Gastrointestinal Bleeding

GENERAL PRINCIPLES

Acute gastrointestinal (GI) bleeding is a common clinical problem that results in substantial morbidity, healthcare resource utilization, and costs, especially when it develops in hospitalized patients.¹

• Overt GI bleeding is the passage of fresh or altered blood in emesis or stool.

• Occult GI bleeding refers to a positive fecal occult blood test (stool guaiac or fecal immunochemical test) or iron deficiency anemia without visible blood in the stool.

• Obscure GI bleeding consists of GI blood loss of unknown origin that persists or recurs after negative initial esophagogastroduodenoscopy (EGD) and ileocolonoscopy.²

DIAGNOSIS

Clinical Presentation

HISTORY

• Hematemesis, coffee-ground emesis, and/or aspiration of blood or coffee-ground material from a nasogastric (NG) tube indicate an upper GI source of blood loss.

• Melena, black sticky stool with a characteristic odor, usually suggests an upper GI source, although small bowel and right-sided colonic bleeds can also result in melena.

• Various shades of bloody stool (hematochezia) are seen with distal small bowel or colonic bleeding, depending on the rate of blood loss and colonic transit. Rapid upper GI bleeding can present with hematochezia, typically associated with hemodynamic compromise.

• Anorectal bleeding usually results in bright red blood coating the exterior of formed stool or with wiping, and can be associated with distal colonic symptoms (e.g., rectal urgency, straining, or pain with defecation).

• Anemia from blood loss can cause fatigue, weakness, abdominal pain, pallor, or dyspnea.

• Estimation of the amount of blood loss is often inaccurate. If the baseline hematocrit is known, the drop in hematocrit provides a rough estimate of blood loss.

• Coagulation abnormalities can propagate bleeding from a preexisting lesion in the GI tract.

• Medications known to affect the coagulation process or platelet function include warfarin, heparin, low-molecular-weight heparin, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), P2Y12 receptor blockers (e.g., clopidogrel [Plavix], prasugrel [Effient], ticagrelor [Brilinta], ticlopidine [Ticlid]), thrombolytic agents, glycoprotein Ilb/IIIa receptor antagonists (abciximab [ReoPro], eptifibatide [Integrilin], tirofiban [Aggrastat]), direct thrombin inhibitors (e.g., argatroban, bivalirudin, dabigatran etexilate), and direct factor Xa inhibitors (e.g., rivaroxaban [Xarelto], apixaban).

• NSAIDs and aspirin can result in mucosal damage anywhere in the GI tract. Therefore, dual antiplatelet therapy (e.g., clopidogrel plus aspirin) or concomitant aspirin and anticoagulation with warfarin can escalate the risk for GI bleeding by both initiating and propagating bleeding.

PHYSICAL EXAMINATION

• Color of stool: Direct examination of spontaneously passed stool or on digital rectal examination (DRE) may help localize the level of bleeding. DRE may also identify anorectal abnormalities including anal fissures, which induce extreme discomfort during the DRE.

• Fresh blood on an NG aspirate may indicate ongoing upper GI bleeding requiring urgent endoscopic attention, but hemodynamic status is equally important.³ The aspirate should be considered positive only if blood or dark particulate matter (“coffee grounds”) is seen; hemoccult testing of NG aspirate has no clinical utility. NG tube placement is not required in the evaluation of a patient with alternate conclusive evidence of acute GI bleeding. A negative NG aspirate does not rule out bleeding from a duodenal source. An NG tube may help clear the stomach of blood and clots to facilitate visualization during endoscopy, but it does not obviate the need for airway protection with massive bleeding.

• Orthostatic hemodynamic changes (drop in systolic BP of gt;20 mm Hg, rise in pulse rate of gt;10 bpm) are seen with loss of 10%-20% of the circulatory volume; supine hypotension suggests a gt;20% loss. Hypotension with a systolic BP of lt;100 mm Hg or baseline tachycardia gt;100 bpm suggests significant hemodynamic compromise that requires urgent volume resuscitation.⁴

Diagnostic Testing

LABORATORIES

• Complete blood cell (CBC) count

• Coagulation parameters (international normalized ratio [INR], partial thromboplastin time)

• Blood group, cross-matching of two to four units of blood

• Comprehensive metabolic profile (creatinine, blood urea nitrogen, liver function tests)

DIAGNOSTIC PROCEDURES

• Endoscopy

ξ Esophagogastroduodenoscopy (EGD), with high diagnostic accuracy and therapeutic capability, is the preferred investigative test in upper GI bleeding. Volume resuscitation or blood transfusion should precede endoscopy in hemodynamically unstable patients. Patients with ongoing bleeding or at risk for an adverse outcome benefit most from urgent EGD, whereas stable patients can undergo endoscopy electively during the hospitalization. Hemodynamically stable patients should undergo endoscopy within 24 hours. A clinical trial demonstrated endoscopy within 6 hours did not improve mortality, but patients with ongoing hemodynamic instability after resuscitation were excluded.⁵ Promotility agents given 30 minutes prior to EGD (IV erythromycin 125-250 mg or IV metoclopramide 10 mg) may empty the stomach of blood and clots to improve visibility for EGD, but endoscopy should not be delayed.⁶ Routine second-look EGD after hemostasis has no proven benefit in reducing surgical intervention or overall mortality.⁷

ξ Colonoscopy can be performed after a rapid bowel purge in clinically stable patients; the purge solution can be infused through an NG tube when not tolerated orally. While diagnostic yield is highest with colonoscopy performed within 24 hours of presentation, patient outcome does not necessarily improve.

ξ Anoscopy may be useful in the detection of internal hemorrhoids and anal fissures but does not replace the need for colonoscopy.

ξ Push enteroscopy allows evaluation of the proximal small bowel beyond reach of a standard EGD, especially if no source is found on careful colonoscopy.⁹

ξ Capsule endoscopy is most useful after the upper gut and the colon have been thoroughly examined and the bleeding source is suspected in the small bowel.⁹

ξ Single- and double-balloon enteroscopy allow visualization of most of the small bowel through either an antegrade or retrograde approach, typically performed when capsule endoscopy localizes bleeding to the small bowel.⁹ Balloons at the endoscope tip and overtube can be consecutively inflated and deflated to facilitate deep insertion into the small bowel.

° Intraoperative enteroscopy may assist endoscopic therapy or surgical resection of an actively bleeding source in the small bowel but carries a high risk of complications.

• Tagged red blood cell (RBC) scanning involves labeling RBCs with technetium-99m that may extravasate into the bowel lumen with active bleeding, detected as pooling of the radioactive tracer on gamma camera scanning, to identify the potential bleeding site. Bleeding rates of 0.2 mL/min can be detected.

• CT angiography (CTA) can localize bleeding exceeding 0.3 mL/min before catheter angiography and has an advantage over CT enterography.⁹ Tagged RBC and CTA are particularly useful in unstable active bleeding precluding urgent colonoscopy.

• Angiography demonstrates extravasation of the dye into the intestine when bleeding rates exceed 0.5 mL/min.

TREATMENT

• Restoration of intravascular volume: Two large-bore (16- to 18-gauge) IV lines or a central venous line should be urgently placed to provide IV fluid resuscitation. The rate at which fluid can be delivered is proportional to the diameter of the catheter and inversely proportional to its length (i.e., a 22-gauge peripheral catheter delivers fluid at a rate of 35 mL/min compared to 154.7 mL/min with a 16-gauge catheter).¹⁰ Importantly, despite their utility in delivering vasopressors and other essential medications for critical care, a typical triple lumen central venous catheter cannot deliver fluids as quickly as an 18-gauge peripheral IV (69.4 mL/min vs. 98.1 mL/min).¹⁰ A wide bore, short central line is ideal for resuscitating patients in hemorrhagic shock.

• Packed RBC transfusion should be utilized when hemoglobin is less than 7 g/dL since a higher transfusion target is associated with increased mortality.¹¹ A higher threshold for initiating transfusion should be considered in patients with cardiovascular disease. In patients presenting with hemorrhagic shock, however, O-negative blood or simultaneous multiple-unit transfusions should be used if available and continued until hemodynamic stability is achieved.

• Oxygen administration: Supplemental oxygen enhances the oxygen-carrying capacity of blood and

should be considered in acute GI bleeding.

• Correction of coagulopathy: Coagulopathy (INR gt; 1.5) or thrombocytopenia should ideally be corrected in patients with GI bleeding, but endoscopy should not be delayed.¹² An elevated INR can be treated with vitamin K, fresh frozen plasma (FFP), or intravenous prothrombin complex concentrate (PCC). Reversal agents are available for many antithrombotic agents (vitamin K, FFP, PCC for warfarin; idarucizumab [Praxbind] for the direct thrombin inhibitor dabigatran; andexanet alfa [AndexXa] for factor Xa inhibitors [e.g., apixaban, edoxaban, rivaroxaban]).

• Endotracheal intubation protects the airway and prevents aspiration in obtunded patients with massive hematemesis and in active variceal bleeding.

• Risk stratification: Validated risk stratification tools, such as the Rockall and Glasgow-Blatchford scores, may be helpful to identify patients that can be safely discharged.¹⁴

Medications

• Nonvariceal upper GI bleeding: High-dose proton pump inhibitors (PPI) (80 mg IV bolus followed by 8 mg/h continuous infusion) reduce rebleeding and mortality in patients with peptic ulcers with high- risk stigmata (active bleeding or nonbleeding visible vessel, see Table 18-1).^15,16 Twice-daily IV bolus dosing (40 mg IV twice daily) may provide sufficient acid suppression compared to an infusion.¹⁷ High-dose PPI should be initiated at presentation with suspected upper GI bleeding, which decreases the need for endoscopic hemostasis, though it does not prevent rebleeding.¹⁸ Patients with high-risk stigmata should continue high-dose PPI for 72 hours, then transitioned to twice-daily oral PPI for 14 days, followed by once daily. Patients without high-risk stigmata may start oral PPI after endoscopy. All patients found to have peptic ulcers should be tested for Helicobacter pylori and treated with eradication therapy if positive (see Peptic Ulcer Disease section).

TABLE 18-1

FORREST CLASSIFICATION OF PEPTIC ULCERS

III

Clean base

5%

Low risk, does not require endoscopic therapy

PPI, proton pump inhibitor.

• Variceal bleeding: Infusion of octreotide (an octapeptide that mimics endogenous somatostatin) acutely reduces portal pressures and controls variceal bleeding, improving the diagnostic yield and therapeutic success of subsequent endoscopy. Octreotide should be initiated immediately (50- to 100- #956;g bolus, followed by infusion at 25-50 #956;g#8725;h) and continued for 3-5 days if variceal hemorrhage is confirmed on EGD.¹⁹ Prophylactic antibiotics (third-generation cephalosporins or fluoroquinolones) should be administered to patients with cirrhosis and variceal bleeding because antibiotics reduce bacterial infections, rebleeding, and mortality.²⁰

• Thalidomide may be an effective approach for refractory chronic bleeding from GI vascular malformations.²¹ Some patients with chronic GI bleeding from arteriovenous malformations are managed with iron supplementation (PO or IV) and as-needed transfusions, reserving endoscopy for acute bleeding with hemodynamic instability.

Nonpharmacologic Therapies

• Endoscopic therapy

° Therapeutic endoscopy offers the advantage of endoscopic hemostasis and should be performed early in acute upper GI bleeding (within 12-24 hours).

ξ Variceal ligation or banding is the endoscopic therapy of choice for esophageal varices, with endotracheal intubation for airway protection if bleeding is massive or the patient is obtunded.¹⁹ Variceal banding can provide both primary and secondary prophylaxis of variceal bleeding, with benefits similar to those from #946;-blocker therapy alone.²² Complications include superficial ulceration, dysphagia, and transient chest discomfort.

ξ Sclerotherapy is also effective but is used mostly when variceal banding is not technically feasible.

• Transjugular intrahepatic portosystemic shunt (TIPS): An expandable metal stent is deployed between the hepatic veins and the portal vein to reduce portal venous pressure in refractory esophageal and/or gastric variceal bleeding from portal hypertension. Early TIPS reduces treatment failure and mortality in acute variceal bleeding.²³ Encephalopathy may occur in up to 25% of patients and is treated medically (see Chapter 19, Liver Diseases). If variceal bleeding recurs or if gastric varices redevelop, duplex Doppler ultrasound can assess for TIPS stenosis.

• Balloon-occluded retrograde transvenous obliteration (BRTO): Gastric varices are obliterated by interventional radiographic access through a patent gastrorenal shunt.²⁴

• Angiography (see above) can be used for bleeding peptic ulcers not amenable to endoscopic therapy or when endoscopic therapy fails.

Surgical Management

• Emergent total colectomy may rarely be required for massive, unlocalized, colonic bleeding; this should be preceded by EGD to rule out a rapidly bleeding upper source whenever possible. Certain lesions (e.g., neoplasia, Meckel diverticulum) require surgical resection for a cure.

• Angiography is typically attempted prior to surgery for peptic ulcer bleeding not amenable to endoscopic therapy. Perforation necessitates surgical consultation.

• Total or partial colectomy may be required for ongoing or recurrent diverticular bleeding.

• Splenectomy is curative in bleeding gastric varices from splenic vein thrombosis.

• Shunt surgery (portacaval or distal splenorenal shunt) is now rarely performed with the wide availability of TIPS, but it remains a consideration in patients with good hepatic reserve.

SPECIAL CONSIDERATIONS

Cardiac Patients and Gastrointestinal Bleeding

• Timing of restarting antiplatelet or antithrombotic therapy following a GI bleed should be individualized based on the risk of rebleeding from the bleed source and the risk of thrombotic events. In general, these agents should be restarted as soon as possible given that a thrombotic event can be more devastating than recurrent bleeding. A randomized clinical trial showed that restarting aspirin immediately after endoscopic hemostasis was associated with reduced mortality, despite a not significant increase in recurrent bleeding.²⁵ PPI should be continued while patients are on antiplatelet or antithrombotic medication.

• PPI prophylaxis decreases the risk of GI bleeding, without significant increase in major cardiovascular events in patients on dual antiplatelet therapy.²⁶ Despite concerns that PPIs competitively inhibit the cytochrome P450 enzyme that activates clopidogrel, randomized controlled trials have not substantiated higher vascular events with concurrent use of clopidogrel and PPI.²⁶

• Left ventricular assist devices (LVADs) are associated with GI bleeding from angiodysplastic lesions, making EGD or push enteroscopy the initial investigation of choice.²⁷