the management of lower gastrointestinal bleeding

Aliment Pharmacol Ther 2005; 21: 1281–1298.

doi: 10.1111/j.1365-2036.2005.02485.x

Review article: the management of lower gastrointestinal bleeding J. J. FARRELL* & L. S. FRIEDMAN à§ *Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, CA; Harvard Medical School, Boston, MA, USA; Departments of Medicine, àNewton Wellesley Hospital, Boston, MA, USA, and §Massachusetts General Hospital, Boston, MA, USA Accepted for publication 30 January 2005

SUMMARY

Several recent advances have been made in the evaluation and management of acute lower gastrointestinal bleeding. This review focuses on the management of lower gastrointestinal bleeding, especially acute severe bleeding. The aim of the study was to critically review the published literature on important management issues in lower gastrointestinal bleeding, including haemodynamic resuscitation, diagnostic evaluation, and endoscopic, radiologic, and surgical therapy, and to develop an algorithm for the management of lower gastrointestinal bleeding, based on this literature review. Publications pertaining to lower gastrointestinal bleeding were identified by searches of the MEDLINE database for the years 1966 to December 2004. Clinical trials and review articles were specifically identified, and their reference citation lists were searched for additional publications not identified in the database searches. Clinical trials and current clinical recommendations were assessed by using commonly applied criteria. Specific recommendations are made based on the evidence reviewed.

INTRODUCTION

Lower gastrointestinal bleeding is one-fifth to one-third as common as upper gastrointestinal bleeding and generally has a less severe course. The annual incidence rate of lower gastrointestinal bleeding in the US ranges Correspondence to: Dr J. J. Farrell, Division of Digestive Diseases, UCLA School of Medicine, UCLA Center for the Health Science, Los Angeles, CA 90095, USA. E-mail: [email protected] 2005 Blackwell Publishing Ltd

Approximately, 200 original and review articles were reviewed and graded. There is a paucity of high-quality evidence to guide the management of lower gastrointestinal bleeding, and current endoscopic, radiologic, and surgical practices appear to reflect local expertise and availability of services. Endoscopic literature supports the role of urgent colonoscopy and therapy where possible. Radiology literature supports the role of angiography, especially after a positive bleeding scan has been obtained. Limited surgical data support the role of segmental resection in the management of persistent lower gastrointestinal bleeding after localization by either colonoscopy or angiography. There is limited high-quality research in the area of lower gastrointestinal bleeding. Recent advances have improved the endoscopic, radiologic and surgical management of this problem. However, treatment decisions are still often based on local expertise and preference. With increased access to urgent therapeutic endoscopy for the management of acute upper gastrointestinal bleeding, diagnostic and therapeutic colonoscopy can be expected to play an increasing role in the management of acute lower gastrointestinal bleeding.

from 20.5 to 27 cases per 100 000 adult population at risk (0.03%). In contrast, the annual incidence rate for upper gastrointestinal bleeding is reported to range from 100 to 200 cases per 100 000. As in upper gastrointestinal bleeding, lower gastrointestinal bleeding stops spontaneously in most cases (80–85%).1 The mean age of patients with lower gastrointestinal bleeding ranges from 63 to 77 years, with a reported mortality rate of 2–4% (Table 1).2–7 The incidence rate of lower gastrointestinal bleeding increases with 1281

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Table 1. Age, mortality rates, and causes of acute lower gastrointestinal bleeding

Study

Mean age (years)

Mortality (%)

Diverticulosis (%)

Angiodysplasia (%)

Cancer/ polyp (%)

Colitis/ ulcer* (%)

Anorectal (%)

Otherà (%)

Boley et al. (1978)2 Jensen and Machicado (1988)3 Leitman et al. (1988)5§ Richter et al. (1995)7 Jensen and Machiado (1997)4 Longstreath (1997)6 Strate and Syngal (2003)69

>65 64.5 63 70 77 67 66

2 NA 21 2 NA 3.6 3

40 20 27 48 23 41 30

11 37 24 12 40 3 3

14 14 15 11 15 9 6

12 11 10 6 12 16 21

NA 5 NA 3 5 5 14

NA 5 NA 6 4 14 28

NA, not available. * Includes inflammatory bowel disease, infectious colitis, radiation colitis, vasculitis and inflammation of unknown origin. Includes haemorrhoids, anal fissure and idiopathic rectal ulcer. à Includes postpolypectomy, aortocolonic fistula, trauma from faecal impaction, and anastomotic bleeding. § Study included only critically ill patients undergoing angiography.

age, with a >200-fold increase from the age of 20–80 years.8, 9 This rise in incidence with age is most likely explained by the increasing prevalence of colonic diverticulosis and colonic angiodysplasia with age. Haematochezia signifies bright red blood per rectum and needs to be differentiated clinically from melaena, the passage of darkened, digested blood per rectum, which suggests an upper gastrointestinal source. Although severe lower gastrointestinal bleeding is defined as blood loss originating from a source distal to the ligament of Treitz and resulting in haemodynamic instability or symptomatic anaemia, approximately 10–15% of patients presenting with acute severe haematochezia have an upper gastrointestinal source of bleeding identified on upper endoscopy. Small bowel sources account for 0.7–9.0% of cases of severe haematochezia. The most common causes of lower gastrointestinal bleeding are diverticulosis, angiodysplasia, haemorrhoids, and ischaemic colitis (see Table 1).3, 10–12 This article focuses on the investigation and management of acute lower gastrointestinal bleeding. A practical approach to the management of lower gastrointestinal bleeding, especially severe bleeding, is proposed. Finally, predictors of outcome in patients with lower gastrointestinal bleeding are discussed. METHODS

This review aims to evaluate existing published data regarding the management of lower gastrointestinal bleeding. Publications pertaining to lower gastrointestinal bleeding were identified by searches of the MEDLINE database for the years 1966 to December

2004, by using the terms ‘gastrointestinal haemorrhage,’ ‘gastrointestinal bleeding,’ and ‘colonoscopy.’ Clinical trials and review articles were specifically identified, and their reference citation lists were searched for additional publications not identified in the database searches. Clinical trials and current clinical recommendations were assessed by using commonly applied criteria. Grade A evidence ranges from single or cumulatively large, well-designed randomized controlled trials (RCTs) with adequate statistical power to extremely positive ‘all vs. none’ outcomes among cohorts receiving alternative therapies and then evidence from smaller or single RCTs or meta-analyses. Grade B evidence ranges from high-quality studies of non-randomized cohorts with and without the index treatment, to high-quality case–control studies, and finally to one or more high-quality case series. Grade C evidence is that of expert opinion based on first principles, known physiology, or bench research but without access to clinical studies of the higher grades. Specific recommendations are made based on the evidence reviewed. MANAGEMENT APPROACH TO PATIENTS WITH ACUTE LOWER GASTROINTESTINAL BLEEDING

The triage and evaluation of patients with lower gastrointestinal haemorrhage remains variable and largely institution-specific (Figure 1). The dynamic nature of severe bleeding leads to limitations with all treatment strategies. To best manage bleeding, it is useful to stratify patients based on the severity of haemorrhage. For the purposes of management, patients with lower gastrointestinal haemorrhage can

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 1281–1298

REVIEW: THE MANAGEMENT OF LOWER GI BLEEDING

Clinical evaluation and resuscitation

Acute severe hematochezia History, physical examination and resuscitation Upper gastrointestinal source?

No

Colonoscopy

Source identified

Treat

Yes –

EGD

Source not identified, adequate exam

Active bleeding?

No Treat

+ Enteroscopy

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+

Treat

Source not identified, inadequate exam

Yes

Angiography +/– treatment +/– surgery

– Video capsule Endoscopy Figure 1. Algorithm for management of lower gastrointestinal bleeding (EGD, oesophagogastroduodenoscopy).

be broadly grouped into four overlapping categories. The first category includes 75–90% of patients and is characterized by minor bleeding that resolves with conservative therapy. The second category is comprised of patients with chronic intermittent bleeding. The aetiology of bleeding in this group is often elusive and probably best evaluated with colonoscopy. Angiography is especially limited in this group of patients because of the slow, sporadic nature of bleeding. The third group has episodes of severe, life-threatening bleeding with haemodynamic stability in between episodes. Because of the inconsistent nature of bleeding in this group, technetium (Tc)-99m red blood cell scans are useful prior to angiography. Alternatively, urgent colonoscopy (with or without colonic purge) may play a diagnostic and therapeutic role in this group. The fourth category comprises patients with continual active bleeding. These patients may be hypotensive and are best served by urgent angiography or even surgery.

The patient who presents with acute lower gastrointestinal haemorrhage may complain of passing bright red blood per rectum, dark blood with clots, or, less commonly, melaena. Pallor, fatigue, chest pain, palpitations, dyspnoea, tachypnoea, tachycardia, postural changes, or syncope are suggestive of haemodynamic compromise. Resuscitation should take place concurrently with the initial evaluation of the patient. Associated symptoms may provide clues to the source of the bleeding. Although lower gastrointestinal bleeding is usually painless, a history of abdominal pain, weight loss, fever, diarrhoea, vomiting, or partial small intestinal or colonic obstruction are important findings in the differential diagnosis of inflammatory, infectious, or malignant lesions. Similarly, the patient’s age, medical history and medication history [e.g. nonsteroidal anti-inflammatory drug (NSAID) use] may prove critical in elucidating the cause of bleeding. For example, colonic diverticula or angiodysplasia are more likely to be a cause of lower gastrointestinal bleeding in a person over 70 years of age (grade B evidence).2, 13, 14 Similarly, a history of pelvic radiation therapy (for prostatic or gynecologic malignancy) may point to radiation proctitis as a cause of rectal bleeding. This may occur anywhere from 9 months to 4 years after radiation therapy.15–17 Assessment should include careful cardiac, pulmonary, abdominal and rectal examinations. A digital rectal examination is helpful in excluding anorectal pathology as well as confirming the patient’s description of the appearance of the stool. In addition, approximately 40% of rectal carcinomas are palpable during a digital rectal examination.18 The presence of coagulopathy [international normalized ratio (INR) >1.5] or thrombocytopenia (75% of diverticula are found in the left colon. When colonoscopy is used to diagnose diverticular bleeding, the bleeding is observed to be from the left colon in 60% of cases.6 When angiography is used for diagnosis, the source is more likely to be from the right colon.51–53 This inconsistency

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may reflect differences in diagnostic sensitivity between the two tests, with angiography being less sensitive than colonoscopy for the diagnosis of less-severe diverticular bleeding.103 At colonoscopy, angiodysplasia are recognized by their characteristic appearance as red, fern-like flat lesions consisting of ectatic blood vessels that appear to radiate from a central feeding vessel; they may have a diameter of 2–10 mm. A pale mucosal halo may be seen around the lesion. When the colon is examined completely, the sensitivity of colonoscopy for detecting angiodysplasia exceeds 80% (grade B evidence).54–57 Colonic angiodysplasia are most common in the caecum and proximal ascending colon (54%), followed by the sigmoid colon (18%) and rectum (14%) (grade B evidence).57 Although angiodysplasia can be found throughout the small intestine, bleeding from angiodysplasia in the small bowel usually presents as irondeficiency anaemia with faecal occult blood and rarely as severe haematochezia. However, a poor bowel preparation may lead to incomplete evaluation of the colonic mucosa. Additionally, the use of a narcotic medication for sedation and analgesia may decrease the sensitivity of colonoscopy for detecting angiodysplasia by transiently decreasing mucosal blood flow. Administration of intravenous naloxone has been demonstrated to enhance the appearance of angiodysplasia during colonoscopy in patients who have received meperidine for sedation (grade B evidence).58 Unfortunately, the use of naloxone may result in discomfort for the patient, particularly when the procedure is prolonged by a therapeutic intervention. Other specific diagnostic features at colonoscopy include NSAID-related disease, ischaemic colitis and radiation colitis. Colonic ulcers caused by NSAIDs are often sharply demarcated, with a predilection for the terminal ileum and proximal colon, where pills may reside for a longer period of time than in other segments of the bowel. The development of diaphragm-like strictures is pathognomonic of NSAID injury.59–63 These strictures are typically multiple in number, with normal intervening mucosa. Non-occlusive colonic ischaemia most commonly involves the so-called watershed areas: splenic flexure, right colon, or rectosigmoid junction. In patients with ischaemic colitis, sigmoidoscopy reveals ulceration of the colonic mucosa, with the exception of the rectum in most cases. Histology reveals necrosis, non-acute and chronic inflammatory changes as seen in inflammatory bowel disease. Radiation


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proctitis typically demonstrates characteristic telangiectasias at colonoscopy. Several recent studies have shown that colonoscopy performed in an emergency (within 12 h of admission) is safe and effective (grade B evidence).4, 64–67 Early intervention, particularly for massive diverticular haemorrhage, may improve the diagnostic and therapeutic outcome and prevent the need for surgical intervention (grade B evidence).4, 65, 66 In addition, early colonoscopic evaluation may reduce the duration of hospitalization and lower overall costs per patient (grade B evidence).4, 65, 67–70 In fact, time to colonoscopy has been shown to be an independent predictor of the length of hospital stay. In a widespread spectrum of patients with lower gastrointestinal bleeding, the reduction in the length of hospital stay was shown to relate primarily to improved diagnostic yield rather than therapeutic intervention.69 There is no consensus regarding the need for a colonic purge prior to colonoscopy in a patient with active lower gastrointestinal bleeding (grade B and C evidence).3, 48, 64, 71, 72 If it is prescribed, extra effort of the nursing staff and patient is required to ensure a successful purge. A sulphate or polyethylene glycol (PEG)-based purge (e.g. GoLytely; Braintree Laboratories, Braintree, MA, USA) is administered orally. [For patients who are not able to drink a litre of purge solution every 30–45 min until the effluent clears (usually 5–8 L total), administration via an NG tube is recommended.] Approximately 30 min before the purge is started, 10 mg metoclopramide can be administered intravenously for its prokinetic and antiemetic properties. The dose can be repeated every 4–6 h if nausea results or if further purge is necessary. Occasionally, patients with chronic kidney disease may require dialysis after purging, and those with severe congestive heart failure may require diuresis. However, complication rates are low with PEG-based purges. Only an experienced endoscopist should perform colonoscopy in an actively bleeding patient with an unprepared colon, because the risk of colonic perforation may be increased in this setting (grade C evidence). Therapeutic colonoscopy. Suitable large-channel endoscopes and endoscopic accessories are necessary for effective diagnostic and therapeutic colonoscopy in the management of acute lower gastrointestinal bleeding. Applications of colonoscopic haemostasis techniques is based on identification of the same stigmata of

haemorrhage that have been identified in the upper gastrointestinal tract as predictors of recurrent upper gastrointestinal haemorrhage from ulcers. Insufficient numbers of patients with these stigmata in the setting of lower gastrointestinal bleeding have been reported to determine their usefulness in predicting outcome. For most actively bleeding lesions or those with adherent clots in the colon, except in association with haemangiomas and internal haemorrhoids, a combination of adrenaline injection and thermal coagulation (with a bipolar or heater probe) is recommended (grade C evidence). This recommendation is supported in part by demonstration of the safety of colonic endotherapy in experimental animals, even with the use of energy and pressure parameters far higher than those used in a clinical setting (grade C evidence).73 Use of either small or large probes, low-power settings (10–15 W), placement of the probe directly on the bleeding point, moderate tamponade pressure, and application of the probe until adequate whitening of the site (i.e. coagulation) is observed are recommended (grade C evidence).74 These guidelines are in contrast to those for gastroduodenal ulcers, for which large probes, firm tamponade, and long coagulation pulses are recommended (Table 2). Colonic diverticular bleeding is amenable to haemostasis with adrenaline injection therapy, bipolar coagulation, or both.65, 75–79 One study reported that patients with demonstrable diverticular bleeding who underwent endoscopic therapy with adrenaline injection, bipolar coagulation, or both, had no recurrence of bleeding during the 30-month follow-up period, when compared with a 53% rebleeding rate in patients who received conservative medical therapy alone (grade A evidence).65 Less frequently employed methods for controlling diverticular bleeding include endoscopic band ligation and placement of haemoclips (grade B and C evidence).80–85 Conventional endoscopic treatment of colonic angiodysplasia is performed with contact thermal probes (grade C evidence).86–88 To prevent brisk bleeding from angiodysplasia when contact electrocautery is performed, large angiodysplasia should be cauterized from the outer margin towards the centre to obliterate feeder vessels. Injection therapy with sclerosing agents, such as ethanolamine, has also been described for control of bleeding from colonic angiodysplasia but is not widely employed.89 Argon plasma coagulation, a noncontact method, has been used increasingly for the treatment of bleeding colonic angiodysplasia (grade B evidence).90–92


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Table 2. UCLA Center for Ulcer Research and Education (CURE) Hemostasis Research Group colonoscopic technical parameters for heater probe and bipolar electrocoagulation of bleeding colonic lesions4

Cause Bipolar coagulation probe size Power setting (W) Pulse duration (s) Heater probe size Power setting (J) Pressure Endpoint

Angiodysplasia, radiation colitis

Polyp stalk bleeding

Diverticulosis, delayed polypectomy bleeding, or ulcer bleed

Active bleeding

Nonbleeding visible vessel

Active bleeding*

Active bleeding*

Nonbleeding visible vessel

Adherent clot*

Large

Large or small 10–16 1 Large or small 10–15 Light White coagulum

Large

Large or small 12–16 1–2 Large 10–15 Moderate Bleeding stops

Large or small

Large or small

12–16 1–2 Large 10–15 Moderate Flatten visible vessel and coagulum

12–16 1–2 Large 10–15 Moderate Clot eliminated, underlyingstigma treated

10–16 1 Large 10–15 Light Bleeding stops

16–20 1–2 Large 15–20 Moderate Bleeding stops

* Consider injection with 1 : 10000 adrenaline prior to endoscopic coagulation with bipolar or heater probe.

Extra care must be taken when treating lesions in the caecum to avoid perforation.90 No comparative prospective studies have compared contact and noncontact endoscopic treatment of bleeding colonic angiodysplasia. Postpolypectomy bleeding is the most frequent complication of colonoscopy performed for polypectomy and accounts for approximately 2–8% of cases of acute lower gastrointestinal bleeding (grade B evidence).3, 7, 48 Massive bleeding that occurs at the time of polypectomy (early postpolypectomy bleeding) is typically arterial in nature and results from inadequate haemostasis of the blood vessel in the polyp stalk. Reduction in the risk of early postpolypectomy bleeding can be achieved by the use of blended, rather than pure cutting electrocautery currents in the polypectomy snare (grade C evidence). In the event of early postpolypectomy bleeding, haemostasis can generally be controlled by resnaring the stalk of the polyp and applying pressure (grade B and C evidence).93, 94 Delayed bleeding may occur up to 15 days after polypectomy, likely as a result of the sloughing of the eschar at the polypectomy site.93, 94 Delayed bleeding is usually self-limited and resolves with supportive care in more than 70% of cases. In contrast to early postpolypectomy bleeding, the frequency of delayed postpolypectomy bleeding as a cause of acute severe haematochezia is increasing, possibly because of the increasing use of a blended (rather than pure coagulation) current in the polypectomy snare (grade C evidence). For persistent or severe bleeding at a

polypectomy site, a variety of endoscopic techniques have proven safe and effective. These include loop ligation of the remaining polyp stalk, endoscopic band ligation, injection of adrenaline followed by thermal therapy, and application of endovascular clipping devices (grade B and C evidence).80, 95–101 The endoscopic management of lower gastrointestinal bleeding from radiation proctitis represents a specific management problem.24, 25, 32, 34, 35, 102–113 Endoscopic coagulation with a variety of devices has been reported to be effective for the control of radiationinduced bleeding. The technique is generally used to coagulate focal bleeding telangiectasias rather than the entire friable mucosa. Several treatment sessions are often required. Scarring and re-epithelization with more normal tissue tend to occur over time. Sixteen relevant studies have looked at the role of local endoscopic control of bleeding from radiation proctitis. Apart from one randomized controlled trial and one prospective series, the remaining 14 have been retrospective series or case reports. Although these case series all refer to the use of ablative therapy in lateradiation proctitis, different types of coagulation probes or lasers have been used: neodynium-YAG laser in eight, argon lasers in four, bipolar electrocautery in three and heater probes in two reports. The only randomized prospective study in this area compared endoscopic bipolar electrocoagulation and heater probe therapy in the treatment of chronic rectal bleeding from rectal telangiectasia (grade A evidence).114 Twenty-one patients were randomized to treatment with either a


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heater probe or a bipolar electrocoagulation probe, and treatment sessions were repeated with the same probe until the bleeding resolved. In both groups, there was a statistically significant decrease in severe bleeding, but a reduction in the number of units of blood transfused per cases was only seen in the heater-probe group. During follow-up endoscopy, there was resolution of the telangiectasias, scarring, or epithelial replacement in all cases in both groups. Patient interviews 6 months after treatment revealed that rectal bleeding, tenesmus, and general health had improved. Other nonrandomized studies that reported success with either heater probe or bipolar electrocautery used either higher or lower power settings than those used in the randomized study (grade B evidence).115, 116 The benefit of YAG laser in the management of bleeding related to radiation proctitis has also been reported in several retrospective series (grade B evidence).17, 27, 112, 117–120 Typically a power setting of 20–90 W has been reported. More recently, argon plasma coagulation has gained popularity for the management of lower gastrointestinal bleeding related to radiation proctitis. Argon plasma coagulation is a noncontact technique of electrocoagulation in which electrosurgical current is delivered to the tissue through argon gas; the depth of coagulation is limited (2–3 mm). The technique can be used to treat large surface areas of mucosa to achieve haemostasis easily, safely, and on an out-patient basis. For large bleeding surfaces, as in radiation-induced proctitis, several treatment sessions usually are required to achieve control of bleeding (grade B evidence).105–107, 113, 121–126 Short-term complications include anorectal pain, tenesmus and abdominal distention; long-term complications include anorectal pain, chronic rectal ulcer and rectal stricture. Some of the more recent developments in endoscopic haemostasis (e.g. endoscopic band ligation, endoscopic clipping and argon plasma coagulation) have been applied to the management of other sources of lower gastrointestinal bleeding (e.g. bleeding colonic varices, bleeding rectal Dieulafoy’s lesion), and are typically reported as single cases without any formal prospective or randomized evaluation (grade B and C evidence).127–129 For example, endoscopic band ligation has gained popularity as an alternative to surgical treatment for persistent or recurrent haemorrhoidal bleeding despite conservative therapy (grade B evidence).130 Yet, there have been no formal prospective

randomized trials that compare surgical and endoscopic management of rectal bleeding from haemorrhoids. Radiography The role of double-contrast barium enema (DCBE) in the evaluation of lower gastrointestinal bleeding is decreasing. In addition to the suboptimal quality of DCBE, patients often prefer colonoscopy. However, plain abdominal radiography should be performed prior to colonoscopy if bowel perforation or obstruction is suspected. Radiographic evidence of thumbprinting is indicative of transmural injury to the colon as a result of ischaemic or infectious colitis. There may be an evolving role for multidetector computed tomography (MDCT) for localizing acute lower gastrointestinal bleeding as well as predicting the treatment potential of arteriography and embolization. MDCT is highly sensitive and specific for the diagnosis of colonic angiodysplasia (grade A evidence).131 Bleeding rates 20%) or readmission for lower gastrointestinal bleeding within 1 week of discharge. Independent correlates of severe bleeding were an initial heart rate of >100/ min, systolic blood pressure of