CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:333–343STATE OF THE ARTThe Role of Colonoscopy and Radiological Procedures...
334     STRATE AND NAUMANN                                                    CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol...
April 2010                                                                     MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDI...
336   STRATE AND NAUMANN                                                   CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8...
April 2010                                                                   MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING...
338      STRATE AND NAUMANN                                                   CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol...
April 2010                                                                     MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDI...
340     STRATE AND NAUMANN                                                      CLINICAL GASTROENTEROLOGY AND HEPATOLOGY V...
April 2010                                                                         MANAGEMENT OF ACUTE LOWER INTESTINAL BL...
342   STRATE AND NAUMANN                                                         CLINICAL GASTROENTEROLOGY AND HEPATOLOGY ...
April 2010                                                                         MANAGEMENT OF ACUTE LOWER INTESTINAL BL...
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  1. 1. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:333–343STATE OF THE ARTThe Role of Colonoscopy and Radiological Procedures in theManagement of Acute Lower Intestinal BleedingLISA L. STRATE and CHRISTOPHER R. NAUMANNDepartment of Medicine, Division of Gastroenterology, University of Washington School of Medicine, Seattle, WashingtonThis article has an accompanying continuing medical education activity on page e44. Learning Objectives—At the endof this activity, the learner should be able to understand the epidemiology of and the current management strategiesfor lower gastrointestinal bleeding. The general goals of the management of LIB are resuscita- Podcast interview: tion, diagnosis, hemostasis, and, in some cases, prevention of recurrent bleeding. The importance of these measures ulti-There are multiple strategies for evaluating and treating mately depends on the source of bleeding. Vascular sourceslower intestinal bleeding (LIB). Colonoscopy has become such as diverticular bleeding, angioectasias, and postpolypec-the preferred initial test for most patients with LIB because tomy bleeding can result in large-volume blood loss and are theof its diagnostic and therapeutic capabilities and its safety. most likely to benefit from urgent interventions and bleedingHowever, few studies have directly compared colonoscopy control. On the other hand, diagnosis and treatment of thewith other techniques and there are controversies regarding underlying condition are priorities in the management of in-the optimal timing of colonoscopy, the importance of colon flammatory sources such as ischemic colitis and bleeding neo-preparation, the prevalence of stigmata of hemorrhage, and plastic lesions. However, predicting the source and severity ofthe efficacy of endoscopic hemostasis. Angiography, radio- hemorrhage at the time of presentation is difficult. In fact, 10%nuclide scintigraphy, and multidetector computed tomog- to 20% of patients presumed to have LIB are found to haveraphy scanning are complementary modalities, but the re- bleeding from the upper-intestinal or midintestinal tract.10 Sev-quirement of active bleeding at the time of the examination eral recent efforts have been made to aid in the systematic risk assessment and triage of patients with LIB (discussed later), butlimits their routine use. In addition, angiography can result current management strategies must address a variety of pre-in serious complications. This review summarizes the avail- sentations and a broad list of potential diagnoses (Table 1).able evidence regarding colonoscopy and radiographic A number of strategies and interventions are available for thestudies in the management of acute LIB. management of LIB. These include colonoscopy, flexible sig-Keywords: Lower Gastrointestinal Bleeding; Angiography; Nu- moidoscopy, angiography, radionuclide scintigraphy or taggedclear Scintigraphy; Multirow Detector CT Scan. red blood cell scanning, and cross-sectional imaging tech- niques. Although colonoscopy has several advantages, there are a number of unresolved issues regarding its use in LIB. The lack of randomized trials and variability in study methods across theA cute lower intestinal bleeding (LIB) is a common problem in Western societies that generally requires hospitalizationand invasive testing. The annual incidence of hospitalization is literature make it difficult to draw firm conclusions regarding the efficacy of colonoscopy and other interventions for LIB. This article addresses the management of LIB with a focus onestimated to be 21 per 100,000 persons, about one third to one issues surrounding the use of colonoscopy.fifth that of upper gastrointestinal bleeding (UGIB).1,2 However,the incidence of LIB increases significantly with age (200 per100,000 by age 80 years)2 and LIB may be more common than ColonoscopyUGIB in the elderly.3 Colonoscopy is the preferred management strategy for Despite advanced age and significant comorbid disease, most most patients with LIB.11,12 A clear advantage of colonoscopypatients with LIB have favorable outcomes. In-hospital mortal- over other tests is its ability to provide both a diagnosis andity is less than 5%, and most often is caused by a comorbid hemostasis. A diagnosis is made in approximately 75% to 100%illness or nosocomial complication rather than uncontrolledhemorrhage.2,4 Indeed, the majority of patients (at least 75%) Abbreviations used in this paper: CT, computed tomography; LIB,with LIB will stop bleeding spontaneously.5– 8 Nonetheless, the lower intestinal bleeding; MDCT, multidetector row computed tomog-costs of managing LIB are substantial because of the need for raphy; UGIB, upper gastrointestinal bleeding.hospitalization and invasive procedures. The estimated cost of © 2010 by the AGA Institutediverticular bleeding alone, the most common source of LIB, 1542-3565/10/$36.00was $1.3 billion dollars in the United States in 2001.9 doi:10.1016/j.cgh.2009.12.017
  2. 2. 334 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4Table 1. Sources of Lower Intestinal Hemorrhage Source Frequency Endoscopic treatment Painless hematocheziaa Other commentsDiverticulosis 30%–65% Yes Yes Large volume, intermittent bleedingAngiodysplasia 4%–15% Yes Yes Occult blood loss more common than acuteHemorrhoids 4%–12% Yes Yes Can result in significant hemorrhageIschemic colitis 4%–11% No No Mild bleeding with diarrheaColitis, other 3%–15% Sometimesb No Mild bleeding with diarrheaNeoplasia 2%–11% Sometimes YesPostpolypectomy 2%–7% Yes Yes Can be delayed 3–4 weeksRectal ulcer 0%–8% Yes Yes Anticoagulants and poor functional status are associated with bleeding118Dieulafoy lesion Rare Yes Yes Usually located in the rectumRectal varices Rare Sometimesc Yes Usually stigmata of chronic liver diseaseNOTE. Data from references.2,8,10,14,15,36,117a The abdominal examination can help differentiate inflammatory disorders such as ischemic colitis, which present with tenderness but generallyresult in mild blood loss from vascular disorders such as diverticula, which produce no tenderness but significant blood loss (hence thedistinction painless hematochezia).36bRadiation proctopathy is amenable to endoscopic therapy. Ulcers with stigmata of hemorrhage also can be treated.cBanding or sclerotherapy for rectal varices is possible but transjugular intrahepatic portosystemic shunt procedures more commonly arerecommended.of patients depending on the definition of the bleeding source, in patients undergoing colonoscopy within 12 hours of ad-patient selection criteria, and timing of colonoscopy (Table mission (1 of 171 colonoscopies).14,15 Although polyethylene2).8,13–17 The diagnostic yield of colonoscopy is higher than glycol bowel preparation is a balanced salt solution, fluidradiographic tests, which require active bleeding at the time of overload, congestive heart failure, and electrolyte abnormal-the examination, and flexible sigmoidoscopy, which visualizes ities have been reported in patients with underlying comor-only the left colon.7,17 In published series, endoscopic therapy is bidites.10,20 Aspiration pneumonia is a potential risk withapplied in 10% to 40% of patients undergoing colonoscopy for rapid, high-volume purges, particularly in patients with al-LIB and immediate hemostasis is achieved in 50% to 100% of tered mental status. Bowel preparation is not believed tothese cases.8,10,13–15,18 dislodge clots or precipitate bleeding. Colonoscopy with endoscopic therapy for LIB appears to be More controversy exists regarding whether colonoscopysafe. In a 1998 review of 13 studies (1561 patients), the overall improves major clinical outcomes in LIB. Jensen et al15 com-complication rate was 1.3%.19 These complications included pared 2 sequential prospective cohorts of patients with se-bowel perforation (5 patients), congestive heart failure (4 vere diverticular hemorrhage who underwent colonoscopypatients), worsened bleeding (2 patients), and septicemia (1 within 6 to 12 hours of admission after aggressive bowelpatient). Of the perforations, 2 were noted to be secondary to preparation. Rebleeding (0% vs 53%; P .005) and surgeryendoscopic therapy (1 neodymium:yttrium-aluminum-garnet (0% vs 35%; P .03) were significantly less common in[Nd-Yag] laser and 1 polypectomy). In 4 more recent studies patients undergoing urgent colonoscopy with endoscopicof colonoscopy after colon purge for all sources of LIB, there therapy compared with urgent colonoscopy without therapy,were 2 complications out of 664 patients (0.3%) (Table respectively. As in peptic ulcer disease, stigmata of recent2).8,14 –16 Both complications were perforations, one after hemorrhage were predictive of rebleeding, with active bleed-biopsy of a cecal ulcer and one after biopolar electrocautery ing having the highest risk (67%) followed by nonbleedingof a cecal angiodysplasia.8,14 The complication rate was 0.6% visible vessels (50%) and adherent clots (43%). No complica-Table 2. Colonoscopy in Lower Intestinal Bleeding Diagnosis, Definitive diagnosis, Endoscopic therapy, Complications, Study Patients, n Mean timing, h n (%) n (%) n (%) n (%)Jensen et al,15 2000 121 12 121 (100) 107 (88)a 10 (37)b 0Angtuaco et al,13 2001 39 24 29 (74) 3 (8) 3 (8) —Schmulewitz et al,8 2003 415 46 369 (89) — 42 (10) 1 (0.2)Smoot et al,16 2003c 78 18 78 (100) 38 (49) 7(9) 0Strate and Syngal,17 2003 144 25d 128 (89) 62 (43) 14 (10) —Green et al,14 2005 50 7 48 (96) 21 (42) 17 (34) 1 (2)Total 847 773 (91) 231 (53) 93 (12) 2 (0.3)NOTE. Studies since 2000 of colonoscopy after colon purge in LIB were included.a Fourteen patients had upper (9) or small bowel (5) sites.bTherapy only reported for 27 patients with diverticular bleeding.cDiverticular bleeding only.dMedian time of colonoscopy.
  3. 3. April 2010 MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING 335Table 3. Endoscopic Treatment of Diverticular Bleeding Endoscopic treatment modality Patients, n Early rebleeding, n (%) Late rebleeding, n (%) Complications, n (%)Banding45 4 0 0 0Thermal contact15,21,47,48,58 17 2 (12) 0 0Epinephrine16,21,46,50–53,56 20 3 (15) 1 (5) 0Thermal contact plus injection14–16,21,55 25 6 (24) 4 (16) 0Endoclip16,41,42,49,54,57,59 71 0 12 (17) 0Total 137 11 (8) 17 (12) 0tions were reported. This study highlights the promise of patients.23 Traditionally, colonoscopy has been performed elec-colonoscopy, particularly when performed early in the course tively after bleeding has stopped owing to fear of increasedof severe diverticular bleeding. However, it also raises a complications, need for colon preparation, and lack of provennumber of issues, including whether the results can be gen- benefit. Recent studies have suggested that performing colonos-eralized to practices without experienced bleeding teams and copy shortly after presentation is advantageous, but studiesto other sources of bleeding. The use of historical controls comparing this approach with delayed colonoscopy are lim-also may have influenced the results. Other reports of endo- ited.8,14,15,17scopic therapy for diverticular bleeding have been inconsis- The primary indication to perform early colonoscopy, astent. Early rebleeding has been reported in 0% to 38% of with UGIB, is to identify and treat bleeding sources. The avail-patients, and late rebleeding has been reported in 0% to able evidence suggests that earlier colonoscopy results in more18%.14,21 In reviewing the 137 cases of endoscopic therapy for definitive diagnoses and therefore more opportunities for ther-diverticular bleeding reported in the literature, early rebleed- apeutic intervention.10,14,15,24 Urgent colonoscopy generally re-ing occurred in 8% and late rebleeding in 12% (Table 3). fers to colonoscopy performed within 12 hours of admis- In 2005, Green et al14 published the first randomized con- sion,14,15 but other studies have achieved good results using atrolled trial in LIB. In this study, 100 patients with severe LIB more lenient time window of 24 hours.24 In a retrospectivewere randomized to colonoscopy within 8 hours or to standard study, earlier colonoscopy, analyzed as a continuous variable,of care, which included elective colonoscopy in all patients and was associated with significantly more diagnostic and therapeu-tagged red blood cell scan followed by angiography if positive in tic interventions.17 Endoscopic therapy was used successfully inpatients with ongoing bleeding (36 patients). A definitive source 29% of colonoscopies performed within 12 hours of admission,of bleeding was identified significantly more often in the urgent 13% of those performed in 12 to 24 hours, 4% in 24 to 48 hours,colonoscopy arm (42% vs 22%; odds ratio, 2.6; P .03). There and 0% in colonoscopies performed after 48 hours.17 However,were no statistical differences in rebleeding (22% vs 30%), sur- this was an unadjusted analysis and patients most likely to havegery (14% vs 12%), mortality (2% vs 4%), blood transfusions (4.2 stigmata may have been selected preferentially for early exami-vs 5.0 units), and length of stay (5.8 vs 6.6 days) between the nations. Indeed, most studies of urgent colonoscopy have en-colonoscopy and standard-of-care arms, respectively, including rolled only patients with significant hemorrhage,14,15 and aa subanalysis of patients receiving interventions. However, there specific time interval is probably less important than the pres-was a general trend in favor of colonoscopy. Importantly, this ence of significant or ongoing hemorrhage. In one study, thestudy, similar to most dealing with LIB, was underpowered to yield of colonoscopy increased from 20% to 85% when per-detect a clinically important and statistically significant differ- formed during active bleeding versus electively.25 Other studiesence in major outcomes and therefore cannot be used to con- have shown a high yield when repeat colonoscopy is performedclude the equivalence of these interventions. In addition, it has promptly for recurrent bleeding.26 It is noteworthy that in thebeen criticized for insufficient colon preparations (64% were fair randomized trial by Green et al,14 no stigmata of hemorrhageto poor),22 did not use current state-of-the-art endoscopic or were found in patients undergoing elective colonoscopy after aangiographic therapy, and was published 10 years after com- positive tagged red blood cell scan (the average time to colonos-pletion of the study. copy in this group was 38 hours). Large-scale, multicenter, randomized trials ultimately are Prompt colonoscopy also offers an opportunity to identifyneeded to determine the best strategy for patients with LIB. In low-risk patients and, therefore, to reduce the need for hospi-the meantime, the existing, albeit imperfect, literature can be talization and costs of care. Several studies have found thatused to address a number of important issues regarding time to colonoscopy is a strong predictor of length of stay aftercolonoscopy in LIB, including the relative importance of timing adjustment for other factors including comorbid illness.8,17of intervention versus colonic preparation, the prevalence of Overall, this appears to be the result of early diagnosis inhigh-risk stigmata, the optimal endoscopic treatment modality, low-risk patients rather than therapeutic interventions.17and the overall impact of endoscopic hemostasis in the colon. Length of hospital stay is a major determinant of costs in gastrointestinal bleeding and, therefore, earlier colonoscopy Timing of Colonoscopy likely translates into decreased costs of care.7,27 In a retrospec- Early endoscopy is the standard of care in UGIB, al- tive, informal cost analysis, urgent colonoscopy was associatedthough the optimal time frame has yet to be defined. Early with an average savings of $10,065 per patient compared withintervention allows identification and treatment of bleeding emergency angiography and elective colonoscopy.28 However,sources, reduces the need for blood transfusion and length of this large savings likely reflects other trends in care includinghospital stay, and facilitates the triage of high- and low-risk length of hospital stay and the use of surgery.
  4. 4. 336 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4 Taken together, the evidence suggests that colonoscopy mata of recent hemorrhage are seen on average in 17% ofshould be performed within 12 to 24 hours in most patients patients.34 Studies of all sources of LIB report stigmata in 8%with LIB—a goal that usually accommodates colon preparation to 35% of patients.13,14,17 However, yields at the upper end ofand the availability of the endoscopy suite. In patients with this range reflect highly selected patients who are recruitedsigns of severe bleeding, colonoscopy close to the time of over a long period.15 The timing of colonoscopy, quality ofbleeding after a rapid bowel preparation is likely to have the colon preparation, selection of patients with severe or ongo-highest yield. However, as in UGIB, an optimal time threshold ing bleeding, and experience and diligence of the endoscopisthas not been determined, and it is unclear how faster timing are factors that impact the yield of colonoscopy in LIB.affects major clinical outcomes such as rebleeding and mortal- Risk-stratification tools that aid in the selection of patientsity. who are most likely to have stigmata of hemorrhage and to benefit from urgent interventions are also likely to improve Colon Preparation the utility of urgent colonoscopy. Adequate colon preparation is an important compo-nent of colonoscopy for LIB. Early studies of unprepped Risk Stratificationcolonoscopy for LIB report low completion rates between 55% One of the major difficulties in the management of LIBand 70%.29 –31 In addition, blood and stool in the colon may is predicting the likelihood of severe bleeding and the need forincrease the risk of perforation and impair the identification of hemorrhage control based on the initial clinical presentation.stigmata of hemorrhage. In the study of urgent colonoscopy by Risk stratification is particularly important in LIB because di-Jensen et al,15 procedures were performed within 1 hour of stool agnostic and therapeutic interventions are time- and resource-clearing after 5 to 6 liters of polyethylene glycol were given over intensive and often entail risk and inconvenience (ie, bowel3 to 4 hours, often via nasogastric tube. This meticulous atten- preparation) for the patient. Furthermore, 75% of patients willtion to preparation likely contributed to the exemplary results, stop bleeding spontaneously and are unlikely to benefit fromand, in general, shortening the time to colonoscopy should not aggressive interventions. In UGIB, there have been dozens ofcome at the expense of the bowel preparation. Ideally, colonos- attempts to predict the risk of poor outcome and the need forcopy is performed within 1 to 2 hours of stool clearing. The use endoscopic interventions.5 The systematic application of suchof promotility agents, such as metoclopramide, may facilitate tools can reduce resource use, mainly through early discharge,the preparation and prevent nausea, but this has not been without deleterious effects on other clinical outcomes.35studied formally.28 Aspiration precautions should be followed Recently, 3 risk-stratification tools have been developed spe-during rapid colon cleansing. Water jet or syringe irrigation cifically for LIB.5,36 –38 Hemodynamic instability, ongoing hema-should be used to clear remaining blood and stool and a tochezia, and comorbid illness consistently have been associ-large-channel therapeutic colonoscope can be helpful. Addi- ated with poor outcome, and parallel findings in UGIB. Studiestional preparation may not be necessary for recurrent bleeding also have shown that patients who bleed while hospitalized foronce the colon has been cleansed because active bleeding in this another process have a particularly poor prognosis.2,39 Otherinstance may improve localization.32 A successful rapid colon risk factors identified in one or more studies are listed in Tablepreparation requires coordination of the medical, nursing, and 4. Strate et al36,37 developed and validated a simple predictionpharmacy staff and the cooperation of the patient. rule for severe bleeding based on 7 independent risk factors Flexible sigmoidoscopy and anoscopy can be performed early (tachycardia, hypotension, syncope, a nontender abdomen, rec-in the evaluation of LIB to evaluate and treat left-sided or tal bleeding within 4 hours of presentation to the hospital,anorectal lesions without the need for a full colon preparation. aspirin use, and 2 major comorbid conditions). The numberThis may be of particular use in patients with a high likelihood of risk factors predicted the risk of severe or recurrent hemor-of a distal source. However, the yield of this approach in the rhage as well as the need for blood transfusions, surgery, andliterature has been quite low ( 10%),7,25,33 and most patients death.37 Patients with 4 or more risk factors (17% of patients)ultimately will require a full colonoscopy to exclude proximal were in the highest risk group (80% chance of severe or ongoingpathology. Stigmata of Recent Hemorrhage Table 4. Risk Factors for Poor Outcome in Lower Intestinal Bleeding The main indication for performing urgent interven-tions and meticulous colon preparations is to identify and treat Hemodynamic instability5,36–38stigmata of recent hemorrhage or active bleeding. However, the Hypotension, tachycardia, orthostasis, syncope Ongoing bleeding5,36–38identification of stigmata in the colon is difficult. The large Blood on rectal examination, hematochezia, rectal bleeding withinsurface area of the colon, residual stool and blood, intermittent 4 hours of presentationbleeding, and multiple potential lesions (eg, diverticulosis) are Age5complicating factors. In addition, only about half of LIB is from Comorbid illness5,36,37endoscopically treatable sources, such as diverticulosis and an- Secondary bleeding (bleeding while hospitalized for another process)2,39giodysplasia (Table 1).2,8,17 Other sources, including ischemic Anticoagulation or antiplatelet medication5,36,37colitis and inflammatory bowel disease, tend to result in diffuse History of diverticular disease or angiodysplasia5injury. Furthermore, more than one third of patients will have Nursing home resident5more than one potential source such as diverticulosis and Nontender abdominal examination5,36,37hemorrhoids.24 Anemia (hematocrit 35%)38 Abnormal creatinine level5 The incidence of stigmata of recent hemorrhage in LIB is Abnormal white blood cell count5unknown. In prospective trials of peptic ulcer disease, stig-
  5. 5. April 2010 MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING 337bleeding) and would be the most appropriate targets for urgent moderate pressure.14,15 This technique appears to be safe (oneinterventions. Patients with 1 to 3 risk factors (designated as cecal perforation reported in the recent literature),14 but shouldmoderate risk) had a 43% chance of severe or recurrent bleeding be used cautiously in the right colon, in the dome of diverticula,and also may warrant urgent interventions. However, the ability and in the presence of mucosal defects. In experimental canineof the rule to aid in risk stratification is limited by the fact that models, electrocoagulation was safe for mucosal lesions even atthe moderate-risk group comprised 78% of the population. high settings, but not for ulcers in which colon thickness wasVelayos et al38 identified hematocrit less than 35%, abnormal compromised.43 In the presence of active bleeding, epinephrinevital signs after 1 hour, and gross blood on initial rectal exam- (dilution, 1:10,000 or 1:20,000) can be injected in 1- to 2-mLination as independent predictors of ongoing or recurrent aliquots in 4 quadrants around the lesion. Injection not onlybleeding. Ongoing or recurrent bleeding occurred in 79% of helps to clear the field of active bleeding, but it also can be usedpatients with 3 risk factors, 54% of patients with 2 risk factors, to better expose stigmata from within a diverticulum (con-17% of patients with 1 risk factor, and 0% in patients with no versely injection distal to a lesion can hamper access).32 Argonrisk factors. Fifty-two percent of patients had 2 or 3 risk factors plasma coagulation is particularly useful for diffuse lesionsand these patients are reasonable candidates for urgent inter- such as radiation proctopathy and large or multiple angiodys-ventions. Das et al5 developed and validated an artificial neural plasia.44 Band ligation also has been used in diverticular hem-network to predict the risk of death, rebleeding, and need for orrhage and for other focal lesions.45intervention. This tool was highly accurate in predicting these In reviewing the 137 cases in the literature (including ab-outcomes, particularly in the external validation group (97%, stract form) of endoscopic treatment of diverticular bleeding,93%, and 94%, respectively). In addition, the negative predictive hemostasis was achieved in 92% of all cases and no complica-values for these outcomes were greater than 98% in the internal tions were reported (Table 3).14 –16,21,26,41,42,46 –59 Four patientsand external validation cohorts, suggesting that this artificial were treated successfully with endoscopic band ligation. Of 20neural network could be used to triage low-risk patients to cases treated with epinephrine injection alone, 15% experiencedoutpatient management. Overall, the artificial neural network early rebleeding. Forty-two patients received thermal contactmodels appear to outperform prediction rules developed using therapy plus/minus epinephrine injection for active bleeding.standard logistic regression techniques. The requirements for The early rebleeding rate in this group was 19% and was highlyspecific software and data entry currently limit their clinical influenced by one study of 13 patients in which 5 (38%) expe-application, but, with the widespread use of computerized med- rienced rebleeding.21 A total of 71 cases treated with endoscopicical records, neural networks are likely to become more clini- clipping have been reported with 100% success, suggesting thatcally applicable. Further studies are needed to determine pro- this is a very effective modality for diverticular bleeding. Latespectively the impact of prediction rules on clinical outcomes recurrent bleeding has been reported in 25% of all patients withand to validate the results in larger diverse settings. Perhaps the diverticular hemorrhage after 4 years of follow-up.2 Late recur-bigger task will be the routine application of risk stratification rent bleeding occurred in 17 of the reported 137 patients (12%)in clinical practice, something that has proven difficult even in treated endoscopically for diverticular bleeding. However, recur-UGIB.40 rent bleeding is often a delayed phenomenon49 and patient follow-up varied substantially in these studies. It is also unclear Endoscopic Hemostasis Techniques how the treatment of one diverticulum affects recurrent bleed- ing given the presence of many diverticula in the colon. Although endoscopic hemostasis in the colon appearsto be effective, the optimal technique has not been delineated.The armamentarium for endoscopic hemostasis in the colon Radiologic Management Optionsparallels that of UGIB and includes injection therapy (eg, epi-nephrine or saline), thermal contact (heater probe, bipolar elec- There are a number of radiographic strategies used introcoagulation, or monopolar electrocoagulation), argon plasma the management of severe LIB including angiography, radionu-coagulation, endoscopic clipping devices, and band ligation. In clide scintigraphy (tagged red blood cell scanning), and com-contrast to UGIB, in which numerous trials (albeit many rela- puted tomography. These tests typically are reserved for pa-tively small) and meta-analyses have investigated endoscopic tients with very brisk bleeding who cannot be stabilized forhemostasis techniques, data in LIB are based largely on small colonoscopy or for ongoing bleeding of obscure etiology. Theynonrandomized trials or retrospective case series. In addition, it can be particularly useful in brisk bleeding because there is nois difficult to compare the efficacy of endoscopic treatment for need for bowel preparation. Radiographic modalities are ofdifferent bleeding sources because of differences in the need for limited use in more routine scenarios because they requireendoscopic therapy and in the natural history of bleeding. In active bleeding at the time of examination for diagnosis andgeneral, the type and location of the lesion, experience of the treatment. Similar to the literature for colonoscopy, studiesendoscopist, and presence of coagulation defects should evaluating radiographic modalities for the management of LIBguide the therapeutic modality. A second technique can be often are limited by small sample sizes, variable inclusion cri-tried if the first attempt fails. teria, and a paucity of prospective randomized trials. In addi- Endoscopic clipping is touted as a safer alternative to ther- tion, there are very few head-to-head comparisons with colonos-mal contact methods.26,41,42 Endoclips can be applied directly to copy. The performance of these modalities continues tothe stigmata, to feeder vessels, or used to oppose the sides of improve as technologic advances are made.small diverticula or postpolypectomy defects.26,32 Care must betaken not to traumatize or partially clip a vessel. Electrocautery Angiographyin the colon should be performed using moderately low power Angiography is the only radiographic modality that cansettings (10 –15 W) in 1- to 3-second bursts with light to be both diagnostic and therapeutic. Bleeding rates of at least 0.5
  6. 6. 338 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4to 1 cc per minute can be detected with angiography.60 Success- success and fewer complications, most notably bowel infarc-ful localization of bleeding is highly dependent on the rate of tion. Embolization is feasible in approximately 82% of patientsbleeding at the time of the examination.61,62 A systolic blood with positive angiograms in the setting of LIB.70 Failure topressure 90 mm Hg and a requirement of at least 5 units of achieve superselective positioning is most commonly the resultpacked red blood cells within a 24-hour period have been of vasospasm, tortuosity, or stenosis.71 In a review of 20 studiesshown to predict a positive angiography.63 Angiography was using current superselective techniques, immediate hemostasispositive in approximately 85% of patients with both of these was achieved in 96% of patients and rebleeding within 30 dayscriteria compared with 15% in more stable patients. Overall, occurred in 22% (Table 5).72–90 Studies suggest that diverticularpositive examinations are reported in 25% to 70% of cases in the bleeding may be more amenable to embolization therapy thanliterature.25,61,64 – 66 This wide range is likely a reflection of non- other sources of bleeding, such as angiodysplasia.62,63 In a meta-standardized patient selection and angiographic technique. analysis of embolization as first-line therapy for LIB, emboliza- Provocative angiography with vasodilators, anticoagulants, tion successfully controlled diverticular bleeding in 85% at 30and thrombolytic agents has been studied as a means of in- days versus 50% in nondiverticular bleeding (P .01).91 Nocreasing the sensitivity of angiography. Studies using provoca- study has shown the superiority of any one of the 3 agents usedtive techniques in patients with obscure bleeding report an for embolization—microcoils, polyvinyl alcohol particles, andoverall yield of about 30% with few complications.67– 69 How- gelfoam. However, polyvinyl alcohol particles can be injectedever, the number of reported cases is small and the risk ofserious complications is high. Therefore, technical expertise and upstream of a bleeding site when superselective positioning iscareful patient selection are required to achieve good results not possible. Gelfoam allows for recanalization over days toand minimize complications. weeks, but rarely is used. Historically, angiographic intervention for LIB involved the The potential for serious complications is a major limitationinfusion of vasoconstrictors, such as vasopressin. This tech- to the use of angiography in LIB, particularly in the elderly andnique often was used to stabilize a patient before surgical in patients with comorbid illness. In reviewing the 338 patientsresection of the culprit segment rather than as a definitive undergoing superselective embolization for LIB, minor compli-intervention because rebleeding occurred in up to 50% and cations were seen in 26% and major complications were seen inserious complications developed in 10% to 20%.61,62 Techno- 17% (Table 5). The most common major complication waslogic advances in coaxial microcatheters and embolic materials bowel infarction. Other complications include contrast allergieshave enabled the embolization of specific distal arterial and nephrotoxicity, hematomas, thromboses, and vascular dis-branches. Superselective embolization has resulted in increased sections.72–90Table 5. Angiography With Embolization in Acute Lower Intestinal Bleeding Immediate Patients/patients hemostasis,a Early rebleeding,b Minor complications,c Major complications,d Study embolized, n n (%) n (%) n (%) n (%)Guy et al, 199282 9/9 9 (100) 3 (33) 3 (33) 3 (33)Gordon et al, 199781 17/14 13 (93) 2 (15) 4 (31) 2 (15)Lederman et al, 199885 7/7 6 (86) 1 (17) 1 (17) 0 (0)Nicholson et al, 1998119 38/13 12 (92) 2 (17) 4 (33) 1 (8)Bulakbasi et al, 199973 10/9 9 (100) 3 (33) 7 (78) 0 (0)Evangelista and Hallisey, 200078 17/17 15 (88) 2 (13) 3 (20) 1 (7)Luchtefeld et al, 200086 48/16 13 (81) 1 (8) 6 (46) 1 (8)Bandi et al, 200172 48/35 33 (94) 11 (33) 9 (27) 8 (24)Funaki et al, 200179 27/25 25 (100) 3 (1) 3 (12) 3 (12)Defreyne et al, 200176 11/11 11 (100) 1 (9) 0 (0) 1 (9)Patel et al, 200188 10/10 10 (100) 2 (20) 1 (10) 1 (10)DeBarros et al, 200275 27/27 27 (100) 6 (22) 2 (7) 6 (22)Kuo et al, 200384 22/22 22 (100) 3 (14) 4 (18) 0 (0)Gady et al, 200380 10/10 10 (100) 3 (30) 0 (0) 4 (40)Burgess and Evans, 200474 15/15 14 (93) 8 (57) 10 (71) 6 (43)Waugh et al, 200490 33/27 26 (96) 6 (23) 7 (27) 3 (12)Neuman et al, 200587 23/23 23 (100) 5 (22) 11 (48) 3 (13)Silver et al, 200589 77/11 10 (91) 1 (10) 2 (20) 6 (60)d’Othee et al, 200677 19/17 17 (100) 5 (29) 6 (35) 4 (24)Kickuth et al, 200883 71/20 20 (100) 2 (10) 2 (10) 2 (10)Total 539/338 325 (96) 70 (22) 85 (26) 55 (17)a Immediate hemostasis calculations were limited to those patients who were embolized.bEarlyrebleeding was defined as bleeding within 30 days of initial embolization. Calculations were limited to patients who were embolized andachieved hemostasis.cMinor complications did not require surgery or result in death among those embolized with immediate hemostasis; late rebleeds were excludedbecause a majority were unrelated to the index procedure.dMajor complications required surgery or resulted in death among those embolized with immediate hemostasis.
  7. 7. April 2010 MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING 339 Studies comparing colonoscopy and angiography in the Table 6. Nuclear Scintigraphy in Lower Intestinal Bleedingmanagement of LIB are limited. As mentioned earlier, there has Total Positive Localization Accuracy ofbeen only one randomized controlled trial comparing colonos- scans, scans, confirmed,a positive scans,copy with tagged red blood cell scan followed by angiography if Study n n (%) n (%) n (%)positive.14 This trial found colonoscopy to be a superior diag-nostic test, but was underpowered for other major outcomes. In Zink et al, 200899 41 19 (46) 17 (89) 6 (35)a prospective study, 22 patients with severe hematochezia un- Czymek et al, 20 8 (40) 8 (100) 8 (100)derwent both angiography and panendoscopy.10 Ultimately, 17 200894were found to have colonic sources. Only 14% had a definitive Lee et al, 200896 22 9 (41) 4 (44) 3 (75)diagnosis made by angiography compared with 86% with pan- Brunnler et al, 92 67 (73) 30 (45) 20 (67) 200893endoscopy. Endoscopic therapy was used in 39% compared with Olds et al, 127 49 (39) 42 (86) 23 (55)1% with angiography. Complications occurred in 9% of angiog- 200598raphies compared with 4% of colonoscopies. Other retrospective Levy et al, 200397 40 28 (70) 28 (100) 18 (64)studies have found colonoscopy to have a better diagnostic and Gutierrez et al, 105 42 (40) 23 (55) 22 (96)therapeutic yield than angiography.7,25,92 In all of these studies, 199895angiography relied on vasopressin infusion, not embolization. Total 447 222 (50) 152 (68) 100 (66)It is important to note that most patients who undergo angiog- NOTE. Table includes studies since 1998.raphy will require elective colonoscopy to confirm the bleeding a Scanlocalization confirmed by endoscopy, angiography, or surgery.source and exclude neoplasia. In practice, angiography probably is used more often thancolonoscopy for patients with severe bleeding. In one retrospec- examinations decreased (9.6% to 3.6%) and the confidence oftive, single-center study, patients with hemodynamic instability reported findings improved.102were more likely to undergo angiography, whereas logistical Despite its sensitivity for bleeding and safety, the role offactors (time of day and day of week) and postpolypectomy radionuclide scintigraphy in LIB remains controversial. Therebleeding were predictive of urgent colonoscopy.92 The fact that have been no randomized trials of angiography with and with-angiography can be performed without a bowel preparation is out radionuclide scanning. Some studies show an increase inlikely to factor significantly into management decisions. How- the diagnostic yield of angiography when performed after aever, in this study, the median times from admission to early positive scan (22% to 53% in one study)103; whereas other stud-initial procedure were similar in patients undergoing angiogra- ies have found no difference.62,104,105 Likewise, the ability ofphy (14 hours) versus colonoscopy (17 hours),92 drawing atten- nuclide scanning to accurately localize bleeding before surgicaltion to the fact that angiography, especially when preceded by resection is debatable.105–107 A significant disadvantage of radio-a nuclear medicine scan, also may take time to orchestrate. In nuclide scintigraphy is the lack of therapeutic possibilities. Thethe absence of data from large randomized trials, the choice of delay between a positive scan and subsequent angiography orintervention in patients with massive bleeding generally is colonoscopy may decrease therapeutic opportunities owing toguided by institutional expertise. However, in patients who can the intermittent nature of LIB. Therefore, if radionuclide scin-be stabilized for bowel preparation, colonoscopy appears to be tigraphy is to be used in LIB, care should be coordinated so thatthe most efficient and safest strategy. a positive scan is followed closely by angiography. Radionuclide Scintigraphy Computed Tomography Radionuclide scintigraphy, or tagged red blood cell Until recently, computed tomography (CT) scanningscanning, often is used as a screening test before angiography has been of limited use in the evaluation of gastrointestinalbecause it is noninvasive and more sensitive (bleeding at a rate of bleeding. However, with the introduction of multidetector row0.05– 0.1 cc per minute can be detected).64 It also can be repeated CT (MDCT), it is being investigated as a potential diagnosticin the setting of intermittent bleeding. However, the ability of tool. MDCT markedly decreases scan time, which enables theradionuclide scanning to localize the bleeding source correctly accurate acquisition of arterial images, which can show contrastvaries widely in the literature in part because of differences in extravasation into any portion of the gastrointestinal tract.108the criteria used for confirming the source and for patient Bleeding rates as low as 0.3 to 0.5 cc per minute have beenselection. In reviewing the 7 most recent studies of radionuclide detected in a swine model.109 Overall, in the 124 patients re-scanning for LIB (447 patients) in which radionuclide scintig- ported in the literature, the average yield of MDCT for LIB israphy findings were confirmed by a different test, the accuracy 60%, with yields ranging from 25% to 95% (Table 7).93–99 Theof a positive test was 66% (Table 6).93–99 Localization appears to yield of MDCT is highest among patients with severe ongoingimprove when scans are positive within 2 hours of injection LIB.99,110 –114 General advantages of CT scanning include its(95%–100%) as opposed to later (55%– 65%).100 This likely re- wide availability and the added diagnostic yield of cross-sec-flects the tendency of blood to spread both antegrade and tional imaging. The primary disadvantage of CT scanning, asretrograde in the colon. Subtraction scintigraphy also may with radionuclide scintigraphy, is its inability to deliver therapy.improve the accuracy of radionuclide scintigraphy. With this Other disadvantages include exposure to radiation, limited abil-technique, the initial frame is subtracted from subsequent im- ity to perform repeat scans, false-positive results generated fromages, theoretically improving visualization of the radionuclide metallic objects or sutures, contrast allergies, and potentiallabel by removing superimposed background structures.101,102 nephrotoxicity with intravenous contrast, particularly if CT isIn a retrospective study of 49 scans processed using both con- followed by angiography.108 Overall, 2 complications have beenventional and subtraction scintigraphy, the rate of false-positive reported in the literature.114 Both of these patients had pre-
  8. 8. 340 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4Table 7. MDCT in Lower Intestinal Bleeding Total scans, Positive scans, Bleeding site confirmed,a Correct localization,b Complications, Study n n (%) n (%) n (%) n (%)Jaeckle et al, 2008111 17 16 (94) 16 (100) 16 (100) 0Zink et al, 200899 41 10 (24) 5 (50) 5 (100) 0Scheffel et al, 2007112 8 5 (63) 5 (100) 5 (100) 0Yoon et al, 2006114 19 16 (84) 16 (100) 16 (100) 2 (11)Sabharwal et al, 2005120 7 5 (71) 2 (40) 2 (100) 0Tew et al, 2004113 13 7 (54) 7 (100) 7 (100) 0Ernst et al, 2003110 19 15 (79) 15 (100) 15 (100) 0Total 124 74 (60) 61 (82) 66 (100) 2 (2)a Confirmation of bleeding site by angiography, endoscopy, and/or surgery.bOf those patients who had confirmation of the bleeding site.existing renal insufficiency secondary to diabetic nephropathy orrhage, but there are few data to guide this practice.6 Decision-and experienced contrast-induced nephrotoxicity requiring he- analysis models using population-based data call into questionmodialysis after MDCT followed by angiography. the practice of surgical resection after 2 episodes of diverticu- A recent study prospectively evaluated MDCT followed by litis.116 Complications of surgery for LIB are reported in asangiography in 26 consecutive patients presenting with acute many as 60% of patients,94 and the mortality rate is as high asmassive gastrointestinal bleeding.114 MDCT detected the extrav- 10%.115 Localization of the bleeding source before surgery isasation of contrast into the intestinal lumen in 16 of the 19 important to prevent the excess morbidity and mortality re-patients with lower GI sources. Bleeding was confirmed in all 16 ported with blind subtotal colectomy and also to prevent re-cases by angiography (100%). When both upper and lower section of the incorrect segment of bowel.6sources were included, MDCT had a sensitivity of 91% and aspecificity of 99%. There were 2 false-negative examinations and Conclusions1 false-positive examination. Localization of the site of bleedingwas accurate in 100% of cases. As noted earlier, contrast-in- Colonoscopy is the preferred intervention for most pa-duced nephropathy was noted in 2 patients who had baseline tients with LIB owing to its high diagnostic yield, varied ther-increases in creatinine level. It is not clear whether MDCT has apeutic capabilities, and low complication rate. Based on thean impact on rebleeding rates, need for surgical intervention, or available literature, it appears that colonoscopy shortly aftermortality. Another study compared MDCT with radionuclide presentation can increase the identification and treatment ofscintigraphy in 41 patients with LIB.99 MDCT identified 10 stigmata of hemorrhage and potentially reduce early rebleeding.cases (25%) of active bleeding and radionuclide scintigraphy However, the identification of stigmata is probably as much aidentified 19 (46%). The yield of nuclear scintigraphy was higher function of ongoing or severe bleeding and meticulous colonbecause the test could be repeated in the event of intermittent preparation as it is the timing of the examination. Promptbleeding. There were discordant results in 13 cases—11 negative colonoscopy in all patients with LIB, regardless of endoscopicMDCT but positive scintigraphy and 2 positive MDCT but intervention, is likely to decrease hospital length of stay andnegative scintigraphy. Both techniques accurately identified the therefore the cost of care. The need for colon preparation, thelocation of bleeding although MDCT provided more detail and difficulty in performing prompt colonoscopy, and the relativeancillary findings. Although the data are encouraging, addi- infrequency of stigmata of hemorrhage in the colon are deter-tional studies are needed with larger sample sizes and stronger rents to the use of urgent colonoscopy in routine practice.end points to determine the appropriate role for MDCT in the Risk-stratification tools that target high-risk patients as well asmanagement of LIB. system-based interventions that address logistical issues prom- ise to improve the utility of urgent interventions. Radiographic modalities, particularly angiography, play a complementary role Surgery in patients with massive bleeding who cannot be stabilized for Surgery generally is reserved for patients with life- colon preparation or who have eluded endoscopic diagnosisthreatening hemorrhage who have failed other management and/or treatment. While we await more definitive trials, it isoptions. Farrell and Friedman115 summarize the following in- reasonable to aim for colonoscopy within 12 to 24 hours ofdications for emergency surgery for severe LIB: hypotension and admission in most patients with LIB. With a thorough bowelshock despite resuscitation; continued bleeding ( 6 U packed preparation and meticulous technique, we just might find thosered blood cells transfused) and lack of a diagnosis despite elusive stigmata of hemorrhage in the colon.thorough work-up of upper, midgut, and lower sources; activebleeding from a segmental gastrointestinal lesion that is ame- Referencesnable to cure or permanent hemostasis by surgery; and patient 1. Longstreth GF. Epidemiology of hospitalization for acute upperis a surgical candidate with a reasonable life expectancy. How- gastrointestinal hemorrhage: a population-based study. Am Jever, it usually is difficult to make decisions based solely on Gastroenterol 1995;90:206 –210.criteria. Surgical consultation should be obtained early in the 2. Longstreth GF. Epidemiology and outcome of patients hospital-course of severe bleeding as a precautionary measure. Surgery ized with acute lower gastrointestinal hemorrhage: a population-also often is used in the setting of recurrent diverticular hem- based study. Am J Gastroenterol 1997;92:419 – 424.
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Voeller GR, Bunch G, Britt LG. Use of technetium-labeled red blood cell scintigraphy in the detection and management of Conflicts of interest gastrointestinal hemorrhage. Surgery 1991;110:799 – 804. The authors disclose no conflicts.106. Hunter JM, Pezim ME. Limited value of technetium 99m-labeled red cell scintigraphy in localization of lower gastrointestinal Funding bleeding. Am J Surg 1990;159:504 –506. This project was funded by a grant from the Agency for Healthcare107. Suzman MS, Talmor M, Jennis R, et al. Accurate localization Research and Quality (K08 HS14062, to L.L.S.).