2016+ACG临床指南：急性下消化道出血患者的管理
nature publishing group
1
? 2016 by the American College of Gastroenterology
The American Journal of GASTROENTEROLOGY
PRACTICE GUIDELINES
I NTRODUCTION
A cute overt lower gastrointestinal bleeding (LGIB) accounts for ~20% of all cases of gastrointestinal (GI) bleeding, usually leads to hospital admission with invasive diagnostic evaluations, and consumes signifi cant medical resources ( 1–3 ). Although most patients with acute LGI
B stop bleeding spontaneously and have favorable outcomes, morbidity and mortality are increased in older patients and those with comorbid medical conditions ( 4 ).
A n individual with acute LG I
B classically presents with the sudden onset of hematochezia (maroon or red blood passed per rectum). However, in rare cases, patients with bleeding from the cecum/right colon can present with melena (black, tarry stools) ( 5 ). In addition, hematochezia can be seen in patients with brisk upper gastrointestinal bleeding (UG IB). Approximately 15% of patients with presumed LG IB are ultimately found to have an upper G I source for their bleeding ( 6 ). Historically, LG IB was defi ned as bleeding from a source distal to the Ligament of Treitz. However, bleeding from the small intestine (middle GI bleeding) is distinct from colonic bleeding in terms of presentation, man-agement, and outcomes ( 7 ). For the purposes of this guideline, we defi ne LGIB as the onset of hematochezia originating from either the colon or the rectum ( 8 ).
I n this practice guideline, we discuss the main goals of manage-ment of patients with LGIB. First, we discuss the initial evaluation and management of patients with acute LGIB including hemody-namic resuscitation, risk stratifi cation, and management of antico-agulant and antiplatelet agents (antithrombotic agents). We then discuss colonoscopy as a diagnostic and therapeutic tool including
A CG Clinical Guideline: Management of Patients With Acute Lower Gastrointestinal Bleeding
L isa L. S trate ,M D, MPH, FACG 1
and I an M. G ralnek ,M D, MSHS 2
T his guideline provides recommendations for the management of patients with acute overt lower gastrointestinal bleeding. Hemodynamic status should be initially assessed with intravascular volume resuscitation started as needed. Risk strati? cation based on clinical parameters should be performed to help distinguish patients at high- and low-risk of adverse outcomes. Hematochezia associated with hemodynamic instability may be indicative of an upper gastrointestinal (GI) bleeding source and thus warrants an upper endoscopy. In the majority of patients, colonoscopy should be the initial diagnostic procedure and should be performed within 24 h of patient presentation after adequate colon preparation. Endoscopic hemostasis therapy should be provided to patients with high-risk endoscopic stigmata of bleeding including active bleeding, non-bleeding visible vessel, or adherent clot. The endoscopic hemostasis modality used (mechanical, thermal, injection, or combination) is most often guided by the etiology of bleeding, access to the bleeding site, and endoscopist experience with the various hemostasis modalities. Repeat colonoscopy, with endoscopic hemostasis performed if indicated, should be considered for patients with evidence of recurrent bleeding. Radiographic interventions (tagged red blood cell scintigraphy, computed tomographic angiography, and angiography) should be considered in high-risk patients with ongoing bleeding who do not respond adequately to resuscitation and who are unlikely to tolerate bowel preparation and colonoscopy. Strategies to prevent recurrent bleeding should be considered. Nonsteroidal anti-in? ammatory drug use should be avoided in patients with a history of acute lower GI bleeding, particularly if secondary to diverticulosis or angioectasia. Patients with established cardiovascular disease who require aspirin (secondary prophylaxis) should generally resume aspirin as soon as possible after bleeding ceases and at least within 7 days. The exact timing depends on the severity of bleeding, perceived adequacy of hemostasis, and the risk of a thromboembolic event. Surgery for the prevention of recurrent lower gastrointestinal bleeding should be individualized, and the source of bleeding should be carefully localized before resection.
A m J Gastroenterol advance online publication, 1 March 2016; doi: 10.1038/ajg.2016.41
1
D ivision of Gastroenterology, University of Washington School of Medicine , S eattle , W ashington , U SA ; 2
C hief, Institute of Gastroenterology and Hepatology, Ha'Emek Medical Center, Afula, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , H aifa , I srael . C orrespondence: L isa L. Strate, MD, MPH, FACG,
D ivision of Gastroenterology, University of Washington School of Medicine , S eattle , W ashington 98104 , U SA . E-mail: l strate@https://www.wendangku.net/doc/c117106924.html, R eceived 30 J uly 2015 ; a ccepted 23 J anuary 2016 https://www.wendangku.net/doc/c117106924.html,
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2Table 1 continued on following page
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bleeding[tiab] OR hematochezia[tiab] OR haematochezia[tiab] OR rectal bleed[tiab] OR diverticular bleeding[tiab] OR diver-ticular bleed[tiab] OR diverticular hemorrhage[tiab] OR severe bleeding[tiab] OR active bleeding[tiab] OR melena[tiab] OR acute bleed[tiab] OR acute bleeding[tiab] OR acute haemorrhage[tiab] OR acute haemorrhage[tiab]) OR (LGIB[tiab] OR LIB[tiab]). Th e fi nal group was limited to English language and human studies. Citations dealing with children and prostatic neoplasms were excluded. Th e following website will pull up the PubMed search strategy: h ttp://https://www.wendangku.net/doc/c117106924.html,/ofnxphu .
S earch strategies in EMBASE and the Cochrane Library data-bases replicated the terms, limits, and features used in the PubMed search strategy.
I n addition to the literature search, we reviewed the references of identifi ed articles for additional studies. We also performed tar-geted searches on topics for which there is relevant literature for UGIB but not LGIB including hemodynamic resuscitation/blood product transfusions and management of anticoagulant and anti-platelet medications. W e used the GRADE system to grade the quality of evidence and rate the strength of each recommendation ( 9 ). Th e quality of evidence, which infl uences the strength of recommendation, ranges from “high” (further research is very unlikely to change
preparation, timing, and endoscopic hemostasis. Next, we outline non-colonoscopic diagnostic and therapeutic strategies for LGIB. Finally, we discuss prevention of recurrent LGIB and the role of repeat colonoscopy for recurrent bleeding events.
E ach section of this document presents key recommendations followed by a summary of supporting evidence. A summary of the key recommendations is presented in T able 1 .
W ith the assistance of a health sciences librarian, a systematic search of the literature was conducted covering the years 1 January 1968 through 2 March 2015 in the PubMed and EMBASE data-bases and the Cochrane Library including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Eff ect, and Cochrane Central Register of Controlled Trials (CEN-TRAL). Th e PubMed search used a combination of Medical Sub-ject Headings (MeSH), as well as terms appearing in titles and abstracts. Th e strategy used to cover the lower gastrointestinal tract included (‘Exp Intestine, Large’[Mesh] OR ‘Exp Lower G as-trointestinal Tract’[Mesh] OR lower gastrointestinal[tiab] OR lower intestinal[tiab]). Th ese terms were combined with terms for gastrointestinal bleeding including ‘G astrointestinal Hemorrhage’[Mesh:noexp] OR rectal bleeding[tiab] OR colonic
hemorrhage[tiab] OR colonic hemorrhages[tiab] OR colonic
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4Th e physical examination should include the measurement of vital
signs, including postural changes, to assess for hypovolemia. A car-diopulmonary, abdominal, and digital rectal examination should also be performed. Th e latter can detect potential anorectal bleed-ing sources and determine the color of the stool. Initial laboratory testing should include a complete blood count, serum electrolytes, coagulation studies, and a type and cross match.
H ematochezia associated with hemodynamic instability should lead to consideration of a brisk UG IB source, especially in at-risk patients such as those with a history of peptic ulcer disease or liver disease with portal hypertension and those using antiplatelet or anti-coagulant medications ( 6,11,12,19 ). An elevated blood urea nitrogen-to-creatinine ratio also suggests an UG IB source (likelihood ratio of UGIB with ratio >30:1 is 7.5) ( 10 ), whereas red blood and clots are unlikely to be from an upper gastrointestinal source (likelihood ratio 0.05) ( 10 ). If the likelihood of UGIB is high, an upper endos-copy should be performed. If suspicion for an UGIB source is mod-est, nasogastric aspirate/lavage can be used to assess possible UGIB ( 6,11,12 ). A positive nasogastric aspirate indicates a very high likeli-hood of an UGIB (likelihood ratio=11), whereas a negative aspirate makes an UGIB less likely but still possible (negative predictive value 64%, likelihood ratio=0.6) ( 20 ). Th erefore, a positive or non-diagnos-tic (non-bloody, non-bilious) aspirate necessitates upper endoscopy before considering colonoscopy ( 12,21 ). Th e nasogastric tube can be left in place to facilitate subsequent colon preparation ( 22 ).
C linical data available at the time of initial patient evaluation can be used to identify patients at high risk for severe bleeding and other adverse outcomes. Several tools have been developed to assess risk in acute LGIB ( T ables 2 and 3)( 13–18 ), although the number of available studies is modest in comparison with UGIB. Risk factors identifi ed for poor outcome in LGIB include markers of hemodynamic instability at presentation (tachycardia, hypo-tension, and syncope), ongoing bleeding (gross blood on initial digital rectal examination and recurrent hematochezia), comorbid illnesses, age >60 years, a history of diverticulosis or angioecta-sia, an elevated creatinine, and anemia (initial hematocrit ≤35%). In general, the likelihood of an adverse outcome increases with the number of risk factors present ( 16 ). Monitoring in an inten-sive care setting should be considered in patients with high-risk features. Th ese patients may also benefi t from colonoscopy aft er a rapid bowel preparation or radiographic interventions.
H emodynamic resuscitation
R ecommendations
4. Patients with hemodynamic instability and/or suspected on-going bleeding should receive intravenous fl uid resuscitation with the goal of normalization of blood pressure and heart rate before endoscopic evaluation/intervention (strong rec-ommendation, very-low-quality evidence) ( 23,24 ).
5. Packed red blood cells (RBCs) should be transfused to main-tain the hemoglobin above 7 g/dl. A threshold of 9 g/dl should be considered in patients with massive bleeding, signifi cant comorbid illness (especially cardiovascular ischemia), or a possible delay in receiving therapeutic interventions (condi-tional recommendation, low-quality evidence) ( 25,26 ).
our confi dence in the estimate of eff ect) to “moderate” (further research is likely to have an important impact on our confi dence in the estimate of eff ect and may change the estimate) to “low” (further research is very likely to have an important impact on our confi dence in the estimate of eff ect and is likely to change the estimate) and “very low” (any estimate of eff ect is very uncertain). Th e strength of a recommendation is graded as strong when the desirable eff ects of an intervention clearly outweigh the undesir-able eff ects and is graded as conditional when uncertainty exists about the trade-off s ( 9 ). Other factors aff ecting the strength of recommendation include variability in values and preferences of patients and whether an intervention represents a wise use of resources ( 9 ). In the GRADE system, randomized trials are con-sidered high-quality evidence but can be downrated depending on the size, quality, and consistency of studies. Observational studies are generally rated as low-quality studies.
I NITIAL ASSESSMENT E valuation and risk strati? cation
R ecommendations
1. A focused history, physical examination, and laboratory eval-uation should be obtained at the time of patient presentation to assess the severity of bleeding and its possible location and etiology. Initial patient assessment and hemodynamic resus-citation should be performed simultaneously (strong recom-mendation, very-low-quality evidence) ( 8,10 ).
2. Hematochezia associated with hemodynamic instability may be indicative of an UGIB source, and an upper endoscopy should be performed. A nasogastric aspirate/lavage may be used to as-sess a possible upper GI source if suspicion of UGIB is moderate (strong recommendation, low-quality evidence) ( 6,11,12 ).
3. Risk assessment and stratifi cation should be performed to help distinguish patients at high- and low-risk of adverse out-comes and assist in patient triage including the timing of co-lonoscopy and the level of care (conditional recommendation, low-quality evidence) ( 13–18 ). S ummary of evidence . I nitial assessment of the patient present-ing with presumed acute LGIB should include a focused history, physical examination, and laboratory testing with the goal of deter-mining the severity of bleeding, its possible location, and etiology ( 8,10 ). Th e history obtained should include the nature and dura-tion of bleeding and any associated symptoms that may suggest a specifi c source such as abdominal pain and diarrhea (colitis), and altered bowel habits and weight loss (malignancy). Likewise, past medical history elements should include any prior G I bleeding events, abdominal and/or vascular surgeries, peptic ulcer disease, infl ammatory bowel disease, or abdominopelvic radiation therapy. It is also important to assess comorbidities including cardiopulmo-nary, renal, or hepatic disease that may put the patient at high risk of poor outcome and alter the management approach. Current or recent medication use should be noted, particularly those medica-tions that may infl uence bleeding risk (nonsteroidal anti-infl am-matory drugs (NSAIDs), antiplatelet agents, and anticoagulants).
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6 S ummary of evidence . P atients with hemodynamic instability should receive intravenous fl uid resuscitation ( 19,23,24 ). In UGIB, an intensive fl uid (crystalloid) resuscitation strategy vs. standard of care may decrease mortality, myocardial infarction, and time in the intensive care unit. However, in the lone small study, these dif-ferences were not statistically signifi cant ( 23,24 ), and a specifi c re-suscitation protocol was not outlined. In the critical care literature in general, there is considerable controversy regarding the timing, amount, and type of fl uid resuscitation ( 2
7 ). However, there does not appear to be a benefi t of colloid over crystalloid fl uids ( 2
8 ). In addition, some patients will require blood transfusions. Transfu-sion strategies specifi c to LGIB have not been developed. Large observational studies and a meta-analysis of three small trials of UGIB suggest that blood transfusion compared with no transfu-sion is associated with an increased risk of rebleeding and pos-sibly death ( 25,29–32 ). Th ese fi ndings are supported by results of a large randomized trial of patients with UG IB that found that a restrictive transfusion strategy with a transfusion threshold of hemoglobin <7 g/dl improved survival (95% vs. 91%) and de-creased rebleeding (10% vs. 16%) when compared with a thresh-old of
9 g/dl ( 26 ). Patients with massive bleeding, acute coronary syndrome, symptomatic peripheral vascular disease, or a history of cerebrovascular disease were excluded, and all patients under-went upper endoscopy within 6 h of presentation. Th erefore, pa-tients with LGIB who have signifi cant comorbid disease, massive, ongoing bleeding, or delayed therapeutic interventions may ben-efi t from a more lenient blood transfusion threshold.
M anagement of coagulation defects
R ecommendations
6. Endoscopic hemostasis may be considered in patients with an inter-national normalized ratio (INR) of 1.5–2.5 before or concomitant with the administration of reversal agents. Reversal agents should be considered before endoscopy in patients with an INR >2.5 (con-ditional recommendation, very-low-quality evidence) ( 33–35 ).
7. Platelet transfusion should be considered to maintain a plate-let count of 50×10
9
/l in patients with severe bleeding and those requiring endoscopic hemostasis (conditional recom-mendation, very-low-quality evidence) ( 36,37 ).
8. Platelet and plasma transfusions should be considered in pa-tients who receive massive RBC transfusions (conditional rec-ommendation, very-low-quality evidence) ( 37–39 ).
9. In patients on anticoagulant agents, a multidisciplinary ap-proach (e.g., hematology, cardiology, neurology, and gastro-enterology) should be used when deciding whether to discon-tinue medications or use reversal agents to balance the risk of ongoing bleeding with the risk of thromboembolic events (strong recommendation, very-low-quality evidence) ( 36,40 ). S ummary of evidence . Th e management of anticoagulants and an-tiplatelet medications in the setting of LGIB requires consideration of the risk of ongoing bleeding and the risk of thromboembolic events and therefore requires an individualized approach. Obser-vational studies of UGIB indicate that there is no increased risk of rebleeding following endoscopic hemostasis in patients with
modest elevations in INR (1.5–2.7) ( 33–35,41–43 ). A retrospec-tive study of 98 patients with GI bleeding suggested that patients with an INR >4 had outcomes comparable to those with an INR in the 3–3.9 range, but these patients were not compared with pa-tients with normal coagulation parameters ( 44 ). In addition, in these studies, the use and timing of reversal agents were diffi cult to discern. An INR >1.5 has been a predictor of mortality but not rebleeding in two large observational cohort studies presumably because INR is a strong indicator of underlying comorbid disease ( 33,34 ). Aft er adjustment for other potential confounders, the odds ratios for mortality in these studies were 1.96 (95% confi dence in-terval (CI), 1.13–3.41) and 5.63 (95% CI, 3.09–10.27), respectively ( 30,32 ). Careful attention should therefore be given to the manage-ment of comorbid illness in patients with coagulopathy.
P ublished standards in the hematology literature recommend platelet transfusion to maintain a platelet count of ≥50×10
9
/l in patients with massive bleeding from any source ( 45,46 ). Th ere are no data to guide a threshold specifi c for gastrointestinal bleeding. Platelet transfusions should also be considered in patients who have a normal platelet count but receive massive RBC transfusions. Traditionally, massive transfusion has been defi ned as more than 10 units of packed RBCs within a 24-h period, but recent studies in the trauma literature defi ne this threshold as 3 or more units of packed RBCs within 1 h ( 47 ). Th e trauma literature suggests a ratio of one unit of platelets and fresh frozen plasma per unit of RBCs transfused ( 38,39,48 ). A recent randomized trial indicated that a 1:1:1 ratio of plasma, platelets, and RBCs was associated with better hemostasis and fewer deaths due to exsanguination than a 1:1:2 protocol without a diff erence in other adverse events or death ( 37 ). Th e 1:1:1 ratio-based transfusion protocol likely applies outside the trauma setting( 49 ), but no study has addressed a ratio-based transfusion protocol in gastrointestinal bleeding.N ew target-specifi c oral anticoagulants including dabigatran, rivaroxaban, and apixaban are associated with an increased risk of GI bleeding. In a meta-analysis of 43 randomized controlled trials, the odds ratio for overall bleeding was 1.45 (95% CI, 1.07–1.97) ( 50 ). However, there is no direct evidence to guide the manage-ment of these agents in the setting of active GI bleeding. For elec-tive procedures, a washout period based on the drug half-life is recommended ( 40 ) but may not be possible in patients with ongo-ing, acute bleeding or at high risk of thromboembolic events. In patients on target-specifi c oral anticoagulants, standard clotting tests may not refl ect the degree of anticoagulation and thus cannot be used to guide the safety of endoscopic interventions. A rever-sal agent for dabigatran (idarucizumab) was recently approved by the Food and Drug Administration, and reversal agents for other non-vitamin K anticoagulants are in development ( 51 ). However, these antidotes may increase the risk of thrombosis ( 36,40 ). Th erefore, a multidisciplinary approach involving hematology, cardiology/neurology, and gastroenterology is necessary when managing patients on anticoagulant medications, particularly if newer target-specifi c oral agents are involved to optimally bal-ance the risk of ongoing bleeding with the risk of thromboembolic events. Please see the section on recurrent bleeding for recommen-dations regarding aspirin and antiplatelet medications.
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C OLONOSCOPY
C olonoscopy as a diagnostic tool
R ecommendations
10. Colonoscopy should be the initial diagnostic procedure for
nearly all patients presenting with acute LGIB (strong recom-mendation, low-quality evidence) ( 52 ).
11.Th e colonic mucosa should be carefully inspected during
both colonoscope insertion and withdrawal, with aggressive attempts made to wash residual stool and blood in order to identify the bleeding site ( 53 ). Th e endoscopist should also intubate the terminal ileum to rule out proximal blood sug-gestive of a small bowel lesion (conditional recommendation, very-low-quality evidence).
S ummary of evidence.C olonoscopy has both diagnostic and therapeutic roles in acute LGIB. Th e goal of colonoscopy in LGIB is to identify the site of bleeding and perform hemostasis, if indi-cated. Th e diagnostic yield of colonoscopy in this patient popula-tion ranges from 48 to 90% ( 52,54 ). Th e most common causes of acute severe LG IB include diverticulosis, angioectasia, post-polypectomy bleeding, and ischemic colitis. Other less common causes include colorectal polyps/neoplasms, Dieulafoy’s lesions, infl ammatory bowel disease, and anorectal conditions including solitary rectal ulcer, radiation proctitis, and rectal varices ( 55,56 ). It is imperative to carefully inspect the colonic mucosa both on insertion and withdrawal, as culprit lesions oft en bleed intermit-tently and may be missed when not actively bleeding. Th e en-doscopist should intubate the terminal ileum to rule out proximal blood suggestive of a small bowel lesion. An adult or pediatric co-lonoscope with a large working channel (at least 3.3 mm) should be used because the larger working channel facilitates suctioning of blood, clots, and residual stool, and allows for the passage of large diameter (e.g., 10 Fr) endoscopic hemostasis tools. In addi-tion, the use of a water-jet irrigation device (foot pedal controlled by the endoscopist) is recommended to facilitate removal of ad-herent material and residue from the colonic mucosa.
B owel preparation
R ecommendations
12. Once the patient is hemodynamically stable, colonoscopy
should be performed aft er adequate colon cleansing. Four to six liters of a polyethylene glycol-based solution or the equiva-lent should be administered over 3–4 h until the rectal effl uent is clear of blood and stool. Unprepped colonoscopy/sigmoi-doscopy is not recommended (strong recommendation, low-quality evidence) ( 10,11,19 ).
13. A nasogastric tube can be considered to facilitate colon prepa-
ration in high-risk patients with ongoing bleeding who are intolerant to oral intake and are at low risk of aspiration (con-ditional recommendation, low-quality evidence) ( 8,57 ).
S ummary of evidence.C olonoscopy should be performed aft er adequate preparation ( 11,12,22,58 ). Preparation of the colon fa-cilitates endoscopic visualization and diagnosis, and may reduce the risk of bowel perforation. Although there have been no head-to-head comparisons, studies using large volume (4–6 l), rapid (3–4 h) purge protocols using polyethylene glycol-based solutions with colonoscopy performed within 1–2 h of preparation com-pletion report high rates of defi nitive diagnosis (22–42%) and hemostasis (34%) ( 11,12,22 ). Lower volume or alternative colon preparation solutions have been evaluated in the setting of colo-rectal cancer screening and surveillance but not in the setting of LGIB ( 59 ). Regardless of the solution used, it is important to clear the colon of stool, clots, and old blood to facilitate visualization and localization of the bleeding source. Many patients with acute LGIB are unable to tolerate rapid colon preparation and thus a nasogastric tube can be placed to facilitate this process ( 11,22 ). In studies of urgent colonoscopy, as many as one-third of patients required a nasogastric tube to facilitate rapid bowel preparation ( 22 ). In addition, administration of a prokinetic/antiemetic agent immediately before initiating the colon preparation may reduce nausea and facilitate gastric emptying ( 8,57 ). Complications of colon preparation with polyethylene glycol are rare but include aspiration pneumonia, as well as fl uid and electrolyte abnormali-ties ( 12,60 ). Aspiration precautions should be used particularly in older and debilitated patients.
U nprepped sigmoidoscopy/colonoscopy in the setting of acute LG IB is not recommended. In studies of urgent colonoscopy without oral or rectal preparation, cecal intubation rates are low (55–70%) ( 61–63 ). Recent prospective pilot data in severe LGIB subjects ( n=12) reported the feasibility and safety of “unprepared hydrofl ush colonoscopy” that combined three 1-liter tap water enemas, a water-jet pump irrigation system, and a mechanical suction device to cleanse the colon ( 64 ). However, localization of bleeding, in particular diverticular bleeding, can be diffi cult in the setting of residual blood and stool, and poor visualization may also increase the risk of perforation. Th erefore, this method is recom-mended only as an adjunct to appropriate oral preparation until further data are available.
T iming of colonoscopy
R ecommendations
14. In patients with high-risk clinical features and signs or symp-
toms of ongoing bleeding, a rapid bowel purge should be initi-ated following hemodynamic resuscitation, and a colonoscopy performed within 24 h of patient presentation aft er adequate colon preparation to potentially improve diagnostic and ther-apeutic yield (conditional recommendation, low-quality evi-dence) ( 11,22 ).
15. In patients without high-risk clinical features or serious co-
morbid disease or those with high-risk clinical features with-out signs or symptoms of ongoing bleeding, colonoscopy should be performed next available aft er a colon purge (con-ditional recommendation, low-quality evidence) ( 52,65 ).
S ummary of evidence.S tudies of timing of colonoscopy in the setting of acute LGIB are limited. T able 4summarizes the three existing prospective studies of urgent colonoscopy for acute LG IB. In a prospective study of 48 patients with severe diver-ticular bleeding who underwent colonoscopy within 12 h with
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8endoscopic hemostasis, and 73 historical controls who underwent colonoscopy within 12 h without endoscopic therapy, outcomes were signifi cantly better in the endoscopic hemostasis group: re-bleeding (0% vs. 53%); emergency surgery (0% vs. 35%); and hos-pital length of stay (median 2 days vs. 5 days) ( 22 ). In addition, untreated stigmata of hemorrhage were predictive of subsequent outcomes in this study and a subsequent larger series, although the overall number of cases in each category is small and there-fore the estimates may be imprecise. Rebleeding was seen in 84% of patients with active bleeding at endoscopy ( n =16/19), 60% of patients with a non-bleeding visible vessel ( n =3/5), and 43% with adherent clot ( n =6/14) ( 22,66 ). A trial of 100 patients with acute LG IB randomized to colonoscopy within 8 h of presentation or standard of care (colonoscopy next available or if unstable nuclear scintigraphy and angiography) found that urgent interventions signifi cantly improved defi nitive diagnoses (42% vs. 22%, odds ratio, 2.6; 95% CI, 1.1–6.2) but not rebleeding, surgery, or length of stay ( 11 ). No stigmata were identifi ed on elective colonoscopy, and the therapeutic yield was higher but not statistically signifi -cantly diff erent in the urgent vs. elective group (34% endoscop-ic therapy vs. 20% angiographic therapy). In another trial of 72 patients randomized to colonoscopy within 12 h or delayed co-lonoscopy (30–60 h), there were no diff erences in rebleeding, di-agnoses, or the need for therapy between the groups ( 6 ). Overall, retrospective studies support that urgent colonoscopy (defi ned variably as colonoscopy within 12–24 h) improves diagnostic and therapeutic yield ( 52 ). In addition, studies have found that earlier time to colonoscopy is associated with reduced hospital length of stay likely because of more effi cient discharge aft er a negative exam ( 52,65,67 ). It is not clear whether urgent colonoscopy im-proves important clinical outcomes such as rebleeding and the need for surgery. However, because diagnostic yield is improved with earlier timing, the lack of a signifi cant benefi t in existing studies may refl ect inadequate statistical power or insuffi cient en-doscopic therapy.
E ndoscopic hemostasis therapy
R ecommendations
16. Endoscopic therapy should be provided to patients with high-risk endoscopic stigmata of bleeding: active bleeding
(spurting and oozing); non-bleeding visible vessel; or adher-ent clot (strong recommendation, low-quality evidence) ( 22 ).
17. Diverticular bleeding: through-the-scope endoscopic clips are recommended as clips may be safer in the colon than contact thermal therapy and are generally easier to perform than band ligation particularly for right-sided colon lesions (conditional recommendation, low-quality evidence) ( 68,69 ).
18. Angioectasia bleeding: noncontact thermal therapy using argon plasma coagulation is recommended (conditional recommendation, low-quality evidence) ( 75,76 ).
19. Post-polypectomy bleeding: mechanical (clip) or contact thermal therapy, with or without the combined use of dilute epinephrine injection, is recommended (strong recommen-dation, very-low-quality evidence) ( 70,71 ).
20. Epinephrine injection therapy (1:10,000 or 1:20,000 dilution with saline) can be used to gain initial control of an active bleeding lesion and improve visualization but should be used in combina-tion with a second hemostasis modality including mechanical or contact thermal therapy to achieve defi nitive hemostasis (strong recommendation, very-low-quality evidence) ( 11,22,52 ). S ummary of evidence . C olonoscopy with endoscopic hemosta-sis for colonic bleeding is safe. Adverse events were reported in 0.3–1.3% of more than 2,400 colonoscopies performed for acute LGIB ( 69,72 ). Moreover, endoscopic hemostasis in the colon ap-pears to be eff ective, although the optimal technique has not yet been fully characterized. Endotherapy options for acute LG IB include injection (most commonly dilute epinephrine), contact thermal therapies (bipolar/multipolar electrocoagulation, heat probe), noncontact thermal therapy (argon plasma coagulation), through-the-scope clipping devices, and band ligation. Emerg-ing endoscopic treatments include hemostatic topical sprays/powders and large-sized over-the-scope clipping devices ( 73,74 ). Each of these therapeutic modalities, used as monotherapy or in combination, has been reported to be safe and eff ective in con-trolling bleeding. In contrast to the numerous randomized com-parative studies and meta-analyses evaluating endoscopic hemo-stasis modalities in acute UGIB, there have been no such studies in acute LGIB. Endoscopic treatments have most commonly been
reported as individual case reports, retrospective cohort studies,
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the diverticulum for more precise localization and treatment of the bleeding lesion ( 68 ). Moreover, injection can also be used to evert the dome of the diverticulum and improve access to the bleeding site followed by clip placement ( 8 ).
I n the aforementioned pooled analysis by Strate and Nau-mann, no early rebleeding was reported aft er endoscopic clip-ping of diverticular bleeding; however, late rebleeding occurred in 17% ( 8 ). More recently, in a retrospective case series from two Veterans Aff airs hospitals, Kaltenbach reported on the short- and long-term outcomes of endoscopic clipping in 24 patients with defi nitive diverticular hemorrhage ( 68 ). Success-ful endoscopic hemostasis was achieved in 21 (88%) using clips as monotherapy or in combination with epinephrine injection in the setting of active bleeding. Th ere was no early rebleed-ing or adverse events (e.g., perforations). Late rebleeding (≥30 days following initial endoscopic hemostasis) occurred in 24%. Of the three patients in whom primary hemostasis was not achieved, two required emergency hemicolectomy and one patient received angiographic embolization.
C ase series including a total of 36 patients report good safety and efficacy of endoscopic band ligation for the treatment of diverticular bleeding with stigmata of recent hemorrhage ( 80–82 ). The banding technique described includes identifi-cation of the culprit diverticulum, marking of the site with a clip or India ink, followed by withdrawal of the colonoscope. A band ligation device is then loaded onto a gastroscope (if the bleeding lesion is located in the left colon) or a pediatric colonoscope. Once the lesion is re-identified, it is suctioned into the banding device, and the band is deployed as is done in the treatment of variceal hemorrhage. Recently, Shibata e t al. ( 83 ) reported on 27 cases of definitive colonic diverticular hemorrhage effectively treated (hemostasis achieved in 96.3%) using band ligation in combination with a disposable, trans-parent soft hood attached to the tip of the colonoscope. The hood allows improved visualization of diverticula and expo-sure of high-risk stigmata. Caution, however, should be exer-cised when contemplating using band ligation for a right side colonic diverticular bleed. E x vivo colon specimen data have demonstrated serosal entrapment and inclusion of the muscu-laris propia post band ligation in the right colon ( 84,85 ). The left colon, likely due to its thicker mucosal wall, had limited submucosal involvement and only a single site of muscularis propria involvement ( 84 ). Th e use of Doppler ultrasound probe monitoring has been reported as an adjunct to endoscopic treatment. In a study of 46 patients with diverticular bleeding, 24 were found to have major stigmata of hemorrhage at the time of colonoscopy ( 66 ). Dop-pler ultrasound probe noted arterial fl ow in 92% (and no fl ow in those without major stigmata). Aft er treatment, no patient had residual blood fl ow and no patient experienced rebleeding at 30 days. However, there was no comparison with patients undergoing endoscopic treatment without Doppler probe guidance. Th erefore, Doppler ultrasound probe guidance holds promise for improving the eff ectiveness of endoscopic hemostasis in diverticular bleed-ing, but further data are needed.
or prospective, non-randomized case series with small numbers of patients. Th us, the endoscopic hemostasis modality selected by the endoscopist is generally guided by the source of bleed-ing, access to the bleeding site, and experience with the various hemostasis device options. Th e most common causes of LGIB amenable to endotherapy are diverticulosis, angioectasia, and post-polypectomy bleeding ( 56 ). Endoscopic therapy for each of these bleeding etiologies will be discussed below.
D iverticular hemorrhage . D iverticular bleeding is arterial, typi-cally presents as painless hematochezia, and usually occurs from either the neck or the dome of the diverticulum ( 22 ). Patients with diverticular bleeding are candidates for endoscopic treatment if active bleeding (spurting or oozing), a non-bleeding visible vessel, or an adherent clot (that cannot be removed with vigorous wash-ing and suctioning) is found at the time of colonoscopy ( 22 ). As noted above, these stigmata of hemorrhage predict a high risk of rebleeding without treatment ( 66 ).J ensen e t al. reported a prospective case series of 10 patients presenting with severe hematochezia found to be from a defi nitive diverticular source at the time of urgent colonoscopy. Endoscopic treatments included injection of dilute epinephrine (1:20,000 admixture with saline, in 1 or 2 ml aliquots per injection in four quadrants), as monotherapy for patients with active bleeding ( n =5), and bipolar thermal coagulation (using 10–15 W with moderate appositional pressure applied in 1-s intervals until vessel fl attening was achieved) for those with a non-bleeding visible vessel ( n =2). For patients with an adherent clot ( n =3), dilute epinephrine was injected circumferentially around the site of bleeding, the clot was removed using a colon polyp snare, and any underlying stigmata were treated with bipolar thermal coagulation as described above ( 22 ). None of the 10 patients treated endoscopically had recurrent bleeding or required surgery. In a pooled analysis of case series (including 847 patients) evaluating colonoscopy and endoscopic hemostasis for diverticular bleeding, Strate e t al.( 69 )reported that following endoscopic hemostasis ( n =137), early rebleeding occurred in 8% and late rebleeding in 12% of patients. Th ere was no apparent advantage to combined endoscopic hemostasis over monotherapy.
E ndoscopic clips are an attractive treatment modality for diver-ticular bleeding. Compared with contact thermal therapies, clips avoid the theoretical risk of transmural injury and perforation in the thin-walled colon. In addition, improved clip design includ-ing greater tensile strength and the ability to rotate and open/close the clip before deployment has made clips easier to use for bleed-ing control ( 75–79 ). Control of diverticular bleeding using clips can be accomplished either by targeted clip placement directly on the bleeding stigma or by closure of the diverticular orifi ce in a “zipper-like” manner resulting in bleeding tamponade ( 79 ). When active bleeding is present, dilute epinephrine (0.5–2 ml per injec-tion) can be injected in or around the diverticulum to slow bleed-ing, improve visibility, and facilitate clip placement ( 68 ). In the setting of a small or deep bleeding diverticulum, a translucent cap can be placed onto the tip of the colonoscope, enabling eversion of
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R ole of repeat colonoscopy in the setting of early recurrent bleeding
R ecommendations
21. Repeat colonoscopy, with endoscopic hemostasis if indicated, should be considered for patients with evidence of recurrent bleeding (strong recommendation, very-low-quality evi-dence) ( 68,79 ). S ummary of evidence . Th e rate of rebleeding in patients with acute LG IB is poorly characterized. In randomized controlled studies, early rebleeding (defi ned as rebleeding prior to hospital discharge) following urgent colonoscopy is reported to be 22% and late rebleeding (defi ned as rebleeding aft er hospital dis-charge) is 16% ( 6,11 ). Factors that may contribute to early or late rebleeding include underlying comorbid conditions, concurrent medication use (e.g., NSAIDs, antiplatelet agents, anticoagulants), source of index bleeding, and initial hemostasis modality ( 100 ). Th ere are no published studies that directly evaluate the role of repeat colonoscopy in patients with early or late recurrent LGIB. However, small case series indicate that the yield of repeat colo-noscopy for early rebleeding from a diverticular source is fairly high (20%) ( 79 ). In this setting, the patient oft en remains in the hospital with a recently prepped colon, and repeat colonoscopy can be performed promptly.
N ON-COLONOSCOPY INTERVENTIONS
R ecommendations
22. A surgical consultation should be requested in patients with high-risk clinical features and ongoing bleeding. In general, surgery for acute LGIB should be considered aft er other thera-peutic options have failed and should take into consideration the extent and success of prior bleeding control measures, se-verity and source of bleeding, and the level of comorbid disease. It is important to very carefully localize the source of bleeding whenever possible before surgical resection to avoid continued or recurrent bleeding from an unresected culprit lesion (condi-tional recommendation, very-low-quality evidence).
23. Radiographic interventions should be considered in patients with high-risk clinical features and ongoing bleeding who have a negative upper endoscopy and do not respond adequately to hemodynamic resuscitation eff orts and are therefore unlikely to tolerate bowel preparation and urgent colonoscopy (strong recommendation, very-low-quality evidence) ( 101,102 ).
24. If a diagnostic test is desired for localization of the bleeding site before angiography, computed tomographic (CT) angi-ography should be considered (conditional recommendation, very-low-quality evidence) ( 69 ). S ummary of evidence . A number of radiographic modalities can be utilized in the setting of presumed acute LG IB. Few studies have compared radiographic interventions with colonoscopy. In one randomized trial evaluating colonoscopy within 8 h of ad-mission compared with elective colonoscopy if hemodynamically stable or tagged RBC scan followed by angiography if ongoing
A ft er endoscopic treatment, an India ink tattoo or clip (if not already used for hemostasis) should be placed adjacent to the culprit lesion to assist in re-localization should rebleeding occur ( 8,82 ).
A ngioectasia . A ngioectasias are common in the right colon and in the elderly ( 86,87 ). Colonic angioectasias, including radiation proctopathy, usually present with occult bleeding but can present with overt hematochezia, especially in patients using anticoagu-lant/antiplatelet therapy ( 8,57 ). Endoscopic hemostasis therapy is indicated if there is evidence of acute or chronic blood loss ( 88 ). Contact and noncontact thermal endoscopic therapies are eff ective for treatment of angiodyplasia. Noncontact thermal therapy (ar-gon plasma coagulation) is more commonly used because it is easy to use, safe, effi cient, and has been shown to improve hemoglobin levels and reduce the frequency of blood transfusions ( 89,90 ). Typ-ical argon plasma coagulation power settings for the treatment of colonic angioectasia are 20–60 W (lower power used in the right colon) with an argon gas fl ow rate 1–2.5 l/min ( 89,90 ). Lesions are obliterated using focal pulses of 0.5–2-s duration. Larger angioec-tasia (>10 mm) and those located in the right colon may be lift ed using submucosal saline injection before coagulation ( 89,91 ). P ost-polypectomy bleeding . P ost-polypectomy bleeding can oc-cur immediately or days to weeks following polyp removal ( 92 ). Risk factors for post-polypectomy bleeding include large polyp size (>2 cm), thick stalk, right colon location, and resumption of antithrombotic therapy. Endoscopic hemostasis treatments for post-polypectomy bleeding include endoscopic clipping, thermal contact, with or without the combined use of dilute epinephrine injection, and band ligation. Use of through-the-scope clipping, with or without epinephrine injection, may be preferred in order to limit additional tissue injury that occurs with contact thermal coagulation therapy ( 92 ).
H emostatic topical powders/sprays have recently been reported as an endotherapy options for acute LGIB ( 93 ). Th ese powders/sprays (Hemostatic Agent TC-325 (Hemospray, Cook Medical, Winston-Salem, NC), EndoClot polysaccharide hemostatic system (EndoClot Plus Inc., Santa Clara, CA), and Ankaferd Bloodstopper (Ankaferd ilac kozmetik A.S., Istanbul, Turkey)) are delivered through the working channel of the endoscope and are intended to control “actively” bleeding lesions. Th ere are a limited number of case reports and small case series reporting on these modalities as primary or salvage therapy in post-polypectomy bleeding, colonic ulcerations including solitary rectal ulcer, radiation proctitis, colorectal neoplasia, and portal hypertensive colopathy ( 94–98 ). In addition, an over-the-scope clip (OTSC, Ovesco Endoscopy, Tubingen, Germany), made from a nitinol alloy, has been applied as salvage therapy in post-polypectomy bleeding ( 99 ). Th is clipping device is loaded onto an endoscope and deployed in a similar manner as a band-ligating device.
A cute LG I
B etiologies such as ischemic colitis, colitis due to infl ammatory bowel disease, and colorectal neoplasms are gen-erally not amenable to durable endoscopic hemostasis and are treated with supportive medical and/or surgical care of the under-lying etiology.
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Some studies report high overall mortality (up to 27%) aft er emer-gent total abdominal colectomy for massive LG IB ( 117 ), whereas others note no diff erence in morbidity or mortality when comparing limited resection with total colectomy for bleeding ( 118 ). Not surpris-ingly, the rebleeding rate is higher in patients aft er limited resection than total colectomy (18% vs. 4% in one study of 77 patients) ( 118 ). In general, surgery for acute LGIB should be considered only aft er other therapeutic options have failed and should take into consideration the extent and success of prior bleeding control measures, severity and source of bleeding, and the level of comorbid disease. It is important to very carefully localize the source of bleeding whenever possible before surgical resection to avoid continued or rebleeding from an unresected culprit lesion.
P REVENTION OF RECURRENT LOWER GI BLEEDING
R ecommendations
25. Non-aspirin NSAID use should be avoided in patients with a history of acute LGIB particularly if secondary to diverticu-losis or angioectasia (strong recommendation, low-quality evidence) ( 119–121 ).
26. In patients with established high-risk cardiovascular disease and a history of LGIB, aspirin used for secondary prevention should not be discontinued. Aspirin for primary prevention of cardiovascular events should be avoided in most patients with LGIB (strong recommendation, low-quality evidence) (122–124).
27. In patients on dual antiplatelet therapy or monotherapy with non-aspirin antiplatelet agents (thienopyridine), non-aspirin antiplatelet therapy should be resumed as soon as pos-sible and at least within 7 days based on multidisciplinary assessment of cardiovascular and GI risk and the adequacy of endoscopic therapy (as above, aspirin use should not be discontinued). However, dual antiplatelet therapy should not be discontinued in patients with an acute coronary syndrome within the past 90 days or coronary stenting within the past 30 days. (strong recommendation, low-quality evidence) (122,125,126).
S ummary of evidence P atients with bleeding from colonic diverticula or angioectasia are prone to recurrent bleeding events. Th e rate of diverticular hemor-rhage recurrence at 1 year in patients who do not undergo surgical treatment was reported at 9% in a population-based study ( 3 ) but was considerably higher (47%) in a single-center study of patients with defi nitive diverticular bleeding ( 127 ). It is not clear that endoscopic therapy of diverticular stigmata decreases the rate of recurrent bleeding, particularly because bleeding may arise from any existing diverticulum. Rates of late rebleeding are reported in ~15% of patients aft er combination injection plus thermal or clip therapy, with variable follow-up periods ( 69 ).
A ngioectasias are also prone to rebleeding, and new lesions may form throughout the G I tract. In a systematic review, the rate of rebleeding with conservative/placebo therapy ranged from 37 to 45% at 1 year and 58 to 64% at 2 years ( 128 ). Th e authors rated the
bleeding, more diagnoses and therapeutic interventions were made in the urgent colonoscopy arm ( 11 ). Retrospective stud-ies also suggest the superior diagnostic and therapeutic yield of colonoscopy over radiographic algorithms ( 101,102 ). In contrast to radiographic modalities, colonoscopy can provide a defi nitive diagnosis and treatment in the absence of active bleeding at the time of the exam. Nonetheless, in some patients brisk, ongoing hematochezia precludes adequate hemodynamic resuscitation and bowel preparation before colonoscopy. In this small subset, angiography can provide both localization and treatment. Angi-ography localizes a LGIB source in 25–70% of exams ( 103,104 ). A systematic review found that super-selective angiographic em-bolization achieves immediate hemostasis in 40–100% of cases of diverticular bleeding with a rebleeding rate ranging from 0 to 50% ( 105 ). Bowel ischemia is reported in as many as one-third of pa-tients following super-selective embolization ( 105 ), although the rate of ischemia is lower (1–4%) in more recent series ( 103,106 ). Because angiography relies on active bleeding and has the poten-tial for serious complications, it should be reserved for patients with very brisk, ongoing bleeding. Th ere is a considerable debate regarding the utility of tagged RBC scintigraphy to localize GI bleeding before angiography. Some retrospective case series suggest that a screening-tagged RBC scin-tigraphy study increases the diagnostic yield of angiography and enables targeted contrast injection ( 107–109 ). Other series have found that the diagnostic yield of angiography is similar with or without a preceding tagged RBC scintigraphy ( 110,111 ). If tagged RBC scintigraphy is positive, angiography should be performed immediately following to maximize the chance of a positive test. Th e ability of tagged RBC scintigraphy to accurately localize a bleeding source is suboptimal (65–80%) ( 69,72,112 ), and bleeding location should be confi rmed before surgical resection particularly if the tagged RBC scintigraphy is positive only on delayed images ( 113,114 ). One advantage of tagged RBC scintigraphy is the ability to perform repeated scans aft er the initial injection of tagged cells. Th is makes RBC scintigraphy most suitable for the evaluation of intermittent, obscure-overt GI bleeding ( 107,115 ).
C T angiography or multi-detector row CT scan is another diag-nostic modality for GI bleeding that is widely available and highly accurate at localizing the bleeding site (nearly 100%) ( 69 ). How-ever, in the only back-to-back comparison, tagged RBC scintig-raphy was positive in 46% of patients and CT angiography in 27% of patients ( 111 ). Nonetheless, only 2 of 11 patients with a positive RBC scintigraphy and negative CT angiography went on to have bleeding requiring treatment. Th erefore, although tagged RBC scintigraphy may be more sensitive for bleeding, CT angiography is a reasonable fi rst-line screening test if needed before angiogra-phy or emergent surgery because it is more expedient and accu-rate than tagged RBC scintigraphy. Standard precautions should be taken to avoid contrast-induced nephropathy, particularly as patients may undergo subsequent angiography with administra-tion of arterial contrast ( 116 ).
A surgery consultation should be requested in patients with brisk, ongoing LGIB. Th e quality of the evidence regarding surgery for acute LGI
B is poor and mostly derived from small, retrospective reviews.
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12evidence for treatment with thalidomide or estrogen plus progester-one as low and that for octreotide as insuffi cient. Medical therapies resulted in a higher rate of complications than placebo. Small, retro-spective studies have examined the use of argon plasma coagulation, heater probe, and monopolar thermal coagulation in the treatment of angioectasia. Rates of rebleeding were no diff erent between any of the endoscopic modalities and conservative care ( 128 ).
R isk factors for recurrent LG IB are not well-studied. In one study of 83 patients with incident diverticular bleeding events who were followed for an average of 34 months, no predictors were identifi ed including age, gender, blood transfusion requirements, hospital length of stay, endoscopic stigmata, or a previous history of bleeding ( 3 ). However, risk factors for incident diverticular bleeding events include obesity, physical inactivity, hypertension, hyperlipidemia, and chronic renal insuffi ciency ( 129–132 ). It is not known whether modifi cation of these risk factors reduces the risk of recurrent events.
S everal studies indicate that NSAIDs increase the risk of both incident and recurrent LGIB. A prospective study of 132 patients hospitalized with diverticular bleeding found that recurrence was 77% among patients who continued NSAID use vs. 9% in those who discontinued ( 121 ). In another study of 342 patients with LGIB (50% due to a diverticular source) with a mean follow-up of 19 months, the cumulative rebleeding rate was 17% in patients on no antiplatelet medications, 31% on monotherapy, and 47% on dual antiplatelet therapy ( 120 ). In a multivariate analysis, the rela-tive risk for NSAID use was 2.0 (95% CI, 1.2–3.3), for non-aspirin antiplatelet drugs 1.8 (95% CI, 1.0–2.3), and for low-dose aspirin 1.3 (95% CI, 0.8–2.3). Th e risk was higher in users of dual therapy than monotherapy (relative risk, 1.8; 95% CI, 1.0–3.2). On the basis of this evidence, non-aspirin NSAID use should be avoided in patients with a history of acute LGIB, particularly if secondary to a diverticular source. Although COX-2 selective agents are asso-ciated with a lower risk of UGIB than non-selective agents, their safety in LGIB is less clear as the results of studies are mixed per-haps due to the relative antiplatelet eff ect of diff erent formulations or concomitant low-dose aspirin use in some studies ( 133–135 ). Th e risk of antiplatelet-associated rebleeding events may be higher in LGIB than UGIB given the lack of prophylactic measures includ-ing proton pump inhibitor (PPI) therapy and H elicobacter pylori treatment. In a study of aspirin, clopidogrel, and PPI therapy follow-ing percutaneous coronary intervention, LGIB was more common than UGIB (74% vs. 26% of bleeds) ( 136 ). Similarly, a large retrospec-tive study of US Veterans found that the incidence of lower GI events in patients on complex antithrombotic therapy was higher than that of upper GI events (70 vs. 20/1,000 patient-years) ( 137 ). In addition, the likelihood of early and late rebleeding in the setting of aspirin is likely to vary according to bleeding etiology and adequacy and type of initial hemostasis (for early rebleeding). As noted above, long-term recurrence is common in patients with bleeding from angioectasia and diverticulosis. Th e risk of early rebleeding in the setting of anti-platelet or anticoagulant use may be higher with thermal contact hemostasis methods than with mechanical methods (clips) ( 138 ). Th e available data on resumption of aspirin in the setting of GIB are from patients with bleeding peptic ulcers. In a randomized
controlled trial of immediate resumption of low-dose aspirin plus PPI vs. placebo plus PPI aft er endoscopic control of ulcer bleed-ing, there was no signifi cant diff erence in rebleeding (10% vs. 5%). However, 60-day all-cause mortality (1% vs. 13%), as well as mor-tality secondary to cardiovascular, cerebrovascular, or gastroin-testinal complications, was signifi cantly lower in patients treated with aspirin ( 123 ). In a hospital-based cohort study, the risk of death was sixfold higher in patients with peptic ulcer bleeding who stopped aspirin vs. those who did not ( 124 ). Data from patients undergoing polypectomy suggest that the risk of bleeding is simi-lar in patients discontinuing vs. continuing aspirin ( 139 ). Th ere-fore, aspirin for secondary prophylaxis in patients with established cardiovascular disease should not be discontinued in the setting of LGIB to avoid thromboembolic events. In contrast, in patients without established cardiovascular disease and who are not at high risk for cardiovascular events, aspirin (as primary prophylaxis) has been shown to have little net benefi t (0.07% absolute risk reduction per year) ( 140 ), and should be avoided in the setting of LGIB. Th e decision to use other antiplatelet and anticoagulant medi-cations aft er an episode of LG IB requires a multidisciplinary approach that takes into consideration the risk of bleeding, as well as the risk of thromboembolic events ( 138 ). During the fi rst 30 days following coronary stenting, the risk of death and myocar-dial infarction is doubled in patients who discontinue clopidogrel ( 126 ). Th e risk associated with discontinuation is also high in the fi rst 90 days following an acute coronary syndrome. However, dis-continuation for up to 7 days in patients with more distant coro-nary stenting or coronary syndrome appears to be safe as long as aspirin therapy is continued.
C ONCLUSION
I n this guideline, we sought to evaluate and summarize the lit-erature on major issues in the management of patients with acute LGIB. In general, we found the quality of the existing evidence to be low. Th ere are only a few small, randomized trials of patients with acute LGIB, and therefore we relied heavily on case–control or cohort studies, case series, systematic reviews, or indirect evi-dence from trials of UGIB. Despite these limitations, we strongly endorse some of the recommendations because the potential ben-efi ts appear to outweigh the risk of harm. An approach to patients presenting with acute LGIB is outlined in F igure 1 . To summa-rize, patients presenting with acute severe hematochezia should undergo a focused evaluation simultaneous with hemodynamic resuscitation. An upper GI bleeding source needs to be excluded in patients with hematochezia and hemodynamic instability. Colonoscopy following a colon purge is the initial test of choice in most patients presenting with acute hematochezia. In patients with high-risk features and ongoing bleeding, colonoscopy should be performed within 24 h of presentation following a colon purge. Urgent colonoscopy (<12 h from presentations) may improve diagnostic and therapeutic yield but has not been shown to reduce rates of rebleeding or surgery. Radiographic interventions should be reserved for the small group of patients with brisk bleeding who cannot be adequately stabilized for colonoscopy. Stigmata of
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of the manuscript. She approved fi nal draft submitted. Ian M. Gralnek:
planning and conducting review, analysis/interpretation of data, and draft ing and revision of the manuscript. He approved fi nal draft submitted.
F inancial support:Th is research was supported in part by
grants from the National Institutes of Health R01 DK095964 and DK084157.
P otential competing interests: Ian M. Gralnek has served as a consultant for EndoChoice, Motus GI, and EndoAid GI View, and is a member of the Data Safety Monitoring Board for Intec Pharma. Lisa L. Strate declares no confl ict of interest.
R EFERENCES 1. C hait M M .L ower gastrointestinal bleeding in the elderly .
W orld J Gastro-intest Endosc 2010 ;2:147 –54 .2.L ongstreth G F .E pidemiology of hospitalization for acute upper gastro-intestinal hemorrhage: a population-based study . A m J Gastroenterol 1995;90:206–10.3.L ongstreth G F .E pidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study . A m J G astroenterol 1997 ;92 :419 –24 .4.S trate L L ,A yanian J Z ,K otler G et al. R isk factors for mortality in lower intestinal bleeding .C lin G astroenterol Hepatol 2008;6:1004–10.q uiz 955hemorrhage can be safely and eff ectively treated endoscopically. Th e management of antiplatelet and anticoagulant medications in patients with acute LGIB requires a multidisciplinary, individual-ized approach that balances the risk of bleeding with the risk of a thrombotic event. However, aspirin should not be discontinued when used as secondary cardiovascular prophylaxis, and dual anti-platelet therapy should not be stopped in patients within 90 days of an acute coronary syndrome or 30 days of coronary stenting.
A CKNOWLEDGMENTS Th is guideline was produced in collaboration with the Practice Parameters Committee of the American College of Gastroenterol-ogy. Th e Committee gives special thanks to Douglas G. Adler, MD, FACG, who served as guideline monitor for this document. We thank Lauren B. Gerson, MD, MSc, for assistance with the GRADE ratings and Sherry Dodson for assistance with the literature search.
C ONFLICT OF INTEREST
G uarantor of the article: Lisa L. Strate, MD, MPH. S pecifi c author contributions: Lisa L. Strate: planning and conduct-ing review, analysis/interpretation of data, and draft ing and revision
Clinical assessment, vital signs, laboratory tests
Aspirin for secondary cardiovascular prevention should not be discontinued. Aspirin for primary prevention should be avoided in LGIB. Dual antiplatelet therapy (DAPT, thienopyridine) should generally be resumed within 7 days. The exact timing of the thienopyridine resumption depends on cardiovascular risk and adequacy of bleeding control. DAPT should not be discontinued in the 90 days post acute coronary syndrome and 30 days post coronary stenting.
a See Table 3 for risk factors.
b Packed red blood cell transfusion to maintain Hgb ≥ 7 g/dl. Consider threshold of 9 g/dl in patients with significant comorbid
condition(s) (especially ischemic cardiovascular disease) or expected delay in intervention. c EGD if high suspicion, NGT if moderate suspicion of UGIB.
d Consider NGT to facilitat
e colonoscopy preparation in patients who are intolerant to oral intake and low aspiration risk.
F igure 1 . A lgorithm for the management of patients presenting with acute LGIB strati? ed by bleeding severity. CTA, computed tomographic angiography; DAPT, dual antiplatelet therapy; EGD, esophagogastroduodenoscopy; LGIB, lower gastrointestinal bleeding; NGT, nasogastric tube; PEG, polyethylene glycol; UGIB, upper gastrointestinal bleeding.
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