Acute effects of the oral administration of midodrine, an ?-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites

Abstract

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available ␣-mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index ( The improvement in systemic hemodynamics, which was also maintained during the the 3-to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 ؎ 43.1 vs. 385.7 ؎ 39.9 mL · min ؊1 ; P F .005), GFR (93.1 ؎ 6.5 vs. 77.0 ؎ 6.7 mL · min ؊1 ; P F .025), and UNaV (92.7 ؎ 16.4 vs. 72.2 ؎ 10.7 Eq · min ؊1 ; P F .025). In addition, a decrease in PRA (5.33 ؎ 1.47 vs. 7.74 ؎ 2.17 ng · mL ؊1 · h; P F .05), ADH (1.4 ؎ 0.2 vs. 1.7 ؎ 0.2 pg · mL ؊1 ; P F .05), and NOx (33.4 ؎ 5.0 vs. 49.3 ؎ 7.3 mol ؊1 ; P F .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 ؎ 3.70 vs. 20.70 ؎ 4.82 ng · mL ؊1 · h; P F .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function. (HEPATOLOGY 1998;28:937-943.)It has been hypothesized that a peripheral arterial vasodilation is the main factor in the pathogenesis of the functional renal abnormalities in patients with cirrhosis. 1-3 Arterial vasodilation is thought to be related to an excess of local or systemic vasodilators such as glucagon, prostacyclin, substance P, vasoactive intestinal peptide, bile acids, and nitric oxide. [3][4][5][6][7] The localization of arterial vasodilation as well as its link with renal sodium retention are also debated. Clinical and experimental studies suggest that the reduction of arterial vascular resistance occurs mainly in the splanchnic area, whereas in many other vascular beds, i.e., in the renal vascular bed, arterial resistance is normal or even increased in cirrhosis with ascites. 8,9 The reflex activation of the neurohumoral pressor systems, sympathetic nervous ...

Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

“…In another study on acute effects of midodrine, an improvement in GFR and U Na was observed in patients with ascites, and no effect was seen in patients with type 2 HRS. 25 Although the V1 receptor agonists induce splanchnic vasoconstriction, the effects of alpha-1-adrenergic agonists on splanchnic vasodilatation, which is considered a key factor in the pathogenesis of ascites, 5 are unknown in patients with cirrhosis.…”

Pathophysiology of renal disease associated with liver disorders: Implications for liver transplantation. Part I

“…Therefore, the administration of agents that decrease bile acid levels, bacterial translocation, or secondary consequences of endotoxin circulation and inflammation could be considered therapeutic options. 2,108,138,[161][162][163][164][165][166][167][168][169] For instance, ursediol (ursodeoxycholic acid) has been shown in some studies to decrease bile acid toxicity and endotoxin levels, as well as soluble ICAM-1 and TNF-␣ levels, and even decrease intestinal production of nitric oxide. 146,152,[170][171][172][173][174][175] In addition, MARS treatments (albumin dialysis with hemofiltration) have been shown to decrease TNF-␣ and IL-6 levels and improve survival in type 1 HRS.…”

Non-Selective Beta-Blockers in Liver Cirrhosis: Friends or Foes? A Review of the Literature

“…Similarly, Krag and colleagues found that patients with a low cardiac index (< 1.5L/ min/m 2 ) significantly developed more hepatorenal syndrome and had decreased survival rate compared to those with a cardiac index above 1.5 L/min/m 2 [33] . Correspondingly, several studies confirmed this concept by showing that midodrine, an alpha-1 adrenergic agonist, was beneficial in patients with advanced cirrhosis [35][36][37][38][39] . Midodrine therapy increased urinary volume, urinary sodium excretion, blood pressure, and decreased plasma renin activity and overall mortality [39] .…”