2021 American College of Gastroenterology Guidelines: Upper Gastrointestinal and Ulcer Bleeding

The American College of Gastroenterology (ACG) released clinical guidelines on upper gastrointestinal (GI) and ulcer bleeding using an evidence-based approach, which was recently published in The American Journal of Gastroenterology.

The researchers used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to develop 16 clinical recommendations for the management of patients with overt upper gastrointestinal bleeding (UGIB).

In the United States (US), GI bleeding is the most common GI diagnosis requiring hospitalization. GI bleeding accounts for more than 500,000 hospital admissions annually. According to the authors, “Nearly 80% of patients visiting emergency departments for UGIB are admitted to the hospital with that principal diagnosis.”

Risk Stratification

The ACG committee recommends emergency department assessment to identify very-low-risk UGIB patients. Patients who are classified as very-low-risk (eg, Glassgow-Blatchford score = 0-1) should not be admitted to the hospital. These patients should be discharged with outpatient management. This will most likely result in reduction of hospitalizations and costs.

Red Blood Cell Transfusion

For patients hospitalized with UGIB, it is recommended that they are transfused when hemoglobin falls below 7 g/dL to reduce further bleeding and death. Patients with UGIB and pre-existing cardiovascular disease may be transfused at higher hemoglobin levels. In these patients, a threshold of 8 g/dL is considered reasonable.

Pre-Endoscopic Medical Therapy

Erythromycin infusion is suggested before endoscopy in patients with UGIB. The researchers note that infusions of 250 mg of erythromycin 20-90 minutes prior to endoscopy may reduce the need for repeat endoscopy and length of hospitalization. However, erythromycin is not documented to reduce further bleeding.

Current evidence suggests that pre-endoscopic proton pump inhibitor (PPI) therapy yields no benefit for clinical outcomes in patients with UGIB. Thus, the panel is unable to provide a full recommendation for or against this therapy.

Endoscopy for UGIB

Endoscopy is suggested for UGIB patients admitted to or under observation in hospital within 24 hours of presentation. This recommendation is based on evidence of potential economic benefit and possible clinical benefit in mortality and need for surgery in observational studies.

Endoscopic therapy is recommended in patients with UGIB due to ulcers with active spurting, active oozing, and nonbleeding visible vessels. The authors note that, “Endoscopic therapy provides important clinical benefit in patients with UGIB due to ulcers with high-risk findings of active bleeding and nonbleeding visible vessels.”

A recommendation could not be reached for or against endoscopic therapy in UGIB patients with adherent clots. The panel attributed this indecisiveness to limited studies, inconsistent results, and the inability to identify the causes of heterogeneity among trials. Based on available evidence, the researchers believed either course of management could be considered acceptable.

For patients with UGIB due to ulcers, the committee recommends endoscopic hemostatic therapy with bipolar electrocoagulation, heater probe, or injection of absolute ethanol. Current evidence strongly supports the clinical benefit of thermal contact devices (bipolar electrocoagulation and heater probe) and absolute ethanol injection.

Despite limited evidence, the researchers support the use of clips, argon plasma coagulation (APC), and soft monopolar electrocoagulation for patients with UGIB due to ulcers.

It is recommended that epinephrine injection should not be used alone in this patient population. Rather, epinephrine injection should be used in combination with another hemostatic modality. Previous research shows that epinephrine plus a second modality is superior for reducing further bleeding compared with epinephrine monotherapy.

Hemostatic therapy with hemostatic powder spray TC-325 is suggested for patients with actively bleeding ulcers. However, the current high cost of hemostatic powder spray TC-325 may subsequently limit its use as the initial endoscopic therapy for this indication in the US.

Over-the-scope clips as a hemostatic therapy appear useful for patients with recurrent ulcer bleeding after previous successful endoscopic hemostasis. The application of over-the-scope clips, which is performed similarly to endoscopic ligation, were described by the authors: “A cap device with a single clip is placed on the distal tip of the endoscope, the bleeding lesion is approached enface, the cap is placed over the lesion encircling it, the lesion is suctioned into the cap, and the clip is released.”

Antisecretory Therapy After Endoscopic Hemostatic Therapy

After endoscopic hemostasis of a bleeding ulcer, high-dose PPI therapy (>80 mg daily for >3 days) is recommended continuously or intermittently for 3 days. The panel asserts that high-dose PPI therapy given continuously or intermittently after endoscopic hemostatic therapy reduces further bleeding as well as mortality.  

Compared with once-daily PPI use, twice-daily PPI therapy from days 4-14 after index endoscopy reduces further bleeding in high-risk patients who underwent endoscopic therapy followed by 3 days of high-dose PPI therapy.

Recurrent Ulcer Bleeding

In patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer, repeat endoscopy and endoscopic therapy is suggested rather than surgery or transcatheter arterial embolization (TAE). The authors report that, “In patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer, repeat endoscopy and endoscopic therapy successfully prevents further bleeding in approximately three-quarters of patients, with fewer complications than surgical therapy.”

Failure of Endoscopic Hemostatic Therapy

In patients who fail endoscopic therapy for bleeding ulcers, TAE is suggested. TAE shows a reduction in complications and hospital stay with no difference in mortality compared with surgery, but is noted to have a higher rate of further bleeding.

Future Directions

The committee acknowledges that the majority of evidence supporting these guideline statements is of low or very low quality. Thus, many opportunities exist to improve upon the management of patients with UGIB. Suggested topics to investigate in the future are the following: 1) improvements in the performance of risk assessment instruments and implementation in electronic health records to allow timely decision support 2) enhancement of initial, pre-endoscopic management 3) refinements in hemostatic therapy.

Table 1. Guideline Statements from the American College of Gastroenterology for Upper Gastrointestinal and Ulcer Bleeding

Category	Guideline
Risk Stratification	1) We suggest that patients presenting to the emergency department with upper gastrointestinal bleeding (UGIB) who are classified as very low risk, defined as a risk assessment score with <1% false negative rate for the outcome of hospital-based intervention or death (e.g., Glasgow-Blatchford score = 0–1), be discharged with outpatient follow-up rather than admitted to hospital (conditional recommendation, very-low-quality evidence).
Red Blood Cell Transfusion	2) We suggest a restrictive policy of red blood cell transfusion with a threshold for transfusion at a hemoglobin of 7 g/dL for patients with UGIB (conditional recommendation, low-quality evidence).
Pre-endoscopic Medical Therapy	We suggest an infusion of erythromycin before endoscopy in patients with UGIB (conditional recommendation, very-low-quality evidence). 4) We could not reach a recommendation for or against pre-endoscopic PPI therapy for patients with UGIB.
Endoscopy for UGIB	5) We suggest that patients admitted to or under observation in hospital for UGIB undergo endoscopy within 24 hours of presentation (conditional recommendation, very-low-quality evidence). 6) We recommend endoscopic therapy in patients with UGIB due to ulcers with active spurting, active oozing, and nonbleeding visible vessels (strong recommendation, moderate-quality evidence). 7) We could not reach a recommendation for or against endoscopic therapy in patients with UGIB due to ulcers with adherent clot resistant to vigorous irrigation. 8) We recommend endoscopic hemostatic therapy with bipolar electrocoagulation, heater probe, or injection of absolute ethanol for patients with UGIB due to ulcers (strong recommendation, moderate-quality evidence). 9) We suggest endoscopic hemostatic therapy with clips, APC, or soft monopolar electrocoagulation for patients with UGIB due to ulcers (conditional recommendation, very-low- to low-quality evidence). 10) We recommend that epinephrine injection not be used alone for patients with UGIB due to ulcers but rather in combination with another hemostatic modality (strong recommendation, very-low- to moderate-quality evidence). 11) We suggest endoscopic hemostatic therapy with hemostatic powder spray TC-325 for patients with actively bleeding ulcers (conditional recommendation, very-low-quality evidence). 12) We suggest over-the-scope clips as a hemostatic therapy for patients who develop recurrent bleeding due to ulcers after previous successful endoscopic hemostasis (conditional recommendation, low-quality evidence).
Antisecratory Therapy After Endoscopic Hemostatic Therapy for Bleeding Ulcers	13) We recommend high-dose PPI therapy given continuously or intermittently for 3 days after successful endoscopic hemostatic therapy of a bleeding ulcer (strong recommendation, moderate- to high-quality evidence). 14) We suggest that high-risk patients with UGIB due to ulcers who received endoscopic hemostatic therapy followed by short-term high-dose PPI therapy in hospital continue on twice-daily PPI therapy until 2 weeks after index endoscopy (conditional recommendation, low-quality evidence).
Recurrent Ulcer Bleeding After Successful Endoscopic Hemostatic Therapy	15) We suggest that patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer undergo repeat endoscopy and endoscopic therapy rather than undergo surgery or TAE (conditional recommendation, low-quality evidence for comparison with surgery, very-low-quality evidence for comparison with TAE).
Failure of Endoscopic Hemostatic Therapy for Bleeding Ulcers	16) We suggest patients with bleeding ulcers who have failed endoscopic therapy next be treated with TAE (conditional recommendation, very-low-quality evidence).

Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG clinical guideline: upper gastrointestinal and ulcer bleeding. Am J Gastroenterol. Published online May 1, 2021. doi: 10.14309/ajg.0000000000001245