Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies.
A massive digitoxin (DGTX) intoxication in a 36-year-old man (35 mg DGTX) was treated by prolonged and repeated i.v.-infusions of Fab fragments of anti-digitalis antibodies (FAB). Blood and urine samples were collected over a 98 h period for monitoring the efficacy and adequacy of FAB treatment. DGTX concentrations were determined after protein precipitation (release of FAB-bound and protein-bound DGTX) in unprocessed serum and urine samples, and after aliquots of these samples had been dialysed in vitro against DGTX-free buffer (elimination of DGTX not bound to FAB). The difference in DGTX concentration between the unprocessed and dialysed samples was the amount of DGTX bound to plasma proteins and the small fraction of unbound DGTX being relevant for the therapeutic and toxic effects of the drug. Before FAB therapy was started, the total serum DGTX concentration was 535 nmol/l. The first FAB infusion (320 mg) was started 11 h after drug ingestion. Since this amount of FAB was insufficient to bind all DGTX present in the serum, cardiac DGTX toxicity (total AV-block) persisted. During a second FAB infusion (400 mg) the patient reverted to regular AV-conduction. At this time most of the DGTX in serum was FAB-bound. Toxic symptoms (sinus arrest) reappeared twice and were accompanied by increasing amounts of non-antibody-bound DGTX in the serum. Additional application of FAB (2 x 80 mg) resulted in the immediate disappearance of arrhythmia. During FAB-treatment total DGTX serum concentrations and renal DGTX clearance rose, indicating redistribution of drug from tissue to serum and urinary elimination of FAB-bound DGTX, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Kurowski
V
V
Clinic for Internal Medicine, Medical University of Lübeck, FRG.
Iven
H
H
Djonlagic
H
H
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000627:therapeutic use*; D004070:Digitalis / Q000276:immunology*; D004074:Digitoxin / Q000097:blood / Q000506:poisoning* / Q000652:urine; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use* / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011041:Poisoning / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D013406:Suicide, Attempted
D000888:Antibodies, Anti-Idiotypic; D007140:Immunoglobulin Fab Fragments; D004074:Digitoxin