Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy

Abstract

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral hemodynamics. Six successive patients with ALF were ventilated electively for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (KetySchmidt technique). Measurements were made before and at 1, 3, and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg), median, 0.25 mg (range, 0.2-0.3 mg). There was no significant change in heart rate, mean arterial pressure, or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (P ‫؍‬ 0.016). Intracranial pressure increased significantly at 1 hour (P ‫؍‬ 0.031), returning back to baseline values at 2 hours. In conclusion, administration of terlipressin, at a dose that did not alter systemic hemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral hemodynamics. (HEPATOLOGY 2004;39:471-475.)

Meta‐analysis: terlipressin therapy for the hepatorenal syndrome

“…This has not been made as most patients with HRS being in the waiting list for LT are frequently treated with vasopressin analogues or other vasoconstrictors because of the potential efficacy of treatment and the absence of alternative therapies. Other factors hampering the use of terlipressin (or other vasoconstrictors) for HRS include the concern that vasoconstrictor therapy may be complicated by important side-effects, 29 and their use is not recommended in patients with cardiac diseases, peripheral vascular and cerebrovascular diseases because of the potential risk of ischaemic events. These complications occurred with ornipressin that was soon abandoned; [5][6] although one of the initial concerns about terlipressin use was the development of ischaemia, no patient of the current review interrupted the terlipressin therapy because of side-effects.…”

Fulminant Hepatitis: Definitions, Causes and Management

“…Norepinephrine is the preferred agent; however, more recently the vasopressin analogue terlipressin has been used in ALF with conflicting results [24] [25]. For the reasons mentioned, patients with ALF require invasive hemodynamic monitoring.…”

Optimal management of patients with fulminant hepatic failure: Targeting the brain

“…Two important clinical studies in this issue of HEPATOLOGY deal with these topics. 3,4 Terlipressin is a vasopressin analog that is increasingly used to reverse hepatorenal syndrome in patients with chronic liver disease. Renal failure also is common in FHF, and the value of terlipressin to prevent or treat renal failure is of considerable interest.…”

“…Renal failure also is common in FHF, and the value of terlipressin to prevent or treat renal failure is of considerable interest. Before launching a randomized controlled trial, Shawcross et al 3 carried out an important safety study, reported in this issue of HEPATOL-OGY at the Scottish Liver Transplant Unit in Edinburgh that included six patients with FHF. Both CBF and ICP were recorded before and after intravenous injection of a minimal dose of terlipressin that did not affect systemic hemodynamics.…”

“…As highlighted by the two papers in this issue, 3,4 both CBF and the colloid osmotic gradient across the bloodbrain barrier are of central pathophysiologic importance to the development of brain edema and high ICP in patients with FHF. 1,8 The consequences of changing plasma tonicity or increasing CBF by administration of vasoactive drugs may be important to emphasize at a time when the number of proposed experimental treatments, using complex and costly artificial and bioartificial liver support systems to secure brain viability, has considerably increased.…”