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

Abstract

Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 ؎ 1 mL/min, UNaV 7 ؎ 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 g/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 ؎ 4 mL/min, UNaV 47 ؎ 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 ؎ 10 mL/min, UNaV 8 ؎ 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation. (HEPATOLOGY 1999;30:870-875.)The hepatorenal syndrome (HRS) is a serious complication in patients with cirrhosis and ascites and associated with a poor prognosis. 1 It is characterized by a marked reduction of renal blood flow and glomerular filtration rate and a progressive increase in blood urea nitrogen and serum creatinine concentration in patients with markedly reduced liver function and ascites refractory to medical therapy. 2,3 Peripheral arterial vasodilation is thought to play an important role in the pathogenesis of HRS: By reducing the central blood volume peripheral vasodilation activates volume-and sodiumretaining neurohumoral systems, such as the renin-aldosterone system and the sympathetic nervous system. These mediators are responsible for renal vasoconstriction and avid sodium retention in advanced cirrhosis. 4,5 So far, liver transplantation is considered the only causal therapy for HRS. The outcome after transplantation, however, seems to be significantly impaired in patients with HRS compared with patients with normal renal function before liver transplantation. 6 Therefore, pharmacological interventions such as low-dose dopamine infusions have been recommended as a bridge to transplantation. 7 Despite improved renal perfusion in patients with HRS...

A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome

“…The rate of adverse events leading to withdrawal in this study (5%) is consistent with findings in the literature and is reported to be lower with terlipressin as compared with vasopressin and other vasopressin analogues. [37][38][39] In summary, terlipressin plus albumin is superior to placebo for reversal of type 1 HRS and produces a significant decrease in SCr compared with placebo and albumin. Administration of albumin by itself also had a modest salutary effect and reversed HRS in 13% of cases.…”

Hepatorenal syndrome in patients with cirrhosis

“…until GFR had increased to above 40 mL/min or until adverse events prevented further treatment. 48 Renal function improved in four patients after 5-27 days. In two patients, treatment was discontinued because renal function did not improve.…”

New challenge of hepatorenal syndrome: Prevention and treatment

“…105 Lack of a natriuretic response after improvement of renal function may be related to severe liver dysfunction in these patients, as onset of natriuresis has been shown to be related to a threshold of liver function. [106][107][108][109] When terlipressin was combined with either intravenous albumin 110 or a renal vasodilator such as low-dose dopamine, 10 the result was even more encouraging, with suppression of the renin-angiotensin activity and normalization of serum creatinine in a number of patients without serious ischemic side effects. These observations further support the concept that both splanchnic and systemic arterial vasodilatation with effective arterial underfilling, resulting in increased circulating levels of vasoconstrictors, play pathogenetic roles in the development of HRS.…”

“…In HRS, systemic vasoconstrictors such as metaraminol improved urinary sodium excretion but not renal function, 111 whereas norepinephrine 112 or dopamine 10 were ineffective. Oral administration of an ␣-adrenergic agonist, midodrine, improved systemic and renal hemodynamics in nonazotemic cirrhotic patients but had no effect in patients with HRS.…”

“…7,8 Furthermore, liver transplantation is not readily available to every patient, nor is every patient with HRS a suitable candidate for this surgery. We review herein possible ways of preventing HRS and how the new therapies for HRS [9][10][11][12] have shed light on the pathophysiology resulting in improvement in the prognosis of patients with HRS.…”