98 Gastrointestinal Hemorrhage
Definitions
Gastrointestinal (GI) bleeding can occur from anywhere throughout the GI tract. Classically, GI hemorrhage was classified into upper (source proximal to the ligament of Treitz) and lower (source distal to the ligament of Treitz) subgroups. However, new insights into the pathology of bleeding and therapeutic strategies have led to proposals for new categories. Bleeding that originates from the small bowel is now viewed as a separate entity,1,2 and the term lower GI hemorrhage is reserved for bleeding that arises in the colon and/or rectum. This chapter follows this classification scheme.
Epidemiology
Upper GI bleeding occurs more frequently than lower GI bleeding.3 In the United States, the annual incidence of hospitalization for upper GI bleeding is approximately 100 cases per 100,000 adults compared to about 20 cases per 100,000 patients for lower GI bleeding.2,4 GI hemorrhage is most common among the elderly; in this population, the reported incidence is as high as 500 cases per 100,000 people per year. As demographic trends lead to increased numbers of elderly people in the general population, the incidence of GI hemorrhage is expected to steadily rise in the coming years.5,6 Compared to patients with upper GI bleeding, patients with lower GI hemorrhage are less likely to experience shock and usually require fewer blood transfusions.2 Despite improvements in the management of GI bleeding, mortality has remained relatively constant over the last 60 years.7,8 Proposed reasons for the persistence of high mortality include an elderly patient population with many associated comorbidities.9–11 This leads to a high death rate independent of the GI bleeding, with 80% of the mortality attributable to other causes.12
Initial Assessment and Management
Patients with GI bleeding need to be approached like any patient with potentially life-threatening hemorrhage. Although most bleeding episodes are of low magnitude and self-limited, the potential for significant bleeding warrants a thorough evaluation of the patient. Evaluation begins with assessing vital signs and looking for signs of hemodynamic instability. As with any actively bleeding patient, obtaining adequate vascular access is essential. Preferably a large-bore intravenous (IV) catheter (at least 16 gauge) should be inserted in the antecubital fossa of each arm. If quick and easy access is needed due to instability of the patient, a central venous catheter can be inserted. However, the most commonly used central venous catheters are those designed for multiple infusions; since these catheters have multiple lumens with relatively small diameter and the catheters are relatively long, resistance to flow is higher than for short, wide-bore peripheral IV catheters, and achievable fluid administration rates are correspondingly slower.13
The initial laboratory panel should include a complete blood count, serum electrolytes, and a coagulation profile. If coagulopathy is detected, every effort should be made to correct the problem. Extra attention should be paid to certain patient populations. Cirrhotic patients and those taking warfarin will have decreased levels of coagulation factors reflected by an elevated international normalized ratio (INR). Consequently, fresh frozen plasma (FFP) should be administered to correct the coagulopathy. Platelets will be dysfunctional in patients taking aspirin or clopidogrel, and platelet transfusions may be indicated. Patients with renal failure and uremia or those with von Willebrand disease may respond to the administration of IV desmopressin (1-deamino-8-D-arginin vasopressin [DDAVP]; 0.3 µg/kg), a vasopressin analog that promotes von Willebrand factor release from endothelial cells.14,15
Routine endotracheal intubation is not recommended.16–18 However, the threshold for intubation should be low for patients who may be at high risk for aspiration secondary to severe vomiting or mental status changes secondary to conditions like shock or hepatic encephalopathy.
Once stabilized, the source of bleeding should be identified to direct treatment. Active vomiting of blood is indicative of a source of bleeding located in the upper GI tract. For patients who are passing blood per rectum, the bleeding can originate from either the upper GI tract (due to brisk bleeding) or the lower GI tract. A nasogastric tube should be inserted first.2 If the nasogastric aspirate contains bile without blood, it is safe to assume the source of bleeding is distal to the ligament of Treitz.19 A rectal examination should always be performed to rule out anorectal pathology and evaluate the color of stool.2
Whatever the type of GI bleeding, prompt endoscopy is of paramount importance, as this modality not only can help identify the source of bleeding but also offer therapeutic options.20,21 For patients with lower GI bleeding, quick preparation of the colon is usually necessary to allow adequate visualization.6,22 If the patient is hemodynamically unstable and cannot undergo timely colonic preparation, angiography is an alternative to identify and potentially treat the source of bleeding. Angiography can detect a bleeding vessel if the rate of hemorrhage is ≥0.5 mL/min.3 Once an arterial source is identified, treatment with embolization is performed, with a success rate of greater than 90%. Ischemic complications are rare in the upper GI tract, owing to the abundance of collaterals as compared to the lower GI tract.
Although done infrequently out of concerns for uncontrolled bleeding, provocative mesenteric angiography can reveal the source of bleeding in up to 60% of patients when an initial angiogram failed to do so.23 This procedure entails systemic heparinization followed by sequential angiographic injections of a vasodilator and tissue plasminogen activator.
Another useful diagnostic modality is computed tomography (CT) angiography. Its role in the management of GI bleeding is less clear. Although CT angiography appears to be as accurate as conventional angiography for identifying the source of massive GI bleeding,24,25,26 this modality is not useful therapeutically. If a bleeding site is identified using CT angiography, an additional procedure (i.e., surgery or conventional angiography) will be required for treatment.27 Therefore, CT angiography should be employed only when conventional angiography is unavailable. Another proposed use is for identifying bleeding sources originating from the pancreatic ducts or biliary system, as these are not accessible by endoscopy.28
Obtaining a gamma camera scan after injecting autologous technetium-99 (99mTc)-labeled (“tagged”) red blood cells is another way to localize bleeding. This modality is more sensitive than angiography, since tagged red blood cell scans can detect bleeding at rates as low as 0.1 mL/min.3 Studies have shown that scans which become positive within 2 hours are more accurate at identifying the source of bleeding (95%–100%) than scans that show extravasation after 2 hours.2,29 Once the source of bleeding is identified, treatment is determined by the stability of the patient. If the patient is hemodynamically unstable, emergency surgery should be performed, whereas a second attempt at angiographic embolization is reasonable for more stable patients.
Upper GI Hemorrhage
Patients with upper GI bleeding tend to present with hematemesis. Upon evaluation, the nasogastric tube aspirate is often bloody. These patients commonly also have melena. If the bleeding is significant, it can be accompanied by hematochezia.2 There are a multitude of potential etiologies for upper GI bleeding, including peptic ulcer disease, variceal hemorrhage, Dieulafoy’s lesion, stress ulceration, Mallory-Weiss tear, esophagitis, and aortoenteric fistulas. Careful evaluation of the patient will help make the appropriate diagnosis.
Common Causes of Upper Gi Bleeding
Peptic Ulcer Disease
Peptic ulcer disease (PUD) is the most common cause of upper GI bleeding. Common underlying etiologies for PUD include the use of nonsteroidal antiinflammatory drugs (NSAIDs) and Helicobacter pylori infection. Many patients with PUD do not have H. pylori infection of the stomach.30 Even when H. pylori infection is present, eradication of H. pylori is unnecessary in the acute setting but is important for long-term prevention of recurrence.31
Significant PUD bleeding is frequently due to a posterior penetrating ulcer in the first portion of the duodenum that erodes into the gastroduodenal artery. The bleeding stops spontaneously in approximately 80% of cases. However, the remaining 20% of patients have recurrent bleeding or do not stop bleeding spontaneously at all.32,33 Historically, surgery was indicated to control the bleeding in a significant number of patients. It is rarely required these days because other less invasive therapies are available.
Early initiation of therapy with a proton pump inhibitor (PPI) is effective in reducing intragastric pH and the need for endoscopic treatment.34 PPIs are more effective than histamine receptor 2 (H2) blockers35–37 or somatostatin.38,39 Administration of large doses of omeprazole after endoscopy (80 mg bolus injection followed by 8 mg/h continuous infusion for 72 hours, and then 40 mg/d orally for 1 week) compared to standard doses has been found to decrease the incidence of recurrent bleeding,32,38,40,41 decrease the need for surgery, and prevent development of shock that leads to death. Unless there is a contraindication, a PPI always should be administered.
Prompt endoscopy is essential, as it allows identification and treatment of the bleeding vessel.20 Some groups report performing endoscopy within 3 hours of admission.9 Endoscopy within 24 hours10,42 has been associated with significant decreases in the incidence of recurrent bleeding, need for surgery, and length of stay. Administration of the prokinetic agent, erythromycin (3 mg/kg IV), before endoscopy can improve visibility during the procedure.43,44
Local injection of epinephrine, thermocoagulation, and application of endoscopic clips are approaches that can be used to stop bleeding. When used alone or in combination,45 these methods are successful in over 90% of cases.46 A detailed description of these endoscopic procedures is beyond the scope of this chapter and will therefore only be discussed briefly to inform the intensivist about possible complications. Injection of diluted epinephrine (1 : 10,000 solution) is effective in stopping bleeding, especially when used in higher volumes.47,48 Several proposed mechanisms include direct vasoconstriction, a tamponade effect related to the volume of injection, and induction of platelet aggregation. Although less frequent with high-volume injections,49 rebleeding can occur in up to 20% of patients treated with epinephrine alone.32 Thermal coagulation is more effective than epinephrine in preventing rebleeding and the need for surgery,32 but it is associated with a 1% risk of perforation.33 Hemoclips can also be applied endoscopically to control a bleeding vessel.50,51 Although very safe, they are difficult to deploy and require expertise that is unavailable in many centers.
Even after initial endoscopic control, rebleeding occurs in as many as 20%33 of patients, resulting in a significant increase in morbidity and mortality.52 In a review of the literature, Elmunzer et al.46 reported several predictive factors for rebleeding, including hemodynamic instability, multiple comorbidities, active bleeding, large ulcer size (>2 cm),33 a posterior duodenal ulcer, and a lesser curvature ulcer.
Identification and treatment of those ulcers with potential for rebleeding is necessary to avoid complications. The Forrest classification is very useful at predicting recurrent bleeding.53 There are three categories based on endoscopic findings. Forrest I lesions are those that are actively bleeding. Forrest II lesions have stigmata of recent bleeding. They are further classified into Forrest IIa lesions where a non-bleeding vessel is visible and Forrest IIb lesions defined by the presence of an adherent clot. Forest III lesions are those that do not have signs of recent bleeding. Forrest I and II lesions have a high incidence of rebleeding. Nearly all Forrest I lesions rebleed.54 In some series, Forrest IIa lesions have rebleeding rates as high as 81%,55–57 although 40% is probably a more accurate number.58 They also are associated with a high mortality rate of 11%. Endoscopic treatment is recommended for Forrest I and IIa lesions.59 The role of endoscopic treatment for Forrest IIb lesions is less clear. Consensus is lacking on the definition of an adherent clot. Many clinicians are reluctant to mobilize a clot because of the potential to promote bleeding.60 Nevertheless, administration of PPIs at high doses can help stabilize the clot and decrease the rebleeding rate.32 Due to poor interobserver reliability in identifying a visible vessel,61,62 Doppler ultrasound has been proposed as another diagnostic modality. Riemann and Rosenbaum55 reported in a prospective randomized controlled trial that Doppler ultrasound is more effective than direct visualization for locating vessels. Patients treated after identification with Doppler ultrasound had a lower incidence of rebleeding and a significant decrease in mortality (0% versus 10%).
Angiography may be needed for patients who continue to bleed despite endoscopic treatment63 or in whom endoscopy cannot be performed. Super-selective embolization controls the bleeding and decreases the complication rate.64 Embolization of an actively bleeding vessel has a high success rate. If a bleeding site cannot be identified, blind embolization is not recommended. However, if the source of bleeding was previously identified endoscopically, blind embolization of the suspected vessels can be as effective as targeted embolization.65–67 A metallic clip placed at the time of endoscopy may be helpful for identifying the area where bleeding occurred.68 If rebleeding takes place, embolization can be attempted a second time for a combined success rate of 95%.65 A potential complication of embolization is contrast-induced acute renal failure, particularly when infusion of a dye load occurs in combination with intravascular volume depletion secondary to hemorrhage.63 Duodenal ischemia is rare and usually can be treated conservatively with PPIs. Mortality is in the range of 10% to 45%, and death is most often related to the presence of comorbid conditions.69,70
A minority of patients require surgical intervention to control the bleeding.71,72 Because surgery is usually performed after failure of endoscopic and/or angiographic embolization, the patients are usually sicker and have a higher mortality rate. Although the reported mortality with surgery is similar to angiographic embolization, the mortality rate after failed embolization has been reported to be as high as 83%.63 The procedure of choice is oversewing of the bleeding vessels with or without an acid-reducing procedure such as a vagotomy and pyloroplasty, a vagotomy and antrectomy, or a highly selective vagotomy. With the current availability of highly effective acid-suppressive medications and H. pylori treatment, extensive surgery is not indicated in these very sick patients.
Variceal Hemorrhage
The second most common cause of upper GI bleeding is variceal hemorrhage. Varices are present in approximately 50% of patients with cirrhosis and become more prominent with advanced liver disease.73 They commonly develop in the lower esophagus and stomach secondary to portal hypertension. The hepatic vein pressure gradient is the main determinant of the propensity for variceal bleeding.74,75 These thin-walled varicose veins, located in the weak lamina propria of the lower esophagus, are especially predisposed to rupture and bleeding.76
Despite recent improvements in medical management of these patients, mortality remains high at 20% in the first 6 weeks.73,77 The rebleeding rate ranges between 30% and 40% in the first 6 weeks and is associated with a 30% mortality rate.78 Because of the high mortality rate, prompt management is crucial. If the diagnosis of variceal hemorrhage is suspected, pharmacologic therapy should be instituted in transit to the hospital.79 If not initiated during transport, vasopressin, the vasopressin analog, terlipressin, somatostatin, or the somatostatin analog, octreotide,80 should be administered upon arrival at the hospital. These agents are effective at controlling hemorrhage from varices in up to 80% of cases. These medications also can facilitate endoscopic visualization by reducing the rate of active bleeding.77,81
Terlipressin is the only agent proven to reduce mortality.82–84 Unfortunately, terlipressin is not available in the United States. It is administered at a dose of 2 mg every 4 to 6 hours for the first 48 hours, followed by half this dose for up to 5 days.85–89 Somatostatin causes splanchnic arteriolar vasoconstriction and decreases the portal venous pressure by decreasing inflow into the portal circulation. It is administered as an initial bolus of 250 µg, which can be repeated up to three times, followed by an infusion of 250 µg/h for up to 5 days to prevent rebleeding.85
The role of octreotide is unclear. Although it has a longer half-life compared to somatostatin, its hemodynamic effects are not as pronounced. It is administered by continuous infusion at 25 or 50 µg/h preceded by a 50- or 100-µg bolus. Although somatostatin and octreotide are similarly successful for controlling variceal hemorrhage, use of these agents alone has not been shown to decrease mortality.90–92 Accordingly, these agents should be used in combination with endoscopic therapy.
Historically, vasopressin has been used successfully to control acute variceal hemorrhage.93 However, administration of vasopressin is associated with serious side effects (myocardial ischemia, mesenteric and limb ischemia, cerebrovascular accidents, and hyponatremia) in a significant number of patients, and it requires the concurrent administration of IV nitroglycerin (10 to 50 µg/minute). Vasopressin is administered as an infusion starting at 0.4 U/min, and the infusion rate can be increased incrementally to 1 U/minute as indicated by the clinical response. Although it controls bleeding in up to 80% of the cases, it does not decrease mortality, most likely because of its propensity to promote ischemia in other vital organs. Therefore, vasopressin should be reserved for those rare circumstances when other more effective drugs are unavailable.
Antibiotics should be started early in a prophylactic fashion, since as many as 20% of patients with cirrhosis and GI bleeding develop infections. Antibiotics have been shown to be effective in reducing the number of infections in these patients, and early administration of appropriate antibiotics has been shown to decrease the incidence of early rebleeding and improve survival.94,95 Ceftriaxone (1 gm IV daily) is the recommended antibiotic. Studies show it to be superior to fluoroquinolones.77 For patients with a history of penicillin allergy, fluoroquinolones can be used as an alternative.73,77
Patients should be admitted to an ICU for close monitoring and management. Endotracheal intubation is usually indicated,77 as these patients are at risk for aspiration and/or hepatic encephalopathy. Resuscitation with crystalloids and packed red blood cells should be initiated promptly to avoid hypovolemia and subsequent complications like renal failure. However, hypervolemia should be avoided. Intravascular volume overload has the potential to exacerbate variceal bleeding.
Esophageal varices can be treated with sclerotherapy or band ligation. The type of endoscopic treatment depends on the experience and expertise of the endoscopist as well as the magnitude of bleeding. Band ligation appears to be superior for reducing the risk of recurrent bleeding after the acute event and has been associated with fewer complications. However, band ligation can be difficult to perform in patients with massive bleeding. In these cases, sclerotherapy is preferred.77 The success of endoscopic treatment is similar to vasoactive drugs, with a rate of 80% to 85%.77,96–99 However, despite similar success rates to vasoactive drugs for controlling bleeding, a recent Cochrane meta-analysis found that sclerotherapy could not be recommended as a first-line treatment, given its higher complication rate. Its use should be reserved for pharmacologic failures.100 Conversely, the combination of pharmacologic and endoscopic treatment in selected patients appears to be superior to vasoactive drugs alone.96,101
Gastric varices bleed less frequently but more intensely than esophageal varices, leading to higher transfusion requirements and mortality.102 The recommended treatment is sclerotherapy with histoacryl glue (N-butyl-2-cyanoacrylate).103 Complications include ulceration of the mucosa and embolic events from the glue.32,77
With massive bleeding, a Sengstaken-Blakemore (S-B) tube or one of its variations can be inserted as a temporizing measure. The S-B tube has fallen out of favor as more effective therapies have become available. The risks of its use include aspiration, esophageal rupture, and an inability to control the bleeding.104–107 However, for selected patients, it can be life saving. The S-B tube has a gastric and an esophageal balloon. The tube does not have to be cooled before insertion.108 Tube placement should be preceded by endotracheal intubation. The tube should be introduced through the nose or, more frequently, through the mouth into the stomach. The position of the distal tube in the stomach should be confirmed by insufflation of air combined with auscultation. Radiographic confirmation has been advocated to avoid insufflation of the gastric balloon in the esophagus, resulting in esophageal rupture.109 After confirming the position of the S-B tube, the gastric balloon is inflated with 500 mL of saline, and gentle traction is applied (approximately 1 kg or the weight of a 1-L IV bag). This maneuver stops bleeding from varices high in the fundus and occludes collaterals from the stomach to the submucosa of the esophagus. If the bleeding stops, the balloon is secured in place using a football helmet or a pulley system connected to an IV pole. If esophageal bleeding persists, the esophageal balloon is inflated next. The inflation port is connected to a manometer, and pressure is gradually increased until the bleeding stops or the pressure equals 45 mm Hg, whichever comes first. Once the bleeding is controlled, the S-B tube is kept in place, usually for 24 hours, before deflating the balloons. This allows preparation for other therapies such as endoscopy or a transjugular intrahepatic portosystemic shunt (TIPS). If bleeding recurs after deflation, the balloons can be reinflated. A method of inserting the S-B under direct vision by endoscopy has been described110; however, it is not clear that this approach reduces the incidence of complications.
If the previously described treatments are unsuccessful, TIPS should be attempted. TIPS placement reduces the hepatic vein pressure gradient and effectively controls bleeding in 90% to 100% of the cases.78 However, emergency TIPS placement is associated with a high incidence of hepatic encephalopathy and a mortality rate as high as 50%.111 In the event TIPS placement is unavailable, a surgical portosystemic shunt should be considered. One surgical approach entails interposition of an 8-mm ringed polytetrafluoroethylene shunt between the portal vein and the inferior vena cava.112 Because of the relatively small diameter of the graft, its placement creates only a “partial” portocaval shunt with preservation of hepatopetal flow, leading to a lower incidence of encephalopathy. In experienced hands, the graft has a 95% patency rate at 7 years. However, even its advocates advise against using this approach if the patient is a candidate for liver transplantation.113 A splenorenal shunt (with or without splenectomy) is another surgical option. The operative mortality for distal splenorenal shunt placement has been reported to be less than for portocaval shunt placement; however, not all experts share this view.113 Although some studies report a similar complication rate and mortality compared to TIPS,114 only a few specialized centers have surgeons who are experienced in performing these difficult procedures for very sick patients.
Less Common Causes of Upper Gi Bleeding
Dieulafoy’s Lesion
A Dieulafoy’s lesion is a large anomalous artery located in the digestive tract; it is responsible for approximately 2% of upper GI bleeds.115–117 These lesions usually are located along the lesser curvature of the stomach near the cardia but can be present anywhere along the GI tract from the mouth to the anal canal.118,119 Dieulafoy’s lesions are most often identified in elderly patients but can occur in younger patients.120,121 Although these lesions may remain asymptomatic, erosion of the overlying mucosa and subsequently into the artery leads to intermittent brisk bleeding. The treatment used to be surgical, but most cases are now treated endoscopically with epinephrine injections, thermal probe coagulation, and/or clips.32,122,123 Occasionally, angiographic embolization is needed to control the bleeding.63,65 Mortality remains high, around 20%, because patients typically have many associated comorbidities.115
Stress Ulceration
Critically ill patients are susceptible to stress-related mucosal damage of the esophagus, stomach, and duodenum. These lesions initially were thought to arise from excessive acid production, but they are now thought to occur as a consequence of insufficient mucosal perfusion. When stress ulcers were first described in the 1960s, approximately 10% to 20% of patients admitted to ICUs with multiple organ failure developed overt hemorrhage; 2% to 5% of them progressed to more extensive and even lethal bleeding. In the past, surgery was commonly needed to control the bleeding, although surgical intervention for stress ulceration is now exceedingly rare. Several surgical procedures were employed, including vagotomy and pyloroplasty, antrectomy, total gastric devascularization, and total or near-total gastrectomy, but the mortality rate for these operations was exceedingly high (33% to 48%).124 In recent years, the combination of stress ulcer prophylaxis, improvements in resuscitation, and other aspects of supportive care have led to a marked decrease in the incidence of hemorrhage from stress erosions. In a landmark paper, Cook et al.125 demonstrated that significant bleeding occurred only in patients who required mechanical ventilation for more than 48 hours or were coagulopathic. The group even suggested that prophylaxis could be withheld unless those risk factors were present. PPIs increase intragastric pH more effectively than H2 blockers126 and are more effective for preventing aspirin-related erosions.127 However, data are insufficient to conclude that PPIs are superior to H2 blockers for preventing stress ulcers.128
Mallory-Weiss Tear
Mallory-Weiss tears are longitudinal lacerations of the mucosa of the distal esophagus, cardia, or a combination of both, resulting in bleeding from submucosal vessels.129 The incidence is variable in different series, but Mallory-Weiss tears account for 3% to 8% of cases of upper GI hemorrhage.10,52,116,117 The laceration is thought to be caused by retching that accompanies vomiting. Mallory-Weiss tears are associated with alcohol abuse, hiatal hernia, and possibly even H. pylori infections. The diagnosis is usually made by endoscopy. The bleeding stops spontaneously in approximately 90% of cases. If the bleeding persists, band ligation or hemoclips are usually effective in controlling it.129,130 Hemoclips appear to be more effective than epinephrine injections. The use of thermocoagulation has not been fully evaluated.32
Esophagitis
Esophagitis previously has been reported as a cause of 5% to 20% of upper GI bleeds.7,116,117 However, recent series report an incidence of around 2%. A possible explanation for this discrepancy is that esophagitis is often observed at endoscopy and presumed to be the source of GI hemorrhage, without actual confirmation that the esophageal mucosa is the site of bleeding.7 Serious bleeding requiring ICU admission is rare and usually caused by an ulcer in the distal esophagus. Hemorrhage from esophagitis is more common in elderly patients,131 and several medications such as potassium chloride and NSAIDs have been associated with this problem.5 The diagnosis is usually made at endoscopy. Treatment, if needed, consists of removing offending medications while adding acid-suppression treatment. Deep ulcers may need endoscopic treatment similar to those described for peptic ulcer disease.
Aortoenteric Fistulas
An aortoenteric fistula is a direct communication between the aorta, or occasionally an iliac artery, and the GI tract. It can happen at any level of the GI tract but is most common at the third portion of the duodenum. Aortoenteric fistula formation is usually the result of aortic reconstruction with a synthetic graft, although other causes have been described, including idiopathic,132 trauma, radiation,133 mycotic aneurysms,134 diverticulitis, and foreign bodies.135–137 Massive bleeding can occur suddenly and is usually fatal, although many patients present with a sentinel bleed days or even weeks prior to the onset of life-threatening hemorrhage. Endoscopy is frequently nondiagnostic, and the diagnosis is usually made by CT scan or angiogram. Endovascular repair has been reported,138–140 but because of the high incidence of delayed bleeding and associated sepsis, it should be used only as a temporizing measure before definitive surgical treatment.141,142 However, for selected patients with a short life expectancy, such as those with advanced cancer, endovascular repair may be an adequate option.143 Definitive treatment involves surgical repair with removal of the graft and creation of an extra-anatomic bypass.
Small-Bowel Bleeding
Bleeding originating in the small bowel has traditionally been classified as lower GI bleeding. However, new diagnostic and therapeutic implications merit its description as a distinct entity. The reported incidence is between 1% and 7% of patients who present with blood per rectum.1,144,145
Prakash and Zuckerman1 described a cohort of 29 patients whose source of bleeding was in the small bowel. In their series, patients bleeding from the small bowel had significantly worse outcomes compared to patients with colonic bleeding. The patients with small-bowel hemorrhage had also undergone more studies before diagnosis of the source was made. A normal upper endoscopy and colonoscopy should alert clinicians to the possibility that the source of bleeding is within the small bowel.
The most common cause of small-bowel bleeding is angiodysplasia, followed by small-bowel tumors.146 Angiodysplasia is associated with advanced age and chronic renal failure.147 Less frequently, the bleeding is caused by inflammation associated with Crohn’s disease,148,149 Meckel’s diverticulum, NSAID or aspirin use,144 Dieulafoy’s lesions,145,150 or small intestinal varices in patients with cirrhosis and portal hypertension.151
The diagnosis is difficult to make and usually is achieved only with the aid of a combination of studies.150 Because of its wide availability, 99mTc-tagged RBC scan is the most commonly used test.1,144 However, because of the high rate of false-positive and false-negative results, the use of this test cannot be recommended.144,152 The intermittent nature of bleeding also results in angiography being positive in only about 50% of cases. Radiographic contrast studies of the small bowel are not advocated. Small-bowel follow-through has very poor sensitivity for identifying the source of bleeding. Enteroclysis, a procedure whereby contrast is instilled directly into the duodenum together with methylcellulose and air to improve visualization, is only marginally better.5
Some experts advocate “push enteroscopy,” whereas others are proponents of capsule endoscopy. Push enteroscopy with a dedicated video enteroscope allows for visualization of the proximal 50 to 100 cm of the small bowel. The advantage of push enteroscopy is that it can be both diagnostic and therapeutic. Although capsule endoscopy appears to be more sensitive than push enteroscopy,153 some patients undergoing this diagnostic approach may need additional procedures afterwards.154,155 In cases of active bleeding, capsule endoscopy has a sensitivity as great as 92%,156 but sensitivity is below 50% in cases characterized by intermittent bleeding.
Double-balloon enteroscopy is a relatively new technique that allows for complete visualization of the small bowel.144,145,150 It uses a dedicated 200-cm enteroscope with two balloons. One of them is attached to the tip of an endoscope and the other to the tip of a flexible overtube. The balloons are sequentially inflated, allowing them to grip the mucosa of the small bowel and advance the endoscope without looping. The enteroscope can be inserted orally, transanally, or both to examine the entire small bowel. Like push endoscopy, double-balloon enteroscopy permits obtaining biopsies and offers the potential for control of the bleeding source. Unfortunately, double-balloon enteroscopy is not yet widely available.
Meckel’s diverticulum is the most common congenital anomaly of the gut and is present in about 1% of the population. Complications due to the presence of a Meckel’s diverticulum are rare. Occasionally, heterotopic gastric mucosa in the diverticulum can cause bleeding. Bleeding related to a Meckel’s diverticulum occurs most frequently in children but should be considered in any patient younger than 40 years of age with evidence of bleeding from the small intestine. If the diagnosis is not established by the techniques discussed earlier, 99mTc-pertechnetate scintigraphy (“Meckel’s scan”) can be used to establish the diagnosis. Surgical resection is the treatment of choice.144
Finally, for patients who continue to bleed, exploratory laparotomy with or without intraoperative enteroscopy is an option to identify and treat the source of bleeding.150
Lower GI Hemorrhage
Colonic Diverticula
Diverticulosis of the colon is an acquired condition that results in herniation of the mucosa through the muscular layer of the colon. Colonic diverticula are prevalent in the western hemisphere but rare in Africa and Asia. Diverticulosis develops with age, being rare before age 40, but with a prevalence of greater than 65% by age 80.2,157 The cause of bleeding episodes is erosion of a vessel (vasa recta) into the diverticulum. Although diverticula are more common in the left colon, a significant number of bleeds originate from the right side. Bleeding stops spontaneously in 80% of cases.2 Identification of the source is usually made with the aid of colonoscopy, which also can be therapeutic. Treatment includes thermocoagulation or epinephrine injection. The use of hemoclips also has been described.158 If endoscopy cannot be performed, angiography can be diagnostic and therapeutic.159 The reported success rate with super-selective embolization exceeds 85%, and the incidence of clinically significant colonic ischemia is very low (<5%).160
Because bleeding tends to be intermittent, and an estimated bleeding rate of greater than 0.5 mL/min is necessary for angiographic visualization, the radiographic procedure sometimes is nondiagnostic. In such cases, provocative angiography can be helpful, leading to identification and successful embolization of the offending vessel in about 30% of cases.23 Provocative angiography entails systemic heparinization plus selective transcatheter injection of a vasodilator and tissue plasminogen activator into the suspected arteries.
If angiography is not possible or available, localization using CT scan may be an option.24,26,161 A limited surgical resection can be undertaken if the source of bleeding is identified. Surgery is indicated when bleeding does not stop. Mortality is high in these patients, approaching 20% even in tertiary centers.160 It is critical to identify the site of bleeding before surgery.162 In retrospective reviews, blind segmental resection is prone to failure and has been associated with a high mortality rate. A subtotal colectomy rather than segmental resection is therefore recommended in those cases where the source cannot be identified preoperatively.157
Angiodysplasia
Angiodysplasias are small, ectatic blood vessels found in the mucosa and submucosa of the GI tract. They are also known as arteriovenous malformations (AVM) or vascular ectasias. Angiodysplastic lesions are present in the GI tract in about 1% of the population.29 They usually are asymptomatic. Angiodysplasia occurs more often in older individuals, and most lesions are located in the right colon, although they can be found in other regions of the GI tract.3 Even though angiodysplasias are arguably the second most common cause of lower GI bleeding, the reported frequency as a cause for lower GI bleeding varies widely from 3% to 37%.22,29,163
Identification by colonoscopy is usually difficult, particularly after administration of opioids or cold water irrigation, as these decrease mucosal blood flow.2 Avoidance of narcotics during colonoscopy or use of a narcotic antagonist have been proposed in small studies as means to facilitate endoscopic visualization of angiodysplasia. However, this approach has not been validated in larger studies.29 Even when angiodysplasias are identified by colonoscopy, they should not be assumed to be the cause of lower GI bleeding unless stigmata of bleeding are visualized.2 Endoscopic treatment entails thermal probe coagulation and injection of epinephrine. It is recommended that for actively bleeding angiodysplasias, treatment should start at the periphery of the lesions to address the feeding vessels before treating the area that is actively bleeding.
Angiography is reserved for patients who cannot undergo colonoscopy because of massive bleeding, or when colonoscopy fails to establish a diagnosis.2 Angiographic diagnosis of angiodysplasia is made by identification of early filling of ectatic veins. Transcatheter embolization can be therapeutic but carries the risk of inducing significant ischemia.3
In selected cases, CT angiography can be as accurate as angiography for establishing the diagnosis and localizing the source of bleeding.24,164,165 If the bleeding cannot be controlled by endoscopic means or angiographic embolization, surgery is indicated.
Inflammatory Bowel Disease
Severe inflammation of the colon accounts for 1%148 to 5%149,166,167 of cases of lower GI hemorrhage. Severe life-threatening bleeding is the primary indication for 10% of emergency colectomies performed for management of complications related to ulcerative colitis. About 1% of patients with Crohn’s disease will also need emergency surgery.29 Medical treatment should be initiated first. Endoscopy can be diagnostic and occasionally therapeutic. Angiography also may have a role in the diagnosis and treatment of these patients. Surgery should be reserved for patients who continue to bleed or experience recurrent bleeding. Colonic bleeding due to ulcerative colitis is usually associated with severe pancolitis149 and should be treated with a subtotal colectomy and ileostomy.168 Identification of the source of hemorrhage is very important in patients with Crohn’s disease; bleeding originates in the small bowel in approximately two-thirds of cases. Limited resections are recommended for these patients.
Neoplasms
Although chronic bleeding from colonic adenocarcinoma or polyps is common,2 massive hemorrhage requiring ICU admission is rare. Colonic polyps can bleed spontaneously or, more commonly, after colonoscopic resection. Nevertheless, in recent series, the incidence of significant post-polypectomy bleeding has been very low (less than 1%).29,120 Major bleeding after polyp resection is usually arterial. It can be treated endoscopically with a combination of thermocoagulation and epinephrine injection.22
Rectal Bleeding
In the elderly population, solitary rectal ulcer must be considered as a possible etiology of lower GI bleeding.169 Patients with this problem usually are bedridden and debilitated with multiple medical comorbidities.170,171 Bleeding can be profuse and life threatening. Multiple therapeutic approaches have been described to control the bleeding, including endoscopic thermocoagulation, placement of vascular clips, and transanal sutures.172
Another cause of rectal bleeding is from radiation-induced proctitis after treatment for prostatic cancer. The mechanism is radiation-induced endarteritis obliterans, which results in neovascularization and the formation of telangiectasias that are prone to bleeding.6 The presentation of bleeding usually occurs within months of radiation but can be delayed for several years.4
Ischemic proctitis,4,173 Dieulafoy’s lesions not associated with solitary rectal ulcers,171,174–176 and stercoral ulcers are less common causes of rectal bleeding and usually can be treated with some variation of the methods described above.
ConclusionKey Points
Lau J, Sung JJ. From endoscopic hemostasis to bleeding peptic ulcers: strategies to prevent and treat recurrent bleeding. Gastroenterology. 2010;138:1252-1254.
Bendtsen F, Krag A, Møller S. Treatment of acute variceal bleeding. Dig Liver Dis. 2008;40:328-336.
Bai Y, Li ZS. Management of variceal hemorrhage: current status. Chin Med J. 2009;122:763-765.
This editorial offers a concise summary of the current strategies to stop acute variceal bleeding.
Prakash C, Zuckerman GR. Acute small bowel bleeding: a distinct entity with significantly different economic implications compared with GI bleeding from other locations. Gastrointest Endosc. 2003;58:330-335.
Barnert J, Messmann H, Medscape. Diagnosis and management of lower gastrointestinal bleeding. Nat Rev Gastroenterol Hepatol. 2009;6:637-646.
A comprehensive review of the causes, diagnosis, and management of lower GI bleeding.
1 Prakash C, Zuckerman GR. Acute small bowel bleeding: a distinct entity with significantly different economic implications compared with GI bleeding from other locations. Gastrointest Endosc. 2003;58:330-335.
2 Barnert J, Messmann H, Medscape. Diagnosis and management of lower gastrointestinal bleeding. Nat Rev Gastroenterol Hepatol. 2009;6:637-646.
3 Walker TG. Acute gastrointestinal hemorrhage. Tech Vasc Interv Radiol. 2009;12:80-91.
4 Zuckerman GR, Prakash C. Acute lower intestinal bleeding: part I: clinical presentation and diagnosis. Gastrointest Endosc. 1998;48:606-617.
5 Lingenfelser T, Ell C. Gastrointestinal bleeding in the elderly. Best Pract Res Clin Gastroenterol. 2001;15:963-982.
6 Barnert J, Messmann H. Management of lower gastrointestinal tract bleeding. Best Pract Res Clin Gastroenterol. 2008;22:295-312.
7 van Leerdam ME. Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol. 2008;22:209-224.
8 Hershcovici T, Haklai Z, Gordon ES, Zimmerman J. Trends in acute non-variceal bleeding in Israel in 1996-2007: A significant decrease in the rates of bleeding peptic ulcers. Dig Liver Dis. 2010;42:477-481.
9 Henrion J, Schapira M, Ghilain JM, et al. Upper gastrointestinal bleeding: What has changed during the last 20 years? Gastroenterol Clin Biol. 2008;32:839-847.
10 Cooper GS, Chak A, Way LE, Hammar PJ, Harper DL, Rosenthal GE. Early endoscopy in upper gastrointestinal hemorrhage: associations with recurrent bleeding, surgery, and length of hospital stay. Gastrointest Endosc. 1999;49:145-152.
11 Imperiale TF, Dominitz J, Provenzale DT, et al. Predicting poor outcome from acute upper gastrointestinal hemorrhage. Arch Intern Med. 2007;167:1291-1296.
12 Sung JJ, Tsoi KK, Ma TK, Yung MY, Lau JY, Chiu PW. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases. Am J Gastroenterol. 2010;105:84-89.
13 Committee on Trauma ACS. Advance Trauma Life Support Student Course Manual, 8th ed. Chicago, IL: American College of Surgeons; 2008.
14 Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. 1997;90:2515-2521.
15 De Meyer SF, Deckmyn H, Vanhoorelbeke K. von Willebrand factor to the rescue. Blood. 2009;113:5049-5057.
16 Allescher HD. Prophylactic endotracheal intubation for emergency endoscopy in critically ill patients? Gastroenterology. 2010;138:1627-1629.
17 Rehman A, Iscimen R, Yilmaz M, et al. Prophylactic endotracheal intubation in critically ill patients undergoing endoscopy for upper GI hemorrhage. Gastrointest Endosc. 2009;69:e55-e59.
18 Rudolph SJ, Landsverk BK, Freeman ML. Endotracheal intubation for airway protection during endoscopy for severe upper GI hemorrhage. Gastrointest Endosc. 2003;57:58-61.
19 Luk GD, Bynum TE, Hendrix TR. Gastric aspiration in localization of gastrointestinal hemorrhage. JAMA. 1979;241:576-578.
20 Spiegel BM. Endoscopy for acute upper GI tract hemorrhage: sooner is better. Gastrointest Endosc. 2009;70:236-239.
21 Cappell MS, Friedel D. Acute nonvariceal upper gastrointestinal bleeding: endoscopic diagnosis and therapy. Med Clin North Am. 2008;92:511-550. vii-viii.
22 Gayer C, Chino A, Lucas C, et al. Acute lower gastrointestinal bleeding in 1,112 patients admitted to an urban emergency medical center. Surgery. 2009;146:600-606. discussion 606-7
23 Kim C, Suhocki P, Miller MJ, Khan M, Janus G, Smith T. Provocative mesenteric angiography for lower gastrointestinal hemorrhage: results from a single-institution study. J Vasc Interv Radiol. 2010;21:477-483.
24 Yoon W, Jeong YY, Shin SS, et al. Acute massive gastrointestinal bleeding: detection and localization with arterial phase multi-detector row helical CT. Radiology. 2006;239:160-167.
25 Ettorre GC, Francioso G, Garribba AP, Fracella MR, Greco A, Farchi G. Helical CT angiography in gastrointestinal bleeding of obscure origin. AJR Am J Roentgenol. 1997;168:727-731.
26 Zink SI, Ohki SK, Stein B, et al. Noninvasive evaluation of active lower gastrointestinal bleeding: comparison between contrast-enhanced MDCT and 99mTc-labeled RBC scintigraphy. AJR Am J Roentgenol. 2008;191:1107-1114.
27 Lim CM, Shridhar I, Tan L, Cheah WK. Contrast CT in localization of acute lower gastrointestinal bleeding. Asian J Surg. 2006;29:92-94.
28 Busch OR, van Delden OM, Gouma DJ. Therapeutic options for endoscopic haemostatic failures: the place of the surgeon and radiologist in gastrointestinal tract bleeding. Best Pract Res Clin Gastroenterol. 2008;22:341-354.
29 Zuckerman GR, Prakash C. Acute lower intestinal bleeding. Part II: etiology, therapy, and outcomes. Gastrointest Endosc. 1999;49:228-238.
30 Adamopoulos AB, Efstathiou SP, Tsioulos DI, et al. Bleeding duodenal ulcer: comparison between Helicobacter pylori positive and Helicobacter pylori negative bleeders. Dig Liver Dis. 2004;36:13-20.
31 Rokkas T, Karameris A, Mavrogeorgis A, Rallis E, Giannikos N. Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc. 1995;41:1-4.
32 Hui AJ, Sung JJ. Endoscopic Treatment of Upper Gastrointestinal Bleeding. Curr Treat Options Gastroenterol. 2005;8:153-162.
33 Wong SK, Yu LM, Lau JY, et al. Prediction of therapeutic failure after adrenaline injection plus heater probe treatment in patients with bleeding peptic ulcer. Gut. 2002;50:322-325.
34 Tajima A, Koizumi K, Suzuki K, et al. Proton pump inhibitors and recurrent bleeding in peptic ulcer disease. J Gastroenterol Hepatol. 2008;23(Suppl 2)):S237-S241.
35 Lin HJ, Lo WC, Cheng YC, Perng CL. Role of intravenous omeprazole in patients with high-risk peptic ulcer bleeding after successful endoscopic epinephrine injection: a prospective randomized comparative trial. Am J Gastroenterol. 2006;101:500-505.
36 Huggins RM, Scates AC, Latour JK. Intravenous proton-pump inhibitors versus H2-antagonists for treatment of GI bleeding. Ann Pharmacother. 2003;37:433-437.
37 Cash BD. Evidence-based medicine as it applies to acid suppression in the hospitalized patient. Crit Care Med. 2002;30:S373-S378.
38 Tsibouris P, Zintzaras E, Lappas C, et al. High-dose pantoprazole continuous infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding. Am J Gastroenterol. 2007;102:1192-1199.
39 Sgouros SN, Bergele C, Viazis N, Avgerinos A. Somatostatin and its analogues in peptic ulcer bleeding: facts and pathophysiological aspects. Dig Liver Dis. 2006;38:143-148.
40 Lau JY, Sung JJ, Lee KK, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med. 2000;343:310-316.
41 Simon-Rudler M, Massard J, Bernard-Chabert B, et al. Continuous infusion of high-dose omeprazole is more effective than standard-dose omeprazole in patients with high-risk peptic ulcer bleeding: a retrospective study. Aliment Pharmacol Ther. 2007;25:949-954.
42 Committee ASGESoPBanerjee S, Cash B, et al. The role of endoscopy in the management of patients with peptic ulcer disease. Gastrointest Endosc. 2010;71:663-668.
43 Frossard JL, Spahr L, Queneau PE, et al. Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Gastroenterology. 2002;123:17-23.
44 Coffin B, Pocard M, Panis Y, et al. Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study. Gastrointest Endosc. 2002;56:174-179.
45 Vergara M, Calvet X, Gisbert JP. Epinephrine injection versus epinephrine injection and a second endoscopic method in high risk bleeding ulcers. Cochrane Database Syst Rev 2007;CD005584.
46 Elmunzer B, Young S, Inadomi J, Schoenfeld P, Laine L. Systematic Review of the Predictors of Recurrent Hemorrhage After Endoscopic Hemostatic Therapy for Bleeding Peptic Ulcers. Am J Gastroenterol. 2008;103:2625-2632.
47 Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD. A prospective, randomized trial of large- versus small-volume endoscopic injection of epinephrine for peptic ulcer bleeding. Gastrointest Endosc. 2002;55:615-619.
48 Park CH, Lee SJ, Park JH, et al. Optimal injection volume of epinephrine for endoscopic prevention of recurrent peptic ulcer bleeding. Gastrointest Endosc. 2004;60:875-880.
49 Liou TC, Lin SC, Wang HY, Chang WH. Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleeding. World J Gastroenterol. 2006;12:3108-3113.
50 Kapetanos D, Beltsis A, Chatzimavroudis G, Katsinelos P. The use of endoclips in the treatment of nonvariceal gastrointestinal bleeding. Surg Laparosc Endosc Percutan Tech. 2009;19:2-10.
51 Quadri A, Vakil N. Peptic ulcer bleeding: clips, heat, and outcome. Am J Gastroenterol. 2002;97:200-201.
52 Kim BJ, Park MK, Kim SJ, et al. Comparison of Scoring Systems for the Prediction of Outcomes in Patients with Nonvariceal Upper Gastrointestinal Bleeding: A Prospective Study. Dig Dis Sci. 2009;54:2523-2529.
53 Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet. 1974;2:394-397.
54 Conrad SA. Acute upper gastrointestinal bleeding in critically ill patients: causes and treatment modalities. Crit Care Med. 2002;30:S365-S368.
55 Riemann JF, Rosenbaum A. The role of Doppler ultrasound in gastrointestinal bleeding. Baillieres Best Pract Res Clin Gastroenterol. 2000;14:495-504.
56 Griffiths WJ, Neumann DA, Welsh JD. The visible vessel as an indicator of uncontrolled or recurrent gastrointestinal hemorrhage. N Engl J Med. 1979;300:1411-1413.
57 Storey DW, Bown SG, Swain CP, Salmon PR, Kirkham JS, Northfield TC. Endoscopic prediction of recurrent bleeding in peptic ulcers. N Engl J Med. 1981;305:915-916.
58 Laine L, Peterson WL. Bleeding peptic ulcer. N Engl J Med. 1994;331:717-727.
59 Consensus conference. Therapeutic endoscopy and bleeding ulcers. National Institutes of Health. Conn Med. 1990;54:22-26.
60 Lennon AM, Kalloo AN. Hydrogen peroxide in upper gastrointestinal bleeding: a coming of age? Dig Dis Sci. 2010;55:223-225.
61 Bour B, Person B, Calès P, et al. Interobserver agreement on endoscopic diagnosis of bleeding peptic ulcers. Gastrointest Endosc. 1997;46:27-32.
62 Lau JY, Sung JJ, Chan AC, et al. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997;46:33-36.
63 Loffroy R, Guiu B. Role of transcatheter arterial embolization for massive bleeding from gastroduodenal ulcers. World J Gastroenterol. 2009;15:5889-5897.
64 Nakasone Y, Ikeda O, Yamashita Y, Kudoh K, Shigematsu Y, Harada K. Shock index correlates with extravasation on angiographs of gastrointestinal hemorrhage: a logistics regression analysis. Cardiovasc Intervent Radiol. 2007;30:861-865.
65 Loffroy R, Guiu B, D’Athis P, et al. Arterial Embolotherapy for Endoscopically Unmanageable Acute Gastroduodenal Hemorrhage: Predictors of Early Rebleeding. Clin Gastroenterol Hepatol. 2009.
66 Loffroy R, Rao P, Ota S, De Lin M, Kwak B, Geschwind J. Embolization of Acute Nonvariceal Upper Gastrointestinal Hemorrhage Resistant to Endoscopic Treatment: Results and Predictors of Recurrent Bleeding. Cardiovasc Intervent Radiol. 2010.
67 Padia SA, Geisinger MA, Newman JS, Pierce G, Obuchowski NA, Sands MJ. Effectiveness of coil embolization in angiographically detectable versus non-detectable sources of upper gastrointestinal hemorrhage. J Vasc Interv Radiol. 2009;20:461-466.
68 Eriksson LG, Sundbom M, Gustavsson S, Nyman R. Endoscopic marking with a metallic clip facilitates transcatheter arterial embolization in upper peptic ulcer bleeding. J Vasc Interv Radiol. 2006;17:959-964.
69 Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol. 1995;90:206-210.
70 Lanas A. Editorial: Upper GI bleeding-associated mortality: challenges to improving a resistant outcome. Am J Gastroenterol. 2010;105:90-92.
71 Lau JY, Chung SC. Surgery in the acute management of bleeding peptic ulcer. Baillieres Best Pract Res Clin Gastroenterol. 2000;14:505-518.
72 Lau J, Sung JJ. From endoscopic hemostasis to bleeding peptic ulcers: strategies to prevent and treat recurrent bleeding. Gastroenterology. 2010;138:1252-1254. 1254.e1
73 Villanueva C, Colomo A, Aracil C, Guarner C. Current endoscopic therapy of variceal bleeding. Best Pract Res Clin Gastroenterol. 2008;22:261-278.
74 Abraldes JG, Villanueva C, Banares R, et al. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48:229-236.
75 Stanley AJ, Hayes PC. Portal hypertension and variceal haemorrhage. Lancet. 1997;350:1235-1239.
76 Sorbi D, Gostout CJ, Peura D, et al. An assessment of the management of acute bleeding varices: a multicenter prospective member-based study. Am J Gastroenterol. 2003;98:2424-2434.
77 Bendtsen F, Krag A, Møller S. Treatment of acute variceal bleeding. Dig Liver Dis. 2008;40:328-336.
78 Kalva SP, Salazar GM, Walker TG. Transjugular intrahepatic portosystemic shunt for acute variceal hemorrhage. Tech Vasc Interv Radiol. 2009;12:92-101.
79 Levacher S, Letoumelin P, Pateron D, Blaise M, Lapandry C, Pourriat JL. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. Lancet. 1995;346:865-868.
80 Moitinho E, Planas R, Bañares R, et al. Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding. J Hepatol. 2001;35:712-718.
81 Avgerinos A, Nevens F, Raptis S, Fevery J. Early administration of somatostatin and efficacy of sclerotherapy in acute oesophageal variceal bleeds: the European Acute Bleeding Oesophageal Variceal Episodes (ABOVE) randomised trial. Lancet. 1997;350:1495-1499.
82 Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev. 2003;CD002147.
83 Bai Y, Gao J, Zou DW, Li ZS. Somatostatin or its analogs and terlipressin: Different evidence levels, Same recommendations? Hepatology. 2008;47:1428.
84 Bai Y, Li ZS. Management of variceal hemorrhage: current status. Chin Med J. 2009;122:763-765.
85 Dell’Era A, de Franchis R, Iannuzzi F. Acute variceal bleeding: pharmacological treatment and primary/secondary prophylaxis. Best Pract Res Clin Gastroenterol. 2008;22:279-294.
86 Döhler KD, Meyer M. Vasopressin analogues in the treatment of hepatorenal syndrome and gastrointestinal haemorrhage. Best Pract Res Clin Anaesthesiol. 2008;22:335-350.
87 Abid S, Jafri W, Hamid S, et al. Terlipressin vs. octreotide in bleeding esophageal varices as an adjuvant therapy with endoscopic band ligation: a randomized double-blind placebo-controlled trial. Am J Gastroenterol. 2009;104:617-623.
88 Krag A, Bendtsen F. Terlipressin vs. octreotide in bleeding esophageal varices. Am J Gastroenterol. 2009;104:2351. author reply 2351-2351; author reply 2352
89 Abid S, Jafri W, Hamid S, Azam Z. Response to Krag and Bendtsen. Am J Gastroenterol. 2009;104:2351-2352.
90 Burroughs AK. Octreotide in variceal bleeding. Gut. 1994;35:S23-S27.
91 Corley DA, Cello JP, Adkisson W, Ko WF, Kerlikowske K. Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology. 2001;120:946-954.
92 Besson I, Ingrand P, Person B, et al. Sclerotherapy with or without octreotide for acute variceal bleeding. N Engl J Med. 1995;333:555-560.
93 Johnson WC, Widrich WC, Ansell JE, Robbins AH, Nabseth DC. Control of bleeding varices by vasopressin: a prospective randomized study. Ann Surg. 1977;186:369-376.
94 Hou MC, Lin HC, Liu TT, et al. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Hepatology. 2004;39:746-753.
95 Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database Syst Rev 2002;CD002907.
96 Villanueva C, Piqueras M, Aracil C, et al. A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol. 2006;45:560-567.
97 Escorsell A, Ruiz del Arbol L, Planas R, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology. 2000;32:471-476.
98 Escorsell A, Bordas JM, del Arbol LR, et al. Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following acute variceal hemorrhage in patients with cirrhosis. Variceal Bleeding Study Group. J Hepatol. 1998;29:779-788.
99 Hartigan PM, Gebhard RL, Gregory PB. Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis. Veterans Affairs Cooperative Variceal Sclerotherapy Group. Gastrointest Endosc. 1997;46:1-7.
100 D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis: a Cochrane meta-analysis. Gastroenterology. 2003;124:1277-1291.
101 Lo GH. Management of acute esophageal variceal hemorrhage. Kaohsiung J Med Sci. 2010;26:55-67.
102 Sarin SK. Long-term follow-up of gastric variceal sclerotherapy: an eleven-year experience. Gastrointest Endosc. 1997;46:8-14.
103 Karnam US, O’Loughlin CJ, Reddy KR. Bleeding gastric varices: stick to the sticky glue. Am J Gastroenterol. 2002;97:199-200.
104 Pinto-Marques P, Romaozinho JM, Ferreira M, Amaro P, Freitas D. Esophageal perforation–associated risk with balloon tamponade after endoscopic therapy. Myth or reality? Hepatogastroenterology. 2006;53:536-539.
105 Seet E, Beevee S, Cheng A, Lim E. The Sengstaken-Blakemore tube: uses and abuses. Singapore Med J. 2008;49:e195-e197.
106 Collyer TC, Dawson SE, Earl D. Acute upper airway obstruction due to displacement of a Sengstaken-Blakemore tube. Eur J Anaesthesiol. 2008;25:341-342.
107 Chien JY, Yu CJ. Images in clinical medicine. Malposition of a Sengstaken-Blakemore tube. N Engl J Med. 2005;352:e7.
108 Dearden JC, Hellawell GO, Pilling J, Besherdas K, Van Someren N. Does cooling Sengstaken-Blakemore tubes aid insertion? An evidence based approach. Eur J Gastroenterol Hepatol. 2004;16:1229-1232.
109 Chong CF. Esophageal rupture due to Sengstaken-Blakemore tube misplacement. World J Gastroenterol. 2005;11:6563-6565.
110 Thomson A. Safe and efficacious placement of Sengstaken-Blakemore tubes. Gastrointest Endosc. 2009;70:401. author reply 401-401; author reply 402
111 Escorsell A, Banares R, Garcia-Pagan JC, et al. TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial. Hepatology. 2002;35:385-392.
112 Collins JC, Ong MJ, Rypins EB, Sarfeh IJ. Partial portacaval shunt for variceal hemorrhage: longitudinal analysis of effectiveness. Arch Surg. 1998;133:590-592. discussion 592-4
113 Klein AS, Smith GW. Portal hypertension. In: Zuidema GD, Turcotte JG, editors. Shackelford’s Surgery of the Alimentary Tract. Philadelphia: W. B. Saunders Company; 1996:413-482.
114 Henderson JM, Boyer TD, Kutner MH, et al. Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial. Gastroenterology. 2006;130:1643-1651.
115 Walmsley RS, Lee YT, Sung JJ. Dieulafoy’s lesion: a case series study. World J Gastroenterol. 2005;11:3574-3577.
116 Marmo R, Koch M, Cipolletta L, et al. Predicting mortality in non-variceal upper gastrointestinal bleeders: validation of the Italian PNED score and prospective comparison with the Rockall score. Am J Gastroenterol. 2010;105:1284-1291.
117 Müller T, Barkun A, Martel M. Non-variceal upper GI bleeding in patients already hospitalized for another condition. Am J Gastroenterol. 2009;104:330-339.
118 Ho KM. Use of Sengstaken-Blakemore tube to stop massive upper gastrointestinal bleeding from Dieulafoy’s lesion in the lower oesophagus. Anaesth Intensive Care. 2004;32:711-714.
119 Jain R, Chetty R. Dieulafoy disease of the colon. Arch Pathol Lab Med. 2009;133:1865-1867.
120 Rockey DC. Lower gastrointestinal bleeding. Gastroenterology. 2006;130:165-171.
121 Njeru M, Seifi A, Salam Z, Ognibene L. Dieulafoy lesion: a rare cause of gastrointestinal bleeding. South Med J. 2009;102:336-337.
122 Yuan Y, Wang C, Hunt RH. Endoscopic clipping for acute nonvariceal upper-GI bleeding: a meta-analysis and critical appraisal of randomized controlled trials. Gastrointest Endosc. 2008;68:339-351.
123 Park CH, Sohn YH, Lee WS, et al. The usefulness of endoscopic hemoclipping for bleeding Dieulafoy lesions. Endoscopy. 2003;35:388-392.
124 Durham RM, Shapiro MJ. Stress gastritis revisited. Surg Clin North Am. 1991;71:791-810.
125 Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330:377-381.
126 Steinberg KP. Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit. Crit Care Med. 2002;30:S362-S364.
127 Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gastroenterology. 2010;138:82-88.
128 Morgan D. Intravenous proton pump inhibitors in the critical care setting. Crit Care Med. 2002;30:S369-S372.
129 Higuchi N, Akahoshi K, Sumida Y, et al. Endoscopic band ligation therapy for upper gastrointestinal bleeding related to Mallory-Weiss syndrome. Surg Endosc. 2006;20:1431-1434.
130 Cho YS, Chae HS, Kim HK, et al. Endoscopic band ligation and endoscopic hemoclip placement for patients with Mallory-Weiss syndrome and active bleeding. World J Gastroenterol. 2008;14:2080-2084.
131 Nahon S, Nouel O, Hagège H, et al. Favorable prognosis of upper-gastrointestinal bleeding in 1041 older patients: results of a prospective multicenter study. Clin Gastroenterol Hepatol. 2008;6:886-892.
132 Bala M, Sosna J, Appelbaum L, Israeli E, Rivkind AI. Enigma of primary aortoduodenal fistula. World J Gastroenterol. 2009;15:3191-3193.
133 Jayarajan S, Napolitano LM, Rectenwald JE, Upchurch GRJ. Primary aortoenteric fistula and endovascular repair. Vasc Endovascular Surg. 2009;43:592-596.
134 Luo CY, Lai CH, Wen JS, Lin BW. Secondary aortocolic fistula: case report and review of the literature. Ann Vasc Surg. 2010;24:256.e5-256.e12.
135 Wilson SE, Owens ML. Aortocolic fistula, a lethal cause of lower gastrointestinal bleeding: report of a case. Dis Colon Rectum. 1976;19:614-617.
136 Kappadath SK, Clarke MJ, Stormer E, Steven L, Jaffray B. Primary aortoenteric fistula due to a swallowed twig in a three-year-old child. Eur J Vasc Endovasc Surg. 2010;39:217-219.
137 Amin S, Luketich J, Wald A. Aortoesophageal fistula: case report and review of the literature. Dig Dis Sci. 1998;43:1665-1671.
138 Burks JAJ, Faries PL, Gravereaux EC, Hollier LH, Marin ML. Endovascular repair of bleeding aortoenteric fistulas: a 5-year experience. J Vasc Surg. 2001;34:1055-1059.
139 Verhey P, Best A, Lakin P, Nachiondo J, Petersen B. Successful endovascular treatment of aortoenteric fistula secondary to eroding duodenal stent. J Vasc Interv Radiol. 2006;17:1345-1348.
140 Biancari F, Romsi P, Perälä J, Koivukangas V, Cresti R, Juvonen T. Staged endovascular stent-grafting and surgical treatment of a secondary aortoduodenal fistula. Eur J Vasc Endovasc Surg. 2006;31:42-43.
141 Baril DT, Carroccio A, Ellozy SH, et al. Evolving strategies for the treatment of aortoenteric fistulas. J Vasc Surg. 2006;44:250-257.
142 Antoniou GA, Koutsias S, Antoniou SA, Georgiakakis A, Lazarides MK, Giannoukas AD. Outcome after endovascular stent graft repair of aortoenteric fistula: A systematic review. J Vasc Surg. 2009;49:782-789.
143 Leonhardt H, Mellander S, Snygg J, Lonn L. Endovascular management of acute bleeding arterioenteric fistulas. Cardiovasc Intervent Radiol. 2008;31:542-549.
144 Gralnek IM. Obscure-overt gastrointestinal bleeding. Gastroenterology. 2005;128:1424-1430.
145 Mönkemüller K, Neumann H, Meyer F, Kuhn R, Malfertheiner P, Fry LC. A retrospective analysis of emergency double-balloon enteroscopy for small-bowel bleeding. Endoscopy. 2009;41:715-717.
146 Pennazio M. Small-bowel endoscopy. Endoscopy. 2008;40:835-842.
147 Yoon W, Kim JK, Kim HK, Han YM, Kang HK. Acute small bowel hemorrhage in three patients with end-stage renal disease: diagnosis and management by angiographic intervention. Cardiovasc Intervent Radiol. 2002;25:133-136.
148 Pardi DS, Loftus EV, Tremaine WJ, et al. Acute major gastrointestinal hemorrhage in inflammatory bowel disease. Gastrointest Endosc. 1999;49:153-157.
149 Berg DF, Bahadursingh AM, Kaminski DL, Longo WE. Acute surgical emergencies in inflammatory bowel disease. Am J Surg. 2002;184:45-51.
150 Raju GS, Gerson L, Das A, Lewis B, Association AG. American Gastroenterological Association (AGA) Institute technical review on obscure gastrointestinal bleeding. Gastroenterology. 2007;133:1697-1717.
151 Lopera JE, Arthurs B, Scheuerman C, Sandoz C, Petersosn S, Castaneda-Zuniga W. Bleeding duodenal: varices treatment by TIPS and transcatheter embolization. Cardiovasc Intervent Radiol. 2008;31:431-434.
152 Zuckerman GR, Prakash C, Askin MP, Lewis BS. AGA technical review on the evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology. 2000;118:201-221.
153 de Leusse A, Vahedi K, Edery J, et al. Capsule endoscopy or push enteroscopy for first-line exploration of obscure gastrointestinal bleeding? Gastroenterology. 2007;132:855-862. quiz 1164-5
154 Laine L, Sahota A, Shah A. Does Capsule Endoscopy Improve Outcomes in Obscure GI Bleeding? Randomized Trial Versus Dedicated Small Bowel Radiography. Gastroenterology. 2010.
155 Cellier C. Obscure gastrointestinal bleeding: role of videocapsule and double-balloon enteroscopy. Best Pract Res Clin Gastroenterol. 2008;22:329-340.
156 Pennazio M. Small-bowel endoscopy. Endoscopy. 2004;36:32-41.
157 Floch MH, White JA. Management of diverticular disease is changing. World J Gastroenterol. 2006;12:3225-3228.
158 Douzinas EE, Bakos D, Andrianakis I, Flevari K, Betrosian AP. Endoclipping in spurting diverticular haemorrhage. Dig Liver Dis. 2009;41:539.
159 Tan KK, Nallathamby V, Wong D, Sim R. Can superselective embolization be definitive for colonic diverticular hemorrhage? An institution’s experience over 9 years. J Gastrointest Surg. 2010;14:112-118.
160 Khanna A, Ognibene SJ, Koniaris LG. Embolization as first-line therapy for diverticulosis-related massive lower gastrointestinal bleeding: evidence from a meta-analysis. J Gastrointest Surg. 2005;9:343-352.
161 Hizawa K, Miura N, Matsumoto T, Iida M. Colonic diverticular bleeding: precise localization and successful management by a combination of CT angiography and interventional radiology. Abdom Imaging. 2009;34:777-779.
162 Kroot EJ, Den Hoed T, De Jonge LC, Jan Bac D. Management of massive lower gastrointestinal bleeding: should there be surgical intervention without initial endoscopy and radiological evidence of the source of bleeding? Eur J Intern Med. 2004;15:193-197.
163 Zuccaro G. Epidemiology of lower gastrointestinal bleeding. Best Pract Res Clin Gastroenterol. 2008;22:225-232.
164 Junquera F, Quiroga S, Saperas E, et al. Accuracy of helical computed tomographic angiography for the diagnosis of colonic angiodysplasia. Gastroenterology. 2000;119:293-299.
165 Mindelzun RE, Beaulieu CF. Using biphasic CT to reveal gastrointestinal arteriovenous malformations. AJR Am J Roentgenol. 1997;168:437-438.
166 Barnacle AM, Aylwin AC, Jackson JE. Angiographic diagnosis of inflammatory bowel disease in patients presenting with gastrointestinal bleeding. AJR Am J Roentgenol. 2006;187:976-985.
167 Farmer RG. Lower gastrointestinal bleeding in inflammatory bowel disease. Gastroenterol Jpn. 1991;26(Suppl 3)):93-100.
168 Hyman NH, Cataldo P, Osler T. Urgent subtotal colectomy for severe inflammatory bowel disease. Dis Colon Rectum. 2005;48:70-73.
169 Tseng CA, Chen LT, Tsai KB, et al. Acute hemorrhagic rectal ulcer syndrome: a new clinical entity? Report of 19 cases and review of the literature. Dis Colon Rectum. 2004;47:895-903. discussion 903-5
170 Motomura Y, Akahoshi K, Matsui N, et al. Clinical and Endoscopic Characteristics of Acute Hemorrhagic Rectal Ulcer, and Endoscopic Hemostatic Treatment: A retrospective study of 95 cases. Colorectal Dis. 2009.
171 Hotta T, Takifuji K, Tonoda S, et al. Risk factors and management for massive bleeding of an acute hemorrhagic rectal ulcer. Am Surg. 2009;75:66-73.
172 Hung HY, Changchien CR, You JF, et al. Massive hematochezia from acute hemorrhagic rectal ulcer in patients with severe comorbid illness: rapid control of bleeding by per anal suturing of bleeder using anoretractor. Dis Colon Rectum. 2006;49:238-243.
173 Yip VS, Downey M, Teo NB, Anderson JR. Management of ischemic proctitis with severe rectal haemorrhage: a case report. World J Gastroenterol. 2006;12:3776-3778.
174 Ruiz-Tovar J, Díe-Trill J, López-Quindós P, Rey A, López-Hervás P, Devesa JM. Massive low gastrointestinal bleeding due to a Dieulafoy rectal lesion. Colorectal Dis. 2008;10:624-625.
175 Azimuddin K, Stasik JJ, Rosen L, Riether RD, Khubchandani IT. Dieulafoy’s lesion of the anal canal: a new clinical entity. Report of two cases. Dis Colon Rectum. 2000;43:423-426.
176 Chen YY, Yen HH. Massive bleeding from a rectal Dieulafoy lesion: combined multidetector-row CT diagnosis and endoscopic therapy. Surg Laparosc Endosc Percutan Tech. 2008;18:398-399.
