Gastrointestinal bleeding

Japanese: 消化管出血

Concept Gastrointestinal bleeding generally refers to a condition with symptoms such as hematemesis, bloody stool, and bloody stool, but also includes cases where a health check reveals positive results for occult blood in the stool. Hematemesis is the vomiting of blood from the mouth, and is believed to be due to bleeding from the upper gastrointestinal tract oral to the ligament of Treitz. Hematemesis can be characterized as fresh blood or coffee ground-like vomit. This change depends on the time the blood remains in the stomach. Bleeding from the esophagus results in fresh blood, but when blood accumulates in the stomach it mixes with gastric acid and the hemoglobin is reduced to hematin, which appears dark red. Vomit that is expelled due to this change in color is described as coffee ground-like vomit.
Hematochezia is defined as the excretion of stool that has turned black or tarry due to blood from the anus. Bloody stool refers to the presence of fresh blood in the stool, or on the surface of the stool, or the excretion of fresh blood itself. Clinically, the term hematochezia is used to refer to any bloody stool. Black stool occurs when bleeding from the upper gastrointestinal tract occurs when the blood is affected by gastric acid, resulting in the excretion of stool mixed with black blood. Bleeding from the left colon/rectum or anus is fresh blood. Upper gastrointestinal bleeding accounts for 60-70% of gastrointestinal bleeding. Half of upper gastrointestinal bleeding is due to gastric or duodenal ulcers. In addition to peptic ulcers, other common causes include ruptured esophageal varices, acute gastroduodenal mucosal lesions (AGML or ADML), Mallory-Weiss syndrome, gastric cancer, and anastomotic ulcers (Table 3-2-8).
Causes of lower gastrointestinal bleeding include ischemic colitis, antibiotic-induced enteritis, colonic diverticulum, hemorrhoids/anal fissures, colon cancer/polyps, and ulcerative colitis (Table 3-2-9). Upper gastrointestinal bleeding must also be kept in mind as a cause of bloody stool. Other causes of hematemesis and bloody stool include diseases of organs adjacent to the gastrointestinal tract, such as the liver, bile duct, and pancreas; blood diseases, such as leukemia, hemophilia, and coagulation disorders; vascular diseases, such as Rendu-Osler-Weber disease; amyloidosis, sarcoidosis, and collagen diseases (Table 3-2-10).
Pathogenesis and differential diagnosis
1) Understanding the patient's overall condition and estimating the amount of bleeding:
In order to determine the severity of hematemesis and bloody stool, it is urgent to assess the patient's overall condition from physical findings, in particular to check for the presence or absence of shock. The amount of bleeding can be estimated from vital signs such as blood pressure, heart rate, and respiratory rate, as well as symptoms such as state of consciousness, urinary volume, and facial pallor (Table 3-2-11, Miyazaki, 1976). The presence or absence of anemia, yellowing of the conjunctiva and skin, and the presence or absence of ascites are also important. Palpation should be used to check for abdominal tenderness, the presence of peritoneal irritation, and the presence or absence of a mass or lymph node swelling. In the case of bloody stool, a rectal examination is necessary to confirm its nature. Other tests that should be performed to assess the patient's overall condition include blood gas tests, oxygen saturation measurements, and an electrocardiogram. A chest X-ray is an essential test to confirm the presence of free air and rule out gastrointestinal perforation.
2) Whole body management:
Systemic management during shock involves securing blood vessels, administering fluids and blood transfusions to stabilize circulatory dynamics. In addition, necessary treatments such as securing the airway and administering oxygen inhalation are performed. In addition, central venous pressure measurements, electrocardiograms, arterial pressure monitoring, and urine volume measurements are performed as necessary.
3) Medical History:
It is important to take a medical history of patients with hematemesis or bloody stool. The source of the bleeding can be estimated based on the amount and color of the blood. In the case of hematemesis, if the blood is fresh, first consider ruptured esophageal varices. If the blood is black, consider bleeding from a gastric or duodenal ulcer. In the case of bloody stool, black stool suggests bleeding from the upper digestive tract, while bright red or fresh blood suggests bleeding from the colon or anus. Accompanying symptoms (abdominal pain, diarrhea, nausea/vomiting, fever) are also important in estimating the underlying disease. Medical history, medications taken, lifestyle habits, and family history should also be confirmed. In addition to a history of gastrointestinal disease, questions should be asked about a history of liver disease such as cirrhosis, the use of NSAIDs (non-steroidal anti-inflammatory drugs), steroids, or antibiotics, and whether or not the patient has consumed alcohol. Recently, the number of cases in which anticoagulants and antiplatelet drugs are used to prevent cerebrovascular disease and ischemic heart disease has been increasing, and these can cause gastrointestinal bleeding, so this should be confirmed during the interview. Fresh blood in the rectum after taking antibiotics raises the possibility of antibiotic-induced hemorrhagic enteritis. Bleeding accompanied by vomiting after heavy alcohol consumption raises the possibility of Mallory-Weiss syndrome. If there is a history of chronic alcohol consumption, rupture of esophageal or gastric varices due to liver disease should also be suspected.
4) Blood and physiological tests : General blood tests include measuring red blood cell count, hemoglobin, and hematocrit values to check for anemia. In cases of sudden, heavy bleeding, the drop in hemoglobin value may only be mild, so caution is required. White blood cell and platelet counts are also checked. Blood biochemistry tests are performed to identify abnormalities in the liver and biliary system, or abnormalities in renal function. A characteristic of upper gastrointestinal bleeding is that blood urea nitrogen (BUN) increases early on as the blood passes through the small intestine. Electrolyte measurements are necessary to estimate fluid balance and determine the amount of fluid administered.
5) Emergency endoscopic examination : In the event of shock, stabilization of hemodynamics is the first priority, but emergency endoscopic examination should be proactively performed to identify the source of bleeding. During the examination, the patient's overall condition should be monitored using an electrocardiogram and pulse oximeter. If there is hematemesis, an upper gastrointestinal endoscopy should be performed, but if there is black stool, an upper gastrointestinal endoscopy should be performed first. If there is fresh blood-like stool, a lower gastrointestinal endoscopy should be performed, but if gastrointestinal perforation or toxic megacolon associated with inflammatory bowel disease is suspected, lower gastrointestinal endoscopy is contraindicated. Furthermore, if the inflammatory response is high due to acute intestinal inflammation, lower gastrointestinal endoscopy may worsen the inflammation, so it is preferable to avoid it if possible.
6) Angiography and hemorrhage scintigraphy:
If the source of bleeding is not identified by endoscopy and bleeding continues, angiography or hemorrhage scintigraphy is performed. Angiography shows extravasation of contrast agent at the site of bleeding. Once the bleeding site is identified, arterial embolization is performed using coils or sponges. Angiography can detect bleeding at a rate of 0.5 mL/min or more, whereas scintigraphy can detect bleeding at a rate of 0.1-0.2 mL/min or more. ^99mTc scintigraphy is usually used.
Treatment : In the event of shock, the first step is to administer fluids and stabilize hemodynamics. Once the patient's condition has stabilized, hemostasis measures are then taken in parallel. An emergency endoscopic examination is performed, and if the source of bleeding can be identified, endoscopic hemostasis is performed. If bleeding cannot be stopped using endoscopic hemostasis, then interventional radiology (IVR) or emergency surgery should be considered.
1) Endoscopic hemostasis : Endoscopic hemostasis is often more effective at stopping bleeding than drug therapy alone. It is also less invasive than surgical treatment, making it the first choice. It is usually performed after circulatory conditions have stabilized, but in cases where recovery of the patient's overall condition is unlikely unless bleeding is stopped, hemostasis may be performed while maintaining strict systemic management.
Endoscopic hemostasis is used for upper gastrointestinal bleeding such as gastric and duodenal ulcers, esophageal and gastric varices, Mallory-Weiss syndrome, gastric cancer, and esophageal ulcers. Endoscopic hemostasis is used for lower gastrointestinal bleeding such as colonic diverticulum and vascular dysplasia. Endoscopic hemostasis can be broadly divided into 1) mechanical method, 2) local injection method, 3) thermal coagulation method, and 4) drug dispersion method (Table 3-2-12). The mechanical method is a method of directly compressing the exposed blood vessels of the bleeding lesion with a clip or other device to achieve hemostasis. It has a high hemostatic effect because it acts directly on the blood vessels. It is used for cases of spurting bleeding or exposed blood vessels. Unlike the local injection method and thermal coagulation method, it is an excellent method in that it causes almost no tissue damage. The local injection method is a method in which a drug with tissue coagulation ability is injected into the bleeding site using a local injection needle. Drugs such as hypertonic sodium-adrenaline (HSE) or pure ethanol are used. Hemostasis with HSE is a method of hemostasis that ultimately leads to the formation of a thrombus in the vascular lumen by the vasoconstriction action of adrenaline, the extension of the adrenaline action time by hypertonic saline, and the fibrinoid denaturation of the vascular wall, which leads to hemostasis. The pure ethanol local injection method utilizes the dehydrating and fixing action of pure ethanol to contract the blood vessels, coagulate and necrotize the vascular wall, and form a thrombus to stop bleeding. Thermal coagulation is a method of hemostasis that uses thermal coagulation of the bleeding site, and includes the heater probe method and argon plasma coagulation (APC). The heater probe method is a method of hemostasis that uses the protein coagulation action of tissue by electrical heat. Argon plasma coagulation is a non-contact high-frequency coagulation hemostasis method that releases ionized argon gas and discharges a high-frequency current to coagulate tissue. It can coagulate tissue over a wide area with a uniform depth, and is effective in treating diffuse bleeding and gastric antral vascular ectasia (GAVE).
The drug spray method involves spraying a drug with a coagulant effect onto the bleeding lesion. Thrombin, sodium alginate, etc. are used, and they are often used to treat oozing bleeding or in combination with other hemostatic methods.
2) Drug therapy:
Drug therapy is used to prevent rebleeding after endoscopic hemostasis or when the source of bleeding cannot be identified by endoscopy. Various drugs are used to suppress acid secretion, reduce local blood flow at the site of hemostasis, cover the site of hemostasis, and reduce tissue defects at the bleeding site and promote healing. Acid secretion inhibitors (proton pump inhibitors (PPIs) and _H2 receptor antagonists) are used to treat bleeding from gastric and duodenal ulcers, Mallory-Weiss syndrome, esophageal ulcers, and other gastric diseases. By suppressing acid secretion, bleeding time is shortened when the gastric juice pH is 6.4 or higher, and platelet aggregation is promoted when the pH is 6.8 or higher (Green et al., 1978). Furthermore, the fibrinolytic activity of the gastric and duodenal mucosa during bleeding is reduced, as is plasmin-dependent fibrinolytic activity (Valenzuela et al., 1989).
For bleeding gastric ulcers positive for Helicobacter pylori, eradication of H. pylori is useful for preventing recurrence. Triple therapy using PPI, amoxicillin (AMPC), and clarithromycin (CAM) is covered by insurance in Japan. Triple therapy using PPI, AMPC, and metronidazole as secondary eradication treatment for unsuccessful cases is also covered by insurance. For ulcers caused by NSAIDs, discontinue NSAIDs. If discontinuing NSAIDs is not possible, administer PPI or prostaglandin preparations. For gastrointestinal bleeding caused by anticoagulants or antiplatelet drugs, suspend these drugs if possible. After confirming hemostasis with another endoscope, resume oral administration. For bleeding caused by ruptured esophageal or gastric varices, vasopressin and β-receptor antagonists are used. As an antiplasmin drug, tranexamic acid is administered intravenously, and thrombin is administered orally as a coagulation factor mimetic drug.
3) Upper gastrointestinal bleeding:
a) Esophagus:
i) Rupture of esophageal varices: In the case of rupture of esophageal varices, endoscopic variceal ligation (EVL) is performed at the bleeding point. After hemostasis is confirmed, endoscopic injection sclerotherapy (EIS) is performed to prevent recurrence. EVL is a simple procedure in which the varices are ligated and collapsed, and is used in emergencies. EIS is a treatment in which a sclerosing agent is injected into or around the varices. 5% ethanolamine oleate is used as a drug to be injected directly into the varices, and 1% ethoxysclerol is used as a drug to be injected around the varices. If the bleeding point cannot be identified because of a large amount of bleeding and visual field cannot be obtained, a Sengstaken-Blakemore tube is inserted and temporary hemostasis is attempted by applying pressure. After hemostasis, endoscopic treatment is performed on an elective basis. Vasopressin, β-receptor antagonists, and nitroglycerin are used as drug therapies to reduce portal vein pressure. Vasopressin causes constriction of intraperitoneal arterioles, mainly in the superior mesenteric artery region, reducing portal vein inflow and lowering portal pressure.
ii) Mallory-Weiss syndrome: Mallory-Weiss syndrome is a condition in which a longitudinal laceration of the mucosa near the junction of the esophagus and stomach occurs during vomiting, causing the submucosal artery to rupture, resulting in sudden gastrointestinal bleeding. This condition often stops bleeding naturally, and drug therapy using acid secretion inhibitors is used. In cases of massive bleeding, endoscopic hemostasis is performed. In cases where it is difficult to stop bleeding, surgical treatment is considered, but this is extremely unlikely. b) Stomach and duodenum:
i) Gastric and duodenal ulcers: The indications for endoscopic hemostasis for gastric and duodenal ulcers are based on the Forrest classification, and endoscopic hemostasis is performed for spurting bleeding (Ia), oozing bleeding (Ib), and ulcers with exposed blood vessels (IIa) (Japan Gastroenterological Association, 2009). In cases where only a blood clot is attached (IIb), endoscopic hemostasis is not necessary. If bleeding can be stopped with endoscopic hemostasis, the patient is fasted and rested for several days and the progress is observed. During this time, an acid secretion inhibitor is administered intravenously. A drug that has the effect of covering the hemostatic site may also be used. An endoscopic examination is performed again to confirm that there is no rebleeding, and then oral acid secretion inhibitor treatment is started. If bleeding cannot be stopped with endoscopic hemostasis or if a large amount of blood transfusion is required, IVR or surgery is performed. ii) Gastric varices: For gastric varices, a cyanoacrynotide drug (histacryl) is injected to stop bleeding. In IVR, balloon-occluded retrograde transvenous obliteration (B-RTO) is performed. It is useful for gastric varices with renal vein shunts. iii) Acute gastric mucosal lesion (AGML): For acute erosive gastritis, acute ulcers, and acute hemorrhagic gastritis, drug therapy is performed by administering acid secretion inhibitors. If a source of bleeding is identified during upper gastrointestinal endoscopy, endoscopic bleeding techniques are performed. The key to treating this disease is to clarify and remove triggers such as psychological stress, medications, alcohol, and spices through questioning.
4) Lower gastrointestinal bleeding:
a) Small intestine: In recent years, balloon enteroscopy and capsule endoscopy have been developed, making it possible to check for bleeding from the small intestine. If the source of bleeding can be identified, hemostasis is performed using balloon enteroscopy. Diseases that can cause small intestinal bleeding include drug-induced (NSAIDs) colitis, small intestinal cancer, submucosal tumors, and vascular dysplasia. b) Large intestine: In the case of bleeding from the large intestine, the underlying disease is generally treated. In addition, in the case of bleeding from a colonic diverticulum, if the diverticulum that is the source of bleeding can be identified, it is sutured with clips. If vascular dysplasia is found, endoscopic hemostasis such as thermal coagulation is performed. [Osaka Toshihito and Yoshino Junji]
■ References
Green WF, et al: Effect of acid and pepsin on blood coagulation and platelet aggeregation. Gastroenterology, 74: 38-43, 1978.
Masao Miyazaki: Overview of shock. Emergency Medicine Seminar (edited by the Japan Emergency Medicine Education Seminar Committee), pp55-85, Health Publishing, Tokyo, 1976.
Edited by the Japanese Society of Gastroenterology: Peptic Ulcer Treatment Guidelines, pp2-10, Nankodo, Tokyo, 2009.
Valenzuela GA, et al: Pepsin fibrinolysis of artificial clot made from fibrinogen concentrate and bovine thrombin: the effect of pH and epilon aminocaproic acid. Surg Endosc, 3: 148-151, 1989.

Table 3-2-8
Diseases that cause upper gastrointestinal bleeding ">

Table 3-2-8

Table 3-2-9
Diseases that cause lower gastrointestinal bleeding ">

Table 3-2-9

Table 3-2-10
Systemic diseases that cause gastrointestinal bleeding

Table 3-2-10

Table 3-2-11
Severity of hemorrhagic shock (excerpted from Miyazaki, 1976)

Table 3-2-11

Table 3-2-12
Endoscopic Hemostasis ">

Table 3-2-12

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

概念
　消化管出血は一般に吐血，下血，血便といった症状を有する病態を指すが，健診にて便潜血陽性である場合も含まれる．吐血とは口腔から血液を嘔吐することで，Treitz靱帯より口側の上部消化管からの出血によるものとされる．吐血の性状は鮮血とコーヒー残渣様吐物がある．こうした変化は血液が胃内に停滞している時間に左右される．食道からの出血は鮮血となるが，胃内に血液が貯留すると胃酸と混合し，ヘモグロビンが還元されヘマチンとなり暗赤色を呈する．この色調の変化により排出された吐物をコーヒー残渣様吐物と表現する．
　下血は血液により黒色やタール様になった便が肛門より排泄することと定義される．血便とは糞便中に新鮮血が混入あるいは便の表面に付着したり，新鮮血そのものを排出することである．臨床的には下血は血便を包括して用いられる．黒色便は上部消化管からの出血で血液が胃酸による影響を受け，黒色の血液が混じった便を排出するものである．左側結腸・直腸あるいは肛門からの出血は鮮血となる．　消化管出血の60～70％を上部消化管出血が占める．上部消化管出血のうち半数は胃・十二指腸潰瘍からの出血である．消化性潰瘍のほか原因疾患としては食道静脈瘤の破綻，急性胃・十二指腸粘膜病変（AGMLあるいはADML），Mallory-Weiss症候群，胃癌，吻合部潰瘍などが高頻度である（表3-2-8）．
　下部消化管出血の原因疾患としては虚血性大腸炎，抗生物質起因性腸炎，大腸憩室，痔疾・裂肛，大腸癌・ポリープ，潰瘍性大腸炎などがあげられる（表3-2-9）．また下血の原因として上部消化管出血も念頭におかねばならない．その他，吐血・下血の原因疾患として肝・胆道・膵といった消化管と隣接する臓器の疾患，白血病・血友病や凝固異常などの血液疾患，Rendu-Osler-Weber病などの血管疾患，アミロイドーシス，サルコイドーシス，膠原病などがある（表3-2-10）．
病態・鑑別診断
1）全身状態の把握・出血量の推定:
吐血・下血の重症度を判定するのに身体的所見による全身状態の把握，特にショック状態の有無を調べるのは急務である．血圧，心拍数，呼吸数などのバイタルサイン，意識状態，尿量，顔面蒼白などの症状から出血量を推定する（表3-2-11，宮崎，1976）．貧血の有無，眼球結膜・皮膚の黄染，腹水の有無なども重要である．触診により腹部圧痛，腹膜刺激症状の存在，腫瘤・リンパ節腫張の有無を確認する．下血の場合，その性状を確認するため直腸診が必要である．　その他，全身状態の把握のため血液ガス検査，酸素飽和度測定，心電図検査などを行う．胸部X線撮影はfree airの存在を確認し，消化管穿孔を否定するために実施しておかねばならない検査である．
2）全身管理:
ショック時の全身管理として循環動態の安定のために血管の確保，輸液，輸血を行う．また気道の確保，酸素吸入などの必要な治療を行う．このほか，中心静脈圧の測定，心電図，動脈圧モニタリング，尿量測定などを必要に応じて行う．
3）病歴の聴取:
吐血・下血患者に対する病歴の聴取は重要である．出血の量・色調により，出血源を推定する．吐血の場合，新鮮血はまず食道静脈瘤破綻が考えられる．黒色の場合は胃・十二指腸潰瘍からの出血を考える．下血なら黒色便は上部消化管からの出血，鮮紅色～新鮮血は結腸・肛門からの出血が疑われる．随伴症状（腹痛，下痢，悪心・嘔吐，発熱）も原因疾患を推定するのに重要である．既往歴，服薬内容，生活習慣，家族歴なども確認する．消化管疾患の既往はもちろん，肝硬変などの肝疾患の既往，NSAIDs （non-steroidal anti-inflammatory drugs）・ステロイド薬あるいは抗菌薬の服用，飲酒の有無などを聴取する．最近では脳血管障害や虚血性心疾患の予防のために抗凝固薬・抗血小板薬が用いられる症例が増加しており，消化管出血の原因となることがあるため問診にて確認する．抗菌薬服用後の新鮮下血は抗菌薬による出血性腸炎を疑う．大量飲酒後の嘔吐に伴う出血はMallory-Weiss症候群を考える．慢性的な飲酒歴がある場合，肝疾患による食道・胃静脈瘤の破綻なども疑う．
4）血液・生理学検査
：血液一般検査として赤血球数・ヘモグロビン・ヘマトクリット値を測定し，貧血の有無を確認する．急激に大量出血した場合はヘモグロビン値の低下が軽度にとどまることがあり，注意を要する．白血球数・血小板数なども調べる．血液生化学検査を行い，肝・胆道系の異常や腎機能の異常などを把握する．上部消化管出血では血液が小腸を通過するために尿素窒素（BUN）の上昇が早期にみられる点が特徴である．電解質の測定は，体液バランスの推定とも輸液量の決定に必要である．
5）緊急内視鏡検査
：ショック時には循環動態の安定が先決であるが，出血源を特定するために緊急内視鏡検査は積極的に行う．検査中には心電図やパルスオキシメーターなどにより全身状態をモニターする．吐血であれば上部消化管内視鏡検査を行うが，下血でも黒色便であれば上部消化管内視鏡検査を先んじて行う．鮮血様の下血を認める場合は下部消化管内視鏡検査を行うが，消化管穿孔を疑う場合や炎症性腸疾患に伴う中毒性巨大結腸症を疑う場合は下部消化管内視鏡検査は禁忌である．また急性の腸管における炎症により，炎症反応が高値を示す場合は下部消化管内視鏡検査を行うと炎症が悪化する可能性があるため，できるだけ避ける方が望ましい．
6）血管造影・出血シンチグラフィ:
内視鏡検査で出血源が同定されずかつ出血が持続する場合，血管造影あるいは出血シンチグラフィを行う．血管造影では出血部位において造影剤が血管外に漏出する．出血部位が同定されればコイルやスポンゼルによる動脈塞栓術を実施する．血管造影は0.5 mL/分以上の出血が持続している場合に検出可能であるが，シンチグラフィでは0.1～0.2 mL/分以上の出血で検出が可能である．^99mTcシンチグラフィが通常用いられる．
治療
　治療の方針としてはショック時にはまず輸液などを行い，循環動態の安定をはかる．状態が落ち着いたら止血処置を並行して行う．緊急内視鏡検査を行い，出血源が同定できれば内視鏡的止血法を実施する．内視鏡的止血法によっても止血できない場合はIVR （interventional radiology）もしくは緊急手術を考慮する．
1）内視鏡的止血法
：内視鏡的止血法は薬物療法単独に比して止血効果がすぐれていることが多い．また，外科的治療に比して侵襲が少ないため，第一選択として行われている．通常は循環状態が安定した後に行うが，止血が得られないかぎり全身状態の回復が望めない場合には厳重な全身管理を行いながら止血を行うことがある．
　内視鏡的止血法の対象となる疾患は上部消化管出血では胃・十二指腸潰瘍，食道・胃静脈瘤，Mallory-Weiss症候群，胃癌，食道潰瘍などである．下部消化管出血では大腸憩室，血管異形成などで内視鏡的止血術が行われる．　内視鏡的止血法は①機械法②局注法③熱凝固法④薬剤散布法に大別される（表3-2-12）．　機械法は出血病変の露出血管をクリップなどにより直接圧迫止血する方法である．血管に対する直接作用のため高い止血効果が得られる．噴出性出血，露出血管を有する例に対して用いられる．局注法や熱凝固法と異なり，組織傷害性がほとんどない点ですぐれた方法といえる．　局注法は局注針を用い，組織凝固能のある薬剤を出血部位に注入する方法である．高張Na-アドレナリン（HSE）あるいは純エタノールなどの薬剤が用いられる．HSEによる止血はアドレナリンによる血管収縮作用に加え，高張食塩水によるアドレナリン作用時間の延長，血管壁のフィブリノイド変性などの作用により最終的に血管内腔の血栓形成へ導き，止血を得る方法である．純エタノール局注法は純エタノールの脱水・固定作用を利用し，血管を収縮させ血管壁の凝固・壊死，血栓を形成させ止血する方法である．　熱凝固法は出血部位を熱凝固させて止血する方法で，ヒータープローブ法，アルゴンプラズマ凝固法（APC）などがある．ヒータープローブ法は電気熱による組織の蛋白凝固作用を利用し止血する方法である．アルゴンプラズマ凝固法はイオン化したアルゴンガスを放出し，高周波電流を放電することで組織を凝固する非接触型の高周波凝固止血法である．広範囲に均一の深さで組織凝固ができ，びまん性の出血や前庭部毛細血管拡張症（gastric antral vascular ectasia：GAVE）の治療に有効である．　
薬剤散布法は凝固作用のある薬物を出血病変に散布する方法である．トロンビン，アルギン酸ナトリウムなどが用いられ，湧出性出血やほかの止血法に併用して用いられることが多い．
2）薬物療法：
内視鏡的止血法実施後の再出血予防または内視鏡検査では出血源が同定できない場合に薬物療法を行う．酸分泌の抑制，止血部位の局所血流の減少，止血部位の被覆，出血部位の組織欠損の縮小・治癒の促進を目的にして各種の薬剤が用いられる．酸分泌抑制薬（プロトンポンプ阻害薬（PPI），H₂受容体拮抗薬）は胃・十二指腸潰瘍，Mallory-Weiss症候群，食道潰瘍，その他の胃疾患からの出血に対して用いられる．酸分泌を抑制することにより胃液pHが6.4以上の環境になると出血時間が短縮し，pH 6.8以上になると血小板凝集が促進される（Greenら，1978）．さらに，出血時の胃・十二指腸粘膜は線維素溶解活性が低下して，かつプラスミン依存性線維素溶解活性も低下する（Valenzuelaら，1989）．
　Helicobacter pyloriが陽性の出血性胃潰瘍にはH．pyloriの除菌が再発予防に有用である．除菌治療薬としてPPI，アモキシシリン（AMPC），クラリスロマイシン（CAM）を用いた3剤併用療法がわが国では保険適用となり用いられている．除菌不成功例に対して二次除菌治療としてPPI，AMPCにメトロニダゾールを加えた3剤療法も保険適用となっている．NSAIDs潰瘍についてはNSAIDsを中止する．NSAIDsの中止が不可能ならばPPIあるいはプロスタグランジン製剤を投与する．抗凝固薬・抗血小板薬による消化管出血については休薬が可能なら，これらの薬剤を休薬する．再度内視鏡により止血を確認した後に内服を再開する．　食道・胃静脈瘤の破綻による出血に対してはバソプレシン，β受容体拮抗薬が用いられる．抗プラスミン薬としてはトラネキサム酸の静脈投与や，凝固因子様作用薬としてトロンビンの経口投与が用いられる．
3）上部消化管出血：
　a）食道：
　ⅰ）食道静脈瘤の破綻：食道静脈瘤破綻は出血点に対して内視鏡的静脈瘤結紮術（endoscopic variceal ligation：EVL）を行う．止血が確認された後，再発防止処置として内視鏡的硬化療法（endoscopic injection sclerotherapy：EIS）を実施する．EVLは静脈瘤を結紮し，虚脱させる手技で簡便であり，緊急時に用いられる．EISは静脈瘤の内部あるいは周囲に硬化剤を注入する治療法である．静脈瘤の中に直接注入する薬剤として5％エタノールアミンオレートが，静脈瘤の周囲に注入する薬剤として1％エトキシスクレロールが用いられる．出血が多量で視野が得られないなど出血点が同定できない場合はSengstaken-Blakemoreチューブを挿入し圧迫による一時止血を試みる．止血後に待機的に内視鏡治療を行う．薬物療法としては門脈圧を低下する目的でバソプレシン，β受容体拮抗薬，ニトログリセリンが用いられる．バソプレシンは上腸間膜動脈領域を中心とした腹腔内細動脈の収縮を生じ，門脈流入量を減少させて門脈圧を低下させる．
　ⅱ）Mallory-Weiss症候群：Mallory-Weiss症候群は嘔吐時に食道・胃接合部付近の縦走する粘膜の裂創により粘膜下の動脈が破綻し，突然の消化管出血を起こす病態である．本症は自然止血することが多く，酸分泌抑制薬などの薬物療法を行う．大量出血する場合は内視鏡的止血法を実施する．止血困難例には外科療法を考慮するが，その可能性はきわめて少ない．　b）胃・十二指腸：
　ⅰ）胃・十二指腸潰瘍：胃・十二指腸潰瘍といった消化性潰瘍に対する内視鏡的止血法の適応はForrest分類に従い，噴出性出血（Ia），湧出性出血（Ib）および露出血管を有する潰瘍（Ⅱa）に内視鏡的止血法を実施する（日本消化器病学会，2009）．血餅が付着のみ（Ⅱb）の症例はあえて内視鏡止血の必要はない．内視鏡的止血法で止血できれば，数日の絶食・安静にて経過を観察する．その間は酸分泌抑制薬の静脈内投与を実施する．止血部位を被覆する効果を有する薬剤を用いることもある．再度内視鏡検査を実施し，再出血がないことを確認した上で酸分泌抑制薬の内服治療に移行する．内視鏡的止血法により止血が得られない場合や，大量の輸血が必要な場合にはIVRや外科手術が行われる．　ⅱ）胃静脈瘤：胃静脈瘤に対してはシアノアクリノート系薬剤（ヒストアクリル）を注入して止血を行う．IVRではバルーン下逆行性経静脈的塞栓術（balloon-occluded retrograde transvenous obliteration：B-RTO）が行われる．腎静脈短絡路を有する胃静脈瘤に有用である．　ⅲ）急性胃粘膜病変（acute gastric mucosal lesion：AGML）：急性びらん性胃炎，急性潰瘍，急性出血性胃炎について酸分泌抑制薬の投与による薬物療法を行う．上部消化管内視鏡検査にて出血源を認めた場合には内視鏡的出血法を行う．本症は心理的ストレスや薬剤，アルコール，香辛料といった誘因を問診により明らかにし，除去することが治療として重要である．
4）下部消化管出血：
　a）小腸：近年，バルーン小腸内視鏡，カプセル内視鏡などが開発され，小腸からの出血についても確認できるようになった．出血源が同定できればバルーン小腸内視鏡により止血術を行う．小腸出血の原因となる疾患としては薬剤性（NSAIDs）腸炎，小腸癌，粘膜下腫瘍，血管異形成などがある．　b）大腸：大腸における出血については基本的には原疾患の治療を行う．また，大腸憩室出血は出血源である憩室が同定できれば，クリップによる縫縮を行う．血管異形成が見つかれば熱凝固法などの内視鏡的止血法を行う．［小坂俊仁・芳野純治］
■文献
Green WF, et al: Effect of acid and pepsin on blood coagulation and platelet aggeregation. Gastroenterology, 74: 38-43, 1978.
宮崎正夫：ショック総説.救急医学セミナー（日本救急医学教育セミナー委員編），pp55-85, へるす出版，東京，1976.
日本消化器病学会編：消化性潰瘍診療ガイドライン，pp2-10, 南江堂，東京，2009.
Valenzuela GA, et al: Pepsin fibrinolysis of artificial clot made from fibrinogen concentrate and bovine thrombin: the effect of pH and epilon aminocaproic acid. Surg Endosc, 3: 148-151, 1989.

表3-2-8
上部消化管出血の原因となる疾患">

表3-2-8

表3-2-9
下部消化管出血の原因となる疾患">

表3-2-9

表3-2-10
消化管出血の原因となる全身性疾患">

表3-2-10

表3-2-11
出血性ショックの重症度（宮崎，1976 より抜粋）">

表3-2-11

表3-2-12
内視鏡的止血法">

表3-2-12

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