Provocative Mesenteric Angiography for Occult Gastrointestinal Bleeding: A Single Center Retrospective Review of 56 Patients

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Gazda, Matthew Abad-Santos, David S. Shin, Jeffrey F. B. Chick, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6388959/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Occult gastrointestinal bleeding is the most common type of bleeding from the gastrointestinal tract and is often a diagnostic challenge. Endoscopic evaluation and radiology studies have relatively low success in identify the source of occult bleeding. Similarly, conventional mesenteric angiography is limited by the intermittent nature of bleeding and bleeding rates below detection threshold. Provocative mesenteric angiography uses pharmacologic agents to promote bleeding for localization and intervention in difficult cases. However, there is significant lack of data regarding the use of provocative mesenteric angiography. This study reports the experience with the largest single cohort of patients undergoing provocative mesenteric angiography for occult gastrointestinal bleeding. Results 56 patients underwent provocative mesenteric angiography for occult gastrointestinal bleeding. 7 (12.5%) patients had a positive study, and 49 (87.5%) patients had a negative study. 41 (73.2%), 36 (64.2%), 27 (48.2%), 8 (14.3%), and 2 (3.5%) patients received intra-arterial nitroglycerin, heparin, tissue plasminogen activator, reteplase, or papaverine, respectively. Mean dose of nitroglycerin, heparin, tissue plasminogen activator, reteplase, and papaverine was 227.8 ± 274.6 mcg, 4,958.3 ± 2839.0 units, 7.8 ± 5.8 mg, 2.9 ± 1.5 units, and 18.1 ± 4.1 mg, respectively. Of those with a positive angiogram, 6 (85.7%) patients were managed successfully with endovascular intervention. There was 1 immediate minor complication of hypotension and bradycardia. There were no major complications. Conclusion With the largest cohort of patients to date undergoing provocative mesenteric angiography for occult gastrointestinal bleeding, this study found a lower positive provocation rate compared to prior reports. Nearly all positive cases underwent successful endovascular intervention, with no mortalities and only one minor complication reported. Future studies are needed with larger patient samples, standardized protocols and comparative arms. Occult gastrointestinal bleeding Provocative mesenteric angiography Nitroglycerin Heparin Tissue plasminogen activator Endovascular management Figures Figure 1 Figure 2 Background Bleeding from the gastrointestinal tract without a known site, classified as occult gastrointestinal bleeding (GIB), is the most common type of GIB and often a diagnostic challenge 1 . Occult GIB manifests as positive fecal occult blood or unexplained iron deficiency anemia. Common diagnostic approaches progress from endoscopic evaluation to radiology studies, and eventually to the interventional procedures of conventional and provocative mesenteric angiography 2 . However, initial endoscopic evaluation identifies the site of bleeding only 48 to 71 percent of the time. Computed tomography angiography (CTA) and tagged red blood cell scintigraphy identify active bleeding in only 38 percent of cases 3 , 4 , 5 . Conventional mesenteric angiography has a detection threshold for bleeding with rates as low as 0.5 to 1.0 ml/min 6 . Intermittent bleeding and bleeding occurring at a rate below detection thresholds can result in a negative conventional mesenteric angiogram 7 . Provocative mesenteric angiography, where pharmacologic agents are administered to promote bleeding, can be considered in these situations. Regimens for provocation are variable but include pharmacologic agents for vasodilation, anticoagulation and thrombolysis. This is frequently achieved with nitroglycerin, heparin, tissue plasminogen activator (tPA), and other thrombolytics, administered as single agents or in various combinations. Provocative mesenteric angiography can provide localization and simultaneously offer intervention through embolization in a single session. However, there is significant lack of data regarding the use of provocative mesenteric angiography in the setting of occult GIB. Most of the literature is composed of small case series, case reports and systematic literature reviews. A recent systematic review identified only 27 total studies on the topic with the majority including fewer than 5 patients 8 . Across all reports the average positive rate for provocative mesenteric angiography is 48.7% 8 . With only a few small studies, definitive conclusions on efficacy and safety are difficult to discern. The aim of this study is to provide real world experience with the largest reported single cohort of patients to date undergoing provocative mesenteric angiography for occult GIB. Methods Study design Retrospective review of a single institution’s electronic medical record over a 15-year period was conducted to identify provocative mesenteric angiography performed in the setting of occult GIB. The aim of the study was to report the success of provocative angiography, analyze the pharmacologic agents used and report the subsequent interventions and complications from the procedure. Record review first identified any mesenteric angiography cases which were then filtered to those specifically meeting provocative mesenteric angiography criteria in the setting of occult GIB. This study was conducted with institutional review board approval and complied with the Health Insurance Portability and Accountability Act of 1996. Informed consent was not required for this study. Eligibility Criteria Patients who underwent an angiogram with a pharmacologic provocation agent with the intention to elucidate bleeding in cases of suspected occult GIB. Pharmacologic agents for vasodilation, anticoagulation or thrombolysis were considered provocative agents. Patient demographics Table 1 Patient demographics56) Gender n (%) Male 34 (61) Female 22 (39) Age (years) Mean 62 ± 15.5 Range 16–90 The study cohort included 34 males (60.7%) and 22 females (39.2%) with mean age of 62 ± 15.5 years (range: 16–90 years) (Table 1 ). Table 1 . Patient demographics of those undergoing provocative mesenteric angiography in the setting of occult GIB. Documented variables Manual chart evaluation was performed for each patient who underwent provocative angiography for occult GIB. The specific pharmacologic agents used and their associated doses for each provocative angiography were recorded, along with the number of different pharmacologic agents used during each procedure. Procedural details recorded included the diagnostic yield of the provocative angiography procedure, the anatomic distribution of any identified bleeding, any intervention following positive bleeding identification, and complications during the procedure. Provocative angiography diagnostic success was defined as identification of contrast extravasation on digital subtraction angiography, indicating active bleeding, following instillation of provocative pharmacologic agents. Complications were classified according to the Society of Interventional Radiology practice guidelines 10 , 11 . Following initial provocative angiography, any reintervention was recorded along with mortality at 30-days and 60-days post procedure. Provocative mesenteric angiography procedural technique Provocative mesenteric angiography is shown in Fig. 1 . All patients were seen by an interventional radiologist in clinic or during inpatient consultation. All procedures were performed with moderate sedation or general anesthesia administered by a registered nurse, certified registered nurse anesthetist, or anesthesiologist. Baseline angiography of the celiac artery, superior mesenteric artery, and/or inferior mesenteric artery was performed prior to provocation. Following negative angiography, the vessel most likely to be the culprit was selected for pharmacologic provocation based on prior radiologic imaging and the clinical judgment of the interventional radiologist. The pharmacologic agents used for provocative angiography along with the number of agents used and their associated doses were also left to the clinical judgment of the interventional radiologist. Immediate and 5-10-minute post-infusion angiography were performed in all patients. Figure 1 . 55-year-old woman with history of Roux-en-Y gastric bypass who presented with melena without an identifiable bleeding source despite esophagogastroduodenoscopy, tagged red blood cell scintigraphy, and double balloon enteroscopy. (A) Digital subtraction angiography of the celiac axis demonstrating mild vasospasm of the gastroduodenal artery (GDA) without active extravasation. (B) Microcatheter selection of the GDA did not demonstrate extravasation, however persistent vasospasm was evident. (C) Delivery of 5 mg tissue plasminogen activator and 100 mcg nitroglycerin, gastroduodenal arteriography demonstrated active arterial extravasation. (D) After coil embolization of the GDA, there is no residual extravasation on repeat celiac arteriography. Results Angiography case selection EMR review identified 24,492 patients underwent angiography. 144 (0.6%) of the angiography cases met the search criteria for “provocative arteriography or arteriogram,” “provocative angiography or angiogram,” or “angiography or arteriography with tissue plasminogen activator” (tPA). Of the 144 cases, 56 (0.2%) patients were found to have undergone provocative pharmacologic angiography for occult GIB. Provocative angiography diagnostic success Of the 56 patients who underwent provocative angiography for occult GIB, 7 (12.5%) patients had a positive study, and 49 (87.5%) patients had a negative study. Provocative pharmacologic agents and protocol The agents used for provocative angiography included nitroglycerin (Baxter, Deerfield, IL), heparin (Sagent Pharmaceuticals, Schaumburg, IL), tissue plasminogen activator (alteplase; Genentech, San Francisco, CA), reteplase (Roche Diagnostics, Risch-Rotkreuz, Switzerland), or papaverine (American Regent; Upton, NY). 41 (73.2%), 36 (64.2%), 27 (48.2%), 8 (14.3%), and 2 (3.5%) patients received intra-arterial nitroglycerin, heparin, tissue plasminogen activator, reteplase, or papaverine, respectively (Table 2 ). Mean dose of nitroglycerin, heparin, tissue plasminogen activator, reteplase, and papaverine was 227.8 ± 274.6 mcg, 4,958.3 ± 2839.0 units, 7.8 ± 5.8 mg, 2.9 ± 1.5 units, and 18.1 ± 4.1 mg, respectively (Table 2 ). Table 2 Provocative pharmacologic Agents Drug Number of Patients Receiving Drug (%) Mean Dose (Range) Number of Positive Findings When Using Drug (%) Nitroglycerin (mcg) 41 (73) 227 (0–2,000) 6 (14.6) Heparin (units) 36 (64) 4,958 (0–11,000) 5 (13.9) tPA (mg) 27 (48) 7.8 (0–30) 1 (3.7) Reteplase (units) 8 (14) 2.9 (0-7.5) 2 (25.0) Papaverine (mg) 2 (4) 18 (0–30) 1 (50.0) Table 2 . Provocative pharmacologic agents in relation to the number of patients who received each agent, mean dose and number of positive exams, regardless of combination for patients receiving more than one agent. Diagnostic success with respective pharmacologic agents The number of positive exams with respect to each agent used are as follows: 6 received nitroglycerin, 5 received heparin, 2 received reteplase, 1 received tissue plasminogen activator, and 1 received papaverine (Table 2 ). When compared to the study cohort who received each agent this yielded a positive exam with respect to the agent itself of 14.6% for nitroglycerin, 13.9% for heparin, 25.0% for reteplase, 3.7% for tissue plasminogen activator, and 50.0% for papaverine, regardless of combination for patients receiving more than one agent (Table 2 ). Proportion of patients receiving multiple provocative agents and success rates 22 (39.2%) patients received 2 provocative agents, 18 (32.1%) patients received 3 provocative agents, 16 (28.6%) patients received 1 provocative agent (Table 3 ). Of the 22 patients that received 2 agents, 4 (18.2%) were positive. Of the 18 patients that received 3 agents, 2 (11.1%) were positive. Of the 16 patients that received 1 agent, 1 (6.3%) was positive. (Table 3 ). Table 3 Number of provocative agents received Number of provocative agents received Number of patients Number of positive cases 1 16 (28.6%) 1 (6.3%) 2 22 (39.2%) 4 (18.2%) 3 18 (32.1%) 2 (11.1%) Table 3 . Positive cases in relation to the number of provocative agents received and related proportion of cohort receiving multiple agents. Anatomic distribution of positive cases Of positive provocative studies, 3 (42.9%) were in the small bowel, 2 (28.6%) were in the ascending colon, 1 (14.3%) was in the ileocolic region, and 1 (14.3%) was in the descending colon (Table 3 ). Table 4 Source of bleeding Anatomic location Number of Patients Small bowel 3 (43%) Ascending colon 2 (29%) Ileocolic 1 (14%) Descending colon 1 (14%) Table 4 . Anatomic distribution of bleeding following provocative mesenteric angiography. Management of positive cases Of those with a positive arteriogram, 6 (85.7%) were managed successfully with endovascular intervention. Specifically, 3 (50.0%) received particles and coils, 2 (33.3%) particles alone, and 1 (16.7%) coils alone. 1 (16.7%) patient was managed conservatively due to concern for ischemia from embolization. No patients underwent surgical resection. (Fig. 2 ). Figure 2 . Management of positive provocative angiograms. 6 patients underwent definitive endovascular intervention, and 1 patient received conservative management due to concern for ischemia with embolization. Reintervention, Complications and Mortality There was 1 immediate minor complication, hypotension and bradycardia, which resolved with hydration and atropine administration. There were no major complications. 4 (7.1%) of the 56 patients underwent a second provocative angiogram. All repeat examinations were negative (n = 4; 100%). 30-day and 60-day mortality were both (n = 2) 3.6%. 1 (1.8%) patient died 3 days after angiography from respiratory arrest and metabolic acidosis. 1 (1.8%) patient died 15 days after angiography from cardiac arrest. Discussion Provocative mesenteric angiography can aid in the difficult evaluation and treatment of occult GIB. Described diagnostic algorithms for occult GIB commonly cite similar approaches progressing from endoscopic evaluation and radiology studies to interventional techniques 4 , 6 . Provocative mesenteric angiography is often considered later in the algorithm and its low use has been attributed to the invasive nature, theoretical complications, and sparse data. However, most of the prior literature is composed of small case series, case reports and systematic literature reviews 7 , 8 , 9 . This retrospective review provides real world single institutional experience with the largest cohort of patients to date undergoing provocative mesenteric angiography for occult GIB. Similar to prior reports, this review demonstrated a low rate of complications and high rate of successful endovascular management of positive cases. In contrast to previous data, this study found only a 12% positive provocative angiography rate, while other reports have shown significantly higher positive provocative rates. A principal consideration for the discordance is the low statistical power with small patient samples in prior reports making it hard to determine an accurate expected positive rate. Most prior reports contain fewer than 5 patients with the vast majority of those involving only 1 patient in a case report format. A recent large systematic review on provocative mesenteric angiography for occult GIB included 27 studies with a total of 230 patients. Various combinations and doses of provocative agents were used and a 48.7% average positive rate across all studies was reported 8 . The two largest studies in the systematic review reported positive rates of 44% and 31–33% but only involved 36 patients each. The explanation for the discordance between the lower positive provocative rates reported herein and prior studies may be explained by several factors. Another explanation for discordance is the significant variability in both the combinations and doses of the provocative agents. The above-mentioned systematic review reported a mean dose of 3000 IU for Heparin when used as the sole agent and an overall mean tPA dose of 24 mg. When systemic heparinization was used in combination with thrombolytics a low dose protocol with 5000 IU was the most common and a high dose protocol used 10,000 IU 8 . This is in contrast to the much lower mean tPA dose of 7.8 mg in this study and mean heparin dose of 4,958 units being similar to a reported low dose protocol. In the review not every study reported doses used and no data was available for the ones that used nitroglycerin or papaverine as was included in this study, further compounding difficulty in comparing protocols. In a separate individual study tPA was used for provocation and a diagnostic yield of 31% in provoking active bleeding was reported 9 . Importantly, the reported average tPA dose administered to patients with a positive provocative angiogram was 11.3 mg compared to an average of 9.6 mg of tPA administered in patients with negative provocative angiogram 9 . Interestingly, the reported average dose of tPA for negative examinations was higher than this studies overall mean tPA dose. This suggests a higher dose of tPA may have resulted in a higher positive rate in this study and emphasizes the need for standardized protocols in future studies. While the above-mentioned factors may have contributed to differences in reported positive rates, it is important to note the intervention success and low rate of complications within this study were similar to prior studies. One of the previously largest single institution retrospective studies involved 34 patients and reported 91% of their positive studies underwent embolization. With this, no hemorrhagic complications occurred, but one case of perforated ischemic bowel was reported 9 . Another single institution retrospective review conducted over a 12-year period included 36 provocative mesenteric angiograms and reported 100% of the 16 (44%) positive examinations underwent successful embolization with no major or minor complications 2 . These are similar to this studies results where 6 (85.7%) of the patients with positive provocative mesenteric angiograms underwent successful endovascular intervention with only 1 immediate minor complication of hypotension and bradycardia occurring. This complication was treated effectively with fluid and atropine administration 10 , 11 . An inherent limitation of this retrospective review is not having a comparative arm. However, the aim of the report is to describe real world experience with provocative mesenteric angiography in occult GIB involving the largest cohort of patients to date. Additionally, with retrospective analysis there was no opportunity to develop a standardized protocol for provocation. This highlights the real-world nature of this study where often protocols differ not only by institution but also by individual interventionalists. Conclusion This study describes real world experience with the largest reported single cohort of patients to date undergoing provocative mesenteric angiography for occult gastrointestinal bleeding. This study demonstrated a lower positive rate compared to prior reports but with similar successful endovascular interventions and low complication rates. Discrepancies may be due to the type of medication used, combination of multiple medications, and variability in dosage. Future studies are needed with larger patient samples, standardized protocols and comparative arms. Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was conducted with institutional review board approval and complied with the Health Insurance Portability and Accountability Act of 1996. Informed consent was not required for this study. Consent for publication Not applicable Availability of data and material The datasets generated and/or analyzed during the current study are not publicly available due to it containing protected health information and following compliance with the Health Insurance Portability and Accountability Act of 1996. Competing interests Jeffrey F. B. Chick is a consultant and speaker for Inari Medical, Guerbet, C. R. Bard, Argon Medical Devices, Boston Scientific, NXT Biomedical, and AiDoc. David S. Shin is a consultant for Inari Medical. The other authors report no competing interests. Funding No funding was received to support this study. Authors’ contributions HG was the major contributor to writing the manuscript. MAS, DS, JC, and MM were major contributors to the study design, analyzing the data and revisions of the manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable Authors’ information Not applicable References Rockey DC (2010) Occult and obscure gastrointestinal bleeding: causes and clinical management. Nat Reviews Gastroenterol Hepatol 7(5):265–279 Thiry GJH, Dhand S, Gregorian A, Shah N (2022) Provocative Mesenteric Angiography: Outcomes and Standardized Protocol for Management of Recurrent Lower Gastrointestinal Hemorrhage. Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract [Internet]. ;26(3):652–4. Available from: https://pubmed.ncbi.nlm.nih.gov/34506023/ Gralnek IM (2005) Obscure-Overt Gastrointestinal Bleeding. Gastroenterology [Internet]. ;128(5):1424–30. Available from: https://www.gastrojournal.org/article/S0016-5085(05)00596-2/fulltext Bull-Henry K, Al-Kawas FH (2013) Evaluation of Occult Gastrointestinal Bleeding. American Family Physician [Internet]. ;87(6):430–6. Available from: https://www.aafp.org/pubs/afp/issues/2013/0315/p430.html He B, Yang J, Xiao J, Gu J, Chen F, Wang L et al (2017) Diagnosis of lower gastrointestinal bleeding by multi-slice CT angiography: A meta-analysis. Eur J Radiol 93:40–45 Durga Thakral DJ, Stein, Saltzman JR (2024) Diagnosis of Occult and Obscure Gastrointestinal Bleeding. Gastrointest Endosc Clin N Am 34(2):317–329 Kim CY, Suhocki PV, Miller MJ, Khan M, Janus G, Smith TP (2010) Provocative Mesenteric Angiography for Lower Gastrointestinal Hemorrhage: Results from a Single-institution Study. J Vasc Interv Radiol 21(4):477–483 Hegde S, Sutphin PD, Zurkiya O, Kalva SP (2023) Provocative mesenteric angiography for occult gastrointestinal bleeding: a systematic review. CVIR Endovascular. ;6(1) Kim CY, Suhocki PV, Miller MJ, Khan M, Janus G, Smith TP (2010) Provocative Mesenteric Angiography for Lower Gastrointestinal Hemorrhage: Results from a Single-institution Study. J Vasc Interv Radiol 21(4):477–483 Omary RA, Bettmann MA, Cardella JF, Bakal CW, Schwartzberg M, Sacks DB et al (2003) Quality Improvement Guidelines for the Reporting and Archiving of Interventional Radiology Procedures. J Vasc Interv Radiol 14(9):S293–S295 Khalilzadeh O, Baerlocher MO, Shyn PB, Connolly BL, Devane AM, Morris CS et al (2017) Proposal of a New Adverse Event Classification by the Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 28(10):1432–1437e3 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-6388959","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":449118249,"identity":"ca917c3f-d3d2-4f31-8f1b-26c2ffa41d07","order_by":0,"name":"Hunter L. 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Occult GIB manifests as positive fecal occult blood or unexplained iron deficiency anemia. Common diagnostic approaches progress from endoscopic evaluation to radiology studies, and eventually to the interventional procedures of conventional and provocative mesenteric angiography\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. However, initial endoscopic evaluation identifies the site of bleeding only 48 to 71 percent of the time. Computed tomography angiography (CTA) and tagged red blood cell scintigraphy identify active bleeding in only 38 percent of cases\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eConventional mesenteric angiography has a detection threshold for bleeding with rates as low as 0.5 to 1.0 ml/min\u003csup\u003e6\u003c/sup\u003e. Intermittent bleeding and bleeding occurring at a rate below detection thresholds can result in a negative conventional mesenteric angiogram\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Provocative mesenteric angiography, where pharmacologic agents are administered to promote bleeding, can be considered in these situations. Regimens for provocation are variable but include pharmacologic agents for vasodilation, anticoagulation and thrombolysis. This is frequently achieved with nitroglycerin, heparin, tissue plasminogen activator (tPA), and other thrombolytics, administered as single agents or in various combinations.\u003c/p\u003e \u003cp\u003e Provocative mesenteric angiography can provide localization and simultaneously offer intervention through embolization in a single session. However, there is significant lack of data regarding the use of provocative mesenteric angiography in the setting of occult GIB. Most of the literature is composed of small case series, case reports and systematic literature reviews. A recent systematic review identified only 27 total studies on the topic with the majority including fewer than 5 patients\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Across all reports the average positive rate for provocative mesenteric angiography is 48.7%\u003csup\u003e8\u003c/sup\u003e. With only a few small studies, definitive conclusions on efficacy and safety are difficult to discern. The aim of this study is to provide real world experience with the largest reported single cohort of patients to date undergoing provocative mesenteric angiography for occult GIB.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eRetrospective review of a single institution\u0026rsquo;s electronic medical record over a 15-year period was conducted to identify provocative mesenteric angiography performed in the setting of occult GIB. The aim of the study was to report the success of provocative angiography, analyze the pharmacologic agents used and report the subsequent interventions and complications from the procedure. Record review first identified any mesenteric angiography cases which were then filtered to those specifically meeting provocative mesenteric angiography criteria in the setting of occult GIB.\u003c/p\u003e \u003cp\u003e This study was conducted with institutional review board approval and complied with the Health Insurance Portability and Accountability Act of 1996. Informed consent was not required for this study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003ePatients who underwent an angiogram with a pharmacologic provocation agent with the intention to elucidate bleeding in cases of suspected occult GIB. Pharmacologic agents for vasodilation, anticoagulation or thrombolysis were considered provocative agents.\u003c/p\u003e\n\u003ch3\u003ePatient demographics\u003c/h3\u003e\n\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient demographics56)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;15.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u0026ndash;90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe study cohort included 34 males (60.7%) and 22 females (39.2%) with mean age of 62\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5 years (range: 16\u0026ndash;90 years) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patient demographics of those undergoing provocative mesenteric angiography in the setting of occult GIB.\u003c/p\u003e\n\u003ch3\u003eDocumented variables\u003c/h3\u003e\n\u003cp\u003eManual chart evaluation was performed for each patient who underwent provocative angiography for occult GIB. The specific pharmacologic agents used and their associated doses for each provocative angiography were recorded, along with the number of different pharmacologic agents used during each procedure. Procedural details recorded included the diagnostic yield of the provocative angiography procedure, the anatomic distribution of any identified bleeding, any intervention following positive bleeding identification, and complications during the procedure. Provocative angiography diagnostic success was defined as identification of contrast extravasation on digital subtraction angiography, indicating active bleeding, following instillation of provocative pharmacologic agents. Complications were classified according to the \u003cem\u003eSociety of Interventional Radiology\u003c/em\u003e practice guidelines\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Following initial provocative angiography, any reintervention was recorded along with mortality at 30-days and 60-days post procedure.\u003c/p\u003e\n\u003ch3\u003eProvocative mesenteric angiography procedural technique\u003c/h3\u003e\n\u003cp\u003e \u003cem\u003eProvocative mesenteric angiography is shown in\u003c/em\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All patients were seen by an interventional radiologist in clinic or during inpatient consultation. All procedures were performed with moderate sedation or general anesthesia administered by a registered nurse, certified registered nurse anesthetist, or anesthesiologist.\u003c/p\u003e \u003cp\u003eBaseline angiography of the celiac artery, superior mesenteric artery, and/or inferior mesenteric artery was performed prior to provocation. Following negative angiography, the vessel most likely to be the culprit was selected for pharmacologic provocation based on prior radiologic imaging and the clinical judgment of the interventional radiologist. The pharmacologic agents used for provocative angiography along with the number of agents used and their associated doses were also left to the clinical judgment of the interventional radiologist. Immediate and 5-10-minute post-infusion angiography were performed in all patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. 55-year-old woman with history of Roux-en-Y gastric bypass who presented with melena without an identifiable bleeding source despite esophagogastroduodenoscopy, tagged red blood cell scintigraphy, and double balloon enteroscopy. (A) Digital subtraction angiography of the celiac axis demonstrating mild vasospasm of the gastroduodenal artery (GDA) without active extravasation. (B) Microcatheter selection of the GDA did not demonstrate extravasation, however persistent vasospasm was evident. (C) Delivery of 5 mg tissue plasminogen activator and 100 mcg nitroglycerin, gastroduodenal arteriography demonstrated active arterial extravasation. (D) After coil embolization of the GDA, there is no residual extravasation on repeat celiac arteriography.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eAngiography case selection\u003c/h2\u003e \u003cp\u003eEMR review identified 24,492 patients underwent angiography. 144 (0.6%) of the angiography cases met the search criteria for \u0026ldquo;provocative arteriography or arteriogram,\u0026rdquo; \u0026ldquo;provocative angiography or angiogram,\u0026rdquo; or \u0026ldquo;angiography or arteriography with tissue plasminogen activator\u0026rdquo; (tPA). Of the 144 cases, 56 (0.2%) patients were found to have undergone provocative pharmacologic angiography for occult GIB.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eProvocative angiography diagnostic success\u003c/h3\u003e\n\u003cp\u003eOf the 56 patients who underwent provocative angiography for occult GIB, 7 (12.5%) patients had a positive study, and 49 (87.5%) patients had a negative study.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eProvocative pharmacologic agents and protocol\u003c/h2\u003e \u003cp\u003eThe agents used for provocative angiography included nitroglycerin (Baxter, Deerfield, IL), heparin (Sagent Pharmaceuticals, Schaumburg, IL), tissue plasminogen activator (alteplase; Genentech, San Francisco, CA), reteplase (Roche Diagnostics, Risch-Rotkreuz, Switzerland), or papaverine (American Regent; Upton, NY).\u003c/p\u003e \u003cp\u003e41 (73.2%), 36 (64.2%), 27 (48.2%), 8 (14.3%), and 2 (3.5%) patients received intra-arterial nitroglycerin, heparin, tissue plasminogen activator, reteplase, or papaverine, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMean dose of nitroglycerin, heparin, tissue plasminogen activator, reteplase, and papaverine was 227.8\u0026thinsp;\u0026plusmn;\u0026thinsp;274.6 mcg, 4,958.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2839.0 units, 7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 mg, 2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 units, and 18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 mg, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProvocative pharmacologic Agents\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Patients Receiving Drug (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean Dose (Range)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of Positive Findings When Using Drug (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNitroglycerin (mcg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e227 (0\u0026ndash;2,000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (14.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeparin (units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,958 (0\u0026ndash;11,000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (13.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etPA (mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.8 (0\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (3.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReteplase (units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9 (0-7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePapaverine (mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (0\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Provocative pharmacologic agents in relation to the number of patients who received each agent, mean dose and number of positive exams, regardless of combination for patients receiving more than one agent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic success with respective pharmacologic agents\u003c/h2\u003e \u003cp\u003eThe number of positive exams with respect to each agent used are as follows: 6 received nitroglycerin, 5 received heparin, 2 received reteplase, 1 received tissue plasminogen activator, and 1 received papaverine (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhen compared to the study cohort who received each agent this yielded a positive exam with respect to the agent itself of 14.6% for nitroglycerin, 13.9% for heparin, 25.0% for reteplase, 3.7% for tissue plasminogen activator, and 50.0% for papaverine, regardless of combination for patients receiving more than one agent (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eProportion of patients receiving multiple provocative agents and success rates\u003c/h2\u003e \u003cp\u003e22 (39.2%) patients received 2 provocative agents, 18 (32.1%) patients received 3 provocative agents, 16 (28.6%) patients received 1 provocative agent (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOf the 22 patients that received 2 agents, 4 (18.2%) were positive. Of the 18 patients that received 3 agents, 2 (11.1%) were positive. Of the 16 patients that received 1 agent, 1 (6.3%) was positive. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNumber of provocative agents received\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of provocative agents received\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of positive cases\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (39.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (18.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (32.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Positive cases in relation to the number of provocative agents received and related proportion of cohort receiving multiple agents.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eAnatomic distribution of positive cases\u003c/h2\u003e \u003cp\u003eOf positive provocative studies, 3 (42.9%) were in the small bowel, 2 (28.6%) were in the ascending colon, 1 (14.3%) was in the ileocolic region, and 1 (14.3%) was in the descending colon (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSource of bleeding\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnatomic location\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Patients\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmall bowel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (43%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscending colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (29%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIleocolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDescending colon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Anatomic distribution of bleeding following provocative mesenteric angiography.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eManagement of positive cases\u003c/h2\u003e \u003cp\u003eOf those with a positive arteriogram, 6 (85.7%) were managed successfully with endovascular intervention. Specifically, 3 (50.0%) received particles and coils, 2 (33.3%) particles alone, and 1 (16.7%) coils alone. 1 (16.7%) patient was managed conservatively due to concern for ischemia from embolization. No patients underwent surgical resection. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Management of positive provocative angiograms. 6 patients underwent definitive endovascular intervention, and 1 patient received conservative management due to concern for ischemia with embolization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eReintervention, Complications and Mortality\u003c/h2\u003e \u003cp\u003eThere was 1 immediate minor complication, hypotension and bradycardia, which resolved with hydration and atropine administration. There were no major complications.\u003c/p\u003e \u003cp\u003e4 (7.1%) of the 56 patients underwent a second provocative angiogram. All repeat examinations were negative (n\u0026thinsp;=\u0026thinsp;4; 100%).\u003c/p\u003e \u003cp\u003e30-day and 60-day mortality were both (n\u0026thinsp;=\u0026thinsp;2) 3.6%. 1 (1.8%) patient died 3 days after angiography from respiratory arrest and metabolic acidosis. 1 (1.8%) patient died 15 days after angiography from cardiac arrest.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eProvocative mesenteric angiography can aid in the difficult evaluation and treatment of occult GIB. Described diagnostic algorithms for occult GIB commonly cite similar approaches progressing from endoscopic evaluation and radiology studies to interventional techniques\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Provocative mesenteric angiography is often considered later in the algorithm and its low use has been attributed to the invasive nature, theoretical complications, and sparse data. However, most of the prior literature is composed of small case series, case reports and systematic literature reviews\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. This retrospective review provides real world single institutional experience with the largest cohort of patients to date undergoing provocative mesenteric angiography for occult GIB. Similar to prior reports, this review demonstrated a low rate of complications and high rate of successful endovascular management of positive cases. In contrast to previous data, this study found only a 12% positive provocative angiography rate, while other reports have shown significantly higher positive provocative rates. A principal consideration for the discordance is the low statistical power with small patient samples in prior reports making it hard to determine an accurate expected positive rate. Most prior reports contain fewer than 5 patients with the vast majority of those involving only 1 patient in a case report format.\u003c/p\u003e \u003cp\u003eA recent large systematic review on provocative mesenteric angiography for occult GIB included 27 studies with a total of 230 patients. Various combinations and doses of provocative agents were used and a 48.7% average positive rate across all studies was reported\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. The two largest studies in the systematic review reported positive rates of 44% and 31\u0026ndash;33% but only involved 36 patients each. The explanation for the discordance between the lower positive provocative rates reported herein and prior studies may be explained by several factors.\u003c/p\u003e \u003cp\u003eAnother explanation for discordance is the significant variability in both the combinations and doses of the provocative agents. The above-mentioned systematic review reported a mean dose of 3000 IU for Heparin when used as the sole agent and an overall mean tPA dose of 24 mg. When systemic heparinization was used in combination with thrombolytics a low dose protocol with 5000 IU was the most common and a high dose protocol used 10,000 IU\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. This is in contrast to the much lower mean tPA dose of 7.8 mg in this study and mean heparin dose of 4,958 units being similar to a reported low dose protocol. In the review not every study reported doses used and no data was available for the ones that used nitroglycerin or papaverine as was included in this study, further compounding difficulty in comparing protocols. In a separate individual study tPA was used for provocation and a diagnostic yield of 31% in provoking active bleeding was reported\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Importantly, the reported average tPA dose administered to patients with a positive provocative angiogram was 11.3 mg compared to an average of 9.6 mg of tPA administered in patients with negative provocative angiogram\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Interestingly, the reported average dose of tPA for negative examinations was higher than this studies overall mean tPA dose. This suggests a higher dose of tPA may have resulted in a higher positive rate in this study and emphasizes the need for standardized protocols in future studies.\u003c/p\u003e \u003cp\u003eWhile the above-mentioned factors may have contributed to differences in reported positive rates, it is important to note the intervention success and low rate of complications within this study were similar to prior studies. One of the previously largest single institution retrospective studies involved 34 patients and reported 91% of their positive studies underwent embolization. With this, no hemorrhagic complications occurred, but one case of perforated ischemic bowel was reported\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Another single institution retrospective review conducted over a 12-year period included 36 provocative mesenteric angiograms and reported 100% of the 16 (44%) positive examinations underwent successful embolization with no major or minor complications\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. These are similar to this studies results where 6 (85.7%) of the patients with positive provocative mesenteric angiograms underwent successful endovascular intervention with only 1 immediate minor complication of hypotension and bradycardia occurring. This complication was treated effectively with fluid and atropine administration\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e An inherent limitation of this retrospective review is not having a comparative arm. However, the aim of the report is to describe real world experience with provocative mesenteric angiography in occult GIB involving the largest cohort of patients to date. Additionally, with retrospective analysis there was no opportunity to develop a standardized protocol for provocation. This highlights the real-world nature of this study where often protocols differ not only by institution but also by individual interventionalists.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study describes real world experience with the largest reported single cohort of patients to date undergoing provocative mesenteric angiography for occult gastrointestinal bleeding. This study demonstrated a lower positive rate compared to prior reports but with similar successful endovascular interventions and low complication rates. Discrepancies may be due to the type of medication used, combination of multiple medications, and variability in dosage. Future studies are needed with larger patient samples, standardized protocols and comparative arms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eThis study was conducted with institutional review board approval and complied with the Health Insurance Portability and Accountability Act of 1996. Informed consent was not required for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to it containing protected health information and following compliance with the Health Insurance Portability and Accountability Act of 1996.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJeffrey F. B. Chick is a consultant and speaker for Inari Medical, Guerbet, C. R. Bard, Argon Medical Devices, Boston Scientific, NXT Biomedical, and AiDoc.\u003c/p\u003e\n\u003cp\u003eDavid S. Shin is a consultant for Inari Medical.\u003c/p\u003e\n\u003cp\u003eThe other authors report no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received to support this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHG was the major contributor to writing the manuscript. MAS, DS, JC, and MM were major contributors to the study design, analyzing the data and revisions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRockey DC (2010) Occult and obscure gastrointestinal bleeding: causes and clinical management. Nat Reviews Gastroenterol Hepatol 7(5):265\u0026ndash;279\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThiry GJH, Dhand S, Gregorian A, Shah N (2022) Provocative Mesenteric Angiography: Outcomes and Standardized Protocol for Management of Recurrent Lower Gastrointestinal Hemorrhage. Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract [Internet]. ;26(3):652\u0026ndash;4. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/34506023/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/34506023/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGralnek IM (2005) Obscure-Overt Gastrointestinal Bleeding. Gastroenterology [Internet]. ;128(5):1424\u0026ndash;30. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.gastrojournal.org/article/S0016-5085(05)00596-2/fulltext\u003c/span\u003e\u003cspan address=\"https://www.gastrojournal.org/article/S0016-5085(05)00596-2/fulltext\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBull-Henry K, Al-Kawas FH (2013) Evaluation of Occult Gastrointestinal Bleeding. American Family Physician [Internet]. ;87(6):430\u0026ndash;6. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.aafp.org/pubs/afp/issues/2013/0315/p430.html\u003c/span\u003e\u003cspan address=\"https://www.aafp.org/pubs/afp/issues/2013/0315/p430.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe B, Yang J, Xiao J, Gu J, Chen F, Wang L et al (2017) Diagnosis of lower gastrointestinal bleeding by multi-slice CT angiography: A meta-analysis. Eur J Radiol 93:40\u0026ndash;45\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDurga Thakral DJ, Stein, Saltzman JR (2024) Diagnosis of Occult and Obscure Gastrointestinal Bleeding. Gastrointest Endosc Clin N Am 34(2):317\u0026ndash;329\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim CY, Suhocki PV, Miller MJ, Khan M, Janus G, Smith TP (2010) Provocative Mesenteric Angiography for Lower Gastrointestinal Hemorrhage: Results from a Single-institution Study. J Vasc Interv Radiol 21(4):477\u0026ndash;483\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHegde S, Sutphin PD, Zurkiya O, Kalva SP (2023) Provocative mesenteric angiography for occult gastrointestinal bleeding: a systematic review. CVIR Endovascular. ;6(1)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim CY, Suhocki PV, Miller MJ, Khan M, Janus G, Smith TP (2010) Provocative Mesenteric Angiography for Lower Gastrointestinal Hemorrhage: Results from a Single-institution Study. J Vasc Interv Radiol 21(4):477\u0026ndash;483\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmary RA, Bettmann MA, Cardella JF, Bakal CW, Schwartzberg M, Sacks DB et al (2003) Quality Improvement Guidelines for the Reporting and Archiving of Interventional Radiology Procedures. J Vasc Interv Radiol 14(9):S293\u0026ndash;S295\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalilzadeh O, Baerlocher MO, Shyn PB, Connolly BL, Devane AM, Morris CS et al (2017) Proposal of a New Adverse Event Classification by the Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 28(10):1432\u0026ndash;1437e3\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Occult gastrointestinal bleeding, Provocative mesenteric angiography, Nitroglycerin, Heparin, Tissue plasminogen activator, Endovascular management","lastPublishedDoi":"10.21203/rs.3.rs-6388959/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6388959/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOccult gastrointestinal bleeding is the most common type of bleeding from the gastrointestinal tract and is often a diagnostic challenge. Endoscopic evaluation and radiology studies have relatively low success in identify the source of occult bleeding. Similarly, conventional mesenteric angiography is limited by the intermittent nature of bleeding and bleeding rates below detection threshold. Provocative mesenteric angiography uses pharmacologic agents to promote bleeding for localization and intervention in difficult cases. However, there is significant lack of data regarding the use of provocative mesenteric angiography. This study reports the experience with the largest single cohort of patients undergoing provocative mesenteric angiography for occult gastrointestinal bleeding.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e56 patients underwent provocative mesenteric angiography for occult gastrointestinal bleeding. 7 (12.5%) patients had a positive study, and 49 (87.5%) patients had a negative study. 41 (73.2%), 36 (64.2%), 27 (48.2%), 8 (14.3%), and 2 (3.5%) patients received intra-arterial nitroglycerin, heparin, tissue plasminogen activator, reteplase, or papaverine, respectively. Mean dose of nitroglycerin, heparin, tissue plasminogen activator, reteplase, and papaverine was 227.8\u0026thinsp;\u0026plusmn;\u0026thinsp;274.6 mcg, 4,958.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2839.0 units, 7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 mg, 2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 units, and 18.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1 mg, respectively. Of those with a positive angiogram, 6 (85.7%) patients were managed successfully with endovascular intervention. There was 1 immediate minor complication of hypotension and bradycardia. There were no major complications.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWith the largest cohort of patients to date undergoing provocative mesenteric angiography for occult gastrointestinal bleeding, this study found a lower positive provocation rate compared to prior reports. Nearly all positive cases underwent successful endovascular intervention, with no mortalities and only one minor complication reported. Future studies are needed with larger patient samples, standardized protocols and comparative arms.\u003c/p\u003e","manuscriptTitle":"Provocative Mesenteric Angiography for Occult Gastrointestinal Bleeding: A Single Center Retrospective Review of 56 Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 08:43:04","doi":"10.21203/rs.3.rs-6388959/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":"fe800677-1f89-4fe5-8265-7dbf410d74a8","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-19T10:09:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 08:43:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6388959","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6388959","identity":"rs-6388959","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}