ACP medicine, 3rd Edition
Elizabeth Rajan MD1
Associate Professor of Medicine
The author has no commercial relationships with manufacturers of products or providers of services discussed in this chapter.
Gastrointestinal (GI) bleeding occurs commonly, has many causes, and ranges from trivial to torrential and life-threatening in severity. Practical classification of GI bleeding—on the basis of presentation, site, and mechanism of the bleed—aids the clinician in selecting an appropriate management algorithm.
GI bleeding is defined as overt when visible red or altered blood is noted in emesis or feces. Overt bleeding is considered major when accompanied by hemodynamic instability and considered minor when not. Occult bleeding is visibly inapparent but is detected directly by stool testing or suggested indirectly by iron deficiency anemia.
GI bleeding occurs when a pathologic process such as ulceration, inflammation, or neoplasia causes erosion of a blood vessel. The size of the eroded artery is an important determinant of the rate of bleeding, the risk of rebleeding, and the clinical outcome. The blood flow and, thus, the rate of blood loss vary directly with the diameter of the vessel; small changes in vessel diameter have dramatic effects on bleeding rates. Most GI bleeds result from erosion of pathologic processes into small vessels and are trivial and self-limited. Erosion into larger vessels can produce lesions that exceed the capacity of normal hemostasis and result in overt major bleeding. A study of the external diameter of arteries in gastric ulcers that bled recurrently showed a range of 0.1 to 1.8 mm, with a mean of 0.7 mm.1 Deep, large ulcers are more likely to erode into large blood vessels. Recurrent or persistent bleeding may result from inadequate vasoconstriction because of large vessel size or inflammatory necrosis of the vessel wall, from pseudoaneurysm formation at the bleeding site, or from systemic coagulopathies.
The reported incidence of GI bleeding varies widely, in part because of varying definitions. Overt minor bleeding, such as from anorectal hemorrhoids, is exceedingly common. Most major bleeding arises from upper GI lesions; the estimated annual incidence ranges from 40 to 150 episodes per 100,000 population.2,3 Mortality from upper GI bleeding has remained at 8% to 10% over the past 50 years.4,5 The fact that, over this period, mortality has failed to decrease substantially despite advances in patient care and technology may reflect the increasing number of elderly patients with complicated comorbidities. Cases in individuals older than 60 years account for 35% to 45% of all cases of acute upper GI bleeding but nearly all of the associated mortality.6 Lower GI sources account for an estimated 15% to 20% of all major GI bleeds. The incidence of lower GI bleeds increases with age.7,8
The causes of GI bleeding are protean [see Table 1]. The most common etiologies are briefly elaborated in this subsection.
Table 1 Major Causes of Gastrointestinal Bleeding
Upper GI Bleeding
Upper GI bleeding is arbitrarily defined as hemorrhage from a source proximal to the ligament of Treitz (i.e., the esophagus, stomach, or duodenum). Hematemesis essentially always reflects upper GI bleeding, and stools may range from black (melena) to bright red (hematochezia), depending on rates of bleeding and intestinal transit.
Peptic ulcer disease
The most common cause of upper GI bleeding is peptic ulcer disease (PUD), accounting for 60% of cases found at emergency endoscopy.9About 50% of patients have a clean-based ulcer with a low probability of rebleeding; only pharmacologic intervention is required in such cases.10 Adherent clots, visible vessels, or active bleeding [see Figure 1] portend progressively less favorable outcomes unless endoscopic or surgical treatment is applied. The two most important risk factors for bleeding in cases of PUD are the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection; heavy alcohol ingestion and smoking are also associated with increased risk.11,12,13
Figure 1. High-risk posterior duodenal bulb ulcer with nonbleeding visible vessel (arrow).
Aspirin and other NSAIDs are responsible for most cases of drug-induced GI bleeding. In the United States, more than 30 billion NSAID tablets are consumed annually. Except for sodium salicylate, all NSAIDs can cause bleeding. Acetaminophen is not associated with GI bleeding.
The elderly are especially susceptible to NSAID-induced GI bleeding.14 NSAIDs may cause bleeding at any level of the GI tract, but they most commonly do so in the stomach or duodenum. Although the bleeding risk increases in proportion to NSAID dose, any amount (including low-dose aspirin taken for prophylaxis against cardiovascular events) may cause bleeding. Use of selective serotonin reuptake inhibitors (SSRIs) is associated with a higher risk of upper GI bleeding, especially in patients who are also taking NSAIDs or low-dose aspirin.15Anticoagulants and nonaspirin antiplatelet drugs do not cause GI bleeding per se, but they can unmask or aggravate hemorrhage from preexisting lesions.
Gastroesophageal variceal bleeding accounts for 10% to 30% of all upper GI hemorrhage. Patients present with overt major bleeding that is sudden in onset. Variceal bleeding is distinctive, with large-volume hematemesis of bright-red blood or clots and associated severe hemodynamic instability [see Figure 2]. Because of the cathartic nature of blood, patients may also present with hematochezia. A prospective review found that 75% of bleeding varices were esophageal and 25% were gastric.16 The most common site of bleeding is the distal 5 cm of the esophagus, because of relatively greater variceal distention and thinner supporting tissue surrounding the veins in this region, compared with the upper and the middle esophagus. Varices are present in 40% to 60% of patients with cirrhosis, and hemorrhage occurs in 25% to 35% of them.17,18,19 Approximately one third of first variceal bleeds are fatal.19 Physicians should bear in mind that in up to half of patients with portal hypertension who experience bleeding, the bleeding has a nonvariceal cause.16
Figure 2. High-risk esophageal varices with red wale marking.
Mallory-Weiss tear is a longitudinal mucosal laceration at the gastroesophageal junction or gastric cardia caused by forceful retching or vomiting. Most tears occur within 2 cm of the gastroesophageal junction on the lesser curvature aspect of the cardia. Mallory-Weiss tears account for 5% to 11% of all major upper GI hemorrhages.20 Most patients present with hematemesis, often associated with alcohol use. Typically, overt bleeding is minor and bleeding ceases spontaneously. Mallory-Weiss tears can also occur with upper GI endoscopy when a patient struggles or retches during the procedure.
Dieulafoy lesions account for approximately 5% of cases of major upper GI bleeding.21 Their characteristic feature is the presence of a large-caliber, tortuous artery in the submucosa close to the mucosal surface, which bleeds upon erosion of the overlying mucosa and artery wall [see Figure 3]. They can be extremely difficult to detect endoscopically unless they are actively bleeding at the time of the procedure. Dieulafoy lesions are usually single lesions located in the proximal stomach. However, these lesions can occur anywhere throughout the GI tract. In a review of 90 Dieulafoy lesions, 34% of the lesions were extragastric.22
Figure 3. Dieulafoy lesion in gastric fundus (arrow).
Lower GI Bleeding
Diverticular disease is one of the most common causes of lower GI bleeding, particularly in the elderly. Diverticulosis is uncommon in persons younger than 40 years, but it affects roughly two thirds of persons older than 80 years.23,24 The mean age period for diverticular hemorrhage is the sixth decade of life. The true incidence of diverticular bleeding is difficult to ascertain, given the different definitions and evaluations used in various studies. Bleeding occurs from an arteriole at either the dome or neck of a diverticulum. Typically, there is no associated diverticulitis. Diverticula are most commonly found in the left colon, but many bleeds arise from diverticula in the right colon. Patients typically present with painless, large-volume hematochezia. Because diverticular bleeding tends to stop spontaneously, the diagnosis is often presumptive and is based on exclusion of other sources of bleeding in a patient with diverticulosis.25
Angiodysplasia is an acquired vascular ectasia that is considered to be degenerative in origin, given its propensity to occur in the elderly. Typically, patients are between 60 and 80 years of age. The pathogenesis of angiodysplasia remains unclear, but a proposed cause is chronic, intermittent, low-grade obstruction of submucosal veins, leading to dilatation of mucosal capillaries [see Figure 4]. The lesions of angiodysplasia are usually small (2 to 5 mm in diameter) and can be single or multiple. These lesions can occur anywhere along the GI tract but are most commonly found in the proximal colon (approximately 80%), particularly the cecum.26 Angiodysplasia is an incidental finding at colonoscopy in 2% of nonbleeding patients older than 65 years.27,28 Fewer than 10% of cases of angiodysplasia are associated with bleeding.27 Bleeding stops spontaneously in the majority of patients, but rebleeding is common.
Figure 4. The lesions of angiodysplasia are usually small (2 to 5 mm in diameter) and can be single or multiple. These lesions can occur anywhere along the GI tract but are most commonly found in the proximal colon, particularly the cecum.
Colonoscopic polypectomy is generally considered a safe procedure, but hemorrhage is reported to occur in 0.3% to 6.0% of cases.29 In a retrospective study of 83 patients who underwent a total of 274 polypectomies, bleeding occurred at a median of 5 days (range, 0 to 17 days) after the procedure.30 Bleeding was associated with advanced age, polyps greater than 1 cm in diameter, sessile polyps, and polyps in the cecum. The prognosis for these patients is favorable. Most cases are managed with observation or endoscopic hemostasis.
Emergent Evaluation and Management
Management of GI bleeding is determined by the severity of the bleed; algorithms differ with regard to major bleeding [see Figure 5] and minor bleeding [see Figure 6]. Patients with overt major bleeding require immediate hospitalization with intensive monitoring. Patients are initially stabilized with fluid and blood component replacement and with correction of any coagulopathy or electrolyte imbalances. Endotracheal intubation may be necessary. Stabilization is followed by immediate endoscopic evaluation and therapy as indicated. If hemorrhage control is ineffective and the patient continues to be hemodynamically unstable, radiologic or surgical interventions are considered.
Figure 5. Evaluation and management of overt major gastrointestinal bleeding
Figure 6. Evaluation and management of overt minor gastrointestinal bleeding. (EGD—esophagogastroduodenoscopy)
Clinical and Laboratory Assessment
The history and physical examination provide vital information on the location, severity, and duration of bleeding and can help identify patients at increased risk for exsanguination and rebleeding [see Table 2]. It is important to remember that patients with overt major bleeding from an upper GI source can present with hematochezia. These patients can experience visceral discomfort and orthostatic symptoms shortly after the onset of bleeding. Abdominal pain—especially periumbilical cramping and gaseous distention—usually indicates rapid intestinal transit of blood and suggests a major bleed.
Table 2 Clinical High-Risk Criteria for Rebleeding and Mortality
The physician should look for evidence of liver disease, PUD, coagulopathy, previous abdominal aortic aneurysm repair, and significant comorbidities such as heart disease and diabetes mellitus. A history of drug or alcohol ingestion may suggest a diagnosis.
After cessation of active upper GI bleeding, patients may experience melena for 2 to 3 days. In itself, such melena is not necessarily an indication of rebleeding, especially if the patient's hemoglobin level does not decrease.
Serial recording of vital signs is crucial in determining whether an overt major bleed has occurred. Significant volume loss is indicated by hypotension (i.e., systolic blood pressure less than 100 mm Hg), orthostasis (i.e., a decrease in systolic pressure of more than 20 mm Hg or an increase in heart rate of more than 20 beats/min), tachycardia (i.e., heart rate greater than 100 beats/min), or a drop in hemoglobin of more than 2 g/dl. Further assessment of skin pallor, features of liver disease or portal hypertension, and stool color as part of the rectal examination can also help with diagnosis or management.
A nasogastric tube can be placed if there is uncertainty about the location of the bleed in a patient with hematochezia or if bleeding persists in a patient with hematemesis. Aspiration of blood indicates a recent upper GI bleed, but absence of blood in the aspirate does not exclude a recent bleed.
The most important laboratory measurement to assess severity of the initial bleed and to monitor rebleeding is the hemoglobin level. An abrupt drop of more than 2 g/dl indicates a significant bleeding episode. An increase in the ratio of blood urea nitrogen to creatinine to more than 25:1 strongly suggests an upper GI source. Measurement of serum electrolyte concentrations, coagulation indices, platelet count, and liver enzyme levels aids in the diagnosis and guides management.
In most patients, the location of the bleed is identified by upper GI endoscopy or colonoscopy. Endoscopy also provides therapeutic options and essential information on the risk of rebleeding [see Table 3]. There are established visual criteria, based on stigmata of recent hemorrhage, that the endoscopist can use to identify patients at high or low risk for rebleeding.
Table 3 Endoscopic High-Risk Stigmata for Rebleeding and Indications for Endoscopic Therapy
During upper GI endoscopy, if massive active bleeding is encountered, it is prudent to discontinue the procedure and protect the airway by endotracheal intubation before proceeding. If visualization is impaired, use of large-bore orogastric lavage or a jumbo-channel (6 mm) therapeutic endoscope to evacuate blood and clots may be effective. Erythromycin lactobionate (125 mg intravenously) can also be used to promote quick intestinal transit of blood when active bleeding has stopped.
Before colonoscopy, whenever possible, patients should receive a rapid colonic lavage with 2 to 3 L of a nonabsorbable polyethylene glycol solution administered through a nasogastric tube over 2 hours to cleanse the colon and facilitate adequate visualization.
Selective visceral angiography is considered when endoscopic therapy for an established lesion has failed and surgery is not an option or when the site of an active bleed remains obscure after endoscopy. An optimal examination with a high positive yield is best obtained when there is active bleeding at rates exceeding 0.5 to 1 ml/min. Significant complications—including contrast reaction, acute renal failure, and femoral artery thrombosis—have been reported in approximately 9% of cases.31,32 The reported sensitivity of angiography varies from 22% to 87%. The specificity approaches 100%.33
Radionuclide Technetium Scan
A technetium-99m-labeled red cell scan should be considered when active bleeding is suspected but the results of endoscopy are negative. Nuclear scans can detect bleeding at rates that exceed 0.1 ml/min. On scans, however, pooled blood may sometimes be mistaken for active bleeding, which contributes to a reported false positive rate of about 22%.34 Upper GI bleeding may be misdiagnosed as lower GI bleeding because of pooling in the distal ileum or right colon. A positive result is more reliable when the scan is done early rather than delayed for several hours.
Endoscopic techniques for examination of the small bowel that are currently available include push enteroscopy, wireless capsule endoscopy, double-balloon enteroscopy, and intraoperative enteroscopy. Push enteroscopy typically reaches into the proximal jejunum only, whereas wireless capsule enteroscopy, double-balloon enteroscopy, and intraoperative enteroscopy reach the entire small bowel.
Push enteroscopy is currently performed using a pediatric colonoscope with or without an overtube. In one study, the diagnostic yield of enteroscopy in overt GI bleeding was 46%; the most common lesions seen were angiodysplasia and ulcers.35
Wireless capsule endoscopy represents a new technology involving an easily swallowed 11 by 26 mm capsule. No sedation is required. The capsule, which is disposable, contains a color video chip, light source, and transmitter. The patient wears an antenna array on a belt (data recorder). While transiting through the intestine by peristalsis, the capsule takes color photos and sends them to the data recorder. These images are then downloaded onto a computer after the examination [see Figure 7]. There is a total of 6 to 8 hours of recording time. This noninvasive technology can provide images of the entire small bowel; however, it is a purely diagnostic modality. This technique may be beneficial in patients with recurrent or occult GI bleeding of obscure origin, but it is not appropriate in hemodynamically unstable patients with major active bleeding. The diagnostic yield of capsule endoscopy in patients with obscure GI bleeding ranges from 45% to 66%.36,37
Figure 7. Capsule endoscopy photograph showing a small-bowel ulcer (arrow) induced by a nonsteroidal anti-inflammatory drug.
Double-balloon enteroscopy is an emerging endoscopic technique that allows visualization of the entire small bowel, as well as tissue acquisition and therapeutic intervention. The procedure is performed using an endoscope and overtube. Two separate latex balloons are attached to the tip of the endoscope and to the overtube; the balloons are inflated and deflated independently, facilitating advancement of the endoscope through the intestine. The endoscope may be passed via an antegrade (oral) or retrograde (anal) approach. The procedure is particularly limited by a long procedure time (approximately 90 minutes), patient discomfort, and need for operator expertise. The diagnostic yield of double balloon enteroscopy in patients with obscure GI bleeding ranges from 60% to 80%.38,39 Its role in the diagnosis and therapy of GI bleeding remains to be defined.
Intraoperative enteroscopy, performed during exploratory laparotomy through single or multiple enterotomy sites, is indicated for the occasional patient with active or recurrent major bleeding of obscure origin. Complications include mucosal laceration, intramural hematoma, mesenteric hemorrhage, and intestinal ischemia.40
A variety of endoscopic modalities are currently available for the management of GI bleeding. These can be categorized as thermal, mechanical, and injection devices. Thermal devices are either contact (e.g., heater probe, multipolar electrocautery) or noncontact (e.g., argon plasma coagulator, laser). These devices generate sufficient heat to create a hemostatic bond through tissue desiccation. The heater probe consists of a Teflon-coated hollow aluminum cylinder with a heating coil. Only heat (no electrical current) is delivered to the tissue. Multipolar or bipolar cautery works by completion of an electrical circuit between two electrodes on the probe tip. The argon plasma coagulator utilizes high-frequency monopolar alternating current delivered to target tissue through ionized argon gas. The conduit of argon gas is called the argon plasma. Electrons flow through a channel of electrically activated, ionized argon gas from the probe electrode to the tissue, causing a thermal effect at the interface. In laser photocoagulation, which is less frequently used, the conversion of light to heat results in coagulation or vaporization of tissue. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser is the most commonly used laser. Mechanical devices for hemostasis include metallic clips and rubber-band ligators. An injection solution that is generally used to achieve hemostasis consists of saline mixed with epinephrine at a 1:10,000 concentration.
These therapeutic modalities are used alone or in combination. A common practice is to start by injecting epinephrine and saline submucosally in the region of active bleeding so as to stop or slow hemorrhaging and therefore allow for adequate inspection. Thermal or mechanical modalities are then used to achieve definitive hemostasis. Prospective, controlled studies have confirmed the benefit of endoscopic intervention in achieving initial hemostasis and in prevention of rebleeding.41 Combination therapy (i.e., injection plus thermal therapy) has been demonstrated to reduce rebleeding rates more successfully than single therapy.42,43 Currently, combination therapy using injection followed by either a thermal or a mechanical intervention is the most effective approach. Rebleeding after endoscopic therapy occurs in approximately 20% of cases, typically within 48 to 72 hours after treatment. However, rebleeding can occur as late as 7 days after therapy.
Initial drug therapy for major nonvariceal upper GI bleeding is directed at gastric acid suppression. In a randomized, double-blind study comparing high-dose omeprazole with placebo, rebleeding after endoscopic therapy occurred less frequently in the omeprazole group (7% versus 23%).44 In general, proton pump inhibitors are administered in doses that reduce gastric acidity. Blood clot stability depends on intragastric pH, with optimum stability at a pH of 6 or higher.45
In patients with PUD, long-term acid suppression and eradication of Helicobacter pylori infection after endoscopic intervention promote ulcer healing, including ulceration at the treatment site, and reduce rebleeding substantially. GI bleeding from NSAIDs is best prevented by avoiding these drugs.
Selective arterial embolization and selective vasoconstriction with intra-arterial infusion of vasopressin are the methods currently available for the control of major nonvariceal GI bleeding. The proponents of embolization favor this form of therapy because it reduces the need for observation in the intensive care unit, and it eliminates indwelling arterial lines, the risk of catheter dislodgement, and problematic systemic side effects of intravenous vasopressin [see Pharmacotherapy, below]. Advances in catheter design have allowed for superselective embolization of vasa recta; in experienced units, this modality is probably the treatment of choice. A study of superselective embolization in 48 patients with lower GI bleeding showed that embolization was the definitive treatment in 44% of patients, with a 27% technical failure rate.46 The risks associated with embolization include misplacement of embolic material, inadvertent distal reflux of embolic agent, and excessive devascularization of an organ leading to ischemia and eventual luminal stenosis. Endoscopy can be helpful in determining ischemic injury if suspected. Microcoils (e.g., stainless steel, platinum), gelfoam pledgets, polyvinyl alcohol particles, and collagen suspensions have been used for embolization.
Intra-arterial vasopressin is the drug of choice for selective vasoconstrictive therapy and is generally infused for a minimum of 24 hours. It is associated with a 70% rate of bleeding control and an 18% rate of rebleeding.47,48,49 Vasopressin may be ineffective when bleeding arises from large arteries that do not constrict in response to therapy. In a study comparing embolization with vasopressin, initial hemostasis rates were similar for the two modalities, but a higher rate of rebleeding was seen with vasopressin.2 The use of intra-arterial provocative mesenteric angiography with heparin and tissue plasminogen activator (t-PA) to aid in diagnosis has been described but is still in the experimental stage.
Despite the high overall success rate of endoscopic therapy in the treatment of major GI bleeding, surgery is still indicated when (1) initial hemostatic control cannot be achieved, (2) rebleeding occurs despite repeated endoscopic sessions, (3) a large (> 2 cm) penetrating ulcer is present, (4) a vessel larger than 2 mm in diameter is visible within the culprit lesion, (5) the ulcer is located in the posterior duodenal bulb (this location is associated with the large gastroduodenal artery), (6) the patient requires substantial transfusion (i.e., four or more units of blood over 24 hours, after preadmission losses have been replaced), and (7) radiologic intervention has failed, is unavailable, or is not appropriate for the particular lesion. The choice of surgery depends on the location of the bleed and the presence of comorbidities. Localization of the site of bleeding is critical for surgical planning.
With variceal bleeding, endoscopic treatment is used primarily for esophageal varices; the techniques include band ligation and sclerotherapy. Band ligation is considered the first-line endoscopic therapy for esophageal varices. The band ligator is readily attached to the distal end of the endoscope, which is advanced to the varix; the endoscopist then suctions the varix into the ligator cap and deploys a rubber band around the varix. This results in the plication of the varices and surrounding submucosal tissue, with fibrosis and eventual obliteration of varices. Comparative studies report a better initial control of bleeding (control rates, 91% versus 77%) and lower rebleeding rates (rebleeding, 24% versus 47%) with band ligation than with sclerotherapy.50 Complications of banding include retrosternal chest pain, dysphagia from compromise of the esophageal lumen, band ulceration (usually superficial ulcers that heal within 2 weeks), or esophageal perforation. Complication rates vary from 2% to 19%.51,52
Sclerotherapy utilizes a variety of sclerosants to induce variceal thrombosis, with sodium tetradecyl sulfate and ethanolamine oleate used most frequently. Intravariceal injections are more effective than paraesophageal injections in controlling bleeding. Compared with a sham injection, sclerotherapy is significantly more likely to stop bleeding (91% versus 60%), reduce mortality during hospitalization (mortality, 25% versus 49%), reduce rebleeding rates (rebleeding, 20% versus 51%), and reduce the need for transfusion (four versus eight units).53Complications of sclerotherapy include retrosternal chest pain, fever, ulceration (usually deep ulcers that heal within 3 weeks), dysphagia, delayed perforation (1 to 4 weeks later), and stricture formation. Complication rates vary from 19% to 35%.50,54,55 The popularity of sclerotherapy has diminished as a result of these complications.
Endoscopic glue injection therapy using cyanoacrylate-based compounds has shown efficacy for the control and prevention of bleeding from gastric varices.56,57 However, this therapy is not yet approved by the Food and Drug Administration.
If bleeding continues despite endoscopic therapy or if endoscopic therapy cannot be initiated, then a modified Sengstaken-Blakemore (Minnesota) tube should be inserted. However, this is only a temporary measure until more definitive treatment—endoscopic, radiologic, or surgical—can be undertaken.
Preventive measures may be indicated in patients with esophageal varices. Preventive measures are generally offered to patients who have a history of GI bleeding and to those who have large esophageal varices without a prior bleeding event. Currently, the accepted preventive measures for variceal bleeding include endoscopic band ligation, beta-blocker therapy, or a combination of both. Ligation is performed every 14 to 21 days until varices are completely eradicated, which typically requires three or four sessions.
In acute variceal bleeding, splanchnic blood flow and portal pressure can be reduced by intravenous infusion of vasoconstrictors such as somatostatin, octreotide, vasopressin, and terlipressin. Somatostatin, a naturally occurring peptide, is reported to stop variceal bleeding in 80% of patients.17,58 Side effects are few and include hyperglycemia and abdominal pain. Octreotide is a synthetic analogue of somatostatin that is preferred because of its longer half-life. The combination of pharmacologic treatment (e.g., octreotide for 5 days) and endoscopic therapy appears to offer better control of acute bleeding than either alone.
Vasopressin is a potent vasoconstrictor that has a reported overall success rate of 50% but a high rebleeding rate when treatment is discontinued.59 It has a short half-life and therefore is given as a continuous infusion. Because of the systemic vasoconstrictive side effects associated with vasopressin that may lead to myocardial or mesenteric ischemia, it is not commonly used. To minimize these side effects, it is given in conjunction with nitroglycerin. Terlipressin is a synthetic analogue of vasopressin that has fewer side effects and a longer half-life and is given in bolus injections.
The role of beta blockers is primarily prophylactic. These agents are not used in the acute management of variceal bleeding. The use of isosorbide mononitrate with beta-blocker therapy does not offer a survival advantage and in fact reduces the tolerability of therapy. In cirrhotic patients with GI bleeding, short-term antibiotic prophylaxis decreases the incidence of infections, particularly spontaneous bacterial peritonitis, and improves survival.60
The radiologic intervention available for variceal bleeding is transjugular intrahepatic portosystemic shunt (TIPS). The accepted indications for TIPS are bleeding or rebleeding that cannot be controlled by either pharmacologic or endoscopic therapy. TIPS is contraindicated in patients with severe hepatic failure, chronic heart failure, hepatic encephalopathy, bile duct obstruction, or cholangitis. TIPS is reported to control bleeding in at least 90% of patients, with rebleeding rates of 12% to 26% at 1 year and 16% to 44% at 2 years.61,62 Patients require close surveillance for shunt dysfunction (evidenced by reduced flow by Doppler ultrasound or the reappearance of varices) because primary shunt patency rates are poor (reported cumulative patency rates of 50% at 1 year and 21% at 3 years), but cumulative secondary shunt patency rates can be as satisfactory as 85% and 55% at 1 and 3 years, respectively.55
TIPS should not be undertaken lightly, because the overall procedure-related mortality can be as high as 1% to 2%,54 largely from intraperitoneal hemorrhage. Other complications include hepatic encephalopathy, portal vein thrombosis, renal failure, sepsis, and stent migration or stenosis.
Surgical intervention is rarely used for variceal bleeding; it is considered when other measures have proved ineffective. Surgical treatments include portosystemic venous shunt operations and esophageal devascularization. A variety of surgical shunts are available. These are generally classified as total, partial, or selective, depending on the intended impact of portal flow diversion. The end-to-side portacaval shunt is a total shunt that diverts all portal blood flow into the inferior vena cava. The side-to-side portacaval shunt diverts only a part of the portal blood flow. Selective shunts decompress variceal flow while preserving portal blood flow. The distal splenorenal shunt is a selective shunt designed to prevent encephalopathy, which is often seen with total shunts. Surgical shunts are used for both esophageal and gastric varices. Encephalopathy, accelerated progression of liver failure, and perioperative morbidity can occur with surgical intervention. Esophageal devascularization may be an effective means of controlling acute variceal bleeding, but bleeding can recur as additional varices develop.
The critical metabolic sequela of occult GI bleeding is iron deficiency.63 Occult GI bleeding causes most cases of iron deficiency in adults, especially in men and postmenopausal women.
Most of the many lesions that cause overt bleeding can also produce occult blood loss. However, variceal and diverticular hemorrhage invariably bleed overtly, whereas lesions such as watermelon stomach (gastric antral vascular ectasia) and diaphragmatic hernia with Cameron erosions tend to bleed occultly. Occult GI bleeding in most patients is suspected only when manifested by fatigue, pallor, or the finding of iron deficiency.
In Western countries, erosive or ulcerative diseases of the esophagus, stomach, and duodenum are the most common GI lesions associated with occult bleeding and iron deficiency anemia. Most peptic ulcer disease is caused by either H. pylori infection or the use of drugs such as aspirin or other NSAIDs. The association between large diaphragmatic hernias and iron deficiency anemia has long been known. A large diaphragmatic hernia is found in about 10% of iron-deficient patients.64 Blood loss in these patients is generally caused by longitudinal mucosal erosions (Cameron erosions) located proximally in the hernia and believed to be secondary to repeated mechanical trauma from respiration.
Cancers and Neoplasms
In adults from Western countries, GI tumors are second only to PUD as a cause of occult bleeding with subsequent iron deficiency anemia.65Colorectal cancer is currently the most common source of occult bleeding from GI tract malignancies.
Vascular malformations are found in approximately 6% of adults with iron deficiency anemia.66,67 Vascular malformations may be acquired or hereditary (hereditary hemorrhagic telan-giectasia). An increasingly recognized and endoscopically treatable vascular lesion is watermelon stomach [see Figures 8a and 8b], which typically presents as iron deficiency anemia in older women.
Figure 8. Watermelon stomach with (a) typical spokes of vascular ectasia radiating from the pylorus into the antrum and (bClose-up view.
When a patient is found to have iron deficiency and occult GI bleeding, it is critical to conduct a thorough GI investigation. Such an evaluation may disclose a health-threatening lesion, in which case specific therapy can be given to prevent associated morbidity and further iron loss. Management with iron therapy and monitoring is not appropriate until a specific lesion has been treated or a lesion has been ruled out as the cause of the iron deficiency [see Figure 9].
Figure 9. Evaluation and management of occult gastrointestinal bleeding.
Regardless of the type of lesion causing the bleeding, treatment with iron supplementation is important to correct iron deficiency. With conditions such as Cameron erosions, iron supplementation is the mainstay of treatment. Most patients can be managed as outpatients. Oral iron therapy with ferrous sulfate is preferred because it is inexpensive, effective, and, in most cases, well tolerated [see 5:II Red Blood Cell Function and Disorders of Iron Metabolism]. The maximal adult dose of ferrous sulfate is 325 mg three times a day. Absorption is not appreciably increased with higher doses. Oral iron is as effective as parenteral iron in repleting iron stores, except in patients with a malabsorption syndrome, and is safer.
Figures 1,2,3,4 and 8 © 2003 Mayo Foundation for Medical Education and Research. Used by permission.
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Editors: Dale, David C.; Federman, Daniel D.