From the Guidelines
Terlipressin can be used in combination with midodrine and octreotide for the treatment of Hepatorenal Syndrome, particularly when terlipressin alone is not available or not tolerated, as evidenced by the most recent study published in 2022 1. The standard approach for HRS type 1 is terlipressin (0.5-2 mg IV every 4-6 hours) plus albumin. However, in countries where terlipressin is unavailable, the combination of midodrine (7.5-12.5 mg orally three times daily), octreotide (100-200 mcg subcutaneously three times daily), and albumin (20-40 g/day IV) has been used as an alternative, as supported by the 2021 practice guidance by the American Association for the Study of Liver Diseases 1. When using these medications together, careful monitoring of blood pressure is essential as all three are vasoconstrictors and could potentially cause excessive vasoconstriction. Some key points to consider when using terlipressin include:
- Predictors of response to terlipressin include a baseline bilirubin of <10 mg/dL, a baseline serum creatinine of <5 mg/dL, and lower stage of acute-on-chronic liver failure, as noted in the 2022 study 1.
- A sustained increase in mean arterial pressure (MAP) by 5–10 mm Hg with treatment is associated with response to terlipressin, as reported in the same study 1.
- Patients on terlipressin need to be monitored for the development of ischemic complications such as arrhythmia, angina, and splanchnic and digital ischemia, as warned by the 2022 study 1. The rationale behind this combination therapy is to counteract the splanchnic and systemic vasodilation that occurs in advanced liver disease, which contributes to reduced effective arterial blood volume and subsequent renal vasoconstriction. Terlipressin acts as a vasopressin analog, while midodrine is an alpha-1 adrenergic agonist, and octreotide inhibits vasodilatory peptides - together they help restore renal perfusion by improving systemic hemodynamics, as explained in the 2021 practice guidance 1. It is essential to weigh the benefits and risks of this combination therapy, considering the potential for ischemic side effects and the need for careful monitoring, as emphasized by both the 2022 study 1 and the 2021 practice guidance 1.
From the Research
Treatment of Hepatorenal Syndrome
- Terlipressin is considered the first-line pharmacological treatment for hepatorenal syndrome 2, 3, 4, 5, 6.
- When terlipressin is unavailable, midodrine/octreotide or norepinephrine, with albumin, represent alternative treatments 2, 3, 4, 5, 6.
Combination Therapy
- There is no direct evidence to support the use of terlipressin in combination with midodrine and octreotide for the treatment of hepatorenal syndrome.
- Studies have compared the efficacy of terlipressin versus midodrine/octreotide, and terlipressin has been shown to be more effective in improving renal function and reducing mortality 3, 4, 5, 6.
- Norepinephrine has also been compared to midodrine/octreotide, and norepinephrine has been shown to be more effective in improving renal function 2, 4.
Efficacy of Terlipressin
- Terlipressin has been shown to increase HRS reversal compared to placebo 4.
- Terlipressin may reduce mortality compared to placebo 4.
- Terlipressin is associated with a higher rate of recovery of renal function compared to midodrine/octreotide 3.