Date of Graduation

8-15-2009

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Mary Von

Second Advisor

Rob Rosenow PharmD, OD

Third Advisor

Annjanette Sommers MS, PA-C

Abstract

Background: Esophageal bleeding has an estimated mortality rate of at least 25% with the index bleed, an estimated 35% to 42% risk of death within the first six weeks, and up to 75% chance of a rebleed at one year. Prevention of chronic variceal rebleeding is critical and most crucial in the first three months following the index bleed. To address this, several medical and surgical therapies have been studied and used with various levels of success. For several years, esophageal variceal ligation (EVL) has been accepted as the best overall prevention for chronic variceal rebleeding, given the advantages and disadvantages of each treatment method. However, recent trials in pharmacological therapy using beta-blockers, in combination with a nitrate, have shown greater efficacy in preventing recurrent variceal bleeding, studies combining pharmacological and nonpharmacological modalities have been performed, and technological advances have decreased the rebleeding rate after transesophageal intrahepatic portosystemic shunt (TIPS) therapy. This has created the possibility that another treatment may be better than EVL alone. Further study and trials are necessary to determine if esophageal variceal ligation is still the treatment of choice for secondary prevention of variceal rebleeding.

Clinical Question: In patients with proven esophageal hemorrhage, is esophageal ligation still the treatment of choice in secondary prophylaxis of variceal bleeding?

Study Design: Exhaustive search of available medical literature employing CINAHL, MEDLINE, Evidence Based Medicine Reviews Multifile, BIOSIS preview databases. Studies were found in key industry journals, and article reference lists were combed for additional trials meeting inclusion criteria.

Methods: Independent review of data and methodology of published randomized control trials addressing long-term prevention of esophageal variceal bleeding using esophageal variceal ligation as compared to another treatment modality, or as compared to EVL plus another therapy, performed within the last 10 years, and free on internet search.

Results: In reviewing the efficacy of esophageal variceal ligation (EVL) therapy to other modes of treatment for secondary prophylaxis of variceal bleeds, one study showed an improved benefit in variceal rebleeding rate and overall bleeding rate when esophageal variceal ligation was compared to propranolol, a nonselective beta-blocker, plus isosorbide mononitrate (ISMN). In two studies comparing EVL to ISMN plus nadolol, a different nonselective beta-blocker, one study reported no significant difference in rebleeding, overall bleed, or mortality rates and the other trial concluded that EVL was less effective than nadolol plus ISMN and EVL, in isolation, had an associated higher rate of major complications. A fourth trial compared variceal ligation to a combination therapy of EVL plus nadolol and found that nadolol plus EVL reduced the incidence of variceal rebleeding as compared to EVL, but did not reduce the risk of mortality. When evaluated against transesophageal intrahepatic portosystemic shunt (TIPS), EVL proved to be less effective than TIPS, nor did it improve the two-year survival rate or encephalopathy rate. In the final study reviewed, a combination therapy of variceal ligation plus propranolol was found to be nearly as effective as TIPS, and with an equally effective survival rate, but ligation plus propranolol had approximately half the risk of encephalopathy. These randomized controlled trial results showed contradictory evidence for the efficacy of esophageal variceal ligation in the control of secondary variceal rebleeding. Esophageal variceal ligation therapy, alone, did not show a clear benefit in the long-term prevention of variceal rebleeding as compared to beta-blocker plus nitrate, EVL plus beta-blocker, or TIPS. However, when EVL was paired with a beta-blocker, and pitted against variceal ligation alone, the combination comparatively reduced the incidence of variceal rebleeding.

Conclusion: Esophageal variceal ligation, in isolation, shows no superiority to treatment with beta-blocker and nitrate, or TIPS procedure, and is less effective than EVL plus nadolol in the prevention of secondary variceal bleeding.

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