Chapter 11. Gastrointestinal Bleeding

Acute gastrointestinal (GI) hemorrhage is a significant cause of morbidity and mortality in the emergency setting. The source of GI bleeding can range from the esophagus through to the colon and is classified into upper or lower GI bleeding depending on the site of bleeding relative to the ligament of Treitz. Upper GI hemorrhage occurs from sites proximal to the ligament of Treitz frequently due to peptic ulcer disease and variceal hemorrhage and accounts for more than 80% of acute bleeding.1 The majority of lower GI bleeding originates from the colon from pathologies such as diverticular disease and angiodysplasias. The small intestine is the site of hemorrhage in fewer than 5% of patients.1 Hemorrhage persisting or recurring after negative endoscopy is termed obscure bleeding. Occasionally patients present with occult bleeding, where there are no signs of overt bleeding, but the presenting symptoms are due to chronic blood loss and anemia. In all cases, thorough investigation to localize the source of bleeding allows rapid and often definitive management.

Incidence of Acute GI Hemorrhage

The annual incidence of acute upper GI hemorrhage is estimated at 170 cases per 100,000 adults, with an increasing incidence with age. The majority of cases are due to upper GI bleeding, with lower GI bleeding having an annual incidence of only 20.5 per 100,000 adults.2,3 There are geographical variations in the incidence, with reported rates varying from 45 per 100,000 in the Netherlands to 172 per 100,000 in Scotland. This difference is likely related to differences in population demographics and prevalence of various etiological factors between the countries.4–10

Morbidity and Mortality

Despite advances in medical and endoscopic therapies, the mortality from upper GI bleeding remains unchanged at 5–14%,4,5,7–11 and is particularly high in the elderly and hospitalized.12 In fact, recent reports from the United Kingdom highlight an increase in the mortality rates of patients with upper GI bleeding, in part due to the aging population.

Economic Effects

Acute GI bleeding exerts a massive drain on health care resources. Rectal bleeding was the 6th most common symptom and melena the 11th most common symptom requiring an outpatient clinic appointment in 2002,13 while colonic diverticular disease with hemorrhage was the 11th most common cause of inpatient admissions in 2002.13 Approximately 5% of surgery for diverticular disease was necessitated by massive bleeding.14 Diverticular bleeding has been estimated to cost over US $1.3 billion15 while upper GI bleeding exerts an even higher burden on health care systems, costing an estimated US $2.5 billion annually in the United States.16 Variceal bleeding incurred particularly high costs, with an estimated cost of $23,207 per admission for complicated variceal bleeding compared to $5632 for complicated nonvariceal upper GI bleeding. Uncomplicated cases cost $3402 per admission (nonvariceal upper GI bleeding) and $6612 per admission (variceal upper GI bleeding).17

A structured approach is recommended in the initial evaluation and management of the patient with acute GI bleeding (Fig. 11-1). Early resuscitation with the aim of restoring hemodynamic stability is of paramount importance, followed by a careful history and physical examination to identify the etiology and source of bleeding. Particular attention should be paid to comorbidities and the drug history as this may further complicate management. Diagnostic tests are subsequently performed to confirm the site of bleeding, and therapeutic interventions commenced to control active bleeding and prevent future recurrent hemorrhage.

Initial Assessment

Management of resuscitation should follow the principles of the ABCs (airway, breathing, and circulation). Once airway and breathing have been managed, adequate hemodynamic resuscitation is of the highest priority. In particular, the clinician needs to assess the amount of blood lost and the extent of ongoing hemorrhage. Initial evaluation should focus on rapid assessment of the magnitude of both the preexisting deficits and of ongoing hemorrhage. This can be determined by history and examination of the presenting symptoms, which may range from occult bleeding to life-threatening hematemesis and melena. In the majority of cases, a wealth of information can be obtained from simple clinical parameters such as conscious level, blood pressure, and heart rate (Table 11-1), and further facilitated by measurement of urine output as a marker of end-organ perfusion. Depending on the hemodynamic status of the patient and existing comorbidities, more invasive forms of monitoring such as central venous pressure measurements may be of use. Measurement of postural changes (drop in systolic blood pressure >10 mm Hg or increased pulse by >20 beats/min after sitting the patient up for approximately 5 minutes) will identify otherwise undetectable changes in circulating volume in patients with less than 20% circulating volume loss. Tachycardia (>100 beats/min) and a reduced pulse pressure suggest loss of 20–30% of circulating volume. Loss of greater than 40% of circulating volume produces impairment of conscious level (obtundation/agitation), cool, clammy peripheries, and drops the systolic blood pressure to less than 90 mm Hg. Note however that not all patients will demonstrate a tachycardic response to bleeding—occasionally severe blood loss may cause vagal-mediated bradycardia. Similarly, signs of hypotension are less reliable in the elderly and in those on beta-blockers.

While initial blood tests including full blood count and a group and save are essential, a normal hematocrit in the early stages of bleeding may be falsely reassuring, as the hematocrit will only decrease following dilution of the blood volume after resuscitation is commenced.

Resuscitation

The importance of adequate resuscitation cannot be overemphasized. The most important contributor to morbidity and mortality in acute GI bleeding is fulminant multiorgan failure resulting from insufficient resuscitation. The extent of resuscitation necessary will depend on the amount of blood lost and severity of ongoing bleeding. The critical care team should be involved early in the resuscitation process, as early intubation and ventilation will reduce the complications of any respiratory compromise. Large-bore venous access is crucial in the hemodynamically unstable, particularly in those still actively bleeding. Fluid resuscitation in unstable patients should be commenced with a 2-L bolus of crystalloid solution of similar electrolyte composition to whole blood, such as lactated Ringer's. Success of fluid resuscitation should be monitored using simple clinical parameters such as heart rate, blood pressure, and urine output. Urine output is an excellent marker of end-organ perfusion and all hemodynamically unstable patients should be catheterized to allow hourly urine output measurement. A central venous catheter will allow accurate measurement of the preload in those with cardiac, pulmonary, or renal comorbidities, thereby facilitating more sensitive assessment of fluid balance and staving off fluid overload. Supplemental oxygen will maximize oxygen delivery to tissues. The basic blood tests of complete blood count, routine chemistries, and liver function tests should be performed. In addition, in this group of patients a coagulation profile and type and cross-match are essential.

Transfusion

Several factors need to be considered when deciding whether a blood transfusion is required. Of these, the most important are the presence and extent of ongoing bleeding and the response of the patient to fluid resuscitation. Other factors include the age of the patient (young patients are more able to tolerate blood loss than the elderly) and the presence of cardiopulmonary comorbidities that might produce preexisting compromise of tissue perfusion. The hematocrit (which can take 12–24 hours to equilibrate) is not a reliable first indicator of acute blood loss, but a hematocrit below 30% in the elderly and 20% in the young can be used as an index for the requirement for transfusion. The suspected likelihood of rebleeding should also be taken into account; for instance, in cases of upper GI bleeding, a transfusion is more likely to be required for pathology such as esophageal varices that have a high propensity for profuse rebleeding. While whole blood may be used in cases of massive blood loss, packed red cells are the optimal form of transfusion but are defective in clotting factors, calcium, and platelets. Patients requiring massive transfusion (>10 units of blood) must therefore also receive fresh frozen plasma, platelets, and calcium.

Risk Stratification

The development of risk stratification scores has greatly facilitated prediction of mortality and rebleeding as well as decision making regarding the need for hospital admission, intensive care unit (ICU) admission, or urgent investigation in patients with GI bleeding. This allows consistent differentiation of patients requiring only outpatient investigation (eg, in patients with transient rectal bleeding) from urgent therapeutic endoscopy in patients with ongoing upper GI bleeding. The BLEED study identified ongoing bleeding, low blood pressure (systolic blood pressure <100 mm Hg), elevated prothrombin time (>1.2 times control), erratic mental status, and unstable comorbid disease as risk factors for significantly higher rates of surgery, and increased recurrent bleeding and mortality in patients with GI bleeding.18 Other studies have identified hepatic cirrhosis, high Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores, active GI bleeding, hypotension, and end-organ dysfunction as independent predictors for the aforementioned outcomes.19 These studies highlight the importance of comorbidities in determining outcome of GI bleeding. A further study confirmed this by identifying a mortality rate of nearly 30% in patients with significant renal disease and of 65% in patients with acute renal failure.20 At present most of these scoring systems are predominantly used in research studies. There is little consensus on a uniform scoring system for use in the clinical domain, and these scoring systems should be applied with appropriate clinical judgment.

A thorough history and examination will not only assist in diagnosing the cause of the bleeding but will also identify any comorbidity likely to influence outcome.

Important Characteristics of GI Bleeding

Time of onset, volume, and frequency of bleeding are key aspects of the history in determining amount of blood loss. The character of bleeding is also extremely important. Hematemesis is defined as the vomiting of blood, and it usually represents upper GI bleeding (rarely bleeding from the nasopharynx or oropharynx). Hematemesis may be bright red when fresh, but older blood will resemble coffee grounds. Melena is defined as the passage of offensive, black, tarry stool, again usually due to upper GI bleeding. The appearance of the stool is a result of gastric acid degradation (which converts hemoglobin to hematin), as well as the effects of intestinal enzymes and bacteria. Rarely, in cases of slow intestinal transit, blood loss from distal small bowel or the right colon may also present as melena. A guaiac test will allow differentiation of the tarry black stool of melena from the dark green stool of patients on iron supplementation (melena will test positive). Rectal bleeding is called hematochezia—this may represent blood on the tissue paper, blood around the stool, or blood mixed in with the stool, all important features to elicit on history taking. Hematochezia usually results from bleeding from the left side of the colon, usually sigmoid colon or rectum, but may manifest in massive upper GI bleeds with rapid transit through the intestine. Occasionally blood loss is occult, resulting in patients presenting with anemia. In these cases, history taking will identify end-organ symptoms suggestive of reduced oxygen delivery such as syncope, angina, or myocardial infarction.

Other Essential Features in the History

Other useful features to elicit in the history include antecedent vomiting (suggesting a Mallory-Weiss tear), recent weight loss or loss of appetite (suggesting malignancy), recent epigastric pain (possibility of peptic ulceration), and alcohol intake or liver disease (likelihood of variceal bleeding). Demographic data such as age will also assist in narrowing down the cause of bleeding—diverticulitis, angiodysplasias, malignancy, and ischemic colitis are likely culprits in the elderly. In contrast, younger patients are more likely to bleed from peptic ulceration, Meckel's diverticula, hemorrhoids, or esophageal varices. Previous abdominal surgery may be of relevance—previous aortic surgery in particular raises suspicion of aortoenteric fistula. Drug history is especially relevant in upper GI bleeding. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common cause of peptic ulceration, and similarly salicylates and selective serotonin reuptake inhibitors (SSRIs) are also associated with upper GI bleeding.21,22 Use of anticoagulants may require administration of fresh frozen plasma to correct the clotting but is not in itself a predisposing factor for GI bleeding.23

Although bleeding is likely to occur from the esophagus or more distal sites, bleeding from the nasopharynx and oropharynx may occasionally present as GI bleeding and so these sites should be routinely examined. Pigmented lesions in the oral mucosa suggest Peutz-Jeghers disease—a rare cause of GI bleeding. The abdomen should be examined to identify any masses or hepatosplenomegaly. A tender epigastrium is a nonspecific indication of possible peptic ulceration. The neck and groins should be examined for lymphadenopathy suggestive of malignancy. The examination should include inspection for stigmata of liver disease. The jaundiced patient with ascites, caput medusae, and palmar erythema may present with GI bleeding secondary to varices. Rectal examination and anoscopy are essential aspects of the examination to exclude rectal cancer or, more frequently, hemorrhoids.

Insertion of a nasogastric (NG) tube and aspiration may assist in identifying the source of the bleeding. An aspirate positive for blood (either fresh blood or coffee grounds) confirms upper GI bleeding, assesses the rate of bleeding, and allows removal of blood from the stomach to ensure good views of the gastric mucosa during esophagogastroduodenoscopy (EGD).

A negative aspiration of the stomach, however, does not rule out bleeding from the duodenum, as a competent pylorus will prevent reflux of bile, or blood from a bleeding duodenal ulcer, into the stomach. A blood-free bilious aspirate strongly suggests a lower GI source for the bleeding; however, a recent study showed that 20% of patients had a blood-free aspirate from the duodenum despite a diagnosis of upper GI bleeding.24

The Use of Endoscopy in the Management of Upper GI Bleeding

EGD remains the gold standard investigation for the diagnosis and management of upper GI bleeding, as it facilitates identification of the source of bleeding, determining the underlying etiology, achieving hemostasis, and providing prognostic information for risk stratification.25 The timing of the endoscopic assessment in patients with GI bleeding remains controversial. Although there is little doubt that early endoscopy in hemodynamically unstable patients is necessary, the ideal timing for endoscopic intervention in stable patients remains less clear. A recent review of the studies examining the utility of early endoscopic intervention in upper GI bleeding concluded that while endoscopy within 24 hours of presentation was of benefit in terms of aiding risk assessment and reduced length of hospital stay, earlier endoscopies (within 12 hours) offered no additional benefit. Indeed, endoscopy within 12 hours of presentation was associated with unnecessarily increased use of therapeutic endoscopy without any benefit in terms of rate of rebleeding or survival. Overall, these studies suggested that endoscopy should be performed within 24 hours of presentation, and in hospitals without a 24-hour endoscopy service this should be offered to patients the following day.26 Several issues need to be considered regarding the use of EGD in acute GI bleeding—first, the sensitivity of EGD may be reduced in the presence of active bleeding as mucosal visibility is impaired, and second, the rate of complications from EGD (perforation and aspiration) increases in the emergency setting. Airway protection and early intubation in the event of aspiration is therefore essential. Similarly, endoscopy in a patient with a low blood count can exacerbate the effects of sedative medications, causing hypotension and hypoxemia; hence resuscitative measures should not be delayed or paused for the endoscopic procedure. All patients undergoing urgent endoscopy should be continuously monitored using electrocardiogram (ECG) and noninvasive measurement of oxygen saturations.

The Use of Endoscopy in the Management of Lower GI Bleeding

Flexible Sigmoidoscopy versus Colonoscopy

Colonoscopy is recommended over flexible sigmoidoscopy in most cases of lower GI bleeding with few exceptions. Colonoscopy has been deemed the most appropriate investigation in patients older than 50 years with hematochezia or iron deficiency anemia. In younger patients colonoscopy is unnecessary if a convincing benign source of bleeding has been demonstrated with flexible sigmoidoscopy but is necessary in the presence of repeated episodes of bleeding.27

Effectiveness in Identifying the Source of Acute Lower GI Bleeding

Colonoscopy has a diagnostic yield of 89–97% in the setting of acute GI bleeding.28,29 Bowel preparation using polyethylene glycol with a prokinetic such as metoclopramide has been recommended to improve endoscopic visualization and thus diagnostic yield.27,30 This step may have to be omitted in patients with severe ongoing GI bleeding, where there is insufficient time for a formal bowel preparation routine.

Capsule Enteroscopy and Deep Enteroscopy

Lesions of the small bowel causing bleeding are rare and account for only 5% of all GI bleeding. In the United States and Europe, angiodysplastic lesions account for 30–40% of such bleeding; the remaining sources are ulceration, Dieulafoy's lesions, and small bowel neoplasms in 1–3% of patients. Several factors make endoscopic access to the small bowel difficult, including the length of the small bowel, the intraperitoneal location, contractility, and overlying loops. Capsule enteroscopy has emerged as a suitable new option for small bowel imaging and is now the third diagnostic test in patients with obscure bleeding following EGD and colonoscopy.31 The capsules measure 11 × 26 mm and contain a lens, white light-emitting diodes for illumination, silver oxide batteries, and an ultra high frequency (UHF) band radio telemetry transmitter. A capsule delivery device is available for patients with dysphagia, dysmotility disorders, and pediatric patients to deliver the capsule directly to the duodenum. Capsule enteroscopy has a much better yield than push enteroscopy or small bowel series, and an equivalent yield to intraoperative enteroscopy without the attendant morbidity and mortality of the operative procedure.32,33 It must, however, be noted that capsule enteroscopy is unsuitable for imaging of the proximal duodenum because it provides poor visualization of the periampullary region, and the success of capsule enteroscopy is dependent on the experience of the reader.34,35

More recently, newer techniques for imaging of the small bowel (“deep enteroscopy”) have been developed, specifically double-balloon enteroscopy, single-balloon enteroscopy, and spiral enteroscopy. The first two techniques use a balloon to grip the intestinal wall, allowing advancement of the endoscope forward through the intestine. Spiral enteroscopy uses a special overtube with helices at the distal end to pleat the small bowel onto the overtube, again allowing advancement of the endoscope through the intestine. Comparative trials are required to determine the advantages of each system in terms of insertion depth and procedure times. The advantage of these enteroscopic systems over capsule enteroscopy is their ability to perform biopsies of lesions, treat bleeding, and execute therapeutic measures such as stent insertion or stricture dilation.36 The most significant disadvantage of deep enteroscopy over capsule enteroscopy is the relatively high rates of perforation (0.3–3.4%), particularly in patients with inflammatory bowel disease, malignancy, and bowel anastomosis.35,37–40

Angiography

Visceral angiography is a relatively insensitive investigation and able to detect bleeding only at a rate of 0.5–1 mL/min.41,42 Although the specificity is 100%, the sensitivity varies from 47% with acute lower GI bleeding to 30% with recurrent bleeding.43 Angiography has a role in patients with massive lower GI bleeding precluding colonoscopies or in patients with negative endoscopies.

Red Cell Labeling (Nuclear Scintigraphy)

Red cell labeling has been found to play a limited role in the diagnosis of GI bleeding and may be useful after other methods have failed. While sensitive (this method can detect GI bleeding at a rate of 0.1 mL/min), the site of bleeding is only localized to an area of the abdomen, and intestinal motility shifts intraluminal blood away from the site of bleeding, resulting in a relatively nonspecific investigation. Specificity is improved when scans are positive within 2 hours after injection of labeled erythrocytes as less motility will have occurred, resulting in correct localization in 95–100% of cases. This decreases to 57–67% when scans are positive more than 2 hours after injection.44 Red cell scans are therefore more often used to identify a potential role for angiography—in red cell scans only positive after 2 hours, angiography is unlikely to be sufficiently sensitive to detect bleeding.

Pharmacologic Management

Pharmacologic management is unlikely to halt active bleeding but instead is aimed at preventing recurrence of bleeding by management of the underlying etiology, such as triple therapy for Helicobacter pylori infection or proton pump inhibitors (PPIs) to prevent recurrence of gastric ulceration and bleeding.

Endoscopic Treatment

Endoscopy remains the mainstay of investigation and often therapy for most causes of upper and lower GI bleeding. Techniques used for control of hemorrhage include thermal coagulation, injection therapy, and the use of mechanical devices such as metallic clips and band ligation. Thermal coagulation probes include bipolar, monopolar, and heat probes, with an overall perforation rate of up to 2.5%, particularly frequent in the thin-walled right hemicolon.45 Argon plasma coagulation (APC) is a means of noncontact coagulation with an almost nonexistent risk of perforation in the colon.46 Laser-mediated coagulation (such as with the Nd:YAG laser) uses high-energy laser light to vaporize the tissue, producing deeper penetration than APC but with a higher perforation rate.

Injection of a 1:10,000 dilution of epinephrine is an effective and inexpensive method of endoscopic treatment, causing vasoconstriction and physical compression of the vessel. Metallic clips, both in reusable and disposable forms, are also suitable for arrest of hemorrhage endoscopically. Rubber band ligation is frequently employed in lower GI bleeding due to hemorrhoids or rectal varices.

Interventional Angiography

While initial attempts of embolization led to high rates of bowel infarction due to the use of large-bore catheters for cannulation, the more recent approach using microcatheters has circumvented this and produces success rates of 70–90% without significant complications and recurrent hemorrhage rates of only 15%.47 Embolization material includes microcoils, Gelfoam (gelatin sponge), and polyvinyl alcohol particles. Selective angiographic embolization has been shown to arrest life-threatening bleeding from gastroduodenal ulcers, with a low rate of early rebleeding and no late rebleeding, obviating the need for emergency surgery in high-operative-risk patients.48

Early bleeding recurrence is associated with coagulation disorders, longer time to angiography, higher preprocedural blood transfusion volume, two or more comorbidities, and the use of coils as the only embolic agent.49 Embolization has also been shown to be of value in patients with diverticular lower GI bleeding, with an 85% success rate, and particularly successful in the left colon compared to the right colon and caecum. Less success was noted in nondiverticular lower GI bleeding, such as from arteriovenous dysplastic lesions, with a greater than 40% rate of rebleeding.50

Angiography may also be coupled with selective infusion of a vasoconstrictor such as vasopressin or the longer-acting analogue terlipressin; however, this is associated with a 50% rate of rebleeding after cessation of the infusion.51 The side effects of vasopressin and terlipressin, including abdominal pain and cardiac complications, have meant that this technique is now only rarely used.

Surgery

Surgery is rarely used as a means of controlling hemorrhage except when a clear bleeding point has been identified, but all other modalities of hemorrhage control have failed. However, surgery remains the treatment of choice in patients with neoplasia and may be used as a last resort in patients with recurrent bleeding without a defined bleeding point or in fulminant hemorrhage. Blind segmental colectomy is associated with unacceptably high rates of rebleeding (up to 75%) and mortality (up to 50%); hence intraoperative endoscopy should be used to aid in determination of the source of bleeding, resulting in a more conservative directed segmental colectomy (6% rebleeding and 4% mortality).52,53

Causes of Upper GI Hemorrhage

Causes of upper GI hemorrhage can be divided into variceal and nonvariceal bleeding (Table 11-2), of which the latter is more common. Nonvariceal bleeding is also more common than variceal bleeding in patients with portal hypertension; however, the higher morbidity and mortality of variceal bleeding means that this should be excluded before bleeding is attributed to any other source.

Nonvariceal Bleeding

Peptic Ulcer Disease and Bleeding.

Numerous studies demonstrated a worldwide reduction in the incidence of peptic ulcers between 1958 and 1999, attributable to the introduction of H. pylori eradication therapy and PPIs. A reduction was also noted in the rate of operation and mortality from peptic ulcer disease; however, the overall incidence of peptic ulcer bleeding did not show a significant decrease over the same period.12 Peptic ulcer bleeding still carries a mortality rate of 5–10%,11,54 and in-hospital care costs more than $2 billion annually in the United States.55

Nonvariceal bleeding accounts for 80–90% of acute upper GI bleeding, the majority of which is due to gastroduodenal peptic ulceration,11 which accounts for 40% of all nonvariceal upper GI bleeding.24 A large proportion of this is associated with use of aspirin and NSAIDs, and the majority of cases occur in the elderly (68% of patients are >60 years of age and 27% >80 years of age).56 At some point during the course of the disease, 10–15% of ulcers will bleed. Patients with bleeding ulcers commonly present with hematemesis and/or melena, and require early and aggressive fluid resuscitation to replace any existing losses. History, examination, and investigations should proceed as outlined previously (Fig. 11-2). Both duodenal and gastric ulcers can bleed profusely; however, this predilection is higher in gastric compared to the more common duodenal ulcers. Bleeding is most significant when involving an artery such as branches of the gastroduodenal or left gastric arteries.

Several risk stratification scores have been developed to assist in identification of patients who require close monitoring and are at risk of rebleeding. The two most commonly used tools are the Rockall score and the lesser used Blatchford score (Table 11-3). The Rockall score utilizes clinical as well as endoscopic findings to risk-stratify patients. The score ranges from 0 to 11; a higher score is associated with greater risk of rebleeding or death.57 The Blatchford score uses hemoglobin, blood urea nitrogen, systolic blood pressure, pulse, melena, syncope, hepatic disease, or cardiac failure to produce a maximum score of 23; again higher scores indicate higher likelihood of rebleeding or death.58

The endoscopic appearance of a bleeding ulcer alone can also be used to stratify the risk of rebleeding using the Forrest criteria (Table 11-4).59 High-grade lesions are those that are actively spurting or oozing blood, or have a nonbleeding visible vessel or adherent clot.

Medical Management

Stop Any Causes (Eg, Drugs).

All ulcerogenic medication such as salicylates, NSAIDs, and SSRIs should be stopped and nonulcerogenic alternatives prescribed. Cyclooxygenase-2 (COX-2) inhibitors, which initially showed promise as a gastroprotective alternative to NSAIDs have recently been shown to demonstrate cardiotoxicity without significant benefit on gastric mucosal protection and are therefore infrequently used.60

Eradication of H. Pylori and Long-Term Acid Suppression.

The association of bleeding with H. pylori infection is not as strong as the association reported for perforated ulcers, with H. pylori infection reported in only 60–70% of bleeding ulcers. However, recent data show that treating patients positive for H. pylori with eradication therapy reduces the risk of rebleeding and obviates the need for long-term acid suppression61; hence H. pylori eradication is recommended in all bleeders infected with H. pylori.

Gastric acid has been shown to impair clot formation, promote platelet disaggregation, and increase fibrinolysis. In keeping with this, PPIs have been shown to significantly reduce the risk of ulcer rebleeding, the need for urgent surgery, and, in patients with high-risk stigmata who have undergone endoscopic therapy, mortality.62,63

Endoscopic Management.

Patients with high-risk stigmata on endoscopy (active bleeding or nonbleeding visible vessel) require haemostatic intervention, such as injection, and thermal or mechanical therapy such as clips (Fig. 11-3). Addition of any one of these to adrenaline injection further reduces rebleeding rates, the need for surgery, and mortality.64–66

Several factors are predictors of failure of endoscopic therapy for peptic ulcer bleeding, including previous ulcer bleeding, shock and presentation, active bleeding during endoscopy, ulcers greater than 2 cm in diameter, a large underlying bleeding vessel greater than 2 mm in diameter, and ulcers on the lesser curve of the stomach or the posterior or superior duodenal bulb.67 Recent studies suggest that second-look endoscopy (within 24 hours of the initial endoscopic therapy) provides only a small reduction in the rate of rebleeding, is not cost-effective in the presence of acid-suppressing medication, and is overall not recommended.25,68,69 Repeat endoscopy should only be considered in cases of recurrent hemorrhage or unsuccessful first treatment.

Surgical Management.

Meta-analysis and surgical registry data show the rate of surgical intervention for bleeding peptic ulcers has decreased to 6.5–7.5%. An improved understanding of peptic ulcer disease as well as the development of newer pharmacologic and endoscopic treatments has meant that surgery is now employed not as first-line or curative treatment, but instead only when other modalities have failed.

There are no consensus guidelines on the appropriate indications for surgery; however in general, persistent blood loss with failure of endoscopic therapy and a blood transfusion requirement in excess of 6 units are often considered an indication for surgical intervention (Table 11-5). Similarly, hypovolemic shock associated with recurrent hemorrhage or a slow continuous blood loss requiring transfusion of more than 3 units per day is also considered indicative. Shock on admission, an elderly patient, severe comorbidity, a rare blood type, refusal of transfusion, and bleeding chronic gastric ulcer with a suspicion of malignancy are considered relative indications for surgery.

In stable patients with evidence of rebleeding, a second attempt at endoscopic hemostasis is often as effective as surgery with fewer complications and is the recommended management.70 The aim of surgery in both gastric and duodenal ulcers is to arrest hemorrhage and perform an acid-reducing procedure if deemed necessary.

Operative Procedure for Duodenal Ulcers.

A longitudinal duodenotomy or duodenopyloromyotomy provides good exposure of bleeding sites in the duodenal bulb, the most common site of duodenal ulcers. Direct pressure provides temporary arrest of the bleeding, and it should be followed by suture ligation with a nonabsorbable suture such as Prolene. Four-quadrant suture ligation will achieve hemostasis in anterior ulcers. Posterior ulcers, particularly if involving the pancreaticoduodenal or gastroduodenal artery, will require suture ligation of the artery both proximal and distal to the ulcer for adequate control of hemorrhage, as well as placement of a U-stitch underneath the ulcer to control the pancreatic branches (Fig. 11-4).

The use of an acid-reducing procedure in duodenal ulcers remains a topic of debate, as theoretically arrest of hemorrhage and H. pylori eradication is likely to be sufficient management. In the absence of trials and convincing data, however, it is hard to make any firm recommendations, and the decision is best left to the surgeon taking into account each patient's condition and their experience with such operations. Surgical options for acid reduction in bleeding duodenal ulcer management include pyloroplasty with truncal vagotomy, parietal cell vagotomy, or antrectomy with truncal vagotomy. The former is the most frequently used as it is facilitated by the longitudinal approach to the pylorus for arrest of hemorrhage. Parietal cell vagotomy is limited by surgeon inexperience. Antrectomy with truncal vagotomy may be suitable in patients refractory to conservative surgery but is a complex procedure that is unsuitable in the shocked patient. Ulcer surgery is covered in greater detail in Chap. 26.

Operative Procedure for Gastric Ulcers.

Management of the bleeding gastric ulcer also prioritizes arrest of the bleeding. However, because of the risk of rebleeding and the 10% risk of malignancy in gastric ulcers, gastrotomy and suture ligation are insufficient in these patients. Resection of the ulcer alone is associated with a 20% rebleeding rate; hence a distal gastrectomy is recommended for ulcers in the antrum and distal stomach. In patients who may be unfit for a distal gastrectomy, resection of the ulcer itself combined with an acid-reducing procedure in the form of a vagotomy and pyloroplasty may be an option. Management of bleeding ulcers at the cardioesophageal junction and the proximal stomach is more challenging. While optimal resection would involve a proximal or near-total gastrectomy, this results in increased morbidity and mortality in patients acutely bleeding. More conservative options may suffice, such as distal gastrectomy with resection of a tongue of proximal stomach to ensure excision of the ulcer, or a wedge resection of the ulcer or simple oversewing with a vagotomy and pyloroplasty.

Mallory-Weiss Tears.

The sensation of nausea is accompanied by closure of the pylorus, gastric distension, and retrograde propulsion of gastric contents toward the cardia. When this is followed by vomiting, the diaphragm moves abruptly upward, associated with rapid increase in intra-abdominal pressure that pushes the gastric cardia into the thorax through the diaphragmatic hiatus. With sufficient force, a longitudinal laceration of the esophagus or stomach can result.71 Hiatus hernias coexist in more than 75% of patients with Mallory-Weiss tears, and the amount of herniated stomach determines the point of maximal dilation (law of Laplace) and therefore the position of the tear.72,73 Large hiatus hernias are associated with more distal tears, while in patients with small or absent hiatus hernias, tears occur at or below the gastroesophageal junction. The majority of tears are situated within 2 cm of the gastroesophageal junction on the lesser curvature.

The highest incidence of Mallory-Weiss tears occurs in patients between 30 and 50 years of age and in men more than women. Some 40–75% of patients have a history of alcohol use74 and 30% a history of aspirin use.75 Patients typically present with a history of several episodes of vomiting or retching followed by hematemesis with fresh red blood. Ten percent of patients may present with only melena.

EGD usually identifies a single tear on the lesser curve of the cardia, or occasionally on the greater curvature of the cardia. Retroflexion during the endoscopic examination is an important maneuver in these patients to ensure the distal gastroesophageal junction and cardia are visualized. The majority of lesions heal spontaneously; hence management is largely supportive, with emphasis on antiemesis and acid suppression. Patients with persistent bleeding may require endoscopic injection or thermocoagulation, or angiographic embolization. Surgery may be required should these options prove unsuccessful, and hemorrhage can be arrested operatively by a high gastrotomy and suture of the mucosal laceration.

Stress-Related Mucosal Bleeding.

Critically ill patients are at risk for the development of diffuse mucosal injury of the stomach, resulting in upper GI bleeding with significant morbidity and mortality. This phenomenon, termed “stress-related mucosal bleeding” or occasionally “stress gastritis,” is a result of a combination of mucosal ischemia and reperfusion injury and impairment of host cytoprotective defenses, and ultimately results in a prolonged ICU stay in a vulnerable population of patients.65 While this phenomenon was previously common, the incidence of clinically significant bleeding in the critically ill population has now decreased to less than 3.5% with the use of prophylaxis.76

The most important risk factors for stress-related mucosal bleeding are prolonged mechanical ventilation (>48 hours) and coagulopathy. Other factors include shock, severe sepsis, neurologic injury/neurosurgery, greater than 30% burns, and multiorgan failure. Patients with these risk factors require prophylaxis with antacids, H2-receptor blockers, PPIs, or Carafate.

Acid suppression is often sufficient to control hemorrhage in stress-related mucosal bleeding. For persistent bleeding, options include selective infusion of octreotide or vasopressin via the left gastric artery, endoscopic measures, or angiographic embolization. Surgery is now rarely performed but, if necessary, involves vagotomy and pyloroplasty with oversewing of discrete regions of hemorrhage or subtotal gastrectomy.

Esophagitis.

In rare cases bleeding may originate in the esophagus and is then often due to esophagitis. Gastroesophageal reflux disease (GERD) repeatedly exposes the mucosa to irritant acidic gastric content, causing chronic inflammation and blood loss (Fig. 11-5). Occasionally ulceration may follow, presenting as occult bleeding with anemia or guaiac-positive stool. While GERD is the most common cause, other causes include Crohn's disease, certain drugs, and radiotherapy. Immunocompromised patients may have esophagitis of an infective etiology; causes most commonly include herpes simplex, Candida, and cytomegalovirus (CMV), but esophagitis can occasionally be due to ulceration directly induced by human immunodeficiency virus (HIV) or Epstein-Barr virus, or secondary involvement of the esophagus in mycobacterial infection of adjacent lymph nodes.77 Infective esophagitis is uncommon but may lead to torrential hemorrhage.

Management, particularly of GERD-induced esophagitis, hinges on acid-suppressive therapy, occasionally requiring therapeutic endoscopy to arrest the bleeding. Treatment of the infective cause is often successful at managing the bleeding in immunocompromised infected patients.

Dieulafoy's Lesion.

Dieulafoy's lesions are an arterial vascular anomaly featuring abnormally large (“caliber persistent”) submucosal end arteries, likely congenital in origin, and with the potential for massive, potentially life-threatening hemorrhage upon erosion of the overlying gastric mucosa. These lesions are most commonly located in the stomach within 5–7 cm of the cardia but may present in small bowel, duodenum, and colon. These account for 1.5% of upper GI bleeding and are more commonly encountered in men.78

Dieulafoy's lesions appear as reddish-brown protrusions on endoscopy with no ulceration. Endoscopic therapy is often successful provided good visualization of the lesion is obtained; mechanical methods such as clipping or banding have been shown to work better than injections for control of hemorrhage.79,80 Angiographic embolization or surgery may be employed for endoscopic failures. Surgical intervention may require prior endoscopic tattooing to facilitate identification of the site, followed by wedge resection of the lesion.78

Gastric Antral Vascular Ectasia (Gave).

GAVE, or “watermelon stomach,” is so named for the dilated, tortuous mucosal capillaries and veins present in the antrum, converging onto the pylorus, and resembling the surface of a watermelon (Fig. 11-6). This condition is more common in women than in men and often presents with occult blood loss and iron deficiency anemia. APC is the treatment of choice for GAVE; treatment may need to be repeated for recurrences, and PPI cover is recommended for 1 month following treatment.78,81 Patients refractory to APC should be considered for surgical intervention in the form of an antrectomy.

Malignancy.

Malignant upper GI lesions rarely present with overt significant hemorrhage and instead are more likely to present with hemoccult-positive stool or iron deficiency anemia. Endoscopy occasionally reveals a recurrent bleeding ulcer, a common feature of GI stromal tumors, which characteristically appear as a submucosal tumor with central umbilication and ulceration (discussed further in Chap. 24), and on occasion leiomyomas and lymphomas (Fig. 11-7). Surgery is necessary as the rate of rebleeding in these malignant lesions is high, and may involve full curative resections or in unfit patients, palliative wedge resections for hemorrhage control.

Aortoenteric Fistula.

Aortoenteric fistula is an important clinical condition, often presenting with torrential GI hemorrhage. Primary fistulae are rare; most commonly fistulation occurs following a previous abdominal aortic aneurysm (AAA) repair and is seen in approximately 1% of these cases. The pathophysiology behind this is likely to be infective in origin, leading to the development of a pseudoaneurysm at the proximal suture line, resulting in fistulization into the duodenum (Fig. 11-8).

Early diagnosis of this problem is critical but can be difficult. A high index of suspicion is required in all patients presenting with GI hemorrhage with known aortic aneurysms or a history of previous aortic aneurysm repair. Often, patients present with several smaller, self-limiting episodes of GI hemorrhage (“sentinel bleeds”). Urgent endoscopy at this stage is essential to preempt a subsequent torrential, often fatal bleed, and usually reveals bleeding at the third or fourth part of the duodenum (Fig. 11-9). CT with IV contrast is a useful adjunct in these patients, often demonstrating air within the aortic thrombus or around the graft (particularly in the context of an infected graft), and rarely a pseudoaneurysm or contrast within the duodenal lumen.

Surgical repair involves extra-anatomic bypass grafting and aortic ligation for primary aortoenteric fistula. For secondary aortoenteric fistula, surgery involves excision of the graft with extra-anatomic bypass or in situ aortic reconstruction. By necessity these procedures are often performed in critically ill, severely exsanguinated, and septic patients and hence associated with high morbidity and mortality.

With the advent of endovascular stenting for primary AAA repair, various studies have been performed to determine the effectiveness of endovascular stenting for aortoenteric fistula. This has been associated with a high incidence of recurrent bleeding and infection, particularly in the presence of preprocedural infection.82

Hemobilia.

Hemobilia is a rare cause of GI bleeding. Causes include trauma, hepatic neoplasms, instrumentation of the biliary tree, percutaneous radiofrequency liver ablation, and following liver transplant. A high index of suspicion is required in patients with these risk factors, as the classic presentation of hemorrhage, right upper quadrant pain, and jaundice is only seen in a minority of patients. Endoscopy may reveal blood at the ampulla, but angiography and embolization remain the diagnostic and therapeutic modality of choice.

Hemosuccus Pancreaticus.

Bleeding from the pancreatic duct (hemosuccus pancreaticus) is another rare cause of upper GI bleeding, due to fistulation of a pancreatic pseudocyst into the splenic or other peripancreatic artery.83 A presentation of abdominal pain, hematemesis, and melena in patients with a previous history of pancreatitis should raise suspicion of hemosuccus pancreaticus. Angiography is again both diagnostic and therapeutic, although in some cases distal pancreatectomy may be employed.

Iatrogenic Bleeding.

Upper GI endoscopy or surgery is another cause of bleeding. Percutaneous gastrostomy is often necessary as a means of nutritional support in certain conditions but is accompanied by a 3% rate of GI hemorrhage. Bleeding may have tracked into the stomach from the incision site but may also be from the stomach mucosa; both causes can be managed endoscopically.

Endoscopic sphincterotomy is increasingly common as a means of accessing the biliary tree during an endoscopic retrograde cholangiopancreatography and facilitates endoscopic clearance of the common bile duct, but it is associated with a 2% risk of bleeding. Bleeding may occur after 48 hours but can often be arrested by local injection of epinephrine, rarely requiring surgical intervention. Bleeding following upper GI surgery may occur from suture or staple lines. This can occasionally be treated endoscopically, with minimal insufflation to avoid disruption of the anastomosis.

Variceal Bleeding and Portal Hypertension

Portal hypertension is a serious cause of upper GI bleeding, often the result of cirrhosis that is the end stage of chronic liver disease. The pathophysiology of portal hypertension is discussed further in Chap. 47 and hence is not covered here. Approximately 50% of patients with cirrhosis will develop gastroesophageal varices as a result of portal hypertension.84 Variceal bleeding occurs in 30% of patients and is one of the most important complications of hepatic cirrhosis. Variceal bleeding is associated with increased risk of rebleeding and transfusion requirement, greater length of hospital stay, and higher morbidity and mortality compared with nonvariceal bleeding.17,84

Gastroesophageal varices represent one site of portosystemic anastomosis, which is dilated as the portal circulation tries to decompress to the systemic circulation. Other sites of portosystemic collaterals are the stomach, the umbilical region (collateral formation leads to formation of caput medusae), and the distal rectum.

Factors that determine variceal bleeding include high variceal wall tension (determined by vessel diameter) and variceal pressure, in turn related to hepatic venous pressure gradient (HPVG). Patients with a HPVG of less than 12 mm Hg are unlikely to develop variceal bleeding.85

Isolated gastric varices (IGV) can occur in the absence of esophageal varices and are located along the gastric fundus (IGV1), or along the body, antrum, or pylorus (IGV2).84 Risk factors for gastric variceal bleeding include variceal size and the presence of a cherry-red spot (localized reddish mucosal area or spots on the mucosal surface of a varix).86

In addition to varices, portal hypertension can also cause the development of portal hypertensive gastropathy, diffuse dilation of the mucosal, and submucosal venous plexus of the stomach with overlying gastritis. The stomach develops a snake-skin appearance with cherry-red spots on endoscopy, and rarely may be the site of major hemorrhage (Fig. 11-10).

The management of variceal upper GI bleeding follows the same principles as those of nonvariceal upper GI bleeding, with emphasis on urgent resuscitation and therapeutic endoscopy because of the higher morbidity and mortality associated with variceal bleeds (Fig. 11-11).

EGD remains the gold standard for diagnosing variceal bleeding. The diagnosis of variceal hemorrhage is based on meeting one of the following criteria: active bleeding from a varix, a “white nipple” overlying a varix, clots overlying a varix, or varices with no other potential source of bleeding.87

Management.

Treatment of variceal bleeding requires a combination of medical and endoscopic management.

Medical.

Somatostatin or its analogues octreotide or terlipressin should be administered as a bolus immediately in cases where there is a high index of suspicion, and continued for 3–5 days after endoscopic confirmation of diagnosis.84 Fluids and blood products should be administered judiciously to maintain a hemoglobin level of greater than 8 g/dL. Current recommendations are that any patients with cirrhosis and GI bleeding should be given up to 7 days of antibiotic prophylaxis, specifically a fluoroquinolone such as norfloxacin or ciprofloxacin.

Endoscopic.

Variceal bleeding should be diagnosed and treated by EGD, either with variceal ligation or sclerotherapy.84 In patients with variceal bleeding, endoscopy should be performed as soon as possible (within 12 hours of admission).88,89 This is of particular importance in patients with hemodynamic instability or features of cirrhosis. Early endoscopy also excludes nonvariceal causes of bleeding, which occur in 15% of patients with varices.90 Variceal ligation is the endoscopic treatment of choice as it has been shown to have lower rates of complications compared to sclerotherapy, which can cause perforation, mediastinitis, and stricture formation. Variceal ligation involves the placement of rubber bands on the varices to completely interrupt blood flow into the ligated varix and arrest hemorrhage acutely. The mucosa and submucosa develop ischemic necrosis and granulation and sloughing of the rubber rings, and necrotic tissue results in replacement of varices by scar tissue. Sequential treatments may be required, as many as three treatments over 24 hours, but will achieve control of hemorrhage in up to 90% of patients.

Mechanical tamponade devices may be useful in temporarily controlling bleeding from esophageal varices where endoscopy and medical management have failed. One example is the Sengstaken-Blakemore tube, which consists of a gastric tube with gastric and esophageal balloons. Inflation of the gastric and esophageal balloons compresses the esophagogastric venous plexus, arresting bleeding, but at the risk of ischemic necrosis and perforation. Deflation of the tube can be associated with recurrent bleeding in 50% of patients; hence this technique is reserved as a temporizing measure in massive hemorrhage before more definitive intervention is commenced.

Gastric varices should be managed initially by pharmacotherapy. Endoscopic therapy is not as successful in gastric varices because of the diffuse nature of portal hypertensive gastropathy. Patients with refractory bleeding should be referred early for decompressive therapy such as TIPS (transjugular intrahepatic portosystemic shunt) or shunting.

IGVs, without associated portal hypertension, can occur in the setting of splenic vein thrombosis, often associated with pancreatitis. Varices occur in the presence of normal central portal pressures due to left-sided hypertension, rerouted from the spleen to the short gastric vessels. Splenectomy may relieve the hypertension, but the risk of variceal bleeding in these patients is low and hence splenectomy should not be routinely undertaken.91

Prevention of Rebleeding.

Prevention of rebleeding is of the utmost importance in this patient population. Rebleeding may occur in up to 70% of patients within 2 months without further definitive therapy.92 The highest risk of rebleeding is in the first few days following the initial episode. A combination of nonselective beta-blockers with isosorbide mononitrate has been shown to be more effective than beta-blockers alone in preventing rebleeding.93 The addition of prophylactic endoscopic band ligation to combination pharmacotherapy did not reduce the risk of rebleeding but instead was associated with more adverse events in a recent randomized controlled trial.94

Radiologic or Surgical Portal Decompression.

In approximately 10% of cases of variceal bleeding, endoscopic management is unsuccessful, necessitating urgent decompression of the portal system. A TIPS procedure involves the creation of an artificial anastomosis between the hepatic and portal veins under fluoroscopic guidance with the use of a covered stent, shunting blood away from the hepatic sinusoids and relieving portal pressure.95 TIPS is, however, associated with a 30-day mortality of up to 30% in the emergency setting, usually a result of hepatic encephalopathy from diversion of blood away from the liver parenchyma.96 Rebleeding may occur in 20% of patients and is often due to occlusion of the anastomosis. Surgery is another therapeutic option for decompression of the portal system. Surgical shunts, such as the selective distal splenorenal shunt (DSRS), have lower rates of rebleeding compared to endoscopic therapy but do not demonstrate any difference in survival.97 DSRS patients have an in-hospital mortality of approximately 5%, a 5–8% rate of rebleeding, and a 75–80% 3-year survival.97 A recent randomized controlled trial comparing TIPS with DSRS in patients with failed medical or endoscopic therapy showed no significant difference in the rate of rebleeding, hepatic encephalopathy, or overall survival, but identified a need for close follow-up and a greater need for reintervention in patients subjected to TIPS, suggesting that in patients with relatively limited access to health care facilities, DSRS may be a more suitable therapeutic option.98 Further details on surgical decompression for portal hypertension are covered in Chap. 47.

Lower GI bleeding can occur from any site distal to the ligament of Treitz, most commonly from the colon. Occasionally bleeding can also occur from the small bowel. Difficulty in diagnosis of lower GI bleeding stems from the large surface area of colon and small intestine, intermittent bleeding, occasional lack of visible mucosal lesions, and difficulties in endoscopic visualization as lesions are obscured by forward movement of blood. The majority of patients with lower GI bleeding experience self-limiting episodes; only 10–20% of patients present with massive unremitting lower GI bleeding. Patients with self-limited bleeding can usually be managed with initial resuscitation, exclusion of an upper GI source, and further investigation using colonoscopy and, if necessary, angiography or nuclear scintigraphy. Younger patients with suspected hemorrhoidal bleeding should be followed up and the hemorrhoids managed appropriately, while older patients should be investigated for malignancy before bleeding is attributed to a benign pathology. Bleeding from the anus or rectum can be identified by digital rectal examination (DRE) and proctoscopy and may on occasion require sigmoidoscopy. Upper GI bleeding can be effectively excluded in the presence of a blood-free bilious NG aspirate; however, an EGD is required for definitive exclusion.

Management of Lower GI Hemorrhage

Lower GI bleeding is often less severe than upper GI bleeding; however, the same principles for resuscitation should be followed (Fig. 11-12), guided by the hemodynamic stability of the patient. Accurate identification of the source of bleeding can be difficult in patients with lower GI bleeding—more than one source for bleeding is found in 40% of patients and in up to 25% of patients no source is identified. A management algorithm is outlined in Fig. 11-13. Patients with hematochezia who are hemodynamically stable should undergo colonoscopy in the first instance to identify a cause for the bleeding. If a bleeding site is identified, endoscopic therapy should be attempted to control the bleeding. If no bleeding site is identified, an EGD should be performed, followed by capsule or deep enteroscopy if this is unsuccessful. Hemodynamically unstable patients should undergo EGD in the first instance as severe upper GI bleeding may often present as hematochezia.

Patients with bleeding refractory to endoscopic management or those with significant hemodynamic instability may require urgent operative intervention. In these patients an exploratory laparotomy is required, and attempts made to determine the location of blood within the GI tract. Although this is relatively nonspecific, it may assist in broadly localizing the origin of bleeding; for instance if blood is only present beyond the ileocecal valve, bleeding is likely to be colonic in origin. The GI tract should be thoroughly examined to exclude bleeding from small bowel tumors or Meckel's diverticulum. A segmental bowel resection is appropriate in localized bleeding, and in relatively fit patients this may be combined with a primary anastomosis. In unfit patients with preexisting hemodynamic instability or severe malnutrition, a mucous fistula and end stoma is a more appropriate option. Segmental colectomies should not be performed as “blind” procedures without localization of the bleeding source, as these have been associated with unacceptably high mortality rates and rebleeding rates between 20 and 50%.99 A better alternative in patients without localization of the bleeding source is a “blind” subtotal colectomy, with a primary ileorectal anastomosis, associated with a less than 10% mortality rate and less than 10% rebleeding rate with the benefit of normal postoperative bowel control. This procedure further allows irrigation of the rectal segment with repeat proctoscopy to rule out rectal bleeding.

On-table lavage may allow identification of a bleeding source, facilitating segmental colectomy, but is best attempted in stable patients who may not retain acceptable bowel function after a total or subtotal colectomy and not advised in the unstable patient.

Causes of Lower GI Hemorrhage

Overt Lower GI Bleeding

The majority of lower GI bleeding originates from the colon as a result of common pathologies such as diverticular disease and neoplasia (Table 11-6). Early identification of the cause of bleeding is essential to initiate appropriate management, in particular for cases of malignancy.

Diverticular Disease.

Diverticular disease is an extremely prevalent and often asymptomatic disease of Western countries. The incidence increases with age; up to 60% of patients older than 80 years have diverticulae.100 In Western countries, 95% of diverticula are in the sigmoid and left colon; however, in Asian countries 70% of cases are in the right colon.101,102 Colonic diverticular are usually pulsion-type pseudodiverticula—outpouchings of the mucosa and submucosa through the muscular layer of the bowel at the sites of penetration of the vasa recta—resulting from high intraluminal pressure and bowel segmentation. Only 4–17% of patients with diverticular disease develop symptoms of bleeding103; however, the frequency of diverticular disease means that diverticular bleeding accounts for 30–40% of lower GI bleeding.104 Eighty percent of diverticular bleeds stop spontaneously, but a small minority will require hemostatic intervention. Ten percent of patients will rebleed within a year and 50% within 10 years.104

Colonoscopy remains the most useful diagnostic and therapeutic investigation for diverticular bleeding (Fig. 11-13), and can be combined with adrenaline injection, mechanical clipping, or thermal or electrical coagulation to achieve hemostasis. A recent meta-analysis showed embolization to be successful at arresting diverticular bleeding in 85% of patients.50 Surgery is indicated in refractory bleeding, and a limited resection may also be considered as a management option in patients with multiple episodes of self-limiting bleeding.

Angiodysplasia.

Angiodysplastic lesions in the intestine are degenerative vascular lesions that develop as a result of progressive dilation of submucosal vessels. Bleeding from these lesions can account for up to 40% of lower GI bleeds.104 Angiodysplastic lesions are frequently found in the elderly and associated with aortic stenosis and renal failure. The majority of cases present with anemia and cease bleeding spontaneously; however, 50% will rebleed in 5 years. Massive bleeding may occur in up to 15% of cases.

In the colon, angiodysplastic lesions are predominantly located in the cecum and ascending colon, particularly in elderly patients. Colonoscopy reveals red stellate lesions with a rim of pale mucosa, while angiographic criteria include early prolonged filling of the draining vein, clusters of small arteries, and a visible vascular tuft (Fig. 11-14). First-line treatment options include injection with intra-arterial vasopressin, selective Gelfoam embolization, endoscopic electrocoagulation, or injection with sclerosing agents. Bleeding refractory to these treatments requires a segmental colectomy, usually in the form of a right hemicolectomy.

Neoplasia.

Neoplasia is a rare cause of lower GI bleeding, accounting for only 2–9% of all hematochezia, but is significant due to the relatively high incidence of colorectal cancer in developed countries.53 Neoplasia-induced hemorrhage presents as chronic painless bleeding, usually associated with iron deficiency anemia.53 This is particularly frequent in tumors of the right side of the colon, while tumors of the left side often present with obstructive symptoms and occasionally ulcerate to produce bright red bleeding (Fig. 11-15). Colonic polyps are the cause of bleeding in 5–11% of patients and of anemia in 3–7% of patients; however, this is most often the case in polyps exceeding 1 cm in diameter (Fig. 11-16).105

A common cause of lower GI bleeding is postpolypectomy bleeding, where the site may bleed for up to 14 days following polypectomy (Fig. 11-17). Several factors influence the risk of postpolypectomy bleeding, including size of polyp, inadequate electrocautery, comorbidity, bowel preparation, and experience of the endoscopist.106 Delayed postpolypectomy bleeding in particular was more likely in large polyps and in polyps in the right side of the colon, and in patients in whom anticoagulant therapy had been resumed within 1 week of polypectomy.107 Colonic polyps and neoplasia are covered in more detail in Chap. 36.

Anorectal Disease.

Anorectal pathology that can cause lower GI bleeding includes anal fissures, hemorrhoids, and colorectal neoplasia. Fissures are associated with significant pain on defecation and examination but rarely cause large amounts of blood loss. Inspection of the anal margin is usually diagnostic and can be made painless following injection of local anesthetic. Bleeding from fissures usually ceases spontaneously. Conservative management includes the use of stool bulking agents, stool softeners, increased fluid intake, and topical nitroglycerin or diltiazem, which facilitate healing of the fissure by reducing sphincter spasm.

Hemorrhoids account for lower GI bleeding in 2–9% of patients.105 Fresh red blood is seen on the tissue paper, in the bowl, and around the stool, and is usually painless in nature. Bleeding usually derives from painless internal hemorrhoids and is associated with prolapse of these hemorrhoids, often requiring manual reduction. Management includes stool-bulking agents and increased consumption of fibre and water. Rubber band ligation, injection sclerotherapy, and infrared coagulation may also be employed, and in refractory cases surgical hemorrhoidectomy can be performed.

Other rarer anorectal causes of lower GI bleeding include solitary rectal ulcers and anorectal varices. Solitary rectal ulcers are postulated to arise as a result of local ischemia, due to internal rectal prolapsed or lack of inhibition of the puborectalis muscle on straining. Bleeding is rare with solitary rectal ulcers but in contrast can be severe with anorectal varices. These arise in patients with portal hypertension and can bleed in 18% of those patients.108

An important point to note is that anorectal causes of bleeding such as fissures and hemorrhoids are relatively common incidental findings and should not be considered the only source of bleeding until more proximal colonic neoplasia has been excluded, particularly in the elderly. Benign anorectal conditions are discussed further in Chap. 39.

Colitis.

Bleeding associated with colitis may be multifactorial in origin.

Bleeding from Inflammatory Bowel Disease.

Bleeding from colonic inflammation may be a feature of inflammatory bowel disease. Lower GI hemorrhage has been reported in the majority of patients with ulcerative colitis and in up to a third of patients with Crohn's disease.109 Most bleeding stops spontaneously, but 35% of patients experience rebleeding.110 Both ulcerative colitis and Crohn's disease are associated with abdominal pain and increased bowel movements. While ulcerative colitis predominantly involves the mucosal layer and begins at the rectum then spreads proximally, Crohn's disease is associated with transmural thickening of the bowel wall, skip lesions, and strictures, and classically involves the terminal ileum (Fig. 11-18). Both Crohn's disease and ulcerative colitis are diagnosed on endoscopy and managed with 5-aminosalicylic acid (5-ASA) compounds, immunomodulatory agents, steroids, and antibiotics as needed. Surgical therapy for ulcerative colitis is needed if the rare complication of toxic megacolon develops or in the event of refractory life-threatening hemorrhage. Surgery is avoided as much as possible in Crohn's disease because of the natural relapsing and remitting nature of the disease and the tendency of the lesions to affect any region of the GI tract. Crohn's disease and ulcerative colitis are discussed further in Chaps. 33 and 34.

Infectious Colitis.

Causes of infectious colitis that may cause bloody diarrhea include CMV colitis, Escherichia coli, Shigella, Salmonella, and Campylobacter. Patients with infectious colitis typically present with bloody diarrhea with positive stool cultures. CMV colitis typically affects the immunocompromised.

Patients with HIV are particularly at risk of GI bleeding and, because of the immune deficiency, are particularly at risk from opportunistic organisms. Causes of GI bleeding in the colon of HIV-positive patients include CMV colitis, lymphoma, colonic histoplasmosis, Kaposi's sarcoma of the colon, and bacterial colitis, with an overall average mortality of 14%.111 Colonoscopy and biopsy confirms the diagnosis, and treatment should be commenced as appropriate.

NSAID-Associated Lower GI Bleeding.

NSAIDs are also able to induce and exacerbate lower GI bleeding. NSAIDs can themselves induce mucosa damage and colonic inflammation, erosions, and ulcers. In addition, they can exacerbate existing colitis and increase the tendency of preexisting lesions such as polyps or angiodysplasia to bleed. NSAID-induced lesions appear as flat, irregularly shaped erosions and ulcerations with otherwise normal mucosa.53

Radiation Proctitis.

Radiation therapy in the pelvic region is another cause of lower GI bleeding, producing a chronic radiation proctopathy due to the neovascularization resulting from radiation-induced endarteritis obliterans. Bleeding occurs in 4–13% of patients receiving radiation therapy for prostatic carcinoma.112 Patients typically present with bloody diarrhea, cramping pelvic pain, and tenesmus. Endoscopy reveals multiple telangiectasias on an otherwise pale mucosa and can be coupled with argon plasma coagulation for treatment (Fig. 11-19). Other treatment options include antidiarrheals and hydrocortisone enemas. Ablation with 4% formalin solution may be considered for refractory bleeding.113

Mesenteric Ischemia.

Mesenteric ischemia, or ischemic colitis, results from a sudden reduction in blood flow to the intestine due to either reduced blood pressure or vasoconstriction. This is particularly frequent in elderly patients with a background of cardiovascular disease; other risk factors include recent abdominal vascular surgery, hypercoagulable states, and vasculitis. Patients on inotropes and vasoconstrictors are particularly prone to mesenteric ischemia due to splanchnic vasoconstriction. The splenic flexure of the colon and the rectosigmoid junction are vascular watershed areas and are especially susceptible to ischemia. Patients present with abdominal pain and bloody diarrhoea. The diagnosis is suspected with the identification of a thickened bowel wall on CT and is confirmed on endoscopy showing bleeding, edematous mucosa with a demarcation between ischemic, and normal bowel (Fig. 11-20). Ulcerations may appear on endoscopy in the later stages of disease progression. Despite the self-limiting nature of the disease in most patients, mesenteric ischemia is associated with a high morbidity and mortality.114 Conservative management is usually employed, with bowel rest, intravenous antibiotics, and cardiovascular support and normalization of the hemodynamic state. In 15% of patients, ischemia is followed by gangrene and perforation, the patient develops sepsis, acidosis, and peritonitis, and requires urgent laparotomy with resection of ischemic bowel and the creation of an end colostomy.115

Obscure Lower GI Bleeding

Bleeding persisting or recurring after negative esophagogastroscopy and colonoscopy occurs in approximately 5% of cases is termed obscure bleeding, often the result of angiodysplastic lesions, Meckel's diverticula, Dieulafoy's lesions, and small bowel neoplasms.116 Bleeding in these cases may be visible (termed obscure-overt bleeding) or only detected by the presence of guaiac-positive stools (obscure-occult bleeding). Further investigation in the form of capsule enteroscopy, deep enteroscopy, angiography, or red cell labeling is often necessary in these cases.

Angiodysplasia.

Angiodysplasia is the most common cause of small bowel hemorrhage, accounting for up to 40% of cases in elderly patients and 10% of cases in younger patients. The jejunum is the most common site for these lesions. While angiodysplasias of the small intestine often present with obscure bleeding, patients with bleeding angiodysplastic lesions may also present with occult bleeding and iron deficiency anemia. Unlike colonic angiodysplasia, angiography is rarely helpful in small intestinal angiodysplasia, and deep enteroscopy or capsule enteroscopy are the investigative modalities of choice. Optimal management involves on-table endoscopy with segmental resection of the affected length of small bowel; however, it is important to note that a significant number of patients may spontaneously cease bleeding.117

Meckel's and Other Small Intestinal Diverticula.

A Meckel's diverticulum is the incomplete obliteration of the remnant of the embryonic vitelline duct, the communication between the yolk sac and the fetal gut, and occurs in approximately 2% of the population. Meckel's diverticulum is usually found within 100 cm of the ileocecal valve and usually ranges from 1 to 10 cm in length (Fig. 11-21).118 Up to 60% of Meckel's diverticula contain heterotopic mucosa, usually of gastric or pancreatic origin. Hemorrhage is a common complication of a Meckel's diverticulum in both adults and children, occurring in 38% of adults and 31% of children, and results from ulceration of the normal mucosa adjacent to the acid-producing heterotopic mucosa.119 Radionuclide scans may assist in the diagnosis of Meckel's diverticulum but is much less accurate in the adult population compared to the pediatric population. The use of cimetidine, which decreases peptic acid secretion without affecting radionuclide uptake, slows the release of the pertechnetate into the lumen and increases the sensitivity of the scan to 95%.120 Laparoscopy may be used for the diagnosis as well as the treatment of Meckel's diverticulum. Operative management hinges on removal of the Meckel's diverticulum and associated bands as well as resection of the adjacent affected bowel.

The incidence of nonmeckelian intestinal diverticulosis is low, ranging from 0.06 to 4.6% on autopsy studies.121 These are particularly common in the elderly but may present in any age group. The pathophysiology of small bowel diverticula is similar to that of colonic diverticula—these are pseudodiverticula involving only mucosa and submucosa, unlike a Meckel's diverticulum that is a true diverticulum. The majority of small intestinal diverticula occur in the jejunum, corresponding with the greatest frequency of vasa rectae in the small intestine. Upper GI contrast series or CT scans may reveal diverticula as contrast-filled sacculations; however, these lack sensitivity. Enteroclysis is a double-contrast radiographic modality involving the use of duodenojejunal intubation and intraluminal distension, allowing even small diverticula to be filled. The lack of cost-effectiveness, however, makes this modality only appropriate if standard radiographic modalities have proved unsuccessful. The incidence of bleeding from jejunal diverticulosis ranges from 5 to 33%.121 Enteroscopy (particularly deep enteroscopy) is suitable for diagnosis of diverticula complicated by bleeding, inflammation, or obstruction, but laparotomy remains the gold standard for diagnosis and management, particularly in the unstable patient. Operative management involves resection of the affected segment of small bowel with a primary end-to-end anastomosis. Rarely a large proportion of the bowel is involved (panjejunoileal diverticulosis), and conservative management may be tried to avoid massive small bowel resection and resultant short bowel syndrome. Selective mesenteric angiography and embolization may assist in the control of hemorrhage in these cases.

Neoplasia.

Although small bowel tumors account for only 5% of all GI tumors, they are the second most common cause of small intestinal bleeding.122 Patients may present either with melena or with fecal occult blood. Leiomyomas and leiomyosarcomas are the most common tumors to bleed and may bleed briskly due to tumor necrosis and mucosal ulceration. These are highly vascular tumors, and hence angiography has an 86% rate of detection for these lesions. Other tumors in the small intestine include adenocarcinoma, carcinoid, and lymphoma. Tumors can be diagnosed on enteroscopy, small bowel contrast series, or CT (Fig. 11-22), and treatment involves surgical resection of the tumor.