Pre-endoscopic Proton Pump Inhibitors Research Articles

S709 Proton-Pump Inhibitor Infusion Misuse in the Community Hospital Setting

Introduction: Proton pump inhibitors (PPIs) are the most potent acid suppressants available. Several studies have shown that in hospitalized patients with acute upper gastrointestinal (GI) bleeding from peptic ulcer disease, high-dose PPI therapy via continuous infusion reduces the rate of high-risk bleeding lesions (active bleeding, visible vessel, adherent clot) on initial endoscopy. While the benefits of PPI infusions have been clearly described for these specific indications, they are often over-prescribed to inpatients. Our study aim was to determine the rate of misuse in a tertiary care community hospital setting. Methods: A retrospective cohort study was conducted at Lankenau Medical Center, a 370 bed community hospital. The usage of pantoprazole infusion was determined among hospitalized patients between March 1, 2018 and March 1, 2021 through review of the EPIC electronic medical record system. Appropriate candidates for pantoprazole infusion were defined as patients with hematemesis, melena, coffee-ground emesis, or hematochezia with hemodynamic instability. All other indications were categorized as inappropriate. Variables including age, sex, race, serum hemoglobin at the time of PPI infusion initiation, and antiplatelet use were collected. The rate of PPI infusion misuse was determined. Factors which significantly affected utilization of PPI infusion were determined through multivariate analysis. Results: A total of 348 pre-endoscopic PPI infusions were ordered during the three-year period. Approximately 35% of these prescriptions were ordered without an appropriate indication. The mean age of patients who were prescribed PPI infusions was 68.8 years. 48.6% were on an antiplatelet agent. The only significant variable between patients who were given a PPI infusion for an appropriate versus inappropriate indication was age, where the mean patient age was 68.8 compared to 71.1 years (p=0.04). Patient sex, race, antiplatelet use, and hemoglobin value did not significantly affect PPI infusion use. (Table) Conclusion: Pre-endoscopic PPI infusion was prescribed inappropriately in 34.8% of patients in a community hospital setting. Misuse of this drug leads to unnecessary healthcare costs and reflects poor understanding among prescribers of its appropriate clinically indicated uses. While PPIs are generally regarded as safe, misuse can increase the risk of adverse side effects. A follow-up study looking at a quality improvement intervention will follow this study. Table 1. - Characteristics and Multivariate Analysis of PPI Infusion Misuse Inappropriate PPI Infusion No Yes Total p-value n = 227 n = 121 n = 348 Age (Mean/SD) 67.6 (14.8) 71.1 (15.1) 68.8 (15.0) 0.04 Sex 0.571 Male 131 (57.7%) 66 (54.6%) 197 (56.6%) Female 96 (42.3%) 55 (45.5%) 151 (43.4%) Race 0.705 White 104 (46.0%) 59 (48.8%) 163 (47.0%) Black 112 (49.6%) 55 (45.5%) 167 (48.1%) Other 10 (4.4%) 7 (5.8%) 17 (4.9%) Ethnicity 0.12 Not Hispanic 225 (99.6%) 116 (97.5%) 341 (98.8%) Hispanic 1 (0.4%) 3 (2.5%) 4 (1.2%) Total Number of Antiplatelets 0.629 0 121 (53.3%) 58 (47.9%) 179 (51.4%) 1 70 (30.8%) 41 (33.9%) 111 (31.9%) 2 36 (15.9%) 22 (18.2%) 58 (16.7%) Antiplatelet Type (n = 169 Yes Only) Aspirin 103 (45.4%) 61 (50.4%) 164 (47.1%) 0.37 Clopidogrel 36 (15.9%) 23 (19.0%) 59 (17.0%) 0.456 Ticagrelor 4 (1.8%) 4 (3.3%) 8 (2.3%) 0.456 Prasugrel 1 (0.4%) 0 1 (0.3%) 1 Last Hemoglobin (Mean/SD, g/dl) 8.9 (2.6) 8.6 (2.9) 8.8 (2.7) 0.344 Missing Hemoglobin 19 8 27 Transfusion Units (median/IQR) 2 (0-6) 2 (0-4) 2 (0-5) 0.478

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.

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. To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding. 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. 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. 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. 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. 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.

Pre-endoscopic intravenous proton pump inhibitors therapy for upper gastrointestinal bleeding: A prospective, multicentre study

Background/AimThe indiscriminate use of high-dose, proton pump inhibitor (PPI) infusion in non-variceal upper gastrointestinal bleeding (UGIB) patients to reduce the rate of peptic ulcers with high-risk stigmata (HRS) has been questioned. We evaluated the prevalence of HRS on peptic ulcer and non-ulcer lesions in patients receiving or not receiving pre-endoscopic PPI therapy. MethodsData of consecutive UGIB patients observed in 50 Italian centres were analysed. The prevalence of both HRS on peptic ulcers and active bleeding on non-ulcer lesions between patients treated or not treated with PPI were compared. Multivariate analysis was performed. ResultsA total of 1,792 (69.8%) out of 2,566 patients received PPI therapy. Prevalence of HRS on ulcers was 51.8% and 53.4% (P = 0.58) in treated and not treated patients, respectively, and the rate of endoscopic therapy did not differ between groups. Prevalence of non-ulcer bleeding lesions was higher in patients treated than in those not treated with PPI (18.7% vs 10.6%; P = 0.023). At multivariate analysis, PPI therapy (OR: 1.16, 95% CI = 0.82–1.64; P = 0.4) was not an independent factor affecting HRS prevalence, which was inversely correlated with timing to endoscopy (OR: 0.85, 95% CI = 0.76–0.95; P = 0.005). ConclusionsOur data failed to detect a significant role of pre-endoscopic PPI therapy in decreasing prevalence of HRS and need for endoscopic treatment in bleeding patients with either peptic ulcer or non-ulcer lesions.

Inappropriate Use of Proton Pump Inhibitor (PPI) Infusion in Upper Gastrointestinal Bleeding (UGIB) Patients and the Impact of Proper Physician Education on Outcome: An Experience in Two Community Hospitals

Introduction: UGIB remains a major health care burden in the United States. Recent ACG guidelines for ulcer bleeding supports no improvement in clinical outcome with pre-endoscopic PPI treatment in UGIB patients. However, if endoscopy is delayed or can't be performed or patient is hemodynamically unstable, IV PPI is recommended to reduce further bleeding. In addition to that, patients with suspected variceal bleeding might be benefited with pre-endoscopic PPI infusion along with vasopressin/octreotide infusion. Aim: To identify the prevalence of inappropriate use of pre-endoscopic PPI infusion in UGIB patients. To educate physicians about appropriate use of pre-endoscopic PPI infusion in UGIB and evaluate the change in clinical outcomes following education. Methods: A retrospective study was conducted in patients admitted with UGIB from July 2015 to May 2016. Physicians were educated via emails & posters about the appropriate use of pre-endoscopic PPI infusion in UGIB patients in January 2016. PPI infusion use was defined appropriate prior to endoscopy if patients were hemodynamically unstable, or EGD was delayed or could not be performed or in patients with history of cirrhosis in which variceal bleeding was suspected. Patients who did not meet the criteria for appropriate use of PPI infusion received PPI intermittent bolus. Patients were divided in two groups: Pre-education cohort and post-education cohort. Data was collected in each group to assess patients' demographics, laboratory values at the time of presentation, length of stay, cost, blood transfusion, complications and death. Results: Of 419 patients admitted with UGIB, 73 patients (17.4%) received PPI infusion prior to endoscopy. Inappropriate use of PPI infusion was reduced in post-education group compared to pre-education group. (35% vs 71%, p value 0.0069) (Table 1). Pre-education group was associated with higher length of stay and higher cost compared to post-education group. There was no difference in mortality, re-bleeding rate, and requirement of blood transfusion between two groups. (table 2).Table 1: Effect of education on inappropriate use of PPI infusion in UGIB patientsConclusion: Inappropriate use of pre-endoscopic PPI infusion in UGIB patients is very prevalent in our hospitals. Proper physician education leads to decrease in the inappropriate use of PPI infusion and was associated with reduce length of stay and hospital cost, without change in mortality, re-bleeding rate and requirement of blood transfusion. Further studies are warranted to support our data.Table 2

Predictive Factors for Endoscopic Hemostasis in Patients with Upper Gastrointestinal Bleeding

Predictive Factors for Endoscopic Hemostasis in Patients with Upper Gastrointestinal Bleeding

Sa1136 Pre-Endoscopic Intravenous Proton Pump Inhibition and the Outcomes of Acute Upper Gastrointestinal Bleeding

Introduction Proton pump inhibitors (PPIs), when given following endoscopy for acute upper gastrointestinal bleeding (UGIB), can reduce the need for blood transfusion and surgery; little is known about their benefit when used in the period before endoscopy. We therefore aimed to investigate the outcomes of UGIB in patients given intravenous PPIs before their endoscopy. Methods A total of 404 patients with UGIB were included; 202 received intravenous omeprazole for a median of 1 day (IQR 0.25–2) before endoscopy and 202 did not, this treatment being at their physician’s discretion. Omeprazole was given either in bolus doses of 40-mg bid (n = 103; 51%), or as an infusion of 8-mg/hour after a loading dose of 80-mg (n = 99; 49%). After endoscopy, omeprazole was continued intravenously or orally in patients found to have ulcers/erosions in their oesophagus, stomach, or duodenum. Patients’ clinical details were noted including their Charlson comorbidity and Blatchford risk scores. Three major outcomes were measured: need for blood transfusion; hospital stay > 6 days; and death within 30 days. The Mann-Whitney test, Chi-squared test and logistic regression were used as appropriate Results The two groups were comparable with respect to their gender, smoking, alcohol intake, and use of NSAIDs, aspirin, anti-thrombotic and other drugs. The treated group was older and had higher Blatchford and Charlson scores. However, when these factors were adjusted for, as shown in Table-1, below, no significant differences were noted between patients who received pre-endoscopic PPI and those who did not in terms of need for blood transfusion, length of hospital stay, or 30-day mortality. Conclusion The administration of intravenous PPI before endoscopy did not affect the outcomes of acute upper gastrointestinal bleeding in this retrospective study. This is relevant to the appropriate management of this common condition. Disclosure of Interest A. Taha Consultant for: Horizon Pharma USA; Vifor Pharma UK, E. Saffouri: None Declared, C. McCloskey: None Declared, T. Carigen: None Declared, W. Angerson: None Declared

Management of Patients With Ulcer Bleeding

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy.

T1954 Pre-Endoscopic Proton Pump Inhibitors in Non-Variceal Upper Gastrointestinal Bleeding; Continuous Infusion vs. Bolus

Aim: to evaluate the influence of anticoagulant therapy upon the course of non-variceal UGB. Methods: From January 2006 to Juny 2007 we carried out a cohort study of consecutive patients admitted in hospital due to UGB shown by haematemesis or melena. Upper gastrointestinal endoscopy was performed during the first 12 hours of admission. Three cohorts were defined: patients receiving vitamin K antagonists (AC), patient with antiplatelet treatment (AP) and patients without anticoagulant therapy (noACAP) as control group. The AC cohort was evaluated according to excess of anticoagulant treatment(INR>o<3). Outcome was assessed by: a) number of days in hospital; b) mortality rate; c) need for urgent surgery; and d) rebleeding. The measure of the association between antithrombotic therapy and the course of UGB was adjusted for confounders (age, sex, comorbidity, and the use of NSAIDs and PPIs at the time of UGB presentation). Other evaluated parameters were: etiology of UGB, initial hemodynamic severity, excess of anticoagulation, initial hemoglobin and blood transfusions. Results: A total of 392 consecutive patients were included. Forty-three were AC, 107 AP and 242 noACAP patients. In the AC cohort, 25 patients (58%) were overanticoagulated. The mean age was 64±19 years (64% men) and AC and AP patients were older than the controls. Significant comorbidity other than diabetes or hypertension was significantly greater in the AC cohort than in the noACAP cohort. Peptic lesions were more frequent in the AP cohort, and hemoglobin upon admission was lower in the AC cohort. There were no significant differences in terms of sex, previous use of PPIs, hemodynamic alterations, or number of units of packed red blood cells transfused. There were no significant differences among groups in terms of rebleeding (AC:11.6%. AP: 7.5%. NoACAP:9.1%), the need for urgent surgery (AC:2.3%. AP: 1.9%. NoACAP:1.2%) or mortality rate (AC:4.7%. AP:5.6%. NoACAP:5.8%). There were no differences in clinical outcome among overanticoagulated patients and the rest of them (INR<3). The number of days in hospital was greater in the AC cohort (4.81 more days; 95%CI 2.83-6.79, p<0.001). After adjusting for age and comorbidity, the increase in days in hospital among the AC patients was 3.24 days (95%CI: 1.22-5.26). CONCLUSION: Anticoagulated patients, including overanticoagulated patients, have similar clinical course that those without this treatment. Nevertheless, anticoagulation is associated with a longer hospital stay. This is partially explained by the older age and increased comorbidity of the patients subjected to such treatment.

Pre‐endoscopic PPI therapy reduces recurrent adverse outcomes in acute non‐variceal upper gastrointestinal bleeding: authors' reply

Sirs, Thank you for the insightful comments regarding our manuscript. We would like to address some of the concerns raised by Dr Lin. First, he comments that there is a much higher incidence of high-risk stigmata in the group who received pre-endoscopic proton pump inhibitor (PPI) therapy. We think he may have misinterpreted the table, as the numbers given are not absolute numbers, but instead are proportions (i.e. not 44/132 but 44% out of a total number of 132). Also, as patients may have had multiple lesions and multiple stigmata (i.e. both a non-bleeding visible vessel and oozing from another site) the proportions are not purely additive. In our study, there was a trend towards a decrease in the risk of having high-risk stigmata with pre-endoscopic PPI therapy (47% vs. 57%, P = 0.085), with high-risk stigmata defined as active arterial bleeding, non-bleeding visible vessel, adherent clot or oozing. This finding suggests that pre-endoscopic PPI therapy may assist in stabilizing clots and improving ulcer healing, leading to increased down-grading of high-risk stigmata. Dr Lin also notes that the majority of our patients received oral and not intravenous PPI therapy prior to endoscopy, and expresses concern that oral administration of PPIs may not have sufficiently elevated intragastric pH to a level necessary to promote clot stabilization and prevent rebleeding. We agree that oral PPIs may not always raise the intragastric pH over six, a level thought to be optimal for clot stabilization, but other studies have suggested that there is a little difference between oral and intravenous PPI administration of their immediate effects on intragastric pH. 1, 2 Furthermore, lesser elevations of intragastric pH may also allow some degree of clot stabilization, thus preventing rebleeding. Moreover, oral PPIs have proven efficacy in the prevention of rebleeding in high-risk patients, and meta-analyses have demonstrated that both oral and intravenous PPIs promote an equivalent reduction in rebleeding rates. 3, 4 We also agree with Dr Lin that endoscopic care among our subjects was not standardized, and that endoscopic therapeutic modalities differ in their efficacy. While this is true, the proportion of subjects undergoing any one type of endoscopic haemostasis was not significantly different between treatment groups, and thus is unlikely to have significantly biased our results. Overall, we concur that a randomized controlled trial is necessary to fully evaluate the role of pre-endoscopic PPI therapy in this setting. In the interim, it remains reasonable to offer this low-risk therapy to any patient presenting with signs and symptoms of acute upper gastrointestinal bleeding, especially in situations where endoscopic management is not immediately available.

Pre‐endoscopic proton pump inhibitor therapy reduces recurrent adverse gastrointestinal outcomes in patients with acute non‐variceal upper gastrointestinal bleeding

Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce rebleeding rates in patients with high-risk acute non-variceal upper gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy, although its incremental benefit is unproven. To determine if providing PPIs before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal upper gastrointestinal bleeding patients. We performed a retrospective review to identify patients presenting to two tertiary care centres with acute non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects receiving PPI therapy before endoscopy were compared with those not receiving pre-endoscopic PPI therapy. The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality, readmission within 30 days for acute non-variceal upper gastrointestinal bleeding). 385 patients were included in our study [132 (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI]. Patients receiving pre-endoscopic PPI therapy were significantly less likely to develop adverse outcomes compared with those not given pre-endoscopic PPIs (25% vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and length of hospital stay were also significantly lower in patients receiving pre-endoscopic PPI. The use of PPIs before endoscopy significantly reduces the risk of developing adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding. Future studies are required to better characterize this relationship.