Cyanide Poisoning — Hydroxocobalamin Protocol

Key Points

• Treat severe suspected cyanide poisoning clinically; do not wait for a cyanide concentration.
• Enclosed-space fire plus severe lactic acidosis, coma, seizure, or cardiovascular collapse should raise concern.
• Hydroxocobalamin is a preferred antidote because it binds cyanide without intentionally reducing oxygen-carrying capacity.
• Give 100% oxygen and standard resuscitation because carbon monoxide and thermal inhalation injury commonly coexist.
• A typical adult hydroxocobalamin dose is 5 g IV, with repeat dosing for persistent severe toxicity when indicated.
• Nitrite antidotes can worsen oxygen delivery through methemoglobinemia and require careful case selection.
• Hydroxocobalamin can interfere with laboratory assays and dialysis equipment.
• Decontaminate ongoing dermal exposure while protecting staff from secondary contamination.

Algorithm

1. Remove the patient from exposure and protect rescuers from contamination.
2. Assess and secure the airway, give 100% oxygen, and support ventilation and circulation.
3. Obtain lactate, blood gas, co-oximetry, ECG, glucose, and basic labs without delaying antidote in a critically ill patient.
4. Give hydroxocobalamin promptly when severe cyanide poisoning is strongly suspected.
5. Treat seizures with benzodiazepines and manage shock with fluids and vasopressors as needed.
6. Treat concurrent carbon monoxide poisoning, burns, and inhalation injury.
7. Consult poison control or medical toxicology for adjunct sodium thiosulfate, unusual exposures, or refractory shock.
8. Admit severe cases to ICU and monitor for organ injury and delayed neurologic effects.

Clinical Synopsis & Reasoning

Cyanide exposure can occur from structural fires, industrial chemicals, electroplating, mining, laboratory compounds, and deliberate ingestion. Smoke inhalation is the most common emergency context, and carbon monoxide poisoning often coexists. Cyanide blocks oxidative phosphorylation, forcing anaerobic metabolism despite oxygenated blood. Severe poisoning therefore produces marked lactate elevation, hypotension, cardiovascular collapse, altered mental status, seizure, and sometimes unusually bright venous blood, although no bedside sign is sufficiently sensitive or specific to confirm the diagnosis.

Do not wait for a cyanide level. In smoke-inhalation victims, consider cyanide when there is enclosed-space exposure plus coma, seizures, persistent hypotension, cardiac arrest, or severe unexplained lactic acidosis. Soot in the airway, facial burns, carbonaceous sputum, and thermal injury increase concern for inhalation injury but are not specific for cyanide. Evaluate simultaneously for carbon monoxide using co-oximetry because standard pulse oximetry can appear normal in CO poisoning. Other causes of high lactate include shock, seizure, metformin toxicity, sepsis, and severe hypoxemia.

Dermal or gastrointestinal cyanide salts can continue releasing toxin, so protect staff and perform decontamination when indicated. Remove contaminated clothing and irrigate exposed skin. Do not induce emesis after ingestion. Airway control may be difficult in fire victims because thermal edema can progress rapidly; early intubation is appropriate when airway injury is evolving.

Treatment Strategy & Disposition

Provide 100% oxygen, ventilation, circulation support, seizure control, and standard cardiac arrest care as needed. Oxygen does not directly reverse cytochrome oxidase inhibition but treats concurrent hypoxemia and carbon monoxide exposure and should not be withheld. Hydroxocobalamin is the preferred modern antidote in many emergency systems because it binds cyanide to form cyanocobalamin and does not induce methemoglobinemia, making it particularly suitable when concomitant carbon monoxide poisoning is possible.

A common adult hydroxocobalamin regimen is 5 g IV over approximately 15 minutes, with a second 5 g dose considered for persistent severe toxicity according to clinical response and product guidance. Sodium thiosulfate enhances conversion of cyanide to thiocyanate and can be used as an adjunct or alternative under toxicology guidance. Nitrite-based antidotes intentionally produce methemoglobin to bind cyanide and are generally less attractive in smoke inhalation because induced methemoglobinemia can further impair oxygen delivery when carbon monoxide poisoning is present.

Expect transient red discoloration of skin, urine, and plasma after hydroxocobalamin. It can interfere with colorimetric laboratory assays and some hemodialysis blood-leak detectors, so notify the laboratory and dialysis team. Severe poisoning requires ICU care and poison-center or medical-toxicology consultation. Continue treatment of inhalation injury, burns, carbon monoxide exposure, shock, and organ failure even after antidote administration.

Epidemiology / Risk Factors

• Cyanide toxicity is uncommon but can affect multiple victims during industrial or fire incidents.
• Structural fires are an important source because combustion of nitrogen-containing synthetic materials can release cyanide.
• Coexisting carbon monoxide exposure is common after enclosed-space smoke inhalation.
• Industrial settings using cyanide salts or hydrogen cyanide present concentrated exposure risk.
• Because confirmatory testing is slow, actual incidence is probably underrecognized in fatal fire cases.

Investigations

Antidote Options

Pharmacology

Prognosis / Complications

• Rapid antidote and resuscitation can produce dramatic recovery even from profound shock.
• Cardiac arrest, prolonged severe acidosis, and anoxic brain injury worsen prognosis.
• Survivors may develop delayed neurocognitive or movement abnormalities after severe poisoning.
• Concurrent burns, inhalation injury, and carbon monoxide toxicity often determine hospital course after fire exposure.
• Outcome is strongly time dependent because cyanide acts rapidly at the cellular level.

Patient Education / Counseling

• Explain the suspected exposure source and ensure occupational or environmental safety review before return to the same setting.
• After fire exposure, review symptoms of delayed respiratory injury and carbon monoxide-related neurologic sequelae.
• Seek urgent care for recurrent confusion, weakness, dyspnea, chest pain, seizure, or new neurologic symptoms.
• Industrial exposures should trigger workplace safety reporting and prevention measures according to local requirements.
• Hydroxocobalamin commonly causes temporary red urine and skin discoloration that can persist for days.
• Arrange follow-up after severe poisoning for neurologic, cardiac, pulmonary, and burn-related complications.

Notes

Cyanide poisoning is one of the settings in which empiric antidotal treatment may be safer than waiting for diagnostic certainty. The exposure context, severity of lactic acidosis, neurologic status, and hemodynamics drive the decision.

Hydroxocobalamin does not end the resuscitation. Fire victims still require treatment for airway edema, carbon monoxide toxicity, thermal injury, shock, trauma, and pulmonary complications.

References

1. CDC Cyanide Emergency Resources — Link
2. American Heart Association 2025 Toxicology Resuscitation Guidance — Link