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Toxic Alcohols

• Overview
  • Toxic metabolites produced by alcohol dehydrogenase which can be inhibited by ethanol or fomepizole
  • Fomepizole: 15mg/kg loading dose, 10mg/kg q12h x4 doses then 15mg/kg q12h (stimulates own metabolism); if dialysis, q4h
• Diagnosis: osmolar gap (>14), 2Na + Glu/18 + BUN/2.8 + EtOH/4.6
• Treatment
  • ADH inhibition
  • HCO₃
  • Hemodialysis
  • Supportive care
  • Hypoglycemia: dextrose

Methanol

• Component of antifreeze, windshield washer fluid
• Metabolite formic acid which causes acidosis and blindness
• Can give folate

Ethylene glycol

• Component of antifreeze, automobile coolants, de-icing agents
• Metabolite oxalic acid which precipitates calcium oxalate crystals and causes acute renal failure
• Can give thiamine (100mg q6h), pyridoxine (500mg q6h), Mg

Isopropanol

• Component of rubbing alcohol
• Metabolite acetone which does not cause acidosis

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Analgesics

Acetaminophen

• Metabolism: glucoronidation, CYP450
  • CYP450 pathway produces toxic metabolite when glucoronidation overwhelmed
  • In pediatrics, sulfation process protective
• Toxic dose: >150mg/kg, >3g/day
• Injury: liver (centrilobular necrosis), renal, pancreatic
• Increased risk: induced CYP450 (chronic EtOH, rifampin, anti-epileptics)
• Nomogram: applicable to single ingestion at 4-hours
• Labs: PT/INR, LFT, lipase, chemistry
• Management: NAC
  • PO: 140mg/kg, 70mg/kg q4h
  • IV: 150mg/kg, 50mg/kg over 4h, 100mg/kg over 16h

NSAID

• Symptoms
  • Acute: GI upset, low risk UGIB
  • Acute massive: acidosis, coma, seizures
  • Chronic: UGIB, nephropathy, agranulocytosis

Aspirin

• Signs: tachycardia, hyperthermia, tachypnea/hyperpnea
• Severe: cerebral and pulmonary edema, CNS hypoglycemia
• Labs: primary respiratory alkalosis with metabolic acidosis
• Management
  • Hypoglycemia (CNS) treatment
  • Bicarbonate infusion (urine pH > 8)
  • Hemodialysis for pulmonary edema, cerebral edema, renal failure, acidemia, level >100mg/dL (acute) or > 60mg/dL (chronic)

Opioids

• Symptoms: respiratory depression, miosis
• Management: naloxone 0.04mg, 0.4mg, 2mg
• Withdrawal: nausea/vomiting, diarrhea, abdominal pain, piloerection
  • Neonates: seizure, death
• Complications with specific agents:
  • Meperidine, tramadol: seizures
  • Methadone: QT prolongation

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Anesthetics

Lidocaine

• Mechanism: Na-channel blockade
• Types:
  • Ester (one “i”): cocaine, procaine, benzocaine
  • Amide (two “i”): lidocaine, bupivacaine
• Toxicity
  • Dose: 4mg/kg, 7mg/kg with epinephrine
  • CNS: perioral numbness, slurred speech, seizure
  • CV: VT, VF, AV block
  • Methemoglobinemia: methylene blue
• Treatment
  • Seizure management
  • Bicarbonate for dysrhythmia
  • Intralipid

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Anti-emetics

Phenothiazines

• Examples: compazine (prochlorperazine), phenergan (promethazine)
• MOA: DA-antagonist
• AE: sedation, dystonia, parkinsonism
• Toxicity: seizure, VT, hypotension (TCA-like)

5-HT3 antagonists

• Examples: zofran (ondansetron), granisetron
• Toxicity: QT-prolongation

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Anti-hypertensives

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Environmental

Carbon monoxide

• Source: combustion (gas heater, indoor barbeque)
• Toxicity
  • General: influenza-like, multiple proximate affected individuals
  • GI: abdominal pain, nausea
  • CNS: headache, dizziness, confusion, ataxia, seizure
  • CV: palpitations, arrhythmia, hypotension, MI
• Treatment
  • T½: RA 6h, NRB 1h, 3atm 0.5h
  • Hyperbaric: neuro deficit, syncope, pregnancy, CV toxicity

Cyanide

• Mechanism: inhibits oxidative phosphorylation
• Source: structural fire (wool, silk)
• Symptoms: syncope, seizure, coma, cardiovascular collapse
• Detection: severe lactic acidosis, “arterialization” of venous blood, “bitter almond” odor
• Treatment
  • Hydroxycobalamin (Cyanokit): 5g IV, may repeat x1
  • Sodium thiosulfate 12.5g IV

Methemoglobinemia

• Mechanism: Fe²⁺ converted to Fe³⁺, “functional anemia”
• Source: nitrite (food), topical/local anesthetics, pyridium, dapsone, reglan
• Detection: normal PaO2, SpO2 85% unresponsive to supplemental oxygen, ABG with co-oximetry
• Management: methylene blue 1-2mg/kg IV if symptomatic or MetHb >25%
  • Contraindicated in G6PD deficiency, treat with exchange transfusion or HBO

Hydrogen Sulfide

• Source: industrial, sulfur spring, sewer
• Detection: “rotten egg” odor
• Management: remove from source, supportive care

Hydrocarbon

• Source: huffing canisters
• Toxicity: VT/VF from myocardial sensitization
• Management: beta-blockade
• Complications: harmless if ingested, aspiration leads to ARDS

Hydrofluoric acid

• Source: rust remover, wheel cleaner, glass etching
• Symptoms: pain-out-of-proportion, delayed onset
• Toxicity: Hypocalcemia (QTc prolongation, VT/VF/TdP), hyperkalemia, hypomagnesemia
• Management: analgesia, topical calcium gluconate gel, intravenous calcium for large BSA involvement

Alkaline ingestion

• Symptoms: esophageal perforation, delayed stricture

Acid ingestion

• Symptoms: gastric perforation (rare), delayed gastric outlet obstruction
• Findings: metabolic acidosis

Botulism

• Sources
  • Adult: ingested preformed toxin
  • Infants: ingested spores (achlorhydric), in vivo toxin production
  • Wound: black tar heroin
• Symptoms: dysphagia, ptosis, diplopia, respiratory failure, descending paralysis
  • Infants: constipation, floppy
• Management: supportive care, intubation
  • Adults: Anti-toxin from CDC or local Department of Health
  • Infants: 100mg/kg IV x 1 dose (BabyBIG)

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Heavy Metals

Iron

• Dose
  • Ferrous sulfate: 20% elemental iron
  • Toxic: >20mg/kg
  • Lethal: >60mg/kg (1 tablet 325mg ferrous sulfate per kilogram)
• Toxicity: corrosive, anti-coagulant, hepatotoxic
• Course
  • Stage I: GI effects, emesis with hematemesis
  • Stage II: Quiescent
  • Stage III: Systemic, multi-organ system dysfunction
  • Stage IV: Resolution, gastric scarring and outlet obstruction
• Workup
  • CBC/BMP
  • LFT
  • Lactate
  • Fe level
  • KUB (if positive consider WBI)
• Treatment
  • Decontamination: no activated charcoal, consider WBI
  • Deferoxamine: 15mg/kg/hr

Lead

• Source: paint, batteries
• Toxicity
  • Acute: headache, encephalopathy, seizure
  • Chronic: malaise, weight loss, arthralgia, anemia (basophilic stippling)
• Diagnosis: lead level, wrist drop
• Management: chelation (BAL, EDTA, DMSA) for level >50ug/dL or asymptomatic >70ug/dL

Lithium

• Source: iatrogenic, drug-drug interaction
• Symptoms
  • GI: nausea/vomiting, diarrhea
  • CNS: tremor, coma
  • CV: TWI, QT-prolongation
• Management
  • IVF, encourage renal elimination
  • Hemodialysis

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Other Drugs

Disulfuram

• MOA: aldehyde dehydrogenase inhibitor
• Symptoms: increased acetaldehyde leads to flushing, headache, nausea/vomiting, tachycardia, hypotension
• Management: antihistamine, IVF, vasopressors
• Other agents causing disulfuram-like reaction: metronidazole, INH, sulfonylurea

Isoniazid

• Toxicity: seizure
• Management: pyridoxine 5g IV, repeat x1

Theophyline

• Toxicity: seizure
• Management
  • Decontamination: AC
  • Seizures: benzodiazepines
  • Tachyarrhythmia (commonly MAT): beta-blockade
  • Hemodialysis: acute > 100mg/L, chronic >30mg/L

Monoamine oxidase inhibitors

• Toxicity: food/drug interaction
• Symptoms: tachycardia, hypertension, hyperthermia, agitation
• Management: cooling, IVF, management of hyper/hypotension

Phenytoin

• Oral: cerebellar dysfunction (ataxia), CNS depression
• IV: hypotension (suspension contains propylene glycol)

Nutritional Supplements

• Fat-soluble vitamins
  • A: benign intracranial hypertension
  • D: hypercalcemia

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Envenomations

Snake

• Crotalid (rattle), elapidae (coral)
• Symptoms
  • Local reaction: edema, hemorrhagic bullae
  • Systemic: perioral numbness, fasciculations
  • Severe: thrombocytopenia, decreased fibrinogen
• Management: Crofab 5 vials

Spider

• Black widow
  • Identification: hourglass on abdomen
  • Symptoms: painful bite, target-appearance, rarely “acute abdomen”
  • Management: analgesia, anti-venom, tetanus
• Brown recluse
  • Identification: violin shape on head
  • Geography: Southeast, Midwest
  • Symptoms: painless bite, local reaction, delayed healing with eschar
  • Rare: hemolysis, DIC, shock
  • Management: supportive care, antibiotics if superinfected, consider dapsone, tetanus

Scorpion (Centruroides)

• Geography: Arizona
• Symptoms
  • Autonomic: HTN, tachycardia, diaphoresis
  • CNS: opsoclonus, slurred speech, dysphagia
• Management: anti-venom, supportive care, analgesia, tetanus

Marine

• Ciguatera
  • Source: toxin bioconcentrated in fish
  • Symptoms: gastroenteritis, hot/cold-reversal, “loose teeth” sensation
  • Management: mannitol
• Scombroid
  • Source: poorly-refrigerated fish, histamine-like
  • Symptoms: flushing trunk/face (distinguish from allergic reaction), gastroenteritis
  • Management: supportive care, IVF, anti-histamine, bronchodilators if indicated
• Paralytic shellfish poisoning
  • Source: bivalve
  • Symptoms: gastroenteritis, paralysis
  • Management: supportive, intubation
• Jellyfish and Cnidaria
  • Source: nematocyst
  • Symptoms: burning pain, pruritus
  • Severe: Irakundji syndrome (HTN, pulmonary edema)
  • Management: supportive, analgesia, box jellyfish antidote, consider vinegar
• Stingray
  • Source: heat-labile toxin
  • Management: affected area in warm water, tetanus, ciprofloxacin (Vibrio)

Mushrooms

• Amanita: centrilobular necrosis, similar to acetaminophen
• Gyronatum: similar to INH (seizure and treatment), may cause methemoglobinemia
• Symptoms: muscarinic (SLUDGE)
  • Early onset generally benign, delayed onset (>6h) suggests more serious course
• Management: atropine, glycopyrrolate, IVF

Pesticides

• Organophosphate: irreversible
• Carbamate: reversible
• Symptoms: muscarinic (SLUDGE)
• Treatment: atropine 2-6mg IV double q5min to control secretions, pralidoxime (for organophosphates)

Strychnine

• Source: rodenticide
• Symptoms: myoclonus, opisthotonus, agitation
• Management: benzodiazepines, airway protection, paralysis