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Thaler J, Tripisciano C, Nieuwland R. Investigations on the Hemostatic Potential of Physiological Body Fluids. Hamostaseologie 2024; 44:377-385. [PMID: 39442510 DOI: 10.1055/a-2374-2903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024] Open
Abstract
Current blood coagulation models consider the interactions between blood, the vessel wall, and other tissues that expose tissue factor (TF), the main initiator of coagulation. A potential role of body fluids other than blood is generally not considered. In this review, we summarize the evidence that body fluids such as mother's milk saliva, urine, semen, and amniotic fluid trigger coagulation. The ability of these body fluids to trigger coagulation is explained by the presence of extracellular vesicles (EVs). These EVs expose extrinsic tenase complexes (i.e., complexes of TF and activated factor VII) that can trigger coagulation. Why these body fluids share this activity, however, is unknown. Possible explanations are that these body fluids contribute to hemostatic protection and/or to the regulation of the epithelial barrier function. Further investigations may help understand the underlying cellular and biochemical pathways regulating or contributing to coagulation and innate immunity, which may be directly relevant to medical conditions such as gastrointestinal bleeding and chronic inflammatory bowel disease.
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Affiliation(s)
- Johannes Thaler
- Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Carla Tripisciano
- Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Rienk Nieuwland
- Laboratory of Experimental Clinical Chemistry, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Vesicle Center, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam, The Netherlands
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2
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Liu S, Luan Z, Wang T, Xu K, Luo Q, Ye S, Wang W, Dan R, Shu Z, Huang Y, Mequanint K, Fan C, Xing M, Yang S. Endoscopy Deliverable and Mushroom-Cap-Inspired Hyperboloid-Shaped Drug-Laden Bioadhesive Hydrogel for Stomach Perforation Repair. ACS NANO 2023; 17:111-126. [PMID: 36343209 DOI: 10.1021/acsnano.2c05247] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.
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Affiliation(s)
- Shuang Liu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Zhaohui Luan
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Tongchuan Wang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Kaige Xu
- Departments of Mechanical Engineering, University of Manitoba, Winnipeg, ManitobaR3T 2N2, Canada
| | - Qiang Luo
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Shaosong Ye
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Wei Wang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Ruijue Dan
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Zhenzhen Shu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Yu Huang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
| | - Kibret Mequanint
- Department of Chemical and Biochemical Engineering, and School of Biomedical Engineering, The University of Western Ontario, London, OntarioN6A 5B9, Canada
| | - Chaoqiang Fan
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
- Chongqing Municipality Clinical Research Center for Gastroenterology, Chongqing400037, China
| | - Malcolm Xing
- Departments of Mechanical Engineering, University of Manitoba, Winnipeg, ManitobaR3T 2N2, Canada
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, No.183, Xinqiao Street, Shapingba District, Chongqing400037, China
- Chongqing Municipality Clinical Research Center for Gastroenterology, Chongqing400037, China
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Horie Y, Horiuchi Y, Ishiyama A, Tsuchida T, Yoshimizu S, Hirasawa T, Fujisaki J, Maetani I, Yoshio T. The effect of antithrombotic drug use on delayed bleeding with esophageal endoscopic resection. J Gastroenterol Hepatol 2022; 37:1792-1800. [PMID: 35844140 DOI: 10.1111/jgh.15944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 07/02/2022] [Accepted: 07/11/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Whether antithrombotic drugs increase the risk of post-esophageal endoscopic resection bleeding is unknown. This study examined the effect of antithrombotic drugs, aspirin, thienopyridine, direct oral anticoagulants (DOAC), and warfarin, on post-esophageal endoscopic resection bleeding. METHODS We enrolled 957 patients (1202 esophageal tumors) treated with endoscopic resection and classified them based on antithrombotic drug use as no use, aspirin, thienopyridine, DOAC, and warfarin. Patients using antiplatelet drugs (i.e. aspirin and thienopyridine) were further sub-classified based on their continued or discontinued use before endoscopic resection. The bleeding rates were compared between these groups to assess the effects of antithrombotic drug use and interruption of antiplatelet therapy on post-esophageal endoscopic resection bleeding. RESULTS The post-endoscopic resection bleeding rate was 0.3% (95% CI, 0.1-1) in the group without antithrombotic drug use, 4.5% (95% CI, 0.1-23) in the aspirin-continued group, 2.9% (95% CI, 0.1-15) in the aspirin-discontinued group, 0% (95% CI, 0-78) in the replaced thienopyridine with aspirin group, 0% (95% CI, 0-26) in the thienopyridine-discontinued group, 13% (95% CI, 1.6-38) in the DOAC group, and 0% (95% CI, 0-45) in the warfarin group. The post-endoscopic resection bleeding rate in the DOAC group was significantly higher than that in the group without antithrombotic drugs (P = 0.003). The post-endoscopic resection bleeding rates did not differ between the other groups. CONCLUSIONS Our results suggest that discontinuing aspirin is not necessary for esophageal endoscopic resection while we must be careful regarding DOAC.
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Affiliation(s)
- Yoshimasa Horie
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Yusuke Horiuchi
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akiyoshi Ishiyama
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Tsuchida
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shoichi Yoshimizu
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiaki Hirasawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junko Fujisaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Iruru Maetani
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Toshiyuki Yoshio
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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4
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Hayashi Y, Hatta W, Tsuji Y, Yoshio T, Yabuuchi Y, Hoteya S, Tsuji S, Nagami Y, Hikichi T, Kobayashi M, Morita Y, Sumiyoshi T, Iguchi M, Tomida H, Inoue T, Mikami T, Hasatani K, Nishikawa J, Matsumura T, Nebiki H, Nakamatsu D, Ohnita K, Suzuki H, Ueyama H, Sugimoto M, Yamaguchi S, Michida T, Yada T, Asahina Y, Narasaka T, Kuribayashi S, Kiyotoki S, Mabe K, Miyake A, Fujishiro M, Masamune A, Takehara T. The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer. J Gastroenterol Hepatol 2022; 37:870-877. [PMID: 35132695 DOI: 10.1111/jgh.15793] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 11/11/2021] [Accepted: 01/12/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. METHODS We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. RESULTS There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. CONCLUSIONS Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.
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Affiliation(s)
- Yoshito Hayashi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yosuke Tsuji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toshiyuki Yoshio
- Division of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan
| | - Yohei Yabuuchi
- Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Shigetsugu Tsuji
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
| | - Masakuni Kobayashi
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Yoshinori Morita
- Department of Gastroenterology, Kobe University International Clinical Cancer Research Center, Kobe, Japan.,Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Japan
| | | | - Mikitaka Iguchi
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hideomi Tomida
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.,Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | - Takuya Inoue
- Division of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan
| | - Tatsuya Mikami
- Division of Endoscopy, Hirosaki University Hospital, Hirosaki, Japan
| | - Kenkei Hasatani
- Department of Gastroenterology, Fukui Prefectural Hospital, Fukui, Japan
| | - Jun Nishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Tomoaki Matsumura
- Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Hiroko Nebiki
- Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan
| | - Dai Nakamatsu
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Ken Ohnita
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
| | - Haruhisa Suzuki
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroya Ueyama
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Kusatsu, Japan
| | | | - Tomoki Michida
- Department of Gastroenterology and Hepatology, Saitama Medical Center, Kawagoe, Japan.,Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Tomoyuki Yada
- Division of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yoshiro Asahina
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Toshiaki Narasaka
- Division of Endoscopic Center, University of Tsukuba Hospital, Tsukuba, Japan
| | - Shiko Kuribayashi
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Shu Kiyotoki
- Department of Gastroenterology, Shuto General Hospital, Yanai, Japan
| | - Katsuhiro Mabe
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, Hakodate, Japan.,Junpukai Health Maintenance Center Kurashiki, Okayama, Japan
| | - Akimitsu Miyake
- Department of Medical Innovation, Osaka University Hospital, Suita, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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5
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Hussein M, Alzoubaidi D, O'Donnell M, de la Serna A, Bassett P, Varbobitis I, Hengehold T, Ortiz Fernandez‐Sordo J, Rey JW, Hayee B, Despott EJ, Murino A, Graham D, Latorre M, Moreea S, Boger P, Dunn J, Mainie I, Mullady D, Early D, Ragunath K, Anderson J, Bhandari P, Goetz M, Kiesslich R, Coron E, Rodriguez de Santiago E, Gonda T, Gross SA, Lovat LB, Haidry R. Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes. J Gastroenterol Hepatol 2021; 36:3027-3032. [PMID: 34132412 PMCID: PMC11497338 DOI: 10.1111/jgh.15579] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/18/2021] [Accepted: 06/05/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy. METHODS Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy. RESULTS One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7-12). The median Rockall score was 8 (IQR, 7-9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P < 0.001) when comparing the number of units transfused 3 weeks before and after treatment. The mean reduction was one unit per patient. CONCLUSIONS Hemospray achieved high rates of immediate hemostasis, with comparable rebleed rates following treatment of tumor-related upper gastrointestinal bleeds. Hemospray helped in improving transfusion requirements in these patients. This allows for patient stabilization and bridges towards definitive surgery or radiotherapy to treat the underlying tumor.
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Affiliation(s)
- Mohamed Hussein
- Division of Surgery and Interventional ScienceUniversity College London (UCL)LondonUK
- Department of GastroenterologyUniversity college London hospital (UCLH)LondonUK
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS)University College LondonLondonUK
| | - Durayd Alzoubaidi
- Division of Surgery and Interventional ScienceUniversity College London (UCL)LondonUK
| | | | - Alvaro de la Serna
- Department of Gastroenterology and HepatologyRamon y Cajal University Hospital, IRYCIS, University of AlcalaMadridSpain
| | | | - Ioannis Varbobitis
- NIHR Nottingham Digestive Diseases Biomedical Research CentreNottingham University HospitalsNottinghamUK
| | - Tricia Hengehold
- Department of GastroenterologyWashington University School of Medicine in St. LouisSt. LouisMissouriUSA
| | | | - Johannes W Rey
- Department of GastroenterologyOsnabrück ClinicOsnabrückGermany
| | | | - Edward J Despott
- Royal Free Unit for Endoscopy and Centre for GastroenterologyRoyal Free NHS Foundation TrustLondonUK
| | - Alberto Murino
- Royal Free Unit for Endoscopy and Centre for GastroenterologyRoyal Free NHS Foundation TrustLondonUK
| | - David Graham
- Department of GastroenterologyUniversity college London hospital (UCLH)LondonUK
| | | | - Sulleman Moreea
- Department of GastroenterologyBradford Teaching Hospitals Foundation TrustBradfordUK
| | - Phillip Boger
- Department of GastroenterologyUniversity Hospital Southampton NHS Foundation TrustSouthamptonUK
| | - Jason Dunn
- Department of GastroenterologyGuy's and St Thomas' Foundation TrustLondonUK
| | - Inder Mainie
- Department of GastroenterologyBelfast Health and Social Care TrustBelfastUK
| | - Daniel Mullady
- Department of GastroenterologyWashington University School of Medicine in St. LouisSt. LouisMissouriUSA
| | - Dayna Early
- Department of GastroenterologyWashington University School of Medicine in St. LouisSt. LouisMissouriUSA
| | - Krish Ragunath
- NIHR Nottingham Digestive Diseases Biomedical Research CentreNottingham University HospitalsNottinghamUK
| | - John Anderson
- Department of GastroenterologyGloucestershire Hospitals NHS Foundation Trust ‐ Cheltenham General HospitalCheltenhamUK
| | - Pradeep Bhandari
- Department of GastroenterologyPortsmouth Hospitals NHS TrustPortsmouthUK
| | | | | | - Emmanuel Coron
- Department of GastroenterologyUniversity Hospital CenterNantesFrance
| | - Enrique Rodriguez de Santiago
- Department of Gastroenterology and HepatologyRamon y Cajal University Hospital, IRYCIS, University of AlcalaMadridSpain
| | - Tamas Gonda
- Columbia University Medical CentreNew YorkUSA
| | | | - Laurence B Lovat
- Division of Surgery and Interventional ScienceUniversity College London (UCL)LondonUK
- Department of GastroenterologyUniversity college London hospital (UCLH)LondonUK
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS)University College LondonLondonUK
| | - Rehan Haidry
- Division of Surgery and Interventional ScienceUniversity College London (UCL)LondonUK
- Department of GastroenterologyUniversity college London hospital (UCLH)LondonUK
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS)University College LondonLondonUK
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Pittayanon R, Rerknimitr R, Barkun A. Prognostic factors affecting outcomes in patients with malignant GI bleeding treated with a novel endoscopically delivered hemostatic powder. Gastrointest Endosc 2018; 87:994-1002. [PMID: 29158179 DOI: 10.1016/j.gie.2017.11.013] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 11/09/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Endoscopic hemostatic techniques remain poorly effective for GI tumor bleeding. We assessed Tc-325 (Hemospray, Cook Medical, Bloomington, Ind, USA) for this indication and determined possible predictors of decreased recurrent bleeding and improved 6-month survival in affected patients. METHODS This retrospective study identified 99 patients with active malignant GI bleeding (primary or metastatic) treated with Tc-325. Eleven patients were excluded because of incomplete data. Data on patient characteristics and possible predictive factors of early (72-hour) and delayed (7-, 14-, and 30-day) recurrent bleeding, as well as 6-month survival, were collected. RESULTS Overall, 70.5% were male (age, 65 ± 14 years). Half had a high Eastern Cooperative Oncology Group (ECOG) score (3 or 4). An upper GI cancer was found in 56.8%, and 72.7% cancers were stage 4. Of those affected, 51.6% received at least 1 non-endoscopic additional definitive hemostatic treatment after Tc-325. Immediate hemostasis with Tc-325 was 97.7%, with recurrent bleeding noted in 15% (early) and 17% (delayed). Six-month survival was 53.4%. On multivariable analysis, no predictive factor for recurrent bleeding was identified, whereas ECOG score 0 to 2 (P = .001; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.47), cancer stage 1 to 3 (P = .04; HR, 0.31; 95% CI, 0.10-0.96), and receiving definite hemostatic treatment alone or in any combination with surgery, chemotherapy, radiotherapy, or radiologic embolization (P = .002; HR, 0.24; 95% CI, 0.09-0.59) were significant prognosticators of 6-month survival after adjusting for comorbidity, type of cancer bleeding, and presence of a coagulopathy. CONCLUSION Before definitive therapy can be offered, Tc-325 provides effective initial hemostasis of tumoral GI bleeding. Good performance status, non-end-stage cancer, and receiving definite hemostatic treatment are independent predictors of 6-month survival. (Clinical trial registration number: NCT03066700.).
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Affiliation(s)
- Rapat Pittayanon
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital of the Thai Red Cross, Bangkok, Thailand; Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Canada
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital of the Thai Red Cross, Bangkok, Thailand
| | - Alan Barkun
- Division of Gastroenterology, McGill University and the McGill University Health Centre, Montreal, Canada
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7
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Redeen S. The Trend of Tranexamic Use in Upper Gastrointestinal Bleeding Ulcers. Gastroenterology Res 2017; 10:159-165. [PMID: 28725302 PMCID: PMC5505280 DOI: 10.14740/gr836w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 05/12/2017] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Bleeding ulcer is a common condition, especially among the elderly population. Tranexamic acid (TXA) has been successfully used for many bleeding conditions. Its use in patients with bleeding ulcer is inclusive yet. The aim of this study was to provide an overview of the prescription of TXA. METHODS This retrospective cohort study was performed as a review of medical records at the Surgery Department, University Hospital in Linkoping. Patients with complete esophagogastroduodenoscopy and ulcer disease were included and divided on the basis of treatment with TXA or not. Differences between the groups were statistically analyzed. RESULTS The main part of the prescription of TXA, 65%, occurred during 2010 and 2011, and 35% between 2012 and 2013 (P < 0.05). In the group treated with TXA, 84% needed blood transfusion, compared to 64% in the control group (P = 0.039). Of the patients treated with TXA, 18% were re-bleeding compared to 14% of the controls (P = 0.594). Median value for days at hospital was 5 in the tranexamic group and 3 in the control group (P = 0.005). CONCLUSION The prescription of TXA has declined between 2010 and 2013. TXA was more often prescribed to patients with more severe gastrointestinal (GI) bleeding ulcer disease. Further investigation is needed to conclude the significance of tranexamic acid in patients with GI bleeding ulcer disease.
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Affiliation(s)
- Stefan Redeen
- Department of Surgery and Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
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8
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Rafeey M, Shoaran M, Ghergherechi R. Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: A randomised controlled trial. Afr J Paediatr Surg 2016; 13:9-13. [PMID: 27251517 PMCID: PMC4955451 DOI: 10.4103/0189-6725.181700] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Peptic ulcers are among the most common causes of upper gastrointestinal (GI) bleeding in children. The standard care for GI bleeding is endoscopy for diagnostic and therapeutic purposes. We aimed to assess the effect of topical tranexamic acid (TXA) via endoscopic procedures in children with GI bleeding caused by bleeding ulcers. PROCEDURE In this randomised controlled trial, 120 children were evaluated by diagnostic procedures for GI bleeding, of which 63 (30 girls, 33 boys) aged 1-month to 15 years were recruited. The patients were randomly divided into case and control groups. In the case group, TXA was administered directly under endoscopic therapy. In the control group, epinephrine (1/10,000) was submucosally injected to the four quadrants of ulcer margins as the routine endoscopic therapy. In both groups, the patients received supportive medical therapy with intravenous fluids and proton pump inhibitor drugs. RESULTS The mean ± standard deviation age of the children was 5 ± 2.03 years. Rebleeding occurred in 15 (11.4%) and 21 (9.8%) patients in the case and control groups, respectively (P = 0.50). The frequency of blood transfusion episodes (P = 0.06) and duration of hospital stay (P = 0.07) were not statistically different between the groups. CONCLUSION Using topical TXA via endoscopic procedures may be effective in cases of GI bleedings caused by active bleeding ulcers. In order to establish this therapeutic effect, a large number of clinical studies are needed.
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Affiliation(s)
- Mandana Rafeey
- Department of Pediatrics, Liver and Gastrointestinal Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Shoaran
- Department of Pediatrics, Pediatric Health Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
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In adult patients presenting as emergencies with upper gastrointestinal bleeding, does tranexamic acid decrease mortality? Afr J Emerg Med 2015. [DOI: 10.1016/j.afjem.2015.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Thibault A, Marteau P, Drouet L, Lavergne Slove A, Bal dit Sollier C, Camus M, Dray X. In vivo effect of proton-pump inhibitors on gastric plasmin-dependent fibrinolysis: a study in a porcine model. Dig Liver Dis 2012; 44:995-8. [PMID: 22890053 DOI: 10.1016/j.dld.2012.06.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Revised: 06/18/2012] [Accepted: 06/24/2012] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Alkalization of gastric fluids could inhibit plasmin-mediated and/or pepsin-mediated fibrinolysis. We evaluated the gastric antifibrinolytic effect of proton pump inhibitors in a live porcine model. MATERIAL AND METHODS Six pigs were randomly assigned to treatment with proton pump inhibitors vs no treatment. After endoscopic mucosal resection, 8 μm sections were incubated on fibrin films. Fibrinolytic activity was assessed through focal lysis time. One-hundred-and-forty-two mucosal sections and 129 submucosal sections were analysed. Twenty-four additional sections were analysed on plates containing tranexamic acid to explore pepsin-mediated fibrinolysis. RESULTS Focal lysis times in treated vs control groups were 21.0 min vs 21.2 min (p = 0.39) in the mucosa, and 22.2 min vs 20.2 min (p = 0.56) in the submucosa. No lysis could be seen on the plasmin-inhibited fibrin plates. CONCLUSION Only plasmin-mediated fibrinolysis was observed. Proton pump inhibitors had no significant plasmin-dependant antifibrinolytic effect. They may enhance haemostasis through different pathways.
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Affiliation(s)
- Aurelie Thibault
- Department of Digestive Diseases, and School of Surgery, Denis Diderot, Paris 7 University, and AP-HP, Paris, France
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Liu BL, Li B, Zhang X, Fei Z, Hu SJ, Lin W, Gao DK, Zhang L. A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage. J Neurosurg 2012; 118:115-20. [PMID: 23061387 DOI: 10.3171/2012.9.jns12170] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT Patients with intracerebral hemorrhage (ICH) are at high risk for severe stress-related upper gastrointestinal (UGI) bleeding, which is predictive of higher mortality. The aim of this study was to evaluate the effectiveness of omeprazole and cimetidine compared with a placebo in the prevention and management of stress-related UGI bleeding in patients with ICH. METHODS In a single-center, randomized, placebo-controlled study, 184 surgically treated patients with CT-proven ICH within 72 hours of ictus and negative results for gastric occult blood testing were included. Of these patients, 165 who were qualified upon further evaluation were randomized into 3 groups: 58 patients received 40 mg intravenous omeprazole every 12 hours, 54 patients received 300 mg intravenous cimetidine every 6 hours, and 53 patients received a placebo. Patients whose gastric occult blood tests were positive at admission (n = 70) and during/after the prophylaxis procedure (n = 48) were treated with high-dose omeprazole at 80 mg bolus plus 8 mg/hr infusion for 3 days, followed by 40 mg intravenous omeprazole every 12 hours for 7 days. RESULTS Of the 165 assessable patients, stress-related UGI bleeding occurred in 9 (15.5%) in the omeprazole group compared with 15 patients (27.8%) in the cimetidine group and 24 patients (45.3%) in the placebo group (p = 0.003). The occurrence of UGI bleeding was significantly related to death (p = 0.022). Nosocomial pneumonia occurred in 14 patients (24.1%) receiving omeprazole, 12 (22.2%) receiving cimetidine, and 8 (15.1%) receiving placebo (p > 0.05). In patients with UGI bleeding in which high-dose omeprazole was initiated, UGI bleeding arrested within the first 3 days in 103 patients (87.3%). CONCLUSIONS Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high-dose omeprazole as the drug of choice for patients presenting with UGI bleeding is warranted. Clinical trial registration no.: ChiCTR-TRC-12001871, registered at the Chinese clinical trial registry (http://www.chictr.org/en/proj/show.aspx?proj=2384).
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Affiliation(s)
- Bo-lin Liu
- Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China
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Liang CM, Lee JH, Kuo YH, Wu KL, Chiu YC, Chou YP, Hu ML, Tai WC, Chiu KW, Hu TH, Chuah SK. Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis. BMC Gastroenterol 2012; 12:28. [PMID: 22455511 PMCID: PMC3352107 DOI: 10.1186/1471-230x-12-28] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Accepted: 03/28/2012] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Many studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs. METHODS Subjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27). RESULTS An initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group). CONCLUSION Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis.
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Affiliation(s)
- Chih-Ming Liang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, 123 Ta-Pei Road, Niaosung Hsiang, Kaohsiung City 833, Taiwan
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Choi CW, Kang DH, Kim HW, Park SB, Park KT, Kim GH, Song GA, Cho M. Somatostatin adjunctive therapy for non-variceal upper gastrointestinal rebleeding after endoscopic therapy. World J Gastroenterol 2011; 17:3441-7. [PMID: 21876636 PMCID: PMC3160570 DOI: 10.3748/wjg.v17.i29.3441] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2010] [Revised: 01/18/2011] [Accepted: 01/25/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effect of pantoprazole with a somatostatin adjunct in patients with acute non-variceal upper gastrointestinal bleeding (NVUGIB).
METHODS: We performed a retrospective analysis of a prospective database in a tertiary care university hospital. From October 2006 to October 2008, we enrolled 101 patients with NVUGIB that had a high-risk stigma on endoscopy. Within 24 h of hospital admission, all patients underwent endoscopic therapy. After successful endoscopic hemostasis, all patients received an 80-mg bolus of pantoprazole followed by continuous intravenous infusion (8 mg/h for 72 h). The somatostatin adjunct group (n = 49) also received a 250-μg bolus of somatostatin, followed by continuous infusion (250 μg/h for 72 h). Early rebleeding rates, disappearance of endoscopic stigma and risk factors associated with early rebleeding were examined.
RESULTS: Early rebleeding rates were not significantly different between treatment groups (12.2% vs 14.3%, P = 0.766). Disappearance of endoscopic stigma on the second endoscopy was not significantly different between treatment groups (94.2% vs 95.9%, P = 0.696). Multivariate analysis showed that the complete Rockall score was a significant risk factor for early rebleeding (P = 0.044, OR: 9.080, 95% CI: 1.062-77.595).
CONCLUSION: The adjunctive use of somatostatin was not superior to pantoprazole monotherapy after successful endoscopic hemostasis in patients with NVUGIB.
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Hussey S, Kelleher KT, Ling SC. Emergency Management of Major Upper Gastrointestinal Hemorrhage in Children. CLINICAL PEDIATRIC EMERGENCY MEDICINE 2010. [DOI: 10.1016/j.cpem.2010.06.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Intravenous pantoprazole as an adjuvant therapy following successful endoscopic treatment for peptic ulcer bleeding. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2009; 23:287-99. [PMID: 19373423 DOI: 10.1155/2009/191706] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
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.
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Høie O, Stallemo A, Matre J, Stokkeland M. Effect of oral lansoprazole on intragastric pH after endoscopic treatment for bleeding peptic ulcer. Scand J Gastroenterol 2009; 44:284-8. [PMID: 19005997 DOI: 10.1080/00365520802538203] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Intravenous proton pump inhibitors (PPIs) induce a high intragastric pH and may thereby improve haemostasis in patients with bleeding peptic ulcer. The aim of this study was to investigate whether a similar therapeutic intragastric pH level could be reached when the PPI was administered orally. MATERIAL AND METHODS Twenty-four-hour intragastric pH was measured in patients treated endoscopically for bleeding peptic ulcer (Forrest class I or II). The patients received lansoprazole capsules (90 mg) after successful endoscopic treatment, followed by 30 mg every third hour for 72 h. The primary end-point was the percentage of the 0 to 24-h registration period with an intragastric pH of 6 or higher. Additionally, the total number of patients obtaining an intragastric pH above 6 for 80% or more of the 0 to 24-h period after start of treatment was evaluated. RESULTS Of the 14 patients included in the study (4 F, mean age 74 years, range 50-84 years), 10 patients had duodenal ulcer and 4 had gastric ulcer; median lowest Hgb: 8.9 mg/ml (range 5.8-12.4), blood transfusions: 2.7 SAG units (range 0-7). In the 0 to 24-h period, the median time duration of pH above 6 was 55% (range 6-99). One out of 14 patients (7%) reached a pH above 6 in at least 80% of this time period. CONCLUSIONS An increase in intragastric pH of therapeutic importance was reached with this oral medication regimen. However, there were large intra-individual differences. Treatment with oral lansoprazole may be a therapeutic alternative to intravenous administration of PPI.
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Affiliation(s)
- Ole Høie
- Sørlandet Sykehus, Kristiansand, Norway.
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Law JK, Andrews CN, Enns R. Intravenous proton pump inhibition utilization and prescribing patterns escalation: a comparison between early and current trends in use. Gastrointest Endosc 2009; 69:3-9. [PMID: 18718583 DOI: 10.1016/j.gie.2008.04.053] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2006] [Accepted: 04/19/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND Approved indications of intravenous (i.v.) proton pump inhibition (PPI) are limited to treatment of reflux esophagitis in patients unable to tolerate oral medications and for patients with pathologic hypersecretory states. OBJECTIVES i.v. PPIs are commonly used after endoscopic evaluation of patients with high-risk endoscopic stigmata (HRES) of nonvariceal upper GI bleeding (NVUGIB). There appears to have been an expansion of indications of this drug at many centers. DESIGN All consecutive patients receiving i.v. PPI (pantoprazole) between 2 study periods, (1) when pantoprazole was restricted to the gastroenterology service and (2) when it was unrestricted, were reviewed. SETTING Tertiary care university hospital. PATIENTS All receiving i.v. PPI. INTERVENTIONS i.v. PPI utilization. MAIN OUTCOME MEASUREMENTS Percentage of patients receiving i.v. PPI for indications other than bleeding during 2 time periods. RESULTS In the early period, 217 patients (67.30% male) received i.v. PPI on 218 occasions compared with 516 patients (65.31% male, P= .61) in the later period on 613 occasions. In the early group, 93.12% of 217 patients received i.v. PPI for NVUGIB compared with 56.12% of 516 patients (P< .0001) with 18% of patients receiving i.v. PPI for nothing by mouth status and 13% for abdominal pain in the later group. A total of 153 (70.18%) patients in the early group underwent upper endoscopy compared with only 275 (44.86%) patients in the later group; 84 of these 153 patients (54.90%) were already on i.v. PPI at the time of endoscopy in the early group compared with 253 (92.00%, P< .0001). CONCLUSIONS i.v. PPI use has escalated at our hospital and is being prescribed in patients before endoscopy with fewer patients noted to have HRES on endoscopy.
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Affiliation(s)
- Joanna K Law
- Division of Gastroenterology, Department of Medicine, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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Hung WK, Li VKM, Chung CK, Ying MWL, Loo CK, Liu CKT, Lam BYK, Chan MCM. RANDOMIZED TRIAL COMPARING PANTOPRAZOLE INFUSION, BOLUS AND NO TREATMENT ON GASTRIC pH AND RECURRENT BLEEDING IN PEPTIC ULCERS. ANZ J Surg 2007; 77:677-81. [PMID: 17635283 DOI: 10.1111/j.1445-2197.2007.04185.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND To study the effects of pantoprazole on gastric pH and recurrent bleeding after endoscopic treatment for bleeding peptic ulcers. METHODS After endoscopic haemostasis, patients were randomly assigned to infusion group (pantoprazole 80 mg i.v. bolus followed by continuous infusion of 8 mg/h for 3 days), bolus group (pantoprazole 80 mg i.v. bolus followed by 40 mg i.v. bolus every 12 h for 3 days) and no-treatment group (no acid suppression in the first 3 days). Gastric pH was monitored. Rebleeding rate within 30 days, the need for surgery, transfusion requirement, total hospital stay, mortality rate and gastric pH were compared. RESULTS One hundred and sixty-eight patients were included, with 15 patients excluded from the analysis. There were 54 patients in the infusion group, 49 in the bolus group and 50 in the no-treatment group. There was fewer rebleeding (3.7 vs 16.0%, P = 0.034), less operative intervention (0 vs 8.0%, P = 0.034) and shorter hospital stay (6.4 vs 8.2 days, P = 0.040) in the infusion group compared with that in no-treatment group. When the bolus group was compared with no-treatment group, there were fewer rebleed (4.1 vs 16.0%, P = 0.049) and less blood transfusion (1.5 vs 2.9 units, P = 0.007). There was no difference in mortality among the three groups. Patients who received either pantoprazole infusion or bolus had significantly higher mean pH and longer duration of pH above 6 compared with the no-treatment group. There was no difference in the rebleeding rate, transfusion requirement, need for operation and hospital stay between the infusion and bolus groups. The mean pH and the duration of pH above 6 were also similar. CONCLUSION Pantoprazole either as infusion or bolus decreased rebleeding after endoscopic treatment for bleeding peptic ulcer.
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Affiliation(s)
- Wai-Ka Hung
- Department of Surgery, Kwong Wah Hospital, Hong Kong, China.
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Simon-Rudler M, Massard J, Bernard-Chabert B, DI Martino V, Ratziu V, Poynard T, Thabut D. Continuous infusion of high-dose omeprazole is more effective than standard-dose omeprazole in patients with high-risk peptic ulcer bleeding: a retrospective study. Aliment Pharmacol Ther 2007; 25:949-54. [PMID: 17402999 DOI: 10.1111/j.1365-2036.2007.03286.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
UNLABELLED High-dose omeprazole reduces the rate of recurrent bleeding after endoscopic treatment of peptic ulcer bleeding. However, the effectiveness of high-dose vs. standard-dose omeprazole in peptic ulcer bleeding has never been shown. AIM To compare the benefits of high-dose vs. standard-dose omeprazole in peptic ulcer bleeding. METHODS We reviewed the medical files of patients admitted between 1997 and 2004 for high-risk peptic ulcer bleeding who had undergone successful endoscopic treatment. We distinguished 2 periods: before 2001, standard-dose omeprazole (40 mg/day intravenously until alimentation was possible, then 40 mg/day orally for 1 week); after 2001, high-dose omeprazole (80 mg bolus injection, then 8 mg/h continuous infusion for 72 h, then 40 mg/day orally for 1 week). During both periods, patients subsequently received omeprazole, 20 mg/day, orally for 3 weeks. RESULTS We enrolled 114 patients (period 1, n = 45, period 2, n = 69). Therapy with high-dose omeprazole significantly decreased the occurrence of poor outcome (27 vs. 12%, P = 0.04), rebleeding (24 vs. 7%, P = 0.01), mortality due to haemorrhagic shock (11 vs. 0%, P < 0.001) and need for surgery (9 vs. 1%, P = 0.05). CONCLUSIONS In this retrospective study, high-dose omeprazole reduced the occurrence of rebleeding, need for surgery and mortality due to hemorrhagic shock in patients with high-risk peptic ulcer bleeding, as compared with standard-dose omeprazole.
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Affiliation(s)
- M Simon-Rudler
- Service d'Hépatologie et de Gastroentérologie, Hôpital Pitié-Salpêtrière AP-HP, Paris, France
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Fisher L, Fisher A, Pavli P, Davis M. Perioperative acute upper gastrointestinal haemorrhage in older patients with hip fracture: incidence, risk factors and prevention. Aliment Pharmacol Ther 2007; 25:297-308. [PMID: 17217452 DOI: 10.1111/j.1365-2036.2006.03187.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND No specific preventive strategy exists for acute gastrointestinal haemorrhage in hip fracture patients. AIMS To determine the effectiveness of prophylactic use of proton pump inhibitors in patients with risk factors for acute gastrointestinal haemorrhage. METHODS Prospective two-stage study of 822 consecutive older (> or =60 years) hip fracture patients. RESULTS Acute gastrointestinal haemorrhage occurred in 16 (3.9%) of 407 patients and was associated with increased length of hospital stay (28.7 vs. 15.9; P = 0.0027) and mortality (18.8% vs. 4.3%; P = 0.043). Multiple analysis identified five independent risk factors for acute gastrointestinal haemorrhage: pre-existing peptic ulcer (OR 4.3; P = 0.043), current smoking (OR 3.1; P = 0.023), post-operative use of an antiplatelet agent (OR 6.5; P = 0.046), post-operative use of non-steroidal anti-inflammatory drug/cyclo-oxygenase-2 inhibitor (OR 4.9; P = 0.06) and blood group O (OR 1.7; P = 0.046). These risk factors were highly sensitive and had a negative predictive value of 99.8%. Prophylactic use of proton pump inhibitors in patients with risk factor for acute gastrointestinal haemorrhage significantly reduced the incidence of this complication (0.72% in treated patients vs. 13.4% in untreated; P < 0.001); the number needed to treat was 7.9. Conclusions In older hip fracture patients perioperative acute gastrointestinal haemorrhage occurs in 3.9% and is associated with poor outcome. Preventive proton pump inhibitor therapy in patients at risk of acute gastrointestinal haemorrhage is effective and safe.
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Affiliation(s)
- L Fisher
- Department of Gastroenterology, The Canberra Hospital, ACT, Australia.
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Gisbert JP. Tratamiento farmacológico de la hemorragia digestiva por úlcera péptica. Med Clin (Barc) 2006; 127:66-75. [PMID: 16801006 DOI: 10.1157/13089992] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, 28669 Boadilla del Monte, Madrid, Spain.
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Pais SA, Nathwani RA, Dhar V, Nowain A, Laine L. Effect of frequent dosing of an oral proton pump inhibitor on intragastric pH. Aliment Pharmacol Ther 2006; 23:1607-13. [PMID: 16696810 DOI: 10.1111/j.1365-2036.2006.02933.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Treatment with a continuous i.v. proton pump inhibitor is presumed to promote clot formation and stability by sustaining intragastric pH > or = 6. AIM We postulated that very frequent oral dosing of proton pump inhibitors should simulate i.v. infusion and achieve similar pH control. METHODS Twenty healthy volunteers were stratified by Helicobacter pylori status (10 positive; 10 negative) and had determination of CYP2C19 status. After an overnight fast, an intragastric pH probe was placed. Subjects received 120 mg of lansoprazole at 8 am and 30 mg every 3 h until 8 pm. Intragastric pH was measured over 24 h, and lansoprazole plasma concentrations were determined at five time points. RESULTS Intragastric pH was > or = 6 for 41% (95% CI: 30-53%) of the 15-h period from 8 am-11 pm and 46% (95% CI: 35-56%) of the 24-h period (8-8 am). The mean proportion of patients with pH > or = 6 was not significantly different in H. pylori-positive vs. negative patients. Only 25% of subjects sustained pH > or = 6 for at least 60% of the 15-h period, and 35% had a sustained pH > or = 6 for at least 60% of the 24-h period. CONCLUSIONS A dose of 120 mg of oral lansoprazole followed by standard 30 mg doses of lansoprazole every 3 h did not reliably sustain pH at the desired level of 6.
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Affiliation(s)
- S A Pais
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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Udd M, Töyry J, Miettinen P, Vanninen E, Mustonen H, Julkunen R. The effect of regular and high doses of omeprazole on the intragastric acidity in patients with bleeding peptic ulcer treated endoscopically: a clinical trial with continuous intragastric pH monitoring. Eur J Gastroenterol Hepatol 2005; 17:1351-6. [PMID: 16292089 DOI: 10.1097/00042737-200512000-00014] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE In peptic ulcer bleeding (PUB), pH level >4 is considered necessary to prevent dissolving of a formed fibrin clot. The effect of regular or high doses of omeprazole on the intragastric pH in patients with acute PUB was studied. METHODS In our earlier study, after endoscopic therapy, PUB patients were randomized to receive a regular dose of intravenous omeprazole (20 mg; i.e. 60 mg/3 days) or a high dose of omeprazole (80 mg bolus + 8 mg/h; i.e. 652 mg/3 days). Of these 142 analysed and reported patients, 13 PUB patients also had intragastric pH monitoring for these 3 days; seven of these patients had a regular dose and six received a high dose of omeprazole. RESULTS The mean 24-h intragastric pH (regular versus high dose) on day 1 was 4.9 +/- 1.6 versus 6.3 +/- 0.5 (P = 0.035), on day 2 was 4.9 +/- 1.8 versus 6.7 +/- 0.3 (P = 0.001), and on day 3 was 5.7 +/- 1.1 versus 6.7 +/- 0.5 (P = NS). The medians of the intragastric pH were 6 versus 6.5 (P = 0.082) on day 1, 5.8 versus 6.8 (P = 0.001) on day 2, and 6.2 versus 6.8 (P = 0.17) on day 3. The proportion of time when pH <4 on day 1 was 29.2 +/- 34.1 versus 5.4 +/- 5.7% (P = NS). CONCLUSIONS A regular dose of omeprazole raises the mean and median 24-h intragastric pH >4 in patients with PUB. This reduction in the acidity together with endoscopic therapy is probably sufficient to maintain haemostasis. A high dose of omeprazole keeps the pH almost constantly >6.
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Affiliation(s)
- Marianne Udd
- Department of Surgery, Central Finland Central Hospital, Jyväskylä.
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Avgerinos A, Sgouros S, Viazis N, Vlachogiannakos J, Papaxoinis K, Bergele C, Sklavos P, Raptis SA. Somatostatin inhibits gastric acid secretion more effectively than pantoprazole in patients with peptic ulcer bleeding: a prospective, randomized, placebo-controlled trial. Scand J Gastroenterol 2005; 40:515-22. [PMID: 16036503 DOI: 10.1080/00365520510015458] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Gastric acid inhibition is beneficial in the management of peptic ulcer bleeding (PUB). The aim of this double-blind study was to test whether somatostatin (SST) increases intragastric pH in PUB as compared with pantoprazole (PAN) and placebo (PLA). MATERIAL AND METHODS Eligible patients were randomized to receive SST (500 microg/h+250 microg bolus), or PAN (8 mg/h+80 mg bolus) or PLA (normal saline) i.v., for 24 h. All patients underwent gastric pH monitoring during the infusion of the trial drugs. RESULTS The three groups (SST, n=14; PAN, n=14; PLA, n=15) were comparable for age, gender, aetiology of PUB and laboratory data at admission. Mean (+/-SE) baseline pH levels in the fundus increased during the administration of the trial drugs (SST: 1.94+/-0.18 to 6.13+/-0.37, p<0.0001; PAN: 1.93+/-0.16 to 5.65+/-0.37, p<0.0001; PLA: 1.86+/-0.12 to 2.10+/-0.15, p=0.0917). During the first 12 h of infusion, the mean (+/-SE) percentage time spent above pH 4.0 and 5.4 was higher with SST versus PAN (84.4%+/-4.8 versus 55.1%+/-8.3, p=0.0049 and 74.2%+/-6.5 versus 47.1%+/-8.3, p=0.0163, respectively) and there was a trend favouring the SST group regarding the time spent above pH 6.0 and 6.8 (65.7%+/-6.4 versus 43.3%+/-8.2, p=0.0669 and 49.2%+/-7.7 versus 28.4+/-6.6, p=0.0738, respectively). CONCLUSIONS In PUB, both SST and PAN inhibit gastric acid secretion as compared with placebo. However, during the first 12 h of the infusion, SST was more effective than PAN in maintaining high intragastric pH. These results may provide a rationale for the administration of SST in PUB.
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Affiliation(s)
- Alec Avgerinos
- Second Department of Gastroenterology, Evangelismos Hospital, Athens, Greece
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25
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Hsu PI, Lo GH, Lo CC, Lin CK, Chan HH, Wu CJ, Shie CB, Tsai PM, Wu DC, Wang WM, Lai KH. Intravenous pantoprazole versus ranitidine for prevention of rebleeding after endoscopic hemostasis of bleeding peptic ulcers. World J Gastroenterol 2004; 10:3666-9. [PMID: 15534928 PMCID: PMC4612014 DOI: 10.3748/wjg.v10.i24.3666] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: The role of intravenous pantoprazole in treatment of patients with high-risk bleeding peptic ulcers following endoscopic hemostasis remains uncertain. We therefore conducted the pilot prospective randomized study to assess whether intravenous pantoprazole could improve the efficacy of H2-antagonist as an adjunct treatment following endoscopic injection therapy for bleeding ulcers.
METHODS: Patients with active bleeding ulcers or ulcers with major signs of recent bleeding were treated with distilled water injection. After hemostasis was achieved, they were randomly assigned to receive intravenous pantoprazole or ranitidine.
RESULTS: One hundred and two patients were enrolled in this prospective trial. Bleeding recurred in 2 patients (4%) in the pantoprazole group (n = 52), as compared with 8 (16%) in the ranitidine group (n = 50). The rebleeding rate was significantly lower in the pantoprazole group (P = 0.04). There were no statistically significant differences between the groups with regard to the need for emergency surgery (0% vs 2%), transfusion requirements (4.9 ± 5.9 vs 5.7 ± 6.8 units), hospital days (5.9 ± 3.2 vs 7.5 ± 5.0 d) or mortality (2% vs 2%).
CONCLUSION: Pantoprozole is superior to ranitidine as an adjunct treatment to endoscopic injection therapy in high-risk bleeding ulcers.
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Affiliation(s)
- Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan, China
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26
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Bustamante Balén M, Ponce García J. Tratamiento antisecretor de la hemorragia digestiva por úlcera péptica: una aproximación a la evidencia disponible. Rev Clin Esp 2004. [DOI: 10.1016/s0014-2565(04)71423-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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27
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Gisbert JP, González L, Calvet X, Roqué M, Gabriel R, Pajares JM. Proton pump inhibitors versus H2-antagonists: a meta-analysis of their efficacy in treating bleeding peptic ulcer. Aliment Pharmacol Ther 2001; 15:917-26. [PMID: 11421865 DOI: 10.1046/j.1365-2036.2001.01012.x] [Citation(s) in RCA: 103] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE To evaluate whether proton pump inhibitors are more effective than H2-antagonists (H2-A) for the treatment of bleeding peptic ulcer. DATA SOURCES PubMed database until January 2000. STUDY SELECTION Comparative randomized trials of proton pump inhibitors (omeprazole, lansoprazole, or pantoprazole) vs. H2-A (cimetidine, ranitidine or famotidine). DATA EXTRACTION Meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). OUTCOMES EVALUATED: Persistent or recurrent bleeding, need for surgery, or mortality. DATA SYNTHESIS Eleven studies fulfilled the inclusion criteria and contained data for at least one of the planned comparisons. Persistent or recurrent bleeding was reported in 6.7% (95% CI: 4.9-8.6%) of the patients treated with proton pump inhibitors, and in 13.4% (95% CI: 10.8-16%) of those treated with H2-A (OR 0.4; 95% CI: 0.27-0.59) (chi2-homogeneity test, 18; P=0.09). Surgery was needed in 5.2% (95% CI: 3.4-6.9%) of the patients treated with proton pump inhibitors, and in 6.9% (95% CI: 4.9-8.9%) of the patients treated with H2-A (OR 0.7; 95% CI: 0.43-1.13). Respective percentages for mortality were 1.6% (95% CI: 0.9-2.9%) and 2.2% (95% CI: 1.3-3.7%) (OR 0.69; 95% CI: 0.31-1.57). SUB-ANALYSIS: Five studies evaluated the effect of both therapies given in bolus injections on persistent or recurrent bleeding rate, which was 6% (95% CI: 3.6-8.3%) and 8.1% (95% CI: 5.3-10.9%), respectively (OR, 0.57; 95% CI: 0.31-1.05). Persistent or recurrent bleeding in high risk patients (Forrest Ia, Ib and IIa) occurred in 13.2% (95% CI: 7.9-8%) of the patients treated with proton pump inhibitors and in 34.5% (27-42%) of those treated with H2-A (OR 0.28; 95% CI: 0.16-0.48). In patients not having endoscopic therapy, persistent or recurrent bleeding was reported, respectively, in 4.3% (95% CI: 2.7-6.7%) and in 12% (95% CI: 8.7-15%) (OR 0.24; 95% CI: 0.13-0.43). Less marked differences were observed in patients having adjunct endoscopic therapy: 10.3% (95% CI: 6.7-13.8%) and 15.2% (11.1-19.3%) (OR 0.59; 95% CI: 0.36-0.97). Moreover, the significance disappeared in this group when a single outlier study was excluded. CONCLUSIONS Proton pump inhibitors are more effective than H2-A in preventing persistent or recurrent bleeding from peptic ulcer, although this advantage seems to be more evident in patients not having adjunct sclerosis therapy. This beneficial effect seems to be similar or even more marked in patients with Forrest Ia, Ib or IIa ulcers. However, proton pump inhibitors are not more effective than H2-A for reducing surgery or mortality rates. Nevertheless, the data are too scarce and heterogeneous to draw definitive conclusions, and further comparative trials are clearly warranted.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital 'La Princesa', Madrid, Spain.
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28
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Vreeburg EM, Levi M, Rauws EA, Deventer SJ, Snel P, Bartelsman JW, Ten Cate JW, Tytgat GN. Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and the beneficial effect of acid suppression. Aliment Pharmacol Ther 2001; 15:639-46. [PMID: 11328257 DOI: 10.1046/j.1365-2036.2001.00978.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re-bleeding. The haemostatic mechanisms that may influence the re-bleeding of ulcers are largely unknown. AIM We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity. METHODS Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D-Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes. RESULTS Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24-h ranitidine infusion. CONCLUSIONS Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.
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Affiliation(s)
- E M Vreeburg
- Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands
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Abstract
Acute gastrointestinal bleeding is a significant worldwide medical problem. Despite modern measures for diagnosis and treatment, morbidity and mortality rates associated with gastrointestinal bleeding remain largely unchanged. Aggressive medical resuscitation while initiating an evaluation to localize the site of blood loss remains the key to successful management of acute gastrointestinal bleeding. A multidisciplinary approach with early involvement of a gastroenterologist, surgeon, and radiologist can be extremely helpful in the management of these patients. With the logical and direct approach to the evaluation of patients with gastrointestinal bleeding described in this article, most episodes can be managed successfully.
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Affiliation(s)
- M A Fallah
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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30
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Barkun AN, Cockeram AW, Plourde V, Fedorak RN. Review article: acid suppression in non-variceal acute upper gastrointestinal bleeding. Aliment Pharmacol Ther 1999; 13:1565-84. [PMID: 10594391 DOI: 10.1046/j.1365-2036.1999.00623.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
Despite a decreased incidence of ulcer disease and improvements in the management of acute upper gastrointestinal (GI) bleeding, mortality remains at about 6-7%. Although endoscopic haemostatic therapy has been demonstrated to be the mainstay of management, the search continues for less invasive medical modalities that might also improve patient outcome. In vitro data have indicated the important role of acid in impairing haemostasis and causing clot digestion. Therefore, theoretically, maintenance of a high intragastric pH (above 6.0) during management of upper GI bleeding is warranted. Until recently, available agents did not permit such a sustained elevation in gastric pH. Early studies with H2-receptor antagonists have not demonstrated significant improvements in important patient outcomes, such as rebleeding, surgery or mortality. With the availability of intravenous formulations of proton pump inhibitors, it is now possible to aim at maintaining gastric pH above 6.0 for 24 h per day. Recent clinical trial data would appear to support the use of proton pump inhibitors to decrease the rate of rebleeding and the need for surgery. This paper provides a review of non-variceal acute GI bleeding, with special reference to the role of proton pump inhibitors in this clinical setting.
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Affiliation(s)
- A N Barkun
- Division of Gastroenterology, McGill University, Montréal, Québec, Canada
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31
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Netzer P, Gaia C, Sandoz M, Huluk T, Gut A, Halter F, Hüsler J, Inauen W. Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours. Am J Gastroenterol 1999; 94:351-7. [PMID: 10022628 DOI: 10.1111/j.1572-0241.1999.857_y.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE In healthy subjects and patients with bleeding peptic ulcers, ranitidine and omeprazole, given parenterally, achieve high intragastric pH values on the first day of therapy. However, data on the antisecretory effect beyond the first 24 h is scanty. In addition, the superiority of either infusion or injection of omeprazole remains unproven. Thus, we have compared the antisecretory effect of high dose omeprazole and ranitidine infusion and injection over the critical first 72 h. METHODS A total of 34 healthy volunteers were randomized into a double-blind crossover 72 h intragastric pH-metry study (data compared: median pH, percentage of time with pH >4 and pH >6). Omeprazole-infusion: initial bolus of 80 mg + 8 mg/h; omeprazole-injection: initial bolus of 80 mg + 40 mg/6 h; Ranitidine-infusion: initial bolus of 50 mg + 0.25 mg/kg/h; ranitidine-injection: 100 mg/6 h. RESULTS Omeprazole-infusion versus ranitidine-infusion: on day 1: median pH 6.1 vs 5.1 (p = 0.01) and 95% vs 70% was pH >4 (p < 0.01); on day 2: median pH 6.2 vs 3.2 (p < 0.01); and 100% vs 38% was pH >4 (p < 0.01); on day 3: median pH 6.3 vs 2.7 (p < 0.01); 100% vs 26% was pH >4 (p < 0.01). Injections of both drugs were significantly less effective than the infusions on day 1. Thereafter, omeprazole injection was almost as effective as omeprazole infusion, whereas ranitidine injection and infusion were equally effective. CONCLUSION Our study shows, for the first time, that omeprazole infusion was significantly superior to all other regimens by having a high median pH >6 on each day. The tolerance effect of ranitidine, however, led to a rapid loss of antisecretory activity on days 2 and 3, rendering it inappropriate for situations in which high intragastric pH-levels appear to be essential.
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Affiliation(s)
- P Netzer
- Inselspital, and Department of Mathematical Statistics, University of Berne, Switzerland
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32
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Affiliation(s)
- P H Katelaris
- Gastroenterology Unit, The University of Sydney, Concord Hospital, NSW.
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33
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Hudson N, Murray FE, Cole AT, Filipowicz B, Hawkey CJ. Effect of sucralfate on aspirin induced mucosal injury and impaired haemostasis in humans. Gut 1997; 41:19-23. [PMID: 9274466 PMCID: PMC1027222 DOI: 10.1136/gut.41.1.19] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Sucralfate does not have potent anti-ulcerogenic actions in users of non-steroidal anti-inflammatory drugs (NSAIDs). However, sucralfate may influence intragastric haemostasis favourably. AIM To investigate separately the effects of sucralfate on acute gastric and duodenal injury and on changes in intragastric bleeding induced by aspirin. METHOD On three occasions, 24 healthy volunteers received three days' treatment with aspirin 900 mg twice daily together with placebo, sucralfate 2 g twice daily or sucralfate 1 g four times daily. Injury was assessed endoscopically and bleeding by spontaneous and biopsy induced bleeding intragastric washings. Ex vivo prostaglandin E2 (PGE2) synthesis and serum thromboxane were measured by using radioimmunoassay. RESULTS Aspirin significantly inhibited ex vivo gastric mucosal PGE2 synthesis, reduced serum thromboxane, caused gastric erosions, and increased spontaneous and biopsy induced bleeding. Sucralfate had no significant effects on endoscopic injury but sucralfate 1 g four times daily significantly reduced spontaneous and biopsy induced bleeding. Similar trends were seen with sucralfate 2 g twice daily but the results were less consistent. CONCLUSION Sucralfate does not affect aspirin induced acute gastric mucosal injury but reduces aspirin associated intragastric bleeding.
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Affiliation(s)
- N Hudson
- Division of Gastroenterology, University Hospital, Nottingham
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34
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Labenz J, Peitz U, Leusing C, Tillenburg B, Blum AL, Börsch G. 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. Gut 1997; 40:36-41. [PMID: 9155573 PMCID: PMC1027005 DOI: 10.1136/gut.40.1.36] [Citation(s) in RCA: 102] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
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.
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Affiliation(s)
- J Labenz
- Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany
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Kolkman JJ, Meuwissen SG. A review on treatment of bleeding peptic ulcer: a collaborative task of gastroenterologist and surgeon. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1996; 218:16-25. [PMID: 8865446 DOI: 10.3109/00365529609094726] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The majority of patients presenting with acute upper gastrointestinal haemorrhage bleed from peptic diseases erosive gastritis and duodenal or gastric ulcers. Early gastroscopy is essential in order to reach a diagnosis, assess the prognosis, and institute appropriate therapy. In a meta-analysis it was shown that H2-antagonists significantly reduced mortality. However, two large, prospective and placebo-controlled studies with famotidine and omeprazole failed to show reduction of rebleeding or death. The value of endoscopic haemostatic therapy in patients with high-risk peptic ulcers (active bleeding and non-bleeding visible vessel) has been firmly established with 75% decrease in rebleeding and operation rate, and a 40% reduction in mortality. Risk factors for an adverse outcome are: elderly patients, concomitant diseases and large ulcers in the posterior duodenal bulb or on the lesser curvature. The mortality for emergency surgery in upper GI bleeding is still 10-50%. The mortality of elective operations is less than 2%. Some studies have reduced mortality by avoiding emergency surgery through early elective surgery in high-risk patients.
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Affiliation(s)
- J J Kolkman
- Dept. of Gastroenterology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
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