to have a pH of 7.3 The frequency of bleeding secondary to stress-induced ulceration of the gastric mucosa has increased because of intensive care which can prolong the lives of critically ill and injured patients. Most recpnt reports of combined Presented at the Annual Meeting of the American Surgical Association, 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.
From the Departments of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois and Tufts University School of Medicine, Boston, Massachusetts
medical and surgical treatment of such patients have shown a high frequency of uncontrolled gastric bleeding and a high mortality. 15,30,35 The purpose of this report is to analyze the results of pH-controlled neutralizations of gastric hydrochloric acid with antacid in the treatment of a group of patients with massive acute gastric mucosal hemorrhage. Materials and Methods The study consisted of 49 patients with documented acute gastric mucosal hemorrhage, hospitalized at the Boston City Hospital between October 1971 and June 1974; the Tufts-New England Medical Center Hospitals between July 1973 and November 1975; and at the University of Chicago Hospitals between July 1974 and November 1975. The diagnosis was based on endoscopic findings in all patients and it was confirmed at surgery in five. There were 35 men and 14 women, ranging in age from 21 to 73 years, with a mean of 56 years. The total blood transfusion requirements per patient were 1500 ml to 7500 ml, with a mean of 4200 ml. Excluded are patients with less that 1500 ml blood transfusion requirement. The bleeding was associated with surgery, trauma, sepsis, and excess intake of alcohol. Patients whose bleeding was secondary to peptic gastric or duodenal ulcers or to esophageal varices, or to associated coagulopathy, were excluded. Table 1 summarizes the stressful factors related to this group of patients. Treatment consisted of removal of blood clots from the stomach, iced saline lavage, followed by instillation of antacid-buffer (magaldrate, Riopan) into a nasogastric
429
430
SIMONIAN AND CURTIS TABLE 1. Associated Factors in 49 Patients With Massive Gastric Musocal Hemorrhage
Associated Factor
No. Patients
Surgery-sepsis Ethanol Trauma-sepsis
26 16 7
tube until the pH of the nasogastric aspirate was returned to 7. In each patient, the amount of buffer required per hour to raise and maintain the intragastric pH at 7 was titrated as follows: a nasogastric tube was passed into the stomach; the gastric contents were aspirated as completely as possible and emptied into a basin by the bedside; using phenaphthazine pH paper (Nitrazine), the pH of the intragastric contents was measured and recorded. In most patients, the pH was 5 or below 5. Sixty ml of antacid was instilled into the stomach by gravity drainage and was allowed to mix for 15 minutes with the nasogastric tube clamped. At the end of 15 minutes, the stomach was reaspirated. If the pH was below 7, an additional increment of 30 ml of antacid (total volume of antacid, 90 ml) was instilled. Again, 15 minutes was allowed for mixing before the next pH measurement was taken. This procedure was continued until the amount of antacid required per 15 minutes to raise and maintain the intragastric pH at 7 was determined, usually in less than an hour. Thereafter, clamping of the nasogastric tube was prolonged to hourly intervals and the predetermined volume of antacid was instilled and reaspirated from the stomach to return the pH to 7. Titration was carried out by a nurse in the intensive care unit, and the measured volumes of antacid and pH value taken at the end of each hour were recorded on the bedside chart. In the majority of patients, the volume of antacid required to completely inactivate the gastric hydrochloric acid at a pH of 7 was 60 to 180 ml per hour. Control of bleeding was usually achieved 4 to 24 hours after neutralizing gastric hydrochloric acid. If at the end of 24 hours there was clinical evidence that the bleeding had stopped (as indicated by blood-free nasogastric aspirate; cessation in blood transfusion requirements; and stabilization of hematocrit and vital signs), the frequency of antacid instillation and nasogastric tube clamping was reduced to 2 hourly intervals and continued for another 24 hours. If after 24 hours there was no further evidence of bleeding, the frequency of instillation and clamping was further decreased to every 4 hours for anTABLE 2. Results of Surgical Treatment Procedure
No. Patient
Rebled
Died
Two-thirds gastrectomy Vagotomy and pyloroplasty
2 3
2 0
2 (100%o) 1 (33%)
Ann. Surg.
o
October 1976
other 12 to 24 hours. The nasogastric tube was removed on 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 being aspirated into the lungs or absorbed in the intestines. Results
Definition of Control of Hemorrhage The therapy was considered successful when the following conditions were met for at least 6 days after the discontinuation of the gastric acid neutralization: clear nasogastric aspirate; no blood transfusion requirements; stable hematocrit, blood pressure and pulse. Patients Treated with pH-Controlled Neutralizations of Gastric Acid with Antacid In 44 of 49 patients (89o) treated with antacid with a controlled pH of 7, the hemorrhage was arrested and no further therapy for gastric mucosal hemorrhage was required. Five patients continued to bleed. In two of these patients, 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 before surgery, the erosions of the mucosa of the fundus were bleeding, probably because the proximal stomach was not in constant contact with sufficient antacid to neutralize the hydrochloric acid secreted. A two-thirds gastric resection was performed in these two patients. Both patients rebled in the immediate postoperative period and died within 6 days of the operation. In another 2 of these 5 patients, organized clot was attached to the fundus at surgery. Prior to operation, the bleeding had ceased with antacid, but there was rebleeding on three occasions within 6 days in one of these patients. On repeat endoscopy, the clots were seen in the stomach, but the hematoma could not be removed except at operation. In the second patient, there was rebleeding within 6 days on two instances, again because of inadequate removal of clots from the stomach. At operation, both patients underwent vagotomy and pyloroplasty, after removing the blood clots. There was immediate blanching of the gastric mucosa with cessation of the hemorrhage in both patients. The phenomenon of post vagotomy blanching has been reported by others.33 The pH of the nasogastric aspirate rose to 7 in the intraoperative period following vagotomy. The pH of the nasogastric aspirate remained at 7, without the addition of any antacid, when it was measured in the immediate postoperative period. There was no further bleeding in either of these patients, but one of them died 10 days later of an undetermined cause. In the fifth patient, the pH could not be maintained at 7.
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TABLE 3. Cause of Death in Eleven of Forty-four Patients It fluctuated between pH 5 and 7, despite instillation of 150 to 180 ml of antacid every hour, and bleeding conCause of Death No. Patients tinued. He underwent vagotomy and pyloroplasty. The Sepsis 4 bleeding was controlled and he survived. For the last three Cardiac failure 2 patients in whom surgery was performed, there was conPulmonary failure 1 trol of bleeding in all, but one died. The results of Hepatic failure 1 Metastatic carcinoma 1 surgery are summarized in Table 2. Undetermined 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 gastrectomy (15%) than with vagotomy and pyloroplasty (29%). Total gastrectomy offers complete protection Complications Related to Neutralization against rebleeding, but it is associated with a high inciof Gastric Acid with Antacid dence of death and cannot be recommended at the present It was not necessary in any of these patients treated time as a primary procedure. Any kind of surgery adds with antacid at pH 7 to discontinue the therapy because further stress to these critically ill patients. The need for of local or systemic complications. In a few patients, non-surgical methods that can control massive gastric antacid administration caused diarrhea with water and stress bleeding is obvious. Many ingenious methods of non-surgical therapy have electrolyte loss. This complication was controlled by careful management of fluid and electrolyte balance intra- been reported for the treatment of this syndrome, such venously. In a small number of patients, the antacid had as gastric cooling,25 intragastric or intraperitoneal instillaa mild alkalemic effect with elevation of the arterial pH tion of levarterenol,1420'21 endoscopic application of acrylic to between 7.5 and 7.6. This was handled by preventing polymer,19 endoscopic electrocoagulation,2'26 laser-inthe elevation of the intragastric pH above 7. A few patients duced hemostasis through a fiberoptic carrier,16 24and emhad mild and transient elevation of serum magnesium bolic arterial occlusion.28 Further data are required to evaluate the effectiveness of these non-surgical treatments. An concentration without apparent ill effect. additional method consists of selective intra-arterial infusion of posterior pituitary extract or other vasoconstricRebleeding after Therapy tor.1'29 Intra-arterial vasopressin has controlled the massive Of the 44 patients treated and controlled by inactivation in 31 of 45 patients (69o).1 The method requires of gastric acid with antacid, three had rebleeding within bleeding specialist personnel and selective catheterization usually 7 days after neutralization was discontinued. They re- of the left gastric artery. The latter has not been possible quired a second series of instillations of antacid and to carry out technically 16 to 28% of the time. neutralization for control of the hemorrhage. Titration of gastric acid with antacid to a pH of 7 seems to provide an alternative to intra-arterial infusion of vasoMortality During Short Term Followup pressor and to surgery. Our present results compare with those obtained by operative procedures favorably Of the 44 patients in whom the bleeding was controlled and other nonsurgical methods, the hemorrhage having by antacid, only 33 survived. Eleven patients died within 44 of 49 patients treated (89o). Our been controlled out hemorrhage one or more weeks later. The causes of observations are a retrospective analysis of a group of these deaths are listed in Table 3. selected patients. A prospective, randomized clinical trial is required to confirm or refute the validity of these obDiscussion servations. We recommend such a study. The method of neutralization of gastric HCl described In most patients, bleeding from the gastric mucosa is mild to moderate in amount and is self-limited. In con- was developed from the physiological concept that a major trast, for some patients, hemorrhage is massive and determinant of the pathogenesis of gastric mucosal ulceracontinues in spite of gastric lavage with iced saline and tion is the presence of gastric HCl. The presence of replacement of blood; surgical intervention becomes acid seems to be necessary for the production of gastric necessary. The operation of choice to control bleeding and mucosal ulcers in restrained animals. Rats stressed by prevent recurrence is still controversial. A literature restraint and pretreated with antacid to raise the gastric survey15 confirms that subtotal gastrectomy alone was pH above 3.5 had a reduced incidence of gastric ulcerafollowed by a high incidence of rebleeding (52%) and tions from 61% in the control group, to 18% in the antacidmortality (30o). The addition of vagotomy significantly treated group. Vagotomy and anticholinergics also signifireduced the recurrence of bleeding and mortality. Control cantly reduced the incidence ofrestraint ulcers.3'4'17'23 Hemof rebleeding was greater with vagotomy and partial orrhagic shock caused mucosal gastric ulcers in rats.27 By
432
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bathing the mucosa with increasingly stronger but still physiological acid solutions, the incidence of ulcers was increased. Interest in back diffusion of acid across the mucosal barrier as a possible cause of ulceration has been generated by gastric pouch studies using various chemicals including acetylsalicylic acid,10 alcohol,1' and bile salts.'2 Back diffusion would also explain the low levels of gastric acid on routine gastric analysis frequently present in these patients. A short period of hemorrhagic shock in the rabbit was shown to have a disruptive effect on the gastric mucosal barrier to hydrogen ions similar to that produced by the above chemicals.31 Back diffusion and gastric ulceration were inhibited by antacids. In a series of critically ill hospitalized patients approximately half demonstrated an increased rate of back diffusion.3' Patients with stress ulcers were helped by antacids. To explain the clinical occurrence of neurogenic stress ulcers, a hypothalamic pituitary and an autonomic pathway have been proposed.22 In a series of comatose patients, almost all bled from the gastrointestinal tract.33 No patient treated with antacids and anticholinergics required gastric surgery to control the bleeding. In another similar series by the same authors, gastric hemorrhage was prevented by the prophylactic use of anticholinergics.34 Neutralizing intragastric acidity with antacid as therapy for hemorrhagic gastritis has been proposed with continuous intragastric infusion of sodium bicarbonate solution.'8 Massive gastrointestinal hemorrhage from a variety of sources was arrested in 23 of 25 patients when intragastric pH of 7 was constantly maintained by hourly administration of antacid.7 Apparently a pH of 7 is necessary to control the hemorrhage, because two patients in whom the bleeding stopped at that pH had rebleeding when the pH was allowed to drift to 5. When the intragastric pH in these patients was raised back to 7 with additional antacid, hemorrhage ceased.7 The pH of the nasogastric aspirate was measured in two patients of the present group following vagotomy and pyloroplasty. The pH was 7 and remained 7 for several days. The hemorrhage in these two patients ceased and there was no rebleeding. Since the earlier descriptions of variants of these lesions by Curling,6 Dieulafoy13 and Cushing,9 considerable expenimental and clinical data indicate that the mechanism of stress ulcers appears to be an interaction among several factors.5 Many of these factors appear to act in the presence of acid. However, in rats, vagotomy was ineffective in reducing the ulcer rate when hemorrhage was superimposed upon restraint.27 The last evidence indicates there is a pathway for the production of gastric mucosal ulcers in the absence of acid. In the present group of patients, the failure to control the hemorrhage in 5 patients was partly due to technique: completely neutralizing the intragastric acid at the bleeding site was not possible. The mechanism of action of controlled intragastric pH of 7 in the treatment of acute mucosal hemorrhage ap-
Ann. Surg. * October 1976
pears to involve: complete neutralization of gastric HCI; inhibition of back diffusion of hydrogen ions; inhibition of pepsin action and, as a result of recent experiments, enhancement of normal coagulation.8
Acknowledgments For the endoscopic studies we thank Dr. Norman Zamchek, Boston City Hospital; Dr. Richard Norton, Tufts-New England Medical Center Hospitals, and Dr. Michael 0. Blackstone, University of Chicago Hospitals.
References 1. 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 Procedes Technique et Pharmacodynamiques. Rev. Fr. Etud. Clin. Biol., 4:146, 1959. 4. Brodie, D. A. and Hanson, H. M.: A Study of Factors Involved in the 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 Cases of Bums. Med. Chir. Trans., 25: 260, 1842. 7. Curtis, L. E., Simonian, S. J., Buerk, C. A., et al.: Evaluation of the Effectiveness of Controlled pH in Management of Massive Upper 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 Acetylsalicylic 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 Detergents 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 Massive Gastrointestinal Bleeding in Poor-Risk Patients. JAMA, 230: 1653, 1974. 15. Drapanas, T., Woolverton, W. C., Reeder, J. W., et al.: Experiences with Surgical Management of Acute Gastric Mucosal Hemorrhage: A Unified Concept in the Pathophysiology. Ann. Surg., 173:628, 1971. 16. Dwyer, R. M., Haverback, B. F., Bass, M., et al.: Laser-Induced Hemostasis in the Canine Stomach: Use of a Flexible Fiberoptic Delivery System. JAMA, 231:486, 1975. 17. Hanson, H. M. and Brodie, D. A.: Use of the Restraint Rat Technique for Study of the Anti-Ulcer Effect of Drugs. J. Appl. Physiol., 15:291, 1960. 18. Ivey, K. J.: Acute Hemorrhagic Gastritis: Modem Concepts Based on Pathogenesis. Gut, 12:750, 1971. 19. Keller, R. T. and Logan, G. M.: Treatment of Hemorrhagic Gastritis by the Endoscopic Application of Acrylic Polymer. Gastroint. Endosc., 21:75, 1974. 20. Kiselow, M. C. and Wagner, M.: Intragastric Instillation of Levarterenol: Method for Control of Upper Gastrointestinal Hemorrhage. Arch. Surg., 107:387, 1973. 21. LeVeen, H. H., Falk, G., Diaz, C., et al.: Control of Gastrointestinal Bleeding. Am. J. Surg., 123:154, 1972. 22. Leonard, A. S., Long, D., French, L., et al.: Pendular Pattern in Gastric Secretion and Blood Flow Following Hypothalamic Stimulation-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 the Pathogenesis of Experimental Stress Ulcers. Psychosom. Med., 32:61, 1970. 24. Nath, G., Gorisch, W. and Kiefhaber, P.: First Laser Endoscopy via a Fiberoptic Transmission System. Endoscopy, 5:208, 1973. 25. Palmer, E. D.: Hemorrhage from Erosive Gastritis and its Surgical Implications. Gastroenterology, 36:856, 1959. 26. Papp, J. P.: Endoscopic Electrocoagulation in Upper Gastrointestinal Hemorrhage: A Preliminary Report. JAMA, 230:1172, 1974. 27. Ritchie, W. P., Jr., Roth, R. R. and Fischer, R. P.: Studies on the Pathogenesis of Stress Ulcer": Effect of Hemorrhage, Transfusion and Vagotomy in the Restrained Rat. Surgery, 71:445, 1972. 28. Rosch, J., Dotter, C. T. and Brown, M. J.: Selective Arterial Embolization. Radiology, 102:303, 1972. 29. Rosch, J., Dotter, C. T., and Antonovic, R.: Selective Vasoconstrictor Infusion in the Management of Arterio-Capillary Gastrointestinal Hemorrhage. Am. J. Roentgenol. Radium Ther. Nucl. Med., 116:279, 1972.
30. Simonian, S. J., Stratoudakis, A., Lawrence, M., et al.: Nonsurgical Control of Massive Acute Gastric Mucosal Hemorrhage with Antacid Neutralization of Gastric Content. Surg. Clin. North Am., 56:21, 1976. 31. Skillman, J., Gould, S., Chung, R., and Silen, W.: The Gastric Mucosal Barrier: Clinical and Experimental Studies in the Critically III and Normal Man, and in the Rabbit. Ann. Surg., 172:564, 1970. 32. Sullivan, R. C., Rutherford, R. B. and Waddall, W. R.: Surgical Management of Hemorrhagic Gastritis by Vagotomy and Pyloroplasty. Ann. Surg., 159:554, 1964. 33. Watts, C. C. and Clark, K.: Gastric Acidity in the Comatose Patient. J. Neurosurg., 30:107, 1969. 34. Watts, C. C. and Clark, K.: Effects of an Anticholinergic Drug on Acid 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
absolute amount of hydrogen ion which disappears through the gastric mucosa in patients who are likely to develop this problem. Recent experiments in Dr. Silen's laboratory would suggest that the absolute amount of acid which is back diffusing may be less important than the relationship between the state of energy metabolism of the mucosa and the relative amount of hydrogen ion which may be available to cause mucosal damage. In other words, the process of acid secretion generates an alkaline tide in the oxyntic cell which may act as a buffer for those cells which are normally perfused, and, by this mechanism, the cell may be capable of absorbing more hydrogen ion without undergoing disruption. Mucosal hypoperfusion might limit the buffering capability 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 patients who develop bleeding after trauma and sepsis are more like the patients who develop this problem after major bums. I would like to know if the five patients who required operation in this study were from the patient group with ethanol or aspirin ingestion since these are the ones, in our experience, who are most likely to stop bleeding? Secondly, in our own patient population, we identified a group of clinical abnormalities: respiratory and renal failure, sepsis, jaundice and hypotension-in other words, a constellation of clinical problems which almost always accompany bleeding in these patients. I would like to know how often these abnormalities were found in the sepsis reported today. Thirdly, it would be of interest to know the distribution of the lesions which were seen on endoscopy. In our experience, these have been largely confined to the fundic portion of the stomach, sometimes in the antrum, and infrequently duodenal. Finally, the best type of operation to perform on patients whose bleeding from this problem requires surgical control is still uncertain. However, it would appear from the collected data in the literature that a vagotomy is definitely important. Our own feeling is that for those patients who bleed in association with drug ingestion-a pyloroplasty and vagotomy may be adequate treatment, if operation is needed. In patiens who have sepsis or trauma as a major factor, a generous resection plus vagotomy is usually necessary.
DR. WILLIAM M. STAHL, JR. (New York, New York): Dr. Simonian has brought to us a simple but effective and important treatment modality in these very difficult patients who are threatening to die of bleeding, in addition to the many other underlying conditions from which 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 care unit, and measured acid, pepsin, and various glycosaminoglycan components of the gastric contents. We found, in contrast to some of the measurements in the literature, that in all of these patients who were highly stressed from a variety of causes, the gastric acidity was significantly higher than in a series of normal patients measured in the same way, and that in the 30%o of these patients who went on to bleed massively, requiring transfusion-essentially the same group as mentioned here-the acid studies were significantly higher than in the stressed patients who did not bleed. Following this, we instituted prophylactic antacid therapy, with a reduction in the amount of massive bleeding in the next 50 patients. I have two questions for Dr. Simonian. One is, there are 16 patients in his group from alcoholic gastritis, whereas the rest are posttraumatic sepsis, either scheduled trauma or accidental trauma, and I wonder if he feels that these are the same lesion. We tend to feel that the alcoholic gastritic will stop, usually, with medical therapy, whereas the stress ulcer patient may not. The second is: Has his group had any experience with the prophylactic, or preventative use of antacid to maintain the pH at seven? And if so, has there been a reduction in a prospective sense in the incidence of bleeding in the stressed patient? DR. JOHN J. SKILLMAN (Boston, Massachusetts): Dr. Simonian has presented some evidence to suggest that neutralization of gastric acid is important in the therapy of patients who are bleeding from acute hemorrhagic gastritis. However, as pointed out in the manuscript, these are uncontrolled observations, which nevertheless are impressive, in that 80%o to 90%o of the patients who were treated for significant bleeding, 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 experimental studies. The results of a non-randomized clinical trial have been published recently in The Lancet in which cimetidine, and an H2 receptor antagonist, was used to treat patients who were bleeding from acute hemorrhagic gastritis. Considerable success in the arrest of hemorrhage was also achieved in this study, although it must again be emphasized that this was also a non-randomized trial. The etiologic role of back diffusion of hydrogen ion has been a subject of considerable controversy in this area. People who have looked at this, including ourselves, have tended to focus in the past on the
DR. WILLIAM V. MCDERMOTT, JR. (Boston, Massachusetts): Discussing this excellent, straightforward, and apparently simplistic report by Drs. Simonian and Curtis, I have no intention in reporting in any detail our corroborating experience, but only to point out the obvious analogy to the famous story of Edgar Allan Poe, The Purloined Letter; namely, that what is most obvious often escapes us in life, and
it is true in surgery as well. Among the innumerable noninvasive programs designed over decades to control upper gastrointestinal hemorrhage, treatment with antacids has always been a tenet of orthodoxy in surgical teaching. What did escape us, however, was the fact that in most instances we were not accomplishing any effective neutralization.
A simple and safe method of nonsurgical treatment for the control of massive acute gastric mucosal hemorrhage is described. The procedure was developed from experimental and clinical observations that the presence of gastric hydrochloric acid played an important part in the development and perpetuation of the entity. The treatment consists of complete neutralization of gastric acid with antacid to a pH of 7. The antacid is intermittently added and aspirated through a nasogastric tube to maintain the pH of the aspirate at 7. In a retrospective analysis, the hemorrhage was controlled in 44 of 49 patients (89%). Five patients who continued to bleed underwent surgery (10%). Three patients had vagotomy and pyloroplasty and their bleeding ceased without recurrence. Two patients underwent partial gastrectomy, but they developed recurrent bleeding and died. One patient whose bleeding has been controlled by vagotomy and pyloroplasty died without hemorrhage 10 days after operation. Of the 44 patients whose bleediung had been controlled by antacid, 11 patients died without hemorrhage one or more weeks later. These results of 89o control of hemorrhage compare favorably with those in the literature.
TrHE THERAPY of massive acute gastric mucosal hemorrhage remains an unsolved problem."130'35 All experimental studies on the restrained animal model for the production of stress ulcers have shown that gastric erosions occur only when acid is present in the stomach. In stressed animqls, pretreatment with antacid to raise the gastric pH, vagotomy or anticholinergics significantly reduces the incidence of these lesions.3'4'17'23 In patients whose bleeding from gastric erosions has been controlled by vagotomy, the nasogastric aspirate was found to have a pH of 7.3 The frequency of bleeding secondary to stress-induced ulceration of the gastric mucosa has increased because of intensive care which can prolong the lives of critically ill and injured patients. Most recpnt reports of combined Presented at the Annual Meeting of the American Surgical Association, 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.
From the Departments of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois and Tufts University School of Medicine, Boston, Massachusetts
medical and surgical treatment of such patients have shown a high frequency of uncontrolled gastric bleeding and a high mortality. 15,30,35 The purpose of this report is to analyze the results of pH-controlled neutralizations of gastric hydrochloric acid with antacid in the treatment of a group of patients with massive acute gastric mucosal hemorrhage. Materials and Methods The study consisted of 49 patients with documented acute gastric mucosal hemorrhage, hospitalized at the Boston City Hospital between October 1971 and June 1974; the Tufts-New England Medical Center Hospitals between July 1973 and November 1975; and at the University of Chicago Hospitals between July 1974 and November 1975. The diagnosis was based on endoscopic findings in all patients and it was confirmed at surgery in five. There were 35 men and 14 women, ranging in age from 21 to 73 years, with a mean of 56 years. The total blood transfusion requirements per patient were 1500 ml to 7500 ml, with a mean of 4200 ml. Excluded are patients with less that 1500 ml blood transfusion requirement. The bleeding was associated with surgery, trauma, sepsis, and excess intake of alcohol. Patients whose bleeding was secondary to peptic gastric or duodenal ulcers or to esophageal varices, or to associated coagulopathy, were excluded. Table 1 summarizes the stressful factors related to this group of patients. Treatment consisted of removal of blood clots from the stomach, iced saline lavage, followed by instillation of antacid-buffer (magaldrate, Riopan) into a nasogastric
429
430
SIMONIAN AND CURTIS TABLE 1. Associated Factors in 49 Patients With Massive Gastric Musocal Hemorrhage
Associated Factor
No. Patients
Surgery-sepsis Ethanol Trauma-sepsis
26 16 7
tube until the pH of the nasogastric aspirate was returned to 7. In each patient, the amount of buffer required per hour to raise and maintain the intragastric pH at 7 was titrated as follows: a nasogastric tube was passed into the stomach; the gastric contents were aspirated as completely as possible and emptied into a basin by the bedside; using phenaphthazine pH paper (Nitrazine), the pH of the intragastric contents was measured and recorded. In most patients, the pH was 5 or below 5. Sixty ml of antacid was instilled into the stomach by gravity drainage and was allowed to mix for 15 minutes with the nasogastric tube clamped. At the end of 15 minutes, the stomach was reaspirated. If the pH was below 7, an additional increment of 30 ml of antacid (total volume of antacid, 90 ml) was instilled. Again, 15 minutes was allowed for mixing before the next pH measurement was taken. This procedure was continued until the amount of antacid required per 15 minutes to raise and maintain the intragastric pH at 7 was determined, usually in less than an hour. Thereafter, clamping of the nasogastric tube was prolonged to hourly intervals and the predetermined volume of antacid was instilled and reaspirated from the stomach to return the pH to 7. Titration was carried out by a nurse in the intensive care unit, and the measured volumes of antacid and pH value taken at the end of each hour were recorded on the bedside chart. In the majority of patients, the volume of antacid required to completely inactivate the gastric hydrochloric acid at a pH of 7 was 60 to 180 ml per hour. Control of bleeding was usually achieved 4 to 24 hours after neutralizing gastric hydrochloric acid. If at the end of 24 hours there was clinical evidence that the bleeding had stopped (as indicated by blood-free nasogastric aspirate; cessation in blood transfusion requirements; and stabilization of hematocrit and vital signs), the frequency of antacid instillation and nasogastric tube clamping was reduced to 2 hourly intervals and continued for another 24 hours. If after 24 hours there was no further evidence of bleeding, the frequency of instillation and clamping was further decreased to every 4 hours for anTABLE 2. Results of Surgical Treatment Procedure
No. Patient
Rebled
Died
Two-thirds gastrectomy Vagotomy and pyloroplasty
2 3
2 0
2 (100%o) 1 (33%)
Ann. Surg.
o
October 1976
other 12 to 24 hours. The nasogastric tube was removed on 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 being aspirated into the lungs or absorbed in the intestines. Results
Definition of Control of Hemorrhage The therapy was considered successful when the following conditions were met for at least 6 days after the discontinuation of the gastric acid neutralization: clear nasogastric aspirate; no blood transfusion requirements; stable hematocrit, blood pressure and pulse. Patients Treated with pH-Controlled Neutralizations of Gastric Acid with Antacid In 44 of 49 patients (89o) treated with antacid with a controlled pH of 7, the hemorrhage was arrested and no further therapy for gastric mucosal hemorrhage was required. Five patients continued to bleed. In two of these patients, 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 before surgery, the erosions of the mucosa of the fundus were bleeding, probably because the proximal stomach was not in constant contact with sufficient antacid to neutralize the hydrochloric acid secreted. A two-thirds gastric resection was performed in these two patients. Both patients rebled in the immediate postoperative period and died within 6 days of the operation. In another 2 of these 5 patients, organized clot was attached to the fundus at surgery. Prior to operation, the bleeding had ceased with antacid, but there was rebleeding on three occasions within 6 days in one of these patients. On repeat endoscopy, the clots were seen in the stomach, but the hematoma could not be removed except at operation. In the second patient, there was rebleeding within 6 days on two instances, again because of inadequate removal of clots from the stomach. At operation, both patients underwent vagotomy and pyloroplasty, after removing the blood clots. There was immediate blanching of the gastric mucosa with cessation of the hemorrhage in both patients. The phenomenon of post vagotomy blanching has been reported by others.33 The pH of the nasogastric aspirate rose to 7 in the intraoperative period following vagotomy. The pH of the nasogastric aspirate remained at 7, without the addition of any antacid, when it was measured in the immediate postoperative period. There was no further bleeding in either of these patients, but one of them died 10 days later of an undetermined cause. In the fifth patient, the pH could not be maintained at 7.
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TABLE 3. Cause of Death in Eleven of Forty-four Patients It fluctuated between pH 5 and 7, despite instillation of 150 to 180 ml of antacid every hour, and bleeding conCause of Death No. Patients tinued. He underwent vagotomy and pyloroplasty. The Sepsis 4 bleeding was controlled and he survived. For the last three Cardiac failure 2 patients in whom surgery was performed, there was conPulmonary failure 1 trol of bleeding in all, but one died. The results of Hepatic failure 1 Metastatic carcinoma 1 surgery are summarized in Table 2. Undetermined 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 gastrectomy (15%) than with vagotomy and pyloroplasty (29%). Total gastrectomy offers complete protection Complications Related to Neutralization against rebleeding, but it is associated with a high inciof Gastric Acid with Antacid dence of death and cannot be recommended at the present It was not necessary in any of these patients treated time as a primary procedure. Any kind of surgery adds with antacid at pH 7 to discontinue the therapy because further stress to these critically ill patients. The need for of local or systemic complications. In a few patients, non-surgical methods that can control massive gastric antacid administration caused diarrhea with water and stress bleeding is obvious. Many ingenious methods of non-surgical therapy have electrolyte loss. This complication was controlled by careful management of fluid and electrolyte balance intra- been reported for the treatment of this syndrome, such venously. In a small number of patients, the antacid had as gastric cooling,25 intragastric or intraperitoneal instillaa mild alkalemic effect with elevation of the arterial pH tion of levarterenol,1420'21 endoscopic application of acrylic to between 7.5 and 7.6. This was handled by preventing polymer,19 endoscopic electrocoagulation,2'26 laser-inthe elevation of the intragastric pH above 7. A few patients duced hemostasis through a fiberoptic carrier,16 24and emhad mild and transient elevation of serum magnesium bolic arterial occlusion.28 Further data are required to evaluate the effectiveness of these non-surgical treatments. An concentration without apparent ill effect. additional method consists of selective intra-arterial infusion of posterior pituitary extract or other vasoconstricRebleeding after Therapy tor.1'29 Intra-arterial vasopressin has controlled the massive Of the 44 patients treated and controlled by inactivation in 31 of 45 patients (69o).1 The method requires of gastric acid with antacid, three had rebleeding within bleeding specialist personnel and selective catheterization usually 7 days after neutralization was discontinued. They re- of the left gastric artery. The latter has not been possible quired a second series of instillations of antacid and to carry out technically 16 to 28% of the time. neutralization for control of the hemorrhage. Titration of gastric acid with antacid to a pH of 7 seems to provide an alternative to intra-arterial infusion of vasoMortality During Short Term Followup pressor and to surgery. Our present results compare with those obtained by operative procedures favorably Of the 44 patients in whom the bleeding was controlled and other nonsurgical methods, the hemorrhage having by antacid, only 33 survived. Eleven patients died within 44 of 49 patients treated (89o). Our been controlled out hemorrhage one or more weeks later. The causes of observations are a retrospective analysis of a group of these deaths are listed in Table 3. selected patients. A prospective, randomized clinical trial is required to confirm or refute the validity of these obDiscussion servations. We recommend such a study. The method of neutralization of gastric HCl described In most patients, bleeding from the gastric mucosa is mild to moderate in amount and is self-limited. In con- was developed from the physiological concept that a major trast, for some patients, hemorrhage is massive and determinant of the pathogenesis of gastric mucosal ulceracontinues in spite of gastric lavage with iced saline and tion is the presence of gastric HCl. The presence of replacement of blood; surgical intervention becomes acid seems to be necessary for the production of gastric necessary. The operation of choice to control bleeding and mucosal ulcers in restrained animals. Rats stressed by prevent recurrence is still controversial. A literature restraint and pretreated with antacid to raise the gastric survey15 confirms that subtotal gastrectomy alone was pH above 3.5 had a reduced incidence of gastric ulcerafollowed by a high incidence of rebleeding (52%) and tions from 61% in the control group, to 18% in the antacidmortality (30o). The addition of vagotomy significantly treated group. Vagotomy and anticholinergics also signifireduced the recurrence of bleeding and mortality. Control cantly reduced the incidence ofrestraint ulcers.3'4'17'23 Hemof rebleeding was greater with vagotomy and partial orrhagic shock caused mucosal gastric ulcers in rats.27 By
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bathing the mucosa with increasingly stronger but still physiological acid solutions, the incidence of ulcers was increased. Interest in back diffusion of acid across the mucosal barrier as a possible cause of ulceration has been generated by gastric pouch studies using various chemicals including acetylsalicylic acid,10 alcohol,1' and bile salts.'2 Back diffusion would also explain the low levels of gastric acid on routine gastric analysis frequently present in these patients. A short period of hemorrhagic shock in the rabbit was shown to have a disruptive effect on the gastric mucosal barrier to hydrogen ions similar to that produced by the above chemicals.31 Back diffusion and gastric ulceration were inhibited by antacids. In a series of critically ill hospitalized patients approximately half demonstrated an increased rate of back diffusion.3' Patients with stress ulcers were helped by antacids. To explain the clinical occurrence of neurogenic stress ulcers, a hypothalamic pituitary and an autonomic pathway have been proposed.22 In a series of comatose patients, almost all bled from the gastrointestinal tract.33 No patient treated with antacids and anticholinergics required gastric surgery to control the bleeding. In another similar series by the same authors, gastric hemorrhage was prevented by the prophylactic use of anticholinergics.34 Neutralizing intragastric acidity with antacid as therapy for hemorrhagic gastritis has been proposed with continuous intragastric infusion of sodium bicarbonate solution.'8 Massive gastrointestinal hemorrhage from a variety of sources was arrested in 23 of 25 patients when intragastric pH of 7 was constantly maintained by hourly administration of antacid.7 Apparently a pH of 7 is necessary to control the hemorrhage, because two patients in whom the bleeding stopped at that pH had rebleeding when the pH was allowed to drift to 5. When the intragastric pH in these patients was raised back to 7 with additional antacid, hemorrhage ceased.7 The pH of the nasogastric aspirate was measured in two patients of the present group following vagotomy and pyloroplasty. The pH was 7 and remained 7 for several days. The hemorrhage in these two patients ceased and there was no rebleeding. Since the earlier descriptions of variants of these lesions by Curling,6 Dieulafoy13 and Cushing,9 considerable expenimental and clinical data indicate that the mechanism of stress ulcers appears to be an interaction among several factors.5 Many of these factors appear to act in the presence of acid. However, in rats, vagotomy was ineffective in reducing the ulcer rate when hemorrhage was superimposed upon restraint.27 The last evidence indicates there is a pathway for the production of gastric mucosal ulcers in the absence of acid. In the present group of patients, the failure to control the hemorrhage in 5 patients was partly due to technique: completely neutralizing the intragastric acid at the bleeding site was not possible. The mechanism of action of controlled intragastric pH of 7 in the treatment of acute mucosal hemorrhage ap-
Ann. Surg. * October 1976
pears to involve: complete neutralization of gastric HCI; inhibition of back diffusion of hydrogen ions; inhibition of pepsin action and, as a result of recent experiments, enhancement of normal coagulation.8
Acknowledgments For the endoscopic studies we thank Dr. Norman Zamchek, Boston City Hospital; Dr. Richard Norton, Tufts-New England Medical Center Hospitals, and Dr. Michael 0. Blackstone, University of Chicago Hospitals.
References 1. 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 Procedes Technique et Pharmacodynamiques. Rev. Fr. Etud. Clin. Biol., 4:146, 1959. 4. Brodie, D. A. and Hanson, H. M.: A Study of Factors Involved in the 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 Cases of Bums. Med. Chir. Trans., 25: 260, 1842. 7. Curtis, L. E., Simonian, S. J., Buerk, C. A., et al.: Evaluation of the Effectiveness of Controlled pH in Management of Massive Upper 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 Acetylsalicylic 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 Detergents 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 Massive Gastrointestinal Bleeding in Poor-Risk Patients. JAMA, 230: 1653, 1974. 15. Drapanas, T., Woolverton, W. C., Reeder, J. W., et al.: Experiences with Surgical Management of Acute Gastric Mucosal Hemorrhage: A Unified Concept in the Pathophysiology. Ann. Surg., 173:628, 1971. 16. Dwyer, R. M., Haverback, B. F., Bass, M., et al.: Laser-Induced Hemostasis in the Canine Stomach: Use of a Flexible Fiberoptic Delivery System. JAMA, 231:486, 1975. 17. Hanson, H. M. and Brodie, D. A.: Use of the Restraint Rat Technique for Study of the Anti-Ulcer Effect of Drugs. J. Appl. Physiol., 15:291, 1960. 18. Ivey, K. J.: Acute Hemorrhagic Gastritis: Modem Concepts Based on Pathogenesis. Gut, 12:750, 1971. 19. Keller, R. T. and Logan, G. M.: Treatment of Hemorrhagic Gastritis by the Endoscopic Application of Acrylic Polymer. Gastroint. Endosc., 21:75, 1974. 20. Kiselow, M. C. and Wagner, M.: Intragastric Instillation of Levarterenol: Method for Control of Upper Gastrointestinal Hemorrhage. Arch. Surg., 107:387, 1973. 21. LeVeen, H. H., Falk, G., Diaz, C., et al.: Control of Gastrointestinal Bleeding. Am. J. Surg., 123:154, 1972. 22. Leonard, A. S., Long, D., French, L., et al.: Pendular Pattern in Gastric Secretion and Blood Flow Following Hypothalamic Stimulation-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 the Pathogenesis of Experimental Stress Ulcers. Psychosom. Med., 32:61, 1970. 24. Nath, G., Gorisch, W. and Kiefhaber, P.: First Laser Endoscopy via a Fiberoptic Transmission System. Endoscopy, 5:208, 1973. 25. Palmer, E. D.: Hemorrhage from Erosive Gastritis and its Surgical Implications. Gastroenterology, 36:856, 1959. 26. Papp, J. P.: Endoscopic Electrocoagulation in Upper Gastrointestinal Hemorrhage: A Preliminary Report. JAMA, 230:1172, 1974. 27. Ritchie, W. P., Jr., Roth, R. R. and Fischer, R. P.: Studies on the Pathogenesis of Stress Ulcer": Effect of Hemorrhage, Transfusion and Vagotomy in the Restrained Rat. Surgery, 71:445, 1972. 28. Rosch, J., Dotter, C. T. and Brown, M. J.: Selective Arterial Embolization. Radiology, 102:303, 1972. 29. Rosch, J., Dotter, C. T., and Antonovic, R.: Selective Vasoconstrictor Infusion in the Management of Arterio-Capillary Gastrointestinal Hemorrhage. Am. J. Roentgenol. Radium Ther. Nucl. Med., 116:279, 1972.
30. Simonian, S. J., Stratoudakis, A., Lawrence, M., et al.: Nonsurgical Control of Massive Acute Gastric Mucosal Hemorrhage with Antacid Neutralization of Gastric Content. Surg. Clin. North Am., 56:21, 1976. 31. Skillman, J., Gould, S., Chung, R., and Silen, W.: The Gastric Mucosal Barrier: Clinical and Experimental Studies in the Critically III and Normal Man, and in the Rabbit. Ann. Surg., 172:564, 1970. 32. Sullivan, R. C., Rutherford, R. B. and Waddall, W. R.: Surgical Management of Hemorrhagic Gastritis by Vagotomy and Pyloroplasty. Ann. Surg., 159:554, 1964. 33. Watts, C. C. and Clark, K.: Gastric Acidity in the Comatose Patient. J. Neurosurg., 30:107, 1969. 34. Watts, C. C. and Clark, K.: Effects of an Anticholinergic Drug on Acid 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
absolute amount of hydrogen ion which disappears through the gastric mucosa in patients who are likely to develop this problem. Recent experiments in Dr. Silen's laboratory would suggest that the absolute amount of acid which is back diffusing may be less important than the relationship between the state of energy metabolism of the mucosa and the relative amount of hydrogen ion which may be available to cause mucosal damage. In other words, the process of acid secretion generates an alkaline tide in the oxyntic cell which may act as a buffer for those cells which are normally perfused, and, by this mechanism, the cell may be capable of absorbing more hydrogen ion without undergoing disruption. Mucosal hypoperfusion might limit the buffering capability 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 patients who develop bleeding after trauma and sepsis are more like the patients who develop this problem after major bums. I would like to know if the five patients who required operation in this study were from the patient group with ethanol or aspirin ingestion since these are the ones, in our experience, who are most likely to stop bleeding? Secondly, in our own patient population, we identified a group of clinical abnormalities: respiratory and renal failure, sepsis, jaundice and hypotension-in other words, a constellation of clinical problems which almost always accompany bleeding in these patients. I would like to know how often these abnormalities were found in the sepsis reported today. Thirdly, it would be of interest to know the distribution of the lesions which were seen on endoscopy. In our experience, these have been largely confined to the fundic portion of the stomach, sometimes in the antrum, and infrequently duodenal. Finally, the best type of operation to perform on patients whose bleeding from this problem requires surgical control is still uncertain. However, it would appear from the collected data in the literature that a vagotomy is definitely important. Our own feeling is that for those patients who bleed in association with drug ingestion-a pyloroplasty and vagotomy may be adequate treatment, if operation is needed. In patiens who have sepsis or trauma as a major factor, a generous resection plus vagotomy is usually necessary.
DR. WILLIAM M. STAHL, JR. (New York, New York): Dr. Simonian has brought to us a simple but effective and important treatment modality in these very difficult patients who are threatening to die of bleeding, in addition to the many other underlying conditions from which 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 care unit, and measured acid, pepsin, and various glycosaminoglycan components of the gastric contents. We found, in contrast to some of the measurements in the literature, that in all of these patients who were highly stressed from a variety of causes, the gastric acidity was significantly higher than in a series of normal patients measured in the same way, and that in the 30%o of these patients who went on to bleed massively, requiring transfusion-essentially the same group as mentioned here-the acid studies were significantly higher than in the stressed patients who did not bleed. Following this, we instituted prophylactic antacid therapy, with a reduction in the amount of massive bleeding in the next 50 patients. I have two questions for Dr. Simonian. One is, there are 16 patients in his group from alcoholic gastritis, whereas the rest are posttraumatic sepsis, either scheduled trauma or accidental trauma, and I wonder if he feels that these are the same lesion. We tend to feel that the alcoholic gastritic will stop, usually, with medical therapy, whereas the stress ulcer patient may not. The second is: Has his group had any experience with the prophylactic, or preventative use of antacid to maintain the pH at seven? And if so, has there been a reduction in a prospective sense in the incidence of bleeding in the stressed patient? DR. JOHN J. SKILLMAN (Boston, Massachusetts): Dr. Simonian has presented some evidence to suggest that neutralization of gastric acid is important in the therapy of patients who are bleeding from acute hemorrhagic gastritis. However, as pointed out in the manuscript, these are uncontrolled observations, which nevertheless are impressive, in that 80%o to 90%o of the patients who were treated for significant bleeding, 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 experimental studies. The results of a non-randomized clinical trial have been published recently in The Lancet in which cimetidine, and an H2 receptor antagonist, was used to treat patients who were bleeding from acute hemorrhagic gastritis. Considerable success in the arrest of hemorrhage was also achieved in this study, although it must again be emphasized that this was also a non-randomized trial. The etiologic role of back diffusion of hydrogen ion has been a subject of considerable controversy in this area. People who have looked at this, including ourselves, have tended to focus in the past on the
DR. WILLIAM V. MCDERMOTT, JR. (Boston, Massachusetts): Discussing this excellent, straightforward, and apparently simplistic report by Drs. Simonian and Curtis, I have no intention in reporting in any detail our corroborating experience, but only to point out the obvious analogy to the famous story of Edgar Allan Poe, The Purloined Letter; namely, that what is most obvious often escapes us in life, and
it is true in surgery as well. Among the innumerable noninvasive programs designed over decades to control upper gastrointestinal hemorrhage, treatment with antacids has always been a tenet of orthodoxy in surgical teaching. What did escape us, however, was the fact that in most instances we were not accomplishing any effective neutralization.
