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THE EFFECT OF MIDODRINE, OCTREOTIDE AND ALBUMIN IN REFRACTORY ASCITES
P Tandon, RT Tsuyuki, L Mitchell, M Hoskinson, MM Ma, WW Wong, AL Mason, K Gutfreund, VG Bain
Department of Medicine, University of Alberta, Edmonton, Alberta
BACKGROUND: Ascites is refractory to treatment in 5-10% of cases. The pathogenesis of refractory ascites (RA) is linked to systemic and splanchnic vasodilation and a reduction in the effective circulating volume. Combination pharmacologic therapies have been beneficial in patients with Type 1 HRS. We hypothesized that a combination of midodrine (alpha-1-adrenergic agonist), octreotide-LAR (long-acting release) and albumin would result in weight loss (ascites-related), increased naturesis and an improvement in renal function and the effective circulating volume in patients with RA with or without Type 2 hepatorenal syndrome (HRS).
METHODS: Nine patients with RA received an intramuscular injection of octreotide-LAR, 50 grams of albumin 3 times per week and midodrine titrated to a maximum of 37.5 mg orally per day for 1 month. Measured outcomes included the change in paracentesis-adjusted body weight, naturesis, renal function (serum creatinine, measured and calculated creatinine clearance, Tc-99m-DTPA clearance), aldosterone and renin. Changes from baseline to end of study were compared using non-parametric analysis for related samples.
RESULTS: There was no significant change in renal function from baseline to study end. There was a significant reduction in paracentesis-adjusted weight (p=0.006), an increase in naturesis (p=0.023) and reduction in the serum aldosterone level (p=0.04). There was a transient but significant worsening in the Model for end-stage liver disease (MELD) score (p=0.01), serum bilirubin (p=0.019) and serum INR (p=0.002) which resolved after therapy was discontinued.
CONCLUSIONS: This study is unique in that this combination of agents has not previously been studied in this patient population. Secondly, the duration of therapy was longer than previous studies. In patients with RA, combination therapy results in a significant reduction in paracentesis-adjusted weight and an increase in naturesis without an effect on renal function. The beneficial effects are at the expense of a mild reversible deterioration in hepatic function. Large randomized controlled trials, preferably with pre-defined, clinically relevant outcome measures and clarification of the deterioration in hepatic function are needed before this therapy can be routinely recommended.