Short-term effects of midodrine and octreotide on renal function and mortality in patients with Type I hepatorenal syndrome.

The hepatorenal syndrome (HRS) was defined by the International Ascites Club (1996) as the development of renal failure in patients with acute or chronic disease in the absence of other identifiable causes of deterioration in renal function. The HRS is classified as Type I or Type II. Type I HRS is characterized by acute onset and rapid clinical deterioration. Renal failure usually occurs with 24 hours and death typically ensues within 14 days. Type II HRS is characterized by a slower onset with subsequent clinical deterioration occurring over several months. The purpose of this study was to determine if oral administration of the alpha agonist midodrine in association with subcutaneous administration of octreotide preserved short-term renal function in patients with Type I HRS. Retrospective chart review of all patients treated with oral midodrine and subcutaneous octreotide over a 3-year period was conducted using pharmacy computer software. Type I HRS was identified in 6 patients (4 males, 2 females). Dosage of midodrine ranged from 5.0-7.5 mg orally 3 times per day. Octreotide was administered at a dosage of 50 micrograms subcutaneously 3 times per day. The duration of therapy ranged from 5 to 10 days. Prior to treatment all patients received appropriate fluid resuscitation. The causes of liver disease were alcoholic cirrhosis in 4, cirrhosis from hepatitis C in 1, and autoimmune hepatitis in 1. Serum creatinine (Cr), blood urea nitrogen (BUN), BUN/Cr ratio, and urine output (UOP) were measured/calculated and mean values obtained during therapy were compared with values obtained just before treatment using the Wilcoxon Rank Sum Test. The table shows the mean serum creatinine, BUN, BUN/creatinine ratios and urine output values prior to and during midodrine/octreotide therapy. All patients died of multiorgan failure. Deaths occurred on days 5, 7, 14, 17, 25 and 64. Administration of oral midodrine in association with subcutaneous octreotide retards but does not reverse the progression of renal failure and death in patients with Type I HRS. By delaying progression, this therapeutic combination has the potential to serve as a bridge to liver transplantation in patients with Type I HRS.

Srinivas R. Puli, MD, Martin A, Alpert, MD, Alex S. Befeler, MD, and Vanaja Puli, MD. St John's Mercy Medical Center, St Louis University School of Medicine, St Louis, MO.