title: 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 (Kety-Schmidt 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.
authors.affiliation: Liver Failure Group, Institute of Hepatology, Royal Free and University College London Medical School, London, UK.
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Shawcross
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Davies
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Alistair
authors.initials: A
authors.lastname: Lee
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006501:Hepatic Encephalopathy / Q000188:drug therapy*; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy*; D007427:Intracranial Pressure / Q000187:drug effects; D017114:Liver Failure, Acute / Q000150:complications*; D008236:Lypressin / Q000009:adverse effects* / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D000077585:Terlipressin; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D008236:Lypressin; D000077585:Terlipressin