Amatoxin Toxicity Treatment & Management

Updated: Jul 17, 2018
  • Author: Douglas S Lee, MD; Chief Editor: Stephen L Thornton, MD  more...
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Treatment

Approach Considerations

Before arrival at the emergency department (ED), supportive measures, such as intravenous (IV) access and oxygen, should be instituted if needed. Suspected amatoxin ingestion should be aggressively treated because mortality after amatoxin ingestion may be as high as 60%. All patients with amatoxin poisoning should be admitted for aggressive supportive care, monitoring of hepatic function, and observation for progression to later stages of poisoning.

The mainstays of treatment of amatoxin ingestion include aggressive IV fluid and electrolyte therapy to correct deficiencies and maintain adequate hydration. Serum electrolyte and glucose levels should be closely monitored. Gastric decontamination may be helpful if instituted promptly (within 1 hour after ingestion) but patients rarely present in this time frame. Liver transplantation may be indicated in selected cases, though the precise indications remain controversial.

Consider transferring any patient with amatoxin poisoning to a facility with a medical toxicologist.  Consultation with a regional poison control center is recommended.  Consider transferring any patient with progressive hepatic dysfunction to a facility with liver transplant capability in order to minimize delays in procuring an appropriate organ.

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Supportive Measures

Airway and fluid support

Early management of airway, breathing, and circulation (the ABCs) and prompt institution of IV access are vital in the treatment of Amanita poisoning. Supportive care with IV hydration and correction of electrolyte abnormalities leads to symptomatic improvement.

A retrospective review of 105 patients with amatoxin poisoning treated from 1988 to 2002 in Italy showed that all patients treated within 36 hours after ingestion were cured without sequelae. Only 2 of the 105 patients died, and both of them were admitted more than 60 hours after ingestion. Their treatment protocols included intensive fluid and supportive therapy, restitution of altered coagulation factors, multiple-dose activated charcoal, mannitol, dexamethasone, glutathione, and penicillin G. [10]

Gastric decontamination

If the patient presents less than 1 hour after known ingestion of cyclopeptide-containing mushrooms and has not already vomited, consider gastric decontamination via gastric lavage or nasoduodenal suctioning. Patients who present with nausea and vomiting within 1-2 hours of ingestion of a mushroom most likely have consumed a less toxic mushroom. 

Administer activated charcoal in all patients who are asymptomatic with suspected Amanita ingestion. Patients who are asymptomatic afer ingesting unknown or unidentified mushrooms may receive activated charcoal and observation for 6-12 hours. Most patients with confirmed Amanita poisoning arrive later than 6 hours after ingestion and are usually vomiting at presentation, which may eliminate the need for lavage. Control nausea and vomiting with antiemetics, preferably ondansetron.

Activated charcoal (1 g/kg) is recommended if the patient is not vomiting and has a protected airway. Multidose activated charcoal (typically 1gram/kg given every 2-4 hours)should be given as it may disrupt enterohepatic circulation and reduce toxicity [21] .

Hemodialysis and hemoperfusion

Hemodialysis and hemoperfusion have been proposed as methods for removing circulating amatoxin from the blood. Clear recommendations cannot be made, but hemodialysis may be necessary in those patients who develop renal failure.

The Molecular Adsorbent Recirculation System (MARS), a form of hepatic albumin dialysis, may have a role in bridging critically ill patients to liver transplantation or to spontaneous recovery of liver function. 

One tertiary center reported successful treatment of six patients with acute liver injury caused by ingestion of amanita mushrooms. Four were listed on admission for liver transplantation. All received extracorporeal albumin dialysis (ECAD) using the MARS system in addition to standard medical treatment. Overall 16 dialysis sessions were performed and all six patients recovered fully without the need for transplantation. No severe adverse events were reported during treatment. [11]  

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Pharmacologic Therapy

No US Food and Drug Administration (FDA)–approved specific antidote for cyclopeptide poisoning exists. Several drugs have been postulated to reduce uptake of amatoxin into hepatocytes; animal data support the use of some of these drugs, but only anecdotal support is available for humans. [12]

Silibinin (derived from the Mediterranean milk thistle plant, Silybum marianum) is the pharmacologic treatment of choice in Europe, but it is not available in the United States. Milk thistle is hypothesized to provide hepatoprotective effects via interruption of the enterohepatic circulation of amanitin and inhibition of penetration into liver cells. [5]

Other suggested therapies include benzylpenicillin (penicillin G), N-acetylcysteine (NAC), thioctic acid, vitamin K, cimetidine, cytochrome C, and hyperbaric oxygen. Given the rarity of toxic mushroom ingestion and the difficulties in designing prospective trials, evidence is limited to animal studies and retrospective analysis in humans. Because these suggested therapies are unapproved, consult with a medical toxicologist from the nearest regional poison control center before undertaking a course of therapy.

NAC is given initially in an intravenous (IV) loading dose of 150 mg/kg IV infused over 15 minutes, diluted in 200 mL of 5% dextrose in water (D5W); some recommend giving the loading dose over 60 minutes to reduce the risk of an anaphylactoid reaction. Subsequently, the first maintenance dose of 50 mg/kg in 500 mL D5W is infused IV over 4 hours, followed by the second maintenance dose of 100 mg/kg in 1000 mL D5W infused IV over 16 hours. For continuation of NAC administration, consult with a poison control center or medical toxicologist.

In a retrospective analysis, the lowest mortality was reported in patients treated with NAC and silibinin, both of which were administered as monotherapy. [13] The polytherapy with the lowest mortality was a combination of high-dose penicillin G with silibinin. Notably, an isolated administration of high-dose penicillin did not yield improved survival.

In a subsequent retrospective analysis of 367 patients with suspected amatoxin poisoning, of whom 118 received silibinin alone and 249 silibinin plus penicillin, the investigators reported lower death and transplantation rates in the silibinin group than in the silibinin-penicillin group, though the difference did not prove statistically significant. [14]

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Liver Transplantation

Some patients recover liver function with medical therapy alone, and some do not. Efforts have been made to facilitate early identification of those patients who will require transplantation, thus expediting location of donors and avoiding unnecessary transplants.

Precise indications for liver transplantation are controversial. The American Association for the Study of Liver Diseases has released guidelines for the evaluation of patients for liver transplantation. [15] Proposed criteria have included graded hepatic encephalopathy, prothrombin time (PT), and creatinine level.

Consider orthotopic liver transplantation in patients who develop any of the following:

  • A 2-fold prolongation of PT despite administration of fresh frozen plasma
  • Persistent hypoglycemia
  • Serum bilirubin levels higher than 25 mg/dL
  • Azotemia
  • Grade III or grade IV hepatic encephalopathy
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Prevention

Ingestion of cyclopeptide-containing mushrooms can be reduced by closely monitoring young children in rural or suburban areas and by educating mushroom pickers about the dangers of amateur mushroom hunting.

No single test can be used to determine the edibility of wild mushrooms. Foragers should abide by the following dictum: “No rule is the only rule.” Immigrants, even if very experienced with the mushrooms that grow in their countries of origin, may not be able to distinguish poisonous mushrooms from edible mushrooms in the United States.

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Consultations

Consultation with a regional poison control center or toxicologist for assistance in case management is often valuable.

Contacting a mycologist for possible mushroom identification may be helpful. Possible sources for mushroom identification include the following:

  • North American Mycological Association
  • Local botanical garden
  • Local mycology club
  • Regional poison control center

If hepatic dysfunction is present, a gastroenterologist should be consulted. If hepatic failure is present, medical personnel who work with a liver transplant program should be consulted to facilitate a preoperative evaluation should spontaneous recovery not occur. If fulminant hepatic failure (FHF) has developed, a liver transplant service should be consulted.

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Long-Term Monitoring

Patients who remain asymptomatic for 12 hours after ingestion of unknown mushrooms may be safely discharged. Results of the following laboratory studies should be monitored for signs of deterioration:

  • Liver function tests (LFTs)

  • Electrolytes and glucose levels

  • Blood urea nitrogen (BUN) and creatinine levels

  • Prothrombin time (PT)

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