Best Practice & Research Clinical Gastroenterology 27 (2013) 633–638

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Best Practice & Research Clinical Gastroenterology

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Acute upper gastrointestinal bleeding (UGIB) – Initial evaluation and management Iyad Khamaysi, MD, Senior Lecturer a, b, Ian M. Gralnek, MD, MSHS, FASGE, Associate Professor of Medicine/ Gastroenterology a, b, * a b

Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel The Endoscopy Unit of the Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel

a b s t r a c t Keywords: Acute upper GI bleeding Non-variceal upper gastrointestinal bleeding/haemorrhage Oesophagogastric variceal bleeding Peptic ulcer bleeding Risk stratification Timing of endoscopy in acute upper GI bleeding

Acute upper gastrointestinal bleeding (UGIB) is the most common reason that the ‘on-call’ gastroenterologist is consulted. Despite the diagnostic and therapeutic capabilities of upper endoscopy, there is still significant associated morbidity and mortality in patients experiencing acute UGIB, thus this is a true GI emergency. Acute UGIB is divided into non-variceal and variceal causes. The most common type of acute UGIB is ‘non-variceal’ and includes diagnoses such as peptic ulcer (gastric and duodenal), gastroduodenal erosions, Mallory–Weiss tears, erosive oesophagitis, arteriovenous malformations, Dieulafoy’s lesion, and upper GI tract tumours and malignancies. This article focuses exclusively on initial management strategies for acute upper GI bleeding. We discuss up to date and evidence-based strategies for patient risk stratification, initial patient management prior to endoscopy, potential causes of UGIB, role of proton pump inhibitors, prokinetic agents, prophylactic antibiotics, vasoactive pharmacotherapies, and timing of endoscopy. Ó 2013 Elsevier Ltd. All rights reserved.

Acute upper GI bleeding (UGIB) refers to gross GI blood loss originating proximal to the ligament of Treitz that usually manifests as fresh blood haematemesis, “coffee ground” emesis, and/or melaena

* Corresponding author. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Tel.: þ972 4 854 1680; fax þ972 4 854 3864. E-mail address: [email protected] (I.M. Gralnek). 1521-6918/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpg.2013.09.002

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with or without haemodynamic compromise [1–5]. Haematochezia may be the presenting sign in patients with extremely brisk UGIB, yet this clinical presentation of acute UGIB is uncommon [6]. The annual rate of hospitalization for acute UGIB in the United States is estimated to be 160 hospital admissions per 100,000 population, which translates into more than 400,000 per year [1]. Traditional negative patient outcomes include re-bleeding and mortality, with patient mortality commonly associated with decompensation of pre-existing co-morbid medical conditions precipitated by the acute bleeding event [1–3,7]. Estimated direct medical costs for in hospital care of patients with acute UGIB are high [8]. In most clinical settings, the vast majority (80%–90%) of episodes of acute upper gastrointestinal bleeding are secondary to non-variceal causes. The most common non-variceal bleeding etiologies include: gastro-duodenal peptic ulcer (20%–50%), gastroduodenal erosions (8%–15%), erosive oesophagitis (5%–15%), Mallory–Weiss tear (8%–15%), arterio-venous malformations/GAVE (5%), and with other conditions (eg, Dieulafoy’s lesion, upper GI tract malignancy) making up the remaining causes [5,9]. Variceal haemorrhage is usually secondary to esophageal variceal bleeding, but can be due to gastric varices, and uncommonly ectopic varices in the upper GI tract (e.g., duodenum). Appropriate endoscopic evaluation, and when indicated endotherapy, of patients with non-variceal UGIB has been shown to translate into improved patient outcomes including significantly reduced rebleeding rates, blood transfusions, surgery, and mortality [1–4,10]. Although numerous factors from the patient history, physical examination, and initial laboratory tests have been examined for an association with the need for endoscopic intervention, no single factor is sufficiently predictive of UGIB severity to be used for patient triage. The most predictive factors are a history of malignancy or cirrhosis, presentation with fresh blood haematemesis, signs of hypovolaemia including hypotension, tachycardia, haemodynamic shock, and a haemoglobin less than 8 g/dL at initial presentation. Using clinical variables alone (i.e., before endoscopy), scoring tools have been developed and validated to facilitate the triage of patients with acute upper gastrointestinal haemorrhage, identify those in need of urgent endoscopic evaluation, predict the risk of poor outcome, and assist in guiding subsequent management [11,12]. The Blatchford Sscore, a validated risk-stratification tool based solely on clinical and laboratory variables, is used to predict the need for endoscopic intervention in patients with acute upper gastrointestinal haemorrhage [11].The Blatchford score ranges from 0 to 23, with higher scores indicating higher likelihood of needing endoscopic intervention. The Rockall score is probably the most widely known risk-stratification tool for upper gastrointestinal haemorrhage and has been validated in numerous health care settings [12]. The clinical Rockall score (i.e., the score before endoscopy is performed) is calculated solely on the basis of clinical variables at the time of patient presentation. The complete Rockall score makes use of both clinical and endoscopic criteria to predict patient risk of re-bleeding and mortality. The Rockall score ranges from 0 to 11 points, with higher scores indicating higher risk of poor outcome. There are comparative data to show that the Blatchford score performs better than the Clinical Rockall score for predicting patients at high likelihood of needing clinical intervention [13–16]. Patients found to have minor bleeding episodes typically may be discharged soon after endoscopy. Use of the Blatchford score at the point of care in the emergency department may allow for early discharge of 16%–25% of all patients presenting with acute UGIB [13–16]. The first priority in patient management is correcting fluid losses and restoring haemodynamic stability. Volume resuscitation should be initiated with crystalloid intravenous fluids with the use of large-bore intravenous-access catheters (e.g., two peripheral catheters of 16–18 gauge or a central venous catheter if peripheral venous access is not attainable). In order to maintain adequate oxygencarrying capacity, especially in older patients with coexisting cardio-pulmonary disease, the use of supplemental oxygen and transfusion of plasma expanders with the use of packed red cells should be considered if tachycardia or hypotension is present or if the haemoglobin level is less than 10 g/dL. When indicated, correction of coagulopathy should be undertaken [1–3]. This can be achieved using fresh frozen plasma and in selected cases transfusion of platelets. The insertion of a nasogastric tube may be helpful in the initial assessment of the patient (specifically, triage), although the additional information this provides remains controversial and patients do

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not like undergoing this procedure [17,18]. It has been suggested that the presence of red blood in the nasogastric aspirate is an adverse prognostic sign that may be useful in identifying patients who require more urgent endoscopic evaluation. However, the absence of bloody or coffee-ground material does not definitively rule out ongoing or recurrent bleeding, since approximately 15% of patients without bloody or coffee-ground material in nasogastric aspirates are found to have high-risk lesions on endoscopy [17]. Oesophagogastric varices are present in approximately 50% of patients with cirrhosis and their presence correlates with the severity of the underlying liver disease. For example, while up to 40% of Child A patients may have varices, yet varices may be present in up to 85% of Child C patients [19]. Variceal haemorrhage occurs at an annual rate of 5%–15%, and the most important predictor of haemorrhage is the size of the varices, with the highest risk of initial haemorrhage occurring in patients with large-size varices. Other predictors of oesophagogastric variceal haemorrhage are decompensated cirrhosis (Child B/C) and the endoscopic presence of red wale markings. Despite improvements in therapy over the last two decades, oesophaogastric variceal haemorrhage is still associated with a 20% mortality rate at six weeks following the variceal bleeding event [20]. Pharmacological therapy in variceal haemorrhage consists of splanchnic vasoconstrictors (vasopressin and its analogues, somatostatin and its analogues), nonselective b-blockers, and venodilators (nitrates). Vasoconstrictors act by producing splanchnic vasoconstriction and reducing portal venous inflow. Venodilators act theoretically by decreasing intrahepatic and/or portocollateral resistance. However, all available venodilators (e.g., isosorbide mononitrate) have a systemic hypotensive effect and the decrease in portal pressure appears to be more related to hypotension (i.e., a decrease in flow) rather than a decrease in resistance. The combination of a vasoconstrictor and a vasodilator has a synergistic portal pressure-reducing effect. Endoscopic therapies, such as sclerotherapy or endoscopic variceal ligation (EVL), are local therapies that have no effect on either portal flow or resistance. Shunting therapy, either radiological (TIPS, transjugular intrahepatic portosystemic shunt) or surgical, by bypassing the site of increased resistance, markedly reduces portal pressure by bypassing the site of increased resistance [21]. Pharmacological therapy has the advantages of being generally applicable and capable of being initiated as soon as a diagnosis of variceal haemorrhage is suspected, even prior to diagnostic upper endoscopy. A meta-analysis of 15 trials comparing emergency sclerotherapy and pharmacological treatment (vasopressin  nitroglycerin, terlipressin, somatostatin, or octreotide) shows a similar efficacy with fewer side effects with pharmacological therapy, thereby suggesting that pharmacological therapy should be considered first-line treatment of variceal bleeding [22]. Beta-blockers should not be used in the acute setting as they will decrease blood pressure and will blunt a physiologic increase in heart rate associated with bleeding. Terlipressin, a synthetic analogue of vasopressin that has a longer biological activity and significantly fewer side effects, is effective in controlling acute variceal haemorrhage and has been associated with decreased mortality, but is not yet available in the United States. Terlipressin is administered at an initial dose of 2 mg IV every 4 h and can be titrated down to 1 mg IV every 4 h once haemorrhage is controlled [22]. Somatostatin and its analogues octreotide and vapreotide also cause splanchnic vasoconstriction at pharmacological doses. Although it has been considered that this effect is due to an inhibition of the release of vasodilatory peptides (mainly glucagon), recent studies suggest that octreotide has a local vasoconstrictive effect. The advantage of octreotide and vapreotide is that they are safe and can be used continuously for five days or even longer. Of these, only octreotide is available in the United States and it has been mostly used as an initial IV bolus of 50 mg followed by a continuous infusion of 50 mg/h. Use of somatostatin consists of a 250 mg IV bolus followed by an infusion of 250 mg/h. Vapreotide is given as a 50 mg IV bolus followed by an infusion of 50 mg per hour [23]. In patients with suspected oesophagogastric variceal bleeding, volume resuscitation should be undertaken promptly but with caution, with the goals of maintaining haemodynamic stability and a haemoglobin of approximately 8 g/dL. Similarly, vigorous resuscitation with saline solution should generally be avoided because, in addition to possibly precipitating recurrent variceal haemorrhage, this can worsen or precipitate the accumulation of ascites or fluid at other extravascular sites. Given that

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aspiration of blood can occur at the time of upper endoscopy, elective endotracheal intubation may be required for airway protection prior to endoscopy, particularly in patients with concomitant hepatic encephalopathy who may have difficulty controlling their airway. The transfusion of fresh frozen plasma and platelets can be considered in patients with significant coagulopathy and/or thrombocytopenia [24]. Cirrhotic patients with acute upper GI bleeding have a high risk of developing severe bacterial infections (e.g., spontaneous bacterial peritonitis and other infections) that are associated with early recurrence of variceal haemorrhage and a greater mortality. Although patients with less-severe liver disease (i.e., Child A) are at an increased risk of developing bacterial infections, this risk is highest in those with more severe liver disease (i.e., Child B and C). The use of short-term prophylactic antibiotics in patients with cirrhosis and GI haemorrhage with or without ascites has been shown not only to decrease the rate of bacterial infections but also to increase patient survival. Improved survival is partly related to a decrease in the incidence of early re-bleeding in patients with variceal haemorrhage who receive prophylactic antibiotics. Therefore, short-term antibiotic prophylaxis should be considered standard practice in all patients with cirrhosis and acute variceal haemorrhage. The recommended antibiotic schedule is norfloxacin administered orally at a dose of 400 mg BID for seven days. The rationale behind the oral administration of norfloxacin, a poorly absorbed quinolone, is the selective eradication (or at least reduction) of gram-negative bacteria in the gut, the source of bacteria. However, quinolone antibiotics with a similar spectrum of activity, such as ciprofloxacin, could also be recommended. When oral administration is not possible, quinolones can be administered intravenously (IV) [25]. In a recent study performed in patients with advanced cirrhosis (Child B/C) and GI haemorrhage, IV ceftriaxone (1 g/day) was more effective than oral norfloxacin in preventing bacterial infections [26,27], mostly those due to gram-negative organisms. Antibiotics were initiated following the emergency endoscopy and always within the first 12 h after admission into the hospital. The role of proton pump inhibitor (PPI) therapy in patients with suspected acute UGIB was systematically reviewed in a Cochrane Collaboration meta-analysis that included six randomized controlled trials including 2223 subjects [28]. Although there was no statistically significant differences in the outcomes of re-bleeding, need for surgery, or mortality, those receiving up-front PPI therapy, given prior to index endoscopy, had significantly reduced the rates of high-risk stigmata identified at endoscopy (odds ratio [OR] 0.67; 95% confidence interval [CI], 0.54–0.84) and thus reduced the need for endoscopic haemostasis (OR 0.68; 95% CI, 0.50–0.93). High-dose intravenous PPI therapy, initiated prior to endoscopy, is now widely recommended for patients who are suspected of having acute UGIB [1–3]. The use of pre-endoscopy IV prokinetic agents should also be considered during the initial patient management phase. A recent meta-analysis evaluated the effectiveness of using prokinetic agents prior to index endoscopy in patients presenting with acute UGIB [29]. This meta-analysis demonstrated that IV erythromycin 250 mg or metoclopramide 10 mg administered 20–120 min before endoscopy in patients with acute UGIB decreased the need for a repeat endoscopy to determine the site and cause of bleeding (OR 0.55; 95% CI, 0.32–0.94). However, there was no improvement in other clinical outcomes, including length of hospital stay, transfusion requirements, or surgery. Although the routine use of prokinetic agents is not recommended, use in patients with a suspected high probability of having fresh blood or a clots in the stomach when undergoing endoscopy may result in a higher diagnostic yield [29]. Recently, video capsule endoscopy has been shown to be an effective way to identify acute UGIB in the emergency department. Capsule endoscopy identifies gross blood in the upper gastrointestinal tract, including the duodenum, significantly more often than nasogastric tube aspiration and identifies inflammatory lesions, equally as well as EGD. Capsule endoscopy may also facilitate patient triage and earlier endoscopy, but at this point in time should not be considered a substitute for standard EGD [30–33]. Conflicts of interest Dr. Iyad Khamaysi – no conflicts of interest to declare. Prof Ian M. Gralnek – Prof Gralnek is a consultant for Given Imaging, Astra-Zeneca.

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Practice points 1. The first priority in patient management is correcting fluid losses and restoring haemodynamic stability. When indicated, correction of coagulopathy should also be undertaken. 2. Performance of early upper endoscopy (defined as within 24 h of patient presentation) is now considered standard of care. 3. High dose IV PPI can be initiated prior to upper endoscopy. 4. Use of vasoactive medications (e.g., glypressin, octreotide) in suspected oesophagogastric variceal bleeding should be initiated prior to upper endoscopy. 5. The selected use of IV prokinetic agents, given prior to upper endoscopy, may facilitate the upper endoscopy examination and provide improved visualization and a higher diagnostic yield.

Research agenda 1. The role of capsule endoscopy in the emergency department setting as part of initial patient evaluation/risk stratification is an evolving area.

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Acute upper gastrointestinal bleeding (UGIB) - initial evaluation and management.

Acute upper gastrointestinal bleeding (UGIB) is the most common reason that the 'on-call' gastroenterologist is consulted. Despite the diagnostic and ...
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