What is the management of terlipressin-induced pulmonary edema?

Management of Terlipressin-Induced Pulmonary Edema

Immediately discontinue terlipressin and withhold albumin administration when pulmonary edema develops, as respiratory failure is a serious and potentially fatal complication that occurs in 14% of patients receiving terlipressin compared to 5% on placebo. 1

Immediate Recognition and Discontinuation

• Stop terlipressin immediately if oxygen saturation (SpO2) drops below 90% or if respiratory symptoms worsen, as mandated by FDA labeling and multiple guidelines 2, 1
• Discontinue albumin infusion, as the combination of terlipressin with excessive albumin (particularly doses of 1 g/kg on day 1 followed by 20-40 g/day) significantly increases the risk of volume overload and respiratory failure 2
• Monitor continuously with pulse oximetry during treatment to detect early hypoxia 1

Risk Factors and Prevention

The risk of terlipressin-induced pulmonary edema is substantially elevated in specific patient populations:

• Patients with ACLF Grade 3 (≥3 organ failures) have markedly increased risk and should ideally receive treatment only in ICU settings with intensive monitoring 2, 1
• Volume overload prior to or during treatment is a major risk factor, particularly when large volumes of albumin are administered 2, 1
• The CONFIRM trial demonstrated respiratory failure in 8% of terlipressin-treated patients, especially those with ACLF-3, with a trend toward higher incidence in patients receiving greater albumin volumes in the pretreatment period 2

Assess volume status and ACLF grade before initiating terlipressin to identify high-risk patients 2, 1

Acute Management Strategy

Once pulmonary edema is recognized:

• Administer diuretics (furosemide, torsemide, or bumetanide) to reduce pulmonary congestion, starting with low-to-intermediate doses 2
• Provide supplemental oxygen to maintain SpO2 ≥90% 1
• Consider non-invasive positive pressure ventilation (CPAP/BiPAP) for respiratory support if oxygenation remains inadequate despite supplemental oxygen 2
• Intubation and mechanical ventilation may be required for frank respiratory failure 2

Monitoring During Recovery

• Continue continuous pulse oximetry until respiratory status stabilizes 1
• Perform serial clinical assessments for signs of persistent volume overload (jugular venous distension, peripheral edema, pulmonary rales) 2
• Monitor fluid balance closely and maintain negative fluid balance until pulmonary edema resolves 2

Alternative Vasoconstrictor Therapy

If hepatorenal syndrome treatment must continue after terlipressin-induced pulmonary edema:

• Switch to norepinephrine as continuous IV infusion starting at 0.5 mg/hour, titrating up to 3 mg/hour to achieve mean arterial pressure increase of ≥10 mm Hg 2
• Norepinephrine requires ICU-level monitoring but may have different risk profile for respiratory complications 2
• Continue albumin at reduced doses (20-40 g/day rather than initial 1 g/kg bolus) with careful volume assessment 2

Critical Pitfalls to Avoid

• Do not restart terlipressin after respiratory failure develops, as this is an absolute contraindication per FDA labeling 1
• Avoid aggressive albumin administration without careful volume status assessment, particularly in patients with underlying cirrhotic cardiomyopathy or diastolic dysfunction 2
• Do not delay diuretic therapy once pulmonary edema is recognized, as rapid intervention improves outcomes 2
• Recognize that some cirrhotic patients have underlying cardiac dysfunction that predisposes them to flash pulmonary edema with volume loading 2

Special Considerations

Patients with pre-existing hypoxia (SpO2 <90%) should never receive terlipressin until oxygenation improves, as this is both an FDA contraindication and guideline recommendation 2, 1

The continuous infusion method of terlipressin administration (starting at 2 mg/day) may reduce ischemic side effects compared to bolus dosing, but does not eliminate the risk of respiratory failure from volume overload 2, 3, 4