Gastrointestinal Intervention

Comprehensive review of outcomes of endoscopic treatment of gastrointestinal bleeding

Additional article information

Abstract

Gastrointestinal bleeding (GIB) is a major cause of hospital admission and death. Endoscopic treatment is an important therapeutic modality for the treatment of GIB, and can involve injection therapy, thermal therapy, hemoclipping, and ligation therapy. In addition to hemostatic devices, new endoscopic techniques such as capsule endoscopy and balloon-assisted enteroscopy have been developed. The causes, therapeutic modalities, and outcomes of GIB differ according to bleeding source. This review comprehensively describes the outcomes of endoscopic treatment of GIB.

Keywords: Endoscopy, Gastrointestinal hemorrhage, Hemostasis, endoscopic, Review, Treatment outcome

Introduction

Gastrointestinal bleeding (GIB) is a common cause of hospital admission and mortality. Traditionally, GIB was classified into two types; upper GIB (UGIB) and lower GIB (LGIB).1 Knowledge about bleeding from the small bowel has been improved following advances in capsule endoscopy, balloon-assisted enteroscopy (BAE), and imaging modalities.2 The causes, incidence, treatment strategies, and outcomes of GIB differ according to the source of bleeding. Endoscopic treatment is the main treatment modality for GIB, and can include injection therapy, thermal therapy, and hemoclipping.3,4 In patients with variceal bleeding, endoscopic variceal ligation (EVL) and sclerotherapy are the main treatment options.5 In this article, we review the overall outcomes of endoscopic treatment of GIB.

Endoscopic Approach to Patients with GI Bleeding

In general, the approach to patients with UGIB or LGIB differs and should be tailored based on the patient’s symptoms and vital signs. In addition to endoscopy, computed tomography or angiography can be used to identify the bleeding source. A brief algorithm outlining the endoscopic approach to patients with GIB is shown in Fig. 1. Common clinical manifestations of UGIB are melena or hematemesis, while patients with LGIB usually present with hematochezia. However, in cases of right colonic bleeding, the stool is sometimes maroon in color, and patients with UGIB and hemodynamic instability may present with hematochezia. Esophagogastroduodenoscopy (EGD) is the gold standard for diagnosis and therapy of UGIB,3 but when the bleeding source cannot be identified with EGD, colonoscopy should be performed. Colonoscopy is the initial diagnostic procedure for LGIB. However, if a patient’s vital signs do not stabilize after initial resuscitation, angiography may be chosen as the initial diagnostic and therapeutic modality. Angiography is indicated in patients with active bleeding where either UGIB or LGIB is suspected, and it can be performed before or after endoscopy. In patients with continuing severe bleeding in whom the bleeding source has not been identified after EGD and colonoscopy, angiography may also be performed,6 noting that active bleeding of 0.5 to 1.0 mL/min is required for the bleeding source to be detectable by angiography. The possibility of small-bowel bleeding should be evaluated when the bleeding source cannot be identified by either EGD or colonoscopy.2

Figure F1
Approach to patients with gastrointestinal bleeding. EGD, esophagogastroduodenoscopy; BAE, balloon-assisted enteroscopy. *Angiography is indicated for patients in whom endoscopy is not possible due to hemodynamic instability.

Upper GI Bleeding

Nonvariceal upper GI bleeding

NVUGIB is a common cause of hospital admission and has a mortality rate ranging from 2% to 14%.1114 The mortality rate of NVUGIB has decreased with advances in endoscopic treatments and the use of proton pump inhibitors (PPIs).15,16 Many patients with NVUGIB are older and have significant comorbidities, which are associated with higher mortality.1720

Conventional endoscopic treatments for NVUGIB include injection therapy (epinephrine), thermal therapy (argon plasma coagulation [APC], bipolar electrocoagulation, or heated probe), and hemoclipping (Fig. 2). The primary rate of hemostasis has been reported to be as high as 90%.21,22 Thermal therapy and hemoclipping showed similar hemostatic efficacy.21,23 However primary hemostasis after injection therapy was inferior to that after thermal therapy, hemoclipping, or dual therapy that included injection therapy plus other hemostatic therapy.21,22 Therefore, injection therapy should not be used alone.24 Conventional hemoclipping is performed through the endoscope. Recently, over-the-scope clipping (OTSC) has been developed (Ovesco Endoscopy AG, Tübingen, Germany), and showed favorable hemostatic efficacy in refractory bleeding that could not be controlled with conventional methods.25 When OTSC was used as the first-line treatment, hemostasis was achieved in 92.4% of cases.26 More studies are needed to verify the hemostatic efficacy of OTSC.

Figure F2
Hemostasis using hemoclip. (A) A 5-mm-sized duodenal ulcer with blood oozing. (B) Hemostasis was achieved using hemoclips.

Hemostatic powder, which rapidly forms a mechanical barrier when it contacts liquid, is a novel endoscopic treatment method for GIB.27 Hemostatic powder can cover a broad area of bleeding and because it can be delivered by a non-contact method, its use is less technically demanding than other methods. Hemostatic powder has been reported to have favorable hemostatic efficacy in NVUGIB, LGIB, and malignant bleeding; e.g., initial hemostasis was achieved in 90% of patients.2831 However, a study showed that hemostatic powder was washed out in all patients by 72 hours after the initial treatment.32 Therefore, hemostatic powder should be considered as a bridging therapy for conventional treatment.

Not all NVUGIB requires hemostasis. The Forrest classification was developed to predict the rate of rebleeding of bleeding peptic ulcers that were not treated by endoscopic hemostasis, based on endoscopic findings.33 Details of the Forrest classification are shown in Table 1. Forrest Ia (Fig. 3), Ib, and IIa are defined as high-risk stigmata and endoscopic treatments are indicated.3436 The Forrest classification is easy to use and guides endoscopists in deciding whether endoscopic hemostasis should be performed. With the development of endoscopic hemostasis and the use of PPIs, the overall rebleeding rate after initial hemostasis has decreased to < 10%.37,38 Reported rebleeding rates differ according to the severity of the included cases and the method of endoscopic hemostasis. Although Forrest Ib is classified as active bleeding, the rebleeding rate of Forrest Ib was lower than that of Forrest IIa with/without endoscopic treatment. The rebleeding rate after endoscopic hemostasis was higher in Forrest IIa than in Forrest Ib (4.9% vs 11.3%, odds ratio 2.61, 95% confidence interval 1.05–6.52).39 This result was supported by another study that showed that the arterial blood flow rate detected by Doppler was lower in Forrest Ib compared with Forrest Ia and IIa.40

Figure F3
Hemostasis of duodenal ulcer bleeding (Forrest Ia). (A) A spurting duodenal ulcer bleeding. (B) Application of coagrasper. (C) Hemostasis was achieved.
Table 1

Prognostic scores

Risk stratification has contributed to effective management of patients with NVUGIB. Low-risk patients can be managed in an outpatient setting, which contributes to the reduction of unnecessary endoscopy during out of office hours and thereby saves costs.41 Major clinical outcomes including rebleeding, surgery, and mortality did not differ between low-risk patients who were discharged early and those who were admitted to hospital.4244

Several predictors have been developed and validated to predict the clinical outcomes of NVUGIB.45 The endpoints of the prediction scores are rebleeding rate, length of hospital stay, need for intervention, and mortality rate. The Rockall score was developed to predict mortality and rebleeding rates in patients with NVUGIB; it ranges from 0 to 11 points, and includes three clinical components (patient age, vital signs, comorbidities) and two endoscopic components (endoscopic diagnosis and evidence of bleeding on endoscopy) (Table 2).46 A higher score indicates increased risk of death. Mortality was 0.1% (1/744) in patients with a Rockall score ≤ 2.46 Low-risk patients are indicated for early discharge and outpatient management. A multicenter trial reported that risk stratification by the Rockall score shortened hospital stay compared with patients who were not stratified.47 The Rockall score has been compared with other prediction scores and validated in various studies.26,46,48 Because the full Rockall score can only be obtained after endoscopy, it cannot stratify the risk of patients before endoscopy. Therefore, a pre-endoscopic Rockall score (0–7), which includes only the clinical components, has been used to predict the clinical outcomes before endoscopy or in an emergency setting.49,50 The limitation of the Rockall score is its inadequate prediction of the need for endoscopic intervention.

Table 2

The Glasgow-Blatchford score (GBS) was developed to predict the need for intervention.51 Composite endpoints for intervention include blood transfusion, endoscopic hemostasis, or surgery. GBS consists of only clinical variables, including laboratory results (blood urea nitrogen, hemoglobin), vital signs (pulse rate, systolic blood pressure), symptoms or signs (melena or syncope), and patients’ comorbidities (hepatic disease, cardiac failure). The score ranges from 0 to 23 (Table 2). A high score predicts a higher likelihood of the composite endpoint and the area under the receiver operating characteristic curve was 0.92.51 A composite endpoint was not necessary in patients with GBS < 3, who comprised 10% to 20% of the included patients with NVUGIB.49,51 Because the GBS can be obtained without endoscopy, it has been compared with the pre-endoscopic Rockall score. GBS was superior to the pre-endoscopic Rockall score in predicting the composite endpoint,49,5254 and European guidelines recommend the use of the GBS score for risk stratification.4 The limitations of GBS are the complexity of its calculation and the imprecise definitions of hepatic disease and cardiac failure.

The AIMS65 score, a novel scoring system designed to predict mortality of patients with UGIB, consists of the five clinical parameters of albumin level, prothrombin time (international normalized ratio), altered mental status, systolic blood pressure and age.55 The AIMS65 score assigns 1 point for each parameter (Table 2). Albumin level and mental status reflect the general condition of patients. Because AIMS65 has fewer parameters than the GBS, it is easy to use and can be routinely calculated in the emergency department.56 Several studies have reported that AIMS65 was superior to GBS or Rockall score for predicting mortality.13,57,58 The usefulness of AIMS65 should be validated in future studies.

Timing of endoscopy

Current guidelines recommend that EGD should be performed within 24 hours of hospital presentation because it is associated with reduced mortality and hospital stay.4,23,59,60 Several studies have investigated the clinical outcomes of urgent endoscopy, defined as occurring within < 6, < 8, or < 12 hours. These clinical outcomes are controversial. Although urgent endoscopy was associated with increased detection of high-risk stigmata, it did not improve clinical outcomes such as death and rebleeding.44,52,60,61 However, these studies did not stratify patients by severity of disease. One retrospective study reported that urgent endoscopy within 13 hours reduced the mortality rate.62 One recent study reported that in high-risk patients urgent endoscopy (within 6 hours) was an independent predictor of lower mortality compared with that of elective endoscopy (6–48 hours).14 Population-based studies have reported that urgent endoscopy could not reduce the mortality rate.63,64 In patients with hemodynamic instability, endoscopy within 6 hours was associated with higher mortality compared with endoscopy after 6 to 24 hours.64 Urgent endoscopy results in a lack of sufficient time for fluid resuscitation and management of underlying comorbidities. However, the results of these studies should be interpreted with caution. To date, there has been no well-designed randomized controlled trial to investigate the efficacy of urgent endoscopy. Initial resuscitation should proceed, but EGD should not be delayed in patients who are suspected of having continuous active bleeding. Therefore, designing a prospective randomized controlled trial in patients with hemodynamic instability is illogical and unethical, and the usefulness of urgent endoscopy remains to be confirmed. European guidelines recommend urgent endoscopy (< 12 hours) in patients with hemodynamic instability that persists despite initial resuscitation.4

Variceal upper GI bleeding

VUGIB is one of the most severe complications of liver cirrhosis. VUGIB accounts for 10% to 20% of cases of UGIB.65 The mortality rate of VUGIB is reported to be as high as 20%, higher than that of NVUGIB.66 Advanced liver cirrhosis is related to higher mortality.67 Guidelines recommend that endoscopy should be performed as soon as possible (within 12 hours).67 Initial hemostasis including a vasoactive agent with or without endoscopic treatment was reported to control VUGIB in up to 90% of patients.66,68 Endoscopic treatments include EVL and sclerotherapy. EVL is the main treatment option for esophageal varix, but because the gastric mucosa is thicker than the esophageal mucosa, EVL has a high rate of failure for the treatment of gastric varix.5 Therefore, sclerotherapy is primarily indicated for the treatment of gastric varix, while EVL is selectively indicated for gastroesophageal varix that is located mainly in the lesser curvature or for isolated gastric varix.5 With the improvement of treatment options for VUGIB, the mortality rate has decreased to < 20%.69 Failure of hemostasis is strongly related to mortality from VUGIB.66 In addition to conventional treatments, esophageal stents and hemostatic powder can be used to treat VUGIB.70 A recent study reported that an esophageal stent controlled refractory VUGIB in 85% of patients.71 Initial hemostasis was achieved in 100% (38/38) of patients using hemostatic powder.72 The treatment efficacy and safety of esophageal stents and hemostatic powder for VUGIB should be validated in future studies.

Lower GI Bleeding

LGIB is defined as bleeding from a source distal to the ileocecal valve.73 LGIB accounts for 20% to 25% of major GIB.1 The most common cause of LGIB is diverticular disease, which accounts for up to 50%. Diverticular bleeding is usually self-limiting and only 20% to 30% of patients need endoscopic treatment.74,75 The other causes of LGIB are vascular ectasia, ischemic colitis, malignancy, and anorectal disease. Colonoscopy is the standard diagnostic procedure, especially for high-risk patients, for whom it is recommended within 24 hours of hospital presentation.76 Risk factors for poor outcomes include hemodynamic instability, ongoing bleeding, comorbidities, and old age. The mortality of LGIB was reported to be < 5%.77 The techniques for endoscopic treatment of LGIB are similar to those for UGIB (Fig. 4).78 Post-polypectomy bleeding (PPB) is the most common type of iatrogenic LGIB and accounts for 2% to 8% of LGIB.76 PPB is categorized as immediate bleeding or delayed bleeding occurring from hours to several days after polypectomy. The rates of immediate and delayed PPB are similar, and the rate of PPB has been reported to be 0.3% to 3.3%7981; a meta-analysis suggested that the rate of PPB was about 1.5%.82 Causes of delayed bleeding are dislodgement of eschar or excavation of necrotic tissue by electrothermal injury (Fig. 5). Hemoclipping is preferred for the treatment of PPB to minimize thermal injury.76 The results of endoscopic treatment of PPB are favorable; initial endoscopic hemostasis was achieved in over 95% of patients.80,83

Figure F4
Hemostasis using argon plasma coagulation (APC). (A) Blood oozing from an angiodysplasia at ascending colon. (B) Hemostasis was achieved after APC application.
Figure F5
Protrusion of necrotic tissue by electrothermal injury.

Small-Bowel Bleeding

Small-bowel bleeding is defined as bleeding from a source distal to the ligament of Treitz and proximal to the ileocecal valve.2 Small-bowel bleeding accounts for 5% to 10% of GIB, and its mortality has been reported to be < 10%.84 Because the small bowel has been regarded as inaccessible,85 small-bowel bleeding was previously defined as “obscure GIB.”73 However, advancements in capsule endoscopy and BAE have enabled the diagnosis and treatment of small-bowel bleeding.85 Angioectasia is the most common cause of small-bowel bleeding. Other causes include inflammatory bowel disease, malignancy, diverticular disease, and nonsteroidal anti-inflammatory drug-induced ulcers.2 However, the types of small-bowel bleeding differ between Western and Eastern countries.86 A systemic review of BAE suggested that inflammatory lesions were the most common findings (40%) in small-bowel bleeding in Eastern countries.86 Capsule endoscopy is recommended as the follow-up diagnostic modality when the bleeding source cannot be identified by EGD and colonoscopy. The diagnostic yield of capsule endoscopy for overt obscure GI bleeding was reported to be up to 50% to 60%.87 Capsule retention is the most common complication of capsule endoscopy.88 A meta-analysis reported that the rate of capsule retention in patients with suspected small-bowel bleeding was 2.1%.89 When capsule retention causes obstructive symptoms, endoscopic or surgical extraction should be performed. BAE enables therapeutic procedures for small-bowel bleeding.85 BAE is indicated when the bleeding source has been identified by capsule endoscopy. Treatment success was reported to be 43% to 84%.90 However, a review suggested that the rebleeding rate for small-bowel bleeding was comparable in patients who did or did not receive endoscopic treatment (42.7% vs 49.2%, respectively).91 These results should be interpreted with caution. Most studies analyzed in that review used APC, which may not be as effective as predicted. Results for other endoscopic hemostasis techniques such as hemoclipping (Fig. 6), heater probe or combination therapy are anticipated. Therefore, it is not possible to draw conclusions about the treatment efficacy for small-bowel bleeding. Although the indications for BAE have been widened recently, more studies regarding its indications and therapeutic outcomes are needed.

Figure F6
Hemostasis of small-bowel bleeding using hemoclip. (A) Blood oozing from an angiodysplasia at jejunum. (B) Hemostasis was achieved after hemoclipping.

Conclusion

The endoscopic treatment of GIB has evolved over time with new endoscopic devices and modalities contributing to improve the outcome of GIB. NVUGIB is the most common cause of GIB, and development of hemostatic devices and prognostic scores have been mainly focused on NVUGIB. Guidelines recommend that endoscopy be performed within 24 hours of hospital presentation in patients with NVUGIB. Of the available hemostatic devices and agents, injection therapy should not be used alone. In VUGIB, EVL and sclerotherapy are indicated. More studies are needed to verify the usefulness of urgent endoscopy. The mortality of GIB is less than 10%, although VUGIB has a higher mortality rate than other causes of GIB. Multiple comorbidities and old age are risk factors for mortality in GIB.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Article information

Gastrointestinal Intervention.Oct 31, 2018; 7(3): 123-130.
Published online 2018-10-31. doi:  10.18528/gii180022
1Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
2Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
*Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. E-mail address: jinsu23@naver.com (J. Kim). ORCID: https://orcid.org/0000-0002-3397-3189
Received June 20, 2018; Accepted August 28, 2018.
Articles from Gastrointestinal Intervention are provided here courtesy of Gastrointestinal Intervention

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Figure 1


Approach to patients with gastrointestinal bleeding. EGD, esophagogastroduodenoscopy; BAE, balloon-assisted enteroscopy. *Angiography is indicated for patients in whom endoscopy is not possible due to hemodynamic instability.

Figure 2


Hemostasis using hemoclip. (A) A 5-mm-sized duodenal ulcer with blood oozing. (B) Hemostasis was achieved using hemoclips.

Figure 3


Hemostasis of duodenal ulcer bleeding (Forrest Ia). (A) A spurting duodenal ulcer bleeding. (B) Application of coagrasper. (C) Hemostasis was achieved.

Figure 4


Hemostasis using argon plasma coagulation (APC). (A) Blood oozing from an angiodysplasia at ascending colon. (B) Hemostasis was achieved after APC application.

Figure 5


Protrusion of necrotic tissue by electrothermal injury.

Figure 6


Hemostasis of small-bowel bleeding using hemoclip. (A) Blood oozing from an angiodysplasia at jejunum. (B) Hemostasis was achieved after hemoclipping.

Table 1

Forrest Classification

Stage Definition Rebleeding rate (%) Rebleeding rate after hemostasis (%)
Active bleeding
 Stage Ia Blood spurting 80–90 15–30
 Stage Ib Oozing 10–28 0–5
Sign of recent hemorrhage
 Stage IIa Visible vessel 40–60 15–30
 Stage IIb Adherent clot 10–20 0–5
 Stage IIc Black spot in ulcer crater 7–10
No hemorrhage
 Stage III Clean base ulcer 3–5

Table 2

Details of the Rockall Score, Glosgow-Blatchford Score, and AIMS65 Score

Rockall score Glasgow-Blatchford score AIMS65 score



Component Point Component Point Component Point
Age (yr) BUN (mg/dL) Albumin < 3.0 mg/dL 1
 < 60 0  18.2–22.4 2 PT INR > 1.5 1
 61–79 1  22.4–28.0 3 Altered mental status 1
 80 2  28.0–70.0 4 SBP < 90 mmHg 1
Shock  ≥ 70.0 6 Age > 65 yr 1
 No shock 0 Hb, men (g/dL)
 Pulse > 100/min, SBP > 100 mmHg 1  12.0–13.0 1
 SBP < 100 mmHg 2  10.0–12.0 3
Comorbidity  <10.0 6
 No major comorbidity 0 Hb, women (g/dL)
 CHF, IHD, or major comorbidity 2  10.0–12.0 1
 Renal failure, liver failure, or metastatic cancer 3  < 10.0 6
Endoscopic diagnosis SBP (mmHg)
 Mallory-Weiss tear or no lesion and no stigmata 0  100–109 1
 All other diagnosis 1  90–99 2
 Malignancy 2  < 90 3
Evidence of bleeding Other clinical parameter
 No stigmata or dark spot on ulcer 0  Heart rate ≥ 100/min 1
 Blood in the GI tract, adherent clot, visible or spurting vessel 2  Melena 1
 Syncope 1
 Liver disease 2
 Cardiac failure 2

BUN, blood urea nitrogen; PT INR, prothrombin time international normalized ratio; SBP, systolic blood pressure; Hb, hemoglobin; CHF, congestive heart failure; IHD, ischemic heart disease; GI, gastrointestinal.