Continuous outpatient terlipressin infusion for hepatorenal syndrome as a bridge to successful liver transplantation

Authors


  • Potential conflict of interest: Nothing to report.

Abbreviations
EASL

European Association for the Study of the Liver

HRS

hepatorenal syndrome

ICU

intensive care unit

Hepatorenal syndrome (HRS) is a life-threatening yet potentially reversible cause of renal dysfunction occurring in patients with advanced cirrhosis, ascites, and liver failure.[1] It is characterized by functional renal impairment due to renal arterial vasoconstriction in the setting of major disturbances in circulatory function.[1, 2] There are two forms of HRS: type 1 is characterized by an acute progressive decrease in kidney function with a median survival time of 2 weeks without treatment, whereas type 2 features more stable and less severe kidney failure and longer survival compared with type 1.[3] Liver transplantation remains the only effective long-term therapy for HRS.[4]

Pharmacologic treatment with vasoconstrictors targeted to reverse splanchnic vasodilation, together with albumin, is effective in reversing renal dysfunction in 34%-44% of patients with type 1 HRS and improves survival in this group.[4, 5] The European Association for the Study of the Liver (EASL) recommend terlipressin (1 mg/4-6 hourly as intravenous bolus) together with albumin as first-line treatment for patients with type 1 HRS.[6] Traditionally, this is done as an inpatient where cardiovascular parameters can be monitored. Multiple case reports now exist describing continuous terlipressin infusion as an alternative to intravenous bolus administration,[7, 8] with similar efficacy and often using a lower total dose, representing a potential cost saving.[7]

We present the first reported case of an outpatient continuous terlipressin infusion for treatment of recurrent HRS as a bridge to successful liver transplantation.

Case

A 59-year-old man with Child-Pugh C cirrhosis due to previous alcohol consumption complicated by recurrent encephalopathy, diuretic-resistant ascites, and hepatocellular carcinoma was admitted to our unit with a rapid deterioration in renal function. This was on a background of three recent admissions with type 1 HRS. On each previous occasion he was treated successfully with bolus administration of terlipressin as per EASL guidelines, resulting in a return of his renal function to baseline (Fig. 1).

Figure 1.

Serum creatinine (μmol/L) pre- and postliver transplantation. Highlighted areas illustrate periods of time when bolus terlipressin (1 mg IV QID) and continuous terlipressin infusion (3 mg over 24 hours) were administered.

A terlipressin infusion, consisting of 3 mg terlipressin in 50 mL 5% dextrose delivered by a GemStar pump at a rate of 2.1 mL/h through a peripherally inserted central venous catheter was begun. Dextrose was chosen as the solute based on evidence that it was superior to normal saline at maintaining optimal pH for terlipressin.[9] The patient initially received a terlipressin infusion as an inpatient, enabling the dose to be titrated and the patient to be screened for complications. During this time the patient's serum creatinine returned to his baseline level (Fig. 1). On day 6 the patient was discharged home with an ambulatory terlipressin infusion under the supervision of our Hospital-in-the-home program. The patient was reviewed in an outpatient clinic twice per week and had renal function monitored at each visit. This continued for a further 22 days at which time the patient underwent successful liver transplantation. Both outpatient terlipressin infusion and inpatient bolus terlipressin were well tolerated by our patient with no adverse effects noted; larger studies would address whether there is a difference in overall adverse events between the two modes of delivery.

Posttransplantation, a renal-sparing immunosuppression regimen consisting of basiliximab, mycophenolate mofetil, and low-dose tacrolimus was implemented. The patient was discharged 10 days posttransplantation with a serum creatinine of 117 μmol/L and has remained stable to day 120 postoperation (Fig. 1).

Discussion

Liver transplantation remains the mainstay of therapy for type 1 HRS; however, vasoconstrictor therapy with terlipressin is recognized as an effective short-term treatment.[4, 5] Terlipressin is traditionally given using a bolus regimen in a hospital setting. This case illustrates the successful use of a continuous outpatient terlipressin infusion in a patient with type 1 HRS over a 4-week period as a bridge to liver transplantation, demonstrating that in the appropriate clinical scenario and under close supervision, outpatient terlipressin is feasible, and in this case efficacious and well tolerated.

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