01Approach to the Critical Patient/attcp55

Immediate stabilization

›Airway and breathing threats

›Bronchorrhea with airway compromise

›Copious secretions obstructing upper airway

›Suction immediately

›If severe bronchorrhea or bronchospasm, proceed to rapid sequence intubation

›Bronchospasm

›Audible wheeze with decreased air entry

›SpO2 falling despite supplemental oxygen

›Respiratory failure triggers

›SpO2 < 90% on high-flow oxygen

›Rising PaCO2 with fatigue

›Circulation threats

›Severe bradycardia

›HR < 40 beats per minute

›Hemodynamic compromise with bradycardia

›Hypotension

›SBP < 90 mmHg

›MAP < 65 mmHg

›Volume depletion from secretory losses

›Profuse diaphoresis

›Vomiting and diarrhea fluid losses

›Antidote priority

›Atropine is the specific antidote — initiate early in any symptomatic patient

›Titrate to secretion drying and oxygenation improvement

›Do NOT titrate to heart rate alone

›No maximum total dose of atropine in this setting

02History/hx73

Ingestion details

›Mushroom source and type

›Wild-foraged vs store-bought

›Wild foraging is the primary risk factor

›Inocybe spp. and Clitocybe spp. are the primary muscarine-containing species

›Any remaining specimens or photographs available

›Single most important diagnostic information

›Mycologist identification should be sought

›Preparation method

›Raw vs cooked — cooking does not reliably destroy muscarine

›Quantity consumed

›Timing and onset

›Time from ingestion to symptom onset

›Muscarinic syndrome: 15 minutes to 2 hours, rarely up to 5 hours

›Onset beyond 6 hours raises concern for amatoxin or orellanine poisoning

›Symptom progression pattern

›Rapid onset cholinergic symptoms typical

›Delayed onset of GI symptoms is a red flag for more dangerous syndrome

Symptom characterization

›Classic SLUDGE symptoms

›Salivation — profuse

›Drooling

›Throat secretions

›Lacrimation

›Urination — urgency or incontinence

›Defecation — diarrhea

›GI distress — cramping, nausea

›Emesis

03Physical Exam/exam63

Vitals and general

›Vital sign pattern

›Heart rate

›Bradycardia — classic finding

›Paradoxical tachycardia may occur

›Blood pressure

›Hypotension in moderate to severe poisoning

›SBP < 90 mmHg indicates significant cardiovascular compromise

›Respiratory rate

›Elevated with bronchospasm or bronchorrhea

›Falling rate with fatigue is an intubation trigger

›Temperature — typically normal

›General appearance

›Diaphoresis — profuse, warm and wet skin

›Contrast with anticholinergic toxidrome: dry as a bone

›Level of distress

›Secretion burden

›Work of breathing

Eyes and oropharynx

›Ocular findings

›Miosis — bilateral pinpoint or small pupils

›Confirms muscarinic receptor activation

›Contrast with anticholinergic toxidrome: mydriasis

›Lacrimation — visible tearing

›Oral and upper airway

›Profuse sialorrhea — pooling secretions

›Gurgling voice

›Aspiration risk

04Differential Diagnosis/ddx46

Cholinergic toxidromes

›Organophosphate or carbamate poisoning

›ICD-10 T60.0 toxic effects of organophosphate pesticides

›Identical peripheral cholinergic toxidrome

›Distinguish by pesticide exposure history

›Nicotinic features present — fasciculations, muscle weakness, paralysis

›Absent in muscarinic mushroom poisoning

›Pralidoxime (2-PAM) indicated in organophosphate poisoning

›NOT indicated in muscarinic mushroom poisoning

›Depressed acetylcholinesterase levels on serum testing

›Normal in muscarinic mushroom poisoning

›Cholinergic medication overdose

›Bethanechol, pilocarpine, donepezil, rivastigmine

›Similar SLUDGE syndrome

›Medication history distinguishes from mushroom exposure

Other mushroom poisoning syndromes

›Amatoxin poisoning — cannot-miss diagnosis

›ICD-10 T62.0X toxic effects of ingested mushrooms

›Amanita phalloides — death cap mushroom

›Onset 6 to 24 hours after ingestion

›Fulminant hepatorenal failure develops in 3 to 7 days

›High mortality without liver transplant

›Early GI symptoms may overlap with muscarinic syndrome

›Delayed onset and absence of autonomic features help differentiate

›Ibotenic acid and muscimol poisoning

›Amanita muscaria — fly agaric

›Predominantly CNS effects — agitation, sedation, hallucinations

›Minimal peripheral cholinergic signs

05Laboratory Tests/lt49

Core metabolic labs

›Basic metabolic panel

›Electrolytes

›Hypokalemia from GI losses common

›Sodium and chloride derangements from secretory losses

›Renal function

›Baseline creatinine and BUN

›Relevant if co-ingestion of nephrotoxic species suspected

›Glucose

›Hypoglycemia in severe illness

›Hepatic function panel

›AST and ALT — critical baseline

›Hepatotoxicity NOT expected from pure muscarine

›Rising transaminases at 12 to 24 hours suggest amatoxin co-ingestion

›Trend serially if species identification uncertain

›Total bilirubin

›Elevation suggests hepatocellular injury from co-ingestion

›PT and INR

›Prolongation indicates hepatic synthetic dysfunction

›If elevated, amatoxin poisoning must be assumed

Hematology and inflammation

›Complete blood count

›Baseline hemoglobin and platelet count

›Leukocytosis in stress response

›Hemoconcentration from dehydration

›Coagulation studies

›PT, INR, aPTT

›If hepatotoxicity concern

06Diagnostic Tests/dt62

Scoring Systems

›Mushroom poisoning classification systems

›White et al. 2019 clinical classification

›Group 2B — autonomic toxicity syndrome

›Muscarinic mushroom poisoning falls in early-onset peripheral cholinergic category

›Distinguishes from Group 4 (amatoxin — hepatotoxic) and Group 6 (orellanine — nephrotoxic)

›Toxidrome severity grading

›Mild — GI symptoms only, no hemodynamic instability

›Moderate — cholinergic secretory syndrome with stable vitals

›Severe — bronchospasm, bronchorrhea, hemodynamic compromise, or airway threat

›Clinical decision framework

›Onset timing as primary risk stratifier

›< 6 hours onset — likely early-onset syndrome including muscarinic

›> 6 hours onset — high suspicion for amatoxin or orellanine requiring admission for monitoring

›No validated emergency-medicine scoring tool specific to muscarinic mushroom poisoning

MRI

›MRI role in mushroom poisoning

›Not routinely indicated

›Standard muscarinic mushroom poisoning does not require MRI

›Availability and time constraints limit acute use

›Brain MRI indications

›Altered mental status disproportionate to expected toxidrome

›Concern for ibotenic acid or muscimol CNS effect from Amanita muscaria co-ingestion

›New focal neurological deficit requiring structural exclusion

›Abdominal MRI

›Not indicated acutely

›Hepatic evaluation in delayed amatoxin poisoning context could use MRI if CT unavailable

07Disposition/dispo39

Admission indications

›Criteria requiring hospital admission

›Hemodynamic instability requiring atropine

›Bradycardia requiring IV atropine

›Hypotension requiring IV fluids or vasopressors

›Respiratory compromise

›Bronchospasm or bronchorrhea

›Any oxygen requirement

›Uncertain mushroom species identification

›Must observe for delayed hepatotoxicity with serial LFTs at 12 to 24 hours

›Amatoxin co-ingestion cannot be excluded without confident identification

›Atropine infusion requirement

›Continuous IV atropine administration

›Extremes of age

›Pediatric patients

›Elderly patients with higher decompensation risk

›ICU indications

›Intubation or imminent intubation

›Severe bronchorrhea or bronchospasm

›Respiratory failure

›Vasopressor requirement

›Continuous atropine infusion with dose escalation

›High-degree AV block requiring pacing

Discharge criteria

›Discharge may be considered when all of the following met

›Symptoms completely resolved

›Typically 6 to 12 hours observation

›Full resolution of SLUDGE symptoms

08Treatment/t66

Antidote — atropine

›Atropine sulfate — specific antidote for muscarinic mushroom poisoning

›Adult dosing

›Initial dose: 1 to 6 mg IV or IM depending on severity

›Mild: 1 to 2 mg IV

›Moderate: 2 to 4 mg IV

›Severe: 4 to 6 mg IV

›Repeat every 3 to 5 minutes

›Double the dose with each repeat until response

›Titrate to drying of secretions and improved oxygenation

›No maximum total dose

›Pediatric dosing

›0.02 to 0.06 mg/kg IV, IM, or IO

›Repeat every 5 minutes

›Double dose with each repeat as needed

›Maintenance infusion

›10 to 20% of total loading dose per hour as continuous IV infusion

›Titrate to secretion control

›Taper once clinical stabilization achieved

›Titration endpoint

›Drying of secretions — primary endpoint

›Improved oxygenation — primary endpoint

›NOT heart rate alone — tachycardia is expected and acceptable

›FDA-approved for muscarinic mushroom poisoning

Airway and decontamination

›Airway management

›Suction oropharyngeal secretions aggressively

›Prevent aspiration of secretions

09Special Populations/sp50

Pregnancy

›Pregnancy considerations

›Atropine use in pregnancy

›Atropine crosses the placenta — fetal tachycardia may occur

›Maternal benefit outweighs fetal risk in severe poisoning

›Fetal heart rate monitoring in viable gestation

›GI symptoms overlap with hyperemesis gravidarum

›Mushroom ingestion history must be specifically sought

›Cholinergic exam findings distinguish from hyperemesis

›Dehydration risk

›Aggressive IV fluid replacement important for placental perfusion

›Maternal SpO2 target >= 95% for fetal oxygenation

›Activated charcoal

›Generally considered safe in pregnancy if airway protected

›Imaging

›CT with fetal dose consideration — only when clinically necessary

›Chest radiograph with abdominal shielding when indicated

Geriatric

›Older adult considerations

›Hemodynamic vulnerability

›Bradycardia and hypotension less well tolerated

›Pre-existing coronary disease — atropine titration 0.03 to 0.04 mg/kg total may be more cautious

›Higher risk of cardiovascular collapse

›Dehydration risk

›Decreased physiologic reserve

›Volume depletion from secretory losses more severe

›Aggressive but careful fluid resuscitation with cardiac status monitoring

›Atropine side effects

10Background/b76

Epidemiology

›Incidence and burden

›Inocybe spp. are the most common cause of muscarinic mushroom poisoning worldwide

›Hundreds of species in the genus Inocybe

›Ubiquitous in temperate and tropical regions

›Clitocybe spp. — second most common muscarine-containing genus

›Clitocybe nebularis and related species

›Seasonal peak

›Late summer through autumn in temperate regions

›Year-round in tropical regions

›Geographic distribution

›North America, Europe, Asia, Africa — worldwide distribution

›Tropical China exposures documented (Deng et al. 2022, Frontiers in Microbiology)

›Mortality and morbidity

›Prognosis excellent with appropriate treatment

›Full recovery typically within 6 to 24 hours

›Deaths rare but can occur from severe bronchospasm or circulatory collapse

›Higher mortality risk in elderly and delayed treatment cases

›Cluster poisonings common

›Multiple family members or group affected from shared meal

Pathophysiology

›Toxin mechanism

›Muscarine — quaternary ammonium compound

›Directly activates muscarinic acetylcholine receptors (M1, M2, M3)

›Does not cross the blood-brain barrier significantly

›Therefore produces peripheral cholinergic toxidrome without CNS effects

›Does NOT inhibit acetylcholinesterase

›Distinguishes from organophosphates and carbamates

›Explains why pralidoxime is ineffective

›Muscarine precursor release

›Muscarine may be released from phosphorylated precursor upon cellular injury (Dorner et al. 2024)

›Cooking does not reliably destroy muscarine

›Organ effects

›Cardiac — M2 receptor activation

›Negative chronotropy — bradycardia

›Negative dromotropy — AV conduction slowing

›Hypotension from vasodilation and reduced cardiac output

›Pulmonary — M3 receptor activation

›Bronchospasm — smooth muscle contraction

›Bronchorrhea — mucous secretion

›Exocrine glands — M3 receptor activation

›Salivation, lacrimation, sweating

›GI tract — M3 receptor activation

›Increased motility — diarrhea, cramping

›Nausea and vomiting

›Eyes — M3 receptor activation

›Miosis — ciliary muscle spasm

›Blurred vision

›Classification in mushroom poisoning syndromes

›White et al. 2019 classification — Group 2B autonomic toxicity

›Early-onset peripheral cholinergic syndrome

›Distinguishes from late-onset hepatotoxic (Group 4) and nephrotoxic (Group 6) syndromes

Therapeutic Considerations

›Atropine pharmacology

›Competitive antagonist at muscarinic receptors

›Blocks M1, M2, M3 receptor activation by muscarine

›Reverses secretory, bronchospasm, cardiac, and GI effects

›Dose titration principle

›Titrate to secretion control — not to heart rate

›Tachycardia is expected and acceptable collateral effect

›Large doses may be required — no ceiling dose

›Maintenance infusion rationale

›Mushroom-derived muscarine has sustained duration of action

›Single bolus doses insufficient for prolonged toxin effect

›10 to 20% of loading dose per hour maintains clinical effect

›Decontamination evidence

›Activated charcoal evidence limited to theoretical benefit

›Most useful if administered within 1 hour of ingestion

›Risk-benefit assessment required — airway protection first

›Why pralidoxime is not indicated

›Muscarine does not form covalent bond with acetylcholinesterase

›Pralidoxime (oxime reactivator) has no target in muscarinic mushroom poisoning

›In organophosphate poisoning, cholinesterase is inhibited — pralidoxime reactivates it

›Confusion between the two syndromes may lead to inappropriate pralidoxime use

›Monitoring for co-ingestion

›Serial LFT monitoring at 12 and 24 hours

›Detects evolving amatoxin hepatotoxicity early

›Treatment window for amatoxin antidotes (silibinin) is narrow

›Monitoring is mandatory if species not definitively identified

11Patient Discharge Instructions/pdi27

copy discharge instructions

›Mushroom poisoning — home care instructions

›You were treated for mushroom poisoning from a mushroom that contains a chemical called muscarine

›This type of poisoning causes excessive saliva, tears, sweating, diarrhea, and stomach cramps

›Your symptoms should fully resolve within 6 to 24 hours

›Drink clear fluids regularly over the next 24 hours to replace lost fluids

›Eat bland foods as your stomach settles — soup, crackers, rice

›Rest for the remainder of the day

›Medications

›Take any prescribed medications as directed

›Do not take any new medications without checking with your doctor or pharmacist first

›Foraging safety

›Do NOT eat wild-foraged mushrooms unless an expert mycologist has confirmed the species is safe

›Many toxic mushrooms closely resemble edible varieties

›If you have any remaining mushrooms from the same batch — do not eat them

›Bring any remaining mushroom specimens to the emergency department or Poison Control Center if requested

›Return to the emergency department immediately if you develop

›Difficulty breathing, wheezing, or chest tightness

›Return of profuse sweating, drooling, or tearing

›Severe stomach cramps or vomiting that prevents fluid intake

›Fainting or near-fainting

›Yellowing of the skin or eyes (jaundice) — this could mean a different type of mushroom toxin affecting the liver

›Dark urine or decreased urination

›Confusion or unusual drowsiness

›Follow-up

›See your family doctor within 2 to 3 days

›If your mushroom species was not fully identified, you may need a repeat blood test to check your liver function

›Report the poisoning to your local Poison Control Center if you have not already done so — this helps track poisoning trends in your area

12References/r27

Guidelines and key sources

›Key clinical references

›Lurie Y et al. Mushroom Poisoning From Species of Genus Inocybe: A Case Series With Exact Species Identification. Clinical Toxicology. 2009. PMID 19566380

›Primary case series for Inocybe muscarinic poisoning

›Onset timing and atropine dosing data

›White J, Weinstein SA, De Haro L et al. Mushroom Poisoning: A Proposed New Clinical Classification. Toxicon. 2019. PMID 30439442

›Group 2B autonomic toxicity classification

›Framework for distinguishing early vs delayed onset syndromes

›Dorner S, Trottmann F, Jordan PM et al. The Fatal Mushroom Neurotoxin Muscarine Is Released From a Harmless Phosphorylated Precursor Upon Cellular Injury. Angewandte Chemie. 2024. PMID 39432715

›Muscarine precursor mechanism

›Xu F et al. Mushroom Poisoning From Inocybe Serotina: A Case Report With Exact Species Identification and Muscarine Detection. Toxicon. 2020. PMID 32345453

›Species-confirmed case and UPLC-MS/MS muscarine detection

›Deng LS et al. A New Muscarine-Containing Inocybaceae Species Discovered From a Poisoning Incident in Tropical China. Frontiers in Microbiology. 2022. PMID 35859745

›Tropical region muscarinic poisoning documentation

›Henretig FM, Kirk MA, McKay CA. Hazardous Chemical Emergencies and Poisonings. New England Journal of Medicine. 2019

›Organophosphate vs muscarinic mushroom distinction

›Atropine and pralidoxime pharmacology

›Pharmacological references

›FDA Drug Label — Atropine Sulfate Injection. DailyMed. Updated 2024

›Approved indication includes muscarinic mushroom poisoning

›Dosing ranges for adults and pediatrics

›Moss MJ, Hendrickson RG. Toxicity of Muscimol and Ibotenic Acid Containing Mushrooms. Clinical Toxicology. 2019. PMID 30073844

›Regional Poison Control Center 14-year case series

›Ibotenic acid and muscimol differentiation from muscarine toxidrome

›ICD-10 coding

›ICD-10 T62.0X1A toxic effect of ingested mushrooms, accidental, initial encounter

›ICD-10 T62.0X2A toxic effect of ingested mushrooms, intentional self-harm, initial encounter

›ICD-10 T62.0X3A toxic effect of ingested mushrooms, assault, initial encounter

Evidence & Review

Evidence & Review