Cyanogen Chloride Poisoning Medication

The Cyanokit and Cyanide Antidote Kit will be briefly reviewed in this section, as well as the use of oxygen administration.

Cyanokit

Cyanokit (hydroxocobalamin) has been approved by the US Food and Drug Administration (FDA) for clinical use in the treatment of cyanide toxicity in the United States. The kit contains two 2.5-g vials, which should be reconstituted with 0.9% sodium chloride (not included).^[13]

Each hydroxocobalamin molecule can bind a cyanide ion by substituting it for the hydroxo ligand linked to the trivalent cobalt ion. This produces cyanocobalamin, which is then excreted in the urine.^[13] Due to its relatively safe profile when compared with sodium nitrite, physicians should consider hydroxocobalamin as a first-line antidote for cyanide toxicity. Administration of hydroxocobalamin is considered safe in the setting of concomitant carbon monoxide poisoning in the setting of smoke inhalation.^[13]

Cyanide Antidote Kit

The Pasadena (formerly Lilly) Cyanide Antidote Kit contains amyl nitrite, sodium nitrite, and sodium thiosulfate. Theoretically, the nitrite components oxidize iron contained in hemoglobin to methemoglobin. This creates an additional site for cyanide binding and promotes dissociation from cytochrome oxidase. Resultant cyanomethemoglobin then may be converted to less toxic thiocyanate through enzymes, such as rhodanese or other sulfurtransferases, in the presence of sodium thiosulfate.

Only use amyl nitrite perles as a temporizing measure if intravenous (IV) access has not been established, as administration of IV sodium nitrite is more effective in creating therapeutic methemoglobin levels. Do not use sodium nitrite or use it only with extreme caution in the setting of concomitant carbon monoxide poisoning, owing to the risk of combined methemoglobin and carboxyhemoglobin. However, in cases of smoke inhalation in which cyanide toxicity is suspected, administration of sodium thiosulfate is safe.

Oxygen

Unlike carbon monoxide, inhibition of cytochrome oxidase by cyanide is thought to be noncompetitive. Therefore, oxygen has only antidotal efficacy in human cyanide poisoning through uncertain mechanisms. Patients probably should be treated with at least 100% oxygen. Humidified oxygen may be beneficial to victims of CK inhalation who are experiencing airway irritation or those with significant signs of cyanide toxicity. In addition, inhaled beta2-agonists may be used to treat bronchospasm resulting from the irritant effects of cyanogen chloride (CK) on the respiratory tract.

Hyperbaric oxygen (HBO) use may be considered for patients with cyanide toxicity that is refractory to other antidotes, especially in the setting of concomitant carbon monoxide poisoning.^{[14, 15, 16, 17]} However, its use in pure cyanide poisoning is controversial, as no human studies have been performed to date, although the animal data are intriguing.

In 1959, Ivanov showed that HBO restored normal activity of the brain in mice poisoned with cyanide.^[18] In 1966, Skene et al demonstrated a drop in mortality from 96% to 20% in a group of mice treated with HBO at 2 atmosphere absolute (ATA) compared with those treated at 1 ATA.^[19] Finally, Takano and Myazaki showed in 1980 that HBO at 2 ATA reduced the pyridine nuclide fluorescence (which represents the degree of blockage of the respiratory chain) in the renal cortices of rabbits poisoned with cyanide.^[20]

Class Summary

Antidotes either directly counteract cyanide's toxicity on the electron transport chain or help the body eliminate the cyanide molecule.

Hydroxocobalamin/Vitamin B-12a (Cyanokit)

The combination of hydroxocobalamin/vitamin B-12a interacts with cyanide to form nontoxic cyanocobalamin, which is excreted in the urine.

Amyl nitrite

Ampoules of amyl nitrate can be crushed into gauze and inhaled or broken into an Ambu bag and ventilated into the patient. However, this agent is used only as a temporary measure until intravenous (IV) access is obtained.

Sodium nitrite and Sodium thiosulfate (Nithiodote)

Sodium nitrite is the drug of choice (DOC) if intravenous (IV) access is available and the patient is not concomitantly poisoned with carbon monoxide. This agent creates methemoglobinemia more effectively than amyl nitrite.

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.

Sodium thiosulfate acts as donor of sulfane sulfur, which is used as a substrate by rhodanese and other sulfurtransferases for conversion of cyanide to thiocyanate. This agent is the drug of choice (DOC) for treating cyanide toxicity with concomitant carbon monoxide poisoning.

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 a first-line drug in controlling seizures related to cyanide toxicity.

Phenobarbital

Phenobarbital is a second-line agent for seizures refractory to benzodiazepines.