GASTROENTEROLOGY. Official Publication of the American Gastroenterological Association RECURRENT UPPER GASTROINTESTINAL HEMORRHAGE IN PEPTIC ULCER

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1 GASTROENTEROLOGY Official Publication of the American Gastroenterological Association COPYRGHT 1967 THE WLLAMS & WLKNS CO. VOLUME 52 April 1967 NUMBER 4 RECURRENT UPPER GASTRONTESTNAL HEMORRHAGE N PEPTC ULCER JAMES L. BORLAND, SR., M.D., W. Roy HANCOCK, M.D., AND JAMES L. BORLAND, JR., M.D. Jacksonville, Florida The decisions to be made when treating patients with bleeding peptic ulcer require evaluation of the danger of subsequent hemorrhage and of the effects of age, severity of hemorrhage, and frequency of prior hemorrhage. Proper values can be assigned to these factors only by a review of the course of the disease. Jacksonville, Florida, is well suited for such a review. t is large enough to supply an adequate number of patients for statistical analysis. t is an industrial, banking, and insurance center of approximately 500,000 population and it is an active seaport. The population changes little with seasons. t is unlikely that patients still in the community who began to bleed again would have left the area for treatment elsewhere during the hemorrhage because there were no large general hospitals outside of Jacksonville within a radius of 50 miles during the period of this study. Received November 24, Accepted September 7, This paper was presented in part at the 1964 Annual Meeting of the American Gastroenterological Association, Dallas, Texas. Address requests for reprints to: Dr. James L. Borland, 1661 Riverside Avenue, Jacksonville, Florida The authors gratefully acknowledge the tireless secretarial assistance of Mrs. Joan Smith, and the direction and help of Mr. Oliver H. Boorde, Director of Public Statistics, Florida State Board of Health. 631 Admissions of all patients with upper gastrointestinal hemorrhage to one typical local hospital during a lo-year period formed the basis for this report. This hospital was a 375-bed general hospital admitting white patients of all ages and sexes. These were primarily private patients; a few were indigent. The patients were comparable in social and economic status to private patients in any southern community of this size. The staff of this hospital included general practitioners and the usual specialists. An attempt has been made, through study of admission records of each hospital in this community during the lo-year period, to account for all possible significant episodes of recurrent bleeding from peptic ulcer in those patients remaining in the area. Definitions "nitial hemorrhage" is defined as the first bleeding episode recorded in the history or in the records of all hospitals in the community. "Surgery" refers to surgery on the gastrointestinal tract related to the control of hemorrhage. "Mortality" is defined as death from any cause during an admission under consideration.! The two commonly used criteria for measuring severity of hemorrhage are the total number of transfusions, and the transfusion rate during the period of worst bleeding. The total number of transfusions during the entire episode of bleed-

2 632 BORLAND ET AL. Vol. 52, No.4 ing was plotted against the largest number of transfusions on any single day. The correlation was such that the relationship was straight line. Consequently, the total number of 500-cc transfusions was used as a valid index of the severity of hemorrhage. Methods Records of all patients having upper gastrointestinal hemorrhage who were admitted to St. Vincent's Hospital between the years 1950 and 1961 were reviewed. All patients having hiatal hernia, esophageal or gastric varices, cirrhosis, malignant disease, telangiectasia, and blood dyscrasia were excluded from the study. Only those with hematemesis or tarry stools on admission, symptoms of peptic ulcer, and/or radiological or pathological evidence of ulcer were included. The X-rays were interpreted in all cases by a board-certified radiologist. Records of this hospital and all other general hospitals in Jacksonville, including the county hospital for indigents, subsequently were checked for any readmission of the patients included in the study. Admissions for reasons other than peptic ulcer were helpful in establishing follow-up period and interim histories. The period of follow-up was computed from the date of initial hemorrhage to the last contact with the patient. The latter was established by (1) the last known hospital admission for any cause, (2) the patient's being dead on arrival at the hospital, (3) communication with the patient by telephone or written questionnaire, or (4) finding his name in the 1963 Duval County telephone directory or the city or suburban directories (published in 1963 by Polk and Company). No contact TABLE 1. Duration of follow-up Years No. of patients nitial could be established with 150 people after discharge from the hospital following the initial hemorrhage. t was established by review of the current city and telephone directories that they no longer lived in Jacksonville. When these patients, who could no longer be located moved from the city is not known. t is known that they did not die in a local hospital; that they were not brought to a hospital as "dead on arrival;" nor were they admitted to a local hospital for any reason during the period of this study. There is no reason to suspect that they left the city for reasons related to hemorrhage. These 150 people were excluded from the study. Therefore, the specified period of follow-up is considered valid, and no conclusions have been drawn beyond this specified period (table 1). Data of individual patients were transferred to punch cards by a statistician and tabulated by computer. n analyzing these data, the chi-square test was used to determine the level of significance where numbers were adequate. When chi-square could not be used, owing to inadequate cell size (expected values less than 5), data were tested for significant differences in proportions. Results A total of 456 patients satisfied the criteria previously discussed. So far as could be determined, these patients had bleeding peptic ulcer-gastric, duodenal, or marginal. Of these, 283 patients were followed for 1 year or longer, and 131 for 5 years or longer. Twenty-five patients were followed for at least 10 years. Of the 173 patients followed for less than 1 year, 23 died with the initial hemorrhage. No contact was established with the remaining 150 patients, and they are not included in the figures or calculations for recurrent hemorrhage. Table 2 shows the mortality from bleeding. Twenty-three deaths occurred in the 456 patients with the initial bleeding, and the mortality rate was 5.0%. Among the 105 patients experiencing 173 recurrent episodes of bleeding, only two deaths occurred (regardless of age or type of therapy), a mortality of 1.9% Table 3 displays the effect of age at initial hemorrhage on the mortality. n the 117 patients who had their initial hemorrhage under age 40, one death occurred, a mortality of only 0.9%. The gradual in-

3 April 1967 HEMORRHAGE N PEPTC ULCER 633 crease in the mortality percentages with advancing age at initial hemorrhage is noteworthy. The percentage of patients uncl er 50 dying at initial hemorrhage was not significantly different from the percentage for those dying in the 50- to 79- year age group (p < 0.05, Chi-square 3.59). Addition of patients 80 and over resulted in a significant difference in mortality when comparing the groups over and under 50 (P < 0.025; chi-square, 5.84). T able 4 demonstrates the effect of seyerity of the initial hemorrhage on the mortality. Patients who required 3 units of blood or less in the initial hemorrhage had a 2.7% mortality. Of patients receiving 4 to 6 units of blood, 4% died. The mortality rate for the patients needing 7 to 9 units was 16.1%, and for those requiring 10 units or more, 26%. The mortality figures for patients given 0 to 6 units were significantly less than for those receiving 7 or more transfusions. n table 5 one sees the effect of the age of the patient at the time of initial hemorrhage 011 the chance of having recurrent TABL E 2. Mortality from hemorrhage No. of patients Deaths no. % J nitial episode Medically treated Surgically treated Total Recurrent episodes (total) TABLE 3. Eifect of age at initial hemorrhage on mortality Age at initial hemorrhage No. of cases Deaths yr. no. % Under and over All ages TABLE 4. Eifect of severity of initial hemorrhage on mortality Severity rating No. of cases Deaths no. % Unknown All cases hemorrhages. Age did not significantly affect the chance of having one or more recurrences for patients followed for 3, 5, and 7 years. The chi-square value for 3 years was 1.81; for 5 years, 0.20; and for 7 years, The P values at 3 degrees of freedom were 0.50, 0.90, and 0.50, respectively. The data were insufficient for statistica,l evaluation of the patients followed for 9 years or more, but their ages at initial hemorrhage had no substantial effect on the number of recurrences. The over-all chance of recurrence is dependent in part on the length of follow-up. Only two deaths occurred from recurrent hemorrhage, no matter how long patients were followed. Table 6 depicts the effect of the severity of the initial hemorrhage on the chances of recurrence. The number of patients followed for 3 years or more did not allow for statistical evaluation, but there was no indication of a direct relationship between chance of recurrence and severity of initial hemorrhage. Table 7 shows the effects of age at the initial hemorrhage on the severity of recurrent hemorrhage. Only the first recurrence is shown. Age at initial hemorrhage had no substantial effect on the severity of first recurrences. There were not enough subsequent recurrences to establish a pattern. Table 8 shows the effect of severity at initial hemonhage on the severity of recurrence. Again, this table refers only to the first recurrence, for the same reasons as in table 7. n groups with enough patients to allow statistical evaluation (0 to 3 units versus 4+ units), the severity of

4 634 BORLAND ET AL. Vol. 52, No. -4 TABLE 5. Effects of age at initial hemorrhage on number of recurrences Number of full years cases were follow ed Age at initial 3 years 5 years 7 years 9 years hemorrhage Total lor more 2 or more Total lor more 2 or more Total 1 or more 12 or more Total 1 Or more 2 or more recur- recurcases recurcases recurcasecases recur- recur- recur- recurrences rences rences rences rences rences rences rences yr. no. % no. % no. % no. % no. % no. % no. % "0. % Under and over ~-; Total TABLE 6. Effect of severity of initial hemorrhage on number of recurrences Number of full years cases were followed No. of transfus- 3 years 5 years 7 years 9 years ions at initial hemorrhage Total lor more 2 or more Total lor more 2 or more recur- recurcases recurrences Tences Total lor more 2 or more Total lor more 2 or more leenrcasecases cases recur- teent- recur- recurrences rences rences rences rences rences no. % no. % no. % no. % no. % no. % no. % no. % Unknown Total the recurrent hemorrhage was not dependent on the severity at initial hemorrhage. n groups not statistically tested, it is apparent that there was no substantial effect on the severity of recurrent hemorrhage relative to the number of transfusions required with initial hemorrhage. Discussion There is general agreement that the majority of initial hemorrhages from peptic ulcer may be managed conservatively,2-4 and that inability to replace blood adequately, or continuation of hemorrhage, demands surgery.5 Fear of the consequences of recurrent hemorrhage 6 and the difficulties of evaluating repeated bleeding 7 have given rise to trite phrases and ideas concerning the care of patients bleeding from peptic ulcer. t was the purpose of this study to evaluate the subsequent course of patients who bled from a peptic ulcer, with particular reference to the effects of age, rate of hemorrhage, and numbers of previous bleeding episodes 8-12 on subsequent bleeding. The effects of treatment were not evaluated, except that it was obvious that hemorrhage recurred at the same rate in patients treated medically as in those treated surgically t is important to emphasize that only patients followed for 1 year or longer are considered in the base line for calculations of results in recurrent hemorrhage. The patients evaluated in this study

5 April 1967 HEMORRHAGE N PEPTC ULCER 635 TABLE 7. Effect of age at initial hemorrhage on severity of recurrent hemorrhage (first recurrence) Age Total cases Severity of recurrence Unknown yr. no. % no. % no. % no. % no. % Under and over Total TABLE 8. Effect of severity of initial hemorrhage on severity of recurrent hemorrhage (first recurrence) Severity of initial hemorrhage Total cases Severity of recurrent hemorrhage Unknown 110. % no. % no. % no. % no. % and over Unknown level Total were a composite group, cared for in general hospitals with the equipment and personnel usually available, and treated by many physicians with varying degrees and types of training. Most of the deaths in this series have been reported previouslyp The effect of the sex of the patients on hemorrhage was not determined. nitial hemorrhage. n the present series, the over-all mortality rate in the initial hemorrhage was 5%, comparing favorably with the experience of others. The 17.8% death rate in surgically treated patients during the initial hemorrhage was similar to t hat in previous reports. The care rendered these patients was judged comparable to that of patients in other studies., 3, 8,11-25 No attempt has been made to evaluate these data with reference t o changes in mortality resulting from differences in selection of patients for surgery. Mortality increased with advancing age. The difference in the percentage of deaths in patients over 50 as opposed to those under 50 was significant. 1, 9, 13, 15, 26 However, there was no significant difference in the percentage of deaths between patients under 50 and those 50 through 79. A sharp increase in percentage of patients dying occurred at 80 years of age and above. No significant difference was noted in the death rate of patients requiring 0 to 3 and those needing 4 to 6 transfusions. Mortality was almost 5 times greater in those patients who received 7 to 9 units of blood, and 9 times higher with 10 or more transfusions. Others have noted this same type of correlation. 25, 26 The sharp rise occurred regardless of whether patients were managed medically or by surgery.27, 28 Recurrent hemorrhage. Of 131 patients surviving the initial hemorrhage, and followed for 5 years or more, 30% had one or more recurrences ;3, 7, 18, 29 these were at random. Eleven per cent had two or more recurrences. A patient with a first recurrence had a 38% chance of a second recur-

6 636 BORLAND ET AL. Vol. 52, No.4- renee. Of those having a second recurrence, 33% had a third. The age of the patient did not correlate with the severity (as determined by comparing groups having 0 to 6 transfusions with those having 7 or more), or the frequency of the recurrences (tables 5 and 7). The severity of each recurrent hemorrhage tended to be no greater than that of the initial or preceding hemorrhage (table 8). For example, an 84-year-old man with multiple bleeding episodes was followed for 18 years. He required no transfusions for his last three hemorrhages, despite the necessity for multiple transfusions previously. The group followed after an initial bleeding episode was a selected one, because 23 patients died with the initial episode. There is no evidence, however, that the type of treatment in the initial episode affected the frequency of recurrences or the mortality rate in these patients. 3o Only two deaths resulted in the 105 patients who had 173 episodes of recurrent hemorrhage. No deaths occurred from bleeding after the second hemorrhage, regardless of the age of the patient, the severity of the initial hemorrhage, the number of bleeding episodes, or the method of management. Each subsequent bleeding episode must be considered individually, and judgment in patient care in the individual episode should not be affected unduly by the specter of what may transpire in subsequent hemorrhages. Summary An evaluation of the effects of age and severity of hemorrhage on recurrent bleeding from peptic ulcer in a series of patients in Jacksonville, Florida, is presented. n the initial bleeding episodes, a marked increase in mortality occurred when more than 7 units of blood were required. There was no positive correlation between the severity of the initial hemorrhage and the number or severity of recurrent hemorrhages. The age of the patient at the initial hemorrhage did not significantly affect the number or severity of recurrent bleeding episodes. The severity of recurrent hemorrhage did not increase with the number of recurrences. n the 173 recurrent hemorrhages, there were only two deaths. No deaths occurred from the bleeding after the second recurrence, regardless of age, severity of initial hemorrhage, or method of treatment. REFERENCES 1. Crohn, B. B Need for aggressive therapy in massive upper gastrointestinal hemorrhage. J.A.M.A. 151: Arias, 1. M., N. Zamcheck, and W. B. Thrower Recurrence of hemorrhage from medically treated gastric ulcers; Fourto eight-year follow-up of forty-seven patients. Arch. ntern. Med. 101: Boles, R. S., Jr., W. J. Cassidy, and S. M. Jordan Medical versus surgical management for the complication of hemorrhage in duodenal ulcer. Gastroenterology 32: Bockus, H. L Gastroenterology, Ed. 2, Vol., p W. B. Saunders Company, Philadelphia. 5. Kelley, H. G., G. N. Grant, and D. W. Elliott Massive gastroduodenal hemorrhage. Arch. Surg. 87: Mustard, R. A Massive gastroduodenal hemorrhage; a plan for management. Canad. Med. Assn. J. 85: Donaldson, R. M., Jr., J. Handy, and S. Papper Five-year follow-up study of patients with bleeding duodenal ulcer with and without surgery. New Eng. J. Med. 259: Cooper, D. R., L. H. Stahlgren, L. E. Sylvester, and L. K. Ferguson Surgical treatment of massive upper gastrointestinal hemorrhage. Gastroenterology 34: Jones, F. A Hematemesis and melena; with special reference to causation and to factors influencing the mortality from bleeding peptic ulcers. Gastroenterology 30: Enquist, 1. F., K. E. Karlson, A. M. Tanaka, C. Dennis, S. Fierst, and L. A. Young Statistically controlled evaluation of three methods of managment of upper gastrointestinal bleeding; a progress report. Gastroenterology 32: Palmer, E. D Observations on vigorous diagnostic approach to severe upper gastrointestinal hemorrhage. Ann. ntern. Med. 36: Brown, R. J., and E. T. Thieme Results of conservative treatment of upper

7 April 1967 HEMORRHAGE N PEPTC ULCER 637 gastrointestinal bleeding. Gastroenterology 14: Ferguson, E. F., Jr., and H. W. Reinstine, Jr Teamwork in massive peptic ulcer bleeding; analysis of thirty-four cases of peptic ulcer deaths. J. Florida Med. Assn. 47: Welch, C. E., A. W. Allen, and G. A. Donaldson Management of massive acute upper gastrointestinal hemorrhage. New Eng. J. Med. f!5f!: Kirsner, J. B Peptic ulcer, Worldwide Abstr. Gen. Med. 4: Weinstein, V. A., B. 1. Korelitz, and C. Diaz Protocol for management of massive upper gastrointestinal hemorrhage. New York J. Med. 6f!: Palmer, E. D Diagnosis of upper gastrointestinal hemorrhage. Charles C Thomas, Springfield, ll., 66 p. 18. Chinn, A. B., A. S. Littell, G. F. Badger, and A. J. Beams Acute hemorrhage from peptic ulcer; a follow-up study of 310 patients. New Eng. J. Med. 255: Stewart, J. D., G. M. Sanderson, and C. E. Wiles, Jr Blood replacement and gastric resection for massively bleeding peptic ulcer. Ann Surg. 136: Karlson, K. E., 1. F. Enquist, C. Dennis, and S. Fierst Results of three methods of therapy for massive gastroduodenal hemorrhage; a statistically valid comparison. Ann. Surg.148: Grace, W. J., and W. F. Mitty Does subtotal gastrectomy in bleeding peptic ulcer prevent recurrence of bleeding? Amer. J. Dig. Dis. 7: Stewart, J. D., J. H. Cosgriff, and J. G. Gray Experiences with the treatment of acutely massively bleeding peptic ulcer by blood replacement and gastric resection. Surg. Gynec. Obstet. 103: Welch, C. D Decisions to be made in the management of patients with massive bleeding from the upper gastrointestinal tract. Surg. Clin. N. Amer. 38: Thompson, H. L., J. M. Oyster, J. B. Heid, and T. M. Morgan Hematemesis; study of underlying causes. Gastroenterology 7: Darin, J. C., M. A. Polacek, and E. H. Ellison Surgical mortality of massive hemorrhage from peptic ulcer. Arch. Surg. (Chicago) 83: Bock, D. G., B. D. Rosenak, and R. H. Moser Bleeding from peptic ulcer; a review of 327 cases. J. ndiana Med. Assn. 47: Wirts, C. W., and T. Bodi Management of hemorrhaging gastroduodenal ulcer. J. A. M. A. 163: Hoerr, S. 0., J. E. Dunphy, and S. J. Fray The place of surgery in the emergency treatment of acute massive upper gastrointestinal hemorrhage. Surg. Gynec. Obstet. 87: Fraenkel, G. J., and S. C. Truelove Hematemesis; with special reference to peptic ulcer. Brit. Med. J. 1: Gardner, B., and 1. D. Baronofsky The massively bleeding duodenal ulcer with special reference to crater. Surgery 45:

SURGERY IN BLEEDING PEPTIC ULCERS*

Gut, 1960, 1, 258. SURGERY IN BLEEDING PEPTIC ULCERS* BY J. N. WARD-McQUAID, J. C. PEASE, A. McEWEN SMITH, and R. J. TWORT Mansfield This paper records a study of 400 patients admitted for haematemesis