Historically, there have been many anecdotal and largely ineffective treatments used to counteract this deadly toxin. Because 80 percent of the toxin is eliminated in the urine, forced diuresis may have some theoretical basis, but no clinical trials have shown efficacy. Amatoxins are dialyzable, and both hemodialysis and hemoperfusion had been a standard for therapy. However, because of the small plasma concentration, early binding in the liver, and rapid clearance from the plasma (within 48 h), hemodialysis and hemoperfusion are of limited usefulness. Many patients who receive hemodialysis actually do worse than patients treated with other forms of therapy. Attempts to interrupt enterohepatic circulation have also been tried but are of limited usefulness. Although high concentrations of amatoxin are excreted into bile, the small amount of liquid produced does not yield a large amount of the amatoxin extracted.
Thioctic acid, which has been used for many years in Europe, is a known free radical scavenger and may be effective in the treatment of acute hepatic failure of undifferentiated cause. Thioctic acid and glutathione appear to protect against microsomal lipid peroxidation and therefore may be of theoretical use in amatoxin poisoning. Animal and human studies, however, have not shown thioctic acid to be effective.
For patients in the United States, penicillin appears to be the most effective therapy. High doses of penicillin appear to block the uptake of amatoxin into the liver by its shared active transport system.10 In addition, penicillin increases renal excretion of the toxin. Other antibiotics, such as rifampin and cephalosporins, have a similar effect in animal studies. Huge doses of penicillin G [300,000 to 1,000,000 U/kg/day] are required to decrease toxicity. Such doses are associated with seizures, and patients should be appropriately monitored. Penicillin should be started very soon after ingestion, if amatoxin ingestion is suspected. Penicillin-allergic patients either should not be treated with penicillin or should undergo desensitization.
Silymarin (silybinin), which has been used successfully in Europe to treat amatoxin ingestion, acts as a free radical scavenger and may interrupt the enterohepatic circulation of amatoxin when given orally. It is not available in the United States, but a recent study in Europe showed success in patients with amatoxin poisoning. 11
Hyperbaric oxygen, which has been used in Europe as a treatment for amatoxin poisoning,12 has been shown to be beneficial in other cases of hepatic failure, perhaps by increasing hepatic regeneration and interfering with free radical formation as well. No controlled studies exist, and animal studies have produced conflicting results.
There have been animal studies of other therapies that have not been yet definitively tested in humans. High-dose cimetidine (10 g/day) has been shown to be effective in animals and recently has been used successfully in humans.5 Vitamin C, zinc, and thiol compounds have also been useful in animal models. Fab monoclonal antibodies have been developed against amatoxin.13 Although successful in reducing hepatic failure, severe renal toxicity has developed. Theoretically, such Fab antibodies could be used with plasmapheresis to remove the antibody-antigen complexes.
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