Primary Treatment for Splanchnic Vasodilation
The primary treatment for splanchnic vasodilation depends on the underlying clinical context: for portal hypertension, non-selective beta-blockers (propranolol or nadolol) are first-line therapy; for hepatorenal syndrome-AKI caused by extreme splanchnic vasodilation, terlipressin combined with albumin is the treatment of choice. 1, 2
Context-Specific Treatment Approach
Portal Hypertension with Splanchnic Vasodilation
Non-selective beta-blockers (NSBBs) are the cornerstone pharmacologic treatment for splanchnic vasodilation in the setting of portal hypertension. 1, 2
NSBBs work through dual mechanisms: β2-adrenergic blockade causes splanchnic vasoconstriction (directly counteracting the pathologic vasodilation), while β1-adrenergic blockade decreases cardiac output, thereby reducing portal venous inflow. 1, 2
Propranolol and nadolol are the recommended agents, as they effectively reduce portal pressure by targeting the increased splanchnic blood flow that maintains portal hypertension. 1, 2
The splanchnic vasodilation in cirrhosis results from increased production of vasodilators (nitric oxide, prostacyclin, carbon monoxide, endocannabinoids) and impaired responsiveness to vasoconstrictors. 1, 3, 4
Hepatorenal Syndrome-AKI from Extreme Splanchnic Vasodilation
Terlipressin is the vasoactive drug of choice, with concurrent albumin considered based on volume status. 1
The pathophysiology of HRS-AKI involves extreme splanchnic vasodilation causing low effective arterial blood volume, which triggers renal vasoconstriction and decreased glomerular filtration rate. 1
Vasoconstrictors counteract splanchnic vasodilation, increasing renal blood flow and glomerular filtration rate. 1
Terlipressin has the strongest evidence from placebo-controlled RCTs, demonstrating improvement in renal function and decreased need for renal replacement therapy. 1
Alternative vasoconstrictors include norepinephrine or the combination of octreotide/midodrine when terlipressin is unavailable. 1
Albumin (1 g/kg daily for 2 consecutive days, capped at 100 g/day) is the volume expander of choice as it more effectively restores effective arterial blood volume than saline in cirrhosis with ascites. 1
Additional Vasoconstrictor Options
Octreotide decreases splanchnic blood flow through its somatostatin-like actions and can be used in combination with midodrine for HRS-AKI when terlipressin is not available. 1, 5
Terlipressin dosing typically starts at 2 mg IV every 4 hours, titrated to 1 mg IV every 4 hours once clinical response is achieved. 2
Critical Timing Considerations
Early initiation of vasoconstrictor therapy is essential. Higher baseline creatinine levels are associated with lower response rates; patients with creatinine >5 mg/dL have low response rates and are unlikely to benefit. 1
The CONFIRM trial lowered the treatment threshold to creatinine ≥2.25 mg/dL, supporting earlier intervention. 1
HRS reversal occurs in 34-60% of patients when treatment is started promptly, with decreased mortality. 6
Important Caveats
Vasoconstrictors should only be used for HRS-AKI, not for other forms of AKI in cirrhosis, as they are only effective when the underlying pathophysiology is extreme splanchnic vasodilation. 1
NSBBs should be temporarily suspended during acute bleeding episodes, as they decrease blood pressure and blunt the physiologic heart rate response. 2
Vasodilators that act on intrahepatic vessels (nitrates, alpha-adrenergic antagonists) should not be used alone for splanchnic vasodilation, as they also cause systemic vasodilation and may worsen sodium retention. 1
Evidence is currently insufficient to recommend vasoconstrictors for spontaneous bacterial peritonitis, despite theoretical benefits. 1