Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 7  |  Issue : 1  |  Page : 13-18

Norepinephrine versus terlipressin in patients with type 1 hepatorenal syndrome refractory to treatment with octreotide, midodrine, and albumin ( a prospective randomized comparative study)


Department of Anesthesia and Intensive Care, Cairo University, Cairo, Egypt

Date of Submission29-Jul-2012
Date of Acceptance01-Oct-2012
Date of Web Publication26-Jun-2014

Correspondence Address:
Sahar S.I. Badawy
Department of Anesthesia and Intensive Care, Cairo University, Cairo
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EJCA.0000431078.82595.1f

Rights and Permissions
  Abstract 

Background and objectives

Hepatorenal syndrome (HRS) is a functional renal failure complicating end-stage liver disease. Management of HRS is based on therapy with vasoconstrictors and albumin. The aim of this prospective, randomized, comparative study was to evaluate the efficacy of norepinephrine versus terlipressin in the management of patients with type 1 HRS refractory to treatment with octreotide, midodrine, and albumin.

Methods

This study included 60 patients with type 1 HRS refractory to treatment with octreotide, midodrine, and albumin for 72 h. Patients were randomized to receive norepinephrine or terlipressin plus albumin. The outcomes assessed were as follows: kidney functions, reversal of HRS, survival rate at day 30, and cost of the study medications.

Results

The final statistical analysis included 51 patients; 26 in the terlipressin group and 25 in the norepinephrine group. Demographic data and baseline patient characteristics were comparable in the two groups. The incidences of HRS reversal were comparable in the two groups. In both groups, there was an improvement in kidney functions. The responders in both groups showed a significant improvement in kidney functions at the end of the study compared with baseline. There was a significant progressive decrease in serum creatinine (P⩽0.05) levels and a significant progressive increase in creatinine clearance (P⩽0.05) and urine output (P⩽0.05) compared with baseline. Both groups were comparable throughout the study. The survival rates at day 30 were comparable in the two groups. The cost of norepinephrine therapy was significantly lower than that of terlipressin therapy (57 560±16 870 vs. 13 492±7694 Egyptian pounds; P⩽0.05).

Conclusion

The results of this study suggested that norepinephrine is as effective as terlipressin in the management of patients with type 1 HRS.

Keywords: cost, hepatorenal syndrome, norepinephrine, patient outcome, terlipressin


How to cite this article:
Badawy SS, Meckawy NM, Ahmed A. Norepinephrine versus terlipressin in patients with type 1 hepatorenal syndrome refractory to treatment with octreotide, midodrine, and albumin ( a prospective randomized comparative study). Egypt J Cardiothorac Anesth 2013;7:13-8

How to cite this URL:
Badawy SS, Meckawy NM, Ahmed A. Norepinephrine versus terlipressin in patients with type 1 hepatorenal syndrome refractory to treatment with octreotide, midodrine, and albumin ( a prospective randomized comparative study). Egypt J Cardiothorac Anesth [serial online] 2013 [cited 2020 Feb 26];7:13-8. Available from: http://www.ejca.eg.net/text.asp?2013/7/1/13/135457


  Introduction Top


Hepatorenal syndrome (HRS) is a potentially reversible clinical syndrome, which is characterized by functional renal failure in end-stage liver disease 1. HRS is classified into two types. Type 1 HRS, as defined by the International Ascites Club criteria, is characterized by a rapidly progressive renal failure, with a doubling of serum creatinine levels (>2.5 mg/dl) or a rapid decrease in creatinine clearance to less than 20 ml/min in less than 2 weeks and failure of renal function to improve after diuretic withdrawal and plasma volume expansion 2. The mortality rate in type 1 HRS exceeds 50% after 1 month 1. Type 2 HRS is characterized by a slower progression in renal failure. It is defined by an increase in serum creatinine levels to more than 1.5 mg/dl or a decrease in creatinine clearance to less than 40 ml/min and a urine sodium level of less than 10 μmol/l 2. The mortality rate in type 2 HRS is about 40% after 6 months 1.

HRS has three major components: liver dysfunction, abnormalities in circulation, and progressive renal failure 1. The key pathogenic cause of HRS is splanchnic vasodilatation, which is mediated by vasoactive substances and other factors released during liver diseases, such as nitric oxide and prostaglandins, leading to a decrease in the ‘effective’ volume of blood sensed by the juxtaglomerular apparatus 3. The stimulation of the juxtaglomerular apparatus leads to the activation of the renin–angiotensin system with increased renin secretion, which results in vasoconstriction of systemic vessels, especially renal vessels, with persistent ‘underfilling’ of the renal circulation and worsening of renal vasoconstriction. The hallmarks of HRS are renal vasoconstriction and the underfill theory, which lead to renal failure 4.

Several studies 5–16 have been carried out to assess the effect of vasoconstrictor therapy on the reversal of HRS. Most of these studies concentrated on type 1 HRS because in this type the patients can derive maximum benefits from vasoconstrictor therapy as they have severely disturbed hemodynamics 1.

There are three classes of vasoconstrictors that have been studied in the management of HRS. The first group comprises vasopressin analogs, which include ornipressin and vasopressin, which bind to V1 receptors of vascular smooth muscle cells, leading to vasoconstrictions in systemic and splanchnic circulations 5. In addition, this group also includes terlipressin, which is a prodrug, the active metabolite of which is lysine vasopressin. Terlipressin is gradually released over several hours, thereby avoiding many of the ischemic side effects of ornipressin and vasopressin without compromising its potency 6. Terlipressin dilates intrahepatic vessels leading to a reduction in intrahepatic resistance and portal pressure, which may have a direct effect on the improvement of renal functions 6. The second group comprises α-adrenergic receptor agonists, including norepinepherine and midodrine, which act by binding to α-1-adrenergic receptors on vascular smooth muscle cells, leading to vasoconstriction 6. The third group includes octreotide, which is a somatostatin analogue and acts by inhibiting the release of glucagon and other vasodilator peptides, leading to vasoconstrictions in splanchnic, portal, and systemic circulations 7.

Many studies 8, 11, 17 suggested that the use of vasoconstrictors in association with albumin is effective in the management of HRS. The rationale for the use of vasoconstrictors together with albumin in the treatment of HRS is to correct the reduction in the effective circulating volume and reverse splanchnic arterial vasodilatation, leading to an improved renal perfusion pressure and hence an improved glomerular filtration rate and renal function 6. Moreover, albumin has an antioxidant effect and a high capacity to bind with nitric oxide-related compounds, endotoxins, and cytokines, which might have deleterious effects on organ functions in patients with hepatic cirrhosis 8.

Recent evidence suggests that administration of octreotide, midodrine, and albumin can have a potential benefit in improving renal functions, reverting HRS, and improving patient survival in HRS 9–11. This combination is commonly used in Egypt in the management of type 1 HRS because it is effective, widely available, and cheap. However, in some patients, this combination fails to revert HRS. In such patients, terlipressin or norepinephrine is commonly used in association with albumin.

Terlipressin is the most extensively studied vasoconstrictor in the management of HRS and is considered as the drug of choice. Several studies reported that the use of terlipressin and albumin in patients with HRS led to reversal of HRS, improved kidney functions, and increased patient survival rates 12–16. However, the use of terlipressin is limited in Egypt because it is an expensive drug and is not easily available in most Egyptian hospitals.

Norepinephrine is a potent vasoconstrictor, which is cheap and widely available in Egypt. It has been suggested as an effective alternative to terlipressin in the management of type 1 HRS. However, the number of randomized comparative studies evaluating the efficacy of norepinephrine in patients with type 1 HRS is small. In a pilot study by Duvoux et al. 18, the authors reported that using norepinephrine in patients with type 1 HRS was associated with a reversal of HRS in 83% of patients as well as an improvement in kidney functions.

Few randomized comparative studies assessed the efficacy of norepinephrine versus terlipressin in the management of HRS. In these studies, the authors reported that norepinephrine was as effective as terlipressin in reverting HRS and improving kidney functions 17, 19, 20 and that the survival rates were comparable in the two groups 17,19.

To date, no randomized comparative studies have been carried out on the management of patients with type 1 HRS not responding to vasoconstrictor therapy. The aim of this prospective, randomized, comparative study was to evaluate the efficacy of norepinephrine versus terlipressin in the management of patients with type 1 HRS refractory to treatment with octreotide, midodrine, and albumin.


  Methods Top


Study design

This was a prospective, randomized, comparative study comparing between intravenous administrations of norepinephrine and terlipressin in patients with type 1 HRS refractory to treatment with midodrine, octreotide, and albumin. Approval of the ethical committee of our institution was obtained before the start of the study. Randomization was done by means of sealed opaque envelops. A written informed consent was obtained from the patient, or from the closest family member, before inclusion in the study. The study included 60 patients and was carried out at two centers: the surgical and emergency intensive care units in New Kasr El Aini Teaching Hospital (Cairo University Hospital) and Wadi El Nile Hospital (Military Hospital).

Population

All patients admitted to the ICUs were included in the study if they were between 18 and 70 years of age and were diagnosed with liver cirrhosis complicated by type 1 HRS refractory to treatment with octreotide, midodrine, and albumin. Type 1 HRS was diagnosed using the criteria of the International Ascites Club 2. Patients were excluded from the study if they had any of the following conditions: multinodular hepatocellular carcinoma, septic shock, parenchymal kidney disease, peripheral vascular disease, coronary artery disease, heart or respiratory failure, previous myocardial infarction, hypersensitivity to any of the study medications, and any contraindication for central venous line insertion. Patients were also excluded if they were on nephrotoxic medications or were enrolled in another trial. Moreover, pregnant and lactating women were also excluded from the study. Data of patients who died within 3 days from randomization were excluded from the final analysis.

Study procedures

Before randomization, all candidate patients admitted to the ICU were subjected to a screening procedure. During screening, all patients with renal failure due to causes other than HRS were excluded. HRS was diagnosed according to the diagnostic criteria of HRS in cirrhosis published by the International Ascites Club in 1996 2. Type 1 HRS is characterized by a rapidly progressive renal failure, with a doubling of serum creatinine levels (>2.5 mg/dl) or a rapid decrease in creatinine clearance to less than 20 ml/min in less than 2 weeks.

In all patients, once type 1 HRS was diagnosed, a central venous line and a urinary catheter were inserted, and human albumin (20%), octreotide, and oral midodrine were started. Albumin was started at a dose of 1 g/kg of body weight on the first day and then was raised to 20–40 g/day in order to maintain the central venous pressure between 10 and 15 cmH2O. Intravenous octreotide was administered as initial bolus of 25 µg, followed by a dose of 25 µg/h as a continuous intravenous infusion. Midodrine was administered orally at an initial dose of 7.5 mg three times per day for 24 h; however, if HRS did not revert within 24 h, the dose of midodrine was increased to 12.5 mg three times per day for 48 h.

All patients who met the criteria for inclusion and whose type 1 HRS did not revert and kidney functions did not improve despite treatment with octreotide, midodrine, and albumin for 72 h were included in this study.

Patients included in the study were randomized to receive either a continuous intravenous infusion of norepinephrine or terlipressin plus human albumin (20%). Once study medication infusions were initiated, octreotide and midodrine were stopped. Treatment with terlipressin or norepinephrine plus albumin was continued until the reversal of HRS or for a maximum of 15 days from randomization. If after 15 days the HRS did not revert, the patient was considered unresponsive to therapy, the study medications were gradually stopped, and the patient was treated according to the ICU protocol for type 1 HRS.

Type 1 HRS reversal was defined as a decrease in serum creatinine levels to 1.5 mg/dl or less without renal dialysis and an increase in creatinine clearance to at least 40 ml/min. Patients who met the criteria of HRS reversal during the study were considered responders to the study medications.

The terlipressin group

Terlipressin was administered at an initial dose of 3 mg/24 h by intravenous continuous infusion. If during the following 48 h the HRS did not revert, the dose of terlipressin was increased to 6 mg/24 h. If HRS reversal was not achieved within48 h, the dose of terlipressin was increased to the maximal dose of 12 mg/24 h.

The norepinephrine group

Norepinephrine was administered at an initial dose of 0.5 mg/h by intravenous continuous infusion to revert type 1 HRS. If the target was not achieved, the norepinephrine dose was increased stepwise by 0.5 mg/h every 4 h until the maximum dose (3 mg/h) was reached. Norepinephrine infusion was titrated guided by the mean arterial blood pressure (MAP). MAP was kept at a level of 85–90 mmHg or less.

Norepinephrine and terlipressin in association with albumin (20%) (200–400 g/day) were continued for 48 h after complete reversal of HRS to prevent the recurrence of HRS and were then stopped gradually. In case of failure of HRS reversal, the study medications were continued for a maximum of 15 days from randomization and then were gradually stopped, the patients were then treated according to the ICU protocol for type 1 HRS.

Measurements

All demographic data, including the patients’ age, sex, weight, Child–Pugh score, APACHE II score, and the diagnosis of liver disease were recorded on admission. Vital signs including the heart rate, MAP, central venous pressure, and arterial oxygen saturation were recorded at admission and then were followed up and recorded as required.

Laboratory investigations including the complete blood profile, liver function, serum albumin levels, coagulation profile, kidney functions, and serum electrolyte levels were recorded at randomization as baseline. Kidney functions including serum creatinine levels and creatinine clearance were assessed daily until completion of the study. The total urine output in 24 h and the daily fluid balance were recorded at the start of the study as baseline and then were assessed daily until the end of the study. The survival rates at day 30 from randomization were recorded for the two groups. Economic analysis was performed by calculating the cost of terlipressin and norepinephrine during the study for the two groups.

Endpoints

The primary endpoint was reversal of type 1 HRS during the study. The secondary endpoints were survival at 30 days from randomization and the cost of the study medications.

Statistical analysis

Data were presented as mean values±SD or percentage and were compared using Student’s t-test or the &khgr;2-test. All statistical analyses were performed using the SPSS (Chicago, USA) software package. A P value of 0.05 or less was considered significant.


  Results Top


Between January 2009 and April 2012, 172 patients diagnosed with type 1 HRS were admitted to the ICU and were considered for inclusion in this study. During treatment with octreotide, midodrine, and albumin (20%), 39 patients died and 73 responded to treatment and their HRS reverted; therefore, these 112 patients were not included in the study. Sixty patients did not respond to treatment with octreotide, midodrine, and albumin (20%) and were included in the study. Among them, nine patients were excluded from the statistical analysis as they died within 72 h from randomization. Thus, a total of 51 patients were included in the study statistical analysis: 26 patients from the terlipressin group and 25 patients from the norepinephrine group.

The demographic data and the baseline patient clinical characteristics at the time of enrollment in the study were comparable in the two groups [Table 1] and [Table 2].
Table 1: Patient demographic data and comorbidities

Click here to view
Table 2: Baseline patient clinical characteristics

Click here to view


In this study, 46.15% (12/26) of patients in the terlipressin group and 40% (10/25) of those in the norepinephrine group responded to vasoconstrictor therapy, and their HRS reverted. In both groups, there was a progressive nonsignificant decrease in serum creatinine levels and a progressive nonsignificant increase in creatinine clearance and urine output throughout the study [Table 3]. Further analysis of the results showed that patients who responded to treatment with terlipressin and norepinephrine and whose HRS reverted (the responders) achieved a significant improvement in their kidney functions. There was a progressive decrease in serum creatinine (P⩽0.05) levels and a significant progressive increase in creatinine clearance (P⩽0.05) and urine output (P⩽0.05) compared with baseline values of the same group [Table 4] and [Figure 1], [Figure 2] and [Figure 3]. The changes in serum creatinine levels, creatinine clearance, and urine output were comparable in the two groups throughout the study [Table 3] and [Table 4] and [Figure 1], [Figure 2] and [Figure 3].
Table 3: Renal functions in terlipressin and norepinephrine groups

Click here to view
Table 4: Renal functions in responders in terlipressin and norepinephrine groups

Click here to view
Figure 1: Serum creatinine (mg/dl) levels in responders in terlipressin and norepinephrine groups. Data are presented as mean±SD. P⩽0.05 is considered significant. *Statistically significant changes when compared with baseline values in the same group.

Click here to view
Figure 2: The creatinine clearance (ml/min) rate in responders in terlipressin and norepinephrine groups. Data are presented as mean±SD. P⩽0.05 is considered significant. *Statistically significant changes when compared with baseline values in the same group.

Click here to view
Figure 3: The urine output (ml/24 h) in responders in terlipressin and norepinephrine groups. Data are presented as mean±SD. P⩽0.05 is considered significant. *Statistically significant changes when compared with baseline values in the same group.

Click here to view


The survival rates at day 30 from randomization were comparable in the two groups: 53.8% (14/26) in the terlipressin group versus 48% (12/25) in the norepinephrine group. The cost of the study medications was significantly lower in the norepinephrine group compared with the terlipressin group (57 560±16 870 vs. 13 492±7694 Egyptian pounds or 8855.38±2595.38 vs. 2075.69±1183.69 American dollars) (P⩽0.05).


  Discussion Top


The main findings of this randomized comparative study suggested that administration of norepinephrine with albumin (20%) is as effective as terlipressin with albumin (20%) in the management of type 1 HRS.

In this study, the incidence of the HRS reversal in the terlipressin and norepinephrine groups was comparable. In both groups, there was a progressive improvement in kidney functions throughout the study. Further analysis of the results showed that for the responders in the terlipressin and norepinephrine groups, the improvement in the kidney functions was statistically significant (P⩽0.05) and that the changes were comparable in the two groups.

The findings of this study correlate with data from many studies that suggest that norepinephrine was as effective as terlipressin in reverting HRS and improving kidney functions. In a study by Singh et al. 17, 46 patients with type 1 HRS were randomized to receive either terlipressin or norepinephrine with albumin. In this study, the authors reported that HRS reversal could be achieved in 39.1% of patients in the terlipressin group and 43.4% of patients in the norepinephrine group.

In an open label, randomized, pilot trial comparing the efficacy of terlipressin and norepinephrine on renal functions and clinical outcomes of 40 patients with type 1 HRS, Sharma et al. 19 reported that patients in both groups had a significant improvement in kidney functions and that the incidences of HRS reversal were comparable. Singh et al. 17 and Sharma et al. 19 suggested that norepinephrine may be an effective alternative to terlipressin in improving renal functions in patients with type 1 HRS.

In another unblinded, pilot study by Alessandria et al. 20, 22 patients with HRS (nine patients with type 1 HRS and 13 patients with type 2 HRS) were randomly assigned to treatment with norepinephrine and albumin (20%) or terlipressin and albumin (20%). Treatment was administered until HRS reversal or for a maximum of 2 weeks. Reversal of HRS was observed in 70% of patients treated with norepinephrine and in 83% of those treated with terlipressin. In both groups, there was a significant improvement in renal and circulatory functions. The results of our study correlate with those of Alessandria and colleagues; however, the incidence of the reversal of HRS was higher in their study compared with ours. This could be explained by the fact that their study included patients with type 2 HRS, whereas ours included only patients with type 1 HRS, in which hemodynamic disturbances and renal dysfunction are more severe compared with type 2 HRS. Moreover, the prognosis of type 2 HRS is better than that of type 1 HRS, with a higher incidence of renal recovery and higher survival rate.

The improvement in renal function after administration of vasoconstrictors in patients with type 1 HRS could be explained by their vasoconstrictive effects on the systemic circulation, which can lead to an improvement in systemic hemodynamics and an amelioration of the hyperdynamic circulation, which occurs in cirrhosis. Moreover, the reduction in the renin–angiotensin–aldosterone system activity due to the EABV leads to an improvement in glomerular filtration rate and renal sodium excretion 6.

Few studies assessed the effect of administration of norepinephrine versus terlipressin with albumin on the survival of cirrhotic patients with type 1 HRS. In a study by Singh et al. 17, the authors reported that the survival rates were comparable in both groups. Sharma et al. 19 reported in their randomized pilot study that the cumulative survival and number of patients who survived until day 15 were comparable in terlipressin and norepinepherine groups. The findings of these two studies correlate with the results of our study in which the survival rates at day 30 from randomization were comparable in both groups: 53.8% (14/26) in the terlipressin group versus 48% (12/25) in the norepinephrine group, suggesting that norepinephrine is as effective as terlipressin in the management of patients with type 1 HRS.

The cost of the study medications was significantly lower in the norepinephrine group compared with the terlipressin group (P⩽0.05). Singh et al. 17 and Sharma et al. 19 also reported in their studies that norepinephrine was significantly less expensive than terlipressin (P⩽0.05).


  Conclusion Top


The results of this randomized comparative study suggest that norepinephrine is as effective as terlipressin in the management of patients with type 1 HRS. The lower cost and wider availability of norepinephrine make it a safe and effective alternative to terlipressin.


  Study limitations Top


The small sample size of this study limits the ability to draw definitive conclusions about the efficacy of norepinephrine and terlipressin in the management of type 1 HRS patients. The treatment was not blinded and hence any bias cannot be excluded. Long-term follow-up (3–6 months) is needed to properly assess the effect of the study medications on the survival of patients. Therefore, further randomized, double-blinded comparative studies are required to properly assess the safety and efficacy of norepinephrine compared with terlipressin in the management of type 1 HRS patients.[20]

 
  References Top

1.Ng CKF, Chan MH, Tai MH, Lam CW.Hepatorenal syndrome.Clin Biochem Rev2007;28:11–17.  Back to cited text no. 1
    
2.Arroyo V, Ginès P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al..Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis.Hepatology1996;23:164–176.  Back to cited text no. 2
    
3.Arroyo V, Guevara M, Ginès P.Hepatorenal syndrome in cirrhosis: pathogenesis and treatment.Gastroenterology2002;122:1658–1676.  Back to cited text no. 3
    
4.Møller S, Bendtsen F, Henriksen JH.Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome.Scand J Gastroenterol2005;40:491–500.  Back to cited text no. 4
    
5.Narahara Y, Kanazawa H, Taki Y, Kimura Y, Atsukawa M, Katakura T, et al..Effects of terlipressin on systemic, hepatic and renal hemodynamics in patients with cirrhosis.J Gastroenterol Hepatol2009;24:1791–1797.  Back to cited text no. 5
    
6.Leung W, Wong F.Hepatorenal syndrome: do the vasoconstrictors work?Gastroenterol Clin North Am2011;40:581–598.  Back to cited text no. 6
    
7.Wiest R, Tsai MH, Groszmann RJ.Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats.Gastroenterology2001;120:975–983.  Back to cited text no. 7
    
8.Martín Llahí M, Pépin M, Guevara M, Díaz F, Torre A, Monescillo A, et al..Terlipressin and albumin vs. albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study.Gastroenterology2008;134:1352–1359.  Back to cited text no. 8
    
9.Wong F, Pantea L, Sniderman K.Midodrine, octreotide, albumin and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome.Hepatology2004;40:55–64.  Back to cited text no. 9
    
10.Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA.Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome.Dig Dis Sci2007;52:742–748.  Back to cited text no. 10
    
11.Skagen C, Einstein M, Lucey MR, Said A.Combination treatment with octreotide, midodrine and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome.J Clin Gastroenterol2009;43:680–685.  Back to cited text no. 11
    
12.Narahara Y, Kanazawa H, Sakamoto C, Maruyama H, Yokosuka O, Mochida S, et al..The efficacy and safety of terlipressin and albumin in patients with type 1 hepatorenal syndrome: a multicenter, open-label, explorative study.J Gastroenterol2012;47:313–320.  Back to cited text no. 12
    
13.Sanyal AJ, 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.Gastroenterology2008;134:1360–1368.  Back to cited text no. 13
    
14.Dobre M, Demirjian S, Sehgal AR, Navaneethan SD.Terlipressin in hepatorenal syndrome: a systematic review and meta-analysis.Int Urol Nephrol2011;43:175–184.  Back to cited text no. 14
    
15.Sagi SV, Mittal S, Kasturi KS, Sood GK.Terlipressin therapy for reversal of type 1 hepatorenal syndrome: a meta-analysis of randomized controlled trials.J Gastroenterol Hepatol2010;25:880–885.  Back to cited text no. 15
    
16.Gluud LL, Christensen K, Christensen E, Krag A.Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome.Hepatology2010;51:576–584.  Back to cited text no. 16
    
17.Singh V, Ghosh S, Singh B, Kumar P, Sharma N, Bhalla A, et al..Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study.J Hepatol2012;56:1293–1298.  Back to cited text no. 17
    
18.Duvoux C, Zanditenas D, Hézode C, Chauvat A, Monin JL, Roudot Thoraval F, et al..Effects of noradrenalin and albumin in patients with type 1 hepatorenal syndrome: a pilot study.Hepatology2002;36:374–380.  Back to cited text no. 18
    
19.Sharma P, Kumar A, Shrama BC, Sarin SK.An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response.Am J Gastroenterol2008;103:1689–1697.  Back to cited text no. 19
    
20.Alessandria C, Ottobrelli A, Debernardi Venon W, Todros L, Cerenzia MT, Martini S, et al..Noradrenalin vs. terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study.J Hepatol2007;47:499–505.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusion
Study limitations
Introduction
Methods
Results
Discussion
Conclusion
Study limitations
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1799    
    Printed61    
    Emailed0    
    PDF Downloaded179    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]