What is the role of Terlipressin (glypressin) in managing upper gastrointestinal (GI) bleeding?

Terlipressin in Upper GI Bleeding: Specific Role in Variceal Hemorrhage

Terlipressin should be initiated immediately at 2 mg IV every 4 hours when variceal bleeding is suspected in any cirrhotic patient with upper GI bleeding, even before endoscopic confirmation, and must always be combined with endoscopic band ligation and prophylactic antibiotics. 1, 2

Critical Indication: Variceal Bleeding Only

• Terlipressin is indicated exclusively for bleeding esophageal or gastric varices secondary to portal hypertension in cirrhotic patients—it has no role in non-variceal upper GI bleeding (peptic ulcers, malignancy, Mallory-Weiss tears). 2

• The drug works by causing splanchnic vasoconstriction, reducing portal venous inflow and lowering portal pressure. 1, 3

• For general upper GI bleeding management without suspected varices, terlipressin should not be used; focus instead on transfusion thresholds (hemoglobin 70 g/L, target 70-100 g/L) and endoscopic intervention. 4

When to Initiate: Immediate Administration

• Start terlipressin as soon as variceal bleeding is suspected clinically based on known cirrhosis and upper GI bleeding presentation—do not wait for endoscopic confirmation. 1, 2

• Clinical suspicion criteria: any patient with known cirrhosis presenting with hematemesis, melena, or hemodynamic instability from upper GI source. 2

• Early administration (even at home by emergency teams) significantly reduces mortality at day 15 (p=0.035) and day 42 (p=0.06) compared to delayed treatment. 5

Dosing Algorithm

Initial Phase (First 48 Hours):

• 2 mg IV bolus every 4 hours until bleeding is controlled 1, 2

Maintenance Phase (After 48 Hours):

• Reduce to 1 mg IV every 4 hours 1, 2

Total Duration:

• Continue for 2-5 days total 1, 2
• Recent evidence suggests 2 days may be sufficient in Child-Pugh class A or B patients with successful endoscopic hemostasis 2
• Extend to 5 days for Child-Pugh class C, active bleeding during endoscopy, or MELD score >19 2

Alternative Dosing:

• Continuous infusion at 4 mg/24 hours is superior to bolus administration, providing greater reduction in hepatic venous pressure gradient (85% vs 58% at 24 hours) and lower rebleeding rates (2% vs 15%). 3

Mandatory Combination Therapy—Never Monotherapy

Terlipressin must be combined with three simultaneous interventions:

1. Endoscopic band ligation within 12 hours of presentation 1, 2
2. Prophylactic antibiotics (ceftriaxone 1g IV daily or norfloxacin) 1, 2
3. Restrictive transfusion strategy (hemoglobin threshold 7 g/dL, target 7-9 g/dL) 1, 2

• Combination therapy achieves 77% five-day hemostasis versus only 58% with endoscopy alone. 2
• Terlipressin as monotherapy is inadequate and not recommended by any guideline. 2

Proven Mortality Benefit

• Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality by 34% (relative risk 0.66,95% CI 0.49-0.88) compared to placebo. 1, 2

• This mortality benefit distinguishes terlipressin from somatostatin and octreotide, which have not consistently demonstrated mortality reduction despite similar hemostasis rates. 1

• Initial bleeding control rates reach 85-90% when combined with endoscopy. 2

Comparative Effectiveness with Other Vasoactive Agents

• While terlipressin, somatostatin, and octreotide show similar efficacy in controlling bleeding (86.2%, 83.4%, and 83.8% respectively at day 5), only terlipressin has proven mortality benefit. 6

• Terlipressin is superior to vasopressin alone and equivalent to vasopressin plus nitroglycerin in controlling variceal bleeding. 1

• When terlipressin is unavailable, octreotide or somatostatin are acceptable alternatives for hemostasis, but lack the mortality advantage. 6

Absolute Contraindications

Do not administer terlipressin in:

• Active coronary, peripheral, or mesenteric ischemia 1, 3
• Hypoxia or worsening respiratory symptoms (oxygen saturation <90%) 1, 2, 3
• Pregnancy 1

Relative Contraindications and Precautions

• Cardiac conditions or coronary artery disease require careful risk-benefit assessment 1
• Progressive hypotension (systolic BP <90 mmHg) 1
• Monitor for hyponatremia, chest pain, and cardiovascular complications 3

Common Adverse Effects

• Abdominal pain, nausea, diarrhea, and dyspnea occur in 10-20% of patients 1, 2, 7
• Respiratory failure is a recognized complication 2
• Adverse effect incidence increases with longer treatment duration (24.32% with 5 days vs 10.8% with 2 days) 2
• Mortality and withdrawal due to adverse events occur in <1% of cases 7

Rescue Therapy for Treatment Failure

• For refractory bleeding despite terlipressin and endoscopic therapy, proceed to early transjugular intrahepatic portosystemic shunt (TIPS) placement, particularly in high-risk patients (Child-Pugh class C or active bleeding during endoscopy). 1, 2

Key Clinical Pitfalls to Avoid

• Do not use terlipressin for non-variceal upper GI bleeding—it has no efficacy in peptic ulcer disease, malignancy, or other non-portal hypertension sources. 2

• Do not delay initiation waiting for endoscopy—start immediately when variceal bleeding is suspected clinically. 1, 2

• Do not use terlipressin alone—always combine with endoscopic therapy and antibiotics. 2

• Do not continue beyond 5 days—prolonged therapy increases adverse effects without additional benefit. 2