Terlipressin Side Effects in Hepatorenal Syndrome
Terlipressin causes ischemic complications in approximately 12% of patients and respiratory failure in 14-30% of patients, with the highest risk occurring in those with ACLF-3, baseline hypoxemia, or underlying cardiac disease. 1
Major Ischemic Complications
The most serious side effects of terlipressin are related to its vasoconstrictive properties:
- Cardiovascular ischemia including angina, myocardial infarction, and arrhythmias occur due to systemic vasoconstriction 1, 2
- Digital ischemia and peripheral cyanosis affecting fingers, toes, and extremities can develop, requiring immediate drug discontinuation 1, 3
- Mesenteric ischemia presenting as abdominal pain and potentially progressing to bowel necrosis 1
- These ischemic events occur in approximately 12% of patients and may require discontinuation of therapy in 6.8% of cases 1, 4
Respiratory Complications
Respiratory failure is a critical concern, particularly in patients with advanced disease:
- Respiratory compromise occurs in approximately 14% of terlipressin-treated patients versus 5% with placebo 5
- The risk increases to 30% in patients with ACLF-3 (≥3 organ failures) 1
- The mechanism involves multifactorial hemodynamic perturbations including increased afterload from cirrhotic cardiomyopathy (particularly diastolic dysfunction) and volume overload from aggressive albumin co-administration 1
- The FDA specifically warns against using terlipressin in patients with SpO2 <90% on room air or supplemental oxygen 6, 5
Gastrointestinal Side Effects
- Abdominal pain and diarrhea result from terlipressin's stimulation of intestinal motility 1
- These effects are generally less severe than ischemic complications but are common 1
Cardiovascular Effects
- Bradycardia with an estimated maximum decrease of 10.6 beats/minute occurs predictably 7
- Increased blood pressure with MAP rising by approximately 16.2 mmHg, which is therapeutic but can be problematic in patients with cardiac dysfunction 7
- QTc prolongation is minimal (<10 ms) and not clinically significant 7
Risk Mitigation Strategy
Continuous infusion reduces side effects compared to bolus dosing:
- Continuous infusion (starting at 2 mg/day) achieves equal efficacy with lower total daily doses and fewer ischemic complications compared to bolus administration 1, 6
- This approach is recommended by the American College of Gastroenterology but is not yet FDA-approved in the United States 6
Absolute Contraindications
Do not use terlipressin in patients with:
- Active coronary, peripheral, or mesenteric ischemia 1, 6
- Baseline SpO2 <90% on room air or supplemental oxygen 6, 5
- Known cardiac failure or underlying respiratory conditions, especially with baseline hypoxemia 1
- ACLF-3 with respiratory failure (FDA warning) 1
Monitoring Requirements
Close surveillance is essential during treatment:
- Monitor vital signs including pulse oximetry every 2-4 hours 6
- Assess for signs of peripheral ischemia (digital cyanosis, skin changes) 3
- Watch for chest pain, abdominal pain, or changes in bowel function 1
- Evaluate volume status carefully to avoid excessive albumin administration that can precipitate respiratory failure 1
Common Pitfall
The most critical error is using terlipressin in patients with ACLF-3 or baseline hypoxemia without ICU-level monitoring, as these patients have the highest risk of respiratory decompensation. Always assess ACLF grade and baseline oxygen saturation before initiating therapy 1, 6. If ischemic complications develop, immediate discontinuation typically leads to rapid resolution 3.