What is the role of terlipressin in managing upper gastrointestinal (UGI) bleeding?

Role of Terlipressin in Upper Gastrointestinal Bleeding

Terlipressin should be initiated immediately as soon as variceal bleeding is suspected in cirrhotic patients with upper GI bleeding, even before endoscopic confirmation, and continued for 2-5 days as adjuvant therapy to endoscopic band ligation. 1, 2

Mechanism and Efficacy

• Terlipressin is a synthetic vasopressin analogue that reduces splanchnic blood flow and portal pressure through V1 receptor-mediated vasoconstriction, with slower conversion to vasopressin providing sustained hemodynamic effects 1, 3
• It reduces bleeding-related mortality by 34% compared to placebo (relative risk 0.66,95% CI 0.49-0.88) and decreases failure to control initial hemostasis by 34% 2, 4
• Terlipressin is superior to vasopressin alone and equivalent to the combination of vasopressin plus nitroglycerin in controlling variceal bleeding 1

Dosing and Administration

Initial dosing: 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled 1, 2, 3

Maintenance dosing: 1 mg IV every 4 hours after the initial 48-hour period 1, 2, 3

Duration: Continue for 2-5 days total, though recent evidence suggests 24 hours may be sufficient when combined with successful endoscopic band ligation 1, 5

Alternative administration: Continuous infusion at 4 mg/24 hours is superior to bolus dosing, providing greater reduction in hepatic venous pressure gradient (85% vs 58% at 24 hours) and lower rebleeding rates (2% vs 15%) with fewer adverse events 3

Treatment Algorithm

1. Immediate initiation: Start terlipressin as soon as variceal bleeding is suspected, before diagnostic endoscopy 1, 2, 3
2. Concurrent therapies: Administer prophylactic antibiotics (ceftriaxone 1g IV daily or norfloxacin) simultaneously 1, 2
3. Volume resuscitation: Use crystalloids with restrictive transfusion strategy (hemoglobin threshold 7 g/dL, target 7-9 g/dL) 1
4. Endoscopic therapy: Perform endoscopic band ligation within 12 hours; the combination of terlipressin plus endoscopic therapy is superior to either alone 1, 2, 3
5. Continue therapy: Maintain terlipressin for 3-5 days to prevent early rebleeding, though 24 hours may suffice after successful endoscopic control 1, 5

Comparative Effectiveness

• Terlipressin, somatostatin, and octreotide show equivalent efficacy in controlling acute variceal bleeding, with 5-day treatment success rates of 86.2%, 83.4%, and 83.8% respectively 6
• Initial hemostasis rates with terlipressin are 88-96%, comparable to somatostatin (76-96%) 1, 7
• Terlipressin is the preferred vasoactive agent when available due to its proven mortality benefit, which has not been consistently demonstrated with somatostatin or octreotide 2, 4

Important Contraindications and Precautions

Absolute contraindications:

• Pregnancy (may cause uterine contraction, decreased uterine blood flow, fetal loss, and placental abruption; use only if endoscopic therapy and octreotide fail) 1
• Active coronary, peripheral, or mesenteric ischemia 3
• Hypoxia or worsening respiratory symptoms 3

Relative contraindications:

• Cardiac conditions or coronary artery disease (consider octreotide instead due to fewer cardiovascular side effects) 1, 2
• Progressive hypotension (systolic BP <90 mmHg) 1

Common adverse events (10-20% of patients):

• Abdominal pain, nausea, diarrhea 3, 4
• Cardiovascular complications related to vasoconstriction 3, 4
• Hyponatremia, chest pain 3

Critical safety note: Mortality and withdrawal due to adverse events occurs in less than 1% of cases, making the benefit-risk ratio highly favorable given the high mortality of untreated variceal bleeding 4

Special Clinical Scenarios

Gastric variceal bleeding: While evidence is limited, terlipressin can be recommended due to its ability to decrease portal hypertension, though endoscopic therapy (cyanoacrylate injection) or balloon-occluded retrograde transvenous obliteration may be preferred for fundal varices 1

Refractory bleeding: If bleeding persists despite terlipressin and endoscopic therapy, proceed to early transjugular intrahepatic portosystemic shunt (TIPS) placement, particularly in high-risk patients 1, 2

Non-variceal upper GI bleeding: Terlipressin has no role in peptic ulcer disease or other non-variceal causes of upper GI bleeding 1