in last few years there is emergent data on use of intermittent PPI in bleeding ulcers compared to continous infusion in this meta-analysis the invistigator select 13 randomized controlled trial Intermittent PPI regimens are comparable to continuous PPIinfusion regimens in patients with bleeding ulcers and high risk endoscopic findings Because of ease of use and lower cost and resource utilization, intermittent PPI therapy may be the regimen of choice after endoscopic therapy in such patients

1. Journal Club
PPI for Bleeding Ulcers
Intermittent vs Continuous
Hassan M. Al Tomy BSc Pharm, BCPS

2. Introduction
 Upper gastrointestinal (GI) bleeding represents a
substantial clinical and economic burden.
 Prevalence: 170 cases per 100 000 adults per year,
at an estimated total cost of $750 million
 Peptic ulcer disease accounts for 50% to 70% of
cases of acute non variceal upper GI bleeding
 Mortality rates have remained essentially unchanged
at 6% to 8%
Jiranek GC, Kozarek RA. Surg Clin North Am. 1996;76:83-103.
Marshall JK, Collins SM, Gafni A. Am J Gastroenterol. 1999;94:1841-6.

3.  What did guidelines recommend for pharmacotherapy
management of bleeding ulcer?
 What is recommended intragastric PH which required
to promote clot formation and stability
 What is the cost of intermittent regimen compared to
recommended regimen

4. Current Recommendations
 For patients with bleeding ulcers who have high-risk
endoscopic findings (active bleeding, non bleeding
visible vessels, and adherent clots) receive an
intravenous bolus dose followed by a continuous
infusion of a proton pump inhibitor after endoscopic
treatment.
 Hwang, J.H., et al., The role of endoscopy in the management of acute non-variceal upper GI
bleeding. Gastrointest Endosc, 2012. 75(6): p. 1132-8.
 Laine, L. and D.M. Jensen, Management of patients with ulcer bleeding. Am J Gastroenterol, 2012.
107(3): p. 345-60; quiz 361.
 Barkun, A.N., International Consensus Recommendations on the Management of Patients With
Nonvariceal Upper Gastrointestinal Bleeding. Annals of Internal Medicine, 2010. 152(2): p. 101.
 Sung, J.J., et al., Asia-Pacific Working Group consensus on non-variceal upper gastrointestinal

5. In Vitro Data
 In vitro data suggested that an intragastric PH
above 6 may
be required to promote clot formation and stability
 Half life
 Intermittent vs continous
Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Gastroenterology.
1978;74(1):38-43

6. Clinical practice issue
 is whether intermittent PPI therapy can be
substituted for the currently recommended bolus
plus continuous-infusion PPI therapy.
 If intermittent PPI treatment achieves comparable
clinical efficacy, it would be the preferred regimen
given the decrease in cost and resources (eg,
infusion pump, nursing and pharmacy personnel
time, and requirement for monitored setting), the
decrease in the PPI dose, and the greater ease of
administration.

7. Sachar, H., K. Vaidya, and L. Laine, JAMA Intern Med, 2014. 174(11): p. 1755-

8. Research hypothesis
 a systematic review and meta-analysis was done
to assess the clinical efficacy of intermittent PPI
regimens vs the standard bolus plus continuous-
infusion regimen after successful endoscopic
therapy in patients with
 The primary hypothesis that intermittent PPI is
noninferior to current regimen

9. Search methods
 3 database were searched MEDLINE, EMBASE,
and the Cochrane Central Register of Controlled
Trials

10. Study Selection
Study
Design and
Population
Inclusion
Criteria
 Randomized clinical trials
 Studies were included if patients
presented with upper GI bleeding
 Have a gastric or duodenal ulcer with
active bleeding
 A non bleeding visible vessel
 Or an adherent clot
 And had received successful
endoscopic hemostatic therapy

11. Study Selection
 Patients who had ulcers with flat
spots and clean bases
 have a very low rate of clinically
significant rebleeding
Study
Design
and
Populatio
n
Exclusion
Criteria

12. Study Selection
Interventi
on
 Intermittent PPI iv or PO
 The control regimenwas the
standard PPI bolus plus continuous
infusion: 80-mg intravenous bolus
followed bya continuous 8-mg/h
intravenous infusion for72 hours

13. Study Selection
Outcom
es
 Studies reporting1or more of the following
outcomes were included
 Recurrent bleeding,
 Mortality,
 Need for urgent intervention(subsequent
endoscopic therapy, surgery)
 Radiologic intervention
 Red blood cell transfusions,
 Length of hospitalization

14. Endpoints
 The primary endpoint was defined as recurrent
bleeding within 7 days
 Secondary endpoints on the
 Recurrent bleeding within3 days and 30 days

18. Forest Plot of Studies Comparing Intermittent With Bolus Plus Continuous-Infusion PPI in Patients
With High-Risk Bleeding Ulcers

19. Strengths and Limitations
Strengths Limitations
 Only randomized
controlled trials were
included
 different databases
were used to ensure
that all were included
in the analysis.
 variations in the study
protocol in the different
studies,
 variation in endoscopic
therapies used across
studies
 the nature of study also
cannot provide the
optimal PPI bolus doses
or length of time, since
these were variable in
the studies.

20. Conclusion
 Intermittent PPI regimens are comparable to
continuous PPI
infusion regimens in patients with bleeding ulcers
and high risk endoscopic findings
 Because of ease of use and lower cost and
resource utilization, intermittent PPI therapy may
be the regimen of choice after endoscopic
therapy in such patients