The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites

Aliment Pharmacol Ther. 2010 Oct;32(8):1044-50. doi: 10.1111/j.1365-2036.2010.04426.x.

Abstract

Background: Resistance to loop diuretics is common in patients with ascites. Diminished glomerular filtration rate (GFR) is thought to mediate resistance to loop diuretics. Midodrine, a commonly used alpha-1 agonist, has been shown to improve GFR in non-azotemic patients with cirrhosis.

Aim: To conduct a randomized, double-blind, placebo-controlled, cross-over study to test the hypothesis that midodrine significantly increases natriuretic response of IV furosemide in non-azotemic cirrhotics with ascites.

Methods: All subjects participated in both phases, which were (i) furosemide IV infusion + oral midodrine 15 mg administered 30 min before furosemide (ii) furosemide IV infusion + oral placebo administered 30 min before furosemide. Primary outcomes were 6-h urine sodium excretion and 6-h total urine volume.

Results: A total of 15 patients (men: 8; age: 52.7 ± 7.6 years; serum creatinine: 1.06 ± 0.2 mg/dL) were studied. Total 6-h urine sodium excretion was 109 ± 42 mmol in the furosemide + midodrine treatment phase and was not significantly different from that in the furosemide + placebo treatment phase (126 ± 69 mmol, P = 0.6). Similarly, mean 6-h total urine volume was not significantly different between two groups (1770 ± 262 mL vs. 1962 ± 170 mL, P = 0.25).

Conclusions: Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Orally administered midodrine does not increase natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Ascites / physiopathology
  • Creatinine / blood
  • Cross-Over Studies
  • Diuretics / pharmacokinetics
  • Diuretics / therapeutic use*
  • Double-Blind Method
  • Female
  • Furosemide / pharmacokinetics
  • Furosemide / therapeutic use*
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Infusion Pumps
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / physiopathology*
  • Male
  • Middle Aged
  • Midodrine / pharmacology*
  • Natriuresis / drug effects*
  • Sodium / urine
  • Urination / drug effects
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Diuretics
  • Vasoconstrictor Agents
  • Midodrine
  • Furosemide
  • Sodium
  • Creatinine