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80 nature clinical practice GASTROENTEROLOGY & HEPATOLOGY fEbRuARY 2008 vOL 5 NO 2
www.nature.com/clinicalpractice/gasthep
SuMMarY
review
Gastrointestinal bleeding in the elderlyPatrick S Yachimski and Lawrence S Friedman*
Continuing Medical Education onlineMedscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 1.0 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To receive credit, please go to http://www.medscape.com/cme/ncp and complete the post-test.
Learning objectivesUpon completion of this activity, participants should be able to: 1 Describe the etiology and management of upper
gastrointestinal bleeding in elderly adults.2 Describe conditions that can cause sudden upper
gastrointestinal bleeding in elderly adults.3 Identify the most common cause of lower gastro-
intestinal bleeding in the elderly.4 Describe the etiology and management of lower
gastrointestinal bleeding in elderly adults.5 Specify diagnostic methods for obscure gastro-
intestinal bleeding in the elderly.
Competing interestsThe authors declared no competing interests. Charles P Vega, the CME questions author, declared that he has served as an advisor or consultant to Novartis, Inc.
INTRODUCTIONMore than 1% of people aged 80 years and older are hospitalized each year because of gastrointestinal bleeding.1 Gastrointestinal bleeding in such elderly people can originate from lesions common to all agegroups or from lesions associated specifically with aging. In elderly people, morbidity and mortality from gastrointestinal bleeding is determined by both the nature of the bleeding lesion and the presence of comorbid medical conditions. The incidence and outcome of gastrointestinal bleeding in elderly people can also be influenced by the use of aspirin and other antiplatelet and anticoagulant agents.
Gastrointestinal bleeding can be classified as acute (presenting as hematemesis, melena, or hematochezia), or chronic, suspected because
Gastrointestinal bleeding affects a substantial number of elderly people and is a frequent indication for hospitalization. Bleeding can originate from either the upper or lower gastrointestinal tract, and patients with gastrointestinal bleeding present with a range of symptoms. In the elderly, the nature, severity, and outcome of bleeding are influenced by the presence of medical comorbidities and the use of antiplatelet medication. This Review discusses trends in the epidemiology and outcome of gastrointestinal bleeding in elderly patients. Specific causes of upper and lower gastrointestinal bleeding are discussed, and recommendations for approaches to endoscopic diagnosis and therapy are given.
Keywords colonoscopy, elderly, gastrointestinal bleeding, gastrointestinal endoscopy, gastrointestinal hemorrhage
PS Yachimski is a Clinical and Research Fellow in the Gastrointestinal Unit, Massachusetts General Hospital, and a Research Fellow in Medicine at Harvard Medical School, and LS Friedman is a Professor of Medicine at Harvard Medical School and Tufts University School of Medicine, Chair of the Department of Medicine, Newton-Wellesley Hospital, and Assistant Chief of Medicine at Massachusetts General Hospital, MA, USA.
Correspondence*Department of Medicine, Newton-Wellesley Hospital, 2014 Washington Street, Newton, MA 02462, USA [email protected]
Received 8 June 2007 Accepted 18 October 2007
www.nature.com/clinicalpracticedoi:10.1038/ncpgasthep1034
REvIEw CRITERIAA PubMed search was performed using the terms “colonoscopy”, “elderly”, “gastrointestinal bleeding”, “gastrointestinal endoscopy”, and “gastrointestinal hemorrhage” to identify Englishlanguage articles related to gastrointestinal bleeding and gastrointestinal endoscopy in both the elderly and the general population. No time limits were specified for the search. Selected articles, but no abstracts, are referenced in this article. The reference list was updated in August 2007.
SuMMarY
cMe
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of the detection of occult gastrointestinal blood loss or anemia. Initial assessment of a patient with suspected gastrointestinal bleeding must include determination of the acuity and pace of blood loss. Subsequent clinical evaluation is undertaken to identify the source of the bleeding. Once a bleeding source has been identified, directed pharmacologic, endoscopic, and nonendoscopic therapy can be offered.
This Review provides an approach to the evaluation and management of gastrointestinal bleeding in the elderly. Although the approach to the diagnosis and management of gastrointestinal bleeding is not specific to elderly people, elderly people with gastrointestinal bleeding differ from younger people with the same condition with respect to several aspects of clinical presentation and outcome (Box 1). For the purposes of this Review, we define ‘elderly’ somewhat arbitrarily as older than 60 years of age. The term ‘very elderly’ is defined as an age greater than 85 years, a cutoff that might be more clinically relevant as the health of the aging population improves. This article also reviews the epidemiology and pathogenesis of the main causes of gastrointestinal bleeding in the elderly—peptic ulcer and diverticular hemorrhage, in particular, are discussed in detail with special reference to the elderly population. Attention is also focused on the utility and safety of endoscopic techniques for the diagnosis of gastrointestinal bleeding in the elderly—including reference to emerging techniques for smallbowel evaluation—and on the role of aspirin and other NSAIDs in gastrointestinal bleeding in the elderly.
UPPER GASTROINTESTINAL BLEEDINGUpper gastrointestinal bleeding (UGIB) is defined as gastrointestinal blood loss that originates proximal to the ligament of Treitz. Although the overall incidence of nonvariceal UGIB seems to have declined since the 1990s,2 time trend analyses suggest that people aged over 60 years and over 80 years each constitute an increasing proportion of those presenting with acute UGIB.3 As many as 70% of acute UGIB episodes occur in patients older than 60 years,4 and the incidence of UGIB increases with increasing age.5,6 Advanced age has been consistently identified as a risk factor for mortality among patients presenting with UGIB,3,5,7,8 presumably because of the high prevalence of comorbid illnesses—including pulmonary9 and
cardiovascular10 disease—in elderly as compared with younger patients with UGIB.
Clinical presentation, initial evaluation and immediate managementPatients with UGIB can present with vomiting of fresh blood (hematemesis) or of coffeeground material, or with rectal passage of blood. Melena is suggestive of bleeding proximal to the ligament of Treitz but can be due to bleeding from more distal gastrointestinal sources, as far as the cecum. Rapid or highvolume UGIB can result in hematochezia. The initial manifestations of UGIB can include syncope, lightheadedness, or postural hypotension, even in the absence of overt bleeding. Nasogastric intubation that returns a bloody aspirate can confirm the presence of UGIB. A clear or bilious nasogastric lavage, however, does not definitively exclude UGIB.
Medical history taking should include details of prior gastrointestinal bleeding, previous abdominal surgery and current medication use, particularly aspirin and other NSAIDs. The physical examination should begin with an assessment of hemodynamics, including postural changes. Physical findings of chronic liver disease are suggestive of underlying portal hypertension. Laboratory evaluation should include serum electrolyte and coagulation parameter measurements, liver biochemical tests and a complete blood count.
Box 1 Clinical features of upper gastrointestinal bleeding in elderly versus younger patients.
similarities■ Presenting manifestations of bleeding:
hematemesis (50%); melena (30%); hematemesis and melena (20%)
■ Peptic ulcer disease most common etiology
■ Safety and efficacy of endoscopic therapy
differences (in elderly patients)■ Fewer antecedent symptoms (abdominal pain,
dyspepsia, heartburn)
■ Prior aspirin and NSAID use
■ Presence of comorbid conditions
■ Higher rates of hospitalization
■ Higher rates of rebleeding (peptic ulcer, see Table 2)
■ Higher mortality rate
With permission from Elsevier Ltd © Farrell JJ and Friedman LS (2000) Gastroenterol Clin North Am 29: 1–36.
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Hypotension at presentation is associated with high mortality among elderly people who present with peptic ulcer hemorrhage,11 and early aggressive volume resuscitation decreases mortality.12 Volume resuscitation in patients with acute UGIB should be aimed at maintaining adequate hemodynamics and endorgan perfusion. The patient’s cardiopulmonary status should be monitored repeatedly during the course of aggressive volume resuscitation to assess for pulmonary edema or signs of rightsided heart failure. Prophylactic endotracheal intubation might be necessary in patients who have an altered mental status and ongoing hematemesis, to protect against aspiration.
Peptic ulcer diseasePeptic ulcer disease is the most common cause of UGIB, including in elderly people (Table 1).3,5,13,14 The discovery of Helicobacter pylori, the recognition of the importance of gastric acid suppression in the early treatment of peptic ulcer hemorrhage, and the development of endoscopic hemostatic techniques have meant that since the 1980s the diagnosis and treatment of bleeding caused by peptic ulcer disease have
improved. Data from the early 1980s, which cite high rates of rebleeding15,16 and mortality16,17 in older people with peptic ulcer hemorrhage, must, therefore, be interpreted with caution. Although the number of hospital admissions and operations for complications of peptic ulcer disease has declined for the overall population (including younger people) since the 1980s,18–20 rates of hemorrhage and hospital admissions have increased among elderly people with peptic ulcers.18–20 The trends among elderly patients might reflect the increasing rates of NSAID and anticoagulant use among the elderly.18,20
Platelet inhibition is impaired at an acidic gastric pH.21 Both platelet inhibition and mucosal fibrinolytic activity can be mitigated by gastric acid suppression.22 Treatment with a PPI is now the standard of care for patients with peptic ulcer hemorrhage and has been shown to decrease ulcer rebleeding rates independent of endoscopic therapy.23 Longterm PPI use can be associated with impaired absorption of supplemental calcium24 and with vitamin B12 deficiency,25 and one case–control analysis reported an increased risk of hip fracture.26 There are, however, no data to suggest that elderly
Table 1 Causes of upper gastrointestinal bleeding in the elderly.
etiology Article
segal and Cello14,a (% of patients)
Kaplan et al.1,b (% of patients)
Cooper et al.13,c (% of patients)
Common
Peptic ulcerd 73 44 42
Esophagitis or esophageal ulcer 11 7 18
Gastropathy 7 28 13
Esophageal or gastric varices 11 NR 2
Mallory–Weiss tear 3 4 2
Upper gastrointestinal malignancy 1 4 4
Less common
Portal hypertensive gastropathy ND ND ND
Dieulafoy lesion ND ND ND
Gastric antral vascular ectasia ND ND ND
Hemobilia ND ND ND
Hemosuccus pancreaticus ND ND ND
Aortoenteric fistula ND ND ND
aAge >60 years, n = 100; some patients had more than one lesion. bAge ≥65 years, n = 162; the cause of upper gastrointestinal bleeding was listed as ‘unknown’ or ‘other’ in 12% of patients. cAge >80 years, n = 103; the cause of upper gastrointestinal bleeding was listed as ‘unknown’ in 18% of patients. dIncludes gastric ulcer, duodenal ulcer, and peptic ulcer not otherwise specified. Abbreviation: ND, not described.
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patients who receive shortterm PPI therapy for acute UGIB experience these adverse effects.
Esophagogastroduodenoscopy (EGD) should be performed once a patient with UGIB has been hemodynamically resuscitated; our practice is to perform EGD within 12 h of presentation. EGD can confirm the presence of peptic ulcer disease, identify stigmata that connote a risk of recurrent or continued hemorrhage, and permit endoscopic therapy to reduce the risk of rebleeding. Endoscopic therapy with an epinephrine injection, thermocoagulation, hemostatic clip placement, or a combination of these modalities, decreases rebleeding rates in patients with a spurting vessel, adherent clot (after removal of the clot), or visible vessel (Table 2).27 Endoscopic therapy for peptic ulcer hemorrhage seems to be well tolerated in the elderly (Table 3).10,28 Combining endoscopic therapy with PPI administration results in lower rebleeding rates than with endoscopic
therapy alone.29 Among patients who experience rebleeding, there are no data to suggest that age influences the timing of rebleeding.
Hypovolemic shock at initial presentation, which is suggestive of massive ulcer hemorrhage, is associated with a poor outcome in the elderly.11 Elderly patients who have ulcers of 2 cm or more in diameter are at a particularly high risk of rebleeding and mortality.30 Surgical therapy for peptic ulcer hemorrhage is reserved for patients who have hemorrhage that is refractory to pharmacologic and endoscopic therapy. Sepsis and multiorgan failure are leading causes of postoperative mortality in elderly people who undergo surgery for peptic ulcer hemorrhage. In one retrospective series of 136 elderly patients with peptic ulcer hemorrhage (median age 77 years), mortality was 31% among the 42 patients who underwent surgery; sepsis accounted for nearly 50% of these deaths.31
Table 3 Peptic ulcer rebleeding and mortality by patient age.
study endoscopic therapy
Age (years) Number of patients
rebleeding (%)
Mortality (%)
Choudari et al. (1995)28,a Injection or heater probe
≤60 102 13 3
61–74 116 20 6
≥75 108 17 5
Chow et al. (1998)30,b Injection and/or heater probe
<60 833 11.9 0.4
60–79 706 17.7 5.9
≥80 205 25.4 11.2
Yamaguchi et al. (2003)10,a Hemostatic clip and/or injection
<80 417 5 0.5
≥80 42 10 2
aAll patients received endoscopic therapy. bNot all patients received endoscopic therapy.
Table 2 Peptic ulcer: endoscopic stigmata of rebleeding and mortality, with and without endoscopic therapy.
Finding rebleeding (%) Mortality (%)
endoscopic therapy
No endoscopic therapy
endoscopic therapy
No endoscopic therapy
Clean base NA <5 NA 2
Flat spot <1 10 <1 3
Adherent clot 5 22 <3 7
Nonbleeding visible vessel 15 43 <5 11
Active arterial bleeding 20 55 <5 11
With permission from Elsevier Ltd © Rockey DC (2006) in Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management, edn 8, 264 (http://www.sciencedirect.com/science/journal/08898553).27 Also based in part on data from Laine L and Peterson WL.107 Abbreviation: NA, not applicable.
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Esophageal varices and portal hypertensive gastropathyEsophageal and gastric varices are caused by increased venous collateral flow from the portal circulation through the gastric coronary veins, usually because of portal hypertension. Variceal hemorrhage can occur when the hepatic venous pressure gradient exceeds 12 mmHg. Features predictive of variceal hemorrhage include large variceal size and the presence of red ‘wale’ marks on varices.32
The mortality of patients who present with variceal hemorrhage has historically exceeded 30%.33 There are data to suggest that the mortality associated with variceal hemorrhage has improved over time, ostensibly as a result of advances in medical and endoscopic therapy; however, these data come from cohorts of patients with a mean age well below 65 years.33,34 Available data suggest that mortality after variceal hemorrhage correlates with the Child–Turcotte–Pugh score (Child class) and not with advanced age.35
Pharmacologic therapy for acute variceal hemorrhage generally includes intravenous administration of a somatostatin analog to reduce splanchnic circulation inflow. Cardiovascular effects can be observed in patients who take these medications; these effects include a decrease in heart rate (with terlipressin)36 and peripheral vasoconstriction (with octreotide).37 Although these effects have not been shown to correlate with adverse outcomes, elderly patients who are taking these medications should be carefully monitored.
Endoscopic variceal band ligation has supplanted injection sclerotherapy as the endoscopic therapy of choice because of the lower rate of complications.38 Nonselective βblockers are effective for both primary and secondary prophylaxis of variceal hemorrhage; however, elderly patients should be monitored closely for adverse effects, which include orthostasis, fatigue, and affective disturbance.
Patients with portal hypertensive gastropathy (PHG) can present with or without endoscopically apparent gastroesophageal varices. If gastrointestinal bleeding occurs in a patient with PHG, it is more commonly chronic and occult than overt and hemodynamically significant.39 Reduction of portal venous pressure with a nonselective βblocker might be beneficial for patients with PHG and gastrointestinal bleeding; however, the data to support this indication are limited as compared with those for variceal bleeding prophylaxis.
Other causes Esophagitis and gastropathy Esophagitis and gastropathy describe mucosal injury to the esophagus and stomach, respectively, and are most commonly caused by gastric acid or specific medications, such as NSAIDs. Although overt hemorrhage is an uncommon manifestation of esophagitis or gastropathy, these lesions are implicated as bleeding sources more frequently in elderly than in younger people.14,40–42 Moreover, severe esophagitis might not be heralded by heartburn in elderly people.42 Esophagitis and gastropathy are not typically amenable to endoscopic therapy unless a single ulcer with hemorrhagic stigmata is identified. Therapy for these two conditions consists of agents to suppress gastric acid secretion and the avoidance of offending medications, particularly aspirin and other NSAIDs. Stressrelated gastric mucosal injury can result in UGIB in critically ill patients in an intensive care unit; risk factors include mechanical ventilation, multiorgan failure, and coagulopathy, but not advanced age.
Gastric antral vascular ectasia Patients with gastric antral vascular ectasia (also known as ‘watermelon stomach’) typically present with occult or subacute blood loss and transfusiondependent anemia. The prevalence of gastric antral vascular ectasia does not increase with age per se, but the condition can be associated with certain medical comorbidities, including endstage renal disease43 and cirrhosis. Ablation therapy with argon plasma coagulation can stabilize hemoglobin levels and ameliorate transfusion requirements;44 multiple treatment sessions may be required.
Aortoenteric fistula An aortoenteric fistula (AEF) develops in 0.5% of patients who have undergone aortoiliac bypass surgery.45 An AEF can also develop after endovascular aortic repair, a procedure that is being performed with increasing frequency in the elderly.46 AEF has been described in patients with native anatomy and after enteral stent placement.47 Both mechanical and inflammatory factors have a role in the development of an AEF.
In a large retrospective series, the median time interval from an aortic intervention to the development of an AEF was 90 months.48 The classic presentation is with a herald (sentinel) bleed followed by exsanguinating hemorrhage.
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An AEF typically involves the third portion of the duodenum but can occur anywhere throughout the gastrointestinal tract, including the esophagus and colon.48 The median time to diagnosis of an AEF after presentation is approximately 10 days.45 Perhaps because of this delay, shortterm mortality exceeds 30% even after accurate diagnosis and repair.48 Noninvasive imaging with CT angiography can enable the diagnosis of an AEF, whereas mesenteric angiography is often not helpful and is not generally indicated. Endoscopy can also be diagnostic and should include careful examination of the third portion of the duodenum for an ulcer, erosion or hematoma, or for visualization of graft material. Biopsy samples should not be taken, and there is no role for endoscopic therapy.
Dieulafoy lesion A Dieulafoy lesion is a dilated submucosal artery that can rupture and result in overt gastrointestinal hemorrhage. These lesions can occur in, but are not specific to, elderly people. They are often found in the cardia of the stomach but can be found throughout the gastrointestinal tract.49 As the lesions are surrounded by normal musosa, endoscopic diagnosis is challenging unless performed at the time of active bleeding. Patients can, therefore, present with recurrent hemorrhage before a diagnosis is made.49 Either endoscopic or angiographic therapies can be applied.
LOwER GASTROINTESTINAL BLEEDINGThe incidence of lower gastrointestinal bleeding (LGIB) is less than that of UGIB but also increases with age. One retrospective study estimated a greater than 200fold increase in the incidence of LGIB from the third to the ninth decade of life.50 The mean age of people with acute LGIB ranges from 63 to 77 years.51 This trend is driven by the ageassociated increase in the incidence of diverticular hemorrhage, which is the most common cause of LGIB in elderly people.1,52 Compared with younger patients with LGIB, elderly people with LGIB incur longer hospital stays and greater healthcare costs.53
Clinical presentation, initial evaluation, and immediate managementIn patients with LGIB, taking a detailed history is critical. The history can distinguish among possible etiologies of LGIB in elderly patients
(Table 4). Characterization of the color, volume, and consistency of blood passed per rectum can help to localize a bleeding site. Passage of formed stool mixed with blood is suggestive of an anorectal bleeding source. The passage of melena is not exclusive to UGIB and can be seen when patients have proximal colonic bleeding sources. Cramping abdominal pain or abdominal tenderness suggests colitis.
The onset and pace of LGIB can provide additional clues as to the underlying etiology. The abrupt onset of painless, hemodynamically significant hematochezia (passage of bright red blood per rectum) is characteristic of diverticular hemorrhage. Bleeding from angiodysplasia, on the other hand, can vary in presentation from overt hemorrhage to chronic occult blood loss.54
Anoscopy is recommended, in addition to a digital rectal examination, as a standard component of the initial physical examination in patients with LGIB to assess for anorectal pathology.55 Nasogastric intubation and lavage can be useful, not only to evaluate for UGIB presenting as rectal hemorrhage, but also to rapidly purge the bowel in preparation for urgent colonoscopy.
Table 4 Causes of lower gastrointestinal bleeding in the elderly.
etiology Kaplan et al.1,a
(% of patients)rios et al.52,b
(% of patients)
Common
Diverticular hemorrhage 23 42
Angiodysplasia 7 16
Hemorrhoids ND 9
Neoplasm 12 7
Inflammatory bowel disease 14 ND
Colitis ND ND
Ischemic colitis ND ND
Infectious colitis ND ND
Drug-associated colitis ND ND
Indeterminate etiology 41 19
Less common
Post-polypectomy ND ND
Radiation proctitis ND ND
Rectal ulcer (solitary or stercoral) ND ND
aAge ≥65 years, n = 99; some patients were listed as etiology ‘unknown’. bAge ≥80 years, n = 43; ‘other’ and ‘small intestine’ were listed for 5% and 2% of patients, respectively.
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The initial management of patients with LGIB should, in the same way as for patients with UGIB, emphasize hemodynamic stabilization. In contrast to UGIB, however, in which EGD is typically the diagnostic and therapeutic modality of choice, the range of diagnostic modalities available for patients with LGIB includes endoscopic, noninvasive radiologic, and angiographic options.
DiverticulosisMost people who have colonic diverticulosis are asymptomatic and have an uncomplicated clinical course, but a small number of patients experience diverticular hemorrhage, which results from rupture of a vasa recta artery located in the wall of the diverticulum.56 Angiographic data, now several decades old, have fueled the clinical belief that hemorrhage originates from rightsided diverticula;57 however, diverticula in any colonic segment can be a source of bleeding. In most cases, and in more than 80% of cases in elderly people, diverticular hemorrhage ceases spontaneously.58 Most cases of diverticular hemorrhage in elderly people can be managed nonsurgically, and overall mortality is less than 5%.58 Massive or recurrent hemorrhage, however, can require a targeted intervention.
Flexible sigmoidoscopy or colonoscopy can be used to deliver endoscopic therapy, which includes epinephrine injection, thermal application,59 or band ligation.56 Skill and familiarity with epinephrine injection and a thermal technique should be in the armamentarium of all practicing endoscopists, whereas certain techniques, such as inversion and band ligation of a bleeding diverticulum, might be best reserved for experienced endoscopists at referral centers. In addition to the achievement of therapeutic hemostasis, the bleeding site should be tattooed to enable its ready localization in the event that repeat endoscopy or surgery is required.
Successful endoscopic therapy is contingent on visualization and identification of an actively bleeding diverticulum. This is especially difficult in patients with numerous diverticula throughout the colon, as is often the case. Additional hurdles to endoscopic therapy include impaired visualization caused by ongoing hemorrhage or inadequate bowel preparation. Moreover, hemorrhage can cease spontaneously before endoscopy. It is advisable to give a rapid purgative bowel preparation to patients who present with suspected
acute diverticular hemorrhage to maximize the diagnostic and therapeutic yield.
Radiologic studies can be used as firstline investigative tools, or to evaluate patients who have ongoing or recurrent hemorrhage when endoscopic evaluation is unsuccessful. Technetiumlabeled red blood cell scintigraphy can theoretically detect active gastrointestinal bleeding that occurs at rates as low as 0.1 ml/min, although the sensitivity of the test may vary among institutions.55 Use of multidetector CT angiography is an option available at selected centers. Some institutions require a positive scintigraphy result as a prelude to the performance of mesenteric angiography, a technique that can both locate a bleeding source and deliver targeted therapy (including intraarterial vasopressin infusion or embolization). The often intermittent nature of diverticular hemorrhage means that scintigraphy and angiography can fail to detect the culprit lesion in patients with diverticular hemorrhage. Among patients with LGIB and a negative scintigraphy result, up to 25% will experience recurrent bleeding.60
In a randomized, prospective study that has compared investigative modalities for acute LGIB, 100 patients with LGIB were randomly allocated to urgent colonoscopy or to technetium labeled red blood cell scintigraphy followed by angiography; 67% of the patients were classified as having definite or presumptive diverticular hemorrhage.61 Colonoscopic therapy was delivered to 17 patients, whereas angiographic therapy was performed in 10 patients. There were no differences between the groups for key outcomes, which included early or late rebleeding rates, transfusion requirements, or the need for emergency surgery.61
Surgery is necessary in a minority of elderly patients who have persistent or refractory diverticular hemorrhage.58 A critical decision is whether a presumptive bleeding source can be identified with sufficient confidence to permit segmental colonic resection. This identification can be a challenge in patients who have pancolonic diverticular disease, in whom subtotal colectomy is an option. Emergency colonic resection confers higher mortality than elective surgery.62 An advanced age also seems to be associated with increased mortality in patients who undergo emergency colectomy for LGIB. One retrospective study reported 37% mortality for patients 70 years of age or older, compared
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with 21% for patients aged less than 70 years, among a subset of patients with LGIB who underwent emergency colectomy with primary anastomosis.63
Ischemic colitisColitis of any etiology, including infectious colitis and idiopathic IBD, can be a source of gastrointestinal blood loss as a result of mucosal injury and sloughing.64 The principal mechanism that underlies acute ischemic colitis—nonocclusive mesenteric ischemia—occurs primarily in the elderly. Episodes of ischemic colitis result from transient colonic hypoperfusion and can be precipitated by dehydration. Additional risk factors include smallvessel vascular disease (including vasculitis) and the use of certain medications, such as diuretics or vasoactive agents. The clinical presentation often includes cramping abdominal pain. Abdominal CT can demonstrate colonic wall thickening, and colonoscopy can demonstrate edema, friable mucosa, and submucosal hemorrhage in affected colonic segments.
Ischemic colitis is distinct from both chronic mesenteric ischemia (intestinal angina) and acute mesenteric ischemia caused by mesenteric arterial or venous occlusion. The incidence of ischemic colitis increases with age, and the disorder is associated with the presence of medical comorbidities, including hypertension64 and dialysisdependent chronic kidney disease.65
The differential diagnosis of ischemic colitis includes infectious colitis, IBD, and drug associated colitis.64 Bleeding from ischemic colitis is rarely hemodynamically significant, and supportive care leads to full recovery in most patients. Patients with recurrent episodes can develop subacute colitis or stricture in the affected colonic segment. The presence of tachycardia, hypotension, or fever might suggest the presence of transmural colonic injury and impending bowel infarction. Death from ischemic colitis is uncommon, but mortality rate seems to increase with age and is associated with the presence of cardiovascular or cerebrovascular disease.66
Other causes Angiodysplasias Angiodysplasias (also referred to as angioectasias) are a common source of gastrointestinal bleeding in the elderly. Although angiodysplasias
are commonly located in the small intestine and colon,67 and most are small and clinically inconsequential, an important minority located in the right side of the colon can cause massive hemorrhage.68 An association between bleeding caused by angiodysplasias and acquired von Willebrand disease associated with aortic stenosis (Heyde syndrome) has been proposed but is controversial.69 Affected individuals can experience either chronic occult blood loss or massive hemorrhage.54,61 Endoscopic therapy can be targeted to actively bleeding lesions, but effective endoscopic therapy is difficult to achieve in patients who have numerous lesions or smallbowel lesions that are inaccessible to standard endoscopy. Single, large, bleeding angiodysplasias in the cecum can be particularly amenable to endoscopic, angiographic, or surgical therapy.
Hemorrhoids Although the prevalence of hemorrhoids seems to decrease after age 65 years,70 the association between hemorrhoids and constipation that is seen in younger patients persists in the elderly.71 Hemorrhoids can be detected during retroflexion in the rectum during an endoscopic examination, although anoscopy, which can easily be performed at the bedside in the early evaluation of rectal bleeding, might be required for optimal visualization.
Stercoral ulcer and solitary rectal ulcer syndrome Stercoral ulcer and solitary rectal ulcer syndrome can result in massive rectal hemorrhage. Most patients with a hemorrhagic rectal ulcer are older than 60 years of age.72 Stercoral ulcers result from mucosal trauma caused by hard or impacted stool in the rectum or from a foreign body such as a rectal tube in a hospitalized patient. Solitary rectal ulcer syndrome is thought to result from rectal mucosal prolapse, also as a result of constipation and straining. When endoscopic stigmata of hemorrhage are identified in a rectal ulcer, hemostatic techniques analogous to those used in the endoscopic treatment of peptic ulcers can be applied.
Colonic neoplasms and post-polypectomy hemorrhage Colonic neoplasms usually cause occult gastrointestinal blood loss, but patients with colonic neoplasms can also present with overt bleeding. Premalignant neoplasms (tubular adenomas)
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can be removed by polypectomy, and post polypectomy hemorrhage, either early or delayed, occurs after a small fraction of polypectomies. One prospective analysis of nearly 10,000 polypectomies identified age greater than 65 years as a risk factor for postpolypectomy bleeding.73
Radiation proctitis Radiation proctitis occurs in people who have undergone radiation therapy for prostate, genitourinary, or gynecologic malignancies. It can develop years after treatment has ended, and can result in either overt rectal hemorrhage or chronic transfusiondependent blood loss. Argon plasma coagulation,74 formalin application,75 sucralfate enemas,76 and hyperbaric oxygen therapy77 have been described as effective treatments for hemorrhagic radiation proctitis; however, comparative controlled data are limited, and it is not known which of these modalities is the most effective.
OBSCURE GASTROINTESTINAL BLEEDINGObscure gastrointestinal bleeding is defined as bleeding from a source that remains undetermined after EGD and colonoscopy. Sources of obscure overt hemorrhage can include lesions that were missed78 or not actively bleeding at the time of initial endoscopy. In instances of acute, overt hemorrhage, repeat endoscopy, scintigraphy, or angiography can be considered. Alternatively, bleeding can originate from a small bowel source beyond the reach of standard endoscopic examination. New endoscopic technologies have an increasing role to play in the investigation of small bowel bleeding. Two such techniques are video capsule endoscopy and doubleballoon endoscopy.
video capsule endoscopy Video capsule endoscopy (VCE, also known as wireless capsule endoscopy) has a diagnostic yield of 58–80% in patients with obscure gastrointestinal bleeding.79–81 In headtohead comparisons, the yield of VCE is superior to push enteroscopy, small bowel enteroclysis, and mesenteric angiography.79 Angiodysplasia is the culprit lesion most commonly identified by VCE.79 In elderly people with impaired swallowing or delayed gastric emptying, the video capsule can be placed beyond the pylorus during EGD. VCE seems to be safe to conduct in people with permanent pacemakers82 and implantable defibrillators.83
Double-balloon enteroscopy Doubleballoon enteroscopy (DBE) makes use of a modified enteroscope and overtube; both parts are equipped with a balloon that is inflated and deflated in sequential fashion to enable deep smallbowel exploration via either oral or rectal intubation. The diagnostic yield of DBE is 60–76% in patients with obscure gastrointestinal bleeding.80,84–86 By use of DBE, the most commonly identified small bowel lesions in older patients are angiodysplasias; small bowel tumors are relatively more common in younger people.84,86 Even though the procedure is time consuming and is more invasive than VCE, it allows for the possibility of therapeutic intervention. The age of patients in published studies of DBE ranges from 48 to 57 years,84–86 and the technique has not been performed extensively, nor its safety established, in elderly patients.
SPECIAL TOPICSNSAIDs and gastrointestinal bleeding Aspirin increases the risk of UGIB in a dose dependent fashion.87 The addition of a nonaspirin antiplatelet agent or NSAID to regular aspirin use has at least an additive impact on this increased risk.88–90 An increasing proportion of patients with UGIB report taking aspirin or other antithrombotic drugs.91 Taking aspirin and other NSAIDs also seems to confer an increased risk for LGIB, in particular diverticular hemorrhage.92,93
The increased risk of UGIB and LGIB associated with the use of aspirin and other NSAIDs is particularly pertinent to elderly people, many of whom require one or more of these medications for management of chronic cardiovascular or rheumatologic conditions. In elderly patients who require aspirin and have risk factors for gastrointestinal bleeding—including a prior history of gastrointestinal bleeding—aspirin should be prescribed in the lowest possible dose needed to achieve cardioprotection. The use of lowdose aspirin (e.g. 100 mg per day) does not, however, eliminate the risk of bleeding (adjusted relative risk for UGIB = 2.7 in aspirin users compared with nonusers88). The longterm risk of UGIB in elderly patients who take aspirin can be reduced by concurrent administration of a PPI.94
NSAID use might also be a risk factor for nosocomial gastrointestinal bleeding in elderly people. In a study of elderly patients (mean age 82.1 years) hospitalized for hip fracture, prior
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use of aspirin or a selective cyclooxygenase 2 inhibitor, and a history of peptic ulcer disease, were among the risk factors associated with the development of perioperative UGIB.95 Prophylactic gastric acid suppression (with a histamine H2receptor antagonist or PPI) seems to reduce the frequency of nosocomial UGIB (0.72% in those receiving prophylaxis versus 13.4% in those not receiving prophylaxis) among patients with identified risk factors for perioperative UGIB.95
Endoscopic safety The relative safety of gastrointestinal endoscopy has been established in an averagerisk population, and this has enabled the widespread acceptance of colonoscopy as a screening tool. Acute hemorrhage and intercurrent illness influence the safety of endoscopy in an individual patient. For instance, the mortality associated with EGD has been estimated to be 0.0004%,96 but increases to 0.1% in patients undergoing EGD for evaluation of gastrointestinal hemorrhage.97
Studies of EGD98 or colonoscopy98–100 carried out in elderly patients report overall procedural success and morbidity similar to that reported for the general population; however, the indication for endoscopy in most patients in these studies was screening or surveillance, and a relatively small percentage underwent endoscopy for evaluation of acute gastrointestinal bleeding.
Factors likely to influence the morbidity and mortality associated with endoscopy in an elderly cohort with acute gastrointestinal bleeding include the acuity and severity of hemorrhage and the presence of comorbid conditions. The presence of certain anatomic lesions such as a Zenker’s diverticulum or cervical spine osteophytes can increase the risk of perforation during upper gastrointestinal intubation in elderly people.101
Tolerance of sedation is an important consideration in elderly patients, who require lower doses of benzodiazepines than nonelderly patients of equivalent weight and body habitus.102,103 Elderly patients prescribed benzodiazepines for sedation can be prone to oxygen desaturation during endoscopy.104,105 Drugs used for sedation and analgesia should be administered at low doses to an elderly patient, with subsequent slow, careful titration. Continuous hemodynamic monitoring, use of pulse oximetry, and suction of oral secretions are necessary to safeguard against aspiration.106
Cognition and the elderly patientThe prevalence of dementia increases with age.51 Even in the absence of clinical dementia, sensory impairment can affect cognition, and in an individual patient these factors can influence both the course of illnesses and interactions with healthcare professionals. The clinician must pay particular attention to these issues during the evaluation, management, and aftercare phases of illness.
Although initial evaluation begins with clinical history taking, several factors can influence an elderly patient’s ability to provide an accurate history at presentation. Relative cerebral hypoperfusion as a result of hemorrhage and hypovolemia can impair cognition in elderly patients. In other cases, sensory impairment can limit an individual’s ability to provide a detailed history. The ability to describe the onset, acuity, and volume of rectal bleeding, for instance, requires intact vision and attention to the physical environment. When dementia or impaired memory prevents direct history taking from an elderly patient, family members or the patient’s primary care physician can serve as valuable sources of information.
Dementia or a clouded sensorium can similarly influence the individual’s ability to participate in decision making, provide informed consent for endoscopy, and generate a plan and goals of care. In these instances, either advanced directives or a formal healthcare proxy can be instrumental. As with all patients, the risk–benefit analysis of an invasive medical procedure such as endoscopy must be performed on an individual basis for each elderly patient.
After stabilization and acute control of hemorrhage, an elderly patient’s cognitive status must be carefully monitored; this approach is particularly relevant for patients who have received sedative medications for endoscopy. Certain elderly people depend heavily on regular environmental cues and can be prone to delirium during a hospital stay. An elderly patient’s ability to care independently for himself or herself, or otherwise access appropriate support, will determine whether the patient can safely return home immediately after hospitalization.
CONCLUSIONSGastrointestinal bleeding occurs frequently in elderly people, and aspirin and antiplatelet
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therapy are associated with an increased risk of both UGIB and LGIB in this population. Knowledge of the gastrointestinal lesions likely to affect elderly patients, thorough history taking, and a complete physical examination should help to determine whether the bleeding source is from the upper or lower gastrointestinal tract. In a patient with acute gastrointestinal bleed ing, hemodynamic stabilization should always precede endoscopic evaluation. In elderly patients with acute hemorrhage, urgent endoscopic evaluation can be undertaken, provided a riskbenefit assessment has been performed and informed consent has been obtained.
The most common source of UGIB in elderly people is peptic ulcer disease. EGD is the investigative study of choice for the evaluation of UGIB, and can be performed safely in elderly people. EGD can identify a bleeding source, deliver targeted hemostatic therapy, and provide estimates of the likelihood of recurrent bleeding in patients with peptic ulcer disease. Pharmacologic gastric acid suppression promotes ulcer healing and reduces the risk of rebleeding.
Diverticular hemorrhage is the most common source of LGIB in the elderly. In an elderly patient with LGIB, urgent colonoscopy should be performed after administration of a purgative bowel preparation. If colonoscopy is suggestive of active bleeding but fails to isolate a bleeding source, mesenteric angiography can be performed. If colonoscopy does not detect active bleeding, the patient should be maintained on a clear liquid diet. If there is evidence of acute (within 24–48 h) recurrent hemorrhage, colonoscopy can be repeated or angiography performed. Early surgical consultation is advisable in any patient who has massive or recurrent LGIB, irrespective of age.
In patients with a suspected smallbowel bleeding source, VCE has emerged as the initial diagnostic study of choice. Review and interpretation of VCE findings should be feasible within 24 h of image acquisition, thereby enabling timely management in cases of ongoing acute hemorrhage.
The care of elderly people with gastrointestinal bleeding can involve internists and intensivists, as well as gastrointestinal, surgical, and radiologic consultants. A coordinated approach to diagnosis and management should serve to optimize favorable outcomes in this vulnerable patient population.
KEy POINTS■ In elderly patients who have gastrointestinal
bleeding, immediate attention should focus on hemodynamic stabilization, followed by diagnostic evaluation to identify the bleeding source
■ The outcome of gastrointestinal bleeding in elderly patients is influenced by the nature of the bleeding lesion, presence of medical comorbidities, and use of anticoagulant or antiplatelet therapy
■ Peptic ulcer disease is the most frequent source of upper gastrointestinal bleeding in elderly patients; gastric acid suppression with a PPI and endoscopic hemostatic therapy reduce the rates of rebleeding and morbidity
■ Diverticulosis is the most frequent source of lower gastrointestinal bleeding in elderly patients, and urgent colonoscopy can be undertaken to identify a bleeding site and provide hemostasis; emergency colectomy is associated with high morbidity and mortality in elderly patients who have persistent or recurrent diverticular bleeding
■ Video capsule endoscopy and double-balloon enteroscopy offer expanded options for diagnosis and therapy of small-bowel bleeding sources
■ Endoscopy can be performed safely and effectively in elderly patients with gastrointestinal bleeding; however, risks and benefits must be considered carefully in each case, with particular attention paid to the tolerance of procedural sedation
References1 Kaplan RC et al. (2001) Risk factors for hospitalized
gastrointestinal bleeding among older persons. J Am Geriatr Soc 49: 126–133
2 Targownik LE and Nabalamba A (2006) Trends in management and outcomes of acute nonvariceal upper gastrointestinal bleeding: 1993–2003. Clin Gastroenterol Hepatol 4: 1459–1466
3 Thomopoulos KC et al. (2004) Changes in aetiology and clinical outcome of acute upper gastrointestinal bleeding during the last 15 years. Eur J Gastroenterol Hepatol 16: 177–182
4 Van Leerdam ME et al. (2003) Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. Am J Gastroenterol 98: 1494–1499
5 Rockall TA et al. (1995) Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Hemorrhage. BMJ 311: 222–226
6 Longstreth GF (1995) Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol 90: 206–210
7 Katschinski B et al. (1994) Prognostic factors in upper gastrointestinal bleeding. Dig Dis Sci 39: 706–712
Nature.indt 1Nature.indt 1 28/11/07 9:46:50 am28/11/07 9:46:50 am
review review
fEbRuARY 2008 vOL 5 NO 2 YACHIMSKI AND fRIEDMAN nature clinical practice GASTROENTEROLOGY & HEPATOLOGY 91
www.nature.com/clinicalpractice/gasthep
8 Clason AE et al. (1986) Clinical factors in the prediction for further haemorrhage or mortality in acute upper gastrointestinal haemorrhage. Br J Surg 73: 985–987
9 Cappell MS and Nadler SC (1995) Increased mortality of acute upper gastrointestinal bleeding in patients with chronic obstructive pulmonary disease. A case controlled, multiyear study of 53 consecutive patients. Dig Dis Sci 40: 256–262
10 YamaguchiY et al. (2003) Endoscopic hemostasis: safe treatment for peptic ulcer patients aged 80 years or older? J Gastroenterol Hepatol 18: 521–525
11 Hasselgren G et al. (1998) Risk factors for rebleeding and fatal outcome in elderly patients with acute peptic ulcer bleeding. Eur J Gastroenterol Hepatol 10: 667–672
12 Baradarian R et al. (2004) Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality. Am J Gastroenterol 99: 619–622
13 Cooper BT et al. (1988) Acute gastrointestinal haemorrhage in patients aged 80 years or more. Q J Med 69: 765–774
14 Segal WN and Cello JP (1997) Hemorrhage in the upper gastrointestinal tract in the older patient. Am J Gastroenterol 92: 42–46
15 Macleod IA and Mills PR (1982) Factors affecting the probability of further haemorrhage after acute upper gastrointestinal haemorrhage. Br J Surg 69: 256–258
16 Permutt RP and Cello JP (1982) Duodenal ulcer disease in the hospitalized elderly patient. Dig Dis Sci 27: 1–6
17 Antler AS et al. (1981) Gastrointestinal bleeding in the elderly. Morbidity, mortality, and cause. Am J Surg 142: 271–273
18 Ohmann C et al. (2005) Time-trends in the epidemiology of peptic ulcer bleeding. Scand J Gastroenterol 40: 914–920
19 Higham J et al. (2002) Recent trends in admission and mortality due to peptic ulcer in England: increasing frequency of hemorrhage among older subjects. Gut 50: 460–464
20 Kang JY et al. (2006) Recent trends in hospital admission and mortality rates for peptic ulcer in Scotland 1982–2002. Aliment Pharmacol Ther 24: 65–79
21 Green FW Jr et al. (1978) Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor to prolonged gastrointestinal hemorrhage. Gastroenterology 74: 38–43
22 Vreeburg EM et al. (2001) Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and the beneficial effect of acid suppression. Aliment Pharmacol Ther 15: 639–646
23 Khuroo MS et al. (1997) A comparison of omeprazole and placebo for bleeding peptic ulcer. N Engl J Med 336: 1054–1058
24 O’Connell MB et al. (2005) Effects of proton pump inhibitors on calcium carbonate absorption: a randomized crossover trial. Am J Med 118: 778–781
25 Valuck RJ and Ruscin JM (2004) A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of Vitamin B12 deficiency in older adults. J Clin Epidemiol 57: 422–428
26 Yang YX et al. (2006) Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 296: 2947–2953
27 Rockey DC (2006) Gastrointestinal bleeding. In Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management, edn 2, 264 (Eds Feldman M et al.) Philadelphia: Elsevier Saunders
28 Choudari CP et al. (1995) Age-related mortality in patients treated endoscopically for bleeding peptic ulcer. Gastrointest Endosc 41: 557–560
29 Lau JY et al. (2000) Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med 343: 310–306
30 Chow LW et al. (1998) Risk factors for rebleeding and death from peptic ulcer in the very elderly. Br J Surg 85: 121–124
31 Bulut OB et al. (1996) Acute surgical treatment of complicated peptic ulcers with special reference to the elderly. World J Surg 20: 574–577
32 Merkel C et al. (2000) Prognostic indicators of risk for first variceal bleeding in cirrhosis: a multicenter study in 711 patients to validate and improve the North Italian Endoscopic Club (NIEC) index. Am J Gastroenterol 95: 2915–2920
33 Chalasani N et al. (2003) Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol 98: 653–659
34 El-Serag HB and Everhart JE (2000) Improved survival after variceal hemorrhage over an 11-year period in the Department of Veterans Affairs. Am J Gastroenterol 95: 3566–3573
35 Hosking SW et al. (1989) Management of bleeding varices in the elderly. BMJ 298: 152–153
36 Villaneuva C et al. (2005) Hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. Am J Gastroenterol 100: 624–630
37 Chatila R et al. (2000) Local arterial vasoconstriction induced by octreotide in patients with cirrhosis. Hepatology 31: 572–576
38 Villanueva C et al. (2006) A randomized trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding. J Hepatol 45: 560–567
39 Primignani M et al. (2000) Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC). Gastroenterology 119: 181–187
40 Nankhonya JM et al. (1997) Acute upper gastrointestinal hemorrhage in older people: a prospective study in two neighboring districts. J Am Geriatr Soc 45: 752–754
41 Zimmerman J et al. (1997) Esophagitis is a major cause of gastrointestinal hemorrhage in the elderly. Scand J Gastroenterol 32: 906–909
42 Johnson DA and Fennerty MB (2004) Heartburn severity underestimates erosive esophagitis severity in elderly patients with gastroesophageal reflux disease. Gastroenterology 126: 660–664
43 Stefanidis I et al. (2006) Gastric antral vascular ectasia (watermelon stomach) in patients with ESRD. Am J Kidney Dis 47: e77–e82
44 Kwan V et al. (2006) Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long-term follow-up. Am J Gastroenterol 101: 58–63
45 Bergqvist D et al. (1996) Secondary aortoenteric fistulate—changes from 1973 to 1993. Eur J Endovasc Surg 11: 425–428
46 Baril DT et al. (2006) Experience with endovascular abdominal aortic aneurysm repair in nonagenarians. J Endovasc Ther 13: 330–337
47 Verhey P et al. (2006) Successful endovascular treatment of aortoenteric fistula secondary to eroding duodenal stent. J Vasc Interv Radiol 17: 1345–1348
48 Cendan JC et al. (2004) Twenty-one cases of aortoenteric fistula: lessons for the general surgeon. Am Surg 70: 583–587
49 Reilly HF III and al-Kawas FH (1991) Dieulafoy’s lesion. Diagnosis and management. Dig Dis Sci 36: 1702–1707
Nature.indt 1Nature.indt 1 28/11/07 9:46:50 am28/11/07 9:46:50 am
review
92 nature clinical practice GASTROENTEROLOGY & HEPATOLOGY YACHIMSKI AND fRIEDMAN fEbRuARY 2008 vOL 5 NO 2
www.nature.com/clinicalpractice/gasthep
review
50 Longstreth GF (1997) Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol 92: 419–424
51 Farrell JJ and Friedman LS (2000) Gastrointestinal bleeding in older people. Gastroenterol Clin North Am 29: 1–36
52 Rios A et al. (2005) Acute lower gastrointestinal hemorrhages in geriatric patients. Dig Dis Sci 50: 898–904
53 Comay D and Marshall JK.(2002) Resource utilization for acute lower gastrointestinal hemorrhage: the Ontario GI bleed study. Can J Gastroenterol 16: 7677–7682
54 Richter JM et al. (1989) Angiodysplasia: natural history and efficacy of therapeutic intervention. Dig Dis Sci 34: 1542–1546
55 Rockey DC (2006) Lower gastrointestinal bleeding. Gastroenterology 130: 165–171
56 Farrell JJ et al. (2003) Treatment of bleeding colonic diverticula by endoscopic band ligation: an in vivo and ex vivo pilot study. Endoscopy 35: 823–829
57 Casarella WJ et al. (1972) Right-sided colonic diverticula as a cause of acute rectal hemorrhage. N Engl J Med 286: 450–453
58 Bokhari M et al. (1996) Diverticular hemorrhage in the elderly—is it well tolerated? Dis Colon Rectum 39: 191–195
59 Jensen DM et al. (2000) Urgent colonoscopy for the treatment of severe diverticular hemorrhage. N Engl J Med 342: 78–82
60 Hammond KL et al. (2007) Implications of negative technetium 99m-labeled red blood cell scintigraphy in patients presenting with lower gastrointestinal bleeding. Am J Surg 193: 404–407
61 Green BT et al. (2005) Urgent colonoscopy for the evaluation and management of acute lower gastrointestinal hemorrhage: a randomized controlled trial. Am J Gastroenterol 100: 2395–2402
62 Ansar MZ et al. (2000) In-hospital mortality and associated complications after bowel surgery in Victorian public hospitals. Aust NZJ Surg 70: 1–2
63 Bender JS et al. (1991) Morbidity and mortality following total abdominal colectomy for massive lower gastrointestinal bleeding. Am Surg 57: 536–540
64 Medina C et al. (2004) Outcome of patients with ischemic colitis: review of fifty-three cases. Dis Colon Rectum 47: 180–184
65 Flobert C et al. (2000) Right colonic involvement is associated with severe forms of ischemic colitis and occurs frequently in patients with chronic renal failure requiring hemodialysis. Am J Gastroenterol 95: 195–198
66 Acosta S et al. (2006) Fatal colonic ischemia: a population-based study. Scand J Gastroenterol 41: 1312–1319
67 Foutch PG (1993) Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol 88: 807–818
68 Baum S et al. (1977) Angiodysplasia of the right colon: a cause of gastrointestinal bleeding. Am J Roentgenol 129: 789–794
69 Imperiale TF and Ransohoff DF (1988) Aortic stenosis, idiopathic gastrointestinal bleeding, and angiodysplasia: is there an association? A methodologic critique of the literature. Gastroenterology 95: 1670–1676
70 Stewart EB et al. (1992) Correlates of constipation in an ambulatory elderly population. Am J Gastroenterol 87: 859–864
71 Johnson JF and Sonnenberg A (1990) The prevalence of hemorrhoids and chronic constipation. An epidemiologic study. Gastroenterology 98: 380–386
72 Tseng CA et al. (2004) Acute hemorrhagic rectal ulcer syndrome: a new clinical entity? Report of 19 cases
and review of the literature. Dis Colon Rectum 47: 895–903
73 Kim HS et al. (2006) Risk factors for immediate postpolypectomy bleeding of the colon: a multicenter study. Am J Gastroenterol 101: 1333–1341
74 Kwan V et al. (2006) Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long-term follow-up. Am J Gastroenterol 101: 58–63
75 Vyas FL et al. (2006) Endoluminal formalin application for haemorrhagic radiation proctitis. Colorectal Dis 8: 342–346
76 Gul YA et al. (2002) Pharmacotherapy for chronic hemorrhagic radiation proctitis. World J Surg 26: 1499–1502
77 Dall’Era MA et al. (2006) Hyperbaric oxygen therapy for radiation induced proctopathy in men treated for prostate cancer. J Urol 176: 87–90
78 Descamps C et al. (1999) “Missed” upper gastrointestinal tract lesions may explain “occult” bleeding. Endoscopy 31: 452–455
79 Neu B et al. (2005) Capsule endoscopy versus standard tests in influencing management of obscure digestive bleeding: results from a German multicenter trial. Am J Gastroenterol 100: 1736–1742
80 Hadithi M et al. (2006) A prospective study comparing video capsule endoscopy with double balloon enteroscopy in patients with obscure gastrointestinal bleeding. Am J Gastroenterol 101: 52–57
81 Sturniolo GC et al. (2006) Small bowel exploration by wireless capsule endoscopy: results from 314 procedures. Am J Med 119: 341–347
82 Leighton JA et al. (2004) Safety of capsule endoscopy in patients with pacemakers. Gastrointest Endosc 59: 567–569
83 Leighton JA et al. (2005) Safety of wireless capsule endoscopy in patients with implantable cardiac defibrillators. Am J Gastroenterol 100: 1728–1731
84 Heine GDN et al. (2006) Double balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small bowel disease. Endoscopy 38: 42–48
85 Manabe N et al. (2006) Double-balloon enteroscopy in patients with GI bleeding of obscure origin. Gastrointest Endosc 64: 135–140
86 Sun B et al. (2006) Diagnostic yield and therapeutic impact of double-balloon enteroscopy in a large cohort of patients with obscure gastrointestinal bleeding. Am J Gastroenterol 101: 2011–2015
87 Slattery J et al. (1995) Risk of gastrointestinal bleeding during secondary prevention of vascular events with aspirin—analysis of gastrointestinal bleeding during the UK-TIA trial. Gut 37: 509–511
88 Lanas A et al. (2006) Risk of upper gastrointestinal bleeding associated with selective cyclo-oxygenase 2-inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 55: 1731–1738
89 Buresly K et al. (2005) Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 165: 784–789
90 Hallas J et al. (2006) Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ 333: 726
91 Taha AS et al. (2005) Upper gastrointestinal haemorrhage associated with low-dose aspirin and anti-thrombotic drugs—a 6-year analysis and comparison with non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 22: 285–289
Nature.indt 1Nature.indt 1 28/11/07 9:46:50 am28/11/07 9:46:50 am
review review
fEbRuARY 2008 vOL 5 NO 2 YACHIMSKI AND fRIEDMAN nature clinical practice GASTROENTEROLOGY & HEPATOLOGY 93
www.nature.com/clinicalpractice/gasthep
92 Wilcox CM et al. (1997) Nonsteroidal anti-inflammatory drugs are associated with both upper and lower gastrointestinal bleeding. Dig Dis Sci 42: 990–997
93 Aldoori WH et al. (1998) Use of acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective study and the risk of symptomatic diverticular disease in men. Arch Fam Med 7: 255–260
94 Pilotto A et al. (2003) The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs. Aging Clin Exp Res 15: 494–499
95 Fisher L et al. (2007) Perioperative acute upper gastrointestinal hemorrhage in older patients with hip fracture: incidence, risk factors and prevention. Aliment Pharmacol Ther 25: 297–308
96 Silvis SE et al. (1976) Endoscopic complications. Results of the 1974 American Society for Gastrointestinal Endoscopy Survey. JAMA 235: 928
97 Gilbert DA et al. (1981) National ASGE survey on upper gastrointestinal bleeding: complications of endoscopy. Dig Dis Sci 26 (suppl 7): 55S–59S
98 Clarke GA et al. (2001) The indications, utilization, and safety of gastrointestinal endoscopy in an extremely elderly patient cohort. Endoscopy 33: 580–584
99 Karajeh MA et al. (2006) Colonoscopy in elderly people is a safe procedure with a high diagnostic
yield: a prospective comparative study of 2000 patients. Endoscopy 38: 226–230
100 Zerey M et al. (2007) Colonoscopy in the very elderly: a review of 157 cases. Surg Endosc 21: 1806–1809
101 Das A et al. (2001) Cervical esophageal perforation during EUS: a national survey. Gastrointest Endosc 53: 599–602
102 Scholer SG et al. (1990) The effect of age on the relative potency of midazolam and diazepam for sedation in upper gastrointestinal endoscopy. J Clin Gastroenterol 12: 145–147
103 Bell GD et al. (1987) Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient. Br J Clin Pharmacol 23: 241–243
104 Christe C et al. (2000) Midazolam sedation for upper gastrointestinal endoscopy in older persons: a randomized, double-blind, placebo-controlled study. J Am Geriatr Soc 48: 1398–1403
105 Yano H et al. (1998) Oxygen desaturation during sedation for colonoscopy in elderly patients. Hepatogastroenterology 45: 2138–2141
106 Qureshi WA et al. (2006) ASGE Guideline: modifications in endoscopic practice for the elderly. Gastrointest Endosc 63: 566–569
107 Laine L and Peterson WL (1994) Bleeding peptic ulcer. N Engl J Med 331: 717–727
AcknowledgmentsCharles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.
Competing interests The authors declared no competing interests.
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