Hydroxocobalamin
Vitamin B12 (Cyano-Kit)
Class:
Water soluble Vitamin
Water soluble Vitamin
Mechanism of Action:
Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis.
In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. The action of hydroxocobalamin in the treatment of cyanide poisoning is based on its ability to bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by submitting it for the hydroxo ligand linked to the trivalent cobalt ion, to form cyanocobalamin, which is then excreted in the urine.
Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis.
In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. The action of hydroxocobalamin in the treatment of cyanide poisoning is based on its ability to bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by submitting it for the hydroxo ligand linked to the trivalent cobalt ion, to form cyanocobalamin, which is then excreted in the urine.
Indications:
Treatment of known or suspected cyanide poisoning.
Treatment of known or suspected cyanide poisoning.
Contraindications:
None.
None.
Adverse reactions:
Serious adverse reactions with hydroxocobalamin include allergic reactions and increases in blood pressure. Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Consideration should be given to use of alternative therapies, if available.
Many patients with cyanide poisoning will be hypotensive; however, elevations in blood pressure have also been observed in known or suspected cyanide poisoning victims. Elevations in blood pressure (>180 mmHg systolic or >110 diastolic) were observed in approximately 18% of healty subjects (not exposed to cyanide) receiving hydroxycobalamin 5g and 28% of subjects receiving 10g. Increases in blood pressure were noted shortly after the infusions were started; the maximal increase in blood pressure was observed toward the end of the infusion. These elevations were generally transient and returned to baseline leveles within 4 hours of dosing.
Serious adverse reactions with hydroxocobalamin include allergic reactions and increases in blood pressure. Use caution in the management of patients with known anaphylactic reactions to hydroxocobalamin or cyanocobalamin. Consideration should be given to use of alternative therapies, if available.
Many patients with cyanide poisoning will be hypotensive; however, elevations in blood pressure have also been observed in known or suspected cyanide poisoning victims. Elevations in blood pressure (>180 mmHg systolic or >110 diastolic) were observed in approximately 18% of healty subjects (not exposed to cyanide) receiving hydroxycobalamin 5g and 28% of subjects receiving 10g. Increases in blood pressure were noted shortly after the infusions were started; the maximal increase in blood pressure was observed toward the end of the infusion. These elevations were generally transient and returned to baseline leveles within 4 hours of dosing.
Adult Dosage and Administration
5 g (i.e., both 2.5g vials) IV infusion over 15 minutes diluted in 100ml of NS (approx. 15 mL/min or 7.5 minutes/vial).
Depending on the severity of the poisoning and the clinical response, a second dose of 5 g may be administered by IV infusion for a total dose of 10 g. The rate of infusion for the second dose may range from 15 minutes (for patients in extremis) to two hours, as clinically indicated.
5 g (i.e., both 2.5g vials) IV infusion over 15 minutes diluted in 100ml of NS (approx. 15 mL/min or 7.5 minutes/vial).
Depending on the severity of the poisoning and the clinical response, a second dose of 5 g may be administered by IV infusion for a total dose of 10 g. The rate of infusion for the second dose may range from 15 minutes (for patients in extremis) to two hours, as clinically indicated.
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Pediatric Dosage and Administration:70 mg/kg over 15 minutes.
Special Considerations:
- Pregnancy safety: Category C.
- Emergency Patient Management:
In addition to Cyanokit, treatment of cyanide poisoning must include immediate attention to airway patency, adequacy of oxygenation and hydration, cardiovascular support, and management of any seizure activity. Consideration should be given to deontamination measures based on the route of the exposure. - Use with other cyanide antidotes:
Caution should be exercised when administering other cyanide antidotes simultaneously with Hydroxocobalamin, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote with Hydroxocobalamin, these drugs should not be administered concurrently in the same IV line. - Preparation of Solution for Infusion
2.5g vial diluted with 100mL NS (or Ringer / D5W)
Visually inspect for particulate matter and color prior to administration. If the reconstituted solution is not dark red or if particulate matter is seen after the solution has been appropriately mixed, the solution should be discarded.