The ACG Clinical Practice Guideline on UpperGastrointestinal and Ulcer Bleeding Review

Abstract and Introduction

Introduction

Gastrointestinal bleeding (GIB) is a common cause of hospitalization. Upper gastrointestinal bleeding (UGIB) is a serious condition defined as bleeding that originates in the esophagus, stomach, or duodenum. Eighty percent of patients with UGIB seen in the emergency department (ED) require admission to the hospital. The 2021 American College of Gastroenterology Clinical Guidelines provides recommendations on risk stratification, preendoscopic therapy, endoscopy timing and techniques, and recurrent UGIB.[1] The guideline offers 16 statements, which we consolidated into five recommendations for this guideline update for the generalist. Based on the outcome of further bleeding, each statement received a designation of strong or conditional to characterize the level of confidence in outcome attainment. Strong recommendations begin with "we recommend" in the guideline, whereas conditional recommendations begin with "we suggest." The certainty with each recommendation was assessed as high, moderate, or low based on confidence in the effect estimate. We chose these recommendations as those that reinforced or would significantly change the clinical practice of practitioners taking care of patients with GIB. We organized these recommendations into three categories: risk stratification, preendoscopic therapy/endoscopic timing, and postendoscopic care.

Risk Stratification

Key point 1: We Suggest Discharging Very-low-risk Patients Presenting to the ED With UGIB (Conditional Recommendation, Very-low-quality Evidence)

The goal of risk stratification tools in patients with UGIB is to triage patients requiring inpatient versus outpatient evaluation and treatment. The Glasgow-Blatchford Bleeding Score and the Shung machine learning model are relevant risk stratification tools with a sensitivity of 99% and a false-negative rate of 1% for hospital intervention or death outcomes. As such, patients with a Glasgow-Blatchford Bleeding Score of 0 to 1 are at very low risk for worse effects because of their UGIB. The benefit of using these tools to inform decisions regarding patient care is primarily economic, and few studies to date have evaluated the actual risks of discharging very-low-risk patients for management outpatient. At present, discharge from the hospital for a patient with UGIB is not routine practice unless the patient lives near medical care and can see Gastroenterology in 3 days.

Preendoscopic Therapy/Endoscopy Timing

Key point 2: We Suggest a Restrictive red Blood Cell Transfusion Strategy With a Hemoglobin Transfusion Threshold of 7 g/dL for Patients With UGIB (Conditional Recommendation, Low-quality Evidence)

In clinical practice, most patients receive blood transfusions to maintain hemoglobin levels >7 unless they undergo cardiac or orthopedic surgeries. For these patients and those with underlying cardiac disease, the hemoglobin transfusion threshold often is 8 g/dL. Liberal transfusion in this setting does not improve outcomes and increases the risk for complications (eg, transfusion- associated circulatory overload, acute kidney injury).

Key point 3: We Suggest That Patients Admitted to the Hospital for UGIB Undergo Endoscopy Within 24 Hours of Presentation (Conditional Recommendation, Very-low-quality Evidence)

Urgent endoscopy within 6 hours of GI consultation did not demonstrate a decrease in further bleeding, mortality, duration of hospitalization, or transfusion needs compared with endoscopy within 6 to 24 hours of GI consultation.[2] Hemodynamically stable patients without severe preexisting conditions and low-risk clinical features have lower inpatient mortality if they underwent endoscopy within 24 hours from admission (adjusted odds ratio 0.59, 95% confidence interval 0.33–1.05), although these data are not derived from observational studies or randomized controlled trials (RCTs). Clinically unstable patients with severe comorbidities (eg, cirrhosis) had increased mortality with early (<6 hours) or late (>24 hours) endoscopy.[3] Patients with UGIB and hypotensive shock should receive urgent endoscopy or interventional radiology evaluation.[2]

Postendoscopic Care

Key point 4: We Recommend High-dose Proton Pump Inhibitor (PPI) Therapy Given Continuously or Intermittently for 3 Days After Successful Endoscopic Hemostatic Treatment of a Bleeding Ulcer (Strong Recommendation, Moderate- to High-quality Evidence)

Acid-reducing therapy with high-dose PPIs is a critical component of UGI bleed management to reduce the risk of surgery or further bleeding.[4] High-dose PPI, ≥80 mg/day, should be administered continuously or intermittently for 3 days based on factors such as ease of administration or cost since there is no difference in treatment effect. The optimal dosage for intermittent administration is uncertain, but a regimen of 80 mg bolus followed by 40 mg 2 to 4 times daily is recommended.[1] High-risk patients receiving endoscopic hemostatic therapy should receive high-dose PPI for 3 days followed by 2 weeks of twice-daily oral PPI.[5] Although not directly addressed in these guidelines, patients with a visible vessel on endoscopy also should receive high-dose PPI for 3 days because of a high risk for rebleeding. No evidence is available to support an additional benefit from extended PPI therapy for this patient population.

Key point 5: We Recommend That Patients With Recurrent Bleeds After Successful Endoscopic Therapy Should First Undergo Repeat Endoscopy Rather Than Surgery or Transcatheter Arterial Embolization (TAE) (Conditional Recommendation With Low-Quality Evidence and Very-low-quality Evidence, Respectively), Whereas Those who Fail Endoscopic Therapy Receive Treatment With TAE Rather Than Surgery (Conditional Recommendation, Very-low-quality Evidence)

A recurrent bleed is bleeding after achieving successful hemostasis during endoscopy; meanwhile, endoscopic failure is not achieving hemostasis during index endoscopy. Repeat endoscopy prevented further bleeding in 75% of patients with recurrent bleeding. Although the bleeding rates were higher after repeat endoscopy as compared with surgery (22.9% vs 6.8%), there was a much lower complication rate (14.6% vs 36.4%) and no statistically significant difference in mortality (10.4% vs 18.2%).[6,7] No direct trials exist to compare TAE with endoscopy in the setting of a recurrence. TAE is recommended as a first-line therapy over surgery in those who continue to bleed despite appropriate endoscopic treatment, citing decreased complication rate and hospital stay with no increased mortality.

Critique and Limitations

A diverse panel of clinicians, researchers, and methodologists used the Grading of Recommendations Assessment, Development, and Evaluations approach to draft recommendations for this guideline. All of the panel members disclosed conflicts of interest according to American College of Gastroenterology policies. The inclusion of many RCTs, observational studies, and meta-analyses provides for good generalizability of the guidelines published by this group.

The guidelines authors highlight that low- to very-low-quality evidence forms the basis for most recommendations. This evidence gap is because it is not feasible to perform RCTs of specific interventions that are standard of care for UGIB management (eg, preendoscopic PPI therapy).[8] Moreover, these guidelines do not address interventions affecting mortality from underpowered studies to assess this outcome.

Discussion

Future research could improve the reliability and accessibility of risk assessment tools available to physicians, particularly in the electronic health record, which could help to screen low-risk patients and provide guidance for those who may be candidates for discharge from the ED. Preendoscopic management remains poorly studied, particularly regarding blood pressure and hemoglobin targets and the timing of endoscopy. Although preendoscopic PPI remains the standard of care, a large study could help determine its overall clinical benefit.

Conclusions

UGIB is a common condition managed by generalists in inpatient and outpatient settings. The appropriate care of patients with GIB includes appropriate risk stratification, preendoscopic therapy optimization with PPIs and transfusion, and the use of advanced approaches if bleeding occurs postendoscopy.

References

1. Laine L, Barkun AN, Saltzman JR, et al. ACG clinical guideline: upper gastrointestinal and ulcer bleeding. Am J Gastroenterol 2021;116:899–917.

2. Lau JYW, Yu Y, Tang RSY, et al. Timing of endoscopy for acute upper gastrointestinal bleeding. N Engl J Med 2020;382:1299–1308.

3. Laursen SB, Leontiadis GI, Stanley AJ, et al. Relationship between timing of endoscopy and mortality in patients with peptic ulcer bleeding: a nationwide cohort study. Gastrointest Endosc 2017;85:936–944.e3.

4. Chaimoff C, Creter D, Djaldetti M. The effect of pH on platelet and coagulation factor activities. Am J Surg 1978;136:257–259.

5. Cheng HC, Wu CT, Chang WL, et al. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut 2014;63:1864–1872.

6. Lau JY, Sung JJ, Lam YH, et al. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. N Engl J Med 1999;340:751–756.

7. Tarasconi A, Baiocchi GL, Pattonieri V, et al. Transcatheter arterial embolization versus surgery for refractory non-variceal upper gastrointestinal bleeding: a meta-analysis. World J Emerg Surg 2019;14:3.

8. Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007;356:1631–1640.