The Role of Colonoscopy and Radiological Procedures in the Management of Acute Lower Intestinal Bleeding

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8: STATE OF THE ART The Role of Colonoscopy and Radiological Procedures in the Management of Acute Lower Intestinal Bleeding LISA L. STRATE and CHRISTOPHER R. NAUMANN Department of Medicine, Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington This article has an accompanying continuing medical education activity on page e44. Learning Objectives At the end of this activity, the learner should be able to understand the epidemiology of and the current management strategies for lower gastrointestinal bleeding. Podcast interview: There are multiple strategies for evaluating and treating lower intestinal bleeding (LIB). Colonoscopy has become the preferred initial test for most patients with LIB because of its diagnostic and therapeutic capabilities and its safety. However, few studies have directly compared colonoscopy with other techniques and there are controversies regarding the optimal timing of colonoscopy, the importance of colon preparation, the prevalence of stigmata of hemorrhage, and the efficacy of endoscopic hemostasis. Angiography, radionuclide scintigraphy, and multidetector computed tomography scanning are complementary modalities, but the requirement of active bleeding at the time of the examination limits their routine use. In addition, angiography can result in serious complications. This review summarizes the available evidence regarding colonoscopy and radiographic studies in the management of acute LIB. Keywords: Lower Gastrointestinal Bleeding; Angiography; Nuclear Scintigraphy; Multirow Detector CT Scan. Acute lower intestinal bleeding (LIB) is a common problem in Western societies that generally requires hospitalization and invasive testing. The annual incidence of hospitalization is estimated to be 21 per 100,000 persons, about one third to one fifth that of upper gastrointestinal bleeding (UGIB). 1,2 However, the incidence of LIB increases significantly with age (200 per 100,000 by age 80 years) 2 and LIB may be more common than UGIB in the elderly. 3 Despite advanced age and significant comorbid disease, most patients with LIB have favorable outcomes. In-hospital mortality is less than 5%, and most often is caused by a comorbid illness or nosocomial complication rather than uncontrolled hemorrhage. 2,4 Indeed, the majority of patients (at least 75%) with LIB will stop bleeding spontaneously. 5 8 Nonetheless, the costs of managing LIB are substantial because of the need for hospitalization and invasive procedures. The estimated cost of diverticular bleeding alone, the most common source of LIB, was $1.3 billion dollars in the United States in The general goals of the management of LIB are resuscitation, diagnosis, hemostasis, and, in some cases, prevention of recurrent bleeding. The importance of these measures ultimately depends on the source of bleeding. Vascular sources such as diverticular bleeding, angioectasias, and postpolypectomy bleeding can result in large-volume blood loss and are the most likely to benefit from urgent interventions and bleeding control. On the other hand, diagnosis and treatment of the underlying condition are priorities in the management of inflammatory sources such as ischemic colitis and bleeding neoplastic lesions. However, predicting the source and severity of hemorrhage at the time of presentation is difficult. In fact, 10% to 20% of patients presumed to have LIB are found to have bleeding from the upper-intestinal or midintestinal tract. 10 Several recent efforts have been made to aid in the systematic risk assessment and triage of patients with LIB (discussed later), but current management strategies must address a variety of presentations and a broad list of potential diagnoses (Table 1). A number of strategies and interventions are available for the management of LIB. These include colonoscopy, flexible sigmoidoscopy, angiography, radionuclide scintigraphy or tagged red blood cell scanning, and cross-sectional imaging techniques. 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 the 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 on issues surrounding the use of colonoscopy. Colonoscopy Colonoscopy is the preferred management strategy for most patients with LIB. 11,12 A clear advantage of colonoscopy over other tests is its ability to provide both a diagnosis and hemostasis. A diagnosis is made in approximately 75% to 100% Abbreviations used in this paper: CT, computed tomography; LIB, lower intestinal bleeding; MDCT, multidetector row computed tomography; UGIB, upper gastrointestinal bleeding by the AGA Institute /10/$36.00 doi: /j.cgh

2 334 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4 Table 1. Sources of Lower Intestinal Hemorrhage Source Frequency Endoscopic treatment Painless hematochezia a Other comments Diverticulosis 30% 65% Yes Yes Large volume, intermittent bleeding Angiodysplasia 4% 15% Yes Yes Occult blood loss more common than acute Hemorrhoids 4% 12% Yes Yes Can result in significant hemorrhage Ischemic colitis 4% 11% No No Mild bleeding with diarrhea Colitis, other 3% 15% Sometimes b No Mild bleeding with diarrhea Neoplasia 2% 11% Sometimes Yes Postpolypectomy 2% 7% Yes Yes Can be delayed 3 4 weeks Rectal ulcer 0% 8% Yes Yes Anticoagulants and poor functional status are associated with bleeding 118 Dieulafoy lesion Rare Yes Yes Usually located in the rectum Rectal varices Rare Sometimes c Yes Usually stigmata of chronic liver disease NOTE. Data from references. 2,8,10,14,15,36,117 a The abdominal examination can help differentiate inflammatory disorders such as ischemic colitis, which present with tenderness but generally result in mild blood loss from vascular disorders such as diverticula, which produce no tenderness but significant blood loss (hence the distinction painless hematochezia). 36 b Radiation proctopathy is amenable to endoscopic therapy. Ulcers with stigmata of hemorrhage also can be treated. c Banding or sclerotherapy for rectal varices is possible but transjugular intrahepatic portosystemic shunt procedures more commonly are recommended. of patients depending on the definition of the bleeding source, patient selection criteria, and timing of colonoscopy (Table 2). 8,13 17 The diagnostic yield of colonoscopy is higher than radiographic tests, which require active bleeding at the time of the examination, and flexible sigmoidoscopy, which visualizes only the left colon. 7,17 In published series, endoscopic therapy is applied in 10% to 40% of patients undergoing colonoscopy for LIB and immediate hemostasis is achieved in 50% to 100% of these cases. 8,10,13 15,18 Colonoscopy with endoscopic therapy for LIB appears to be safe. In a 1998 review of 13 studies (1561 patients), the overall complication rate was 1.3%. 19 These complications included bowel perforation (5 patients), congestive heart failure (4 patients), worsened bleeding (2 patients), and septicemia (1 patient). Of the perforations, 2 were noted to be secondary to endoscopic therapy (1 neodymium:yttrium-aluminum-garnet [Nd-Yag] laser and 1 polypectomy). In 4 more recent studies of colonoscopy after colon purge for all sources of LIB, there were 2 complications out of 664 patients (0.3%) (Table 2). 8,14 16 Both complications were perforations, one after biopsy of a cecal ulcer and one after biopolar electrocautery of a cecal angiodysplasia. 8,14 The complication rate was 0.6% in patients undergoing colonoscopy within 12 hours of admission (1 of 171 colonoscopies). 14,15 Although polyethylene glycol bowel preparation is a balanced salt solution, fluid overload, congestive heart failure, and electrolyte abnormalities have been reported in patients with underlying comorbidites. 10,20 Aspiration pneumonia is a potential risk with rapid, high-volume purges, particularly in patients with altered mental status. Bowel preparation is not believed to dislodge clots or precipitate bleeding. More controversy exists regarding whether colonoscopy improves major clinical outcomes in LIB. Jensen et al 15 compared 2 sequential prospective cohorts of patients with severe diverticular hemorrhage who underwent colonoscopy within 6 to 12 hours of admission after aggressive bowel preparation. Rebleeding (0% vs 53%; P.005) and surgery (0% vs 35%; P.03) were significantly less common in patients undergoing urgent colonoscopy with endoscopic therapy compared with urgent colonoscopy without therapy, respectively. As in peptic ulcer disease, stigmata of recent hemorrhage were predictive of rebleeding, with active bleeding having the highest risk (67%) followed by nonbleeding visible vessels (50%) and adherent clots (43%). No complica- Table 2. Colonoscopy in Lower Intestinal Bleeding Study Patients, n Mean timing, h Diagnosis, Definitive diagnosis, Endoscopic therapy, Complications, Jensen et al, (100) 107 (88) a 10 (37) b 0 Angtuaco et al, (74) 3 (8) 3 (8) Schmulewitz et al, (89) 42 (10) 1 (0.2) Smoot et al, c (100) 38 (49) 7(9) 0 Strate and Syngal, d 128 (89) 62 (43) 14 (10) Green et al, (96) 21 (42) 17 (34) 1 (2) Total (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. b Therapy only reported for 27 patients with diverticular bleeding. c Diverticular bleeding only. d Median time of colonoscopy.

3 April 2010 MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING 335 Table 3. Endoscopic Treatment of Diverticular Bleeding Endoscopic treatment modality Patients, n Early rebleeding, n (%) Late rebleeding, n (%) Complications, n (%) Banding Thermal contact 15,21,47,48, (12) 0 0 Epinephrine 16,21,46,50 53, (15) 1 (5) 0 Thermal contact plus injection 14 16,21, (24) 4 (16) 0 Endoclip 16,41,42,49,54,57, (17) 0 Total (8) 17 (12) 0 tions were reported. This study highlights the promise of colonoscopy, particularly when performed early in the course of severe diverticular bleeding. However, it also raises a number of issues, including whether the results can be generalized to practices without experienced bleeding teams and to other sources of bleeding. The use of historical controls also may have influenced the results. Other reports of endoscopic therapy for diverticular bleeding have been inconsistent. Early rebleeding has been reported in 0% to 38% of patients, and late rebleeding has been reported in 0% to 18%. 14,21 In reviewing the 137 cases of endoscopic therapy for diverticular bleeding reported in the literature, early rebleeding occurred in 8% and late rebleeding in 12% (Table 3). In 2005, Green et al 14 published the first randomized controlled trial in LIB. In this study, 100 patients with severe LIB were randomized to colonoscopy within 8 hours or to standard of care, which included elective colonoscopy in all patients and tagged red blood cell scan followed by angiography if positive in patients with ongoing bleeding (36 patients). A definitive source of bleeding was identified significantly more often in the urgent colonoscopy arm (42% vs 22%; odds ratio, 2.6; P.03). There were no statistical differences in rebleeding (22% vs 30%), surgery (14% vs 12%), mortality (2% vs 4%), blood transfusions (4.2 vs 5.0 units), and length of stay (5.8 vs 6.6 days) between the colonoscopy and standard-of-care arms, respectively, including a subanalysis of patients receiving interventions. However, there was a general trend in favor of colonoscopy. Importantly, this study, similar to most dealing with LIB, was underpowered to detect a clinically important and statistically significant difference in major outcomes and therefore cannot be used to conclude the equivalence of these interventions. In addition, it has been criticized for insufficient colon preparations (64% were fair to poor), 22 did not use current state-of-the-art endoscopic or angiographic therapy, and was published 10 years after completion of the study. Large-scale, multicenter, randomized trials ultimately are needed to determine the best strategy for patients with LIB. In the meantime, the existing, albeit imperfect, literature can be used to address a number of important issues regarding colonoscopy in LIB, including the relative importance of timing of intervention versus colonic preparation, the prevalence of high-risk stigmata, the optimal endoscopic treatment modality, and the overall impact of endoscopic hemostasis in the colon. Timing of Colonoscopy Early endoscopy is the standard of care in UGIB, although the optimal time frame has yet to be defined. Early intervention allows identification and treatment of bleeding sources, reduces the need for blood transfusion and length of hospital stay, and facilitates the triage of high- and low-risk patients. 23 Traditionally, colonoscopy has been performed electively after bleeding has stopped owing to fear of increased complications, need for colon preparation, and lack of proven benefit. Recent studies have suggested that performing colonoscopy shortly after presentation is advantageous, but studies comparing this approach with delayed colonoscopy are limited. 8,14,15,17 The primary indication to perform early colonoscopy, as with UGIB, is to identify and treat bleeding sources. The available evidence suggests that earlier colonoscopy results in more definitive diagnoses and therefore more opportunities for therapeutic intervention. 10,14,15,24 Urgent colonoscopy generally refers to colonoscopy performed within 12 hours of admission, 14,15 but other studies have achieved good results using a more lenient time window of 24 hours. 24 In a retrospective study, earlier colonoscopy, analyzed as a continuous variable, was associated with significantly more diagnostic and therapeutic interventions. 17 Endoscopic therapy was used successfully in 29% of colonoscopies performed within 12 hours of admission, 13% of those performed in 12 to 24 hours, 4% in 24 to 48 hours, and 0% in colonoscopies performed after 48 hours. 17 However, this was an unadjusted analysis and patients most likely to have stigmata may have been selected preferentially for early examinations. Indeed, most studies of urgent colonoscopy have enrolled only patients with significant hemorrhage, 14,15 and a specific time interval is probably less important than the presence of significant or ongoing hemorrhage. In one study, the yield of colonoscopy increased from 20% to 85% when performed during active bleeding versus electively. 25 Other studies have shown a high yield when repeat colonoscopy is performed promptly for recurrent bleeding. 26 It is noteworthy that in the randomized trial by Green et al, 14 no stigmata of hemorrhage were found in patients undergoing elective colonoscopy after a positive tagged red blood cell scan (the average time to colonoscopy in this group was 38 hours). Prompt colonoscopy also offers an opportunity to identify low-risk patients and, therefore, to reduce the need for hospitalization and costs of care. Several studies have found that time to colonoscopy is a strong predictor of length of stay after adjustment for other factors including comorbid illness. 8,17 Overall, this appears to be the result of early diagnosis in low-risk patients rather than therapeutic interventions. 17 Length of hospital stay is a major determinant of costs in gastrointestinal bleeding and, therefore, earlier colonoscopy likely translates into decreased costs of care. 7,27 In a retrospective, informal cost analysis, urgent colonoscopy was associated with an average savings of $10,065 per patient compared with emergency angiography and elective colonoscopy. 28 However, this large savings likely reflects other trends in care including length of hospital stay and the use of surgery.

4 336 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4 Taken together, the evidence suggests that colonoscopy should be performed within 12 to 24 hours in most patients with LIB a goal that usually accommodates colon preparation and the availability of the endoscopy suite. In patients with signs of severe bleeding, colonoscopy close to the time of bleeding after a rapid bowel preparation is likely to have the highest yield. However, as in UGIB, an optimal time threshold has not been determined, and it is unclear how faster timing affects major clinical outcomes such as rebleeding and mortality. Colon Preparation Adequate colon preparation is an important component of colonoscopy for LIB. Early studies of unprepped colonoscopy for LIB report low completion rates between 55% and 70% In addition, blood and stool in the colon may increase the risk of perforation and impair the identification of stigmata of hemorrhage. In the study of urgent colonoscopy by Jensen et al, 15 procedures were performed within 1 hour of stool clearing after 5 to 6 liters of polyethylene glycol were given over 3 to 4 hours, often via nasogastric tube. This meticulous attention to preparation likely contributed to the exemplary results, and, in general, shortening the time to colonoscopy should not come at the expense of the bowel preparation. Ideally, colonoscopy is performed within 1 to 2 hours of stool clearing. The use of promotility agents, such as metoclopramide, may facilitate the preparation and prevent nausea, but this has not been studied formally. 28 Aspiration precautions should be followed during rapid colon cleansing. Water jet or syringe irrigation should be used to clear remaining blood and stool and a large-channel therapeutic colonoscope can be helpful. Additional preparation may not be necessary for recurrent bleeding once the colon has been cleansed because active bleeding in this instance may improve localization. 32 A successful rapid colon preparation requires coordination of the medical, nursing, and pharmacy staff and the cooperation of the patient. Flexible sigmoidoscopy and anoscopy can be performed early in the evaluation of LIB to evaluate and treat left-sided or anorectal lesions without the need for a full colon preparation. This may be of particular use in patients with a high likelihood of a distal source. However, the yield of this approach in the literature has been quite low ( 10%), 7,25,33 and most patients ultimately will require a full colonoscopy to exclude proximal pathology. Stigmata of Recent Hemorrhage The main indication for performing urgent interventions and meticulous colon preparations is to identify and treat stigmata of recent hemorrhage or active bleeding. However, the identification of stigmata in the colon is difficult. The large surface area of the colon, residual stool and blood, intermittent bleeding, and multiple potential lesions (eg, diverticulosis) are complicating factors. In addition, only about half of LIB is from endoscopically treatable sources, such as diverticulosis and angiodysplasia (Table 1). 2,8,17 Other sources, including ischemic colitis and inflammatory bowel disease, tend to result in diffuse injury. Furthermore, more than one third of patients will have more than one potential source such as diverticulosis and hemorrhoids. 24 The incidence of stigmata of recent hemorrhage in LIB is unknown. In prospective trials of peptic ulcer disease, stigmata of recent hemorrhage are seen on average in 17% of patients. 34 Studies of all sources of LIB report stigmata in 8% to 35% of patients. 13,14,17 However, yields at the upper end of this range reflect highly selected patients who are recruited over a long period. 15 The timing of colonoscopy, quality of colon preparation, selection of patients with severe or ongoing bleeding, and experience and diligence of the endoscopist are factors that impact the yield of colonoscopy in LIB. Risk-stratification tools that aid in the selection of patients who are most likely to have stigmata of hemorrhage and to benefit from urgent interventions are also likely to improve the utility of urgent colonoscopy. Risk Stratification One of the major difficulties in the management of LIB is predicting the likelihood of severe bleeding and the need for hemorrhage control based on the initial clinical presentation. Risk stratification is particularly important in LIB because diagnostic and therapeutic interventions are time- and resourceintensive and often entail risk and inconvenience (ie, bowel preparation) for the patient. Furthermore, 75% of patients will stop bleeding spontaneously and are unlikely to benefit from aggressive interventions. In UGIB, there have been dozens of attempts to predict the risk of poor outcome and the need for endoscopic interventions. 5 The systematic application of such tools can reduce resource use, mainly through early discharge, without deleterious effects on other clinical outcomes. 35 Recently, 3 risk-stratification tools have been developed specifically for LIB. 5,36 38 Hemodynamic instability, ongoing hematochezia, and comorbid illness consistently have been associated with poor outcome, and parallel findings in UGIB. Studies also have shown that patients who bleed while hospitalized for another process have a particularly poor prognosis. 2,39 Other risk factors identified in one or more studies are listed in Table 4. Strate et al 36,37 developed and validated a simple prediction rule for severe bleeding based on 7 independent risk factors (tachycardia, hypotension, syncope, a nontender abdomen, rectal bleeding within 4 hours of presentation to the hospital, aspirin use, and 2 major comorbid conditions). The number of risk factors predicted the risk of severe or recurrent hemorrhage as well as the need for blood transfusions, surgery, and death. 37 Patients with 4 or more risk factors (17% of patients) were in the highest risk group (80% chance of severe or ongoing Table 4. Risk Factors for Poor Outcome in Lower Intestinal Bleeding Hemodynamic instability 5,36 38 Hypotension, tachycardia, orthostasis, syncope Ongoing bleeding 5,36 38 Blood on rectal examination, hematochezia, rectal bleeding within 4 hours of presentation Age 5 Comorbid illness 5,36,37 Secondary bleeding (bleeding while hospitalized for another process) 2,39 Anticoagulation or antiplatelet medication 5,36,37 History of diverticular disease or angiodysplasia 5 Nursing home resident 5 Nontender abdominal examination 5,36,37 Anemia (hematocrit 35%) 38 Abnormal creatinine level 5 Abnormal white blood cell count 5

5 April 2010 MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING 337 bleeding) and would be the most appropriate targets for urgent interventions. Patients with 1 to 3 risk factors (designated as moderate risk) had a 43% chance of severe or recurrent bleeding and also may warrant urgent interventions. However, the ability of the rule to aid in risk stratification is limited by the fact that the moderate-risk group comprised 78% of the population. Velayos et al 38 identified hematocrit less than 35%, abnormal vital signs after 1 hour, and gross blood on initial rectal examination as independent predictors of ongoing or recurrent bleeding. Ongoing or recurrent bleeding occurred in 79% of patients with 3 risk factors, 54% of patients with 2 risk factors, 17% of patients with 1 risk factor, and 0% in patients with no risk factors. Fifty-two percent of patients had 2 or 3 risk factors and these patients are reasonable candidates for urgent interventions. Das et al 5 developed and validated an artificial neural network to predict the risk of death, rebleeding, and need for intervention. This tool was highly accurate in predicting these outcomes, particularly in the external validation group (97%, 93%, and 94%, respectively). In addition, the negative predictive values for these outcomes were greater than 98% in the internal and external validation cohorts, suggesting that this artificial neural network could be used to triage low-risk patients to outpatient management. Overall, the artificial neural network models appear to outperform prediction rules developed using standard logistic regression techniques. The requirements for specific software and data entry currently limit their clinical application, but, with the widespread use of computerized medical records, neural networks are likely to become more clinically applicable. Further studies are needed to determine prospectively the impact of prediction rules on clinical outcomes and to validate the results in larger diverse settings. Perhaps the bigger task will be the routine application of risk stratification in clinical practice, something that has proven difficult even in UGIB. 40 Endoscopic Hemostasis Techniques Although endoscopic hemostasis in the colon appears to be effective, the optimal technique has not been delineated. The armamentarium for endoscopic hemostasis in the colon parallels that of UGIB and includes injection therapy (eg, epinephrine or saline), thermal contact (heater probe, bipolar electrocoagulation, or monopolar electrocoagulation), argon plasma coagulation, endoscopic clipping devices, and band ligation. In contrast to UGIB, in which numerous trials (albeit many relatively small) and meta-analyses have investigated endoscopic hemostasis techniques, data in LIB are based largely on small nonrandomized trials or retrospective case series. In addition, it is difficult to compare the efficacy of endoscopic treatment for different bleeding sources because of differences in the need for endoscopic therapy and in the natural history of bleeding. In general, the type and location of the lesion, experience of the endoscopist, and presence of coagulation defects should guide the therapeutic modality. A second technique can be tried if the first attempt fails. Endoscopic clipping is touted as a safer alternative to thermal contact methods. 26,41,42 Endoclips can be applied directly to the stigmata, to feeder vessels, or used to oppose the sides of small diverticula or postpolypectomy defects. 26,32 Care must be taken not to traumatize or partially clip a vessel. Electrocautery in the colon should be performed using moderately low power settings (10 15 W) in 1- to 3-second bursts with light to moderate pressure. 14,15 This technique appears to be safe (one cecal perforation reported in the recent literature), 14 but should be used cautiously in the right colon, in the dome of diverticula, and in the presence of mucosal defects. In experimental canine models, electrocoagulation was safe for mucosal lesions even at high settings, but not for ulcers in which colon thickness was compromised. 43 In the presence of active bleeding, epinephrine (dilution, 1:10,000 or 1:20,000) can be injected in 1- to 2-mL aliquots in 4 quadrants around the lesion. Injection not only helps to clear the field of active bleeding, but it also can be used to better expose stigmata from within a diverticulum (conversely injection distal to a lesion can hamper access). 32 Argon plasma coagulation is particularly useful for diffuse lesions such as radiation proctopathy and large or multiple angiodysplasia. 44 Band ligation also has been used in diverticular hemorrhage and for other focal lesions. 45 In reviewing the 137 cases in the literature (including abstract form) of endoscopic treatment of diverticular bleeding, hemostasis was achieved in 92% of all cases and no complications were reported (Table 3) ,21,26,41,42,46 59 Four patients were treated successfully with endoscopic band ligation. Of 20 cases treated with epinephrine injection alone, 15% experienced early rebleeding. Forty-two patients received thermal contact therapy plus/minus epinephrine injection for active bleeding. The early rebleeding rate in this group was 19% and was highly influenced by one study of 13 patients in which 5 (38%) experienced rebleeding. 21 A total of 71 cases treated with endoscopic clipping have been reported with 100% success, suggesting that this is a very effective modality for diverticular bleeding. Late recurrent bleeding has been reported in 25% of all patients with diverticular hemorrhage after 4 years of follow-up. 2 Late recurrent bleeding occurred in 17 of the reported 137 patients (12%) treated endoscopically for diverticular bleeding. However, recurrent bleeding is often a delayed phenomenon 49 and patient follow-up varied substantially in these studies. It is also unclear how the treatment of one diverticulum affects recurrent bleeding given the presence of many diverticula in the colon. Radiologic Management Options There are a number of radiographic strategies used in the management of severe LIB including angiography, radionuclide scintigraphy (tagged red blood cell scanning), and computed tomography. These tests typically are reserved for patients with very brisk bleeding who cannot be stabilized for colonoscopy or for ongoing bleeding of obscure etiology. They can be particularly useful in brisk bleeding because there is no need for bowel preparation. Radiographic modalities are of limited use in more routine scenarios because they require active bleeding at the time of examination for diagnosis and treatment. Similar to the literature for colonoscopy, studies evaluating radiographic modalities for the management of LIB often are limited by small sample sizes, variable inclusion criteria, and a paucity of prospective randomized trials. In addition, there are very few head-to-head comparisons with colonoscopy. The performance of these modalities continues to improve as technologic advances are made. Angiography Angiography is the only radiographic modality that can be both diagnostic and therapeutic. Bleeding rates of at least 0.5

6 338 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4 to 1 cc per minute can be detected with angiography. 60 Successful localization of bleeding is highly dependent on the rate of bleeding at the time of the examination. 61,62 A systolic blood pressure 90 mm Hg and a requirement of at least 5 units of packed red blood cells within a 24-hour period have been shown to predict a positive angiography. 63 Angiography was positive in approximately 85% of patients with both of these criteria compared with 15% in more stable patients. Overall, positive examinations are reported in 25% to 70% of cases in the literature. 25,61,64 66 This wide range is likely a reflection of nonstandardized patient selection and angiographic technique. Provocative angiography with vasodilators, anticoagulants, and thrombolytic agents has been studied as a means of increasing the sensitivity of angiography. Studies using provocative techniques in patients with obscure bleeding report an overall yield of about 30% with few complications However, the number of reported cases is small and the risk of serious complications is high. Therefore, technical expertise and careful patient selection are required to achieve good results and minimize complications. Historically, angiographic intervention for LIB involved the infusion of vasoconstrictors, such as vasopressin. This technique often was used to stabilize a patient before surgical resection of the culprit segment rather than as a definitive intervention because rebleeding occurred in up to 50% and serious complications developed in 10% to 20%. 61,62 Technologic advances in coaxial microcatheters and embolic materials have enabled the embolization of specific distal arterial branches. Superselective embolization has resulted in increased success and fewer complications, most notably bowel infarction. Embolization is feasible in approximately 82% of patients with positive angiograms in the setting of LIB. 70 Failure to achieve superselective positioning is most commonly the result of vasospasm, tortuosity, or stenosis. 71 In a review of 20 studies using current superselective techniques, immediate hemostasis was achieved in 96% of patients and rebleeding within 30 days occurred in 22% (Table 5) Studies suggest that diverticular bleeding may be more amenable to embolization therapy than other sources of bleeding, such as angiodysplasia. 62,63 In a metaanalysis of embolization as first-line therapy for LIB, embolization successfully controlled diverticular bleeding in 85% at 30 days versus 50% in nondiverticular bleeding (P.01). 91 No study has shown the superiority of any one of the 3 agents used for embolization microcoils, polyvinyl alcohol particles, and gelfoam. However, polyvinyl alcohol particles can be injected upstream of a bleeding site when superselective positioning is not possible. Gelfoam allows for recanalization over days to weeks, but rarely is used. The potential for serious complications is a major limitation to the use of angiography in LIB, particularly in the elderly and in patients with comorbid illness. In reviewing the 338 patients undergoing superselective embolization for LIB, minor complications were seen in 26% and major complications were seen in 17% (Table 5). The most common major complication was bowel infarction. Other complications include contrast allergies and nephrotoxicity, hematomas, thromboses, and vascular dissections Table 5. Angiography With Embolization in Acute Lower Intestinal Bleeding Study Patients/patients embolized, n Immediate hemostasis, a Early rebleeding, b Minor complications, c Major complications, d Guy et al, /9 9 (100) 3 (33) 3 (33) 3 (33) Gordon et al, /14 13 (93) 2 (15) 4 (31) 2 (15) Lederman et al, /7 6 (86) 1 (17) 1 (17) 0 (0) Nicholson et al, /13 12 (92) 2 (17) 4 (33) 1 (8) Bulakbasi et al, /9 9 (100) 3 (33) 7 (78) 0 (0) Evangelista and Hallisey, /17 15 (88) 2 (13) 3 (20) 1 (7) Luchtefeld et al, /16 13 (81) 1 (8) 6 (46) 1 (8) Bandi et al, /35 33 (94) 11 (33) 9 (27) 8 (24) Funaki et al, /25 25 (100) 3 (1) 3 (12) 3 (12) Defreyne et al, /11 11 (100) 1 (9) 0 (0) 1 (9) Patel et al, /10 10 (100) 2 (20) 1 (10) 1 (10) DeBarros et al, /27 27 (100) 6 (22) 2 (7) 6 (22) Kuo et al, /22 22 (100) 3 (14) 4 (18) 0 (0) Gady et al, /10 10 (100) 3 (30) 0 (0) 4 (40) Burgess and Evans, /15 14 (93) 8 (57) 10 (71) 6 (43) Waugh et al, /27 26 (96) 6 (23) 7 (27) 3 (12) Neuman et al, /23 23 (100) 5 (22) 11 (48) 3 (13) Silver et al, /11 10 (91) 1 (10) 2 (20) 6 (60) d Othee et al, /17 17 (100) 5 (29) 6 (35) 4 (24) Kickuth et al, /20 20 (100) 2 (10) 2 (10) 2 (10) Total 539/ (96) 70 (22) 85 (26) 55 (17) a Immediate hemostasis calculations were limited to those patients who were embolized. b Early rebleeding was defined as bleeding within 30 days of initial embolization. Calculations were limited to patients who were embolized and achieved hemostasis. c Minor complications did not require surgery or result in death among those embolized with immediate hemostasis; late rebleeds were excluded because a majority were unrelated to the index procedure. d Major complications required surgery or resulted in death among those embolized with immediate hemostasis.

7 April 2010 MANAGEMENT OF ACUTE LOWER INTESTINAL BLEEDING 339 Studies comparing colonoscopy and angiography in the management of LIB are limited. As mentioned earlier, there has been only one randomized controlled trial comparing colonoscopy with tagged red blood cell scan followed by angiography if positive. 14 This trial found colonoscopy to be a superior diagnostic test, but was underpowered for other major outcomes. In a prospective study, 22 patients with severe hematochezia underwent both angiography and panendoscopy. 10 Ultimately, 17 were found to have colonic sources. Only 14% had a definitive diagnosis made by angiography compared with 86% with panendoscopy. Endoscopic therapy was used in 39% compared with 1% with angiography. Complications occurred in 9% of angiographies compared with 4% of colonoscopies. Other retrospective studies have found colonoscopy to have a better diagnostic and therapeutic yield than angiography. 7,25,92 In all of these studies, angiography relied on vasopressin infusion, not embolization. It is important to note that most patients who undergo angiography will require elective colonoscopy to confirm the bleeding source and exclude neoplasia. In practice, angiography probably is used more often than colonoscopy for patients with severe bleeding. In one retrospective, single-center study, patients with hemodynamic instability were more likely to undergo angiography, whereas logistical factors (time of day and day of week) and postpolypectomy bleeding were predictive of urgent colonoscopy. 92 The fact that angiography can be performed without a bowel preparation is likely to factor significantly into management decisions. However, in this study, the median times from admission to early initial procedure were similar in patients undergoing angiography (14 hours) versus colonoscopy (17 hours), 92 drawing attention to the fact that angiography, especially when preceded by a nuclear medicine scan, also may take time to orchestrate. In the absence of data from large randomized trials, the choice of intervention in patients with massive bleeding generally is guided by institutional expertise. However, in patients who can be stabilized for bowel preparation, colonoscopy appears to be the most efficient and safest strategy. Radionuclide Scintigraphy Radionuclide scintigraphy, or tagged red blood cell scanning, often is used as a screening test before angiography because it is noninvasive and more sensitive (bleeding at a rate of cc per minute can be detected). 64 It also can be repeated in the setting of intermittent bleeding. However, the ability of radionuclide scanning to localize the bleeding source correctly varies widely in the literature in part because of differences in the criteria used for confirming the source and for patient selection. In reviewing the 7 most recent studies of radionuclide scanning for LIB (447 patients) in which radionuclide scintigraphy findings were confirmed by a different test, the accuracy of a positive test was 66% (Table 6) Localization appears to improve when scans are positive within 2 hours of injection (95% 100%) as opposed to later (55% 65%). 100 This likely reflects the tendency of blood to spread both antegrade and retrograde in the colon. Subtraction scintigraphy also may improve the accuracy of radionuclide scintigraphy. With this technique, the initial frame is subtracted from subsequent images, theoretically improving visualization of the radionuclide label by removing superimposed background structures. 101,102 In a retrospective study of 49 scans processed using both conventional and subtraction scintigraphy, the rate of false-positive Table 6. Nuclear Scintigraphy in Lower Intestinal Bleeding Study Total scans, n Positive scans, Localization confirmed, a Accuracy of positive scans, Zink et al, (46) 17 (89) 6 (35) Czymek et al, 20 8 (40) 8 (100) 8 (100) Lee et al, (41) 4 (44) 3 (75) Brunnler et al, (73) 30 (45) 20 (67) Olds et al, (39) 42 (86) 23 (55) Levy et al, (70) 28 (100) 18 (64) Gutierrez et al, (40) 23 (55) 22 (96) Total (50) 152 (68) 100 (66) NOTE. Table includes studies since a Scan localization confirmed by endoscopy, angiography, or surgery. examinations decreased (9.6% to 3.6%) and the confidence of reported findings improved. 102 Despite its sensitivity for bleeding and safety, the role of radionuclide scintigraphy in LIB remains controversial. There have been no randomized trials of angiography with and without radionuclide scanning. Some studies show an increase in the diagnostic yield of angiography when performed after a positive scan (22% to 53% in one study) 103 ; whereas other studies have found no difference. 62,104,105 Likewise, the ability of nuclide scanning to accurately localize bleeding before surgical resection is debatable A significant disadvantage of radionuclide scintigraphy is the lack of therapeutic possibilities. The delay between a positive scan and subsequent angiography or colonoscopy may decrease therapeutic opportunities owing to the intermittent nature of LIB. Therefore, if radionuclide scintigraphy is to be used in LIB, care should be coordinated so that a positive scan is followed closely by angiography. Computed Tomography Until recently, computed tomography (CT) scanning has been of limited use in the evaluation of gastrointestinal bleeding. However, with the introduction of multidetector row CT (MDCT), it is being investigated as a potential diagnostic tool. MDCT markedly decreases scan time, which enables the accurate acquisition of arterial images, which can show contrast extravasation into any portion of the gastrointestinal tract. 108 Bleeding rates as low as 0.3 to 0.5 cc per minute have been detected in a swine model. 109 Overall, in the 124 patients reported in the literature, the average yield of MDCT for LIB is 60%, with yields ranging from 25% to 95% (Table 7) The yield of MDCT is highest among patients with severe ongoing LIB. 99, General advantages of CT scanning include its wide availability and the added diagnostic yield of cross-sectional imaging. The primary disadvantage of CT scanning, as with radionuclide scintigraphy, is its inability to deliver therapy. Other disadvantages include exposure to radiation, limited ability to perform repeat scans, false-positive results generated from metallic objects or sutures, contrast allergies, and potential nephrotoxicity with intravenous contrast, particularly if CT is followed by angiography. 108 Overall, 2 complications have been reported in the literature. 114 Both of these patients had pre-

8 340 STRATE AND NAUMANN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 4 Table 7. MDCT in Lower Intestinal Bleeding Study Total scans, n Positive scans, Bleeding site confirmed, a Correct localization, b Complications, Jaeckle et al, (94) 16 (100) 16 (100) 0 Zink et al, (24) 5 (50) 5 (100) 0 Scheffel et al, (63) 5 (100) 5 (100) 0 Yoon et al, (84) 16 (100) 16 (100) 2 (11) Sabharwal et al, (71) 2 (40) 2 (100) 0 Tew et al, (54) 7 (100) 7 (100) 0 Ernst et al, (79) 15 (100) 15 (100) 0 Total (60) 61 (82) 66 (100) 2 (2) a Confirmation of bleeding site by angiography, endoscopy, and/or surgery. b Of those patients who had confirmation of the bleeding site. existing renal insufficiency secondary to diabetic nephropathy and experienced contrast-induced nephrotoxicity requiring hemodialysis after MDCT followed by angiography. A recent study prospectively evaluated MDCT followed by angiography in 26 consecutive patients presenting with acute massive gastrointestinal bleeding. 114 MDCT detected the extravasation of contrast into the intestinal lumen in 16 of the 19 patients with lower GI sources. Bleeding was confirmed in all 16 cases by angiography (100%). When both upper and lower sources were included, MDCT had a sensitivity of 91% and a specificity of 99%. There were 2 false-negative examinations and 1 false-positive examination. Localization of the site of bleeding was accurate in 100% of cases. As noted earlier, contrast-induced nephropathy was noted in 2 patients who had baseline increases in creatinine level. It is not clear whether MDCT has an impact on rebleeding rates, need for surgical intervention, or mortality. Another study compared MDCT with radionuclide scintigraphy in 41 patients with LIB. 99 MDCT identified 10 cases (25%) of active bleeding and radionuclide scintigraphy identified 19 (46%). The yield of nuclear scintigraphy was higher because the test could be repeated in the event of intermittent bleeding. There were discordant results in 13 cases 11 negative MDCT but positive scintigraphy and 2 positive MDCT but negative scintigraphy. Both techniques accurately identified the location of bleeding although MDCT provided more detail and ancillary findings. Although the data are encouraging, additional studies are needed with larger sample sizes and stronger end points to determine the appropriate role for MDCT in the management of LIB. Surgery Surgery generally is reserved for patients with lifethreatening hemorrhage who have failed other management options. Farrell and Friedman 115 summarize the following indications for emergency surgery for severe LIB: hypotension and shock despite resuscitation; continued bleeding ( 6 U packed red blood cells transfused) and lack of a diagnosis despite thorough work-up of upper, midgut, and lower sources; active bleeding from a segmental gastrointestinal lesion that is amenable to cure or permanent hemostasis by surgery; and patient is a surgical candidate with a reasonable life expectancy. However, it usually is difficult to make decisions based solely on criteria. Surgical consultation should be obtained early in the course of severe bleeding as a precautionary measure. Surgery also often is used in the setting of recurrent diverticular hemorrhage, but there are few data to guide this practice. 6 Decisionanalysis models using population-based data call into question the practice of surgical resection after 2 episodes of diverticulitis. 116 Complications of surgery for LIB are reported in as many as 60% of patients, 94 and the mortality rate is as high as 10%. 115 Localization of the bleeding source before surgery is important to prevent the excess morbidity and mortality reported with blind subtotal colectomy and also to prevent resection of the incorrect segment of bowel. 6 Conclusions Colonoscopy is the preferred intervention for most patients with LIB owing to its high diagnostic yield, varied therapeutic capabilities, and low complication rate. Based on the available literature, it appears that colonoscopy shortly after presentation can increase the identification and treatment of stigmata of hemorrhage and potentially reduce early rebleeding. However, the identification of stigmata is probably as much a function of ongoing or severe bleeding and meticulous colon preparation as it is the timing of the examination. Prompt colonoscopy in all patients with LIB, regardless of endoscopic intervention, is likely to decrease hospital length of stay and therefore the cost of care. The need for colon preparation, the difficulty in performing prompt colonoscopy, and the relative infrequency of stigmata of hemorrhage in the colon are deterrents to the use of urgent colonoscopy in routine practice. Risk-stratification tools that target high-risk patients as well as system-based interventions that address logistical issues promise to improve the utility of urgent interventions. Radiographic modalities, particularly angiography, play a complementary role in patients with massive bleeding who cannot be stabilized for colon preparation or who have eluded endoscopic diagnosis and/or treatment. 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