Amanita phalloides 19.Jan.2019-Expires: 7 days - Do not archive IDENTIFICATION The correct identification of the mushroom is imperative. If the identity is uncertain, or the patient’s signs and symptoms differ from those listed or are delayed in onset, seek clarification from a reliable source such as a mycologist or your local Poisons Information Center.   Further information on unidentified mushrooms can also be found by following the below link:   Unknown Mushroom Ingestion.   FAMILY NAME Amanitaceae   GENUS NAME Amanita   SPECIES NAME Amanita phalloides   IMAGE Click here for full-size image   To search for more images, please click on the following link that will take you to Google Images. The content of this site is not controlled by TOXINZ and care should be used when assessing this information.   Google Images   HABITAT Amanita phalloides occurs mainly in deciduous and mixed deciduous forests, especially under oak trees but also near hornbeam or beech. The fungus avoids colder localities.[1]   USES This mushroom is poisonous, however it may be mistaken for other edible mushrooms. INTERVENTION CRITERIA Intervention Level Child and Adult Medical assessment, observation, and, if appropriate, decontamination, is recommended for: - Any ingestion of a cyclopeptide mushroom - Exposures with intent to self-harm   Observation Period Observation at Home All patients require medical attention.   Medical Observation Any patient known to have ingested this type of mushroom must be admitted for monitoring and treatment, certainly those with symptoms or deranged biochemistry.   Investigations If it is suspected that the patient has ingested cyclopeptide mushrooms, every effort should be made to get the mushroom identified by a mycologist. When possible, a sample of the mushroom should be collected for identification. A whole mushroom, including the stalk and its base is preferable. The sample should be placed in a paper (not plastic) bag and then put in a sturdy container to protect the mushroom from damage. If the mushroom needs to be stored, it should be placed in the refrigerator, not the freezer.   Diagnostic Tests Wieland (Meixner) Test:[2]   Determines presence of amatoxin Methods - Perform indoors away from sunlight and excessive heat - Squeeze a small drop of fungus juice onto a piece of pulp paper i.e. newspaper, phone book page - Encircle wet stop with pencil to mark location - Dry the spot with warm air - Add a drop of concentrated hydrochloric acid to the dry spot The presence of amatoxins is indicated by the formation of a blue color   False positives - Use a control without amatoxins so false positives can be identified - A false positive reaction can occur at high temperatures or exposure to sunlight - Psilocybin, bufotenine, and certain terpines can give false positives[3][4]   This test is limited but can be helpful in the rapid testing in cases of suspected cyclopeptide poisoning.   Admission Criteria Any patient who has ingested cyclopeptide mushrooms must be admitted.   Furthermore, any patient who has ingested an unknown mushroom but has features or biochemical changes indicative of cyclopeptide poisoning must be admitted.   The admission hospital will require the following resources: Specific antidotes Advanced care/ICU Enhanced elimination   TREATMENT TREATMENT SUMMARY Any patient suspected of ingesting cyclopeptide-containing mushrooms should be admitted to hospital. Initial management consists of vigorous monitoring and replacement of expected fluid losses, which may be several liters per day.[5] Along with fluid replacement correction of metabolic disturbances such as acidosis, hypoglycemia, and electrolyte imbalances should be undertaken. The patient should be hemodynamically monitored and biochemical parameters followed closely.   Due to the low oral bioavailability of cyclopeptide mushrooms and the difficulty humans have in digesting large amounts of mushrooms, single dose activated charcoal may be given up to 12 hours following ingestion.[6][7] The use of multiple dose activated charcoal in the enhanced elimination of amatoxins is indicated up to 48 hours post-ingestion due to the extensive enterohepatic circulation of these toxins.[8] It is important that a good renal output is established during the first 48 hours following ingestion.   Supportive care is the mainstay of management. Although there is no clinically proven antidote for cyclopeptide mushroom poisoning, common therapies used have included silibinin, N-Acetylcysteine, benzylpenicillin, thioctic acid, and steroids. None of the antidotes used have undergone randomized, prospective clinical trials. Silibinin and N-Acetylcysteine appear to be the treatments of choice and should be considered in the management of these poisonings.[9][10][11][12] Efficacy has not been shown for the other therapies.[10] Benzylpenicillin, thioctic acid, and steroids are no longer recommended.[10]   Use of sedating drugs is not recommended due to their impact on the assessment of mental function/encephalopathy. Acute hepatic failure is a well-recognized concern and transplantation may be required.[13][14]   Advice should be sought from a specialist liver transplant unit if: The International Normalized Ratio (INR) is greater or equal to 2 at 24 hours or, 3 at any time or Creatinine is greater or equal to 200 umol/L (2.2 mg/dL) or pH is less than or equal to 7.3 or bicarbonate less than or equal to 18 mmol/L (18 mEq/L) or Blood pressure is low after volume loading (mean arterial pressure less than or equal to 60 mmHg) or The patient becomes encephalopathic   Early discussion of patients with a liver transplant unit is essential. Advice may be given and a decision to transport dependent upon results. In general it is considered desirable to transport patients prior to development of grade 2 encephalopathy.   Emergency Stabilization Ensure adequate cardiorespiratory function Correct hypovolemia Decontamination Ingestion Single dose activated charcoal Antidote(s) Silibinin Acetylcysteine Enhanced Elimination Maintain good renal output Multiple dose activated charcoal Supportive Care Monitoring Gastrointestinal Gastrointestinal irritation Cardiovascular Hypovolemia Hepatic Acute hepatic failure Renal Acute renal failure Metabolic Metabolic acidosis Hypoglycemia Fluid and electrolytes Electrolyte abnormalities Hematologic Coagulopathy Neurologic Seizure EMERGENCY STABILIZATION Ensure Adequate Cardiopulmonary Function Correct Hypovolemia Immediately establish secure intravenous access.   Profound hypotension may occur requiring volume replacement. CHILD Where the systolic blood pressure is below normal blood pressure ranges for the age group:[15]   Age (years) Normal Systolic Blood Pressure (mm Hg) < 1 70 to 90 1 to 2 80 to 95 2 to 5 80 to 100 5 to 12 90 to 110 > 12 100 to 120   Administer normal (0.9%) saline 10 mL/kg IV over 5 to 10 minutes   If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight normal saline over 5 to 10 minutes.   The intraosseous route can be used if IV access is difficult or delayed.   ADULT Administer a bolus of normal saline if systolic blood pressure is less than 100 mmHg.   Normal (0.9%) saline dose: 10 mL/kg IV over 5 to 10 minutes   If the systolic blood pressure does not return to the normal range, give a further 10 mL/kg body weight normal saline over 5 to 10 minutes.   The intraosseous route can be used if IV access is difficult or delayed.   If hypotension can not be reversed then follow standard protocols for the management of hypotension. Emergency Monitoring Seizure activity Blood pressure Heart rate ECG Fluid balance Serum electrolytes Renal function Liver function   DECONTAMINATION Ingestion Single Dose Activated Charcoal Administer activated charcoal up to 12 hours following a potentially toxic ingestion.   Single dose activated charcoal[16] CHILD 1 to 2 g/kg orally ADULT 50 to 100 g orally   ANTIDOTE(S) Silibinin Animal studies have shown that silibinin (Milk thistle) prevents the uptake of amatoxins by hepatocytes, reducing enterohepatic circulation and therefore enhancing renal elimination. Furthermore, silibinin stimulates DNA-dependent RNA polymerases, leading to an increase in RNA synthesis.[17] However, controlled human studies are still pending. Unfortunately, silibinin is not widely available.   Indications Silibinin is indicated in:[18] All patients presenting with cyclopeptide mushroom ingestion   Dose and Administration Silibinin dose:[19][20]   CHILD IV Initial dose 5 mg/kg IV over 1 hour Maintenance dose of 20 mg/kg as a continuous infusion   ADULT IV Initial dose 5 mg/kg IV over 1 hour Maintenance dose of 20 mg/kg as a continuous infusion   Treatment should be continued for up to 72 hours, or until significant declines in INR and liver function tests are apparent.   Precautions Documented hypersensitivity to silibinin. Pregnancy Recommended doses could be administered during pregnancy without being harmful to the fetus.[21]   Adverse Effects Silibinin appears to be well tolerated. However the following adverse effects have been reported following administration:[22][10] Gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain) Intermittent episodes of sweating Arthralgia Pruritus Headache Urticaria Weakness   Acetylcysteine Animal studies indicate that sublethal doses of amatoxins deplete hepatic glutathione content.[23] N-acetylcysteine is thought to serve as a glutathione precursor and consequently, the administration of N-acetylcysteine in cyclopeptide mushroom poisoning may prevent reduced glutathione levels and subsequent hepatocellular damage.[11][24] Additionally N-acetylcysteine has been shown to reduce morbidity and mortally in severe hepatic failure irrespective of origin.[25] It is therefore recommended in cyclopeptide mushroom poisoning.   Indications N-acetylcysteine should be administered in:[21] All patients presenting with cyclopeptide mushroom ingestion   Dose and Administration While acetylcysteine is recommended to be administered intravenously in 5% dextrose in water, 1/2 normal (0.45%) saline or normal saline (0.9%) may be substituted if necessary.[26] In children there is a risk of hyponatremia with 5% dextrose alone[27] and therefore 5% dextrose in normal (0.9%) saline should be used.   It is recommended that acetylcysteine dose for adults be calculated for actual body weight rounded up to the nearest 10 kg with a ceiling weight of 110 kg.[28]   CHILD   Children 20 kg or less body weight: 200 mg/kg in 7 mL/kg of 5% dextrose in normal saline over 4 hours Followed by 100 mg/kg in 14 mL/kg of 5% dextrose in normal saline over 16 hours   Children > 20 kg body weight: 200 mg/kg in 250 mL of 5% dextrose in normal saline over 4 hours Followed by 100 mg/kg in 500 mL of 5% dextrose in normal saline over 16 hours   Closely monitor fluid and electrolyte balance.   ADULT[29][30]   Administer: 200 mg/kg in 500 mL of 5% dextrose over 4 hours Followed by 100 mg/kg in 1,000 mL of 5% dextrose over 16 hours   Link to acetylcysteine dosing table for adults.   Precautions Pregnancy Acetylcysteine should be administered to pregnant patients following the standard adult regimen. Transplacental transport of acetylcysteine is not thought to be clinically significant,[31] however, delay in initiation of acetylcysteine treatment is associated with increased incidence of spontaneous abortion and fetal death.[32] Acetylcysteine is not considered teratogenic.[33]   Adverse Effects Anaphylactoid Reaction Six to 23% of patients receiving IV acetylcysteine develop an anaphylactoid reaction.[34][35] These do not represent an immunological (allergic) reaction; rather, they are thought due to a direct dose-dependent effect on histamine release and generally occur within the first two hours of an infusion.   History of previous anaphylactoid reaction to acetylcysteine does not contraindicate use. If there is concern of recurrence of the reaction the patient may be pre-treated 15 minutes before commencement of the infusion with an antihistamine.[36]   Effects range from mild flushing to urticaria, angioedema, or bronchospasm. Hypotension may occasionally occur. Asthmatics appear more at risk. However, effects are usually easily managed and there is no reason to withhold acetylcysteine from any patient when indicated.[36]   Management recommendations for acetylcysteine induced anaphylactoid reaction   Hyponatremia Hyponatremia has been reported in children if administered acetylcysteine in 5% dextrose following adult protocols for dilution of infused dose.[27]   SIGNS AND SYMPTOMS Cyclopeptide mushroom ingestion produces the Phalloides syndrome, which typically exhibits a quadriphasic course, and appears to be dose related.   Phase 1 and 3 are latent periods where the patient generally feels relatively well. Phase 2 begins approximately 12 hours after mushroom ingestion and consists predominantly of severe gastrointestinal symptoms, which leads to significant water and electrolyte loss. The final phase is hepatorenal, where severe hepatotoxicity may occur and hepatic and renal failure can ensue. In fatal cases, death may occur six to 16 days following ingestion.[37]   Routes of Exposure Cyclopeptide mushrooms are usually ingested in fresh condition. Poisoning typically occurs as a result of amateur mushroom gatherers mistaking the mushrooms for various edible varieties. The toxins remain stable when boiled, thus poisoning is possible whether the mushrooms are eaten raw or cooked.[38]   Onset/Duration of Symptoms Symptoms following the ingestion of amatoxin-containing mushrooms occur in four phases.   NOTE: Time frames may vary considerably to those listed below.   Latent asymptomatic phase (< 24 hours and usually up to 12 hours post-ingestion) No symptoms Gastrointestinal phase (6 to 24 hours post-ingestion) Abdominal pain Vomiting Severe diarrhea Hypovolemia Electrolyte disturbances Acid-base disturbance Period of well-being (24 to 48 hours post-ingestion) Hepatic and renal function deteriorates Hepatic phase (3 to 5 days post-ingestion) LFT increases Acute hepatic failure Acute renal failure   In fatal cases, death may occur 6 to 16 days following ingestion due to hepatic and/or renal failure.[37]   Severity of Poisoning Mild Cyclopeptide Toxicity Moderate Cyclopeptide Toxicity Severe Cyclopeptide Toxicity Nausea Vomiting Diarrhea Abdominal pain Electorlyte imbalances Hypoglycemia Right upper quadrant tenderness Hepatitis Renal dysfunction Metabolic acidosis Coagulopathy Fulminant hepatic failure Acute renal failure Hepatic encephalopathy Death   REFERENCES [1] Bresinsky A, Besl H. A colour atlas of poisonous fungi. London: Wolfe Publishing Ltd; 1990. p. 26-35. [2] Benjamin DR. Mushrooms: poisons and panaceas: a handbook for naturalists, mycologists, and physicians. New York: WH Freeman and Company; 1995. p. 191-2. [3] Beuhler M, Lee DC, Gerkin R. The Meixner test in the detection of alpha-amanitin and false-positive reactions caused by psilocin and 5-substituted tryptamines. Ann Emerg Med 2004 Aug; 44 (2): 114-20. [4] Beutler JA, Vergeer PP. Amatoxins in American mushrooms: Evaluation of the Meixner test. Mycologia 1980; 72 (6): 1142-9. [5] Pinson CW, Daya MR, Benner KG, Norton RL, Deveney KE, Ascher NL, Roberts JP, Lake JR, Kurkchubasche AG, Ragsdale JW. Liver transplantation for severe Amanita phalloides mushroom poisoning. Am J Surg 1990 May; 159 (5): 493-9. [6] Vesconi S, Langer M, Iapichino G, Costantino D, Busi C, Fiume L. Therapy of cytotoxic mushroom intoxication. Crit Care Med 1985 May; 13 (5): 402-6. [7] Bergoz R. Trehalose malabsorption causing intolerance to mushrooms. Report of a probable case. Gastroenterology 1971 May; 60 (5): 909-12. [8] Busi C, Fiume L, Costantino D, Langer M, Vesconi F. Amanita toxins in gastroduodenal fluid of patients poisoned by the mushroom, Amanita phalloides. [Letter] N Engl J Med 1979 Apr 5; 300 (14): 800. [9] Karlson-Stiber C, Persson H. Cytotoxic fungi--an overview. Toxicon 2003 Sep 15; 42 (4): 339-49. [10] Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 2002; 40 (6): 715-57. [11] Montanini S, Sinardi D, Pratico C, Sinardi AU, Trimarchi G. Use of acetylcysteine as the life-saving antidote in Amanita phalloides (death cap) poisoning. Case report on 11 patients. Arzneimittelforschung 1999 Dec; 49 (12): 1044-7. [12] Roberts DM, Hall MJ, Falkland MM, Strasser SI, Buckley NA. Amanita phalloides poisoning and treatment with silibinin in the Australian Capital Territory and New South Wales. Med J Aust 2013 Jan 21; 198 (1): 43-7. [13] Panaro F, Andorno E, Morelli N, Casaccia M, Bottino G, Ravazzoni F, Centanaro M, Ornis S, Valente U. Liver transplantation represents the optimal treatment for fulminant hepatic failure from Amanita phalloides poisoning. [Letter] Transpl Int 2006 Apr; 19 (4): 344-5. [14] Araz C, Karaaslan P, Esen A, Zeyneloglu P, Candan S, Torgay A, Haberal M. Successful treatment of a child with fulminant liver failure and coma due to Amanita phalloides poisoning using urgent liver transplantation. Transplant Proc 2006 Mar; 38 (2): 596-7. [15] Mackway-Jones K, Molyneux E, Phillips B, Wieteska S, editors. Advanced paediatric life support: the practical approach. 3rd ed. London: BMJ Books; 2001. [16] Fountain JS, Beasley DM. Activated charcoal supercedes ipecac as gastric decontaminant. N Z Med J 1998 Oct 23; 111 (1076): 402-4. [17] Hruby K, Csomos G, Fuhrmann M, Thaler H. Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 1983 Apr; 2 (2): 183-95. [18] Floersheim GL. Treatment of human amatoxin mushroom poisoning. Myths and advances in therapy. Med Toxicol 1987 Jan-Feb; 2 (1): 1-9. [19] Murray L, Little M, Pascu O, Hoggett K. Toxicology handbook. 3rd ed. Sydney, Australia: Elsevier; 2015. p. 51. [20] Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, editors. Goldfrank’s toxicologic emergencies. 10th ed. New York: McGraw-Hill; 2014. p. 1515-6. [21] Boyer JC, Hernandez F, Estorc J, De La Coussaye JE, Bali JP. Management of maternal Amanita phalloides poisoning during the first trimester of pregnancy: a case report and review of the literature. Clin Chem 2001 May; 47 (5): 971-4. [22] An adverse reaction to the herbal medication milk thistle (Silybum marianum). Adverse Drug Reactions Advisory Committee. Med J Aust 1999 Mar 1; 170 (5): 218-9. [23] Kawaji A, Sone T, Natsuki R, Isobe M, Takabatake E, Yamaura Y. In vitro toxicity test of poisonous mushroom extracts with isolated rat hepatocytes. J Toxicol Sci 1990 Aug; 15 (3): 145-56. [24] Chyka PA, Butler AY, Holliman BJ, Herman MI. Utility of acetylcysteine in treating poisonings and adverse drug reactions. Drug Saf 2000 Feb; 22 (2): 123-48. [25] Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991 Jun 27; 324 (26): 1852-7. [26] Cumberland-Pharmaceuticals. Acetadote (Acetylcsyteine) Injection - Package Insert. Nashville TN: Cumberland Pharmaceuticals Inc, 2011: [Cited 27 Jan 2012]. URL: http://www.acetadote.net [27] Sung L, Simons JA, Dayneka NL. Dilution of intravenous N-acetylcysteine as a cause of hyponatremia. Pediatrics 1997 Sep; 100 (3 Pt 1): 389-91. [28] Chiew AL, Fountain JS, Graudins A, Isbister GK, Reith D, Buckley NA. Summary statement: new guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust 2015 Sep 7; 203 (5): 215-8. [29] McNulty R, Lim JME, Chandru P, Gunja N. Fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose. Clin Toxicol (Phila) 2018 Jul; 56 (7): 618-621. [30] Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol (Phila) 2016; 54 (2): 115-9. [31] Selden BS, Curry SC, Clark RF, Johnson BC, Meinhart R, Pizziconi VB. Transplacental transport of N-acetylcysteine in an ovine model. Ann Emerg Med 1991 Oct; 20 (10): 1069-72. [32] Riggs BS, Bronstein AC, Kulig K, Archer PG, Rumack BH. Acute acetaminophen overdose during pregnancy. Obstet Gynecol 1989 Aug; 74 (2): 247-53. [33] Janes J, Routledge PA. Recent developments in the management of paracetamol (acetaminophen) poisoning. Drug Saf 1992 May-Jun; 7 (3): 170-7. [34] Mant TG, Tempowski JH, Volans GN, Talbot JC. Adverse reactions to acetylcysteine and effects of overdose. Br Med J (Clin Res Ed) 1984 Jul 28; 289 (6439): 217-9. [35] Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med 1998 Jun; 31 (6): 710-5. [36] Schmidt LE, Dalhoff K. Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning. Br J Clin Pharmacol 2001 Jan; 51 (1): 87-91. [37] Fineschi V, Di Paolo M, Centini F. Histological criteria for diagnosis of amanita phalloides poisoning. J Forensic Sci 1996 May; 41 (3): 429-32. [38] Yocum RR. New laboratory scale purification of beta-amanitin from American Amanita phalloides. Biochemistry 1978 Sep 5; 17 (18): 3786-9. Do Not Archive. This document is current on day of issue, NZ: 19.Jan.2019

Disclaimer

All information contained on this database is as accurate and up-to-date as our resources allow. Since the University of Otago, the New Zealand National Poisons Centre and Intergen cannot anticipate or control the conditions under which this information may be used, each user should view the information in the specific context of the intended application.

The University of Otago, the New Zealand National Poisons Centre and Intergen will not be responsible for damages of any nature resulting from use or reliance upon this information.

© National Poisons Centre, New Zealand. Portions © Intergen.

If you would like further information about TOXINZ, or wish to make comment, please contact us on +64 3 479 7248 or email us at TOXINZ@otago.ac.nz.