From the Guidelines
Midodrine acts in hepatorenal syndrome by stimulating alpha-1 adrenergic receptors, causing peripheral vasoconstriction which increases systemic vascular resistance and blood pressure. In hepatorenal syndrome, patients experience splanchnic vasodilation and decreased effective arterial blood volume, leading to renal vasoconstriction and reduced kidney function. By constricting peripheral blood vessels, midodrine redirects blood flow from the dilated splanchnic circulation back to the central circulation, improving renal perfusion pressure and glomerular filtration rate. This helps counteract the pathophysiological cascade of hepatorenal syndrome.
Key Points
- Midodrine is typically administered orally at doses of 7.5–15 mg orally three times daily, often in combination with other vasoconstrictors like octreotide 1.
- Treatment duration depends on clinical response but is generally continued until improvement in renal function or as a bridge to liver transplantation.
- Side effects may include supine hypertension, bradycardia, and piloerection (goosebumps), so blood pressure monitoring is essential during therapy.
- The combination of midodrine and octreotide is less effective than terlipressin and should not be used as a first-line treatment for hepatorenal syndrome 1.
- Midodrine can be used as an alternative to terlipressin in countries where terlipressin is not available, or in patients who have failed terlipressin therapy 1.
From the Research
Mechanism of Action of Midodrine in Hepatorenal Syndrome
The mechanism of action of midodrine in hepatorenal syndrome is related to its vasoconstrictive properties. Midodrine is an oral adrenergic vasoconstrictor that is used to treat hepatorenal syndrome, particularly in patients who do not respond to other treatments or when terlipressin is not available 2, 3, 4, 5.
Vasoconstrictive Effects
- Midodrine works by constricting blood vessels, which increases blood pressure and improves renal perfusion 2, 3.
- The vasoconstrictive effects of midodrine are thought to be mediated by its action on alpha-adrenergic receptors, which causes blood vessels to constrict 4, 5.
- Midodrine is often used in combination with octreotide, a somatostatin analogue that inhibits the release of vasodilatory hormones, to enhance its vasoconstrictive effects 2, 3.
Clinical Efficacy
- The clinical efficacy of midodrine in hepatorenal syndrome has been evaluated in several studies, with mixed results 2, 3, 4, 5.
- Some studies have shown that midodrine can improve renal function and reduce mortality in patients with hepatorenal syndrome 2, 3.
- However, other studies have found that midodrine is less effective than other treatments, such as terlipressin or norepinephrine, in improving renal function and reducing mortality 3, 4, 5.
- A study found that midodrine is not effective in preventing hepatorenal syndrome type 2 recurrence 6.
Limitations and Uncertainties
- The evidence for the use of midodrine in hepatorenal syndrome is limited by the small number of studies and the variability in study design and outcomes 2, 3, 4, 5.
- Further research is needed to fully understand the mechanism of action of midodrine in hepatorenal syndrome and to determine its optimal use in clinical practice 2, 3, 4, 5.