title: No elevation of glutathione S-transferase-a1-1 by amiodarone loading in intensive care unit patients with atrial fibrillation.
abstract: Hepatocellular toxicity is a putative side-effect of amiodarone. The hepatic detoxification enzyme glutathione S-transferase-A1-1 (GSTA1-1) is a sensitive indicator of hepatocellular damage. We investigated the occurrence of subclinical liver injury, as measured by plasma GSTA1-1 in intensive care unit patients with atrial fibrillation receiving amiodarone. Sixteen haemodynamically stable intensive care unit patients with atrial fibrillation were treated with amiodarone intravenously. Patients were given a loading dose of 150 mg followed by another 150 mg followed by a continuous infusion of 1200 mg/hour if atrial fibrillation persisted. Blood samples for GSTA1-1 (measured by an enzyme-linked immunosorbent assay) were taken at zero, one, three, six, 12 and 24 hours, transaminases and bilirubin at zero, six, 12 and 24 hours. Blood pressure and heart rate were continuously monitored. Effects were analysed for time-dependent changes (one-way analysis of variance for repeated measures). Blood pressure increased from 125 +/- 8/60 +/- 3 mmHg at t = 0 to 144 +/- 9/66 +/- 4 mmHg at t = 24 hours (P < 0.05), heart rate decreased from atrial fibrillation 124 +/- 5 to sinus rhythm 86 +/- 6 beats per minute (P < 0.05). There was no significant elevation of GSTA1-1, transaminases or bilirubin during the observation period of 24 hours. Amiodarone does not cause elevation of GSTA1-1 as a marker of subclinical liver injury in haemodynamically stable intensive care unit patients with atrial fibrillation.
authors.affiliation: Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hilkens
authors.forename: P
authors.initials: P
authors.lastname: Pickkers
authors.forename: W H M
authors.initials: WH
authors.lastname: Peters
authors.forename: J G
authors.initials: JG
authors.lastname: van der Hoeven
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000638:Amiodarone / Q000009:adverse effects*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D007362:Intensive Care Units; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
chemical_list: D000889:Anti-Arrhythmia Agents; C484555:GSTA1 protein, human; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000638:Amiodarone