Antidote

Hydroxocobalamin (Cyanokit)

Also called Cyanokit

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

Indications

• Known or suspected cyanide poisoning, treated on suspicion: smoke inhalation with altered mentation, shock or a high lactate
• Cyanide toxicity from nitroprusside, industrial exposure, or ingested cyanide salts or plants
• Refractory vasoplegia after cardiopulmonary bypass or in sepsis, mainly when methylene blue is contraindicated (off-label)
• Vitamin B₁₂ deficiency (a separate 1 mg/mL IM product)

Dosing

Mechanism of action

Hydroxocobalamin (vitamin B₁₂a) holds a cobalt(III) ion in a corrin ring, and cyanide binds this cobalt more avidly than the ferric iron of cytochrome c oxidase. Each molecule swaps its hydroxo or aquo ligand for one cyanide ion, forming cyanocobalamin (vitamin B₁₂), which is nontoxic and excreted in urine; 5 g (3.7 mmol) binds about 100 mg of cyanide. Cytochrome oxidase then restarts oxidative phosphorylation and lactate clears. It also binds nitric oxide and hydrogen sulfide, which raises vascular tone.

Pharmacology

• Cardiovascular: BP rises during the infusion and settles within 4 h; systolic ≥180 or diastolic ≥110 in 18% of volunteers at 5 g (label)
• Metabolic: lactate falls as aerobic metabolism returns; no methemoglobin forms, so it suits combined CO poisoning
• Renal: oxalate crystals in urine in 61%; AKI, with an adjusted OR of 1.6 after smoke inhalation (Dépret 2019)
• Skin: erythema in 94%; acneiform rash in 20% at 7–28 days

Pharmacokinetics

Chemistry

• Cobalt(III) in a corrin ring, with a dimethylbenzimidazole nucleotide below and a hydroxo group above; C₆₂H₈₉CoN₁₃O₁₅P, MW 1346; dark red and water-soluble
• The upper ligand trades between hydroxide and water (pKa near 8), so at pH 7.4 most is labile aquocobalamin, which cyanide displaces quickly
• Cyanokit: one 5 g lyophilized vial reconstituted with 200 mL 0.9% NaCl (LR or D5W if needed) to 25 mg/mL, pH 3.5–6.0; rock, do not shake; use within 6 h
• Incompatible with sodium thiosulfate, sodium nitrite, ascorbic acid, blood products and many drugs: give through its own line

Adverse effects and cautions

In the one-pagers

• BurnsInhalation injury, CO and cyanide: Hydroxocobalamin 5 g IV over 15 min, may repeat once; own line; red skin and urine. Follow your institution's or agency's protocols.
• Vasopressors and InotropesChoosing the agent by shock type and patient: Post-bypass vasoplegia: Norepinephrine + vasopressin: Methylene blue, hydroxocobalamin
• After Cardiac SurgeryTamponade, low output or vasoplegia?: Vasoplegia: MAP under 65, CI over 2.2, SVR under 800 (risks: long bypass, preop ACE inhibitors). Norepinephrine plus vasopressin; if refractory, methylene blue 1 to 2 mg/kg (serotonin syndrome with SSRIs, falsely low SpO2, G6PD hemolysis) or hydroxocobalamin 5 g (red urine, lab interference, CRRT blood-leak alarms). Follow your institution's protocols.
• Toxidromes and AntidotesReversal antidotes: Cyanide (smoke inhalation): Hydroxocobalamin 5 g IV over 15 min, plus 100% oxygen: Preferred over nitrite if CO likely; red skin, urine

Other antidote drugs

• Acetylcysteine
• Fomepizole
• Lipid emulsion 20%

Sources

1. FDA label: Cyanokit (2021)
2. Dépret 2019 (AKI after smoke inhalation)
3. Charles 2019 (vasoplegia review)

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.