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Patients with significant toxicity (manifested by severe metabolic acidosis, altered mental status, and markedly elevated osmolar gap) should undergo hemodialysis as soon as possible to remove the parent compound and the toxic metabolites Treatment with folic acid, thiamine, and pyridoxine may enhance the breakdown of toxic metabolites

Boyer EW et al The serotonin syndrome N Engl J Med 2005 Mar 17;352(11):1112 20 [PMID: 15784664] Gillman PK Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity Br J Anaesth 2005 Oct;95(4):434 41 [PMID: 16051647]

Administer high-flow oxygen If the causative agent was recently ingested, administer activated charcoal (see p 1362) Repeat-dose activated charcoal may enhance dapsone elimination (see p 1363)

There are thousands of mushroom species that cause a variety of toxic effects The most dangerous species of mushrooms are Amanita phalloides, Amanita verna, Amanita virosa, Gyromitra esculenta, and the Galerina species, all of which contain amatoxin, a potent cytotoxin Ingestion of even a portion of one mushroom of a dangerous species may be sufficient to cause death The characteristic pathologic finding in fatalities from amatoxin-containing mushroom poisoning is acute massive necrosis of the liver

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Methylene blue enhances the conversion of methemoglobin to hemoglobin by increasing the activity of the enzyme methemoglobin reductase For symptomatic patients, administer 1 2 mg/kg (01 02 mL/kg of 1% solution) intravenously The dose may be repeated once in 15 20 minutes if necessary Patients with hereditary methemoglobin reductase deficiency or glucose-6-phosphate dehydrogenase deficiency may not respond to methylene blue treatment

BheemReddy S et al Methemoglobinemia following transesophageal echocardiography: a case report and review Echocardiography 2006 Apr;23(4):319 21 [PMID: 16640711] Dahshan A et al Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature Pediatrics 2006 Apr;117 (4):e806 9 [PMID: 16585290]

Clinical Findings (Table 38 8)

1 Amatoxin-type cyclopeptides (A phalloides, A verna, A virosa, and Galerina species) After a latent interval of 8 12 hours, severe abdominal cramps and vomiting begin and progress to profuse diarrhea, followed in 1 2 days by hepatic necrosis, hepatic encephalopathy, and frequently renal failure The fatality rate is about 20% Cooking the mushrooms does not prevent poisoning 2 Gyromitrin type (Gyromitra and Helvella species) Toxicity is more common following ingestion of uncooked mushrooms Vomiting, diarrhea, hepatic necrosis, convulsions, coma, and hemolysis may occur after a latent period of 8 12 hours The fatality rate is probably less than 10% 3 Muscarinic type (Inocybe and Clitocybe species) Vomiting, diarrhea, bradycardia, hypotension, salivation, miosis, bronchospasm, and lacrimation occur shortly after ingestion Cardiac arrhythmias may occur Fatalities are rare 4 Anticholinergic type (Eg, Amanita muscaria, Amanita pantherina) This type causes a variety of symptoms that may be atropine-like, including excitement, delirium, flushed skin, dilated pupils, and muscular jerking tremors, beginning 1 2 hours after ingestion Fatalities are rare 5 Gastrointestinal irritant type (Eg, Boletus, Cantharellus) Nausea, vomiting, and diarrhea occur shortly after ingestion Fatalities are rare 6 Disulfiram type (Coprinus species) Disulfiram-like sensitivity to alcohol may persist for several days Toxicity is characterized by flushing, hypotension, and vomiting after coingestion of alcohol 7 Hallucinogenic (Psilocybe and Panaeolus species) Mydriasis, nausea and vomiting, and intense visual hallucinations occur 1 2 hours after ingestion Fatalities are rare 8 Cortinarius orellanus This mushroom may cause acute renal failure due to tubulointerstitial nephritis Amanita smithiana has also been reported to cause acute renal failure

FIGURE 10-24

Overdoses of MAO inhibitors (isocarboxazid, phenelzine, selegiline, moclobemide) cause ataxia, excitement, hypertension, and tachycardia, followed several hours later by hypotension, convulsions, and hyperthermia Ingestion of tyramine-containing foods may cause a severe hypertensive reaction in patients taking MAO inhibitors Foods containing tyramine include aged cheese and red wines Hypertensive reactions may also occur with any sympathomimetic drug Severe or fatal hyperthermia (serotonin syndrome) may occur if patients receiving MAO inhibitors are given meperidine, fluoxetine, paroxetine, fluvoxamine, venlafaxine, tryptophan, dextromethorphan, tramadol, or other serotonin-enhancing drugs This reaction can also occur with the newer selective MAO inhibitor moclobemide, and the antibiotic linezolid, which has MAO-inhibiting properties The serotonin syndrome has also been reported in patients taking selective serotonin reuptake inhibitors (SSRIs) in large doses or in combination with other SSRIs, even in the absence of an MAO inhibitor or meperidine

Administer activated charcoal (see p 1362) Treat severe hypertension with nitroprusside, phentolamine, or other rapid-acting vasodilators (see p 1360) Treat hypotension with fluids and positioning, but avoid use of pressor agents if possible Observe patients for at least 24 hours, since hyperthermic reactions may be delayed Treat hyperthermia with aggressive cooling; neuromuscular paralysis may be required (see p 1361) Cyproheptadine, 4 mg orally (or by gastric tube) every hour for three or four doses, has been reported to be effective against serotonin syndrome

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