Comparison of Midodrine and Albumin in the Prevention of Paracentesis-induced Circulatory Dysfunction in Cirrhotic Patients: A Randomized Pilot Study

Goals: In this pilot study, we compared midodrine and albumin in the prevention of paracentesis-induced circulatory dysfunction (PICD). Background: PICD with pronounced arterial vasodilatation in cirrhotics with tense ascites can be prevented by the infusion of albumin, which is an expensive treatment modality. Various vasoconstrictors have also been used to prevent PICD, but there are few studies about the usage of midodrine. Study: Fifty patients with cirrhosis and tense refractory ascites were randomly assigned to be treated with either midodrine (n=25) (12.5 mg 3 times/d; over 3 d) or albumin (n=25) (8 g/L of removed ascites) after a large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring serum creatinine, serum sodium, plasma renin activity, and aldosterone concentration before and 6 days after paracentesis. Results: Midodrine therapy was cheaper compared with albumin therapy, but serum creatinine, serum sodium, plasma renin activity, and plasma aldosterone concentration values after treatment [0.99±0.19 to 3.02±2.58 mg/dL (P=0.001), 132.36±3.2 to 130.2±4.1 mEq/L (P<0.001), 3.03±0.33 to 4.2±0.76 ng/mL/h (P<0.001), and 166.72±64.26 to 298.64±130 pg/mL (P<0.001), respectively] significantly differed in the midodrine group from that in the albumin group [1.10±0.22 to 1.11±0.161 mg/dL (P=0.885), 132.2±3.524 to 131.88±3.09 mEq/L (P=0.246), 4±0.91 to 4.11±0.74 ng/mL/h (P=0.440), and 204.88±115.9 to 177.08±100.5 pg/mL (P<0.001), respectively]. Seven patients, among whom 6 were hepatocellular carcinoma (HCC) positive, in the midodrine group of our study died as a consequence of liver failure complicated by acute renal failure, followed by hepatic encephalopathy. Whereas in the albumin group, even among the 7 patients with HCC, no patient died or developed hepatorenal syndrome or developed hepatic encephalopathy. Conclusions: This pilot study suggests that midodrine is not as effective as intravenous albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and tense ascites, especially with HCC-positive patients.

[1]  A. Bhalla,et al.  Midodrine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. , 2012, Journal of hepatology.

[2]  Hoda Aly Aly Abd El Moety,et al.  Evaluation of nitric oxide as a novel diagnostic marker for hepatocellular carcinoma , 2011 .

[3]  M. Rizzetto,et al.  Midodrine in the prevention of hepatorenal syndrome type 2 recurrence: a case-control study. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[4]  D. García-Compeán,et al.  Total therapeutic paracentesis (TTP) with and without intravenous albumin in the treatment of cirrhotic tense ascites: a randomized controlled trial. , 2008, Liver.

[5]  F. Lammert,et al.  Prevention of paracentesis‐induced circulatory dysfunction: midodrine vs albumin. A randomized pilot study , 2008, Liver international : official journal of the International Association for the Study of the Liver.

[6]  A. Bhalla,et al.  Midodrine Versus Albumin in the Prevention of Paracentesis-Induced Circulatory Dysfunction in Cirrhotics: A Randomized Pilot Study , 2008, The American Journal of Gastroenterology.

[7]  T. Sauerbruch,et al.  Vascular dysfunction in human and rat cirrhosis: Role of receptor‐desensitizing and calcium‐sensitizing proteins , 2007, Hepatology.

[8]  A. Fotopoulos,et al.  Effects of a 7-day treatment with midodrine in non-azotemic cirrhotic patients with and without ascites. , 2007, Journal of hepatology.

[9]  A. Bhalla,et al.  Noradrenaline and albumin in paracentesis‐induced circulatory dysfunction in cirrhosis: a randomized pilot study , 2006, Journal of internal medicine.

[10]  K. Jakobs,et al.  Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats. , 2006, Gastroenterology.

[11]  T. Asselah,et al.  Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study , 2002, Gut.

[12]  B. Runyon.  Albumin infusion for spontaneous bacterial peritonitis , 1999, The Lancet.

[13]  P. Angeli,et al.  Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide , 1999, Hepatology.

[14]  T. Sauerbruch,et al.  Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis. , 1999, Gastroenterology.

[15]  L. Molina,et al.  Hemodynamic changes in patients developing effective hypovolemia after total paracentesis. , 1998, Journal of hepatology.

[16]  B. Runyon.  Management of adult patients with ascites caused by cirrhosis , 1998, Hepatology.

[17]  W. Jiménez,et al.  Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis. , 1997, Gastroenterology.

[18]  R. Freeman,et al.  Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. , 1997, JAMA.

[19]  W. Jiménez,et al.  Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. , 1996, Gastroenterology.

[20]  J. Schölmerich,et al.  Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis , 1996, Hepatology.

[21]  W. Jiménez,et al.  Beneficial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis , 1995, Hepatology.

[22]  G. Grassi,et al.  Time course of circulatory and humoral effects of rapid total paracentesis in cirrhotic patients with tense, refractory ascites. , 1994, Gastroenterology.

[23]  S. Badalamenti,et al.  Randomized comparative study of hemaccel vs. albumin infusion after total paracentesis in cirrhotic patients with refractory ascites , 1991, Hepatology.

[24]  J. Llach,et al.  Dextran-70 versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis. Results of a randomized study. , 1990, Gastroenterology.

[25]  Vicente Arroyo,et al.  Peripheral arterial vasodilation hypothesis: A proposal for the initiation of renal sodium and water retention in cirrhosis , 1988, Hepatology.

[26]  J. Llach,et al.  Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. , 1988, Gastroenterology.

[27]  W. Jiménez,et al.  Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. , 1987, Gastroenterology.

[28]  H. Bonkovsky,et al.  Effects of therapeutic paracentesis on systemic and hepatic hemodynamics and on renal and hormonal function , 1987, Hepatology.

[29]  K. Goa,et al.  Midodrine , 2012, Drugs.

[30]  V. Arroyo,et al.  Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. , 2003, Journal of hepatology.