Upper Gastrointestinal Bleeding

Upper gastrointestinal bleeding (UGIB) is bleeding arising proximal to the ligament of Treitz — most often from a peptic ulcer, gastric or esophageal erosions, a Mallory-Weiss tear, a Dieulafoy lesion, or a malignancy (nonvariceal causes), or from ruptured esophageal or gastric varices in a patient with portal hypertension and cirrhosis (variceal causes).^[1] Initial management is identical regardless of cause — resuscitation, risk stratification, and prompt endoscopy — but the two pathways diverge sharply once the source is identified: variceal bleeding needs vasoactive drug therapy, prophylactic antibiotics, and band ligation that a nonvariceal ulcer does not, and a nonvariceal ulcer needs high-dose acid suppression that variceal bleeding does not depend on.^[2] Recognizing which pathway a patient is on — often before endoscopy confirms it — is the pharmacist's first decision point in this condition.

Typical presentation

Presentation depends on the site, rate, and volume of bleeding. Hematemesis may be fresh red blood or coffee-ground material; melena (black, tarry, foul-smelling stool) reflects blood altered by transit through the gut; brisk bleeding can produce hematochezia (red or maroon stool) that mimics a lower GI source. Associated symptoms from volume loss include dizziness, syncope, dyspnea, chest pain, altered mental status, tachycardia, and hypotension. Retching or vomiting immediately before the onset of hematemesis suggests a Mallory-Weiss tear.

• Current or recent use of ASA, a nonsteroidal anti-inflammatory drug (NSAID), or a P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel).
• Anticoagulant therapy (warfarin or a direct oral anticoagulant), especially combined with an antiplatelet agent.
• Known or untreated Helicobacter pylori infection.
• A personal history of peptic ulcer disease or a prior episode of UGIB.
• Critical illness, mechanical ventilation, or major trauma/burns (stress-related mucosal disease).
• Retching or forceful vomiting (Mallory-Weiss tear risk).
• Chronic liver disease or cirrhosis from any cause, and its risk factors — heavy alcohol use, chronic viral hepatitis B or C, and long-standing nonalcoholic fatty liver disease (variceal bleeding risk).
• Advanced age and significant comorbidity (renal disease, hepatic disease, malignancy), which worsen prognosis once bleeding occurs.
• Tobacco use, which impairs mucosal healing.

Distinguishing an upper from a lower GI source

History

• Characterize the bleeding — hematemesis (fresh vs. coffee-ground), melena, or hematochezia — and how long it has been occurring.
• Ask specifically about ASA, NSAID, anticoagulant, and antiplatelet use, prior ulcer disease or UGIB, and alcohol intake.
• Ask about symptoms of chronic liver disease and known risk factors for cirrhosis.
• Ask whether retching or vomiting preceded the bleeding (Mallory-Weiss tear).
• Assess for comorbidities that worsen prognosis — malignancy, renal disease, hepatic disease, and cardiovascular disease.

Physical examination and bedside assessment

Resuscitate while taking a focused history and examining the patient, with particular attention to signs of chronic liver disease. At the bedside, suspect clinically significant intravascular volume loss when systolic blood pressure is under 100 mmHg, heart rate is over 100 bpm, or hemoglobin is under 100 g/L.

Investigations

• Type and crossmatch (typically at least 4 units of packed red blood cells, more with severe bleeding), hemoglobin/hematocrit, electrolytes, creatinine and blood urea nitrogen, and coagulation studies (platelet count, INR, PTT).
• A 12-lead ECG in older patients or those with suspected ischemic heart disease, and before giving erythromycin, to exclude a prolonged QTc interval.
• Formal risk stratification with the Glasgow-Blatchford score before endoscopy, and the Rockall score after endoscopy (see below).

The nasogastric tube and upper GI series

A nasogastric tube is not needed if the patient has current or previously witnessed hematemesis, or if gastroscopy will be performed imminently. When placed, fresh blood in the aspirate indicates more severe bleeding and localizes the source to the upper GI tract; a clear or bile-stained aspirate does not reliably exclude an upper source, since the tube tip may not reach a pool of blood or the bleeding site may be beyond a closed pylorus. Nasogastric lavage is no longer routinely performed; a prokinetic (erythromycin) to clear retained blood before endoscopy has replaced it.^[3] An upper GI series (e.g., barium swallow) must not be performed — its diagnostic accuracy is poor in active bleeding, and residual barium obscures the field for a subsequent endoscopy.

Endoscopy timing

Refer every patient with UGIB for endoscopy once resuscitation is underway. For nonvariceal bleeding, perform endoscopy within 24 hours of presentation — earlier, urgent endoscopy (within 6-12 hours) has not been shown to improve outcomes and may be harmful if performed before adequate resuscitation. For suspected variceal bleeding, endoscopy is performed earlier, generally within 12 hours, once the patient is hemodynamically stabilized.^[3]

Pre-endoscopic risk stratification: Glasgow-Blatchford score

The Glasgow-Blatchford score (GBS) is calculated from history, vital signs, and a basic metabolic panel — entirely before endoscopy — and identifies patients at very low risk who may be safe for outpatient management without hospital admission.^[4]

Add the points for every criterion the patient meets; the maximum possible score is 23. A GBS of 0 or 1 identifies a patient at very low risk of needing transfusion, endoscopic therapy, or surgery — outpatient management with prompt endoscopy and reliable follow-up can be considered in a stable, reliable patient with adequate support and transportation. A GBS of 12 or higher identifies a high-risk patient who needs urgent inpatient management.^[1]

Post-endoscopic risk stratification: Rockall score

The complete Rockall score is calculated after endoscopy and adds the endoscopic diagnosis and stigmata of recent hemorrhage to the pre-endoscopic clinical variables (age, shock, comorbidity); it predicts rebleeding and mortality.^[5]

The pre-endoscopic (clinical) Rockall score uses only age, shock, and comorbidity (maximum 7); the complete score adds the endoscopic diagnosis and stigmata after EGD (maximum 11). A complete score of 2 or less identifies a low-risk patient. A complete score above 6 identifies a high-risk patient in whom an extended 10-day course of twice-daily oral PPI, after the initial high-dose IV course, reduces recurrent bleeding compared with the standard once-daily step-down regimen (see Drug Tables).^[5][1]

Helicobacter pylori testing

Test every patient with a bleeding ulcer for H. pylori. Testing performed during the acute bleeding episode has a meaningfully higher false-negative rate than testing performed later, so a negative result obtained during active bleeding should not be treated as definitive — retest once the acute episode has resolved if the initial result is negative and clinical suspicion remains.^[6]

• Restore and maintain hemodynamic stability and adequate tissue oxygen delivery.
• Achieve endoscopic hemostasis of the bleeding lesion within the appropriate time window for its cause.
• Heal the underlying lesion (ulcer, erosion, or esophagitis) with an adequate course of acid suppression.
• Prevent early rebleeding in the first 72 hours after endoscopic hemostasis, when the risk is highest.
• Eradicate H. pylori when present, to prevent recurrent bleeding.
• For variceal bleeding: control the acute hemorrhage, prevent bacterial infection, and establish secondary prophylaxis against future variceal bleeding.
• Establish a safe long-term antithrombotic and NSAID strategy that minimizes recurrent-bleeding risk without leaving the patient unprotected from thrombosis.

• Two large-bore IV lines, crystalloid resuscitation, supplemental oxygen, and airway protection or elective intubation before endoscopy when hematemesis is active or mental status is impaired.
• A nasogastric tube is not routinely required; do not perform an upper GI series (barium study).
• Angiographic embolization for nonvariceal bleeding refractory to a second attempt at endoscopic hemostasis; surgery is reserved for refractory or special cases.
• A transjugular intrahepatic portosystemic shunt (TIPS), placed within 72 hours and ideally within 24 hours, for variceal bleeding at high risk of treatment failure or after early rebleeding or failed endoscopic hemostasis.
• Balloon tamponade or a dedicated esophageal self-expandable stent as a bridge to more definitive therapy in refractory variceal bleeding.
• Counsel every patient to avoid alcohol and NSAIDs going forward, and support smoking cessation, since tobacco use impairs mucosal healing.

Breastfeeding: PPIs (omeprazole, pantoprazole) are considered compatible with breastfeeding, based on low milk concentrations and destruction of ingested drug in the infant's acidic stomach. Data on octreotide in breastfeeding are limited; weigh the benefit of controlling active variceal hemorrhage against the uncertainty in consultation with the care team.

Older adults

Older patients carry a higher risk of rebleeding and death from UGIB, and more often have the comorbidities that raise the Glasgow-Blatchford and Rockall scores. Apply the same resuscitation, PPI, and endoscopy protocols, with a lower threshold for admission and close monitoring given the reduced physiologic reserve to tolerate ongoing blood loss.

Renal and hepatic impairment

PPI dosing does not require adjustment for renal or hepatic impairment. In cirrhosis, classify severity by Child-Pugh class — it directly changes variceal-bleeding management, since a high-risk-of-failure profile (Child-Pugh class C above 14 points, or class B with active bleeding) is itself the trigger for early TIPS. Prophylactic antibiotics are mandatory in cirrhotic patients with UGIB regardless of renal function. Gastrointestinal bleeding is a recognized precipitant of hepatic encephalopathy in cirrhosis, from the protein/blood load delivered to the gut — monitor mental status closely and manage encephalopathy per standard protocol if it develops.

During the acute admission, monitor vital signs, urine output, and serial hemoglobin, with the frequency guided by bleeding severity and ongoing losses, and watch for signs of rebleeding — recurrent hematemesis or melena, new hemodynamic instability, or a falling hemoglobin. Most rebleeding occurs within the first 72 hours after endoscopic hemostasis, exactly the window the high-dose IV PPI course is timed to cover. In variceal bleeding, monitor for hepatic encephalopathy, and continue endoscopic band-ligation surveillance on a defined schedule until varices are eradicated, then periodically thereafter. Confirm H. pylori eradication with a urea breath test, stool antigen test, or biopsy at least 4 weeks after antibiotic therapy ends and at least 1-2 weeks after stopping the PPI, since ongoing acid suppression can produce a false-negative result; if eradication fails, retreat with an appropriate second-line or salvage regimen (see Drug Tables) and retest again after that course.^[6] At every follow-up, confirm the patient's antithrombotic and NSAID plan matches what was intended at discharge — long-term PPI co-therapy should be documented on the chart and on any ongoing ASA, NSAID, or anticoagulant prescription. Community pharmacists are well placed to catch a patient who has silently stopped a necessary long-term PPI, or who has resumed a held anticoagulant without the intended follow-up plan.

1. Confirm true rebleeding — recurrent hematemesis or melena, new hemodynamic instability, or a significant hemoglobin drop — rather than the expected tail of the initial bleed.
2. Repeat endoscopy for a second attempt at hemostasis; most rebleeding after initially successful endoscopic therapy can still be controlled endoscopically.
3. If a second endoscopic attempt fails or is not feasible, escalate to angiographic embolization for nonvariceal bleeding, or early TIPS for variceal bleeding, especially in a patient with a high-risk Child-Pugh profile.^[13]
4. Obtain surgical consultation for refractory nonvariceal bleeding once endoscopic and angiographic options are exhausted.
5. For refractory variceal bleeding, bridge to definitive therapy with balloon tamponade or a dedicated esophageal self-expandable stent.
6. If bleeding recurs weeks to months after apparent healing, reassess for the most common preventable causes first — unconfirmed or untreated H. pylori, and resumed ASA, NSAID, or antithrombotic therapy without PPI co-therapy — before assuming a new or missed lesion.

• Placing a nasogastric tube or ordering a barium upper GI series when neither is needed — this delays endoscopy and can obscure the endoscopic field.
• Using an oral or IV H2-receptor antagonist instead of a PPI for acute UGIB.
• Waiting for endoscopy or GI consultation before starting IV PPI therapy — start it empirically as soon as UGIB is suspected.
• Managing a patient with cirrhosis and hematemesis on the nonvariceal pathway — missing empiric octreotide and prophylactic antibiotics delays interventions that measurably improve outcomes in variceal bleeding.
• Treating prophylactic antibiotics in cirrhotic UGIB as optional — they are a mandatory, independent intervention, not an afterthought to endoscopy.
• Continuing high-dose IV PPI infusion beyond 72 hours, or beyond the need for it once endoscopy shows a low-risk lesion (clean-based ulcer).
• Holding cardiac-dose ASA for a prolonged period after hemostasis instead of resuming it on the day hemostasis is confirmed.
• Accepting a negative H. pylori test obtained during active bleeding as definitive, given its high false-negative rate in that setting, and failing to retest later.
• Discharging a patient who must continue an NSAID or ASA without co-prescribing a PPI.
• Transfusing to a liberal hemoglobin target instead of the evidence-based restrictive threshold.
• Missing that octreotide can blunt opioid analgesia, or that clarithromycin in an H. pylori regimen is a meaningful CYP3A4 interaction risk.

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Proton pump inhibitors, parenteral

Pantoprazole IV is the standard parenteral PPI used for UGIB in Canada.

Proton pump inhibitors, oral

Used as the step-down after IV therapy, or as initial therapy where IV PPI is unavailable. All share the adverse-effect profile noted below. The initial 10-day course matches the high-dose IV induction phase; continue twice daily for esophagitis, or step down to once daily for a duodenal or gastric ulcer.

Somatostatin analogue

Reduces portal pressure, splanchnic blood flow, and acid/pepsin secretion. Terlipressin, used for variceal bleeding in some countries, is not currently marketed in Canada — octreotide is the vasoactive agent of choice domestically.

Prokinetic

Prophylactic antibiotics, variceal bleeding in cirrhosis

Start at admission, before endoscopy, in every cirrhotic patient with UGIB — this reduces bacterial infection, rebleeding, and mortality.

Helicobacter pylori eradication regimens

Treat every H. pylori-positive patient with a bleeding ulcer; confirm eradication at least 4 weeks after therapy ends. Component doses use the ComboDose "+" notation for each multi-drug regimen.

NSAID-associated ulcer risk reduction

For a patient who requires ongoing NSAID therapy despite a prior UGIB — always co-prescribe gastroprotection.

Secondary prophylaxis of variceal bleeding: nonselective beta-blockers

First-line secondary prophylaxis, combined with an endoscopic band-ligation program, for every patient after variceal bleeding. Reduce or discontinue if systolic BP falls below 90 mmHg, hyponatremia (under 130 mEq/L) develops, or acute kidney injury occurs.