A bad trip… to the ICU – A Resident Clinical Pearl  on poisonous mushroom ingestion

Scott Fenwick 

PGY-1 Family Medicine, Dalhousie University

Reviewed by: Liam Walsh, Clinical Pharmacist

Copyedited by: Dr. Mandy Peach

Case Presentation:

A 43yo otherwise healthy female presents to the ED with 30 hours of intractable nausea, vomiting, diarrhea, and diffuse crampy abdominal pain. 12 hours prior to the onset of these symptoms, she had foraged six wild mushrooms, fried them with butter, and ate them with her dinner. She had used a wild mushroom reference guide and thought these “pristine white” mushrooms would be a safe steak topping.

In the ED, she was alert and oriented with a GCS of 15 and no apparent encephalopathy. Her vitals were BP 109/68, P 93, T 37, RR 16, O2 97% RA. She was retching and vomiting clear emesis, which settled some with ondansetron 8mg IV. Clinically, she looked dehydrated but otherwise not toxic. Her abdomen was soft and diffusely tender. Cardiorespiratory exams were unremarkable. There were no skin findings.

A 1L bolus of normal saline was administered. Serum laboratory studies, drawn approximately 42 hours post-ingestion returned as follows:

Urinalysis showed trace blood, ketones and protein. ECG showed normal sinus rhythm.

The marked elevation in liver enzymes and abnormal coagulation studies were concerning for hepatocellular injury and fulminant hepatic failure. The local Internal Medicine consultant was contacted, and the patient was transferred to the ICU at the nearest liver transplant center.

In consultation with pharmacy and poison control, it was determined that the most likely offending mushroom was Amanita virosa, more commonly know as a Destroying Angel.

The patient was started on NAC, activated charcoal, penicillin G, cimetidine, vitamin C, and IV silibinin (milk thistle). Consideration was given to percutaneous cholecystostomy, as the toxin can accumulate in the gallbladder, but this was not anatomically feasible at the time.
Laboratory studies peaked at 72 hours post-ingestion as follows

Vitamin K was given to lower the INR. Creatinine continued to climb and was 835 prior to initiation of hemodialysis. Liver studies slowly trended downward with ALT 9774, AST 4586, and INR 1.7 at 96-hours post-ingestion. Ultimately, liver function values returned to normal and enzymes levels continued to trend downward—making liver transplant not necessary.

Overview of Toxic Mushroom Ingestion:

Epidemiology:

According to the 2019 Annual Report of the American Association of Poison Control Centers’ National Poison Data System, more than half of toxic mushroom ingestions occur in children under the age of 6. Serious toxicity and mortality, however, is more common in foraging adults, as they are more likely to consume larger quantities of a misidentified mushroom. Data for Atlantic Canada was difficult to obtain, but the Ontario Poison Centre received 72 calls related to mushroom exposures in September 2020, generally the peak month for exposures.

Poisoning Syndromes:

Only 20% of the time is the offending mushroom correctly identified, so we often rely on the clinical presentation to identify the likely species and relevant treatment. UpToDate lists 12 different mushroom toxins and 14 unique corresponding syndromes:

• Acute gastroenteritis (<6hrs) without liver failure
• Delayed gastroenteritis (6-12hrs) and delayed liver failure
• Acute gastroenteritis and delayed renal failure
• Hallucinogenic
• CNS depression and excitation
• Disulfiram-like reaction
• Cholinergic excess
• Delayed renal failure
• Delayed rhabdomyolysis
• Erythromelalgia
• Delayed encephalopathy
• Immune-mediate hemolytic anemia
• Shiitake dermatitis
• Allergic bronchioalveolitis

The syndrome from this case, bolded above, is delayed liver toxicity and delayed gastroenteritis.

This syndrome follows 3 phases:

• Phase I: Dysentery – nausea, vomiting, diarrhea (6-24hrs post-ingestion)
• Phase II: Apparent recovery (24-36hrs post-ingestion)
• Phase III: Fulminant hepatic and multisystem organ failure (48-96hrs post-ingestion)

Poisonous Mushrooms in New Brunswick:

The New Brunswick Museum has compiled a catalog of the mushroom species discovered in the province. One of the deadliest mushrooms in the province is the Destroying Angel. This nickname refers to a group of mushroom species under the genus Amanita. Amanita virosa is commonly found in New Brunswick and Nova Scotia. They are pristine white and often located in wooded areas or next to trees/shrubs in suburban areas. They are most prevalent in the summer and fall.

In their button stage, Destroying Angels can be confused with white mushrooms that you might buy at the grocery store. Destroying Angels produce an amatoxin—a selective inhibitor of RNA polymerase II, leading to an interruption in protein synthesis and cell death. Amatoxins are especially toxic to the GI tract, liver and kidneys.

Notably, in the NB Museum catalog, there are no reports of Amanita phalloides, aka the Death Cap, in New Brunswick. In Canada, they are more commonly found in British Columbia.

EM Approach:

History:

1. What did they look like? Ask for photos from the patient’s phone or samples if they have them. Identification assays are available but not always useful in the acute setting.
2. Were the mushrooms collected in a field or along/underneath trees? Many toxic mushrooms are in wooded areas.
3. How many types of mushrooms were ingested?
4. How long after ingestion did symptoms develop? Less than 6hrs is associated with lower risk of—but does not exclude—potentially lethal ingestion.
5. How much was eaten? Were there multiple times of ingestion?
6. Did others eat the mushrooms? If so, do they have similar symptoms?

Physical Exam:

• Assess hydration status
• Assess for encephalopathy or other signs of fulminant hepatic failure

Laboratory studies:

Treatment:

• Ondansetron for N/V, do not use anti-diarrheal agents
• IVF for dehydration and electrolyte abnormalities
• If a serious ingestion cannot be excluded, patients should be admitted for 24-48hrs for observation and serial bloodwork

Evidence-based recommendations for suspected amatoxin poisoning:
o Multiple dose activated charcoal: 0.5g/kg (max 50g) q4h for 4 days post-ingestion.

o Silibinin: loading dose of 5 mg/kg IV, followed by a continuous infusion at a dose of 20 mg/kg/day for 6 days or until clinical recovery.

If IV silibinin is not available, oral milk thistle capsules (Silymarin) are an effective alternative. The initial dose is 50-100mg/kg q8h, and titrated up to 200mg/kg q8h as tolerated, with a maximum single dose of 2-3g. IV Silibinin is available only through Health Canada’s Special Access Program. Pharmacy should be contacted early to assist with this process if it’s being considered.

o Penicillin G: 300,000 to 1,000,000 units/kg/day given as a continuous IV infusion. A small amount of research shows no benefit to adding this if IV silibinin is available. If penicillin allergy, consider ceftazidime 4.5 g every 2 hours.

o NAC protocol: initial loading dose of 150 mg/kg (max 10g), next a 4-hour infusion at 12.5 mg/kg/hr, then a 16-hour infusion at 6.25 mg/kg/hr. The 16-hour dose may be repeated if significant hepatic dysfunction persists.

o Cimetidine: 300 mg IV every 8 hours until clinical improvement (evidence in animal studies only)

o Vitamin C: 3 g IV daily until clinical improvement (evidence in animal studies only)

o Dextrose for hypoglycemia

o Lactulose for hyperammonemia

o Vitamin K +/- FFP for coagulopathy

o Dialysis for AKI

o Early consultation with liver transplant center

• Treatments for other mushroom poisoning syndromes can be found in this chart

Bottom Line:

Ask if the patient has photos of the mushrooms on their phone, or if they can describe their appearance. Call local poison control with this information.

Obtain a clear history to determine the interval between time of ingestion and time of symptom onset. Acute gastroenteritis onset (<6hrs from ingestion) is associated with favourable outcomes, and delayed gastroenteritis (usually 6-12hrs from ingestion) is more likely to have liver and/or renal failure.

Liver studies may be normal until 24-36 hours and generally peak at 72-96 hours post-ingestion.

Early treatment and consultation/transfer to a liver transplant center is imperative.

 

References:

Cover photo: https://www.deviantart.com/dreadillustrations/art/Poison-Mushrooms-774297817

Gummin, D. D., Mowry, J. B., Beuhler, M. C., Spyker, D. A., Brooks, D. E., Dibert, K. W., Rivers, L. J., Pham, N., & Ryan, M. L. (2020). 2019 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 37th Annual Report. Clinical toxicology (Philadelphia, Pa.), 58(12), 1360–1541. https://doi.org/10.1080/15563650.2020.1834219

Nelson, L. S., Howland, M. A., Lewin, N. A., Smith, S. W., Goldfrank, L. R., Hoffman, R. S., & Flomenbaum, N. E. (2019). Goldfrank’s toxicologic emergencies (11th ed.). Mc Graw Hill Education.

Shannon, M. (2007). Haddad and Winchester’s clinical management of poisoning and drug overdose (4th ed.). Saunders.

NB Museum Mushroom Checklist: http://website.nbm-mnb.ca/mycologywebpages/Checklists/NBMushrooms/NBMushroomChecklist.html

Tavassoli, M., Afshari, A., Arsene, A. L., Mégarbane, B., Dumanov, J., Bastos Paoliello, M. M., Tsatsakis, A., Carvalho, F., Hashemzaei, M., Karimi, G., & Rezaee, R. (2019). Toxicological profile of Amanita virosa – A narrative review. Toxicology Reports, 6, 143–150. https://doi.org/10.1016/J.TOXREP.2019.01.002

Amanita virosa photo: https://www.tehrantimes.com/news/423947/Mushroom-poisoning-kills-18-in-Iran

White mushroom photo: https://www.stockfood.com/images/00395464-Several-button-mushrooms

Amanita phalloides photo: http://www.bccdc.ca/about/news-stories/stories/2020/death-cap-mushrooms-make-fall-appearance-in-urban-areas