Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: A pilot study

Abstract

Treatment of hepatorenal syndromes (HRSs) is currently based on vasopressin analogs. The aim of this pilot study was to evaluate the efficacy and safety of noradrenalin (NA) in the treatment of type 1 HRS. Between 1998 and 2000, 12 consecutive patients with type 1 HRS (7 men, 5 women; mean age, 54 ؎ 11 years; mean Child-Pugh score, 11.3 ؎ 1.7) were treated with intravenous NA (0.5-3 mg/h), in combination with intravenous albumin and furosemide. NA was given for 10 ؎ 3 days, at a mean dose of 0.8 ؎ 0.3 mg/h. Reversal of HRS was observed in 10 of 12 patients (83%; 95% confidence interval, 52%-98%) after a median of 7 days (range, 5-10 days). Serum creatinine levels fell from 358 ؎ 161 to 145 ؎ 78 mol/L (P < .001), creatinine clearance rose from 13 ؎ 9 to 40 ؎ 15 mL/min (P ‫؍‬ . H epatorenal syndrome (HRS) is a frequent and major complication of end-stage cirrhosis. It is considered as a functional renal failure caused by marked renal vasoconstriction, related to peripheral (mainly splanchnic) arterial vasodilation. 1 Type 1 HRS usually occurs in patients with end-stage liver disease and shows a poor prognosis. The median survival time is about 10 days. It is defined as rapidly progressive renal failure with a 50% reduction in initial creatinine clearance to below 20 mL/min within 15 days. 2 Type 2 HRS occurs instead in patients with refractory ascites and is characterized by moderate and more stable impairment of renal function. Liver transplantation is the only treatment to improve survival in patients with type I HRS 3 ; however, because of the very poor prognosis of type 1 HRS and because of organ shortage, a donor is usually not found quickly enough to avoid death. HRS management thus focuses on improving renal function and thereby extending survival pending liver transplantation. This has recently been addressed by assessing the effects of vasoconstrictors that, combined with plasma expanders, restore the collapse of systemic vascular resistances (SVRs) underlying HRS. 1,4-9 Thus, vasopressin analogs such as ornipressin 4-6 and terlipressin 7-9 improve renal perfusion and glomerular filtration in patients with HRS by inducing vasoconstriction of the splanchnic circulation.Noradrenalin (NA) is a catecholamine with predominantly ␣-adrenergic activity. Given its vasoconstricting effects in venous and arterial systems, and its limited action on the myocardium, it is currently the drug of choice for vasoplegic shock. These pharmacologic properties suggest that NA might also counteract the collapse in SVRs leading to HRS. After a case report of successful treatment of HRS with a combination of NA and dopamine, 10 we conducted a pilot study to Abbreviations: HRS, hepatorenal syndrome; SVR, systemic vascular resistance; NA, noradrenalin; CVP, central venous pressure; MAP, mean arterial pressure. From the

Hepatorenal Syndrome

“…Patients who were treated with vasopressin had a significantly higher HRS recovery rate and improved survival and were more likely to receive a liver transplant (100). Finally, the administration of intravenous norepinephrine in association with albumin and furosemide resulted in reversal of HRS in 10 (83%) of 12 patients with type 1 HRS, and ischemic episodes were observed in only two (104). It is interesting that two of the responders to norepinephrine had previously failed terlipressin therapy.…”

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.…”

Combination octreotide, midodrine, and albumin may improve survival in patients with hepatorenal syndrome, but the evidence is weak

“…One small pilot study (N=12) looked at the effect of norepinephrine and found norepinephrine effective. 2 One study found that norepinephrine had similar outcomes compared to terlipressin 3 . However, the use of norepinephrine on general medical wards is usually not possible, and therefore was not an option for our patient.…”