Gastrointestinal
Bleeding
Margaret Shuhart, M.D. , Kris Kowdley, M.D., and Bill Neighbor,
M.D.
1.0.
INTRODUCTION
Gastrointestinal (GI) bleeding is among the most common gastrointestinal disorders.
In this chapter we review the many causes of both upper and lower GI bleeding,
and the diagnostic and therapeutic approaches in patients with GI bleeding.
General guidelines for the initial management and appropriate referral to a
gastroenterologist for patients presenting with GI bleeding are discussed in
this chapter.
MeSH search strings used in this review included GASTROINTESTINAL BLEEDING,
UPPER GASTROINTESTINAL BLEEDING, LOWER GASTROINTESTINAL BLEEDING, OCCULT GASTROINTESTINAL
BLEEDING, AND OBSCURE GASTROINTESTINAL BLEEDING. MeSH terms also included specific
causes of GI bleeding as outlined in Sections 3.1 and 4.1. These terms were
used in a search of Medline for the years 1990 to 2002. Certain articles published
prior to 1990 were also included if they were landmark studies or illustrative
case reports.
2.0. MANAGEMENT OF GI BLEEDING
2.1. Initial assessment, resuscitation and triage
Patients with GI bleeding may have different clinical presentations ranging
from hematemesis
or hematochezia
with hemodynamic instability, to melena
or rectal bleeding without hemodynamic compromise. Finally, patients may have
chronic GI bleeding with asymptomatic iron-deficiency
anemia, or hemoccult-positive stool on screening for colorectal cancer.
The severity of illness at presentation dictates the initial patient assessment
and resuscitative efforts. Patients presenting to the emergency room with hemodynamic
instability require rapid clinical assessment, intravenous access with at least
two large-bore lines, nasogastric tube placement, determination of hematocrit
and coagulation studies, and type and cross for blood products. Patients with
altered mental status should undergo endotracheal intubation for airway protection.
Emergent evaluation by a gastroenterologist should be requested. The
patient should be stabilized before proceeding to endoscopy, unless there is
massive bleeding and no response to resuscitation.
During the initial assessment, it is important to determine whether the bleeding
is from an upper or lower GI source (proximal or distal to the ligament of Treitz,
respectively) as this will guide the diagnostic approach. Distinguishing between
an upper and lower source of bleeding is usually relatively straightforward.
However, approximately 5%-10% of patients who present with hematochezia are
bleeding from an upper GI source, and some may not have blood in a gastric aspirate.
If there is uncertainty about the presence of an upper GI bleeding source, such
as when the gastric aspirate is not bile-stained, patients with hematochezia
and hemodynamic compromise should undergo upper endoscopy before evaluation
of the lower GI tract.
Admission to the hospital is required for most patients presenting with GI bleeding.
Those who present with frank hypotension or who have evidence for ongoing bleeding
require monitoring in an intensive care unit and urgent endoscopic evaluation.
Those who present with mild or no orthostasis, have no evidence for continued
bleeding, but have had a significant drop in hematocrit are generally hospitalized
on a medical/surgical floor. In general, young patients with self-limited GI
bleeding who present without orthostasis or hemodynamic instability and who
have no significant comorbid conditions may be managed as outpatients. Early
endoscopy may also assist in the identification of patients with a low rebleeding
risk who can be managed as outpatients
[Rockall, 1990].
2.2. Diagnosis
2.2.1. History and physical
During the initial stabilization and evaluation, a complete history and physical
should be performed. First, a detailed history of current and past GI bleeding
should be elicited. Patients with upper GI bleeding should be questioned about
known ulcer disease, liver disease, malignancy, abdominal surgery or bleeding
disorder, weight loss, and alcohol, aspirin or non-steroidal antiinflammatory
drug (NSAID) use. A history of antecedent retching suggests a Mallory-Weiss
tear. Patients with suspected lower GI bleeding should also be asked about hemorrhoids,
associated diarrhea, change in bowel habits, personal or family history of inflammatory
bowel disease, and a history of radiation therapy. A family history of GI disorders,
malignancy or bleeding disorders should also be obtained. Physical examination
should include orthostatic blood pressure and pulse even if the patient appears
stable and has no symptoms of orthostasis. Although the physical examination
seldom leads to a specific diagnosis, certain findings may provide helpful clues.
Such findings include cutaneous stigmata of liver disease, splenomegaly or ascites,
abdominal tenderness, an abdominal mass or lymphadenopathy, and cutaneous or
mucocutaneous manifestations of systemic disorders associated with GI bleeding
(Table 1).
2.2.2. Diagnostic studies
2.2.2.1. Upper GI endoscopy
Gastrointestinal endoscopy is the preferred diagnostic modality in patients
with upper GI bleeding. Barium studies generally have limited sensitivity and
may interfere with subsequent endoscopy or angiography. Furthermore, many abnormalities
seen on barium study will require endoscopic evaluation. In addition to its
superior sensitivity, other advantages of endoscopy include the ability to obtain
biopsies for an accurate histologic diagnosis, to determine the risk of rebleeding
(thus influencing decisions such as level of hospital care, when to resume feeding,
and the duration of hospitalization), and to provide endoscopic therapy. Endoscopic
therapy of bleeding esophageal varices and peptic ulcers with a high risk of
rebleeding can reduce the incidence of further bleeding and the need for surgery,
and improve survival
[Westaby,1985;
Williams,1993;
Thomopoulos,1997].
Early, judicious use of endoscopy can be of benefit from the standpoint of diagnosis,
therapy, and prognosis. Patients with severe upper GI bleeding should have an
upper endoscopy, or esophagogastroduodenoscopy
(EGD), performed as soon as they are stable. If resuscitation is unsuccessful,
an attempt at EGD is still warranted as it might provide useful information.
Patients in whom endoscopy cannot be performed due to torrential bleeding should
be considered for laparotomy, with or without prior mesenteric angiography.
Such decisions must be made in consultation with surgery, gastroenterology and
interventional radiology. Early endoscopy is also helpful in patients with milder
degrees of upper GI bleeding. The endoscopic findings in such cases can help
predict the risk of rebleeding. This information can be helpful in decision-making
regarding continued hospitalization versus early discharge. Variables predictive
of mortality in patients with upper GI bleeding are listed in (Table
2)
[Sanders,2002].
Patients who are young and who present with trivial bleeding may not require
endoscopic evaluation, particularly if there is a history of antecedent vomiting,
suggesting the presence of a Mallory-Weiss tear. Guidelines for the evaluation
of patients with upper GI bleeding are provided in Algorithm 1.
2.2.2.2. Sigmoidoscopy and colonoscopy
Patients with bright red hematochezia and minimal blood loss can undergo
initial evaluation with anoscopy and flexible sigmoidoscopy,
unless the patient is age 50 or older. In the latter setting, a full
colonoscopy is generally
recommended to rule out a colonic neoplasm. Those with dark hematochezia or
bright red blood per rectum and evidence for significant blood loss should undergo
full colonoscopy after a complete bowel preparation. In such patients bowel
preparation with an oral lavage solution is preferred unless there is evidence
for bowel obstruction. The solution can be administered rapidly via NG tube
in order to expedite the procedure. Active, brisk bleeding and continued hemodynamic
instability despite ongoing resuscitation is an indication for emergency angiography
rather than colonoscopy. Since lower GI bleeding can originate anywhere in the
small bowel or colon, angiography is also preferable to laparotomy in the setting
of such bleeding. Surgery is generally reserved for patients whose bleeding
site is identified by angiography but who are inappropriate for, or fail, angiographic
therapy. Guidelines for the evaluation of patients with lower GI bleeding
are provided in Algorithm 1.
2.2.2.3.
Angiography
Angiography is helpful in the patient with massive GI bleeding from either an
upper or lower source. Selective mesenteric angiography reveals a bleeding site
in up to 75% of patients with massive upper GI bleeding
[Laine,1997].
Among lower GI bleeding sources, diverticular bleeding and angiodysplastic lesions
are the most common lesions diagnosed by angiography
[Fioritto,1989].
Animal studies have demonstrated that a bleeding rate of 0.5 mL/min is necessary
in order for angiography to be positive
[Nusbaum,1963].
Contrast extravasation during angiography localizes the site of bleeding,
and in some instances can also define the lesion even when extravasation is
not noted (e.g., arteriovenous malformation, tumor).
Finally, selective angiography
allows for therapy with embolization or vasopressin infusion.
2.2.2.4. Radionuclide scanning
Radionuclide scanning is sometimes helpful in localizing the source of lower
GI bleeding. Red blood cells obtained by venipuncture are labeled with technetium
99m (99mTc) and reinjected into the patient. The abdomen is then
scanned with a gamma counter. Since prolonged or repeated scanning is possible,
bleeding can be detected even if it is intermittent or too slow to be detected
on angiography. However, 99mTc-labeled red blood cell scans have
their limitations. In earlier studies, the red blood cell scan was negative
in up to 70% of patients with a lower GI source of bleeding
[Bentley,1991;
Voeller,1991]
and in up to 50% of positive scans the predicted bleeding location was in correct
[Bentley,1991;
Dusold,1991].
More recently, digital equipment has allowed for more frequent imaging and cinematic
display. In one study using this technology, the site of bleeding was accurately
localized in 88% of positive scans
[O'Neill,2000].
Despite their limitations, 99mTc-labeled red blood cell scans may be helpful in some patients
with recurrent lower GI bleeding in whom all other diagnostic studies are negative.
Since red blood cell scans
detect lower rates of bleeding (0.1cc/min) than angiography, these scans are
often used as a screen to determine which patients should undergo angiography.
If the red blood cell scan is negative, the angiogram is very unlikely to demonstrate
active bleeding.
Radionuclide scanning is particularly helpful in the setting of bleeding from
a Meckel’s diverticulum. 99mTc pertechnetate is given intravenously,
and is taken up by the ectopic gastric mucosa in the Meckel’s diverticulum.
Using surgery as the gold
standard, the sensitivity of a Meckel's scan ranges from 75% to 91%, while the
specificity is 97% to 100%
[Fries,1984;
Kong,1993]. This
study should be considered early in the evaluation of a
young patient with lower GI bleeding.
2.2.2.5. Radiographic and endoscopic studies of
the small bowel
As previously discussed, barium studies are not immediately helpful in the setting
of overt GI bleeding. However, a small bowel follow-through or enteroclysis
is generally recommended to evaluate the small bowel when endoscopic studies
are unrevealing and bleeding has ceased. Enteroscopy also may be helpful in
this setting, particularly if small bowel
angiodysplasia is suspected.
Wireless capsule endoscopy is currently being studied undergoing study in the
evaluation of GI bleeding from a possible small bowel source. The Given Diagnostic
Imaging System (Given Imaging Ltd, Norcross, GA) was recently approved by the
Food and Drug Administration. The capsule endoscope, which is slightly larger
than a large vitamin capsule, is swallowed with water and is propelled through
the GI tract by peristalsis. Prior to capsule administration, patients either
fast or complete a limited purge to rid the distal small bowel of debris. Images
are transmitted to an antenna array worn on the abdomen and stored on a portable
data recorder. The capsule battery allows for 8 hours of imaging, after which
time the data are downloaded to a personal computer for viewing. In one recent
study, video capsule endoscopy was superior to small bowel radiographs in the
evaluation of 13 patients with obscure GI bleeding; 12 of 13 capsule endoscopy
studies yielded a source of bleeding, while only 1 of 13 small bowel radiographs
was positive
[Costamanga,2002].
Angiodysplasia was the most common finding. It should be noted that capsule
endoscopy has no role in the patient with acute GI bleeding because the test
takes 8 hours and the results are not immediately available. Furthermore, capsule
endoscopy will not replace push enteroscopy in patients with obscure GI bleeding,
since the latter has the ability to provide therapy. It also should not be performed
in lieu of a small bowel radiograph. A small bowel follow-through or enteroclysis
is generally recommended before capsule endoscopy because a stricture is a contraindication
to capsule administration. Finally, the interpretation of nonspecific findings
remains problematic, and to date no study has determined its sensitivity and
specificity.
2.3. Empiric treatment
Treatment of specific causes of GI bleeding is discussed below. To date,
no study has demonstrated any benefit from empiric treatment of acute upper
GI bleeding with intravenous H2 receptor antagonists
[Zuckerman,1984;
Collins,1985].
Furthermore, a large, randomized controlled trial of omeprazole in patients
presenting with acute upper GI bleeding found no significant difference between
the treatment and placebo groups with respect to transfusion requirements, rates
of rebleeding, surgery, and mortality
[Daneshmend,1992].
Patients who have known portal hypertension and esophageal or gastric varices
may be treated empirically with agents that reduce portal pressure. These agents
are discussed in more detail below.
3.0. UPPER GASTROINTESTINAL BLEEDING
3.1. Epidemiology
Upper GI bleeding is defined as bleeding from a gastrointestinal source that
is proximal to the ligament of Treitz. It is more common than lower GI bleeding.
Over 50% of upper GI bleeds are due to erosive or ulcerative disease of the
stomach or duodenum
[Gilbert,1990].
Etiologies of upper GI bleeding are listed in (Table
3).
Epidemiologic data from Europe indicated an upper GI bleeding annual incidence
of 48 to 145 per 100,000 population in the 1960s and 1970s
[Gilbert,1990].
In 1978 it was estimated that the total number of hospital admissions for upper
GI bleeding in the U.S. was 150 per 100,000 population
[Cutler,1990].
A more recent single HMO population-based study found an annual incidence
of 102 hospitalizations for upper GI bleeding per 100,000
[Longstreth,1995].
Finally, 1992-1999 data from the National Hospital Discharge Sruvey found an annual
hospitalization rate for UGI bleeding ranging from 149-172/100,000
[Lewis,2002].
Despite recent advances in endoscopic therapy, the mortality associated with
GI bleeding remains significant at 5% to 11%
[Lonstreth,1995;
Laine,1993;
Rockall,1995a;
Rockall,1995b;
Lewis,2002].
Factors associated with mortality due to upper GI bleeding have been identified
in prospective studies
[Rockall,1996;
Gilbert,1990].
These included underlying renal, liver, neoplastic, central nervous system or
lung disease, and physical findings consistent with cardiorespiratory or hemodynamic
compromise, or liver failure. Patients with active bleeding at the time of endoscopy,
blood transfusion requirement greater than 5 units, and requirement for surgery
also had increased mortality. In addition, patients requiring emergency surgery
had increased mortality compared with those undergoing more elective surgery.
Other patients with increased mortality include those with recurrent bleeding
after hospitalization
[Fleischer,1983]
and those who develop GI bleeding after hospitalization for other reasons
[Longstreth,1995].
3.2. Pathogenesis, diagnosis and therapy of specific
lesions
3.2.1. Gastric and duodenal erosive or ulcerative
disease
Peptic ulcer disease
is the most common cause of upper GI bleeding; over 50% of episodes are due
to gastric or duodenal erosions or ulcers
[Longstreth,1995;
Silverstein,1981].
GI bleeding due to ulcer
disease may be brisk, subacute or chronic. In erosive disease, the mucosal defect
by definition is not deep enough to result in brisk bleeding. Patients with
gastric/duodenal erosions typically have modest blood loss and may present with
coffee-ground emesis or melena. If gastric and/or duodenal erosive disease is
diagnosed on EGD, therapy should be initiated with either proton-pump inhibitors
or H2-receptor
antagonists.
In patients with acute GI bleeding from a gastric or duodenal ulcer, endoscopic
findings can be used to guide medical therapy. While treatment with H2-receptor
antagonists, when compared to placebo, has not been shown to reduce the risk
of rebleeding in such patients
[Laine,1994],
several studies have shown that omeprazole is beneficial in selected patients
[Khuroo,1997;
Schaffalitzdy,1997;
Hasselgren,1997;
Lau,2000;
Javid,2001].
Specifically, in those who have undergone endoscopic therapy for acute UGI bleeding from a peptic ulcer that is at high
risk of rebleeding, treatment with omeprazole therapy is associated with a significant reduction in rebleeding rates
[Khuroo,1997;
Schaffalitzdy,1997;
Lau,2000;
Javid,2001], emergency surgery
[Khuroo,1997;
Schaffalitzdy,1997;
Javid,2001], transfusion requirement
[Schaffalitzdy,1997;
Javid,2001], and length of hospital stay
[Javid,2001].
Studies have differed with respect
to route of administration (p.o or I.V.) and duration of treatment (3 or 5 days).
Since patients with a high risk of rebleeding should be kept NPO, the I.V. route
is generally preferred. Both of the positive studies with I.V. omeprazole used
an 80 mg bolus followed by an 8 mg/hour continuous infusion for 72 hours, after
which time patients were transitioned to omeprazole 20 mg p.o. daily for up
to 8 weeks
[Schaffalitzdy,1997;
Lau,2000]. Finally, two studies have
compared omeprazole and H2 antagonists in patients with acute GI bleeding from high-risk ulcers
[Lin,1998;
Lanas,1995]. One of the studies
found a significant reduction in rebleeding rates in the omeprazole group
[Lin,1998],
while the second study found trends toward decreased rates of rebleeding and surgery in those receiving omeprazole
[Lanas,1995].
IV omeprezole is currently unavailable
in the United States. The only intravenous PPI available in the U.S. is pantoprazole,
and we await studies of this agent in acute ulcer bleeds. Given that the beneficial
effect of IV omeprezole is likely related to the ability of an IV PPI to maintain
continuous elevation of the intragastric pH, it appears reasonable to extrapolate
from the IV omeprezole studies and use IV pantoprazole at a dose of 80 mg bolus,
8 mg/hr for ulcers at high risk of rebleeding.
There is no evidence that high-dose I.V. PPI therapy is beneficial in patients
with GI bleeding from an ulcer that has a low risk of rebleeding (i.e., a clean-based
ulcer on endoscopy). In these patients, oral PPI therapy can be instituted after
the patient has recovered from the endoscopy. PPIs are generally recommended
over H2 blockers because healing of uncomplicated gastric and duodenal ulcers
is more rapid with proton-pump inhibitors (PPIs) than with H2-antagonists
[Lauritsen,1985;
McFarland,1990;
Marks,1991;
Hotz,1992;
Delle,1992].
3.2.1.1. Helicobacter pylori
The discovery of Helicobacter
pylori (H. pylori) infection has revolutionized our diagnostic
and therapeutic approaches to ulcer disease. Over 90% of duodenal ulcers
and 80% of gastric ulcers can be attributed to H. pylori, while the vast
majority of remaining ulcers are due to NSAID
use [Graham,1996].
The pathogenesis of H. pylori-related ulcer disease, and H. pylori testing and treatment are discussed in
Chapter 2.
Patients who are found to have a gastric
ulcer, duodenitis or duodenal
ulcer on endoscopy should have gastric mucosal biopsies to assess for H.
pylori infection. Infection with H. pylori can be diagnosed by rapid
urease testing of a single antral biopsy or by submitting biopsies for histologic
examination. Non-invasive tests such as the urea breath test or stool antigen
test are as sensitive and specific as endoscopic biopsy and may be more appropriate
in patients with brisk bleeding (performed once bleeding has stopped), when
it may be unwise to prolong the endoscopy in order to take biopsies. Patients
with duodenitis or duodenal/gastric ulcer who test positive for H.
pylori should
be treated with an acid-reducing agent (PPI BID) and at least two antibiotics
(clarithromycin 500 mg BID, amoxicillin 1 gm BID) for at least 1 week. More
information about specific H. pylori treatment regimens can be found
in Chapter 2. Patients with complicated ulcer disease (bleeding or perforation)
should have confirmation of H. pylori cure by either urea breath test,
stool antigen test or endoscopic biopsy. Repeat testing should be performed
a minimum of four weeks after completion of therapy
[Rollan,1997].
Proton pump inhibitor therapy should also be discontinued for 1 week prior to
repeat testing for H. pylori because of the suppressive effect of these drugs
on H. pylori growth, which may lead to false negative urea breath tests and
stool antigen tests [Laine,1998].
Because serology for H. pylori may remain positive for up to two years
following successful eradication, it cannot be relied upon for confirmation
of successful cure patients.
3.2.1.2. NSAID erosions/ulcer
It is well recognized that NSAID use is associated with an increased risk
of gastric or duodenal ulcer. Antral erosions are present within 1 to 2 days
in virtually all individuals taking NSAIDs
[O'Laughlin,1981;
Larkai,1987]. However,
these erosions are usually
asymptomatic, often disappear with continued NSAID use, and do not predict ulcer
development. Symptomatic ulcers and ulcer complications develop in only 2% to
4% of patients taking NSAIDs for a year
[Paulus,1985].
The risk of hospitalization or death from such complications is 1.3% to 1.6%
per year in patients with rheumatoid arthritis
[Fries,1991].
Although the risk appears
small, the millions of U.S. patients taking NSAIDS for arthritis or aspirin
for cardiovascular prophylaxis translates into a large number of patients at
risk. Even low-dose aspirin, with or without enteric coating, is associated
with an increased risk of UGI bleeding (standardized incidence ratio 2.6 in
both groups) [Sorenson,2000].
The pathogenesis of NSAID-induced ulcer disease relates to both local and systemic
effects [Bjorkman,1995].
Aspirin and NSAIDs
are lipid soluble at acid pH and thus diffuse across gastric epithelial cell
membranes. Furthermore, these agents are cytotoxic, leading to a breakdown of
the gastric mucosal barrier. These local effects rarely lead to acute ulceration
and symptomatic disease. It is the systemic inhibition of prostaglandins that
leads to symptomatic chronic ulceration. Such inhibition further compromises
the gastric mucosal barrier by decreasing mucus and bicarbonate secretion and
mucosal blood flow. NSAIDs also inhibit platelet function, and their use has
been associated with GI bleeding from throughout the GI tract
[Lanas,1996].
Nabumetone and etodolac, NSAIDs that have partial selectivity for prostaglandin
synthesis inhibition in inflamed tissues, appear to have lower rates of GI ulceration
and related complications. In three large postmarketing survey studies of nabumetone,
GI ulcer and complication rates ranged from .02% to .7%
[Jenner,1990;
Stroelmann,1990;
Willkens,1990].
Two large open-label studies of etodolac reported adverse reactions in 0.1% and .005%, respectively
[Benhamou,1990].
Although these newer agents appear promising with respect to GI complications,
complication rates attributed to newer versus older NSAIDs cannot be directly
compared due to differences in dose, patient characteristics and study design.
Large, randomized trials comparing these newer agents with older NSAIDs are
lacking. Small, short-term endoscopic studies have reported fewer GI erosions
and/or ulcers in patients taking nabumetone or etodolac compared with other
NSAIDs
[Roth,1987;
Bianchi,1991;
Laine,1995].
Newer NSAIDs (celecoxib, rofecoxib)
that are even more selective for prostaglandin synthesis in inflamed tissues
are now available. In prospective endoscopic studies, these drugs caused fewer
ulcers when compared with other NSAIDs
[Simon,1999;
Laine,1999;
Hawkey,2000;
Goldstein,2001],
and caused no more ulcers than placebo
[Simon,1999;
Laine,1999;
Hawkey,2000].
Two large randomized trials also found
significantly reduced rates of symptomatic ulcer and ulcer complications in
patients assigned to rofecoxib
[Bombardier,2000]
or celecoxib [Silverstein,2000]
when compared to nonselective
NSAIDs (naproxen and ibuprofen/diclofenac, respectively). In the latter study,
subjects were allowed to take low-dose aspirin for cardiovascular prophylaxis.
Interestingly, aspirin use appeared to negate the GI benefits of celecoxib.
A recently published study randomized over 8000 patients with rheumatoid arthritis
to rofecoxib or naproxen and followed them for a median of 9 months
[Laine,2002].
Overall, upper GI events (symptomatic
or complicated ulcer) were significantly decreased in the rofecoxib group, and
the number needed to treat to prevent an event was 31. However, when taking
into account the highest risk patients (age = 75, prior upper GI event, or severe
rheumatoid arthritis), the number needed to treat was only 10-12.
3.2.1.2.1. Risk factors for NSAID ulcer complications
Risk factors for NSAID-induced ulcer complications include age greater than
65-75 years, history of peptic ulcer or gastrointestinal bleeding, history of
heart disease, prednisone or warfarin use, and severe rheumatoid arthritis
[Fries,1991;
Silverstein,1995;
Wolfe,1999;
Laine,2002].
NSAIDs should be avoided, if possible, in these high-risk patients. If an NSAID
is necessary, rofecoxib or celecoxib should be considered, although the cost-effectiveness
of this approach has not been determined. Other options includeprophylaxis with
misoprostol or omeprazole.
3.2.1.2.2. Prevention of NSAID ulcers and ulcer
complications
In a randomized, placebo-controlled study of three misoprostol
dosing regimens in the prophylaxis of NSAID-related ulcer disease, doses
of 200 mcg bid, tid and qid all significantly decreased the rate of gastric
and duodenal ulcer when compared to placebo
[Raskin,1995].
A dose-reponse effect was noted in
the prevention of gastric, but not duodenal, ulcer. Due to side effects such
as abdominal pain, nausea, flatulence, and diarrhea, twice daily dosing is generally
better tolerated than more frequent dosing
[Silverstein,1995;
Raskin,1995].
Misoprostol also has been show to reduce the risk of NSAID-related ulcer complications
[Silverstein,1995].
Prophylaxis with H2-blockers
is as effective as misoprostol in reducing the rate of NSAID-induced duodenal
ulcer, but is significantly less effective in the prevention of gastric ulcers
[Raskin,1996].
Three randomized, placebo controlled studies have demonstrated that omeprazole, 20 mg daily, is
effective in the primary prophylaxis against gastroduodenal ulcers in patients
taking NSAIDs [Ekstrom,1996;
Cullen1998;
Bianchi,1998].
In a recently published randomized,
placebo-controlled trial of omeprazole
versus misoprostol for the prophylaxis of NSAID-related ulcer, omeprazole 20
mg daily was more effective than misoprostol 200 mcg twice daily in patients
with prior NSAID-related erosive or ulcerative disease, and either drug was
more effective than placebo [Hawkey,1998].
Finally, a recent placebo-controlled
trial demonstrated that lansoprazole 30 mg daily significantly reduced the risk
of recurrent aspirin-related ulcer complications in patients who continued on
low dose aspirin [Lai,2002].
In a two-week placebo-controlled study of sucralfate gel prophylaxis in NSAID
users, the incidence of gastroduodenal erosions and/or ulcers on 2-week endoscopy
were significantly less frequent in the sucralfate group
[Miglioli,1996].
However, no study has demonstrated
that long-term prophylaxis with sucralfate prevents gastroduodenal ulcer or
ulcer complications. A randomized trial comparing misoprostol to sucralfate
found that the former was significantly more effective in preventing gastric
ulcers in patients on chronic NSAID therapy
[Agrawai,1991].
Thus sucralfate and related agents have no role in the prophylaxis of NSAID-related ulceration.
3.2.1.2.3. Treatment
In patients with
GI bleeding from an NSAID-induced gastric or duodenal ulcer, it is best to discontinue
the NSAID and treat with a PPI for four weeks. If it is necessary to continue
the NSAID, the ulcer is likely to heal if treated, but PPIs rather than H2 blockers
should be used in this setting
[Yeomans,1998].
In a recently published randomized
trial of NSAID ulcer treatment, omeprazole 20 mg or 40 mg daily and misoprostol
200 mcg qid all were equally effective in healing NSAID-related erosive or ulcerative
disease in patients who continued to take NSAIDs, with healing rates of 71%
to 76% at 8 weeks
[Hawkey,1998].
However, patients with "clinically
important" GI bleeding were excluded from this study. Certain factors should
be considered before deciding if NSAID use should be continued in the setting
of GI bleeding. Such variables include the significance of the GI bleed, patient
comorbidity (that is, the ability to tolerate another bleed), and whether or
not the patient had warning symptoms such as dyspepsia before presenting with
GI bleeding. If long-term NSAID therapy is deemed necessary, ulcer prophylaxis
should be continued indefinitely. Whether to use misoprostol or a proton
pump inhibitor in this setting is uncertain. Hawkey and colleagues recently
reported that duodenal ulcer recurrence was significantly lower with omeprazole
maintenance at 20 mg daily (39%) than with misoprostol maintenance at 200 mcg
bid (52%), but that both agents were superior to placebo (73%)
[Hawkey,1998].
3.2.1.2.4. Role of H. pylori infection in
NSAID ulcer
The role of H. pylori infection in NSAID ulcer is not certain. Furthermore,
it may be difficult to definitively prove that an ulcer is due to NSAIDs rather
than H. pylori, since an ulcer may have been present before NSAID therapy was
initiated. In general, all patients who develop an ulcer while on NSAIDs should
be tested for H. pylori infection and treated if positive. However, although
there are some data to indicate that endoscopic ulcers may be less frequent
if patients are treated for H.pylori before beginning NSAIDs, we await
further clinical outcome studies of this question before recommending routine
testing and treatment of H. pylori prior to initiating NSAIDs.
3.2.1.3. Ulcers not associated with H. pylori or
NSAID use
An increasing proportion of gastric and duodenal ulcers cannot be attributed
to H. pylori infection or NSAID use
[Laine,1998].
In the case of gastric ulcers, it is
important to rule out malignancy. If malignancy (in the case of gastric ulcer)
and Zollinger-Ellison syndrome have been excluded, it is recommended that the
patient with a complicated ulcer continue on life-long acid-suppression therapy
once the ulcer has healed. In the majority of cases a single dose of H2-antagonist
at bedtime will reduce the risk of ulcer recurrence to approximately 15% to
25%, although some patients will require twice this dose
[Strum,1986;
Texter,1986]
or a proton pump inhibitor for effective prophylaxis . In general the appropriate
dose for prophylaxis can be individualized according to the patient’s symptoms.
Patients who develop recurrent ulcer disease despite medical prophylaxis should
be considered for anti-ulcer surgery.
3.2.1.4. Indications for follow-up endoscopy
Since approximately 1% of gastric ulcers are malignant, gastric ulcers should
be biopsied at the time of diagnosis. If they are not, follow-up endoscopy to
document ulcer healing is recommended regardless of endoscopic appearance or
evidence for H. pylori infection or NSAID use. The follow-up endoscopy is performed
approximately 8 weeks after the initial diagnosis. If the ulcer is still present
and has not shown significant healing, several biopsies are taken from its edge.
Further management is individualized and obviously depends on whether the non-healing
ulcer is benign or malignant.
3.2.1.5. Stress gastritis
Stress gastritis
refers to hemorrhagic gastric erosions in patients who are critically ill
[Ben-Menachem,1994;
Maier,1994].
These lesions can be diffuse and typically
involve the gastric body and fundus. With extensive involvement bleeding can
be massive. Physiologic stress associated with trauma, burns, major surgery
or severe medical illness requiring ICU hospitalization have been associated
with the development of hemorrhagic gastritis
[Chamberlain,1993].
The pathogenesis is due to an
imbalance between aggressive and protective mucosal factors. While infection
with H. pylori may coexist, it is thought to play no role in the pathogenesis
of stress gastritis. In a recent study, the independent risk factors for development
of stress ulcer bleeding were respiratory failure and coagulopathy
[Cook,1994].
These patients should receive prophylaxis with H2 antagonists
[Cook,2000].
The diagnosis of stress gastritis is readily made on endoscopy and treatment is with aggressive reduction of gastric
pH using H2 antagonists or proton pump inhibitors
[Collier,1989;
Hadi,1989].
3.2.2. Bleeding associated with portal
hypertension
3.2.2.1. Esophageal and gastric varices
At the time of diagnosis of cirrhosis, esophageal and/or gastric varices
are present in approximately 60% with decompensated cirrhosis and in approximately
30% with compensated cirrhosis
[D'Amico,1995].
A discussion of other causes
of portal hypertension is beyond the scope of this chapter. The incidence of
bleeding in patients with known esophageal varices is approximately 10%
to 15% per year, and in patients with large varices is 20% to 30%
[D'Amico,1995].
Gastrointestinal bleeding due to varices is typically brisk and associated with hemodynamic compromise, although
sometimes patients with variceal bleeding present with melena and are hemodynamically
stable. The mortality associated with the first variceal bleed ranges from 30%
to 50% [D'Amico,1995].
Endoscopic sclerotherapy and band ligation of varices are the
mainstay of emergent therapy in patients presenting with esophageal variceal
bleeding. Patients in whom early rebleeding is successfully prevented with endoscopic
therapy should undergo repeated sessions until varices are eradicated. With
such therapy the risk of rebleeding is significantly reduced but remains as
high as 50% with sclerotherapy and 35% with band ligation
[Steigmann,1992;
Laine,1993;
Gimson,1993].
Data from recent trials indicate that band ligation, when compared to sclerotherapy, is associated with fewer treatment-related complications
[Stiegmann,1992;
Laine,1995;
Lo,1995] and requires
fewer sessions to achieve variceal eradication
[Gimson,1993;
Laine,1995;
Lo,1995]. Lower rebleeding rates
[Gimson,1993;
Lo,1995] and improved survival
[Stiegmann,1992;
Lo,1995]
have also been reported in patients undergoing variceal ligation. Band ligation of esophageal varices has largely supplanted
sclerotherapy.
Although medical therapy for variceal hemorrhage has been extensively studied,
the benefit of such therapy remains uncertain. Earlier studies demonstrated
that vasopressin or vasopressin analogue reduced early rebleeding rates,
but often at the expense of significant toxicity from systemic vasoconstriction
[Mallory,1980;
Fogel,1982].
More recently somatostatin and
the somatostatin analogue, octreotide, have replaced vasopressin in the
acute treatment of variceal hemorrhage (only octreotide is available in the
U.S.). These agents reduce portal pressure by decreasing splanchnic blood flow
[Bosch,1981].
While many studies have demonstrated a benefit of using somatostatin or octreotide
in acute variceal hemorrhage, overall results have been mixed
[Valenzuela,1989;
Burroughsk,1990;
Saari,1990;
Hwang,1992;
Shields,1992;
Planas,1994;
Sung,1995;
Goetschze,1995].
In some studies, somatostatin and octreotide were as effective as endoscopic
therapy in controlling acute variceal hemorrhage
[Shields,1992;
Planas,1994].
In addition, patients with acute variceal hemorrhage treated with both octreotide
and endoscopic therapy had significantly lower rebleeding rates than those treated
with endoscopic therapy alone
[Besson,1995;
Sung,1995;
Avgerinos,1997;
Zuberi,2000;
Cales,2001].
In all studies, somatostatin or one of its derivatives was continued
for a duration of 5 days. A meta-analysis was recently published that included
these trials and three additional studies published only in abstract form
[Banares,2002].
This analysis found that somatostatin/somatostatin
analogues, when combined with endoscopic treatment, improved initial and 5-day
hemostasis compared to endoscopic therapy alone. Given the demonstrated benefit
of these agents and the significant mortality associated with variceal hemorrhage,
it is reasonable to use octreotide in patients with documented bleeding from
esophageal varices. A loading dose of 50 mcg IV is given, followed by an infusion
of 25 mcg to 50 mcg per hour for a duration of 5 days. Two of the studies initiated
somatostatin or its analogue before endoscopy
[Avgerinos,1997;
Cales,2001].
In clinical practice, octreotide is often initiated before the endoscopy
if variceal hemorrhage is suspected. This is a reasonable approach, provided
that the endoscopy can be expedited and the octreotide can be discontinued if
an alternate source of bleeding is discovered.
The Senkstaken-Blakemore or Minnesota tube remains an important
therapeutic tool in patients with brisk esophageal or gastric variceal hemorrhage
that cannot be controlled on initial endoscopy.
It is generally felt that the gastric balloon on these tubes should not remain inflated for more than 48 hours at one time. The esophageal balloon should be inflated only if bleeding continues despite inflation of the gastric balloon, and for no more than 8 hours at a time due to the high risk of tissue necrosis. Patients who continue to bleed or who have more than one rebleeding episode despite endoscopic and medical therapy should be considered for portal decompression. Due to the morbidity and mortality associated with surgical portal decompression in patients with Childs B or C cirrhosis, transjugular intrahepatic shunting (TIPS) is generally preferred in these patients, particularly if portal decompression is serving as a bridge to liver transplantation.
Patients with Childs A cirrhosis
should be considered for surgical decompression, as they may not require liver
transplantation for several years and TIPS is associated with occlusion due
to neointimal hyperplasia in the majority of patients within two years
[Somberg,1997].
Once acute esophageal variceal bleeding has been controlled, patients are generally
treated with repeat outpatient endoscopic therapy until varices are eradicated.
Oral beta-blocker
therapy is used in combination with endoscopic therapy as it has been shown
to decrease the rebleeding rate over endosocopic therapy alone
[Vinel,1992].
Non-selective beta-blockers are preferred because their effect on portal pressure
likely results from both splanchnic vasodilation and decreased cardiac output.
It is recommended that the dose is titrated to reduce the resting pulse by 25%.
Following the eradication of esophageal varices, endoscopy is repeated every
3 to 6 months in order to monitor for recurrent varices and provide further
endoscopic therapy if indicated.
Some investigators
have compared medical therapy (propranolo/nadolol plus isosorbide mononitrate)
to endoscopic therapy for the prevention of variceal rebleeding
[Villanueva,1996;
Patch,2002;
Lo,2002].
In one study, the combination of nadolol
and isosorbide mononitrate was superior to endoscopic sclerotherapy in the prevention of rebleeding
[Villanueva,1996].
Two other studies compared medical therapy to band ligation
[Patch,2002;
Lo,2002].
One found them to be equivalent in preventing rebleeding
[Patch,2002],
while the second found that band ligation was more effective than nadolol and isosorbide mononitrate
[Lo,2002].
Because medical therapy
has not yet been compared to the current standard of care (band ligation and
beta-blocker therapy in combination), these findings are unlikely to change
clinical practice.
Finally, several studies have compared TIPS to sclerotherapy
[Cabrera,1996;
Cello,1997;
Sanyal,1997;
Garcia-Vilareal,1999;
Sauer,1997;
Merli,1998] or band ligation
[Jalan,1997;
Pomier_layrargues,2001]
in the prevention of esophageal variceal rebleeding. All but one
[Sanyal,1997]
found that rebleeding rates were
significantly reduced in those treated with TIPS. These studies were included in a recent
meta-analysis that confirmed reduced rebleeding rates in those undergoing TIPS
[Papatheodoridis,1999].
However, encephalopathy was increased in TIPS
patients, and there was no difference in overall survival
[Papatheodoridis,1999].
Thus TIPS is not routinely recommended for the prevention of rebleeding from esophageal varices, but
is reserved for the treatment of bleeding that is refractory to endoscopic therapy.
The management of bleeding from gastric varices is more difficult. Although medical and/or
endoscopic therapy may be successful in controlling acute bleeding, endoscopic therapy does
not lead to effective variceal obliteration. These patients should be referred for TIPS
[Barange,1999]
or surgical decompression, preferably after control of the initial bleeding episode.
3.2.2.2. Portal hypertensive gastropathy
Patients with portal hypertension also may develop portal
hypertensive gastropathy.
Although the pathogenesis
is not well understood, increased mucosal blood flow and passive congestion
of the submucosa appear to play a role
[Panes,1992;
Ohta,1994].
Gastropathy accounts for 8% to 20% of acute bleeding in patients with portal
hypertension and can also lead to chronic blood loss
[Sarin,1992;
Gostout,1993].
Many patients presenting with bleeding from portal hypertensive gastropathy have recurrent bleeding
[Gostout,1993].
Propranolol may be effective in preventing recurrent hemorrhage from portal hypertensive gastropathy
[Hosking,1987;
P'Erez,1991].
Occasionally transjugular
intrahepatic stent (TIPS) placement or surgical portal decompression is
required for severe, intractable bleeding
[Babb,1988;
Orloff,1995].
3.2.2.3. Other
Duodenal varices
may cause significant upper GI bleeding. If varices are within the reach of
the endoscope, sclerotherapy or band ligation may successfully control the acute hemorrhage
[Tazawa,1995].
However, the long-term management of duodenal varices generally requires
portal decompression.
3.2.3. Mallory-Weiss tear
The Mallory-Weiss
tear, a mucosal laceration of the gastric cardia or gastroesophageal junction,
was first described in 1929 by Kenneth Mallory and Soma Weiss
[Mallory,1929].
These tears account for approximately 5% to 15% of all cases of upper GI bleeding
and are relatively common in alcoholics
[Harris,1993].
The classic presentation is that of repeated retching, vomiting or coughing
followed by hematemesis. However, up to 50% of patients with Mallory-Weiss tears
do not give a history of antecedent retching or vomiting
[Harris,1993].
Blood loss is usually modest and only 10% present with hemodynamic compromise.
The typical endoscopic appearance is a mucosal tear in the cardia either just
below the gastroesophageal (GE) junction or bridging the GE junction.
Bleeding is self-limited
in 90% of cases and patients in whom bleeding has ceased at endoscopy require
no therapeutic intervention. Active bleeding at the time of endoscopy is treated
with injection of saline or 1:10,000 epinephrine and/or electrocautery. Angiography
with vasopressin infusion or embolization has been reported to be successful
in small, uncontrolled series
[Carsen,1978;
Fisher,1980].
Rarely patients with severe or recurrent bleeding require surgery and oversewing of the tear
[Harris,1993].
3.2.4. Esophagitis
Heartburn and regurgitation due to gastroesophageal reflux are common
GI symptoms . Since most patients with persistent symptoms are treated with
acid-reducing agents, bleeding from esophagitis
or esophageal ulceration
is not very common. One exception is the alcoholic patient, who may not present
until overt signs of bleeding develop. Prolonged nasogastric tube placement
in hospitalized patients may also lead to bleeding from erosive esophagitis.
3.2.5. Alcohol and upper GI bleeding
It is a common misconception that "alcoholic gastritis" is a significant
cause of upper GI bleeding in patients with excess alcohol use. Although both
animal and human studies have shown that alcohol
is directly injurious to gastric mucosa
[Guth,1984;
Tarnawski,1987],
alcohol use is most commonly associated with a reactive gastropathy. Only rarely
does this entity lead to GI bleeding. Patients who are actively drinking more
commonly bleed from ulcer disease, disorders related to portal hypertension, Mallory-Weiss tears, or esophagitis
[Wilcox,1996].
A recent multinational case-control study found that heavy alcohol consumption was a risk factor for major gastric and duodenal bleeding
[Kelly,1995].
3.2.6. Neoplasms
Adenocarcinoma of the stomach is the most common malignant neoplasm
of the upper GI tract and often presents with frank or occult GI bleeding. With
the exception of vascular tumors and stromal tumors
[Senewiratne,1987],
benign neoplasms of the upper GI tract seldom bleed. Stromal tumors, formerly
called leiomyomas, are prone to ulceration and thus may bleed. They can be found
throughout the GI tract.
Hemangiomas are the most common vascular tumor of the GI tract, but are a rare
cause of GI bleeding. Almost all bleeding hemangiomas are cavernous hemangiomas
and they most commonly occur in the small intestine. Endoscopically they appear
as single or multiple red, purple or blue nodular lesions. Cavernous hemangiomas
of the skin, GI tract and other viscera are seen in patients with the blue rubber
bleb nevus syndrome. Hemangiosarcomas, malignant vascular tumors, are rare in
the GI tract. The treatment of hemangiomas and hemangiosarcomas is surgical.
3.2.7. Vascular anomalies
Vascular anomalies are an unusual cause of upper GI bleeding, accounting for
only 5% of cases. True arteriovenous malformations are rare. Angiodysplasia,
whether sporadic or secondary, is the most common vascular anomaly seen in the
GI tract.
3.2.7.1. Angiodysplasia
Gastrointestinal angiodysplastic lesions are dilated, tortuous vessels
in the mucosa and submucosa. These lesions may be sporadic, usually developing
in the elderly, or may be found in association with a number of disorders including
renal failure, cirrhosis, the CREST syndrome, radiation injury, von Willebrand’s
disease, and aortic stenosis. Angiodysplastic lesions may occur anywhere in
the GI tract, but are more commonly found in the colon, followed by the small
intestine and the stomach. These lesions usually lead to occult blood loss,
but can also cause overt GI bleeding. They are usually apparent at endoscopy,
at which time therapy with laser or thermal probes may be applied. Bleeding
that is refractory to endoscopic or medical therapy is an indication for surgical
resection. In the case of small bowel angiodysplastic lesions where endoscopic
therapy is not possible due to the location or multiplicity of lesions, low-dose
combination estrogen/progesterone therapy may be beneficial
[Van Custem,1990].
Hereditary hemorrhagic
telangiectasia (Osler-Weber-Rendu syndrome) encompasses a group of autosomal
dominant disorders associated with vascular ectasia and arteriovenous malformations
of the nose, skin, lungs, brain and GI tract. Epistaxis is the most common manifestation
and occurs in most patients before the third decade. Recurrent bleeding from
the stomach, small intestine and colon usually begins in the fifth or sixth
decade and occurs in only a minority of patients. Endoscopic therapy with laser
or thermal probes is usually helpful in controlling actively bleeding ectasias,
but bleeding frequently recurs due to the presence of multiple lesions. As previously
mentioned, combined estrogen/progesterone therapy may be useful
[Van Custem,1990].
Because multiple lesions are present throughout the GI tract, surgical therapy is not an option.
3.2.7.2. Arteriovenous malformations
True arteriovenous
malformations (AVMs) are rare in the GI tract. They are present in younger
patients, suggesting that they are congenital, but their true etiology remains
uncertain. On endoscopy AVMs
appear as nodular lesions.
Unlike angiodysplasia, they
may involve any layer of the gut wall. Surgical resection is the treatment of
choice, although poor surgical candidates may be treated with arterial embolization.
3.2.7.3. Dieulafoy lesion
This lesion, first described by Gallard in 1884 and later by the French surgeon
Dieulafoy in 1896, is characterized by an aberrantly large and tortuous submucosal
artery that may erode through a small mucosal defect, resulting in massive hemorrhage
[Juler,1984].
Approximately 75% to 95% occur in the proximal stomach, usually on the lesser
curvature and within 6 cm of the gastroesophageal junction, although they have
been reported to occur thoughout the GI tract
[Scheider,1994;
Dy,1995;
Goins,1995;
Farrell,1992].
The initial endoscopy in patients bleeding from a Dieulafoy
lesion may reveal no obvious bleeding because of the lesion’s small
size, rapid healing of the mucosal defect, or the presence of large amounts
of retained blood obscuring the lesion. Not infrequently a second endoscopy
is required to identify the lesion; in some patients the diagnosis is made only
on angiography or during surgery
[Reilly,1991].
The typical endoscopic appearance is that of a bright or dark red "nipple"
protruding from the mucosa without an associated ulcer base, distinguishing
it from a visible vessel in an ulcer.
These lesions often respond
to endoscopic therapy with injection of saline or 1:10,000 epinephrine and/or
endoscopic application of thermal probes
[Pointner,1988;
Baettig,1993].
Patients who do not respond
to endoscopic therapy require surgical intervention. Although the literature
in this area is limited, it is generally felt that a wide wedge resection of
the artery and bleeding site is preferable to oversewing the artery in the area of the mucosal defect
[Veldhuyzen-van-Zanten,1986].
Patients who are poor surgical candidates may respond to angiographic embolization
[Sherman,1979].
3.2.7.4. Gastric antral vascular ectasia
Gastric
antral vascular ectasia (GAVE), or watermelon stomach,
is an unusual cause of upper GI bleeding. Patients typically present with melena
or occult blood loss with iron deficiency anemia
[Katz,1993].
GAVE is usually idiopathic, but has been reported in association with several disorders including scleroderma,
cirrhosis and after bone marrow transplantation
[Watson,1996;
Payen,1995;
Tobin,1996].
Endoscopy is often diagnostic, revealing a watermelon-like striped pattern of mucosal erythema
radiating proximally from the pylorus and usually limited to the antrum.
Small mucosal vascular
malformations may also be seen. Mucosal biopsy typically reveals foveolar hyperplasia,
fibromuscular hyperplasia of the lamina propria and dilated mucosal capillaries with intraluminal thrombi
[Suit,1987].
Although the pathogenesis is unknown, the histologic
appearance suggests that prolapse of antral folds through the pylorus may play
a role. Endoscopic laser or thermal probe therapy of the lesions is usually successful
[Bourke,1996;
Ng,1996].
Rare refractory cases may require surgical resection of the involved area.
3.2.8. Miscellaneous causes
Aortoduodenal fistulas, representing 80% of all aortoenteric fistulas, are a
very unusual but catastrophic cause of bleeding from the upper GI tract. It
is estimated that 0.4% to 4% of patients with aortic grafts develop an aortoenteric fistula
[Champion,1982].
Primary aortoduodenal fistulas associated with atherosclerotic
aneurysms or trauma are much less common
[Voorhoeve,1996].
The classic presentation of
an aortoduodenal fistula is that of a "herald bleed" (brief, with
spontaneous resolution), followed anywhere from hours to weeks later by a massive
upper GI bleed. A high index of suspicion and rapid diagnosis is imperative
as exsanguinating hemorrhage may occur. Intermittent or occult bleeding can
occur in patients who have an aortoenteric erosion rather than a true fistula
[Bessen,1985].
An aortoduodenal fistula or erosion rarely is seen endoscopically [139,140].
More commonly fresh blood or clots may be found in the third portion of the
duodenum. Angiography is seldom helpful unless a pseudoaneurysm is seen
[Bessen,1985].
Although CT visualization of an aneurysm with associated extraluminal gas is
virtually diagnostic, this finding is also uncommon. The diagnosis is
usually made or confirmed on laparotomy. Surgical repair is the only therapeutic
option.
Hemobilia, another rare cause of UGI bleeding, is usually associated with intraductal
neoplasm, trauma, or iatrogenic injury such as percutaneous liver biopsy
[Bloechle,1994].
Other reported causes include cystic artery pseudoaneurysm
[Nakajima,1996].
The diagnosis is suggested by jaundice, right upper quadrant pain and gastrointestinal bleeding.
Hemobilia may be confirmed at endoscopy by finding blood limited to the second
portion of the duodenum or blood emanating from the ampulla, but often requires
angiography. Angiographic therapy is the treatment of choice, although occasionally surgical therapy is necessary
[Katz,1993].
Bleeding from the ampulla may also be due to hemosuccus pancreaticus. This is
most commonly due to a pseudoaneurysm of the splenic artery in patients with
a pancreatic pseudocyst or chronic pancreatitis but rarely may occur in patients
with pancreatic duct malignancy
[Risti,1995].
Diagnosis and therapy are dictated by the underlying pathology.
Finally, patients who present with symptoms of upper GI bleeding may occasionally
be bleeding from a non-GI source, as in patients with epistaxis and swallowed
blood. Factitious bleeding from ingestion of animal blood or human blood
after auto-phlebotomy has also been reported
[Rose,1996].
4.0. LOWER GASTROINTESTINAL BLEEDING
4.1. Epidemiology
Bleeding from a site distal to the ligament of Treitz is less common than upper
GI bleeding. More commonly bleeding is from a colonic rather than a small bowel
source. Causes of lower GI bleeding are listed in (Table
4).
A recent U.S. population-based study estimated an annual incidence rate of lower GI bleeding at 20.5/100,000
[Longstreth,1997].
The most common diagnoses were diverticulosis, colorectal
cancer and ischemic
colitis. Bleeding rate was increased in males and in older patients. The
mortality rate was 2.4% in patients admitted with lower GI bleeding compared
with 23.1% in patients who developed lower GI bleeding after hospitalization
for another reason. Among all patients presenting with lower GI bleeding, hemorrhoidal
bleeding is probably the most common cause, followed by diverticula,
vascular anomalies, colorectal cancer, and infectious or inflammatory colitis.
4.2.
Pathogenesis, diagnosis and therapy of specific lesions
4.2.1. Hemorrhoids
Hemorrhoidal bleeding is the most common cause of lower GI bleeding. Bleeding
is typically small volume and intermittent, with bright red blood on the surface
of the stool, on the toilet paper and/or in the toilet bowl. Patients often
describe blood dripping into the toilet bowl following a bowel movement. Occasionally
bleeding is severe. The diagnosis can be confirmed on anoscopy and/or flexible
sigmoidoscopy.
Patients with small volume,
bright red hematochezia should undergo flexible sigmoidoscopy if anoscopy does
not reveal bleeding hemorrhoids.
Fiber supplementation is the mainstay of therapy. Severe or recurrent bleeding
are indications for hemorrhoidal
band ligation or hemorrhoidectomy.
Anal
fissures may
also bleed, but bleeding is usually minimal (blood on the toilet paper or scant
blood on the stool surface) and is associated with anal discomfort. Fiber supplementation
is advised. Sitz baths may also be helpful in relieving anal
discomfort.
4.2.2. Colonic diverticula
After hemorrhoids, colonic diverticular bleeding is the most common cause of lower GI bleeding
[Longstreth,1997].
Colonic diverticula are felt to develop as a result
of increased intraluminal pressure and occur at sites of natural weakness in
the colonic wall where transmural arteries are located. Local erosion into one
of these arteries leads to brisk but usually self-limited bleeding. Rarely bleeding
is massive on presentation, requiring emergent diagnostic angiography followed
by intra-arterial infusion of vasopressin or segmental resection. In patients
with self-limited bleeding the diagnosis is often made by finding diverticula
on colonoscopy in the absence of another identifiable cause of lower GI bleeding.
Rarely a clot is seen in the diverticulum that has bled
[Bokhari,1996].
Patients with a single self-limited episode of diverticular hemorrhage can be managed conservatively.
Stool bulking agents are generally recommended. Recurrent bleeding, which develops
in 9% and 10% of patients at 1 and 2 years, respectively
[Longstreth,1997],
is an indication for surgical resection if the bleeding location can be identified.
4.2.3. Vascular anomalies
Sporadic and secondary angiodysplasia are a common cause of bleeding
from the small bowel and colon. These are discussed in detail in section 3.2.6.1.
As previously mentioned, Dieulafoy lesions rarely lead to bleeding from the
small bowel and colon.
4.2.4.
Colorectal neoplasm
Although colorectal cancer is most commonly associated with
occult blood loss rather than overt bleeding, patients with rectosigmoid
lesions may present with hematochezia. The diagnosis is readily made on endoscopy.
Although endoscopic laser
therapy can slow bleeding, surgical resection is usually recommended to control
the bleeding and to treat the cancer.
4.2.5. Infectious, inflammatory or ischemic colitis
A variety of infectious, inflammatory and ischemic colitides may present
with bloody diarrhea. The diagnosis of infectious
colitis is usually confirmed by stool culture or assay for Clostridium
difficile toxin, but occasionally stool studies are negative. Sigmoidoscopy
is indicated in the setting of negative stool studies and persistent bloody
diarrhea. Endoscopy may reveal pseudomembranes characteristic of C. difficile,
and mucosal biopsies may help to distinguish among infection, inflammatory bowel
disease, or ischemia. However, certain infectious agents (C. difficile and E.
Coli O157:H7) may mimic ischemia on histology. Endoscopy is always indicated
in the setting of possible inflammatory or ischemic colitis, unless there is
clinical evidence for perforation. Again, mucosal biopsies are usually diagnostic.
4.2.6. Solitary rectal ulcer syndrome
A solitary rectal ulcer may develop in the setting of rectal prolapse and is
due to mucosal ischemia. These patients may present with hematochezia. The absence
of obvious rectal prolapse on history or exam does not reliably exclude this
diagnosis. Endoscopic biopsies are usually diagnostic.
4.2.7. Other causes
Jejunal and rarely mesenteric varices may cause significant lower GI bleeding
[Hansen,1990;
Yuki,1992].
Accurate diagnosis requires angiography and therapy is portal decompression.
Rectal varices may also be a cause of significant hematochezia and are readily
detected on sigmoidoscopy.
Small bowel diverticula are uncommon and rarely lead to lower GI bleeding
[Akhrass,1997].
Duodenal diverticula are more common than jejunoileal diverticula. Approximately
5% of both duodenal and jejunoileal diverticula may bleed
[Akhrass,1997].
Meckel’s diverticulum
is the most common congenital anomaly of the small intestine, occurring in up to 4% of the general population
[Arnold,1997],
and is the most frequently recognized cause of bleeding small bowel diverticula.
It represents a persistence of the Vitelline duct and often has heterotopic
gastric mucosa resulting in ulceration and bleeding. The roles of H. pylori
infection and NSAID ingestion in the pathogenesis of bleeding in patients
with Meckel’s diverticulum remain uncertain
[Mathur,1992;
Bemelman,1993;
Cserni,1996].
The diagnosis is made on a "Meckel’s scan," a technetium pertechnetate
scan where ectopic gastric mucosa is identified by taking up radiolabeled technetium.
Definitive treatment with
diverticulectomy or segmental intestinal resection is necessary
[Cullen,1996].
Small intestinal ulcers are found on autopsy in 8% of patients taking NSAIDs at the time of their death
[Allison,1992].
NSAID induced small bowel and colonic ulcers should be considered in every
patient with lower GI bleeding who is taking these drugs.
Small bowel neoplasms are a particularly uncommon cause of GI bleeding;
in one study of 258 patients with bleeding of obscure etiology (normal upper
endoscopy, colonoscopy and small bowel series), small bowel tumors were diagnosed
by enteroscopy in only 5%
[Lewis,1991].
5.0. OCCULT GASTROINTESTINAL BLEEDING
Occult GI bleeding manifests as either iron deficiency anemia or a positive
test for fecal occult blood, and should be evaluated with endoscopy. As previously
discussed, barium studies have limited sensitivity for many sources of GI bleeding
and should not be utilized as the primary diagnostic modality in patients with
occult GI bleeding. Guidelines for the evaluation of patients with occult GI
bleeding are provided in Algorithm 2.
5.1. Iron-deficiency anemia
The initial
evaluation of iron deficiency anemia should be guided by the patient’s
symptoms. If the patient is asymptomatic, the evaluation should begin with a
colonoscopy, particularly if the patient is age 50 years or older. If the initial
endoscopy (whether EGD or colonoscopy) is normal, the alternate exam should
be performed. In the patient whose initial endoscopy reveals a source of occult
GI bleeding, it is difficult to make definitive statements regarding the yield
of further endoscopic evaluation. While some authors report a low yield of further
endoscopy in this setting
[Rockey,1993],
others have found lesions in both the upper and lower GI tracts in the setting of iron-deficiency anemia
[Zuckerman,1992;
McIntyre,1993].
Clearly, if the lesion seen on initial endoscopy is not deemed "significant"
enough to be the source of iron deficiency anemia, further endoscopic evaluation
should be performed. If no lesions are identified on endoscopy, a duodenal biopsy
should be considered at the time of EGD in order to rule out iron malabsorption
due to celiac sprue and other small bowel disorders. Finally, if all tests are
negative, a small bowel series or enteroclysis is usually recommended,
although the yield of these studies is quite low
[Rockey,1993;
McIntyre,1993].
5.2. Positive fecal occult blood testing
When a positive
fecal occult blood
test is obtained in the context of evaluating upper abdominal symptoms,
an EGD should be the first diagnostic study. If the EGD is negative, patients
who are age 40 or older should undergo colonoscopy. Patients with positive fecal
occult blood testing obtained in the context of screening for colorectal cancer
should first undergo evaluation with colonoscopy. If the colonoscopy is normal,
it is reasonable to conclude the evaluation unless the patient has previously
unrecognized upper GI symptoms, is anemic, or fecal occult blood remains positive
on subsequent testing. This approach can be recommended based on the high false
positive rate of a single fecal occult blood test and its limited ability to
detect bleeding from an upper GI source. On the other hand, some studies have
reported a "significant" upper GI source of occult bleeding in up
to 30% of patients with hemoccult-positive
stool and normal colonoscopy
[Zuckerman,1992;
Hsia,1992].
More recently, Rockey and colleagues reported that 60% of patients with hemoccult-positive
stool on rectal exam or routine screening had an upper GI tract lesion
[Rockey,1998].
The higher prevalence of upper GI lesions in this study may in part be due the
inclusion of positive hemoccults on rectal examination, since the latter is
ostensibly being done as part of a physical examination in an individual with
GI symptoms. However, although the presence of upper GI symptoms was predictive
of a positive finding on EGD, more lesions were found in the upper GI tract
than the lower GI tract in both patients with upper GI symptoms and those without
symptoms. Until these findings are confirmed, the approach recommended above
is likely to remain the standard.
NSAID use in the context of hemoccult-positive stool warrants some mention.
Although NSAID use is frequently associated with GI mucosal injury, a positive
test for fecal occult blood should not be attributed to NSAID use. Furthermore,
even if NSAID-related GI injury is found on endoscopy, such lesions are common
enough that they cannot be presumed to be the main source of GI blood loss.
Such patients may have clinically important lower GI lesions and should undergo
evaluation of the lower GI tract with colonoscopy
[Bahrt,1984;
Pye,1987].
6.0. OBSCURE GASTROINTESTINAL BLEEDING
Obscure GI bleeding
is defined as recurrent acute or chronic GI bleeding for which no source has
been found despite evaluation with EGD and colonoscopy with or without routine
small bowel follow-through. The optimal diagnostic study in such patients is
not certain, but additional studies should be considered in patients who require
blood transfusions or repeated hospitalizations for obscure GI bleeding. In
general, EGD and colonoscopy are repeated once in such patients in order to
exclude lesions that may have been missed on the prior endoscopic exams. Further
diagnostic options include enteroscopy (endoscopy to approximately the midjejunum
using an enteroscope or pediatric colonoscope), capsule endoscopy, small bowel
enteroclysis, or 99mTc-labeled red blood cell scintigraphy. Enteroscopy
can also be performed intraoperatively, where the entire small bowel is "sleeved"
over the enteroscope and the mucosa is visualized upon withdrawal. This approach
is most useful in patients with significant bleeding who are candidates for
bowel resection. Guidelines for the evaluation of patients with obscure GI bleeding
are provided in Obscure Bleeding Algorithm.
Patients who present
with recurrent acute bleeding should undergo a 99mTc-labeled red
blood cell scan while actively bleeding. Although this study is not always
accurate with respect to the site of bleeding, it is noninvasive and may give
valuable information either when used alone or in combination with other studies.
Patients with a positive red blood cell scan can then undergo mesenteric angiography
for more definitive diagnosis as well as possible therapy. If the bleeding site
identified on red blood cell scan is within the reach of an endoscope (via EGD,
enteroscopy or colonoscopy), confirmation can be sought endoscopically rather
than angiographically and endosocopic therapy can be applied at the same time.
Finally, patients who are being considered for exploratory laparotomy with or
without enteroscopy also should undergo mesenteric arteriography. Lesions such
as vascular anomalies or vascular tumors may be visualized, even in the absence
of active bleeding.
Patients with slow, chronic blood loss should initially undergo enteroclysis
as it is simple and noninvasive. In two recent case series, 20% of patients
with obscure GI bleeding and negative EGD and colonoscopy had a positive finding
on enteroclysis, and lesions were surgically proven in the majority of cases
[Rex,1989;
Moch,1994].
Similarly, case series of
patients undergoing enteroscopy for obscure GI bleeding have reported positive
findings in 38% to 47% of patients
[Foutch,1990;
Schmit,1996].
Not uncommonly, the site of bleeding is found in the stomach or proximal small
bowel, within reach of the standard upper endoscope
[Foutch,1990;
Schmit,1996;
Berner,1994].
Finally, capsule endoscopy may be useful in patients with obscure GI bleeding
(see Section 2.2.2.5 for a discussion of this technique). In one recent study,
video capsule endoscopy was superior to small bowel radiographs in the evaluation
of 13 patients with obscure GI bleeding; 12 of 13 capsule endoscopy studies
yielded a source of bleeding, while only 1 of 13 small bowel radiographs was positive
[Costamanga,2002].
Angiodysplasia was the most common
finding. As previously mentioned, a small bowel stricture should be excluded
with a radiographic study before proceeding to capsule endoscopy.
7.0. WHO TO REFER
In general, most patients presenting with GI bleeding will need referral to
a gastroenterologist for a definitive diagnosis of the bleeding source. However,
young patients with minor bleeding, particularly from an obvious anorectal source,
may be managed without the assistance of a gastroenterologist. General guidelines
for referral are provided in (Table 5).