2. 2
Daneshmend et al. Omeprazole vs placebo for
acute upper gastrointestinal bleeding: randomised
double blind controlled trial. BMJ 1992 Jan
18;304(6820):143-7.
Kaviani et al. Effect of oral omeprazole in reducing
re-bleeding in bleeding peptic ulcers: a prospective,
double-blind, randomized clinical trial. Aliment
Pharmacol Ther 2003; 17: 211-216.
Baradarian et al. Early intensive resuscitation of
patients with upper gastrointestinal bleeding
decreases mortality. Am J Gastroenterol 2004;
99:619.
Studies
3. 3
Study Design
Prospective, double blind, randomized,
placebo controlled, intent to treat.
Omeprazole 80mg IV, then 40mg IV TID
x3, then 40mg PO BID.
1147 patients (569 placebo 578 treated)
Outcomes: all cause mortality, rate of
rebleed, transfusion requirement, (and
effect of treatment on 1o endoscopy).
Daneshmend et al. Omeprazole vs placebo for acute upper
gastrointestinal bleeding: BMJ 1992
4. 4
Criteria
Inclusion criteria: all patients with overt UGIB,
hematemesis or melena <24 hrs.
Exclusion criteria: age < 18, pregnant, severe
illness (terminal or advanced malignancy),
bleeding requiring immediate surgery, trivial
bleed, bleeding during previous admission,
prior participation in this study or inability to
start treatment in <12 hours, or
contraindication to medications (warfarin,
phenytoin)
Daneshmend et al. Omeprazole vs placebo for acute upper
gastrointestinal bleeding: BMJ 1992
5. 5
Results
Death: Tx: 6.9% Placebo: 5.3% (ns)
Transfusion: Tx: 53% Placebo: 52% (ns)
Rebleed: Tx: 18% Placebo: 15% (ns)
Bleed Stigmata: Tx: 33% Placebo: 45% (p<0.0001)
Blood in stomach, red clot on lesion, active bleed,
black spot on lesion, visible vessel
“Our data do not justify the routine use of acid
inhibiting drugs in the management of haematemesis
or melaena.”
Daneshmend et al. Omeprazole vs placebo for acute upper
gastrointestinal bleeding: BMJ 1992
6. 6
Cochrane Collaboration
Dorward et al. Proton pump inhibitor
treatment initiated prior to endoscopic
diagnosis in upper gastrointestinal bleeding
(review). The Cochrane Library 2007, Issue 1
No difference in mortality, rebleed, or surgery.
Non-robust reduction of stigmata of recent
hemorrhage.
Reduction in stigmata may reduce rate of endoscopic
intervention, and thus be cost effective.
7. 7
IV vs PO PPIs?
IV is quicker in onset, and more
expensive than PO.
There are currently no trials of IV vs PO
published
Is PO effective?
8. 8
Study design
Prospective, double blind, randomized,
placebo controlled trial.
149 patients (treatment:71, placebo:78)
Omeprazole PO 20mg Q 6 hours
Kaviani et al. Effect of oral omeprazole in reducing re-
bleeding in bleeding peptic ulcers: 2003;
9. 9
Criteria
Inclusion criteria: UGIB with active
bleeding ulcer on EGD.
Exclusion criteria: age<15, low risk
bleeds, uncertain or unknown bleed
sites, patients on H2RA or PPI, probable
gastric malignancy, or failure of
endoscopic treatment.
Kaviani et al. Effect of oral omeprazole in reducing re-
bleeding in bleeding peptic ulcers: 2003;
10. 10
Results
Death: Tx: 0% Placebo: 1% (ns)
Rebleed: Tx: 12% Placebo: 26% (0.022)
Transfuse: Tx: 40% Placebo: 72% (0.049)
Hospital >5d: Tx: 1% Placebo: 8% (0.034)
Unable to compare to IV trials due to different
patient populations
Kaviani et al. Effect of oral omeprazole in reducing re-
bleeding in bleeding peptic ulcers: 2003;
11. 11
What about early
resuscitation?
Risk factors for bad outcomes are:
Advanced age
Co-morbid conditions
Hemodynamic compromise
(Rockall et all. Incidence & mortality from acute upper gastrointestinal
hemorrhage in the UK. Br Med J 1995; 311: 222-6)
Baradarian et al. Early intensive resuscitation of patients
with UGIB decreases mortality. 2004.
12. 12
Study Design
Consecutive cohort
72 patients (36 standard, 36 intensive)
Observe & collect data for first 4 months
Then early and intensive resuscitation
for 4 months
Baradarian et al. Early intensive resuscitation of patients
with UGIB decreases mortality. 2004.
13. 13
Criteria
Inclusion:
melena, hematemesis, or massive
hematochezia
positive NG aspirate for blood
HR > 100 or SBP <100
No exclusion criteria
Baradarian et al. Early intensive resuscitation of patients
with UGIB decreases mortality. 2004.
14. 14
Methods
Timed correction of instability:
HR < 100 for > 10 minutes
SBP > 100 for > 10 minutes
HCT > 28%
INR < 1.8
Additional physician to follow UGIB.
Baradarian et al. Early intensive resuscitation of patients
with UGIB decreases mortality. 2004.
15. 15
Results
Baradarian et al. Early intensive resuscitation of patients
with UGIB decreases mortality. 2004.
Observe Intervene p Value
Hemo-
dynamics
260 +/- 88 111 +/- 33 0.002
Hct >28 243 +/- 109 188 +/- 39 0.03
INR <1.8 277 +/- 74 213 +/- 89 0.04
Scope 765 +/- 232 861 +/- 312 0.21
16. 16
Results
Observe Intervene p Value
Hospital
Days
7.2 +/- 13.8 5.8 +/- 8.3 0.06
ICU Days 2.4 +/- 2.5 3.9 +/- 3.8 0.04
MI 5 2 0.04
Death 4 1 0.04
Baradarian et al. Early intensive resuscitation of patients
with UGIB decreases mortality. 2004.
17. 17
In Practice
Prior to EGD, PPIs do not reduce
mortality, rebleeds or surgery, (might
make our GI colleagues job easier)
PO PPIs are effective in bleeding ulcers
(but only after receiving an EGD)
No data for PO vs IV
Early intervention in UGIB is a Good
Thing™
