ACUTE EFFECTS OF THE ORAL-ADMINISTRATION OF MIDODRINE, AN ALPHA-ADRENERGIC AGONIST, ON RENAL HEMODYNAMICS AND RENAL-FUNCTION IN CIRRHOTIC-PATIENTS WITH ASCITES

The effects of the acute administration of arterial vasoconstrictors o n renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrh otic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not ac tually 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 vaso constrictor probably represents a further reason for this omission. Co nsequently, the present study was made to evaluate the acute effects o f the oral administration of midodrine, an orally available ar-mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic pat ients with ascites. Mean arterial pressure (MAP), heart rate (HR), car diac index (CI), systemic vascular resistance (SVR), left forearm bloo d flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitra te (NOx) were evaluated in 25 cirrhotic patients with ascites (17 with out HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hou rs after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1,313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm(-5); P < .0001) accompanied by a d ecrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/ - 131.4 vs. 3,152.5 +/- 131.4 mL . min(-1) . m(2) BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and L LBE The improvement in systemic hemodynamics, which was also maintaine d during the the 3- to 6-hour period after midodrine administration, w as accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 38 5.7 +/- 39.9 mL . min(-1); P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6 .7 mL . min(-1); P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 mu Eq . min(-1); P < .025). In addition, a decrease in PRA (5.33 +/- 1 .47 vs. 7.74 +/- 2.17 ng . mL(-1) . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL(-1); P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 mu mol(-1); P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Acco rdingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 v s. 20.70 +/- 4.82 ng . mL(-1) h; P < .0025) in patients with HRS, no s ignificant improvement was observed in RPF, GFR, or UNaV. In conclusio n, the acute oral administration of midodrine is associated with a sig nificant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also imp rove in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on r enal hemodynamics and renal function.