Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide

Abstract

The aim of the study was to verify the effects of the administration of an inhibitor of the release of endogenous vasodilators together with a vasoconstrictor agent in patients with hepatorenal syndrome (HRS). This new medical perspective was compared with a traditional medical approach for HRS, such as the infusion of nonpressor doses of dopamine to produce renal vasodilation. Thirteen patients with type 1 HRS were enrolled in the study. Five of them were treated with the oral administration of midodrine and the parenteral administration of octreotide. In addition, the patients received 50 to 100 mL of 20% human albumin solution daily for 20 days. Midodrine and octreotide were dosed to obtain a stable increase of at least 15 mm Hg of mean arterial pressure. Eight patients were treated with the intravenous administration of nonpressor doses of dopamine (2-4 g/kg/min) and the same daily amount of albumin. After 20 days of treatment with midodrine and octreotide, an impressive improvement in renal plasma flow (RPF), glomerular filtration rate, and urinary sodium excretion was observed in patients. This was accompanied by a significant reduction in plasma renin activity, plasma vasopressin, and plasma glucagon. No side effects were observed. Three patients were discharged from the hospital. One of them successfully underwent liver transplantation. One of the two remaining patients is still alive after 472 days with a preserved renal function, and the other died from terminal liver failure after 76 days. One of the two patients who were not discharged from the hospital successfully underwent liver transplantation, and the other died from pneumonia after 29 days. Seven out of eight patients who were treated with dopamine experienced a progressive deterioration in renal function and died during the first 12 days. Only one patient recovered renal function and underwent liver transplantation. In conclusion, the long-term administration of midodrine and octreotide seems to be an effective and safe treatment of type 1 HRS in patients with cirrhosis. (HEPATOLOGY 1999;29:1690-1697.)Hepatorenal syndrome (HRS) occurs in 18% of cirrhotic patients with ascites. HRS is characterized by intense vasoconstriction, low glomerular filtration rate (GFR), preserved tubular function, and normal renal histology. 1 The diagnostic criteria of HRS have been recently reviewed, and HRS has been classified on a clinical basis into two different types: type 1 characterized by rapidly progressive renal function impairment and type 2 in which renal failure does not have a rapidly progressive course. 2 From a pathophysiological point of view HRS is considered to be the extreme expression of a reduced effective circulating volume because of arteriolar vasodilation, particularly in the splanchnic area. 3 Consequently, the extreme increase in the activity of both renin-angiotensin and sympathetic nervous system as well as the elevated circulating levels of endothelin are the most likely cause of HRS. [4][5][6][7][8][9]

Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine

“…21,23 In the present study we did not observe any beneficial effect of low-dose dopamine infusion on renal function after central venous pressure had been normalized with albumin infusions. This is in accordance with the observation by Angeli et al 24 who report that mortality in patients with type 1 HRS treated with low-dose dopamine is not reduced compared with the natural course of the disease. 1 Using a combined infusion of dopamine and ornipressin we could show improved glomerular filtration rate, urine flow, and natriuresis during 5 of 9 treatment episodes.…”

Hepatorenal syndrome, hepatopulmonary syndrome, and now, hepatospinal syndrome?

“…The pathogenesis of renal changes in hepatorenal syndrome is starting to be understood, and a novel therapy using vasoconstrictors in preliminary clinical trials appears promising. 1,2 Hepatopulmonary syndrome with intrapulmonary shunts and hypoxia in patients with portal hypertension also is well described, but less well understood. 3 These stand as just two examples of how otherwise healthy organs remote from the liver can be adversely affected in the face of cirrhosis and portal hypertension.…”

Short-Term Pretransplant Renal Replacement Therapy and Renal Nonrecovery after Liver Transplantation Alone

“…In the absence of LT, the outcomes of these candidates are poor, and are associated with very high mortality rates (1). Pre-LT medical management to reduce portal pressure and the need for RRT are not very successful, but are often used to bridge patients to LT (3)(4)(5)(6)(7)(8).…”