- Activated Charcoal
- Atropine
- Flumazenil
- Fomepizole
- Intralipid
- Pralidoxime
- N-Acetylcysteine
- Naloxone
- Thiamine
Activated Charcoal
Rapid Review
- Mechanism of Action: Adsorbent agent. Large surface area of charcoal binds to toxins and prevents systemic absorption.
- Indications: Toxic ingestions/drug overdoses (solids only); should be administered within 1-2 hours of ingestion.
- Contraindications: Risk of aspiration, ingestion of caustic material
- Dosage: 25-100mg PO
- Onset: Begins within 1 minute; achieves equilibrium within 10-25 minutes.
- Duration: Up to 4 hours
- Adverse Reactions: aspiration, bowel obstruction.
- Special Considerations: N/A
Pearls
- Activated charcoal is rarely used anymore due to lack of efficacy and the risk of aspiration, though it may be useful if delivered immediately after solid toxic ingestions (within 30-60 minutes).
- Should not be used with ingestants that are poorly adsorbed (ex. heavy metals, alcohols, oils, solvents, organophosphates, inorganic ions
Atropine
Rapid Review
- Mechanism of Action: Anticholinergic and parasympatholytic; antagonizes acetylcholine receptors and prevents activation of parasympathetic nervous system.
- Indications: organophosphate toxicity; bradycardia. May also be used to reverse effects of paralytics.
- Contraindications: allergy; primary glaucoma
- Dosage: symptomatic bradycardia: 0.5 mg rapid IV push; organophosphate toxicity: 1-3 mg IV/IM/SC. Paralytic reversal: 1.2 mg IV push
- Onset: 2-4 minutes
- Duration: 5 hours
- Adverse Reactions: dry mouth, blurred vision, tachycardia, hyperthermia
Pearls
- Since atropine interacts specifically with the AV node, it may be ineffective in treating pathology distal to this structure, such as in 2nd or 3rd degree heart blocks
- Although several factors may lead to bradycardia during rapid sequence intubation (ex. hypoxia, paralytics), the bradycardic effects of vasovagal stimulation from laryngoscopy are negligible and atropine is no longer recommended for routine pretreatment for this procedure.
Deep Dive
Flumazenil
Rapid Review
- Mechanism of Action: Benzodiazepine antagonist; competitively inhibits GABA/benzodiazepine receptor sites
- Indications: Benzodiazepine overdose
- Contraindications: Hypersensitivity, use of benzodiazepine to control seizures
- Dosage: 0.2 mg slow IV push initially. Repeat every 60 seconds prn. Max dose 1 mg.
- Onset: 1-2 minutes
- Duration: 19-50 minutes
- Adverse Reactions: Sedation, seizure, arrhythmias, confusion, nausea/vomiting
Pearls
- Use caution when administering flumazenil, as it may precipitate acute withdrawal in chronic benzodiazepine users and result in seizures. For this reason, flumazenil should not be used routinely for the undifferentiated AMS patient.
- Routine use of flumazenil to reverse the effects of benzodiazepines following procedural sedation is not recommended unless a life-threat is present.
Fomepizole
Rapid Review
- Mechanism of Action: Antidote; inhibits alcohol dehydrogenase
- Indications: Methanol or ethylene glycol toxicity
- Contraindications: Allergy
- Dosage: 15 mg/kg IV loading dose, then 10 mg/kg q12 hours
- Onset: 1.5 – 2 hours
- Duration: Half life not determined
- Adverse Reactions: Headache, nausea, bradycardia, hypotension
Pearls
- Fomepizole may have a role in massive acetaminophen overdose as an adjunct to N-acetylcysteine.
- Fomepizole has largely replaced ethanol as the antidote of choice for toxic alcohol poisoning. That being said, fomepizole is expensive and limited in supply, and thus ethanol remains a reasonable alternative.
Deep Dive
Intralipid
Rapid Review
- Mechanism of Action: Lipid emulsion; unknown mechanism, but thought to create a “lipid sink” in the blood where lipophilic anesthetic agents can dissolve, thus reducing systemic circulation. Available in 10%, 20%, and 30%.
- Indications: Local anesthetic systemic toxicity (LAST)
- Contraindications: Severe egg allergy,
- Dosage:
- Weight > 70kg: 100mL bolus (20%), followed by 200-250mL infusion over 20-30 minutes
- Weight <70kg: 1.5mL/kg bolus (20%), followed by 0.25 mL/kg/minute infusion
- Half-Life: 15 minutes
- Adverse Reactions: Fat embolism, hypersensitivity reactions, pancreatitis, hypertriglyceridemia
Pearls
- Because intralipid is sequestered into muscle, patients with low muscle mass are less likely to benefit from intralipid therapy
- Intralipid is possibly beneficial for overdose of oral lipophilic medications as well (olanzapine, diltiazem, caffeine, TCAs, cocaine, bupropion, etc.)
Deep Dive
Pralidoxime
Rapid Review
- Mechanism of Action: Oxime antidote. Reactivates the acetylcholinesterase enzyme to promote clearance of acetylcholine at muscarinic and nicotinic sites.
- Indications: Organophosphate toxicity
- Contraindications: Allergy to drug/class
- Dosage: 1-2 grams IV over 5-10 minutes or 600 mg IM X 3 doses (15 minutes apart)
- Onset: 5-15 minutes
- Duration: 3-4 hours
- Adverse Reactions: Blurred vision, diplopia, dizziness, tachycardia, hypertension
Pearls
- In order to be effective, pralidoxime must be administered within 48 hours of organophosphate exposure.
- Pralidoxime has a synergistic effect when co-administered with atropine, which is why they are commonly included together in auto-injectors.
Deep Dive
N-Acetylcysteine
Rapid Review
- Mechanism of Action: Antidote/Mucolytic; helps replete glutathione reserves in the liver, which helps protect the liver from hepatotoxic NAPQI metabolite. Also functions as a mucolytic to help break down thick pulmonary secretions.
- Indications: Acetaminophen toxicity
- Contraindications: Allergy to drug/class
- Dosage: Three separate infusions:
- First dose: 150mg/kg in 100 mL D5W over 60 minutes
- Second dose: 50mg/kg in 250 mL D5W over 4 hours
- Third dose: 100 mg/kg in 500 mL D5W over 16 hours
- Onset: Generally rapid onset
- Duration: Generally short duration
- Adverse Reactions: Nausea/vomiting, anaphylaxis
Pearls
- N-Acetylcysteine is nearly 100% effective if given within 8 hours of acetaminophen ingestion, but efficacy reduces significantly overtime.
- Due to high rates of adverse reactions with the 3-bag NAC regimen, there is increasing research on alternative regimens, such as the 2-bag regimen or SNAP protocol.
Deep Dive
Naloxone
Rapid Review
- Mechanism of Action: Opiate antagonist; competitively binds to mu, kappa, and sigma opiate receptor sites in the CNS for reversal of opiate toxicity and improvement of respiratory drive.
- Indications: Opioid toxicity (recreational or iatrogenic)
- Contraindications: Allergy to class/drug
- Dosage: 0.4 – 2.0 mg (IV/IM/SC), repeat q 2-3 minutes prn. Max dose 10 mg
- Onset: 1-2 minutes
- Duration: 20-90 minutes
- Adverse Reactions: Non-cardiogenic pulmonary edema, opioid withdrawal (diaphoresis, tachycardia, agitation)
- Special Considerations: Patients with opiate overdose should be held in the ED until naloxone wears off (usually 1-3 hours). Consider discharging patients with naloxone in-hand.
Pearls
- The goal of naloxone is to reverse respiratory depression without precipitating an acute opiate withdrawal. Start with low doses (ex. 0.04-2 mg) and titrate gradually to achieve an increase in respiratory rate.
- Naloxone may require multiple doses or even continuous infusion. Do not wait for the effects of naloxone before oxygenating/ventilating patients.
Thiamine
Rapid Review
- Mechanism of Action: Vitamin; combines with ATP in liver, kidneys, and leukocytes to produce thiamine diphosphate, which acts as a coenzyme in carbohydrate metabolism. Used to prevent brain damage (encephalopathy) from thiamine-depleted states.
- Indications: Alcoholism, beriberi anorexia, bulimia, pregnancy, malignancies
- Contraindications: Allergic reactions to vitamin supplements
- Dosage:
- Beriberi: 5-30 mg TID x 1 month
- Wernicke’s Encephalopathy: 500mg IV TID x 2 days
- Onset: Rapid
- Duration: Depends on degree of deficency
- Adverse Reactions: Anaphylaxis, pruritus, injection site pain
- Special Considerations: None
Pearls
- It was previously thought that administering glucose for hypoglycemia prior to treating thiamine deficiency would precipitate Wernicke’s encephalopathy, however the most recent literature does not support this.
- Thiamine is poorly absorbed in the gastrointestinal tract, which is why thiamine is preferentially delivered intravenously.
