9. Treatment of Amatoxin Poisoning-20 year retrospective analysis

742
procedures in order to assess a beneficial toxin
elimination for each applied chemotherapy.
A ranking of therapies was based on significant
differences in effectiveness as measured by decreasing
mortality rates (Fig. 1, Tables 8 and 9). The highest
mortality/lowest efficacy was observed with combinations
of benzylpenicillin with thioctic acid, steroid,
and other drugs except silybin as bi-, tri-, and polychemotherapies.
The lowest mortality rates were
observed with silybin and NAC both administered as
mono-chemotherapy, and silybin associations with
benzylpenicillin as bi, tri-, and poly-chemotherapies.
Since no significant difference between silybin singly
and silybin/benzylpenicillin combinations was found,
it appears that the flavonolignan complex is effective
in reducing mortality and/or avoid LT whereas
benzylpenicillin singly is ineffective. Similarly, NAC
statistically appears to be a potentially more effective
chemotherapy than the other drug options.
Review of the modes of care reported for amatoxinintoxicated
patients over the last 20 years demonstrates
wide variability in treatment and response to treatment.
Of particular interest in the environment of evidencebased
medicine is the prevalent use of a therapy,
benzylpenicillin, which has little theoretical foundation
and little evidence of efficacy when compared to
treatment alternatives. It exemplifies the fallacy of
consensus judgments and recommendations based solely
on widespread use of a treatment. These case analyses
and literature review have a number of limitations due to
the disparity in severity grades. However, our work
suggests the most successful orientation for prospective
clinical research and provides a basis for the discontinuation
of the clearly less effective chemotherapies.
Efficacy of several drugs is not supported in this review:
the most widely used agent, benzylpenicllin, as well as
thioctic acid and steroids; perhaps their use should be
discontinued. Amatoxin poisoning cases whose treatment
focuses on detoxication procedures, silybin, and
NAC would be useful to confirm their relevance revealed
by our statistical analysis. Future research should be
directed towards the iridoid glycosides being potential
agents to inhibit amatoxins and stimulate hepatocyte
regeneration.
ACKNOWLEDGMENTS
The authors are grateful to J. ApSimon (Canada),
S. Badalian (Armenia), R. Courtecuisse (France),
J. Elguero (Spain), G. Eyssartier (France), E. Florac
MARCEL DEKKER, INC. 270 MADISON AVENUE NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
(France), F. Fons (France), A. Fraiture (Belgium),
J. Guillot (France), D. Guez (Japan), J. Guinberteau
(France), G. Guzman (Mexico), M. Heil (Germany),
G. Konska (Poland), M. J. Mauruc (France), J. Melot
(Iceland), P. A. Moreau (France), and G. Redeuilh
(France) for providing literature data.
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