Timing of endoscopy in high-risk patients with acute upper gastrointestinal bleeding: Multicenter and international cohort study

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Aims To determine whether endoscopy timing would affect outcomes in high-risk patients with AUGIB. Methods We conducted a retrospective, international and multicentre cohort study. High-risk patients (modified Glasgow Blatchford score > 7 points) with AUGIB between 2016–2022 and received therapeutic endoscopy (n = 511) were recruited. Patients were classified based on endoscopic timing in urgent (t ≤ 6 hours), early (6 24) group. Using descriptive statistics and logistic regression analyses, the optimal timing for endoscopy was identified and we analyzed the association between endoscopy and 30-day outcomes after adjusting for confounding factors. Results The results showed that urgent timing (n = 130) had worse outcomes than early (n = 205) and elective (n = 176) endoscopy with higher 30-day all-causes mortality (p = 0.047), repeat endoscopy (p = 0.034), 30-day transfusion rates (p = 0.021) and longer length of stay (p = 0.038). These findings were more consistent when patients were admitted with non-variceal bleeding. In multivariate analysis, urgent endoscopy (OR 1.83, 1.11–3.69; p = 0.034), Charlson index (OR 1.39, 1.01–1.93; p = 0.043), systolic blood pressure < 90mmHg (OR 3.66, 1.44–9.31; p = 0.006) and malignancy (OR 1.68, 95%CI 1.37–7.73; p = 0.047) were worse prognostic factors. Conclusions High-risk patients with AUGIB who have received urgent endoscopy presented worse outcomes, especially among patients with non-variceal bleeding. Comorbidities, shock, urgent endoscopy and malignancy were predictors for 30-day mortality. This emphasies the need of prior resuscitation and pharmacotherapy and early endoscopy. Endoscopy Interventions Mortality Timing Upper gastrointestinal bleeding Figures Figure 1 INTRODUCTION Acute upper gastrointestinal bleeding (AUGIB) is a common medical emergency and is associated with a significant mortality. In Western countries, the incidence of AUGIB was estimated to be over 103 cases per 100000 adults per year [ 1 ]. Overall mortality from GIB in 30-day hospital-admitted patients was 2.4-6% [ 2 , 3 ]. Moreover, incidence and mortality increased markedly with age and comorbidities [ 4 ]. The use of prognostic scores for digestive bleeding is recommended, which can quickly determine the risk of mortality, intervention, and accurately identify mild cases suitable for early hospital discharge. In fact, international guidelines on this pathology [ 5 ] recommend clinicians systematically use these scores. Several risk-stratification tools have been developed. Among these, the Glasgow-Blatchford (GB) [ 6 ] is the most classic score to discriminate mild cases and be a good predictor of mortality. However, the GB score cut-off value for high-risk patients still is ambiguous, patients with a GB score greater than 7 were shown to have increased risk of significant bleeding and mortality [ 7 ]. The difficulty of its calculation has led to the emergence of other scores such as AIMS65 [ 8 ], ABC [ 9 ], MAP (ASH) [ 10 ] and Rockall scores [ 4 ], which have demonstrated greater practicality due to their simpler calculation in an emergency setting. Timely endoscopy plays a central role in the management of AUGIB with the importance of endoscopic therapy. Currently, it is recommended that endoscopy should be performed within 24 hours on presentation to identify the source of bleeding and provide endoscopic treatments. However, there is limited data regarding high-risk patients with AUGIB and the optimal timing of endoscopy. Conflicting results have been observed with observational and randomized controlled studies favoring urgent endoscopy performed early after admission with a lower mortality rate, hospital stay and costs [ 11 – 13 ]. A nationwide cohort study concluded a lower mortality in patients with a timing of between 6 and 24 hours [ 14 ]. However, other studies showed no statistically significant difference and different timings were used [ 15 – 17 ]. In this study, we investigated outcomes in high-risk patients with AUGIB and aimed to determine if urgent timing endoscopy improves short-term outcomes within 30 days. MATERIALS AND METHODS PATIENT SELECTION From January 1, 2016 to December 31, 2022, high-risk adult patients who underwent therapeutic endoscopy for AUGIB at the Emergency of tertiary care center were included. Patients did not have evidence of AUGIB and chronic bleeding were excluded. Endoscopy was classified according to the time interval between the admission time and the endoscopic procedure: urgent endoscopy, fewer than 6 hours; early endoscopy, 6 to 24 hours and elective endoscopy, later than 24 hours. Endoscopy was available 7 days per week in the Emergency depending on the on-call endoscopist´s decision. For all patients with suspicion of acute variceal or non-variceal UGIB, a somatostatin or proton pump inhibitor (PPI) infusions were initiated as soon as possible at Emergency prior to endoscopy, respectively. Intravenous PPI (72 hours) or somatostatin (5 days) were continued after the first endoscopy if active or stigmata of recent haemorrhage were observed. Restrictive transfusion strategy and iron therapy were performed according to Patient Blood Management (PBM) [ 18 , 19 ]. This study was approved by our institutional review board. DATA COLLECTION AND DEFINITION Data on demography, clinical features (including comorbidities and risk factors for AUGIB) laboratory findings, anticoagulation, transfusion, endoscopy (including timing, bleeding activity according the Forrest classification [ 20 ] and endoscopic therapy), length of stay (LOS) and mortality were extracted from the hospital records. Hemodynamic status at presentation (the first recorded pulse and blood pressure) was used along with age and medical comorbidities to calculate GB [ 6 ] and clinical Rockall scores [ 4 ] for all patients. All deaths within 30 days of presentation were included. High-risk patients were defined as those with a GB score > 7 points and a pre-endoscopy Rockall score ≥ 5 points at the Emergency presentation. The primary outcome was mortality within 30 days of the emergency visit according timing endoscopy. The secondary outcomes were second-look endoscopy, red blood cell transfusion, intensive care unit stay and length of hospital stay. STATISTICAL ANALYSIS Descriptive statistics are used to report characteristics of patients. Continuous variables are shown as mean (± standard deviation [SD]), and median (± interquartile range [IQR]) whenever appropriate. Categorical variables are presented as frequencies and percentages. Differences in continuous variables were analyzed with the Student t test. Differences in categoric variables were assessed with the chi-square test. Univariate analysis was performed to assess differences in baseline characteristics of patients with AUGIB, only variables with a p-value < 0.20 according to univariate analysis were considered for the multivariate model. The results of univariate and multivariate logistic regression analyses were summarized by estimation the odds ratio (OR) and 95% confidence interval (CI). Kaplan-Meier analysis was used for comparing the survival according to timing endoscopy. After the comparison of times by using the log-rank test, the 30-day all-causes mortality rate, 30-day repeated endoscopy therapy rate and 30-day ICU admission rate were calculated using Cox proportional hazard regression model, by estimation the hazard ratio (HR) and 95% CI. Statistical analyses were performed using SPSS Statistic for mac (Version 24.0. IBM Corp, NY, USA). For all analyses, 2-tailed p-value less than 0.05 was considered statistically significant. RESULTS PATIENTS CHARACTERISTICS We identified 857 adult patients who were admitted for AUGIB and received a therapeutic endoscopy. Finally, 511 patients were included. The urgent group had 130 patients, the early group had 205 patients and the elective group had 176 patients. The urgent group received endoscopy at a median of 3.4 hours (IQR 2.1–4.6) after admission, the early groups received endoscopy at a median of 12.1 hours (9.7–20.3) after admission and the elective group received endoscopy at a median of 37.6 hours (30.1–35.3) after admission. Detailed data about demographics are shown in Table 1 . Patients who underwent elective patients were older than urgent and early endoscopy. Cirrhosis and malignancy were observed in 23.8% and 8% of patients, respectively. Charlson comorbidity index was not different among groups (p = 0.352). Anticoagulant and antiplatelet use were observed in 15.9% and 10.6% patients, respectively. There was a significant difference in GB score (p = 0.014) but not in Rockall score (p = 0.062), being the highest score in the urgent group. Moreover, shock index was higher in urgent group than rest of groups. Hb levels was significantly lower in patients with urgent endoscopy than in patients with early and elective endoscopy (8.7 ± 2.5 vs 10.1 ± 2.6 vs 9.4 ± 2.5 mg/dL; p = 0.001). ENDOSCOPIC FEATURES No intravenous sedation was administered to 32.1% (164/511). Of remainder, 67,9% (347/511) received endoscopist-guided intravenous sedation (midazolam and/or propofol). Patients with severe AUGIB and variceal bleeding received airway protection by means of endotracheal intubation (and thus general anaesthesia). No patients presented any sedation-related adverse events. Among endoscopic diagnoses, peptic ulcers, including gastric and duodenal ulcers, was observed in 194 (38%) patients, followed by variceal bleeding in 176 (34.4%) patients, vascular lesions in 53 (10.4%), neoplasm in 20 (3.9%) (Table 1 ). The miscellaneous category included esophagitis, gastritis, a Mallory-Weiss tear and mucosal oozing. Number of patients according to timing endoscopy showed significant differences in bleeding cause (p < 0.001). Active hemorrhage was identified on endoscopy more often in patient with urgent endoscopy than in patients with early and elective endoscopy (55.8% vs 23.2% vs 6.3%; p < 0.001). Use of endoscopic therapy was performed in 87.7% (448/511) of patients. Table 1 shows details of the use of significant variation in therapy at the first endoscopy according to the specific endoscopic high-risk stigmata of bleeding. The commonest endoscopic therapy was ulcer base injection which comprised 62.9% (122/194) of therapeutic procedures at the first endoscopy. For patients with non-variceal AUGIB who received therapy, combined haemostasis was used in 46.3% (151/326). For patients with varices at the first endoscopy 69.3% (122/176) underwent variceal banding. OUTCOMES ACCORDING TO ENDOSCOPY TIMING Outcomes of endpoints on mortality, repeat endoscopy, ICU admission and long length of stay are described in Table 2 . In the Cox regression analyses, we observed the highest 30-day mortality rate in the urgent endoscopy group. Using the early group as a reference, the urgent group had an adjusted hazard ratio (aHR) of 2.57 (95% CI 1.04–6.78, p = 0.047), while the elective group had an aHR of 0.91 (95% CI 0.71–1.13, p = 0.198). The urgent groups had significantly more in-hospital deaths compared with the early and elective group (urgent 11.54% vs early 6.83% vs elective 3.98%, p = 0.040). Of 511 patients with AUGIB, 36 (7%) patients died within 30-day. The causes of death were 13 hemorrhagic shock, 7 sepsis, 5 respiratory failure, 5 advanced-stage cancer, 4 decompensated cirrhosis, 1 decompensated advanced heart failure, 1 unknown. Seventeen per cent (87/511) of patients needed second-look endoscopy or had a repeat inpatient endoscopy. We analysed the rebleeding rate using Cox regression analyses. Compared with the urgent group, we observed a higher rate of repeat therapeutic endoscopy in the urgent group (aHR 1.83, 95% CI 1.11–3.69, p = 0.034). The respective rate for the elective endoscopy group was not significantly different (aHR 0.99, 95% CI 0.32–1.30, p = 0.220). Similarly, when compared with early group, patient in the urgent group (aHR 3.57, 95% CI 0.58– 8.96, p = 0.170) were more likely to require an ICU admission after index endoscopy, while the elective group had a lower rate of admission (aHR 0.92, 95% CI 0.16–5.17, p = 0.910). Moreover, the average units of blood transfused within 30 days of admission among the three group was compared. Patients in the urgent group received numerically more units per patients, being the difference was statistically significant [2.7 (SD 2.5) vs 1.2 (1.9) vs 1.1 (SD 1.5), p = 0.021]. Regarding the LOS, patients in the urgent group had significantly longer LOS compared with the early group (aHR 1.58, 95% CI 1.42– 1.69, p = 0.038). SUBGROUP ANALYSIS BASED ON SOURCE OF BLEEDING The cohort was further analysed based on the etiology of variceal versus non-variceal AUGIB. A total of 176 (34.4%) patients suffered variceal bleeding while 194 (38%) patients had non-variceal bleeding. Urgent endoscopy timing was associated with worse outcomes in patients with non-variceal bleeding, having significantly higher 30-day all-cause mortality (aHR 1.28, 95% CI 1.08–1.97, p = 0.045), 30-day ICU admission (aHR 1.19, 95% CI 1.04–1.95, p = 0.043) and longer length of stay (aHR 1.45, 95% CI 1.22–1.93, p = 0.031). In contrast, urgent timing was not associated with significant difference in 30-day repeat therapeutic endoscopy in patients with non-variceal bleeding and any outcomes among patients with variceal bleeding. PREDICTORS OF 30-DAY MORTALITY Table 3 shows the results of univariate and multivariate logistic regression analyses for predictors of 30-day mortality. On univariate analysis, 30-day mortality was associated significantly with older age (OR 1.03, 95% CI 1.01–1.05, p = 0.011), urgent endoscopy (t < 6 hours) (OR 1.48, 95% CI 1.11–1.70, p = 0.018), cirrhosis (OR 1.69, 95% CI 1.49–1.97, p = 0.311), higher Charlson comorbidity index (OR 1.52, 95% CI 1.14–2.04, p = 0.011), shock defined as systolic blood pressure < 90mmHg (OR 5.45, 95% CI 2.73–10.9, p < 0.001) and tachycardia (OR 1.04, 95% CI 1.02–1.06, p < 0.001) and malignancy (OR 3.86, 95% CI 1.12–13.3, p = 0.033). On multivariate analysis, the independent predictors of 30-day mortality were urgent endoscopy (OR 1.83, 95% CI 1.11–3.69, p = 0.034, higher Charlson comorbidity index (OR 1.39, 95% CI 1.01–1.93, p = 0.043), systolic blood pressure < 90mmHg (OR 3.66, 95% CI 1.44–9.31, p = 0.006) and malignancy (OR 1.68, 95% CI 1.37–7.73, p = 0.047). DISCUSSION Our findings demonstrate that early endoscopy (6 < t ≤ 24 hours) achieves better outcomes compared with urgent endoscopy (t ≤ 6 hours) in high-risk patients with AUGIB. However, the outcomes for elective endoscopy group (t < 24 hours) were more variable and statistically non-significant. When also taking into account bleeding etiology, the results were consistent with non-variceal bleeding. Our results can be explained be the longer time for thorough initial medical management with a structured approach with appropriate intravenous fluid resuscitation, use of a restrictive transfusion, pharmacological therapies and pre-endoscopic scoring tools to classify the patient at high or low-risk who might benefit from specific treatment [ 21 ]. Moreover, patients with active bleeding may have large amount of fresh blood in the stomach and duodenum, possibly obscuring the examination of the mucosa and the visualization of the site of bleeding when urgent endoscopy is performed. The endoscopy timing in high-risk patients with AUGIB is controversial. Early endoscopy within 12 and 24 hours of admission is recommended for most patients with variceal and non-variceal bleeding respectively according to the European Society of Gastrointestinal Endoscopy [ 22 ] and International Consensus Recommendations [ 23 ]. However, previous study findings from retrospective cohort studies and RCTs were conflicting over the precise timing of endoscopy, several studies suggested that urgent endoscopy may benefit high-risk patients [ 12 , 24 , 25 ], large nationwide studies demonstrated that early endoscopy was superior [ 3 , 14 ] while some studies suggested no significant differences [ 26 – 28 ]. In this study, we conducted a retrospective, international multicenter cohort study based on a database of consecutive high-risk patients, that is larger than previous and includes variceal and non-variceal etiologies. This means that our study has a greater statistical power. Although the etiology of GI bleeding was heterogeneous but data from the different subpopulations were analysed separately, meaning that conclusions may be applicable to each specific etiology of GI bleeding, independently. While our findings indicated that early endoscopy timing may be superior to urgent endoscopy, the results of the subgroup analyses suggest that variceal bleeding was less affected by the endoscopy timing according to Jung et al [ 29 ]. This outcome of variceal bleeding is a severe complication of decompensated sever liver disease and advanced portal hypertension. Moreover, it is associated to worse prognosis compared with non-variceal bleeding. There are some limitations in this study. The retrospective nature limits our data recording to the available medical records. Despite, database being thoroughly screened, we cannot exclude some degree of underreporting due to inherent limitations of non-standardized clinical documentations. In general, patients with hemodynamic instability and suspected severe AUGIB will undergo early endoscopy and mortality could be related to disease severity rather than to timing of endoscopy. In some cases with coexisting life-threatening disease, performance of endoscopy may delay an optimal medical management [ 23 ]. On other hand, endoscopy could be deferred if it was deemed futile depends on some patients with severe AUGIB. Our data show differences in baseline characteristics of patients and bleeding according to timing of endoscopy. These factors may confound our results. Therefore, multivariate analysis and logistic regression were performed to control this. Moreover, the degree and in which direction these factors affect our results are unknown. In conclusion, our results show a lower mortality rate in AUGIB patients receiving early endoscopy between 6 and 24 hours compared with urgent endoscopy within 6 hours. An initial period of time to optimize active resuscitation and medical treatment before index endoscopy is recommended in high-risk patients with comorbidities. Declarations CONFLICTS OF INTEREST: Javier Tejedor-Tejada: None Benito Hermida: None Cristina Camblor: None Laura Sanchez: None Eduany Hernandez: None Mohamed Emara: None Salem Youssef Mohamed: None Zhuraida Salman: None Aranzazu Alvarez-Alvarez: None Jose M. Perez-Pariente: None AUTHOR CONTRIBUTIONS Javier Tejedor-Tejada – Study concept and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of manuscript, technical support, final approval. Benito Hermida – Acquisition of data, critical revision of manuscript, technical support, final approval. Cristina Camblor – Acquisition of data, critical revision of manuscript, technical support, final approval. Laura Sanchez – Acquisition of data, critical revision of manuscript, technical support, final approval. Eduany Hernandez – Acquisition of data, critical revision of manuscript, technical support, final approval. Mohamed Emara – Acquisition of data, critical revision of manuscript, technical support, final approval. Salem Youssef Mohamed – Acquisition of data, critical revision of manuscript, technical support, final approval. Zhuraida Salman: – Critical revision of manuscript, technical support, final approval. Aranzazu Alvarez-Alvarez – Critical revision of manuscript, technical support, final approval. Jose M. Perez-Pariente – Critical revision of manuscript, technical support, final approval. ACKNOWLEDGEMENTS The authors are grateful to the staff and other health-care professionals who have collaborated in handling of the clinical cases and contributed data. References Van Leerdam ME, Vreeburg EM, Rauws EA, et al. Acute upper GI bleeding: did any- thing change? Time trend analysis of incidence and outcome of acute upper GI bleed- ing between 1993/1994 and 2000. 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The role of rapid endoscopy for high-risk patients with acute nonvariceal upper gastrointestinal bleeding. Can J Gastroenterol. 2007 Jul;21(7):425-9. doi: 10.1155/2007/636032. PMID: 17637943; PMCID: PMC2657961. Tai CM, Huang SP, Wang HP, et al. High-risk ED patients with nonvariceal upper gastrointestinal hemorrhage undergoing emergency or urgent endoscopy: a retrospective analysis. Am J Emerg Med. 2007 Mar;25(3):273-8. doi: 10.1016/j.ajem.2006.07.014. PMID: 17349900. Bjorkman DJ, Zaman A, Fennerty MB, et al. Urgent vs. elective endoscopy for acute non-variceal upper-GI bleeding: an effectiveness study. Gastrointest Endosc. 2004 Jul;60(1):1-8. doi: 10.1016/s0016-5107(04)01287-8. PMID: 15229417. Jung DH, Huh CW, Kim NJ, et al. Optimal endoscopy timing in patients with acute variceal bleeding: A systematic review and meta-analysis. Sci Rep. 2020 Mar 4;10(1):4046. doi: 10.1038/s41598-020-60866-x. PMID: 32132589; PMCID: PMC7055310. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files TABLES.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5340232","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":373315211,"identity":"59e28e85-fc05-4cce-ad61-9f13ecfa5b12","order_by":0,"name":"Javier Tejedor-Tejada","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIie2RsWrDMBCGTwQyGbQqZOgryARCA6F6FRmDp5C5QwmCQrsEvCpv0QfIcEbgSalXQaZS8OwsJUMpVdsQsijNmEHfIN2gj/vvBBCJXCFEAeBficAAppcr7KAUl3djh8P8/7T3bFPcrWFBiancbt0ISjdVB/eLcLDljFe6BTZQdT7R7TZb6XnOwIbbEVVIk/gxONrxMMGt5C7hjDxhWClbaT69IrD58MqrEI0d7cnXmWA6R/OzLA627xUkLzAbM6J6Z5R3rJbIBhrr0URjnmk3L25lHZ4lLbPHbo9TSrV5cx3eCVpujOsewsFS9Xv5H2HHgRMAGRQAbo4VVSdKJBKJRE74Bm33XUd+cVlNAAAAAElFTkSuQmCC","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":true,"prefix":"","firstName":"Javier","middleName":"","lastName":"Tejedor-Tejada","suffix":""},{"id":373315213,"identity":"d08c4581-b6f0-487b-90df-d591f9c80f88","order_by":1,"name":"Benito Hermida","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Benito","middleName":"","lastName":"Hermida","suffix":""},{"id":373315214,"identity":"3979db6b-a525-4046-b926-1ff15818b6e5","order_by":2,"name":"Cristina Camblor","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Camblor","suffix":""},{"id":373315215,"identity":"a20fbb1c-afba-4f2c-a69b-fe24261779b4","order_by":3,"name":"Laura Sanchez","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Sanchez","suffix":""},{"id":373315216,"identity":"72dfbad2-d139-497f-a64f-ff9e7c9a7d7a","order_by":4,"name":"Eduany Hernandez","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Eduany","middleName":"","lastName":"Hernandez","suffix":""},{"id":373315217,"identity":"6251a3b9-7684-48a2-8aa2-f142d7c9a069","order_by":5,"name":"Mohamed Emara","email":"","orcid":"","institution":"Kafrelshiekh University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Emara","suffix":""},{"id":373315220,"identity":"a0335b17-eb16-4848-adcf-55bcfe2e974e","order_by":6,"name":"Salem Youssef Mohamed","email":"","orcid":"","institution":"Zagazug University","correspondingAuthor":false,"prefix":"","firstName":"Salem","middleName":"Youssef","lastName":"Mohamed","suffix":""},{"id":373315223,"identity":"be863430-8e94-436c-9e93-4af1f17e5dec","order_by":7,"name":"Zhuraida Salman","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Zhuraida","middleName":"","lastName":"Salman","suffix":""},{"id":373315225,"identity":"36975acf-8f3c-4e64-9082-3b2675713404","order_by":8,"name":"Aranzazu Alvarez-Alvarez","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Aranzazu","middleName":"","lastName":"Alvarez-Alvarez","suffix":""},{"id":373315226,"identity":"ffeb13d4-5570-46bb-b033-46ab1d9c92b0","order_by":9,"name":"Jose M. Perez-Pariente","email":"","orcid":"","institution":"Hospital Universitario de Cabueñes","correspondingAuthor":false,"prefix":"","firstName":"Jose","middleName":"M.","lastName":"Perez-Pariente","suffix":""}],"badges":[],"createdAt":"2024-10-27 08:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5340232/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5340232/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69356403,"identity":"b189a1b2-e441-4e53-b070-c57252977272","added_by":"auto","created_at":"2024-11-19 13:49:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84884,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier plots for 30-day mortality after index endoscopy.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5340232/v1/9336926ea69e1465405b17ee.png"},{"id":69358427,"identity":"367b478c-2c59-4e1e-a5d4-f862c8a2fe60","added_by":"auto","created_at":"2024-11-19 14:05:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":412099,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5340232/v1/82d11fdf-3610-42c6-b14c-d442cd0b5d16.pdf"},{"id":69356402,"identity":"460c24b5-8af9-4996-9681-dc97f56ada15","added_by":"auto","created_at":"2024-11-19 13:49:45","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":26381,"visible":true,"origin":"","legend":"","description":"","filename":"TABLES.docx","url":"https://assets-eu.researchsquare.com/files/rs-5340232/v1/032df45c1cc9fa0de40c38f3.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Timing of endoscopy in high-risk patients with acute upper gastrointestinal bleeding: Multicenter and international cohort study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcute upper gastrointestinal bleeding (AUGIB) is a common medical emergency and is associated with a significant mortality. In Western countries, the incidence of AUGIB was estimated to be over 103 cases per 100000 adults per year [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Overall mortality from GIB in 30-day hospital-admitted patients was 2.4-6% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Moreover, incidence and mortality increased markedly with age and comorbidities [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe use of prognostic scores for digestive bleeding is recommended, which can quickly determine the risk of mortality, intervention, and accurately identify mild cases suitable for early hospital discharge. In fact, international guidelines on this pathology [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] recommend clinicians systematically use these scores. Several risk-stratification tools have been developed. Among these, the Glasgow-Blatchford (GB) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] is the most classic score to discriminate mild cases and be a good predictor of mortality. However, the GB score cut-off value for high-risk patients still is ambiguous, patients with a GB score greater than 7 were shown to have increased risk of significant bleeding and mortality [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The difficulty of its calculation has led to the emergence of other scores such as AIMS65 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], ABC [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], MAP (ASH) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and Rockall scores [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which have demonstrated greater practicality due to their simpler calculation in an emergency setting.\u003c/p\u003e \u003cp\u003eTimely endoscopy plays a central role in the management of AUGIB with the importance of endoscopic therapy. Currently, it is recommended that endoscopy should be performed within 24 hours on presentation to identify the source of bleeding and provide endoscopic treatments. However, there is limited data regarding high-risk patients with AUGIB and the optimal timing of endoscopy. Conflicting results have been observed with observational and randomized controlled studies favoring urgent endoscopy performed early after admission with a lower mortality rate, hospital stay and costs [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A nationwide cohort study concluded a lower mortality in patients with a timing of between 6 and 24 hours [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, other studies showed no statistically significant difference and different timings were used [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we investigated outcomes in high-risk patients with AUGIB and aimed to determine if urgent timing endoscopy improves short-term outcomes within 30 days.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePATIENT SELECTION\u003c/h2\u003e \u003cp\u003eFrom January 1, 2016 to December 31, 2022, high-risk adult patients who underwent therapeutic endoscopy for AUGIB at the Emergency of tertiary care center were included. Patients did not have evidence of AUGIB and chronic bleeding were excluded.\u003c/p\u003e \u003cp\u003eEndoscopy was classified according to the time interval between the admission time and the endoscopic procedure: urgent endoscopy, fewer than 6 hours; early endoscopy, 6 to 24 hours and elective endoscopy, later than 24 hours. Endoscopy was available 7 days per week in the Emergency depending on the on-call endoscopist\u0026acute;s decision. For all patients with suspicion of acute variceal or non-variceal UGIB, a somatostatin or proton pump inhibitor (PPI) infusions were initiated as soon as possible at Emergency prior to endoscopy, respectively. Intravenous PPI (72 hours) or somatostatin (5 days) were continued after the first endoscopy if active or stigmata of recent haemorrhage were observed. Restrictive transfusion strategy and iron therapy were performed according to Patient Blood Management (PBM) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. This study was approved by our institutional review board.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDATA COLLECTION AND DEFINITION\u003c/h3\u003e\n\u003cp\u003eData on demography, clinical features (including comorbidities and risk factors for AUGIB) laboratory findings, anticoagulation, transfusion, endoscopy (including timing, bleeding activity according the Forrest classification [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and endoscopic therapy), length of stay (LOS) and mortality were extracted from the hospital records. Hemodynamic status at presentation (the first recorded pulse and blood pressure) was used along with age and medical comorbidities to calculate GB [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and clinical Rockall scores [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] for all patients. All deaths within 30 days of presentation were included. High-risk patients were defined as those with a GB score \u0026gt; 7 points and a pre-endoscopy Rockall score \u0026ge; 5 points at the Emergency presentation. The primary outcome was mortality within 30 days of the emergency visit according timing endoscopy. The secondary outcomes were second-look endoscopy, red blood cell transfusion, intensive care unit stay and length of hospital stay.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSTATISTICAL ANALYSIS\u003c/h2\u003e \u003cp\u003eDescriptive statistics are used to report characteristics of patients. Continuous variables are shown as mean (\u0026plusmn;\u0026thinsp;standard deviation [SD]), and median (\u0026plusmn;\u0026thinsp;interquartile range [IQR]) whenever appropriate. Categorical variables are presented as frequencies and percentages. Differences in continuous variables were analyzed with the Student t test. Differences in categoric variables were assessed with the chi-square test. Univariate analysis was performed to assess differences in baseline characteristics of patients with AUGIB, only variables with a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.20 according to univariate analysis were considered for the multivariate model. The results of univariate and multivariate logistic regression analyses were summarized by estimation the odds ratio (OR) and 95% confidence interval (CI).\u003c/p\u003e \u003cp\u003eKaplan-Meier analysis was used for comparing the survival according to timing endoscopy. After the comparison of times by using the log-rank test, the 30-day all-causes mortality rate, 30-day repeated endoscopy therapy rate and 30-day ICU admission rate were calculated using Cox proportional hazard regression model, by estimation the hazard ratio (HR) and 95% CI. Statistical analyses were performed using SPSS Statistic for mac (Version 24.0. IBM Corp, NY, USA). For all analyses, 2-tailed p-value less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePATIENTS CHARACTERISTICS\u003c/h2\u003e \u003cp\u003eWe identified 857 adult patients who were admitted for AUGIB and received a therapeutic endoscopy. Finally, 511 patients were included. The urgent group had 130 patients, the early group had 205 patients and the elective group had 176 patients. The urgent group received endoscopy at a median of 3.4 hours (IQR 2.1\u0026ndash;4.6) after admission, the early groups received endoscopy at a median of 12.1 hours (9.7\u0026ndash;20.3) after admission and the elective group received endoscopy at a median of 37.6 hours (30.1\u0026ndash;35.3) after admission. Detailed data about demographics are shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients who underwent elective patients were older than urgent and early endoscopy. Cirrhosis and malignancy were observed in 23.8% and 8% of patients, respectively. Charlson comorbidity index was not different among groups (p\u0026thinsp;=\u0026thinsp;0.352). Anticoagulant and antiplatelet use were observed in 15.9% and 10.6% patients, respectively. There was a significant difference in GB score (p\u0026thinsp;=\u0026thinsp;0.014) but not in Rockall score (p\u0026thinsp;=\u0026thinsp;0.062), being the highest score in the urgent group. Moreover, shock index was higher in urgent group than rest of groups. Hb levels was significantly lower in patients with urgent endoscopy than in patients with early and elective endoscopy (8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 vs 10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 vs 9.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 mg/dL; p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eENDOSCOPIC FEATURES\u003c/h2\u003e \u003cp\u003eNo intravenous sedation was administered to 32.1% (164/511). Of remainder, 67,9% (347/511) received endoscopist-guided intravenous sedation (midazolam and/or propofol). Patients with severe AUGIB and variceal bleeding received airway protection by means of endotracheal intubation (and thus general anaesthesia). No patients presented any sedation-related adverse events. Among endoscopic diagnoses, peptic ulcers, including gastric and duodenal ulcers, was observed in 194 (38%) patients, followed by variceal bleeding in 176 (34.4%) patients, vascular lesions in 53 (10.4%), neoplasm in 20 (3.9%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The miscellaneous category included esophagitis, gastritis, a Mallory-Weiss tear and mucosal oozing. Number of patients according to timing endoscopy showed significant differences in bleeding cause (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Active hemorrhage was identified on endoscopy more often in patient with urgent endoscopy than in patients with early and elective endoscopy (55.8% vs 23.2% vs 6.3%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eUse of endoscopic therapy was performed in 87.7% (448/511) of patients. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows details of the use of significant variation in therapy at the first endoscopy according to the specific endoscopic high-risk stigmata of bleeding. The commonest endoscopic therapy was ulcer base injection which comprised 62.9% (122/194) of therapeutic procedures at the first endoscopy. For patients with non-variceal AUGIB who received therapy, combined haemostasis was used in 46.3% (151/326). For patients with varices at the first endoscopy 69.3% (122/176) underwent variceal banding.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOUTCOMES ACCORDING TO ENDOSCOPY TIMING\u003c/h3\u003e\n\u003cp\u003eOutcomes of endpoints on mortality, repeat endoscopy, ICU admission and long length of stay are described in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In the Cox regression analyses, we observed the highest 30-day mortality rate in the urgent endoscopy group. Using the early group as a reference, the urgent group had an adjusted hazard ratio (aHR) of 2.57 (95% CI 1.04\u0026ndash;6.78, p\u0026thinsp;=\u0026thinsp;0.047), while the elective group had an aHR of 0.91 (95% CI 0.71\u0026ndash;1.13, p\u0026thinsp;=\u0026thinsp;0.198). The urgent groups had significantly more in-hospital deaths compared with the early and elective group (urgent 11.54% vs early 6.83% vs elective 3.98%, p\u0026thinsp;=\u0026thinsp;0.040). Of 511 patients with AUGIB, 36 (7%) patients died within 30-day. The causes of death were 13 hemorrhagic shock, 7 sepsis, 5 respiratory failure, 5 advanced-stage cancer, 4 decompensated cirrhosis, 1 decompensated advanced heart failure, 1 unknown.\u003c/p\u003e \u003cp\u003eSeventeen per cent (87/511) of patients needed second-look endoscopy or had a repeat inpatient endoscopy. We analysed the rebleeding rate using Cox regression analyses. Compared with the urgent group, we observed a higher rate of repeat therapeutic endoscopy in the urgent group (aHR 1.83, 95% CI 1.11\u0026ndash;3.69, p\u0026thinsp;=\u0026thinsp;0.034). The respective rate for the elective endoscopy group was not significantly different (aHR 0.99, 95% CI 0.32\u0026ndash;1.30, p\u0026thinsp;=\u0026thinsp;0.220).\u003c/p\u003e \u003cp\u003eSimilarly, when compared with early group, patient in the urgent group (aHR 3.57, 95% CI 0.58\u0026ndash; 8.96, p\u0026thinsp;=\u0026thinsp;0.170) were more likely to require an ICU admission after index endoscopy, while the elective group had a lower rate of admission (aHR 0.92, 95% CI 0.16\u0026ndash;5.17, p\u0026thinsp;=\u0026thinsp;0.910). Moreover, the average units of blood transfused within 30 days of admission among the three group was compared. Patients in the urgent group received numerically more units per patients, being the difference was statistically significant [2.7 (SD 2.5) vs 1.2 (1.9) vs 1.1 (SD 1.5), p\u0026thinsp;=\u0026thinsp;0.021]. Regarding the LOS, patients in the urgent group had significantly longer LOS compared with the early group (aHR 1.58, 95% CI 1.42\u0026ndash; 1.69, p\u0026thinsp;=\u0026thinsp;0.038).\u003c/p\u003e\n\u003ch3\u003eSUBGROUP ANALYSIS BASED ON SOURCE OF BLEEDING\u003c/h3\u003e\n\u003cp\u003eThe cohort was further analysed based on the etiology of variceal versus non-variceal AUGIB. A total of 176 (34.4%) patients suffered variceal bleeding while 194 (38%) patients had non-variceal bleeding. Urgent endoscopy timing was associated with worse outcomes in patients with non-variceal bleeding, having significantly higher 30-day all-cause mortality (aHR 1.28, 95% CI 1.08\u0026ndash;1.97, p\u0026thinsp;=\u0026thinsp;0.045), 30-day ICU admission (aHR 1.19, 95% CI 1.04\u0026ndash;1.95, p\u0026thinsp;=\u0026thinsp;0.043) and longer length of stay (aHR 1.45, 95% CI 1.22\u0026ndash;1.93, p\u0026thinsp;=\u0026thinsp;0.031). In contrast, urgent timing was not associated with significant difference in 30-day repeat therapeutic endoscopy in patients with non-variceal bleeding and any outcomes among patients with variceal bleeding.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePREDICTORS OF 30-DAY MORTALITY\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;3 shows the results of univariate and multivariate logistic regression analyses for predictors of 30-day mortality. On univariate analysis, 30-day mortality was associated significantly with older age (OR 1.03, 95% CI 1.01\u0026ndash;1.05, p\u0026thinsp;=\u0026thinsp;0.011), urgent endoscopy (t\u0026thinsp;\u0026lt;\u0026thinsp;6 hours) (OR 1.48, 95% CI 1.11\u0026ndash;1.70, p\u0026thinsp;=\u0026thinsp;0.018), cirrhosis (OR 1.69, 95% CI 1.49\u0026ndash;1.97, p\u0026thinsp;=\u0026thinsp;0.311), higher Charlson comorbidity index (OR 1.52, 95% CI 1.14\u0026ndash;2.04, p\u0026thinsp;=\u0026thinsp;0.011), shock defined as systolic blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;90mmHg (OR 5.45, 95% CI 2.73\u0026ndash;10.9, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and tachycardia (OR 1.04, 95% CI 1.02\u0026ndash;1.06, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and malignancy (OR 3.86, 95% CI 1.12\u0026ndash;13.3, p\u0026thinsp;=\u0026thinsp;0.033). On multivariate analysis, the independent predictors of 30-day mortality were urgent endoscopy (OR 1.83, 95% CI 1.11\u0026ndash;3.69, p\u0026thinsp;=\u0026thinsp;0.034, higher Charlson comorbidity index (OR 1.39, 95% CI 1.01\u0026ndash;1.93, p\u0026thinsp;=\u0026thinsp;0.043), systolic blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;90mmHg (OR 3.66, 95% CI 1.44\u0026ndash;9.31, p\u0026thinsp;=\u0026thinsp;0.006) and malignancy (OR 1.68, 95% CI 1.37\u0026ndash;7.73, p\u0026thinsp;=\u0026thinsp;0.047).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur findings demonstrate that early endoscopy (6\u0026thinsp;\u0026lt;\u0026thinsp;t \u0026le;\u0026thinsp;24 hours) achieves better outcomes compared with urgent endoscopy (t\u0026thinsp;\u0026le;\u0026thinsp;6 hours) in high-risk patients with AUGIB. However, the outcomes for elective endoscopy group (t\u0026thinsp;\u0026lt;\u0026thinsp;24 hours) were more variable and statistically non-significant. When also taking into account bleeding etiology, the results were consistent with non-variceal bleeding.\u003c/p\u003e \u003cp\u003eOur results can be explained be the longer time for thorough initial medical management with a structured approach with appropriate intravenous fluid resuscitation, use of a restrictive transfusion, pharmacological therapies and pre-endoscopic scoring tools to classify the patient at high or low-risk who might benefit from specific treatment [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Moreover, patients with active bleeding may have large amount of fresh blood in the stomach and duodenum, possibly obscuring the examination of the mucosa and the visualization of the site of bleeding when urgent endoscopy is performed.\u003c/p\u003e \u003cp\u003eThe endoscopy timing in high-risk patients with AUGIB is controversial. Early endoscopy within 12 and 24 hours of admission is recommended for most patients with variceal and non-variceal bleeding respectively according to the European Society of Gastrointestinal Endoscopy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and International Consensus Recommendations [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, previous study findings from retrospective cohort studies and RCTs were conflicting over the precise timing of endoscopy, several studies suggested that urgent endoscopy may benefit high-risk patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], large nationwide studies demonstrated that early endoscopy was superior [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] while some studies suggested no significant differences [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In this study, we conducted a retrospective, international multicenter cohort study based on a database of consecutive high-risk patients, that is larger than previous and includes variceal and non-variceal etiologies. This means that our study has a greater statistical power. Although the etiology of GI bleeding was heterogeneous but data from the different subpopulations were analysed separately, meaning that conclusions may be applicable to each specific etiology of GI bleeding, independently. While our findings indicated that early endoscopy timing may be superior to urgent endoscopy, the results of the subgroup analyses suggest that variceal bleeding was less affected by the endoscopy timing according to Jung et al [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This outcome of variceal bleeding is a severe complication of decompensated sever liver disease and advanced portal hypertension. Moreover, it is associated to worse prognosis compared with non-variceal bleeding.\u003c/p\u003e \u003cp\u003eThere are some limitations in this study. The retrospective nature limits our data recording to the available medical records. Despite, database being thoroughly screened, we cannot exclude some degree of underreporting due to inherent limitations of non-standardized clinical documentations. In general, patients with hemodynamic instability and suspected severe AUGIB will undergo early endoscopy and mortality could be related to disease severity rather than to timing of endoscopy. In some cases with coexisting life-threatening disease, performance of endoscopy may delay an optimal medical management [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. On other hand, endoscopy could be deferred if it was deemed futile depends on some patients with severe AUGIB. Our data show differences in baseline characteristics of patients and bleeding according to timing of endoscopy. These factors may confound our results. Therefore, multivariate analysis and logistic regression were performed to control this. Moreover, the degree and in which direction these factors affect our results are unknown.\u003c/p\u003e \u003cp\u003eIn conclusion, our results show a lower mortality rate in AUGIB patients receiving early endoscopy between 6 and 24 hours compared with urgent endoscopy within 6 hours. An initial period of time to optimize active resuscitation and medical treatment before index endoscopy is recommended in high-risk patients with comorbidities.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONFLICTS OF INTEREST:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJavier Tejedor-Tejada: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eBenito Hermida: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eCristina Camblor: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eLaura Sanchez: None\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Eduany Hernandez: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eMohamed Emara: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eSalem Youssef Mohamed: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eZhuraida Salman: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eAranzazu Alvarez-Alvarez: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003eJose M. Perez-Pariente: \u0026nbsp;None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eJavier Tejedor-Tejada \u0026ndash; Study concept and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eBenito Hermida \u0026ndash; Acquisition of data, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eCristina Camblor \u0026ndash; Acquisition of data, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eLaura Sanchez \u0026ndash; Acquisition of data, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eEduany Hernandez \u0026ndash; Acquisition of data, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eMohamed Emara \u0026ndash; Acquisition of data, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eSalem Youssef Mohamed\u0026nbsp;\u0026ndash; Acquisition of data, critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eZhuraida Salman: \u0026ndash; Critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eAranzazu\u0026nbsp;Alvarez-Alvarez \u0026ndash;\u0026nbsp;Critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n \u003cli\u003eJose M. Perez-Pariente\u0026nbsp;\u0026ndash; Critical revision of manuscript, technical support, final approval.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are grateful to the staff and other health-care professionals who have collaborated in handling of the clinical cases and contributed data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVan Leerdam ME, Vreeburg EM, Rauws EA, et al. Acute upper GI bleeding: did any- thing change? Time trend analysis of incidence and outcome of acute upper GI bleed- ing between 1993/1994 and 2000. Am J Gastroenterol 2003;98:1494\u0026ndash;9 \u003c/li\u003e\n\u003cli\u003eRockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ 1995;311:222\u0026ndash;226.\u003c/li\u003e\n\u003cli\u003eGuo CLT, Wong SH, Lau LHS, et al. Timing of endoscopy for acute upper gastrointestinal bleeding: a territory-wide cohort study. Gut. 2022 Aug;71(8):1544-1550. doi: 10.1136/gutjnl-2020-323054. Epub 2021 Sep 21. PMID: 34548338; PMCID: PMC9279843.\u003c/li\u003e\n\u003cli\u003eRockall TA, Logan RF, Devlin HB, et al. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996 Mar;38(3):316-21. doi: 10.1136/gut.38.3.316. PMID: 8675081; PMCID: PMC1383057.\u003c/li\u003e\n\u003cli\u003eMullady DK, Wang AY, Waschke KA. AGA Clinical Practice Update on Endoscopic Therapies for Non-Variceal Upper Gastrointestinal Bleeding: Expert Review. Gastroenterology. 2020 Sep;159(3):1120-1128.\u003c/li\u003e\n\u003cli\u003eBlatchford O, Davidson LA, Murray WR, et al. Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study. BMJ. 1997 Aug 30;315(7107):510-4. doi: 10.1136/bmj.315.7107.510. PMID: 9329304; PMCID: PMC2127364\u003c/li\u003e\n\u003cli\u003eBryant RV, Kuo P, Williamson K, et al. Performance of the Glasgow-Blatchford score in predicting clinical outcomes and intervention in hospitalized patients with upper GI bleeding. Gastrointest Endosc. 2013 Oct;78(4):576-83. doi: 10.1016/j.gie.2013.05.003. Epub 2013 Jun 18. PMID: 23790755.\u003c/li\u003e\n\u003cli\u003eSaltzman JR, Tabak YP, Hyett BH, et al. A simple risk score accurately predicts in-hospital mortality, length of stay, and cost in acute upper GI bleeding. Gastrointest Endosc. 2011 Dec;74(6):1215-24. doi: 10.1016/j.gie.2011.06.024. Epub 2011 Sep 10. PMID: 21907980.\u003c/li\u003e\n\u003cli\u003eLaursen SB, Oakland K, Laine L, et al. ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study. Gut. 2021 Apr;70(4):707-716. doi: 10.1136/gutjnl-2019-320002. Epub 2020 Jul 28. PMID: 32723845.\u003c/li\u003e\n\u003cli\u003eRedondo-Cerezo E, Vadillo-Calles F, Stanley AJ, et al. MAP(ASH): A new scoring system for the prediction of intervention and mortality in upper gastrointestinal bleeding. J Gastroenterol Hepatol. 2020 Jan;35(1):82-89. doi: 10.1111/jgh.14811. Epub 2019 Aug 19. PMID: 31359521.\u003c/li\u003e\n\u003cli\u003eLee JG, Turnipseed S, Romano PS, et al. Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial. Gastrointest Endosc 1999;50:755\u0026ndash;761.\u003c/li\u003e\n\u003cli\u003eCho S-H, Lee Y-S, Kim Y-J, et al. Outcomes and role of urgent endoscopy in high-risk patients with acute Nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol 2018;16:370\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eLim LG, Ho KY, Chan YH, et al. Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. Endoscopy 2011;43:300\u0026ndash;306\u003c/li\u003e\n\u003cli\u003eLaursen SB, Leontiadis GI, Stanley AJ, et al. Relationship between timing of endoscopy and mortality in patients with peptic ulcer bleeding: a nationwide cohort study. Gastrointest Endosc 2017;85:936\u0026ndash;44.\u003c/li\u003e\n\u003cli\u003eJairath V, Kahan BC, Logan RFA, et al. Outcomes following acute nonvariceal upper gastrointestinal bleeding in relation to time to endoscopy: results from a nationwide study. Endoscopy 2012;44:723\u0026ndash;30.\u003c/li\u003e\n\u003cli\u003eSaleem SA, Kudaravalli P, Riaz S, et al. Outcomes of upper gastrointestinal bleeding based on time to endoscopy: a retrospective study. Cureus 2020;12:e7325.\u003c/li\u003e\n\u003cli\u003eSchacher GM, Lesbros-Pantoflickova D, Ortner MA, et al. Is early endoscopy in the emergency room beneficial in patients with bleeding peptic ulcer? A \u0026quot;fortuitously controlled\u0026quot; study. Endoscopy 2005;37:324\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eSpanish Association of Gastroenterology. Management of Anemia and Iron Deficiency in Gastrointestinal Bleeding according to Healthcare PROtocols to improve interDIsciplinary manaGEment of gaSTrointestinal diseases in hospital settings. [Internet]; 2017. Available in: https://www.aegastro.es/documents/prodiggest/Prodiggest-Management-of-anaemia-and-iron-deficiency-in-gastrointestinal-bleeding.pdf (Accessed June 7, 2024).\u003c/li\u003e\n\u003cli\u003eTejedor-Tejada J, Ballester MP, Del Castillo-Corzo FJ, et al. Adherence to patient blood management strategy in patients with gastrointestinal bleeding: a prospective nationwide multicenter study. Eur J Gastroenterol Hepatol. 2024 Sep 23. doi: 10.1097/MEG.0000000000002843. Epub ahead of print. PMID: 39324889.\u003c/li\u003e\n\u003cli\u003eForrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet 1974;2:394\u0026ndash;397.\u003c/li\u003e\n\u003cli\u003eOrpen-Palmer J, Stanley AJ. Update on the management of upper gastrointestinal bleeding. BMJ Med. 2022 Sep 28;1(1):e000202. doi: 10.1136/bmjmed-2022-000202. PMID: 36936565; PMCID: PMC9951461.\u003c/li\u003e\n\u003cli\u003eGralnek IM, Camus Duboc M, Garcia-Pagan JC, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022 Nov;54(11):1094-1120. doi: 10.1055/a-1939-4887. Epub 2022 Sep 29. PMID: 36174643.\u003c/li\u003e\n\u003cli\u003eBarkun AN, Almadi M, Kuipers EJ, et al. Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019 Dec 3;171(11):805-822. doi: 10.7326/M19-1795. Epub 2019 Oct 22. PMID: 31634917; PMCID: PMC7233308.\u003c/li\u003e\n\u003cli\u003eLim LG, Ho KY, Chan YH, et al. Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding. Endoscopy. 2011 Apr;43(4):300-6. doi: 10.1055/s-0030-1256110. Epub 2011 Feb 28. PMID: 21360421.\u003c/li\u003e\n\u003cli\u003eLin HJ, Wang K, Perng CL, et al. Early or delayed endoscopy for patients with peptic ulcer bleeding. A prospective randomized study. J Clin Gastroenterol. 1996 Jun;22(4):267-71. doi: 10.1097/00004836-199606000-00005. PMID: 8771420.\u003c/li\u003e\n\u003cli\u003eTargownik LE, Murthy S, Keyvani L, et al. The role of rapid endoscopy for high-risk patients with acute nonvariceal upper gastrointestinal bleeding. Can J Gastroenterol. 2007 Jul;21(7):425-9. doi: 10.1155/2007/636032. PMID: 17637943; PMCID: PMC2657961.\u003c/li\u003e\n\u003cli\u003eTai CM, Huang SP, Wang HP, et al. High-risk ED patients with nonvariceal upper gastrointestinal hemorrhage undergoing emergency or urgent endoscopy: a retrospective analysis. Am J Emerg Med. 2007 Mar;25(3):273-8. doi: 10.1016/j.ajem.2006.07.014. PMID: 17349900.\u003c/li\u003e\n\u003cli\u003eBjorkman DJ, Zaman A, Fennerty MB, et al. Urgent vs. elective endoscopy for acute non-variceal upper-GI bleeding: an effectiveness study. Gastrointest Endosc. 2004 Jul;60(1):1-8. doi: 10.1016/s0016-5107(04)01287-8. PMID: 15229417.\u003c/li\u003e\n\u003cli\u003eJung DH, Huh CW, Kim NJ, et al. Optimal endoscopy timing in patients with acute variceal bleeding: A systematic review and meta-analysis. Sci Rep. 2020 Mar 4;10(1):4046. doi: 10.1038/s41598-020-60866-x. PMID: 32132589; PMCID: PMC7055310.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endoscopy, Interventions, Mortality, Timing, Upper gastrointestinal bleeding","lastPublishedDoi":"10.21203/rs.3.rs-5340232/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5340232/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWhile early endoscopy is recommended in patients with acute upper gastrointestinal bleeding (AUGIB), the optimal timing in high-risk patients is still uncertain.\u003c/p\u003e\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eTo determine whether endoscopy timing would affect outcomes in high-risk patients with AUGIB.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective, international and multicentre cohort study. High-risk patients (modified Glasgow Blatchford score\u0026thinsp;\u0026gt;\u0026thinsp;7 points) with AUGIB between 2016\u0026ndash;2022 and received therapeutic endoscopy (n\u0026thinsp;=\u0026thinsp;511) were recruited. Patients were classified based on endoscopic timing in urgent (t\u0026thinsp;\u0026le;\u0026thinsp;6 hours), early (6\u0026thinsp;\u0026lt;\u0026thinsp;t\u0026thinsp;\u0026le;\u0026thinsp;24) and elective (t\u0026thinsp;\u0026gt;\u0026thinsp;24) group. Using descriptive statistics and logistic regression analyses, the optimal timing for endoscopy was identified and we analyzed the association between endoscopy and 30-day outcomes after adjusting for confounding factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe results showed that urgent timing (n\u0026thinsp;=\u0026thinsp;130) had worse outcomes than early (n\u0026thinsp;=\u0026thinsp;205) and elective (n\u0026thinsp;=\u0026thinsp;176) endoscopy with higher 30-day all-causes mortality (p\u0026thinsp;=\u0026thinsp;0.047), repeat endoscopy (p\u0026thinsp;=\u0026thinsp;0.034), 30-day transfusion rates (p\u0026thinsp;=\u0026thinsp;0.021) and longer length of stay (p\u0026thinsp;=\u0026thinsp;0.038). These findings were more consistent when patients were admitted with non-variceal bleeding. In multivariate analysis, urgent endoscopy (OR 1.83, 1.11\u0026ndash;3.69; p\u0026thinsp;=\u0026thinsp;0.034), Charlson index (OR 1.39, 1.01\u0026ndash;1.93; p\u0026thinsp;=\u0026thinsp;0.043), systolic blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;90mmHg (OR 3.66, 1.44\u0026ndash;9.31; p\u0026thinsp;=\u0026thinsp;0.006) and malignancy (OR 1.68, 95%CI 1.37\u0026ndash;7.73; p\u0026thinsp;=\u0026thinsp;0.047) were worse prognostic factors.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eHigh-risk patients with AUGIB who have received urgent endoscopy presented worse outcomes, especially among patients with non-variceal bleeding. Comorbidities, shock, urgent endoscopy and malignancy were predictors for 30-day mortality. This emphasies the need of prior resuscitation and pharmacotherapy and early endoscopy.\u003c/p\u003e","manuscriptTitle":"Timing of endoscopy in high-risk patients with acute upper gastrointestinal bleeding: Multicenter and international cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 13:49:40","doi":"10.21203/rs.3.rs-5340232/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ed4a6646-a173-4e83-8202-9780abdf6f14","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-19T13:49:43+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-19 13:49:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5340232","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5340232","identity":"rs-5340232","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}