9. Treatment of Amatoxin Poisoning-20 year retrospective analysis

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720 Table 3 Amatoxin Poisoning Cases Treated with Mono-chemotherapy, with/without Detoxication Procedures and with/without Liver Transplant Treatments Detoxication Date/Country T/E Cases Mushroom Drugs Oral C/GA Urin. FD ECP HD–HP/PL LT Surv. References 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. 1988 Turkey 1/27; child L.cas, L.hel 1ATB 0/0 0 1–0/0 0 0 [82] 1971–1995 Slovak Republic 103/103; 14 children A.ph, a.sp B.pen 0/0 (FD) (HD–HP)/0 0 95 [113,114] 1981 Spain 2/2 A.ph B.pen 0/2 0 2–0/0 0 2 [115] 1982 Spain 6/8 A.ph B.pen 0/0 0 0–0/6 0 5 [98] 1982–1986 Spain 13/85; 1 child 5 A.ph, 2 A.ve, 3 L.bi, B.pen 2/2 9 0–1/2 0 12 [43,50] 3 a.sp; amat 1986 Spain 2/3 L.bi B.pen 0/0 0 0–0/0 0 2 [77] 1986–1989 Italy 12/12 A.ph B.pen 12/0 0 12–0/0 0 9 [116] 1988 Croatia 18/18; (children) A.ph B.pen 18/18 18 2–0/16 0 14 [117] 1991 Ohio 1/1 G.sp B.pen 1/0 0 0–0/0 0 1 [36] 1994 Missouri 2/2 A.bis B.pen 0/0 0 0–0/0 0 1 [118] 1996 California 3/3 A.ph B.pen 0/0 0 0–0/0 1 a 3 [119,120] 1998 France 1/1 A.ph B.pen 1/0 0 0–0/0 0 1 [121] 1998 Minnesota 1/1; child A.vi B.pen 1/0 0 0–0/0 0 1 [122] 1982 U.K. 2/2 A.ph Cimetid 0/0 0 0–2/0 0 0 [123] 1999 Pennsylvania 1/6 a.sp Cimetid 1/0 0 0–0/0 0 1 [124] 1987–1993 Italy 86/86 A.ph NAC 86/0 86 0–0/0 0 80 [125] 1994 Italy 1/1; pregnant A.ph, amat NAC 1/0 1 0–0/1 0 1 [126] 1996–1997 California 1/10 A.ph NAC 1/0 0 0–0/0 0 1 [109] 1997 California 1/4 a.sp NAC 1/0 0 0–0/0 0 1 [90] 1980–1986 Europe 25/252 A.ph, a.sp Silybin 0/0 (FD) (HD–HP)/0 0 24 [127,128] 1991–1999 Slovak Republic 20/20; (children) A.ph, a.sp Silybin 20/0 20 0–0/0 0 20 [129] 1993 Germany 26/154 a.sp Silybin 0/0 0 0–0/0 0 26 [130] 1994 Germany 3/12 A.ph Silybin 0/0 0 0–0/0 3 2 [88] 1981 California 1/10 A.ph Steroid 0/0 0 0–0/0 0 1 [74] 1982–1983 California 2/21 a.sp, amat Steroid 2/0 0 0–2/0 0 0 [42] 1982–1983 California 3/21 a.sp Steroid 3/0 0 0–0/0 0 3 [42] 1988 Turkey 1/27 L.cas, L.hel Steroid 0/0 0 0–0/0 0 1 [82] 1997 Italy 1/1 A.ph Steroid 0/0 0 0–0/1 0 1 [131] 1981 New York 2/3 a.sp Thioc.a 0/0 0 1–0/0 0 2 [73] 1981 California 1/10 a.sp Thioc.a 0/0 0 0–0/0 0 0 [74] 1982 Indiana 1/1 A.vi Thioc.a 0/0 0 0–0/0 0 1 [132] 1982–1986 Spain 4/85; 1 child A.ph, amat Thioc.a 2/3 3 0–2/0 0 4 [43,50] Enjalbert et al. T/E Cases ¼ treated/exposed individuals; Oral ¼ oral detoxication using C ¼ activated charcoal and GA ¼ gastroduodenal aspiration; Urin. ¼ urinary detoxication by FD ¼ forced diuresis; ECP ¼ extra-corporeal detoxication including HD ¼ hemodialysis, HP ¼ hemoperfusion, and PL ¼ plasmapheresis; LT ¼ liver transplant; Surv. ¼ survivors; amat ¼ amatoxins in biological fluids; undefined cases are reported in brackets. Drugs: ATB ¼ antibiotic agent; B.pen ¼ benzylpenicillin; Cimetid ¼ cimetidine; NAC ¼ N-acetylcysteine; Thioc.a ¼ thioctic acid. a.sp ¼ amatoxin-containing species; A.bis ¼ Amanita bisporigera; A.ph ¼ A. phalloides; A.ve¼A. verna; A.vi ¼ A. virosa; G.sp ¼ Galerina species; L.bi ¼ Lepiota brunneoincarnata; L.cas ¼ L. castanea; L.hel ¼ L. helveola. a Auxiliary liver transplant.
poisoning cases is the mushroom species actually identified. [222] When the species attribution is uncertain the onset of clinical symptoms may be a useful indicator of potential amatoxin ingestion. Amatoxin exposures were more frequently caused by A. phalloides in Central and Southern Europe, A. virosa in Northern Europe, and A. phalloides and related deadly white Amanitas in North America. Unidentified amatoxin-containing species caused 21% of poisonings and are listed as a.sp. in Tables 1–6. STATISTICAL ANALYSIS An overall table (189 rows, 12 columns) was constituted from Tables 1–6 with the actual or coded values of the following parameters: date; country; modes of care, number of exposed individuals and treated patients; number and percentage of survivors and nonsurvivors; mushroom or mixture of mushrooms; single drug or drug combination; and LTs. A general frequency table was constructed of the observed frequencies for each mode of care. Eleven modes of care had a sufficient representation for analysis: one treatment mode (supportive measures alone, Table 1) and 10 specific treatments: detoxication procedures (Table 2) and nine chemotherapies from Tables 3–6 (monochemotherapies: benzylpenicillin, N-acetylcysteine (NAC), silybin; bi-chemotherapies: benzylpenicillin/ antioxidant drug, b-lactam antibiotic (benzylpenicillin or ceftazidime)/silybin, benzylpenicillin/steroid, benzylpenicillin/thioctic acid; and tri- and poly-chemotherapies: benzylpenicillin combinations with any before mentioned drug, with or without silybin). Due to small numbers of treated victims, 13 other specific chemotherapies were not analyzed: monochemotherapy with cimetidine, vitamin C, thioctic acid, steroid or antibiotic agent (20 cases from Table 3); and bi-, tri-, and poly-chemotherapies with silybin/thioctic acid, antibiotic/antiseptic/vitamin C, steroid/thioctic acid/vitamin C, antibiotic/thioctic acid/vitamin C, two antibiotics/steroid, two antibiotics/NAC, antiseptic/silybin/steroid/vitamin C and three antibiotics/steroid (26 cases from Tables 5 and 6). Outcome without surgery for the 32 cases who received liver transplant (LT . 0) combined with one or more from the 11 analyzed therapeutic modes cannot be known. Therefore, in order to assess the effectiveness of the nontransplant therapies in preventing the fatal stage of the disease, statistical analyses were performed both with and without the transplanted cases. The suffixes LTi and LTe 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. Amatoxin Treatment 721 were added to all numbers, percentages, and probabilities listed or calculated including or excluding the LT cases, respectively. For each observation (line of the general table) with LT . 0, the number of treated patients, survivors, and deceased persons were corrected as follows: (i) for mortality rate excluding the transplant cases (MRLTe), the LT cases were removed from the data set, i.e., both treated patient and survivor numbers were decreased by the number of transplants, (ii) for mortality rate including the transplant cases (MRLTi), each LT patient was considered as a deceased person; only survivor numbers were decreased by the number of transplants. Complementary statistical analyses were carried out for 2062 LTi patients (2108 victims minus 46 nonanalyzed-treatment cases) and 2031 LTe cases (2062 victims minus 31 LT cases); one LT case was in an unanalyzed mode of care. The global performance evaluation of each therapeutic mode was achieved by a statistical comparison of the number of survivors and nonsurvivors using a Chisquare calculation from the two rows (survivors, fatalities) and six columns (six tables) contingency table. The effect of each mode of care was studied by comparison of survivor and dead numbers in the 2 £ 2 tables constituted from the general table. The Chi-square test applied to the general frequency tables rejected the hypothesis that outcome and treatment were independent; the distribution of survivors and deceased persons was statistically different for Tables 1–6, both including and excluding the LT patients. When the p-value was #0.05, the null hypothesis was rejected at the 95% confidence level. The Yates’ correction was applied when the number of survivors or deceased patients was #5, and the Fischer’s exact test was calculated in the case of contingency table 2 £ 2 with less than 100 observations. The statistical analysis was carried out using STATGRAPHICS w PLUS software version 3.3 (Manugistics, Inc., Rockville, MD, USA). DESCRIPTION OF TREATMENTS The management of amatoxin poisoning involves four main categories of therapy: preliminary medical care, supportive measures, specific treatments, and LT. Since there is a relative consensus of opinion about the preliminary medical care and supportive measures, [14,18 – 20,23,223 – 228] only their major features are described. The specific treatments consisting of detoxication procedures, chemotherapies, and LT are described below in detail.
Page 1 and 2: ARTICLE MARCEL DEKKER, INC. 270 MAD
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9. Treatment of Amatoxin Poisoning-20 year retrospective analysis

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