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

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

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

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

Anti-hypertensives

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)

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

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

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

The post Toxicology appeared first on Differential Diagnosis of.

38M, unknown medical history, brought in after being found unresponsive next to an empty bottle of Seroquel. Presenting vital signs notable for blood pressure of 96/43, heart rate 103. Examination reveals tentatively protected airway (GCS E2 M5 V3, SpO2 100%, RR 14), normal pupil diameter and reactivity, dry mucous membranes with thick vomitus in oral cavity.

Laboratory evaluation was unremarkable, and there was no evidence of aspiration on chest radiography. ECG showed sinus tachycardia without QT prolongation. Blood pressure increased to normal range with fluid resuscitation. The patient’s mental status progressively improved and he was discharged after six hours of uneventful continuous cardiac monitoring.

Toxidrome Summary¹

Evaluation^1,2

• POC Glucose
• ECG (QT interval)
• Serum acetaminophen, salicylate, EtOH level
• Serum drug levels if known (anti-epileptics)
• Urine toxicology screen
• Chemistry (metabolic acidosis, electrolytes, renal function)
• LFT (hepatotoxicity)
• CK (rhabdomyolysis)
• Serum osmolarity (osmolar gap)
• UA with microscopy (crystals in ethylene glycol poisoning)
• ABG (carboxyhemoglobin, methemoglobin)

Pharmacology, Toxicity and Management of Second Generation Antipsychotic (SGA) Overdose³

References

1. Kulig, K. (2013). General Approach to the Poisoned Patient. In Rosen’s Emergency Medicine – Concepts and Clinical Practice (8th ed., Vol. 1, pp. 1954-1959). Elsevier Health Sciences.
2. Wittler, M., & Lavonas, E. (2013). Antipsychotics. In Rosen’s Emergency Medicine – Concepts and Clinical Practice (8th ed., Vol. 1, pp. 2047-2051). Elsevier Health Sciences.
3. Levine M, Ruha A-M. Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management. CNS Drugs. 2012;26(7):601–611.
4. WikEM: Antipsychotic toxicity

The post Atypical Antipsychotic Overdose appeared first on Differential Diagnosis of.