Endoscopic management of procedure-related bleeding
Louis M. Wong Kee Song, Todd H. Baron
Abstract
Bleeding is a common adverse event following invasive endoscopic procedures within the gastrointestinal tract. In a recent lexicon of adverse events following endoscopic procedures, severity of bleeding was defined as mild, moderate, and severe. These definitions are based on need for hospitalization, transfusion, and subsequent interventions. Therapy for procedure-related bleeding includes hemodynamic stabilization, transfusion of blood products, reversal of coagulopathy (if present), and endoscopic, radiologic, and/or surgical interventions. In this article, the approach to procedurally induced bleeding will be reviewed, with an emphasis on endoscopic intervention.
Introduction
Therapeutic endoscopy has become increasingly complex and invasive. Most endoscopic interventions breach vascular structures coursing through the wall of the gastrointestinal (GI) lumen and carry a risk of immediate or delayed bleeding as these vessels are severed. Other interventions can produce cautery-induced ulcers which may then erode into vessels and cause delayed bleeding.
Post-procedural bleeding can range from mild and easily treatable to severe and life-threatening hemorrhage, requiring additional endoscopic, angiographic, or surgical interventions.1 Fortunately, procedure-related bleeding in most instances can be controlled endoscopically (Table 1). Medical stabilization and supportive therapy are also paramount to a successful outcome. In this article, the management of procedure-related bleeding will be discussed, with an emphasis on endoscopic therapy.
Immediate versus delayed bleeding
Immediate bleeding
Intra-procedural bleeding is only considered an adverse event if it causes the procedure to be aborted or alters procedural management.1 For example, post-sphincterotomy bleeding which prevents complete ductal clearance (e.g., a temporary biliary stent is placed) during Endoscopic retrograde cholangiopancreatography (ERCP) and extraction of a bile duct stone is considered an adverse event even if the patient does clinically well without need for transfusion, since an additional procedure will be required for subsequent stone removal. On the other hand, bleeding which does not prevent procedural completion and does not alter management (no need for blood transfusion and hospital admission) is not considered an adverse event. Indeed, intra-procedural bleeding is expected in some procedures, such as endoscopic submucosal dissection (ESD), which is readily managed using monopolar grasping forceps for coagulation of small blood vessels. Site-specific intra-procedural bleeding scenarios that are commonly encountered and their management will be discussed below.
Delayed bleeding
Clinically significant delayed bleeding is defined by hematemesis, melena, and/or hematochezia, with a drop in hemoglobin ≥2 g/dL.1
Initial management
It is important to emphasize that medical stabilization is of utmost importance before endoscopic therapy is undertaken for delayed bleeding. This initial approach is similar to non-procedural related GI bleeding (e.g., variceal, peptic ulcer, diverticular).2 Measures to stabilize the patient include adequate volume resuscitation while avoiding volume overexpansion, transfusion of blood products as appropriate (target hemoglobin levels of 8–9 g/dL in most patients), and reversal of coagulopathy (international normalized ratio <2.5). An increasing number of patients (e.g., those with coronary stents) are receiving antithrombotic agents (anticoagulants and antiplatelet agents), which may require reversal agents, administration of fresh frozen plasma, or platelet transfusion, although this should be done in conjunction with the advice of a cardiologist or internist so that fatal thrombotic events (such as occlusion of coronary stents) do not occur.3 Patients with coagulopathy due to liver disease and those with significant thrombocytopenia (platelet count <50,000) from any cause may benefit from transfusion of fresh frozen plasma and platelets, respectively.
Depending on the severity of bleeding, admission to an intensive care unit may be indicated, especially in elderly patients and those with severe underlying medical conditions (e.g., coronary artery disease). The procedure can then be performed at the bedside with critical care support rather than transporting the patient to the endoscopy suite. In patients with active post-procedural upper GI bleeding (e.g., repeated hematemesis), consideration should be made for endotracheal intubation for airway protection. Adequate sedation is important and may also require anesthesia assistance.
In patients with suspected lower GI bleeding (e.g., recent colon polypectomy), rapid colonic purge administered orally or via a nasogastric tube4 can be performed in those who require urgent colonoscopy based on clinical presentation and severity of bleeding. Standard colonic preparation is adequate in an otherwise stable patient, followed by colonoscopy the following day.
The decision to perform and timing of colonoscopy in patients with post-polypectomy bleeding is not standardized. As most post-polypectomy bleeding stops without intervention, particularly following resection of small polyps, one approach is to administer a bowel preparation and follow the stool pattern. If the patient presented with clinically mild bleeding, has few comorbid medial illnesses, remains hemodynamically stable and the bloody effluent clears with preparation, withholding colonoscopy may be a reasonable option, and one could choose to simply monitor the patient. The other option is colonoscopy within 24 hours for all patients, followed by early discharge in otherwise healthy patients if there are no high-risk stigmata of recent hemorrhage or active bleeding, and when definitive endoscopic therapy is provided. This latter approach is similar to that used for peptic ulcer bleeding.5
Classification of severity of bleeding
Until recently, assessment of the severity of bleeding was not standardized. Standardization of the grade of severity for bleeding is important for several reasons. First, it allows meaningful comparative outcomes between different techniques and among different centers. Second, it allows proper education of the patient so that an informed consent can be made. Finally, it is believed that some health-care systems third-party payers will rely on such information to determine reimbursement in the future.
In an initiative led by Dr Peter Cotton, a working group proposed a lexicon of adverse events.1 In this lexicon, the severity of bleeding is defined the same regardless of the type of procedure. For example, post-polypectomy colonic bleeding is graded the same as post-sphincterotomy bleeding.
There are four grades of bleeding severity: mild, moderate, severe, and fatal (Table 2). The severity is based on effect on the procedure, need for hospitalization, blood transfusion, intensive care unit stay, and additional procedures (endoscopic, radiologic, and surgical). Death due to bleeding is categorized as fatal.
If initial endoscopic therapy is successful but bleeding recurs, additional endoscopic therapy may be useful. Although there are no data to support the benefit of additional endoscopic therapy, data on endoscopic therapy for peptic ulcer bleeding supports this approach.6 If one form of endoscopic therapy has been tried, the same or alternative endoscopic therapies can be employed. For refractory bleeding, interventional radiologic approaches with embolization should be considered before surgery. Surgery may be more appropriate when otherwise indicated (e.g., malignant invasive colorectal polyp).
Hemostatic modalities
Endoscopic
A variety of endoscopic hemostatic approaches can be used to treat bleeding in any area within the GI tract (Table 1). The selection of a particular device(s) is influenced by location and features of the lesion, operator preference, and device availability.
Injection therapies
A dilute epinephrine solution (1:10,000) is typically used to control rapid intra-procedural bleeding which obscures endoscopic visualization. A ceiling volume has not been established, but as much as 30 mL of dilute epinephrine can be injected in a single treatment session. An advantage of epinephrine injection is the field effect achieved via vasoconstriction and tamponade, such that precise localization of the bleeding site is not mandatory and the injection can be applied with relative ease. Since the effects of epinephrine injection are short-lived, the use of adjunctive thermal (e.g., bipolar coagulation) or mechanical (e.g., clips and bands) modalities is recommended, when feasible, to secure hemostasis. Absorption of epinephrine into the bloodstream can lead to tachycardia and hypertension, and though rarely clinically significant, large volume injection should be avoided in patients with underlying coronary artery disease and/or tachyarrhythmias.
Although effective, the injection of sclerosants, such as absolute alcohol, ethanolamine, polidocanol, and sodium tetradecyl sulfate, is generally avoided for non-variceal lesions due to lesion extension and the unpredictable depth of tissue injury caused by these agents. Similarly, the injection of cyanoacrylate (glue) is rarely used for post-procedural bleeding, except for recurrent gastric variceal hemorrhage.7
Thermal therapies
As mentioned above, intra-procedural bleeding commonly occurs during ESD as submucosal vessels are severed. Devices specifically used to control such bleeding include the monopolar coagulation forceps with short, serrated metal jaws to grasp, tent, and coagulate the vessels (Coagrasper®; Olympus Inc., Center Valley, PA, USA) (Fig. 1). This device has the potential to treat other non-variceal lesions in which precise vessels can be grasped.
Contact thermal probes include bipolar electrocoagulation probes (e.g., Gold Probe; Boston Scientific Inc., Natick, MA, USA) and the heater probe (Olympus Inc., Tokyo, Japan). Non-contact thermal probes include argon plasma coagulation (APC; ERBE USA Inc., Marietta, GA, USA; Beamer, ConMed Endoscopic Technologies, Utica, NY, USA). Although thermal probes enable treatment of lesions that are either en face or tangential in location, a disadvantage of coagulation therapy is tissue injury which, when compounded by tissue damage already caused by prior therapy (e.g., hot snare resection), can lead to perforation. In addition, the coaptation pressure applied by contact thermal probes can lead to perforation as well. Inadvertent probe–tissue contact during APC may dissect into tissue causing localized pneumatosis, although this is rarely of clinical consequence.
Mechanical hemostasis
Endoscopic clip placement is attractive for procedure-related bleeding as it does not extend tissue injury. Several through-the-scope (TTS) clips are available for use (Quickclip2, Olympus Inc.; Resolution Clip, Boston Scientific Inc.; Instinct Endoscopic Hemoclip, Cook Endoscopy, Winston–Salem, NC, USA). The goal is to place the clip directly onto the visible vessel or surrounding tissue, which stops the flow of feeding vessels, and multiple clips are often required to secure hemostasis.8 However, disadvantages of clip placement during intra-procedural bleeding include interference with further dissection or resection, use of adjunctive tissue ablation measures, and coagulation hemostatic methods. The long-term clip retention rate is unknown but can occur and interfere with follow-up endoscopic surveillance of neoplastic lesions.9 These clips are also difficult to use with side-viewing endoscopes because of the angulation through which they exit the endoscope.
Recently, an over-the-scope clip (OTSC; Ovesco Endoscopy AG, Tuebingen, Germany) has become available. The setup and deployment are similar to that of a variceal band ligator. The advantage of this device is that it can grasp a much wider area and larger volume of tissue than TTS clips. The device has been used primarily for closure of perforations, but also shown to be effective for control of post-polypectomy bleeding (Fig. 2).10 The rate of OTSC retention long term is unknown but presumably occurs more commonly than with TTS clips.
Although there are little data to support endoscopic band ligation (EBL) for treatment of immediate bleeding other than esophageal varices, they are theoretically useful for this purpose and have been used to treat various non-variceal bleeding lesions.11–14 However, they can only be used with short-length forward-viewing endoscopes because a cap is required and the length of the tripwire (string) is limited. The cap may interfere with endoscopic visualization, particularly in a bloody field, and the deployment string through the working channel impairs suction capability. In addition, areas of deep resection or induration (e.g., delayed post-polypectomy ulcer bleed) might not be amenable to EBL.
One commercially available detachable snare that constricts and ligates tissue (PolyLoop, formerly Endoloop, Olympus Inc.) is most often used for prevention of bleeding during resection of large pedunculated polyps with thick stalks. The detachable loop can be used to treat bleeding after endoscopic resection of pedunculated polyps, but residual stalk at the base of the polyp must be present for the loop to hold.
Hemostatic sprays
Chitosan- and mineral-based hemostatic granules or powders are integrated in first-aid kits used by the military to treat external bleeding from combat wounds. The non-contact spray delivery of similar agents during endoscopy has several advantages, including ease of use, non-requirement for precise targeting, access to lesions at difficult locations (e.g., gastric lesser curve), and ability to rapidly treat a large surface area.12
A dedicated device has received regulatory clearance in some countries for endoscopic delivery of TC-325, a proprietary, inorganic, absorbent powder which rapidly concentrates clotting factors at the treated site to form an adherent coagulum (Hemospray, Cook Endoscopy). Another hemostatic agent used off-label for endoscopic hemostasis is the plant-derived Ankaferd Blood Stopper (Ankaferd Health Products Ltd., Istanbul, Turkey), which forms a protein mesh-work for rapid anchoring of erythrocytes without significantly interfering with individual coagulation factors or platelets.15
The potential for hemostatic sprays is in the treatment of oozing-type bleeding.13 Based on their mechanism of action, they may be of limited value in the absence of active bleeding (e.g., non-bleeding visible vessel), or when bleeding is torrential leading to a rapid “wash away” effect of the hemostatic agent by blood flow.
Cryogenic sprays (liquid nitrogen or CO2) are used primarily for mucosal ablation (e.g., Barrett’s esophagus) and, to a lesser extent, for treatment of chronic hemorrhage caused by gastric antral vascular ectasia or radiation proctopathy. However, cryotherapy is unlikely to be used in most settings of post-procedural hemorrhage as it aggravates bleeding in the immediate thawing period from mucosal friability.
Endoscopic ultrasound-guided hemostasis
Endoscopic ultrasound-guided therapy can be used in centers where this expertise is available and other treatment options have failed. The culprit vessel is identified and targeted injection performed under Doppler control using a standard fine needle aspiration (FNA) needle.14 A variety of injectants have been delivered via endoscopic ultrasound guidance including cyanoacrylate glue, polidocanol, and thrombin.15
Radiologic
Percutaneous intervention consists of selective16–18 or superselective17 angiographic identification and embolization of the feeding vessel(s) causing bleeding. While it is preferable that the lesion is actively bleeding so that vessels(s) can be precisely identified, embolization can still be performed based on knowledge of the endoscopic site and the vascular distribution to the area (e.g., gastroduodenal artery for bleeding duodenal ulcer). In situations where endoscopic intervention was unsuccessful, placement of endoscopic clips in an around the lesion can aid the interventional radiologist to more selectively target the vascular territory of the bleeding site for embolization.
Surgical
At institutions where endoscopists and interventional radiologists are readily available, surgery is considered a last resort for management of procedure-induced bleeding that cannot be controlled by endoscopic or radiologic means. Emergent salvage surgery is rarely needed to prevent death from exsanguination and carries a worse outcome than elective surgery. Ideal lesions for surgical management include small bowel lesions where the area of bleeding can readily be identified and resected, and colonic (non rectal) lesions that are localized, and if proven malignant, would otherwise be best managed surgically. When resection cannot be undertaken (e.g., duodenal bleeding), surgical management consists of duodenotomy and local hemostasis.
Specific conditions
Esophageal varices
Immediate bleeding rarely occurs from band ligation of esophageal varices and may be due to variceal avulsion during suction of the varix into the cap followed by a misfired band or by band slippage after initial successful deployment (Fig. 3), particularly when targeting residual varices amid a scarred esophagus from prior EBL.19 Treatment may consist of a repeat attempt at band ligation, or injection of sclerosant or cyanoacrylate. The use of a detachable loop, with or without glue injection, has also been reported, although it may be technically difficult to entrap smaller varices with surrounding scarring.18,20,21 The experience regarding the use of hemostatic sprays is limited in this setting.
The prevalence of clinically significant delayed bleeding from post-EBL ulcers was 2.74% (23 episodes among 837 EBL) in one study.21 In conjunction with octreotide infusion and a proton pump inhibitor, endoscopic treatment options include EBL and clip placement (Fig. 4), although ulcer induration may hinder their efficacy. The successful use of cyanoacrylate injection has been reported, as well as esophageal balloon tamponade and emergent transjugular intrahepatic portosystemic shunts for uncontrolled and massive bleeding with hemodynamic instability. An alternative option to balloon tamponade is placement of a fully covered, removable esophageal self-expandable metal stent (SEMS), and the successful use of SEMS for EBL-induced ulcer bleeding has also been described.23 Recently, a SEMS designed for esophageal variceal tamponade and atraumatic removability (SX-Ella Danis stent; Ella-CS, Hradec Kralove, Czech Republic) was shown to be effective for the management of esophageal variceal bleeding refractory to conventional therapies,24,25 and should also be effective for post-EBL ulcer bleeding.
Gastric varices
Endoscopic glue injection is the preferred treatment modality for gastric variceal bleeding since sclerotherapy and EBL are associated with high re-bleeding rates.26 Furthermore, post-EBL ulcer bleeding can be massive and fatal due to the ulcer size overlying the gastric varix.27 Intra-procedural and delayed hemorrhage from glue injection occurs typically at the site of the needle puncture. Bleeding is generally controlled with additional injection of glue in the varix. When procedure-related bleeding is uncontrollable during endoscopy, treatment options include emergent transjugular intrahepatic portosystemic shunts or balloon tamponade using a large capacity gastric balloon (e.g., Linton–Nachlas tube).
Endoscopic mucosal resection and ESD
Procedure-related bleeding is most often associated with polypectomy, and post-polypectomy colonic bleeding accounts for 2–6% of acute lower GI bleeding.28,29 Immediate bleeding during ESD is typically managed with the coagulation grasping forceps (Coagrasper®), as described above. Epinephrine injection is used initially for immediate severe bleeding that interferes with visualization during standard snare polypectomy or endoscopic mucosal resection (EMR) techniques, which include cap-assisted EMR, band-assisted EMR, and piecemeal polypectomy with or without submucosal fluid lift. Control of bleeding following epinephrine injection enables completion polypectomy before use of additional techniques, such as clips or thermal coagulation, for definitive hemostasis. Of note, however, placement of endoclips in the midst of a polypectomy procedure may interfere with subsequent resection and completion. When feasible, clip placement is preferable as it does not add to tissue injury, and risk of perforation is likely less compared to thermal modalities (Fig. 5).
In most instances, delayed bleeding from EMR and ESD can be treated successfully via endoscopic means. As noted above, clip placement is recommended, with or without epinephrine injection, although this may not be feasible in the setting of an indurated ulcer base (Fig. 6). The latter may be more conducive to a contact thermal probe and offers some protection to perforation.
Another option for closure of EMR or ESD bleeding defects that are wide is the clip-loop technique. This has been used in treatment of peptic ulcer bleeding22,30 and consists of placing multiple clips at the periphery of the lesion. A detachable snare is then used to bring all the clips together for approximation of the defect. Hemostatic sprays are an attractive alternative for post-EMR or ESD bleeding, although data on long-term efficacy and safety are not available.
Peptic ulcer bleeding
Procedure-related bleeding may occur during attempted endoscopic therapy of a peptic ulcer with high-risk stigmata of recent hemorrhage, such as during coaptive coagulation of a non-bleeding visible vessel or when removing a densely adherent clot overlying an exposed vessel. Such bleeding can be dramatic. Initial therapy consists of epinephrine injection, followed by attempted clip placement or contact thermal coagulation as appropriate. The efficacy of hemostatic sprays in this setting has yet to be determined. If massive uncontrollable bleeding occurs, especially when arising from the posterior duodenal bulb, immediate angiography or surgery is indicated.
Post-sphincterotomy bleeding
Endoscopic management of post-sphincterotomy bleeding differs from other types of endoscopic bleeding because the use of a side-viewing instrument (duodenoscope) is required for optimal visualization of the papilla.31,32 TTS clips have been used to control post-sphincterotomy bleeding (Fig. 7),33 although they tend to function poorly through the duodenoscope. Cap-fitted devices (e.g., EBL and OTSC) are not compatible with a duodenoscope. Injection therapy is easily administered, although a needle designed to work through a side-viewing endoscope (Carr–Locke injection needle; US Endoscopy, Mentor, OH, USA) functions better than standard injection needles with a plastic sheath, which becomes kinked by the elevator of the duodenoscope preventing the needle from exiting the sheath.
Similar to the treatment of peptic ulcer bleeding, 10F contact coagulation probes are preferable to 7F probes, although the 7F probe is easier to pass through the duodenoscope and to bring into position using the elevator.
Tamponade of post-sphincterotomy bleeding has been reported using compliant stone retrieval balloons and rigid dilating balloons. More recently, removable covered biliary SEMS have been used to treat post-sphincterotomy bleeding.34,35
Miscellaneous
Dilation-related bleeding using balloon or polyvinyl dilators is typically self-limited and requires no therapy. Instances of ongoing hemorrhage despite several minutes of observation are usually managed with clip closure of the focal site(s) of bleeding, with or without epinephrine injection.
Clinically significant intra-procedural bleeding following percutaneous endoscopic gastrostomy (PEG) is uncommon but can occur if a vessel is punctured during passage of the trocar through the abdominal wall, as occurs following radiologic percutaneous gastrostomy.36 Pseudoaneurysm formation can occur.18 Endoscopic therapy can be attempted although transmural compression, and tamponade of the bleeding vessel can usually e achieved by securing the external bumper at the skin against the internal bumper of the feeding tube. Delayed bleeding can also occur from ulcers developing beneath the internal bumper that result from excessive traction on the PEG tube. Thus, it is important to loosen the external bumper and advance the PEG tube inward so that endoscopic inspection of the mucosa compressed by the internal bumper can be achieved (Fig. 8).
Direct percutaneous endoscopic jejunostomy is performed less frequently than PEG placement, although it can also cause bleeding, which may occur after traction removal of initially placed tubes that have an internal disk bumper.37 Endoscopic therapy can be undertaken to identify an intraluminal bleeding site; this may require use of balloon enteroscopes. Unlike PEG placement, mesenteric vessels may be injured during initial direct percutaneous endoscopic jejunostomy placement, which are not amenable to endoscopic therapy.15
Transmural (transgastric, transduodenal) drainage of pancreatic fluid collections (pseudocysts, abscess, and necrosis) may result in bleeding as a result of puncture of a blood vessel. Such blood vessels may be coursing through the wall of the organ and can be arterial or venous (intervening varices seen with splenic vein thrombosis). Additional bleeding can be due to vessels coursing within the cavity, such as the splenic artery. Finally, during direct endoscopic necrosectomy, vessels within the cavity, including branches of the portal vein, can be injured during debridement.38 Management of bleeding caused by vessels punctured within the gastric or duodenal wall can be managed by endoscopic injection of epinephrine in combination with coagulation and/or clipping. More recently, endoscopic placement of covered esophageal SEMS across the transmural puncture site to tamponade bleeding has been described.39,40 The SEMS diameter depends on the degree of dilation (if any) of the transmural entry site. One or more side-by-side, covered, 10-mm biliary stents and large diameter (esophageal stents) can also be used.41 In the event of failed endoscopic therapy, embolization is effective for arterial bleeding.21 Surgical therapy may be necessary in some cases.41
Colonoscopy-induced barotrauma is characterized by several linear mucosal breaks, particularly in the right colon, that may result in blood pooling in the colonic lumen. No specific treatment is required aside from decompressing the colon during endoscope withdrawal.42
Initial APC of a large spidery vascular ectasia may result in brisk bleeding, and further APC applications may be ineffective as coagulum formation involves primarily accumulating blood rather than the underlying vascular lesion. Before APC, injection of a small amount of dilute epinephrine close to the center of the vascular ectasia can significantly constrict the size of the lesion and lessen the risk of significant bleeding during APC.
Conclusions
Intra-procedural or delayed bleeding after endoscopic therapy is not uncommon. Procedure-related bleeding can be severe and a source of significant morbidity. In addition to hemodynamic support, most procedure-related bleeding can be managed with a variety of endoscopic hemostatic techniques. The selection of a particular technique(s) is dependent on lesion characteristics and location, device availability, and operator preference. Angiographic and/or surgical interventions are required when endoscopic therapy is not feasible or has failed.
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