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1236 Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
G Javid et al. i.v. vs p.o. PPI in bleeding peptic ulcer
Methods pH monitoring
Eligible patients after successful endoscopic hemostasis under
Study population went 72-h intragastric pH metery using a pH electrode connected
This study was conducted in the Department of Gastroenterology, to a data recorder (Proxima Light 2; Mentova, Italy). The patients
Sher-i-Kashmir Institute of Medical Sciences, from May 2004 to were enrolled after written informed consent was obtained and
January 2007 and was approved by the Postgraduate Clinical received treatment protocol as described. The electrode was posi-
Research and Ethical Committee of Medicine. All consecutive tioned in the gastric body under fluoroscopic guidance and con-
patients above 18 years of age with proven peptic ulcer (gastric or tinuously recorded pH at 6-s intervals.
duodenal) bleeding were included in this study.
After the documentation of gastrointestinal bleeding, patients
were resuscitated. All patients admitted to this hospital with a Randomization and pharmacological treatment
history of peptic ulcer bleeding (i.e. hematemesis and/or melena) Immediately after endoscopic control of bleeding and successful
or who bled while in hospital, underwent emergency endoscopy as placing probe of the pH monitor in the corpus of the stomach
soon as possible, always within 12 h of bleeding or immediately (fluoroscopically documented), eligible patients were randomly
after resuscitation in patients with massive bleeding or shock. The assigned to receive different PPI (pantoprazole, omeprazole and
possibility of endoscopic therapy was discussed with the patient rabeprazole) through different routes (p.o. and infusion). No other
and/or their relatives and written informed consent was obtained treatment in the form of antacid, H2-receptor antagonist or others
before the endoscopy. Endoscopic therapy was given if endoscopy was given.
showed a peptic ulcer in the stomach or duodenum with active In the omeprazole group (Dr Reddy’s Laboratories, Hyderabad,
bleeding (spurting hemorrhage, oozing hemorrhage) or stigmata of India), patients were randomly assigned to receive omeprazole
recent hemorrhage (a non-bleeding visible vessel). Assessment of either as an i.v. bolus of 80 mg followed by continuous infusion of
presence of those stigmata was made after adherent clots and 8 mg/h for 72 h, or 80 mg p.o. bolus followed by 40 mg after every
debris of the ulcer base had been vigorously washed away.19 Initial 12 h for 72 h and i.v. saline.
hemostasis was defined as no visible hemorrhage lasting for 5 min In the pantoprazole group (Sun Pharmaceutical Industries,
after endoscopy therapy. Patients who achieved hemostasis with Mumbai, India), patients were randomly assigned to receive pan-
endoscopic therapy (witnessed by endoscopy) were eligible for toprazole either as an i.v. bolus of 80 mg followed by 8 mg/h
entry into the study. infusion for 72 h, or 80 mg p.o. bolus followed by 80 mg after
every 12 h for 72 h and i.v. saline.
In the rabeprazole group (Cadila Pharmaceutical, Ahmedabad,
India), patients were randomly assigned to receive rabeprazole
Method of endoscopic treatment
either as an i.v. bolus of 80 mg followed by 8 mg/kg continuous
Endoscopic hemostasis was achieved using a combination of heat infusion for 72 h, or 80 mg p.o. bolus followed by 40 mg after
probe preceded by epinephrine injection. Epinephrine (1 : 10 000 every 12 h for 72 h and i.v. saline. Patients in all groups were
diluted in normal saline) was injected in aliquots of 0.5–1 mL into allowed to take clear liquids only.
and around the bleeding area. After injection therapy, heater probe Randomization was carried out in the endoscopy laboratory by
thermocoagulation was given to the ulcer using an Olympus heater opening an opaque sealed numbered envelope by the senior endo-
probe unit with 2.8-mm probe (Olympus USE-2; Olympus, Tokyo scopy technologist. Treatment assignments were made based on
Japan). The energy output of the heater probe was set at 25 J and random numbers derived from a table of random numbers in
coaptive pulses (minimum of three) were applied until cavitation blocks of four. Patients and the attending physicians taking care of
and adequate coagulation was obtained. The bleeding site was the patient were blinded to the nature of treatment. The treatment
observed for 5 min and challenged with maximum water irrigation code was known only to the senior endoscopy technologist and
for 10 s. If any further bleeding occurred, the above procedure was pharmacist.
repeated.20 The endoscope used in the study was a fibro-optic We also studied 72-h intragastric pH in five patients who had
endoscope, FG-29V (Pentax, Tokyo, Japan). successful endoscopic hemostasis and did not receive any PPI
except i.v. saline thus acted as control group. After 72 h, patients
who were Helicobacter pylori-infected received triple therapy and
p.o. PPI daily for 8 weeks and patients who were not H. pylori-
Exclusion criteria infected received daily PPI for 8 weeks irrespective of treatment
Patients were excluded if they: were under 18 years of age; unable protocol. Three out of five patients in no PPI group were H.
or unwilling to give written informed consent; pregnant or lactat- pylori-infected and received triple therapy and p.o. PPI for
ing; taking anticoagulants; had more than one possible source of 8 weeks; those who were not H. pylori-infected received p.o. PPI
bleeding; had severe coagulopathy (prothrombin time 30% less for 8 weeks.
than normal) or platelet count less than 50 000/mm3;2 had previous
acid reducing surgeries (vagotomy, gastric resection); were mori-
Clinical monitoring
bund because of terminal cancer or severe comorbid illness; or had
bleeding gastric cancer. Patients who did not obtain initial hemo- Patients were observed for re-bleeding in a high-care facility of the
stasis with endoscopic therapy or re-bled within 3 days were also gastroenterology ward. Every patient was serially monitored for
excluded. vital signs, hemoglobin concentration, need for blood transfusion,
Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors 1237
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
i.v. vs p.o. PPI in bleeding peptic ulcer G Javid et al.
need for surgery and length of hospital stay. Demographic fea- 119 patients were taken for our study; of them, seven patients
tures, comorbid illness, ulcer size, initial hemoglobin level, use of refused to give consent for pH monitoring, and in six patients there
non-steroidal anti inflammatory drugs (NSAIDs) and H. pylori was difficulty in placing the pH probe because of deformed nasal
status as determined by enzyme-linked immunosorbent assay septa or previous surgery in the nose. Re-bleeding occurred in
(ELISA) were recorded. Re-bleeding was defined by fresh hemate- eight patients during 72-h pH monitoring who required second
mesis, melena or both, with either shock (systolic blood pressure endoscopy or surgery as necessary and eight patient refused 72-h
of ⱕ100 mmHg or a pulse rate of ⱖ100 b.p.m., accompanied by pH monitoring after giving initial consent. The remaining 90
cold sweats, pallor and oliguria); or a fall in hemoglobin of 2 g/dL patients underwent randomization to receive omeprazole, panto-
or more over a 24-h period after initial stabilization of vital signs. prazole and rabeprazole either in p.o. or infusion form in higher
Patients meeting these criteria were excluded from our study and doses. Five patients were taken for 72-h intragastric pH study, who
underwent emergency endoscopy within 4 h to confirm the diag- received endoscopic therapy but no PPI and i.v. saline thus acted as
nosis of re-bleeding. Re-bleeding was managed in both groups the control group.
with repeat endoscopic therapy as before or by surgery as Omeprazole was given either as 80 mg p.o. bolus followed by
necessary. 40 mg p.o. every 12 h for 72 h and i.v. saline or 80 mg i.v. bolus
The pH monitor was also continuously checked to see the posi- followed by 8 mg/h infusion for 72 h. A total of 15 patients were
tion of the electrode and was subsequently manipulated under included in each group. Pantoprazole was given either as 80 mg
fluoroscope if needed. The primary end-point was to see the time p.o. bolus followed by 80 mg p.o. every 12 h for 72 h and i.v.
for which intragastric pH remained above 6 over 72 h with various saline or 80 mg i.v. bolus followed by 8 mg/h infusion for 72 h. A
PPI when given through different routes. total of 15 patients were included in each group. Rabeprazole was
given either 80 mg i.v. bolus followed by 8 mg/h infusion for 72 h
or 80 mg p.o. bolus followed by 40 mg p.o. every 12 h for 72 h and
Statistical analysis
i.v. saline. A total of 15 patients were included in each group. The
The primary comparison was between the mean 72-h intragastric groups were well matched with respect to the patient and endo-
pH with p.o. PPI and that with PPI infusion. If the difference scopic features (Table 1).
between these two measurements was less than 10% of the mean The mean 72-h intragastric pH in the omeprazole group when
pH with PPI infusion, then the two group forms were considered given through the p.o. route was 6.56 ⫾ 0.99 (standard error of
therapeutically equivalent, provided the minimum pH achieved mean [SEM], 0.11) versus 6.93 ⫾ 0.96 (SEM, 0.10) when given as
with p.o. PPI was more than 6. For that reason, it was estimated infusion with a statistically insignificant difference between the
that 43 evaluable patients would be required to provide 95% over two groups of P = 0.48. The median 72-h intragastric pH with p.o.
all power to detect a difference of 10% between the p.o. PPI group omeprazole was 6.76 versus 7.14 for omeprazole infusion. The
and PPI infusion group, assuming the variance to be 0.16 and the minimum pH for omeprazole p.o. was 0.96 versus 1.12 for ome-
significance level (type 1 error) to be 0.05. The trial was designed prazole infusion group. The maximum pH for omeprazole p.o. and
to randomize 45 patients in each group so that 15 patients each for omeprazole infusion was 7.26 and 7.54, respectively. The 25th
would receive omeprazole, pantoprazole or rabeprazole p.o., or by and 75th percentile of 72-h intragastric pH with p.o. omeprazole
infusion. was 6.60 and 6.94 versus 6.90 and 7.28, respectively with ome-
Statistical analysis was performed on an intention-to-treat basis. prazole infusion. The 95% CI for mean 72-h intragastric pH with
All data were expressed as the mean ⫾ standard deviation. Quan- p.o. omeprazole was 6.33–6.79 versus 6.71–7.15 with omeprazole
titative data between different treatment groups were compared infusion. There was no statistically significant difference between
using the Student’s t-test and Mann–Whitney U-test. Categorical the two groups.
data were compared with Pearson’s test and Fisher’s exact test.21 The mean 72-h intragastric pH in the pantoprazole group when
The 95% confidence intervals (CI) associated with proportions given through the p.o. route was 6.34 ⫾ 0.90 (SEM, 0.10) versus
were calculated. A two-tailed P-value < 0.05 was considered sig- 6.32 ⫾ 0.81 (SEM, 0.09) when given as infusion with no statisti-
nificant. Statistical analysis was carried out with SPSS for cally significant difference between the two groups (P = 0.62).
Windows (ver. 11.5; SPSS, Chicago, IL, USA). The median 72-h intragastric pH with pantoprazole p.o. was 6.52
versus 6.48 with pantoprazole infusion. The minimum pH for
pantoprazole p.o. was 1.22 versus 1.54 for the pantoprazole infu-
Results sion group. The maximum pH for pantoprazole p.o. was 6.84
During the study period, 326 patients with peptic ulcer bleeding versus 6.88 for the pantoprazole infusion group. The 25th and 75th
were seen. The prevalence of various types of stigmata of recent percentile of 72-h intragastric pH with pantoprazole p.o. was 6.38
hemorrhage were as follows: 45 (13.80%) active bleeders (spurt- and 6.68 versus 6.32 and 6.64, respectively, with pantoprazole
ing and oozing); 78 (23.90%) non-bleeding visible vessel; 54 infusion. The 95% CI for the mean with pantoprazole p.o. was
(16.56%) adherent clot or flat red spot; and 149 (45.70%) clean 6.13–6.55 versus 6.12–6.50 with pantoprazole infusion. There was
base. Of these, 123 patients who revealed active bleeding (45 no statistically significant difference between the two groups.
patients) or non-bleeding visible vessel (78 patients) underwent The mean 72-h intragastric pH in the rabeprazole group, when
emergency endoscopic therapy. Initial endoscopic hemostasis was given through the p.o. route was 6.11 ⫾ 0.86 (SEM, 0.99) versus
obtained in 119 (96.74%) patients. Endoscopic treatment was 6.18 ⫾ 0.83 (SEM, 0.09) with rabeprazole infusion with no statis-
unsuccessful in four patients due to torrential bleeding that tically significant difference between the two groups P = 0.55. The
obscured the bleeding area and prevented adequate endoscopic minimum pH for p.o. rabeprazole was 1.44 versus 1.56 with
treatment; these patients were treated by emergency surgery. Thus, rabeprazole infusion. The maximum pH for p.o. rabeprazole was
1238 Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
G Javid et al. i.v. vs p.o. PPI in bleeding peptic ulcer
No. of patients 15 15 15 15 15 15
Mean age (years) 35.6 ⫾ 7 35 ⫾ 15.8 35.6 ⫾ 11.7 35.8 ⫾ 10 35 ⫾ 15.8 33.4 ⫾ 10.8
Age range (years) 28–45 18–60 22–50 22–50 18–60 22–50
Presentation
Hemetemesis 7 6 8 6 5 7
Melena 12 13 14 13 13 14
Both 7 6 7 6 6 6
Shock at presentation 1 1 0 0 0 1
Mean Hb at presentation 9.2 ⫾ 2.1 (5–13) 9.5 ⫾ 2.1 (6–12) 9.1 ⫾ 2.1 (6–13) 9.1 ⫾ 2.1 (6–13) 9.3 ⫾ 2.2 (5–13) 9.5 ⫾ 2.1 (6–12)
(g/dL) range
Comorbid illness 0 0 0 0 0 0
H. pylori† infected 10 9 10 9 10 8
NSAID intake 2 1 1 1 2 1
Stigmata of bleeding
Spurting 4 3 2 3 3 2
Oozing 3 4 3 4 2 4
Non-bleeding vessel 8 8 10 8 10 9
Mean ulcer size (cm) 1.4 ⫾ 07 1.4 ⫾ 07 1.4 ⫾ 07 1.2 ⫾ 0.8 1.2 ⫾ 0.8 1.2 ⫾ 0.8
Mean dose of epinephrine 11.6 11.6 11.5 11.5 11.5 11.6
(mL)
No. of heater probe pulses 4 4 4 4 4 4
used (mean)
*No statistical significant difference between the two groups. †Helicobacter pylori. NSAID, non-steroidal anti-inflammatory drug; PPI, proton pump
inhibitors.
Table 2 Effects of various PPI when given in p.o. or infusion form on 72-h intragastric pH*
*P-value for: omeprazole p.o. vs omeprazole infusion (P = 0.48); omeprazole infusion vs pantoprazole infusion (P = 0.15); pantoprazole p.o. vs
pantoprazole infusion (P = 0.62); omeprazole infusion vs rabeprazole infusion (P = 0.09); rabeprazole p.o. vs rabeprazole infusion (P = 0.55); panto-
prazole infusion vs rabeprazole infusion (P = 0.73). This shows there is statistically no difference between PPI when given p.o.ly or as infusion. CI,
confidence interval; PPI, proton pump inhibitors; SEM, standard error of the mean.
6.78 versus 6.78 with rabeprazole infusion. The 25th and 75th The mean pH on day 1 with omeprazole p.o. was 6.63 versus
percentile pH with rabeprazole p.o. was 6.16 and 6.44 versus 6.26 6.61 with omeprazole infusion. The mean pH on day 2 with ome-
and 6.58, respectively, with the rabeprazole infusion group. The prazole p.o. was 6.82 versus 6.92 with omeprazole infusion. The
95% CI for the mean with rabeprazole p.o. was 5.91–6.30 versus mean pH on day 3 with omeprazole p.o. was 6.72 versus 6.92 with
5.99–6.37 with rabeprazole infusion. There was no statistically omeprazole infusion. The median time to reach a gastric pH of 6 or
significant difference between the two groups (Table 2). above was 60 min. (range, 50–140 min) after an initial p.o. bolus
Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors 1239
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
i.v. vs p.o. PPI in bleeding peptic ulcer G Javid et al.
8 8
7 7
6 6
5
5
pH 4 pH 4
3
3
2
2
1
1
0
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 70 0
Time in h 1 4 7 1013 16 1922 25 2831 34 3740 4346 49 5255 58 6164 67 70
Figure 1 Graph showing effect of administration of omeprazole Time in Hours
through different routes on 72-h intragastric pH. Mean pH (omepra-
Figure 3 Graph showing effect of administration of rabeprazole
zole p.o.); — Mean pH (omeprazole infusion).
through different routes on 72-h intragastric pH. — Mean pH (Rabepra-
zole Oral); Mean pH (Rabeprazole Infusion).
8
7
6
sisted above 6 for 96% of the time in the first 24 h and 100% of the
5
pH
time in the next 2 days of 72-h pH monitoring. The median time to
4
reach a gastric pH of 6 or above was 42 min (range, 35–115 min)
3
after the initial i.v. bolus of rabeprazole and persisted above 6 for
2
approximately 97% of the time in the first 24 h and remained
1
above 6 for 100% of the time in the next 2 days of 72-h pH
0
monitoring (Fig. 3).
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 70
Time in h
1240 Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
G Javid et al. i.v. vs p.o. PPI in bleeding peptic ulcer
Mean 2.05
Median 2.20
Standard deviation 0.55
SEM 0.06
Minimum 1.15
Maximum 3.45
Percentiles
25 1.65
50 2.20
75 2.35
95% CI (mean) 1.92–2.17
Figure 4 Graph showing effect of administration of various proton
CI, confidence interval; PPI, proton pump inhibitors; SEM, standard error
pump inhibitors (PPI) in infusion form on 72-h intragastric pH and in
of the mean.
non-PPI group. - - - MEAN pH (Omeprazole Infusion); — MEAN pH
(Rabeprazole infusion); MEAN pH (Pantoprazole infusion).
Table 4 Outcome of patients with bleeding peptic ulcer according to
treatment received after successful endoscopic hemostasis
Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors 1241
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
i.v. vs p.o. PPI in bleeding peptic ulcer G Javid et al.
Philips et al.17 conducted a five-way cross-over study to eva- maintaining the intragastric pH at a level 6 or higher and thereby
luate and compare 24-h intragastric pH following standard doses promoting hemostasis. In our study, intragastric pH for 72 h with
of esomeprazole, lansoprazole, omeprazole, pantoprazole and omeprazole when given in different routes (infusion vs p.o.)
rabeprazole, administered once daily in 34 H. pylori-negative showed that intragastric pH raised to above 4 within 1 h in both
patients aged 18–60 years with significant gastro-esophageal groups and remained above 6 for more than 98% of the time for the
reflux disease. This randomized open-label comparative five-way remaining 72 h. Almost the same results were obtained with the
cross-over study evaluated 24-h intragastric pH profile. On day 5, pantoprazole and rabeprazole groups of drugs on intragastric pH
intragastric pH was maintained for a mean of 14.0 h with esome- when given through different routes. There was no significant
prazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h statistical difference on intragastric pH with group of drugs (ome-
with lansoprazole and 10.1 h with pantoprazole (P ⱕ 0.001). prazole, rabeprazole and pantoprazole) when given in different
Esomeprazole at the standard dose of 40 mg once daily provided routes (p.o. vs infusion; P > 0.05). The median pH remained above
more effective control of gastric acidity at steady state than stan- 6 in all forms of drugs for more than 98% of the time in the first
dard doses of lansoprazole, omeprazole, pantoprazole and rabepra- day and 100% of the time in the second and third days.
zole (P < 0.05). We conducted a 72-h intragastric pH study on i.v. We excluded patients with re-bleeding or continuous bleed as
pantoprazole and found that the median time to reach a gastric pH presence of blood would interfere with the study of pH. There
of 6 was 45 min (range, 29–118) after the initial bolus of panto- were eight patients who re-bled and were evenly distributed in
prazole infusion and persisted approximately 5.6–7.1 for the each group. We studied other outcome parameters like number of
remaining 72 h.9 Oral and i.v. dosage of pantoprazole have been blood transfusions, hospital stay, surgery, re-bleed and deaths.
found to be equivalent in their ability to suppress gastric acid There was no statistical significance in outcome.
secretion in patients with gastro-esophageal reflux disease.23 In conclusion, our results demonstrated that high doses of dif-
Pantoflickova et al.24 conducted a cross-over study on 18 H. ferent groups of PPI (omeprazole, rabeprazole, pantoprazole)
pylori-negative subjects. Twenty-four hour intragastric pH moni- when given in different forms (p.o. or infusion) after successful
toring was performed on day of treatment (once daily for rabepra- endoscopic therapy achieved an intragastric pH of 6 and above
zole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, omeprazole within 1 h of administration and maintained a pH of more than 6
20 mg, omeprazole multiple unit pellet system [MUPS] tablets for more than 98% of the time. There was an insignificant differ-
20 mg or placebo). The intragastric pH (3.4) and time at pH of ence among various PPI on 72-h intragastric pH, however, there
more than 4 during the 24-h post-dose (8 h) were significantly was a significant difference between the PPI group and non-PPI
greater with rabeprazole than with lansoprazole, pantoprazole, group. Thus, we conclude that a high dose of PPI maintains intra-
omeprazole capsule, omeprazole MUPS or placebo (P ⱕ 0.04 for gastric pH above 6 regardless of route of administration.
rabeprazole vs others).
Observations of therapeutic and physiological variability among
the five different PPI continue to arise as our experience with these Acknowledgments
agents increases. Theories behind these observations include dif-
ferences in parietal cell mass among different populations and The authors thank Mr Nazir Ahmad Patoo, chief pharmacist, and
cytochrome P450 polymorphism resulting in different PPI phar- his staff; Mr Ghulam Nabi Dar, technical officer of the endoscopic
macokinetic profiles among individual patients. PPI therapy for unit; Mr Ghulam Mustafa, technical officer of the motility labora-
ulcer bleeding has been more efficacious in Asia than else- tory, and his staff for assistance in this study. We also thank
where.25,26 Most pH studies have been on volunteers or cross-over Mr Gulzar Ahmad and Mr Nazir Ahmad for their secretarial
studies or in small groups; this is a first randomized trial to study assistance.
72-h pH in various PPI after successful endoscopic therapy in
patients of peptic ulcer bleed. Katz and colleagues27 reported the
results of their evaluation of gastric acid suppression achieved with References
five available PPI at a standard recommended dose for erosive
1 Consensus Development Panel. Consensus statement on therapeutic
esophagitis, and found that healing was better with esomeprazole
endoscopy and bleeding ulcer. JAMA 1989; 262: 1369–72.
than other PPI. However, all of the PPI resulted in a pH value of 2 Lin J, Wang K, Perng CL, Lee CH, Lee SD. Heat probe thermal
more than 4 for at least 8–10 h. The acid suppressive efficacy of coagulation and multiple electrocoagulation for arrest of peptic ulcer
rabeprazole 20 mg has been shown to be similar to that of ome- bleeding a prospective randomized comparative trial. J. Clin.
prazole,28,29 as is the case with omeprazole and esomeprazole.30 We Gastroenterol. 1995; 21: 99–102.
used high p.o. and i.v. forms of three PPI (omeprazole, pantopra- 3 Kubba AK, Murphy W, Palmer KR. Endoscopic injection for
zole, rabeprazole); as in these three PPI, both p.o. and i.v. forms bleeding peptic ulcer, a comparison of adrenaline alone with
are available, and only recently has esomeprazole i.v. become adrenaline plus human thrombin. Gastroenterology 1996; 111:
available; this why we could compare only these three PPI. 623–8.
We used high doses of PPI as it has been shown that a rapid 4 Laine L, Peterson WL. Bleeding peptic ulcer. N. Engl. J. Med. 1994;
331: 717–27.
increase of intragastric pH above 6 can be reliably achieved only
5 Rockall TA, Logan RFA, Devlin HD, Northfield TC. Risk
by continuous infusion with a large initial bolus dose of PPI.31 In assessment after acute upper gastro intestinal hemorrhage. Gut 1996;
bleeding peptic ulcer patients, the risk of ulcer re-bleeding is 38: 316–21.
highest during first 3 days and most re-bleed in the first 24 h;32 this 6 Clason AE, Macleod DAD, Elton RA. Clinical factors in the
was the rationale of choosing a high-dose treatment period of prediction of further hemorrhage mortality in acute upper
3 days with PPI. The treatment regime was aimed at elevating and gastro-intestinal hemorrhage. Br. J. Surg. 1986; 73: 985–7.
1242 Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
G Javid et al. i.v. vs p.o. PPI in bleeding peptic ulcer
7 Lau JYW, Sug JJY, Lee KC et al. Effect of intravenous Omeprazole 21 Altman DG. Practical Statistics for Medical Research. London:
on recurrent bleeding after endoscopic treatment of bleeding peptic Chapman & Hall, 1991.
ulcers. N. Engl. J. Med. 2000; 343: 310–16. 22 Fresten J, Chiu Y-L, Pan WJ, Lukasik N, Täubel J et al. Effect on 24
8 Javid G, Masoodi I, Zargar SA. Omeprazole as adjuvant therapy to intragastric pH: A comparison of Lansoprazole administered
endoscopic combination injection sclerotherapy for treating bleeding nasogastrically in apple juice and Pantoprazole administered
peptic ulcer. Am. J. Med. 2001; 111: 280–84. intravenously. Am. J. Gastroenterol. 2001; 96: 2058–65.
9 Zargar SA, Javid G, Khan BA. Pantoprazole infusion as adjuvant 23 Metz DC, Pratha V, Martin P et al. Oral and intravenous dosage
therapy to endoscopic treatment in patients in peptic ulcer bleeding. forms of pantoprazole are equivalent in their ability to suppress
Prospective randomized controlled trial. J. Gastroenterol. Hepatol. gastric acid secretion in patients within gastroenterooesophageal
2006; (4): 716–21 reflux disease. Am. J. Gastroenterol. 2000; 95: 626–33.
10 Barkham P, Tocantins TM. Action of human gastric juice on human 24 Pantafickova D, Dorta G, Ravic M, Jornod P, Blum AL. Acid
blood clot. J. Appl. Physiol. 1953; 6: 1–7. inhibition on first day of dosing Comparison of four Proton pump
11 Peterson WI, Cook DJ. Anti secretary therapy for bleeding peptic inhibitors. Aliment. Pharmacol. Ther. 2003; 17: 1507–14.
ulcer. JAMA 1998; 280: 877–8. 25 Leontidias GI, Sharma VK, Horiden CW. Systemic review and
12 Green FW, Kaplan MM, Curtis LE, Levine PH. Effect of acid meta analysis, enhanced efficacy of proton pump inhibitors
and pepsin on blood coagulation and platelet aggregation. therapy for peptic ulcer bleeding in Asia a posthoc analysis from
Gastroenterology 1978; 74: 38–43. Cochrane collaboration. Aliment. Pharmacol. Ther. 2005; 21:
13 Patchett SE, Enright H, Atdhal N, O’Connell W, O’Donoghue DP. 1055–61.
Clot lysis by gastric juice, an in vitro study. Gut 1989; 30: 1704–7. 26 Leher JK, Gideon RM, Braitman L et al. Intragastric pH control with
14 Yacyshyn BR, Thomson ABR. Clinical importance of proton pumps Esomeprazole once daily all ethnic groups are not equal [Abstract
inhibitor pharmacokinetics. Digestion 2002; 66: 67–8. #100]. Am. J. Gastroenterol. 2004; 99: S33.
15 Rohan K, Hassel G, Hedenstron H. Effects of Esomeprazole 40 mg 27 Katz P, Miner P, Chen Y et al. Effect of 5 marketed proton pump
versus Omeprazole 40 mg on 24 h intragastric pH in patients with inhibitors on acid suppression relative to a range of pH threshold
symptoms of gastrroesophageal reflux disease. Dig. Dis. Sci. 2002; [Abstract #102]. Am. J. Gastroenterol. 2004; 99: S34.
47: 954–8. 28 Galamiche JP, Zerbib F, Ducrotte P et al. Decreasing esophageal
16 Rohss K, Wilder Smith C, Claor Nilsson C et al. Esomeprazole acid exposure in patients with GERD. A comparison with
40 mg provided effective control than standard doses of all other Rabeprazole and Omeprazole. Aliment. Pharamacol. Ther. 2001; 15:
proton pump inhibitors [A 418 Abstract]. Gastroenterology 2001; 1343–50.
120: 2140. 29 Stedman CAM, Barclay ML. Review article comparison of
17 Miner P Jr, Kartz PO, Chen Y, Sostek M. Gastric acid control with pharmacokinetics acid suppression and efficacy of proton pump
Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole and inhibitors. Aliment. Pharmacol. Ther. 2000; 14: 963–78.
Rabeprazole. A five way cross over study. Am. J. Gastroenterol. 30 Andersson T, Röhss K, Bredberg E, Hassan-Alin M.
2003; 98: 2616–20. Pharmacokinetics and pharmacodynamics of Esomeprazole the
18 Andrivlli A, Aneese V, Caruso N et al. Proton pump inhibitors and S-isomer of Omeprazole. Aliment. Pharmacol. Ther. 2001; 15:
outcome of endoscopic hemostasis in bleeding peptic ulcer. A series 1563–9.
of meta analysis. Am. J. Gastroenterol. 2005; 100: 207–19. 31 Brunner G, Luna P, Hartman M, Wurst W. Optimising the
19 Johnston JH. Endoscopic risk factors of bleeding peptic ulcer. intra-gastric pH as a supportive therapy in upper GI bleeding.
Gastrointest. Endosc. 1990; 36 (Suppl. 5): 16–20. Yale J Biol Med 1996; 69: 225–31.
20 Lin HJ, Lo WC, Cheng YC, Perng CL. Role of intravenous 32 Lau JYW, Chan SCS, Lenuing JW. Evaluation of stigmata of
Omeprazole in patients with high risk, peptic ulcer bleeding after hemorrhage in bleeding peptic ulcer a sequential endoscopic study.
successful endoscopic epinephrine injection. A prospective Endoscopy 1989; 30: 513–8.
randomized comparative trial. Am. J. Gastroentrol. 2006; 101:
500–5.
Journal of Gastroenterology and Hepatology 24 (2009) 1236–1243 © 2009 The Authors 1243
Journal compilation © 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd