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Randomized Controlled Trial
. 2010 Oct;32(8):1044-50.
doi: 10.1111/j.1365-2036.2010.04426.x.

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

V L Misra  1 , R Vuppalanchi, D Jones, M Hamman, P Y Kwo, C Kahi, N Chalasani
Affiliations
Randomized Controlled Trial

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

V L Misra et al. Aliment Pharmacol Ther. 2010 Oct.

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.

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Conflict of interest statement

Declaration of personal interests: V. Misra has recruited and followed up patients, abstracted data, wrote and edited the manuscript. R. Vuppalanchi and C. Kahi recruited and followed up patients and edited the manuscript. D. Jones has performed and analysed furosemide and iothalamate assays, and edited the manuscript. M. Hamman has performed assays and edited the manuscript. P. Kwo has edited the manuscript. N. Chalasani has developed concept, recruited and followed up subjects and edited the manuscript. Drs. Chalasani, Vuppalanchi and Kwo have multiple consulting agreements with pharmaceutical companies, but none represent a conflict to the current paper. Drs. Misra, Jones, Kahi and Hamman have no conflicts of interest.

Figures

Figure 1
Figure 1
Graphical representation of the study protocol. A state of equilibration was achieved by acquisition of sodium balance defined as change in body weight ≤0.5 kg on two consecutive days while on metabolic diet (30 mmol Na, 80 mmol K/day).
Figure 2
Figure 2
Urinary sodium excretion rate produced by furosemide (given at time 0), with midodrine and placebo (administered 30 min before IV furosemide) in cirrhotic patients with ascites. There was no difference between two groups (P = 0.9).
Figure 3
Figure 3
Glomerular filtration rate during the study period with midodrine and placebo. There was no difference between two groups (P = 0.4).
Figure 4
Figure 4
Strong relationship between baseline glomerular filtration rate (GFR) and 6-h urinary sodium excretion following furosemide administration (r = 0.62, P = 0.003).
Figure 5
Figure 5
Furosemide pharmacokinetics with midodrine and placebo were not different (P = 0.7).
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