Mushroom Toxicity Treatment & Management

In the absence of a definitive identification of the mushroom, all ingestions should be considered serious and possibly lethal. Once diagnosed, treatment of mushroom poisoning is largely supportive.

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 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 with thiamine.

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

GI decontamination, including whole-bowel irrigation, may be necessary. Beyond the first postprandial hour, orogastric lavage is not recommended because of the procedure's questionable efficacy. Activated charcoal plays a much more important role in limiting absorption of most toxins and is indicated for all patients with mushroom poisoning, regardless of the timing of presentation. When amatoxins are suspected, repeated doses of activated charcoal should be administered for 3-4 days to interrupt enterohepatic circulation of these toxins.

Once absorbed, the toxin may be neutralized with inhibition of the tissue uptake of the toxin, inhibition of the metabolic pathways involved in the development of toxicity, or enhanced elimination of the toxin. Specific therapy depends on the presumed toxin ingested.

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 injection of psilocybin, is treated with intravenous methylene blue.

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

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

Anticholinergic poisoning may be treated with benzodiazepines and rarely requires physostigmine.

Severe muscarinic symptoms may require the infusion of small doses of atropine.

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.

Renal failure, commonly observed with orellanine poisoning, may require hemodialysis. Patients with orellanine and orelline poisoning may benefit from hemoperfusion when it is performed within a week of ingestion, prior to the development of renal failure. Acute renal failure may also follow the ingestion of Amanita smithiamna and A 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.

Fulminant hepatic failure is a common complication observed with amatoxin and gyromitrin poisoning, and it should be treated aggressively because it commonly follows a fatal course.

The development of hepatic encephalopathy, hyperbilirubinemia greater than 4.6 mg/dL, prolongation of the prothrombin time to greater than twice the reference range, and a serum creatinine level greater than 1.4 mg/dL signal a fatal course. For these patients, orthotopic liver transplantation may be the only life-saving therapy. Therefore, transfer to a liver transplant center should be undertaken early in the setting of amanita poisoning and prior to 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 elevations of liver transaminases also should be considered for immediate orthotopic liver transplantation, even in the absence of hepatic encephalopathy, azotemia, and hyperbilirubinemia.

While waiting for an orthotopic liver transplant, patients with fulminant hepatic failure 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 fresh frozen plasma. Lactulose may be administered to patients who exhibit hepatic encephalopathy.

The development of renal failure in patients with fulminant hepatic failure warrants an attentive search for the etiology of the renal failure. Patients with hepatorenal syndrome are candidates for liver transplantation. Prerenal azotemia may be treated with cautious infusions of crystalloids, albumin, and fresh frozen plasma. Low-dose dopamine occasionally may aid in reversing renal failure. Should hemodialysis be required, continuous renal replacement therapy (CRRT) is the dialysis mode of choice because standard hemodialysis can cause rapid elevations in intracranial pressure and decreased cerebral perfusion.

Specific therapies include the following:

Amatoxin

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

The most frequently recommended therapy for amatoxin poisoning is intravenous benzyl penicillin, combined with silibinin (an extract of milk thistle) and cimetidine. N -acetylcysteine (NAC) has also been frequently recommended. Benzyl penicillin and silibinin appear to reduce the uptake of amatoxin by hepatocytes. Of the 2 modalities, silibinin has been purported to offer a better survival advantage compared to benzyl penicillin.

Cimetidine (a cytochrome P-450 inhibitor) is used to inhibit the uptake of amatoxins by the mixed function oxidase system, thereby reducing toxicity. N -acetylcysteine, a glutathione precursor, capable of binding amatoxin-related free radicals, has been found in one case series to be efficacious.

In a murine model, however, none of the proposed antidotal therapies were found to significantly affect the hepatic aminotransferase levels compared with controls; nor did any of them demonstrate an important decrease in hepatic necrosis histologically.^[5]

The intravenous form of silibinin is not currently available in the United States; however, an oral form (ie, silymarin) may be obtained. Silymarin is a dietary supplement found in health food stores.

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 formed, the toxin is excreted rapidly by the kidneys.

Plasma exchange transfusions have also been used with some success, but controlled studies are lacking. MARS (Molecular Absorbent Regenerating System), a new extracorporeal liver-assistance method that uses an albumin dialysate for the removal of albumin-bound toxins, has shown promising survival results in amatoxin-related hepatic failure. Hyperbaric oxygen therapy has been advocated for amatoxin poisoning and should be considered, when available.

Gyromitrin

In the case of gyromitrin poisoning, in which systemic toxicity results from reduced concentrations of GABA, seizures may be overcome by the infusions of pyridoxine if they do not respond to benzodiazepines. Phenobarbital increases the metabolism of hydrazines to toxic compounds and should be avoided in the treatment of seizures in this setting. Hydrazines also inhibit the transformation of folic acid to tetrahydrofolic acid. Therefore, patients with gyromitrin toxicity should receive folinic acid.

Indications for immediate orthotopic liver transplant include the following:

• Stage III hepatic encephalopathy
• Serum bilirubin levels greater than 4.6 mg/dL
• Prothrombin time prolongation greater than twice the reference range and unresponsive to fresh frozen plasma infusions (Patients with a prothrombin time >100 s should be considered for transplant.)
• Quick-test value less than 20%
• Other suggested indications include age younger than 12 years, serum creatinine level greater than 1.4 mg/dL, hemorrhage, shock, acidosis, hypoglycemia, and factor V deficiency (concentration < 10% of the reference range).

• Identification of the mushroom: Specialists from the regional poison center, toxicologists, botanists, and mycologists may assist in the identification of the mushroom. The Internet may also provide answers. However, decontamination and treatment should not await the identification of the mushroom.
• Transplant surgery: Consultation is indicated as soon as the diagnosis of amanita-induced fulminant hepatic liver failure is entertained.
• Nephrology: Consultation is indicated for renal failure or when dialysis or hemoperfusion is required.

• Hepatic failure: The catabolic rate of patients with fulminant hepatic failure (FHF) is quadruple the reference range catabolic rate, and patients in FHF 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 rate. Patients with acute FHF also are at risk for hypoglycemia and require close monitoring of their glucose levels along with infusions of 10% dextrose solutions. Patients receiving high-carbohydrate solutions also must receive thiamine.
• 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 acute renal failure should include amino acids and glucose, with a relatively normal calorie-to-nitrogen ratio.