Gastroesophageal variceal hemorrhage is a medical emergency with high morbidity and mortality. Endoscopic therapy is the mainstay of management of bleeding varices. It requires attention to technique and the appropriate choice of therapy for a given patient at a given point in time. Subjects must be monitored continuously after initiation of therapy for control of bleeding, and second-line definitive therapies must be introduced quickly if endoscopic and pharmacologic treatment fails.
Key points
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Gastroesophageal variceal hemorrhage is a medical emergency with high morbidity and mortality.
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Endoscopic therapy is the mainstay of management of bleeding varices.
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It requires attention to technique and the appropriate choice of therapy for a given patient at a given point in time.
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Subjects must be monitored continuously after initiation of therapy for control of bleeding, and second-line definitive therapies must be introduced quickly if endoscopic and pharmacologic treatment fails.
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An appropriate surveillance plan must be established for prevention of future bleedings.
Introduction
Gastroesophageal varices (GOVs) are present in approximately 50% of patients with cirrhosis, more so with Child C cirrhosis (up to 85%). Rupture of these varices constitutes a medical emergency and can be rapidly fatal unless quickly controlled. Acute variceal bleeding occurs in a yearly rate of about 5% to 15% in subjects with varices and, despite advancement in diagnostics and therapy, the 6-week mortality from variceal bleeding can be as high as 20%. Prompt diagnosis is a key factor in effective and timely management of these patients. Focused history, directed physical examination, and basic laboratory measurements are important parts of the triage to plan resuscitative measures, timing of endoscopy, other therapies, and for prognostication. In later discussion, the role of endoscopy in the diagnosis and management of bleeding gastr-esophageal varices is discussed.
Introduction
Gastroesophageal varices (GOVs) are present in approximately 50% of patients with cirrhosis, more so with Child C cirrhosis (up to 85%). Rupture of these varices constitutes a medical emergency and can be rapidly fatal unless quickly controlled. Acute variceal bleeding occurs in a yearly rate of about 5% to 15% in subjects with varices and, despite advancement in diagnostics and therapy, the 6-week mortality from variceal bleeding can be as high as 20%. Prompt diagnosis is a key factor in effective and timely management of these patients. Focused history, directed physical examination, and basic laboratory measurements are important parts of the triage to plan resuscitative measures, timing of endoscopy, other therapies, and for prognostication. In later discussion, the role of endoscopy in the diagnosis and management of bleeding gastr-esophageal varices is discussed.
Endoscopic diagnosis of variceal hemorrhage
The key objectives of the initial evaluation of a subject with suspected variceal bleed include assessment of the severity of bleeding, identification of the source of bleeding, and risk assessment of prognosis, including the presence of infection and complications. Once therapy is initiated, ongoing assessment of bleeding control is required to determine the need for second-line interventions. Endoscopy plays a critical role in these processes and is central to the management of active variceal bleeding.
Any upper gastrointestinal bleeding in a patient with known cirrhosis or evidence of portal hypertension should be considered and managed as a case of variceal bleeding until proven otherwise by endoscopy. Esophagogastroduodenoscopy is considered the gold standard for the diagnosis of gastroesophageal variceal bleeding. It can be performed at the bedside in the emergency department, and therapy can be provided at the same time when diagnostic assessment is performed. In the setting of active bleeding, a diagnosis of variceal hemorrhage is based on demonstration of bleeding varices, stigmata of recent bleeding (eg, an adherent clot over a varix or a platelet plug [white nipple sign]), or the presence of varices and upper gastrointestinal bleeding without other obvious identifiable sources of bleeding ( Box 1 ). The location of the varices is also identifiable at the time of endoscopy along with assessment of the size of the varices. These data are needed for both the diagnosis and the determination of the optimal approach for long-term bleeding control.
Esophagogastroduodenoscopy is the gold standard for the diagnosis of acute variceal bleeding. A diagnosis of gastroesophageal variceal bleeding is made if any of the following criteria is satisfied:
- 1.
Direct visualization of blood (spurting or oozing) arising from an esophageal or gastric varix.
- 2.
Presence of gastroesophageal varix with signs of recent bleed (stigmata) such as white nipple sign or overlying clot.
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Presence of varix with red signs plus presence of blood in the stomach in the absence of another source of bleeding.
- 4.
Presence of varix with red signs (cherry red spots: small, ∼2 mm, red, spotty flat spot on the variceal surface, red wale signs, longitudinal read streaks on the variceal surface, hematocystic spots, large, >3 mm, round, discrete, red raised spots on the variceal surface) and clinical signs of upper gastrointestinal bleeding, without blood in the stomach.
Timing of Endoscopy
Ideally, endoscopy should be performed as soon as the proper resuscitation has taken place and hemodynamics have been stabilized. American Association for the Study of Liver Diseases guidelines suggest timing of endoscopy to be within 12 hours for acute variceal bleeding. In a retrospective study of patients who presented with acute variceal bleeding but were hemodynamically stable, there was no significant difference in mortality in patients with endoscopy performed within 4 hours versus 8 hours or 12 hours. In contrast, another study found delayed endoscopy (endoscopy time >15 hours) as a risk factor for increased mortality in acute variceal bleeding. It is the authors’ opinion that the urgency is dictated by the severity of bleeding and the clinical setting. For example, a patient who is exsanguinating needs immediate therapy to stop bleeding, whereas care could be delayed until hemodynamics are fully stabilized in those with less severe bleeding. Also, the presence of comorbidities, such as cardiac disease and such, and the ability to tolerate hemorrhagic anemia must also be taken in to account when making the decision to proceed rapidly versus not so rapidly toward endoscopy.
Utility of Endoscopy for Diagnosis of Variceal Hemorrhage
Endoscopy provides direct visualization of varices and is the cornerstone of the diagnostic approach to confirm the presence of variceal hemorrhage. There are, however, occasional situations wherein it may be difficult to visualize bleeding varices. The most common situation is a large clot in the fundus of the stomach that prevents an adequate retroflexed view of the cardia and the gastroesophageal junction. Several modalities can be attempted to improve the ability to diagnose variceal bleeding in this setting. If the blood pressure permits, one may raise the head end of the bed to allow the clot to pass to the antrum. There are only anecdotal reports of the utility of this maneuver. More commonly, a prokinetic agent such as erythromycin has been used for this purpose. A recent meta-analysis suggests that this may improve visualization of gastric varices. It must be noted, however, that none of the published trials are of very high quality.
Is Airway Protection Required for Urgent Endoscopy for Bleeding Varices?
This topic is frequently debated. Airway compromise can occur before endoscopy, during endoscopy, and in the period after endoscopy when the subject may not have fully recovered from sedation. One retrospective study did not find any benefit for prophylactic airway intubation before endoscopy. However, this study did not address the expertise of the intubators and the potential for selection bias. In a previous uncontrolled study, prevention of aspiration was associated with a substantial improvement in mortality in a subset of patients with severe uncontrolled variceal bleeding despite first-line therapies. Based on these first-line therapies, the authors currently recommend airway protection in those subjects with severe active hematemesis and those who are unable to protect their airway and are at high risk in the periprocedural period.
Specific therapies for esophageal variceal bleeding
Endoscopic Variceal Band Ligation
Principles of band ligation
Endoscopic variceal band ligation (EVBL) is the cornerstone for the management of acute variceal bleeding. The principle for band ligation is based on the venous drainage system in the esophagus. Vianna and colleagues described 4 zones in the esophagus: gastric, palisade, perforating, and truncal zones. The gastric zone extends 2 to 3 cm below the gastroesophageal junction and drains in short gastric and left gastric veins. The palisade zone extends 2 to 3 cm superior to the gastric zone and is a watershed area between portal and systemic circulation. The perforating zone extends 2 cm further above the palisade zone and has perforating veins joining submucosal venous plexuses to paraesophageal venous plexuses. The truncal zone is 8 to 10 cm long and has perforating veins joining submucosal veins to extraesophageal veins. The palisade and perforating zones are important for esophageal varices ligation. The objective is to obliterate the submucosal veins in the palisade zone, which is followed by thrombosis and obliteration of the perforating veins that connect the submucosal varices to extraesophageal collaterals.
Consequences of endoscopic variceal band ligation
The pathologic changes after EVBL have been evaluated in canine models and humans. Variceal ligation results in ischemic necrosis of banded tissue and thrombosis of varices (24–48 hours). The resultant mucosal ulceration takes 2 to 3 weeks for complete re-epithelialization. It has been reported that with complete variceal obliteration, the risk of portal vein thrombosis may be increased and the development of gastric varices may be facilitated. Portal hypertensive gastropathy may also worsen after successful esophageal variceal eradication by EVBL.
Technique
Initially, single-band devices were used. It was cumbersome to use single-band devices because it involved reloading and reintubating the esophagus multiple times. To overcome this limitation, multiple band shooters, including the Saeed Multiple Ligator (Wilson-Cook Medical, Inc, Winston-Salem, NC, USA) and the Speedband (Boston Scientific Corporation, Natick, MA, USA), were developed. The Saeed Six-Shooter is a safe and effective method to eradicate varices. The band ligator is attached to the shaft of endoscope. After advancing the endoscope toward the varix that needs to be banded, suction is applied until “red out” occurs and then the band is fired. It is important at this point not to release suction until after a band has been successfully applied; this is required to minimize the risk of iatrogenic bleeding. The bands are placed in distal 5 cm of the esophagus in a spiral fashion from the gastroesophageal junction and moving upwards. This placement is dictated by the thickness of the overlying mucosa, which is the least at the gastroesophageal junction, thereby making this region particularly prone to bleeding.
Efficacy
In 1991, Stiegmann and colleagues published a landmark study on the superiority of EVBL over endoscopic injection sclerotherapy (EIS) for active variceal bleeding. EVBL had fewer complications and rebleeding rates compared with EIS. The 2 techniques were equally effective (approximately 90%). EVBL required a smaller mean number of sessions (3.5 sessions) compared with EIS (4 sessions). A recent meta-analysis showed better bleeding control and low mortality with EVBL compared with EIS. In another meta-analysis, a combination of EVBL with EIS offered no advantage over EVBL alone in the prevention of rebleeding or reducing mortality. On the other hand, stricture formation was higher after EIS compared with EVBL alone.
Complications
Risk of complications after banding varies from 2% to 23%. Chest pain, infection, stricture, and ulcers are complications seen. The incidence of ulcer bleeding after banding is 2.6% to 7.3% and has been associated with Child B or C cirrhosis. In the absence of active bleeding, it can be managed conservatively. For actively bleeding ulcers, one needs to consider alternate endoscopic therapies including sclerotherapy or transjugular intrahepatic portosystemic shunt (TIPS). Pantoprazole given for 10 days has been shown to decrease the size of the ulcers. It does not affect symptoms like chest pain and dysphagia, however.
Combination endoscopic treatment with pharmacologics is better than either treatment alone for active bleeding and has been confirmed in numerous trials, which have now been assessed by meta-analyses. Combination therapy was associated with improved bleeding-related outcomes (relative risk [RR] = 1.21, confidence interval [CI] −1.13 to 1.30, P <.001) and survival advantage (RR 0.74, 95% CI 0.57–0.95, P = .02) compared with EVBL alone.
Endoscopic Injection Sclerotherapy
Sclerosants are chemical agents that are an oily or an aqueous solution when injected in or around the varices, inducing sclerosis. Several such agents have been used to induce phlebitis and thrombosis of varices with subsequent obliteration. Sodium tetradecyl sulfate, sodium morrhuate (5%), sodium ethanolamine (5%), polidocanol, and absolute alcohol have all been used for control of variceal hemorrhage. Only sodium tetradecyl sulfate is US Food and Drug Administration (FDA) approved for this indication.
Technique
The type of needle used is usually a 23 G or 25 G. Injections can be made in to the varices (intravariceal injection) or around the varices (paravariceal injection). For the intravariceal technique, the first injection is usually made just below the bleeding site in the varix. Subsequent injections are made at all the varices around the gastroesophageal junction. Proximal injections are made at 2-cm intervals up to 5 to 6 cm from the gastroesophageal junction. For the paravariceal technique, the injection is made adjacent to the varix. There is no convincing evidence that one technique is better than the other. Also, even in expert hands, intravariceal injections often result in paravariceal spillover.
Efficacy
EIS is 60% to 100% effective in controlling active esophageal variceal bleeding. Treatment is repeated at 1- to 3-week intervals until obliteration and then every 3 months. EIS is not recommended for primary prophylaxis. Effectiveness of different sclerosants has been studied. From currently available data, one agent cannot be recommended over the others. Currently, EIS is generally restricted to the very uncommon situation wherein EVBL is not technically feasible, mainly due to its adverse event profile noted in later discussion. Nonetheless, EIS can and should be considered a rescue therapy if EVBL is not successful or results in further bleeding. However, TIPS should be the preferred alternate whenever feasible because it has been shown to improve survival.
Complications
Chest pain is noted in about 10% of patients after sclerotherapy. Ulcer formation is noted in 20% to 60% of cases. The volume of sclerosant and Child C cirrhosis has been associated with the risk of ulcer formation. When performed, the volume of sclerosant per site should not exceed the recommended amount (volume injected depends on sclerosant used) to avoid the risks associated with EIS. Ranitidine has been shown to hasten healing of ulcers but does not prevent ulcer formation. Stricture formation may occur in up to 40% of cases. Most strictures are asymptomatic. Symptomatic strictures respond well to endoscopic dilation. Risk of rebleeding is 15% to 50% in the first 24 hours. Other rare complications include perforation, mediastinitis, pericarditis, pneumothorax, spinal cord paralysis, and mesenteric vein thrombosis. There are few case reports of esophageal squamous cell carcinoma after sclerotherapy.
Esophageal Stents
Endoscopic stent placement for control of active esophageal bleeding
Over the last 5 years, several studies have demonstrated the feasibility of controlling active bleeding from esophageal varices with an endoscopically placed stent in the esophagus. Initial bleeding control rates of 80% to 90% have been reported with minimal side effects. Also, the stent placement can occur at the bedside, can come in handy as a rescue therapy, and can buy time for those with severe bleeding who will need a more definitive treatment such as TIPS. One of the stents evaluated in such settings is a fully covered self-expandable metal stent, SX-Ella Danis stent (135 × 25 mm; ELLA-CS, Hradec Kralove, Czech Republic). It has atraumatic edges and is a fully covered metal stent. The stent can be easily removed after 7 days.
Endoscopic Therapy for Secondary Prophylaxis of Esophageal Variceal Hemorrhage
Left untreated, survivors of an index bleed have a 70% probability of rebleeding within a year; this is associated with a high mortality as well. It is therefore imperative to plan treatment to prevent subsequent bleeds. TIPS is rapidly becoming a front-line approach for secondary prophylaxis and should be considered especially among patients with high risks of treatment failure with EVBL. In its absence, a combination of EVBL and nonselective β-blockers constitutes the standard of care of prevention of variceal rebleeding. Multiple trials have evaluated and demonstrated that combination therapy is superior to either EVBL alone or pharmacologic therapy alone for secondary prophylaxis. Combination therapy reduces the risk of esophageal variceal rebleeding by more than 20%. EVBL is generally performed at 2- to 4-week intervals until varices are obliterated. Generally about 3 to 5 sessions are needed for complete obliteration. There are, however, rare instances where varices persist despite 5 to 6 sessions. In such cases, it has been the authors’ personal experience that one should suspect underlying portal vein thrombosis and, in the absence thereof, move toward TIPS.
Once varices are obliterated, repeat endoscopy is indicated at 3- to 6-month intervals to detect recurrent varices. When present, EVBL should be used again to obliterate these varices. Endoscopic ultrasound was at one time advocated for early diagnosis of recurrent varices. However, currently its use is not supported by evidence from clinical trials. The authors typically perform endoscopy at 2- to 4-week intervals until obliteration of varices. Surveillance endoscopy is performed at 3 to 6 months and then every 6 to 12 months to check for variceal recurrence.
Endoscopic management of gastric variceal hemorrhage
Anatomy of Gastric Varices
Gastric varices occur approximately 20% of the time among patients with cirrhotic portal hypertension. Unlike esophageal varices, gastric varices are a rather heterogeneous group of disorders and their cause and pathophysiology can be different. Gastric varices can also develop in the absence of cirrhosis, primarily due to splenic vein thrombosis or other thrombophilic conditions, such as polycythemia vera and other hypercoagulable conditions.
Classification of Gastric Varices
The most widely used classification system is the Sarin classification, which categorizes gastric varices into 4 types based on location and in relation to esophageal varices. Gastric varices in the presence of esophageal varices are defined as GOVs. GOVs are thought to be an extension of the esophageal varices. Type 1 GOVs (GOV1) are gastric varices that occur along the lesser curvature, whereas gastric varices present along the fundus are defined as type 2 GOVs (GOV2). Gastric varices with no concurrent esophageal varices are called isolated gastric varices (IGVs). IGVs are further classified into type 1 (IGV1) when they are present in the gastric fundus or type 2 (IGV2) if present elsewhere in the stomach or first portion of the duodenum. GOV2 and IGV1 are sometimes grouped together and referred to as “fundic varices” ( Fig. 1 ).
Related posts:
Advances and Improvements in the Management of Upper Gastrointestinal Bleeding
Epidemiology and Risk Factors for Upper Gastrointestinal Bleeding
Role of Medical Therapy for Nonvariceal Upper Gastrointestinal Bleeding
Injection and Cautery Methods for Nonvariceal Bleeding Control
Unusual Causes of Upper Gastrointestinal Bleeding
Tips and Tricks on How to Optimally Manage Patients with Upper Gastrointestinal Bleeding
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