Introduction
An antidote is a specific agent designed to counteract the toxic effects caused by drugs or poisons [1]. These substances play a crucial role in toxicology, as they can effectively mitigate or reverse the harmful consequences of various toxic exposures. In clinical practice, the availability of antidotes is somewhat limited, with only a select number approved for use depending on the type of toxin involved [2].
It’s important to note that antidotes are not administered indiscriminately; instead, they are used based on clearly defined clinical guidelines. Each antidote has specific indications that dictate when it should be given, ensuring that patients receive the appropriate treatment in situations of toxicity. Proper identification of the toxin and the clinical scenario is essential to determine the need for an antidote and to maximize its therapeutic efficacy.
Many poisons have no true antidote, and the poison(s) involved may initially be unknown [3, 4]. Furthermore, limiting the differential diagnosis to poisoning can deter the identification of other pathologies that may exist in these patients [3, 4]. Therefore, the initial approach should be to assess and stabilize [4, 5] thoroughly. Similar to any compromised patient, the attention is directed toward securing the airway, breathing, circulation, and decontamination [4, 5]. There are only a few indications where antidotes are prioritized over cardiopulmonary stabilization, i.e., naloxone for opioid toxicity, cyanide antidotes for cyanide toxicity, and atropine for organophosphate poisoning [5]. Otherwise, most patients will have good outcomes with supportive management and a period of observation [1, 3, 4, 5].
Administration of pharmacologic antagonists may worsen the outcome in some situations and is not recommended [2, 3]. Therefore, the physician should know the indications and contraindications of each antidote [2, 3]. When in doubt, consult a poison control center or a medical or clinical toxicologist [2, 4].
In summary, it’s important to understand that antidotes should be utilized as complementary treatments rather than the sole focus in managing poisoning cases [1]. The primary objective should always be to address the patient’s overall condition, taking into account their symptoms and needs, rather than concentrating exclusively on the specific toxin involved [4]. This approach ensures a more comprehensive and effective care strategy for individuals affected by poisoning.
Pregnant Patients and Antidotes
Limited data is available on the use of antidotes in pregnancy [4]. Hence, the teratogenic potential of antidotes is not fully understood [7]. The general initial management principles are the same, and stabilization of the mother is the priority [6].
The risks and benefits of using or withholding antidotes must be assessed. In general, antidotes are not used for uncertain indications, but proven effective treatments should not be withheld from the mother based on theoretical danger to the fetus [4].
There is no known indication for fetal antidote therapy [7]. However, if an antidote is to be given for fetal benefit, it should be done rapidly in the acute setting [7]. This specifically applies to chelators such as dimercaprol, calcium EDTA, and deferoxamine, which will prevent the toxin from passing into fetal circulation [7].
The following section presents information about various antidotes, organized in alphabetical order.
Antidotes
Atropine
General Information
- Anticholinergic agent, competitive muscarinic antagonist [3, 4, 5, 8].
Indications
- Organophosphate poisoning, carbamates, nerve agents [3, 4, 5, 8].
Precautions
- Excessive doses may cause anticholinergic symptoms [5].
Dose/Administration
- Adults: Start with 1-2 mg IV, double the dose every 2-3 minutes to reach the goal [3, 4, 5, 8].
- Children: 0.02 mg/kg IV (minimum of 0.1 mg) [3].
Other Notes
- Large doses may be required.
- Goal: Drying of respiratory secretions/improved work of breathing [3, 8].
- Tachycardia is not the endpoint (atropine helps with muscarinic effects; pralidoxime is used for nicotinic effects) [3, 8].
Calcium
General Information
- Calcium chloride 10% (1 g/10 mL, 27.2 mg/mL elemental Ca).
- Calcium gluconate 10% (9 mg/mL elemental Ca), one-third strength of calcium chloride [5].
Indications
- Calcium channel blocker toxicity, hydrofluoric acid exposure, hyperkalemia, hypermagnesemia [4, 5, 9].
Precautions
- Calcium chloride extravasation can cause soft tissue necrosis; prefer central line administration [9].
- Continuous monitoring is recommended [9].
Dose/Administration
- Adults:
- Calcium chloride: 0.5-1 g IV (5-10 mL) [5, 9].
- Calcium gluconate: 1-3 g IV (10-30 mL) [5].
- Children: 0.15 mL/kg calcium chloride IV [5].
- IV bolus over 5-10 minutes; repeated doses every 10-20 minutes as needed, guided by serum Ca+ or QT interval [9].
- Infusion available [9].
Other Notes
- For HF acid skin burns: Topical 2.5% calcium gel or local injection of calcium gluconate [9].
- Regional block with intra-arterial or IV calcium gluconate for extremity exposure [9].
- Nebulized calcium gluconate for HF acid inhalation injury [9].
Cyproheptadine
General Information
- Antihistaminic and antiserotonergic agent; also has anticholinergic activity [10].
Indications
- Serotonin syndrome [4, 10].
Dose/Administration
- Adults: 8 mg every 8 hours for 24 hours (if response observed) [10].
- Children: 4 mg (not well established) [10].
Deferoxamine
General Information
- Iron-chelating agent that converts iron to a water-soluble complex for renal clearance [3, 11].
Indications
- Systemic iron toxicity (e.g., severe gastroenteritis, shock, metabolic acidosis, altered mental status) [3, 4, 11].
- Iron levels >500 µg/dL or multiple pills on radiography [3, 4, 11].
- Chronic iron overload [3, 4, 11].
Precautions
- Hypotension may occur at rapid infusion rates; ensure adequate hydration [3].
- Cardiac monitoring is needed [11].
Dose/Administration
- Start with IV infusion: 15 mg/kg/h (maximum 1 g/h) over 6 hours; re-evaluate [3, 11].
- Infusion rate can be increased in critical patients if blood pressure allows [11].
Other Notes
- Urine may become rusty-red as iron is excreted [3, 11].
Digoxin Immune Fab
General Information
- Fab fragments of antibodies to digoxin, reversing cardiotoxic effects [1, 3].
Indications
- Digoxin overdose with potassium >5 mEq/L after acute ingestion, hemodynamic instability, or life-threatening dysrhythmias [3].
- Poisoning by other cardiac glycosides (e.g., Oleander) [1, 3, 5, 12].
Precautions
- Close monitoring of digoxin serum levels, vital signs, and ECG. Resuscitation equipment should be ready [12].
Dose/Administration
- Acute overdose:
- Stable patients: 5 vials.
- Unstable patients: 10-20 vials [3, 5].
- Chronic overdose: Start with 1-2 vials, repeat after 60 minutes if needed [12].
- Calculate dose if the ingested dose is known (40 mg Fab binds 0.6 mg digoxin) [3, 5].
- Bolus in life-threatening conditions (e.g., cardiac arrest) or infusion over 30 minutes, monitoring clinical response [3, 12].
Other Notes
- For other cardiac glycoside poisoning: Start with 5 vials [3, 12].
Dimercaprol (BAL)
General Information
- Heavy metal chelator [1, 14].
Indications
- Severe lead, inorganic arsenic, and mercury poisoning [1, 4, 13].
Precautions
- Severe adverse effects include nephrotoxicity; consider using EDTA or succimer instead if possible [13].
Dose/Administration
- 3 mg/kg IM every 4 hours for 48 hours, then every 12 hours for 7-10 days based on clinical response [13].
Ethanol
General Information
- Blocks formation of toxic metabolites of alcohols [14].
Indications
- Methanol and ethylene glycol poisoning (second-line to fomepizole) [5, 14].
Precautions
- Maintain blood ethanol concentration between 100-150 mg/dL [14].
Dose/Administration
- IV:
- Loading: 10 mL/kg of 10% ethanol.
- Maintenance: 1-2 mL/kg/h of 10% ethanol [14].
- Oral:
- Loading: 1.8 mL/kg of 43% ethanol.
- Maintenance: 0.2-0.4 mL/kg/hour of 43% ethanol [14].
Flumazenil
General Information
- Competitive antagonist of GABA-benzodiazepine receptors [1, 2, 3, 15].
Indications
- Benzodiazepine overdose (limited role), reversal of procedural sedation, accidental pediatric ingestion [1, 3, 5, 15].
Precautions
- May cause withdrawal or seizures, especially in benzodiazepine dependence or mixed overdoses [2, 3, 15].
Dose/Administration
- Adults: 0.2 mg IV over 30 seconds, repeat every minute until reversal (maximum 3 mg) [1, 3, 5, 15].
- Children: 0.01-0.02 mg/kg, repeat every minute [1, 5, 15].
Other Notes
- Limited role due to risk of seizures [1, 3, 15].
Fomepizole
General Information
- Alcohol dehydrogenase inhibitor [1, 3, 16].
Indications
- Methanol and ethylene glycol toxicity (first-line due to better side effect profile) [1, 3, 5, 16].
Dose/Administration
- Loading dose: 15 mg/kg IV infusion in 100 mL normal saline or 5% dextrose over 30 minutes [1, 3, 16].
- Maintenance dose: 10 mg/kg every 12 hours for 48 hours, then 15 mg/kg every 12 hours until alcohol concentrations <20 mg/dL [1, 16].
- In dialyzed patients: Give every 4 hours or continuous infusion of 1 mg/kg/h [16].
Other Notes
- Continue therapy until alcohol concentrations are <20 mg/dL and the patient is asymptomatic [3].
Glucagon
General Information
- Increases cyclic AMP (cAMP).
- Positive inotropic and chronotropic properties, similar to beta-agonists [18].
Indications
- β-blocker toxicity (adjunct).
- Calcium channel blocker toxicity [5, 17, 18].
Precautions
- Induces vomiting; consider anti-emetics and airway management [18, 19].
Dose/Administration
- Adults: 5-10 mg IV bolus over 1-2 minutes [5, 18, 19].
- Children: 0.05-0.1 mg/kg IV [19].
Other Notes
- If there is a clinical response, start an infusion [18].
- Intravenous fluids, vasopressors, and high-dose insulin with dextrose are first-line treatments for β-blocker toxicity [19].
Hydroxocobalamin
General Information
- Precursor of Vitamin B12 [20].
Indications
- Cyanide toxicity (forms cyanocobalamin by displacing hydroxyl group) [3, 5, 20].
Precautions
- Safe drug with low side effects.
Dose/Administration
- Adults: 5 g in 100 mL normal saline IV infusion over 15 minutes; repeat if needed [3, 5, 20].
- Children: 70 mg/kg IV over 15 minutes (maximum 5 g) [3, 5].
Other Notes
- Causes orange-red discoloration of skin and urine, resolving within 24-48 hours [3].
Insulin (High Dose)
General Information
- Strong inotropic effects [21].
Indications
- Calcium channel blocker and β-blocker toxicity [5, 21].
Precautions
- Monitor for hypoglycemia, hypokalemia, hypomagnesemia, and hypophosphatemia [21].
Dose/Administration
- Adults:
- Glucose 25 g (50 mL of dextrose 50%) IV bolus → 1 IU/kg IV bolus of short-acting insulin → 25 g/h glucose and 0.5-1 IU/kg/h short-acting insulin infusion [21].
- Titrate glucose to maintain levels between 6-8 mmol/L [21].
Intravenous Lipid Emulsion
General Information
- 20% lipid emulsion as a parenteral nutrient.
- Expands the lipid compartment within the intravascular space, sequestering lipid-soluble drugs from tissues [1, 5].
Indications
- Overdose by drugs with high protein binding and large volume of distribution, e.g., local anesthetics (bupivacaine), β-blockers, and calcium channel blockers [1, 5].
Dose/Administration
- Adults: 100 mL IV bolus over 1 minute (repeat every 5 minutes, maximum 2 doses) → 18 mL/min IV infusion for 20 minutes [5].
- Children: 1.5 mL/kg IV bolus over 1 minute (repeat every 5 minutes, maximum 2 doses) → 0.25 mL/kg/min IV infusion for 20 minutes [5].
Methylene Blue
General Information
- Reduces methemoglobin (MetHb) to hemoglobin [5, 22].
Indications
- Symptomatic methemoglobinemia.
- MetHb levels >20% in asymptomatic patients.
- Oxidizing toxins (e.g., nitrites, benzocaine, sulfonamides) [5, 22].
Precautions
- Pulse oximetry is unreliable in methemoglobinemia.
- May cause hemolysis in G6PD deficiency [3, 22].
Dose/Administration
- 1-2 mg/kg slow IV injection over 5 minutes; may repeat after 30-60 minutes [5, 22].
Other Notes
- Monitor MetHb levels frequently until a consistent decrease is observed [22].
N-acetylcysteine (NAC)
General Information
- Prevents hepatocellular injury by restoring glutathione stores, which conjugate the toxic metabolite NAPQI [1, 3, 23].
Indications
- Serum acetaminophen levels above toxic threshold (>4 hours after ingestion).
- Single ingestion >150 mg/kg.
- Evidence of liver injury [1, 3, 4, 23].
Dose/Administration
- Oral: 140 mg/kg loading dose → 70 mg/kg every 4 hours for 17 doses [1, 3, 23].
- IV: 150 mg/kg in 200 mL of 5% dextrose over 60 minutes → 50 mg/kg diluted in 500 mL of 5% dextrose over 4 hours → 100 mg/kg diluted in 1000 mL of 5% dextrose over 16 hours [1, 3, 23].
Other Notes
- Oral therapy may not be well tolerated due to taste and odor [23].
Naloxone
General Information
- Opioid antagonist, diagnostic, and therapeutic agent [1, 2, 3].
Indications
- Opioid toxicity with respiratory and CNS depression [1, 2, 3, 5].
Precautions
- Re-sedation may occur due to naloxone’s short half-life; monitor for at least 4 hours.
- Withdrawal in chronic/opioid-dependent users [1, 2, 3].
Dose/Administration
- Adults: 0.4-2 mg IV; repeat every 2-3 minutes up to a maximum of 10 mg [1, 2, 3].
- Children: 0.01 mg/kg IV [1, 3].
Other Notes
- Goal: Adequate respiratory rate, normal oxygen saturation on room air, improved level of consciousness [3, 5].
- Miosis is an unreliable indicator [5].
Octreotide
General Information
- Synthetic analogue of somatostatin [24].
Indications
- Hypoglycemia secondary to sulfonylurea [24].
Precautions
- Breakthrough hypoglycemia may occur [24].
Dose/Administration
- Adults:
- 50 µg IV bolus → 25 µg/h infusion.
- Alternatively, 100 µg IM or SC every 6 hours [24].
- Children: 1 µg/kg IV bolus or SC → 1 µg/kg/h IV infusion [24].
Other Notes
- Euglycemia needs to be maintained for 12 hours off the infusion before the patient is medically cleared [24].
Physostigmine
General Information
- Reversible acetylcholinesterase inhibitor [25].
Indications
- Neurological anticholinergic symptoms, e.g., delirium and seizures (crosses the blood-brain barrier) [5, 25].
Precautions
- Contraindicated in bradycardia, AV block, and bronchospasm [25].
Dose/Administration
- Adults: 0.5-1 mg slow IV push over 5 minutes; repeat in 10-30 minutes if needed [25].
- Children: 0.02 mg/kg IV (maximum dose of 0.5 mg) [25].
Other Notes
- Confirm absence of conduction defects on a 12-lead ECG before administration.
- Rapid administration may cause a cholinergic crisis; treat with atropine if this occurs [25].
Pralidoxime
General Information
- Reactivates acetylcholinesterase inhibition [1, 3, 26].
Indications
- Early organophosphate poisoning (<2 hours).
- Nerve agents [1, 3, 5, 26].
Precautions
- Rapid administration can cause laryngospasm, muscle rigidity, and transient respiratory impairment [3].
Dose/Administration
- Adults: 1-2 g IV in 100 mL of 0.9% saline over 15-30 minutes → 500 mg/h IV infusion [3, 26].
- Children: 25-50 mg/kg → 10-20 mg/kg/h infusion [3, 26].
Other Notes
- Administer in the early phase before irreversible acetylcholinesterase binding occurs.
- Adequate atropine doses should be given concurrently [1, 3, 26].
Pyridoxine (Vitamin B6)
General Information
- Vitamin B6, essential for GABA production [3, 27].
Indications
- Isoniazid, hydrazine, and Gyromitra poisoning.
- Ethylene glycol poisoning (adjunct therapy) [3, 5, 27].
Dose/Administration
- Adults:
- For isoniazid poisoning: 1 g per gram of ingested isoniazid, given as 0.5 g/min infusion until seizures stop. If unknown, give 5 g IV empirically [3, 5, 27].
- Children: 70 mg/kg IV, maximum 5 g [5, 27].
Other Notes
- For ethylene glycol toxicity: 50 mg IV every 6 hours [27].
Sodium Bicarbonate
General Information
- Hyperosmolar sodium bicarbonate injection [28].
Indications
- Cardiotoxicity due to fast sodium channel blockade presenting as QRS widening and ventricular dysrhythmias (e.g., TCA poisoning).
- Urine alkalinization [2, 5, 28].
Precautions
- Monitor for hypokalemia and hypernatremia.
- Maintain serum pH between 7.50-7.55 [28].
Dose/Administration
- Start with 1-2 mEq/kg IV over 1-2 minutes → 0.3 mEq/kg per hour IV infusion if needed [5].
- Repeated doses may require intubation and hyperventilation to maintain pH >7.5-7.55 [28].
Sodium Calcium Edetate (EDTA)
General Information
- IV heavy metal chelator [29].
Indications
- Severe lead toxicity with lead levels >70 µg/dL [29].
Precautions
- Risk of nephrotoxicity, ECG changes, and transaminitis.
- Hospital admission required [29].
Dose/Administration
- Dilute 25-50 mg/kg in 500 mL of 0.9% saline or 5% dextrose; infuse over 24 hours, starting 4 hours after the first dose of dimercaprol [29].
- In encephalopathy, continuous infusion for 5 days until stabilization [29].
Other Notes
- Once clinically improved, switch to oral succimer if tolerated [29].
Sodium Thiosulfate
General Information
- Assists the body in detoxifying cyanide [1, 30].
Indications
- Cyanide poisoning [1, 5, 30].
Precautions
- In severe cases, use with other antidotes (e.g., hydroxocobalamin) [30].
Dose/Administration
- Adults: 50 mL of 25% solution (12.5 g; 1 ampoule) IV over 10 minutes [1, 5, 30].
- Children: 1.65 mL/kg IV; repeat after 30 minutes if clinically indicated [30].
Succimer (DMSA)
General Information
- Oral heavy metal chelator [31].
Indications
- Symptomatic lead poisoning.
- Asymptomatic lead poisoning with lead levels >60 µg/dL in adults or >45 µg/dL in children [5, 31].
Precautions
- Reversible neutropenia, gastrointestinal upset, and liver function abnormalities [31].
Dose/Administration
- 10 mg/kg three times a day for 1 week → two times a day for 2 weeks [31].
Other Notes
- Monitor serum lead levels during treatment [31].
Antidotes play a crucial role in managing toxicological emergencies in the emergency department. While their use is often specific and limited, they provide life-saving interventions in cases of confirmed poisonings such as opioid overdoses, cyanide poisoning, or organophosphate exposure. However, their administration requires careful assessment of indications, contraindications, and potential adverse effects. Emergency clinicians must prioritize stabilizing airway, breathing, and circulation before considering antidote administration, except in scenarios where antidotes are critical to immediate survival. The decision to use an antidote should be guided by clinical judgment, toxicology consultation, and evidence-based guidelines. Ultimately, antidotes should be viewed as adjunctive therapies, emphasizing the principle of treating the patient comprehensively rather than focusing solely on the poison.
Author
Sarah Alzaabi
Sarah Alzaabi, MD is a graduate from the United Arab Emirates University. She is currently a medical intern at Sheikh Shakhbout Medical City, Abu Dhabi, with a longstanding interest in Emergency Medicine. She is a big advocate for the FOAMed movement; and is proud to be a part of the fantastic team at iEM. She is excited to develop innovative ways to provide accessible education for anyone in need. Sarah has a particular interest in lifestyle and nutrition and spends time learning about how to educate others about succeeding in medicine while maintaining a healthy lifestyle.
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Reviewed and Edited By
Arif Alper Cevik, MD, FEMAT, FIFEM
Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.
