UMEM Educational Pearls

Question

Bottom Line:

  1. The most often cited meta-analysis regarding route of PPI use in bleeding peptic ulcer disease evaluates rebleeding AFTER endoscopic treatment and only ulcers with high-risk features.  There is no good data on optimal pre-endoscopy dosing.
  2. These studies appear to show non-inferiority of intermittent dosing with a trend towards superiority when compared with continuous dosing.
  3. The proper dosing, frequency, and route of intermittent PPI use is widely variable without good data on an optimal regimen.
  4. ED decision of intermittent vs continuous PPI should consider other patient factors including severity of illness, compatibility of IV lines (pantoprazole is often incompatible), and patient disposition.

 

 

Answer

Continuous vs intermittent dosing of PPIs in bleeding peptic ulcer disease

There continues to be debate as to the optimal dose, frequency, and route of proton pump inhibitors (PPIs) in bleeding ulcers, especially prior to endoscopy.  Multiple guidelines including from the American Journal of Gastroenterology continue to recommend continuous dosing of PPIs.1,2,3  However, multiple studies appear to show at least non-inferiority when compared with intermittent dosing of PPIs.

The most frequently cited study for non-inferiority is a meta-analysis of 13 randomized control trials by Sachar et al. which evaluated PPI use in patients presenting with upper GI bleeds who were endoscopically found to have a bleeding gastric or duodenal ulcer with high risk features (active bleeding, non-bleeding visible vessel, or adherent clot)4.  There was non-inferiority of intermittent dosing in rebleeding, need for repeat endoscopy/surgery, RBC transfusions, and mortality with a non-statistically significant trend towards superiority of intermittent dosing.

However, the patients were only randomized to continuous vs intermittent dosing AFTER endoscopic treatment.  In addition, the dosing regimen of intermittent dosing was quite variable.

 

Continuous dosing:

  • All studies used 80mg IV bolus followed by IV drip at 8mg/hr

Intermittent dosing:

  • 1 study used 40mg IV Q12H
  • 2 studies used 40mg PO Q12H
  • 1 study used 20mg PO Q12H
  • 5 studies used loading dose of 80mg IV or PO followed by 40-80mg IV or PO Q6H-Q12H
  • 4 studies used 40mg IV daily

 

Bottom Line:

  1. The most often cited meta-analysis regarding route of PPI use in bleeding peptic ulcer disease evaluates rebleeding AFTER endoscopic treatment and only ulcers with high-risk features.  There is no good data on optimal pre-endoscopy dosing.
  2. These studies appear to show non-inferiority of intermittent dosing with a trend towards superiority when compared with continuous dosing.
  3. The proper dosing, frequency, and route of intermittent PPI use is widely variable without good data on an optimal regimen.
  4. ED decision of intermittent vs continuous PPI should consider other patient factors including severity of illness, compatibility of IV lines (pantoprazole is often incompatible), and patient disposition.

References

References:

  1. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60.
  2. Barkun A, Bardou M, Marshall JK. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2003;139(10):843-57.
  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):101-13.
  4. Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014;174(11):1755-62.