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Original Investigation |

A Prospective Randomized Comparative Trial Showing That Omeprazole Prevents Rebleeding in Patients With Bleeding Peptic Ulcer After Successful Endoscopic Therapy FREE

Hwai-Jeng Lin, MD, FACG; Wen-Ching Lo, MD; Fa-Yauh Lee, MD; Chin-Lin Perng, MD; Guan-Ying Tseng, MD
[+] Author Affiliations

From the Division of Gastroenterology, Department of Medicine, Veterans General Hospital, and National Yang-Ming University, School of Medicine, Taipei, Taiwan.


Arch Intern Med. 1998;158(1):54-58. doi:10.1001/archinte.158.1.54.
Text Size: A A A
Published online

Background  A blood clot in a peptic ulcer is unstable in a low pH environment. The use of omeprazole may prevent rebleeding by elevating intragastric pH in patients with bleeding peptic ulcer after hemostasis has been achieved.

Objectives  To assess the influence of using omeprazole and cimetidine on 24-hour intragastric pH and to determine their ability to prevent rebleeding after having achieved initial hemostasis in patients with active bleeding or nonbleeding visible vessels.

Methods  One hundred patients with bleeding peptic ulcers who had obtained initial hemostasis were enrolled in this randomized comparative trial. In the cimetidine group (n=50), a 300-mg intravenous bolus of cimetidine was given, followed by a 1200-mg continuous infusion daily for 3 days. Thereafter, 400 mg of cimetidine was given orally twice daily for 2 months. In the omeprazole group (n=50), a 40-mg intravenous bolus of omeprazole was given, followed by 160 mg of continuous infusion daily for 3 days. Thereafter, 20 mg of omeprazole was given orally once daily for 2 months. A pH meter was inserted in each patient's fundus under fluoroscopic guidance after the intravenous bolus of cimetidine or omeprazole had been administered.

Results  The stigmata of recent hemorrhage before endoscopic therapy in the omeprazole and cimetidine groups were, respectively, spurting (9 vs 12), oozing (4 vs 9), and nonbleeding visible vessel (37 vs 29) (P>.05). The duration of intragastric pH higher than 6.0 was longer in the omeprazole group (mean[±SD], 84.4±22.9%) than that of the cimetidine group (mean[±SD], 53.5±32.3%) (P<.001). Rebleeding occurred in 2 patients (4%) in the omeprazole group and in 12 patients (24%) in the cimetidine group by day 14 after enrollment (P=.004). There was a tendency for patients in the omeprazole group to require less blood transfusion (median, 0 mL; range, 0-2500 mL) than those in the cimetidine group (median, 0 mL; range, 0-5000 mL) (P=.08). The hospital stay and number of operations and mortality rate were similar between both groups.

Conclusions  The use of omeprazole is more effective than cimetidine in increasing intragastric pH and reducing rebleeding episodes in patients with bleeding peptic ulcers after successful endoscopic therapy. This suggests that omeprazole should be used routinely after successful endoscopic therapy.

Figures in this Article

PATIENTS WITH major bleeding and endoscopic evidence of an ulcer with active bleeding or a nonbleeding visible vessel (NBVV) are at high risk for persistent or recurrent bleeding and should receive endoscopic therapy.1 In the various endoscopic treatments for peptic ulcer hemorrhage, heater probe thermocoagulation (HPT) and multipolar electrocoagulation (MPEC) are the 2 most promising techniques.1

Although a high initial hemostatic rate can be obtained with endoscopic therapy, rebleeding occurs in 10% to 30% of these patients.25 Rebleeding has been consistently described as the most important prognostic factor.6,7 If it can be prevented, the mortality rate is reduced accordingly.

A stable blood clot in a peptic ulcer is crucial to hemostasis. However, in a low pH environment, platelet dysfunction has been observed.8,9 In addition, pepsin can lyse the blood clots that plug vessels in the ulcer base and induce rebleeding thereafter.911 Thus, the hypothesis that by suppressing the intragastric acid, use of omeprazole might benefit patients at risk for further hemorrhage was proposed.

Omeprazole inhibits H+-K+ adenosine triphosphatase, dose-dependently suppressing basal and stimulated gastric acid secretion.12 Omeprazole administered intravenously appears effective in maintaining an intragastric pH higher than 4 for a 24-hour period.1315 The role of omeprazole in preventing rebleeding in patients with peptic ulcer bleeding has been controversial.1623 The aims of this study were to assess the influence of omeprazole and cimetidine on 24-hour intragastric pH and to determine their ability to prevent rebleeding after having achieved initial hemostasis in patients with active bleeding or NBVV.

CRITERIA FOR INCLUSION AND EXCLUSION

Patients were accepted for endoscopic therapy if a peptic ulcer with active bleeding or an NBVV was observed within 12 hours of hospital admission. The possibility of endoscopic therapy was discussed with patients and/or their relatives and a written informed consent was obtained before the trial. After initial hemostasis was achieved with either HPT or MPEC, the patients were enrolled in this study. The study was approved by the Clinical Research Committee of the Veterans General Hospital, Taipei, Taiwan.

Patients were excluded from the study if they were pregnant, did not give written informed consent, had bleeding tendency (platelet count <50×109/L, serum prothrombin <30% of normal, or were taking anticoagulants), uremia, or bleeding gastric cancer.

ENDOSCOPIC THERAPY

Endoscopic hemostasis was performed by one of us (H.-J. L.) who had experience with at least 1000 patients in endoscopic hemostatic therapy. Two therapeutic modalities (HPT or MPEC) were used according to the availability of the hemostatic machine (we used HPT in the emergency department, and MPEC after admission). The methods of performing HPT or MPEC are described in our previous study.4

RANDOMIZATION AND MEDICINE

Patients enrolled in the study were randomly allocated into 2 groups using sealed envelopes containing a therapeutic option (cimetidine or omeprazole) derived from a randomized table. In the cimetidine group, a 300-mg intravenous bolus of cimetidine was given followed by a 1200-mg continuous infusion daily for 3 days. Thereafter, 400 mg of cimetidine was given orally twice daily for 2 months. In the omeprazole group, a 40-mg intravenous bolus of omeprazole was given followed by a 160-mg continuous infusion daily for 3 days. Thereafter, 20 mg of omeprazole was given orally once daily for 2 months. A nasogastric tube and a pH meter (Gastrograph Mark III, Medical Instruments Corporation, Solothurn, Switzerland) were inserted in each patient's fundus under fluoroscopic guidance after the intravenous bolus of cimetidine or omeprazole had been administered. The intragastric pH was recorded and stored at 6-second intervals for 24 hours.

MONITORING

Patients' vital signs were checked every hour for the first 12 hours, every 2 hours for the second 12 hours, and every 4 hours for the following 24 hours until they became stable, then 4 times daily. The hemoglobin level and hematocrit were checked at least once daily, and a blood transfusion was given if the hemoglobin level decreased to lower than 90 g/L or if the patient's vital signs deteriorated. The attending physicians or surgeons were made aware of the exact endoscopic findings and treatment given in each case. Endoscopy was undertaken 72 hours later. If no blood clot or hemorrhage was observed at the ulcer base, the patient was discharged and followed up in the outpatient department.

Active bleeding was defined as a continuous blood flow spurting or oozing from the ulcer base. An NBVV at endoscopy was defined as a discrete protuberance at the ulcer base that was resistant to washing and was often associated with the freshest clot in the ulcer base. Shock was defined as systolic blood pressure lower than 100 mm Hg and a pulse rate of more than 100/min accompanied by cold sweats, pallor, and oliguria. Initial hemostasis was defined as no visible hemorrhage lasting for 5 minutes after endoscopic therapy. Ultimate hemostasis was defined as no rebleeding during the 14 days after endoscopic therapy.

Rebleeding was suspected if unstable vital signs, continued tarry, bloody stools, or a drop in the hemoglobin level of more than 20 g/L within 24 hours was observed during hospitalization. For these patients, an emergency endoscopy was performed immediately. Rebleeding was concluded if either blood in the stomach 24 hours after therapy or a fresh blood clot or bleeding in the ulcer base was found. All patients with rebleeding were treated a second time by endoscopic hemostasis unless they refused. An emergency operation was performed if bleeding could not be controlled with HPT or MPEC or if rebleeding occurred after 2 attempts with HPT or MPEC therapy.

At entry to the study, the following data were recorded: age, sex, signs of bleeding (hematemesis or melena), the location of the ulcer (esophagus, stomach, duodenum, or stoma), ulcer size, presence of overlying clot, the appearance of gastric contents (clear, coffee grounds, and blood), stigmata of bleeding (spurting, oozing, and NBVV), volume of blood transfusion at entry, presence of shock, hemoglobin level, nonsteroidal anti-inflammatory drug ingestion, cigarette smoking, alcohol drinking, and comorbid illness.

END POINTS

The outcome of measure was the rebleeding rate at day 3 and day 14 after entry to the study. At day 14, volume of blood transfused, number of procedures performed, and the mortality rates of the 2 groups were compared as well.

STATISTICS

The sample size estimation was based on an expected rebleeding rate of 30% in the cimetidine group. The trial was designed to detect a 25% difference in favor of the omeprazole group with a type I error of 0.05 and type II error of 0.2. At least 43 patients were essential for each group.

We used the Student t test (paired, 2-tailed) to compare the basic data of age, ulcer size, volume of blood transfused after entry, initial hemoglobin level, intragastric pH, and hospital stay between both groups. The χ2 test, with or without Yates correction, and Fisher exact test were used when appropriate to compare sex, number of rebleeding episodes, emergency operations, mortality rate, the location of the bleeding, presence of overlying clot, gastric contents, stigmata of bleeding, presence of shock, nonsteroidal anti-inflammatory drug ingestion, cigarette smoking, alcohol drinking, comorbid illness, and the hemostatic effect between the 2 groups. A probability value of less than .05 was considered significant.

Between November 1995 and June 1996, 617 patients received emergency endoscopy in our hospital because of hematemesis and/or tarry stool. We found obscure bleeding in 15 patients, a clear ulcer in 184 patients, pigmented spots in 127 patients, adherent blood clots in 96 patients, an NBVV in 61 patients, active bleeding in 47 patients, and esophageal or fundic varices in 87 patients.

Of the patients with active bleeding or an NBVV (n=108), we obtained initial hemostasis in 107 patients. Seven patients were excluded from the study because of inability to give informed consent (n=4), bleeding tendency (n=1), and the presence of a bleeding gastric malignant neoplasm (n=2). Hence, a total of 100 patients were enrolled in the trial. Fifty patients received omeprazole and the same number received cimetidine intravenously.

There was no statistical difference in the clinical parameters of the 2 groups (Table 1). We performed HPT for 30 and 39 patients and MPEC for 20 and 11 patients in the omeprazole and cimetidine groups, respectively (P>.05). Eleven patients rebled after receiving HPT and 3 patients rebled after receiving MPEC (P>.10).

Table Graphic Jump LocationTable 1. Clinical Parameters of the Omeprazole and the Cimetidine Groups

The mean intragastric pH rose to 6.0 one hour after the initial bolus of omeprazole in the omeprazole group; it persisted around this value for the rest of the 24 hours (Figure). In the cimetidine group, the mean intragastric pH rose to 4.0 one hour after the initial bolus of cimetidine and persisted around 4.5 to 5.5 for the rest of the 24 hours. The duration in time of the raised intragastric pH (>6.0) was 84.4±22.9% (mean±SD) in the omeprazole group, compared with 53.5±32.3% in the cimetidine group (P<.001).

Place holder to copy figure label and caption

Mean intragastric pH profile in the omeprazole group and the cimetidine group during the 24 hours following initial bolus injection and sustained infusion.

Graphic Jump Location

By day 3 after entry, no patient rebled in the omeprazole group, whereas 8 patients rebled in the cimetidine group (P=.003). By 2 weeks after entry, 2 patients rebled in the omeprazole group and 12 patients rebled in the cimetidine group (P=.004) (Table 2).

Table Graphic Jump LocationTable 2. Major Clinical Outcomes of Both Groups

Rebleeding episodes occurred in 2 patients in the omeprazole group 8 days after endoscopic therapy. One had uneventful recovery after conservative treatment, while another received HPT twice plus omeprazole and recovered smoothly. In the rebleeding patients in the cimetidine group, rebleeding occurred at 1 day (3 patients), 2 days (2 patients), 3 days (2 patients), 5 days (1 patient), 6 days (2 patients), 8 days (1 patient), and 10 days (1 patient) after endoscopic therapy. Six received MPEC plus omeprazole therapy, 2 received MPEC plus cimetidine therapy, 1 received HPT plus omeprazole therapy, and 1 received HPT plus cimetidine therapy. These 10 patients recovered uneventfully. The remaining 2 patients died despite further endoscopic therapy (one had cholangiocarcinoma with metastasis and died of bleeding after a second administration with MPEC plus omeprazole, while the other had renal cell carcinoma with metastasis and died of sepsis after endoscopic therapy was provided 3 times).

Patients with ulcers located at the lesser curvature of the gastric high body (n=2, cimetidine group) and posterior wall of the duodenal bulb (n=5, 4 in the omeprazole group and 1 in the cimetidine group) did not have a higher rebleeding rate than patients with ulcers in other locations (2/7 vs 12/93, respectively; P=.25).

There was a tendency for the patients in omeprazole group to have a lower volume of blood transfused (median, 0 mL; range, 0-2500 mL) compared with those in the cimetidine group (median, 0 mL; range, 0-5000 mL). The length of hospital stay, number of procedures performed, and mortality rates of the 2 groups were not statistically different.

A bleeding peptic ulcer remains a serious medical problem with significant morbidity and mortality. Endoscopic therapy significantly reduces further bleeding, surgery, and mortality in patients with bleeding peptic ulcers24 and is now recommended as the first hemostatic modality for these patients.1,24

After obtaining initial hemostasis, rebleeding is another important impact to the prognosis. An ideal therapy includes a successful endoscopic therapy plus a low rebleeding rate. Rebleeding episodes occur within 3 days in most instances.2527 In addition, an intragastric pH higher than 6.0 is a prerequisite for preventing rebleeding in patients with bleeding peptic ulcers.8 Therefore, a drug that rapidly increases intragastric pH and lasts for 3 to 4 days is necessary to prevent rebleeding.

With conventional recommended doses of histamine2 blockers, intragastric pH cannot be maintained higher than 4.0 for a long period in patients with a bleeding peptic ulcer.15,2830 Continuous intravenous histamine2-blocker infusion does not influence the natural history of bleeding peptic ulcers.16 In this study, we achieved a similar intragastric recording and rebleeding rate.

Pharmacologically, omeprazole can quickly achieve an optimal intragastric pH condition for support of the physiological cascade of hemostasis.14 The optimal dose was found to be continuous infusion of 8 mg/h or 160 mg/24 h of omeprazole.14,19,31 In this study, we used a similar dose of omeprazole and obtained intragastric pH of 6.0 or more in 84.4±22.9% (mean±SD) time period in the omeprazole group.

The use of omeprazole is reported to be ineffective in patients with peptic ulcer bleeding either with17 or without endoscopic therapy.16 In these 2 studies, the authors used an 80-mg intravenous bolus of omeprazole followed by 40 mg every 8 hours. There are at least 3 pitfalls in their studies. First, the dose of omeprazole was suboptimal. Second, the interval of omeprazole injection administered intravenously (8 hours) was too long. Because proton pumps are continuously being generated,32 and the half-life of omeprazole in the circulation is short (50 minutes), it needs to be given more frequently (eg, every 3 hours) or continuously.14 According to the published data, it will fail to raise intragastric pH higher than 4.0 continuously in the studied period with the above-mentioned methods.1416,33 Third, Daneshmend et al16 did not restrict their patients to those from high-risk groups. Hence, a type II error may occur under these conditions.

In this study, we obtained remarkable acid suppression in the omeprazole group; no rebleeding episodes occurred during continuous infusion of omeprazole. The 2 rebleeding episodes occurred after patients received 20 mg of omeprazole once daily (8 days after enrollment). One had minor rebleeding, which subsided spontaneously, while the other had an uneventful recovery after HPT was given a third time as well as 20 mg of omeprazole twice daily. Whether an increased dosage of omeprazole (eg, 20 mg twice daily) after continuous infusion can prevent rebleeding awaits further study.

Hospital stay, number of procedures, and mortality rate of the 2 groups were similar. This may be due to the early detection of rebleeding episodes and the aggressive endoscopic therapy given, thus minimizing the difference between the 2 groups.

Omeprazole administered intravenously as a 40-mg bolus followed by a 160-mg continuous infusion daily can elevate intragastric pH remarkably and prevent rebleeding in patients with peptic ulcer bleeding after initial hemostasis has been achieved. It should be used routinely in these patients after successful endoscopic therapy.

Accepted for publication April 23, 1997.

Reprints: Hwai-Jeng Lin, MD, FACG, Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, Republic of China.

Consensus Development Panel, Consensus statement on therapeutic endoscopy and bleeding ulcers. Gastrointest Endosc. 1990;36S62- S65
Link to Article
Lin  HJLee  FYKang  WMTsai  YTLee  SDLee  CH Heat probe thermocoagulation and pure alcohol injection in massive peptic ulcer haemorrhage: a prospective, randomized controlled trial. Gut. 1990;31753- 757
Link to Article
Llach  JBordas  JMSalmerón  JM  et al.  A prospective randomized trial of heater probe thermocoagulation versus injection therapy in peptic ulcer hemorrhage. Gastrointest Endosc. 1996;43117- 120
Link to Article
Lin  HJWang  KPerng  CLLee  CHLee  SD Heat probe thermocoagulation and multipolar electrocoagulation for arrest of peptic ulcer bleeding: a prospective, randomized comparative trial. J Clin Gastroenterol. 1995;2199- 102
Link to Article
Laine  L Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers: a prospective, randomized trial. Gastroenterology. 1990;991303- 1306
Allan  RDykes  P A study of the factors influencing mortality rates from gastrointestinal haemorrhage. QJM. 1976;45533- 550
Turner  IBJones  MPiper  DW Factors influencing mortality from bleeding peptic ulcers. Scand J Gastroenterol. 1991;26661- 666
Link to Article
Green  FWKaplan  MMCurtis  LELevine  PH Effect of acid and pepsin on blood coagulation and platelet aggregation. Gastroenterology. 1978;7438- 43
Low  JDodds  AJBiggs  JC Fibrinolytic activity of gastroduodenal secretions: a possible role in upper gastrointestinal haemorrhage. Thromb Res. 1980;17819- 830
Link to Article
Patchett  SEEnright  HAfdhal  NO'Connell  WO'Donoghue  DP Clot lysis by gastric juice: an in vitro study. Gut. 1989;301704- 1707
Link to Article
Barkham  PTocantins  TM Action of human gastric juice on human blood clots. J Appl Physiol. 1953;61- 7
Wilde  MIMcTavish  D Omeprazole: an update of its pharmacology and therapeutic use in acid-related disorders. Drugs. 1994;4891- 132
Link to Article
Andersen  JStröm  MNÆsdal  JLeire  KWalan  A Intravenous omeprazole: effect of a loading dose on 24-h intragastric pH. Aliment Pharmacol Ther. 1990;465- 72
Link to Article
Brunner  GLuna  PThiesemann  C Drugs for pH control in upper gastrointestinal bleeding. Aliment Pharmacol Ther. 1995;9 (suppl 1) 47- 50
Link to Article
Cederberg  CThompson  ABRKirdeikis  PKristersson  C Effect of continuous intravenous infusion of omeprazole on 24-hour intragastric pH in fasting DUpatients: comparison to repeated bolus doses of omeprazole or ranitidine. Gastroenterology. 1992;102 (suppl) A48
Daneshmend  TKHawkey  CJLangman  MJSLogan  RFALong  RGWalt  RP Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. Gut. 1992;304143- 147
Villanueva  CBalanzó  JTorras  X  et al.  Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study. Endoscopy. 1995;27308- 312
Link to Article
Brunner  GChang  J Intravenous therapy with high doses of ranitidine and omeprazole in critically ill patients with bleeding peptic ulcerations of the upper intestinal tract: an open randomized controlled trial. Digestion. 1990;45217- 225
Link to Article
Brunner  GHGThiesemann  C The potential clinical role of intravenous omeprazole. Digestion. 1992;51 (suppl 1) 17- 20
Link to Article
Muckadell  OBSHavelund  THarling  H  et al.  Omeprazole improved outcome in peptic ulcer bleeding. Gastroenterology. 1995;108A212Abstract
Link to Article
Lind  TAadland  EEriksson  SFernström  PHasselgren  GLundell  L Beneficial effects of I.V. omeprazole (OME) in patients with peptic ulcer bleeding (PUB). Gastroenterology. 1995;108A150Abstract
Link to Article
Lanas  AArtal  ABlás  JMArroyo  MTLopez-Zaborras  JSáinz  R Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol. 1995;21103- 106
Link to Article
Grosso  CRossi  AGambitta  P  et al.  Non-bleeding visible vessel treatment: perendoscopic injection therapy versus omeprazole infusion. Scand J Gastroenterol. 1995;30872- 875
Link to Article
Cook  DJGuyatt  GHSalena  BJLaine  LA Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology. 1992;102139- 148
Lin  HJPerng  CLLee  FYLee  CHLee  SD Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. Gut. 1994;351389- 1393
Link to Article
Lin  HJPerng  CLWang  KLee  SDLee  CH Long-term results of heater probe thermocoagulation for patients with massive peptic ulcer bleeding: a prospective observation. Am J Gastroenterol. 1995;9044- 47
Lin  HJWang  KPerng  CLLee  FYLee  CHLee  SD Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation. Gastrointest Endosc. 1996;43470- 473
Link to Article
Reynolds  JRWalt  RPClark  AGHardcastle  JDLangman  MJS Intragastric pH monitoring in acute upper gastrointestinal bleeding and the effect of intravenous cimetidine and ranitidine. Aliment Pharmacol Ther. 1987;123- 30
Link to Article
Peterson  WLBarnett  CFeldman  MRichardson  CT Reduction of twenty-four-hour gastric acidity with combination drugs therapy in patients with duodenal ulcer. Gastroenterology. 1979;771015- 1020
Merki  HSWitzel  LKaufman  D  et al.  Continuous intravenous infusions of famotidine maintain high intragastric pH in duodenal ulcer. Gut. 1988;29453- 457
Link to Article
Walt  RPReynolds  JRLangman  MJS  et al.  Intravenous omeprazole rapidly raises intragastric pH. Gut. 1985;26902- 906
Link to Article
Sachs  G Therapeutic control of acid secretion: pharmacology of the parietal cell. Curr Opin Gastroenterol. 1990;6859- 866
Link to Article
Baak  LCBiemond  IJansen  JBMJLamers  CBHW Repeated intravenous bolus injections of omeprazole: effects on 24-hour intragastric pH, serum gastrin, and serum pepsinogen A and C. Scand J Gastroenterol. 1991;26737- 746
Link to Article

Figures

Place holder to copy figure label and caption

Mean intragastric pH profile in the omeprazole group and the cimetidine group during the 24 hours following initial bolus injection and sustained infusion.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Clinical Parameters of the Omeprazole and the Cimetidine Groups
Table Graphic Jump LocationTable 2. Major Clinical Outcomes of Both Groups

References

Consensus Development Panel, Consensus statement on therapeutic endoscopy and bleeding ulcers. Gastrointest Endosc. 1990;36S62- S65
Link to Article
Lin  HJLee  FYKang  WMTsai  YTLee  SDLee  CH Heat probe thermocoagulation and pure alcohol injection in massive peptic ulcer haemorrhage: a prospective, randomized controlled trial. Gut. 1990;31753- 757
Link to Article
Llach  JBordas  JMSalmerón  JM  et al.  A prospective randomized trial of heater probe thermocoagulation versus injection therapy in peptic ulcer hemorrhage. Gastrointest Endosc. 1996;43117- 120
Link to Article
Lin  HJWang  KPerng  CLLee  CHLee  SD Heat probe thermocoagulation and multipolar electrocoagulation for arrest of peptic ulcer bleeding: a prospective, randomized comparative trial. J Clin Gastroenterol. 1995;2199- 102
Link to Article
Laine  L Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers: a prospective, randomized trial. Gastroenterology. 1990;991303- 1306
Allan  RDykes  P A study of the factors influencing mortality rates from gastrointestinal haemorrhage. QJM. 1976;45533- 550
Turner  IBJones  MPiper  DW Factors influencing mortality from bleeding peptic ulcers. Scand J Gastroenterol. 1991;26661- 666
Link to Article
Green  FWKaplan  MMCurtis  LELevine  PH Effect of acid and pepsin on blood coagulation and platelet aggregation. Gastroenterology. 1978;7438- 43
Low  JDodds  AJBiggs  JC Fibrinolytic activity of gastroduodenal secretions: a possible role in upper gastrointestinal haemorrhage. Thromb Res. 1980;17819- 830
Link to Article
Patchett  SEEnright  HAfdhal  NO'Connell  WO'Donoghue  DP Clot lysis by gastric juice: an in vitro study. Gut. 1989;301704- 1707
Link to Article
Barkham  PTocantins  TM Action of human gastric juice on human blood clots. J Appl Physiol. 1953;61- 7
Wilde  MIMcTavish  D Omeprazole: an update of its pharmacology and therapeutic use in acid-related disorders. Drugs. 1994;4891- 132
Link to Article
Andersen  JStröm  MNÆsdal  JLeire  KWalan  A Intravenous omeprazole: effect of a loading dose on 24-h intragastric pH. Aliment Pharmacol Ther. 1990;465- 72
Link to Article
Brunner  GLuna  PThiesemann  C Drugs for pH control in upper gastrointestinal bleeding. Aliment Pharmacol Ther. 1995;9 (suppl 1) 47- 50
Link to Article
Cederberg  CThompson  ABRKirdeikis  PKristersson  C Effect of continuous intravenous infusion of omeprazole on 24-hour intragastric pH in fasting DUpatients: comparison to repeated bolus doses of omeprazole or ranitidine. Gastroenterology. 1992;102 (suppl) A48
Daneshmend  TKHawkey  CJLangman  MJSLogan  RFALong  RGWalt  RP Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. Gut. 1992;304143- 147
Villanueva  CBalanzó  JTorras  X  et al.  Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study. Endoscopy. 1995;27308- 312
Link to Article
Brunner  GChang  J Intravenous therapy with high doses of ranitidine and omeprazole in critically ill patients with bleeding peptic ulcerations of the upper intestinal tract: an open randomized controlled trial. Digestion. 1990;45217- 225
Link to Article
Brunner  GHGThiesemann  C The potential clinical role of intravenous omeprazole. Digestion. 1992;51 (suppl 1) 17- 20
Link to Article
Muckadell  OBSHavelund  THarling  H  et al.  Omeprazole improved outcome in peptic ulcer bleeding. Gastroenterology. 1995;108A212Abstract
Link to Article
Lind  TAadland  EEriksson  SFernström  PHasselgren  GLundell  L Beneficial effects of I.V. omeprazole (OME) in patients with peptic ulcer bleeding (PUB). Gastroenterology. 1995;108A150Abstract
Link to Article
Lanas  AArtal  ABlás  JMArroyo  MTLopez-Zaborras  JSáinz  R Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol. 1995;21103- 106
Link to Article
Grosso  CRossi  AGambitta  P  et al.  Non-bleeding visible vessel treatment: perendoscopic injection therapy versus omeprazole infusion. Scand J Gastroenterol. 1995;30872- 875
Link to Article
Cook  DJGuyatt  GHSalena  BJLaine  LA Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology. 1992;102139- 148
Lin  HJPerng  CLLee  FYLee  CHLee  SD Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. Gut. 1994;351389- 1393
Link to Article
Lin  HJPerng  CLWang  KLee  SDLee  CH Long-term results of heater probe thermocoagulation for patients with massive peptic ulcer bleeding: a prospective observation. Am J Gastroenterol. 1995;9044- 47
Lin  HJWang  KPerng  CLLee  FYLee  CHLee  SD Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation. Gastrointest Endosc. 1996;43470- 473
Link to Article
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