INTRODUCTION — Bleeding was the most feared complication when therapeutic biliary endoscopy was first introduced [1]. Because of advances in equipment and experience, it has become a relatively uncommon complication of endoscopic retrograde cholangiopancreatography (ERCP), and it is mostly observed after sphincterotomy. Clinically significant bleeding is uncommon with diagnostic ERCP, apart from sporadic Mallory-Weiss tears and from minor submucosal hemorrhages observed following manipulation of the papilla, particularly in patients with ampullary tumors, a bleeding diathesis, or anatomical variants such as Billroth II gastrectomy [2-4]. Exceptions are case reports in which serious bleeding occurs from injury to the spleen, liver, or abdominal vessels. (See "Uncommon complications of endoscopic retrograde cholangiopancreatography (ERCP)".)
This topic review will focus on the risk factors and treatment of bleeding following ERCP with endoscopic sphincterotomy. An overview of the complications of ERCP and detailed discussions of individual complications are presented separately. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults".)
ASSESSING SEVERITY — Post-ERCP bleeding can be defined as clinically significant or not clinically significant [5] and can be graded as mild, moderate, or severe based upon a consensus definition [6]:
●Mild – clinical evidence of bleeding (ie, not just endoscopic), hemoglobin drop <3 g/dL, and no need for transfusion
●Moderate – need for transfusion (4 units or less), and no angiographic intervention or surgery
●Severe – transfusion of 5 units or more, or intervention (angiographic or surgical)
TIMING — Approximately one-half of bleeding complications occur immediately after sphincterotomy; a delay of 24 hours up to several days is observed in other patients [7-12]. The possibility of late bleeding raises some concern in the context of outpatient therapeutic ERCP [9,13,14].
INCIDENCE — In multiple prospective studies, the reported rate of bleeding related to ERCP is approximately 1 to 2 percent [1,2,7,15-19]. In a review of 21 studies of over 16,000 patients undergoing ERCP, there were a total of 226 bleeding episodes (1.3 percent), with eight deaths (0.05 percent) [20]. Bleeding was severe in 66 of the 226 episodes (29 percent).
RISK FACTORS — The risk factors for bleeding as a result of ERCP that have been identified in one or more studies can be categorized as follows:
●Patient-related factors:
•Coagulopathy [7,21-23]
•Anticoagulation within three days after procedure [7]
•Antiplatelet drugs before and after high risk procedures
•Cirrhosis (Child class C (table 1)) [24]
•Renal failure [23]
•Hemodialysis [21,25]
●Technique-related factors:
•Rapid cutting (ie, "zipper" cut) [22]
•Sphincterotomy length [7,9,26]
•Needle-knife sphincterotomy [22]
•Papillectomy
●Operator-related factor: Low case volume of the endoscopist [2,7] and less experienced endoscopist [27]
Other potential risk factors include extension of a previous sphincterotomy [28], peripapillary diverticulum [28], Billroth II gastrectomy [9], stenosis of the orifice of the papilla of Vater [15], ampullary cancer [22], stone impaction [22], and cholangitis [7]. (See "Endoscopic retrograde cholangiopancreatography (ERCP) after Billroth II reconstruction".)
Risk factors for rebleeding after initial successful endoscopic hemostasis have also been studied. In a single center study including 161 patients with delayed post-endoscopic sphincterotomy bleeding, 35 patients (21.7 percent) had rebleeding after initial endoscopic hemostasis. Factors associated with a higher risk of rebleeding included bilirubin level >10 mg/dL and severe bleeding at the initial presentation [29]. Other potential risk factors for delayed bleeding after endoscopic sphincterotomy include intraprocedural bleeding and skewed direction of incision [30].
PREVENTION — The risk of bleeding can be minimized by identifying patients at risk, taking measures to correct coagulopathy, and using careful technique.
Prothrombin time and platelet count — Our approach is to obtain a complete blood count and prothrombin time/international normalized ratio (INR) before ERCP, particularly if an intervention (such as sphincterotomy) is anticipated [7,31]. A platelet count exceeding 50,000 to 80,000/microL and an INR <1.2 are generally found to be safe [7,32-35]. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Patient preparation'.)
The guidelines from the American Society for Gastrointestinal Endoscopy recommend coagulation studies only in selected patients with active bleeding, a known or suspected bleeding disorder (including a history of abnormal bleeding), an increased risk of bleeding due to medication use (eg, use of anticoagulants, prolonged antibiotic use), prolonged biliary obstruction, malnutrition, or other conditions associated with acquired coagulopathies [36]. However, some endoscopists restrict pre-ERCP coagulation screening to patients with an elevated bilirubin, who are receiving an anticoagulant, or who have a history of a bleeding diathesis [37].
Identifying patients at risk — As a general rule, sphincterotomy is contraindicated in patients with severe coagulation disorders, such as patients with advanced liver disease, in patients with hematologic diseases, and in patients with disorders of hemostasis, such as hemophilia and von Willebrand disease.
Postprocedure observation should be extended in patients with portal hypertension or cirrhosis.
Patients with known platelet dysfunction (such as patients on hemodialysis) should receive appropriate preventive measures, which may include infusion of desmopressin (DDAVP). (See "Uremic platelet dysfunction".)
In addition to the risk factors discussed above, caution is advisable in patients with a papillary tumor. This condition is probably a risk factor for bleeding based upon pathophysiologic and technical considerations and clinical experience [38]. Bleeding rates after papillectomy (also called ampullectomy) range from 2 to 18 percent [39]. (See "Ampullary adenomas: Management".)
Optimizing coagulation abnormalities
Correction of clotting defects — Controversy remains regarding the appropriate use of platelet and coagulation factor transfusions in high-risk patients. Correction of clotting defects with fresh-frozen plasma, vitamin K, or platelet transfusion has permitted successful endoscopic sphincterotomy in patients with cirrhosis [9,32]. Consultation with an expert in coagulation disorders is recommended before performing endoscopic procedures in patients with disorders of hemostasis. (See "Gastrointestinal endoscopy in patients with disorders of hemostasis".)
Antiplatelet drugs — Aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and antiplatelet drugs (ie, ticlopidine, clopidogrel, and prasugrel) have the potential to increase the risk of bleeding [40-43]. The management of antiplatelet therapy can be individualized depending on the thrombotic risk of the patient and the bleeding risk related to the endoscopic procedure. Several professional societies recommend discontinuing clopidogrel and prasugrel before endoscopic sphincterotomy, while aspirin can be continued [4,44]. However, for patients undergoing high-risk procedures (ie, endoscopic ampullectomy), some clinicians elect to also stop aspirin and NSAIDs five to seven days prior to the procedure. Further recommendations regarding the management of antiplatelet agents in patients undergoing endoscopic procedures are discussed separately. (See "Management of antiplatelet agents in patients undergoing endoscopic procedures".)
In a retrospective study of 132 patients taking antiplatelet drugs (aspirin users comprised the largest proportion) who were undergoing endoscopic sphincterotomy, 49 patients continued antiplatelet therapy, while 83 patients stopped antiplatelet therapy <7 days prior to procedure [45]. Post-endoscopic sphincterotomy delayed bleeding was more frequent in patients who continued antiplatelet therapy compared with patients who discontinued antiplatelet agents (14 versus 2 percent).
In a case-control study of over 61,000 patients who underwent ERCP with either sphincterotomy or papillary balloon dilation for choledocholithiasis, the rate of severe bleeding was increased in those receiving anticoagulants compared with non-users for both sphincterotomy (1.6 versus 0.8 percent) and balloon dilation (3.0 versus 0.7 percent) [46].
Anticoagulants — In patients receiving warfarin or heparin, the decision to reverse anticoagulation and the extent of anticoagulation reversal should be individualized based upon the relative risk of the procedure and the underlying condition.
Our approach is consistent with guidelines from several societies:
●For high risk endoscopic procedures in patients at low risk of thrombotic risk, society guidelines recommend discontinuing warfarin five days before the procedure and checking INR prior to the procedure (goal INR <1.5) [44].
●For high risk endoscopic procedures in patients at high risk of thrombosis, warfarin should be temporarily discontinued and substituted with low molecular weight heparin. The approach to bridge therapy and resumption of oral anticoagulants is discussed separately. (See "Perioperative management of patients receiving anticoagulants", section on 'Bridging anticoagulation'.)
●For patients receiving rivaroxaban, apixaban, or edoxaban, the guidelines from multiple societies recommend that the last dose be taken >48 hours before a high-risk endoscopic procedure, and that patients on dabigatran receive the last dose >72 hours before the procedure. The timing of reintroduction of anticoagulation also should be individualized [42]. (See "Management of anticoagulants in patients undergoing endoscopic procedures".)
Endoscopic techniques — The risk of bleeding is increased when sphincterotomy is performed in settings with relatively inexperienced endoscopists [27] or when the endoscopy unit volume is low [2,7]. These observations underscore that technique is of primary importance. Improvement in endoscopic methods may explain the slight decrease in the sphincterotomy-induced bleeding rate observed over time [1,20].
Bleeding can be prevented or limited by proper orientation of the wire, avoidance of "zipper" cuts and unnecessarily long cuts, and judicious use of the electrocautery current [47]. Optimal electrocautery settings are uncertain because of a tradeoff in the risk of pancreatitis versus bleeding. Pure-cut electrocautery current is associated with an increase in the frequency of localized bleeding, which may temporarily obscure the view and interfere with the procedure [48].
Some endoscopists combine pure-cut and blended current in sequence, starting with pure cut and completing the sphincterotomy with blended current [49]. However, this approach did not reduce the rate of clinically significant post-sphincterotomy bleeding in two comparative studies [50,51]. (See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".)
Mixed-current settings automatically vary the intensity of current and current blend according to tissue resistance. A randomized trial from Germany found a reduced rate of minor bleeding following sphincterotomy compared with a conventional current generator [52]. There were no episodes of moderate or severe bleeding. Similar conclusions were reached in a large retrospective study [53] and in a randomized trial [54]. Endoscopically observed bleeding occurred less often in the mixed-current group, but there were no significant differences in clinically evident bleeding. (See "Endoscopic biliary sphincterotomy".)
A retrospective study compared the rate of post-ERCP bleeding in patients with cirrhosis who underwent sphincterotomy with different electrosurgical current generators in two consecutive periods: a conventional electrosurgical current generator applying blended current used up to 2009, at which time it was replaced by a generator applying mixed current. Bleeding was observed in 3 out of 15 patients in the first period, and none out of 14 patients in the more recent period (p = 0.07) [55].
For treatment of small bile duct stones in patients with hemostatic disorders, endoscopic balloon dilation (EBD) can reduce the risk of bleeding compared with standard sphincterotomy [56]. However, EBD has been associated with an increased risk of pancreatitis. (See "Endoscopic balloon dilation for removal of bile duct stones".)
A technique of combining a small sphincterotomy with balloon dilation may reduce the risk of perforation and bleeding [57,58].
Use of a covered sphincterotome to decrease the risk of bleeding was examined in a prospective study [59]. The rationale for using such a device is to provide more controlled cutting and to avoid "zipper" cuts. Use of a partially covered sphincterotome was not associated with a lower frequency of post-endoscopic sphincterotomy bleeding compared with an uncovered sphincterotome.
Submucosal injections have also been studied for the prevention of postsphincterotomy bleeding. In a randomized prospective trial, prophylactic submucosal injection of hypertonic saline-epinephrine seemed to be effective for the prevention of bleeding [60]. Additional studies are needed to determine if this technique should routinely be employed for patients at increased for bleeding.
MANAGEMENT — Post-sphincterotomy bleeding often stops spontaneously and is rarely life-threatening, except in patients with a bleeding diathesis. Most clinically significant bleeding can be managed with medical treatment and endoscopic therapy, which should be performed without delay in patients who have immediate bleeding [1,7]. Angiography or surgery is usually reserved for patients with refractory bleeding. In one study [7], surgery was required in only 2 of 48 bleeding patients (0.08 percent of the overall series). In a study involving 1827 patients, two of 21 patients (0.11 percent) with clinically relevant bleeding required surgery [2].
Endoscopic therapy — A number of endoscopic techniques are used to control bleeding, singularly or in combination: injection therapy, mechanical methods, and thermal methods. When performing endoscopic hemostasis of bleeding after biliary sphincterotomy, it is advisable to avoid any trauma to the pancreatic orifice, which is located below the lower "rim" of the sphincterotomy (image 1) [61].
Injection therapy
●Injection therapy with epinephrine – The most used and generally effective endoscopic intervention is injection therapy with diluted epinephrine (1:10,000) (picture 1 and picture 2) through a sclerotherapy needle [9,11]. Injection of sclerosing agents in combination with epinephrine has also been described [11,17,22,62-64], but extreme caution is required when injecting sclerosants due to the risk of nonselective inflammatory or necrotic effects, which have been documented when these agents have been used to treat bleeding peptic ulcers [65,66].
The efficacy of injection therapy was illustrated in a study that included 1304 patients, 10 percent of whom developed bleeding [22]. Bleeding was initially treated by spraying the area with epinephrine followed by epinephrine injection if bleeding persisted. Patients with a visible vessel were treated with combination therapy with epinephrine injection and absolute alcohol injection (mean volume 0.3 mL). Initial hemostasis was achieved in all patients. However, rebleeding occurred in eight (all of whom initially had moderate to severe bleeding); bleeding was controlled in all these patients with repeated endoscopic therapy.
In a retrospective study, epinephrine injection alone was as effective as epinephrine injection combined with thermotherapy for the management of delayed post-endoscopic sphincterotomy bleeding, but this study had severe limitations. One of the primary limitations is that it is not clear whether the patients were undergoing dual therapy because of epinephrine monotherapy failure [67].
●Injection therapy with fibrin sealant – The injection of fibrin sealant, a two-component adhesive consisting of human fibrin and thrombin with the addition of coagulation factor XIII, has also been successfully used to stop postsphincterotomy bleeding in the case of rebleeding after injection therapy with epinephrine [68]. The injection of a fibrin sealant has potential advantages over sclerosants. (See "Fibrin sealants".)
However, a number of drawbacks should be considered: difficulty of preparation and injection, high cost, potential risk of transmission of infection, and possible occlusion of the pancreatic orifice if the injection is not carefully targeted in the upper rim of the sphincterotomy. It is advisable to secure biliary and pancreatic outflow by placing pancreatic and biliary stents [69].
Mechanical methods
●Endoscopic clip – When injection therapy with epinephrine fails or bleeding recurs, hemostasis can be achieved by precise placement of one or more endoscopic clips at the bleeding site [70,71]. However, clips may be difficult to apply with the side-viewing duodenoscope in the setting of active bleeding. In addition, clips may be inadvertently applied to the pancreatic orifice with the associated risk of pancreatitis. In one series of patients who had uncontrolled endoscopic sphincterotomy-induced hemorrhage, the bleeding was successfully treated by cap-assisted application of endoscopic clip with a forward-viewing endoscope in 9 of 10 patients, with one patient developing mild pancreatitis after the procedure [72].
●Balloon tamponade – Balloon tamponade can be achieved with a standard stone extraction balloon catheter [7,73]. The efficacy of this method has not been well studied.
●Temporary self-expandable metal stent – Temporary placement of a fully covered self-expandable metal stent resulted in immediate hemostasis in five patients with post-endoscopic biliary sphincterotomy bleeding [74]. Other case series described this endoscopic hemostatic technique [75-77]. This form of mechanical tamponade can be considered in select situations, such as in patients with bleeding not responding to other endoscopic measures [78]. However, this method has a number of drawbacks, and stent migration is the main concern. On the other hand, this technique may be effective for both bleeding originating from the papilla and bleeding due to trauma of the common bile duct [76].
Metallic stents are generally not used in the pancreatic duct, but in a case report, a covered pancreatic metal stent (6 mm diameter) stopped massive bleeding after endoscopic pancreatic sphincterotomy for removal of a pancreatic stone [79]. Percutaneous placement of a covered self-expandable stent proved effective in a case of post-ERCP massive delayed bleeding in which endoscopic hemostasis was unachievable [80].
●Endoscopic band ligation – Successful hemostasis by using endoscopic band ligation was reported in a case of severe post-endoscopic sphincterotomy bleeding uncontrolled by other methods [81]. However, endoscopic band ligation at the site of bleeding from sphincterotomy is likely to be technically difficult because it requires use of a forward-viewing endoscope. It also requires that plastic biliary stents be inserted prior to banding in order to protect the biliary orifice.
Thermal methods — Application of electrocautery current is more difficult than injection therapy but can be attempted with the sphincterotome wire [6] or with an electrocautery [82] or heater probe [83] if a visible vessel or a specific bleeding point can be identified [34]. Argon plasma coagulation is another thermal method that can be used cautiously to achieve permanent hemostasis after injection therapy with epinephrine [84].
An extension of the sphincterotomy has been suggested to allow full retraction of a partially severed vessel in cases when brisk bleeding occurs during the procedure [85]. However, sphincterotomy should be fully completed only if required for stone removal.
Hemostatic nanopowder — A nanopowder that promotes hemostasis is being studied in prospective trials. (See "Overview of the treatment of bleeding peptic ulcers".)
In a case of severe delayed bleeding, post-sphincterotomy hemostasis was achieved through the application of 4 g of the hemostatic agent, with no evidence of secondary biliary obstruction [86]. The use of hemostatic nanopowder should be considered as a possible alternative to standard endoscopic therapy in cases where the position, site, or size of the bleeding site makes conventional endoscopic therapy difficult.
Pharmacologic treatment
Recombinant factor VIIa — Recombinant human factor VIIa was effective in stopping bleeding in a patient with a coagulopathy who had delayed bleeding after sphincterotomy [87]. Use of recombinant human factor VIIa as a preventive measure has also been reported in a patient with inherited factor VII deficiency who successfully underwent ERCP with sphincterotomy without bleeding [88]. (See "Gastrointestinal endoscopy in patients with disorders of hemostasis".)
Vasoactive drugs — Infusion of terlipressin in four patients [89] and infusion of nitroglycerin in another case report [90] were effective in controlling hemobilia during therapeutic ERCP in patients with portal biliopathy (intra- and extrahepatic bile duct abnormalities that are a result of portal hypertension).
Angiographic treatment — Celiac or superior mesenteric angiography with transcatheter infusion of vasopressin or embolization of the bleeding artery can be effective but is uncommonly performed as underscored by the paucity of data on this approach [9,91]. It is also worth remembering that arterial embolization is technically difficult and may cause infarction of abdominal organs [92], although studies have shown a reduction in the risk of bowel infarction due to technical improvements and increased experience of advanced endoscopists [93].
In one series, over eight years, 12 embolization procedures were performed in 11 patients for management of post-sphincterotomy bleeding not controlled by endoscopy. Technical success was achieved in 11 of 12 procedures, clinical success was achieved in 10 of 11 patients, and 1 patient was referred for surgical intervention due to rebleeding [94]. (See "Angiographic control of nonvariceal gastrointestinal bleeding in adults".)
Surgery — As mentioned above, the need for surgery has decreased during the past two decades because of success with endoscopic methods [1]. The most commonly performed operation involves conversion of the sphincterotomy into a sutured sphincteroplasty and oversewing the bleeding artery at the apex of the sphincterotomy. If anatomic changes make direct access to the ampulla through the duodenal wall impossible, a Fogarty catheter can be inserted into the common bile duct (either through the cystic duct or a choledochotomy) permitting balloon tamponade of the bleeding point [95]. In older series, surgery was associated with postoperative mortality rates as high as 50 percent, largely because many of the patients treated by ERCP were considered to be too ill for surgery [96].
The infusion of a topical gelatin matrix-thrombin hemostatic agent into the distal portion of the common bile duct during urgent surgical exploration was effective in a patient with life-threatening bleeding after endoscopic sphincterotomy [97]. Further experience is needed to confirm the efficacy of this topical hemostatic agent in cases of bleeding after ERCP. (See "Overview of topical hemostatic agents and tissue adhesives".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endoscopic retrograde cholangiopancreatography (ERCP)".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Clinically significant bleeding is an uncommon complication of diagnostic endoscopic retrograde cholangiopancreatography (ERCP). Bleeding related to ERCP is most often seen following sphincterotomy. (See 'Introduction' above.)
●Post-ERCP bleeding can be defined as mild, moderate, or severe based upon a consensus definition. (See 'Assessing severity' above.):
•Mild – clinical evidence of bleeding (ie, in addition to endoscopic visualization), hemoglobin drop <3 g/dL, and no need for transfusion.
•Moderate – need for transfusion (4 units of packed red blood cells or less), and no angiographic intervention or surgery.
•Severe – transfusion 5 units or more, or intervention (angiographic or surgical).
●The overall risk of bleeding in patients undergoing sphincterotomy is approximately 1 to 2 percent. Most bleeding episodes are mild to moderate in severity. (See 'Incidence' above.)
●The risk of bleeding can be minimized by identifying patients at risk, correcting coagulation abnormalities, and careful technique. (See 'Prevention' above.)
●Post-sphincterotomy bleeding often stops spontaneously and is rarely life-threatening, except in patients with a bleeding diathesis. Most clinically relevant bleeds can be managed with medical treatment and endoscopic therapy, which should be performed without delay in patients who have immediate bleeding. Angiography or surgery is usually reserved for patients with refractory bleeding. (See 'Management' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Francesco Ferrara, MD for his contributions as author to prior versions of this topic review.
