Mushroom Toxicity Treatment & Management

Updated: Dec 29, 2015
  • Author: B Zane Horowitz, MD, FACMT; Chief Editor: Asim Tarabar, MD  more...
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Treatment

Approach Considerations

In the absence of a definitive identification of the mushroom, all ingestions should be considered serious and possibly lethal. Once mushroom toxicity is diagnosed, treatment is largely supportive. Early volume resuscitation is important for liver and renal toxic syndromes.

Gut decontamination, including whole-bowel irrigation, may be necessary for amatoxins. Beyond the first postprandial hour, orogastric lavage is not recommended, because of its questionable efficacy. Activated charcoal plays a much more important role in limiting absorption of most toxins and is indicated for all patients with amatoxin mushroom poisoning, regardless of the timing of presentation. When amatoxins are suspected, multiple doses of activated charcoal should be administered repeatedly to interrupt enterohepatic circulation of these toxins.

In general, children are more susceptible to volume depletion and mushroom toxicity (mushroom poisoning) than are healthy adults. Elderly patients are more susceptible to volume depletion than are healthy adults.

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Supportive Measures

Once a toxin is absorbed, it may potentially be neutralized in the following ways:

  • Inhibition of tissue uptake of the toxin
  • Inhibition of the metabolic pathways involved in the development of toxicity
  • Enhanced elimination of the toxin

Specific therapy depends on the presumed toxin ingested (see Toxin-Specific Management Approaches). Other complications of mushroom poisoning are treated in a standard manner.

Methemoglobinemia, which may occur after the ingestion of gyromitrins and, occasionally, after an intravenous (IV) injection of psilocybin, is treated with IV methylene blue. The US Food and Drug Administration (FDA) warns against the concurrent use of methylene blue with serotonergic psychiatric drugs, unless such therapy is indicated for life-threatening or urgent conditions. Methylene blue may increase CNS serotonin levels, increasing the risk of serotonin syndrome. [23]

Hemolysis, which may occur with gyromitrin toxicity, is usually mild, necessitates the administration of large amounts of IV fluids only to prevent renal complications; blood transfusions are rarely required. Hemolysis due to Paxillus species may be more severe and may result in acute renal failure.

Rhabdomyolysis has been reported with several species. Direct damage to myocytes with resultant onset on rhabdomyolysis occurs after ingestion of the so-called “man-on-horseback” mushroom, Tricholoma equestre (also known as Tricholoma flavovirens). Patients may present with muscle pain and have been reported with elevated creatinine phosphokinase levels, in the 10,000 U/L to 100,000 U/L range. Other mushrooms implicated in less severe forms of rhabdomyolysis are Russula subnigricans (blackening Russula), Boletus edulis (king boletus), Leccinium versipelle (brown birch boletus), and Albatrellus ovinus (sheep polypore). Many of these are identified in field guides as edible. Treatment is with aggressive IV fluid resuscitation and consideration for IV sodium bicarbonate to alkalinize the urine. In rare cases, dialysis may be needed if renal failure occurs.

Agitation, commonly observed with hallucinogenic mushrooms, is treated with benzodiazepines; phenothiazines are best avoided in this setting. Other causes of agitation (eg, hypoxia, hypovolemia, and shock) should also be sought and corrected.

Anticholinergic poisoning may be treated with benzodiazepines; in rare cases, physostigmine may be required.

Severe muscarinic symptoms may be treated with the infusion of small doses of atropine. In muscarine poisoning, the entire episode usually subsides in 6-8 hours; some symptoms may take up 24 hours to fully resolve. Atropine should be considered only when excessive bronchial secretions compromise breathing and cause shortness of breath. Monitoring with pulse oximetry is indicated. Clinicians should be prepared to support the airway and perform orotracheal suctioning if necessary. [11]

Patients with severe poisoning from disulfiram-containing mushrooms may benefit from fomepizole (4-methylpyrazole), which blocks alcohol dehydrogenase and, hence, the formation of the toxic aldehyde.

Fulminant hepatic failure (FHF) is a common complication observed with amatoxin and gyromitrin poisoning, and it should be treated aggressively because it commonly follows a fatal course. Orthotopic liver transplantation (OLT) may be indicated (see Liver Transplantation).

Renal failure, commonly observed with norleucine and orellanine poisoning, may have to be treated with hemodialysis. Acute renal failure (ARF) with mild reversible liver injury may also follow the ingestion of Amanita smithiana and Amanita proxima.

Conventional indications for dialysis include uremic encephalopathy, fluid overload (with pulmonary edema), severe hyperkalemia, and acidosis. Patients with unremitting renal failure are candidates for renal transplantation, but since most cases resolve slowly over time, several months of hemodialysis should occur before this is considered.

The development of renal failure in patients with FHF warrants an attentive search for the cause of the renal failure. Patients with hepatorenal syndrome (HRS) are candidates for liver transplant.

Endotracheal intubation is recommended in all patients at risk of aspiration, and mechanical ventilation should be initiated in all patients with hypoxia, hypercarbia, acidemia, and shock. Aggressive rehydration in the intensive care unit (ICU) may be necessary in patients with choleralike gastroenteritis, and infusions of large amounts of electrolytes with dextrose solutions may be necessary to maintain vital functions.

Blood transfusions may be required in patients with hemorrhagic diarrhea, blood loss, and severe hemolytic anemia. Blood pressure support with dopamine and norepinephrine may be required when crystalloids and colloid infusions fail. Hypoglycemia is treated with infusions of 10% dextrose.

Cerebral edema is also treated in a conventional manner, which is aimed at reducing intracerebral pressure and preventing herniation. Hyperventilation, fluid restriction, osmotic diuresis, hypertonic saline, positioning the head of the bed at 30° from the horizontal plane, barbiturate coma, and anticonvulsants may be necessary.

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Toxin-Specific Management Approaches

Amatoxin poisoning

In addition to intensive airway and aggressive rehydration with fluid therapy, correction of coagulation factors, and multiple doses of activated charcoal, a number of therapeutic options for amatoxin poisoning have been proposed, but to date, no controlled studies comparing the efficacy of different modalities have been published.

The IV form of silibinin is not currently available in the United States, but is used in Europe; however, an oral form (silymarin) may be obtained. Silymarin is a dietary supplement found in health food stores as an extract from milk thistle. (Silymarin) is given at 1 g orally 4 times daily, or its purified alkaloid silibinin is given intravenously at 5 mg/kg IV over 1 hour, followed by 20 mg/kg/day as a constant infusion. Silibinin is thought to interfere with hepatic uptake of alpha-amanitin, so early institution of therapy offers the best chance for clinical efficacy.

Other recommended therapies for amatoxin poisoning include the following:

  • IV benzyl penicillin - Reduces the uptake of amatoxin by hepatocytes
  • Cimetidine - Inhibits CYP450 enzymes, presumably reducing metabolism of alpha-amanitin into hepatotoxic metabolites
  • N -acetylcysteine (NAC) - A thiol containing glutathione precursor with free radical binding capacity and antioxidant effects

In a murine model, however, none of the proposed antidotal therapies was found to have a significant effect on hepatic aminotransferase levels when compared with controls, nor did any of them demonstrate an important decrease in hepatic necrosis histologically. [24] A large human case series found an association between both silibinin and NAC and higher survival rates. [25]

Corticosteroids, vitamin C, kutkin, aucubin, and thioctic acid have been used in the past but have no proven benefit and are no longer recommended. Charcoal hemoperfusion and hemodialysis are also ineffective in removing toxins because once the toxin is formed, it is rapidly excreted by the kidneys.

Plasma exchange transfusions have been used with some success, but controlled studies are lacking. MARS (Molecular Absorbent Regenerating System), an extracorporeal liver-assistance method using an albumin dialysate to remove albumin-bound toxins, has shown promising survival results in amatoxin-related hepatic failure. [26] The Prometheus (Fresenius Medical Care, Bad Homburg, Germany) fractionated plasma separation and adsorption (FPSA) system also may prove useful for safely eliminating amatoxin and potentially obviating OLT. [27]

Further inpatient care of patients who survive amatoxin poisoning focuses on management of direct complications of poisoning and on management of the liver transplant (if OLT was performed).

Gyromitrin poisoning

In gyromitrin poisoning, in which systemic toxicity results from reduced concentrations of gamma-aminobutyric acid (GABA), seizures may be overcome by the infusions of pyridoxine (vitamin B-6) if they do not respond to benzodiazepines. Hydrazines also inhibit the transformation of folic acid to tetrahydrofolic acid. Therefore, patients with severe gyromitrin toxicity should receive folinic acid, as an adjunctive therapy.

Further inpatient care of patients who survive gyromitrin poisoning focuses on the management of complications of poisoning (eg, rhabdomyolysis, methemoglobinemia, and hemolysis) and management of the liver transplant (if OLT was performed).

Muscarine poisoning

Most patients with poisoning due to mushrooms containing muscarine can be treated without medications. If patients exhibit excessive bronchial secretions or other symptoms of cholinergic excess (bradycardia) that are of significant concern, atropine may decrease these symptoms.

If the patient presents within 1 hour of ingestion, oral administration of activated charcoal may be considered, [28] but adsorption to activated charcoal has not been demonstrated for these constituents. [29] No evidence suggests that routine administration of multiple doses of activated charcoal is useful. Ipecac syrup should generally be avoided, because vomiting often occurs spontaneously and evidence for effectiveness is lacking.

Administer IV fluids if vomiting becomes prominent, though this rarely proves necessary. Provide psychiatric care to patients with intentional ingestions and suicidal thinking.

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Liver Transplantation

Indications for immediate OLT include the following:

  • Stage III hepatic encephalopathy
  • Serum bilirubin levels higher than 4.6 mg/dL
  • Prothrombin time (PT) prolongation unresponsive to FFP infusions (patients with a PT >100 s should be considered for transplantation)

Other suggested factors to consider include the following:

  • Age younger than 12 years
  • Serum creatinine level higher than 1.4 mg/dL
  • Hemorrhage
  • Shock
  • Acidosis
  • Hypoglycemia
  • Factor V deficiency (concentration < 10% of the reference range)

In patients with these indications, OLT may be the only life-saving therapy. Therefore, transfer to a liver transplantation center should be undertaken early in the setting of amatoxin poisoning and before the development of stage III encephalopathy, jaundice, or renal failure. Patients who develop shock, acidosis, hypoglycemia, and coagulopathy with hemorrhage and those who exhibit marked liver transaminase elevations should also be considered for immediate OLT, even in the absence of hepatic encephalopathy, azotemia, and hyperbilirubinemia.

FHF patients awaiting OLT should be intubated early in order to prevent the added burden of aspiration pneumonia and hypoxia. Hypovolemia is treated with crystalloids. Hemorrhage is treated with blood transfusions and, when accompanied by coagulopathy, infusions of FFP. Lactulose may be administered to patients who exhibit hepatic encephalopathy.

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Diet

Patients with FHF have a catabolic rate that is quadruple the reference range; accordingly, they should receive adequate protein and carbohydrates so that hepatocyte regeneration may be optimized. Limiting protein in patients with FHF is associated with an increased mortality. Patients with acute FHF also are at risk for hypoglycemia and require close monitoring of their glucose levels, along with infusion of 10% dextrose solutions. Patients receiving high-carbohydrate solutions also must receive thiamine.

In patients with renal failure, use of essential amino acids is not associated with better outcomes than is the use of standard amino acids. Nutrition of patients with ARF should include amino acids and glucose, with a relatively normal calorie-to-nitrogen ratio.

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Prevention

Prevention is best achieved by eating only commercially cultivated mushrooms, and identification of mushrooms is best left to experts. Mushrooms should be regularly removed from sites where children are routinely present.

Education regarding the poisonous nature of wild mushrooms may act as a deterrent to careless mushroom foraging and ingestion. Mushroom hunters who are appropriately cautious eat only 1 type of mushroom and save a sample in a dry paper bag for later identification, if needed.

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Consultations

Specialists from the regional poison center, medical toxicologists, botanists, and mycologists may assist in the identification of the mushroom. A mycologist can be contacted through the local poison center (in the United States, call 800-222-1222), a mycology club, the North American Mycological Association, a botanical garden, or local university. The Internet may also provide answers. However, decontamination and treatment should not wait for the identification of the mushroom.

Consultation with a transplant surgeon is indicated as soon as the diagnosis of amatoxin-induced FHF is entertained.

Consultation with a nephrologist is indicated for renal failure or when dialysis or hemoperfusion is required.

Consultation with a psychiatrist is warranted when there is reason to think that the ingestion may have been a suicidal gesture.

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