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Meticulous Investigation: Wins the Day when Diagnosing and Treating Unusual Toxicology Cases

Gussow, Leon MD

doi: 10.1097/01.EEM.0000342740.77649.e7
Special Report

Dr. Gussow is a voluntary attending physician at the John H. Stroger Hospital of Cook County in Chicago (formerly Cook County Hospital), an assistant professor of emergency medicine at Rush Medical College, and a consultant to the Illinois Poison Center.



At the recent North American Congress of Clinical Toxicology annual meeting in Toronto, more than 300 abstracts were presented as posters or platform sessions. Many of these described research projects, but there were also a number of unusual and instructive case reports. Among those were cases that drive home the message that emergency physicians have to be thorough, whether they are taking a history, testing for residual toxicity, or looking to the Internet for information about new substances.

Amanita smithiana Mushroom Ingestion: A Case of Delayed Renal Failure

West PL, et al

Clin Toxicol


A 55-year-old man came to the emergency department with severe nausea and vomiting that started less than six hours after he ingested a wild foraged mushroom. His pulse was 84 bpm, blood pressure 133/92 mm Hg, respirations 12 bpm, and temperature 95.9°F. Initially the hepatic transaminases were slightly elevated (AST 56 IU/L, ALT 131 IU/L), but tests of renal function were unremarkable. Because it was assumed that the patient had consumed a hepatotoxic mushroom such as Amanita phalloides, treatment was started with N-acetylcysteine, penicillin, and milk thistle extract.

His renal function deteriorated, and dialysis was started on day 4 when his creatinine reached 6.5 mg/dl. Samples of the ingested mushroom were obtained and identified by a mycologist as Amanita smithiana. After an approximately five-week course of inpatient and outpatient dialysis, his renal function recovered close to baseline, and the dialysis catheter was removed.

Amanita smithiana is a white mushroom found in many parts of the Pacific Northwest, including Oregon, Washington, and British Columbia. Toxicity can occur when inexperienced foragers mistake it for the tasty and valuable matsutake mushroom (Tricholoma magnivelare), whose distinctive aroma has been described as a “provocative compromise between Red Hots candy and dirty socks.” Onset of symptoms from A. smithiana can occur as early as 20 minutes after ingestion, with severe GI distress, nausea, and vomiting. Note that this is one of the exceptions to the general rule that seriously toxic mushrooms do not cause symptoms until at least six hours after they are consumed.

A. smithiana contains the heat-stable nephrotoxin allenic norleucine. Anuric or oliguric renal failure becomes apparent four to six days after ingestion, often requiring several weeks of hemodialysis. There is no antidote or other specific treatment, but patients generally recover without significant renal impairment.

A Case of Life-Threatening Cesium Chloride Poisoning Treated by Prussian Blue

Chan YC, et al

Clin Toxicol


A 65-year-old woman was admitted to the hospital complaining of diarrhea and multiple syncopal episodes. She had a history of rectal cancer but had not experienced syncope in the past. Initial workup revealed hypokalemia (2.8 mmol/L) and normal serum levels of calcium and magnesium. An electrocardiogram (Figure 1) showed a prolonged corrected QT interval of 0.549 sec (normal QTc < 0.450 sec).

Figure 1. Prolonged QTc caused by cesium toxicity. A QTc greater than 0.500 sec is a risk factor for torsades de pointes.

Figure 1. Prolonged QTc caused by cesium toxicity. A QTc greater than 0.500 sec is a risk factor for torsades de pointes.

Even after infusion of supplemental potassium, several runs of symptomatic polymorphic ventricular tachycardia (torsades de pointes) occurred (Figure 2). These were treated with intravenous magnesium. On further questioning, the patient stated that she had been self-treating her cancer with a naturopathic medicine, which was later confirmed to contain cesium chloride. Testing revealed that her serum cesium level was 288 micromol/L, approximately 27,000 times normal. She was treated with oral Prussian blue (3 gm TID), which decreased the serum cesium half-life by a factor of five. Her symptoms resolved, and after a two-week hospital stay she was discharged. Her QTc at that time was normal.

Figure 2. Polymorphic ventricular tachycardia (torsades de pointes) caused by cesium toxicity.

Figure 2. Polymorphic ventricular tachycardia (torsades de pointes) caused by cesium toxicity.

The use of cesium salts as an alternative or “natural” treatment for cancer is based on the unproven theory that somehow they raise the pH inside neoplastic cells, damaging them. Advocates of cesium believe that the low incidence of cancer seen in the Hunza tribe of North Pakistan can be attributed to a diet high in cesium. These claims have never been tested. Unfortunately, the adverse effects caused by cesium have been well demonstrated both clinically and in the laboratory, and are all too real.

Cesium (atomic number 55) is an alkali metal with an ionic charge of +1. It appears on the periodic table in the same column as sodium and potassium. When ingested, it is absorbed in the small intestine and distributed throughout the body as if it were potassium. Manifestations of cesium toxicity include diarrhea, hypo-kalemia, and cardiac arrhythmia. Cesium blocks potassium re-entry into the myocardial cell during phase 3 of the action potential, delaying repolarization and prolonging the QT interval. This predisposes to dysrhythmias such as torsades de pointes.

The fact that this patient had not experienced syncope in the past and her EKG findings suggest the diagnosis of acquired long-QT syndrome. Medications (prescribed or “natural”) are a frequent cause of this syndrome, making acquisition of a meticulous drug history crucial in managing these cases.

Treatment of cesium toxicity includes careful monitoring and correction of electrolyte abnormalities. Cesium undergoes enterohepatic circulation. Because it does not bind well to charcoal, the treatment of choice to enhance elimination is insoluble Prussian blue (Radiogardase). (I always remember this by thinking of the sequence: cesium → Caesar → militaristic → Prussian → Prussian blue.) Prussian blue binds monovalent cations, especially those with relatively large ionic radii such as cesium. Multidose Prussian blue will increase elimination of cesium through several mechanisms: binding unabsorbed cesium in the gut, interrupting the enterohepatic circulation, and creating “gut dialysis.” Radiogardase was approved by the FDA in 2003 for the treatment of radioactive cesium poisoning. This is the first published case that I'm aware of describing its use for nonradioactive cesium exposure.

Acetaminophen-Induced Hepatotoxicity Despite Early Individualized Treatment

Dolcourt BA, et al

Clin Toxicol


A 32-year-old woman was seen in the emergency department approximately six to nine hours after a massive acute acetaminophen (APAP) ingestion (1400 mg/kg). Serum APAP level upon presentation was 534 mcg/ml. She was given activated charcoal, and treated with the standard 21-hour protocol for intravenous N-acetylcysteine (NAC). IV NAC was continued for an additional three hours at a rate of 6.25 mg/kg/hr until the serum APAP level was less than 10 mcg/ml.

At that time (27 hours after presentation), the serum AST and ALT were 48 and 31 IU/L, respectively, but her liver enzymes continued to be measured and were seen to increase five hours after NAC was initially discontinued. NAC was restarted and continued until aminotransferase levels were clearly decreasing. Peak AST and ALT were 2289 and 948 IU/L, respectively, occurring at 48 hours after presentation. The patient did not develop any signs or symptoms of hepatic failure, and was discharged approximately 200 hours after the initial ingestion.

This is a fascinating case. In my Toxicology Rounds column in the September issue of Emergency Medicine News, I discussed the emerging concept of patient-tailored NAC treatment for acetaminophen toxicity. The idea, which is becoming accepted by increasing numbers of medical toxicologists and poison centers, is that we should move away from time-based protocols (for example, 72 hours or 21 hours of treatment), and instead administer NAC until the APAP level is essentially zero and liver enzymes are normal. At that point, with no APAP present and no evidence of hepatotoxicity, it would seem that further therapy is not needed.

This is the first report I'm aware of that suggests things may be more complicated. In this case, the 21-hour IV NAC protocol was used, and then continued appropriately until the APAP level was below 10 mcg/ml. At this point, many clinicians would have stopped treatment and not obtained follow-up labs. By happenstance, however, AST and ALT were re-checked five hours later, and found to be increasing. They eventually reached levels that meet the definition of hepatotoxicity. After a lapse of 12 hours, IV NAC was restarted and continued for an additional 56 hours.

It is difficult to think of a logical explanation for why onset of liver damage would occur after APAP had been essentially eliminated from the system, and was not available to form more of the hepatotoxic metabolite NAPQI. One has to wonder if some laboratory error occurred in the determination of serum APAP and AST/ALT levels. It is also possible that this late bump in liver enzymes occurs more frequently than we believe, but is usually not detected because testing stops when treatment is terminated.

In any case, despite the laboratory abnormalities, there is still no evidence that this phenomenon — even if real — has any clinical significance. This patient recovered, and never developed liver failure. The outcome might well have been the same even if NAC had not been restarted after the initial 24 hours of treatment. In any event, this case suggests that we still may not know all there is to know about the treatment of acetaminophen toxicity.

Kratom: A Case of a Legal High

Roche KM, et al

Clin Toxicol


A 32-year-old man was brought to the emergency department after he was observed having seizure-like activity. On arrival, his vitals signs were normal. Work-up included head CT and EEG, and both were unremarkable. White blood count, arterial blood gas, electrolytes, and cardiac enzymes were also within normal limits. Serum and urine toxicology screens were negative. His medications included Adalimumab, mesalamine, and fluoxetine. Friends revealed that he had recently purchased something over the Internet that was supposed to be “legal, and get you high.”

The patient was intubated, and treated with benzodiazepines. His hospital course was complicated by aspiration pneumonia. He was extubated 24 hours after presentation, and admitted to obtaining and ingesting “kratom” from an Internet web site.

Kratom is used to denote the leaf and derived products of the Mitragyna speciosa tree native to Malaysia and Thailand. The leaf contains a number of psychoactive alkaloids including mitragynine and 7-hydroxymitragynine. This plant has been used in Southeast Asia for its psychoactive properties for centuries. The leaves can be chewed, smoked, or made into a tea. Effects reported from the use of kratom vary. In Thailand the leaves are chewed by laborers as a stimulant and to increase work output, similar to the use of coca leaves in South America. Opiate-like effects from ingestion of kratom also have been described, and this has led to its use as a “natural” self-treatment to reduce symptoms of opiate withdrawal. Adverse effects from kratom include dry mouth, increased urination, and constipation. Significant respiratory depression has not been described. A previous case of seizure activity has been reported when kratom was ingested along with modafinil. Addiction to kratom has occurred.

Although several observational and historical articles on kratom have appeared in publications such as the Journal of Ethnopharmacology and the Journal of Psychoactive Drugs, there has been little real scientific research into its pharmacology. Recently, studies have determined that kratom acts as an agonist at the mu-opioid receptor and as an alpha-2 agonist (similar to clonidine). Either of these effects could explain why kratom seems to be successful at reducing symptoms of opiate withdrawal.

It is not clear why this patient had seizure-like activity. While seizure activity has not been reported following use of kratom alone, it has been seen when kratom was ingested with modafinil. It is certainly possible that kratom interacted with one or more of the drugs that this patient was taking in ways that have yet to be elucidated. Of course, because no identifying tests were done, it is also possible that the substance purchased over the Internet purported to be kratom was something else entirely.

Kratom is a controlled substance in Malaysia, Thailand, and a number of other countries. While it is legal in the United States as of October 2008, that status can be changed at any time by the FDA.

© 2008 Lippincott Williams & Wilkins, Inc.