Epinephrine

Because of its widespread availability, low cost, and simplicity, local epinephrine is the most commonly used injective therapy. Epinephrine is usually injected as diluted 1:10,000 or 1:20,000 saline solution by a standard needle at 0.5- to 2-mL aliquots per injection. Higher doses of injected epinephrine are more likely to cause cardiovascular side effects, particularly when injected around the region of gastroesophageal junction and the distal esophagus; some endoscopists advocate the use of more diluted solution (1: 100,000) to avoid complications.

Injections are placed tangentially into and around the bleeding source until the bleeding halts or slows and the surface becomes pale.

The proposed mechanisms of action of epinephrine injection involve the following :

• 1.
  

  Local tamponade effect induced by the volume of solution injected with vessel squeezing;

  
  
• 2.
  

  Vasoconstriction but not vessel thrombosis;

  
  
• 3.
  

  Direct effect on the clotting process at the site of the arterial defect (platelet aggregation).

Different studies have investigated the optimal volume needed to obtain a hemostatic effect of epinephrine. Injection of large volumes (13–20 mL) of epinephrine is superior to low volumes (5–10 mL) in reducing the rate of recurrent bleeding in high-risk patients. Also, data from Korea showed that injection of 35 to 45 mL of epinephrine was more effective in preventing recurrent bleeding from ulcers in the gastric body than injection of 15 to 25 mL (0% vs 17.1%). Although endoscopic injection of epinephrine is considered safe, the injected volume of epinephrine should not be unlimited, because of the risk of systemic absorption. Even if infrequent, adverse cardiac events have been described after a high volume (30 mL) of epinephrine for treatment of a bleeding Mallory-Weiss tear.

Sclerosants

Sclerosants agents, such as polidocanol, ethanol, and ethanolamine, induce local inflammation and subsequent fibrosis, obliterating the lumen of the vessel. The technique is similar to that used for epinephrine, but volumes are much smaller (usually a maximum of 1 mL, divided in 0.1–0.3 mL aliquots per injection at 3–4 sites around or into the visible vessel) due to the potential risk of ulceration, necrosis, and perforation described for those agents. In clinical trials, when tested in combination with epinephrine, no additive effect of sclerosants was observed, either as a subsequent injection or as a mixture of the 2. Moreover, polidocanol has been associated with transmural necrosis, and injections in the gastric fundus are contraindicated because of the risk of late perforations. If ethanol is used, caution is recommended to avoid tissue necrosis and perforation.

The use of sclerosants for NVUGIB should be avoided in routine practice but still can be considered a valuable alternative option to treat bleeding lesions when a second method is not feasible.

Cyanoacrylate

N -butyl-2-cyanoacrylate is a tissue adhesive that on contact with water polymerizes into a firm clot. It is commonly used in Europe in the treatment of bleeding varices and has been tested also for the treatment of refractory peptic ulcer bleeding.

The glue can be used either undiluted or as a mixture of cyanoacrylate and lipiodol, an oily contrast agent to delay polymerization. The injection technique is not as user-friendly as an epinephrine injection because the glue hardens quickly and there is the potential risk of damaging the endoscope, the operator, and patient if the glue is accidentally dispersed.

Briefly, the technique of acrylate injection is as follows:

• •
  

  The 21-G or 23-G metal luer-lock injector needle must be preinjected with sterile water;

  
  
• •
  

  Acrylate glue is then slowly injected directly into the bleeding point (the glue is sticky with a considerable resistance to injection). To minimize the risk of embolization, not more than 1 or 2 mL glue is injected.

  
  
• •
  

  Glue injection is immediately followed by 2 to 4 mL of distilled water to deliver the glue from the “dead space” of the catheter. The endoscopy assistant announces the end of this second injection, and the operator retracts the needle.

At the end of the injection procedure, the glue spills with formation of a hard plug obliterating the bleeding point. If the bleeding persists more than 60 seconds after the first injection, a second 1 mL can be injected with the same modality. If the glue sticks to the lens, the endoscope should be withdrawn and cleaned with ethanol or nail polish remover immediately. The endoscopy assistant should be well trained in the injection technique; the presence of a second nurse is recommended for preparing the additional injection catheters and cyanoacrylate vials. Care must be taken to protect the eyes of the patient and the clinical personnel. Goggles are required for eye protection during preparation and injection of the glue.

In a randomized trial comparing cyanoacrylate with hypertonic saline-epinephrine injection in 126 patients with high-risk bleeding peptic ulcers, there were no differences in outcomes between the 2 groups, but 2 cases (1 fatal) of arterial embolization occurred in the cyanoacrylate group. This complication was also reported in other case series (as both arterial and portal venous embolization). Cyanoacrylate has also been successfully used to treat bleeding Dieulafoy lesions and as a spray to treat difficult-to-control malignant and nonmalignant GI bleeding.

In the endoscopy setting, acrylate glue injection should be limited to selected cases of refractory nonvariceal bleeding as rescue therapy in patients after failure of conventional endoscopic therapies.

Fibrin glue

Fibrin glue is a 2-component system in which concentrated fibrinogen and factor XIII are combined with thrombin and calcium to simulate the final stage of the clotting cascade. Components are injected either as a subsequent injection in a standard 23-G injector needle or as a mixture of the 2 trough, a special dual-channel needle, to mix and activate the clotting cascade only when injected.

In patients pretreated with epinephrine, multiple fibrin sealant injections were associated with less recurrent bleeding compared with polidocanol. Other studies did not confirm any advantage in adding the fibrin glue to epinephrine injection alone. The precise role for fibrin sealant remains to be defined. Moreover, because the substance is relatively expensive and its use can be associated with the potential transmission of infectious diseases today, the use of fibrin glue is discouraged as a primary treatment modality.

Sodium hyaluronate

Sodium hyaluronate is a natural polysaccharide with peculiar viscoelastic characteristics that make it an excellent candidate for endoscopic submucosal dissection because of its ability to create a persistent submucosal cushion. In 2 case reports, sodium hyaluronate has been used to successfully achieve endoscopic hemostatic in bleeding ulcers; however, clinical trials are needed.