Upper gastrointestinal hemorrhage--diagnosis and management.

THE WESTERN Journal of Medicine Refer to: Midgley RC, Cantor D: Upper gastrointestinal hemorrhage-Diagnosis and management. West J Med 127: 371-377, Nov 1977

Upper Gastrointestinal HemorrhageDiagnosis and Management ROBERT C. MIDGLEY, MD, and DAVID CANTOR, MD, Sacramento

The current management of a patient with upper gastrointestinal hemorrhage involves three steps: initial correction of unstable hemodynamics, obtaining the specific diagnosis of the lesion responsible for gastrointestinal blood loss, and therapy directed at the specific bleeding lesion. The current approach to upper gastrointestinal hemorrhage is carrying out upper gastrointestinal endoscopy following stabilization of the patient. Although improved morbidity and mortality statistics have been slow to appear, the use of endoscopy permits appropriate therapy directed at the specific lesion. Specific therapeutic measures have been outlined for seven common causes of upper gastrointestinal hemorrhage. The advent of therapeutic endoscopy promises to bring further advances in therapy in the near future.

ACUTE UPPER GASTROINTESTINAL HEMORRHAGE is a subject which should be periodically reviewed by all physicians treating patients with this disorder. Although the overall mortality has remained fairly stable at 8 to 10 percent over the last 25 years according to various studies,1-3 the methods of diagnosis and treatment have been changing rapidly. This article will review some of the concepts necessary for the current management of a patient with acute upper gastrointestinal hemorrhage. The topic will be discussed in the order that the patient is seen; that is, initial management of the patient before the specific diagnosis is known, methods for obtaining a specific diagnosis, and therapy directed at the specific

diagnosis. From the Section of Gastroenterology, Department of Internal Medicine, University of California, Davis, School of Medicine, Sacramento Medical Center. Submitted, revised, March 14, 1977. Reprint requests to: Robert C. Midgley, MD, Department of Internal Medicine, Section of Gastroenterology, UCD Professional Building, 4301 X Street, Sacramento, CA 95817.

Initial Management The immediate resuscitation of a patient who has bled from his gastrointestinal tract demands precedence over all else. If the initial blood pressure is below 100 mm of mercury systolic or pulse above 120 beats per minute, about 20 percent volume depletion has occurred. In such a patient a large bore intravenous catheter should be placed with immediate administration of fluid, plasma or volume expanders (or both) before the remainder of the evaluation is undertaken. In the initial workup of the patient a pertinent history, physical examination and initial laboratory data should be obtained in a short time. Important points in the history of a patient with gastrointestinal blood loss is the presence or absence of emesis, its approximate quantity and type -this is, clear versus coffee ground versus bright red blood. Melena is indicative of passage of blood through the digestive tract. But, as transit THE WESTERN JOURNAL OF MEDICINE

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UPPER GASTROINTESTINAL HEMORRHAGE

time of blood in thd digestive tract will vary, the absence of melena does not necessarily exclude a major gastrointestinal hemorrhage. The history of initial vomiting of nonbloody emesis followed by hematemesis is especially suggestive of the Mallory-Weiss syndrome. Orthostatic dizziness or syncope is indicative that severe volume depletion has occurred. The patient should always be questioned about alcohol consumption. The history of ingestion of salicylates is extremely important to elicit, in that gastric erosions induced by salicylates can bleed massively. It is important to elicit the past history of peptic ulcer disease because recurrent ulceration is common. It is important to remember, however, that in patients with a known upper gastrointestinal lesion, the acute bleeding episode will be from a different source than the known lesion in 40 percent of these patients,2 therefore limiting the amount of useful information obtainable by history alone. A pertinent physical examination can be carried out quickly. Blood pressure and pulse taken with the patient supine, combined with sitting or standing values, can give important information about the intravascular volume status of the patient. The absence of orthostatic changes usually signifies that a massive hemorrhage has not occurred. The presence of signs of chronic liver disease are readily available on physical examination. Abdominal surgical scars are clues that may indicate a previous operation for peptic ulcer or previous portacaval shunt surgical procedures. Rectal examination or a stool specimen study is important. Nasogastric aspiration, preferably with a large bore Ewald tube, gives much information about the present status of bleeding. The mere passage of the nasogastric tube can produce positive hematest examinations of gastric aspirate. A clear nasogastric aspirate speaks against gastrointestinal hemorrhage above the pylorus although the stomach may be free of blood if bleeding has ceased two to three hours previously. Coffee ground appearing nasogastric aspirate or dark blood aspirated from the stomach signifies that upper gastrointestinal bleeding has occurred and this implies the presence of acid hematin, that is, hemoglobin modified by hydrochloric acid. If this initial coffee ground or dark red aspirate clears after saline or water lavage then this is good evidence that active bleeding has ceased. If there is a persistent pinkish tinge to the nasogastric aspirate after repeated lavage then active hemorrhage persists. 372

NOVEMBER 1977 *

127 * 5

Initial laboratory data will give much information in upper gastrointestinal bleeding. The hematocrit and hemoglobin determinations are more an indicator of the duration of gastrointestinal hemorrhage rather than providing information as to the amount of acute blood loss. Just as the patient can exsanguinate with no blood or melanotic stool in the rectum, so can the patient exsanguinate with a normal hematocrit and hemoglobin. It takes from 12 to 36 hours for the hematocrit and hemoglobin values to drop in acute gastrointestinal hemorrhage. These values are important in assessing the relative amounts of initial packed red cell replacement necessary. The blood urea nitrogen (BUN) level is more an indicator of the volume of blood loss than the hemoglobin. If in a patient with no previous history of renal disease there is a BUN level of above 40 mg per 100 ml, then there is a good likelihood that the patient has had a significant upper gastrointestinal hemorrhage.4 The BUN iS elevated for two reasons. First, the blood in the upper gastrointestinal tract is partially digested and blood proteins are absorbed. Second, the volume depletion produces a prerenal azotemia with consequent elevation of blood urea nitrogen. A serum creatinine determination with the specimen drawn simultaneously with that for the blood urea nitrogen study will rule out significant renal disease as a contributing factor. The prothrombin time is important mainly in alcoholic patients, for abnormal prothrombin time causing a coagulopathy may have to be corrected before control of hemorrhage can be obtained. Estimation of platelets or peripheral smear of blood should be done routinely in that thrombocytopenia associated with chronic liver disease is common. Arterial blood pH should be drawn initially in patients with evidence of massive blood loss in that lactic acidemia can occur due to severe tissue hypoxia seen with massive volume and oxygen carrying capacity depletion present in gastrointestinal hemorrhage. An electrocardiogram should be done. The incidence of silent myocardial infarction in association with gastrointestinal hemorrhage and volume depletion is significant and is an association that can easily be overlooked. The management of the patient will obviously vary if signs of myocardial ischemia are present. Total bilirubin and serum glutamic oxaloacetic transaminase (SGOT) are indicators of acute or chronic liver disease, and the amylase value is helpful in screening for pancreatitis associated with upper

UPPER GASTROINTESTINAL HEMORRHAGE TABLE 1.-Categories of Upper Gastrointestinal Hemorrhage

Nonbleeder Normal Hct/Hgb Negative N/G aspirate No orthostatic BP, P changes Guaiac negative stools Chronic Bleeder Normal or decreased Hct/Hgb Clear N/G aspirate, guaiac negative or positive No orthostatic BP, P changes Guaiac positive stools Acuite, Nonmassive Bleeder Normal Hct/Hgb Coffee ground N/G aspirate, clears with lavage No orthostatic BP, P changes Guaiac positive or negative stools Acute, Massive Bleeder Normal or decreased Hct/Hgb N/G aspirate; bright red blQod, does not fully clear with lavage Orthostatic BP, P changes Guaiac positive or negative stools (See text for further explanation) Hct = hematocrit

Hgb = hemoglobin N/G = nasogastric

BP = blood pressure P = pulse

gastrointestinal hemorrhage. Of course, blood for type and crossmatch should be drawn with the initial laboratory work in all cases where significant hemorrhage is being considered. Serum alcohol or salicylate level determination may be helpful in unreliable patients. Following the above evaluation, the physician treating a patient with gastrointestinal hemorrhage can often categorize the type of bleeding (Table 1). The nonbleeder is a patient who may have had dark emesis and suspected blood loss, who may be malingering, or who may have ingested beets and noticed dark stools, or may have ingested iron or bismuth and noted black stools. In these patients there are normal hematocrit and hemoglobin values, the nasogastric aspirate does not contain blood, there are no orthostatic changes, and the stools are guaiac negative. This patient can be easily managed with reassurance. If there is any doubt whether the patient belongs in this category the patient should be observed, worked-up appropriately and assigned a new category if the diagnosis remains in doubt. The chronic bleeder is a patient who is losing blood through the gastrointestinal tract but is not acutely volume depleted. The patient may have normal or decreased hematocrit and hemoglobin values, he will have clear nasogastric aspirate which may be either guaiac negative or positive, he has no orthostatic blood pressure or pulse

changes, and guaiac positive stools are present. This patient deserves thorough evaluation to determine the source of bleeding. This can be done as an outpatient or the patient can be admitted to hospital, this decision usually dependent upon the hemoglobin level. It is appropriate in this patient to do barium gastrointestinal x-ray studies to determine the possible site of lesion before endoscopy. But endoscopy should follow a noncontributory radiological examination. The next category is the acute nonmassive bleeder. This is the patient who has an acute blood loss from the upper gastrointestinal tract but has not bled enough to cause volume depletion. There is a normal hematocrit and hemoglobin values, coffee ground appearing nasogastric aspirate is present which quickly clears with saline or water lavage. No orthostatic blood pressure nor pulse changes are noted. Stools may be guaiac positive or negative. This patient should be admitted to the hospital for observation and specific therapy. Use of endoscopy within 24 hours will be discussed in a later section, as well as appropriate therapy. The acute massive bleeder represents a medical emergency. In these patients there are normal or decreased hematocrit and hemoglobin levels. The nasogastric aspirate contains bright red blood which does not fully clear with repeated lavage. Orthostatic blood pressure and pulse changes are present and guaiac positive or negative stools may be present in the rectum. The mortality in the acute massive bleeder is significant. In one study5 a high-risk group of patients were defined: that is, patients over 60 years of age with a presenting hemoglobin value below 10 grams per 100 ml who required greater than 6 units of blood transfusion had a mortality between 20 and 50 percent. A systolic blood pressure below 80 mm of mercury on admission is also associated with increased mortality. The acute massive bleeder should be admitted to an intensive care unit. A central venous pressure line should be placed and blood and volume replacement should be begun. With the patient stabilized endoscopy should be carried out as soon as possible. This will be discussed in a later section. Surgical consultation is imperative in all cases of acute massive bleeding.

Obtaining a Specific Diagnosis After the initial management a specific diagnosis should be obtained. Barium x-ray studies THE WESTERN JOURNAL OF MEDICINE

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UPPER GASTROINTESTINAL HEMORRHAGE TABLE 2.-Comparison of Urgent Endoscopy and Radiology* Endoscopy (Percent)

Allen et al (1973) 71 patients positive diagnosis ....... ...... correct diagnosis ....... ...... Wilken (1973) 69 patients positive diagnosis ....... ...... correct diagnosis ....... ......

Endoscopy Group

Radiology

(Percent)

90 88

54 32

80 78

46 41

Number of patients ........ Diagnosis achieved ......... correct

*From Truelove and Goodman: Topics in Gastroenterology, 19751

have no place at present in the early diagnosis of acute upper gastrointestinal blood loss. Forty percent of duodenal ulcers and 50 percent of gastric ulcers will be missed by an upper gastrointestinal series.6 All acute superficial mucosal lesions will be missed. If more than one lesion is shown present on a barium x-ray study there is no way to definitely know which lesion is responsible for the bleeding. A barium upper gastrointestinal x-ray study may interfere with carrying out arteriography if it is needed in the diagnosis of a massive gastrointestinal hemorrhage. In comparing x-ray studies with endoscopy, recent studies have shown statistically that endoscopy is superior to radiology in obtaining a positive diagnosis (Table 2) .1,7 One recent study has shown that improved overall mortality and improved operative mortality accompany patients in whom diagnosis is made by emergency endoscopy as opposed to those who are handled with a conventional approach (Table 3).8 The approach to diagnosis of upper gastrointestinal hemorrhage has changed greatly since the widespread use of flexible fiberoptic endoscopes. The complication rate is low, being estimated at 1.3 per 1,000 cases.9 Complications are possible and include perforation of the esophagus or stomach, laryngospasm, cardiac arrhythmias in a predisposed patient, aspiration pneumonia and aggravation of bleeding. Upper endoscopy should not be done when a patient is in shock, or when a patient has suffered an acute myocardial infarction or has severe myocardial ischemia as evident on electrocardiogram. Endoscopy should not be done on uncooperative patients or patients with acute respiratory failure. A thoracic aneurysm is a relative contraindication since deaths have been caused by rupture of the aneurysm into the esophagus during endoscopy.10 The exact timing of endoscopy in a patient with gastrointestinal blood loss is important for the

374

TABLE 3.-Results of Urgent Endoscopy and Radiology*

NOVEMBER 1977 * 127 * 5

.........

Radiology Group

105 37% firm +21% possible 30% 92% 15.2% 5.9% 5 days 2 days 14.3% 25.9% 53 96%

Overall mortality .......... Preoperative delay (mean) . . Operative mortality ........ Mean hospital stay in patients not operated upon ..... 1...11 days

19 days

*From Hoare A: Br Med J 1:27-30, 19758

patient's safety, for making an accurate diagnosis and, practically, in relation to the availability of a physician trained in endoscopy. If endoscopy is done prematurely the patient may still be in shock and may be agitated, both precluding adequate sedation and thereby hampering a satisfactory examination. Adequate gastric lavage is important to prevent retained blood obscuring the endoscopist's view. If endoscopy is delayed for undue lengths of time then the lesion responsible for the bleeding may heal. If more than one lesion is present on delayed endoscopy, all nonbleeding, then occasionally it is impossible to know which was the responsible lesion. Also if endoscopy is delayed, therapy cannot be directed at a specific lesion-this requires the use of endoscopic findings. In one study,6 endoscopy done within 24 hours of admission gave the diagnosis in 78 percent of cases. Within 48 hours, 66 percent of lesions were diagnosed. When endoscopy was not done until after 48 hours after admission a diagnosis of a bleeding lesion was obtained in only 32 percent of the cases. Therefore optimal timing in carrying out endoscopy would appear to be within 24 hours of an acute nonmassive hemorrhage, and in acute massive hemorrhage endoscopy should probably be done as soon as the patient is adequately lavaged and volume status is corrected as much as possible. Angiography is important to do in selected cases because it can be therapeutic as well as diagnostic. The patient needs to be actively bleeding at the time of angiography at a rate of greater than or equal to 30 ml per hour in order to visualize extravasation of dye into the bowel lumen which is the only diagnostic sign. Angiography can be done on a rapid bleeder when blood obscures the endoscopist's view, although

UPPER GASTROINTESTINAL HEMORRHAGE TABLE 4.-Causes of Bleeding in 1,400 Patients With Upper Gastrointestinal Hemorrhage* No. of Patients Percent of Patients

Duodenal ulcer .......... Varices ................. Gastric ulcer ............ Gastritis ................ Esophagitis .............. Esophagogastritis ........ Mallory-Weiss syndrome Anastomotic ulcer ........ 24 other diagnoses ....... Undetermined or incorrect .

388 262 176 174 93 16 72 42 79 98

27.71 18.71 12.57

TOTAL ................

1,400

99.98

12.43 6.64 1.14 5.14 3.00 5.64 7.00

*From Palmer E: JAMA 207:1479, 19692

most radiologists recommend that angiography should be preceded by endoscopy so that an idea of which artery to initially cannulate can be obtained." In cases of gastric hemorrhage due to ulcer, gastritis, stress ulcer or Mallory-Weiss tear, selective catheterization of the left gastric artery gives the best results." Control of gastric bleeding with left gastric artery infusion of vasopressin occurred in 82 percent of patients with a 16 percent incidence of recurrent bleeding.'2 In esophageal variceal bleeding, superior mesenteric artery vasopressin infusion is effective in a high percentage of cases.13

The Possible Diagnosis Standard gastrointestinal textbooks can be consulted for an extensive list of possible sources of upper gastrointestinal bleeding. Of all the possible lesions, there are about seven common causes of acute upper gastrointestinal hemorrhage. These are esophagitis, esophageal varices, Mallory-Weiss tear, gastritis and gastric erosions, gastric ulcers, duodenal ulcer and stomal ulcer. In various studies the exact frequency of each specific lesion will vary. In an extensive study published by Palmer in 1969 duodenal ulcer was the most common diagnosis being present in 28 percent of patients, with esophageal varices accounting for 19 percent of the cases (Table 4).2 In a different study at a New York general hospital, acute erosive gastritis was the most common lesion being present in 37 percent of the cases, with esophageal varices being present in 13 percent of the cases.'4 It is important to note that in both studies there was a significant percentage of undiagnosed patients.

Specific Therapy A guide to the relative merits of the various therapeutic measures in the common causes of gastrointestinal bleeding is illustrated in Table 5. In esophagitis, elevation of the head of the bed, abstinence from ethanol and tobacco, and small frequent meals are all useful adjunctive therapeutic measures. Hourly antacid therapy is perhaps the most important measure. Metoclopramide can be used to increase the pressure of the lower esophageal sphincter and thereby reduce acid reflux, although this medication is not available in this country at present. Cholinergic medications also have been shown to decrease symptoms by increasing the lower esophageal sphincter pressure.'5 With the advent of cimetidine, pharmacologic efforts aimed at acid reduction may also be helpful. Continuous close monitoring of the patient is the most important therapeutic measure for early detection of recurrent hemorrhage. Anticholinergics should not be used in the treatment of esophagitis since they will increase gastroesophageal acid reflux by lowering esophageal sphincter pressure. The use of pitressin has been advocated, and surgical intervention may be required in a small percentage of cases. Esophageal variceal bleeding is the cause of death in a third of patients with cirrhosis4 and in one study variceal bleeding carried a 31 percent mortality.' Treatment of variceal bleeding includes volume replacement, although one should be cautious in overenthusiastic or excessive replacement of intravascular volume, in that some studies have suggested that this therapeutic measure may increase portal pressure and lead to increased or recurrent variceal bleeding.'6 Hepatic function should be monitored closely and coagulopathy treated appropriately. Close watch for delirium tremens, withdrawal seizures and hepatic encephalopathy should be maintained. The placement of a Sengstaken-Blakemore tube can temporarily stop esophageal variceal bleeding. Some authors have reported good results with the use of this therapeutic measure.17 Others have noted a high rate of morbidity and mortality from aspiration pneumonia, asphyxiation and esophageal necrosis.'8"19 The use of vasopressin through a catheter placed with radiologic guidance in the superior mesenteric artery is an alternative to the Sengstaken-Blakemore tube. This procedure has been shown to reduce portal pressure by about THE WESTERN JOURNAL OF MEDICINE

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50 percent and, in some reported series, to control variceal bleeding in 85 to 90 percent of cases, although overall survival rate is not altered by the procedure.'3 The use of intravenously given pitressin versus mesenteric arterial administration of pitressin is currently undergoing study.' Emergency portacaval shunt surgical procedures to decompress portal hypertension are associated with a mortality approaching 70 percent when done on an emergency basis.4 A Mallory-Weiss tear is a mucosal and submucosal tear of the esophagus or stomach at or near the gastroesophageal junction. Some 70 to 90 percent of these tears will heal with medical therapy.20 The therapy is mainly supportive including volume replacement, frequent antacids and antireflux measures as outlined above under treatment of esophagitis. In 73 to 100 percent of these cases a tear is associated with a hiatal hernia.20 The tear is often seen with a history of combined salicylate and ethanol ingestion, and the tear is often seen associated with other mucosal abnormalities such as gastritis.20 Occasionally surgical intervention with oversewing of the tear is necessary to control hemorrhage. Hemorrhagic gastritis is often seen with the ingestion of salicylates or ethanol, or both. This lesion may bleed massively on occasion; however, it is often controlled with intensive antacid therapy, and volume replacement. Anticholinergics and the use of pitressin may be of some value. Surgical therapy in these patients is tolerated poorly. A total gastrectomy carries a high morbidity and mortality. A lesser surgical procedure such as partial gastrectomy and vagotomy may be satisfactory in controlling hemorrhage in cases of gastritis that do require operation. The treatment of ulcer diseases such as gastric ulcer, duodenal ulcer and stomal ulcer is basically similar. Antacid therapy and volume replacement and monitoring are the initial important measures. Patients should not be allowed to smoke or to

drink caffeinated or noncaffeinated coffee because it has been shown that ulcer healing is impaired by caffeine or coffee consumption or cigarette smoking. The use of cimetidine has been shown to reduce acid secretion and aid in healing acute duodenal ulcers, although studies are needed in cases of gastric and stomal ulcers. Surgical operation in duodenal ulcer disease can effectively control bleeding. The major decision is the type of surgery to do. A vagotomy and pyloroplasty is simple and can be quickly carried out; however, there is a substantial recurrence rate. The operation, consisting of vagotomy and partial gastrectomy, carries a lower recurrence rate but is a more extensive operation and may not be warranted in an acutely bleeding unstable patient.

New Aspects of Therapy in Upper Gastrointestinal Hemorrhage Perhaps one of the most exciting new aspects in the management of upper gastrointestinal hemorrhage is the advent of therapeutic upper gastrointestinal endoscopy. There are two major mechanisms whereby bleeding can be attacked through the endoscope. The first of these is electrosurgery. Coagulating electrodes are available which can be passed through the conventional endoscope. Coagulation of a bleeding lesion can be done and some researchers have reported good results.2' Problems include the possibility of a through-and-through burn of the gastric wall producing perforation. Also some researchers have noted increased bleeding in certain cases.22 Electrosurgery is still considered experimental but is very promising as an additional useful tool in the therapy of upper gastrointestinal hemorrhage. Laser photocoagulation is now being developed.2"'4 It also can be done through the conventional endoscope. Problems include the expense and the fact that the laser equipment is bulky and may not be transported easily. The problem with perforation due to too intense a laser beam

TABLE 5.-Relative Merits of Various Therapeutic Measures in Common Causes of Gastrointestinal Bleeding Esophagitis

Therapy

Volume replacement and monitoring . . + + + Antacids ...................... + + +

Anticholinergics. Pitressin ............ ........ + Sengslaken-Blakemore tube .......... Nonshunt surgery

..................

.

Portacaval shunt ................... 376

NOVEMBER 1977

*

127

Esophageal Varices

+ ++ +

MalloryWeiss

Gastritis

Gastric Ulcer

+ ++ ++

+ ++ + ++

++ + ++ +

+

+

+

+ ++

_-

++

+

++

+

+

+

+

+

-

++

-

_

*

5

_

Dutodenal Ulcer

+++ +++

Stomal Ulcer

+

+ ++

+


is present. The laser photocoagulation is also considered experimental at this time. Other modalities for endoscopic control of hemorrhage that have been tested but have not been proved yet to be of definitive value are the following: tissue adhesives;25-28 intragastric instillation of norepinephine, 8 mg in 100 mg of saline;29 vasopressin or prostaglandin,30 and compressed air causing a local drying effect.31 Other modalities that require special skills and training include the use of sclerosing agents,32 the use of hemoclips, transhepatic embolization of esophageal varices33 and cryosurgery.34 These newer techniques should be carefully assessed before becoming part of the armamentarium for the treatment of gastrointestinal bleeding.

Conclusions In the management and diagnosis of upper gastrointestinal hemorrhage, initial management is important in stabilization of the patient so that diagnostic measures can be safely undertaken. Although the overall mortality in upper gastrointestinal hemorrhage has remained stable at 8 to 10 percent over the last 25 years, newer studies are beginning to show improved survival with the aggressive use of fiberoptic endoscopy. The era of therapeutic endoscopy is on the horizon and will undoubtedly play a major role in the treatment of acute upper gastrointestinal hemorrhage in the future. REFERENCES 1. Acute uppergastrointestinal hemorrhage, chap 1-5, Itz Truelove SC, Goodman MJ (Eds): Topics in Gastroenterology, Vol. 3, Oxford, Blackwell Scientific Publications, 1975 2. Palmer E: The vigorous diagnostic approach to upper-gastrointestinal tract hemorrhage. JAMA 207:1477-1480, 1969 3. Katon RM, Smith FW: Panendoscopy in the early diagnosis of acute upper gastrointestinal bleeding. Gastroenterology 65:728-734, 1973 4. Law DH, Gregory DH: Gastrointestinal bleeding, chap 16, In Sleisenger MH, Fordtran JS (Eds): Gastrointestinal Disease. Philadelphia, W. B. Saunders, 1973 5. Himal u.S, Watson W, Jones C, et al: The management of upper gastrointestinal hemorrhage. Ann Surg 179:489-4z3, 1972 6. Forrest JA, Finlayson ND, Shearman DJ: Endoscopy in gastrointestinal bleeding. Lancet 2.394-397, 1974 7. Morris DW, Levine GM, Soloway RD, et at: Prospective randomized study of diagnosis and outcome in acute upper

gastrointestinal bleeding: Endoscopy versus conventional radiography. Am J Dig Dis 20:1102-1109, 1975 8. Hoare A: Comparative study between endbscopy and radiology in acute upper gastrointestinal hemorrhage. Br Med J 1:27-30, 1975 9. Silvis SE, Nebel 0, Rogers G, et al: Endoscopic complications. JAMA 235:928-930, 1976 10. Imperato TJ: Personal communication 11. Athanasoulis CA: Angiographic methods for the control of gastric hemorrhage. Am J Dig Dis 21:174-181, 1976 12. Athanasoulis CA, Baum S, Waltman A, et al: Control of acute gastric mucosal hemorrhage. N Engl J Med 290:597-603, 1974 13. Baum S, Nusbaum M: The control of gastrointestinal hemorrhage by selective mesenteric arterial infusion of vasopressin. Radiology 98:497-595, 1971 14. Katz D, Pitchumoni C, Thomas E, et al: The endoscopic diagnosis of upper gastrointestinal hemorrhage-Changing concepts of etiology and management. Am J Dig Dis 21:182-189, 1976 15. Farrell RL, Roling GT, Castell DO: Cholinergic therapy of chronic heartburn-A controlled trial. Ann Intern Med 80:573-576, 1974 16. Reynolds TB: Portal hypertension, chap 13, In Schiff L (Ed): Diseases of the Liver, 4th Ed. Philadelphia, J B Lippincott Co, 1975 17. Pitcher JL: Safety and effectiveness of the modified Sengstaken-Blakemore tube: A prospective study. Gastroenterology 61: 291-298, 1971 18. Conn HO: Hazards attending the use of esophageal tamponade. N Engl J Med 259:701-707, 1958 19. Conn HO, Simpson JA: Excessive mortality associated with balloon tamponade of bleeding varices. JAMA 202:587-591, 1967 20. Knauer C: Characterization of 75 Mallory-Weiss lacerations in 528 patients with upper gastrointestinal hemorrhage. Gastroenterology 71:5-8, 1976 21. Papp JP: Endoscopic electrocoagulation in upper gastrointestinal henmorrhage. JAMA 230:1172-1173, 1974 22. Blackwood WD, Silvis SE: Electrocoagulation of hemorrhagic gastritis. Gastrointest Endosc 18:53-55, 1971 23. Silverstein F, Protell R, Auth D, et al: Comparison of high-power and low-power argon photocoagulation using an animal model of acute bleeding ulcer. Gastroenterology 70:938, 1976 24. Fruhmorgen P: The first successful endoscopic laser coagulations of bleeding and potential bleeding lesions in the human gastrointestinal tract. Presented at the American Society of Gastrointestinal Endoscopy. Miami Beach, Florida, May 1976 25. Lowry ML: Synthetic adhesives-A new hemostatic agent. Arch Surg 60:793, 1950 26. Matsumoto T, Hardaway R, Heisterkamp C, et al: Higher homologous cyanoacrylate tissue adhesives in surgery of internal organs. Arch Surg 94:861, 1967 27. Macoomb RK: Polyurethane foam (ostamer): Its use in experimental animals and in the investigation of tissue reactions. S Forum 11:454, 1960 28. Skeist I (Ed): Handbook of Adhesives. New York, Reinhold Publishing Corp, 1962 29. Kiselow MC, Wagner M: Intragastric instillation of levarterenol. Arch Surg 107:387-389, 1973 30. Wilson DE, Levine RA: Decreased canine gastric mucosal blood flow induced by prostaglandin E A mechanism for its inhibitory effect on gastric secretion. Gastroenterology 56:1268, 1969 31. Katon R: Experimental control of gastrointestinal hemorrhage via the endoscope: A new era dawns. Gastroenterology 70:272-277, 1976 32. Rachail M: Sclerosis of esophageal varices under fiberscope control. Presse Med 4:1659-1660, 1975 33. Coyon D: Transhepatic embolization of esophageal varices. J Radiol Electro Med Nucl 56:117-121, 1975 34. Cahan WG. Five years of cryosurgical experience: Benign and malignant tumors with hemorrhagic conditions, In Rand RW, et al (Eds): Cryosurgery. Springfield, Ill, Charles C Thomas, Publisher, 1968, p 358

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