by Hamidreza Reihani and Elham Pishbin
An antidote is an agent or drug that can reverse the toxic effects of poisoning. The base of clinical practice in the treatment of toxicities is cardiopulmonary stabilization, decontamination, enhancing elimination and supportive management. Antidotes are indicated in some specific and well-defined situations, and they are not routinely administered in toxin exposures. Therefore, the physician should know the indications and contraindications of each antidote. Administration of the pharmacologic antagonists may worsen the outcome in some situations and are not recommended.
There is usually enough time to start the treatment after supportive care and evaluation of the patient. However, there are a few indications that antidotes should be administered as soon as possible to prevent major complications and death. Cyanide antidotes for cyanide toxicity, naloxone for severe opium overdose and atropine for organophosphate poisoning and gas agents are some examples.
The antidotes administered in clinical practice are not a great deal. There is a list of essential antidotes and a brief explanation of their character and application.
Antidotes and their characteristics (A - E)
| Antidote | Indications/precautions | Dosage/administration |
|---|---|---|
| Atropine | General information • Anticholinergic agent • Competitive muscarinic antagonist Indications • Organophosphate poisoning • Carbamates • Nerve agents Precautions • Excessive doses lead to anticholinergic symptoms | Dose • Start with 1-2 mg IV (adults), 0.02 mg/kg IV (children) • Double the dose every 2-3 minute to achieve atropinization Administration • Infusion of 10-20% of stabilizing dose/hour • Large doses may be required • There are auto-injectors for rapid use Other • Drying of respiratory secretions is the goal • Tachycardia is not the endpoint |
| 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 of the calcium in strength of calcium chloride Indications • Calcium channel blockers toxicity • Hydrofluoric acid exposure • Hyperkalemia • Hypermagnesaemia Precautions • Calcium chloride extravasation can lead to soft tissue necrosis, preferably administered via central line • Continuous monitoring is recommended | Dose • 1 gram calcium chloride (10 mL), (0.15mL/kg in children) • 10-30 mL of calcium gluconate Administration • IV bolus over 5 minutes • Repeated doses every 10-20 minutes if needed • Infusion can be administered Other • Topical calcium gel or local injection of calcium gluconate for hydrofluoric acid skin burns • Intra-arterial or IV with a Bier block for extremity exposure |
| Ciproheptadine | General information • An antihistaminic and antiserotonergic agent • Has anticholinergic effects as well Indications • Control of symptoms in serotonin syndrome Precautions • May cause anticholinergic effects | Dose • 8 mg (adults), 4 mg (children) not approved Administration • Oral • Can be repeated every 8 hours until 24 hours |
| Deferoxamin | General information • Iron-chelating agent • Converts it to a water-soluble complex excreted by urine Indications • Systemic iron toxicity • Iron levels > 500 µg/dL • Multiple pills on radiography Precautions • Hypotension may occur at rapid rates • Cardiac monitoring is needed • Avoid infusion more than 24 hours | Dose • Start with15 mg/kg/h Administration • IV infusion • Infusion rate could be increased Other • Evaluate patient after 6 hours • The urine color will become red |
| Digoxin immune Fab | General information • Fab fragments of antibodies to digoxin • Reverse the dangerous cardiac effects of digitalis Indications • Acute and chronic digoxin overdose • Other cardiac glycosides poisoning Precautions • Close monitoring; ready for resuscitation • Monitor serum free level of digoxin | Dose • Acute overdose: 5 vials; for unstable patients 10-20 vials; can be calculated if the ingested dose is known • Chronic overdose: can be calculated by serum digoxin level; start with 2 vials Administration • Bolus in life threatening conditions, otherwise infusion Other • For other cardiac glycoside poisoning start with 5 vials |
| Dimercaprol (BAL) | General information • Heavy metal chelator Indications • Severe lead, inorganic arsenic and mercury poisoning Precautions • Many severe adverse effects • Nephrotoxic • Administered in ICU | Dose • 3 mg/kg Administration • IM every 4 hours for 48 hours |
| Ethanol | General information • Blocks the formation of toxic metabolites of alcohols Indications • Methanol and ethylene glycol poisoning Precautions • Serum ethanol levels monitored every 1-2 hours • The dose should be doubled during dialysis | Dose/ Administration • IV: loading (10 mL/kg of 10% IV solution), maintenance (1-2 mL/kg/h of 10% IV solution) • Oral: loading (1.5-2 mL/kg 80-proof liquor), maintenance (0.2-0.5 mL/kg/h) Other • Maintain blood ethanol concentration between 100-150 mg/dl |
Antidotes and their characteristics (F - I)
| Antidote | Indications/precautions | Dosage/administration |
|---|---|---|
| Flumazenil | General information • Competitive benzodiazepine antagonist • Not used routinely in benzodiazepine poisoning Indications • Reversal of procedural sedation • Pediatric poisoning (limited use) Precautions • May cause withdrawal • May induce seizure | Dose • 0.2 mg, 0.01 mg/kg (children) • Repeat up to the desired effect or 3 mg Administration • IV over 30 seconds Other • Not used in mixed drug overdose |
| Fomepizole | General information • An alcohol dehydrogenase inhibitor Indications • Methanol and ethylene glycol toxicity | Dose • Loading dose = 15 mg/kg • Maintenance dose = 10 mg/kg q12 hours Administration • Infusion in 100 ml normal saline or 5% dextrose in 30 minutes Other • In dialyzed patients is given every 4 hours or continuous infusion |
| Glucagon | General information • Increase cAMP** • Positive inotropic and chronotropic similar to beta-agonists Indications • β-blocker toxicity • Calcium channel blocker toxicity Precautions • Induces vomiting, consider airway management | Dose • 5-10 mg (adults), 0.05-0.1 mg/kg (children) Administration • The first dose is IV bolus, if there is a clinical response, start infusion |
| Hydroxocobalamin | General information • A precursor of Vitamin B12 • Hydroxyl group is displaced by cyanide and form cyanocobalamin Indications • Cyanide toxicity Precautions • It's a safe drug | Dose • 5 g, repeat if needed; 70 mg/kg (children) Administration • Infusion in 100 normal saline in 15 minutes Other • Skin and urine orange-red discoloration |
| Insulin (High dose) | General information • It has strong inotropic effects Indications • Calcium channel blocker toxicity • Βeta-blocker toxicity Precautions • Glucose level should be monitored every 10 minutes • Hypokalemia be considered | Dose/ Administration • 1 IU/kg IV bolus of short acting insulin, followed by 0.5-1 IU/kg/hr • Glucose 25 g (dextrose 50%) before starting insulin, then 25 g/hr according to glucose level Other • Higher doses were administered in studies |
| Intravenous Lipid Emulsion | General information • 20% lipid emulsion as a parenteral nutrient Indications • Overdose by drugs with high protein binding and large volume of distribution, e.g. Local anesthetics, β-blockers and calcium channel blockers | Dose/Administration • 1.5 ml/kg IV bolus • 0.25 ml/kg/minute Other • Until hemodynamic stability restored |
Antidotes and their characteristics (M - S)
| Antidote | Indications/precautions | Dosage/administration |
|---|---|---|
| Methylen blue | General information • It reduces methemoglobin (MetHb) to hemoglobin Indications • Methemoglobin-forming agents toxicity • Symptomatic methemoglobinemia • MetHb levels >20% in asymptomatic patients Precautions • Pulse oximetry is unreliable in methemoglobinemia • Hemolysis in G6PD deficiency | Dose • 1-2 mg/kg IV, 1 mg/kg (children) Administration • Slow IV injection, may repeat 30-60 minutes later Other • MetHb levels measured frequently |
| N-acetylcysteine | General information • Preventing hepatocellular injury in severe acetaminophen toxicity Indications • Serum acetaminophen concentration above toxic level • Hepatocellular injury Precautions • Oral therapy may not be tolerated due to its taste and odor | Dose/Administration • Oral: loading (140 mg/kg), then (70 mg/kg q 4 hours) for 17 doses • IV: loading 150 mg/kg in 30-60 minutes then 50 mg/kg over 4 hours, 100 mg/kg infused over next 16 hours |
| Naloxone | General information • An opioid antagonist Indications • For reversing the opioid effects, respiratory and CNS depression Precautions • Re-sedation may occur due to short half-life of naloxone • Withdrawal in chronic users | Dose • Start: 0.1 to 0.4 mg; 0.01 mg/kg (children) • Repeat every 2-3 minutes up to 10 mg Administration • Intravenously, intramuscularly, or subcutaneously Other • Start with larger doses if respiratory depression exist • Infusions may be required |
| Octreotide | General information • Synthetic analogue of somatostatin Indications • Hypoglycemia due to sulfonylurea Precautions • Break through hypoglycemia may occur | Dose/Administration • 50 µg IV then 25 µg/h or • 100 µg IM or SC every 6 hours |
| Physostigmine | General information • Reverse anticholinergic syndrome Indications • For CNS symptoms (delirium, seizure) due to anticholinergic drugs Precautions • Contraindicated in bradycardia, AV block and bronchospasm | Dose • 0.5 – 1 mg (adults), 0.02 mg/kg (children) Administration • IV slowly in 2 minutes or IM • Repeat in 10 to 30 minutes if needed Other • In rapid administration cholinergic symptoms may occur |
| Pralidoxime | General information • Reactivate cholinesterase inhibition due to organophosphates Indications • Organophosphates poisoning • Nerve agents | Dose • Loading: 1-2 g IV; 25-50 mg/kg (children) • Maintenance: 500 mg/hr or 1-2 g q4-6h; 10-20 mg/kg/hour (children) Administration • IV infusion in 0.9% saline Other • Should be administered in the early phase before irreversible binding occurs |
| Pyridoxine | General information • Vitamin B6 is essential for GABA production Indications • Isoniazid, hydrazine and Gyromitra poisoning • Ethylene glycol poisoning | Dose/Administration • 1 gram for each gram of isoniazid, 70 mg/kg (children), maximum 5 gram • 50 mg IV every 6 hours for ethylene glycol toxicity • 0.5 g/min infusion until the seizure stops |
| Sodium bicarbonate | General information • Hyperosmolar Sodium Bicarbonate Injection Indications • Cardiotoxicity due to fast sodium channel blockade (e.g., TCA* poisoning) • Urine alkalinization Precautions • Hypokalemia is a concern • Serum pH maintained between 7.50-7.55 | Dose • Start with 1-2 mEq/kg, further doses may be needed Administration • First dose administered bolus • Other bolus doses or infusion if required Other • Given only if there is evidence of cardiotoxicity, such as QRS widening and ventricular dysrhythmias |
| Sodium calcium edetate (EDTA) | General information • IV heavy metal chelator Indications • Severe lead toxicity • Lead level > 70 µg/dl Precautions • Patient should be admitted in hospital • Nephrotoxicity, ECG changes and liver test disturbance may occur | Dose • 25-75 mg/kg/day Administration • Continuous infusion for 5 days Other • Usually starts 4 hours after first dimercaprol (BAL) injection |
| Sodium thiosulfate | General information • Help the body to detoxify cyanide Indications • Cyanide poisoning Precautions • In severe cases with other antidotes | Dose • 50 ml of 25% (12.5 g; 1 ampoule) in adults; 1.65 ml/kg (children) Administration • IV over 10 minutes • Repeat after 30 minutes if clinically needed |
| Succimer (DMSA) | General information • Oral metal chelator Indications • Symptomatic lead poisoning • Asymptomatic lead poisoning, lead level > 60 µg/dl (adults), > 45 µg/dl (children) Precautions • May cause neutropenia, gastrointestinal upset and liver abnormalities | Dose • 10 mg/kg three times a day for 1 week, then two times a day for 2 weeks Administration • Orally Other • The serum level should be monitored |
References and Further Reading
- contributors W. Antidote: Wikipedia, The Free Encyclopedia. ; 2016 [cited 2016 20 july]. Available from: https://en.wikipedia.org/w/index.php?title=Antidote&oldid=708590648.
- Holstege CP, Dobmeier SG, Bechtel LK. Critical care toxicology. Emergency medicine clinics of North America. 2008;26(3):715-39.
- Erickson TB, Thompson TM, Lu JJ. The approach to the patient with an unknown overdose. Emergency medicine clinics of North America. 2007;25(2):249-81.
- Greene S. General Management of Poisoned Patients. Tintinalli’s emergency medicine. 1. 8 ed: MC Graw Hill; 2014. p. 1207.