Overview of the complications of peptic ulcer
diseaseAuthorsAndrew H Soll, MDNimish B Vakil, MD, AGAF, FACP,
FACG, FASGESection EditorsMark Feldman, MD, MACP, AGAF, FACGDavid I
Soybel, MDDeputy EditorShilpa Grover, MD, MPHDisclosures:Andrew H
Soll, MDNothing to disclose.Nimish B Vakil, MD, AGAF, FACP, FACG,
FASGEConsultant/Advisory Boards: AstraZeneca [GERD (Esomeprazole)];
Baxter [Probiotics]. Other Financial Interest: Salix [GERD
(web-based review article)].Mark Feldman, MD, MACP, AGAF,
FACGNothing to disclose.David I Soybel, MDNothing to
disclose.Shilpa Grover, MD, MPHEmployee of UpToDate,
Inc.Contributor disclosures are reviewed for conflicts of interest
by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to
UpToDate standards of evidence.Conflict of interest policyAll
topics are updated as new evidence becomes available and ourpeer
review processis complete.Literature review current through:Feb
2015.|This topic last updated:Dec 02,
2013.INTRODUCTIONComplications of peptic ulcer disease (PUD)
include bleeding, perforation, penetration, and gastric outlet
obstruction. With time, there have been major shifts in the
etiologies of complicated peptic ulcers and in the affected patient
populations. In addition, management has undergone dramatic
changes. Management now includes the early use of high-dose
intravenous proton pump inhibitors (PPIs), treatment to eradicate
Helicobacter pylori (H. pylori), improved endoscopic methods for
control of hemorrhage, and changes in surgical indications and
procedures. (See"Treatment regimens for Helicobacter
pylori"and"Overview and comparison of the proton pump inhibitors
for the treatment of acid-related disorders"and"Overview of the
treatment of bleeding peptic ulcers".)This topic will provide an
overview of the major complications of PUD. The approach to
patients with complicated PUD, the endoscopic management of peptic
ulcer bleeding, and the surgical approaches to complications of PUD
are discussed separately. (See"Diagnosis of peptic ulcer
disease"and"Overview of the natural history and treatment of peptic
ulcer disease"and"Overview of the treatment of bleeding peptic
ulcers"and"Surgical management of peptic ulcer
disease".)INCIDENCEWith time, there has been a dramatic fall in the
prevalence of peptic ulcer disease (PUD) in developed countries.
While older studies suggested that hospitalizations for potentially
life-threatening ulcer complications were stable or even increasing
[1-7], several more recent studies indicate a consistent decrease
in hospitalization rates and in the incidence of bleeding and
perforation [8]. For example, using analysis of a large database
from the United States found an approximate 30 to 40 percent fall
in hospitalizations for PUD complications between 1993 and 2006
[9]. Another study from the United States evaluated the National
Inpatient Database and found that the rate of perforation and
bleeding has been decreasing in the United States, presumably
reflecting the fall in H. pylori prevalence [10]. A large
systematic review estimated that the annual incidence of peptic
ulcer hemorrhage is on the order of 19 to 57 cases per 100,000
individuals, and that the annual incidence of ulcer perforation is
on the order of 4 to 14 cases per 100,000 individuals [11].
(See"Epidemiology and etiology of peptic ulcer disease", section on
'Epidemiology'.)Peptic ulcer bleeding is seen most commonly in
older patients [1,2,5-8]. Sixty percent of patients are above the
age of 60 years and 20 percent are over the age of 80 years [12].
This age distribution likely reflects increasing nonsteroidal
anti-inflammatory drug (NSAID) use among older adults, combined
with decreasing prevalence of H. pylori infection among younger
patients.Complications of PUD vary in frequency geographically. In
the United States, hemorrhage is the most common complication of
PUD (73 percent), followed by perforation (9 percent), and
obstruction (3 percent) [9]. The mortality rate from complications
of PUD is more than 10 times that of acute appendicitis or acute
cholecystitis. Perforation has the highest mortality rate, followed
by obstruction and hemorrhage. By contrast, a 13-year review of all
surgical procedures for peptic ulcer complications at a Nigerian
hospital found that obstruction was the most common complication
(56 percent), followed by perforation (30 percent), and bleeding
(10 percent) [13]. Some regional factors that may account for these
differences include the rates of NSAID use, the prevalence of H.
pylori infection, and the distribution and extent of gastritis.
(See"Epidemiology and etiology of peptic ulcer disease", section on
'Regional and other demographic variation'.)ETIOLOGY AND RISK
FACTORS FOR COMPLICATED PUDComplications can occur in patients with
peptic ulcer disease (PUD) due to any etiology. (See"Epidemiology
and etiology of peptic ulcer disease".) Although controversial in
early studies because of difficulty detecting H. pylori in the
setting of acute bleeding, evidence now clearly implicates both H.
pylori and nonsteroidal anti-inflammatory drugs (NSAIDs), including
low-doseaspirin, as the primary causes of ulcer bleeding and
perforation [14-17]. (See"Indications and diagnostic tests for
Helicobacter pylori infection", section on 'Recently bleeding
gastric or duodenal ulcers'.)NSAIDsThe use of NSAIDs is the most
commonly identified risk factor for peptic ulcer bleeding,
especially in the elderly. Studies have found relative risks for
bleeding ranging from 2.7 to 33.9 [11]. Studies have also shown
that the risk is drug-specific and dose-dependent. As an example,
in a study of 2777 patients, the overall relative risk (RR) of
bleeding associated with NSAID use was 5.3 (95% CI 4.5-6.2).
However, the risk varied by drug and was lowest for aceclofenac (RR
3.1, 95% CI 2.3-4.2) and was highest forketorolac(RR 14.4, 95% CI
5.2-39.9) [18]. The risk was higher in patients taking high-dose
NSAIDs compared with those taking medium- or low-dose NSAIDs (RR
6.8, 95% CI 5.3-8.8 versus 4.0, 95% CI 3.2-5.0). There was also an
increased risk of bleeding withaspirinuse (RR 5.3) that again was
dose-dependent (RR 7.5 with 500 mg per day versus 2.7 with 100 mg
per day). The concurrent use of aspirin and NSAIDs conferred an
even greater risk of bleeding than was seen with either agent alone
(RR 12.7). Finally, the risk was highest in the first 30 days of
NSAID use, with a RR of 7.6 (95% CI 6.0-9.5). The risk remained
high between days 31 and 90 days (RR 7.3, 95% CI 4.0-13.2), but
dropped after 91 days (RR 2.6, 95% CI 1.6-4.1).NSAID use has also
been identified as a risk factor for ulcer perforation [16,19]. In
a study of 176 patients from Spain, NSAID use was the only risk
factor that was significantly associated with perforation (odds
ratio [OR] 3.6) [16].H. pylori infectionMultiple studies have
identified H. pylori infection as a risk factor for complicated PUD
[20-22]. In one study with 370 patients with peptic ulcers,
patients with H. pylori were at significantly increased risk for
bleeding from duodenal (RR 6.0, 95% CI 2.9-12.3) but not gastric
ulcers (RR 1.7, 95% CI 0.7-4.1) [21]. However, identifying H.
pylori can be difficult in the setting of acute bleeding or in
patients receiving PPIs. (See"Indications and diagnostic tests for
Helicobacter pylori infection", section on 'Recently bleeding
gastric or duodenal ulcers'.)With regard to testing for H. pylori,
it should be kept in mind that:Biopsy-based tests for H. pylori,
such as the rapid urease test, are less sensitive in a patient with
recent bleeding [14]. However, specificity remains high.A stool H.
pylori antigen test provides a useful adjunct to diagnosis;
however, the sensitivity and specificity of this test may be
compromised by the presence of blood [23,24].A urea breath test for
H. pylori performed as soon as the patient has resumed oral
feedings is a reasonably sensitive predictor of H. pylori
infection, even following initiation of PPIs. In one study, 113 of
131 patients (86 percent) had positive urea breath tests performed
the day after resuming oral feeding [25]. The sensitivity was
better early in the hospitalization. Of the 18 patients who were
initially negative, 15 had positive urea breath tests two weeks
after stopping the PPI.Any H. pylori test dependent upon the number
of organisms present may be falsely negative with recent use of
PPIs, antibiotics, orbismuth. Two weeks off of these agents
provides adequate time for recovery of test sensitivity.Serology is
a useful test for complicated ulcers [26], especially when there is
concern about false-negative results on other tests due to the
presence of blood or medication use. Although a positive serology
when other H. pylori tests are negative may be a false-positive, it
may be a true-positive if there has been suppression of organism
number or if there is isolated duodenal H. pylori colonization
[27], an important cause of apparent H. pylori-negative,
NSAID-negative ulcer. (See"Unusual causes of peptic ulcer
disease".)In the face of a demonstrated peptic ulcer the pretest
probability of H. pylori is high, so any positive test has high
predictive value for H. pylori infection. However, a single
negative test has low predictive value, so two tests must be
performed under appropriate conditions to confirm that H. pylori is
absent. For tests dependent upon the number of organisms (eg,
biopsy urease test, urea breath test, stool antigen test, or
histology), the patient must have been off of PPIs, antibiotics,
orbismuthfor at least two weeks before negative results can be
interpreted as reflecting a true absence of organisms. Some
patients are very reluctant to stop PPIs, in particular, so it is
important to confirm that the drugs have been stopped.
(See"Indications and diagnostic tests for Helicobacter pylori
infection".)NSAID use in patients with H. pyloriStudies looking at
the relationship between H. pylori and NSAID use in patients with
peptic ulcer complications have had variable results [21,28,29]. A
meta-analysis that identified nine case-control studies that
assessed the prevalence of H. pylori infection and NSAID use in
patients with peptic ulcer bleeding suggested that the H. pylori
infection combined with NSAID use increases the risk of bleeding
above that seen with either risk factor alone [30]. The analysis
found that individually, the odds ratios for bleeding peptic ulcers
associated with H. pylori and NSAIDs use were 1.8 (95% CI 0.97-3.3)
and 4.9 (95% CI 3.8-6.2), respectively, whereas the odds ratio
increased to 6.1 when both H. pylori and NSAID were present (95% CI
3.9-9.6).Non-H. pylori, non-NSAID ulcersThe development of
complications in patients with non-H. pylori, non-NSAID ulcers is
an increasing problem, with a high incidence of recurrent ulcer
bleeding. Many H. pylori negative, non-NSAID ulcers are associated
with medical comorbidity. (See"Unusual causes of peptic ulcer
disease", section on 'Comorbid peptic ulcers'.)Once H. pylori and
NSAIDs have been confidently excluded, acid hypersecretion should
be considered in patients with complicated ulcers. While acid
hypersecretion leading to complicated PUD may be due to gastrinoma,
idiopathic acid hypersecretion should also be considered [31,32].
(See"Clinical manifestations and diagnosis of Zollinger-Ellison
syndrome (gastrinoma)".)Ulcer characteristicsCertain ulcer
characteristics are associated with an increased risk of
complications. Refractory, giant (>2 cm), and pyloric channel
ulcers are associated with higher complications rates. In addition,
most complicated ulcers are chronic and fibrosed. Chronic ulcers
may penetrate deeply into the wall to form a dense fibrotic scar
that is slow to heal, erodes blood vessels, or reaches the serosa.
However, some complicated ulcers, especially in new NSAID users or
in hospitalized patients (stress ulcers), are acute and occur
without dense fibrosis or a prolonged ulcer history. (See"Clinical
manifestations of peptic ulcer disease".)PregnancyComplicated
peptic ulcers are very uncommon during pregnancy, with fewer than
100 cases reported in the literature [33]. However, peptic ulcers
are in the differential diagnosis for the very common dyspeptic
symptoms of pregnancy and for the very uncommon events of upper
gastrointestinal bleeding or gastrointestinal perforation
[33].PREDICTORS OF POOR OUTCOMESRisk factors associated with poor
outcomes in patients with complicated peptic ulcer disease (PUD)
include comorbid disease, older age, and the patient's
physiological status at the time of presentation.Comorbid
diseaseComorbid disease is a consistent risk factor for poor
outcomes [9,34-45]. For example:In a study of 96 patients with
perforated peptic ulcers, there was a ninefold increase in
postoperative complications in patients with concomitant medical
illness [36].In a study of 9375 patients with peptic ulcer
bleeding, overall mortality was 6.2 percent; 80 percent of the
deaths were associated with comorbid disease, primarily multiorgan
failure, pulmonary conditions, and advanced malignancy [41].In a
large population study, diabetic patients had significantly
increased 30-day mortality from ulcer bleeding (RR 1.40, 95% CI
1.15-1.70) and perforation (RR 1.51, 95% CI 1.15-1.98)
[35].Advanced ageAge is clearly linked to comorbid disease.
However, a population-based study of 7232 patients hospitalized for
bleeding ulcers indicated that age was also an independent risk
factor for poor outcomes [46], as have other studies [39,45].
Increased age has also been shown to be associated with increased
mortality after ulcer perforation [11].The magnitude of the
physiological insultHypotension upon admission [39,40,47,48],
metabolic acidosis, acute renal failure, or hypoalbuminemia [39,48]
predicts poor outcomes. In a study of 101 patients who underwent
surgery for gastric ulcer bleeding after failing endoscopic
treatment, mortality was 5 percent with Apache II scores
(calculator 1) less than 15 and 58 percent with scores of 15 or
greater [49].Complication-specific risk factorsFactors that delay
ulcer healing, large ulcer size, and dense fibrosis are also risk
factors for poor outcomes. (See"Peptic ulcer disease: Genetic,
environmental, and psychological risk factors and
pathogenesis".)Bleeding Active bleeding at presentation,
hematemesis, rebleeding, and the need for surgery all predict
increased overall risk [38]. Certain factors predict failure of
endoscopic therapy, such as hypotension and ulcers larger than 2
cm.Perforation Persisting or advancing signs of peritonitis and a
preoperative delay of greater than 12 hours increase risk
[39,40,48,50,51]. Perforated gastric ulcers appear to have a poorer
prognosis than duodenal ulcers [51].Obstruction Poor nutritional
status predicts poor outcomes. Preoperative gastric atony predicts
postoperative emptying problems.PRECEDING SYMPTOMSAlthough a
careful history will reveal typical ulcer symptoms in many patients
with complications [52], there is an important subset of patients
with silent ulcers in whom complications develop with no or
insufficient heralding dyspeptic symptoms to bring them to timely
medical attention [53-56]. One study using gastric distension with
a nutrient meal suggested that patients with bleeding ulcers have
lower visceral sensitivity compared with patients with
uncomplicated ulcers [57], providing a possible mechanism for the
absence of symptoms. (See"Clinical manifestations of peptic ulcer
disease".)In particular, older patients with complicated ulcers
related to nonsteroidal anti-inflammatory drugs (NSAIDs) or medical
comorbidity tend to not report antecedent dyspeptic symptoms. This
point was underlined in an autopsy study of 2121 individuals over
age 70 years who died suddenly; acute abdominal causes were found
in 111 cases and peptic ulcer perforation and hemorrhage accounted
for one-fourth of these 111 deaths [58].GENERAL APPROACH TO
PATIENTS WITH COMPLICATED ULCERSAll patients with complicated
peptic ulcer disease (PUD) require appropriate supportive care,
such as taking in nothing by mouth and fluid resuscitation.
(See"Approach to acute upper gastrointestinal bleeding in adults",
section on 'General management'.)In addition,certain management
principles apply to all patients with complicated ulcers,
regardless of the type of complication (bleeding, perforation,
penetration, or gastric outlet obstruction). These principles
include coordination of care among the medical, surgical, and
radiologic teams, administration of acid suppressive therapy,
treatment of H. pylori if present, and discontinuation of NSAIDs if
possible (table 1).Coordination of careThe importance of early
collaboration among the medical, surgical, and radiologic teams for
patients with ulcer complications cannot be overemphasized. In
addition to aiding in resuscitation of an unstable patient,
collaboration between thegastroenterologist/endoscopist,the
intensive care unit team, the surgical team, and the radiologist
permits the establishment of goals and limits for initial
nonoperative therapy. Early surgical consultation also allows more
time for preoperative preparation and evaluation and for education
of patients and families, should urgent surgical intervention
become necessary.
If surgery is indicated, it should be done as soon as the
indication is clear and the patient is appropriately resuscitated.
Excellent results are possible with well coordinated, skilled,
timely decision-making and implementation. For example, with
skilled, timely care, in one study all 66 high-risk patients with
ulcer bleeding (shock on admission, age older than 65 years, an
ulcer size greater than 2 cm, stigmata of recent bleeding, or a
history of prior gastric surgery) survived five years [59].Acid
suppressive therapyAll patients with complicated peptic ulcers
should receive acid suppressive therapy with an intravenous proton
pump inhibitor (PPI). Althoughomeprazolehas been the most
extensively studied intravenous PPI, other intravenous formulations
given in doses that are known to inhibit gastric acid secretion are
probably acceptable alternatives.Pantoprazoleandesomeprazoleare the
only intravenous formulations available in the United States,
andlansoprazole, which was previously available, has been removed
from the world market. For patients with bleeding ulcers, the
suggested doses of intravenous pantoprazole, omeprazole, and
esomeprazole are all 80 mg bolus followed by 8mg/hrinfusion.
However, considerable evidence is accumulating that lower-dose
continuous infusions and bolus intravenous dosing may produce
comparable results [60-63]. Frequent, high-dose oral PPI use may
also be comparable in effectiveness [64]. In light of the currently
available evidence (and the inability to identify rapid
metabolizers who are likely to benefit from higher dosing), use of
either continuous infusions or intravenous bolus dosing appears
reasonable. (See"Approach to acute upper gastrointestinal bleeding
in adults", section on 'Acid suppression'.)Intravenous PPIs have a
dramatic impact on ulcer bleeding, which starts to take effect
within hours [65]. Starting intravenous PPI therapy before
endoscopy decreased the rate of active bleeding, the need for
endoscopic treatment, and the number of patients with clean based
ulcers [66]. These findings suggest a very rapid effect of profound
acid inhibition on fibrin formation and ulcer healing.Once patients
are tolerating oral medications, they should be switched to an oral
PPI. Initially, high-dose twice daily treatment is reasonable to
enhance healing (eg,omeprazole40 mg twice daily), but dosing should
generally be reduced to once daily after four weeks. However, for
patients with giant ulcers, it is reasonable to continue twice
daily dosing until a repeat endoscopy has been performed and
confirmed ulcer healing (see'Follow-up'below).Treatment of H.
pyloriEarly diagnosis of H. pylori is important to guide
management. Since curing H. pylori dramatically reduces recurrent
ulcers and complications, management must include careful
investigation for H. pylori infection, appropriate antibiotic
treatment, and a confirmation of cure after antibiotic treatment.
As noted above, H. pylori testing in the setting of bleeding or PPI
use may result in false-negative results, so repeat testing is
required for patients whose initial tests are negative [14].
(See"Indications and diagnostic tests for Helicobacter pylori
infection"and"Treatment regimens for Helicobacter pylori"and'H.
pylori infection'above.)The efficacy of intravenous antibiotics for
the treatment of H. pylori has not been established. Therefore, it
is necessary to wait until patients are tolerating oral feedings to
start oral antibiotics. Interrupted treatment may encourage
resistance and should be avoided.We emphasize that because curing
H. pylori reduces the recurrence of complications, following
treatment for H. pylori it is critical to confirm successful
eradication of the organism. (See"Treatment regimens for
Helicobacter pylori", section on 'Eradication
confirmation'.)Discontinue NSAIDsIfaspirinor non-aspirin NSAIDs can
be discontinued, even complicated ulcers readily heal and
uncommonly recur. If non-aspirin NSAIDs must be continued, the
incidence of recurrent PUD can be decreased by switching to a COX-2
inhibitor with concomitant therapy with a PPI ormisoprostol(for
patients who are unable to take PPIs or have contraindications to
PPI use). Likewise, when continued low-dose aspirin is justified,
concomitant co-therapy with a PPI is indicated. (See"NSAIDs
(including aspirin): Secondary prevention of gastroduodenal
toxicity".)Urgent or emergent surgeryUrgent or emergent surgery is
necessary in patients with uncontrolled hemorrhage or with a
perforated ulcer with continued leakage [67]. The specifics of the
surgery depend on the complication, ulcer location and
characteristics, and the patient's overall status.
(See'Bleeding'below and'Operative versus nonoperative
management'below and"Surgical management of peptic ulcer disease",
section on 'Management of peptic ulcer disease
complications'.)BLEEDINGUpper gastrointestinal bleeding secondary
to peptic ulcer disease (PUD) is a common medical condition that
results in high morbidity and medical care costs. Patients often
present with hematemesis, melena, or both. However, in the setting
of massive bleeding, hematochezia may be seen. The diagnosis of a
bleeding ulcer is typically made with upper endoscopy.
(See"Approach to acute upper gastrointestinal bleeding in
adults".)Most patients with bleeding ulcers can be managed acutely
with fluid resuscitation, blood transfusions, proton pump inhibitor
(PPI) therapy, and endoscopic intervention, as appropriate. As
noted above, early intravenous PPI treatment promotes rapid ulcer
healing and reduces rebleeding rates. (See"Overview of the
treatment of bleeding peptic ulcers".)However, in a minority of
patients with bleeding ulcers, surgery will be required.Surgery for
peptic ulcer hemorrhage is indicated in the following
circumstances:Failed endoscopic therapy.Hemodynamic instability
despite vigorous volume resuscitation (>3 unit transfusion
during initial resuscitation).Recurrent hemorrhage following
initial hemostasis, especially with hypotension, after a second
attempt at endoscopic treatment. Repeat endoscopic treatment is
suggested in most cases of recurrent hemorrhage because a second
attempt has a reasonable chance of success and lower risk than
surgery [68]. However, if two attempts have failed to achieve
permanent hemostasis, additional attempts at endoscopy are unlikely
to be successful.Continued slow bleeding with a transfusion
requirement exceeding three units per day.Secondary or relative
indications for surgery include rare blood type or difficult
crossmatch, or refusal of transfusion.An alternative to surgery for
some patients is angiography (see"Angiographic control of
nonvariceal gastrointestinal bleeding in adults"). Indications for
angiography for acute nonvariceal upper gastrointestinal bleeding
have been suggested in a consensus statement from the American
College of Radiology [69]:Endoscopy is the best initial diagnostic
and therapeutic procedure.Surgery and
transcatheterarteriography/intervention(TAI) are equally effective
following failed therapeutic endoscopy and the choice of procedure
should be based upon local experience and expertise. However, TAI
should be considered in patients at high risk for surgery.TAI is
less likely to be successful in patients with impaired
coagulation.TAI is the best technique for treatment of bleeding
into the biliary tree or pancreatic duct.Delaying surgery for
high-risk patients compromises outcomes. Prolonged resuscitation,
large volume transfusion, and periods of hypotension are poorly
tolerated in high-risk patients. Therefore, risks such as giant
ulcers, very rapid bleeding rates, shock on presentation, advanced
age, severe comorbid disease, acute coronary syndromes, and
transient ischemic attacks are relative indications for early
surgery. As noted above, urgent surgery may be appropriate when
hemodynamic instability persists after 3 units of rapid
resuscitation. However, continued management with transfusion and
pressors may be necessary while comorbidities are being evaluated
or consent obtained, and in patients who refuse surgery.The
specifics of the surgery depend upon the ulcer location, ulcer
characteristics, and the patient's overall status. (See"Surgical
management of peptic ulcer disease", section on 'Bleeding peptic
ulcer'.)PERFORATIONUlcer perforation should be suspected in
patients who suddenly develop severe, diffuse abdominal pain.
Perforations complicate 2 to 10 percent of peptic ulcers [70].
Duodenal, antral, and gastric body ulcers account for 60, 20, and
20 percent of perforations due to peptic ulcer disease (PUD),
respectively [71,72].Clinical manifestationsThe following three
phases have been described when there is free perforation [73]:In
the initial phase (within two hours of onset), abdominal pain is
usually sudden, sometimes producing collapse or syncope.
Localization is usually epigastric, but it quickly becomes
generalized. This catastrophic onset reflects bathing of the
peritoneal cavity with acidic fluid, which likely results in the
release of the vasoactive mediators that underlie the physiologic
response. Tachycardia, a weak pulse, cool extremities, and a low
temperature are characteristic features. The stage may last only a
few minutes or up to two hours. The severity of the onset depends
upon how much fluid is released. Pain may radiate to the top of the
right shoulder or to both shoulders. As this phase progresses,
abdominal rigidity begins to develop.In the second phase (usually 2
to 12 hours after onset), abdominal pain may lessen and an
inexperienced observer may be led to believe that the patient is
getting better. Pain is usually generalized, often markedly worse
upon movement, and the abdomen consistently displays marked
board-like rigidity. There may be obliteration of liver dullness to
percussion due to peritoneal air. The pelvic peritoneum, palpated
at rectal examination, is often tender due to irritation from
collected inflammatory fluid. Right lower quadrant tenderness may
develop from fluid moving down the pericolic gutter.In the third
phase (usually >12 hours after onset), increasing abdominal
distention is noted, but abdominal pain, tenderness, and rigidity
may be less evident. Temperature elevation and hypovolemia due to
"third-spacing" into the peritoneal cavity develop and acute
cardiovascular collapse may occur as peritonitis advances.
Persisting or advancing signs of peritonitis and a preoperative
delay greater than 12 hours increase the risk of a poor outcome
[39,40,48,50,51,74]. In addition, perforated gastric ulcers appear
to have a poorer prognosis than duodenal ulcers [51].If the
perforation is walled off or if the gastric fluid is confined by
fibrosis, symptoms may be much less severe and these phases may not
be apparent. Posterior (retroperitoneal) perforation is another
situation where symptoms are less dramatic. Compared to free
intraperitoneal perforations, the upper abdominal pain is more
insidious, the presentation often delayed, and the abdominal
examination is frequently equivocal [75].DiagnosisRapid diagnosis
is essential, since the prognosis is excellent within the first six
hours, but deteriorates with more than a 12-hour delay [50,73].
Perforation is largely a clinical diagnosis with the history and
physical examination providing essential clues (see'Clinical
manifestations'above).If imaging is required, plain x-rays are
typically obtained first. Careful interpretation of upright chest
and abdominal films can detect diagnostic free air in many cases of
perforated gastric and duodenal ulcers [76]. The presence of free
air on abdominal imaging is highly indicative of a perforated
viscus (image 1andimage 2andimage 3), although about 10 to 20
percent of patients with a perforated duodenal ulcer will not have
free air [76]. If free air is found, no other diagnostic studies
are necessary. Leakage of water soluble oral contrast may be useful
in selected cases. Once the oral contrast is given, the patient
should be rotated 360 degrees and placed on the right side to fill
the antrum and duodenum with contrast. However, many perforations
have already sealed spontaneously by the time of presentation [77],
so the absence of a leak does not exclude the diagnosis of a
perforated ulcer.If there is no free air on the plain film,
computed tomography (CT) or ultrasound can be useful to detect
small amounts of free air or fluid. In a small proportion of cases,
free fluid will be the only clue indicating perforation on imaging
studies and a few percent of cases will have neither free air nor
fluid [76]. Spiral and multidetector-row CTs, especially 64 slice
scanners, allow the entire abdomen to be examined on a single
breath-hold and improve detection of small amounts of air and
indirect findings (eg, fluid, phlegmon, abscess, wall pathology and
adjacent inflammation) and can provide very useful indirect clues
to pathology (image 3) [78,79]. Spiral CTs are undoubtedly much
more sensitive than ultrasound for detecting fluid, air, or other
clues to perforation. Spiral CT with oral contrast sensitively
detects persisting leaks across perforated ulcers.ManagementOnce
the diagnosis of an ulcer perforation has been made, initial
management includes insertion of a nasogastric tube, intravenous
volume replacement, treatment with an intravenous proton pump
inhibitor (PPI), and broad spectrum antibiotics. A decision is then
made about whether the patient requires surgery. (See'Operative
versus nonoperative management'below.)Intravenous PPIAlthough
high-dose intravenous PPIs given at presentation promote the
cessation of bleeding and healing of ulcers, the impact of such
early treatment on perforated ulcers has not yet been reported.
Based on the experience with bleeding, it is reasonable to
anticipate that intravenous PPIs will enhance fibrin formation and
promote rapid sealing of perforations. Therefore, we recommend
starting an intravenous PPI as early as possible, with an 80 mg
loading dose and 8 mg per hour of the PPI; however, lower doses and
twice daily bolus dosing may be equally effective, as noted above.
(See'Acid suppressive therapy'above.)AntibioticsThe antibiotic
regimen for a patient with a perforated ulcer should cover enteric
gram negative rods, anaerobes, and mouth flora. The antimicrobial
susceptibility patterns for gram negative rods such as Escherichia
coli have changed, with increasing resistance to antibiotics. Thus,
knowledge of local and regional susceptibility patterns for
Enterobacteriaceae is essential in selecting empiric therapy
[80-82].Reasonable choices for initial empiric antibiotic therapy
in the setting of perforated ulcer include a combination
betalactam/betalactamase inhibitor (such asampicillin-sulbactam,
ticarcillin-clavulanic acid, orpiperacillin-tazobactam), or a
combination of a third-generation cephalosporin andmetronidazole.
In areas where the local prevalence of extended spectrum
beta-lactamase (ESBL) producing organisms and pathogenic E. coli is
common, empiric monotherapy with a carbapenem such
asertapenem,imipenem, ormeropenemis appropriate. (See"Pathogenic
Escherichia coli"and"Extended-spectrum beta-lactamases".)The
importance of administering an appropriate initial empiric
antibiotic regimen was illustrated in a review of 425 patients who
required surgery for community-acquired secondary peritonitis,
including patients with perforated peptic ulcers [83]. In 13
percent of patients, the initial antibiotic regimen was
inappropriate, defined as not covering all bacteria subsequently
isolated or not covering both aerobic and anaerobic organisms in
the absence of culture results. Resolution of the infection after
primary surgery was significantly less likely with an inappropriate
regimen (53 versus 79 percent) and failure to achieve clinical
success was associated with a six-day prolongation in
hospitalization (20 versus 14 days).Operative versus nonoperative
managementA major decision when treating patients with ulcer
perforation is whether and when to operate. After resuscitation,
emergent operation and closure with a piece of omentum is the
standard of care for patients with an acute perforation and a rigid
abdomen with free intraperitoneal air. If the patient is stable or
improving, especially if spontaneous sealing of the perforation has
been demonstrated, nonoperative management with close monitoring is
a reasonable option. With any free perforation, regardless of the
presence or size of the leak, if the patients status is
deteriorating, urgent surgery is indicated. Prolonged efforts to
establish a diagnosis or pursue nonoperative care despite worsening
status can be counterproductive, since a needed operation will be
delayed. In addition, surgery is indicated in circumstances where
the cause of an acute abdomen has not been established or the
patients status cannot be closely monitored. (See"Surgical
management of peptic ulcer disease", section on 'Management of
peptic ulcer disease complications'.)The management of patients
with small to moderate leaks who are clinically stable is less
clear. Currently, the standard of care for such patients is
surgery, but some studies suggest that these patients can be
managed nonoperatively:The efficacy of initial conservative therapy
with a nasogastric tube, antibiotics, and H2 blockers was compared
with immediate laparoscopic surgical repair in a randomized trial
of 83 patients with a perforated peptic ulcer [84]. Surgery was
required in 11 of 40 patients (28 percent) in the conservative
therapy group because of failure to improve clinically after 12
hours. The other 29 patients in the conservative therapy arm were
successfully managed without surgery. The two groups did not differ
significantly in terms of morbidity or mortality. However, the
hospital stay was 35 percent longer in the group treated
conservatively. Also, patients over 70 years old were less likely
to respond to conservative treatment. The authors concluded that an
initial period of nonoperative treatment with careful observation
was safe in patients under age 70 years.A prospective study of 82
patients with perforated peptic ulcers treated patients with
nasogastric suction and intravenous H2 receptor antagonists [85].
If patients did not show clinical improvement after 24 hours,
surgery was performed. With this approach, surgery was avoided in
44 patients (54 percent). Factors associated with surgery included
the size of the pneumoperitoneum, abdominal distension, heart rate
>94 beats per minute, pain on digital rectal examination, and
age >59 years. Overall mortality in the study was 1 percent.Data
also suggest that if spontaneous sealing occurs, patients do well
without surgery. A study of 152 patients whose perforations sealed
spontaneously found re-leakage in only two patients, comparing
favorably with postoperative re-leak rates [77]. The probability of
sealing with nonoperative care and intravenous PPIs or H2 receptor
antagonists has not been studied; however, over 50 percent of
patients with perforated duodenal ulcers have sealed spontaneously
when first examined.Some patients require nonoperative management
because severe comorbid illnesses preclude surgery [86,87]. In a
retrospective series of 30 high-risk patients treated
nonoperatively, 11 patients were treated with H2 receptor
antagonists (prior to 1996) and 19 were treated withomeprazole40 mg
daily (1996 and later) [86]. Mortality was 64 percent in the early
period and 11 percent in the later period. Hypotension upon
presentation was a major risk factor for a poor outcome. These data
raise the hypothesis that PPI treatment promotes sealing of
perforations. However, a low mortality rate (3.5 percent) was also
seen in a series of 84 high-risk patients treated with percutaneous
drainage and H2 receptor antagonists [87].Nonoperative management
may also be considered for patients with delayed presentations. If
the patient has a persistent leak across the perforation, surgery
may be indicated, but can be complicated by peritoneal
contamination. Other options in this setting include nonoperative
care with percutaneous peritoneal drainage, especially for patients
who are not good surgical candidates [87].Patients with perforated
ulcers should have an upper endoscopy to look for evidence of
malignancy, to biopsy for H. pylori, and to assess for ulcer
healing. To allow the perforation to heal, we suggest waiting at
least two weeks prior to performing an upper endoscopy. If the
procedure does not need to be done urgently, we prefer to wait six
to eight weeks to allow for ulcer healing. At that time, biopsies
can be obtained to look for infection with H. pylori and to rule
out malignancy (particularly in the case of a nonhealing gastric
ulcer). (See"Overview of the natural history and treatment of
peptic ulcer disease", section on 'Follow-up after initial therapy
for peptic ulcer'.)Surgical approachFor patients who require
surgery for a perforated ulcer, the surgical approach depends upon
the location of the ulcer. This topic is discussed in detail
elsewhere. (See"Surgical management of peptic ulcer disease",
section on 'General principles of ulcer surgery'.)PENETRATIONUlcer
penetration refers to penetration of the ulcer through the bowel
wall without free perforation or leakage of luminal contents into
the peritoneal cavity. A longstanding ulcer history is common, but
not invariable, in patients who develop penetration. Penetration
often comes to attention because of a change in symptoms or
involvement of adjacent structures. The change in symptom pattern
may be gradual or sudden; it usually involves a loss of cyclicity
of the pain with meals, and loss of food and antacid relief. The
pain typically becomes more intense, of longer duration, and is
frequently referred to the lower thoracic or upper lumbar
region.Surgical series suggest that penetration occurs in 20
percent of ulcers, but only a small proportion of penetrating
ulcers become clinically evident [88]. Penetration occurs in
descending order of frequency into the pancreas, lesser omentum,
biliary tract, liver, greater omentum, mesocolon, colon, and
vascular structures. Antral and duodenal ulcers can penetrate into
the pancreas. Pyloric or prepyloric ulcers can penetrate the
duodenum, eventually leading to a gastroduodenal fistula evident as
a "double" pylorus.Penetration can be associated with a wide array
of uncommon complications including perivisceral abscess (evident
on computed tomography or ultrasonography) [89], erosion into
vascular structures leading to exsanguinating hemorrhage
(aortoenteric fistula) [90], or erosion into the cystic artery
[91]. Rare biliary tract complications include erosion into the
biliary tree with choledochoduodenal fistula, extrahepatic
obstruction, or hemobilia [92]. Fistulization into the pancreatic
duct has also been reported with penetrating duodenal ulcers
[93].Gastrocolic fistulae are seen with greater curvature gastric
ulcers, particularly marginal ulcers [72,94]. Typical features of
this complication include pain, weight loss, and diarrhea; feculent
vomiting is an uncommon, but diagnostic, symptom. A duodenocolic
fistula can also occur.A penetrating ulcer is suspected clinically
when an ulcer in the proper region is found (image 4) [68]. Mild
hyperamylasemia can develop with posterior penetration of either a
gastric or duodenal ulcer, but clinical pancreatitis is uncommon.No
rigorous studies are available to guide the management of
penetrating ulcers. Management should follow the intensive measures
outlined for refractory ulcers. (See"Refractory or recurrent peptic
ulcer disease".)GASTRIC OUTLET OBSTRUCTIONGastric outlet
obstruction is the least frequent complication of peptic ulcer
disease (PUD) in developed countries. Most cases are associated
with duodenal or pyloric channel ulceration. As peptic ulcers have
become less frequent, malignancy has emerged as a predominant cause
of gastric outlet obstruction despite the lower overall rates of
gastric cancer. Peptic ulcer disease accounts for only about 5
percent of gastric outlet obstructions [72,95,96]. (See"Gastric
outlet obstruction in adults", section on 'Etiology'.)Epidemiology
and pathogenesisObstruction accounted for 10 to 30 percent of
patients undergoing ulcer surgery in past series, but this
proportion appears to be dropping relative to bleeding and
perforation. Some of this decrease may be due to more effective
endoscopic and medical management, including the ability to
identify and reverse underlying causes [72,97].No distinct
pathophysiologic factors have been identified that promote
obstruction, though several elements can contribute to the
development of gastric outlet obstruction:Rapidly reversible
elements include spasm, edema, inflammation, and pyloric
dysmotility related to the ulcer or inflammatory changesFibrosis,
scarring, and deformity underlie slowly reversible or irreversible
obstructionGastric atony, which develops after prolonged
obstruction, contributes to gastric retentionClinical
manifestationsSymptoms of gastric retention include early satiety,
bloating, indigestion, anorexia, nausea, vomiting, epigastric pain,
and weight loss [72,98]. In a surgical series, vomiting was the
presenting symptom in 80 percent of cases; it occurred more
frequently than once daily in 41 percent of patients, once daily in
34 percent, and less often in 25 percent [99]. The presence of
recognizable food more than 8 to 12 hours after eating was
uncommon, but highly suggestive of gastric retention. The presence
of a succussion splash on abdominal examination several hours after
eating or drinking is a useful clue if present. The average
duration of symptoms was one month, although one-third had symptoms
for longer than three months.Patterns drawn from surgical series
are useful, but the presentation in a general medical setting may
be different. Important variables include the patient's response to
these symptoms, age, comorbid conditions, and general health
status. Some patients with chronic organic disease (peptic ulcers
in particular) have visceral hyposensitization (see'Preceding
symptoms'above). In such patients, high-grade outlet obstruction
may be present without perceived gastric distress. Appetite and
food intake may be preserved in association with delayed, large
volume vomiting of undigested food. Conversely, some patients may
have minimal or intermittent obstruction, but complain of
considerable nausea, pain, and indigestion.Diagnosis and
differential diagnosisThe first step is to determine whether the
symptoms are due to gastric retention and, if so, whether outlet
obstruction is the underlying cause. Measuring gastric residual
volumes and performing a saline load test (table 2) can establish
the diagnosis of mechanical outlet obstruction.Definitive diagnosis
of gastric pathology must await gastric cleansing, decompression,
and correction of fluid and electrolyte abnormalities. Endoscopic
inspection and biopsy are indicated in suspected cases of gastric
outlet obstruction and usually provide a definitive diagnosis of
the underlying pathology, especially for excluding malignancy.
Conventional upper gastrointestinal radiography can provide useful
information, but is often not definitive [100]. A computed
tomographic scanand/orsurgery may be required if there is a
heightened suspicion for malignancy and biopsies are unrevealing.A
number of entities must be excluded in the differential diagnosis
of gastric outlet obstruction, which is described separately.
(See"Gastric outlet obstruction in adults", section on
'Etiology'.)ManagementAfter correction of fluid and electrolyte
abnormalities, the initial step in the management of presumed
gastric outlet obstruction is to confirm the diagnosis of gastric
retention. If gastric retention is confirmed, the nasogastric tube
should be replaced by a large bore Ewald tube and the stomach
lavaged to remove debris. The nasogastric tube should then be
reinserted, good function confirmed, and intermittent suction
continued for three to five days to decompress the stomach while
intravenous fluid and electrolytes are administered.Prolonged
vomiting and poor fluid intake may lead to prerenal azotemia,
hyponatremia, and a hypokalemic, hypochloremic metabolic alkalosis.
Intravenous saline will restore the volume status and urine
output;potassium chlorideshould also be administered as indicated.
Intravenous proton pump inhibitors (PPIs) are used, as considered
below. Careful assessment of nutritional status is required and
intravenous hyperalimentation should be considered in malnourished
patients. (See"Nutrition support in critically ill patients: An
overview".)In the past, patients with gastric outlet obstruction
due to PUD traditionally were sent to surgery if they failed to
respond to three days of nasogastric suction. However, in cases
where the cause can be reversed (eg, H. pylori or NSAIDs), a more
conservative approach deserves consideration. Approximately
one-half of cases of gastric outlet obstruction due to peptic ulcer
and associated spasm, edema, inflammation, or pyloric dysmotility
respond initially to medical treatment, although some initial
responders may eventually require surgery [101] or endoscopic
dilatation.Gastric outlet obstruction is not an emergency; in
patients who fail to respond to medical therapy, both endoscopic
and surgical intervention should be delayed until the patient has
been stabilized and fluid and electrolyte balance restored. Delays
are also appropriate if the patient's nutritional status is
compromised (a serum albumin levelless than 2.8g/dLis a strong
predictor of a poor surgical outcome) or if the stomach is markedly
dilated (postoperative gastric atony is more likely and may be
prevented by preoperative decompression).Identifying and treating
underlying causesOnce the patient has been stabilized and gastric
outlet obstruction has been confirmed, the next steps are to
identify and treat the underlying cause of the obstruction. Even
cases with a good clinical response require endoscopy and biopsy to
exclude malignancy, diagnose ulcer disease, and determine if H.
pylori is present. (See"Gastric outlet obstruction in adults",
section on 'Diagnosis'.)There is evidence for [102-104] and against
[105] an association between H. pylori and obstruction, probably
due to the low frequency of the complication, the small size of the
studies, and patient selection. There are case reports and small
series which indicate that cure of H. pylori infection heals the
ulcers, resolves the outlet obstruction, and prevents recurrence of
obstruction in most, but not all, cases [102,106-108].Although data
are limited, there is sufficient evidence to indicate that
nonsteroidal anti-inflammatory drugs (NSAIDs) are an important
cause of obstruction. Furthermore, a substantial proportion of
patients with outlet obstruction due to NSAID-induced PUD respond
to medical therapy as long as NSAID use is discontinued [109]. In a
study of 119 elderly patients undergoing endoscopy for PUD, 12
cases with obstruction were found, 11 of whom were consuming NSAIDs
[110]. All cases responded to medical management alone. If NSAID
use is continued, there is a risk of recurrent obstruction [109].
In particular, great caution should be exercised in using surgical
intervention in patients who are likely to continue NSAID use,
since continued use predicts postoperative ulcer recurrence [111].
(See"NSAIDs (including aspirin): Pathogenesis of gastroduodenal
toxicity".)Antisecretory agentsEven though the benefit of
antisecretory therapy has not been formally established for the
acute or long-term management of ulcer obstruction, these agents
are the mainstay of initial treatment. Intravenous PPI therapy is
warranted during the initial gastric decompression phase to reduce
intravenous fluid requirements, control gastric pH, and facilitate
ulcer healing. Based on the precedent for the acute management of
bleeding peptic ulcers, a high-dose PPI regimen using an 80 mg
loading dose, followed by 8 mg per hour ofomeprazoleor equivalent
PPI, seems appropriate until the obstruction has resolved; however,
lower doses and twice daily bolus dosing may be equally effective,
as noted above (see'Acid suppressive therapy'above).After the
patient resumes oral intake and is emptying liquids, a liquid
antisecretory preparation is needed, such asomeprazoleandsodium
bicarbonatepowder. Since standard preparations of the five proton
pump inhibitors (omeprazole,esomeprazole,lansoprazole,rabeprazole,
andpantoprazole) use enteric-coated formulations, good emptying of
solids is required for effective drug delivery; their oral use is
therefore limited until the obstruction has resolved and motility
has recovered. (See"Pharmacology of antiulcer medications".)Oral
antisecretory therapy with PPIs or H2 receptor antagonists is
appropriate for long-term management of patients who have had a
gastric outlet obstruction due to PUD. After H. pylori infection is
treated (if present), full dose oral antisecretory medication
should probably be continued until successful cure of the infection
has been confirmed and antral-duodenal deformities have resolved.
Although only documented anecdotally, the combination of curing H.
pylori infection, continued antisecretory therapy, and time will
eventually reverse antral-duodenal deformity and tendency for
recurrent obstruction.Endoscopic balloon dilationPatients who fail
to respond to medical therapy may require endoscopic dilation or
surgery. Before surgery is contemplated, endoscopy with biopsy is
required to identify the cause of the obstruction and to rule out
malignancy, which has been reported in as many as 66 percent of
patients in this setting [95,112].If the pyloric channel can be
identified and a balloon passed, dilation is an appropriate option
in experienced hands. A Gastrografin study may be helpful to define
the anatomy of the pylorus before dilation. If the pylorus can be
opened sufficiently to allow the patient to tolerate a liquid diet,
especially when an underlying cause can be reversed, then
continuing medical treatment is a reasonable option as long as the
patient is carefully monitored to ensure that retention does not
recur. Monitoring symptoms is important, but it is advisable to
also check a gastric residual, especially in patients who were
previously asymptomatic despite large gastric residuals. Cases that
clearly warrant surgery are ones where the pylorus is obstructed
and cannot be safely dilated, or where the obstruction persists or
recurs during medical and endoscopic management.Dilation can be
accomplished by using endoscopy and a through-the-scope (TTS)
balloon dilator, or by using a balloon placed over a guidewire
positioned under fluoroscopic guidance. While fluoroscopy may not
be required for dilation using a TTS balloon in the case of mild
strictures (eg, strictures that allow passage of an endoscope),
most other stricture dilations are carried out using fluoroscopic
guidance. The amount of dilation in a single session is determined
by the initial diameter of the stricture. Narrow strictures may
require stepwise dilation performed over multiple sessions, as is
done with esophageal strictures. (See"Management of benign
esophageal strictures", section on 'Technique'.)Balloon dilation
should be monitored by a pressure gauge. The balloon is inflated to
the chosen diameter and inflation is sustained for thirty to sixty
seconds. The dilation may then be repeated at the same diameter,
though it is not certain that repeated dilations to the same
diameter yield better results. Using dilute contrast medium to fill
the balloon allows progress to be followed fluoroscopically; a
waist forms initially during dilation, but is effaced during
balloon distention. Successful dilation is usually confirmed by
pulling the balloon through the strictured segment, although
failure to accomplish this does not preclude a successful
procedure. Symptoms are usually considerably improved with
successful dilation to 12 mm. There may be an advantage to
postponing dilation beyond 15 mm until after a period of medical
management [72].Long duodenal strictures are the most difficult to
dilate. Multiple sessions using stepwise dilation for tight
obstructions will likely lower the risk of perforation.
Nevertheless, because of the risk of perforation, patients should
be appropriately prepared for surgery before duodenal dilation and
monitored closely after dilation before resuming oral intake. If
there is concern about a possible perforation or if the dilation is
unusually difficult to perform, an immediate postprocedure
Gastrografin study should be obtained.Multiple sessions of
endoscopic balloon dilation are necessary in some cases
[98,109,113,114]. In one study, for example, 24 of 30 patients (80
percent) achieved sustained symptom relief; 17 had a single
procedure, while seven required multiple sessions [98]. Dilation
failed in four patients with long duodenal strictures, while two
dilated to 18 mm suffered perforation; both recovered uneventfully
after surgery. A good long-term response following dilation is
achieved when H. pylori can be cured or NSAID use discontinued
[109].SurgeryFor patients who require surgery, the choice of
procedure is usually made during the operation. (See"Surgical
management of peptic ulcer disease".)FOLLOW-UPUpper endoscopy is
indicated for most patients after four to six weeks to exclude
neoplasia and other diagnoses and to establish healing. In
addition, biopsies should be obtained to look for H. pylori or to
confirm H. pylori eradication in those who have been treated. To
increase the yield for diagnosing H. pylori, patients should be
switched to H2 receptor antagonists for the two weeks prior to the
endoscopy. In addition, they should be off of antibiotics
andbismuthfor two weeks. (See"Overview of the natural history and
treatment of peptic ulcer disease", section on 'Follow-up after
initial therapy for peptic ulcer'and"Treatment regimens for
Helicobacter pylori", section on 'Eradication
confirmation'.)PREVENTION OF RECURRENCEThe natural history of
complicated peptic ulcer disease (PUD) is for the recurrence of
complications unless the underlying cause can be treated.Stop
NSAIDsThe recurrence of ulcer complications with continuing
nonsteroidal anti-inflammatory drug (NSAID) use is well established
[115,116] and is an indication for co-therapy with antisecretory
agents, which reduces recurrences. (See"NSAIDs (including aspirin):
Secondary prevention of gastroduodenal toxicity".) The decision to
discontinueaspirinshould be based on a careful appraisal of the
patient's cardiovascular risk.Although we are unaware of rigorous
studies, when NSAIDs are the cause of ulceration and are stopped,
complicated and refractory ulcers tend to heal rapidly and do not
recur [117]. Important exceptions are giant or densely fibrosed
ulcers for which healing may be delayed.
It is important to recall that a subset of patients who consume
NSAIDs fail to disclose their use even when directly asked [118].
Such patients are also likely to continue NSAID use even in the
face of ulcer complications, clear instructions to stop the
medication, and even failed ulcer surgery [100,119,120]. Therefore,
particularly with complicated ulcers, a diligent search for NSAID
use is critical. In addition, some patients with a history of
complicated ulcers are prescribed NSAIDs. In a study of 26,618
NSAID prescriptions, 2244 patients reported a prior peptic ulcer
and 489 reported upper gastrointestinal tract bleeding. However,
among patients with a history of bleeding, physicians recorded the
history of prior bleeding in only 8 percent of cases [121],
suggesting that NSAIDs are frequently prescribed when they are
contraindicated in the absence of proton pump inhibitor (PPI)
cotherapy or careful monitoring.Ulcers can recur despite definitive
ulcer surgery (eg, vagotomy) in the setting of continued NSAID use.
Uncontrolled series and case reports highlight problematic
recurrences following definitive ulcer surgery when NSAIDs,
andaspirinin particular, are continued [111,119,120,122].
Therefore, every effort should be made to discover NSAID use in
patients with complicated ulcers, especially before surgery; a
careful history from the patient and family and, in selected cases,
measuring salicylate levels and platelet function may be justified
[111]. Any role of definitive ulcer surgery in patients with
continued NSAID use remains to be elucidated.Treat H. pyloriA
confident diagnosis of H. pylori is essential because treatment can
prevent life-threatening recurrences. However, as noted above,
making a diagnosis of H. pylori in the setting of acute bleeding
may be difficult. (See'H. pylori infection'above and"Indications
and diagnostic tests for Helicobacter pylori infection".)With H.
pylori-associated ulcer bleeding, successful cure of the infection
dramatically reduces recurrent ulceration and recurrent
complications [123,124]. Although much less extensively studied, in
two randomized trials with a total of 173 patients with perforated
ulcers, H. pylori antibiotic treatment reduced the recurrence rate
of duodenal, prepyloric, and pyloric ulcers after simple surgical
closure of the perforation from 30 to 6.1 percent in the first
study and from 38 percent to 4.8 percent in the second [15,125].
Three other case series support similar conclusions [53,126,127].
Following treatment for H. pylori, patients should be tested to
confirm successful eradication of the organism. (See"Treatment
regimens for Helicobacter pylori", section on 'Eradication
confirmation'.)The role of H. pylori in ulcer recurrences following
acid reducing surgery remains controversial [122]. Postoperative
ulcer recurrences can clearly result from incomplete vagotomy and
continued NSAID use. No studies resolve the question of whether
curing H. pylori reduces recurrences following definitive ulcer
surgery in the subset of patients with H. pylori. However, two
reports indicated that persistent postoperative H. pylori infection
is associated with advancing atrophic gastritis or precursor
lesions that may underlie the increased rate of gastric cancer
observed after definitive peptic ulcer surgery [128,129].
Considering these factors and the weight of evidence implicating H.
pylori in ulcer recurrence, we suggest that the organism be
eradicated (if present) even in patients who have undergone
definitive ulcer surgery [122].Non-H. pylori, non-NSAID ulcersWhile
less common, ulcers not due to H. pylori infection or NSAIDs are
prone to frequent recurrences that often require continued
maintenance medical therapy or surgery. This point was illustrated
in a prospective study that compared 120 patients with a history of
H. pylori-negative, NSAID-negative bleeding ulcers to 213 patients
with a history of H. pylori positive bleeding ulcers who were
treated successfully with eradication therapy [130]. At follow-up
of up to seven years, the H. pylori negative patients had a
significantly higher rate of recurrent bleeding (42 versus 11
percent). (See"Epidemiology and etiology of peptic ulcer disease",
section on 'H. pylori'.)
In patients with presumed non-H. pylori, non-NSAID ulcers, every
effort must be made to exclude H. pylori infection and NSAID use
and to determine the cause of the ulcer. A cause for most non-H.
pylori, non-NSAID ulcers can be established (table 3). For example,
crack cocaine use can cause perforated ulcers. The ulcers should be
diligently treated and reversible factors contributing to ulcer
development should be addressed to decrease the risk of recurrent
complications. (See"Unusual causes of peptic ulcer
disease".)Maintenance acid suppressive therapyPatients with
complicated PUD due to an identifiable cause that can be addressed
(eg, treatment for H. pylori or discontinuation of NSAIDs)
generally do not require maintenance acid suppressive therapy. Such
patients are typically treated with a PPI for at least four to six
weeks. The duration of therapy depends upon the etiology and
characteristics of the ulcer (particularly size and presence of
dense scarring):In patients with H. pylori infection, eradication
should be confirmed prior to stopping antisecretory treatment
(see"Treatment regimens for Helicobacter pylori", section on
'Eradication confirmation')In patients requiring endoscopic
confirmation of ulcer healing (eg, gastric ulcers at high-risk of
malignancy, giant duodenal ulcers, or deformed ulcers with dense
scarring), the PPI should be continued until healing has been
demonstrated (see"Overview of the natural history and treatment of
peptic ulcer disease", section on 'Follow-up after initial therapy
for peptic ulcer')For patients with NSAID-associated ulcer
complications where NSAIDs have been stopped (and H. pylori
excluded or eradicated), it is reasonable to stop maintenance
therapy after healing has been confirmedAlthough the natural
history of complicated non-NSAID, non-H. pylori ulcers has received
only limited study, recurrence rates are likely to be high and
sustained maintenance therapy is probably indicatedAny patient who
has had a prior ulcer complication should be carefully educated
about the ways recurrent complications can present and about the
critical importance of immediately seeking emergent medical
attention for any suspicion of recurrent complicationsIn patients
requiring maintenance therapy, once the ulcer has healed, the PPI
can be tapered by cutting the dose by 50 percent every week until
the patient is on a low dose of the medication (eg,omeprazole20 mg
daily). (See"Overview of the natural history and treatment of
peptic ulcer disease", section on 'Maintenance therapy'and"Overview
of the natural history and treatment of peptic ulcer disease",
section on 'Antisecretory therapy after H. pylori
eradication'and"Overview of the natural history and treatment of
peptic ulcer disease", section on 'Antisecretory
therapy'.)Acid-reducing surgical proceduresAlthough definitive
acid-reducing surgical procedures (parietal cell vagotomy or
vagotomy with drainage or partial gastrectomy) have the potential
of decreasing recurrent complications, their performance
(especially during emergency ulcer surgery) adds operative time,
perioperative risk, and long-term adverse side effects, such as
dumping syndrome. Most large studies of definitive ulcer surgery
were performed prior to the recognition of H. pylori, the role of
NSAIDs, and potent antisecretory agents [131-134]. Over the past
two decades, gastric resections and definitive acid-reducing
procedures have continued to decline with no changes in outcomes
[135].An illustrative report included 159 patients who were
followed more than 10 years after vagotomy and pyloroplasty for
perforated duodenal ulcer [133]. The perioperative mortality was
5.5 percent, ulcers recurred in 8.8 percent, and postoperative
digestive sequelae, notably diarrhea and dumping, developed in 16
percent. Similar recurrence rates (but with less morbidity) have
been described in patients who underwent parietal cell vagotomy
[134].Even though no data are available to compare the risks of
definitive ulcer surgery to current medical treatment, a few points
are relevant:In light of the demonstrated benefits of medical
treatment (curing H. pylori, eliminating NSAIDs, and using potent
antisecretory agents) for decreasing complicated ulcer recurrence,
the rates of performing definitive ulcer procedures during
emergency surgery have fallen dramatically, without any obvious
deleterious impact on outcomes [38,56,135,136]. As a result, there
is a decline in surgical expertise for performing these definitive
procedures, especially in the community, which inevitably further
compromises the outcomes of surgery.If patients who require
emergency surgery for ulcer complications have failed all forms of
medical management, definitive surgery deserves consideration.By
contrast, definitive surgery is generally not appropriate if
medical management has not been tried. Although the cause of the
ulcer disease may not be known at the time of surgery, all forms
respond quite well to medical management. However, the proportion
of patients who will not tolerate, be adherent with, or respond to
medical treatment is likely to be very small and elective
definitive ulcer surgery can be reserved for this subset [137].In
patients with acid hypersecretion, definitive ulcer surgery (eg,
vagotomy) should be avoided because there is a high risk of
postoperative ulcer recurrence. This approach is well established
for patients with gastrinomas, but also appears to pertain to
patients with nongastrinoma acid hypersecretion [138].
(See"Management and prognosis of the Zollinger-Ellison syndrome
(gastrinoma)".)SUMMARY AND RECOMMENDATIONSThe major complications
of peptic ulcer disease (PUD) include perforation, gastric outlet
obstruction, penetration, and bleeding. For reasons that have not
been defined, the relative prominence of these complications varies
in different regions. (See'Introduction'above.)Although a history
of preceding ulcer symptoms is common, many patients have no
preceding typical peptic ulcer symptoms or known disease.
(See'Preceding symptoms'above.)Certain management principles apply
to all patients with complicated ulcers, regardless of type (table
1). These principles include coordination of care among the
surgical and medical teams, early administration of intravenous
proton pump inhibitors (PPIs) for acid suppression, treatment of H.
pylori if present (after the patient resumes oral feedings), and
discontinuation of nonsteroidal anti-inflammatory drugs (NSAIDs),
at least until healing has been established. (See'General approach
to patients with complicated ulcers'above.)Appropriate treatment
for patients with bleeding ulcers generally includes fluid
resuscitation to correct hypovolemia; blood transfusions as
necessary; early, high-dose intravenous PPI (80 mg loading and 8 mg
per hour ofomeprazoleor equivalent is usually recommended, though
lower doses administered by intravenous bolus appear equally
effective); and endoscopic intervention for ulcers with stigmata of
active bleeding. Surgery or angiography is required when two
endoscopic treatment sessions have failed or bleeding recurs after
these interventions, especially in hemodynamically unstable
patients. (See'Bleeding'above and'Acid suppressive
therapy'above.)Ulcer perforation should be suspected in patients
with or without a history of peptic ulcer symptoms or disease who
develop the sudden onset of severe epigastric or diffuse abdominal
pain or, especially in elderly patients, sudden decompensation.
Once the diagnosis of an ulcer perforation has been made, initial
management includes insertion of a nasogastric tube, intravenous
volume replacement, treatment with an intravenous PPI, and
appropriate antibiotics. A decision then is made about whether the
patient requires surgery. (See'Perforation'above.)For patients with
an acute perforation and a rigid abdomen with free intraperitoneal
air, emergent operation and closure with a piece of omentum is the
standard of care. Furthermore, with an established ulcer
perforation, regardless of the presence or size of the leak, if the
patients status is deteriorating, urgent surgery is indicated.
Lastly, surgery is indicated in circumstances where the cause of an
acute abdomen has not been established or the patients status
cannot be carefully monitored. (See'Management'above.)
Despite this standard of care, there are several situations
where continuing nonoperative care appears justifiable, especially
because there are no rigorous data available to guide treatment
decisions. If the patient is stable or improving, especially if
imaging studies show spontaneous sealing of the perforation, then
continued nonoperative management with close monitoring is a
reasonable option. Furthermore, for patients with small to moderate
leaks who are clinically stable, some studies suggest that
nonoperative management with close monitoring is reasonable.
Lastly, patients who are at very high risk for surgery because of
comorbidity can have surprisingly low mortality with rigorous,
nonoperative management. There are two critical unknowns: the
ability of intravenous PPIs to accelerate sealing of the
perforation and the role for percutaneous drainage. The latter
appears to be very useful for patients with persisting leaks across
perforated ulcers who are adequately stable to tolerate
nonoperative care. (See'Operative versus nonoperative
management'above.)Ulcer penetration refers to penetration of the
ulcer through the bowel wall without free perforation and leakage
of luminal contents into the peritoneal cavity. Penetration often
comes to attention because of a change in symptoms or involvement
of adjacent structures. Patients are typically managed in a manner
similar to patients with refractory peptic ulcers.
(See'Penetration'above and"Refractory or recurrent peptic ulcer
disease", section on 'Treatment'.)Gastric outlet obstruction is the
least common ulcer complication. Most cases are associated with
duodenal or pyloric channel ulceration. Symptoms of gastric outlet
obstruction include early satiety, bloating, indigestion, anorexia,
nausea, vomiting, epigastric pain, and weight loss. Malignancy is a
more common cause of gastric outlet obstruction and must be
excluded. Some patients can be managed medically, whereas others
require endoscopic balloon dilation or surgery. (See'Gastric outlet
obstruction'above.)Use of UpToDate is subject to theSubscription
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