Reply to: “Noradrenaline in the treatment of patients with hepatorenal syndrome – Back to the roots?”
Authors: Virendra Singh, Souvik Ghosh, Narendra S. Choudhary
Journal: Journal of Hepatology (2012)

Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: A randomized studyJournal of HepatologyVol. 56Issue 6PreviewVarious vasoconstrictors are useful in the management of hepatorenal syndrome (HRS). Terlipressin is the drug of choice; however, it is expensive. In this study, we evaluated safety and efficacy of terlipressin and noradrenaline in the treatment of HRS. Full-Text PDF Noradrenaline in the treatment of patients with hepatorenal syndrome – Back to the roots?Journal of HepatologyVol. 57Issue 4PreviewIn a randomized study, Singh et al. evaluated the efficacy of noradrenaline vs. terlipressin in the treatment of patients with HRS1 [1]. According to their results, they suggest that noradrenaline is as safe and effective as terlipressin, but less expensive. The response of noradrenaline is mostly due to its vasoconstricting α-mimetic and perhaps additional ß-mimetic effects. The first report on a vasopressor therapy in a patient with renal dysfunction was published fifty years ago [2]. Metaraminol, an α- and ß-mimetic substance, increased the excretion of water, sodium, and potassium, as well as the inulin and PAH clearance in cirrhotic patients with and without renal insufficiency. Full-Text PDF Open Access We thank Dr. Lenz for his interest in our paper. We agree with his view on noradrenaline and terlipressin therapy in hepatorenal syndrome (HRS). It would have been ideal to compare the two vasopressors if given as infusion and dose monitored by mean arterial pressure. However, terlipressin has been used as bolus therapy in most of the studies [[1]Sanyal A. Boyer T. Garcia-Tsao G. Regenstein F. Rossaro L. Appenrodt B. et al.A randomized prospective double-blind placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome.Gastroenterology. 2008; 134: 1360-1368Abstract Full Text Full Text PDF PubMed Scopus (464) Google Scholar]. Gerbes et al. [[2]Gerbes A.L. Huber E. Gulberg V. Terlipressin for hepatorenal syndrome: continuous infusion as an alternative to iv bolus administration.Gastroenterology. 2009; 137: 1179Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar] treated 32 consecutive patients with HRS with continuous terlipressin infusion and reported reversal of HRS in 42% of patients in a retrospective study. They concluded that continuous terlipressin infusion may achieve response rates comparable with those of bolus administration, but possibly at a lower daily dose (3 mg) and with less severe complications (9%). In our study also, dose, adverse effects, and response rates with bolus administration were comparable. However, more studies focusing specifically on this aspect are needed to answer this question. High urinary sodium was unusual in our patients. However, the following factors may explain this finding:(1)In patients with the hepatorenal syndrome, there is renal sodium retention, and urinary sodium is characteristically less than 10 mmoles per liter throughout their clinical course [[3]Papper S. Hepatorenal syndrome.in: Epstein M. The kidney in liver disease. 2nd ed. Elsevier Biomedical, New York1983: 87-106Google Scholar]. However, occasional patients with the hepatorenal syndrome have been recognized in whom urinary sodium is consistently greater than 10 mmoles per liter [[3]Papper S. Hepatorenal syndrome.in: Epstein M. The kidney in liver disease. 2nd ed. Elsevier Biomedical, New York1983: 87-106Google Scholar]. In some of these patients, urinary sodium is initially low but increases to levels of approximately 40 mmoles per liter as renal impairment progresses, and it has been suggested that this late increase in urinary sodium concentration may represent the possible transition to acute tubular necrosis [[3]Papper S. Hepatorenal syndrome.in: Epstein M. The kidney in liver disease. 2nd ed. Elsevier Biomedical, New York1983: 87-106Google Scholar]. Trawale et al. [[4]Trawale J.M. Paradis V. Rautou P.E. et al.The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study.Liver Int. 2010; 30: 725-732Crossref PubMed Scopus (132) Google Scholar], also demonstrated acute tubular necrosis in cirrhotic patients with HRS (high serum creatinine levels, proteinuria <0.5 g/day and no haematuria).(2)The current diagnostic criteria for HRS include presence of cirrhosis, ascites, serum creatinine >1.5 mg/dl after at least 48 h of diuretic withdrawal and volume expansion with albumin plus absence of shock, treatment with nephrotoxic drugs, and parenchymal renal disease [[5]Salerno F. Gerbes A. Gines P. Wong F. Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis.Gut. 2007; 56: 1310-1318Crossref PubMed Scopus (75) Google Scholar]. The use of minor criteria (urine sodium <10 mEq/L) and exclusion of patients with infections is abandoned. The majority of the trials published showed low urinary sodium and used the previously established criteria [[6]Arroyo V. Gines P. Gerbes A.L. et al.Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club.Hepatology. 1996; 23: 164-176Crossref PubMed Google Scholar], and might have excluded patients with urine sodium >10 mEq/L.(3)All our patients were admitted in emergency, hence were consuming salt without any restriction in their diet and some of the patients were on diuretics which were withdrawn only after admission.(4)A relatively high urinary sodium concentration has been observed in patients with HRS and alcoholic hepatitis [[7]Dudley F.J. Kanel G.C. Wood L.J. Reynolds T.B. Hepatorenal syndrome without avid sodium retention.Hepatology. 1986; 6: 248-251Crossref PubMed Scopus (39) Google Scholar] and more than 60% of our patients were alcoholic in etiology.(5)Relative adrenal dysfunction is a common problem in patients with cirrhosis with or without sepsis [8Tsai M.H. Peng Y.S. Chen Y.C. et al.Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock.Hepatology. 2006; 43: 673-681Crossref PubMed Scopus (219) Google Scholar, 9Risso A. Alessandria C. Elia C. Mezzabotta L. Andrealli A. Spandre M. et al.Adrenal dysfunction in nonseptic cirrhotic patients with ascites: impact on survival [Abstract].Digest Liver Dis. 2011; 43: S74-S75Abstract Full Text PDF Google Scholar] and adrenal insufficiency is associated with high urinary sodium [[10]Hoorn E.J. Zietse R. Hyponatremia revisited: translating physiology to practice.Nephron Physiol. 2008; 108: 46-59Crossref Scopus (80) Google Scholar]. As pointed out by Dr. Lenz, in some of our patients ongoing infection cannot be excluded which might have contributed to the adrenal insufficiency and high urinary sodium, however, all our patients were covered with broad spectrum antibiotics. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.