Medication Summary
Oxygen is the initial agent used in suspected or confirmed cyanide poisoning. Sodium bicarbonate is used in patients with severe poisoning that has produced marked lactic acidosis. Epinephrine is used to support cerebral and coronary perfusion in low-flow states.
Antidotal therapy is indicated for any patient in whom the diagnosis of cyanide toxicity is considered on clinical grounds, even before laboratory confirmation. Activated charcoal can be used in patients presenting soon after ingestion of cyanide salts or organic cyanides.
Anticonvulsants are used as indicated. Lorazepam is the drug of choice; midazolam and phenobarbital are second-line agents.
Cyanide antidotes are the key medications for hydrogen cyanide (HCN) poisoning. Hydroxocobalamin (HCO, vitamin B12) is the first-line therapy for cyanide toxicity. It functions by binding cyanide to its cobalt ion to form cyanocobalamin, which is essentially nontoxic and is cleared by the kidneys. [42, 39] HCO can be combined with sodium thiosulfate for accelerated detoxification. Amyl nitrite is an alternative temporizing therapy; it may be useful in the absence of intravenous (IV) access (eg, in industrial settings).
Sodium thiosulfate enhances the conversion of cyanide to thiocyanate, which is excreted by the kidneys. Thiosulfate has a somewhat delayed effect and thus is typically used with sodium nitrite for faster antidote action. Sodium nitrite must be used with caution because it may result in significant hypotension and cardiovascular collapse, in addition to generating dangerous levels of methemoglobin. However, in cases of smoke inhalation in which cyanide toxicity is suspected, administration of sodium thiosulfate is safe.
Antidotes
Class Summary
Cyanide is a cellular toxin that binds to cytochrome oxidase, inhibiting cellular respiration. Antidotes either directly counteract cyanide's toxicity on the electron transport chain or help the body eliminate the cyanide molecule. Administration of antidotes is critical for life-threatening intoxication.
Gastrointestinal (GI) decontamination with oral activated charcoal is selectively used in the emergency treatment of poisoning caused by some drugs and chemicals. The network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Consider decontamination with activated charcoal in any patient who presents within 4 hours after the ingestion.
Alkalinizing agents are used in severe poisoning, which causes marked lactic acidosis.
Hydroxocobalamin (Cyanokit)
Hydroxocobalamin contains cobalt ion, which is able to bind to cyanide with greater affinity than cytochrome oxidase to form nontoxic cyanocobalamin (vitamin B12), which is excreted in urine. Hydroxocobalamin has few adverse effects and is tolerated by critically ill patients. It is well tolerated by patients with concomitant carbon monoxide poisoning, because unlike sodium nitrite it has no effect on the oxygen-carrying capacity of hemoglobin.
Hydroxocobalamin may be used in combination with sodium thiosulfate for treatment of acute cyanide toxicity. Low-dose hydroxocobalamin in combination with sodium thiosulfate has been used successfully to prevent cyanide toxicity in patients receiving prolonged sodium nitroprusside infusions.
The disadvantages of hydroxocobalamin are that a large dose is required for antidotal efficacy and that it is available in the United States only in very dilute solutions. It can cause transient hypertension, allergic reactions (rarely including anaphylaxis and angioedema), and a reddish discoloration of body fluids and urine.
Sodium thiosulfate & sodium nitrite (Nithiodote)
Sodium nitrite induces methemoglobin formation and vasodilation. Sodium thiosulfate has a slower mechanism of action. It donates sulfur, which is used as a substrate by rhodanese and other sulfur transferases for detoxification of cyanide to thiocyanate. In patients with concomitant carbon monoxide poisoning, for whom sodium nitrite is contraindicated, sodium thiosulfate can be used alone; sodium thiosulfate can also be administered with hydroxocobalamin in severe cases.
The recommended dose assumes a patient hemoglobin level of 12 mg/dL; dosage adjustment may be necessary in patients with anemia. Half the original dose may be repeated in 1 hour if the patient continues to exhibit signs of cyanide toxicity.
Amyl nitrite
The nitrite ions in amyl nitrite react with hemoglobin to form methemoglobin, which unites with cyanide to form cyanomethemoglobin. Amyl nitrite rushed and contents poured onto a gauze and placed in front of patient's mouth pearls can be crushed and inhaled by a spontaneously breathing patient or ventilated into an apneic patient using a bag-valve-mask device; this is a temporizing measure until IV access can be established.
The effect of an ampule lasts approximately 3 minutes; separate administration by at least 30 seconds to allow patient to oxygenate. Due to the volatile nature of this compound, rescuers should ensure that they themselves have an adequate fresh air supply and can maintain a sufficient distance from the amyl nitrite source.
Activated charcoal (Actidose-Aqua, EZ-Char, Kerr Insta-Char)
Activated charcoal binds cyanide poorly; 1 g of charcoal adsorbs only 35 mg of cyanide. Nonetheless, a 1-g/kg dose of charcoal could potentially bind a lethal dose of cyanide and has a low risk profile. Consequently, charcoal should be administered as soon as possible following oral ingestion of cyanide salts or organic cyanides.
Sodium bicarbonate (Neut)
Sodium bicarbonate may be required in large doses for alkalization.
Anticonvulsants, Other
Class Summary
Cyanide inhibits brain glutamate decarboxylase, which causes a decrease in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and contributes to convulsions. Therefore, anticonvulsant drugs such as benzodiazepines or barbiturates, which act at the GABA receptor complex, can help control seizures.
Lorazepam (Ativan)
Lorazepam is the drug of choice for cyanide-induced seizures. It is a sedative hypnotic with a rapid onset of effect and a relatively long half-life. By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the central nervous system, including the limbic and reticular formation.
Pentobarbital (Nembutal)
Pentobarbital is a short-acting barbiturate that interferes with transmission of impulses from the thalamus to the cortex. It has sedative, hypnotic, and anticonvulsant properties. It is a second-line drug for treatment of drug-induced seizures.
Alpha/Beta Adrenergic Agonists
Class Summary
These agents augment coronary and cerebral blood flow during the low-flow states associated with cyanide poisoning.
Epinephrine (EpiPen, EpiPen Jr, Adrenaclick, Auvi-Q, Adrenalin)
Epinephrine is the drug of choice for treating anaphylactoid reactions. It has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Its beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
