Terlipressin for Hepatorenal Syndrome: Continuous Infusion as an Alternative to IV Bolus Administration
Article Outline
Dear Sir:
Vasoconstrictor therapy with terlipressin and concomitant albumin can improve renal function in patients with hepatorenal syndrome (HRS). The recent publication of the first 2 randomized controlled trials1, 2 has received great attention. Sanyal et al,2 with a bolus dose regimen of 4 mg/d, which could be increased to 8 mg/d, achieved reversal of HRS type 1 in 34% of 56 patients. Serious adverse events, mostly cardiovascular, considered to be treatment related were observed in 9% of patients. By comparison, the Spanish trial using a bolus regimen of 6 mg starting dose, which could be doubled to 12 mg/d, observed renal response to the combination of terlipressin and albumin in 6 of 17 patients with type 1 HRS, corresponding to 35%. Cardiovascular complications occurred in 43% of patients in the terlipressin arm, and even after excluding circulatory overload, there was still a 22% complication rate, including myocardial infarction. Accordingly, the editorial3 raised several important questions and concerns such as uncertainty about the optimal dose and timing of terlipressin and the potential for severe ischemic events. It was recommended that terlipressin should be used only in an intensive care unit or a unit with hemodynamic monitoring because of the severe adverse events.
In our department in recent years, we have adopted continuous infusion rather than IV bolus dosing of terlipressin on a regular ward without observing very severe adverse events. We, therefore, decided to retrospectively analyze a series of 32 consecutive patients with HRS4, 5 treated with continuous IV terlipressin (starting dose, 3 mg/d) and albumin (20–30 g/d) for 11 ± 2 days. If serum creatinine decreased by <30%, the terlipressin dose was increased by 1 mg/d. Twenty-six patients had HRS type 1. Pretreatment patient characteristics were similar to those reported in the 2 randomized controlled trials: Child–Pugh score, 11.8 ± 3; Model for End-Stage Liver Disease score, 30 ± 1.2; and serum creatinine, 3.2 ± 0.2 mg/dL. Reversal of HRS defined as serum creatinine <1.5 mg/dL was observed in 42% of those treated. The only cardiovascular adverse events observed were arrhythmias occurring in 3 patients (9%) and requiring discontinuation of treatment in 1 patient. Thus, our small series of patients suggests that continuous terlipressin infusion may achieve response rates comparable with those of IV bolus administration, but possibly at a lower daily dose and with less severe complications (Table 1). Therefore, it may be worthwhile to compare in a randomized prospective trial bolus with continuous administration of terlipressin for HRS.
Table 1. Features of Terlipressin Treatment
| Spanish trial | Sanyal et al. | Continuous infusion | |
|---|---|---|---|
| Complete response in HRS type 1 | 35% | 34% | 42% |
| Severe adverse events related to terlipressin | 22% | 9% | 9% |
| Minimum daily dose (mg) | 6 | 4 | 3 |
| Mean daily dose at end of treatment (mg) | 7.8a | 4.9 | 4.3 |
aData available only for responders. |
References
- Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134:1352–1359
- A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360–1368
- . Vasoconstrictor therapy for the hepatorenal syndrome. Gastroenterology. 2008;134:1608–1611
- Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis (International Ascites Club). Hepatology. 1996;23:164–176
- Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310–1318
Conflicts of interest The authors disclose no conflicts.
PII: S0016-5085(09)01144-5
doi:10.1053/j.gastro.2009.03.064
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
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- Reply , 24 July 2009
