Evidence-based, cost-effective management of upper gastrointestinal hemorrhage. An algorithm of the Journal of Trauma and Acute Care Surgery emergency general surgery algorithms work group

This algorithm, developed by the Journal of Trauma and Acute Care Surgery Emergency General Surgery algorithms work group, addresses the initial evaluation and management of upper gastrointestinal (UGI) hemorrhage in the acute setting (Fig. 1). The algorithm is intended to serve as a bedside reference for clinicians. The algorithm is annotated with letters linked to corresponding text, providing the rationale and evidence to support these recommendations. The algorithm is not a substitute for the clinical judgment and experience of bedside clinicians and should not be considered as the “standard of care.” We encourage institutions to utilize these recommendations to formulate local protocols, but recognize that there are patient-specific factors and institutional resource availability that may require deviation from this algorithm. UGI hemorrhage is typically defined as bleeding into the GI tract proximal to the ligament of Treitz. Emergency department visits for UGI hemorrhage are common, with an incidence of 130 visits per 100,000 persons.1 UGI hemorrhage has a mortality rate of up to 20% depending on etiology1–3 and can require high resource utilization in the form of massive transfusion, procedural intervention, and/or surgery. The emergency general surgeon’s expertise is frequently sought in cases of UGI bleeding due to their experience in managing critically ill patients with shock, as well as their ability to intervene surgically to achieve definitive bleeding control should the need arise.4 INITIAL PRESENTATION OF PATIENTS WITH UPPER GASTROINTESTINAL HEMORRHAGE Hematochezia While hematochezia is often associated with lower GI hemorrhage, between 10% and 25% of cases are due to UGI hemorrhage.5,6 For this reason, patients presenting with active bleeding per rectum should undergo evaluation for both upper and lower GI bleeding.7–9 Nasogastric tube lavage is no longer routinely recommended due to its low sensitivity and low negative predictive value for detecting UGI bleeding;4,7 however, patients with lower GI bleeding who undergo this diagnostic procedure may have a shorter time to upper endoscopy.10 The current recommendation for patients with bright red blood per rectum and hemodynamic instability is to proceed directly to upper endoscopy for earlier diagnosis and intervention.11 Hematemesis Hematemesis is a more overt sign of UGI hemorrhage, and patients presenting in this manner should undergo immediate airway assessment and resuscitation. Treatment should be directed at prompt intervention for hemorrhage control. Hospital Admission Versus Outpatient Management The Glasgow-Blatchford Score (Table 1) for pre-endoscopy risk stratification has been well validated to predict patients who are at risk of rebleeding, mortality within 30 days, and need for hospital-based intervention.4,8,12,13 Patients with a score of ≤1 should be considered for close outpatient follow-up, while patients with higher scores should be considered for hospital admission. TABLE 1 - Glasgow-Blatchford Score for UGI Bleeding Risk Parameter Score Hemoglobin, g/dL Male 12–13 1 10–11.9 3 <10 6 Female 10–12 1 <10 6 Systolic blood pressure, mm Hg 100–109 1 90–99 2 <90 3 Heart rate, beats per minute ≥100 1 Blood urea nitrogen, mg/dL 18.2–22.3 2 22.4–28 3 28.1–70 4 >70 6 Melena 1 Syncope 2 Liver disease 2 Heart failure 2 Scoring interpretation: Score 0–1: low risk of requiring intervention. Score 2–5: intermediate risk. Score 6 or higher: high risk. INITIAL MANAGEMENT OF PATIENTS WITH UPPER GASTROINTESTINAL HEMORRHAGE Airway Assessment and Resuscitation A. Patients with brisk UGI hemorrhage who present with hematemesis are at risk for aspiration with subsequent pulmonary complications. An early assessment for airway protection should be made and, if necessary, a definitive airway should be established. Damage control resuscitation should be initiated before intubation to prevent hemodynamic collapse.14 Rapid sequence intubation is the preferred method for induction, and video laryngoscopy with easy access to a suction catheter will make for ideal visualization. The emergency general surgeon is familiar with managing hemorrhagic shock, as most data on the subject have been derived from the trauma literature.14–16 Obtaining adequate intravenous access is the first step in resuscitation. Patients should be monitored closely in real time with continuous cardiac monitoring, pulse oximetry, and frequent noninvasive blood pressure cuff measurements, or arterial line placement. Hemodynamically unstable patients or those requiring continuous blood product transfusion to maintain normal vital signs should be admitted to the intensive care unit. For hemodynamically unstable patients with UGI hemorrhage, the massive transfusion protocol should be activated to gain access to blood products in a timely manner and to facilitate appropriate transfusion ratios. Landmark studies have demonstrated that, in the absence of whole blood availability, a 1:1:1 ratio of packed red blood cells, platelets, and plasma is ideal for actively bleeding patients.15 Patients requiring massive transfusion protocol and receiving >3 units of blood are likely to develop hypocalcemia due to citrate binding.17 The most recent recommendation is to add 1g of calcium for every 4 units of blood products administered.18 Appropriate diagnosis and prompt treatment of coagulopathy and thrombocytopenia are also important to achieve early gastrointestinal hemorrhage control. Tranexamic acid (TXA) has been studied in bleeding trauma patients and has recently seen expanded use for other etiologies of bleeding. An international randomized placebo-controlled study investigated the use of TXA in patients with acute GI bleeding.19 There was no difference in the primary outcome of death due to bleeding, but the TXA group had a higher rate of venous thromboembolic events, leading to a recommendation that TXA not be used in acute GI bleed.4,19 A systematic review and meta-analysis including 7 randomized controlled trial with 13,608 patients reported that intravenous TXA reduced rebleeding rates and decreased rates of failure to control gastrointestinal bleeding; however, there was no difference in mortality or blood transfusion requirements, and thrombotic events remained a concern in the fixed-effects model.20 Therefore, TXA is not recommended for routine use in UGI hemorrhage but can be considered in patients with severe bleeding or those at high risk for rebleeding, with attention to the risk of subsequent thrombotic complications. Patients who are on anticoagulant medications before admission should be evaluated for reversal, if an appropriate agent is available, and with careful consideration of the risks of thromboembolic events based on the specific indication for systemic anticoagulation.2,21 Laboratories to monitor the effectiveness of resuscitation and direct further plans can include, but are not limited to, a complete metabolic panel, a complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, ionized calcium, lactic acid, arterial blood gas, and thromboelastography. In patients with cirrhosis and portal hypertension presenting with esophageal variceal hemorrhage, it is important to consider baseline derangements in platelets and/or prothrombin time and avoid attempting to overcorrect labs if the patient is no longer requiring resuscitation for active bleeding.2 ETIOLOGIES The etiology of UGI hemorrhage largely determines initial management as well as subsequent treatment strategies, including adjunct medications and the need for intervention. UGI hemorrhage is initially stratified as variceal or nonvariceal causes. NONVARICEAL UPPER GASTROINTESTINAL HEMORRHAGE B. The most common cause of UGI hemorrhage is nonvariceal upper gastrointestinal hemorrhage (NVUGIH; Table 2), and the most common cause of NVUGIH remains peptic ulcer disease (PUD).1,7 Ulcers can form as a result of increased acid production, decreased mucosal protection against acid, or due to Helicobacter pylori (H. pylori).4,22 Mallory-Weiss tear is another relatively common cause of NVUGIH and should be suspected when the patient has a history of forceful vomiting/retching, coughing, or straining, followed closely by abdominal pain and hematemesis. Tumors of the esophagus, stomach, and proximal duodenum are also causes of NVUGIH.23 Adenocarcinoma of the lower esophagus or stomach and gastrointestinal stromal tumors can present with acute bleeding. There are additional nuances to be considered in treating these patients, as they require appropriate staging and oncologic margins at the time of resection. Gastric arteriovenous malformations (AVMs) and Dieulafoy vascular lesions are relatively rare causes of NVUGIH, can be difficult to definitively manage endoscopically, and more often require bleeding control using interventional radiology (IR) through an arterial or venous approach to occlude vascular flow. Aortoenteric fistula is a rare and catastrophic cause of massive UGI bleeding, which can present with sentinel or massive bleeding and is classified as either primary (native aorta to bowel) or secondary (after previous aortic surgery, aortic graft to bowel, usually duodenum). TABLE 2 - Common Causes of Nonvariceal UGI Hemorrhage Causes of Nonvariceal UGI Hemorrhage PUD Mallory-Weiss tear Dieulafoy lesion AVM Erosive esophagitis Gastritis Gastrointestinal stromal tumor Malignancy MANAGEMENT OF NONVARICEAL UPPER GASTROINTESTINAL HEMORRHAGE C. Patients with NVUGIH should receive a proton pump inhibitor (PPI) and a dose of erythromycin or metoclopramide before endoscopic intervention.24 Intermittent dosing of a PPI has been shown to be equivalent to continuous PPI infusion in terms of rebleeding risk and mortality in some studies,25 and consensus guidelines recommend high-dose PPI therapy given either continuously or intermittently for three days after successful endoscopic hemostasis.8,21,24 Histamine-2 receptor antagonists are not recommended for UGI bleeding from peptic ulcers.21 Erythromycin or metoclopramide is recommended as a motility agent to clear old blood products from the stomach before attempted endoscopy.3,8,21 Endoscopic Management D. Early (within 24 h of presentation) endoscopic management of NVUGIH is recommended. While evidence does not demonstrate improved 30-day mortality for urgent (within 6 or 12 h) endoscopy,13 select patients with severe bleeding and hemodynamic instability should undergo more urgent endoscopy after resuscitation.3,7,13,24 Endoscopic intervention and risk of rebleeding are guided by the Forrest classification system (Table 3).26 Patients with active bleeding (spurting or oozing) or a visible vessel should undergo endoscopic intervention.7,8,21 If an adherent clot is seen during endoscopy, an attempt at removal can be made with assessment of the underlying ulcer for high-risk stigmata.7,8 Ulcers with a clean base or flat pigmented spot should not undergo intervention.7 Erosive esophagitis (Los Angeles Grades B/C/D) and gastritis are treated with long-term PPI therapy.27,28 Gastric AVM typically cannot be definitively managed endoscopically and should be referred to IR or surgery in a multidisciplinary approach. Similarly, bleeding from Dieulafoy lesions in the stomach can be controlled endoscopically but may need angioembolization for definitive management.4,29 Bleeding from gastrointestinal stromal tumors and gastric cancer may be controlled endoscopically with topical hemostatic agents, with subsequent coordination and planning of definitive surgical management with a multidisciplinary tumor board.23 TABLE 3 - Forrest Classification of Endoscopic Findings for Rebleeding Risk Classification Risk Category Forrest I (active hemorrhage) Ia—active spurting High mortality, high risk Ib—active oozing High risk of rebleeding Forrest II (signs of recent hemorrhage) IIa—visible vessel High risk of rebleeding IIb—adherent clot Moderate to high risk IIc—flat pigmented spot Low risk Forrest III (clean ulcer base) Lowest risk Bleeding After Initial Endoscopic Management E. Patients with UGI hemorrhage with early rebleeding after initial endoscopic intervention should undergo repeat endoscopy.7,21 Patients who have UGI hemorrhage that cannot be controlled endoscopically and continue to bleed after endoscopic management should be considered for angioembolization by IR, where available. Operative Intervention for Upper Gastrointestinal Hemorrhage F. Surgery should be considered for refractory bleeding if IR embolization is unavailable or not feasible.7 Surgical intervention should also be considered for gastric AVMs that are not amenable to catheter-based embolization or balloon occlusion, or if these services are not available.30 Surgeons may wish to review endoscopic findings for faster localization of bleeding in cases of gastric ulcers, and in cases of AVMs or Dieulafoy lesions, tattooing of the area or tandem endoscopy can be helpful. Proximal duodenal ulcers eroding into the posterior wall usually bleed from the gastroduodenal artery and require a longitudinal duodenotomy extending across the pylorus with superior, inferior, and medial configuration of sutures, avoiding the common bile duct. The longitudinal opening is closed transversely (Heineke-Mikulicz manner) to avoid stricture. Historically, vagotomy and/or antrectomy were considered at the time of surgical intervention for complications of ulcer disease; however, patients who are unstable from acute hemorrhage should not undergo prolonged acid-reducing operations, and most will improve on postoperative medical therapy.21,31,32 Operative management of aortoenteric fistula requires repair by either endovascular stent or open surgical reconstruction. Postendoscopy Management There is no evidence-based recommendation for when to restart an oral diet after intervention for NVUGIH, but a recent randomized clinical trial was unable to demonstrate noninferiority of refeeding at 24 hours compared with the more traditional 48 hours after endoscopy.33 PUD is commonly caused by H. pylori, so once bleeding is controlled, the patient should be tested for H. pylori, and antibiotic therapy should be initiated. For treatment-naïve patients, the American College of Gastroenterology now recommends quadruple therapy with a PPI, bismuth, a tetracycline, and metronidazole.32 Patients with PUD without H. pylori should be maintained on an IV PPI for 72 hours and twice-daily oral PPI for two weeks thereafter.7,8,21 Routine repeat endoscopy is not recommended after control of bleeding in NVUGIH.4,7,21 ESOPHAGOGASTRIC VARICEAL UPPER GASTROINTESTINAL HEMORRHAGE G. Patients with cirrhosis have elevated portal venous pressure, which can lead to dilated gastroesophageal veins, among other complications. Bleeding from these veins can be massive, and esophagogastric variceal upper gastrointestinal hemorrhage (EVUGIH) is the leading cause of mortality among patients with elevated portal venous pressure.2,34–36 Surveillance endoscopy, variceal banding, and medications such as propranolol are used to prevent variceal bleeding,35,37 but 5% to 15% of patients with cirrhosis still experience EVUGIH each year, with EVUGIH representing over two-thirds of all UGI hemorrhage cases in patients with cirrhosis.38,39 Medical Management H. Vasoactive medications to reduce portal vein pressure should be started immediately upon presentation if variceal bleeding is suspected.2,8,34,40 The most commonly available of these is octreotide, a somatostatin analog, which is given as an infusion for 1 to five days total. The traditional duration of octreotide infusion is two to five days; however, shorter durations have been studied, and one recent randomized clinical trial demonstrated no difference between one day and five days of therapy.41 Another option is terlipressin, a vasopressin analog, which may not be available at all hospitals but has been shown to have largely equivalent outcomes to octreotide when combined with endoscopic management of EVUGIH.42 The second traditional pillar of medical management of EVUGIH is prophylactic antibiotics against spontaneous bacterial peritonitis. The most widely recommended agent for prophylaxis is IV ceftriaxone 1 g daily, though the recommended antibiotic and its duration vary and can be based on the severity of cirrhosis.2,34,43 A recent systematic review and meta-analysis has challenged this dogma and called for high-quality randomized controlled trials to further investigate the need for prophylactic antibiotics given advancements in endoscopic intervention and transjugular intrahepatic portosystemic shunt (TIPS) placement, citing high risk of bias in previous studies.43 However, current society guidelines still recommend prophylactic antibiotics in this patient population.34,37 Endoscopic Management I. It is widely accepted that patients with acute EVUGIH should undergo endoscopy within 12 hours of presentation,2,34,44 as there is improved mortality after urgent (within 12 h) endoscopy for EVUGIH.45 The endoscopic treatment of choice is band ligation for esophageal varices and injection of sclerosing agents or glue for gastric varices.2,34–36 Postendoscopy Prophylaxis and Rescue Therap J. Following band ligation of EVUGIH, patients should be started on nonselective beta blocker therapy (propranolol or carvedilol) for secondary prophylaxis and continued on this indefinitely in the outpatient setting.34,46 For patients at high risk of rebleeding after endoscopic band ligation (Child-Pugh B >7 with active bleeding at time of endoscopy, Child-Pugh C 10–13, or prior hepatic venous pressure gradient >20 mm Hg), pre-emptive transjugular TIPS should be considered within 72 hours and ideally within 24 hours of upper endoscopy.2,34–36 K. Urgent TIPS can also be used as rescue therapy for esophageal variceal bleeding that is refractory to combined medical and endoscopic management.34 For refractory bleeding of isolated gastric varices in patients with cirrhosis, balloon-occluded retrograde transvenous obliteration by IR has gained popularity in recent years.47 At the time of discharge, patients with acute EVUGIH should be scheduled for follow-up endoscopic band ligation to eradicate remaining/new esophageal varices at 1-4 week intervals, depending on risk2,37 (Fig. 1).Figure 1: Algorithm for management of upper GI hemorrhage in the acute setting. IV, intravenous.