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Geeratragool T, Kaosombatwattana U. Reply. Gastroenterology 2025; 168:431-432. [PMID: 39447845 DOI: 10.1053/j.gastro.2024.10.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024]
Affiliation(s)
- Tanawat Geeratragool
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Mahidol University; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Uayporn Kaosombatwattana
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Mahidol University; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
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Adamou F, Faivre M, Briot C. Ulcer in a Bulbar Diverticulum: An Atypical Localization and Rare Complication of Gastrointestinal Hemorrhage. Cureus 2024; 16:e74551. [PMID: 39734956 PMCID: PMC11671815 DOI: 10.7759/cureus.74551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2024] [Indexed: 12/31/2024] Open
Abstract
Gastrointestinal bleeding remains a frequent reason for emergency consultations, with a mortality rate that is still worrying despite advances in treatment. The most common cause is gastro-duodenal ulcers, mainly linked to Helicobacter pylori. Unusual causes such as gastroduodenal diverticular haemorrhage, a rare and serious complication, can also be detected during endoscopy. Although duodenal diverticula are the second most common localization after the colon, gastric intra-diverticular ulcers are extremely rare and rarely described in the literature. Treatment of diverticular haemorrhage can range from medical therapy to diverticulotomy. We present a case of upper gastrointestinal bleeding due to an unusual localization, specifically a gastro-duodenal ulcer situated within a diverticulum of the bulb. This article emphasizes the importance of meticulous exploration of gastric diverticula during gastroscopy, as they may conceal ulcers. Such endoscopic interventions can significantly impact patient management and prognosis, potentially altering outcomes from simple proton pump inhibitor therapy to preventing mortality, which remains alarmingly high according to existing literature.
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Affiliation(s)
- Fatima Adamou
- Gastroenterology, Mohammed VI University Hospital, Oujda, MAR
| | - Morgane Faivre
- Gastroenterology, Groupe Hospitalier de la Haute Saone, Vesoul, FRA
| | - Charline Briot
- Gastroenterology, Groupe Hospitalier de la Haute Saone, Vesoul, FRA
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Geeratragool T, Kaosombatwattana U, Boonchote A, Chatthammanat S, Preechakawin N, Srichot J, Sudcharoen A, Sirisunhirun P, Termsinsuk P, Rugivarodom M, Limsrivilai J, Maneerattanaporn M, Pausawasdi N, Leelakusolvong S. Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial. Gastroenterology 2024; 167:778-787.e3. [PMID: 38582271 DOI: 10.1053/j.gastro.2024.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 03/13/2024] [Accepted: 03/24/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND & AIMS High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. METHODS A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. CONCLUSION In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).
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Affiliation(s)
- Tanawat Geeratragool
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Uayporn Kaosombatwattana
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand.
| | - Arpapun Boonchote
- Division of Medicine, School of Medicine, Vachira Phuket Hospital, Phuket, Thailand
| | | | | | - Jompol Srichot
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Asawin Sudcharoen
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand
| | | | - Panotpol Termsinsuk
- Gastroenterology Unit, School of Medicine, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima, Thailand
| | - Manus Rugivarodom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Monthira Maneerattanaporn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Nonthalee Pausawasdi
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
| | - Somchai Leelakusolvong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj GI Endoscopy Center, Siriraj Hospital, Bangkok, Thailand
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Pattarapuntakul T, Wong T, Wetwittayakhlang P, Netinatsunton N, Keeratichananont S, Kaewdech A, Jandee S, Chamroonkul N, Sripongpun P, Lakatos PL. Efficacy of Vonoprazan vs. Intravenous Proton Pump Inhibitor in Prevention of Re-Bleeding of High-Risk Peptic Ulcers: A Randomized Controlled Pilot Study. J Clin Med 2024; 13:3606. [PMID: 38930134 PMCID: PMC11204564 DOI: 10.3390/jcm13123606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/03/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Background: Proton pump inhibitor (PPI) therapy is well-established for its effectiveness in reducing re-bleeding in high-risk peptic ulcer patients following endoscopic hemostasis. Vonoprazan (VPZ) has demonstrated the capacity to achieve gastric pH levels exceeding 4, comparable to PPIs. This study aims to evaluate the comparative efficacy of intravenous PPI infusion versus VPZ in preventing re-bleeding after endoscopic hemostasis in patients with high-risk peptic ulcers. Methods: A randomized, double-blind, controlled, and double-dummy design was employed. Patients with peptic ulcer bleeding (Forrest class IA/IB or IIA/IIB) who underwent endoscopic hemostasis were randomly assigned to either the PPI group or the VPZ group. Re-bleeding rates at 3, 7, and 30 days, the number of blood transfusions required, length of hospitalization, and ulcer healing rate at 56 days were assessed. Results: A total of 44 eligible patients were enrolled, including 20 patients (PPI group, n = 11; VPZ group, n = 9) with high-risk peptic ulcers. The mean age was 66 years, with 70% being male. Re-bleeding within 72 h occurred in 9.1% of the PPI group versus 0% in the VPZ group (p = 1.000). There was no significant difference in re-bleeding rates within 7 days and 30 days (18.2% vs. 11.1%, p = 1.000). Additionally, the ulcer healing rate did not significantly differ between the groups (87.5% vs. 77.8%). Conclusions: This pilot study demonstrates comparable efficacy between oral vonoprazan and continuous PPI infusion in preventing recurrent bleeding events among high-risk peptic ulcer patients following successful endoscopic hemostasis.
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Affiliation(s)
- Tanawat Pattarapuntakul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Thanawin Wong
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Panu Wetwittayakhlang
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Nisa Netinatsunton
- Nanthana-Kriangkrai Chotiwattanaphan (NKC) Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.N.); (S.K.)
| | - Suriya Keeratichananont
- Nanthana-Kriangkrai Chotiwattanaphan (NKC) Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (N.N.); (S.K.)
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Sawangpong Jandee
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; (T.P.); (T.W.); (A.K.); (S.J.); (N.C.); (P.S.)
| | - Peter L. Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Department of Internal Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary
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Xiao X, Liu X, Yan H, Xing X, Luo X, Yang J. Proton pump inhibitor therapy after transcatheter angiography in refractory nonvariceal acute upper gastrointestinal bleeding patients: a cohort study. BMC Gastroenterol 2024; 24:168. [PMID: 38760713 PMCID: PMC11100103 DOI: 10.1186/s12876-024-03261-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 05/13/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND Transcatheter angiography (TA) could help to diagnose and treat refractory nonvariceal upper gastrointestinal bleeding (NVUGIB). Proton pump inhibitors (PPIs) are the key medication for reducing the rebleeding rate and mortality and are usually continued after TA. It is unknown whether high-dose PPIs after TA are more effective than the standard regimen. METHODS We retrospectively collected data from patients who received TA because of refractory NVUGIB from 2010 to 2020 at West China Hospital. 244 patients were included and divided into two groups based on the first 3 days of PPIs treatment. All baseline characteristics were balanced using the inverse probability of treatment weighting method. The 30-day all-cause mortality, rebleeding rate and other outcomes were compared. The propensity score matching method was also used to verify the results. RESULTS There were 86 patients in the high-dose group and 158 in the standard group. The average daily doses of PPI were 192.1 ± 17.9 mg and 77.8 ± 32.0 mg, respectively. Cox regression analysis showed no difference in the 30-day all-cause mortality (aHR 1.464, 95% CI 0.829 to 2.584) or rebleeding rate (aHR 1.020, 95% CI 0.693 to 1.501). There were no differences found in red blood cell transfusion, hospital stay length and further interventions, including endoscopy, repeating TA, surgery and ICU admission. The results were consistent in the subgroup analysis of patients with transcatheter arterial embolization. CONCLUSION In refractory NVUGIB patients who received TA, regardless of whether embolization was performed, high-dose PPI treatment did not provide additional benefits compared with the standard regimen.
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Affiliation(s)
- Xue Xiao
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan Province, China
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Chengdu, Sichuan Province, China
| | - Xinbing Liu
- Endoscopy Center, Sichuan Cancer Hospital, Chengdu, Sichuan Province, China
| | - Hailin Yan
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan Province, China
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Chengdu, Sichuan Province, China
| | - Xiaocun Xing
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan Province, China
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Chengdu, Sichuan Province, China
| | - Xuefeng Luo
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan Province, China
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Chengdu, Sichuan Province, China
| | - Jinlin Yang
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, 37 GuoXue Xiang, Chengdu, 610041, Sichuan Province, China.
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Chengdu, Sichuan Province, China.
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Jensen DM. The Importance of Arterial Blood Flow Detection for Risk Stratification and Eradication to Achieve Definitive Hemostasis of Severe Non-Variceal UGI Hemorrhage. J Clin Med 2023; 12:6473. [PMID: 37892610 PMCID: PMC10607067 DOI: 10.3390/jcm12206473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/14/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common medical problem worldwide. Independent endoscopic risk factors for rebleeding and mortality of NVUGIB that are treatable are stigmata of recent hemorrhage (SRH) and arterial blood flow underneath SRH. The specific aims of this paper are to describe the importance of arterial blood flow detection for risk stratification and as a guide to definitive hemostasis of severe NVUGIB. METHODS This is a review of randomized controlled trials and prospective cohort study methodologies and results which utilized a Doppler endoscopic probe (DEP) for the detection of arterial blood underneath SRH, for risk stratification, and as a guide to definitive hemostasis. The results are compared to visually guided hemostasis based upon SRH. RESULTS Although SRH have been utilized to guide endoscopic hemostasis of NVUGIB for 50 years, when most visually guided treatments are applied to lesions with major SRH, arterial blood flow underneath SRH is not obliterated in 25-30% of patients and results in rebleeding. Definitive hemostasis, significantly lower rebleeding rates, and improvements in other clinical outcomes resulted when DEP was used for risk stratification and as a guide to obliteration of arterial blood flow underneath SRH. CONCLUSIONS DEP-guided endoscopic hemostasis is a very effective and safe new method to improve patient outcomes for NVUGIB.
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Affiliation(s)
- Dennis M Jensen
- David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center and The VA Greater Los Angeles Healthcare System, Los Angeles, CA 90095, USA
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Monti G, Konkayev A, Carta S, Bradic N, Bruni A, Kotani Y, Guarracino F, Redkin I, Biondi-Zoccai G, Benedetto U, D'Ascenzo F, Garofalo E, Baiardo Redaelli M, Brizzi G, Forfori F, Borghi G, Scapol S, Momesso E, Cuffaro R, Boffa N, Rauch S, D'Amico F, Montrucchio G, Pace MC, Galbiati C, Bosso S, Savelli F, Giardina G, Silvetti S, Tripodi VF, Labanca R, Lembo R, Marmiere M, Marzaroli M, Nakhnoukh C, Valsecchi D, Finco G, Agrò FE, Bove T, Corradi F, Longhini F, Landoni G, Bellomo R, Zangrillo A. High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial. Contemp Clin Trials 2023; 133:107319. [PMID: 37625587 DOI: 10.1016/j.cct.2023.107319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 08/12/2023] [Accepted: 08/22/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. METHODS This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DISCUSSION This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.
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Affiliation(s)
- Giacomo Monti
- IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Aidos Konkayev
- Astana Medical University, National Scientific Center of Traumatology and Orthopedia, Astana, Kazakhstan
| | - Sonia Carta
- IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Nikola Bradic
- University Hospital Dubrava, Zagreb, Croatia; University North, Varazdin, Croatia
| | - Andrea Bruni
- Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Yuki Kotani
- IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Kameda Medical Center, Kamogawa, Japan
| | | | - Ivan Redkin
- Federal Research and Clinical Center of Reanimatology and Rehabilitology, Moscow, Russia
| | | | | | - Fabrizio D'Ascenzo
- University of Turin, Turin, Italy; Città Della Salute e Della Scienza Hospital, Turin, Italy
| | - Eugenio Garofalo
- Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | | | - Giulia Brizzi
- Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | | | | | - Sara Scapol
- Department of Medicine (DAME), University of Udine, Udine, Italy
| | - Elena Momesso
- Ospedale San Donà di Piave, San Donà di Piave (VE), Italy
| | | | | | | | | | - Giorgia Montrucchio
- University of Turin, Turin, Italy; Città Della Salute e Della Scienza Hospital, Turin, Italy
| | | | | | | | | | | | | | | | - Rosa Labanca
- IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Rosalba Lembo
- IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | | | | | | | | | | | - Tiziana Bove
- Department of Medicine (DAME), University of Udine, Udine, Italy; University of Udine, Udine, Italy
| | | | - Federico Longhini
- Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Giovanni Landoni
- IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
| | - Rinaldo Bellomo
- The University of Melbourne, Melbourne, Australia; Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
| | - Alberto Zangrillo
- IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
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Cha B, Noh JH, Ahn JY, Lee JS, Kim GH, Na HK, Jung KW, Lee JH, Kim DH, Choi KD, Song HJ, Lee GH, Jung HY. Clinical Outcomes of Patients with Benign Peptic Ulcer Bleeding After an Emergency Endoscopy Based on Patient Location. Dig Dis Sci 2023; 68:1539-1550. [PMID: 36284035 DOI: 10.1007/s10620-022-07708-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 09/20/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS In the efforts toward reducing bleeding-related mortality, it is crucial to determine the risk factors for rebleeding after endoscopic hemostasis in benign peptic ulcer (BPU). METHODS Between 2013 and 2017, the medical records of 864 BPU patients were selected from 5076 who had undergone emergency endoscopy for suspected upper gastrointestinal bleeding. Patients who visited the emergency room or were hospitalized for other illnesses were selected. The primary end point was rebleeding within 30 days after initial endoscopy. The risk factors of rebleeding and subgroup analyses according to patient location were evaluated. RESULTS Among 864 BPU bleeding patients, rebleeding after completion of BPU bleeding occurred in 140 (16.2%). Initial indicators of hypotension (OR 1.878, p = 0.005) and Forrest classes Ia (OR 25.53, p < 0.001), Ib (OR 27.91, p = 0.005), IIa (OR 21.41, p < 0.001), and IIb (OR 23.74, p < 0.001) were independent risk factors of rebleeding compared to Forrest class III, and being inpatients (OR 1.75, p = 0.01). Compared to the outpatients, the inpatients showed significantly higher rebleeding rates (25.6% vs 13.8%, p < 0.001), predictive bleeding scores, red blood transfusion counts, proportion of Forrest classes Ia, Ib, and IIb (p < 0.001), and overall mortality rates (68.8% vs 34.0%, p < 0.001). CONCLUSIONS Patient location was a novel predictive factor of BPU rebleeding. Particularly, being an inpatient correlated with increased rebleeding. Furthermore, Forrest classes Ia, Ib, IIa, and IIb were predictive of rebleeding not only the included BPUs, but also in the inpatient or outpatient groups.
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Affiliation(s)
- Boram Cha
- Department of Internal Medicine, Digestive Disease Center, Inha University School of Medicine, Incheon, Republic of Korea
| | - Jin Hee Noh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
| | - Jun Su Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ga Hee Kim
- Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
| | - Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
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Hemostatic Powders in Non-Variceal Upper Gastrointestinal Bleeding: The Open Questions. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59010143. [PMID: 36676767 PMCID: PMC9863809 DOI: 10.3390/medicina59010143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/03/2023] [Accepted: 01/05/2023] [Indexed: 01/12/2023]
Abstract
Hemostatic powder (HP) is a relatively recent addition to the arsenal of hemostatic endoscopic procedures (HEPs) for gastrointestinal bleeding (GIB) due to benign and malignant lesions. Five types of HP are currently available: TC-325 (Hemospray™), EndoClot™, Ankaferd Blood Stopper®, and, more recently, UI-EWD (NexpowderTM) and CEGP-003 (CGBio™). HP acts as a mechanical barrier and/or promotes platelet activation and coagulation cascade. HP may be used in combination with or as rescue therapy in case of failure of conventional HEPs (CHEPs) and also as monotherapy in large, poorly accessible lesions with multiple bleeding sources. Although the literature on HP is abundant, randomized controlled trials are scant, and some questions remain open. While HP is highly effective in inducing immediate hemostasis in GIB, the rates of rebleeding reported in different studies are very variable, and conditions affecting the stability of hemostasis have not yet been fully elucidated. It is not established whether HP as monotherapy is appropriate in severe GIB, such as spurting peptic ulcers, or should be used only as rescue or adjunctive therapy. Finally, as it can be sprayed on large areas, HP could become the gold standard in malignancy-related GIB, which is often nonresponsive or not amenable to treatment with CHEPs as a result of multiple bleeding points and friable surfaces. This is a narrative review that provides an overview of currently available data and the open questions regarding the use of HP in the management of non-variceal upper GIB due to benign and malignant diseases.
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10
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Iqbal H, Maharaj D, Chaudhry H, Gulati A, Roytman M. Refractory gastric ulcer bleeding responsive to long-term octreotide. SAGE Open Med Case Rep 2023; 11:2050313X231164856. [PMID: 37051262 PMCID: PMC10084531 DOI: 10.1177/2050313x231164856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 03/03/2023] [Indexed: 04/14/2023] Open
Abstract
Upper gastrointestinal tract bleeding is a common condition that can cause hemodynamic instability and death if left untreated. Endoscopic hemostasis is often successful; however, some patients may develop refractory bleeding. Pharmacologic management with octreotide is beneficial in patients with variceal bleeding and has been shown in some studies to be effective in refractory bleeding due to angiodysplasia. There is a paucity of literature regarding the usage of long-term octreotide in refractory bleeding secondary to a peptic ulcer. We present a case of a bleeding gastric ulcer that was refractory to endoscopic management but responsive to long-term octreotide therapy.
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Affiliation(s)
- Humzah Iqbal
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
- Humzah Iqbal, Department of Internal Medicine, University of California, San Francisco, 155 N. Fresno St., Fresno, CA 93701, USA.
| | - Dashmeet Maharaj
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
| | - Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
| | - Alakh Gulati
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA, USA
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA, USA
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11
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Pittayanon R, Suen BY, Kongtub N, Tse YK, Rerknimitr R, Lau JYW. Scheduled second look endoscopy after endoscopic hemostasis to patients with high risk bleeding peptic ulcers: a Randomized Controlled Trial. Surg Endosc 2022; 36:6497-6506. [PMID: 35020056 DOI: 10.1007/s00464-021-09004-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 12/31/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND The recommendation of second look endoscopy (SLOGD) in selected patients at high risk for rebleeding has been inconclusive. This study aimed to evaluate the benefit of SLOGD in selected patients predicted at high risk of recurrent bleeding. METHODS From a cohort of 939 patients with bleeding peptic ulcers who underwent endoscopic hemostasis, we derived a 9-point risk score (age > 60, Male, ulcer ≥ 2 cm in size, posterior bulbar or lesser curve gastric ulcer, Forrest I bleeding, haemoglobin < 8 g/dl) to predict recurrent bleeding. We then validated the score in another cohort of 1334 patients (AUROC 0.77). To test the hypothesis that SLOGD in high-risk patients would improve outcomes, we did a randomized controlled trial to compare scheduled SLOGD with observation alone in those predicted at high risk of rebleeding (a score of ≥ 5). The primary outcome was clinical bleeding within 30 days of the index bleed. RESULTS Of 314 required, we enrolled 157 (50%) patients (SLOGD n = 78, observation n = 79). Nine (11.8%) in SLOGD group and 14 (18.2%) in observation group reached primary outcome (absolute difference 6.4%, 95% CI - 5.0% to 17.8%). Twenty-one of 69 (30.4%) patients who underwent SLOGD needed further endoscopic treatment. No surgery for bleeding control was needed. There were 6 vs. 3 of 30-day deaths in either group (p = 0.285, log rank). No difference was observed regarding blood transfusion and hospitalization. CONCLUSIONS In this aborted trial that enrolled patients with bleeding peptic ulcers at high-risk of recurrent bleeding, scheduled SLOGD did not significantly improve outcomes. CLINICALTRIALS gov:NCT02352155.
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Affiliation(s)
- Rapat Pittayanon
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Bing-Yee Suen
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Natanong Kongtub
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - James Y W Lau
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
- Department of Surgery, Prince of Wales Hospital, Room 64026, Lui Chee Woo Clinical Science Building, 32 Ngan Shing Street, Shatin, NT, Hong Kong SAR, China.
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12
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Mao X, Yang Z. Association between hospital-acquired pneumonia and proton pump inhibitor prophylaxis in patients treated with glucocorticoids: a retrospective cohort study based on 307,622 admissions in China. J Thorac Dis 2022; 14:2022-2033. [PMID: 35813745 PMCID: PMC9264073 DOI: 10.21037/jtd-21-1886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 05/12/2022] [Indexed: 11/06/2022]
Abstract
Background Prophylaxis with proton pump inhibitor (PPI) in patients treated with glucocorticoid therapy is a common phenomenon in the general wards of Chinese hospitals. Many of these prescriptions are inappropriate and lead to overuse. Hospital-acquired pneumonia (HAP) is a possible adverse effect for this combination but remains controversial. Methods We designed a retrospective cohort study using electronic medical record databases from multiple hospitals to investigate whether PPI prophylaxis increases the risk of HAP in hospitalized patients receiving glucocorticoid therapy. The study population was adult patients who were not critical and treated with at least 1 dose of glucocorticoid during hospitalization and the exposure factor was PPIs prophylaxis. The odds ratio of HAP between the exposed and unexposed groups was calculated based on the cohort which was established by propensity score matching. The dose-effect relationship between PPI prophylaxis and HAP was also evaluated. Results Among the 307,622 admissions eligible for the study, a total of 217,460 (70.7%) admissions had a record of PPI prophylaxis. After reconstructed the cohort by propensity score matching, the exposed and unexposed groups both included 83,786 admissions. The incidence of HAP in the exposed group was higher than that in the unexposed group (2.1% vs. 1.5%, OR: 1.4, 95% CI: 1.3 to 1.5). The risk of HAP increased when the cumulative dose of PPI during hospital was more than 2 defined drug doses. Compared to the unexposed group, the adjusted odds ratio was 1.3 (95% CI: 1.2 to 1.4) in the medium-dose group (2-7 defined drug doses) and 1.9 (95% CI: 1.8 to 2.1) in the high-dose group (>7 defined drug doses). Conclusions PPI prophylaxis increased the risk of HAP in hospitalized patients treated with glucocorticoid therapy and the risk of HAP increased as the dose of PPIs accumulated.
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Affiliation(s)
- Xufeng Mao
- Department of Pharmacy, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhangwei Yang
- Department of Information, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
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13
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Randomized controlled trial of early endoscopy for upper gastrointestinal bleeding in acute coronary syndrome patients. Sci Rep 2022; 12:5798. [PMID: 35388113 PMCID: PMC8986851 DOI: 10.1038/s41598-022-09911-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 03/30/2022] [Indexed: 12/14/2022] Open
Abstract
Acute upper gastrointestinal bleeding (UGIB) in acute coronary syndrome (ACS) patients are not uncommon, particularly under dual antiplatelet therapy (DAPT). The efficiency and safety of early endoscopy (EE) for UGIB in these patients needs to be elucidated. This multicenter randomized controlled trial randomized recent ACS patients presenting acute UGIB to non-EE and EE groups. All eligible patients received intravenous proton pump inhibitor therapy. Those in EE group underwent therapeutic endoscopy within 24 h after bleeding. The data regarding efficacy and safety of EE were analyzed. It was early terminated because the UGIB rate was lower than expected and interim analysis was done. In total, 43 patients were randomized to non-EE (21 patients) and EE (22 patients) groups. The failure rate of control hemorrhage (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and 3-day rebleeding rate (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in EE than non-EE group. The mortality, minor and major complication rates were not different between two groups. Male patients were at higher risk of minor and major complications after EE with OR (95% CI) of 3.50 (1.15–10.63) and 4.25 (1.43–12.63), respectively. In multivariate analysis, EE was associated with lower needs for blood transfusion (HR 0.13, 95% CI 0.02–0.98). Among patients who discontinued DAPT during acute UGIB, a higher risk (OR 5.25, 95% CI 1.21–22.74) of coronary artery stent re-thrombosis within 6 months was noticed. EE for acute UGIB in recent ACS patients has higher rate of bleeding control, lower 3-day rebleeding rate and lower needs for blood transfusion, but more complications in male patients. Further enrollment is mandatory to avoid bias from small sample size (ClinicalTrial.gov Number NCT02618980, registration date 02/12/2015).
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14
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Pittayanon R, Lau JYW. Comparison of a Hemostatic Powder and Standard Treatment in the Control of Active Bleeding From Upper Nonvariceal Lesions. Ann Intern Med 2022; 175:W45-W46. [PMID: 35436427 DOI: 10.7326/l22-0069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Rapat Pittayanon
- Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - James Y W Lau
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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15
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Kanno T, Yuan Y, Tse F, Howden CW, Moayyedi P, Leontiadis GI. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev 2022; 1:CD005415. [PMID: 34995368 PMCID: PMC8741303 DOI: 10.1002/14651858.cd005415.pub4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding. OBJECTIVES To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding. SEARCH METHODS We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials. SELECTION CRITERIA We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis. AUTHORS' CONCLUSIONS There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
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Affiliation(s)
- Takeshi Kanno
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Japan
- Department of Education and Support for Regional Medicine, Tohoku University Hospital, Sendai, Japan
| | - Yuhong Yuan
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Frances Tse
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Colin W Howden
- Division of Gastroenterology, University of Tennessee, Memphis, TN, USA
| | - Paul Moayyedi
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Grigorios I Leontiadis
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
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16
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Romstad KK, Detlie TE, Søberg T, Thomas O, Ricanek P, Jahnsen ME, Lerang F, Jahnsen J. Treatment and outcome of gastrointestinal bleeding due to peptic ulcers and erosions - (BLUE study). Scand J Gastroenterol 2022; 57:8-15. [PMID: 34663154 DOI: 10.1080/00365521.2021.1988701] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Peptic ulcers and erosions are the most common causes of upper gastrointestinal bleeding. The aim of this study was to investigate the management and outcomes of these patients. MATERIALS AND METHODS A total of 543 patients with endoscopically confirmed bleeding from peptic ulcers and erosions were included from March 2015 to December 2017. The patient characteristics, endoscopic findings, Forrest classification and endoscopic treatment were recorded. Moreover, the rebleeding rates, repeated endoscopies and transcatheter angiographic embolization and surgery incidences were registered. A follow-up endoscopy after discharge from the hospital was scheduled. RESULTS Among the patients, high-risk stigmata ulcers were present in 36% (198/543) and low-risk stigmata ulcers and erosions in 60% (327/543) at first endoscopy. Endoscopic therapy was performed in 30% (165/543) of the patients, and hemostasis was achieved in 94% (155/165). The incidence of rebleeding was 9% (49/543) for the whole cohort and 14.8% (23/155) for those patients who had received successful endoscopic treatment. Moreover, rebleeding was significantly more frequent in duodenal ulcers than in gastric ulcers (11.9% vs 4.0%, p = .004). In a multivariable analysis, rebleeding was significantly related to comorbidity and Forrest classification. Transcatheter angiographic embolization and surgery were required in 6% (34/543) and 0.07% (4/543) of patients, respectively. Complete peptic ulcer healing was found at follow-up in 73.3% (270/368) of patients. CONCLUSIONS Endoscopic hemostasis was achieved in the majority of patients with high-risk ulceration, although the occurrence of rebleeding is a significant challenge, especially in patients with duodenal ulcers. Clinical trial registration: Bleeding Ulcer and Erosions Study (BLUE Study), ClinicalTrials.gov identifier: NCT03367897.
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Affiliation(s)
- Katrine Kauczynska Romstad
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trond Espen Detlie
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Taran Søberg
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway
| | - Owen Thomas
- Division of Research and Innovation, Akershus University Hospital, Lørenskog, Norway
| | - Petr Ricanek
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Marte Eide Jahnsen
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Frode Lerang
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
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17
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Yu Q, Liu C, Collura B, Navuluri R, Patel M, Yu Z, Ahmed O. Prophylactic transcatheter arterial embolization for high-risk ulcers following endoscopic hemostasis: a meta-analysis. World J Emerg Surg 2021; 16:29. [PMID: 34112185 PMCID: PMC8194167 DOI: 10.1186/s13017-021-00371-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 05/18/2021] [Indexed: 12/21/2022] Open
Abstract
Background To conduct a meta-analysis to assess the safety and efficacy of prophylactic transcatheter arterial embolization (PTAE) for the treatment of high-risk bleeding peptic ulcers after achieving endoscopic hemostasis. Methods PubMed and Cochrane Library were queried for full-text articles published up to December 2019. The following keywords were used: “prophylactic embolization”, “supplement embolization”, “gastrointestinal bleeding”, and “ulcer bleeding”. High-risk ulcers were defined based on endoscopic findings (i.e., large ulcers, Forrest class I-IIb) and/or clinical presentation (i.e., hypotension, decreased hemoglobin during endoscopy). Only comparative studies investigating PTAE versus conservative treatment after achieving endoscopic hemostasis were included. Baseline study characteristics, rebleeding rate, need for surgery, mortality, and PTAE-related complication rates were investigated. Quantitative analyses were performed with Stata 15.1. Results Among the five included original studies, a total of 265 patients received PTAE and 617 were managed conservatively after endoscopy. The rebleeding rate (6.8% vs 14.3%, p = 0.003) and mortality (4.5% vs 8.8%, p = 0.032) of patients from the PTAE group were lower than the control group. PTAE also reduced the cumulative need for future surgical intervention (3.0% vs 14.4%, p = 0.005). The PTAE-related major and minor events were 0.75% and 14.4%, respectively. Conclusion PTAE had therapeutic potentials in reducing rebleeding risk, need for surgical intervention, and morality in high-risk peptic ulcers after achieving endoscopic hemostasis. The embolization-associated adverse events were minimal. Future studies should aim to increase the sample size and resources for performing endovascular interventions. Supplementary Information The online version contains supplementary material available at 10.1186/s13017-021-00371-2.
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Affiliation(s)
- Qian Yu
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, Shandong Province, China.,Department of General Surgery, Cleveland Clinic Florida, Florida, USA
| | - Chenyu Liu
- School of Medicine, George Washington University, Washington DC, USA
| | | | - Rakesh Navuluri
- Division of Interventional Radiology, Department of Radiology, University of Chicago, Chicago, IL, USA
| | - Mikin Patel
- Department of Radiology, University of Arizona Medical Center, Tucson, AZ, USA
| | - Zhiyong Yu
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, Shandong Province, China.
| | - Osman Ahmed
- Division of Interventional Radiology, Department of Radiology, University of Chicago, Chicago, IL, USA
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18
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Sun XC, Yuan WF, Ma WJ, Zhang WJ, Xu SG. Study on the preventive effect of intravenous esomeprazole in the management of nonvarices upper gastrointestinal bleeding. Medicine (Baltimore) 2021; 100:e25420. [PMID: 34011021 PMCID: PMC8137025 DOI: 10.1097/md.0000000000025420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 03/09/2021] [Indexed: 01/05/2023] Open
Abstract
This retrospective study investigated the preventive effect of intravenous esomeprazole (IVEO) in the prevention of nonvarices upper gastrointestinal bleeding (NUGIB).This study enrolled 130 patients with NUGIB and all of them underwent successful endoscopic hemostasis, of which 65 cases received routine management and IVEO (Group A) and the other 65 cases received routine management alone (Group B). The primary outcome (recurrent bleeding rate within 72-hour, 7-day, and 30-day), and secondary outcomes ((all-cause mortality, bleeding-related mortality, blood transfused, hospital stay (day), and incidence of adverse events)) were compared between 2 groups.Patients in the group A showed lower recurrent bleeding rate within 72-hour(P < .05), 7-day (P < .05), and 30-day (P < .05), than that of patients in the group B. However, no significant differences were identified in all-cause mortality(P = .26), bleeding-related mortality (P = .57), blood transfused (P = .33), and hospital stay (P = .74) between 2 groups. In addition, both groups had similar safety profile.This study found that routine management and IVEO was superior to the routine management alone for preventing the recurrent bleeding rate after successful endoscopic hemostasis in patients with NUGIB.
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19
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ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol 2021; 116:899-917. [PMID: 33929377 DOI: 10.14309/ajg.0000000000001245] [Citation(s) in RCA: 272] [Impact Index Per Article: 68.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 01/07/2021] [Indexed: 02/06/2023]
Abstract
We performed systematic reviews addressing predefined clinical questions to develop recommendations with the GRADE approach regarding management of patients with overt upper gastrointestinal bleeding. We suggest risk assessment in the emergency department to identify very-low-risk patients (e.g., Glasgow-Blatchford score = 0-1) who may be discharged with outpatient follow-up. For patients hospitalized with upper gastrointestinal bleeding, we suggest red blood cell transfusion at a threshold of 7 g/dL. Erythromycin infusion is suggested before endoscopy, and endoscopy is suggested within 24 hours after presentation. Endoscopic therapy is recommended for ulcers with active spurting or oozing and for nonbleeding visible vessels. Endoscopic therapy with bipolar electrocoagulation, heater probe, and absolute ethanol injection is recommended, and low- to very-low-quality evidence also supports clips, argon plasma coagulation, and soft monopolar electrocoagulation; hemostatic powder spray TC-325 is suggested for actively bleeding ulcers and over-the-scope clips for recurrent ulcer bleeding after previous successful hemostasis. After endoscopic hemostasis, high-dose proton pump inhibitor therapy is recommended continuously or intermittently for 3 days, followed by twice-daily oral proton pump inhibitor for the first 2 weeks of therapy after endoscopy. Repeat endoscopy is suggested for recurrent bleeding, and if endoscopic therapy fails, transcatheter embolization is suggested.
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20
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Sung JJY, Laine L, Kuipers EJ, Barkun AN. Towards personalised management for non-variceal upper gastrointestinal bleeding. Gut 2021; 70:818-824. [PMID: 33649044 DOI: 10.1136/gutjnl-2020-323846] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/15/2021] [Accepted: 02/16/2021] [Indexed: 02/06/2023]
Abstract
Guidelines from national and international professional societies on upper gastrointestinal bleeding highlight the important clinical issues but do not always identify specific management strategies pertaining to individual patients. Optimal treatment should consider the personal needs of an individual patient and the pertinent resources and experience available at the point of care. This article integrates international guidelines and consensus into three stages of management: pre-endoscopic assessment and treatment, endoscopic evaluation and haemostasis and postendoscopic management. We emphasise the need for personalised management strategies based on patient characteristics, nature of bleeding lesions and the clinical setting including available resources.
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Affiliation(s)
- Joseph J Y Sung
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Loren Laine
- Section of Digestive Diseases, Yale School of Medicine and VA Connecticut Healthcare System, New Haven, Connecticut, USA
| | - Ernst J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Alan N Barkun
- Gastroenterology, McGILL University health centre, Montreal, Quebec, Canada
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Mille M, Engelhardt T, Stier A. Bleeding Duodenal Ulcer: Strategies in High-Risk Ulcers. Visc Med 2021; 37:52-62. [PMID: 33718484 PMCID: PMC7923890 DOI: 10.1159/000513689] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 12/09/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Acute peptic ulcer bleeding is still a major reason for hospital admission. Especially the management of bleeding duodenal ulcers needs a structured therapeutic approach due to the higher morbidity and mortality compared to gastric ulcers. Patient with these bleeding ulcers are often in a high-risk situation, which requires multidisciplinary treatment. SUMMARY This review provides a structured approach to modern management of bleeding duodenal ulcers and elucidates therapeutic practice in high-risk situations. Initial management including pharmacologic therapy, risk stratification, endoscopy, surgery, and transcatheter arterial embolization are reviewed and their role in the management of bleeding duodenal ulcers is critically discussed. Additionally, a future perspective regarding prophylactic therapeutic approaches is outlined. KEY MESSAGES Beside pharmacotherapeutic and endoscopic advances, bleeding management of high-risk duodenal ulcers is still a challenge. When bleeding persists or rebleeding occurs and the gold standard endoscopy fails, surgical and radiological procedures are indicated to manage ulcer bleeding. Surgical procedures are performed to control hemorrhage, but they are still associated with a higher morbidity and a longer hospital stay. In the meantime, transcatheter arterial embolization is recommended as an alternative to surgery and more often replaces surgery in the management of failed endoscopic hemostasis. Future studies are needed to improve risk stratification and therefore enable a better selection of high-risk ulcers and optimal treatment. Additionally, the promising approach of prophylactic embolization in high-risk duodenal ulcers has to be further investigated to reduce rebleeding and improve outcomes in these patients.
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Affiliation(s)
- Markus Mille
- Department of General and Visceral Surgery, HELIOS Hospital Erfurt, Erfurt, Germany
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Zhu Z, Lai Y, Ouyang L, Lv N, Chen Y, Shu X. High-Dose Proton Pump Inhibitors Are Superior to Standard-Dose Proton Pump Inhibitors in High-Risk Patients With Bleeding Ulcers and High-Risk Stigmata After Endoscopic Hemostasis. Clin Transl Gastroenterol 2021; 12:e00294. [PMID: 33448708 PMCID: PMC7810506 DOI: 10.14309/ctg.0000000000000294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 11/23/2020] [Indexed: 01/10/2023] Open
Abstract
INTRODUCTION To define the best cutoff of the Glasgow-Blatchford score (GBS) for identifying high- and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis and compare the efficacy of high-dose and standard-dose intravenous proton pump inhibitors (HD-IVPs and SD-IVPs, respectively) in this patient population. METHODS We retrospectively reviewed the data of 346 patients with bleeding ulcers and high-risk stigmata who underwent endoscopic hemostasis between March 2014 and September 2018 in our center and were divided into an HD-IVP group and an SD-IVP group. Propensity score-matching analysis was performed to control for selection bias and other potential confounders. Recurrent bleeding rates were calculated according to the GBS. RESULTS Overall, 346 patients meeting the inclusion criteria were enrolled, with 89 patients in the SD-IVP group and 89 patients in the HD-IVP group after matching with all baseline characteristics balanced (P > 0.05). GBS = 8 was the best cutoff for identifying high-risk rebleeding patients (GBS ≥ 8) with a significant difference (P = 0.015) in recurrence rate between the SD-IVP (17/61, 27.9%) and HD-IVP (7/65, 10.8%) groups and low-risk rebleeding patients (GBS < 8) with no difference (P = 1) in recurrence rate between the SD-IVP (2/28, 7.1%) and HD-IVP (2/24, 8.3%) groups. DISCUSSION The best cutoff for identifying high-risk and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis was GBS = 8. Although HD-IVP is more effective than SD-IVP in high-risk patients, they are equally effective in low-risk patients.
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Affiliation(s)
- Zhenhua Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Yongkang Lai
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Liu Ouyang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Nonghua Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Youxiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
| | - Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China
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Surek A, Gemici E, Bozkurt MA, Karabulut M. UPPER GASTROINTESTINAL BLEEDING:IS ONLY AN INJECTION OF EPINEPHRINE SUFFICIENT? SUCCES RATES BY FORREST CLASSIFICATION. SANAMED 2020. [DOI: 10.24125/sanamed.v15i3.457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Chuang CH, Chen CC, Wu JH, Hong MY, Kang JW, Kuo HY, Huang CJ, Chen CY. Novel upper gastrointestinal monitoring system to track upper gastrointestinal bleeding: A pilot study. Endosc Int Open 2020; 8:E1811-E1816. [PMID: 33269314 PMCID: PMC7671761 DOI: 10.1055/a-1266-3501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/20/2020] [Indexed: 11/17/2022] Open
Abstract
Background and study aims Early detection of upper gastrointestinal (UGI) rebleeding is not easy by observing clinical symptoms. We developed a novel UGI monitoring system and aimed to test its feasibility of continuous tracking of UGI bleeding. Patients and methods A prospective study was conducted on patients with moderate to high risk of rebleeding. The UGI monitoring system was installed to monitor their gastric contents. It would alarm if rebleeding was suspected and the physician could review the images to make a further decision. The patient's comfort level was also evaluated. Results Sixteen patients were enrolled. Rebleeding occurred in one patient and was detected by this system more than 5 hours earlier than with clinical symptoms. The interobserver reliability for reviewing the images to define the blood clearance in the stomach was excellent (intraclass correlation coefficient 0.79-0.96). The comfort level assessed by patients was 1.90 ± 1.39 (on the scale of 0-5). Conclusions This pilot study demonstrated the potential of this UGI monitoring system for early detection of rebleeding.
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Affiliation(s)
- Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan,Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Chien-Cheng Chen
- Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Jhong-Han Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Yuan Hong
- Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jui-Wen Kang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsin-Yu Kuo
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chien-Jui Huang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chiung-Yu Chen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Endoscopist's Judgment Is as Useful as Risk Scores for Predicting Outcome in Peptic Ulcer Bleeding: A Multicenter Study. J Clin Med 2020; 9:jcm9020408. [PMID: 32028639 PMCID: PMC7073534 DOI: 10.3390/jcm9020408] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 01/22/2020] [Accepted: 01/31/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Guidelines recommend using prognostic scales for risk stratification in patients with non-variceal upper gastrointestinal bleeding. It remains unclear whether risk scores offer greater accuracy than clinical evaluation. Objective: Compare the diagnostic accuracy of the endoscopist’s judgment against different risk-scoring systems (Rockall, Glasgow–Blatchford, Baylor and the Cedars–Sinai scores) for predicting outcomes in peptic ulcer bleeding (PUB). Methods: Between February 2006 and April 2010 we prospectively recruited 401 patients with peptic ulcer bleeding; 225 received endoscopic treatment. The endoscopist recorded his/her subjective assessment (“endoscopist judgment”) of the risk of rebleeding and death immediately after endoscopy for each patient. Independent evaluators calculated the different scores. Area under the receiver-operating-characteristics (ROC) curve, sensitivity, specificity, positive and negative predictive values were calculated for rebleeding and mortality. Results: The areas under ROC curve of the endoscopist’s clinical judgment for rebleeding (0.67–0.75) and mortality (0.84–0.9) were similar or even superior to the different risk scores in both the whole group and in patients receiving endoscopic therapy. Conclusions: The accuracy of the currently available risk scores for predicting rebleeding and mortality in PUB patients was moderate and not superior to the endoscopist’s judgment. More precise prognostic scales are needed.
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Mujtaba S, Chawla S, Massaad JF. Diagnosis and Management of Non-Variceal Gastrointestinal Hemorrhage: A Review of Current Guidelines and Future Perspectives. J Clin Med 2020; 9:402. [PMID: 32024301 PMCID: PMC7074258 DOI: 10.3390/jcm9020402] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/21/2020] [Accepted: 01/24/2020] [Indexed: 01/30/2023] Open
Abstract
Non-variceal gastrointestinal bleeding (GIB) is a significant cause of mortality and morbidity worldwide which is encountered in the ambulatory and hospital settings. Hemorrhage form the gastrointestinal (GI) tract is categorized as upper GIB, small bowel bleeding (also formerly referred to as obscure GIB) or lower GIB. Although the etiologies of GIB are variable, a strong, consistent risk factor is use of non-steroidal anti-inflammatory drugs. Advances in the endoscopic diagnosis and treatment of GIB have led to improved outcomes. We present an updated review of the current practices regarding the diagnosis and management of non-variceal GIB, and possible future directions.
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Affiliation(s)
| | | | - Julia Fayez Massaad
- Division of Digestive Diseases, Emory University, 1365 Clifton Road, Northeast, Building B, Suite 1200, Atlanta, GA 30322, USA; (S.M.); (S.C.)
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27
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Tarasconi A, Coccolini F, Biffl WL, Tomasoni M, Ansaloni L, Picetti E, Molfino S, Shelat V, Cimbanassi S, Weber DG, Abu-Zidan FM, Campanile FC, Di Saverio S, Baiocchi GL, Casella C, Kelly MD, Kirkpatrick AW, Leppaniemi A, Moore EE, Peitzman A, Fraga GP, Ceresoli M, Maier RV, Wani I, Pattonieri V, Perrone G, Velmahos G, Sugrue M, Sartelli M, Kluger Y, Catena F. Perforated and bleeding peptic ulcer: WSES guidelines. World J Emerg Surg 2020; 15:3. [PMID: 31921329 PMCID: PMC6947898 DOI: 10.1186/s13017-019-0283-9] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 12/18/2019] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Peptic ulcer disease is common with a lifetime prevalence in the general population of 5-10% and an incidence of 0.1-0.3% per year. Despite a sharp reduction in incidence and rates of hospital admission and mortality over the past 30 years, complications are still encountered in 10-20% of these patients. Peptic ulcer disease remains a significant healthcare problem, which can consume considerable financial resources. Management may involve various subspecialties including surgeons, gastroenterologists, and radiologists. Successful management of patients with complicated peptic ulcer (CPU) involves prompt recognition, resuscitation when required, appropriate antibiotic therapy, and timely surgical/radiological treatment. METHODS The present guidelines have been developed according to the GRADE methodology. To create these guidelines, a panel of experts was designed and charged by the board of the WSES to perform a systematic review of the available literature and to provide evidence-based statements with immediate practical application. All the statements were presented and discussed during the 5th WSES Congress, and for each statement, a consensus among the WSES panel of experts was reached. CONCLUSIONS The population considered in these guidelines is adult patients with suspected complicated peptic ulcer disease. These guidelines present evidence-based international consensus statements on the management of complicated peptic ulcer from a collaboration of a panel of experts and are intended to improve the knowledge and the awareness of physicians around the world on this specific topic. We divided our work into the two main topics, bleeding and perforated peptic ulcer, and structured it into six main topics that cover the entire management process of patients with complicated peptic ulcer, from diagnosis at ED arrival to post-discharge antimicrobial therapy, to provide an up-to-date, easy-to-use tool that can help physicians and surgeons during the decision-making process.
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Affiliation(s)
- Antonio Tarasconi
- Emergency Surgery Department, Parma University Hospital, Parma, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | | | - Matteo Tomasoni
- General, Emergency and Trauma Surgery Department, Bufalini hospital, Cesena, Italy
| | - Luca Ansaloni
- General, Emergency and Trauma Surgery Department, Bufalini hospital, Cesena, Italy
| | - Edoardo Picetti
- Department of Anesthesia and Intensive Care, Parma University Hospital, Parma, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | | | - Stefania Cimbanassi
- General Surgery and Trauma Team, ASST Niguarda Milano, University of Milano, Milan, Italy
| | - Dieter G. Weber
- Royal Perth Hospital, Perth, Australia & The University of Western Australia, Crawley, Australia
| | - Fikri M. Abu-Zidan
- Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates
| | - Fabio C. Campanile
- Division of Surgery, ASL VT - Ospedale “Andosilla”, Civita Castellana, Italy
| | - Salomone Di Saverio
- Cambridge Colorectal Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Claudio Casella
- Department of Molecular and Translational Medicine, Surgical Clinic, University of Brescia, Brescia, Italy
| | - Michael D. Kelly
- Department of General Surgery, Albury Hospital, Albury, Australia
| | - Andrew W. Kirkpatrick
- General, Acute Care, Abdominal Wall Reconstruction, and Trauma Surgery, Foothills Medical Centre, Calgary, Alberta Canada
| | | | - Ernest E. Moore
- Ernest E Moore Shock Trauma Center at Denver Health, Denver, CO USA
| | - Andrew Peitzman
- University of Pittsburgh, School of Medicine, UPMC – Presbyterian, Pittsburgh, PA USA
| | - Gustavo Pereira Fraga
- Division of Trauma Surgery, School of Medical Sciences, University of Campinas, Campinas, SP Brazil
| | - Marco Ceresoli
- Department of General and Emergency Surgery, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Ronald V. Maier
- Department of Surgery, Harborview Medical Centre, University of Washington, Seattle, USA
| | - Imtaz Wani
- Department of Surgery, Sheri-Kashmir Institute of Medical Sciences, Srinagar, India
| | | | - Gennaro Perrone
- Emergency Surgery Department, Parma University Hospital, Parma, Italy
| | - George Velmahos
- Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, USA
| | - Michael Sugrue
- Letterkenny University Hospital, Donegal Clinical Research Academy Centre for Personalized Medicine, Donegal, Ireland
| | | | - Yoram Kluger
- Department of General Surgery, Rambam Health Care Campus, Haifa, Israel
| | - Fausto Catena
- Emergency Surgery Department, Parma University Hospital, Parma, Italy
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Olsen AMS, McGettigan P, Gerds TA, Fosbøl EL, Olesen JB, Sindet-Pedersen C, Staerk L, Lock Hansen M, Pallisgaard JL, Køber L, Torp-Pedersen C, Gislason GH, Lamberts M. Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2019; 6:292-300. [DOI: 10.1093/ehjcvp/pvz069] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/30/2019] [Accepted: 11/18/2019] [Indexed: 11/12/2022]
Abstract
Abstract
Aims
Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs.
Methods and results
Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41 183 patients [median age 70 years (interquartile range 64–78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04–0.18%) for NOACs and 0.13% (0.03–0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69–0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40–2.61)] and with VKA [HR 1.95 (95% CI 1.21–2.69)].
Conclusion
Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.
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Affiliation(s)
- Anne-Marie Schjerning Olsen
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Patricia McGettigan
- William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, EC1M 6BQ London, UK
| | | | - Emil Loldrup Fosbøl
- The Danish Heart Foundation, Vognmagergade 7, 1120 Copenhagen, Denmark
- Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Jonas Bjerring Olesen
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Caroline Sindet-Pedersen
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Laila Staerk
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Morten Lock Hansen
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Jannik Langtved Pallisgaard
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Lars Køber
- Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Christian Torp-Pedersen
- Institute of Health, Science and Technology, Frederik Bajersvej 7K, 9920 Aalborg University, Aalborg, Denmark
| | - Gunnar Hilmar Gislason
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
- The Danish Heart Foundation, Vognmagergade 7, 1120 Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
- The National Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9B, 5000 Odense, Denmark
| | - Morten Lamberts
- Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
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Farhat N, Fortin Y, Haddad N, Birkett N, Mattison DR, Momoli F, Wu Wen S, Krewski D. Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents. Crit Rev Toxicol 2019; 49:215-261. [DOI: 10.1080/10408444.2019.1583167] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Nawal Farhat
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Yannick Fortin
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Nisrine Haddad
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Nicholas Birkett
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Donald R. Mattison
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
- Risk Sciences International, Ottawa, Canada
| | - Franco Momoli
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Shi Wu Wen
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
- Ottawa Hospital Research Institute, Ottawa, Canada
| | - Daniel Krewski
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
- Risk Sciences International, Ottawa, Canada
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30
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Lau JYW, Pittayanon R, Wong KT, Pinjaroen N, Chiu PWY, Rerknimitr R, Holster IL, Kuipers EJ, Wu KC, Au KWL, Chan FKL, Sung JJY. Prophylactic angiographic embolisation after endoscopic control of bleeding to high-risk peptic ulcers: a randomised controlled trial. Gut 2019; 68:796-803. [PMID: 29802172 DOI: 10.1136/gutjnl-2018-316074] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 05/03/2018] [Accepted: 05/04/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES In the management of patients with bleeding peptic ulcers, recurrent bleeding is associated with high mortality. We investigated if added angiographic embolisation after endoscopic haemostasis to high-risk ulcers could reduce recurrent bleeding. DESIGN After endoscopic haemostasis to their bleeding gastroduodenal ulcers, we randomised patients with at least one of these criteria (ulcers≥20 mm in size, spurting bleeding, hypotensive shock or haemoglobin<9 g/dL) to receive added angiographic embolisation or standard treatment. Our primary endpoint was recurrent bleeding within 30 days. RESULTS Between January 2010 and July 2014, 241 patients were randomised (added angiographic embolisation n=118, standard treatment n=123); 22 of 118 patients (18.6%) randomised to angiography did not receive embolisation. In an intention-to-treat analysis, 12 (10.2%) in the embolisation and 14 (11.4%) in the standard treatment group reached the primary endpoint (HR 1.14, 95% CI 0.53 to 2.46; p=0.745). The rate of reinterventions (13 vs 17; p=0.510) and deaths (3 vs 5, p=0.519) were similar. In a per-protocol analysis, 6 of 96 (6.2%) rebled after embolisation compared with 14 of 123 (11.4%) in the standard treatment group (HR 1.89, 95% CI 0.73 to 4.92; p=0.192). None of 96 patients died after embolisation compared with 5 (4.1%) deaths in the standard treatment group (p=0.108). In a posthoc analysis, embolisation reduced recurrent bleeding only in patients with ulcers≥15 mm in size (2 (4.5%) vs 12 (23.1%); p=0.027). CONCLUSIONS After endoscopic haemostasis, added embolisation does not reduce recurrent bleeding. TRIAL REGISTRATION NUMBER NCT01142180.
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Affiliation(s)
- James Y W Lau
- Institute of Digestive Disease, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Rapat Pittayanon
- Department of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Ka-Tak Wong
- Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong, China
| | - Nutcha Pinjaroen
- Department of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Philip Wai Yan Chiu
- Institute of Digestive Disease, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Rungsun Rerknimitr
- Department of Gastroenterology, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Ingrid Lisanne Holster
- Department of Gastroenterology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Ernst J Kuipers
- Department of Gastroenterology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Kai-Chun Wu
- Institute of Digestive Disease, Xijing Hospital, Xian, China
| | - Kim W L Au
- Institute of Digestive Disease, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Francis K L Chan
- Institute of Digestive Disease, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Joseph J Y Sung
- Institute of Digestive Disease, Prince of Wales Hospital, the Chinese University of Hong Kong, Shatin, Hong Kong, China
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Hajiagha Mohammadi AA, Reza Azizi M. Prognostic factors in patients with active non-variceal upper gastrointestinal bleeding. Arab J Gastroenterol 2019; 20:23-27. [PMID: 30770260 DOI: 10.1016/j.ajg.2019.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 09/22/2018] [Accepted: 01/08/2019] [Indexed: 01/18/2023]
Abstract
BACKGROUND AND STUDY AIMS Acute upper gastrointestinal bleeding is one of the main causes of hospitalisation. The purpose of this study was to determine the prognostic factors in non-variceal upper gastrointestinal bleeding. PATIENTS AND METHODS Clinical outcomes, demographic and laboratory variables of the subjects were collected from the HIS software and national code with the SQL format from three hospitals in Qazvin. The data were linked to the database software designed by the author. Clinical and upper endoscopic findings of patients' records were collected through a questionnaire form in the designed software database. RESULTS In this study, 29.2% of patients with favourable outcome and 64.2% of patients with unfavourable clinical outcomes had a history of anticoagulant drug use before hospitalisation (p < 0.001). The prevalence of chronic cardiovascular disease, chronic liver disease, chronic lung disease, diabetes and dialysis was higher in subjects with poor clinical outcomes than those with a favourable clinical outcome. 53.1% of subjects with favourable clinical outcome and 90.5% of subjects with undesirable clinical outcomes received packed red blood cell transfusion (p < 0.001). 16.1% of subjects with desirable clinical outcome and 86.3% of subjects with undesirable clinical outcomes received endoscopic haemostatic treatment which was statistically significant (p < 0.001). CONCLUSION Undesirable clinical outcome in patients with acute non-variceal upper gastrointestinal bleeding has a significant statistical association with longer hospitalisation, chronic underlying disease, anticoagulant administration, packed red blood cell infusion, higher Forrest stage, low systolic blood pressure, higher age, low haemoglobin, low platelet count, high INR and high BUN at the onset of diagnosis.
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Affiliation(s)
- Ali Akbar Hajiagha Mohammadi
- Department of Internal Medicine, Metabolic Diseases Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mohammad Reza Azizi
- Department of Internal Medicine, Metabolic Diseases Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
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Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Pellegatta G, Coppo C, Savarino E. Proton pump inhibitors: use and misuse in the clinical setting. Expert Rev Clin Pharmacol 2018; 11:1123-1134. [PMID: 30295105 DOI: 10.1080/17512433.2018.1531703] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.
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Affiliation(s)
- Vincenzo Savarino
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Elisa Marabotto
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Patrizia Zentilin
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Manuele Furnari
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Giorgia Bodini
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Costanza De Maria
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Gaia Pellegatta
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Claudia Coppo
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Edoardo Savarino
- b Gastrointestinal Unit, Department of Surgery , Oncology and Gastroenterology, University of Padua , Padua , Italy
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Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Pellegatta G, Coppo C, Savarino E. The appropriate use of proton-pump inhibitors. Minerva Med 2018; 109. [PMID: 29856192 DOI: 10.23736/s0026-4806.18.05705-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Savarino V, Tosetti C, Benedetto E, Compare D, Nardone G. Appropriateness in prescribing PPIs: A position paper of the Italian Society of Gastroenterology (SIGE) - Study section "Digestive Diseases in Primary Care". Dig Liver Dis 2018; 50:894-902. [PMID: 30093304 DOI: 10.1016/j.dld.2018.07.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 07/04/2018] [Accepted: 07/09/2018] [Indexed: 02/06/2023]
Abstract
The introduction of proton pump inhibitors (PPIs) into clinical practice about thirty years ago has greatly improved our therapeutic approach to acid-related diseases for their well-recognized efficacy and safety. Despite the well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and this phenomenon poses serious queries that include the onset of potential adverse effects and the increase in health care costs. The major reason explaining this worrying market expansion is the inappropriate use of PPIs. In order to re-establish a correct use of these effective drugs in daily clinical practice, the Italian Society of Gastroenterology (SIGE), nominated a panel of experts who reviewed the available clinical literature and produced a series of updated position statements on the use of PPIs in clinical practice.
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Affiliation(s)
| | | | | | - Debora Compare
- Department of Clinical Medicine and Surgery, University Federico II of Naples, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, University Federico II of Naples, Italy.
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Schmidt A, Gölder S, Goetz M, Meining A, Lau J, von Delius S, Escher M, Hoffmann A, Wiest R, Messmann H, Kratt T, Walter B, Bettinger D, Caca K. Over-the-Scope Clips Are More Effective Than Standard Endoscopic Therapy for Patients With Recurrent Bleeding of Peptic Ulcers. Gastroenterology 2018; 155:674-686.e6. [PMID: 29803838 DOI: 10.1053/j.gastro.2018.05.037] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 05/15/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Endoscopic hemostasis is effective in treatment of bleeding peptic ulcers. However, rebleeding is difficult to treat and associated with substantial morbidity and mortality. We performed a prospective randomized trial to determine whether over-the-scope clips (OTSCs) are more effective than standard treatment of severe recurrent upper gastrointestinal bleeding. METHODS We performed our study at 9 academic referral centers (in Germany, Switzerland, and Hong Kong) from March 2013 through September 2016. Adult patients with recurrent peptic ulcer bleeding following initially successful hemostasis (66 patients in the intent-to-treat analysis) were randomly assigned to groups (1:1) that underwent hemostasis with either OTSC or standard therapy. Standard therapy was defined as hemostasis with through-the-scope clips (TTSC, n = 31) or thermal therapy plus injection with diluted adrenaline (n = 2). The primary endpoint was further bleeding (a composite endpoint of a persistent bleeding despite endoscopic therapy according to the protocol or recurrent bleeding within 7 days after successful hemostasis). Patients with further bleeding were allowed to cross over to OTSC therapy. Main secondary endpoints were mortality, necessity of surgical or angiographic salvage therapy, duration of stay in the hospital or intensive care, number of blood units transfused, and complications associated with endoscopic therapy. RESULTS Persistent bleeding after per-protocol hemostasis was observed in 14 patients (42.4%) in the standard therapy group and 2 patients (6.0%) in the OTSC group (P = .001). Recurrent bleeding within 7 days occurred in 5 patients (16.1%) in the standard therapy group vs 3 patients (9.1%) in the OTSC group (P = .468). Further bleeding occurred in 19 patients (57.6%) in the standard therapy group and in 5 patients (15.2%) in the OTSC group (absolute difference 42.4%; 95% confidence interval 21.6-63.2; P = .001) Within 30 days of follow-up, 1 patient in the standard therapy group (3.0%) and 1 patient in the OTSC group (3.0%) required surgical therapy (P = .999). Within 30 days of the procedure, 2 patients died in the standard therapy group (6.3%) and 4 patients died in the OTSC group (12.1%) (P = .672). There were no significant differences in the other secondary endpoints. CONCLUSIONS In prospective randomized trial, we found endoscopic treatment with OTSCs to be superior to standard therapy with TTSCs for patients with recurrent peptic ulcer bleeding. STING Study, Clinicaltrials.gov no: NCT1836900.
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Affiliation(s)
- Arthur Schmidt
- Department of Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany; Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Stefan Gölder
- Department of Gastroenterology, Klinikum Augsburg, Augsburg, Germany
| | - Martin Goetz
- Interdisciplinary Endoscopy, University of Tübingen, Tübingen, Germany
| | | | - James Lau
- Department of Surgery, University of Hong Kong, Hong Kong
| | - Stefan von Delius
- Department of Gastroenterology, Klinikum Rechts der Isar, TU München, München, Germany
| | - Markus Escher
- Department of Gastroenterology, Robert Bosch Krankenhaus Stuttgart, Stuttgart, Germany
| | - Arthur Hoffmann
- Department of Gastroenterology, Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany
| | - Reiner Wiest
- Department of Gastroenterology, Inselspital Bern, Bern, Switzerland
| | - Helmut Messmann
- Department of Gastroenterology, Klinikum Augsburg, Augsburg, Germany
| | - Thomas Kratt
- Department of Gastroenterology, Klinikum Augsburg, Augsburg, Germany
| | - Benjamin Walter
- Department of Gastroenterology, University of Ulm, Ulm, Germany
| | - Dominik Bettinger
- Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Karel Caca
- Department of Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany.
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Chang MA, Savides TJ. Endoscopic Management of Nonvariceal, Nonulcer Upper Gastrointestinal Bleeding. Gastrointest Endosc Clin N Am 2018; 28:291-306. [PMID: 29933776 DOI: 10.1016/j.giec.2018.02.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Nonvariceal, nonulcer upper gastrointestinal hemorrhage (UGIH) is a less common cause for acute upper gastrointestinal bleeding. However, nonvariceal, nonulcer UGIH is an important entity to identify and treat appropriately to prevent bleeding-related morbidity and mortality. Over the past 40 years, there has been a revolution in gastrointestinal endoscopy and a similar revolution in the management of UGIH. The aim of this article is to focus on the endoscopic management of nonvariceal, nonulcer UGIH, with a focus on the newer diagnostic and treatment modalities currently available.
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Affiliation(s)
- Michael A Chang
- Division of Gastroenterology, University of California, 9500 Gilman Drive #0956, La Jolla, CA 92093-0956, USA.
| | - Thomas J Savides
- Division of Gastroenterology, University of California, 9500 Gilman Drive #0956, La Jolla, CA 92093-0956, USA
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Abstract
Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of ∼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range ∼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.
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Value of Oral Proton Pump Inhibitors in Acute, Nonvariceal Upper Gastrointestinal Bleeding: A Network Meta-Analysis. J Clin Gastroenterol 2017; 51:707-719. [PMID: 27505402 DOI: 10.1097/mcg.0000000000000625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Intravenous (IV) proton pump inhibitors (PPI) are the standard medical treatment in acute nonvariceal upper gastrointestinal bleeding (ANVGIB). Optimal route of PPI delivery has been questioned. AIM The aim was to perform a systematic review and network meta-analysis for the endpoints of risk of rebleeding, length of stay (LOS), surgery (ROS), mortality, and total units of blood transfused (UBT) among trials evaluating acid suppressive medications in ANVGIB. METHODS A total of 39 studies using IV PPI drip, IV scheduled PPI, oral PPI, H2-receptor antagonists, and placebo were identified. Network meta-analysis was used for indirect comparisons and Bayesian Markov Chain Monte Carlo methods for calculation of probability superiority. RESULTS No difference was observed between IV PPI drip and scheduled IV PPI for mortality (relative risk=1.11; 95% credibility interval, 0.56-2.21), LOS (0.04, -0.49 to 0.44), ROS (1.27, 0.64-2.35) and risk of rebleeding within 72 hours, 1 week, and 1 month [(0.98, 0.48-1.95), (0.59, 0.13-2.03), (0.82, 0.28-2.16)]. Oral PPIs were as effective as IV scheduled PPIs and IV PPI drip for LOS (0.22, -0.61 to 0.79 and 0.16, -0.56 to 0.80) and UBT (-0.25, -1.23 to 0.65 and -0.06, -0.71 to 0.65) and superior to IV PPI drip for ROS (0.30, 0.10 to 0.78). CONCLUSION Scheduled IV PPIs were as effective as IV PPI drip for most outcomes. Oral PPIs were comparable to scheduled IV for LOS and UBT and superior to IV PPI drip for ROS. Conclusions should be tempered by low frequency endpoints such as ROS, but question the need for IV PPI drip in ANVGIB.
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Tringali A, Manta R, Sica M, Bassotti G, Marmo R, Mutignani M. Comparing intravenous and oral proton pump inhibitor therapy for bleeding peptic ulcers following endoscopic management: a systematic review and meta‐analysis. Br J Clin Pharmacol 2017; 83:1619-1635. [DOI: 10.1111/bcp.13258 pmid: 28181291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025] Open
Abstract
Background and AimsThe efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies have demonstrated that high‐dose oral PPIs are as effective as intravenous PPIs in reducing recurrent bleeding. However, current guidelines recommend intravenous PPIs after endoscopic treatment. Previous data based on numbers that were too small to enable a firm conclusion to be reached suggested that oral and intravenous PPIs had equivalent efficacy. We undertook a meta‐analysis to compare oral and intravenous PPIs in patients with bleeding peptic ulcers after endoscopic management.MethodsA literature search was undertaken using MEDLINE, EMBASE and the Cochrane Library, between 1990 and February 2016, to identify all randomized controlled trials (RCTs) that assessed the efficacy of PPIs administered by different routes. Nine RCTs, involving 1036 patients, were analysed. Outcomes were: recurrent bleeding, blood transfusion requirement, duration of hospital stay, a need for repeat endoscopy, surgery and 30‐day mortality.ResultsThere were no differences in the rebleeding rates [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.60, 1.46; P = 0.77], need for surgery (OR 0.77, 95% CI 0.25, 2.40; P = 0.65), need for repeat endoscopy (OR 0.69, 95% CI 0.39, 1.21; P = 0.19), need for blood transfusion [(MD) –0.03, 95% CI –0.26, 0.19; P = 0.76], duration of hospital stay (MD –0.61, 95% CI –1.45, 0.23; P = 0.16) or 30‐day mortality (OR 0.89, 95% CI 0.27, 2.43; P = 0.84) according to the route of administration.ConclusionsOral PPIs represent better value for money, with clinical efficacy equivalent to intravenous PPIs.
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Affiliation(s)
- Alberto Tringali
- Endoscopy Unit Niguarda Hospital Piazza Ospedale Maggiore 3 20162 Milan Italy
| | - Raffaele Manta
- Endoscopy Unit Niguarda Hospital Piazza Ospedale Maggiore 3 20162 Milan Italy
| | - Mariano Sica
- Endoscopy Unit Niguarda Hospital Piazza Ospedale Maggiore 3 20162 Milan Italy
| | - Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of Medicine University of Perugia Medical School Perugia Italy
| | - Riccardo Marmo
- Gastroenterologia ed Endoscopia Digestiva del PO di Polla Salerno Italy
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Tringali A, Manta R, Sica M, Bassotti G, Marmo R, Mutignani M. Comparing intravenous and oral proton pump inhibitor therapy for bleeding peptic ulcers following endoscopic management: a systematic review and meta-analysis. Br J Clin Pharmacol 2017; 83:1619-1635. [PMID: 28181291 PMCID: PMC5510065 DOI: 10.1111/bcp.13258] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Revised: 12/28/2016] [Accepted: 01/31/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND AIMS The efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies have demonstrated that high-dose oral PPIs are as effective as intravenous PPIs in reducing recurrent bleeding. However, current guidelines recommend intravenous PPIs after endoscopic treatment. Previous data based on numbers that were too small to enable a firm conclusion to be reached suggested that oral and intravenous PPIs had equivalent efficacy. We undertook a meta-analysis to compare oral and intravenous PPIs in patients with bleeding peptic ulcers after endoscopic management. METHODS A literature search was undertaken using MEDLINE, EMBASE and the Cochrane Library, between 1990 and February 2016, to identify all randomized controlled trials (RCTs) that assessed the efficacy of PPIs administered by different routes. Nine RCTs, involving 1036 patients, were analysed. Outcomes were: recurrent bleeding, blood transfusion requirement, duration of hospital stay, a need for repeat endoscopy, surgery and 30-day mortality. RESULTS There were no differences in the rebleeding rates [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.60, 1.46; P = 0.77], need for surgery (OR 0.77, 95% CI 0.25, 2.40; P = 0.65), need for repeat endoscopy (OR 0.69, 95% CI 0.39, 1.21; P = 0.19), need for blood transfusion [(MD) -0.03, 95% CI -0.26, 0.19; P = 0.76], duration of hospital stay (MD -0.61, 95% CI -1.45, 0.23; P = 0.16) or 30-day mortality (OR 0.89, 95% CI 0.27, 2.43; P = 0.84) according to the route of administration. CONCLUSIONS Oral PPIs represent better value for money, with clinical efficacy equivalent to intravenous PPIs.
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Affiliation(s)
- Alberto Tringali
- Endoscopy UnitNiguarda HospitalPiazza Ospedale Maggiore 320162MilanItaly
| | - Raffaele Manta
- Endoscopy UnitNiguarda HospitalPiazza Ospedale Maggiore 320162MilanItaly
| | - Mariano Sica
- Endoscopy UnitNiguarda HospitalPiazza Ospedale Maggiore 320162MilanItaly
| | - Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of MedicineUniversity of Perugia Medical SchoolPerugiaItaly
| | - Riccardo Marmo
- Gastroenterologia ed Endoscopia Digestiva del PO di PollaSalernoItaly
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Cheng HC, Yang EH, Wu CT, Wang WL, Chen PJ, Lin MY, Sheu BS. Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use. J Formos Med Assoc 2017; 117:316-325. [PMID: 28751088 DOI: 10.1016/j.jfma.2017.07.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 06/08/2017] [Accepted: 07/07/2017] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND/PURPOSE Peptic ulcer bleeding remains a deadly disease, and a simple indicator of long-term outcomes is crucial. This study validated whether hypoalbuminemia and its related factors in patients with peptic ulcer bleeding can indicate long-term mortality and rebleeding under proton pump inhibitor use. METHODS The prospective cohort study enrolled 426 patients with peptic ulcer bleeding who had high risk stigmata at endoscopy and had received endoscopic hemostasis. They were divided into 79 patients in the hypoalbuminemia group (Hypo-AG, serum albumin <28 g/L), 135 in the marginal hypoalbuminemia group (Margin-AG, serum albumin 28-34.9 g/L), and 212 in the normal albuminemia group (Normal-AG, serum albumin ≥35 g/L). Each subject received 72-h of intravenous infusion and then the oral form of proton pump inhibitors and were monitored for 84 days to assess all-cause mortality and recurrent bleeding. RESULTS The primary outcome of all-cause mortality rates were increased in a stepwise fashion in a trend from Normal-AG, Margin-AG, to Hypo-AG (0-28th day: 1.9%, 2.2%, 12.8%, p < 0.001; 29th-84th day: 2.5%, 8.0%, 10.6%, p < 0.01). The secondary outcome of recurrent bleeding rates were also increased in the same fashion (0-28th day: 6.4%, 15.4%, 24.6%, p < 0.001; 29th-84th day: 0%, 3.0%, 4.2%, p = 0.01). Abnormal albuminemia was <30 g/L related to hemoglobin levels <70 g/L, nosocomial bleeding, cirrhosis, age ≥70 years, shock, and ulcer size ≥1.0 cm independently (p < 0.05). CONCLUSION Hypoalbuminemia in patients with peptic ulcer bleeding can be an alarm indicator of all-cause mortality and recurrent bleeding in a long-term follow-up situation under proton pump inhibitor use (NCT01591083).
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Affiliation(s)
- Hsiu-Chi Cheng
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan.
| | - Er-Hsiang Yang
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan.
| | - Chung-Tai Wu
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan.
| | - Wen-Lun Wang
- Department of Internal Medicine, E-Da Hospital, I-Shou University, 1 Yida Road, Yanchao District, Kaohsiung, 82445, Taiwan.
| | - Po-Jun Chen
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan.
| | - Meng-Ying Lin
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan.
| | - Bor-Shyang Sheu
- Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70403, Taiwan; Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Executive Yuan, Tainan, Taiwan.
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Jensen DM, Kovacs TOG, Ohning GV, Ghassemi K, Machicado GA, Dulai GS, Sedarat A, Jutabha R, Gornbein J. Doppler Endoscopic Probe Monitoring of Blood Flow Improves Risk Stratification and Outcomes of Patients With Severe Nonvariceal Upper Gastrointestinal Hemorrhage. Gastroenterology 2017; 152:1310-1318.e1. [PMID: 28167214 PMCID: PMC5613762 DOI: 10.1053/j.gastro.2017.01.042] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 01/22/2017] [Accepted: 01/26/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS For 4 decades, stigmata of recent hemorrhage in patients with nonvariceal lesions have been used for risk stratification and endoscopic hemostasis. The arterial blood flow that underlies the stigmata rarely is monitored, but can be used to determine risk for rebleeding. We performed a randomized controlled trial to determine whether Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes in patients with severe nonvariceal upper gastrointestinal hemorrhage. METHODS In a single-blind study performed at 2 referral centers we assigned 148 patients with severe nonvariceal upper gastrointestinal bleeding (125 with ulcers, 19 with Dieulafoy's lesions, and 4 with Mallory Weiss tears) to groups that underwent standard, visually guided endoscopic hemostasis (control, n = 76), or endoscopic hemostasis assisted by Doppler monitoring of blood flow under the stigmata (n = 72). The primary outcome was the rate of rebleeding after 30 days; secondary outcomes were complications, death, and need for transfusions, surgery, or angiography. RESULTS There was a significant difference in the rates of lesion rebleeding within 30 days of endoscopic hemostasis in the control group (26.3%) vs the Doppler group (11.1%) (P = .0214). The odds ratio for rebleeding with Doppler monitoring was 0.35 (95% confidence interval, 0.143-0.8565) and the number needed to treat was 7. CONCLUSIONS In a randomized controlled trial of patients with severe upper gastrointestinal hemorrhage from ulcers or other lesions, Doppler probe guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with standard, visually guided hemostasis. Guidelines for nonvariceal gastrointestinal bleeding should incorporate these results. ClinicalTrials.gov no: NCT00732212 (CLIN-013-07F).
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Affiliation(s)
- Dennis M. Jensen
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA,Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Thomas OG Kovacs
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA,Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Gordon V. Ohning
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA,Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Kevin Ghassemi
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Gustavo A. Machicado
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA,Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Gareth S. Dulai
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA,Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Alireza Sedarat
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA,Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA
| | - Rome Jutabha
- CURE Digestive Diseases Research Center (DDRC) - GI Hemostasis Unit, Los Angeles, CA,David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Jeffrey Gornbein
- Department of Biomathematics at the David Geffen School of Medicine at UCLA
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de la Coba Ortiz C, Argüelles Arias F, Martín de Argila de Prados C, Júdez Gutiérrez J, Linares Rodríguez A, Ortega Alonso A, Rodríguez de Santiago E, Rodríguez-Téllez M, Vera Mendoza MI, Aguilera Castro L, Álvarez Sánchez Á, Andrade Bellido RJ, Bao Pérez F, Castro Fernández M, Giganto Tomé F. Proton-pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Española de Patología Digestiva. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:207-24. [PMID: 27034082 DOI: 10.17235/reed.2016.4232/2016] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION In the last few years a significant number of papers have related the use of proton-pump inhibitors (PPIs) to potential serious adverse effects that have resulted in social unrest. OBJECTIVE The goal of this paper was to provide a literature review for the development of an institutional position statement by Sociedad Española de Patología Digestiva (SEPD) regarding the safety of long-term PPI use. MATERIAL AND METHODS A comprehensive review of the literature was performed to draw conclusions based on a critical assessment of the following: a) current PPI indications; b) vitamin B12 deficiency and neurological disorders; c) magnesium deficiency; d) bone fractures; e) enteric infection and pneumonia; f) interactions with thienopyridine derivatives; e) complications in cirrhotic patients. RESULTS Current PPI indications have remained unchanged for years now, and are well established. A general screening of vitamin B12 levels is not recommended for all patients on a PPI; however, it does seem necessary that magnesium levels be measured at therapy onset, and then monitored in subjects on other drugs that may induce hypomagnesemia. A higher risk for bone fractures is present, even though causality cannot be concluded for this association. The association between PPIs and infection with Clostridium difficile is mild to moderate, and the risk for pneumonia is low. In patients with cardiovascular risk receiving thienopyridines derivatives it is prudent to adequately consider gastrointestinal and cardiovascular risks, given the absence of definitive evidence regardin potential drug-drug interactions; if gastrointestinal risk is found to be moderate or high, effective prevention should be in place with a PPI. PPIs should be cautiously indicated in patients with decompensated cirrhosis. CONCLUSIONS PPIs are safe drugs whose benefits outweigh their potential side effects both short-term and long-term, provided their indication, dosage, and duration are appropriate.
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Affiliation(s)
| | | | | | - Javier Júdez Gutiérrez
- Departamento de Gestión del Conocimiento, Sociedad Española de Patología Digestiva SEPD, España
| | | | - Aida Ortega Alonso
- UGC Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, España
| | | | - Manuel Rodríguez-Téllez
- UGC Intercentros de Aparato Digestivo , Hospital Universitario Virgen de la Macarena (HUVM), España
| | | | | | - Ángel Álvarez Sánchez
- Servicio de Aparato Digestivo, Hospital Clínico San Carlos. Universidad Complutense de Madrid., España
| | - Raúl Jesús Andrade Bellido
- Unidad de Gestión Clinica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, España
| | | | | | - Froilán Giganto Tomé
- Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias, España
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Reassessment of Rebleeding Risk of Forrest IB (Oozing) Peptic Ulcer Bleeding in a Large International Randomized Trial. Am J Gastroenterol 2017; 112:441-446. [PMID: 28094314 PMCID: PMC5612665 DOI: 10.1038/ajg.2016.582] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 10/01/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Our aims were to assess risks of early rebleeding after successful endoscopic hemostasis for Forrest oozing (FIB) peptic ulcer bleeding (PUBs) compared with other stigmata of recent hemorrhage (SRH). METHODS These were post hoc multivariable analyses of a large, international, double-blind study (NCT00251979) of patients randomized to high-dose intravenous (IV) esomeprazole (PPI) or placebo for 72 h. Rebleeding rates of patients with PUB SRH treated with either PPI or placebo after successful endoscopic hemostasis were also compared. RESULTS For patients treated with placebo for 72 h after successful endoscopic hemostasis, rebleed rates by SRH were spurting arterial bleeding (FIA) 22.5%, adherent clot (FIIB) 17.6%, non-bleeding visible vessel (FIIA) 11.3%, and oozing bleeding (FIB) 4.9%. Compared with FIB patients, FIA, FIIB, and FIIA had significantly greater risks of rebleeding with odds ratios (95% CI's) from 2.61 (1.05, 6.52) for FIIA to 6.66 (2.19, 20.26) for FIA. After hemostasis, PUB rebleeding rates for FIB patients at 72 h were similar with esomeprazole (5.4%) and placebo (4.9%), whereas rebleed rates for all other major SRH (FIA, FIIA, FIIB) were lower for PPI than placebo, but the treatment by SRH interaction test was not statistically significant. CONCLUSIONS After successful endoscopic hemostasis, FIB patients had very low PUB rebleeding rates irrespective of PPI or placebo treatment. This implies that after successful endoscopic hemostasis the prognostic classification of FIB ulcers as a high-risk SRH and the recommendation to treat these with high-dose IV PPI's should be re-evaluated.
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Aguilera-Castro L, Martín-de-Argila-dePrados C, Albillos-Martínez A. Practical considerations in the management of proton-pump inhibitors. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:145-53. [PMID: 26666270 DOI: 10.17235/reed.2015.3812/2015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Proton-pump inhibitors (PPIs) are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a new-generation PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy.
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Lau J, Lind T, Persson T, Eklund S. Effect of baseline characteristics on response to proton pump inhibitors in patients with peptic ulcer bleeding. J Dig Dis 2017; 18:99-106. [PMID: 28070941 DOI: 10.1111/1751-2980.12447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 12/22/2016] [Accepted: 01/04/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The rate of rebleeding from peptic ulcers could differ between Asian and Western populations. This study aimed to determine whether the observed twofold difference in rebleeding rates in two similarly designed clinical trials (one in Hong Kong [n = 240], the other in a predominantly Western population [n = 764, ClinicalTrials.gov identifier: NCT00251979]) can be explained by differences in baseline patient characteristics. METHODS Two-factor and multifactor analyses (adjusted by demographics, established risk factors for peptic ulcer and peptic ulcer bleeding, and disease severity variables) were performed using pooled data from the two studies. Cox regression analysis was used to predict the rebleeding risk at 3 days. RESULTS In the two-factor analysis (placebo vs esomeprazole/omeprazole and Western study vs Hong Kong study), data trended towards a reduced risk of rebleeding in the Western study (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.44-1.07, P = 0.094). The risk of rebleeding was similar in both studies after adjusted for multiple factors (HR 1.10, 95% CI 0.60-1.99, P = 0.767). The strongest predictor of rebleeding (apart from study drug) was a classification of American Society of Anesthesiologists (ASA) grade IV (HR 4.15, 95% CI 1.49-11.56, P = 0.006). When such patients were excluded, the difference in rebleeding rates between the studies reduced. CONCLUSION The difference in rebleeding rates between the two studies is explained by the factors in our analysis, most importantly a classification of ASA grade IV, suggesting that other differences, including ethnicity, did not influence the rebleeding rate.
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Affiliation(s)
- James Lau
- Department of Surgery, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Tore Lind
- AstraZeneca Gothenburg, Mölndal, Sweden
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Scarpignato C, Gatta L, Zullo A, Blandizzi C. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med 2016; 14:179. [PMID: 27825371 PMCID: PMC5101793 DOI: 10.1186/s12916-016-0718-z] [Citation(s) in RCA: 286] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 10/14/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. METHODS The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. RESULTS Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. CONCLUSIONS Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .
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Affiliation(s)
- Carmelo Scarpignato
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125, Parma, Italy.
| | - Luigi Gatta
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125, Parma, Italy
- Gastroenterology & Endoscopy Unit, Versilia Hospital, Azienda USL Toscana Nord Ovest, Lido di Camaiore, Italy
| | - Angelo Zullo
- Division of Gastroenterology & Digestive Endoscopy, Nuovo Regina Elena Hospital, Rome, Italy
| | - Corrado Blandizzi
- Division of Pharmacology, Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
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Timing or Dosing of Intravenous Proton Pump Inhibitors in Acute Upper Gastrointestinal Bleeding Has Low Impact on Costs. Am J Gastroenterol 2016; 111:1389-1398. [PMID: 27140030 DOI: 10.1038/ajg.2016.157] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 03/28/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES High-dose intravenous proton pump inhibitors (PPIs) post endoscopy are recommended in non-variceal upper gastrointestinal bleeding (UGIB), as they improve outcomes of patients with high-risk lesions. Determine the budget impact of using different PPI regimens in treating non-variceal UGIB, including pre- and post-endoscopic use, continuous infusion (high dose), and intermittent bolus (twice daily) dosing. METHODS A budget impact analysis using a decision model informed with data from the literature adopting a US third party payer's perspective with a 30-day time horizon was used to determine the total cost per patient (US$2014) presenting with acute UGIB. The base-case employing high-dose pre- and post-endoscopic IV PPI was compared with using only post-endoscopic PPI. For each, continuous or intermittent dosing regimens were assessed with associated incremental costs. Deterministic and probabilistic sensitivity analyses were performed. RESULTS The overall cost per patient is $11,399 when high-dose IV PPIs are initiated before endoscopy. The incremental costs are all inferior in alternate-case scenarios: $106 less if only post-endoscopic high-dose IVs are used; with intermittent IV bolus dosing, the savings are $223 if used both pre and post endoscopy and $191 if only administered post endoscopy. Subgroup analysis suggests cost savings in patients with clean-base ulcers who are discharged early after endoscopy. Results are robust to sensitivity analysis. CONCLUSIONS The incremental costs of using different IV PPI regimens are modest compared with total per patient costs.
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Mössner J. The Indications, Applications, and Risks of Proton Pump Inhibitors. DEUTSCHES ARZTEBLATT INTERNATIONAL 2016; 113:477-83. [PMID: 27476707 PMCID: PMC4973002 DOI: 10.3238/arztebl.2016.0477] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 03/17/2016] [Accepted: 03/17/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are the most effective drugs for inhibiting gastric acid secretion. They have been in clinical use for more than 25 years, In 2014, 3.475 billion daily defined doses (DDD) of PPI were prescribed in Germany. This high number alone calls for a critical analysis of the spectrum of indications for PPI and their potential adverse effects. METHODS This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane Library databases, with particular emphasis on randomized, prospective multicenter trials, cohort studies, case-control studies, and meta-analyses. RESULTS The inhibition of gastric acid secretion with PPI is successfully used for the treatment of gastroesophageal reflux disease and of gastric and duodenal ulcers, for the secondary prevention of gastroduodenal lesions that have arisen under treatment with nonsteroidal anti-inflammatory drugs and acetylsalicylic acid, and for the prevention of recurrent hemorrhage from ulcers after successful endoscopic hemostasis. PPI are given along with practically all antibiotic regimens for the eradication of Helicobacter pylori infection. The number of prescriptions for PPI has risen linearly over the past 25 years. As there has been no broadening of indications, one may well ask whether the current, extensive use of PPI is justified. There is evidence that patients taking PPI are at greater risk for fractures. Moreover, the vitamin B12 level should be checked occasionally in all patients taking PPI. CONCLUSION PPI are among the more effective drugs for the treatment of diseases associated with gastric acid. In view of their cost and potential adverse effects, they should only be prescribed for scientifically validated indications.
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Affiliation(s)
- Joachim Mössner
- Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital of Leipzig, Germany: Mössner
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Successful Endoscopic Hemostasis Is a Protective Factor for Rebleeding and Mortality in Patients with Nonvariceal Upper Gastrointestinal Bleeding. Dig Dis Sci 2016; 61:2011-8. [PMID: 26923946 DOI: 10.1007/s10620-016-4082-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Accepted: 02/05/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Rebleeding and mortality rates remain high in patients with nonvariceal upper gastrointestinal bleeding. AIM To identify clinical and endoscopic risk factors for rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding. METHODS This study was performed in patients with nonvariceal upper gastrointestinal bleeding who underwent upper endoscopic procedures between July 2006 and February 2013. Clinical and endoscopic characteristics were compared among patients with and without rebleeding and mortality. Logistic regression analysis was performed to determine independent risk factors for rebleeding and mortality. RESULTS After excluding 64 patients, data for 689 patients with nonvariceal upper gastrointestinal bleeding were analyzed. Peptic ulcer (62.6 %) was by far the most common source of bleeding. Endoscopic intervention was performed within 24 h in 99.0 % of patients, and successful endoscopic hemostasis was possible in 80.7 % of patients. The 30-day rebleeding rate was 13.1 % (n = 93). Unsuccessful endoscopic hemostasis was found to be the only independent risk factor for rebleeding (odds ratio 79.6; 95 % confidence interval 37.8-167.6; p = 0.000). The overall 30-day mortality rate was 3.2 % (n = 23). Unsuccessful endoscopic hemostasis (odds ratio 4.9; 95 % confidence interval 1.7-13.9; p = 0.003) was also associated with increased 30-day mortality in patients with nonvariceal upper gastrointestinal bleeding. CONCLUSIONS Successful endoscopic hemostasis is an independent protective factor for both rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding.
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