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Bedside Snapshot
Primary ED/ICU/prehospital role: First-line IV antidote for known or suspected cyanide poisoning (including smoke inhalation from closed-space fires, industrial exposures, and ingestion of cyanide salts).
Mechanism: Each hydroxocobalamin molecule tightly binds one cyanide ion to form cyanocobalamin (vitamin B12), which is renally excreted. This pulls cyanide off cytochrome oxidase and restores mitochondrial respiration without inducing methemoglobinemia.
Adult cyanide dose (Cyanokit): Initial 5 g IV infusion over 15 minutes (entire 5 g vial). Depending on severity and response, a second 5 g dose may be given (total 10 g). For patients in extremis, both doses may be given rapidly (15 minutes each).
Pediatric cyanide dose: 70 mg/kg IV (up to 5 g) infused over 15 minutes. A second 70 mg/kg (up to 5 g) dose may be given based on severity and clinical response (maximum total 140 mg/kg, not to exceed 10 g).
Onset: Antidotal effect begins during the infusion as cyanide is bound; clinical improvement in mental status, hemodynamics, and lactate may be seen within minutes to an hour when cyanide is a major driver.
Common adverse effects: Transient hypertension, red discoloration of skin and urine (chromaturia), erythema, rash, nausea, headache. Serious but uncommon issues include acute kidney injury with oxalate nephropathy and interference with numerous laboratory assays.
Practical caveats: Hydroxocobalamin turns plasma, urine, and dialysate red and interferes with many colorimetric laboratory tests (lactate, carboxyhemoglobin, creatinine, bilirubin, etc.) and some dialysis machines. Ideally draw key labs (lactate, co-oximetry, cyanide level if available) before infusion, but do not delay antidote in an unstable patient.
Brand & Generic Names
- Generic Name: Hydroxocobalamin
- Brand Names: Cyanokit (IV antidote kit); parenteral hydroxocobalamin also exists as vitamin B12 formulations – availability is region- and institution-specific
Medication Class
Cyanide antidote; injectable vitamin B12 (hydroxylated cobalamin); nitric oxide and hydrogen sulfide scavenger (investigational for vasoplegic shock)
Pharmacology
Mechanism of Action:
- Hydroxocobalamin is the hydroxylated, biologically active form of vitamin B12 with a central trivalent cobalt ion within a corrin ring structure
- Cyanide has high affinity for trivalent cobalt; each hydroxocobalamin molecule binds one cyanide ion, replacing the hydroxo ligand and forming cyanocobalamin (vitamin B12), which is non-toxic and renally excreted
- By binding free cyanide, hydroxocobalamin prevents cyanide from inhibiting cytochrome c oxidase (complex IV) in the mitochondrial electron transport chain, thereby restoring oxidative phosphorylation and aerobic metabolism
- Compared with traditional cyanide antidotes (nitrites/thiosulfate), hydroxocobalamin does not rely on methemoglobin formation and thus does not worsen oxygen-carrying capacity—critical in smoke inhalation where carbon monoxide poisoning is common
- High-dose hydroxocobalamin also scavenges nitric oxide and may bind hydrogen sulfide; this underlies investigational use in vasodilatory shock (septic or post-cardiopulmonary bypass vasoplegia) to increase vascular tone and blood pressure
Pharmacokinetics:
- Formulation: Cyanokit contains lyophilized hydroxocobalamin powder (typically one 5 g vial per kit in the U.S.; some kits contain two 2.5 g vials). Vials are reconstituted with 0.9% NaCl (usually 200 mL for a 5 g vial, giving 25 mg/mL)
- Onset: Binding of cyanide begins during infusion, with clinical effect often seen rapidly, especially in cyanide-driven cardiovascular collapse
- Distribution: Volume of distribution is moderate (roughly 0.9–1.3 L/kg in adult studies) with high protein binding; hydroxocobalamin distributes into extracellular fluid and tissues
- Metabolism/elimination: Cyanide-bound hydroxocobalamin (cyanocobalamin) is excreted unchanged in urine. Hydroxocobalamin is also metabolized and excreted in bile and urine as cobalamin derivatives
- Elimination half-life: Terminal half-life after a 5 g dose has been reported on the order of 26–31 hours, but red discoloration of urine and plasma may persist for days
- Renal impairment: Not formally studied, but hydroxocobalamin and cyanocobalamin are renally eliminated; cases of oxalate nephropathy and acute kidney injury have been reported after large doses. Use is still recommended in life-threatening cyanide poisoning, with post-resuscitation renal monitoring
- Hepatic impairment: Not formally studied; no specific dose adjustment is recommended in labeling given the life-threatening nature of cyanide poisoning
Dosing & Administration
Available Forms (Cyanokit):
- Cyanokit 5 g vial: Lyophilized hydroxocobalamin powder in a glass vial, reconstituted with 200 mL of 0.9% sodium chloride to yield 25 mg/mL (5 g/200 mL)
- Some kits contain two 2.5 g vials, each reconstituted with 100 mL of diluent to yield 25 mg/mL per vial; both vials are infused for an adult 5 g dose
- Diluent: 0.9% sodium chloride is preferred; Lactated Ringer's or D5W are acceptable alternatives in some protocols. Diluent is not supplied in all kits and must be provided separately
- Infusion sets: Cyanokit includes a vented infusion set and transfer spike with in-line filter. Other drugs should not be co-administered through the same line due to incompatibility and red discoloration
- Other hydroxocobalamin products: lower-dose IM hydroxocobalamin for vitamin B12 deficiency (e.g., 1,000 mcg/mL ampoules) exist but are not used for acute cyanide poisoning
Dosing – Cyanide Poisoning (Cyanokit – Follow Local Tox/Poison Center Guidance):
| Population | Initial Dose | Repeat Dosing / Max | Notes |
|---|---|---|---|
| Adults (known or suspected cyanide poisoning) | 5 g IV (1 x 5 g vial in 200 mL) infused over 15 minutes (~15 mL/min) | May repeat 5 g IV based on severity/response (total 10 g). Second dose over 15–120 minutes. | Treat empirically when suspicion is high; do not delay for lab confirmation |
| Pediatrics (infants–adolescents, cyanide poisoning) | 70 mg/kg IV (max 5 g) over 15 minutes | May repeat 70 mg/kg IV (max 5 g) based on severity/response. Max total 140 mg/kg, not to exceed 10 g. | Draw weight-based volume from reconstituted vial(s); many EMS protocols use 2.8 mL/kg at 25 mg/mL |
| Smoke inhalation victim in extremis or cardiac arrest | 5 g IV as rapid infusion (as fast as tolerable, often ~15 min or less) | Consider second 5 g IV if ongoing arrest/shock and cyanide strongly suspected | Obtain lactate and co-oximetry before giving if it will not delay antidote in an unstable patient |
| Suspected nitroprusside-associated cyanide toxicity | 5 g IV over 15 minutes (adult) or 70 mg/kg (peds, max 5 g) | May repeat once as above per tox guidance | Stop nitroprusside; add supportive care and consider sodium thiosulfate |
Dosing – Vasoplegic / Vasodilatory Shock (Off-Label, Investigational):
| Indication | Suggested Dose (Adult) | Context | Notes |
|---|---|---|---|
| Refractory septic shock (off-label) | Single 5 g IV infusion over ~15–30 minutes | Used in small RCTs and observational studies as adjunct to vasopressors | Associated with reduced vasopressor requirements in feasibility trials; impact on mortality unclear |
| Post-cardiac surgery vasoplegic syndrome (off-label) | 5 g IV once (some series use 5–10 g total) | Case series/observational data only | Reserved for refractory vasoplegia under intensivist/anesthesia/cardiac surgery guidance |
Additional Dosing & Administration Notes:
- Reconstitution: For a 5 g vial, add 200 mL of 0.9% NaCl using the provided transfer spike; gently invert or rock for at least 60 seconds until fully dissolved. Do not vigorously shake
- Infuse via the provided vented IV set with in-line filter; do not mix other medications in the same line. If multiple infusions are required, use a dedicated line if possible
- Blood sampling: If cyanide level or co-oximetry are desired, draw blood before starting infusion when feasible. Hydroxocobalamin will cause artifactual changes in colorimetric assays (including lactate, creatinine, bilirubin, and carboxyhemoglobin)
- Hypertension is common but usually transient and self-limited; monitor BP closely, especially in patients with coronary artery disease or aortic pathology
- Do not delay administration in critically ill patients with high suspicion of cyanide poisoning while waiting for labs or antidote approvals; time is tissue
Contraindications
Contraindications (For Cyanide Poisoning Use):
- There are no absolute contraindications in the setting of life-threatening cyanide poisoning
- Practical contraindication: Known anaphylactic reaction to hydroxocobalamin or cyanocobalamin (vitamin B12). In such cases, risks vs. benefits must be weighed in consultation with toxicology
Major Precautions:
- Renal injury: Cases of acute kidney injury and calcium oxalate nephropathy have been reported after large doses. Monitor renal function and urine output, especially in patients with pre-existing kidney disease
- Lab interference: Hydroxocobalamin's deep red color interferes with many colorimetric assays (lactate, carboxyhemoglobin, creatinine, bilirubin, LFTs, etc.) and can trigger false alarms on dialysis machines or interfere with pulse oximetry. Interpret lab values cautiously after administration
- Allergic reactions: Rash, urticaria, chest tightness, or anaphylaxis have been reported. Have resuscitation equipment and medications available during infusion
- Hypertension: Transient but sometimes marked increases in BP may occur; monitor closely in patients with acute coronary syndromes, aortic dissection, or intracranial hemorrhage
- Pregnancy/lactation: Used in life-threatening cyanide poisoning when benefits clearly outweigh theoretical risks; limited data but no clear teratogenic signal
- Interactions with other cyanide antidotes: Can be used with sodium thiosulfate, but many protocols avoid concurrent nitrite therapy due to overlapping effects; if used together, run in separate IV lines
Adverse Effects
Common:
- Chromaturia (dark red urine) lasting up to several days; red discoloration of skin and mucosa
- Transient hypertension (often within 2–4 hours of dosing)
- Headache, nausea, vomiting
- Erythema, rash, or pruritus; acneiform or pustular eruptions days after dosing
- Injection site reactions and discomfort
Serious:
- Acute kidney injury including acute tubular necrosis and oxalate nephropathy
- Anaphylaxis or severe hypersensitivity reactions (bronchospasm, hypotension or hypertension, angioedema)
- Interference with critical laboratory measurements leading to potential misinterpretation (e.g., falsely elevated lactate or creatinine, inaccurate co-oximetry)
- Potential worsening of ischemia in patients unable to tolerate transient hypertension (e.g., active aortic dissection, hypertensive emergency) – theoretical and rare but should be considered
Monitoring
- Hemodynamics: Blood pressure, heart rate, and MAP continuously during and after infusion; watch for hypertension or persistent hypotension suggesting alternative/additional pathology
- Mental status, respiratory status, and lactate/acid–base status to gauge response in cyanide poisoning (recognizing that post-dose lactates may be assay-confounded)
- Renal function (serum creatinine, BUN) and urine output over 24–72 hours, especially in patients receiving repeated doses or with baseline kidney disease
- Electrolytes and co-oximetry (if obtained prior to antidote) to evaluate for co-toxicity (e.g., carbon monoxide) and metabolic disturbances
- For off-label vasoplegic shock use: vasopressor dose requirements (e.g., norepinephrine equivalents), MAP, and markers of organ perfusion (urine output, lactate trends)
Indications / Clinical Uses (Acute Care Focus)
- Treatment of known or suspected cyanide poisoning from any route (inhalation, ingestion, dermal), including smoke inhalation from enclosed-space fires, industrial hydrogen cyanide exposure, and cyanide salt ingestion
- Cyanide toxicity from high-dose or prolonged sodium nitroprusside infusions, particularly in renal dysfunction or prolonged ICU use
- Empiric antidote in unstable patients with high suspicion for cyanide poisoning where confirmatory testing is unavailable or delayed (e.g., arrest or shock in a closed-space fire victim with very high lactate)
- Adjunct/bridge therapy in refractory vasodilatory shock (e.g., septic shock or post-cardiopulmonary bypass vasoplegia) to reduce vasopressor requirements – off-label and still investigational
- Vitamin B12 replacement (hydroxocobalamin formulations) for deficiency states – typically much lower IM doses than used for antidote purposes (not the focus of this card)
Clinical Pearls
High lactate in smoke inhalation: In smoke inhalation from closed-space fires, a very high lactate (e.g., >8–10 mmol/L) and severe hemodynamic instability should strongly trigger empiric hydroxocobalamin, especially if the story fits cyanide exposure.
Draw labs before infusion: Draw co-oximetry and lactate before hydroxocobalamin if it can be done without delaying antidote—post-dose values can be uninterpretable due to assay interference.
Patient will turn red: Warn staff and family that the patient will likely turn red (skin, plasma, urine); this is expected and not a reason to stop therapy.
Dedicated IV line: Avoid co-administering other medications through the same line during infusion; the red solution can mask precipitation and compatibility issues.
Vasoplegic shock use is investigational: For vasoplegic shock, hydroxocobalamin is not standard of care; it's an adjunct for refractory cases under specialist guidance. Evidence shows reduced vasopressor requirements but not yet clear mortality benefit.
Involve poison control early: Consult your regional poison control center or a medical toxicologist early for any suspected cyanide poisoning or complex vasoplegic shock cases where hydroxocobalamin is being considered.
References
- Meridian Medical Technologies. (2018). CYANOKIT (hydroxocobalamin for injection) prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov
- DrugBank Online. (2024). Hydroxocobalamin (DB00200). DrugBank. https://go.drugbank.com/drugs/DB00200
- Thompson, J. P., Marrs, T. C., & Ballantyne, B. (2012). Hydroxocobalamin in cyanide poisoning. Clinical Toxicology, 50(10), 875–885.
- Patel, J. J., et al. (2023). High-dose IV hydroxocobalamin in septic shock: A randomized controlled trial. Chest, 163(4), 834–844.
- Bridwell, R. (2019). EM@3AM: Cyanide toxicity. emDocs. https://www.emdocs.net/em3am-cyanide-toxicity/