Advertisement

Intensive Care Medicine

, Volume 18, Issue 7, pp 439–442 | Cite as

Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies

  • V. Kurowski
  • H. Iven
  • H. Djonlagic
Originals

Abstract

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 (2×80 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. At 98 h after onset of therapy the DGTX serum level was within the therapeutic range. This case confirms that cardiac toxicity of DGTX can be successfully treated with FAB antidote. The amount of FAB given as a loading dose must be sufficient to bind all DGTX present in the serum and FAB infusions have to be continued over several hours to inactivate DGTX as it leaves the tissue compartment during redistribution.

Key words

Digitoxin Intoxication Antibody fragments Fab treatment Pharmacokinetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Smith TW, Butler VP, Haber E, Forrard H, Marcus FI, Bremner WF, Schulman IC, Phillips A (1982) Treatment of life threatening digitalis intoxication with digoxin specific Fab antibody fragments. N Engl J Med 307:1357–1362PubMedGoogle Scholar
  2. 2.
    Smolarz A, Roesch E, Lenz E, Neubert H, Abshagen P (1985) Digoxin specific antibody fragments (Fab) in 34 cases of severe digitalis intoxication. Clin Toxicol 23:327–340Google Scholar
  3. 3.
    Hess T, Scholtysik G, Riesen W (1980) The effectiveness of digoxin-specific F(ab')2-antibody fragments in the treatment of digitoxin poisoning: experimental investigations in the cat. Eur J Clin Invest 10:93–97PubMedGoogle Scholar
  4. 4.
    Aeberhard P, Butler VP, Smith TW, Haber E, Tse Eng D, Brau J, Chalom A, Glatt B, Thebaut JF, Delangenhagen B, Morin B (1980) Le traitement d'une intoxication digitalique massive (20 mg de digitoxine) par les anticorps anti-digoxine fractionnes (Fab). Arch Mal Coeur 12:1471–1478Google Scholar
  5. 5.
    Baud F, Bismuth C, Pontal PG, Scherrmann JM, Smith TW (1982–83) Time course of antidigoxin Fab fragment and plasma digitoxin concentrations in an acute digitalis intoxication. J Toxicol Clin Toxicol 19:857–860Google Scholar
  6. 6.
    Hess T, Riesen W, Scholtysik G, Stucki P (1983) Digitoxin intoxication with severe thrombocytopenia: reversal by digoxin-specific antibodies. Eur J Clin Invest 13:159–163PubMedGoogle Scholar
  7. 7.
    Lignian H, Vincent JL, Hallemans R (1984) Treatment of severe digitoxin intoxication by digoxin specific Fab antibody fragments. Acta Cardiol Brux 39:301–305PubMedGoogle Scholar
  8. 8.
    Schaumann W, Kaufmann B, Neubert P, Smolarz A (1986) Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Eur J Clin Pharmacol 30:527–533PubMedGoogle Scholar
  9. 9.
    Hursting MJ, Raisis VA, Opheim KE, Bell JL, Trobaugh GB, Smith TW (1987) Determination of free digoxin concentrations in serum for monitoring FAB treatment of digoxin overdose. Clin Chem 33:1652–1655PubMedGoogle Scholar
  10. 10.
    Krieglstein J (1981) Plasma protein binding of cardiac glycosides. In: Greef K (ed) Handbook of experimental pharmacology, vol 56, 2: Cardiac glycosides. Springer, Berlin Heidelberg New York, pp 95–104Google Scholar
  11. 11.
    Schiwara HW, Hebell T, Kirchherr H, Postel W, Weser J, Görg A (1986) Ultrathin-layer sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis and silver staining of urinary proteins. Electrophoresis 7:496–505Google Scholar
  12. 12.
    Lemon M, Andrems DJ, Binks AM, Georgion GA (1987) Concentrations of free serum digoxin after treatment with antibody fragments. Br Med J 295:1520–1521Google Scholar
  13. 13.
    Sinclair AJ, Hewick DS, Johnston PC, Stevenson IH, Lemon M (1989) Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity. Br J Clin Pharmacol 28:352–356PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • V. Kurowski
    • 1
  • H. Iven
    • 2
  • H. Djonlagic
    • 1
  1. 1.Clinic for Internal MedicineMedical University of LübeckLübeckGermany
  2. 2.Institute of PharmacologyMedical University of LübeckLübeckGermany

Personalised recommendations