Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea

Background and Aim:  The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6.
Methods:  Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.
Results:  Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (−) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% ( P  = 0.026).
Conclusions:  A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6.     

High-dose pantoprazole continuous infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding

BACKGROUND: The best antisecretory treatment after endoscopic hemostasis in patients with ulcer bleeding is still in quest. OBJECTIVES: To compare pantoprazole and somatostatin continuous infusion after endoscopic hemostasis in patients with bleeding peptic ulcers. PATIENTS AND METHODS: A total of 164 consecutive patients with a bleeding peptic ulcer, after successful endoscopic hemostasis, were randomly assigned to receive, double blindly, continuous IV infusion of pantoprazole 8 mg/h for 48 h after a bolus of 40 mg (group P) or somatostatin 250 microg/h for 48 h after a bolus of 250 microg (group-S). Twenty-four-hour pH-metry was performed in the last 30 patients in each group. Endoscopy was performed, in case of bleeding nonrecurrence, every 48 h until disappearance of stigmata. RESULTS: Bleeding recurrence: group S 14 patients (17%) versus group P 4 (5%) (P=0.046). In multivariate analysis, bleeding recurrence was 4.57 (CI 1.31-15.91) times more frequent in group S (P=0.02). There was no difference in the need for surgery and mortality. Acid suppression over pH 6: group S 82.9% of the time versus group P 81.5% (P=0.97). Acid suppression over pH 6 for >85% of the time: group S 14 (47%) patients versus group P 17 (57%) (P=0.44). Disappearance of endoscopic stigmata after 48 h: group S 25/68 patients (37%) versus group P 72/78 (92%) (P<0.0001). No major side effects identified in either study group. CONCLUSIONS: In patients with a bleeding ulcer, after successful endoscopic hemostasis, despite equipotent acid suppression, pantoprazole continuous infusion was superior to somatostatin to prevent bleeding recurrence and quick disappearance of the endoscopic stigmata. Nevertheless, no differences were seen in the need for surgery and mortality.     

Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer

Background and Aims:  After successful endoscopic hemostasis in bleeding peptic ulcer, addition of proton pump inhibitors reduce the rate of recurrent bleeding by maintaining intragastric pH at neutral level. The aim of the present study was to evaluate the effect of various proton pump inhibitors given through different routes on intragastric pH over 72 h after endoscopic hemostasis in bleeding peptic ulcer.
Methods:  Ninety consecutive patients who had successful endoscopic therapy of bleeding peptic ulcer underwent 72-h continuous ambulatory intragastric pH study, were randomly assigned to receive p.o. omeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg omeprazole followed by infusion 8 mg/h for 72 h. Oral pantoprazole 80 mg bolus followed by 80 mg every 12 h for 72 h or i.v. 80 mg pantoprazole followed by infusion of 8 mg/h for 72 h. Oral rabeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg rabeprazole followed by infusion 8 mg/h for 72 h. Five patients received no treatment after successful endoscopic therapy and underwent 72-h pH study.
Results:  Mean 72-h intragastric pH for p.o. omeprazole was 6.56 versus 6.93 for omeprazole infusion ( P  = 0.48). Mean 72-h intragastric pH for p.o. pantoprazole was 6.34 versus 6.32 for pantoprazole infusion ( P  = 0.62). Mean 72-h intragastric pH for rabeprazole p.o. was 6.11 versus 6.18 rabeprazole i.v. ( P  = 0.55). Mean 72-h pH for the no proton pump inhibitor group was 2.04.
Conclusion:  There was no significant difference among various proton pump inhibitors given through different routes on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.     

Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial

BACKGROUND AND AIM: Following successful endoscopic therapy in patients with peptic ulcer bleeding, rebleeding occurs in 20% of patients. Rebleeding remains the most important determinant of poor prognosis. We investigated whether or not administration of pantoprazole infusion would improve the outcome in ulcer bleeding following successful endoscopic therapy. METHODS: In this double-blind, placebo-controlled, prospective trial, patients who had gastric or duodenal ulcers with active bleeding or non-bleeding visible vessel received combined endoscopy therapy with injection of epinephrine and heater probe application. Patients who achieved hemostasis were randomly assigned to receive pantoprazole (80 mg intravenous bolus followed by an infusion at a rate of 8 mg per hour) or placebo for 72 h. The primary end-point was the rate of rebleeding. RESULTS: Rebleeding was lower in the pantoprazole group (8 of 102 patients, 7.8%) than in the placebo group (20 of 101 patients, 19.8%; P = 0.01). Patients in the pantoprazole group required significantly fewer transfusions (1 +/- 2.5 vs 2 +/- 3.3; P = 0.003) and days of hospitalization (5.6 +/- 5.3 vs 7.7 +/- 7.3; P = 0.0003). Rescue therapies were needed more frequently in the placebo group (7.8% vs 19.8%; P = 0.01). Three (2.9%) patients in the pantoprazole group and eight (7.9%) in the placebo group required surgery to control their bleeding (P = 0.12). Two patients in the pantoprazole group and four in the placebo group died (P = 0.45). CONCLUSION: In patients with bleeding peptic ulcers, the use of high dose pantoprazole infusion following successful endoscopic therapy is effective in reducing rebleeding, transfusion requirements and hospital stay.     

Effect of intravenous application of esomeprazole 40 mg versus pantoprazole 40 mg on 24-hour intragastric pH in healthy adults

BACKGROUND: It has been demonstrated that therapy with proton pump inhibitors reduces recurrence of bleeding following initial endoscopic treatment of bleeding peptic ulcers. AIM: This study compared the effects of esomeprazole 40 mg and pantoprazole 40 mg on intragastric acid control. Both substances were administered intravenously as 15-min infusion and as bolus injection. METHODS: Healthy men and women volunteers were enrolled in this single-center, open, randomized, three-way crossover study. After administration of esomeprazole 40 mg and pantoprazole 40 mg intravenously as 15-min infusion, and pantoprazole 40 mg intravenously as bolus injection, continuous 24-h intragastric pH monitoring was carried out. RESULTS: pH data were available for 21 Helicobacter pylori-negative and seven H. pylori-positive volunteers. In H. pylori-negative volunteers, esomeprazole 40 mg intravenously resulted in 11.8 h with an intragastric pH>4 compared with 5.6 h for pantoprazole 40 mg intravenously as infusion (P<0.0001), and 7.2 h for pantoprazole 40 mg intravenously as bolus injection (P<0.001). During the first 6 h of administration, the corresponding values were 3.4, 1.1 (P<0.000001), and 2.1 h (P<0.001), respectively. CONCLUSIONS: In H. pylori-negative patients, a single dose of esomeprazole 40 mg intravenously provides an intragastric acid control that is faster and more pronounced than administration of pantoprazole 40 mg intravenously.     

Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study.

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance.     

Pentagastrin-stimulated gastric acid secretion and pharmacokinetics following single and repeated intravenous administration of the gastric H+, K(+)-ATPase-inhibitor pantoprazole (BY1023/SK&F96022) in healthy volunteers

The objective of the study was to investigate the pharmacodynamics and pharmacokinetics of the gastric H+, K(+)-ATPase inhibitor pantoprazole in man following repeated i.v. dosing. 8 healthy male volunteers aged from 25 to 31 years (median: 29 years), body weight between 72 and 95 kg (median: 82 kg) entered this single-blind two-period cross-over study. Each subject underwent two treatment periods of 5 days each with daily infusion of 15 mg or 30 mg pantoprazole, respectively. A placebo day preceeded the trial. On the placebo day as well as on days 1, 4 and 5 of each treatment period, gastric secretion was stimulated submaximally by a pentagastrin infusion of 0.6 micrograms/h/kg over a period of 4 h, starting one hour before administration of drug or placebo. Repeated once-daily infusion (15 min) of pantoprazole resulted in a rapidly increasing pharmacodynamic effect: as compared to placebo the mean percent inhibition of acid output measured from 1 to 3 h after start of infusion was 22%, 63% and 78% for the 15 mg dose, and 56%, 97% and 99% for the 30 mg dose on days 1, 4 and 5, respectively. The pH also increased in relation to the dose and the duration of treatment. Mean fasting gastrin serum concentrations increased by about 50%, yet remained within the normal range. Only in one subject, one of the individual values was above the upper limit of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Poor responders to intravenous omeprazole in patients with peptic ulcer bleeding

BACKGROUND/AIMS: Although proton pump inhibitors are highly effective in raising intragastric pH, there still remains a small group of patients who resist acid suppression. A high dose of omeprazole has been shown to reduce rebleeding rate in patients with bleeding peptic ulcers after endoscopic therapy. The primary objective of this study was to assess the incidence of peptic ulcer bleeding patients who were resistant to intravenous omeprazole. The secondary objective was to evaluate the relationship between intragastric pH and rebleeding rate in studied patients after successful endoscopic therapy. METHODOLOGY: Between Oct. 1996 and Aug. 1999, 88 bleeding peptic ulcer patients who had obtained initial hemostasis with endoscopic therapy were enrolled in this study. In these patients, 40 mg of omeprazole was given as intravenous bolus followed by 40 mg intravenously every 6 h for 3 days. Thereafter, omeprazole was given 20 mg orally once daily for 2 months. The intragastric pH was recorded for 24 hours after the first dose of omeprazole. The occurrence of rebleeding was observed for 14 days. RESULTS: The mean intragastric pH value of these 88 patients was 6.07, (95% CI: 5.91-6.23). Four patients (5%) were found to have omeprazole resistance (pH < 4.0, 50% of the time). By the 3rd days after entering the study, more patients with a mean pH < 6 rebled (5/25 vs. 3/63, p<0.05). CONCLUSIONS: About five percent of patients with peptic ulcer bleeding respond poorly to intravenous omeprazole. Rebleeding rate is higher in patients with a mean intragastric pH of less than 6.     

Prospective,Randomized Trial Comparing Effect of Oral Versus Intravenous Pantoprazole on Rebleeding After Nonvariceal Upper Gastrointestinal Bleeding: A Pilot Study

Proton pump inhibitors (PPIs) reduce the rate of rebleeding in patients with nonvariceal upper GI bleed (NVGIB). Oral (PO) and intravenous (IV) pantoprazole are equipotent in raising gastric pH. We conducted a pilot study comparing the efficacy of PO vs. IV pantoprazole for reducing rebleeding after NVGIB. Patients with NVGIB were randomized to receive PO (80 mg BID for 3 days) or IV (80-mg IV bolus and 8 mg/hr infusion for 3 days) pantoprazole followed by pantoprazole, 40 mg PO BID, for 30 days. All patients underwent endoscopy within 24 hr and endotherapy was applied where necessary. Twelve patients randomized to the PO and 13 to the IV pantoprazole group were comparable in age, hematocrit, Rockall scores, ulcer characteristics, and endoscopic interventions. Two patients in the IV arm rebled and another in the IV arm developed reversible renal failure. No patient in the PO arm rebled, had organ failure, or had to be changed to IV pantoprazole. We conclude that in this pilot study, the effect of PO pantoprazole on 30-day rebleeding rate in patients with NVGIB was similar to that of IV pantoprazole.     

Intragastric pH monitoring during antisecretory therapy in patient with gastrointestinal bleeding

This study was undertaken to evaluate the effect of various cimetidine and ranitidine administration schedules on intragastric pH in patients with recent episodes of hematemesis. The investigation was performed on 10 subjects whose hemorrhage had ceased either spontaneously or after pharmacological treatment for at least 24-36 h. The following therapeutic regimens were randomly evaluated: bolus infusions of ranitidine (100 mg/6 h and 50 mg/4 h) and cimetidine (400 mg/6 h and 200 mg/4 h) and continuous infusions of ranitidine (0.2 and 0.4 mg/kg/h) and cimetidine (100 mg/h). Each study evaluated at least two consecutive boli or an 8-h continuous infusion. All treatments produced significant elevations in the basal intragastric pH (p less than 0.001). With bolus administrations, however, the pH displayed consistent oscillations. The pH fell below 4 approximately 6 h after the administration in all the patients treated with 400 mg of cimetidine and in three treated with 50 mg of ranitidine. The administration of histamine H2-receptor antagonists every 4 h allowed better control of intragastric acidity. The pH dropped below 4 in seven of the 10 patients in the 4-h period after the administration of 200 mg cimetidine, and in one of the 10 patients treated with 50 mg of ranitidine/4 h. Increasing bolus dose did not reduce the time lapse or increase the inhibition of intragastric acidity. Continuous infusions were efficacious in maintaining pH values constantly above 6. Ranitidine (0.2 mg/kg/h) achieved the same inhibitory efficiency as cimetidine (100 mg/h). These data indicate that continuous venous infusion of both ranitidine and cimetidine is significantly more efficacious than repeated single bolus administrations.     

The Efficacy of High- and Low-Dose Intravenous Omeprazole in Preventing Rebleeding for Patients with Bleeding Peptic Ulcers and Comorbid Illnesses

This study sought to determine if high-dose omeprazole infusion could improve the control of rebleeding in patients with comorbid illnesses and bleeding peptic ulcers. After achieving hemostasis by endoscopy, 105 patients were randomized into high-dose (n = 52) and low-dose (n = 53) groups, receiving 200 and 80 mg/day omeprazole, respectively, as a continuous infusion for 3 days.Thereafter, oral omeprazole, 20 mg/day, was given. The cumulative rebleeding rates comparatively rose in both groups (high-dose vs. low-dose group), beginning on day 3 (15.4% vs. 11.3%), day 7 (19.6% vs. 20%), and day 14 (32.7% vs. 28.9%), until day 28 (35.4% vs. 33.3%), and were not significantly different between the two groups (P > 0.50). Multiple logistic regression confirmed that a serum albumin level < 3 g/dL was an independent factor associated with rebleeding (P = 0.002). For patients with comorbidities, 3-day omeprazole infusion, despite increasing the daily dose from 80 to 200 mg, was not adequate to control peptic ulcer rebleeding.This work was supported by a research grant from the National Cheng Kung University Hospital, Tainan, Taiwan (NCKUH-92-03). Some of the data were presented as an abstract at the annual meeting of the Gastroenterology Society of Taiwan, March 27, 2004.     

The influence of intravenous omeprazole on intragastric pH and outcomes in patients with peptic ulcer bleeding after successful endoscopic therapy--a prospective randomized comparative trial.

BACKGROUND/AIMS: The role of omeprazole in preventing rebleeding in patients with peptic ulcer bleeding after successful endoscopic therapy has been controversial. In this study, we used 3 different formulas of intravenous omeprazole in the above patients. We wished to compare the intragastric pH and outcomes among them. METHODOLOGY: Between July 1996 and May 1997, after having obtained initial hemostasis with endoscopic therapy, a total of 20 patients with peptic ulcer bleeding (spurting/oozing/non-bleeding visible vessel: 6/4/10) received intravenous bolus of omeprazole 20 mg every 3 hours; 20 patients (3/5/12) received intravenous bolus of omeprazole 40 mg every 6 hours; and, 20 patients (5/4/11) received intravenous bolus of omeprazole 80 mg every 12 hours for 3 days. One intragastric pH meter (Gastrograph Mark III, Medical Instruments Corp. Switzerland) was used to record 24-hour intragastic pH. RESULTS: The intragastric pH in the patients receiving omeprazole 20 mg every 3 hours was 6.1, 6.0-6.2 (mean: 95% CI); in patients receiving omeprazole 40 mg every 6 hours it was 6.4, 6.2-6.5; and, in patients receiving omeprazole 80 mg every 12 hours it was 5.8, 5.7-5.9. The duration of intragastric pH > 6.0 in omeprazole 20 mg every 3 hours was 70.9%, 57.3%-84.4% (mean: 95% CI); in omeprazole 40 mg every 6 hours it was 83.1%, 73.1%-93.1%; and, in omeprazole 80 mg every 12 hours it was 66%, 51.5%-80.4%. Patients with peptic ulcers receiving omeprazole 40 mg intravenous bolus every 6 hours had the highest intragastric pH as compared with the other 2 groups (p < 0.0001). There were no significant differences concerning rebleeding rates, volume of blood transfusion, hospital stay, numbers of operation and mortality among the 3 groups. CONCLUSIONS: After initial hemostasis had been obtained, patients with peptic ulcer bleeding receiving 40 mg intravenous bolus every 6 hours had the highest intragastric pH. However, they had similar outcomes with the other 2 groups.     

Continuous Infusion of Pantoprazole versus Ranitidine for Prevention of Ulcer Rebleeding: A U.S. Multicenter Randomized, Double-Blind Study CME

OBJECTIVES:  No North American randomized study has compared ulcer rebleeding rates after endoscopic hemostasis in high-risk patients treated with high-dose intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN) would be lower than with IV ranitidine (RAN).
METHODS:  This was a multicenter, randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with or without epinephrine injection, then were randomly assigned to IV PAN 80 mg plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding rates up to 30 days were compared in an intention-to-treat analysis.
RESULTS:  The study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN 77). Demographics, APACHE II scores, ulcer type/location, stigmata, and hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72 patients) with PAN and 14.3% (11 of 77) for RAN ( p = 0.19). Rebleeds occurred within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day mortality rate was 4%. Nonbleeding severe adverse events were more common in the RAN than in the PAN group (14 [18.1%] vs 7 [9.7%], p = 0.16).
CONCLUSIONS:  Because of the small sample size of this study, there was an arithmetic but not significant difference in ulcer rebleeding rates.     

Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: a U.S. multicenter randomized, double-blind study

OBJECTIVES: No North American randomized study has compared ulcer rebleeding rates after endoscopic hemostasis in high-risk patients treated with high-dose intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN) would be lower than with IV ranitidine (RAN). METHODS: This was a multicenter, randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with or without epinephrine injection, then were randomly assigned to IV PAN 80 mg plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding rates up to 30 days were compared in an intention-to-treat analysis. RESULTS: The study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN 77). Demographics, APACHE II scores, ulcer type/location, stigmata, and hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72 patients) with PAN and 14.3% (11 of 77) for RAN (p= 0.19). Rebleeds occurred within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day mortality rate was 4%. Nonbleeding severe adverse events were more common in the RAN than in the PAN group (14 [18.1%]vs 7 [9.7%], p= 0.16). CONCLUSIONS: Because of the small sample size of this study, there was an arithmetic but not significant difference in ulcer rebleeding rates.     

Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome

BACKGROUND & AIMS: Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings). METHODS: We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours. RESULTS: The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7). No serious or unexpected adverse events were observed. CONCLUSIONS: Intravenous pantoprazole, 160-240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients.     

Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients

BACKGROUND AND AIM: Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients. METHODS: A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed. RESULTS: Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers. CONCLUSION: A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes.     

The role of sustained achlorhydria in bleeding peptic ulcer

Twenty-five patients with bleeding peptic ulcers were randomized to receive either ranitidine 50 mg 8 hourly i.v. (control group) or a continuous nasogastric antacid infusion at the rate of 0.5 ml/min along with an i.v. injection of cimetidine 100 mg/h (treatment group). Twelve patients were included in the control group and 13 in the treatment group. The mean gastric pH on therapy was significantly higher in the treatment group (7.88 +/- 0.37) than in the control group (5.00 +/- 0.55) (p less than 0.001), and the gastric pH was noted to be greater than 7 on 95% of the occasions in the treatment group and on 8.6% of the occasions in the control group. An overall control of bleeding was achieved in 92.3% of the patients in the treatment group and 50% of the patients in the control group (p less than .05). Thus, the failure of therapy was significantly more common in the control group than in the treatment group (p less than 0.05), and more patients of the control group had to undergo emergency surgery than that in the treatment group. None of the patients in the treatment group, but 16.6% of the patients in the control group, died during the study period in the hospital stay. We conclude that in patients with bleeding peptic ulcer an intensive medical therapy comprising hourly injections of cimetidine (or presumably of other H2 blockers) and continuous nasogastric antacid infusion can achieve sustained achlorhydria, better control of bleeding, and reduce the need for emergency surgery.     

Intravenous pantoprazole as an adjuvant therapy following successful endoscopic treatment for peptic ulcer bleeding

BACKGROUND:

Several studies have suggested that proton pump inhibitors are efficacious in preventing rebleeding when administered immediately after endoscopic treatments. However, there are limited clinical outcome data on the use of intravenous pantoprazole.

OBJECTIVE:

To evaluate the efficacy of intravenous pantoprazole after successful endoscopic treatment for peptic ulcer bleeding using evidence from randomized controlled trials (RCTs).

METHODS:

The Cochrane Library, MEDLINE, EMBASE and several Chinese databases up to July 2008 were searched. RCTs that compared the relative effectiveness of intravenous pantoprazole with placebo, H₂ receptor antagonist or other agents for patients with peptic ulcer bleeding who were pretreated with successful endoscopic therapies were retrieved.

RESULTS:

Five RCTs comprising a total of 821 participants were included in the final meta-analysis. Overall, there were significant differences in ulcer rebleeding (RR 0.31; 95% CI 0.18 to 0.53; pooled rates were 4.7% for pantoprazole and 15.0% for control), surgical intervention (RR 0.28, 95% CI 0.09 to 0.83; pooled rates were 1.4% in pantoprazole group versus 6.5% in control) and total length of hospital stay (weighted mean difference −1.53; 95% CI −1.91 to −1.16), but not on mortality (RR 0.72, 95% CI 0.29 to 1.81; pooled mortality rates were 1.9% for pantoprazole versus 2.8% for control) and blood transfusion requirements (weighted mean difference −0.53; 95% CI for random effects −1.04 to −0.02) when compared with control treatments. A series of subgroup analyses supported the results from the main analysis.

CONCLUSIONS:

Intravenous administration of pantoprazole after endoscopic therapy for peptic ulcer bleeding reduces rates of ulcer rebleeding, surgical intervention and overall duration of hospital stay, but not mortality and blood transfusion requirements compared with placebo, H₂ receptor antagonist or somatostatin.     

Will Helicobacter pylori affect short-term rebleeding rate in peptic ulcer bleeding patients after successful endoscopic therapy?

OBJECTIVE: Helicobacter pylori (H. pylori) can augment the pH-increasing effect of omeprazole in patients with peptic ulcer. A high intragastric pH may be helpful in preventing recurrent hemorrhage by stabilizing the blood clot at the ulcer base of bleeding peptic ulcer patients. Therefore, we hypothesized that omeprazole may reduce short-term rebleeding rate in these patients with H. pylori infection after initial hemostasis had been obtained. METHODS: Between July 1996 and December 1998, 65 bleeding peptic ulcer patients (24 gastric ulcer, 41 duodenal ulcer) who had obtained initial hemostasis with endoscopic therapy were enrolled in this trial. Thirty (46.2%) of them were found to have H. pylori infection by a rapid urease test and pathological examination. For all studied patients, omeprazole was given 40 mg intravenously every 6 h for 3 days. Thereafter, omeprazole was given 20 mg per os (p.o.) once daily for 2 months. A pH meter was inserted in the fundus of each patient under fluoroscopic guidance after intravenous omeprazole had been administered. The occurrence of rebleeding episode was observed for 14 days. RESULTS: In patients with H. pylori infection, intragastric pH (median, 95% confidence interval [CI]: 6.54, 5.90-6.68) was higher than in those without H. pylori infection (6.05, 5.59-6.50, p < 0.001). However, the patients with rebleeding (2 vs 3), volume of blood transfusion (median, range: 1000 ml, 0-2250 vs 750, 0-2000), number of operations (0 vs 1), mortality caused by bleeding (0 vs 0), and hospital stay (median, range: 6 days, 3-14 vs 7, 5-16) were not statistically different from those without H. pylori infection. CONCLUSIONS: Omeprazole does increase intragastric pH in bleeding peptic ulcer patients with H. pylori infection. However, the presence of H. pylori infection does not affect the short-term rebleeding rate in these patients.     

Comparison of the effects of intravenous infusion of omeprazole and H2‐receptor antagonists on intragastric pH in bleeding duodenal ulcer patients

OBJECTIVE : To evaluate the effects of intravenous infusion of omeprazole and H₂‐receptor antagonists on 24‐h intragastric pH levels in patients with bleeding duodenal ulcers. METHODS : Fifty patients with active bleeding duodenal ulcers were randomly assigned to receive one of four treatment regimens: 40 mg omeprazole by intravenous infusion every 12 h, 40 mg famotidine intravenously every 12 h, 50 mg ranitidine intravenously every 6 h, 200 mg cimetidine intravenously every 6 h. Intragastric pH values were monitored in each subject at the baseline level and continuously for 24 h after treatment. RESULTS : Only the omeprazole group produced mean and median intragastric pH values of above 6. The famotidine group had mean and median intragastric pH values above 4. In the other two groups, pH values were both below 4. The mean percentages of time that intragastric pH levels were < 4, < 5 and < 6 over the 24 h period in each of the treatment groups were found to increase in the following order (smallest percentage to largest percentage): omeprazole, famotidine, ranitidine and cimetidine. CONCLUSIONS : The effect of intravenous use of omeprazole in active duodenal ulcer bleeding is superior to that of H₂‐receptor antagonists and the increase in intragastric pH is maintained for a longer period.