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Journal of the American Academy of Physician Assistants:
doi: 10.1097/01.JAA.0000430343.95024.5a
Pharmacology Consult

Which drugs are indicated for upper GI bleeding?

DeDea, Larissa PharmD, BCPS, PA-C

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Larissa DeDea is a clinical pharmacist with Northern Arizona Healthcare in Flagstaff. In addition to being board-certified in pharmacotherapy, she is a graduate of the Yale University PA program.

Pharmacologic therapy of upper GI bleeding depends on the cause and severity of the bleeding. The two most common causes of upper GI bleeding are peptic ulcers and gastroesophageal varices. PAs should be familiar with the basic differences in pharmacologic treatment between variceal and nonvariceal bleeding, and recognize that drugs are primarily used as an adjunct to endoscopic therapy.

For all patients with GI bleeding, assess hemodynamic status and implement appropriate resuscitative measures. Bolus infusions of isotonic crystalloids are usually considered first-line therapy. Consider transfusions for patients with hemodynamic instability despite adequate crystalloid therapy or for patients with hemoglobin levels less than 7 mg/dL. The hemoglobin threshold may be higher for older patients or those with coronary artery disease. However, a recent trial showed that a restrictive transfusion strategy (transfusing when the hemoglobin level was below 7 mg/dL compared to below 9 mg/dL) improved survival in certain patients with upper GI bleeding, particularly those with cirrhosis and Child-Pugh class A or B disease.1 Consider fresh frozen plasma for reversing coagulopathy, or platelets for thrombocytopenia.

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NONVARICEAL UPPER GI BLEEDING

The American College of Gastroenterology's 2012 guidelines for managing patients with ulcer bleeding recommend risk stratification and treatment based on endoscopic findings.2 Patients with active bleeding and those at high risk of recurrent bleeding (defined as a nonbleeding visible vessel or adherent clot) should receive high-dose, continuous infusion therapy with a proton pump inhibitor (PPI) such as pantoprazole or esomeprazole (80 mg bolus followed by a continuous infusion of 8 mg/hour).

After successful endoscopic therapy, continuous-infusion PPIs have been shown to reduce rebleeding rates, need for surgery, and mortality. Treatment should be continued for 72 hours after endoscopy; patients who have no signs of recurrent bleeding can then be switched to a standard dose oral PPI.

If endoscopy is not immediately available, consider IV therapy with PPI until endoscopy can be performed. Although PPIs started before endoscopy reduce the proportion of patients with stigmata of recent hemorrhage, a meta-analysis of pre-endoscopic PPIs did not show any improvement in mortality, rebleeding, or need for surgery.

Continuous-infusion PPIs should be discontinued after endoscopy in patients at low risk for rebleeding. Patients with ulcers that have flat pigmented spots or clean bases should receive standard doses of once-daily oral PPIs. Twice-daily oral PPIs may be needed for patients with severe or complicated esophagitis due to low healing rates.3

Octreotide should not be routinely used to manage ulcer-induced bleeding, as no convincing evidence supports this use. Most studies showing benefit with octreotide were in the setting of failed endoscopic treatment or before the routine use of PPIs. Octreotide can be considered if endoscopy is unavailable or to help stabilize patients before endoscopy.

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VARICEAL UPPER GI BLEEDING IN CIRRHOSIS

The American Association for the Study of Liver Diseases has practice guidelines for managing variceal hemorrhage in patients with cirrhosis.4 Pharmacologic therapy should be initiated even before endoscopy when variceal bleeding is suspected. Drug therapy includes antibiotics and somatostatin analogues such as octreotide. Because the pathophysiology of variceal bleeding is unrelated to acid production, PPIs have no role in treatment.

Octreotide helps control variceal bleeding by decreasing splanchnic blood flow. The dose is a 50 mcg bolus, followed by an infusion of 50 mcg/hour for about 5 days (the period of time in which the risk of rebleeding is highest). Although octreotide monotherapy has not been shown to improve mortality, it does reduce the need for transfusions. The preferred approach is endoscopic therapy plus octreotide, as this improves the initial control of bleeding and hemostasis at five days.

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ANTIBIOTIC THERAPY

Prophylactic antibiotics have been shown to reduce mortality in patients with cirrhosis and upper GI bleeding. Norfloxacin (400 mg orally every 12 hours) or ceftriaxone (1 g IV daily for 7 days) are the preferred regimens. Antibiotics aren't recommended for patients with acute ulcer-induced bleeding who do not have cirrhosis. However, patients with peptic ulcer disease should be evaluated for risk factors, such as Helicobacter pylori, and treated as appropriate when the bleeding episode has resolved.

In summary, an endoscopic diagnosis is crucial to appropriately stratify and treat patients with upper GI bleeding. Resuscitate appropriately with crystalloids and be cautious not to over-transfuse, particularly patients with variceal bleeding. Avoid indiscriminate use of PPIs in patients with non-ulcerative GI bleeding. Finally, prescribing antibiotics to patients with cirrhosis who have upper GI bleeding, regardless of etiology, will improve mortality.

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REFERENCES

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1. Villaneuva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11–21.

2. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345–360.

3. Barkun AN, Bardou M, Kuipers EJ, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101–113.

4. Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922–38.

© 2013 American Academy of Physician Assistants.

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