|Year : 2017 | Volume
| Issue : 1 | Page : 173-176
Perioperative terlipressin infusion in living donor liver transplantation: effects on sodium and water balance
Tarek S Shabana, Sherif G Anis, Fady A Abdelmalek
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Tarek S Shabana
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Background Although terlipressin is being used perioperatively in recipients of liver transplantation to improve splanchnic hemodynamics and postoperative renal functions, its associated antidiuretic effect has not been specifically investigated in this group of patients. The aim of this study is to assess the effect of terlipressin infusion started intraoperatively and continued for 48 h postoperatively in recipients of living donor liver transplantation on serum sodium and water/sodium excretion.
Materials and methods Thirty patients with end-stage liver disease and portal hypertension scheduled for living donor liver transplantation were randomized into two groups including 15 patients each. Group 1 (control): patients did not receive terlipressin. Group 2: terlipressin was administered as an infusion at a rate of 2 µg/kg/h continued for 48 h after postoperative ICU admission. Comparisons were performed between both groups in terms of serum sodium, urine sodium, urine osmolarity, and the urine : sodium osmolarity ratio.
Results There were no significant changes between the control group and the terlipressin group in serum sodium, urine sodium, urine osmolarity, and the urine : sodium osmolarity ratio.
Conclusion Terlipressin infusion started intraoperatively at a rate of 2 µg/kg/h and continued for 48 h postoperatively in recipients of living donor liver transplantation did not result in significant changes in serum sodium and sodium/water excretion.
Keywords: liver transplantation, sodium, terlipressin, water excretion
|How to cite this article:|
Shabana TS, Anis SG, Abdelmalek FA. Perioperative terlipressin infusion in living donor liver transplantation: effects on sodium and water balance. Ain-Shams J Anaesthesiol 2017;10:173-6
|How to cite this URL:|
Shabana TS, Anis SG, Abdelmalek FA. Perioperative terlipressin infusion in living donor liver transplantation: effects on sodium and water balance. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2018 Dec 17];10:173-6. Available from: http://www.asja.eg.net/text.asp?2017/10/1/173/238450
| Introduction|| |
Owing to its powerful vasopressin V1 receptor-mediated vasoconstrictive effects, terlipressin, a long-acting analogue of vasopressin, has long been used in patients with portal hypertension developing upper gastrointestinal bleeding and hepatorenal syndrome .
In the organ transplantation era, terlipressin has also been used perioperatively in recipients of liver transplantation to improve splanchnic hemodynamics and postoperative renal functions .
The V2 receptor-mediated antidiuretic effect associated with the use of terlipressin has not been specifically investigated in liver transplant recipients. This effect may contribute toward retention of electrolyte-free water, resulting in hypotonic hyponatremia in the face of increased urine osmolarity and urine sodium .
The aim of this study is to assess the effect of terlipressin infusion, started intraoperatively and continued for 48 h postoperatively, in recipients of living donor liver transplantation on serum sodium and water/sodium excretion.
| Patients and methods|| |
After obtaining approval from the local ethical committee and written patient consent, the study was carried out in Ain Shams University Specialized Hospital on 30 patients with end-stage liver disease and portal hypertension scheduled for living donor liver transplantation. Recepients were randomized using computer-generated random numbers into two groups of 15 patients each. Group 1 (control): patients did not receive terlipressin. Group 2 (terlipressin): after induction of general anesthesia, terlipressin was administered as an intravenous bolus dose (1 mg over 30 min), followed immediately by an infusion at a rate of 2 µg/kg/h, continued for 48 h after postoperative ICU admission. Participants, but not researchers, were blinded to the allocated treatment (controlled, randomized, single-blind study).
Exclusion criteria included patients with renal impairment (serum creatinine>2 mg/dl), cardiac disease, hypothyroidism, diabetes mellitus, and adrenal insufficiency. Patients who required intraoperative diuretic therapy were also excluded from the study.
Serum sodium was measured at baseline (before starting terlipressin), intraoperatively (4 h after starting terlipressin), on postoperative admission to ICU, and then every 12 hours after ICU admission for 48 h. Urine sodium and urine osmolarity were measured in 24 h urine samples at baseline (preoperatively) and then every 24 hours for 48 h after ICU admission. The urine : serum osmolarity ratio was calculated at baseline (preoperatively) and then every 24 hours for 48 h after ICU admission. Serum osmolarity was calculated using the equation [2×(Na+K)+(BUN/2.8)+(glucose/18)]. All patients received albumin 2% in ringer acetate as the maintenance fluid. Comparisons were performed between both groups in serum sodium, urine sodium, urine osmolarity, and the urine : sodium osmolarity ratio.
On the basis of the intention to detect a 3.4 difference in the mean change in serum sodium level with a SD of 2.8 (on the basis of a pilot study), we calculated that 15 patients/group were required to yield a significant P value less than 0.05 with a study power of 85%. SPSS (V.210.0, 2012; IBM Corp., Armonk, New York, USA) were used for data analysis. Data were expressed as mean±SD for quantitative parametric measures. Comparisons between two independent mean groups for parametric data were performed using an unpaired Student’s t-test. The probability of error at 0.05 was considered significant.
| Results|| |
Demographic data and model for end-stage liver disease scores were comparable between both groups ([Table 1]).
|Table 1 Demographic data and the mean model for end-stage liver disease score|
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There were no significant changes in serum sodium in the terlipressin group compared with the control group at baseline (P=0.41), intraoperatively (P=0.68), on admission to ICU (P=0.54), and at 12, 24, 36, and 48 h after ICU admission (P=0.85, 0.67, 0.92, and 0.75, respectively) ([Table 2]).
In terms of urine sodium, there were no statistically significant changes in the terlipressin group compared with the control group at baseline (P=0.43), 24 h (P=0.37), and 48 h (P=0.74) after ICU admission ([Table 3]).
Urine osmolarity levels were comparable at baseline (P=0.91). There were no statistically significant changes in urine osmolarity between groups at 24 h (P=0.73) and 48 h (P=0.89) after ICU admission ([Table 4]).
There were also no significant changes between the terlipressin group and the control group in the urine : serum osmolarity ratios at baseline (P=0.76), 24 h (P=0.06), and 48 h (P=0.74) after ICU admission ([Table 5]).
| Discussion|| |
In the current study, terlipressin infusion, started intraoperatively and continued for 48 h postoperatively in recepients of living donor liver transplantation, did not result in significant changes in serum sodium levels compared with the control group. Although the antidiuretic effects of terlipressin (including its effects on serum sodium) remain unvisited in liver transplant recipients, studies carried on terlipressin in the field of hepatology have shown conflicting results.
Supporting the results of our study, in a randomized study comparing terlipressin combined with albumin to albumin alone in patients with hepatorenal syndrome, there were no adverse event reports of hyponatremia throughout the study .
Other studies yielded results that were discrepant from the results of our study. In a study carried out by Krag et al.  on 62 patients with bleeding esophageal varices, serum sodium level decreased from 136±6 to 130±7 after starting terlipressin at a dose of 2 mg/4 h for a mean of 1.7 days. Bruha et al.  carried out a study on 25 patients with bleeding esophageal varices in which 15 patients were treated with 1 mg terlipressin every 4 h for 5 days and 10 patients for 10 days. Serum sodium levels decreased in both groups, but returned to normal after discontinuation of terlipressin treatment.
Solà et al. , in their study on the effects of terlipressin in patients with acute variceal bleeding, showed a decrease in serum sodium from 134.9±6.6 to 130.5±7.7 mEq/l (P=0.002). A reduction in sodium in the blood was found in 67% of patients. Surprisingly, Prakoso et al.  came to the conclusion that terlipressin is effective in treating moderate to severe hyponatremia in liver failure.
In view of the duration of terlipressin therapy and the doses used in the aforementioned studies, the discrepancy in the results from the current study may reinforce the possibility that terlipressin-induced hyponatremia is dose and time dependent.
Explanations for the different effects of terlipressin on serum sodium level should also consider the age of the patient and advanced stage of the disease. Normal aging is accompanied by many changes in the regulatory systems that control sodium and water balance . In advanced liver cirrhosis, serum sodium decreases progressively and hypervolemic hyponatremia develops in a considerable proportion of these patients .
In the current study, there were no significant changes in urine osmolarity, urine sodium, and the urine : sodium osmolarity ratio. However, the results of studies on the effects of terlipressin on sodium and water excretion are variable. There was a significant increase in urine osmolarity and urine sodium in the studies carried out by Krag et al. , on the effect of terlipressin on the aquaretic system and epithelial sodium channels. A study investigating the effects of terlipressin for 2 days on the glomerular filtration rate showed a significant increase in urine output and creatinine clearance, but not urine sodium concentrations . In the work of Solà et al. , urine osmolarity increased in patients with nonrefractory ascites, but not in patients with refractory ascites.
Terlipressin, by itself, has low V2 receptor affinity and thus should have little effect on water reabsorption in the collecting ducts . However, terlipressin is slowly metabolized in the liver to vasopressin, which exerts strong agonistic effects on V2 receptors .
In patients with end-stage liver disease, V2 receptors are likely to be occupied by endogenous vasopressin; thus, the administration of other drugs with agonistic effects on V2 receptors may not have significant antidiuretic effects . The major reasons for increased natriuresis after terlipressin are most likely the increased mean arterial pressure and the improvement in the hemodynamics .
| Conclusion|| |
Terlipressin infusion started intraoperatively at a rate of 2 µg/kg/h and continued for 48 h postoperatively in recipients of living donor liver transplantation did not result in significant changes in serum sodium and sodium/water excretion.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Krag A, Borup T, Moller S, Bendsten F. Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome. Adv Ther 2008; 25:1105–1140.
Mukhtar A, Salah M, Aboulfetouh F, Obayah G, Samy M, Hassanien A et al.
The use of terlipressin during living donor liver transplantation: effects on systemic and splanchnic hemodynamics and renal function. Crit Care Med 2011; 39:1329–1334.
Biswas M, Davie JS. Hyponatraemia in clinical practice. Postgrad Med J 2007; 83:373–378.
Martín-Llahí M, Pépin MN, Guevara M, Díaz F, Torre A, Monescillo A et al.
TAHRS Investigators Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008; 134:1352–1359.
Krag A, Hobolth XX, Moller S, Bendtsen F. Hyponatraemia during terlipressin therapy. Gut 2010; 59:417–418.
Bruha R, Marecek Z, Prochaza V, Lata J, Spicak J, Ehrmann J et al.
Double-blind randomized multicenter study comparing the efficacy and safety of 10-day to 5-day terlipressin treatment of bleeding esophageal varices. Hepatogastroenterology 2009; 56:390–394.
Solà E, Lens S, Guevara M, Martín-Llahí M, Fagundes C, Pereira G et al.
Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension. Hepatology 2010; 52:1783–1790.
Prakoso E, Jones C, Koorey DJ, Strasser SI, Bowen D, McCaughan GW, Shackel NA. Terlipressin therapy for moderate-to-severe hyponatraemia in patients with liver failure. Intern Med J 2013; 43:240–246.
Miller M. Hyponatremia: age-related risk factors and therapy decisions. Geriatrics 1998; 53:32–33.
Schrier RW. Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med 2006; 119(Suppl 1):S47–S53.
Krag A, Bendtsen F, Pedersen EB, Holstein-Rathlou NH, Møller S. Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects. Am J Physiol Renal Physiol 2008; 295:F1295–F1300.
Krag A, Pedersen EB, Møller S, Bendtsen F. Effects of the vasopressin agonist terlipressin on plasma cAMP and ENaC excretion in the urine in patients with cirrhosis and water retention. Scand J Clin Lab Invest 2011; 71:112–116.
Hadengue A, Gadano A, Moreau R, Giostra E, Durand F, Valla D et al.
Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome. J Hepatol 1998; 29:565–570.
Bernadich C, Bandi JC, Melin P, Bosch J Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension. Hepatology 1998; 27:351–356.
Zaki SA. Terlipressin-induced hyponatremic seizure in a child. Indian J Pharmacol 2013; 45:403–404.
] [Full text]
Nazar A, Pereira GH, Guevara M, Martin-Llahi M, Pepin MN, Marinelli M et al.
Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology 2010; 51:219–226.
Krag A, Møller S, Henriksen JH, Holstein-Rathlou NH, Larsen FS, Bendtsen F Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology 2007; 46:1863–1871.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]