The combination of octreotide and midodrine is not superior to albumin in preventing recurrence of ascites after large-volume paracentesis

Abstract

Background & aims: Large-volume paracentesis (LVP) is the treatment of choice for patients with cirrhosis and refractory ascites. However, LVP can lead to postparacentesis circulatory dysfunction (PCD), which is associated with faster ascites recurrence and renal failure. PCD results from vasodilatation, which reduces effective blood volume, and is prevented by intravenous administration of albumin. Vasoconstrictors could be used instead of albumin and, with longer use, prevent PCD and delay ascites recurrence.

Methods: We performed a multicenter, randomized, double-blind, placebo-controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP. Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide (n = 13). Patients in the vasoconstrictor group received saline solution (as a placebo for albumin), 10 mg of oral midodrine (3 times/day), and a monthly 20-mg intramuscular injection of long-acting octreotide (n = 12). Patients were followed up until recurrence of ascites.

Results: The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group (P = .318). There were no significant differences in PCD between the albumin group (18%) and the vasoconstrictor group (25%, P = .574). When ascites recurred, serum levels of creatinine were higher in the vasoconstrictor group (1.2 vs 0.9 mg/dL in the albumin group; P = .051).

Conclusions: The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis. Outcomes appear to be worse in patients given octreotide and midodrine. ClinicalTrials.gov number, NCT00108355.

Figure 1

Flowchart of patients considered and entered into the study

Figure 2

Probability of developing recurrent ascites in the albumin (control) group compared to the vasoconstrictor (study) group. There were no differences in recurrence of ascites with a median time to recurrence of 10 days in the albumin group and 8 days in the vasoconstrictor group (p=0.318)

Figure 3

A. Changes in individual plasma renin activity at randomization (day 1) and at day 6 in the albumin (control group). 2/11 (18%) patients (continuous line) developed post-paracentesis circulatory dysfunction B. Changes in individual plasma renin activity at randomization (day 1) and at day 6 in the vasoconstrictor (study group). 2/8 (25%) patients (continuous line) developed post-paracentesis circulatory dysfunction.

Figure 3

A. Changes in individual plasma renin activity at randomization (day 1) and at day 6 in the albumin (control group). 2/11 (18%) patients (continuous line) developed post-paracentesis circulatory dysfunction B. Changes in individual plasma renin activity at randomization (day 1) and at day 6 in the vasoconstrictor (study group). 2/8 (25%) patients (continuous line) developed post-paracentesis circulatory dysfunction.