ANVUGIB and Hemostasis

ANVUGIB World Data and Chinese Data

ANVUGIB refers to bleeding caused by non-varicose diseases of the digestive tract above the Treitz ligament, including bleeding of the pancreatic duct or bile duct and bleeding caused by diseases near the anastomosis after gastrojejunal anastomosis. The incidence of ANVUGIB has been declining for nearly 20 years and is now stable. For example, the incidence of ANVUGIB in the United States has decreased from 78.4 per 100,000 in 2001 to 60.6 per 100,000 in 2009, among which the incidence of ANVUGIB caused by peptic ulcer has also decreased from 48.7 per 100,000 to 32.1 per 100,000. The incidence of ANVUGIB in Europe dropped from 55 per 100,000 to 60 per 100,000 in 1990 to the data 25 per 100,000 to 35 per 100,000 in 2000.

A recent retrospective analysis of large number cases in China showed that, compared with that of year 1997 ~ 1998, peptic ulcer bleeding in 2012~2013 was still the most important cause of upper gastrointestinal bleeding (52.7%).

The detection rate of high risk ulceration (Forrest Ⅰ, Ⅰ b, Ⅱ Ⅱ and b) increased (28.2% vs 15.7%). There was no significant decrease in overall case fatality rate (1.7% vs. 1.1%).

Diagnosis of ANVUGIB

1. Symptoms and signs:

Acute upper gastrointestinal bleeding can be diagnosed when the patient presents hematemesis and black stool symptoms with or without dizziness, palpitation, pallor, increased heart rate, decreased blood pressure and other signs of peripheral circulatory failure. Some patients with large blood loss, intestinal peristalsis may also appear with bloody stool. A few patients only have signs of peripheral circulatory failure, without overt bleeding, such patients should be paid with attention to avoid escape of diagnosis.

2. Endoscopic examination:

ANVUGIB can be diagnosed in the cases without esophageal or gastric varices, and bleeding lesions are found in the upper gastrointestinal tract.

3. Misdiagnosis as ANVUGIB should be avoided in the following cases:

Bleeding from certain diseases of the mouth, nose, pharynx or respiratory tract is swallowed into the digestive tract, and certain medications (such as iron, bismuth, etc.) and food (such as animal blood, etc.) can cause black stool. Gastric juice, vomit or fecal occultation blood test should be performed on suspicious patients.

Hemostasis drugs and Endoscopic hemostasis

1．Acid suppression drugs

Acid inhibitors can improve the PH value in the stomach, which can not only promote platelet aggregation and fibrin clot formation, avoid premature dissolution of blood clot, which is conducive to hemostasis and prevent rebleeding, but also can treat peptic ulcer. Commonly used antacid inhibitors in clinical practice include proton pump inhibitors (PPI) and H2 receptor antagonists (H2RA). Commonly used PPI injections include: esomeprazole, omeprazole, pantoprazole, lansoprazole, rabeprazole, epprazole, etc. Commonly used H2RA injections include ranitidine, famotidine, etc. Clinical studies show that:

(1) PPI has a significantly better acid inhibition effect than H2RA, which has a faster onset and can significantly reduce the incidence of re-bleeding. Recently, a large sample size, multi-center, randomized controlled double-blind high-quality study in China showed that the overall hemostasis rate of patients in the epprazole group reached 97.69% in 72 h, which was equivalent to the efficacy of omeprazole in treating peptic ulcer bleeding, and the medication frequency was comparably less.

(2) PPI should be applied as early as possible. It is recommended to give large doses of PPI (80 mg/h) before endoscopic treatment, and continue intravenous infusion (8 mg/h) until endoscopic examination begins. PPI before endoscopic examination can improve the endoscopic performance of bleeding lesions, thus reducing the need for endoscopic hemostasis.

(3) After endoscopic treatment, high-dose PPI can reduce the incidence of re-bleeding in high-risk patients and reduce the mortality. A foreign randomized controlled study showed that after endoscopic hemostasis, intravenous application of large dose of esomeprazole (80 mg intravenous injection +8 mg/h continuous infusion for 72 h) can significantly reduce the risk of postoperative re-bleeding, and also reduce the rate of endoscopic treatment, surgical rate and mortality compared with placebo group.

A multi-center randomized controlled study in China also confirmed the value of intravenous application of large dose of esomeprazole to prevent re-bleeding after endoscopic hemostasis in high-risk ulcers. In addition, studies have confirmed the safety of large dose intravenous administration of esprazole and subsequent oral therapy without increasing adverse events.

For low-risk patients, conventional PPI treatment can be adopted, such as intravenous infusion of esprazole 40 mg for 2 times /d, which is highly practical and suitable for primary hospitals. Suggestions for high-risk patients after endoscopic hemostatic treatment, such as Forrest grading Ⅰ ~ Ⅱ b ulcer, endoscopic hemostatic difficulties or endoscopic hemostatic effect is not decree, merge antiplatelet drugs or NSAIDs, given intravenous high-dose PPI (such as escitalopram omeprazole) in 72 h, Extend high-dose PPI therapy, and then change to a standard dose intravenous, PPI 2 times/d, 3 ~ 5 d, after oral standard dose PPI and ulcer healing. If the condition permits and can tolerate oral drugs, large doses of oral PPI can also be considered to prevent re-bleeding (e.g., esprazole 40 mg/ time, 1 time /12 h, continuous use for 3 days).

For artificial ulcers formed after endoscopic submucosal dissection/endoscopic mucosal resection (ESD/EMR), acid inhibition therapy should be given according to the standards of peptic ulcer. PPI is the preferred drug to prevent bleeding and promote the healing of artificial ulcers after gastric ESD. At present, most studies suggest that the standard dose of PPI should be applied intravenously from the day of operation, 2 times /d, and then change to the standard dose of PPI orally after 2-3 days, 1 time /d, for a course of 4-8 weeks treatment. For high-risk ulcers formed after ESD surgery, the regimen of 80 mg intravenous infusion +8 mg/h continuous infusion for 72 hours can also be used. Studies have shown that the use of PPI before ESD can promote the healing of artificial ulcers, but does not significantly reduce the risk of postoperative bleeding. Currently, there are only a few high-quality studies on whether the use of PPI before ESD can reduce postoperative complications, and more high-quality, large-sample randomized controlled studies are needed. A meta-analysis of 1, 283 patients undergoing endoscopic treatment for upper gastrointestinal bleeding in 10 randomized controlled trials showed that PPI significantly reduced the rate of re-bleeding and the number of patients requiring surgical treatment compared with H2RA. Therefore, large dose of intravenous PPI is recommended for patients with delayed bleeding after gastric ESD after endoscopic hemostasis. Patients with the risk factors of delayed bleeding after ESD surgery and the risk factors of delayed healing of artificial ulcer can increase the dosage of PPI, extend the course of treatment or add protective agents of gastric mucosa .

2．Endoscopic hemostasis

The effect of endoscopic hemostasis is rapid and effective. We recommend endoscopic hemostatic treatment for Forrest grading Ⅰ ~ Ⅱ b bleeding lesions.  Before hemostasis under endoscopy, erythromycin (250 mg intravenous infusion) can be used when necessary for patients with severe massive bleeding or acute active bleeding, which can significantly reduce gastric blood volume and improve endoscopic field of vision, and there is no significant increase in adverse events.

The commonly used endoscopic hemostasis methods include local drug injection, thermal coagulation and mechanical hemostasis. 1∶10000 noradrenalin saline and hypertonic sodium - adrenalin solution (HSE) can be used for drug injection. Thermo coagulation hemostasis includes high-frequency electric coagulation, argon ion coagulation (APC), thermal probe, microwave and other methods. The hemostasis effect is reliable, but certain equipment and technical experience are required. Mechanical hemostasis mainly adopts various hemostatic clips, which are especially suitable for active bleeding, but difficult to operate on some lesions. Clinical evidence shows that the treatment, which combines with thermo coagulation or mechanical hemostasis method, based on drug injection therapy, can further improve the hemostasis effect of local lesions. For part of the initial bleeding after hemorrhage patients with high risks, such as unstable hemodynamic status, severe anemia (Hb < 80 g/L), active bleeding (Forrest Ⅰ/Ⅰ b), giant ulcer (diameter > 2 cm), hemostasis and Forrest Ⅱ class ulcer, etc., can consider to have endoscopic inspection after the hemostasis treatment by PPI. Over-the-scope-clip (OTSC) system is an effective remedy for patients with difficulty in controlling bleeding by conventional hemostasis methods. A recent use of OTSC for recurrent bleeding peptic ulcer hemorrhage in randomized controlled studies have shown that, compared with the standard endoscopic treatment, OTSC therapy could significantly decrease the recurrent rate of bleeding (15% vs 58%). Therefore for the bleeding lesions which are not effective by routine hemostatic methods or recurrent peptic ulcer hemorrhage, OTSC is recommended. For other new hemostasis methods, such as antihaemal powder spraying (Hemospray and polysaccharide antihaemal powder, etc.) and tissue glue injection, it is lacking in high-quality control studies, to compare with traditional hemostasis methods.