title: The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure.
abstract: Uncontrolled increase in intracranial pressure (ICP) continues to be one of the most significant causes of early death in patients with acute liver failure (ALF). In this study, we aimed to determine the effects of indomethacin on ICP and cerebral perfusion pressure in twelve patients with ALF and brain edema (9 females/3 males, median age 49,5 (range 21 to 64) yrs.). Also changes in cerebral perfusion determined by transcranial Doppler technique (Vmean) and jugular bulb oxygen saturation (SvjO2) were measured, as well as brain content of lactate and glutamate by microdialysis technique. Finally, we determined the cerebral blood flow autoregulation before and after indomethacin injection. We found that indomethacin reduced ICP from 30 (7 to 53) to 12 (4 to 33) mmHg (P < 0.05). The cerebral perfusion pressure increased from 48 (0 to 119) to 65 (42 to 129) mmHg (P < 0.05), while Vmean and SvjO2 on average remained unchanged at 68 (34 to 126) cm/s and 67 (28 to 82) %, respectively. The lactate and glutamate in the brain tissue were not altered (2.1 (1.8 to 7.8) mmol/l and 34 (2 to 268) micromol/l, respectively) after injection of indomethacin. Cerebral blood flow autoregulation was impaired in all patients before injection of indomethacin, but was not restored after administration of indomethacin. We conclude that a bolus injection of indomethacin reduces ICP and increases cerebral perfusion pressure without compromising cerebral perfusion or oxidative metabolism in patients with ALF. This finding indicates that indomethacin may be valuable as rescue treatment of uncontrolled intracranial hypertension in fulminant hepatic failure.
authors.affiliation: Department of Hepatology, Rigshospitalet, Copenhagen University Hospital, Denmark. tofteng@dadlnet.dk
authors.forename: Flemming
authors.initials: F
authors.lastname: Tofteng
authors.forename: Fin Stolze
authors.initials: FS
authors.lastname: Larsen
mesh_terms: D000328:Adult; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D001923:Brain Chemistry; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D018698:Glutamic Acid / Q000032:analysis*; D006706:Homeostasis; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007427:Intracranial Pressure / Q000187:drug effects*; D019344:Lactic Acid / Q000032:analysis*; D017093:Liver Failure / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage
chemical_list: D019344:Lactic Acid; D018698:Glutamic Acid; D009638:Norepinephrine; D007213:Indomethacin