Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome

Saló, Joan; Ginés, Àngels; Quer, Juan Carlos; Fernández‐Esparrach, Glòria; Guevara, Mónica; Ginès, Pere; Bataller, Ramón; Planas, Ramón; Jiménez, Wladimiro; Arroyo, Vicente; Rodés, Juan

doi:10.1016/s0168-8278(96)80297-2

Cited by 52 publications

(27 citation statements)

References 30 publications

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“…This resulted in a variable duration of treatment between 5 and 27 days (median, 14 days) in the patients treated successfully. Although shortterm ornipressin infusion cannot revert HRS, 11,18 prolonged ornipressin treatment considerably improves renal function or completely reverses HRS. 16,19 Derived from the present data the duration of therapy required seems quite variable.…”

Section: Discussionmentioning

confidence: 99%

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

Gülberg¹,

Bilzer²,

Gerbes³

1999

Hepatology

186

100

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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 The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia.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...

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Section: Discussionmentioning

confidence: 99%

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

Gülberg¹,

Bilzer²,

Gerbes³

1999

Hepatology

186

100

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“…13,14 Likewise, controversial results were obtained with the administration of vasoconstrictor agents in patients with cirrhosis and ascites and hepatorenal syndrome (HRS). [15][16][17] The acute administration of ornipressin, an arterial vasoconstrictor with a preferential effect on splanchnic circulation, improved systemic hemodynamics with slight 15,16 or no 17 effect on renal hemodynamics and function. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention in patients with cirrhosis and ascites with or without HRS.…”

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confidence: 99%

Acute effects of the oral administration of midodrine, an ?-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites

et al. 1998

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The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available ␣-mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index ( The improvement in systemic hemodynamics, which was also maintained during the the 3-to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 ؎ 43.1 vs. 385.7 ؎ 39.9 mL · min ؊1 ; P F .005), GFR (93.1 ؎ 6.5 vs. 77.0 ؎ 6.7 mL · min ؊1 ; P F .025), and UNaV (92.7 ؎ 16.4 vs. 72.2 ؎ 10.7 Eq · min ؊1 ; P F .025). In addition, a decrease in PRA (5.33 ؎ 1.47 vs. 7.74 ؎ 2.17 ng · mL ؊1 · h; P F .05), ADH (1.4 ؎ 0.2 vs. 1.7 ؎ 0.2 pg · mL ؊1 ; P F .05), and NOx (33.4 ؎ 5.0 vs. 49.3 ؎ 7.3 mol ؊1 ; P F .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 ؎ 3.70 vs. 20.70 ؎ 4.82 ng · mL ؊1 · h; P F .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function. (HEPATOLOGY 1998;28:937-943.)It has been hypothesized that a peripheral arterial vasodilation is the main factor in the pathogenesis of the functional renal abnormalities in patients with cirrhosis. 1-3 Arterial vasodilation is thought to be related to an excess of local or systemic vasodilators such as glucagon, prostacyclin, substance P, vasoactive intestinal peptide, bile acids, and nitric oxide. [3][4][5][6][7] The localization of arterial vasodilation as well as its link with renal sodium retention are also debated. Clinical and experimental studies suggest that the reduction of arterial vascular resistance occurs mainly in the splanchnic area, whereas in many other vascular beds, i.e., in the renal vascular bed, arterial resistance is normal or even increased in cirrhosis with ascites. 8,9 The reflex activation of the neurohumoral pressor systems, sympathetic nervous ...

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“…As potential renal vasodilators, dopamine (in nonpressor dose) [23][24][25][26][27][28][29], prostaglandin A 1 [25], misoprostol (synthetic prostaglandin E 1 ) [30,31], prostaglandin E 2 [31], and prostacyclin (prostaglandin I 2 ) [28] have all been tried without success in the treatment of hepatorenal syndrome. In particular, dopamine has never been shown to improve renal function in hepatorenal syndrome despite its ability to increase renal blood flow [24,26,27].…”

Section: The Rationale Behind Pharmacological Treatment Of Hepatorenamentioning

confidence: 99%

“…In 1996, Saló et al studied the effect of a 1-hour infusion of noradrenalin (0.45 µg/kg/min) in five patients with cirrhosis and hepatorenal syndrome [28]. Despite achieving the intended increase in mean arterial pressure of 15 mm Hg, no effect was observed in GFR, renal plasma flow, free water clearance, urine volume, or sodium excretion.…”

Section: Noradrenalinmentioning

confidence: 99%

Vasoconstrictor Therapy for Hepatorenal Syndrome in Liver Cirrhosis

Schmidt¹,

Ring‐Larsen²

2006

CPD

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Hepatorenal syndrome is a severe, but not uncommon complication of decompensated liver cirrhosis. In particular, the rapidly progressive form of hepatorenal syndrome (type 1) is associated with a dismal prognosis. Established hepatorenal syndrome has a spontaneous reversibility below 5%. Hepatorenal syndrome is involved in more than 50% of cirrhosis-related mortality. Thus, any treatment capable of reversing hepatorenal syndrome would be expected to reduce morbidity and mortality from liver cirrhosis. A pathophysiological hallmark of hepatorenal syndrome is arterial underfilling due to an extreme splanchnic vasodilatation. Consequently, potent vasoconstrictors capable of reversing this vasodilatation have been investigated in hepatorenal syndrome. Several vasoconstrictors including the alpha-adrenergic agonists, midodrine and noradrenalin, and the vasopressor analogues, ornipressin and terlipressin, have all been associated with a significant improvement in renal function in 57 to 100% of cases and even reversal of hepatorenal syndrome in 42 to 100% of cases. The majority of recent studies are on terlipressin. A randomized, controlled trial showed a significant effect of terlipressin on reversal of hepatorenal syndrome. The contribution of volume expansion to the beneficial effects of vasoconstrictors on hepatorenal syndrome remains to be determined. In general, reversal of hepatorenal syndrome was associated with an improved survival. However, it remains to be determined if vasoconstrictor therapy should be used in hepatorenal syndrome in general, or if it should be reserved for potential candidates for liver transplantation. In conclusion, evidence for a beneficial effect of vasoconstrictor therapy for the treatment of hepatorenal syndrome is steadily accumulating. Confirmation of the preliminary data in larger randomized, controlled trials looking at long-term survival is required.

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Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome

Cited by 52 publications

References 30 publications

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

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

Acute effects of the oral administration of midodrine, an ?-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites

Vasoconstrictor Therapy for Hepatorenal Syndrome in Liver Cirrhosis

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