Journal Club

PPI for Bleeding UlcersIntermittent vs Continuous

Hassan M. Al Tomy BSc Pharm, BCPS

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.

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

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 bleeding. Gut, 2011. 60(9): p. 1170-7.

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

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.

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

62.

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

Search methods

3 database were searched MEDLINE, EMBASE,

and the Cochrane Central Register of Controlled

Trials

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

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

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

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

Endpoints

The primary endpoint was defined as recurrent

bleeding within 7 days

Secondary endpoints on the

Recurrent bleeding within3 days and 30 days

Forest Plot of Studies Comparing Intermittent With Bolus Plus Continuous-Infusion PPI in Patients

With High-Risk Bleeding Ulcers

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.

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